Consensus summary statement of the International Multidisciplinary Consensus Conference on Multimodality Monitoring in Neurocritical Care : A statement for healthcare professionals from the Neurocritical Care Society and the European Society of Intensive Care Medicine.

Neurocritical care depends, in part, on careful patient monitoring but as yet there are little data on what processes are the most important to monitor, how these should be monitored, and whether monitoring these processes is cost-effective and impacts outcome. At the same time, bioinformatics is a rapidly emerging field in critical care but as yet there is little agreement or standardization on what information is important and how it should be displayed and analyzed. The Neurocritical Care Society in collaboration with the European Society of Intensive Care Medicine, the Society for Critical Care Medicine, and the Latin America Brain Injury Consortium organized an international, multidisciplinary consensus conference to begin to address these needs. International experts from neurosurgery, neurocritical care, neurology, critical care, neuroanesthesiology, nursing, pharmacy, and informatics were recruited on the basis of their research, publication record, and expertise. They undertook a systematic literature review to develop recommendations about specific topics on physiologic processes important to the care of patients with disorders that require neurocritical care. This review does not make recommendations about treatment, imaging, and intraoperative monitoring. A multidisciplinary jury, selected for their expertise in clinical investigation and development of practice guidelines, guided this process. The GRADE system was used to develop recommendations based on literature review, discussion, integrating the literature with the participants' collective experience, and critical review by an impartial jury. Emphasis was placed on the principle that recommendations should be based on both data quality and on trade-offs and translation into clinical practice. Strong consideration was given to providing pragmatic guidance and recommendations for bedside neuromonitoring, even in the absence of high quality data.

Recommandations pour la prise en charge des formes oligoarticulaire et polyarticulaires (en dehors de la polyarthrite rhumatoïde) d'arthrite juvénile idiopathique [Guidelines for diagnosis and treatment of oligoarticular and polyarticular juvenile idiopathic arthritis].

A guideline group of pediatric rheumatologist experts elaborated guidelines related to the management of idiopathic juvenile arthritis in association with the Haute Autorité de santé (HAS). A systematic search of the literature published between 1998 and August 2008 and indexed in Pubmed was undertaken. Here, we present the guidelines for diagnosis and treatment in oligoarticular and polyarticular juvenile idiopathic arthritis (except for spondylarthropathy and rheumatoid arthritis).

An introduction to model-independent diffusion magnetic resonance imaging.

ABSTRACT: q-Space-based techniques such as diffusion spectrum imaging, q-ball imaging, and their variations have been used extensively in research for their desired capability to delineate complex neuronal architectures such as multiple fiber crossings in each of the image voxels. The purpose of this article was to provide an introduction to the q-space formalism and the principles of basic q-space techniques together with the discussion on the advantages as well as challenges in translating these techniques into the clinical environment. A review of the currently used q-space-based protocols in clinical research is also provided.

Antiretroviral treatment of adult HIV infection: 2014 recommendations of the International Antiviral Society-USA Panel.

