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Geneva, Switzerland

The University of Geneva is a public research university located in Geneva, Switzerland. It was founded in 1559 by John Calvin, as a theological seminary and law school. It remained focused on theology until the 17th century, when it became a center for Enlightenment scholarship. In 1873, it dropped its religious affiliations and became officially secular. Today, the university is the second-largest university in Switzerland by number of students. In 2009, the University of Geneva celebrated the 450th anniversary of its founding.UNIGE has programs in various fields but has academic and research programs in international relations , law, astrophysics, astronomy, genetics . The university holds and actively pursues teaching, research, and community service as its primary objectives. In 2011, it was ranked 73rd worldwide by the Academic Ranking of World Universities, and 69th in the QS World University Rankings.UNIGE is a member of the League of European Research Universities, the Coimbra Group and the European University Association. Wikipedia.


Degruyter W.,University of California at Berkeley | Bonadonna C.,University of Geneva
Geophysical Research Letters | Year: 2012

We introduce a novel analytical expression that allows for fast assessment of mass flow rate of both vertically-rising and bent-over volcanic plumes as a function of their height, while first order physical insight is maintained. This relationship is compared with a one-dimensional plume model to demonstrate its flexibility and then validated with observations of the 1980 Mount St. Helens and of the 2010 Eyjafjallajkull eruptions. The influence of wind on the dynamics of volcanic plumes is quantified by a new dimensionless parameter () and it is shown how even vertically-rising plumes, such as the one associated with the Mount St. Helens 1980 eruption, can be significantly affected by strong wind. Comparison between a one-dimensional model and the analytical equation gives an R 2-value of 0.88, while existing expressions give negative R 2-values due to their inability to adapt to different source and atmospheric conditions. Therefore, this new expression has important implications both for current strategies of real-time forecasting of ash transport in the atmosphere and for the characterization of explosive eruptions based on the study of tephra deposits. In addition, this work provides a framework for the application of more complete three-dimensional numerical models as it greatly reduces the parameter space that needs to be explored. © 2012. American Geophysical Union. All Rights Reserved.


Abdulcadir J.,University of Geneva
Swiss medical weekly | Year: 2011

In multi-ethnic European society medical professionals are faced with an increasing number of women originating from countries where female genital mutilations/cuttings (FGM/C) are practised. Recent studies, however, emphasise the lack of knowledge on this subject. This review article aims to present FGM/C as a complex socio-healthcare and multidisciplinary issue, outlining the definition, classification, epidemiology and anthropologico-legal aspects of FGM/C. It explains the approach to be adopted to FGM/C women, focusing on defibulation, clitoral restoration/repair and re-infibulation. Finally, it reports on the discussions surrounding pricking/nicking and the proposals for alternative rituals in recent years.


Bakker E.,University of Geneva
TrAC - Trends in Analytical Chemistry | Year: 2014

This review aims to highlight a recent important direction to place ion-selective electrodes based on polymeric sensing materials under dynamic electrochemistry control. This allows one to design sensors with a range of improved characteristics. This review also showcases developments to achieve calibration-free ion-sensing strategies by using thin layer coulometry at ion-selective membranes. Finally, strategies to fabricate electrochemically-addressable ion-selective thin membrane layers are discussed, especially in view of realizing stripping ion-transfer voltammetric sensors. © 2013 Elsevier Ltd.


Bastide L.,University of Geneva
Health, Risk and Society | Year: 2015

In Indonesia, transnational labour migrations have become a major source of foreign currency over the past 20 years. On migration routes and abroad, migrants are often subjected to abusive, sometimes violent or even deadly experiences. Yet, the ‘migration industry’ can count on increasing numbers of candidates. Drawing on 20-month multi-sited ethnographic fieldwork conducted between 2006 and 2009 in Java (Indonesia), Kuala Lumpur (Malaysia) and Singapore, I explore how, under these circumstances, migrant workers relate to this risky adventure. As it appears, local conceptions of ‘fate’ help to overcome fear: as future is perceived in terms of destiny, and since destiny lies ultimately in the hands of God, dealing with potential risks is a matter of religious faith: only by surrendering sincerely to Allah is the migrant able to secure his or her future in this dangerous milieu. In this cognitive framework, incidents are conceived of as cobaan Tuhan – godly trials – full of meanings, which are meant to test one’s faith in God. And bad experiences, rather than being seen as contingent, are perceived as godly signs, which need to be interpreted in order to comply with God’s will. I aim to show how this worldview formulates risk and/or uncertainty in terms of nasib and/or takdir (fate; destiny). This relation to risk, in turn, challenges Western-centred risk theories in adding nuance to the relationship between agency and risk, by tracing a singular conceptual tension between risk and fate. © 2015 Taylor & Francis.


Vauthey E.,University of Geneva
ChemPhysChem | Year: 2012

Molecular systems where several apparently equivalent charge separation pathways exist upon photoexcitation are presented. They encompass MQ n (n≥2) architectures, where M is a chromophore and Q an electron transfer quencher (either donor or acceptor), and M-M systems where M acts as both electron donor and acceptor. In all cases, charge separation involves symmetry breaking. The conditions for such process to be operative as well as the origin of the symmetry breaking are discussed. © 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.


Gonzalez-Gaitan M.,University of Geneva | Julicher F.,Max Planck Institute for the Physics of Complex Systems
Cold Spring Harbor Perspectives in Biology | Year: 2014

Morphogens are signaling molecules that are secreted by a localized source and spread in a target tissue where they are involved in the regulation of growth and patterning. Both the activityofmorphogenetic signaling and the kineticsof ligand spreadingin atissue depend on endocytosis and intracellular trafficking. Here, we review quantitative approaches to study how large-scale morphogen profiles and signals emerge in a tissue from cellular trafficking processes and endocytic pathways. Starting from the kinetics of endosomal networks, we discuss the role of cellular trafficking and receptor dynamics in the formation of morphogen gradients. These morphogen gradients scale during growth, which implies that overall tissue size influences cellular trafficking kinetics. Finally, we discuss how such morphogen profiles can be used to control tissue growth. We emphasize the role of theory in efforts to bridge between scales. © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.


Badaut J.,Loma Linda University | Badaut J.,University of Geneva
Neuroscience | Year: 2010

Aquaglyceroporins belong to the aquaporin family and are permeable to water and also to small solutes such as glycerol and urea. In this review, we will compare the expression of aquaporin 9 (AQP9), an aquaglyceroporin, with that of AQP4, a pure water channel, in pathological conditions. In astrocytes, AQP4 is mainly involved in water and ionic homeostasis. Its expression is highly modified in several brain disorders and it plays a key role in cerebral edema formation. AQP9 is expressed in astrocytes and in catecholaminergic neurons. The level of expression of brain AQP9 is under the control of blood insulin concentrations, and its expression is increased in diabetes, suggesting that AQP9 could be involved in brain energy metabolism. The induction of AQP9 in astrocytes is observed over time after stroke onset, suggesting participation in the clearance of excess lactate in the extracellular space. In some models, AQP9 is also induced in non-catecholaminergic neurons after global ischemia and in the periphery of gliomas, however functional roles are still unclear. The review of literature underlies that each AQP has several distinctive roles which depend on the AQP and cell types. © 2010 IBRO.


Published studies where antimony association with colloidal and particulate phases is studied in waters, soils and sediments are reviewed. The techniques considered range from the simple calculation of partition coefficients, the application of size-based speciation methods or sequential extraction techniques to the use of more sophisticated techniques such as X-ray absorption spectroscopy (XAS). What these methods have in common is that they are applied directly to bulk samples and that, with the exception of XAS, they give operationally defined results, which are very often difficult to interpret and compare. In the case of the extraction methods, which are the most commonly used, this difficulty is compounded by the tendency of many authors to endlessly modify the experimental procedures. Antimony does not seem to associate to any significant extent with colloidal and particulate phases in waters. However, at the same time, it appears not to be easily extractable from soils where, even if it is usually present to a certain extent in 'iron oxide' fractions in sequential extraction methods, most remains in the so called 'residual' fraction. Unfortunately, the direct application of XAS techniques to real environmental samples, which could help to clarify antimony binding by solid phases, is precluded in most systems because of their insensitivity; only a few heavily polluted systems have been studied so far using these techniques. In these studies antimony is present as Sb(V) in soils and significantly bound by iron oxide phases. © 2011.


Noetzli M.,University of Lausanne | Eap C.B.,University of Lausanne | Eap C.B.,University of Geneva
Clinical Pharmacokinetics | Year: 2013

With the aging population and its rapidly increasing prevalence, dementia has become an important public health concern in developed and developing countries. To date, the pharmacological treatment is symptomatic and based on the observed neurotransmitter disturbances. The four most commonly used drugs are donepezil, galantamine, rivastigmine and memantine. Donepezil, galantamine and rivastigmine are acetylcholinesterase inhibitors with different pharmacodynamic and pharmacokinetic profiles. Donepezil inhibits selectively the acetylcholinesterase and has a long elimination half-life (t1/2) of 70 h. Galantamine is also a selective acetylcholinesterase inhibitor, but also modulates presynaptic nicotinic receptors. It has a t1/2 of 6-8 h. Donepezil and galantamine are mainly metabolised by cytochrome P450 (CYP) 2D6 and CYP3A4 in the liver. Rivastigmine is a so-called 'pseudo-irreversible' inhibitor of acetylcholinesterase and butyrylcholinesterase. The t1/2 of the drug is very short (1-2 h), but the duration of action is longer as the enzymes are blocked for around 8.5 and 3.5 h, respectively. Rivastigmine is metabolised by esterases in liver and intestine. Memantine is a non-competitive low-affinity antagonist of the NMDA receptor with a t1/2 of 70 h. Its major route of elimination is unchanged via the kidneys. Addressing the issue of inter-patient variability in treatment response might be of special importance for the vulnerable population taking anti-dementia drugs. Pharmacogenetic considerations might help to avoid multiple medication changes due to non-response and/or adverse events. Some pharmacogenetic studies conducted on donepezil and galantamine reported an influence of the CYP2D6 genotype on the pharmacokinetics of the drugs and/or on the response to treatment. Moreover, polymorphisms in genes of the cholinergic markers acetylcholinesterase, butyrylcholinesterase, choline acetyltransferase and paraoxonase were found to be associated with better clinical response to acetylcholinesterase inhibitors. However, confirmation studies in larger populations are necessary to establish evidence of which subgroups of patients will most likely benefit from anti-dementia drugs. The aim of this review is to summarize the pharmacodynamics and pharmacokinetics of the four commonly used anti-dementia drugs and to give an overview on the current knowledge of pharmacogenetics in this field. © 2013 Springer International Publishing Switzerland.


Durrer R.,University of Geneva
Classical and Quantum Gravity | Year: 2015

This review describes the discovery of the cosmic microwave background (CMB) radiation in 1965 and its impact on cosmology in the 50 years that followed. This discovery established the big bang model of the Universe, and the analysis of its fluctuations has confirmed the idea of inflation and led to the present era of precision cosmology. I discuss the evolution of cosmological perturbations and their imprint on the CMB as temperature fluctuations and polarization. I also show how a phase of inflationary expansion generates fluctuations in the spacetime curvature and primordial gravitational waves. In addition I present the findings of CMB experiments, from the earliest to the most recent ones. The accuracy of these experiments has helped us to estimate the parameters of the cosmological model with unprecedented precision, so that in the future we shall be able to test not only cosmological models but general relativity itself on cosmological scales. © 2015 IOP Publishing Ltd.


Bravar A.,University of Geneva
Nuclear and Particle Physics Proceedings | Year: 2015

The Mu3e experiment will search for the lepton flavor violating neutrinoless muon decay μ+→e+e-e+ with a sensitivity down to 10-16 (90% C.L.) using the world most intense continuous muon beam at the Paul Scherrer Institute. This decay is strongly suppressed in the Standard Model (BR<10-56). Several Beyond the SM models predict observable effects accessible to the new generation of LFV experiments. The search for the μ+→e+e-e+ decay requires excellent momentum, spacial, and time resolution to suppress backgrounds, high rate capability (detect more than 109 stopped muons per second), and large acceptance. The required detector performance is possible thanks to tracking detectors based on thin monolithic active silicon pixel sensors with high granularity (HV-MAPS), which incorporate the complete read-out electronics on the sensor chip, and very precise timing measurements using scintillating fibers and tiles coupled to silicon photo-multipliers operating at very high particle rates. © 2015 Elsevier B.V.


Williams A.F.,University of Geneva
Coordination Chemistry Reviews | Year: 2011

Coordination chemistry may be used to synthesise large molecules with a closed cavity of molecular dimensions and of roughly equal size in three dimensions. The systems discussed here will involve polytopic ligands linked into spherical shapes by metal coordination. After discussing general strategies for their synthesis using the coordinate bond, studies on systems possessing five-fold symmetry are discussed. This is particularly favourable for the formation of spherical molecules, and some of the problems of multicomponent self-assembly are discussed. After reviewing some recent work, it is suggested that either the combination of three-fold symmetry with four-fold or five-fold symmetry is particularly suitable for sphere formation. © 2011 Elsevier B.V.


Piguet C.,University of Geneva
Dalton Transactions | Year: 2011

Intermolecular connections play a crucial role in biology (recognition, signalling, binding), in physics (material cohesion) and in chemistry ((supra)molecular engineering). While a phenomenological thermodynamic free-energy approach for modelling self-assemblies is now at hand, a more satisfying description based on the chemically-intuitive enthalpic and entropic contributions remains elusive. On the other hand, the innumerable reports of empirical enthalpy/entropy correlations characterizing intermolecular interactions justify a questioning about the emergence and exploitation of an apparent 'fourth law of thermodynamics', which could provide a simple manipulation of intermolecular binding processes. This tutorial Perspective aims at highlighting the current level of non-quantum rationalization of enthalpy-entropy correlations and their chemical consequences on the tuning and on the programming of intermolecular interactions in pure materials, and in diluted solutions. © The Royal Society of Chemistry 2011.


Suveges M.,University of Geneva
Monthly Notices of the Royal Astronomical Society | Year: 2014

I propose a new procedure to estimate the false alarm probability, the measure of significance for peaks of periodograms. The key element of the new procedure is the use of generalized extreme-value distributions, the limiting distribution for maxima of variables from most continuous distributions. This technique allows reliable extrapolation to the very high probability levels required by multiple hypothesis testing, and enables the derivation of confidence intervals for the estimated levels. The estimates are stable against deviations from distributional assumptions, which are otherwise usually made either about the observations themselves or about the theoretical univariate distribution of the periodogram. The quality and the performance of the procedure are demonstrated on simulations and on two multimode variable stars from Sloan Digital Sky Survey Stripe 82. © 2014 The Author Published by Oxford University Press on behalf of the Royal Astronomical Society.


Boehncke W.-H.,University of Geneva | Menter A.,Baylor University
American Journal of Clinical Dermatology | Year: 2013

Psoriatic arthritis (PsA) increases the disease burden associated with psoriasis by further diminishing quality of life, increasing health care costs and cardiovascular risk, and potentially causing progressive joint damage. The presence of PsA influences psoriasis treatment by increasing overall disease complexity and, within the framework of current guidelines and recommendations, requiring the use of conventional disease-modifying anti-rheumatic drugs or tumor necrosis factor-α inhibitors in order to prevent progressive joint damage. Despite its important impact, PsA is still under-diagnosed in dermatology practice. Dermatologists are well positioned to recognize and treat PsA, given that it characteristically presents, on average, 10 years subsequent to the appearance of skin symptoms. Regular screening of psoriasis patients for early evident joint symptoms should be incorporated into daily dermatologic practice. Although drugs effective in PsA are available, not all patients may respond to treatment, and others may lose their initial response over time. New investigational therapies, such as inhibitors of interleukin-17A, interleukin-12/23, Janus kinase 3, or phosphodiesterase-4, may address unmet needs in psoriatic disease, with further research needed to determine the role of these agents in reducing joint damage and other comorbidities. © 2013 Springer International Publishing Switzerland.


Marceau G.,University of Geneva
Review of European, Comparative and International Environmental Law | Year: 2014

The Appellate Body (AB) Report in EC-Seal Products has potential ramifications for the environmental or social concerns in the World Trade Organization. It refines the jurisprudence on the balance between members' market access obligations and their right to give priority consideration to non-trade concerns under the General Agreement on Tariffs and Trade (GATT) and the Agreement on Technical Barriers to Trade (TBT). This article outlines the main points of the AB Report, particularly related to what measures constitute technical regulations within the scope of the TBT Agreement, and the relationship between the GATT and TBT Agreement in the context of the pursuit of legitimate non-trade concerns. It further highlights one of the issues raised in the report concerning processes and production methods (PPMs). In particular, it offers comments on what could constitute product-related and non-product related PPMs - a categorization that has emerged in the trade-environment doctrine over the last 40 years and that should now be informed by the AB's interpretation of the TBT Agreement in this case. © 2014 John Wiley & Sons Ltd.


Burkhard P.R.,University of Geneva
Parkinsonism and Related Disorders | Year: 2014

Many pharmacological agents may induce a variety of movement disorders, including dystonia, tremor, parkinsonism, myoclonus and dyskinesia, with an acute, subacute or more chronic time course. Motor symptoms may be isolated or part of a more extensive cerebral or systemic condition, such as the neuroleptic malignant syndrome or the serotonin syndrome. Drug-induced movement disorders share a number of features that should make them easy to identify, including a clear temporal relationship between medication initiation and symptom onset, a dose-effect, and, with the exception of tardive syndromes, complete resolution after discontinuation of the offending agent. Diagnosis relies on a thorough medication history. Medications commonly involved include dopamine receptor blockers, antidepressants and anti-epileptics, among many others. Mechanisms underlying drug-induced movement disorders involve blockade, facilitation or imbalance of dopamine, serotonin, noradrenaline and cholinergic neurotransmission in the basal ganglia. The present review focuses on drug-induced movement disorders that typically develop as an acute (hours to days) or subacute (days to weeks) event, including acute dystonic reactions, akathisia, drug-induced parkinsonism, neuroleptic malignant syndrome, serotonin syndrome, parkinsonism-hyperpyrexia syndrome, drug-induced tremor, drug-induced hyperkinesias and movement disorders associated with the use of recreational drugs. © 2013 Elsevier Ltd.


Waldburger J.-M.,University of Geneva
Current Rheumatology Reports | Year: 2010

In inflammatory disorders such as rheumatoid arthritis, cytokines and danger signals are sensed by the central nervous system, which adapts behavior and physiologic responses during systemic stress. The central nervous system can also signal the periphery to modulate inflammation through efferent hormonal and neuronal pathways. The brain and spinal cord are involved in this bidirectional interaction. A variety of neuronal pathways that modulate synovial inflammation have been implicated, including the sympathetic and the parasympathetic branches of the autonomic system. Another mechanism, the dorsal root reflex, involves antidromic signaling along somatic afferent fibers that influences joint inflammation by releasing neuropeptides and other neuromediators in the periphery. Some of the neurotransmitters and neuroreceptors involved have been identified in preclinical models and represent novel targets for the treatment of rheumatic diseases. © The Author(s) 2010.


Cooremans C.,University of Geneva
Energy Efficiency | Year: 2011

Profitability is not the main driver of capital investment decision-making; financial evaluation tools often play a secondary role in corporate investment choices; businesses do not follow capital finance theory prescriptions, contrary to what mainstream claims; the strategic character of investments has a heavier decisional weight than profitability. These findings are based on a review of different streams of literature (mainly organizational finance and strategic decision-making) which is described in the second part of the paper, after a first part summarizing the main stances of mainstream energy economics and the main findings of the alternative literature on energy-efficiency investments. Yet, what is a strategic investment? To fill the existing conceptual gap, we propose a definition of strategic investment and a new theoretical framework to analyze investment projects. An example of applying this framework to an energy-efficiency project is described. The partial influence of financial factors and the importance of strategic factors in investment decisions entail several implications for energy-efficiency practitioners, scholars, and public program developers, which are described in the last part of the paper. © 2011 Springer Science+Business Media B.V.


Negro F.,University of Geneva
Journal of Viral Hepatitis | Year: 2012

This review will focus on the impact of steatosis and insulin resistance on the response to antiviral therapy for chronic hepatitis C. Hepatitis C virus (HCV) infection is known to have direct and/or indirect effects on lipid and glucose metabolism, leading to, among other disturbances, steatosis and insulin resistance, respectively. Some of these disturbances have a marked HCV genotype distribution. For example, on average, patients with HCV genotype 3 have the highest prevalence and severity of viral fatty liver. On the other hand, the current global spread of the metabolic syndrome represents a formidable cofactor of morbidity in HCV-related chronic liver disease. Thus, the pathogenesis of steatosis and insulin resistance in patients with chronic hepatitis C may often be dual, i.e. viral and metabolic. This distinction is relevant because the effect (if any) of steatosis or insulin resistance on the response to antiviral agents seems to depend on their pathogenesis. Accumulating data suggest that viral fatty liver may not impact on response to therapy, while metabolic steatosis does. Similarly, viral insulin resistance may not reduce the rate of response to therapy to the same extent that metabolic insulin resistance does. Some implications for patient management are discussed. © 2012 Blackwell Publishing Ltd.


Baertschi B.,University of Geneva
Brain Topography | Year: 2014

Human enhancement is a much debated topic in the bioethical literature. Human beings have long tried to improve their capacities and their performances through training and with the aid of tools; but more recently new means have come to the fore, such as drugs and biotechnological devices, especially in the domain of bodily strength and cognitive powers. Moral enhancement has been more seldom discussed. However, this question has recently been hotly debated between two philosophers, Thomas Douglas and John Harris. Douglas claims that modulating certain ugly emotions directly would consist in moral progress - directly, that is, without using cognitive means like persuasion or deliberation. Harris makes three objections against this thesis: such a direct neuromodulation would be inefficacious, would put our liberty in jeopardy and would lead to a moral decline. In this paper, I examine the third argument: with direct modulation, we risk intervening too much or too little, inducing an inappropriate emotion or an inappropriate level of an otherwise appropriate emotion - two upshots that will put morality in jeopardy. I conclude that the validity of this objection depends on several meta-ethical positions: if you are a rationalist or think that intentionality and consciousness are at the core of morality, you will agree with Harris, but if you are a sentimentalist or someone for whom results count, you will disagree. Here as elsewhere, ethical questions cannot be divorced from meta-ethical ones. © 2012 Springer Science+Business Media New York.


Gendolla G.H.E.,University of Geneva
International Journal of Psychophysiology | Year: 2012

This article introduces a new theory about implicit affect's influence on resource mobilization-the implicit-affect primes effort (IAPE) model-and discusses a series of experiments testing its predictions. The theory posits that affect primes (e.g., facial expressions or emotion words) implicitly activate mental representations of the respective affective states, containing information about ease and difficulty. This in turn influences the extent of subjective task demand during performance. A series of experiments assessing implicit affect's impact on effort-related cardiovascular response in cognitive tasks (especially cardiac pre-ejection period) supports this idea: (1) sadness primes processed during task performance led to stronger cardiovascular responses than both happiness and anger primes. (2) Affect primes moderated the effect of objective task difficulty: compared with sadness primes, both anger and happiness primes led to weaker response for easy tasks but to stronger response for difficult tasks. (3) The effort deficit of people primed with sadness during a difficult task could be compensated by high success incentive. Perspectives for future research on implicit affect and motivation are discussed. © 2012 Elsevier B.V.


Unger R.H.,University of Texas Southwestern Medical Center | Orci L.,University of Geneva
Proceedings of the National Academy of Sciences of the United States of America | Year: 2010

New results have brought to light the importance of the regulation of glucagon by β-cells in the development of diabetes. In this perspective, we examine the normal paracrinology of α- and β-cells in nondiabetic pancreatic islets. We propose a Sherringtonian model of coordinated reciprocal secretory responses of these juxtaposed cells that secrete glucagon and insulin, hormones with opposing actions on the liver. As insulin is a powerful inhibitor of glucagon, we propose that within-islet inhibition of α-cells by β-cells creates an insulin-to-glucagon ratio that maintains glycemic stability even in extremes of glucose influx or efflux. By contrast, in type 1 diabetes mellitus, α-cells lack constant action of high insulin levels from juxtaposed β-cells. Replacement with exogenous insulin does not approach paracrine levels of secreted insulin except with high doses that "overinsulinize" the peripheral insulin targets, thereby promoting glycemic volatility. Based on the stable normoglycemia of mice with type 1 diabetes during suppression of glucagon with leptin, we conclude that, in the absence of paracrine regulation of α-cells, tonic inhibition of α-cells improves the dysregulated glucose homeostasis. These results have considerable medical implications, as they suggest new approaches to normalize the extreme volatility of glycemia in diabetic patients.


In a changing climate, it is likely that precipitation patterns will experience shifts in amount and seasonality, with a tendency towards increased drought in many parts of Europe. In order to investigate what could be some of the feedbacks of dry conditions on temperature, this paper has investigated close to 30 European locations to assess the influence of observed dry summer days on daily maximum temperature (Tmax) as well as a clustering of rainless days, and finally the temperature impact related to drought conditions as defined by the Standardized Precipitation Index. The results show that for the three main European climatic regions investigated ('Mediterranean', 'Maritime', 'Continental'), the influence of rainless days is discernible, with an average difference between mean summer Tmax and Tmax during rainless days only of up to 1.5 °C. A further aim of the study is to determine whether recent shifts in the occurrence of rainless days during the summer have a bearing on temperature trends. Results show that shifts in rainless days explain only a fraction of the observed temperature change at the locations studied, thereby hinting that the enhanced greenhouse effect remains the dominant mechanism for temperature change. Finally, using a regional climate model, very preliminary insight into a 'greenhouse climate' highlights the fact that changes in dry conditions seem to confirm the findings for current climate, i.e. they account for only a fraction of the increase in temperatures. © 2012 Royal Meteorological Society.


Stoffel M.,University of Bern | Huggel C.,University of Geneva
Progress in Physical Geography | Year: 2012

Changes in temperature and precipitation have a range of impacts, including change of glacier extent, extent and duration of snow cover, and distribution and thermal properties of permafrost. Similarly, it is likely that climatic changes affect frequency and magnitude of mass movements, such as shallow landslides, debris flows, rock slope failures, or ice avalanches. However, so far changes in mass-movement activity can hardly be detected in observational records. In this progress report we document the role of climate variability and change on mass-movement processes in mountains through the description and analysis of selected, recent mass movements where effects of global warming and the occurrence of heavy precipitation are thought to have contributed to, or triggered, events. In addition, we assess possible effects of future climatic changes on the incidence of mass-movement processes. The report concentrates on high-mountain systems, including processes such as glacier downwasting and the formation of new ice-marginal lakes, glacier debuttressing and the occurrence of rock slope instability, temperature increase and permafrost degradation, as well as on changing sediment reservoirs and sediment supply, with a clear focus on studies from the European Alps. © The Author(s) 2012.


Ristivojevic Z.,Ecole Normale Superieure de Paris | Petkovic A.,Ecole Normale Superieure de Paris | Le Doussal P.,Ecole Normale Superieure de Paris | Giamarchi T.,University of Geneva
Physical Review Letters | Year: 2012

Interacting bosons generically form a superfluid state. In the presence of disorder it can get converted into a compressible Bose glass state. Here we study such a transition in one dimension at moderate interaction using bosonization and renormalization group techniques. We derive the two-loop scaling equations and discuss the phase diagram. We find that the correlation functions at the transition are characterized by universal exponents in a finite region around the fixed point. © 2012 American Physical Society.


Ferretti F.,University of Geneva
Antipode | Year: 2013

Abstract: The anarchist and geographer Élisée Reclus (1830-1905) argued for the idea of universal brotherhood for all the peoples of the world in his encyclopaedic work the Nouvelle Géographie Universelle (NGU) (1876-1894). The nature of Reclus' argument and its representations of Europe, otherness and colonialism, however, are contested today, and it is unclear what insights it might offer to contemporary students of colonialism and post-colonialism. In this paper I engage with two emblematic cases-British rule over India and French occupation of Algeria-as they are presented in the NGU, considering Reclus' analysis of imperialism and his novel critique of colonial power. In doing so I wish to demonstrate that far from being conventional, the NGU is a radical and interesting resource for those struggling to construct a critical discourse on Europe, otherness and colonialism. © 2013 Antipode Foundation Ltd.


Fall J.J.,University of Geneva
Environment and Planning D: Society and Space | Year: 2012

In this paper I suggest fleshing out and making material the authorial voice by exploring pathways for writing a critical biography of Claude Raffestin, a Swiss geographer writing since the late 1970s up to the present day. In exploring his life and contribution as part of the wider Francophone tradition of social and political geography, I aim to engage further with the debate on the circulation of knowledge and the alleged hegemony of the English language within geography. In doing this, I suggest that the term 'disciplinary Orientalism' might help to think through some of the contradictions in geography, which both draws heavily from foreign critical thinkers, often removed from the spaces and contexts of debate they are/were writing in, and simultaneously ignores foreign geographical traditions and contributions. Building on Raffestin's workóand drawing from diverse sources, including his writings, reviews of his work, and new interview materialóI explore how his geographies might make sense here and now, to the extent that 'here' is inevitably an uncertain place, not only in where this paper is written and read but also because reading always takes place in-between contexts. Through this example I explore how scholars are emboacuted and located in uncertain places and points to the multiple circulations and noncirculations of theory and praxis within geography. © 2012 Pion Ltd and its Licensors.


Bonadonna C.,University of Geneva | Costa A.,Italian National Institute of Geophysics and Volcanology
Bulletin of Volcanology | Year: 2013

The Weibull distribution between volume and square root of isopach area has been recently introduced for determining volume of tephra deposits, which is crucial to the assessment of the magnitude and hazards of explosive volcanoes. We show how the decay of the size of the largest lithics with the square root of isopleth area can also be well described using a Weibull function and how plume height correlates strongly with corresponding Weibull parameters. Variations of median grain size (Mdφ{symbol}) values with square root of area of the associated contours can be, similarly, well fitted with a Weibull function. Weibull parameters, derived for both the thinning of tephra deposits and the decrease of grain size (both maximum lithic diameter and Mdφ{symbol}), with a proxy for the distance from vent (e.g., square root of isoline areas) can be combined to classify the style of explosive volcanic eruptions. Accounting for the uncertainty in the derivation of eruptive parameters (e.g., plume height and volume of tephra deposits) is crucial to any classification of eruptive style and hazard assessment. Considering a typical uncertainty of 20 % for the determination of plume height, a new eruption classification scheme based on selected Weibull parameters is proposed. Ultraplinian, Plinian, Subplinian, and small-moderate explosive eruptions are defined on the ground of plume height and mass eruption rate. Overall, the Weibull fitting represents a versatile and reliable strategy for the estimation of both the volume of tephra deposits and the height of volcanic plumes and for the classification of eruptive style. Nonetheless, due to the typically large uncertainties (mainly due to availability of data, compilation of isopach and isopleth maps, and discrepancies from empirical best fits), plume height, volume, and magnitude of explosive eruptions cannot be considered as absolute values, regardless of the technique used. It is important that various empirical and analytical methods are applied in order to assess such an uncertainty. © 2013 Springer-Verlag Berlin Heidelberg.


Nica A.C.,University of Geneva
Philosophical transactions of the Royal Society of London. Series B, Biological sciences | Year: 2013

The last few years have seen the development of large efforts for the analysis of genome function, especially in the context of genome variation. One of the most prominent directions has been the extensive set of studies on expression quantitative trait loci (eQTLs), namely, the discovery of genetic variants that explain variation in gene expression levels. Such studies have offered promise not just for the characterization of functional sequence variation but also for the understanding of basic processes of gene regulation and interpretation of genome-wide association studies. In this review, we discuss some of the key directions of eQTL research and its implications.