IMPORTANCE: New data and antiretroviral regimens expand treatment choices in resource-rich settings and warrant an update of recommendations to treat adults infected with human immunodeficiency virus (HIV). OBJECTIVE: To provide updated treatment recommendations for adults with HIV, emphasizing when to start treatment; what treatment to start; the use of laboratory monitoring tools; and managing treatment failure, switches, and simplification. DATA SOURCES, STUDY SELECTION, AND DATA SYNTHESIS: An International Antiviral Society-USA panel of experts in HIV research and patient care considered previous data and reviewed new data since the 2012 update with literature searches in PubMed and EMBASE through June 2014. Recommendations and ratings were based on the quality of evidence and consensus. RESULTS: Antiretroviral therapy is recommended for all adults with HIV infection. Evidence for benefits of treatment and quality of available data increase at lower CD4 cell counts. Recommended initial regimens include 2 nucleoside reverse transcriptase inhibitors (NRTIs; abacavir/lamivudine or tenofovir disoproxil fumarate/emtricitabine) and a third single or boosted drug, which should be an integrase strand transfer inhibitor (dolutegravir, elvitegravir, or raltegravir), a nonnucleoside reverse transcriptase inhibitor (efavirenz or rilpivirine) or a boosted protease inhibitor (darunavir or atazanavir). Alternative regimens are available. Boosted protease inhibitor monotherapy is generally not recommended, but NRTI-sparing approaches may be considered. New guidance for optimal timing of monitoring of laboratory parameters is provided. Suspected treatment failure warrants rapid confirmation, performance of resistance testing while the patient is receiving the failing regimen, and evaluation of reasons for failure before consideration of switching therapy. Regimen switches for adverse effects, convenience, or to reduce costs should not jeopardize antiretroviral potency. CONCLUSIONS AND RELEVANCE: After confirmed diagnosis of HIV infection, antiretroviral therapy should be initiated in all individuals who are willing and ready to start treatment. Regimens should be selected or changed based on resistance test results with consideration of dosing frequency, pill burden, adverse toxic effect profiles, comorbidities, and drug interactions.

La contrefaçon de billets de banque face à l'évolution des technologies d'impression

La contrefaçon de billets de banque a considérablement évolué avec l'apparition des technologies numériques de reproduction. Gouverné autrefois par des professionnels bien organisés, le phénomène de la contrefaçon n'est plus aujourd'hui l'apanage de quelques initiés mais est répandu dans une large communauté de faussaires. Les systèmes et les acteurs de la lutte contre la contrefaçon doivent s'adapter à ce nouveau modèle afin de pallier les impacts économiques, personnels et psychologiques de la contrefaçon sur la société. Au coeur des débats sociologiques et éthiques, les autorités politiques, les banques nationales, la police et les experts tentent d'endiguer le problème de façon parfois quelque peu inadéquate et obsolète. L'analyse de données statistiques permet de dégager les tendances actuelles et d'identifier les changements majeurs entre deux époques.

International consensus conference on PFAPA syndrome: evaluation of a new set of classification criteria

INTRODUCTION: PFAPA syndrome is characterized by periodic fever, associated with pharyngitis, cervical adenitis and/or aphthous stomatitis and belongs to the auto-inflammatory diseases. Diagnostic criteria are based on clinical features and the exclusion of other periodic fever syndromes. An analysis of a large cohort of patients has shown weaknesses for these criteria and there is a lack of international consensus. An International Conference was held in Morges in November 2008 to propose a new set of classification criteria based on a consensus among experts in the field.OBJECTIVE: We aimed to verify the applicability of the new set of classification criteria.PATIENTS & METHODS: 80 patients diagnosed with PFAPA syndrome from 3 centers (Genoa, Lausanne and Geneva) for pediatric rheumatology were included in the study. A detailed description of the clinical and laboratory features was obtained. The new classification criteria and the actual diagnostic criteria were applied to the patients.RESULTS: Only 40/80 patients (50%) fulfilled all criteria of the new classification. 31 patients were excluded because they didn't meet one of the 7 diagnostic criteria, 7 because of 2 criteria, and one because of 3 criteria. When we applied the current criteria to the same patients, 11/80 patients (13.7%) needed to be excluded. 8/80 patients (10%) were excluded from both sets. Exclusion was related only to some of the criteria. Number of patients for each not fulfilled criterion (new set of criteria/actual criteria): age (1/6), symptoms between episodes (2/2), delayed growth (4/1), main symptoms (21/0), periodicity, length of fever, interval between episodes, and length of disease (20/0). The application of some of the new criteria was not easy, as they were both very restrictive and needed precise information from the patients.CONCLUSION: Our work has shown that the new set of classification criteria can be applied to patients suspected for PFAPA syndrome, but it seems to be more restrictive than the actual diagnostic criteria. A further work of validation needs to be done in order to determine if this new set of classification criteria allow a good discrimination between PFAPA patients and other causes of recurrent fever syndromes.

Anti-angiogenic therapies for metastatic colorectal cancer.

BACKGROUND: Angiogenesis inhibitors have been developed to block tumour angiogenesis and target vascular endothelial cells. While some of them have already been approved by the health authorities and are successfully integrated into patient care, many others are still under development, and the clinical value of this approach has to be established. OBJECTIVES: To assess the efficacy and toxicity of targeted anti-angiogenic therapies, in addition to chemotherapy, in patients with metastatic colorectal cancer. Primary endpoints are both progression-free and overall survival. Response rates, toxicity and secondary resectability were secondary endpoints. Comparisons were first-line chemotherapy in combination with angiogenesis inhibitor, to the same chemotherapy without angiogenesis inhibitor; and second-line chemotherapy, to the same chemotherapy without angiogenesis inhibitor. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, as well as proceedings from ECCO, ESMO and ASCO until November 2008. In addition, reference lists from trials were scanned, experts in the field and drug manufacturers were contacted to obtain further information. SELECTION CRITERIA: Randomized controlled trials on targeted anti-angiogenic drugs in metastatic colorectal cancer (MCRC). DATA COLLECTION AND ANALYSIS: Data collection and analysis was performed, according to a previously published protocol. Because individual patient data was not provided, aggregate data had to be used for the analysis. Summary statistics for the primary endpoints were hazard ratios (HR's) and their 95% confidence intervals. MAIN RESULTS: At present, eligible first line trials for this meta-analysis were available for bevacizumab (5 trials including 3101 patients) and vatalanib (1 trial which included 1168 patients). The overall HR s for PFS (0.61, 95% CI 0.45 - 0.83) and OS (0.81, 95% 0.73 - 0.90) for the comparison of first-line chemotherapy, with or without bevacizumab, confirms significant benefits in favour of the patients treated with bevacizumab. However, the effect on PFS shows significant heterogeneity. For second-line chemotherapy, with or without bevacizumab, a benefit in both PFS (HR 0.61, 95% CI 0.51 - 0.73) and OS (HR 0.75, 95% CI 0.63-0.89) was demonstrated in a single, randomized trial. While differences in treatment-related deaths and 60-day mortality were not significant, higher incidences in grade III/IV hypertension, arterial thrombembolic events and gastrointestinal perforations were observed in the patients treated with bevacizumab. For valatanib, currently available data showed a non-significant benefit in PFS and OS. AUTHORS' CONCLUSIONS: The addition of bevacizumab to chemotherapy of metastatic colorectal cancer prolongs both PFS and OS in first-and second-line therapy.

Treating pulmonary hypertension in pediatrics.

INTRODUCTION: Pulmonary hypertension is a hemodynamic condition occurring rarely in pediatrics. Nevertheless, it is associated with significant morbidity and mortality. When characterized by progressive pulmonary vascular structural changes, the disease is called pulmonary arterial hypertension (PAH). It results in increased pulmonary vascular resistance and eventual right ventricular failure. In the vast majority of cases, pediatric PAH is idiopathic or associated with congenital heart disease, and, contrary to adult PAH, is rarely associated with connective tissue, portal hypertension, HIV infection or thromboembolic disease. AREAS COVERED: This article reviews the current drug therapies available for the management of pediatric PAH. These treatments target the recognized pathophysiological pathways of PAH with endothelin-1 receptor antagonists, prostacyclin analogs and PDE type 5 inhibitors. New treatments and explored pathways are briefly discussed. EXPERT OPINION: Although there is still no cure for PAH, quality of life and survival have been improved significantly with specific drug therapies. Nevertheless, management of pediatric PAH remains challenging, and depends mainly on results from adult clinical trials and pediatric experts. Further research on PAH-specific treatments in the pediatric population and data from international registries are needed to identify optimal therapeutic strategies and treatment goals in the pediatric population.