McKeown Walker S.,University of Geneva
Nature Materials | Year: 2016

Surfaces and interfaces offer new possibilities for tailoring the many-body interactions that dominate the electrical and thermal properties of transition metal oxides. Here, we use the prototypical two-dimensional electron liquid (2DEL) at the SrTiO3(001) surface to reveal a remarkably complex evolution of electron–phonon coupling with the tunable carrier density of this system. At low density, where superconductivity is found in the analogous 2DEL at the LaAlO3/SrTiO3 interface, our angle-resolved photoemission data show replica bands separated by 100 meV from the main bands. This is a hallmark of a coherent polaronic liquid and implies long-range coupling to a single longitudinal optical phonon branch. In the overdoped regime the preferential coupling to this branch decreases and the 2DEL undergoes a crossover to a more conventional metallic state with weaker short-range electron–phonon interaction. These results place constraints on the theoretical description of superconductivity and allow a unified understanding of the transport properties in SrTiO3-based 2DELs. © 2016 Nature Publishing Group


Hillairet M.,University of Paris Dauphine | Wittwer P.,University of Geneva
Archive for Rational Mechanics and Analysis | Year: 2012

We consider the problem of a body moving within an incompressible fluid at constant speed parallel to a wall in an otherwise unbounded domain. This situation is modeled by the incompressible Navier-Stokes equations in a planar exterior domain in a half space with appropriate boundary conditions on the wall, the body, and at infinity. We focus on the case where the size of the body is small. We prove in a very general setup that the solution of this problem is unique and we compute a sharp decay rate of the solution far from the moving body and the wall. © 2012 Springer-Verlag.


Dorn G.W.,University of Washington | Scorrano L.,University of Geneva | Scorrano L.,Venetian Institute of Molecular Medicine
Circulation Research | Year: 2010

Mitochondria are key organelles in cell life whose dysfunction is associated with a variety of diseases. Their crucial role in intermediary metabolism and energy conversion makes them a preferred target in tissues, such as the heart, where the energetic demands are very high. In the cardiomyocyte, the spatial organization of mitochondria favors their interaction with the sarcoplasmic reticulum, thereby offering a mechanism for Ca-mediated crosstalk between these 2 organelles. Recently, the molecular basis for this interaction has begun to be unraveled, and we are learning how endoplasmic reticulum-mitochondrial interactions are often exploited by death signals, such as proapoptotic Bcl-2 family members, to amplify the cell death cascade. Here, we review our present understanding of the structural basis and the functional consequences of the close interaction between sarcoplasmic reticulum and mitochondria on cardiomyocyte function and death. © 2010 American Heart Association, Inc.


Maggiolini M.,University of Calabria | Picard D.,University of Geneva
Journal of Endocrinology | Year: 2010

Steroid hormones such as estrogens are known to signal through ligand-regulated transcription factors of the nuclear receptor superfamily. In addition, they elicit rapid nongenomic responses from membrane-associated receptors. One of these receptors belongs to an entirely different family of proteins. The G protein-coupled and seventransmembrane receptor, GPR30, is now widely recognized as an estrogen receptor (ER), hence its official new acronym GPER. It appears to mediate a wide range of responses to estrogen in a large variety of cell types. Its functions are clearly distinct from those of the classical nuclear ERs, although these pathways may overlap and interact in some cases. Here, we review the history of the discovery of this new ER, the evidence for the claim that it is an ER, its signal transduction, and its potential functions in physiology and disease. © 2010 Society for Endocrinology.


Koban L.,University of Colorado at Boulder | Koban L.,University of Geneva | Pourtois G.,Ghent University
Neuroscience and Biobehavioral Reviews | Year: 2014

Action monitoring allows the swift detection of conflicts, errors, and the rapid evaluation of outcomes. These processes are crucial for learning, adaptive behavior, and for the regulation of cognitive control. Our review discusses neuroimaging and electrophysiological studies that have explored the contribution of emotional and social factors during action monitoring. Meta-analytic brain activation maps demonstrate reliable overlap of error monitoring, emotional, and social processes in the dorsal mediofrontal cortex (dMFC), lateral prefrontal areas, and anterior insula (AI). Cumulating evidence suggests that action monitoring is modulated by trait anxiety and negative affect, and that activity of the dMFC and the amygdala during action monitoring might contribute to the 'affective tagging' of actions along a valence dimension. The role of AI in action monitoring may be the integration of outcome information with self-agency and social context factors, thereby generating more complex situation-specific and conscious emotional feeling states. Our review suggests that action-monitoring processes operate at multiple levels in the human brain, and are shaped by dynamic interactions with affective and social processes. © 2014 Elsevier Ltd.


Garzoni C.,University of Bern | Kelley W.L.,University of Geneva
EMBO Molecular Medicine | Year: 2011

Staphylococcus aureus small colony variants (SCVs), which are characterized by slow growth and a range of morphological and metabolic changes including altered antibiotic resistance profiles, have been studied for several decades. This Closeup highlights findings described in this issue of EMBO Molecular Medicine by Tuchscherr et al (2011), who present strong evidence that SCVs can arise in chronic infection models when S. aureus is internalized in non-professional phagocytes and survives intracellularly. As the intracellular residency time increases, the proportion of SCVs grows and the host cell inflammatory response diminishes. The study suggests that this mode of phenotype switching is an essential feature of the S. aureus infection process and can explain an underlying cause of chronic and relapsing infections. See related article in EMBO Mol Med (Tuchscherr et al (2011) EMBO Mol Med 3: 129-141) Copyright © 2011 EMBO Molecular Medicine.


Soriano M.E.,Venetian Institute of Molecular Medicine | Scorrano L.,Venetian Institute of Molecular Medicine | Scorrano L.,University of Geneva
Cell | Year: 2011

Antiapoptotic Bcl-2 proteins on mitochondria inhibit prodeath proteins, such as Bax, which are found primarily in the cytosol. In this issue, Edlich et al.; (2011) show that Bax and Bcl-xL interact on the mitochondrial surface and then retrotranslocate to the cytosol, effectively preventing Bax-induced permeabilization of mitochondria. © 2011 Elsevier Inc.


Casartelli L.,University of Geneva | Casartelli L.,Scientific Institute | Molteni M.,Scientific Institute
Neuroscience and Biobehavioral Reviews | Year: 2014

The relationships between mirror neurons (MNs) and motor imitation, and its clinical implications in autism spectrum disorder (ASD) have been widely investigated; however, the literature remains - at least partially - controversial. In this review we support a multi-level action understanding model focusing on the mirror-based understanding. We review the functional role of the parieto-frontal MNs (PFMN) network claiming that PFMNs function cannot be limited to imitation nor can imitation be explained solely by the activity of PFMNs. The distinction between movement, motor act and motor action is useful to characterize deeply both act(ion) understanding and imitation of act(ion). A more abstract representation of act(ion) may be crucial for clarifying what, why and how an imitator is imitating. What counts in social interactions is achieving goals: it does not matter which effector or string of motor acts you eventually use for achieving (proximal and distal) goals. Similarly, what counts is the ability to recognize/imitate the style of act(ion) regardless of the way in which it is expressed. We address this crucial point referring to its potential implications in ASD. © 2014 Elsevier Ltd. All rights reserved.


Allali G.,University of Geneva
Movement disorders : official journal of the Movement Disorder Society | Year: 2010

The main diagnostic criteria of the behavioural variant of frontotemporal degeneration (bvFTD) include neurobehavioral and dysexecutive syndromes, but not specific gait characteristics although strong relationship between gait and prefrontal functions are increasingly recognized. Accordingly, we tested the hypothesis that patients with bvFTD would have more gait changes than older healthy controls and demented patients with Alzheimer's disease (AD). Sixty subjects were included in the study: 19 with bvFTD, 19 with AD and 22 healthy controls. Mean values and coefficients of variation (CV) of stride time while just walking (i.e., single tasking) and while walking with backward counting (i.e., dual tasking) were measured using the SMTEC-footswitch system. Stride time, mean value, and CV were significantly increased in both patient groups compared with healthy controls during single task or walking alone (P < 0.001) and during dual tasking (P < 0.001). After adjusting for age, Mini-mental examination, psychoactive drugs, gender, and history of previous fall, only the patients with bvFTD group was associated with an increase of CV of stride time during single walking (P < 0.001) and dual tasking (P < 0.001). These data suggest that gait instability during single and dual tasking could represent a supportive argument for bvFTD. In clinical practice, such a diagnosis should be at least considered in any demented patient with gait instability. 2010 Movement Disorder Society


Bergeron F.C.,University of Geneva
Resources, Conservation and Recycling | Year: 2014

Waste wood recovery by thermal treatment with energy recovery or by recycling allows the substitution and conservation of primary resources. Swiss government notes the potential presence of tensions between policies which simultaneously encourage the cascade use of wood, the recycling or the energy recovery by thermal treatment of waste wood. The aim of the present research is to assess the coherence of waste wood management in Switzerland by a quantitative and qualitative approach. First, a material flow analysis allows to model the wood resources and waste wood metabolism over one century. The simulation results of various scenarios of waste wood management establish that the additional impacts of the immediate thermal treatment are less significant for the reduction of CO2eq emissions but more significant for the energy production than its cascade treatments on Swiss territory. Secondly, a documentary analysis examines the determinants of the current waste wood treatments prevailing in Switzerland. Thus, the causes of the strong presence on Swiss territory of the sector of thermal treatment, the export of almost half of waste wood generated and the sub-exploitation of Swiss forest act as barriers or drivers that result in introducing a crowding-out effect where no amount of waste wood is available for recycling in Switzerland. The comparison of the results of the two approaches leads to the conclusion that the current waste wood management is coherent in relation to the various goals of the Swiss federal policies but the waste wood potential for energy production is not fully exploited. The recommendations on the waste wood management and the possibilities to use the model for other case studies are given in the conclusion. © 2014 Elsevier B.V. All rights reserved.


Dumonceau J.-M.,University of Geneva
Gastrointestinal Endoscopy Clinics of North America | Year: 2012

Sampling at ERCP may be performed at the level of the papilla or of the biliopancreatic ducts. Samples collected at the level of the biliopancreatic ducts allow for diagnosing malignancy with a specificity close to 100% but present a moderate sensitivity in most studies. In this article, the different aspects of sampling at ERCP are discussed, and a special focus is placed on the means that are routinely available to the endoscopist for obtaining a high sensitivity for the diagnosis of malignancy. © 2012 Elsevier Inc.


Hamamy H.,University of Geneva
Journal of Community Genetics | Year: 2012

Consanguinity is a deeply rooted social trend among one-fifth of the world population mostly residing in the Middle East, West Asia and North Africa, as well as among emigrants from these communities now residing in North America, Europe and Australia. The mounting public awareness on prevention of congenital and genetic disorders in offspring is driving an increasing number of couples contemplating marriage and reproduction in highly consanguineous communities to seek counseling on consanguinity. Primary health care providers are faced with consanguineous couples demanding answers to their questions on the anticipated health risks to their offspring. Preconception and premarital counseling on consanguinity should be part of the training of health care providers particularly in highly consanguineous populations. © Springer-Verlag 2011.


Mulligan C.,Oxford PharmaGenesis Ltd | Beghetti M.,University of Geneva
Pediatric Critical Care Medicine | Year: 2012

OBJECTIVE: Inhaled iloprost is attracting growing interest as a potential alternative and/or adjuvant to inhaled nitric oxide in the management of pediatric pulmonary hypertension in the acute and intensive care settings. However, there are currently no formal evidence-based guidelines regarding the use of inhaled iloprost in children with pulmonary hypertension. The aim of this systematic review is to assess the literature concerning the use of inhaled iloprost in children with pulmonary hypertension in the acute setting. DATA SOURCES: Studies were identified from PubMed and Embase. Internal literature databases and recent congress abstracts (2009 onward) were also searched for relevant publications. STUDY SELECTION: Studies were included if they examined the use of inhaled iloprost in children with pulmonary hypertension in an acute or intensive care setting. DATA EXTRACTION AND SYNTHESIS: Twenty-eight studies were included in the review. The majority were case studies or case series (n = 17), and in total, the 28 studies represented the treatment of 195 children with iloprost. Iloprost was most frequently studied in children undergoing cardiac surgery (as a bridge to surgery and postoperatively), in children undergoing acute pulmonary vasoreactivity testing, and in neonates with persistent pulmonary hypertension of the newborn. The results of the included studies suggested that inhaled iloprost may have a diverse role in the acute treatment of pediatric pulmonary hypertension and that its acute effects are similar to those of inhaled nitric oxide. However, the iloprost dose was not consistently reported and varied greatly between studies, and several different administration devices were used. CONCLUSIONS: Inhaled iloprost may be useful in the acute treatment of children and neonates with pulmonary hypertension, but clinical data are scarce, and the appropriate dosing of iloprost in different scenarios is uncertain. Well-designed prospective clinical trials are needed. Copyright © 2012 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.


Jarlborg T.,University of Geneva
Journal of Superconductivity and Novel Magnetism | Year: 2016

The electron-phonon and spin-phonon coupling in typical high- TC cuprates are peaked for just a few q-vectors because of the two-dimensional Fermi surface shape. Few spin-phonon excitations compensate for the low electronic density-of-states, and the superconducting TC can be high. Thermal disorder of the lattice makes incoherent potential fluctuations which perturbs the strongly coupled waves. This effect puts a limit on long-range superconductivity, while fluctuations can persist on a shorter length scale at higher temperatures. BCS-type model calculations are used to show how disorder can reduce the superconducting gap and TC. Ordering of dopants into stripes can improve superconducting properties, mainly through an increased DOS, and make TC more resistant to thermal disorder at low doping. © 2015, Springer Science+Business Media New York.


Cazalilla M.A.,Donostia International Physics Center | Citro R.,University of Salerno | Giamarchi T.,University of Geneva | Orignac E.,French National Center for Scientific Research | Rigol M.,Georgetown University
Reviews of Modern Physics | Year: 2011

The physics of one-dimensional interacting bosonic systems is reviewed. Beginning with results from exactly solvable models and computational approaches, the concept of bosonic Tomonaga-Luttinger liquids relevant for one-dimensional Bose fluids is introduced, and compared with Bose-Einstein condensates existing in dimensions higher than one. The effects of various perturbations on the Tomonaga-Luttinger liquid state are discussed as well as extensions to multicomponent and out of equilibrium situations. Finally, the experimental systems that can be described in terms of models of interacting bosons in one dimension are discussed. © 2011 American Physical Society.


Kayser B.,University of Geneva | Verges S.,Joseph Fourier University
Obesity Reviews | Year: 2013

High altitude exposure is often accompanied by weight loss. Postulated mechanisms are a reduction of nutritional energy intake, a reduction of intestinal energy uptake from impaired intestinal function and increased energy expenditure. Beyond the field of altitude, there are good reasons for renewed interest in the relationship between hypoxia and energy balance. The increasing prevalence of obesity and associated comorbidities represent a major health concern. Obesity is frequently associated with sleep disorders leading to intermittent systemic hypoxia with deleterious cardiovascular and metabolic consequences. Hypoxic regions may be present within hypertrophic white adipose tissue leading to chronic systemic inflammation. Among the increasing number of people commuting to altitude for work or leisure, obesity is a risk factor for acute mountain sickness. Paradoxically, exposure to intermittent hypoxia might be considered as a means to lose body mass and to improve metabolic risk factors. Daytime exposure to intermittent hypoxia has been used to treat hypertension in former Soviet Union countries and is now being experimented elsewhere. Such intermittent hypoxic exposure at rest or during exercise may lead to improvement in body composition and health status with improved exercise tolerance, metabolism and systemic arterial pressure. Future research should confirm whether hypoxic training could be a new treatment strategy for weight loss and comorbidities in obese subjects and elucidate the underlying mechanisms and signalling pathways. © 2013 International Association for the Study of Obesity.


Seeck M.,University of Geneva
Nature reviews. Neurology | Year: 2013

In patients with chronic epilepsy, MRI-based detection of an underlying brain lesion can offer the potential for surgical treatment, but a substantial proportion of patients have normal MRI scans. A recent study has shown that repeat neuroimaging with improved MRI technology can enable detection of previously unidentified epileptogenic lesions.


Passweg J.R.,University of Geneva
Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program | Year: 2010

Newly diagnosed aplastic anemia is a serious condition, with more than 75% (higher in young patients) becoming long-term survivors if diagnosed and treated appropriately. First-line treatment approaches include immunosuppressive treatment using the combination of antithymocyte globulin and cyclosporine A for patients without a sibling donor and HLA identical sibling transplant for patients younger than age 40 with a donor. Best transplant strategies have been defined and include conditioning with cyclophosphamide and antithymocyte globulin, marrow as a stem cell source, and graft-versus-host diease prophylaxis using cyclosporine A and methotrexate. It is against these standard treatment approaches that any therapeutic progress has to be measured.


Rinaldi M.,University of Geneva
Classical and Quantum Gravity | Year: 2011

We propose an inflationary scenario inspired by a recent formulation, in terms of coherent states, of non-commutative quantum field theory. We consider the semiclassical Einstein equations, and exploit the ultraviolet finiteness of the non-commutative propagator to construct the expectation value of the energy-momentum tensor associated with a generic scalar field. It turns out that the latter is always finite and dominated by an effective cosmological constant. By combining this general feature with the intrinsic fuzziness of spacetime, we show that non-commutativity governs the energy density of the early Universe in such a way that the strong energy condition is violated. Thus, there might be a bounce and a subsequent inflationary phase, which does not need any ad hoc scalar field. © 2011 IOP Publishing Ltd.


Schaller K.,University of Geneva
Acta neurochirurgica. Supplement | Year: 2011

We aimed at the integration of recent flat panel technology in a joint interventional suite for neurosurgeons and neuroradiologists. A Flat Panel system, allowing for intraoperative performance of 2D and 3D DSA, for automated segmentation of vascular structures, and for performance of computed tomography, was connected with a surgical microscope and neuronavigation. All surgical and neurointerventional cases were monitored and stored in a prospective data base. N=99 patients were treated neurosurgically: N=63 aneurysm clippings in n=51 patients; n=12 resections of arteriovenous malformations (AVM); n=6 clippings/excisions of dural AV fistulae (dAVF); n=3 EC-IC bypass procedures; n=10 resections of skull base tumours; n=17 spine procedures. All patients had intraoperative imaging for angiographic control and/or for anatomical allocation. Intraoperative 3D-rotational angiography was performed n=54 times in n=42 patients in < 15 min each, with repositioning of aneurysm clips in n=9 patients. This hybrid neuro-interventional suite opens a new avenue for intraoperative imaging by the provision of highly resoluted angiographic or CT images, which may be co-registered with a navigation system. In addition, the workflow in treatment of aneurysmal SAH can be improved, as all diagnostic and therapeutic measures can be taken without having to move the patient to other facilities.


Goyette S.,University of Geneva
Climate Dynamics | Year: 2011

This paper reports on a method using composites for studying synoptic conditions of a series of windstorm events selected on the basis of maximum wind speeds in Switzerland. The composite storm-averaged conditions indicate how flow fields, as well as related surface conditions, are organised so as to produce high wind speeds near the surface. On average, high winds in Switzerland, mainly generated by transient synoptic-scale eddies, are characterised by a minimum in the mean sea level pressure field over southern Norway, anticyclonic conditions south of 35°N and a steep pressure gradient over continental western Europe. The geopotential aloft has a predominant zonal structure, producing high winds between 45°N and 50°N over the eastern Atlantic and further inland; the jet stream has its maximum speed at 50°N over the Celtic Sea and Brittany at 250 hPa. Close to the surface, large temperature contrasts between the warm waters of the Atlantic Ocean and Mediterranean Sea and the cooler continent are diagnosed. The results thus obtained differ to those produced by other methods based on the analysis of deep cyclones or of strong vorticity in the northern North Atlantic Ocean basin. Differences of the composite mean synoptic conditions for current (1961-1990) and future climate (2071-2100) as simulated by the Global Climate Model HadAM3H in the context of the EU PRUDENCE project indicate that windstorms in a warmer world are generated by a subtle modification of the atmospheric baroclinicity, especially over the ocean and where greater ocean-continent temperature contrasts are simulated during winters. However, there are no signs of reduced storm activity as the climate warms by the end of the twenty-first century. © 2010 Springer-Verlag.


Field observations and geophysical data indicate that many igneous bodies grow by amalgamation of successive magma pulses that commonly take the shape of horizontal sheets (sills). Emplacement styles and emplacement rates of magma bodies have fundamental implications on magma differentiation, country rock metamorphism and assimilation, and for the formation of large magma chambers in the upper crust. When a magma body begins to grow by slow accretion of sills, each successive intrusion solidifies before the injection of the next one. When the system is thermally mature, sill temperatures equilibrate above the solidus, melts accumulate and older sills can re-melt. The time needed for each magma injection to cool down and equilibrate with its surrounding is short relatively to the total emplacement time of the body. The transition from a mafic crystal-poor magma to a partially molten rock that retains a highly differentiated melt is fast, whereas the resulting evolved residual melt can reside in the crust for protracted periods. As long as temperatures in the system are relatively low, highly differentiated melts are generated, which may explain the bi-modal character and the absence of intermediate compositions in some magmatic provinces. The level of emplacement of successive magma pulses controls the shape of the thermal anomaly associated with the magma body growth. Metamorphism, partial melting and assimilation of the country rock are favoured if successive magma sheets are emplaced at or close to the country rock-magma body boundary. If the magma emplacement rate is low, the size of the thermal aureole is controlled by the size of one pulse and not by the size of the entire igneous body. Understanding emplacement of magma bodies is fundamental for our understanding of the plutonism-volcanism relationship. Magma emplacement rates of several centimetres per year are needed for a magma body to evolve into a large magma chamber able to feed large silicic explosive eruptions. The time-averaged emplacement rates of plutons are lower than this critical emplacement rate. Eruptions of 100s to 1000s cubic kilometres of silicic products show that such high volumes of magmas can accumulate in the upper crust. This suggests that the emplacement of magma bodies is a multi-timescale process with the development of large magma chambers corresponding to the highest magma fluxes. Because they control magmatic processes and the impact of magma intrusion on the country rock, future studies should focus on magma emplacement rates and on magma emplacement geometries. These studies should integrate field observation on plutons and geophysical data on active magmatic systems, coupled with laboratory experiments and numerical simulations. © 2009 Elsevier B.V.


To compare rates of treatment interruption because of side effects and completion rates between subjects treated for latent tuberculosis infection (LTBI) by isoniazid (INH) for 6 months and subjects treated with rifampicin (RIF) for 4 months. Retrospective analysis of all patients treated for LTBI by INH (1993-2002) or RIF (2004-2007) based on a database including age, gender, prior liver diseases, alcohol consumption, completion rates, time and cause of interruption and monthly analysis of ASAT and ALAT. 624 subjects were included, 426 treated by INH and 198 by RIF. Gender, origin, history of prior hepatic disease and alcohol excess did not differ between groups. Treatment interruption because of hepatotoxicity was significantly higher in the INH group than in the RIF group (6.1% vs 2.0%; p = 0.03). Completion of treatment was significantly higher in the RIF group compared to the INH group (83% vs 74%; p = 0.02). A 4-month RIF treatment was associated with significantly less interruption of treatment because of hepatotoxicity and higher completion rates compared to a 6-month INH regimen. These results support the RIF regimen as an alternative to the presently recommended 9 months of INH in clinical practice.


Etter J.-F.,University of Geneva
European Addiction Research | Year: 2015

Aims: To describe cannabis 'vaping' with electronic cigarettes (e-cigarettes) or electronic vaporizers (e-vaporizers). Methods: Internet survey in 2013-2014. Participants were 11 people who 'vaped' cannabis with e-cigarettes and 44 people who vaped cannabis with e-vaporizers, enrolled online. Results: Most participants were men (78%). They had used e-cigarettes for 6 days and e-vaporizers for 50 days on average to vape cannabis. Current users of e-cigarettes vaped cannabis on 2 days/week versus 6 days/week for users of e-vaporizers. In these devices, they mostly inserted cannabis buds and oil rather than hashish or wax/butane honey oil. Dual users, who both smoked and vaped cannabis, currently smoked 5 joints/week compared to 14 joints/week before they started to vape cannabis (p = 0.004). Half the participants (45%) reported that vaping cannabis helped them stop or reduce their total cannabis use, 37% that it had no impact on their cannabis use, and 6% that it increased it. Vaping cannabis was perceived as healthier and more discrete than smoking it (less odor). Disadvantages included dry mouth and fewer positive cannabis effects. Conclusions: Cannabis vaping via e-cigarettes or e-vaporizers is an infrequent behavior that was previously almost undocumented. E-cigarettes do not appear to be a very appealing way to use cannabis. © 2015 S. Karger AG, Basel.


Chiaradia M.,University of Geneva | Muntener O.,University of Lausanne | Beate B.,National Polytechnic School of Ecuador
Journal of Petrology | Year: 2011

The origin of andesite is an important issue in petrology because andesite is the main eruptive product at convergent margins, corresponds to the average crustal composition and is often associated with major Cu-Au mineralization. In this study we present petrographic, mineralogical, geochemical and isotopic data for basaltic andesites of the latest Pleistocene Pilavo volcano, one of the most frontal volcanoes of the Ecuadorian Quaternary arc, situated upon thick (30-50 km) mafic crust composed of accreted Cretaceous oceanic plateau rocks and overlying mafic to intermediate Late Cretaceous-Late Tertiary magmatic arcs. The Pilavo rocks are basaltic andesites (54-57·5 wt % SiO. 2) with a tholeiitic affinity as opposed to the typical calc-alkaline high-silica andesites and dacites (SiO. 2 59-66 wt %) of other frontal arc volcanoes of Ecuador (e.g. Pichincha, Pululahua). They have much higher incompatible element contents (e.g. Sr 650-1350 ppm, Ba 650-1800 ppm, Zr 100-225 ppm, Th 5-25 ppm, La 15-65 ppm) and Th/La ratios (0·28-0·36) than Pichincha and Pululahua, and more primitive Sr (.87Sr/.86Sr ∼0·7038-0·7039) and Nd (e{open}. Nd ∼ +5·5 to +6·1) isotopic signatures. Pilavo andesites have geochemical affinities with modern and recent high-MgO andesites (e.g. low-silica adakites, Setouchi sanukites) and, especially, with Archean sanukitoids, for both of which incompatible element enrichments are believed to result from interactions of slab melts with peridotitic mantle. Petrographic, mineral chemistry, bulk-rock geochemical and isotopic data indicate that the Pilavo magmatic rocks have evolved through three main stages: (1) generation of a basaltic magma in the mantle wedge region by flux melting induced by slab-derived fluids (aqueous, supercritical or melts); (2) high-pressure differentiation of the basaltic melt (at the mantle-crust boundary or at lower crustal levels) through sustained fractionation of olivine and clinopyroxene, leading to hydrous, high-alumina basaltic andesite melts with a tholeiitic affinity, enriched in incompatible elements and strongly impoverished in Ni and Cr; (3) establishment of one or more mid-crustal magma storage reservoirs in which the magmas evolved through dominant amphibole and clinopyroxene (but no plagioclase) fractionation accompanied by assimilation of the modified plutonic roots of the arc and recharge by incoming batches of more primitive magma from depth. The latter process has resulted in strongly increasing incompatible element concentrations in the Pilavo basaltic andesites, coupled with slightly increasing crustal isotopic signatures and a shift towards a more calc-alkaline affinity. Our data show that, although ultimately originating from the slab, incompatible element abundances in arc andesites with primitive isotopic signatures can be significantly enhanced by intra-crustal processes within a thick juvenile mafic crust, thus providing an additional process for the generation of enriched andesites. © The Author 2011. Published by Oxford University Press. All rights reserved.


Mardling R.A.,Monash University | Mardling R.A.,University of Geneva
Monthly Notices of the Royal Astronomical Society | Year: 2013

Modern applications of celestial mechanics include the study of closely packed systems of exoplanets, circumbinary planetary systems, binary-binary interactions in star clusters and the dynamics of stars near the Galactic centre. While developments have historically been guided by the architecture of the Solar System, the need for more general formulations with as few restrictions on the parameters as possible is obvious. Here, we present clear and concise generalizations of two classic expansions of the three-body disturbing function, simplifying considerably their original form and making them accessible to the non-specialist. Governing the interaction between the inner and outer orbits of a hierarchical triple, the disturbing function in its general form is the conduit for energy and angular momentum exchange and as such, governs the secular and resonant evolution of the system and its stability characteristics. Focusing here on coplanar systems, the first expansion is one in the ratio of inner to outer semimajor axes and is valid for all eccentricities, while the second is an expansion in eccentricity and is valid for all semimajor axis ratios, except for systems in which the orbits cross (this restriction also applies to the first expansion). Our generalizations make both formulations valid for arbitrary mass ratios. The classic versions of these appropriate to the restricted three-body problem are known as Kaula's expansion and the literal expansion, respectively. We demonstrate the equivalence of the new expansions, identifying the role of the spherical harmonic order m in both and its physical significance in the three-body problem, and introducing the concept of principal resonances. Several examples of the accessibility of both expansions are given including resonance widths, and the secular rates of change of the elements. Results in their final form are gathered together at the end of the paper for the reader mainly interested in their application, including a guide for the choice of expansion. © 2013 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society.


Neronov A.,University of Geneva | Semikoz D.,Paris West University Nanterre La Defense
Astroparticle Physics | Year: 2016

We show that the Galactic latitude distribution of IceCube astrophysical neutrino events with energies above 100 TeV is inconsistent with the isotropic model of the astrophysical neutrino flux. Namely, the Galactic latitude distribution of the events shows an excess at low latitudes |b| < 10° and a deficit at high Galactic latitude |b| ≳50°. We use Monte-Carlo simulations to show that the inconsistency of the isotropic signal model with the data is at ≳3σ level, after the account of trial factors related to the choice of the low-energy threshold and Galactic latitude binning in our analysis. © 2015 Elsevier B.V.


Steiner F.A.,Fred Hutchinson Cancer Research Center | Steiner F.A.,University of Geneva | Henikoff S.,Fred Hutchinson Cancer Research Center
Current Opinion in Genetics and Development | Year: 2015

Centromeric chromatin is distinguished primarily by nucleosomes containing the histone variant cenH3, which organizes the kinetochore that links the chromosome to the spindle apparatus. Whereas budding yeast have simple 'point' centromeres with single cenH3 nucleosomes, and fission yeast have 'regional' centromeres without obvious sequence specificity, the centromeres of most organisms are embedded in highly repetitive 'satellite' DNA. Recent studies have revealed a remarkable diversity in centromere chromatin organization among different lineages, including some that have lost cenH3 altogether. We review recent progress in understanding point, regional and satellite centromeres, as well as less well-studied centromere types, such as holocentromeres. We also discuss the formation of neocentromeres, the role of pericentric heterochromatin, and the structure and composition of the cenH3 nucleosome. © 2015 Elsevier Ltd.


Rizzoli R.,University of Geneva
Best Practice and Research: Clinical Endocrinology and Metabolism | Year: 2014

Bone mass, geometry and microstructure, and bony tissue material level properties determine bone strength, hence the resistance to fracture. At a given age, all these variables are the consequence of the amount accumulated and of the structure developed during growth, up to the so-called peak bone mass, and of the bone loss and microstructure degradation occurring later in life. Genetic factors primarily contribute to the variance of the determinants of bone strength. Nutritional intakes are environmental factors that influence both processes, either directly by modifying modelling and remodelling, or indirectly through changes in calcitropic hormone secretion and action. Some effects of nutrition on the offspring bone could take place during foetal life. There are interplays between genetic factors, nutritional intakes and physical exercise. Among the nutrients, sufficient dietary intakes of calcium and protein are necessary for bone health in childhood and adolescence as well as later in life. © 2014 Elsevier Ltd. All rights reserved.