Machine learning algorithms for spatial data. Case studies: Environmental pollution, natural hazards, renewable resources

This paper presents general problems and approaches for the spatial data analysis using machine learning algorithms. Machine learning is a very powerful approach to adaptive data analysis, modelling and visualisation. The key feature of the machine learning algorithms is that they learn from empirical data and can be used in cases when the modelled environmental phenomena are hidden, nonlinear, noisy and highly variable in space and in time. Most of the machines learning algorithms are universal and adaptive modelling tools developed to solve basic problems of learning from data: classification/pattern recognition, regression/mapping and probability density modelling. In the present report some of the widely used machine learning algorithms, namely artificial neural networks (ANN) of different architectures and Support Vector Machines (SVM), are adapted to the problems of the analysis and modelling of geo-spatial data. Machine learning algorithms have an important advantage over traditional models of spatial statistics when problems are considered in a high dimensional geo-feature spaces, when the dimension of space exceeds 5. Such features are usually generated, for example, from digital elevation models, remote sensing images, etc. An important extension of models concerns considering of real space constrains like geomorphology, networks, and other natural structures. Recent developments in semi-supervised learning can improve modelling of environmental phenomena taking into account on geo-manifolds. An important part of the study deals with the analysis of relevant variables and models' inputs. This problem is approached by using different feature selection/feature extraction nonlinear tools. To demonstrate the application of machine learning algorithms several interesting case studies are considered: digital soil mapping using SVM, automatic mapping of soil and water system pollution using ANN; natural hazards risk analysis (avalanches, landslides), assessments of renewable resources (wind fields) with SVM and ANN models, etc. The dimensionality of spaces considered varies from 2 to more than 30. Figures 1, 2, 3 demonstrate some results of the studies and their outputs. Finally, the results of environmental mapping are discussed and compared with traditional models of geostatistics.

Integration and development in schizotypy research : an introduction to the special supplement

In its fifth decade of existence, the construct of schizotypy is recapturing the early scientific interest it attracted when Paul E. Meehl (1920-2003), who coined the term, pioneered the field of schizotypy research. The International Lemanic Workshop on Schizotypy, hosted at the University of Geneva in December 2013, recently offered an opportunity to address some of the fundamental questions in contemporary schizotypy research and situate the construct in the greater scheme of future scientific projects on schizophrenia and psychological health research. What kind of knowledge has schizotypy research provided in furthering our understanding of schizophrenia? What types of questions can schizotypy research tackle, and which are the conceptual and methodological frameworks to address them? How will schizotypy research contribute to future scientific endeavors? The International Lemanic Workshop brought together leading experts in the field around the tasks of articulating the essential findings in schizotypy research, as well as providing some key insights and guidance to face scientific challenges of the future. The current supplement contains 8 position articles, 4 research articles, and 1 invited commentary that outline the state of the art in schizotypy research today

Monitoring de la problématique du cannabis en Suisse: étude sentinelle 2004-2009

Le monitoring de la problématique du cannabis en Suisse constitue un ensemble de travaux qui permettent le suivi de la situation au niveau national et qui sont mis en oeuvre par un consortium d'institutions de recherche. Ce monitoring comprend l'étude présentée dans ce rapport, l'étude sentinelle. Celle-ci s'intéresse à l'évolution de la situation en matière de cannabis ainsi qu'à la gestion de cette situation au niveau local. Il s'agit de répondre aux questions suivantes : - quelle est la situation en matière de consommation de cannabis et de marché et quelle est son évolution ? - quels sont les principaux problèmes rencontrés sur le terrain ? - quelles sont les mesures et interventions qui ont été développées dans ce domaine ? Pour y répondre, on a choisi de suivre la situation dans quatre cantons suisses dits "sentinelle" (St-Gall, Tessin, Vaud, Zurich). Les critères de choix de ces cantons font appel à leur taille, au rapport ville/campagne et à la présence de frontière avec des états voisins, à la langue, au type de politique drogue pratiqué. Dans chaque canton on a constitué des panels d'experts formés par des profes-sionnels de terrain dans trois domaines différents (santé et social, école, police et justice). Leurs observations ainsi que les données cantonales disponibles sont récoltées et discutées lors d'un workshop et analysées sur plusieurs années. Le présent rapport fait état des résultats des quatre workshops de suivi (2005, 2006, 2008, 2009). [Résumé, p. 5]