Gencer B.,University of Geneva
Current Opinion in Lipidology | Year: 2016

PURPOSE OF REVIEW: Familial hypercholesterolemia is a frequent genetic disorder characterized by elevated LDL-cholestrol and premature coronary heart disease. Familial hypercholesterolemia remains largely underdiagnosed in the general population and for many patients the initial clinical manifestation is acute coronary syndromes (ACS). Furthermore, many missed diagnosis of familial hypercholesterolemia can also occur during hospitalization for ACS. In this review, we aim to discuss the identification and prognosis of familial hypercholesterolemia after hospitalization for ACS. RECENT FINDINGS: The prevalence of familial hypercholesterolemia was about 10 times higher among patients hospitalized for ACS compared with the general population. Although 70% of patients with familial hypercholesterolemia were discharged with high-intensity statins, and 65% attended cardiac rehabilitation, less than 5% reached the recommended LDL-cholesterol target less than 1.8?mmol/l 1 year after ACS. Furthermore, patients with familial hypercholesterolemia and ACS were at high-risk of recurrence of cardiovascular events after discharge. SUMMARY: A systematic screening strategy to identify patients with familial hypercholesterolemia at the time ACS is required to maximize secondary prevention and improve lipid management. It is expected that a substantial number of familial hypercholesterolemia patients would benefit from more effective lipid-lowering drugs after ACS, in addition to statins. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.


Perret C.,University of Paris 13 | Laganaro M.,University of Geneva
Brain Topography | Year: 2012

Behavioral and neuropsychological studies on written production suggested that some cognitive processes are common with spoken production. In this study, we attempted to specify the time course of common processes between the two modalities with event-related brain potentials (ERPs). High density EEG was recorded on twenty two healthy participants during a handwritten and an oral picture naming task on the same 120 stimuli. Waveform analyses and topographical pattern analyses were combined on stimulus- and response-aligned ERPs in order to cover the whole word encoding processing. Similar electrophysiological correlates between writing and speaking appeared until about 260 ms. According to previous estimations of the time course of spoken production, the time period of identical electrophysiological activity corresponds to visual (0-150 ms) semantic (150-190 ms) and lexical-semantic (190-275 ms) processes. Then, spoken and handwritten picture naming starts diverging and display different and modality specific topographical configurations from around 260 ms, i.e., at the beginning of the time-window associated to the encoding of the surface phonological form in spoken production. These results suggested shared conceptual and lexical-semantic processes between speaking and writing and different neurophysiological activity during word-form (phonological or orthographic) encoding.© 2011 Springer Science+Business Media, LLC.


Strambio-De-Castillia C.,University of Geneva | Strambio-De-Castillia C.,Rockefeller University | Niepel M.,Harvard University | Rout M.P.,Rockefeller University
Nature Reviews Molecular Cell Biology | Year: 2010

Although the nuclear pore complex (NPC) is best known for its primary function as the key regulator of molecular traffic between the cytoplasm and the nucleus, a growing body of experimental evidence suggests that this structure participates in a considerably broader range of cellular activities on both sides of the nuclear envelope. Indeed, the NPC is emerging as an important regulator of gene expression through its influence on the internal architectural organization of the nucleus and its apparently extensive involvement in coordinating the seamless delivery of genetic information to the cytoplasmic protein synthesis machinery. © 20 Macmillan Publishers Limited. All rights reserved.


Farina A.,University of Geneva
Biochimica et Biophysica Acta - Proteins and Proteomics | Year: 2014

Most digestive malignancies have asymptomatic course, often progressing to poor outcome stages. Surgical resection usually represents the only potentially curative option but a prior assumption of the malignant nature of the lesion is mandatory to avoid exposing patients to unnecessary risks. Unfortunately, currently available diagnostic tools lack accuracy in many cases, consequently more reliable markers are needed to improve detection of malignant lesions. In this challenging context, fluids surrounding digestive malignancies represent a valuable source for the search of new potential biomarkers and proteomic tools offer the opportunity to achieve this goal. The new field of proximal fluid proteomics is thus emerging in the arena of digestive cancer biomarker discovery. In the present review, the state-of-the-art of proteomic investigations aimed at identifying new cancer biomarkers in fluids surrounding gastrointestinal malignancies is summarized. A comprehensive catalog of proteomic studies in which potential cancer biomarkers from gastrointestinal fluids have been identified and assessed for their diagnostic performances is also provided. This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge. © 2013 Elsevier B.V.


Luscher C.,University of Geneva | Malenka R.C.,Stanford University
Cold Spring Harbor Perspectives in Biology | Year: 2012

Long-term potentiation and long-term depression (LTP/LTD) can be elicited by activating N-methyl-D-aspartate (NMDA)-type glutamate receptors, typically by the coincident activity of pre- and postsynaptic neurons. The early phases of expression are mediated by a redistribution of AMPA-type glutamate receptors: More receptors are added to potentiate the synapse or receptors are removed to weaken synapses. With time, structural changes become apparent, which in general require the synthesis of new proteins. The investigation of the molecular and cellular mechanisms underlying these forms of synaptic plasticity has received much attention, because NMDA receptor-dependent LTP and LTD may constitute cellular substrates of learning and memory. © 2012 Cold Spring Harbor Laboratory Press; all rights reserved.


Tikkanen M.,University of Turku | Tikkanen M.,University of Geneva | Aro E.-M.,University of Turku
Biochimica et Biophysica Acta - Bioenergetics | Year: 2012

In higher plants, the photosystem (PS) II core and its several light harvesting antenna (LHCII) proteins undergo reversible phosphorylation cycles according to the light intensity. High light intensity induces strong phosphorylation of the PSII core proteins and suppresses the phosphorylation level of the LHCII proteins. Decrease in light intensity, in turn, suppresses the phosphorylation of PSII core, but strongly induces the phosphorylation of LHCII. Reversible and differential phosphorylation of the PSII-LHCII proteins is dependent on the interplay between the STN7 and STN8 kinases, and the respective phosphatases. The STN7 kinase phosphorylates the LHCII proteins and to a lesser extent also the PSII core proteins D1, D2 and CP43. The STN8 kinase, on the contrary, is rather specific for the PSII core proteins. Mechanistically, the PSII-LHCII protein phosphorylation is required for optimal mobility of the PSII-LHCII protein complexes along the thylakoid membrane. Physiologically, the phosphorylation of LHCII is a prerequisite for sufficient excitation of PSI, enabling the excitation and redox balance between PSII and PSI under low irradiance, when excitation energy transfer from the LHCII antenna to the two photosystems is efficient and thermal dissipation of excitation energy (NPQ) is minimised. The importance of PSII core protein phosphorylation is manifested under highlight when the photodamage of PSII is rapid and phosphorylation is required to facilitate the migration of damaged PSII from grana stacks to stroma lamellae for repair. The importance of thylakoid protein phosphorylation is highlighted under fluctuating intensity of light where the STN7 kinase dependent balancing of electron transfer is a prerequisite for optimal growth and development of the plant. This article is part of a Special Issue entitled: Photosystem II. © 2011 Elsevier B.V. All rights reserved.


Wehrle-Haller B.,University of Geneva
Current Opinion in Cell Biology | Year: 2012

Integrin-dependent cell adhesions come in different shapes and serve in different cell types for tasks ranging from cell-adhesion, migration, and the remodeling of the extracellular matrix to the formation and stabilization of immunological and chemical synapses. A major challenge consists in the identification of adhesion-specific as well as common regulatory mechanisms, motivating the need for a deeper analysis of protein-protein interactions in the context of intact focal adhesions. Specifically, it is critical to understand how small differences in binding of integrins to extracellular ligands and/or cytoplasmic adapter proteins affect the assembly and function of an entire focal adhesion. By using the talin-integrin pair as a starting point, I would like to discuss how specific protein-protein and protein-lipid interactions can control the behavior and function of focal adhesions. By responding to chemical and mechanical cues several allosterically regulated proteins create a dynamic multifunctional protein network that provides both adhesion to the extracellular matrix as well as intracellular signaling in response to mechanical changes in the cellular environment. © 2011 Elsevier Ltd.


Rochaix J.-D.,University of Geneva
Annual Review of Plant Biology | Year: 2014

Photosynthetic organisms are continuously subjected to changes in light quantity and quality, and must adjust their photosynthetic machinery so that it maintains optimal performance under limiting light and minimizes photodamage under excess light. To achieve this goal, these organisms use two main strategies in which light-harvesting complex II (LHCII), the light-harvesting system of photosystem II (PSII), plays a key role both for the collection of light energy and for photoprotection. The first is energy-dependent nonphotochemical quenching, whereby the high-light-induced proton gradient across the thylakoid membrane triggers a process in which excess excitation energy is harmlessly dissipated as heat. The second involves a redistribution of the mobile LHCII between the two photosystems in response to changes in the redox poise of the electron transport chain sensed through a signaling chain. These two processes strongly diminish the production of damaging reactive oxygen species, but photodamage of PSII is unavoidable, and it is repaired efficiently. Copyright © 2014 by Annual Reviews.


Picard F.,University of Geneva | Friston K.,Wellcome Trust Center for Neuroimaging
Neurology | Year: 2014

In recent years there has been a paradigm shift in theoretical neuroscience in which the brain-as a passive processor of sensory information-is now considered an active organ of inference, generating predictions and hypotheses about the causes of its sensations. In this commentary, we try to convey the basic ideas behind this perspective, describe their neurophysiologic underpinnings, and highlight the potential importance of this formulation for clinical neuroscience. The formalism it provides-and the implementation of active inference in the brain-may have the potential to reveal aspects of functional neuroanatomy that are compromised in conditions ranging from Parkinson disease to schizophrenia. In particular, many neurologic and neuropsychiatric conditions may be understandable in terms of a failure to modulate the postsynaptic gain of neuronal populations reporting prediction errors during action and perception. From the perspective of the predictive brain, this represents a failure to encode the precision of-or confidence in- sensory information. We propose that the predictive or inferential perspective on brain function offers novel insights into brain diseases. © 2014 American Academy of Neurology.


Sorg O.,University of Geneva
Toxicology Letters | Year: 2014

Dioxins are a family of molecules associated to several industrial accidents such as Ludwigshafen in 1953 or Seveso in 1976, to the Agent Orange used during the war of Vietnam, and more recently to the poisoning of the former president of Ukraine, Victor Yushchenko. These persistent organic pollutants are by-products of industrial activity and bind to an intracellular receptor, AhR, with a high potency. In humans, exposure to dioxins, in particular 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) induces a cutaneous syndrome known as chloracne, consisting in the development of many small skin lesions (hamartoma), lasting for 2-5 years. Although TCDD has been classified by the WHO as a human carcinogen, its carcinogenic potential to humans is not clearly demonstrated. It was first believed that AhR activation accounted for most, if not all, biological properties of dioxins. However, certain AhR agonists found in vegetables do not induce chloracne, and other chemicals, in particular certain therapeutic agents, may induce a chloracne-like syndrome without activating AhR. It is time to rethink the mechanism of dioxin toxicity and analyse in more details the biological events following exposure to these compounds and other AhR agonists, some of which have a very different chemical structure than TCDD. In particular various food-containing AhR agonists are non-toxic and may on the contrary have beneficial properties to human health. © 2013 Elsevier Ireland Ltd.


Vargas M.I.,University of Geneva
Clinical nuclear medicine | Year: 2013

The study of peripheral nerves (PN) is a challenge because of the orientation, size, and also because of the fact that these pathologies are not well known. The diagnosis of PN damage was based exclusively on clinical examination and electrophysiologic testing until few years ago. MRI is the examination of choice for studying peripheral nerves; recently, magnetic resonance neurography has been added as a part of clinical routine. However, the analysis of PN after surgical treatment remains difficult. This clinical case of a sarcoma of the right brachial plexus illustrates how hybrid PET-MRI in postsurgical evaluation will clearly improve the exact delimitation of residual metabolically active tumor after surgery.


Tiercy J.-M.,University of Geneva
Haematologica | Year: 2016

Recognition of HLA incompatibilities by the immune system represents a major barrier to allogeneic hematopoietic stem cell transplantation. HLA genotypically identical sibling donors are, therefore, the gold standard for transplantation purposes, but only 30% patients have such a donor. For the remaining 70% patients alternative sources of stem cells are a matched unrelated adult volunteer donor, a haploidentical donor or a cord blood unit. The definition of ‘HLA matching’ depends on the level of resolution and on which loci are tested. The development of HLA molecular typing technologies and the availability of more than 27 million donors in the international database has greatly facilitated unrelated donor searches. The gold standard is high resolution typing at the HLA-A, -B, -C, -DRB1, and -DQB1 loci (10/10 match). Single disparities for HLA-A, -B, - C, or -DRB1 are associated with increased risk of post-transplant complications, but less so in patients with advanced disease, and in those undergoing Tcell- depleted allografting. HLA-DQB1 mismatches seem to be better tolerated and some HLA-C, -DRB1 and -DPB1 disparities are potentially less immunogenic. HLA typing by next-generation sequencing methods is likely to change matching algorithms by providing full sequence information on all HLA loci in a single step. In most European populations a 10/10 matched donor can be found for at least 50% of patients and an additional 20-30% patients may have a 9/10 matched donor. Genetic factors that help in identifying donors with less immunogenic mismatches are discussed. Haploidentical donors are increasingly used as an alternative source of stem cells for those patients lacking a matched unrelated donor. © 2016 Ferrata Storti Foundation.


Blanke O.,Ecole Polytechnique Federale de Lausanne | Blanke O.,University of Geneva | Slater M.,Catalan Institution for Research and Advanced Studies | Slater M.,University College London | Serino A.,Ecole Polytechnique Federale de Lausanne
Neuron | Year: 2015

Recent work in human cognitive neuroscience has linked self-consciousness to the processing of multisensory bodily signals (bodily self-consciousness [BSC]) in fronto-parietal cortex and more posterior temporo-parietal regions. We highlight the behavioral, neurophysiological, neuroimaging, and computational laws that subtend BSC in humans and non-human primates. We propose that BSC includes body-centered perception (hand, face, and trunk), based on the integration of proprioceptive, vestibular, and visual bodily inputs, and involves spatio-temporal mechanisms integrating multisensory bodily stimuli within peripersonal space (PPS). We develop four major constraints of BSC (proprioception, body-related visual information, PPS, and embodiment) and argue that the fronto-parietal and temporo-parietal processing of trunk-centered multisensory signals in PPS is of particular relevance for theoretical models and simulations of BSC and eventually of self-consciousness. © 2015 Elsevier Inc.


Poburko D.,Simon Fraser University | Demaurex N.,University of Geneva
Pflugers Archiv European Journal of Physiology | Year: 2012

Mitochondria convert the energy stored in carbohydrate and fat into ATP molecules that power enzymatic reactions within cells, and this process influences cellular calcium signals in several ways. By providing ATP to calcium pumps at the plasma and intracellular membranes, mitochondria power the calcium gradients that drive the release of Ca 2+ from stores and the entry of Ca 2+ across plasma membrane channels. By taking up and subsequently releasing calcium ions, mitochondria determine the spatiotemporal profile of cellular Ca 2+ signals and the activity of Ca 2+-regulated proteins, including Ca 2+ entry channels that are themselves part of the Ca 2+ circuitry. Ca 2+ elevations in the mitochondrial matrix, in turn, activate Ca 2+-dependent enzymes that boost the respiratory chain, increasing the ability of mitochondria to buffer calcium ions. Mitochondria are able to encode and decode Ca 2+ signals because the respiratory chain generates an electrochemical gradient for protons across the inner mitochondrial membrane. This proton motive force (Δp) drives the activity of the ATP synthase and has both an electrical component, the mitochondrial membrane potential (ΔΨ m ), and a chemical component, the mitochondrial proton gradient (ΔpH m ). ΔΨ m contributes about 190 mV to Δp and drives the entry of Ca 2+ across a recently identified Ca 2+-selective channel known as the mitochondrial Ca 2+ uniporter. ΔpH m contributes ~30 mV to Δp and is usually ignored or considered a minor component of mitochondria respiratory state. However, the mitochondrial proton gradient is an essential component of the chemiosmotic theory formulated by Peter Mitchell in 1961 as ΔpH m sustains the entry of substrates and metabolites required for the activity of the respiratory chain and drives the activity of electroneutral ion exchangers that allow mitochondria to maintain their osmolarity and volume. In this review, we summarize the mechanisms that regulate the mitochondrial proton gradient and discuss how thermodynamic concepts derived from measurements in purified mitochondria can be reconciled with our recent findings that mitochondria have high proton permeability in situ and that ΔpH m decreases during mitochondrial Ca 2+ elevations. © 2012 Springer-Verlag.


Jeannot E.,University of Geneva
Swiss medical weekly | Year: 2010

In view of the alarming trend in childhood obesity (O) and overweight (OW) observed in certain countries, the aim of the study is to measure the prevalence of O and OW in successive cohorts of elementary school children in Geneva. All 5-6-year-old children attending public schools in the Canton of Geneva were measured and weighed during a systematic health check at school from 2003 to 2008. BMI was calculated and plotted on standardised BMI for age tables, using Cole's and Kromeyer's references. Using Cole's references, the overall trend was a small non-significant decrease for OW 0.7 points (p = 0.33) and O 0.5 points (p = 0.23) over the 5-year period. For girls, OW decreased by 1.1 point (p = 0.47) and O decreased by 0.5 points (p = 0.61), whilst for boys OW decreased by 0.3 points (p = 0.54) and O decreased by 0.6 points (p = 0.23). A non-significant decrease or stabilisation in the prevalence of overweight and obesity was observed over the 5-year period in both boys and girls. These observations corroborate observations from Sweden and France, showing a levelling off in obesity and overweight in young children.


Singer P.,Institute for Nutrition Research | Pichard C.,University of Geneva
Current Opinion in Clinical Nutrition and Metabolic Care | Year: 2013

Purpose of Review: Recent studies on the optimal modalities to feed patients during the ICU stay show divergent results. The level and the timing of energy provision is a critical issue, associated with the clinical outcome. These results questioned the clinical relevance of the recent guidelines issued by American, Canadian and European academic societies. Recent Findings: Four recent prospective randomized studies enrolled critically ill patients who received various nutritional regimens and tested the effect of nutritional support on outcome. The Tight Calorie balance Control Study (TICACOS) targeted on calorie administration according to measured energy expenditure and found increased ICU morbidity but improved hospital mortality. The large EpaNIC study compared 'early' with 'late' (parenteral nutrition) nutrition, mostly in patients after cardiac surgery, and found an increased morbidity associated with early parenteral nutrition. The supplemental parenteral nutrition (SPN) study randomized the patients after 3 days and targeted the calories administered by parenteral nutrition as a complement to unsuccessful enteral nutrition using indirect calorimetry. The SPN resulted in less nosocomial infections and shorter duration of mechanical ventilation. Finally, a recent Australian study enrolled patients unable to be early fed enterally to receive, or not, parenteral nutrition targeted at 1500kcal. No complications were noted in the parenteral nutrition group. Lessons from all these studies are summarized and should help in designing better studies and guidelines. Summary: The critical analysis of recent prospective studies comparing various levels of calorie administration, enteral versus parenteral nutrition and enteral versus SPN confirms the recommendations to avoid underfeeding and overfeeding. Parenteral nutrition, required if enteral feeding is failing, and if adjusted up to a measured optimal level, may improve outcome. More studies on the optimal level of energy and protein administration to optimize the clinical outcome are required to fine tune current guidelines. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Weissert R.,University of Geneva
Journal of Neuroimmunology | Year: 2011

Progressive multifocal leukoencephalopathy (PML) is a disease of the central nervous system (CNS) with destructive infection of oligodendrocytes by JC virus. PML belongs to the opportunistic infections. It is observed in patients with HIV infection, lymphoid malignancies, after organ- and stem cell transplantations and more recently in the context of modern immune-therapies with monoclonal antibodies (mAb) like natalizumab, rituximab, infliximab and efalizumab. The natural course of PML is fatal within months. More recently, the Immune Reconstitution Inflammatory Syndrome (IRIS) has been observed in patients with HIV infection treated with combination antiretroviral therapy (cART) as well as patients in whom the PML-inducing immune therapy has been terminated. In PML-IRIS the immune system contributes to the elimination of JC virus from the CNS and if PML-IRIS emerges, PML can be survived but can lead as well to catastrophic outcomes with brain herniation and death. Therefore the management of IRIS requires special knowledge in JC virus biology and patient care. JC virus infection is possibly involved in a variety of additional neurological conditions and cancer. Much will be learned within the next years that could change our view on the understanding of JC virus and human disease. © 2010 Elsevier B.V.


Georgy C.,Keele University | Saio H.,Tohoku University | Meynet G.,University of Geneva
Monthly Notices of the Royal Astronomical Society: Letters | Year: 2014

Recent stellar evolution computations show that the blue supergiant (BSG) stars could come from two distinct populations: a first group arising from massive stars that just left the main sequence and are crossing the Hertzsprung-Russell diagram (HRD) towards the red supergiant (RSG) branch, and a second group coming from stars that have lost considerable amount of mass during the RSG stage and are crossing the HRD for a second time towards the blue region. Due to very different luminosity-to-mass ratio, only stars from the second group are expected to have excited pulsations observable at the surface. In a previous work, we have shown that our models were able to reproduce the pulsational properties of BSGs. However, these models failed to reproduce the surface chemical composition of stars evolving back from an RSG phase. In this Letter, we show how the use of the Ledoux criterion instead of the Schwarzschild one for convection allows us to significantly improve the agreement with the observed chemical composition, while keeping the agreement with the pulsation periods. This gives some support to the Ledoux criterion. © 2013 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society.


Karch F.,University of Geneva
Advances in Experimental Medicine and Biology | Year: 2010

The discovery of the first homeotic mutation by Calvin Bridges in 19151 profoundly influenced the way we think about developmental processes. Although many mutations modify or deform morphological structures, homeotic mutations cause a spectacular phenotype in which a morphological structure develops like a copy of a structure that is normally found elsewhere on an organism's body plan. This is best illustrated in Drosophila where homeotic mutations were first discovered. For example, Antennapedia mutants have legs developing on their head instead of antennae. Because a mutation in a single gene creates such complete structures, homeotic genes were proposed to be key "selector genes" regulating the initiation of a developmental program.2 According to this model, once a specific developmental program is initiated (i.e., antenna or leg), it can be executed by downstream "realizator genes" independent of its location along the body axis. Consistent with this idea, homeotic genes have been shown to encode transcription factor proteins that control the activity of the many downstream targets to "realize" a developmental program. Here, we will review the first and perhaps, best characterized homeotic complex, the Bithorax Complex (BX-C). © 2010 Landes Bioscience and Springer Science+Business Media.


Yu J.,University of Geneva
Journal of controlled release : official journal of the Controlled Release Society | Year: 2011

The physicochemical properties and stability requirements of therapeutic proteins necessitate their parenteral administration even for local therapy; however, unnecessary systemic exposure increases the risk of avoidable side-effects. The objective of this study was to use fractional laser ablation to enable the delivery of intact, functional therapeutic antibodies into the skin in vitro and in vivo. The laser-assisted delivery of Antithymocyte globulin (ATG) and Basiliximab - FDA-approved therapeutics for the induction of immunosuppression - was investigated. In vitro delivery experiments were performed using dermatomed porcine ear and human abdominal skins; an in vitro/in vivo correlation was shown using C57 BL/10 SCSnJ mice. Antibody transport was quantified by using ELISA methods developed in-house. Results showed that increasing the pore number from 300 to 450 and 900, increased total antibody delivery (sum of amounts permeated and deposited); e.g., for ATG, from 1.18±0.10 to 3.98±0.64 and 4.97±0.83 μg/cm(2), respectively - corresponding to 19.7-, 66.3- and 82.8-fold increases over the control (untreated skin). Increasing laser fluence from 22.65 to 45.3 and 135.9J/cm(2) increased total ATG delivery from 1.70±0.65 to 4.97±0.83 and 8.70±1.55 μg/cm(2), respectively. The Basiliximab results confirmed the findings with ATG. Western blot demonstrated antibody identity and integrity post-delivery; human lymphocyte cytotoxicity assays showed that ATG retained biological activity post-delivery. Immunohistochemical staining was used to visualize ATG distribution in the epidermis. Total ATG delivery across porcine ear and human abdominal skin was statistically equivalent and an excellent in vitro/in vivo correlation was observed in the murine model. Based on published data, the ATG concentrations achieved in the laser-porated human skins were in the therapeutic range for providing local immunosuppression. These results challenge the perceived limitations of transdermal delivery with respect to biopharmaceuticals and suggest that controlled laser microporation provides a less invasive, more patient-friendly "needle-less" alternative to parenteral administration for the local delivery of therapeutic antibodies. Copyright © 2011 Elsevier B.V. All rights reserved.


Negro F.,University of Geneva
Gut | Year: 2010

Hepatitis C virus (HCV) is a human pathogen responsible for acute and chronic liver disease, infecting an estimated 130-170 million persons worldwide. An intriguing feature of HCV infection is its peculiar relationship with lipids: (1) HCV virions circulate in serum bound to lipoproteins; (2) lipids have been shown to modulate (and, indeed, are essential to) the HCV life cycle; and (3) an occasionally severe accumulation of triglycerides is found in a distinct subgroup of patients in the form of hepatic steatosis. As a result, lipid metabolism is overall altered, conferring an idiosyncratic profile to HCV infection. The scope of this review is to discuss these aspects, focusing on both their molecular mechanisms and their clinical consequences.


Thalli of the foliose lichen species Parmelina tiliacea were studied to determine responses of the photosynthetic apparatus to high temperatures in the dry and wet state. The speed with which dry thalli were activated by water following a 24 h exposure at different temperatures decreased as the temperature was increased. But even following a 24 h exposure to 50 °C the fluorescence induction kinetics OJIP reflecting the reduction kinetics of the photosynthetic electron transport chain had completely recovered within 128 min. Exposure of dry thalli to 50 °C for 24 h did not induce a K-peak in the fluorescence rise suggesting that the oxygen evolving complex had remained intact. This contrasted strongly with wet thalli were submergence for 40 s in water of 45 °C inactivated most of the photosystem II reaction centres. In wet thalli, following the destruction of the Mn-cluster, the donation rate to photosystem II by alternative donors (e.g. ascorbate) was lower than in higher plants. This is associated with the near absence of a secondary rise peak (~1 s) normally observed in higher plants. Analysing the 820 nm and prompt fluorescence transients suggested that the M-peak (occurs around 2-5 s) in heat-treated wet lichen thalli is related to cyclic electron transport around photosystem I. Normally, heat stress in lichen thalli leads to desiccation and as consequence lichens may lack the heat-stress-tolerance-increasing mechanisms observed in higher plants. Wet lichen thalli may, therefore, represent an attractive reference system for the evaluation of processes related with heat stress in higher plants. © Springer Science+Business Media B.V. 2012


Liver-first reversed management (RM) for the treatment of patients with simultaneous colorectal liver metastases (CRLM) includes liver-directed chemotherapy, the resection of the CRLM, and the subsequent resection of the primary cancer. Retrospective data have shown that up to 80% of patients can successfully undergo a complete RM, whereas less than 30% of those undergoing classical management (CM) do so. This registry-based study compared the 2 approaches. The study was based on the LiverMetSurvey (January 1, 2000 to December 31, 2010) and included patients with 2 or more metastases. All patients had irinotecan and/or oxaliplatin-based chemotherapy before liver surgery. Patients undergoing simultaneous liver and colorectal surgery were excluded. A total of 787 patients were included: 729 in the CM group and 58 in the RM group. Patients in the 2 groups had similar numbers of metastases (4.20 vs 4.80 for RM and CM, P = 0.231) and Fong scores of 3 or more (79% vs 87%, P = 0.164). Rectal cancer, neoadjuvant rectal radiotherapy, and the use of combined irinotecan/oxaliplatin chemotherapy were more frequent in the RM group (P < 0.001), whereas colorectal lymph node involvement was more frequent in the CM group (P < 0.001). Overall survival and disease-free survival were similar in the RM and CM groups (48% vs 46% at 5 years, P = 0.965 and 30% vs 26%, P = 0.992). Classical and reversed managements of metastatic liver disease in colorectal cancer are associated with similar survival when successfully completed.


Allet L.,University of Geneva
Sensors (Basel, Switzerland) | Year: 2010

The use of wearable motion sensing technology offers important advantages over conventional methods for obtaining measures of physical activity and/or physical functioning in individuals with chronic diseases. This review aims to identify the actual state of applying wearable systems for monitoring mobility-related activity in individuals with chronic disease conditions. In this review we focus on technologies and applications, feasibility and adherence aspects, and clinical relevance of wearable motion sensing technology. PubMed (Medline since 1990), PEdro, and reference lists of all relevant articles were searched. Two authors independently reviewed randomised trials systematically. The quality of selected articles was scored and study results were summarised and discussed. 163 abstracts were considered. After application of inclusion criteria and full text reading, 25 articles were taken into account in a full text review. Twelve of these papers evaluated walking with pedometers, seven used uniaxial accelerometers to assess physical activity, six used multiaxial accelerometers, and two papers used a combination approach of a pedometer and a multiaxial accelerometer for obtaining overall activity and energy expenditure measures. Seven studies mentioned feasibility and/or adherence aspects. The number of studies that use movement sensors for monitoring of activity patterns in chronic disease (postural transitions, time spent in certain positions or activities) is nonexistent on the RCT level of study design. Although feasible methods for monitoring human mobility are available, evidence-based clinical applications of these methods in individuals with chronic diseases are in need of further development.


Soldati T.,University of Geneva | Neyrolles O.,CNRS Institute of Pharmacology and Structural Biology | Neyrolles O.,Toulouse 1 University Capitole
Traffic | Year: 2012

Ancient protozoan phagocytes and modern professional phagocytes of metazoans, such as macrophages, employ evolutionarily conserved mechanisms to kill microbes. These mechanisms rely on microbial ingestion, followed by maturation of the phagocytic vacuole, or so-called phagosome. Phagosome maturation includes a series of fusion and fission events with the host cell endosomes and lysosomes, leading to a rapid increase of the degradative properties of the vacuole and to the destruction of the ingested microbe within a very hostile intracellular compartment, the phagolysosome. Historically, the mechanisms and weapons used by phagocytes to kill microbes have been separated into different classes. Phagosomal acidification, together with the production of reactive oxygen and nitrogen species, the selective manipulation of various ions in the phagosomal lumen, and finally the engagement of a battery of acidic hydrolases, are well-recognized players in this process. However, it is relatively recently that interconnections among these mechanisms have become apparent. In this review, we will focus on some emerging concepts about these interconnected aspects of the warfare at the host-pathogen interface, using mostly Mycobacterium tuberculosis as an example of intracellular pathogen. In particular, recent discoveries on the role of phagosomal ions and other chemicals in the control of pathogens, as well as mechanisms evolved by intracellular pathogens to circumvent or even exploit the weapons of the host cell will be discussed. © 2012 John Wiley & Sons A/S.


Kolakofsky D.,University of Geneva | Kowalinski E.,Max Planck Institute of Biochemistry | Cusack S.,French National Center for Scientific Research
RNA | Year: 2012

A series of high-resolution crystal structures of RIG-I and RIG-I:dsRNA cocrystals has recently been reported. Comparison of these structures provides considerable insight into how this innate immune pattern recognition receptor is activated upon detecting and binding a certain class of viral RNAs. Copyright © 2012 RNA Society.


Jacques T.,University of Geneva | Nordstrom K.,University of Glasgow
Journal of High Energy Physics | Year: 2015

Abstract: The move towards simplified models for Run II of the LHC will allow for stronger and more robust constraints on the dark sector. However there already exists a wealth of Run I data which should not be ignored in the run-up to Run II. Here we reinterpret public constraints on generic beyond-standard-model cross sections to place new constraints on a simplified model. We make use of an ATLAS search in the monojet + missing energy channel to constrain a representative simplified model with the dark matter coupling to an axial-vector Z′. We scan the entire parameter space of our chosen model to set the strongest current collider constraints on our model using the full 20.3 fb−1 ATLAS 8 TeV dataset and provide predictions for constraints that can be set with 20 fb−1 of 14 TeV data. Our technique can also be used for the interpretation of Run II data and provides a broad benchmark for comparing future constraints on simplified models. © 2015, The Author(s).


Saudan S.,University of Geneva
Current Opinion in Anaesthesiology | Year: 2010

Purpose of review: Albumin has been regarded as the gold standard for maintaining adequate colloid osmotic pressure in children, but increased cost, the lack of clear-cut benefits for survival, and fear of transmission of unknown viruses have contributed to its replacement by hydroxyethyl starch and gelatin preparations. Each of the synthetic colloids has unique physicochemical characteristics that determine their likely efficacy and adverse effect profile. This review will examine the advantages and disadvantages of the use of different colloid solutions in children with a particular focus on their safety profile. Recent findings: Dextrans are rarely used because of their negative effects on coagulation and potential for anaphylactic reactions. Gelatin and albumin have little effect on hemostasis, but the disadvantages of gelatin include its high anaphylactoid potential and limited beneficial volume effect. Tetrastarches have significantly fewer adverse effects on coagulation and renal function than the older hydroxyethyl starches and are now approved for children. Dissolving tetrastarches in a plasma-adapted, balanced solution rather than in saline further improves safety with regard to coagulation and acid-base balance. Summary: Tetrastarches offer the best currently available compromise between cost-effectiveness and safety profile in children with preexisting normal renal function and coagulation. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Many mountain ranges in regions of plate convergence are flanked by foreland sedimentary basins that are usually thought to result from flexing of the elastic lithosphere under the passive weight of sediments and thrust sheets emplaced in the mountain belt. However, in some places the depth of the foreland basin bears little relation to the weight of basin sediments and neighboring mountains, implying that this model is too simple and/or that additional forces must affect subsidence. Here I investigate this problem using a numerical model that incorporates coupling between an upthrusting mountain range and a subsiding basin. I show that only part of the subsidence reflected in the shape of a foreland basin is a flexural isostatic response to crustal thickening and sediment loading. The remaining subsidence results from dragging of the basin margin downward by slip on a range-front fault and related flexural deformation of the surrounding lithosphere. The maximum basin depth is shown to increase with increasing fault displacement and can become decoupled from the elevation of the mountain range, especially as erosion becomes increasingly important. Deeply eroded model mountain belts may have foreland basins several times deeper than flexural models predict on the basis of surface loads. These results challenge the prevailing view that fault-bounded foreland basins result solely from the passive weight of mountains and sediments acting on the lithosphere and they highlight that slip on major range-front reverse faults, when repeated over many earthquake cycles, may be recorded in their geometry and stratigraphic records. © 2014 Geological Society of America.


Bohanes P.,University of Geneva
Swiss medical weekly | Year: 2011

There are very limited data suggesting a benefit for second-line chemotherapy in advanced gastric cancer. Therefore, the number of patients who receive further treatment after failure of first-line chemotherapy varies considerably, ranging from 14% to 75%. In the absence of a demonstrated survival benefit of second-line chemotherapy, appropriate selection of patients based on survival predictors is essential. However, no clinico-pathologic parameters are currently widely adopted in clinical practice. We looked exclusively at Caucasian patients with metastatic gastric cancer treated with second-line chemotherapy to see if we could establish prognostic factors for survival. This study retrospectively evaluated 43 Caucasian patients with metastatic gastric cancer treated with second-line chemotherapy at the Geneva University Hospital. Prognostic values of clinico-pathologic parameters were analysed by Cox regression for overall survival (OS). Univariate analysis found three variables to be associated with survival: progression-free survival (PFS) at first-line chemotherapy of more than 26 weeks (hazard ratio (HR) = 0.33, confidence interval (CI) 95% 0.16-0.65, p = 0.002), previous curative surgery (HR = 0.51, CI 95% 0.27-0.96, p = 0.04) and carcinoma embryonic antigen (CEA) >6.5 μg/l (HR = 1.97, CI 95% 1.06-3.65, p = 0.03). In line with published data, sensitivity to previous chemotherapy identifies Caucasian patients who will survive the longest following second-line chemotherapy. A low tumour burden and previous curative gastrectomy also seem to have a positive prognostic value.


Golay A.,University of Geneva
Journal of Medical Economics | Year: 2011

Background: Poor adherence to medical treatment is one of the main reasons why patients do not achieve the full benefits of their therapy. It also has a substantial financial weight in terms of money wasted for unused medication and increased healthcare costs including hospitalization due to clinical complications. Objective: To provide an overview and examples of the financial and economic consequences of poor adherence to treatment, techniques and devices for monitoring adherence and interventions for improvement of treatment adherence. Results: New electronic devices with monitoring features may help to objectively monitor patients' adherence to a treatment regimen that can help a healthcare professional determine how to intervene to improve adherence and subsequent clinical outcome. Interventions that aim to enhance adherence may confer cost-effectiveness benefits in some indications and settings. The nature of the intervention(s) used depends on a range of factors, including patient preference, therapy area and cost of the intervention. However, there is a pressing need for rigorous trials, as current studies often have major flaws in the economic methodology, especially in terms of incremental analysis and sensitivity analysis. Limitations: This review has focused on a limited number of therapeutic areas as coverage of a more extensive range of diseases may be beyond the scope of such a summary. Nevertheless, the examples are representative of the challenges encountered in many other diseases. Conclusions: The clinical and economic consequences of non-adherence and interventions to improve compliance reflect the nature and severity of non-adherence, as well as the pathophysiology and severity of the disease. Interventions that aim to enhance adherence may confer cost-effectiveness benefits in some indications and settings, and good adherence can help payers and providers contain costs by extracting maximum value from their investment in therapies. © 2011 Informa UK Ltd All rights reserved.


Maggiore M.,University of Geneva | Riotto A.,CERN | Riotto A.,National Institute of Nuclear Physics, Italy
Astrophysical Journal | Year: 2010

In excursion set theory, the computation of the halo mass function is mapped into a first-passage time process in the presence of a barrier, which in the spherical collapse model is a constant and in the ellipsoidal collapse model is a fixed function of the variance of the smoothed density field. However, N-body simulations show that dark matter halos grow through a mixture of smooth accretion, violent encounters, and fragmentations, and modeling halo collapse as spherical, or even as ellipsoidal, is a significant oversimplification. In addition, the very definition of what is a dark matter halo, both in N-body simulations and observationally, is a difficult problem. We propose that some of the physical complications inherent to a realistic description of halo formation can be included in the excursion set theory framework, at least at an effective level, by taking into account that the critical value for collapse is not a fixed constant δc, as in the spherical collapse model, nor a fixed function of the variance σ of the smoothed density field, as in the ellipsoidal collapse model, but rather is itself a stochastic variable, whose scatter reflects a number of complicated aspects of the underlying dynamics. Solving the first-passage time problem in the presence of a diffusing barrier we find that the exponential factor in the Press-Schechter mass function changes from exp{-δ2 c/2σ2} to exp{-aδ2 c/2σ2}, where a = 1/(1 + DB) and DB is the diffusion coefficient of the barrier. The numerical value of DB, and therefore the corresponding value of a, depends among other things on the algorithm used for identifying halos. We discuss the physical origin of the stochasticity of the barrier and, from recent N-body simulations that studied the properties of the collapse barrier, we deduce a value DB ≃ 0.25. Our model then predicts a ≃ 0.80, in excellent agreement with the exponential fall off of the mass function found in N-body simulations, for the same halo definition. Combining this result with the non-Markovian corrections computed in Paper I of this series, we derive an analytic expression for the halo mass function for Gaussian fluctuations and we compare it with N-body simulations. © 2010. The American Astronomical Society. All rights reserved.


Maggiore M.,University of Geneva | Riotto A.,CERN | Riotto A.,National Institute of Nuclear Physics, Italy
Astrophysical Journal | Year: 2010

A classic method for computing the mass function of dark matter halos is provided by excursion set theory, where density perturbations evolve stochastically with the smoothing scale, and the problem of computing the probability of halo formation is mapped into the so-called first-passage time problem in the presence of a barrier. While the full dynamical complexity of halo formation can only be revealed through N-body simulations, excursion set theory provides a simple analytic framework for understanding various aspects of this complex process. In this series of papers we propose improvements of both technical and conceptual aspects of excursion set theory, and we explore up to which point the method can reproduce quantitatively the data from N-body simulations. In Paper I of the series, we show how to derive excursion set theory from a path integral formulation. This allows us both to derive rigorously the absorbing barrier boundary condition, that in the usual formulation is just postulated, and to deal analytically with the non-Markovian nature of the random walk. Such a non-Markovian dynamics inevitably enters when either the density is smoothed with filters such as the top-hat filter in coordinate space (which is the only filter associated with a well-defined halo mass) or when one considers non-Gaussian fluctuations. In these cases, beside "Markovian" terms, we find "memory" terms that reflect the non-Markovianity of the evolution with the smoothing scale. We develop a general formalism for evaluating perturbatively these non-Markovian corrections, and in this paper we perform explicitly the computation of the halo mass function for Gaussian fluctuations, to first order in the non-Markovian corrections due to the use of a top-hat filter in coordinate space. In Paper II of this series we propose to extend excursion set theory by treating the critical threshold for collapse as a stochastic variable, which better captures some of the dynamical complexity of the halo formation phenomenon, while in Paper III we use the formalism developed in this paper to compute the effect of non-Gaussianities on the halo mass function. © 2010. The American Astronomical Society.


Britz J.,University of Geneva | Pitts M.A.,University of California at San Diego
Psychophysiology | Year: 2011

We used an intermittent stimulus presentation to investigate event-related potential (ERP) components associated with perceptual reversals during binocular rivalry. The combination of spatiotemporal ERP analysis with source imaging and statistical parametric mapping of the concomitant source differences yielded differences in three time windows: reversals showed increased activity in early visual (~120 ms) and in inferior frontal and anterior temporal areas (~400-600 ms) and decreased activity in the ventral stream (~250-350 ms). The combination of source imaging and statistical parametric mapping suggests that these differences were due to differences in generator strength and not generator configuration, unlike the initiation of reversals in right inferior parietal areas. These results are discussed within the context of the extensive network of brain areas that has been implicated in the initiation, implementation, and appraisal of bistable perceptual reversals. © 2011 Society for Psychophysiological Research.


Somm E.,University of Geneva
Archivum Immunologiae et Therapiae Experimentalis | Year: 2014

Nicotinic acetylcholine receptors (nAChRs) are membrane ligand-gated cation channels whose activation is triggered by the binding of the endogenous neurotransmitter acetylcholine or other biologic compounds including nicotine. Their roles in synaptic transmission in the central and peripheral nervous system as well as in the neuromuscular junction have been extensively studied. Recent implications of nAChRs in intracellular signaling and their detection in peripheral nonneural cells (including epithelial cells and immune cells) have renewed the interest for this class of ionotropic receptors. In the present review, we focus our attention on the potential use of nicotinic cholinergic signaling in the treatment of metabolic diseases (such as obesity and diabetes) in browsing functions of nAChRs in adipose tissue and pancreatic islet biology. In fact, different nAChR subunits can be detected in these metabolic tissues, as well as in immune cells interacting with them. Various rodent models of obesity and diabetes benefit from stimulation of the nicotinic cholinergic pathway, whereas mice deficient for some nAChRs, in particular the α7 nAChR subunit, harbor a worsened metabolic phenotype. In contrast to potential therapeutic applications in metabolic diseases, an overstimulation of this signaling pathway during the early stage of development (typically through nicotine exposure during fetal life) presents deleterious consequences on ontogeny and functionality of adipose tissue and the endocrine pancreas which persist throughout life. © 2013 L. Hirszfeld Institute of Immunology and Experimental Therapy.


A two-dimensional mathematical model considering coupling between a deforming elasto-visco-plastic fold-thrust belt, flexural subsidence and diffusional surface processes is solved using the Finite Element Method to investigate how the mechanical behaviour of brittle-ductile wedges influences the development of foreland basins. Results show that, depending mainly on the strength of the basal décollement, two end-member types of foreland basin are possible. When the basal detachment is relatively strong, the foreland basin system is characterised by: (1) Highly asymmetrical orogen formed by thrusts concentrated in the incoming pro-wedge. (2) Sedimentation on retro-side takes place in one major foredeep basin which grows throughout orogen evolution. (3) Deposition on the pro-side occurs initially in the foredeep, and continues in the wedge-top before isolated basins are advected towards the orogen core where they become uplifted and exhumed. (4) Most pro-wedge basins show an upward progression from low altitude, foredeep deposits at the base to high altitude, wedge-top deposits near the surface. In contrast, when the basal detachment behaves weakly due to the presence of low viscosity material such as salt, the foreland basin system is characterised by (1) Broad, low relief orogen showing little preferential vergence and predominance of folding relative to faulting. (2) Deposition mainly in wedge-top basins showing growth strata. (3) Many basins are initiated contemporaneously but form discontinuously due to the locus of active deformation jumping back and forth between different structures. Model results successfully reproduce first order observations of deforming brittle-ductile wedges and foreland basins. Moreover, the results support and provide a framework for understanding the existence of two main end-member foreland basin types, simple and complex, associated with fold-thrust belts whose detachments are relatively strong and weak, respectively. © 2009 The Authors. Journal Compilation © Blackwell Publishing Ltd, European Association of Geoscientists & Engineers and International Association of Sedimentologists.


Luban J.,University of Geneva | Luban J.,University of Massachusetts Medical School
Cell Host and Microbe | Year: 2012

HIV-1-specific antibodies and CD8+ cytotoxic T cells are detected in most HIV-1-infected people, yet HIV-1 infection is not eradicated. Contributing to the failure to mount a sterilizing immune response may be the inability of antigen-presenting dendritic cells (DCs) to sense HIV-1 during acute infection, and thus the inability to effectively prime naive, HIV-1-specific T cells. Recent findings related to DC-expressed innate immune factors including SAMHD1, TREX1, and TRIM5 provide a molecular basis for understanding why DCs fail to adequately sense invasion by this deadly pathogen and suggest experimental approaches to improve T cell priming to HIV-1 in prophylactic vaccination protocols. © 2012 Elsevier Inc.


Cardiovascular diseases are the principal cause of death in women in developed countries and are importantly promoted by hypertension. The salt sensitivity of blood pressure (BP) is considered as an important cardiovascular risk factor at any BP level. Preeclampsia is a hypertensive disorder of pregnancy that arises as a risk factor for cardiovascular diseases. This study measured the salt sensitivity of BP in women with a severe preeclampsia compared with women with no pregnancy hypertensive complications. Forty premenopausal women were recruited 10 years after delivery in a case-control study. Salt sensitivity was defined as an increase of >4 mm Hg in 24-hour ambulatory BP on a high-sodium diet. The ambulatory BP response to salt was significantly increased in women with a history of preeclampsia compared with that of controls. The mean (95% confidence interval) daytime systolic/diastolic BP increased significantly from 115 (109-118)/79 (76-82) mm Hg on low-salt diet to 123 (116-130)/80 (76-84) on a high-salt diet in women with preeclampsia, but not in the control group (from 111 [104-119]/77 [72-82] to 111 [106-116]/75 [72-79], respectively, P<0.05). The sodium sensitivity index (SSI=Δmean arterial pressure/Δurinary Na excretion×1000) was 51.2 (19.1-66.2) in women with preeclampsia and 6.6 (5.8-18.1) mm Hg/mol per day in controls (P=0.015). The nocturnal dip was blunted on a high-salt diet in women with preeclampsia. Our study shows that women who have developed preeclampsia are salt sensitive before their menopause, a finding that may contribute to their increased cardiovascular risk. Women with a history of severe preeclampsia should be targeted at an early stage for preventive measures of cardiovascular diseases.


Bounameaux H.,University of Geneva
Journal of Internal Medicine | Year: 2010

Pulmonary embolism (PE) cannot be diagnosed solely on a clinical basis, because of the lack of sensitivity and specificity of clinical signs and symptoms. Pulmonary angiography is invasive and resource demanding. Because the prevalence of PE is relatively low (20% or less) amongst individuals who are clinically suspected of having the disease, submitting all of them to imaging (multi-detector CT angiography or ventilation/perfusion lung scintigraphy) would not be cost-effective. Therefore, diagnostic algorithms have been developed that include clinical probability assessment and D-dimer measurement to select the patients who require noninvasive imaging. Once the diagnosis is suspected or confirmed, therapy must be started to avoid potentially fatal recurrence. Treatment starts for an initial 3-month period with a 5-day course of parenteral unfractionated or low-molecular-weight heparin or fondaparinux overlapping with and followed by oral vitamin K antagonists monitored to maintain an international normalized ratio of 2-3. This initial period of 3 months may then be followed by a long-term secondary prevention period in patients who experience an idiopathic thromboembolic event and are at low risk of bleeding. New oral anticoagulants that do require patient monitoring and might exhibit a more favourable benefit-risk balance are currently under extensive clinical testing and might change the situation in the near future. A critical appraisal of the contemporary management of suspected PE is given in this overview with the discussion of 10 practical questions. © 2010 Blackwell Publishing Ltd.


Stevan S.,University of Geneva
Annales Henri Poincare | Year: 2015

We study the invariant of knots in lens spaces defined from quantum Chern–Simons theory. By means of the knot operator formalism, we derive a generalization of the Rosso-Jones formula for torus knots in L(p,1). In the second part of the paper, we propose a B-model topological string theory description of torus knots in L(2,1). © 2014, Springer Basel.


Severa P.,University of Geneva
Letters in Mathematical Physics | Year: 2015

Poisson–Lie T-duality is explained using the language of Courant algebroids. © 2015, Springer Science+Business Media Dordrecht.


Maechler P.,University of Geneva
Molecular and Cellular Endocrinology | Year: 2013

In the endocrine fraction of the pancreas, the β-cell rapidly reacts to fluctuations in blood glucose concentrations by adjusting the rate of insulin secretion. Glucose-sensing coupled to insulin exocytosis depends on transduction of metabolic signals into intracellular messengers recognized by the secretory machinery. Mitochondria play a central role in this process by connecting glucose metabolism to insulin release. Mitochondrial activity is primarily regulated by metabolic fluxes, but also by dynamic morphology changes and free Ca2+ concentrations. Recent advances of mitochondrial Ca2+ homeostasis are discussed; in particular the roles of the newly-identified mitochondrial Ca2+ uniporter MCU and its regulatory partner MICU1, as well as the mitochondrial Na+-Ca2+ exchanger. This review describes how mitochondria function both as sensors and generators of metabolic signals; such as NADPH, long chain acyl-CoA, glutamate. The coupling factors are additive to the Ca2+ signal and participate to the amplifying pathway of glucose-stimulated insulin secretion. © 2013 Elsevier Ireland Ltd.


Etter J.-F.,University of Geneva | Bullen C.,University of Auckland
Addiction | Year: 2011

Aims To assess the profile, utilization patterns, satisfaction and perceived effects among users of electronic cigarettes ('e-cigarettes'). Design and Setting Internet survey in English and French in 2010. Measurements Online questionnaire. Participants Visitors of websites and online discussion forums dedicated to e-cigarettes and to smoking cessation. Findings There were 3587 participants (70% former tobacco smokers, 61% men, mean age 41 years). The median duration of electronic cigarette use was 3 months, users drew 120 puffs/day and used five refills/day. Almost all (97%) used e-cigarettes containing nicotine. Daily users spent $33 per month on these products. Most (96%) said the e-cigarette helped them to quit smoking or reduce their smoking (92%). Reasons for using the e-cigarette included the perception that it was less toxic than tobacco (84%), to deal with craving for tobacco (79%) and withdrawal symptoms (67%), to quit smoking or avoid relapsing (77%), because it was cheaper than smoking (57%) and to deal with situations where smoking was prohibited (39%). Most ex-smokers (79%) feared they might relapse to smoking if they stopped using the e-cigarette. Users of nicotine-containing e-cigarettes reported better relief of withdrawal and a greater effect on smoking cessation than those using non-nicotine e-cigarettes. Conclusions E-cigarettes were used much as people would use nicotine replacement medications: by former smokers to avoid relapse or as an aid to cut down or quit smoking. Further research should evaluate the safety and efficacy of e-cigarettes for administration of nicotine and other substances, and for quitting and relapse prevention. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.


Rinaldi M.,University of Geneva
Modern Physics Letters A | Year: 2010

We consider the coherent state approach to noncommutativity and we derive from it an effective quantum scalar field theory. We show how the noncommutativity can be taken into account by a suitable modification of the KleinGordon product, and of the equal-time commutation relations. We prove that, in curved space, the Bogoliubov coefficients are unchanged, hence the number density of the produced particle is the same as for the commutative case. What changes though is the associated energy density, and this offers a simple solution to the transplanckian problem. © 2010 World Scientific Publishing Company.


de Rham C.,University of Geneva | Gabadadze G.,New York University
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2010

We calculate the cubic order terms in a covariant theory that gives a nonlinear completion of the Fierz-Pauli massive spin-2 action. The resulting terms have specially tuned coefficients guarantying the absence of a ghost at this order in the decoupling limit. We show in this limit that: (1) The quadratic theory propagates helicity-2, 1, and helicity-0 states of massive spin-2. (2) The cubic terms with six derivatives - which would give ghosts on local backgrounds - cancel out automatically. (3) There is a four-derivative cubic term for the helicity-0 field, that has been known to be ghost-free on any local background. (4) There are four-derivative cubic terms that mix two helicity-0 fields with one helicity-2, or two helicity-1 fields with one helicity-0; none of them give ghosts on local backgrounds. (5) In the absence of external sources, all the cubic mixing terms can be removed by nonlinear redefinitions of the helicity-2 and helicity-1 fields. Notably, the helicity-2 redefinition generates the quartic Galileon term. These findings hint to an underlying nonlinearly realized symmetry, that should be responsible for what appears as the accidental cancellation of the ghost. © 2010 Elsevier B.V.


Sawicki I.,University of Geneva | Bellini E.,University of Barcelona
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2015

We investigate the limits of applicability of the quasistatic approximation in cosmologies featuring general models of dark energy or modified gravity. We show that, at best, the quasistatic approximation breaks down outside of the sound horizon of the dark-energy, rather than the cosmological horizon as is frequently assumed. When the sound speed of dark energy is significantly below that of light, the quasistatic limit is only valid in a limited range of observable scales and this must be taken into account when computing effects on observations in such models. As an order of magnitude estimate, in the analysis of data from today's weak-lensing and peculiar-velocity surveys, dark energy can be modeled as quasistatic only if the sound speed is larger than order 1% of that of light. In upcoming surveys, such as Euclid, it should only be used when the sound speed exceeds around 10% of the speed of light. In the analysis of the cosmic microwave background, the quasistatic limit should never be used for the integrated Sachs-Wolf effect and for lensing only when the sound speed exceeds 10% of the speed of light. © 2015 American Physical Society.


Parsons S.,University of Edinburgh | Flack H.D.,University of Geneva | Wagner T.,Novartis
Acta Crystallographica Section B: Structural Science, Crystal Engineering and Materials | Year: 2013

Several methods for absolute structure refinement were tested using single-crystal X-ray diffraction data collected using Cu Kα radiation for 23 crystals with no element heavier than oxygen: conventional refinement using an inversion twin model, estimation using intensity quotients in SHELXL2012, estimation using Bayesian methods in PLATON, estimation using restraints consisting of numerical intensity differences in CRYSTALS and estimation using differences and quotients in TOPAS-Academic where both quantities were coded in terms of other structural parameters and implemented as restraints. The conventional refinement approach yielded accurate values of the Flack parameter, but with standard uncertainties ranging from 0.15 to 0.77. The other methods also yielded accurate values of the Flack parameter, but with much higher precision. Absolute structure was established in all cases, even for a hydrocarbon. The procedures in which restraints are coded explicitly in terms of other structural parameters enable the Flack parameter to correlate with these other parameters, so that it is determined along with those parameters during refinement. © 2013 International Union of Crystallography Printed in Singapore - all rights reserved.


Dalla Torre E.G.,Weizmann Institute of Science | Demler E.,Harvard University | Giamarchi T.,University of Geneva | Altman E.,Weizmann Institute of Science
Nature Physics | Year: 2010

Quantum critical points are characterized by scale-invariant correlations and therefore by long-range entanglement. As such, they present fascinating examples of quantum states of matter and their study is an important theme in modern physics. However, little is known about the fate of quantum criticality under non-equilibrium conditions. Here we investigate the effect of external noise sources on quantum critical points. It is natural to expect that noise will have a similar effect to finite temperature, that is, destroying the subtle correlations underlying the quantum critical behaviour. Surprisingly, we find that the ubiquitous 1/f noise does preserve the critical correlations. The emergent states show an intriguing interplay of intrinsic quantum critical and external-noise-driven fluctuations. We illustrate this general phenomenon with specific examples describing solid-state and ultracold-atoms systems. Moreover, our approach shows that genuine quantum phase transitions can exist even under non-equilibrium conditions. © 2010 Macmillan Publishers Limited. All rights reserved.


Noordermeer D.,Ecole Polytechnique Federale de Lausanne | Duboule D.,Ecole Polytechnique Federale de Lausanne | Duboule D.,University of Geneva
Current Topics in Developmental Biology | Year: 2013

Ever since the observation that collinearity, that is, the sequential activity of Hox genes based on their relative positions within their gene clusters, is conserved throughout most of the animal kingdom, the question has been raised as to what are the underlying molecular mechanisms. In recent years, technological advances have allowed to uncover changes in chromatin organization that accompany collinearity at Hox gene clusters. Here, we discuss insights in the dynamics of histone modifications and 3D organization in Drosophila and mammals and relate these findings to genomic organization of Hox gene clusters. Using these findings, we propose a framework for collinearity, based on five components: clustering, coating, compaction, compartmentalization, and contacts. We argue that these five components may be sufficient to provide a mechanistic ground for the readout of collinearity in Drosophila and vertebrates. © 2013 Elsevier Inc.


Negro F.,University of Geneva
Digestive and Liver Disease | Year: 2014

The advent of potent and safe direct-acting antivirals against the hepatitis C virus has the potential of fulfilling the dream of eliminating this infection and its impact on global public health. However, even if effective drugs are at hand, most patients remain unaware of their infection, which may be recognized only in late stages when dire complications have occurred. Europe is not spared by this scourge, with its estimated 19,000,000 persons infected, and knowledge of the epidemiology of HCV and its drivers is a critical tool in fighting this virus. A thorough review is provided on the extent of the HCV epidemic across Europe, with a discussion of the most important subgroups affected, and of the risk factors of infection, both traditional and new. © 2014 Editrice Gastroenterologica Italiana S.r.l.


Negro F.,University of Geneva
Nature Reviews Gastroenterology and Hepatology | Year: 2014

Successful treatment with antivirals reduces the incidence of some extrahepatic manifestations of HCV. Thus, the advent of well-tolerated and highly potent antiviral regimens might enable extension of the indication for therapy to patients at risk of developing serious extrahepatic disorders, irrespective of the severity of the underlying liver disease.


Pictet A.,University of Geneva
Frontiers in Human Neuroscience | Year: 2014

Current cognitive models of social phobia converge on the view that negative imagery is a key factor in the development and maintenance of the disorder. Research to date has predominantly focussed on the detrimental impact of negative imagery on cognitive bias and anxiety symptoms, while the potential benefit of promoting positive imagery has been relatively unexplored. Emerging evidence suggests however that positive imagery could have multiple benefits such as improving positive affect, self-esteem and positive interpretation bias, and enhancing social performance. The present article defends the view that combining bias induction with a repeated practice in generating positive imagery in a cognitive bias modification procedure could represent a promising area for future research and clinical innovation in social anxiety disorder. © 2014 Pictet.


Heisenberg L.,Perimeter Institute for Theoretical Physics | Heisenberg L.,University of Geneva
Journal of Cosmology and Astroparticle Physics | Year: 2014

We consider the Lagrangian of a vector field with derivative self-interactions with a priori arbitrary coefficients. Starting with a flat space-time we show that for a special choice of the coefficients of the self-interactions the ghost-like pathologies disappear. This constitutes the Galileon-type generalization of the Proca action with only three propagating physical degrees of freedom. The longitudinal mode of the vector field is associated to the usual Galileon interactions for a specific choice of the overall functions. In difference to a scalar Galileon theory, the generalized Proca field has more free parameters. We then extend this analysis to a curved background. The resulting theory is the Horndeski Proca action with second order equations of motion on curved space-times. © 2014 IOP Publishing Ltd and Sissa Medialab srl.


Ferretti G.,University of Geneva | Ferretti G.,University of Brescia
European Journal of Applied Physiology | Year: 2014

This article reviews the concept of maximal oxygen consumption ((Formula presented.)) from the perspective of multifactorial models of (Formula presented.) limitation. First, I discuss procedural aspects of (Formula presented.) measurement: the implications of ramp protocols are analysed within the theoretical work of Morton. Then I analyse the descriptive physiology of (Formula presented.), evidencing the path that led to the view of monofactorial cardiovascular or muscular (Formula presented.) limitation. Multifactorial models, generated by the theoretical work of di Prampero and Wagner around the oxygen conductance equation, represented a radical change of perspective. These models are presented in detail and criticized with respect to the ensuing experimental work. A synthesis between them is proposed, demonstrating how much these models coincide and converge on the same conclusions. Finally, I discuss the cases of hypoxia and bed rest, the former as an example of the pervasive effects of the shape of the oxygen equilibrium curve, the latter as a neat example of adaptive changes concerning the entire respiratory system. The conclusion is that the concept of cardiovascular (Formula presented.) limitation is reinforced by multifactorial models, since cardiovascular oxygen transport provides most of the (Formula presented.) limitation, at least in normoxia. However, the same models show that the role of peripheral resistances is significant and cannot be neglected. The role of peripheral factors is greater the smaller is the active muscle mass. In hypoxia, the intervention of lung resistances as limiting factors restricts the role played by cardiovascular and peripheral factors. © 2014, Springer-Verlag Berlin Heidelberg.


Melzer K.,University of Geneva | Schutz Y.,University of Lausanne
International Journal of Obesity | Year: 2010

Obesity has progressively become a global epidemic that constitutes one of the biggest current health problems worldwide. Pregnancy is a risk factor for excessive weight gain. Factors that may predict development of obesity in later life mainly include gestational weight gain, pre-pregnancy nutritional status, age, parity and race. Change in lifestyle factors, such as eating habits, enrollment in physical activity, smoking and duration of lactation, in addition to the above factors, may also contribute to the development of obesity but are still not fully understood. Women who retain more body weight after pregnancy have, in general, larger pregnancy body weight gain, higher pre-pregnancy body mass index, marked weight changes in previous pregnancies, lactate slightly less and stop smoking during pregnancy to a larger extent. In addition, irregular eating habits and decreased leisure time activity after delivery influence postpartum weight retention. Taking into consideration the epidemic of obesity, with all its adverse long-term consequences, there is an increasing need to promote counseling before, during and after pregnancy on the role of diet and physical activity in reproductive health. © 2010 Macmillan Publishers Limited All rights reserved.


Boritchev A.,University of Geneva
Archive for Rational Mechanics and Analysis | Year: 2014

We consider the generalised Burgers equation (Formula presented.) where f is strongly convex and ν is small and positive. We obtain sharp estimates for Sobolev norms of u (upper and lower bounds differ only by a multiplicative constant). Then, we obtain sharp estimates for the dissipation length scale and the small-scale quantities which characterise the decaying Burgers turbulence, i.e., the structure functions and the energy spectrum. The proof uses a quantitative version of an argument by Aurell et al. (J Fluid Mech 238:467-486, 1992). Note that we are dealing with decaying, as opposed to stationary turbulence. Thus, our estimates are not uniform in time. However, they hold on a time interval [T1, T2], where T1 and T2 depend only on f and the initial condition, and do not depend on the viscosity. These results allow us to obtain a rigorous theory of the one-dimensional Burgers turbulence in the spirit of Kolmogorov's 1941 theory. In particular, we obtain two results which hold in the inertial range. On one hand, we explain the bifractal behaviour of the moments of increments, or structure functions. On the other hand, we obtain an energy spectrum of the form k-2. These results remain valid in the inviscid limit. © 2014 Springer-Verlag Berlin Heidelberg.