The nature of leadership

With contributions from leading authors in the most important areas of current research, this book provides insight into the streams that are driving leadership theory and practice today. The Nature of Leadership, Second Edition provides students with an updated and complete yet concise handbook that solidifies and integrates the vast and disparate leadership literature.Key Features of the Second Edition· Provides contributions from twenty-three subject-matter experts-ranging from the eminent to the up-and-coming-giving students an unsurpassed breadth of knowledge and perspective· Organizes the material into the three key thematic areas of Leadership-Science, Nature, and Nurture; the Major Schools of Leadership; and Leadership and Special Domains· Includes nine brand new chapters that provide students with the state-of-the-art of leadership theory and practice such as evolutionary and biological perspectives, individual differences, and shared leadership· Updates the content of seven retained chapters, with reference to recent research and developments in the field· Adds pedagogical features, including discussion questions, a list of practice-focused supplemental readings, and references to case studies

The new EASL guidelines for the management of chronic hepatitis B infection adapted for Swiss physicians.

Since the arrival of several new antivirals and due to the growing molecular and clinical knowledge of hepatitis B virus (HBV) infection, therapy of hepatitis B has become complex. Clinical guidelines aim at streamlining medical attitudes: in this respect, the European Association for the Study of the Liver (EASL) recently issued clinical practice guidelines for the management of chronic hepatitis B. Guidelines made by international experts need however to be adapted to local health care systems. Here, we summarise the EASL guidelines with some minor modifications in order to be compatible with the particular Swiss situation, while discussing in more detail some aspects. Chronic hepatitis B is a complex disease with several phases where host and viral factors interact: the features of this continuous interplay need to be evaluated when choosing the most appropriate treatment. The EASL guidelines recommend, as first-line agents, using the most potent antivirals available with the optimal resistance profile, in order to abate HBV DNA as rapidly and as sustainably as possible. Once therapy has been started, the infection evolves and resistant viral strains may emerge. Rescue therapy needs to be started early with more potent agents lacking cross-resistance.

Associer et évaluer

Le forensicien joue fréquemment le rôle d'expert judiciaire. Dans cette responsabilité, il doit par exemple évaluer le lien qu'est susceptible d'entretenir une trace avec une source putative (une personne, un objet) donnée. L'expert examine aussi parfois la relation entre deux traces (proviennent-elles de la même source ?), combine les indices, ou interprète les activités possibles en regard des traces recueillies. Un mouvement dominant et intégrateur préconise d'effectuer cette évaluation au moyen de probabilités qui expriment dans un cadre formel les incertitudes inhérentes à ce genre de questions. Basé sur le théorème découvert par le révérend Bayes sur la probabilité des causes, le rapport de vraisemblance équilibre le point de vue de l'accusation (par exemple, probabilité de la trace, sachant que x en est à l'origine) et de la défense (la probabilité de la trace si la source n'est pas x). L'exploitation de ce modèle fait appel à l'expérience de l'expert, mais aussi à de grandes quantités de données représentatives qui doivent encore être rassemblées. Une tendance consiste aussi à exploiter pour cela les données stockées par l'utilisation de systèmes automatisés (empreintes digitales, projectiles, etc.). De nouvelles possibilités d'extraire des caractéristiques encore inexplorées à partir des traces sont susceptibles d'augmenter considérablement les moyens pour les experts judiciaires d'apporter des réponses probabilistes dans des circonstances toujours plus variées aux autorités judiciaires qui les mandatent.