Melzer K.,University of Geneva
Sports medicine (Auckland, N.Z.) | Year: 2010

Regular physical activity is associated with improved physiological, metabolic and psychological parameters, and with reduced risk of morbidity and mortality. Current recommendations aimed at improving the health and well-being of nonpregnant subjects advise that an accumulation of > or =30 minutes of moderate physical activity should occur on most, if not all, days of the week. Regardless of the specific physiological changes induced by pregnancy, which are primarily developed to meet the increased metabolic demands of mother and fetus, pregnant women benefit from regular physical activity the same way as nonpregnant subjects. Changes in submaximal oxygen uptake (VO(2)) during pregnancy depend on the type of exercise performed. During maternal rest or submaximal weight-bearing exercise (e.g. walking, stepping, treadmill exercise), absolute maternal VO(2) is significantly increased compared with the nonpregnant state. The magnitude of change is approximately proportional to maternal weight gain. When pregnant women perform submaximal weight-supported exercise on land (e.g. level cycling), the findings are contradictory. Some studies reported significantly increased absolute VO(2), while many others reported unchanged or only slightly increased absolute VO(2) compared with the nonpregnant state. The latter findings may be explained by the fact that the metabolic demand of cycle exercise is largely independent of the maternal body mass, resulting in no absolute VO(2) alteration. Few studies that directly measured changes in maternal maximal VO(2) (VO(2max)) showed no difference in the absolute VO(2max) between pregnant and nonpregnant subjects in cycling, swimming or weight-bearing exercise. Efficiency of work during exercise appears to be unchanged during pregnancy in non-weight-bearing exercise. During weight-bearing exercise, the work efficiency was shown to be improved in athletic women who continue exercising and those who stop exercising during pregnancy. When adjusted for weight gain, the increased efficiency is maintained throughout the pregnancy, with the improvement being greater in exercising women. Regular physical activity has been proven to result in marked benefits for mother and fetus. Maternal benefits include improved cardiovascular function, limited pregnancy weight gain, decreased musculoskeletal discomfort, reduced incidence of muscle cramps and lower limb oedema, mood stability, attenuation of gestational diabetes mellitus and gestational hypertension. Fetal benefits include decreased fat mass, improved stress tolerance, and advanced neurobehavioural maturation. In addition, few studies that have directly examined the effects of physical activity on labour and delivery indicate that, for women with normal pregnancies, physical activity is accompanied with shorter labour and decreased incidence of operative delivery. However, a substantial proportion of women stop exercising after they discover they are pregnant, and only few begin participating in exercise activities during pregnancy. The adoption or continuation of a sedentary lifestyle during pregnancy may contribute to the development of certain disorders such as hypertension, maternal and childhood obesity, gestational diabetes, dyspnoea, and pre-eclampsia. In view of the global epidemic of sedentary behaviour and obesity-related pathology, prenatal physical activity was shown to be useful for the prevention and treatment of these conditions. Further studies with larger sample sizes are required to confirm the association between physical activity and outcomes of labour and delivery.


Golay P.,University of Geneva | Lecerf T.,University of Lausanne
Psychological Assessment | Year: 2011

According to the most widely accepted Cattell-Horn-Carroll (CHC) model of intelligence measurement, each subtest score of the Wechsler Intelligence Scale for Adults (3rd ed.; WAIS-III) should reflect both 1st- and 2nd-order factors (i.e., 4 or 5 broad abilities and 1 general factor). To disentangle the contribution of each factor, we applied a Schmid-Leiman orthogonalization transformation (SLT) to the standardization data published in the French technical manual for the WAIS-III. Results showed that the general factor accounted for 63% of the common variance and that the specific contributions of the 1st-order factors were weak (4.7%-15.9%). We also addressed this issue by using confirmatory factor analysis. Results indicated that the bifactor model (with 1st-order group and general factors) better fit the data than did the traditional higher order structure. Models based on the CHC framework were also tested. Results indicated that a higher order CHC model showed a better fit than did the classical 4-factor model; however, the WAIS bifactor structure was the most adequate. We recommend that users do not discount the Full Scale IQ when interpreting the index scores of the WAIS-III because the general factor accounts for the bulk of the common variance in the French WAIS-III. The 4 index scores cannot be considered to reflect only broad ability because they include a strong contribution of the general factor. © 2010 American Psychological Association.


Roux A.,University of Geneva
Soft Matter | Year: 2013

Lipid membranes under shear or tension can form surprising, cylindrical structures called membrane tubes with diameters varying between a few hundreds of nanometers to a few tens of nanometers. These structures can be formed in multiple ways, and provide a clear signature of membrane fluidity and elasticity. In vivo, tubular structures are used during intracellular transport to exchange material between compartments, and their formation depends upon the same principles as in vitro. Recent studies of the specific physico-chemical properties of membrane tubes have shed light on how tubular structures are formed in vivo. In addition, the controlled formation of such membrane tubes in vitro has proven to be an elegant way to study many dynamic processes during membrane trafficking. © 2013 The Royal Society of Chemistry.


Shapiro I.L.,University of Geneva | Shapiro I.L.,Federal University of Juiz de fora | Shapiro I.L.,Tomsk State Pedagogical University
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2015

In the recently proposed non-local theory of quantum gravity one can avoid massive tensor ghosts at the tree level by introducing an exponential form factor between the two Ricci tensors. We show that at the quantum level this theory has an infinite amount of massive unphysical states, mostly corresponding to complex poles. © 2015 The Author.


Bender T.,University of Geneva
Cold Spring Harbor perspectives in biology | Year: 2013

Although mitochondria are usually considered as supporters of life, they are also involved in cellular death. Mitochondrial outer membrane permeabilization (MOMP) is a crucial event during apoptosis because it causes the release of proapoptotic factors from the mitochondrial intermembrane space to the cytosol. MOMP is mainly controlled by the Bcl-2 family of proteins, which consists of both proapoptotic and antiapoptotic members. We discuss the current understanding of how activating and inhibitory interactions within this family lead to the activation and oligomerization of MOMP effectors Bax and Bak, which result in membrane permeabilization. The order of events leading to MOMP is then highlighted step by step, emphasizing recent discoveries regarding the formation of Bax/Bak pores on the outer mitochondrial membrane. Besides the Bcl-2 proteins, the mitochondrial organelle contributes to and possibly regulates MOMP, because mitochondrial resident proteins and membrane lipids are prominently involved in the process.


Reguera J.,French National Center for Scientific Research | Cusack S.,French National Center for Scientific Research | Kolakofsky D.,University of Geneva
Current Opinion in Virology | Year: 2014

Negative strand RNA virus (NSV) genomes are never free, but always found assembled with multiple copies of their nucleoprotein, as RNPs. A flurry of papers describing the X-ray crystal structures of several segmented NSV nucleoproteins have recently appeared. The most significant feature of these various structures is that the arms that are used to oligomerize the nucleoproteins on their genome RNAs are highly flexible, permitting these RNPs to assume virtually unlimited geometries. The structural flexibility of segmented NSV RNPs is undoubtedly important in all aspects of their biology, including genome replication and circularization, and the selection of one copy of each segment for packaging into virus particles. © 2014 Elsevier B.V.


Hajek P.,Queen Mary, University of London | Etter J.-F.,University of Geneva | Benowitz N.,University of California at San Francisco | Eissenberg T.,Virginia Commonwealth University | Mcrobbie H.,Queen Mary, University of London
Addiction | Year: 2014

Aims: We reviewed available research on the use, content and safety of electronic cigarettes (EC), and on their effects on users, to assess their potential for harm or benefit and to extract evidence that can guide future policy. Methods: Studies were identified by systematic database searches and screening references to February 2014. Results: EC aerosol can contain some of the toxicants present in tobacco smoke, but at levels which are much lower. Long-term health effects of EC use are unknown but compared with cigarettes, EC are likely to be much less, if at all, harmful to users or bystanders. EC are increasingly popular among smokers, but to date there is no evidence of regular use by never-smokers or by non-smoking children. EC enable some users to reduce or quit smoking. Conclusions: Allowing EC to compete with cigarettes in the market-place might decrease smoking-related morbidity and mortality. Regulating EC as strictly as cigarettes, or even more strictly as some regulators propose, is not warranted on current evidence. Health professionals may consider advising smokers unable or unwilling to quit through other routes to switch to EC as a safer alternative to smoking and a possible pathway to complete cessation of nicotine use. © 2014 Society for the Study of Addiction.


Pugin J.,University of Geneva
Annals of Intensive Care | Year: 2012

Systemic inflammation is very prevalent among critically ill patients, particularly those with extensive tissue injury. Although downstream mediators (cytokines) and effector cells (phagocytes) have been identified, proximal mediators originating from injured tissues remained elusive. Alarmins ("danger signals") released by necrotic/injured cells have been identified recently and certainly play a role in triggering local and systemic inflammation in critically ill patients. The most promising alarmin candidates are of mitochondrial origin, i.e. mitochondrial DNA and the chemotactic factor fMet-Leu-Phe (fMLP). ATP also is released from necrotic tissues and stimulates the assembly of the inflammasome, leading to the production of proinflammatory cytokines, such as interleukin (IL)-1ß. The identification of novel alarmins opens new therapeutic avenues for the treatment of severe SIRS, and SIRS-dependent organ dysfunction. © 2012 Pugin; licensee Springer.


Khan R.,University of Geneva
Substance abuse treatment, prevention, and policy | Year: 2012

Substance use disorders seem to be an under considered health problem amongst the elderly. The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST), was developed by the World Health Organization to detect substance use disorders. The present study evaluates the psychometric properties of the French version of ASSIST in a sample of elderly people attending geriatric outpatient facilities (primary care or psychiatric facilities). One hundred persons older than 65 years were recruited from clients attending a geriatric policlinic day care centre and from geriatric psychiatric facilities. Measures included ASSIST, Addiction Severity Index (ASI), Mini-International Neuropsychiatric Interview (MINI-Plus), Alcohol Use Disorders Identification Test (AUDIT), Revised Fagerstrom Tolerance Questionnaire-Smoking (RTQ) and MiniMental State(MMS). Concurrent validity was established with significant correlations between ASSIST scores, scores from ASI, AUDIT, RTQ, and significantly higher ASSIST scores for patients with a MINI-Plus diagnosis of abuse or dependence. The ASSIST questionnaire was found to have high internal consistency for the total substance involvement along with specific substance involvement as assessed by Cronbach's α, ranging from 0.66, to 0.89 . The findings demonstrate that ASSIST is a valid screening test for identifying substance use disorders in elderly.


Carmona A.,University of Geneva
Earth, Moon and Planets | Year: 2010

Protoplanetary disks are composed primarily of gas (99% of the mass). Nevertheless, relatively few observational constraints exist for the gas in disks. In this review, I discuss several observational diagnostics in the UV, optical, near-IR, mid-IR, and (sub)-mm wavelengths that have been employed to study the gas in the disks of young stellar objects. I concentrate in diagnostics that probe the inner 20 AU of the disk, the region where planets are expected to form. I discuss the potential and limitations of each gas tracer and present prospects for future research. © 2010 Springer Science+Business Media B.V.


Zaidi H.,University of Geneva | El Naqa I.,University of Washington
European Journal of Nuclear Medicine and Molecular Imaging | Year: 2010

Historically, anatomical CT and MR images were used to delineate the gross tumour volumes (GTVs) for radiotherapy treatment planning. The capabilities offered by modern radiation therapy units and the widespread availability of combined PET/CT scanners stimulated the development of biological PET imaging-guided radiation therapy treatment planning with the aim to produce highly conformal radiation dose distribution to the tumour. One of the most difficult issues facing PET-based treatment planning is the accurate delineation of target regions from typical blurred and noisy functional images. The major problems encountered are image segmentation and imperfect system response function. Image segmentation is defined as the process of classifying the voxels of an image into a set of distinct classes. The difficulty in PET image segmentation is compounded by the low spatial resolution and high noise characteristics of PET images. Despite the difficulties and known limitations, several image segmentation approaches have been proposed and used in the clinical setting including thresholding, edge detection, region growing, clustering, stochastic models, deformable models, classifiers and several other approaches. A detailed description of the various approaches proposed in the literature is reviewed. Moreover, we also briefly discuss some important considerations and limitations of the widely used techniques to guide practitioners in the field of radiation oncology. The strategies followed for validation and comparative assessment of various PET segmentation approaches are described. Future opportunities and the current challenges facing the adoption of PET-guided delineation of target volumes and its role in basic and clinical research are also addressed. © 2010 Springer-Verlag.


Gatto R.,University of Geneva | Ruggieri M.,University of Catania
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2012

We analyze the phase diagram of hot quark matter in presence of an axial chemical potential, μ 5. The latter is introduced to mimic the chirality transitions induced, in hot quantum chromodynamics, by the strong sphaleron configurations. In particular, we study the curvature of the critical line at small μ 5, the effects of a finite quark mass and of a vector interaction. Moreover, we build the mixed phase at the first order phase transition line and draw the phase diagram in the chiral density and temperature plane. We finally compute the full topological susceptibility in presence of a background of topological charge. © 2012 American Physical Society.


Vuilleumier P.,University of Geneva
Annals of the New York Academy of Sciences | Year: 2013

Spatial neglect is generally defined by various deficits in processing information from one (e.g., left) side of space contralateral to focal (e.g., right) hemisphere damage. Although classically associated with parietal lobe functions, there is now compelling evidence that neglect can follow lesions in many different cortical and subcortical sites, suggesting a dysfunction in distributed brain networks. In addition, neglect is likely to result from a combination of distinct deficits that co-occur due to concomitant damage affecting juxtaposed brain areas and their connections, but the exact nature of core deficits and their neural substrates still remains unclear. The present review describes recent progress in identifying functional components of the neglect syndrome and relating them to distinct subregions of parietal cortex. A comprehensive understanding of spatial neglect will require a more precise definition of cognitive processes implicated in different behavioral manifestations, as well as meticulous mapping of these processes onto specific brain circuits, while taking into account functional changes in activity that may arise in structurally intact areas subsequent to damage in distant portions of the relevant networks. © 2013 New York Academy of Sciences.


Ruiz I Altaba A.,University of Geneva
Science Signaling | Year: 2011

The Hedgehog (Hh)-Gli signaling pathway is an essential pathway involved in development and cancer. It controls the Gli code - the sum of all activator and repressor functions of the Gli transcription factors. Through the Gli code, and Gli1 in particular, it modulates the fate and behavior of stem and cancer stem cells, as well as tumor growth and survival in many human cancer types. It also affects recurrence and metastasis and is enhanced in advanced tumors, where it promotes an embryonic stem (ES) cell-like gene expression signature. A central component of this signature, Nanog, is critical for glioblastoma and cancer stem cell survival and expansion. Gli1 activity is also enhanced by several oncogenic proteins, including Ras, Myc, and Akt, and by loss of tumor suppressors, such as p53 and PTEN. The oncogenic load boosts Gli1 levels, which supports tumor progression, and promotes a critical threshold of Gli1 activity that allows cells to enter the metastatic transition. In colon cancers, this transition is defined by enhanced Hh-Gli and, surprisingly, by repressed Wnt-Tcf signaling. Together our data support a model in which the Gli code, and Gli1 in particular, acts as a key sensor that responds to both Hh signals and the oncogenic load. We hypothesize that, in turn, the Gli-regulated ES-like factors induce a reprogramming event in cancer stem cells that promotes high invasion, growth and/or metastasis. Targeting the Gli code, the autoregulatory Gli1-Nanog module and interacting partners and pathways thus offers new therapeutic possibilities.


Riotto A.,University of Geneva
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2012

If one is not ready to pay a large fine-tuning price within supersymmetric models given the current measurement of the Higgs boson mass, one can envisage a scenario where the supersymmetric spectrum is made of heavy scalar sparticles and much lighter fermionic superpartners. We offer a cosmological explanation of why nature might have chosen such a mass pattern: the opposite mass pattern is not observed experimentally because it is not compatible with the plausible idea that the Universe went through a period of primordial inflation. © 2012 American Physical Society.


Jain R.K.,University of Geneva | Sloth M.S.,University of Southern Denmark
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2012

If cosmic magnetic fields are indeed produced during inflation, they are likely to be correlated with the scalar metric perturbations that are responsible for the cosmic microwave background anisotropies and large scale structure. Within an archetypical model of inflationary magnetogenesis, we show that there exists a new simple consistency relation for the non-Gaussian cross correlation function of the scalar metric perturbation with two powers of the magnetic field in the squeezed limit where the momentum of the metric perturbation vanishes. We emphasize that such a consistency relation turns out to be extremely useful to test some recent calculations in the literature. Apart from primordial non-Gaussianity induced by the curvature perturbations, such a cross correlation might provide a new observational probe of inflation and can in principle reveal the primordial nature of cosmic magnetic fields. © 2012 American Physical Society.


Schorderet P.,Ecole Polytechnique Federale de Lausanne | Schorderet P.,Research Frontiers | Duboule D.,Ecole Polytechnique Federale de Lausanne | Duboule D.,Research Frontiers | Duboule D.,University of Geneva
PLoS Genetics | Year: 2011

Long non-coding RNAs regulate various biological processes such as dosage compensation, imprinting, and chromatin organization. HOTAIR, a paradigm of this new class of RNAs, is localized within the human HOXC gene cluster and was shown, in human cells, to regulate HOXD genes in trans via the recruitment of Polycomb Repressive Complex 2 (PRC2), followed by the trimethylation of lysine 27 of histone H3. We looked for the presence of Hotair in mice to assess whether this in trans mechanism was conserved, in particular at the developmental stages, when Hoxd genes must be tightly regulated. We show that the cognate mouse Hotair is poorly conserved in sequence; and its absence, along with the deletion of the HoxC cluster, has surprisingly little effect in vivo, neither on the expression pattern or transcription efficiency, nor on the amount of K27me3 coverage of different Hoxd target genes. We conclude that Hotair may have rapidly evolved within mammals and acquired a functional importance in humans that is not easily revealed in mice. Alternatively, redundant or compensatory mechanisms may mask its function when studied under physiological conditions. © 2011 Schorderet, Duboule.


Huppi P.S.,University of Geneva
Topics in Magnetic Resonance Imaging | Year: 2011

Brain function is tightly linked to the development of the cortex. Until recently, assessing the human cortical development and folding was not possible in vivo. It is magnetic resonance imaging and new post-processing image analysis tools that have improved the understanding of cortical development. The combination of conventional magnetic resonance imaging and diffusion tensor imaging has further allowed depiction of the relationship of changes in intracortical layering and cortical folding. Being able to follow these early developmental processes has elucidated changes in early brain development due to changed environmental conditions in fetal life such as twinning and fetal growth restriction and postnatal conditions such as prematurity. This review further illustrates new data on brain structural asymmetries linked to the emergence of early language functions. Copyright © 2011 by Lippincott Williams & Wilkins.


The Identification of Senior At Risk (ISAR) and the Triage Risk Stratification Tool (TRST) are the two most studied screening tools to detect high-risk patients for unplanned readmission after an emergency department (ED)-visit. Since their performance was unclear among ED-patients over 75 years, we evaluated their capacities to predict readmission at 1, 3, 6 and 12 months as well as their usefulness in avoiding unnecessary further comprehensive geriatric assessment (CGA) in negative screened patients. Historical cohort study with systematic routine data collection of functional status, comorbid conditions and readmission rate of patients released home after an ED-visit between 2007 and 2009 at the Geneva University Hospitals. 345 patients were included (mean age 84y; 63% female). Readmission rates were 25%, 38%, 49%, and 60% at 1, 3, 6, and 12 months, respectively. Positive ISAR (≥2/6) and TRST (≥2/5) predicted modestly unplanned readmission at each time point (AUC range: 0.607-0.664). Prediction of readmission with ISAR or TRST was not modified after adjustment for variables significantly associated with readmission (being male, having poor functional or comorbid scores). In case of negative ISAR or TRST, their high negative predictive values (NPV) would safely allow avoiding 64 useless CGA (ISAR <2: 7/64 readmissions at 1 month). Both ISAR and TRST tools predicted modestly unplanned readmission after an ED-visit among patients over 75 years. Nevertheless, due to their low specificity and high NPV these screening tools are useful to select elderly ED-patients who can safely return home without any further CGA.


Venail P.A.,University of Los Andes, Colombia | Vives M.J.,University of Geneva
Ecology | Year: 2013

Our understanding of how biodiversity influences ecosystem functioning is entering a new stage of its development through the incorporation of information about the evolutionary relatedness of species. Bacteria are prime providers of essential ecosystem services, representing an excellent model system to perform biodiversity-ecosystem function research. By using bacteria isolated from petroleum-contaminated sites, we show that communities composed of poorly related species were more productive than those containing highly related species. The nature of the forces controlling this positive effect of phylogenetic diversity on community productivity depended on the number of species in culture. In communities of two species the positive effect of phylogenetic diversity on productivity was driven by changes in the selection effect. Communities of two distantly related species were dominated by the most productive species in monoculture, whereas communities of two closely related species were dominated by the less productive species in monoculture. In communities of four species the positive effect of phylogenetic diversity on productivity was driven by changes in the complementarity effect. In communities composed of four distantly related species the influence of positive interactions such as facilitation, cross-feeding, and niche partitioning seemed to outweigh the influence of negative interactions such as interference. As a consequence the proportion of species favored by the presence of other species increased as they became less related. Multiple facets of biodiversity may influence ecosystem functioning. Here, we present evidence of an interaction between phylogenetic and taxonomic diversity on community productivity, underlining the importance of considering multiple aspects of biodiversity when studying its impact on ecosystem functioning. © 2013 by the Ecological Society of America.


Galliot B.,University of Geneva
International Journal of Developmental Biology | Year: 2012

The discovery of Hydra regeneration by Abraham Trembley in 1744 promoted much scientific curiosity thanks to his clever design of experimental strategies away from the natural environment. Since then, this little freshwater cnidarian polyp flourished as a potent and fruitful model system. Here, we review some general biological questions that benefitted from Hydra research, such as the nature of embryogenesis, neurogenesis, induction by organizers, sex reversal, symbiosis, aging, feeding behavior, light regulation, multipotency of somatic stem cells, temperature-induced cell death, neuronal transdifferentiation, to cite only a few. To understand how phenotypes arise, theoricists also chose Hydra to model patterning and morphogenetic events, providing helpful concepts such as reaction-diffusion, positional information, and autocatalysis combined with lateral inhibition. Indeed, throughout these past 270 years, scientists used transplantation and grafting experiments, together with tissue, cell and molecular labelings, as well as biochemical procedures, in order to establish the solid foundations of cell and developmental biology. Nowadays, thanks to transgenic, genomic and proteomic tools, Hydra remains a promising model for these fields, but also for addressing novel questions such as evolutionary mechanisms, maintenance of dynamic homeostasis, regulation of stemness, functions of autophagy, cell death, stress response, innate immunity, bioactive compounds in ecosystems, ecotoxicant sensing and science communication. © UBC Press.


Dermitzakis E.T.,University of Geneva | Dermitzakis E.T.,Institute of Genetics and Genomics in Geneva iGE3
Nature Reviews Genetics | Year: 2012

Recent developments in the collection and analysis of cellular multilayered data in large cohorts with extensive organismal phenotyping promise to reveal links between genetic variation and biological processes. The use of these cellular resources as models for human biology-known as 'cellular phenotyping'-is likely to transform our understanding of the genetic and long-term environmental influences on complex traits. I discuss the advantages and caveats of a deeper analysis of cellular phenotypes in large cohorts and assess the methodological advances, resource needs and prospects of this new approach. © 2012 Macmillan Publishers Limited. All rights reserved.


Coppari R.,University of Texas Southwestern Medical Center | Coppari R.,University of Geneva | Coppari R.,University of California at Irvine | Bjorbaek C.,Beth Israel Deaconess Medical Center
Nature Reviews Drug Discovery | Year: 2012

Since the discovery of leptin in 1994, we now have a better understanding of the cellular and molecular mechanisms underlying its biological effects. In addition to its established anti-obesity effects, leptin exerts antidiabetic actions that are independent of its regulation of body weight and food intake. In particular, leptin can correct diabetes in animal models of type 1 and type 2 diabetes. In addition, long-term leptin replacement therapy improves glycaemic control, insulin sensitivity and plasma triglycerides in patients with severe insulin resistance due to lipodystrophy. These results have spurred enthusiasm for the use of leptin therapy to treat diabetes. Here, we review the current understanding of the glucoregulatory functions of leptin, emphasizing its central mechanisms of action and lessons learned from clinical studies, and discuss possible therapeutic applications of leptin in the treatment of type 1 and type 2 diabetes. © 2012 Macmillan Publishers Limited. All rights reserved.


Ikhlef Y.,University of Geneva
Journal of Physics A: Mathematical and Theoretical | Year: 2012

In two-dimensional statistical models possessing a discretely holomorphic parafermion, we introduce a modified discrete CauchyRiemann equation on the boundary of the domain, and we show that the solution of this equation yields integrable boundary Boltzmann weights. This approach is applied to (i) the square-lattice O(n) loop model, where the exact locations of the special and ordinary transitions are recovered, and (ii) the FateevZamolodchikov spin model, where a new rotation-invariant, integrable boundary condition is discovered for generic N. © 2012 IOP Publishing Ltd.


Bottazzi P.,University of Bern | Dao H.,University of Geneva
Land Use Policy | Year: 2013

Previous studies have shown that collective property rights offer higher flexibility than individual property and improve sustainable community-based forest management. Our case study, carried out in the Beni department of Bolivia, does not contradict this assertion, but shows that collective rights have been granted in areas where ecological contexts and market facilities were less favourable to intensive land use. Previous experiences suggest investigating political processes in order to understand the criteria according to which access rights were distributed. Based on remote sensing and on a multi-level land governance framework, our research confirms that land placed under collective rights, compared to individual property, is less affected by deforestation among Andean settlements. However, analysis of the historical process of land distribution in the area shows that the distribution of property rights is the result of a political process based on economic, spatial, and environmental strategies that are defined by multiple stakeholders. Collective titles were established in the more remote areas and distributed to communities with lower productive potentialities. Land rights are thus a secondary factor of forest cover change which results from diverse political compromises based on population distribution, accessibility, environmental perceptions, and expected production or extraction incomes. © 2012 Elsevier Ltd.


The discovery of genes that can be used to increase plant tolerance to environmental stress has practical implications for agriculture, since knowledge at the molecular level can potentially be translated from model plants to crops or from tolerant to sensitive cultivars. For more than a decade, researchers have attempted to identify transcriptional and metabolic pathways involved in stress tolerance using functional genomics tools. In some cases, promising results were obtained when a clear causal link was found between transcripts and tolerance/sensitivity to stress. However, recent reports question the global translational power of functional genomics for biotechnological applications, as one of the main limitations seems to be the large variability in gene expression. Transcript-level variability under stress has not been considered of interest in the scientific literature because it is intuitively obvious, but most reports seem to naively overlook the consequences. Here, three case situations are reviewed (variability between genotypes, variability due to environmental interactions and variability between stressors) in support of the concept that inherent transcript-level variation in biological systems may limit our knowledge of environmental plant tolerance and of functional genomics in molecular stress physiology. © 2013 German Botanical Society and The Royal Botanical Society of the Netherlands.


Wehrle-Haller B.,University of Geneva
Current Opinion in Cell Biology | Year: 2012

The formation of tissues and organs requires cells to adhere to each other and/or to migrate and polarize in contact with components of the extracellular matrix. The connection between the cytoskeleton and the extracellular environment is provided by heterodimeric transmembrane receptors of the integrin family. In response to extracellular ligand binding, integrins undergo a conformational switch that permits the recruitment of cytoplasmic adapter proteins, eventually linking the integrin receptors to the actin cytoskeleton, progressively forming highly complex cell-matrix adhesions. A major challenge in the field consists in identifying the regulatory mechanisms, which drive the assembly of cell-matrix adhesions as they are based on posttranslational modifications as well as allosteric conformational changes caused by protein-protein as well as protein-lipid interactions. In response to mechanical tension, generated either by intra-cellular acto-myosin contraction, shear stress or mechanical strain on the extracellular scaffold, the composition and signaling of cell-matrix adhesion changes, leading either to increased anchorage or controlled disassembly of cell matrix adhesions, both processes critically involved in cell migration. The aim of this review is to provide insight into the mechanisms leading to the progressive assembly of focal adhesions, how they are modulated in response to mechanical challenges and which mechanisms are used for their disassembly. © 2012 Elsevier Ltd.


Beran D.,University of Geneva
Current Diabetes Reports | Year: 2015

This review will highlight the current challenges and barriers to diabetes management in low and lower middle income countries using the World Health Organization’s 6 Building Blocks for Health Systems (service delivery; healthcare workforce; information; medical products, vaccines and technologies; financing; and leadership and governance). Low and lower middle income countries are characterized by low levels of income and insufficient health expenditure. These countries face a shift in disease burden from communicable to non-communicable diseases including diabetes. Many argue that health systems in these countries do not have the capacity to meet the needs of people with chronic conditions such as diabetes. A variety of barriers exist in terms of organization of health systems and care, human resources, sufficient information for decision-making, availability and affordability of medicines, policies, and alleviating the financial burden of care. These health system barriers need to be addressed, taking into account the need to have diabetes included in the global development agenda and also tailoring the response to local contexts including the needs of people with diabetes. © 2015, Springer Science+Business Media New York.


Aberger F.,University of Salzburg | Ruiz i Altaba A.,University of Geneva
Seminars in Cell and Developmental Biology | Year: 2014

Canonical Hedgehog (HH) signaling leads to the regulation of the GLI code: the sum of all positive and negative functions of all GLI proteins. In humans, the three GLI factors encode context-dependent activities with GLI1 being mostly an activator and GLI3 often a repressor. Modulation of GLI activity occurs at multiple levels, including by co-factors and by direct modification of GLI structure. Surprisingly, the GLI proteins, and thus the GLI code, is also regulated by multiple inputs beyond HH signaling. In normal development and homeostasis these include a multitude of signaling pathways that regulate proto-oncogenes, which boost positive GLI function, as well as tumor suppressors, which restrict positive GLI activity. In cancer, the acquisition of oncogenic mutations and the loss of tumor suppressors - the oncogenic load - regulates the GLI code toward progressively more activating states. The fine and reversible balance of GLI activating GLIA and GLI repressing GLIR states is lost in cancer. Here, the acquisition of GLIA levels above a given threshold is predicted to lead to advanced malignant stages. In this review we highlight the concepts of the GLI code, the oncogenic load, the context-dependency of GLI action, and different modes of signaling integration such as that of HH and EGF. Targeting the GLI code directly or indirectly promises therapeutic benefits beyond the direct blockade of individual pathways. © 2014 The Authors.


Patil S.P.,University of Geneva | Schwaller P.,CERN
Journal of High Energy Physics | Year: 2016

Abstract: Recently, a novel mechanism to address the hierarchy problem has been proposed [1], where the hierarchy between weak scale physics and any putative ‘cutoff’ M is translated into a parametrically large field excursion for the so-called relaxion field, driving the Higgs mass to values much less than M through cosmological dynamics. In its simplest incarnation, the relaxion mechanism requires nothing beyond the standard model other than an axion (the relaxion field) and an inflaton. In this note, we critically re-examine the requirements for successfully realizing the relaxion mechanism and point out that parametrically larger field excursions can be obtained for a given number of e-folds by simply requiring that the background break exact de Sitter invariance. We discuss several corollaries of this observation, including the interplay between the upper bound on the scale M and the order parameter ϵ associated with the breaking of dS symmetry, and entertain the possibility that the relaxion could play the role of a curvaton. We find that a successful realization of the mechanism is possible with as few as (Formula presented.) e-foldings, albeit with a reduced cutoff M ∼ 106 GeV for a dark QCD axion and outline a minimal scenario that can be made consistent with CMB observations. © 2016, The Author(s).


Thibault R.,University of Auvergne | Pichard C.,University of Geneva
Annals of Nutrition and Metabolism | Year: 2012

Undernutrition is insufficiently detected in in- and outpatients, and this is likely to worsen during the next decades. The increased prevalence of obesity together with chronic illnesses associated with fat-free mass (FFM) loss will result in an increased prevalence of sarcopenic obesity. In patients with sarcopenic obesity, weight loss and the body mass index lack accuracy to detect FFM loss. FFM loss is related to increasing mortality, worse clinical outcomes, and impaired quality of life. In sarcopenic obesity and chronic diseases, body composition measurement with dual-energy X-ray absorptiometry, bioelectrical impedance analysis, or computerized tomography quantifies the loss of FFM. It allows tailored nutritional support and disease-specific therapy and reduces the risk of drug toxicity. Body composition evaluation should be integrated into routine clinical practice for the initial assessment and sequential follow-up of nutritional status. It could allow objective, systematic, and early screening of undernutrition and promote the rational and early initiation of optimal nutritional support, thereby contributing to reducing malnutrition-induced morbidity, mortality, worsening of the quality of life, and global health care costs. Copyright © 2011 S. Karger AG.


Nicolini P.,Goethe University Frankfurt | Rinaldi M.,University of Geneva
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2011

In this Letter we study the radiation measured by an accelerated detector, coupled to a scalar field, in the presence of a fundamental minimal length. The latter is implemented by means of a modified momentum space Green's function. After calibrating the detector, we find that the net flux of field quanta is negligible, and that there is no Planckian spectrum. We discuss possible interpretations of this result, and we comment on experimental implications in heavy ion collisions and atomic systems. © 2010 Elsevier B.V.


Blondon M.,University of Geneva
Thrombosis Research | Year: 2011

Although venous thromboembolism (VTE) is the leading cause of maternal mortality in developed countries, the usefulness of preventive low-molecular weight heparin (LMWH) after cesarean section remains a matter of controversy. This article will review a recent decision analysis addressing this question, comparing a 7-day LMWH with none in this setting. Prophylaxis with LMWH yielded the highest quality-adjusted life expectancy, with a net gain of 1.5 days per treated patient. Sensitivity analyses showed the incidence of VTE after cesarean section and the haemorrhagic risk related to LMWH to be critical, at threshold values of 0.22 and 0.24 respectively. In the hypothetical cases created by the authors, LMWH was safe but only marginally more effective in women with no risk factors. With the addition of other risk factors, reductions in VTE greatly outnumbered the increase in major hemorrhages. This study highlights the need to assess the individual thrombotic risk in women after a cesarean section. © 2010 Elsevier B.V. All rights reserved.


Brunner N.,University of Geneva | Brunner N.,University of Bristol | Linden N.,University of Bristol
Nature Communications | Year: 2013

In 1964, Bell discovered that quantum mechanics is a nonlocal theory. Three years later, in a seemingly unconnected development, Harsanyi introduced the concept of Bayesian games. Here we show that, in fact, there is a deep connection between Bell nonlocality and Bayesian games, and that the same concepts appear in both fields. This link offers interesting possibilities for Bayesian games, namely of allowing the players to receive advice in the form of nonlocal correlations, for instance using entangled quantum particles or more general no-signalling boxes. This will lead to novel joint strategies, impossible to achieve classically. We characterize games for which nonlocal resources offer a genuine advantage over classical ones. Moreover, some of these strategies represent equilibrium points, leading to the notion of quantum/no-signalling Nash equilibrium. Finally, we describe new types of question in the study of nonlocality, namely the consideration of nonlocal advantage given a set of Bell expressions. © 2013 Macmillan Publishers Limited. All rights reserved.


Baertschi B.,University of Geneva
Bioethics | Year: 2013

Biotechnologies - synthetic biology in particular - are sometimes blamed for playing God or manifesting hubris, that is, for evincing the vicious attitude of transcending the limits of human agency. In trying to create living organisms, we would adopt an attitude that is immoral for human beings. In this article, I want to show that this blame is unwarranted. I distinguish two aspects of the argument, which claims that it is impossible for human beings to create life and immoral to attempt it. I argue that if we adopt a conception of what life consists of in agreement with the scientific world view, there is no place for hubris. Finally, I maintain that even if we accept a non-scientific conception of life (a vitalist or a supernatural one), we are not in a position to formulate the blame against synthetic biologists because what they do cannot contravene this vitalist or supernaturalist view. © 2013 John Wiley & Sons Ltd.


Ginovart N.,University of Geneva | Kapur S.,Kings College London
Handbook of Experimental Pharmacology | Year: 2012

This review summarizes the current state of knowledge regarding the proposed mechanisms by which antipsychotic agents reduce the symptoms of schizophrenia while giving rise to adverse side effects. The first part summarizes the contribution of neuroimaging studies to our understanding of the neurochemical substrates of schizophrenia, putting emphasis on direct evidence suggestive of a presynaptic rather than a postsynaptic dysregulation of dopaminergic neurotransmission in this disorder. The second part addresses the role of D2 and non-D2 receptor blockade in the treatment of schizophrenia and highlights a preponderant role of D2 receptors in the mechanism of antipsychotic action. Neuroimaging studies have defined a narrow, but optimal, therapeutic window of 65-78 % D2 receptor blockade within which most antipsychotics achieve optimal clinical efficacy with minimal side effects. Some antipsychotics though do not conform to that therapeutic window, notably clozapine. The reasons for its unexcelled clinical efficacy despite subthreshold levels of D2 blockade are unclear and current theories on clozapine's mechanisms of action are discussed, including transiency of its D2 receptor blocking effects or preferential blockade of limbic D2 receptors. Evidence is also highlighted to consider the use of extended antipsychotic dosing to achieve transiency of D2 blockade as a way to optimize functional outcomes in patients. We also present some critical clinical considerations regarding the mechanisms linking dopamine disturbance to the expression of psychosis and its blockade to the progressive resolution of psychosis, keeping in perspective the speed and onset of antipsychotic action. Finally, we discuss potential novel therapeutic strategies for schizophrenia. © 2012 Springer-Verlag Berlin Heidelberg.


Baertschi B.,University of Geneva
Environmental Values | Year: 2012

Recently at the J. Craig Venter Institute, a microorganism has been created through synthetic biology. In the future, more complex living beings will very probably be produced. In our natural environment, we live amongst a whole variety of beings. Some of them have moral status - they have a moral importance and we cannot treat them in just any way we please; some do not. When it becomes possible to create artificially living beings who naturally possess moral status, will this artificiality modify their status? Many people contend that it will, but I am not of the same mind and will develop three arguments against it. © 2012 The White Horse Press.


Delplace P.,University of Geneva | Ullmo D.,University Paris - Sud | Montambaux G.,University Paris - Sud
Physical Review B - Condensed Matter and Materials Physics | Year: 2011

We develop a method to predict the existence of edge states in graphene ribbons for a large class of boundaries. This approach is based on the bulk-edge correspondence between the quantized value of the Zak phase Z(k), which is a Berry phase across an appropriately chosen one-dimensional Brillouin zone, and the existence of a localized state of momentum k at the boundary of the ribbon. This bulk-edge correspondence is rigorously demonstrated for a one-dimensional toy model as well as for graphene ribbons with zigzag edges. The range of k for which edge states exist in a graphene ribbon is then calculated for arbitrary orientations of the edges. Finally, we show that the introduction of an anisotropy leads to a topological transition in terms of the Zak phase, which modifies the localization properties at the edges. Our approach gives a new geometrical understanding of edge states, and it confirms and generalizes the results of several previous works. © 2011 American Physical Society.


Drepper M.D.,University of Geneva
World journal of gastroenterology : WJG | Year: 2012

Clopidogrel in association with aspirine is considered state of the art of medical treatment for acute coronary syndrome by reducing the risk of new ischemic events. Concomitant treatment with proton pump inhibitors in order to prevent gastrointestinal side effects is recommended by clinical guidelines. Clopidogrel needs metabolic activation predominantly by the hepatic cytochrome P450 isoenzyme Cytochrome 2C19 (CYP2C19) and proton pump inhibitors (PPIs) are extensively metabolized by the CYP2C19 isoenzyme as well. Several pharmacodynamic studies investigating a potential clopidogrel-PPI interaction found a significant decrease of the clopidogrel platelet antiaggregation effect for omeprazole, but not for pantoprazole. Initial clinical cohort studies in 2009 reported an increased risk for adverse cardiovascular events, when under clopidogrel and PPI treatment at the same time. These observations led the United States Food and Drug Administration and the European Medecines Agency to discourage the combination of clopidogrel and PPI (especially omeprazole) in the same year. In contrast, more recent retrospective cohort studies including propensity score matching and the only existing randomized trial have not shown any difference concerning adverse cardiovascular events when concomitantly on clopidogrel and PPI or only on clopidogrel. Three meta-analyses report an inverse correlation between clopidogrel-PPI interaction and study quality, with high and moderate quality studies not reporting any association, rising concern about unmeasured confounders biasing the low quality studies. Thus, no definite evidence exists for an effect on mortality. Because PPI induced risk reduction clearly overweighs the possible adverse cardiovascular risk in patients with high risk of gastrointestinal bleeding, combination of clopidogrel with the less CYP2C19 inhibiting pantoprazole should be recommended.


Fragos T.,University of Geneva | Mcclintock J.E.,Harvard - Smithsonian Center for Astrophysics
Astrophysical Journal | Year: 2015

Galactic field black hole (BH) low-mass X-ray binaries (LMXBs) are believed to form in situ via the evolution of isolated binaries. In the standard formation channel, these systems survived a common envelope phase, after which the remaining helium core of the primary star and the subsequently formed BH are not expected to be highly spinning. However, the measured spins of BHs in LMXBs cover the whole range of spin parameters. We propose here that the BH spin in LMXBs is acquired through accretion onto the BH after its formation. In order to test this hypothesis, we calculated extensive grids of detailed binary mass-transfer sequences. For each sequence, we examined whether, at any point in time, the calculated binary properties are in agreement with their observationally inferred counterparts of 16 Galactic LMXBs. The "successful" sequences give estimates of the mass that the BH has accreted since the onset of Roche-Lobe overflow. We find that in all Galactic LMXBs with measured BH spin, the origin of the spin can be accounted for by the accreted matter, and we make predictions about the maximum BH spin in LMXBs where no measurement is yet available. Furthermore, we derive limits on the maximum spin that any BH can have depending on current properties of the binary it resides in. Finally we discuss the implication that our findings have on the BH birth-mass distribution, which is shifted by ∼1.5 M⊙ toward lower masses, compared to the currently observed one. © 2015. The American Astronomical Society. All rights reserved.


Etter J.F.,University of Geneva
Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco | Year: 2010

Cloninger's neuropsychopharmacological theory identifies four temperament traits and three character traits that are largely heritable and are associated with addictions. We tested whether these personality traits were associated with smoking behavior and predicted smoking cessation and tobacco withdrawal symptoms. We conducted an Internet cohort study in 2005-2009. The Temperament and Character Inventory (TCI, 226 items, French version) was assessed in 2,993 people (1,593 current, 969 former, and 419 never-smokers). Subsets of participants indicated their smoking status after 30 days (n = 1,452, 48.5%) and answered the TCI again and reported tobacco withdrawal symptoms after 61 days (n = 644, 21.5%). Compared with never- and former smokers, daily smokers had higher scores of Harm Avoidance (HA) and lower scores of Persistence and Self-Directedness (SD). Daily smokers had higher scores of Novelty Seeking than never-smokers. In daily smokers, the level of tobacco dependence was associated with higher scores of HA and lower scores of SD. In the 60 daily smokers who had stopped smoking after 61 days, after adjustment for tobacco dependence level and baseline tobacco withdrawal ratings, SD predicted lower scores of depressed mood and anxiety at 61-day follow-up and HA predicted higher scores of depressed mood at 61-day follow-up. Personality ratings did not predict smoking cessation at follow-up in daily smokers or relapse in former smokers. A consistent association was found between smoking and high HA and low SD. Knowledge about these associations may be useful to clinicians to tailor counseling.


Etter J.-F.,University of Geneva
Drug and Alcohol Dependence | Year: 2011

Aims: To compare abrupt and gradual smoking cessation. Design and setting: Randomized trial and observational study, Internet, 2007-2010. Participants: Smokers with no strong preference for abrupt or gradual quitting were randomly assigned to quitting immediately (n= 472), or to gradually reducing their cigarette consumption over 2 weeks and then quit (n= 502). Smokers who strongly preferred to quit abruptly were instructed to do so immediately (n= 2456), those who strongly preferred gradual were instructed to reduce their cigarette consumption over 2 weeks, then quit (n= 1801). Follow-up was conducted 4 weeks after target quit dates. Findings: Those who preferred abrupt quitting were the most motivated to quit and the most confident in their ability to quit. At follow-up, quit rates were 16% in those who preferred abrupt cessation, 7% in those who preferred gradual cessation and 9% in those who had no preference (p< 0.001). In the latter group, quit rates were equal for those randomized to abrupt or gradual (9%, p= 0.97). In those who expressed a strong preference for either method, there were interactions between quitting method, motivation to quit and confidence in ability to quit: those who had low levels of motivation or low levels of confidence were more likely to quit at follow-up if they preferred and used abrupt rather than gradual. Conclusions: In those who had no strong preference for either method, abrupt and gradual produced similar results. Those who preferred and used the abrupt method were more likely to quit than those who preferred and used the gradual method, in particular when they had low motivation and confidence. © 2011 Elsevier Ireland Ltd.


Czekalski N.,Eawag - Swiss Federal Institute of Aquatic Science and Technology | Gascon Diez E.,University of Geneva | Burgmann H.,Eawag - Swiss Federal Institute of Aquatic Science and Technology
ISME Journal | Year: 2014

Antibiotic-resistance genes (ARGs) are currently discussed as emerging environmental contaminants. Hospital and municipal sewage are important sources of ARGs for the receiving freshwater bodies. We investigated the spatial distribution of different ARGs (sul1, sul2, tet(B), tet(M), tet(W) and qnrA) in freshwater lake sediments in the vicinity of a point source of treated wastewater. ARG contamination of Vidy Bay, Lake Geneva, Switzerland was quantified using real-time PCR and compared with total mercury (THg), a frequently particle-bound inorganic contaminant with known natural background levels. Two-dimensional mapping of the investigated contaminants in lake sediments with geostatistical tools revealed total and relative abundance of ARGs in close proximity of the sewage discharge point were up to 200-fold above levels measured at a remote reference site (center of the lake) and decreased exponentially with distance. Similar trends were observed in the spatial distribution of different ARGs, whereas distributions of ARGs and THg were only moderately correlated, indicating differences in the transport and fate of these pollutants or additional sources of ARG contamination. The spatial pattern of ARG contamination and supporting data suggest that deposition of particle-associated wastewater bacteria rather than co-selection by, for example, heavy metals was the main cause of sediment ARG contamination. © 2014 International Society for Microbial Ecology All rights reserved.


Spierer L.,University of Fribourg | Chavan C.F.,University of Fribourg | Manuel A.L.,University of Geneva
Frontiers in Human Neuroscience | Year: 2013

Deficits in inhibitory control, the ability to suppress ongoing or planned motor or cognitive processes, contribute to many psychiatric and neurological disorders. The rehabilitation of inhibition-related disorders may therefore benefit from neuroplasticitybased training protocols aiming at normalizing inhibitory control proficiency and the underlying brain networks. Current literature on training-induced behavioral and brain plasticity in inhibitory control suggests that improvements may follow either from the development of automatic forms of inhibition or from the strengthening of top-down, controlled inhibition. Automatic inhibition develops in conditions of consistent and repeated associations between inhibition-triggering stimuli and stopping goals. Once established, the stop signals directly elicit inhibition, thereby bypassing slow, top-down executive control and accelerating stopping processes. In contrast, training regimens involving varying stimulus-response associations or frequent inhibition failures prevent the development of automatic inhibition and thus strengthen top-down inhibitory processes rather than bottom-up ones. We discuss these findings in terms of developing optimal inhibitory control training regimens for rehabilitation purposes. © 2013 Spierer, Chavan and Manuel.


Etter J.-F.,University of Geneva | Bullen C.,University of Auckland
Addictive Behaviors | Year: 2014

Objective: To assess behavior change over 12. months in users of e-cigarettes ("vapers"). Methods: Longitudinal Internet survey, 2011 to 2013. Participants were enrolled on websites dedicated to e-cigarettes and smoking cessation. We assessed use of e-cigarettes and tobacco among the same cohort at baseline, after one month (n= 477) and one year (n= 367). Results: Most participants (72%) were former smokers, and 76% were using e-cigarettes daily. At baseline, current users had been using e-cigarettes for 3. months, took 150 puffs/day on their e-cigarette and used refill liquids containing 16. mg/ml of nicotine, on average. Almost all the daily vapers at baseline were still vaping daily after one month (98%) and one year (89%). Of those who had been vaping daily for less than one month at baseline, 93% were still vaping daily after one month, and 81% after one year. In daily vapers, the number of puffs/day on e-cigarettes remained unchanged between baseline and one year. Among former smokers who were vaping daily at baseline, 6% had relapsed to smoking after one month and also 6% after one year. Among dual users (smokers who were vaping daily at baseline), 22% had stopped smoking after one month and 46% after one year. In dual users who were still smoking at follow-up, cigarette consumption decreased by 5.3 cig/day after one month (from 11.3 to 6.0 cig./day, p= 0.006), but remained unchanged between baseline and 1-year follow-up. Conclusions: E-cigarettes may contribute to relapse prevention in former smokers and smoking cessation in current smokers. © 2013 Elsevier Ltd.


Jugun K.,University of Geneva
Annals of Surgery | Year: 2015

OBJECTIVE:: In this study, we assess interdisciplinary surgical and medical parameters associated to recurrences of infected pressure ulcers. BACKGROUND:: There is a little in the published literature regarding factors associated with the outcome of treatment of infected pressure ulcers. METHODS:: We undertook a single-center review of spinal injured adults hospitalized for an infected pressure ulcer or implant-free osteomyelitis and reviewed the literature on this topic from 1990–2015. RESULTS:: We found 70 lesions in 31 patients (52 with osteomyelitis) who had a median follow-up of 2.7 years (range, 4 months to 19 years). The median duration of antibiotic therapy was 6 weeks, of which 1 week was parenteral. Clinical recurrence after treatment was noted in 44 infected ulcers (63%), after a median interval of 1 year. In 86% of these recurrences, cultures yielded a different organism than the preceding episode. By multivariate analyses, the following factors were not significantly related to recurrence: number of surgical interventions (hazard ratio 0.9, 95% confidence interval 0.5–1.5); osteomyelitis (hazard ratio 1.5; 0.7–3.1); immune suppression; prior sacral infections, and duration of total (or just parenteral) antibiotic sue. Patients with antibiotic treatment for <6 weeks had the same failure rate as those with as >12 weeks (χ test; P?=?0.90). CONCLUSIONS:: In patients with infected pressure ulcers, clinical recurrence occurs in almost two-thirds of lesions, but in only 14% with the same pathogen(s). The number of surgical debridements, flap use, or duration of antibiotic therapy was not associated with recurrence, suggesting recurrences are caused by reinfections caused by other extrahospital factors. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.


Tiercy J.-M.,University of Geneva
Frontiers in Immunology | Year: 2014

An increasingly larger fraction of patients with hematological diseases are treated by hematopoietic stem cells transplantation (HSCT) from HLA matched unrelated donors. Polymorphisms of HLA genes represent a major barrier to HSCT because HLA-A, -B, -C and DRB1 incompatibilities confer a higher risk of acute graft-versus-host disease (aGVHD) and mortality. Although >22 million volunteer HLA-typed donors are available worldwide, still a significant number of patients do not find a highly matched HSC donor. Because of the large haplotypic diversity in HLA-B-C associations, incompatibilities occur most frequently at HLA-C, so that unrelated donors with a single HLA-C mismatch often represent the only possible choice. The ratio of HLA-C-mismatched HSCT over the total number of transplants varies from 15 to 30%, as determined in 12 multicenter studies. Six multicenter studies involving >1800 patients have reported a 21-43% increase in mortality risk. By using in vitro cellular assays, a large heterogeneity in T-cell allorecognition has been observed. Yet the permissiveness of individual HLA-C mismatches remains poorly defined. It could be linked to the position and nature of the mismatched residues on HLA-C molecules, but also to variability in the expression levels of the mismatched alleles. The permissive C*03:03-03:04 mismatch is characterized by full compatibility at residues 9, 97, 99, 116, 152, 156, and 163 reported to be key positions influencing T-cell allorecognition. With a single difference among these seven key residues the C*07:01-07:02 mismatch might also be considered by analogy as permissive. High variability of HLA-C expression as determined by quantitative RT-PCR has been observed within individual allotypes and shows some correlation with A-B-C-DRB1 haplotypes. Thus in addition to the position of mismatched amino acid residues, expression level of patient's mismatched HLA-C allotype might influence T-cell allorecognition, with patients low expression-C alleles representing possible permissive mismatches. © 2014 Tiercy.


Camos V.,University of Fribourg | Barrouillet P.,University of Geneva
Frontiers in Human Neuroscience | Year: 2014

Working memory is the structure devoted to the maintenance of information at short term during concurrent processing activities. In this respect, the question regarding the nature of the mechanisms and systems fulfilling this maintenance function is of particular importance and has received various responses in the recent past. In the time-based resource-sharing (TBRS) model, we suggest that only two systems sustain the maintenance of information at the short term, counteracting the deleterious effect of temporal decay and interference. A non-attentional mechanism of verbal rehearsal, similar to the one described by Baddeley in the phonological loop model, uses language processes to reactivate phonological memory traces. Besides this domain-specific mechanism, an executive loop allows the reconstruction of memory traces through an attention-based mechanism of refreshing. The present paper reviews evidence of the involvement of these two independent systems in the maintenance of verbal memory items. © 2014 Camos and Barrouillet.


Simpson G.,University of Geneva
Tectonophysics | Year: 2011

The mechanics of fold-thrust belts and accretionary wedges is investigated using a two dimensional, plane strain, elastic-plastic (cohesive Mohr-Coulomb) mechanical model solved with the Finite Element Method. Results show that when a layer with an initially non-critical geometry is compressed from the rear, it does not form a wedge that is at failure throughout, as assumed in critical wedge theory. Rather, the wedge consists of narrow plastic shear zones that propagate sequentially outward with time, loading rocks ahead while unloading rocks behind. Not only are stress states within the wedge not everywhere at failure but principal stress orientations vary strongly in time and space, particularly across shear zones, near the basal detachment and in the hanging wall of active structures, where local surface extension may be observed. The reason the investigated wedges are not stressed to compressive failure throughout is related to strength reduction associated with strain localisation that enables material outside shear zones to unload and return to an elastic stress state. This mechanism is intrinsic to elastic-plastic materials and occurs regardless of any material degradation such as loss of cohesion. Even though the stress state of the investigated wedges is generally non-critical, the overall geometry may still be consistent with cohesionless critical wedge theory, since the local surface slope is created when a particular part of the wedge is at a limit state. Prowedge tapers display non self-similar growth through time but eventually evolve to the minimum critical taper. Retrowedges on the other hand, may get caught within this initial transient state and thus may have tapers anywhere between the minimum and maximum critical taper. However, if the basal detachment is such that lateral propagation is not kinematically inhibited, retrowedges are shown to also eventually evolve towards minimum critical tapers, resulting in a symmetrical doubly-vergent orogen. Because all of these wedges have non-critical stress states, both pro- and retrowedges are predicted to display stable non-equilibrium taper angles in the presence of external perturbations, for example related to erosion or sediment deposition. © 2011 Elsevier B.V.


Rubbia-Brandt L.,University of Geneva
Clinics in Liver Disease | Year: 2010

Sinusoidal obstruction syndrome (SOS), formerly named venoocclusive disease, is a well-known complication of hematopoietic stem cell transplantation and ingestion of food or drinks contaminated by pyrrolizidine alkaloids. Many other drugs and toxins have been associated with SOS, including several chemotherapeutic agents and immunosuppressors. SOS contributes to significant morbidity and mortality in all these settings. This review describes the histologic lesions of SOS, details its pathogenesis as it is understood today, specifies the recent data on its causes and how it may influence clinical management of colorectal liver metastases, and discusses the current knowledge on diagnosis and preventive options. © 2010 Elsevier Inc.


Arigoni F.,University of Geneva
Swiss medical weekly : official journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology | Year: 2010

Over the last decade the Swiss health care system has undergone several changes, resulting in stronger economic constraints, a heavier administrative workload and limited work autonomy for doctors. In this context we examined the change in burnout prevalence over time among Swiss doctors surveyed during this period. Cross-sectional survey data collected by mail in 2002, 2004 and 2007 throughout the country were used. Measures included the Maslach Burnout Inventory (MBI), several socio-demographics (gender, living alone, having children), and work-related characteristics (number of years in current workplace, hours worked). Answers to the MBI were used to classify respondents into moderate (high score on either the emotional exhaustion or the depersonalisation/cynicism subscale) and high degree of burnout (scores in the range of burnout in all three scales). Rates of moderate-degree burnout increased from 33% to 42% among general practitioners (p = 0.002) and from 19% to 34% among paediatricians (p = 0.001) (high degree of burnout: 4% to 6% [p = 0.17] and 2% to 4% [p = 0.42] respectively). After adjustment for significant socio-demographic and work-related characteristics, an increased risk of moderate burnout was found for doctors surveyed in 2004 and 2007 (OR 1.6, 95%CI 1.3 to 2.0), general practitioners (OR 1.6, 95%CI 1.3 to 2.0) and French-speaking doctors (OR 1.5, 95%CI 1.3 to 1.9). An increased risk of high-degree burnout was found only for general practitioners (OR 1.8, 95%CI 1.05 to 3.0). Burnout levels among Swiss doctors have increased over the last decade, in particular among French-speaking doctors.


Schmidt F.,Princeton University | Jeong D.,Johns Hopkins University | Desjacques V.,University of Geneva
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

We present a derivation of two-point correlations of general tracers in the peak-background split (PBS) framework by way of a rigorous definition of the PBS argument. Our expressions only depend on connected matter correlators and "renormalized" bias parameters with clear physical interpretation, and are independent of any coarse-graining scale. This result should be contrasted with the naive expression derived from a local bias expansion of the tracer number density with respect to the matter density perturbation δL coarse-grained on a scale RL. In the latter case, the predicted tracer correlation function receives contributions of order âŸ̈δLn⟩ at each perturbative order n, whereas, in our formalism, these are absorbed in the PBS bias parameters at all orders. Further, this approach naturally predicts both a scale-dependent bias â̂k2 such as found for peaks of the density field, and the scale-dependent bias induced by primordial non-Gaussianity in the initial conditions. The only assumption made about the tracers is that their abundance at a given position depends solely on the matter distribution within a finite region around that position. © 2013 American Physical Society.


Asfandiyarov R.,University of Geneva
Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment | Year: 2013

The Electron-Muon Ranger (EMR) is a totally active scintillator detector to be installed in the muon beam of the Muon Ionization Cooling Experiment (MICE) [1] - the main R&D project for the future neutrino factory. It is aimed at measuring the properties of the low energy beam composed of muons, electrons and pions, performing the identification particle by particle. The EMR is made of 48 stacked layers alternately measuring the X- and the Y-coordinate. Each layer consists of 59 triangular scintillator bars. It is shown that the granularity of the detector permits to identify tracks and to measure particle ranges and shower shapes. The read-out is based on FPGA custom made electronics and commercially available modules. Currently it is being built at the University of Geneva. © 2013 Elsevier B.V.


Barrett J.,Royal Holloway, University of London | Gisin N.,University of Geneva
Physical Review Letters | Year: 2011

If nonlocality is to be inferred from a violation of Bell's inequality, an important assumption is that the measurement settings are freely chosen by the observers, or alternatively, that they are random and uncorrelated with the hypothetical local variables. We demonstrate a connection between models that weaken this assumption, allowing partial correlation, and (i) models that allow classical communication between the distant parties, (ii) models that exploit the detection loophole. Even if Bob's choices are completely independent, all correlations from projective measurements on a singlet can be reproduced, with mutual information between Alice's choice and local variables less than or equal to one bit. © 2011 American Physical Society.


Mowlavi N.,University of Geneva
Astronomy and Astrophysics | Year: 2014

Aims. A new method is presented to identify transient candidates in large-scale surveys based on the variability pattern in their light curves. Methods. The method is based on the Abbe value, A, that estimates the smoothness of a light curve, and on a newly introduced value called the excess Abbe and denoted €A, that estimates the regularity of the light curve variability pattern over the duration of the observations. Results. Based on simulated light curves, transients are shown to occupy a specific region in the A versus €A diagram, distinct from sources presenting pulsating-like features in their light curves or having featureless light curves. The method is tested on real light curves taken from EROS-2 and OGLE-II surveys in a 0.50° × 0.17° field of the sky in the Large Magellanic Cloud centered at RA(J2000) = 5h25m56.5s and Dec(J2000) = -69 d29m43.3s. The method identifies 43 EROS-2 transient candidates out of a total of ~1300 variable stars, and 19 more OGLE-II candidates, 10 of which do not have any EROS-2 variable star matches and which would need further confirmation to assess their reliability. The efficiency of the method is further tested by comparing the list of transient candidates with known Be stars in the literature. It is shown that all Be stars known in the studied field of view with detectable bursts or outbursts are successfully extracted by the method. In addition, four new transient candidates displaying bursts and/or outbursts are found in the field, of which at least two are good new Be candidates. Conclusions. The new method proves to be a potentially powerful tool to extract transient candidates from large-scale multi-epoch surveys. The better the photometric measurement uncertainties are, the cleaner the list of detected transient candidates is. In addition, the A diagram is shown to be a good diagnostic tool to check the data quality of multi-epoch photometric surveys. A trend of instrumental and/or data reduction origin, for example, will manifest itself by an unexpected distribution of points in the diagram. © ESO, 2014.


Mitra A.,New York University | Giamarchi T.,University of Geneva
Physical Review Letters | Year: 2011

An interaction quench in a Luttinger liquid can drive it into an athermal steady state. We analyze the effects on such an out of equilibrium state of a mode coupling term due to a periodic potential. Employing a perturbative renormalization group approach we show that even when the periodic potential is an irrelevant perturbation in equilibrium, it has important consequences on the athermal steady state as it generates a temperature as well as a dissipation and hence a finite lifetime for the bosonic modes. © 2011 American Physical Society.


Posfay-Barbe K.M.,University of Geneva
Swiss Medical Weekly | Year: 2012

Paediatric infectious diseases have been reported since Hippocrates, and were always closely linked with the evolution of medicine. Current insights and recommendations by the Pediatric Infectious Diseases Group of Switzerland for the management of common paediatric diseases, such as acute otitis media, pharyngitis, and acute viral gastroenteritis are reviewed. The emergence of "old" vaccine-preventable diseases - pertussis and measles - is also discussed. Furthermore, the impact of the appearance of new hosts in paediatric - very low birthweight infants, immunosuppressed patients - is evaluated. Finally, new emerging paediatric infectious diseases caused by newly discovered viruses, such as human metapneumovirus, human bocavirus, or human coronavirus NL63 are explored. This overview gives a general idea on some topics that are currently significant and specific to paediatric infectious diseases.