Vascular-endothelial-growth-factor (VEGF) targeting therapies for endocrine refractory or resistant metastatic breast cancer.

BACKGROUND: Vascular-endothelial-growth-factor (VEGF) is a key mediator of angiogenesis. VEGF-targeting therapies have shown significant benefits and been successfully integrated in routine clinical practice for other types of cancer, such as metastatic colorectal cancer. By contrast, individual trial results in metastatic breast cancer (MBC) are highly variable and their value is controversial. OBJECTIVES: To evaluate the benefits (in progression-free survival (PFS) and overall survival (OS)) and harms (toxicity) of VEGF-targeting therapies in patients with hormone-refractory or hormone-receptor negative metastatic breast cancer. SEARCH METHODS: Searches of CENTRAL, MEDLINE, EMBASE, the Cochrane Breast Cancer Group's Specialised Register, registers of ongoing trials and proceedings of conferences were conducted in January and September 2011, starting in 2000. Reference lists were scanned and members of the Cochrane Breast Cancer Group, experts and manufacturers of relevant drug were contacted to obtain further information. No language restrictions were applied. SELECTION CRITERIA: Randomised controlled trials (RCTs) to evaluate treatment benefit and non-randomised studies in the routine oncology practice setting to evaluate treatment harms. DATA COLLECTION AND ANALYSIS: We performed data collection and analysis according to the published protocol. Individual patient data was sought but not provided. Therefore, the meta-analysis had to be based on published data. Summary statistics for the primary endpoint (PFS) were hazard ratios (HRs). MAIN RESULTS: We identified seven RCTs, one register, and five ongoing trials from a total of 347 references. The published trials for VEGF-targeting drugs in MBC were limited to bevacizumab. Four trials, including a total of 2886 patients, were available for the comparison of first-line chemotherapy, with versus without bevacizumab. PFS (HR 0.67; 95% confidence interval (CI) 0.61 to 0.73) and response rate were significantly better for patients treated with bevacizumab, with moderate heterogeneity regarding the magnitude of the effect on PFS. For second-line chemotherapy, a smaller, but still significant benefit in terms of PFS could be demonstrated for patients treated with bevacizumab (HR 0.85; 95% CI 0.73 to 0.98), as well as a benefit in tumour response. However, OS did not differ significantly, neither in first- (HR 0.93; 95% CI 0.84 to 1.04), nor second-line therapy (HR 0.98; 95% CI 0.83 to 1.16). Quality of life (QoL) was evaluated in four trials but results were published for only two of these with no relevant impact. Subgroup analysis stated a significant greater benefit for patients with previous (taxane) chemotherapy and patients with hormone-receptor negative status. Regarding toxicity, data from RCTs and registry data were consistent and in line with the known toxicity profile of bevacizumab. While significantly higher rates of adverse events (AEs) grade III/IV (odds ratio (OR) 1.77; 95% CI 1.44 to 2.18) and serious adverse events (SAEs) (OR 1.41; 95% CI 1.13 to 1.75) were observed in patients treated with bevacizumab, rates of treatment-related deaths were lower in patients treated with bevacizumab (OR 0.60; 95% CI 0.36 to 0.99). AUTHORS' CONCLUSIONS: The overall patient benefit from adding bevacizumab to first- and second-line chemotherapy in metastatic breast cancer can at best be considered as modest. It is dependent on the type of chemotherapy used and limited to a prolongation of PFS and response rates in both first- and second-line therapy, both surrogate parameters. In contrast, bevacizumab has no significant impact on the patient-related secondary outcomes of OS or QoL, which indicate a direct patient benefit. For this reason, the clinical value of bevacizumab for metastatic breast cancer remains controversial.