BACKGROUND:: There are few objective measures of functional impairment to support clinical decision making in lumbar degenerative disc disease (DDD). OBJECTIVE:: We present the validation (and reliability measures) of the Timed Up and Go (TUG) test. METHODS:: In a prospective, 2-center study, 253 consecutive patients were assessed using the TUG test. A representative cohort of 110 volunteers served as control subjects. The TUG test values were assessed for validity and reliability. RESULTS:: The TUG test had excellent intra- (intraclass correlation coefficient: 0.97) and interrater reliability (intraclass correlation coefficient: 0.99), with a standard error of measurement of 0.21 and 0.23 seconds, respectively. The validity of the TUG test was demonstrated by a good correlation with the Visual Analog Scale (VAS) back (Pearsonʼs correlation coefficient [PCC]: 0.25) and VAS (PCC: 0.29) leg pain, functional impairment (Roland-Morris Disability Index [PCC: 0.38] and Oswestry Disability Index [PCC: 0.34]), as well as with health-related quality of life (Short Form-12 Mental Component Summary score [PCC: −0.25], Short Form-12 Physical Component Summary score [PCC: −0.32], and EQ-5D [PCC: −0.28]). The upper limit of “normal” was 11.52 seconds. Mild (lower than the 33rd percentile), moderate (33rd to 66th percentiles), and severe objective functional impairment (higher than the 66th percentile) as determined by the TUG test was <13.4 seconds, 13.4 to 18.4 seconds, and >18.4 seconds, respectively. CONCLUSION:: The TUG test is a quick, easy-to-use, valid, and reliable tool to evaluate objective functional impairment in patients with lumbar degenerative disc disease. In the clinical setting, patients scoring a TUG test time of over 12 seconds can be considered to have functional impairment. ABBREVIATIONS:: BMI, body mass indexDDD, degenerative disc diseaseHRQOL, health-related quality of lifeICC, intraclass correlationLDH, lumbar disc herniationLSS, lumbar spinal stenosisODI, Oswestry Disability IndexOFI, objective functional impairmentPCC, Pearsonʼs correlation coefficientPCS, Physical Component SummaryRMDI, Roland-Morris Disability IndexSF, Short FormVAS, visual analog scale Copyright © by the Congress of Neurological Surgeons


Tonka L.,University of Geneva
Regional Environmental Change | Year: 2014

Traditional hydropower creates a number of adverse environmental effects, nowadays largely recognized but still in conflict with rights granted in previous era of development. The Upper Rhone River basin is heavily developed for hydropower generation. As this region undergoes a period of new concession grants, environmental legislation should eventually be implemented to its full extent. This turning point also allows changes in dams' ownership and institutional setting, and these aspects attract much of the political attention. The article compares the US hydropower regulatory framework and the country's experience in dam relicensing to highlight shortcomings in the Swiss regulatory framework and possible outcomes of the concession reversion process in Canton Valais. © 2014 Springer-Verlag Berlin Heidelberg.


Mohd Omar F.,University of Geneva
The Science of the total environment | Year: 2014

The surface charge and average size of manufactured ZnO nanoparticles (NPs) were studied as a function of pH to understand the aggregation behavior and importance of the electrostatic interactions in solution. The interactions between ZnO and Suwannee River humic acid (SRHA) were then investigated under a range of environmentally relevant conditions with the ZnO nanoparticles pHPZC as the point of reference. The anionic charges carried by aquatic humic substances were found to play a major role in the aggregation and disaggregation of ZnO nanoparticles. At low concentrations of SRHA (<0.05 mg/L) and below the pHPZC, anionic SRHA was rapidly adsorbed onto the positively charged ZnO NPs hence promoting aggregation. With similar SHRA concentrations, at pHPZC, SRHA was able to control the suspension behavior of the ZnO and promote partial disaggregation in small volumes. This was more distinguishable when the pH was greater than pHPZC as SRHA formed a surface coating on the ZnO nanoparticles and enhanced stability via electrostatic and steric interactions. In most cases, the NP coating by SRHA induced disaggregation behavior in the ZnO nanoparticles and decreased the aggregate size in parallel to increasing SRHA concentrations. Results also suggest that environmental aquatic concentration ranges of humic acids largely modify the stability of aggregated or dispersed ZnO nanoparticles. © 2013.


Picard F.,University of Geneva
Cortex | Year: 2010

We describe the case of a patient who during a simple focal epileptic seizure due to vascular cerebral sequelae, reported the paroxysmal convincing feeling of the presence of several familiar persons in her peripersonal and extrapersonal space. Because the patient reported sensing multiple presences and recognizing them as family members, her case appears to contradict the hypothesis that the feeling of a non-existent human presence is an autoscopic phenomenon involving the neural " reduplication of the body" As an alternative hypothesis, I propose that the feeling of a non-existent presence may be only a hallucination of an ordinary " perception of the presence of another" Otherwise, the closest presence was felt in front of the patient, without lateralization in one hemispace, suggesting the importance to take into account other spatial dimensions than the left/right dimension, such as the front/back dimension, in the feeling of a presence. Illusory perceptive phenomena could participate in future in better understanding brain regions involved in the front/back dimension of the space perceptive representation. © 2010 Elsevier Srl.


Branciard C.,University of Queensland | Gisin N.,University of Geneva
Physical Review Letters | Year: 2011

The simulation of quantum correlations with finite nonlocal resources, such as classical communication, gives a natural way to quantify their nonlocality. While multipartite nonlocal correlations appear to be useful resources, very little is known on how to simulate multipartite quantum correlations. We present a protocol that reproduces tripartite Greenberger-Horne-Zeilinger correlations with bounded communication: 3bits in total turn out to be sufficient to simulate all equatorial VonNeumann measurements on the tripartite Greenberger-Horne- Zeilinger state. © 2011 American Physical Society.


De Rham C.,University of Geneva | Gabadadze G.,New York University | Tolley A.J.,Case Western Reserve University
Physical Review Letters | Year: 2011

We construct four-dimensional covariant nonlinear theories of massive gravity which are ghost-free in the decoupling limit to all orders. These theories resum explicitly all the nonlinear terms of an effective field theory of massive gravity. We show that away from the decoupling limit the Hamiltonian constraint is maintained at least up to and including quartic order in nonlinearities, hence excluding the possibility of the Boulware-Deser ghost up to this order. We also show that the same remains true to all orders in a similar toy model. © 2011 American Physical Society.


Pettorino V.,University of Geneva
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

The Planck collaboration has recently published maps of the cosmic microwave background (CMB) radiation, in good agreement with a ΛCDM model, a fit especially valid for multipoles ℓ>40. We explore here the possibility that dark energy is dynamical and gravitational attraction between dark matter particles is effectively different from the standard one in general relativity: this is the case of coupled dark energy models, where dark matter particles feel the presence of a fifth force, larger than gravity by a factor 2β2, defining an effective gravitational constant Geff= G(1+2β2). We investigate constraints on the strength of the coupling β in view of Planck data. Interestingly, we show that a nonzero coupling is compatible with data and find a likelihood peak at β=0.036±0.016 [Planck+WMAP polarization (WP)+baryonic acoustic oscillations (BAO)] (compatible with zero at 2.2σ). The significance of the peak increases to β=0.066±0.018 [Planck+WP+Hubble Space Telescope (HST)] (around 3.6σ from zero coupling) when Planck is combined to HST data by. This peak comes mostly from the small difference between the Hubble parameter determined with CMB measurements and the one coming from astrophysics measurements and is already present in the combination with BAO. Future observations and further tests of current observations are needed to determine whether the discrepancy is due to systematics in any of the data sets. Our aim here is not to claim new physics but rather to show that a clear understanding of such tension has a considerable impact on dark energy models: it can be used to provide information on dynamical dark energy and modified gravity, allowing us to test the strength of an effective fifth force. © 2013 American Physical Society.


Desjacques V.,University of Geneva
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

Maxima of the linear density field form a point process that can be used to understand the spatial distribution of virialized halos that collapsed from initially overdense regions. However, owing to the peak constraint, clustering statistics of discrete density peaks are difficult to evaluate. For this reason, local bias schemes have received considerably more attention in the literature thus far. In this paper, we show that the two-point correlation function of maxima of a homogeneous and isotropic Gaussian random field can be thought of, up to second order at least, as arising from a local bias expansion formulated in terms of rotationally invariant variables. This expansion relies on a unique smoothing scale, which is the Lagrangian radius of dark matter halos. The great advantage of this local bias approach is that it circumvents the difficult computation of joint probability distributions. We demonstrate that the bias factors associated with these rotational invariants can be computed using a peak-background split argument, in which the background perturbation shifts the corresponding probability distribution functions. Consequently, the bias factors are orthogonal polynomials averaged over those spatial locations that satisfy the peak constraint. In particular, asphericity in the peak profile contributes to the clustering at quadratic and higher order, with bias factors given by generalized Laguerre polynomials. We speculate that our approach remains valid at all orders, and that it can be extended to describe clustering statistics of any point process of a Gaussian random field. Our results will be very useful to model the clustering of discrete tracers with more realistic collapse prescriptions involving the tidal shear for instance. © 2013 American Physical Society.


Foffa S.,University of Geneva | Sturani R.,Sao Paulo State University
Classical and Quantum Gravity | Year: 2014

In this short review we present a self-contained exposition of the effective field theory method approach to model the dynamics of gravitationally bound compact binary systems within the post-Newtonian approximation to General Relativity. Applications of this approach to the conservative sector, as well as to the radiation emission by the binary system are discussed in their salient features. Most important results are discussed, as in-depths and details can be found in the referenced papers. © 2014 IOP Publishing Ltd.


Burri H.,University of Geneva
Europace | Year: 2013

Remote device management involves remote follow-up (which replace periodic in-clinic device interrogations for assessing device function), remote monitoring (with unscheduled transmissions of alerts such as atrial fibrillation), and patient-initiated interrogations (that are initiated manually due to a perceived or real clinical event). This article overviews the different aspects related to these functions. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2013.


Schwitzgebel V.M.,University of Geneva
Journal of Diabetes Investigation | Year: 2014

Monogenic diabetes represents a heterogeneous group of disorders resulting from defects in single genes. Defects are categorized primarily into two groups: disruption of β-cell function or a reduction in the number of β-cells. A complex network of transcription factors control pancreas formation, and a dysfunction of regulators high in the hierarchy leads to pancreatic agenesis. Dysfunction among factors further downstream might cause organ hypoplasia, absence of islets of Langerhans or a reduction in the number of β-cells. Many transcription factors have pleiotropic effects, explaining the association of diabetes with other congenital malformations, including cerebellar agenesis and pituitary agenesis. Monogenic diabetes variants are classified conventionally according to age of onset, with neonatal diabetes occurring before the age of 6 months and maturity onset diabetes of the young (MODY) manifesting before the age of 25 years. Recently, certain familial genetic defects were shown to manifest as neonatal diabetes, MODY or even adult onset diabetes. Patients with neonatal diabetes require a thorough genetic work-up in any case, and because extensive phenotypic overlap exists between monogenic, type 2, and type 1 diabetes, genetic analysis will also help improve diagnosis in these cases. Next generation sequencing will facilitate rapid screening, leading to the discovery of digenic and oligogenic diabetes variants, and helping to improve our understanding of the genetics underlying other types of diabetes. An accurate diagnosis remains important, because it might lead to a change in the treatment of affected subjects and influence long-term complications. Monogenic diabetes represents a heterogeneous group of disorders resulting from defects in single genes. Defects are categorized primarily into two groups: disruption of beta cell function or a reduction in the number of beta cells. An accurate diagnosis is important because it may lead to a change in the treatment of affected subjects and influence long-term complications. © 2014 The Author.


Zufferey S.,University of Geneva
Journal of Pragmatics | Year: 2012

In French, a causal relation is often conveyed by the connectives car, parce que or puisque. Since the seminal work of the Lambda-l Group (1975), it has generally been assumed that parce que, used to relate semantic content, contrasts with car and puisque, both used to connect either speech act or epistemic content. However, this analysis leaves a number of questions unanswered. In this paper, I present a reanalysis of this trio, using empirical methods such as corpus analysis and constrained elicitation. Results indicate that car and parce que are interchangeable in many contexts, even if they are still prototypically used in their respective domain in writing. As for puisque, its distribution does not overlap with car, despite their similar domains of use. I argue that the specificity of puisque with respect to the other two connectives is to introduce a cause with an echoic meaning. © 2011 Elsevier B.V.


Etter J.-F.,University of Geneva
European Respiratory Journal | Year: 2010

Smoking is the first risk factor for chronic obstructive pulmonary disease (COPD). Some recent reports suggest that, unexpectedly, some respiratory symptoms may increase transiently after smoking cessation, but there is a dearth of short-term data to test this hypothesis. The aim of the present study was to assess the validity of an online screening tool and to describe short-term associations between smoking behaviour and self-reported respiratory symptoms, in cross-sectional and longitudinal data. An internet survey was conducted in 2003-2009, on a smoking cessation website, with a follow-up survey after 30 days. There were 15,916 participants at baseline and 1,831 at follow-up. In the 252 baseline smokers who had quit smoking at 30-day follow-up, there was a substantial decrease in the proportion of participants who declared that they often coughed even without a cold (from 51.6% at baseline to 15.5% at follow-up), expectorated when they coughed in the morning (from 47.6% to 19.4%), were out of breath after climbing stairs or after a quick walk (from 75.0% to 48.4%), and who had a wheezing respiration (from 33.7% to 10.3%) (p<0.001 for all before/after comparisons). In participants who did not change their smoking behaviour between assessments, the test-retest reliability was r=0.87 for a score summing these four symptoms. Smoking cessation was followed by a rapid and substantial improvement in self-reported respiratory symptoms. COPD is largely underdiagnosed and undertreated. Internet screening is reliable and may allow for the early detection of COPD symptoms at a large scale, in patients who may otherwise have no access to COPD case-finding efforts. Copyright©ERS 2010.


Kirkpatrick C.L.,University of Geneva
Cold Spring Harbor perspectives in biology | Year: 2011

While polar organelles hold the key to understanding the fundamentals of cell polarity and cell biological principles in general, they have served in the past merely for taxonomical purposes. Here, we highlight recent efforts in unraveling the molecular basis of polar organelle positioning in bacterial cells. Specifically, we detail the role of members of the Ras-like GTPase superfamily and coiled-coil-rich scaffolding proteins in modulating bacterial cell polarity and in recruiting effector proteins to polar sites. Such roles are well established for eukaryotic cells, but not for bacterial cells that are generally considered diffusion-limited. Studies on spatial regulation of protein positioning in bacterial cells, though still in their infancy, will undoubtedly experience a surge of interest, as comprehensive localization screens have yielded an extensive list of (polarly) localized proteins, potentially reflecting subcellular sites of functional specialization predicted for organelles.


Epstein R.H.,University of Geneva
Genetics | Year: 2012

We have isolated a large number of mutants of bacteriophage T4D that are unable to form plaques on strain B of Escherichia coli, but are able to grow (nearly) normally on some other strains of E. coli, in particular strain CR63. These mutants, designated amber (am), have been characterized by complementation tests, by genetic crosses, and by their response to chemical mutagens. It is concluded that a particular subclass of base substitution mutations may give rise to amber mutants and that such mutants occur in many genes, which are widely distributed over the T4 genome.


Hannich J.T.,University of Geneva
Cold Spring Harbor perspectives in biology | Year: 2011

Sterols and sphingolipids are considered mainly eukaryotic lipids even though both are present in some prokaryotes, with sphingolipids being more widespread than sterols. Both sterols and sphingolipids differ in their structural features in vertebrates, plants, and fungi. Interestingly, some invertebrates cannot synthesize sterols de novo and seem to have a reduced dependence on sterols. Sphingolipids and sterols are found in the plasma membrane, but we do not have a clear picture of their precise intracellular localization. Advances in lipidomics and subcellular fractionation should help to improve this situation. Genetic approaches have provided insights into the diversity of sterol and sphingolipid functions in eukaryotes providing evidence that these two lipid classes function together. Intermediates in sphingolipid biosynthesis and degradation are involved in signaling pathways, whereas sterol structures are converted to hormones. Both lipids have been implicated in regulating membrane trafficking.


Tignino M.,University of Geneva
Water International | Year: 2011

On 26 July 2010, the United Nations General Assembly formally recognized a human right to water and sanitation. The damages that an armed conflict causes to water infrastructure and sanitation services stand as great obstacles to the realization of this right. Taking a rights-based approach in post-conflict settings can benefit the water sector by providing international standards to which political and economic decisions may refer in the creation of water policies and decisions. International criminal tribunals and human rights courts also provide potential avenues to redress violations of the right to water and sanitation during an armed conflict. © 2011 International Water Resources Association.


Carrera E.,University of Geneva
Brain | Year: 2014

After a century of false hopes, recent studies have placed the concept of diaschisis at the centre of the understanding of brain function. Originally, the term 'diaschisis' was coined by von Monakow in 1914 to describe the neurophysiological changes that occur distant to a focal brain lesion. In the following decades, this concept triggered widespread clinical interest in an attempt to describe symptoms and signs that the lesion could not fully explain. However, the first imaging studies, in the late 1970s, only partially confirmed the clinical significance of diaschisis. Focal cortical areas of diaschisis (i.e. focal diaschisis) contributed to the clinical deficits after subcortical but only rarely after cortical lesions. For this reason, the concept of diaschisis progressively disappeared from the mainstream of research in clinical neurosciences. Recent evidence has unexpectedly revitalized the notion. The development of new imaging techniques allows a better understanding of the complexity of brain organization. It is now possible to reliably investigate a new type of diaschisis defined as the changes of structural and functional connectivity between brain areas distant to the lesion (i.e. connectional diaschisis). As opposed to focal diaschisis, connectional diaschisis, focusing on determined networks, seems to relate more consistently to the clinical findings. This is particularly true after stroke in the motor and attentional networks. Furthermore, normalization of remote connectivity changes in these networks relates to a better recovery. In the future, to investigate the clinical role of diaschisis, a systematic approach has to be considered. First, emerging imaging and electrophysiological techniques should be used to precisely map and selectively model brain lesions in human and animals studies. Second, the concept of diaschisis must be applied to determine the impact of a focal lesion on new representations of the complexity of brain organization. As an example, the evaluation of remote changes in the structure of the connectome has so far mainly been tested by modelization of focal brain lesions. These changes could now be assessed in patients suffering from focal brain lesions (i.e. connectomal diaschisis). Finally, and of major significance, focal and non-focal neurophysiological changes distant to the lesion should be the target of therapeutic strategies. Neuromodulation using transcranial magnetic stimulation is one of the most promising techniques. It is when this last step will be successful that the concept of diaschisis will gain all the clinical respectability that could not be obtained in decades of research. © The Author (2014).


Kachelriess M.,Norwegian University of Science and Technology | Neronov A.,University of Geneva | Semikoz D.V.,Paris West University Nanterre La Defense
Physical Review Letters | Year: 2015

The locally observed cosmic ray spectrum has several puzzling features, such as the excess of positrons and antiprotons above ∼20 GeV and the discrepancy in the slopes of the spectra of cosmic ray protons and heavier nuclei in the TeV-PeV energy range. We show that these features are consistently explained by a nearby source which was active approximately two million years ago and has injected (2-3)×1050 erg in cosmic rays. The transient nature of the source and its overall energy budget point to the supernova origin of this local cosmic ray source. The age of the supernova suggests that the local cosmic ray injection was produced by the same supernova that has deposited Fe60 isotopes in the deep ocean crust. © 2015 American Physical Society. © 2015 American Physical Society.


Balsiger J.,University of Geneva | VanDeveer S.D.,University of New Hampshire
Global Environmental Politics | Year: 2012

Global environmental governance is growing increasingly complex and recent scholarship and practice raise a number of questions about the continued feasibility of negotiating and implementing an ever-larger set of global environmental agreements. In the search for alternative conceptual models and normative orders, regional environmental governance (REG) is (re)emerging as a significant phenomenon in theory and practice. Although environmental cooperation has historically been more prevalent at the regional than at the global level, and has informed much of what we know today about international environmental cooperation, REG has been a neglected topic in the scholarly literature on international relations and international environmental politics. This introduction to the special issue situates theoretical arguments linked to REG in the broader literature, including the nature of regions, the location of regions in multilevel governance, and the normative arguments advanced for and against regional orders. It provides an overview of empirical work; offers quantitative evidence of REG's global distribution; advances a typology of REG for future research; and introduces the collection of research articles and commentaries through the lens of three themes: form and function, multilevel governance, and participation. © 2012 by the Massachusetts Institute of Technology.


Abanin D.A.,University of Geneva | De Roeck W.,Catholic University of Leuven | Huveneers F.,University of Paris Dauphine
Physical Review Letters | Year: 2015

We derive general bounds on the linear response energy absorption rates of periodically driven many-body systems of spins or fermions on a lattice. We show that, for systems with local interactions, the energy absorption rate decays exponentially as a function of driving frequency in any number of spatial dimensions. These results imply that topological many-body states in periodically driven systems, although generally metastable, can have very long lifetimes. We discuss applications to other problems, including the decay of highly energetic excitations in cold atomic and solid-state systems. © 2015 American Physical Society.


Telephone or text-message reminders have been shown to significantly reduce the rate of missed appointments in different medical settings. Since text-messaging is less resource-demanding, we tested the hypothesis that text-message reminders would be as effective as telephone reminders in an academic primary care clinic. A randomized controlled non-inferiority trial was conducted in the academic primary care division of the Geneva University Hospitals between November 2010 and April 2011. Patients registered for an appointment at the clinic, and for whom a cell phone number was available, were randomly selected to receive a text-message or a telephone call reminder 24 hours before the planned appointment. Patients were included each time they had an appointment. The main outcome was the rate of unexplained missed appointments. Appointments were not missed if they were cancelled or re-scheduled before or independently from the intervention. We defined non-inferiority as a difference below 2% in the rate of missed appointments and powered the study accordingly. A satisfaction survey was conducted among a random sample of 900 patients (response rate 41%). 6450 patients were included, 3285 in the text-message group and 3165 in the telephone group. The rate of missed appointments was similar in the text-message group (11.7%, 95% CI: 10.6-12.8) and in the telephone group (10.2%, 95% CI: 9.2-11.3 p = 0.07). However, only text message reminders were cost-effective. No patient reported any disturbance by any type of reminder in the satisfaction survey. Three quarters of surveyed patients recommended its regular implementation in the clinic. Text-message reminders are equivalent to telephone reminders in reducing the proportion of missed appointments in an academic primary care clinic and are more cost-effective. Both types of reminders are well accepted by patients.


Schmid G.,University of Geneva
Climate Policy | Year: 2012

Technology transfer is not an explicit objective of the Clean Development Mechanism (CDM). However, it constitutes a potential co-benefit by helping to improve living conditions in developing countries. Understanding the drivers and barriers of technology transfer in CDM projects is therefore essential to direct investment flows in host countries and enhance the current CDM framework. In this respect, the contribution of this article is twofold. First, it identifies stepping stones and stumbling blocks to technology transfer in the CDM. Higher applied tariff rates on environmental goods and services as well as burdensome administrative procedures to start a new business are found to be negatively associated with the likelihood of a technology transfer. The results are robust to the exclusion of large host countries such as China and India from the sample. Second, as an extension, the article analyses the correspondence of these supporting factors and barriers with the likelihood of a transfer of the different types of technology (equipment, knowledge, or both). The article concludes with policy recommendations for non-Annex I governments, and suggestions for improvements to the CDM to better assess technology transfer in offsetting projects. © 2012 Copyright Taylor and Francis Group, LLC.


Panduranga Rao M.V.,Indian Institute of Technology Hyderabad | Jakobi M.,University of Geneva
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2013

Symmetrically private information retrieval, a fundamental problem in the field of secure multiparty computation, is defined as follows: A database D of N bits held by Bob is queried by a user Alice who is interested in the bit D b in such a way that (1) Alice learns Db and only D b and (2) Bob does not learn anything about Alice's choice b. While solutions to this problem in the classical domain rely largely on unproven computational complexity theoretic assumptions, it is also known that perfect solutions that guarantee both database and user privacy are impossible in the quantum domain. Jakobi proposed a protocol for oblivious transfer using well-known quantum key device (QKD) techniques to establish an oblivious key to solve this problem. Their solution provided a good degree of database and user privacy (using physical principles like the impossibility of perfectly distinguishing nonorthogonal quantum states and the impossibility of superluminal communication) while being loss-resistant and implementable with commercial QKD devices (due to the use of the Scarani-Acin-Ribordy-Gisin 2004 protocol). However, their quantum oblivious key distribution (QOKD) protocol requires a communication complexity of O(NlogN). Since modern databases can be extremely large, it is important to reduce this communication as much as possible. In this paper, we first suggest a modification of their protocol wherein the number of qubits that need to be exchanged is reduced to O(N). A subsequent generalization reduces the quantum communication complexity even further in such a way that only a few hundred qubits are needed to be transferred even for very large databases. © 2013 American Physical Society.


Gisin N.,University of Geneva
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2013

We show how communication without a physical system carrying the information from the sender to the receiver can be realized. The main point is that sending the vacuum state is not nothing. This extends the recent work by Salih. © 2013 American Physical Society.


Purpose: We report a case of failure of corneal collagen cross-linking (CXL) for progressive keratoconus after preoperative stromal swelling with hypoosmolar riboflavin solution in an extremely thin cornea. Methods: CXL was performed using the protocol established for the treatment of thin corneas. Preoperative minimal thickness after abrasion was 268 μm and increased to 406 μm after swelling with hypoosmolar riboflavin solution. Results: Despite CXL, a distinct progression of up to 1.9 diopters was observed at 3 months after the procedure on the anterior corneal surface. At 6 months after CXL, progression had increased to 2.3 diopters. Although swelling with hypoosmolar riboflavin solution was effective and led to a preoperative thickness of more than 400 μm, the increase in biomechanical resistance was not sufficient to arrest the progression of the disease. Conclusions: Little is known about the minimal stromal thickness required for effective CXL to occur. Although swelling with hypoosmolar riboflavin solution over 400 μm and safety of the procedure can be achieved in even thinner corneas, the outcome of this case suggests that a minimal preoperative stromal thickness of 330 μm needs to be respected for a successful CXL procedure. Copyright © 2011 by Lippincott Williams & Wilkins.


Eigenmann P.A.,University of Geneva
Current Opinion in Allergy and Clinical Immunology | Year: 2013

PURPOSE OF REVIEW: Infantile eczema, and in particular atopic dermatitis are, in many children, the first manifestation of their predisposition to an atopic disease. Among existing prevention strategies, supplementation with probiotics and prebiotics belong to the most promising beneficial interventions. Highlighting the most recent literature, we review here the most recent studies on probiotics and prebiotics and hypothesize on the most efficient intervention strategies. RECENT FINDINGS: Various probiotics and prebiotics, either alone or in combinations, have been administered, in general, during the late phase of pregnancy and up to 6 months of age. In general, a combination of probiotics and prebiotics given from pregnancy until early infancy has a higher potential for protecting the infant from developing early manifestations of eczema than short administration of one specific microorganism. SUMMARY: The effect of probiotics and prebiotic supplementations on early manifestations of atopy such as infantile eczema are conflicting. Nevertheless, prevention strategies should aim for an enhanced efficacy by addressing not only interventions on the microbiota, but by combining them to other interventions, for example, to those aiming at actively inducing antigen-specific tolerance. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Dietschi D.,University of Geneva
Quintessence international (Berlin, Germany : 1985) | Year: 2010

Various bleaching modalities are now offered to patients, either monitored by the dental office or self-directed, for which relative efficiency is unknown. The aim of this in vitro study was to evaluate the ability of bleaching products and protocols to lighten enamel and dentin. Bovine tooth specimens of standardized thickness (2.5 +/- 0.025 mm with similar dentin and enamel thickness) were prepared and stained with whole blood and hemolysate before being submitted to seven supervised or self-directed bleaching regimens: tray-based bleaching using 10% (Opalescence, Ultradent; Nite White, Discus Dental) or light-activated 30% (Metatray, Metatray) carbamide peroxide (CP); 6% (Zoom, Discus Dental) or 9% (TresWhite, Ultradent) hydrogen peroxide (HP); strips (Whitening Strips, Oral B-Rembrandt); and paint-on gel (Paint on Plus, Ivoclar Vivadent) containing 8.1% and 6% HP, respectively. Colorimetric measurements were performed on each specimen side, according to the CIE L*a*b* system, before and after staining, as well as after 5, 10, and the recommended number of bleaching applications. Color change after recommended number of applications (DEr) varied from 15.72 (Metatray) to 29.67 (Nite White) at enamel and 14.91 (Paint on Plus) to 41.43 (Nite White) at dentin side; Nite White (10% CP) and TresWhite (9% HP) were more effective than Metatray (30% CP) and Paint on Plus (6% HP) after 5 or the recommended number of applications. In this in vitro study based on bovine teeth, tray-based systems produced the faster and better bleaching effect, regardless of the product and concentration used, at both enamel and dentin sides.


Basov D.N.,University of California at San Diego | Averitt R.D.,Boston University | Van Der Marel D.,University of Geneva | Dressel M.,University of Stuttgart | Haule K.,Rutgers University
Reviews of Modern Physics | Year: 2011

Studies of the electromagnetic response of various classes of correlated electron materials including transition-metal oxides, organic and molecular conductors, intermetallic compounds with d and f electrons, as well as magnetic semiconductors are reviewed. Optical inquiry into correlations in all these diverse systems is enabled by experimental access to the fundamental characteristics of an ensemble of electrons including their self-energy and kinetic energy. Steady-state spectroscopy carried out over a broad range of frequencies from microwaves to UV light and fast optics time-resolved techniques provides complimentary prospectives on correlations. Because the theoretical understanding of strong correlations is still evolving, the review is focused on the analysis of the universal trends that are emerging out of a large body of experimental data augmented where possible with insights from numerical studies. © 2011 American Physical Society.


Michel J.-P.,University of Geneva
Expert Review of Vaccines | Year: 2010

There is a high burden of infectious diseases in the older population, which is associated with increased morbidity and mortality compared with younger age groups. Too many of these diseases are vaccine preventable yet there is a low vaccine coverage rate across Europe. These findings led the European Union Geriatric Medicine Society and the International Association of Gerontology and Geriatrics - European Region to convene an expert Working Group to address the issue of why vaccination programs have failed to provide adequate protection in older European populations and to recommend immunization guidelines to ensure that they contribute to a healthy aging strategy. This review addresses some of the main issues relating to poor vaccine uptake in older adults and presents the recommendations of the joint Working Group regarding the optimal use of the following vaccines: tetanus-diphtheria-pertussis, influenza, pneumococcal (PV23) and herpes zoster. To improve vaccine coverage, communication and awareness of vaccine preventable diseases in the general community is an important starting point, and all healthcare professionals and public health/social workers can play a key role in this regard. © 2010 Expert Reviews Ltd.


Clackdoyle R.,Dalhousie University | Defrise M.,University of Geneva
IEEE Signal Processing Magazine | Year: 2010

Image reconstruction from projections is the field that lays the foundations for computed tomography (CT). For several decades, the established principles were applied not only to medical scanners in radiology and nuclear medicine but also to industrial scanning. When speaking of image reconstruction from projections, one is generally considering the problem of recovering some density function from measurements taken over straight lines, or the line-integral model for short. Image reconstruction can be performed by directly applying analytic formulas derived from the theory or by using general optimization methods adapted to handling large linear systems. The latter techniques are referred to as iterative to distinguish them from the analytic (or direct) methods. This article considers only the analytic methods. The two-dimensional (2-D) reconstruction problem (or classical tomography) refers to a density function in two dimensions with measurement lines lying in the plane, and the three-dimensional (3-D) problem considers 3-D density functions and lines with arbitrary orientations in space. The widely used term 3-D imaging is potentially confusing in this context, because there are some 3-D forms of image reconstruction that are mathematically equivalent to performing 2-D reconstruction on a set of parallel contiguous planes. To emphasize the distinction between 2-D and 3-D reconstruction, the terminology fully 3-D image reconstruction (or sometimes truly 3-D reconstruction) was introduced in the late 1980s when there seemed to be very little left to do in two dimensions but a rich unexplored 3-D theory to be developed. © 2006 IEEE.


Uckay I.,University of Geneva
Swiss medical weekly : official journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology | Year: 2010

QUESTIONS UNDER STUDY / PRINCIPLES: The value of postoperative pro-calcitonin (PCT) in the follow-up of patients with localised infections in the orthopaedic domain is unknown. We conducted a retrospective study comparing postoperative ultra-sensitive serum PCT (upper normal level 0.25 μg/l) and C-reactive protein (CRP; upper normal level 10 mg/l) levels in adult patients with localised non-bacteremic orthopaedic infections. A total of 165 paired PCT and CRP samples were retrieved from 60 infected patients. PCT levels exceeded normal in only half of the patients and practically only on the first postoperative day, despite a clinically active infection in all cases. PCT values did not differ between patients with or without surgical re-interventions (36 patients; median 0.09 mg/l vs. 24 patients; median 0.08 μg/l; Wilcoxon-rank sum-test, p = 0.34). CRP was elevated in 54 patients (90%) with a maximum at day 2, and normalised by the tenth day. Both markers correlated poorly with each other (Kendall-tau-test 0.47). The cost for one analysis (phlebotomy by nurses, transport and laboratory) was US$70 for PCT and $20 for CRP. Postoperative serum PCT levels in orthopaedic infections were rarely elevated, even if patients continued to be infected. They quickly fell to within a normal range at day 2. PCT does not seem to be better than the less expensive CRP in the follow-up of these patients.


Kilpinen H.,University of Geneva | Kilpinen H.,Swiss Institute of Bioinformatics | Barrett J.C.,Wellcome Trust Sanger Institute
Trends in Genetics | Year: 2013

Progress in understanding the genetics of human disease is closely tied to technological developments in DNA sequencing. Recently, next-generation technology has transformed the scale of sequencing; compared to the methods used in the Human Genome Project, modern sequencers are 50. 000-fold faster. Complex disease genetics presents an immediate opportunity to use this technology to move from approaches using only partial information (linkage and genome-wide association studies, GWAS) to complete analysis of the relationship between genomic variation and phenotype. We first describe sequence-based improvements to existing study designs, followed by prioritization of both samples and genomic regions to be sequenced, and then address the ultimate goal of analyzing thousands of whole-genome sequences. Finally, we discuss how the same technology will also fundamentally change the way we understand the biological mechanisms underlying disease associations discovered through sequencing. © 2012 Elsevier Ltd.


Degruyter W.,Georgia Institute of Technology | Bonadonna C.,University of Geneva
Earth and Planetary Science Letters | Year: 2013

The collapse of volcanic plumes has significant implications for eruption dynamics and associated hazards. We show how eruptive columns can collapse and generate pyroclastic density currents as a result of not only the source conditions, but also of the atmospheric environment. The ratio of the potential energy and the kinetic energy at the source quantified by the Richardson number, and the entrainment efficiency quantified by the radial entrainment coefficient have already been identified as key parameters in controlling the transition between a buoyant and collapsing plume. Here we quantify how this transition is affected by wind using scaling arguments in combination with a one-dimensional plume model. Air entrainment due to wind causes a volcanic plume to lower its density at a faster rate and therefore to favor buoyancy. We identify the conditions when wind entrainment becomes dominant over radial entrainment and quantify the effect of wind on column collapse. These findings are framed into a generalized regime diagram that also describes previous regime diagrams for the specific case of choked flows. Many observations confirm how bent-over plumes typically do not generate significant collapses. A quantitative comparison with the 1996 Ruapehu and the 2010 Eyjafjallajökull eruptions shows that the likelihood of collapse is reduced even at moderate wind speeds relative to the exit velocity at the vent. © 2013 Elsevier B.V.


Fontana P.,University of Geneva
Journal of the American Heart Association | Year: 2013

Between 20% and 50% of cardiovascular patients treated with clopidogrel, an anti-P2Y12 drug, display high on-treatment platelet reactivity (HTPR) and are not adequately protected from major adverse cardiovascular events (MACE). Despite a minor influence of the CYP2C19*2 genetic variant on the pharmacodynamic response to clopidogrel (5% to 12%) and a limited or absent value for predicting stent thrombosis and MACE, this latter polymorphism is currently considered an important candidate to tailor anti-P2Y12 therapy during percutaneous coronary intervention. Seven studies have examined the value of CYP2C19*2 for predicting HTPR in comparison to a specific pharmacodynamic assay (VASP assay). Overall, the summarized sensitivity of the CYP2C19*2 genotype for predicting HTPR was 37.6% (95% CI: 32.2 to 43.3%), yielding a negative likelihood ratio of only 0.77 (95% CI: 0.68 to 0.86) which confirms its limited value as a routine clinical aid. A tailored anti-P2Y12 treatment strategy restricted to CYP2C19*2 carriers may be of some help, but this restrictive approach leaves out noncarriers with HTPR. As for platelet function testing, there is currently no convincing data to support that using CYP2C19*2 genotyping as a tailored anti-P2Y12 treatment would be an effective strategy and there is no urgency for CYP2C19 genotyping in clinical practice. Strategies incorporating genotyping, phenotyping, and clinical data in a stratified and sequential approach may be more promising.


Genevay S.,University of Geneva | Atlas S.J.,Massachusetts General Hospital
Best Practice and Research: Clinical Rheumatology | Year: 2010

Lumbar spinal stenosis (LSS) is most commonly due to degenerative changes in older individuals. LSS is being more commonly diagnosed and may relate to better access to advanced imaging and to an ageing population. This review focusses on radicular symptoms related to degenerative central and lateral stenosis and updates knowledge of LSS pathophysiology, diagnosis and management. Since patients with anatomic LSS can range from asymptomatic to severely disabled, the clinical diagnosis focusses on symptoms and examination findings associated with LSS. Imaging findings are helpful for patients with persistent, bothersome symptoms in whom invasive treatments are being considered. There is limited information from high-quality studies about the relative merits and demerits of commonly used treatments. Interpreting and comparing results of available research are limited by a lack of consensus about the definition of LSS. Nevertheless, evidence supports decompressive laminectomy for patients with persistent and bothersome symptoms. Recommendations favour a shared decision-making approach due to important trade-offs between alternative therapies and differences among patients in their preferences and values. © 2009 Elsevier Ltd. All rights reserved.


We present the first quantitative spectroscopic modeling of an early-time supernova (SN) that interacts with its progenitor wind. Using the radiative transfer code CMFGEN, we investigate the recently reported 15.5 h post-explosion spectrum of the type IIb SN 2013cu. We are able to directly measure the chemical abundances of a SN progenitor and find a relatively H-rich wind, with H and He abundances (by mass) of X = 0.46 ± 0.2 and Y = 0.52 ± 0.2, respectively. The wind is enhanced in N and depleted in C relative to solar values (mass fractions of 8.2 × 10-3 and 1.0 × 10-5, respectively). We obtain that a slow, dense wind or circumstellar medium surrounds the precursor at the pre-SN stage, with a wind terminal velocity vwind ? 100 km s-1 and mass-loss rate of ? ? 3 × 10-3 (vwind/ 100 km s-1) M? yr-1. These values are lower than previous analytical estimates, although ? /υ? is consistent with previous work. We also compute a CMFGEN model to constrain the progenitor spectral type; the high ? and low vwind imply that the star had an effective temperature of ? 8000 K immediately before the SN explosion. Our models suggest that the progenitor was either an unstable luminous blue variable or a yellow hypergiant undergoing an eruptive phase, and rule out a Wolf-Rayet star. We classify the post-explosion spectra at 15.5 h as XWN5(h) and advocate for the use of the prefix "X" (eXplosion) to avoid confusion between post-explosion, non-stellar spectra, and those of massive stars. We show that the XWN spectrum results from the ionization of the progenitor wind after the SN, and that the progenitor spectral type is significantly different from the early post-explosion spectral type owing to the huge differences in the ionization structure before and after the SN event. We find the following temporal evolution: LBV/YHG → XWN5(h) → SN IIb. Future early-time spectroscopy in the UV will further constrain the properties of SN precursors, such as their metallicities. © ESO, 2014.


Rizzoli R.,University of Geneva
American Journal of Clinical Nutrition | Year: 2014

Fracture risk is determined by bone mass, geometry, and microstructure, which result from peak bone mass (the amount attained at the end of pubertal growth) and from the amount of bone lost subsequently. Nutritional intakes are an important environmental factor that influence both bone mass accumulation during childhood and adolescence and bone loss that occurs in later life. Bone growth is influenced by dietary intake, particularly of calcium and protein. Adequate dietary calcium and protein are essential to achieve optimal peak bone mass during skeletal growth and to prevent bone loss in the elderly. Dairy products are rich in nutrients that are essential for good bone health, including calcium, protein, vitamin D, potassium, phosphorus, and other micronutrients and macronutrients. Studies supporting the beneficial effects of milk or dairy products on bone health show a significant inverse association between dairy food intake and bone turnover markers and a positive association with bone mineral content. Fortified dairy products induce more favorable changes in biochemical indexes of bone metabolism than does calcium supplementation alone. The associations between the consumption of dairy products and the risk of hip fracture are less well established, although yogurt intake shows a weakly positive protective trend for hip fracture. By consuming 3 servings of dairy products per day, the recommended daily intakes of nutrients essential for good bone health may be readily achieved. Dairy products could therefore improve bone health and reduce the risk of fractures in later life. © 2014 American Society for Nutrition.


Brini A.,University of Geneva | Cavalieri R.,Colorado State University
Selecta Mathematica, New Series | Year: 2011

We develop a mathematical framework for the computation of open orbifold Gromov-Witten invariants of [ℂ3 /ℤn and provide extensive checks with predictions from open string mirror symmetry. To this aim, we set up a computation of open string invariants in the spirit of Katz-Liu [23], defining them by localization. The orbifold is viewed as an open chart of a global quotient of the resolved conifold, and the Lagrangian as the fixed locus of an appropriate anti-holomorphic involution. We consider two main applications of the formalism. After warming up with the simpler example of [ℂ3 /ℤ3, where we verify physical predictions of Bouchard, Klemm, Mariño and Pasquetti [4,5], the main object of our study is the richer case of [ℂ3 /ℤ4, where two different choices are allowed for the Lagrangian. For one choice, we make numerical checks to confirm the B-model predictions; for the other, we prove a mirror theorem for orbifold disc invariants, match a large number of annulus invariants, and give mirror symmetry predictions for open string invariants of genus ≤ 2. © 2011 Springer Basel AG.


Environmental context Microplastics, either purposefully manufactured or formed by fragmentation of discarded 'end-of-life' macroplastic items, are accumulating in environmental compartments. As more and more data are collected on microplastics in the environment, discussion of two issues has become indispensable: (i) how reliable are the results in terms of the inherent capabilities and limitations of current methods used for sampling, counting and measuring microplastic particles; and (ii) how can the fate of microplastics be understood in the context of natural particles and colloids? Abstract A first important step in evaluating the impact of microplastic pollution in natural systems is assessing the reliability of the results obtained according to the inherent capabilities and limitations of the methods used for sampling, counting and measuring microplastic particles. This study, based on the critical reading of 55 studies containing quantitative microplastic data in waters and sediments, is an attempt to analyse these issues in the light of existing knowledge in the field of natural colloid studies. Existing results are highly dependent on the sampling and methodological procedure chosen and are essentially descriptive. Moreover, often they lack standardisation and adequate reporting of basic information such as the meaning of the size parameter measured. Colloid theory may provide the theoretical background needed to explain microplastic behaviour or, at least, to identify the parameters (e.g. density, surface characteristics, shape) that need to be known in order to gain a predictive knowledge of the subject. They are introduced and discussed. Finally, microplastics are not alone in environmental compartments. For this reason, when possible, published microplastic particle size distributions in natural waters have been quantitatively situated in the context of natural particles. © CSIRO 2015.


Bonvin C.,Kavli Institute for Cosmology Cambridge | Bonvin C.,University of Cambridge | Durrer R.,University of Geneva | Maartens R.,University of the Western Cape | Maartens R.,University of Portsmouth
Physical Review Letters | Year: 2014

If the B-mode signal in the cosmic microwave background polarization seen by the BICEP2 experiment is confirmed, it has dramatic implications for models of inflation. The result is also in tension with Planck limits on standard inflationary models. It is, therefore, important to investigate whether this signal can arise from alternative sources. If so, this could lessen the pressure on inflationary models and the tension with Planck data. We investigate whether vector and tensor modes from primordial magnetic fields can explain the signal. We find that, in principle, magnetic fields generated during inflation can indeed produce the required B mode, for a suitable range of energy scales of inflation. In this case, the primordial gravitational wave amplitude is negligible, so that there is no tension with Planck and no problems posed for current inflationary models. However, the simplest magnetic model is in tension with Planck limits on non-Gaussianity in the trispectrum. It may be possible to fine tune the magnetogenesis model so that this non-Gaussianity is suppressed. Alternatively, a weaker magnetic field can pass the non-Gaussianity constraints and allow the primordial tensor mode to be reduced to r≃0.09, thus removing the tension with Planck data and alleviating the problems with simple inflationary models. © 2014 American Physical Society.


Dur W.,University of Innsbruck | Skotiniotis M.,University of Innsbruck | Frowis F.,University of Innsbruck | Frowis F.,University of Geneva | Kraus B.,University of Innsbruck
Physical Review Letters | Year: 2014

We consider quantum metrology in noisy environments, where the effect of noise and decoherence limits the achievable gain in precision by quantum entanglement. We show that by using tools from quantum error correction this limitation can be overcome. This is demonstrated in two scenarios, including a many-body Hamiltonian with single-qubit dephasing or depolarizing noise and a single-body Hamiltonian with transversal noise. In both cases, we show that Heisenberg scaling, and hence a quadratic improvement over the classical case, can be retained. Moreover, for the case of frequency estimation we find that the inclusion of error correction allows, in certain instances, for a finite optimal interrogation time even in the asymptotic limit. © 2014 American Physical Society.


Goldman J.-P.,University of Geneva
Proceedings of the Annual Conference of the International Speech Communication Association, INTERSPEECH | Year: 2011

We provide a user-friendly automatic phonetic alignment tool for continuous speech, named EasyAlign. It is developed as a plug-in of Praat, the popular speech analysis software, and it is freely available. Its main advantage is that one can easily align speech from an orthographic transcription. It requires a few minor manual steps and the result is a multi-level annotation within a TextGrid composed of phonetic, syllabic, lexical and utterance tiers. Evaluation showed that the performances of this HTK-based aligner compare to human alignment and to other existing alignment tools. It was originally fully available for French, English. Community's interests for its extension to other languages helped to develop a straight-forward methodology to add languages. While Spanish and Taiwan Min were recently added, other languages are under development. Copyright © 2011 ISCA.


Galliot B.,University of Geneva
Development Genes and Evolution | Year: 2013

The freshwater Hydra polyp provides a unique model system to decipher the mechanisms underlying adult regeneration. Indeed, a single cut initiates two distinct regenerative processes, foot regeneration on one side and head regeneration on the other side, the latter relying on the rapid formation of a local head organizer. Two aspects are discussed here: the asymmetric cellular remodeling induced by mid-gastric bisection and the signaling events that trigger head organizer formation. In head-regenerating tips (but not in foot ones), a wave of cell death takes place immediately, leading the apoptotic cells to transiently release Wnt3 and activate the β-catenin pathway in the neighboring cycling cells to push them through mitosis. This process, which mimics the apoptosis-induced compensatory proliferation process deciphered in Drosophila larvae regenerating their discs, likely corresponds to an evolutionarily conserved mechanism, also at work in Xenopus tadpoles regenerating their tail or mice regenerating their skin or liver. How is this process generated in Hydra? Several studies pointed to the necessary activation of the extracellular signal-regulated kinase (ERK) 1-2 and mitogen-activated protein kinase (MAPK) pathways during early head regeneration. Indeed inhibition of ERK 1-2 or knockdown of RSK, cAMP response element-binding protein (CREB), and CREB-binding protein (CBP) prevent injury-induced apoptosis and head regeneration. The current scenario involves an asymmetric activation of the MAPK/CREB pathway to trigger injury-induced apoptosis in the interstitial cells and in the epithelial cells a CREB/CBP-dependent transcriptional activation of early genes essential for head-organizing activity as wnt3, HyBra1, and prdl-a. The question now is how bisection in the rather uniform central region of the polyp can generate this immediately asymmetric signaling. © 2012 Springer-Verlag.


Camm A.J.,St Georges, University of London | Bounameaux H.,University of Geneva
Drugs | Year: 2011

Edoxaban is an oral direct factor Xa inhibitor that is currently undergoing investigation in phase III clinical trials for the prevention of stroke in patients with atrial fibrillation (AF) and for the prevention and treatment of venous thromboembolic events (VTE).Factor Xa is an attractive target for anticoagulant treatment, as it is the primary and rate-limiting source of amplification in the coagulation cascade. Edoxaban is a competitive inhibitor of factor Xa and has >10000-fold greater selectivity for factor Xa relative to thrombin. In phase I clinical trials, the anticoagulant effects of edoxaban included dose-dependent increases in activated partial thromboplastin time and prothrombin time following single edoxaban doses of 10150mg and after multiple ascending doses (60mg twice daily, 90mg daily and 120mg daily). The anticoagulant effects of edoxaban were rapid in onset (time to peak plasma concentration 12 hours) and sustained for up to 24 hours. Prolongation of bleeding time in 8 of subjects was >9.5 minutes (none of which appeared to be clinically significant) 2 hours after initial dosing, and was independent of edoxaban dose, formulation or dietary state. In general, plasma edoxaban concentrations were linearly correlated with coagulation parameters. Phase II clinical trials in patients with AF and VTE suggest that the edoxaban 30mg once-daily and 60mg once-daily regimens had a similar or better safety profile compared with dose-adjusted warfarin (international normalized ratio 2.03.0) in terms of bleeding events, and that edoxaban was not associated with hepatotoxicity. In addition, edoxaban was associated with statistically significant dose-dependent reductions in VTE after orthopaedic surgery compared with placebo or dalteparin sodium. Further clinical investigation of the efficacy and safety of once-daily edoxaban is being conducted in phase III clinical trials in comparison with warfarin in patients with AF in the phase III ENGAGE AF-TIMI 48 trial (NCT00781391), and in comparison with low-molecular weight heparinwarfarin in the prevention of recurrent VTE in patients with symptomatic deep vein thrombosis andor pulmonary embolism in the HOKUSAI VTE trial (NCT00986154). © 2011 Adis Data Information BV. All Rights Reserved.


Barrouillet P.,University of Geneva
Developmental Review | Year: 2011

Dual-process theories have gained increasing importance in psychology. The contrast that they describe between an old intuitive and a new deliberative mind seems to make these theories especially suited to account for development. Accordingly, this special issue aims at presenting the latest applications of dual-process theories to cognitive development. Dual-process theoreticians mainly focused on adult functioning have been invited to elaborate the developmental implications of their theory, while developmental psychologists who have proposed dual-process theories of development in the domain of thinking and reasoning present the most recent formulation of their theory and review supporting empirical evidence. © 2011 Elsevier Inc.


Hodinka R.L.,Childrens Hospital of Philadelphia | Kaiser L.,University of Geneva
Journal of Clinical Microbiology | Year: 2013

Conventional tube culture systems have long been the mainstay in clinical virology for the growth and identification of viruses from clinical specimens. Innovations such as centrifugation-enhanced shell vial and multiwell plate cultures and the use of genetically engineered and mixed cell lines, coupled with faster detection of viral replication, have allowed for reasonable turnaround times for even some of the most slowly growing clinically important human viruses. However, molecular methods, in particular, the PCR, have usurped the role of viral culture in many laboratories, limiting the use of this traditional method of virus detection or replacing it altogether. Advances and improvements in molecular technology over time have also resulted in newer generations of more rapid and accurate molecular assays for the detection, quantification, and genetic characterization of viruses. For this point-counterpoint, we have asked two individuals, Richard L. Hodinka of the Children's Hospital of Philadelphia, a clinical virologist whose laboratory has completely eliminated viral culture in favor of molecular methods, and Laurent Kaiser, head of the Virology Laboratory at the University of Geneva Hospital, who continues to be a strong advocate of viral culture, to discuss the relevance of viral culture in the molecular age. Copyright © 2013, American Society for Microbiology. All Rights Reserved.


Daumke O.,Max Delbruck Centrum fur Molekulare Medizin | Daumke O.,Free University of Berlin | Roux A.,University of Geneva | Haucke V.,Leibniz Institute for Molecular Pharmacology | Haucke V.,Charite - Medical University of Berlin
Cell | Year: 2014

Biological membranes undergo constant remodeling by membrane fission and fusion to change their shape and to exchange material between subcellular compartments. During clathrin-mediated endocytosis, the dynamic assembly and disassembly of protein scaffolds comprising members of the bin-amphiphysin-rvs (BAR) domain protein superfamily constrain the membrane into distinct shapes as the pathway progresses toward fission by the GTPase dynamin. In this Review, we discuss how BAR domain protein assembly and disassembly are controlled in space and time and which structural and biochemical features allow the tight regulation of their shape and function to enable dynamin-mediated membrane fission. © 2014 Elsevier Inc.


Martin I.,Los Alamos National Laboratory | Morpurgo A.F.,University of Geneva
Physical Review B - Condensed Matter and Materials Physics | Year: 2012

In a variety of rare-earth-based compounds, singlet superconductivity coexists with helical magnetism. Here we demonstrate that surfaces of these systems should generically host a finite density of zero-energy Majorana modes. In the limit of vanishing disorder, these modes lead to a divergent contribution to zero-energy density of states and to zero-temperature entropy proportional to the sample surface area. When confined to a wire geometry, a discrete number of Majorana modes can be isolated. The relatively large characteristic energy scales for superconductivity and magnetism, compared to other proposals, as well as the lack of need for fine tuning, make helical magnetic superconducting compounds favorable for the observation and experimental investigation of Majorana fermions. © 2012 American Physical Society.


Mitra A.,New York University | Giamarchi T.,University of Geneva
Physical Review B - Condensed Matter and Materials Physics | Year: 2012

A perturbative renormalization group approach is employed to study the effect of a periodic potential on a system of one-dimensional bosons in a nonequilibrium steady state due to an initial interaction quench. The renormalization group flows are modified significantly from the well-known equilibrium Berezinski-Kosterlitz-Thouless form. They show several new features such as a generation of an effective temperature, generation of dissipation, as well as a change in the location of the quantum critical point separating the weak- and strong-coupling phases. Detailed results on the weak-coupling side of the phase diagram are presented, such as the renormalization of the parameters and the asymptotic behavior of the correlation functions. The physical origin of the generated temperature and friction is discussed. © 2012 American Physical Society.


Soshnikova N.,University of Geneva
Birth Defects Research Part A - Clinical and Molecular Teratology | Year: 2011

Dynamic changes in gene expression are tightly controlled during development, as a single totipotent zygote gives rise to distinct cell lineages. The establishment and maintenance of these diverse transcriptional programs rely on changes of chromatin state, mainly through histone modifications. Polycomb and Trithorax complexes participate in setting apart active and inactive genes by respectively repressing and activating key developmental regulators in different cell types. Over the last decade, our understanding of the biochemical mechanisms underlying their activities has greatly improved, but the signals targeting these proteins to specific regions of the genome are still poorly understood, particularly in vertebrates. Recent findings highlight the highly dynamic activities of Polycomb and Trithorax complexes in vivo. Surprisingly, although their role in transcriptional regulation is deeply conserved during evolution, the time sequence in which they act seems to vary across species. © 2011 Wiley-Liss, Inc.


Loewith R.,University of Geneva | Hall M.N.,University of Basel
Genetics | Year: 2011

TOR (Target Of Rapamycin) is a highly conserved protein kinase that is important in both fundamental and clinical biology. In fundamental biology, TOR is a nutrient-sensitive, central controller of cell growth and aging. In clinical biology, TOR is implicated in many diseases and is the target of the drug rapamycin used in three different therapeutic areas. The yeast Saccharomyces cerevisiae has played a prominent role in both the discovery of TOR and the elucidation of its function. Here we review the TOR signaling network in S. cerevisiae. © 2011 by the Genetics Society of America.


Panasenko O.O.,University of Geneva
Frontiers in Genetics | Year: 2014

Cotranslational quality control (QC) is the mechanism by which the cell checks the integrity of newly synthesized proteins and mRNAs. In the event of mistakes these molecules are degraded. The Ccr4-Not complex has been proposed to play a role in this process. It contains both deadenylation and ubiquitination activities, thus it may target both aberrant proteins and mRNAs. Deadenylation is the first step in mRNA degradation. In yeast it is performed by the Ccr4 subunit of the Ccr4-Not complex. Another complex subunit, namely Not4, is a RING E3 ligase and it provides the ubiquitination activity of the complex. It was found associated with translating ribosomes. Thus, it has been suggested that Not4 is involved in ribosome-associated ubiquitination and degradation of aberrant peptides. However, several other E3 ligases have been associated with peptide ubiquitination on the ribosome and the relevance of Not4 in this process remains unclear. In this review we summarize the recent data and suggest a role for Not4 in cotranslational protein QC. © 2014 Panasenko.


Rasola A.,CNR Institute of Neuroscience | Rasola A.,University of Padua | Neckers L.,Urologic | Picard D.,University of Geneva
Trends in Cell Biology | Year: 2014

Many tumors undergo a dramatic metabolic shift known as the Warburg effect in which glucose utilization is favored and oxidative phosphorylation is downregulated, even when oxygen availability is plentiful. However, the mechanistic basis for this switch has remained unclear. Recently several independent groups identified tumor necrosis factor receptor-associated protein 1 (TRAP1), a mitochondrial molecular chaperone of the heat shock protein 90 (Hsp90) family, as a key modulator of mitochondrial respiration. Although all reports agree that this activity of TRAP1 has important implications for neoplastic progression, data from the different groups only partially overlap, suggesting that TRAP1 may have complex and possibly contextual effects on tumorigenesis. In this review we analyze these recent findings and attempt to reconcile these observations. © 2014 Elsevier Ltd.


Bonilla X.,University of Geneva
Nature Genetics | Year: 2016

Basal cell carcinoma (BCC) of the skin is the most common malignant neoplasm in humans. BCC is primarily driven by the Sonic Hedgehog (Hh) pathway. However, its phenotypic variation remains unexplained. Our genetic profiling of 293 BCCs found the highest mutation rate in cancer (65 mutations/Mb). Eighty-five percent of the BCCs harbored mutations in Hh pathway genes (PTCH1, 73% or SMO, 20% (P = 6.6 × 10-8) and SUFU, 8%) and in TP53 (61%). However, 85% of the BCCs also harbored additional driver mutations in other cancer-related genes. We observed recurrent mutations in MYCN (30%), PPP6C (15%), STK19 (10%), LATS1 (8%), ERBB2 (4%), PIK3CA (2%), and NRAS, KRAS or HRAS (2%), and loss-of-function and deleterious missense mutations were present in PTPN14 (23%), RB1 (8%) and FBXW7 (5%). Consistent with the mutational profiles, N-Myc and Hippo-YAP pathway target genes were upregulated. Functional analysis of the mutations in MYCN, PTPN14 and LATS1 suggested their potential relevance in BCC tumorigenesis. © 2016 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.


Krumhuber E.G.,University of Geneva
Emotion (Washington, D.C.) | Year: 2012

In this article, we present FACSGen 2.0, new animation software for creating static and dynamic three-dimensional facial expressions on the basis of the Facial Action Coding System (FACS). FACSGen permits total control over the action units (AUs), which can be animated at all levels of intensity and applied alone or in combination to an infinite number of faces. In two studies, we tested the validity of the software for the AU appearance defined in the FACS manual and the conveyed emotionality of FACSGen expressions. In Experiment 1, four FACS-certified coders evaluated the complete set of 35 single AUs and 54 AU combinations for AU presence or absence, appearance quality, intensity, and asymmetry. In Experiment 2, lay participants performed a recognition task on emotional expressions created with FACSGen software and rated the similarity of expressions displayed by human and FACSGen faces. Results showed good to excellent classification levels for all AUs by the four FACS coders, suggesting that the AUs are valid exemplars of FACS specifications. Lay participants' recognition rates for nine emotions were high, and comparisons of human and FACSGen expressions were very similar. The findings demonstrate the effectiveness of the software in producing reliable and emotionally valid expressions, and suggest its application in numerous scientific areas, including perception, emotion, and clinical and neuroscience research. (PsycINFO Database Record (c) 2012 APA, all rights reserved).


Recent genome-wide analyses have revealed patterns of positive selection acting on protein-coding genes in humans and mammals. To assess whether the conclusions drawn from these analyses are valid for other vertebrates and to identify mammalian specificities, I have investigated the selective pressure acting on protein-coding genes of the puffer fishes Tetraodon and Takifugu. My results indicate that the strength of purifying selection in puffer fishes is similar to previous reports for murids but stronger in hominids, which have a smaller population size. Gene ontology analyses show that more than half of the biological processes targeted by positive selection in mammals are also targeted in puffer fishes, highlighting general patterns for vertebrates. Biological processes enriched with positively selected genes that are shared between mammals and fishes include immune and defense responses, signal transduction, regulation of transcription and several of their descendent terms. Mammalian-specific processes displaying an excess of positively selected genes are related to sensory perception and neurological processes. The comparative analyses also revealed that, for both mammals and fishes, genes encoding extracellular proteins are preferentially targeted by positive selection, indicating that adaptive evolution occurs more often in the extra-cellular environment rather than inside the cell. Moreover, I present here the first genome-wide characterization of neutrally-evolving regions of protein-coding genes. This analysis revealed an unexpectedly high proportion of genes containing both positively selected motifs and neutrally-evolving regions, uncovering a strong link between neutral evolution and positive selection. I speculate that neutrally-evolving regions are a major source of novelties screened by natural selection. © 2011 Juan I. Montoya-Burgos.


Korff C.M.,University of Geneva | Scheffer I.E.,University of Melbourne
Current Opinion in Neurology | Year: 2013

Purpose of Review: This review presents the new terms and concepts proposed by the International League Against Epilepsy (ILAE) Classification Commission in 2010 to describe seizures and epilepsies. This is the first major revision in 21 years and reflects the rapid evolution in our understanding of the epilepsies. Purpose of Review: The article places these changes in an historical perspective, summarizes elements of the lively debate that followed publication, presents refinements addressing those concerns and discusses issues that remain to be addressed. It describes the thinking behind the new terminology as the basis for framing further discoveries in the epilepsies. Summary: The purpose of the ILAE classification is primarily for clinical use to assist in patient care; a secondary purpose is for research. The 2010 Organization of the Epilepsies is therefore one of the most important clinical tools in the neurologist's armamentarium and impacts on virtually every epilepsy consultation. By necessity, the organization is dynamic and evolving. The new concepts reflect current understanding and were introduced as outdated terms and frameworks were no longer valid for clinical practice. These changes represent a major step forward that will improve patient management and understanding of the neurobiology of the epilepsies. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Furstenberg A.,University of Geneva | Heilemann M.,Goethe University Frankfurt
Physical Chemistry Chemical Physics | Year: 2013

Fluorescence imaging beyond the diffraction limit has grown into a method of choice to elucidate questions related to biological structure and organisation. Among super-resolution techniques, imaging based on the localization of individual photoswitchable fluorescent probes has become particularly popular due to its relative ease of implementation and the nature of qualitative and quantitative answers it can offer. We review the field of single-molecule localization microscopy (SMLM) by providing an overview of its underlying principles and of different categories of photoswitchable fluorophores. In addition to summarizing target-specific labelling strategies and presenting examples of successful applications of SMLM in fixed and living systems, we show how SMLM data offer unique opportunities for quantitative biomolecular counting and distribution analysis. © the Owner Societies 2013.


Buchs N.C.,University of Geneva
The British journal of surgery | Year: 2013

The natural history of sigmoid diverticulitis has been inferred from population-based or retrospective studies. This study assessed the risk of a recurrent attack following the first episode of uncomplicated diverticulitis. Patients admitted between January 2007 and December 2011 with a first episode of uncomplicated sigmoid diverticulitis confirmed on computed tomography were enrolled in this prospective study. After successful medical management of the first episode, follow-up was conducted through yearly telephone interviews. Cox proportional hazards regression was performed to model the impact of various parameters on eventual recurrences and complications. During a median follow-up of 24 (range 3-63) months, 46 (16·4 per cent) of 280 patients experienced a second episode of diverticulitis. Six patients (2·1 per cent) subsequently developed complicated diverticulitis and four (1·4 per cent) underwent emergency surgery for peritonitis. In multivariable analysis, a raised serum level of C-reactive protein (over 240 mg/l) during the first attack was associated with early recurrence (hazard ratio 1·75, 95 per cent confidence interval 1·04 to 2·94; P = 0·035). Uncomplicated sigmoid diverticulitis follows a benign course with few recurrences and little need for emergency surgery. Registration number: NCT01015378 (http://www.clinicaltrials.gov). © 2013 British Journal of Surgery Society Ltd. Published by John Wiley & Sons Ltd.


Rodriguez I.,University of Geneva