Iron in arterial plaque: A modifiable risk factor for atherosclerosis

It has been proposed that iron depletion protects against cardiovascular disease. There is increasing evidence that one mechanism for this protection may involve a reduction in iron levels within atherosclerotic plaque. Large increases in iron concentration are seen in human atherosclerotic lesions in comparison to levels in healthy arterial tissue. In animal models, depletion of lesion iron levels in vivo by phlebotomy, systemic iron chelation treatment or dietary iron restriction reduces lesion size and/or increases plaque stability. A number of factors associated with increased arterial disease or increased cardiovascular events is also associated with increased plaque iron. In rats, infusion of angiotensin 11 increases ferritin levels and arterial thickness which are reversed by treatment with the iron chelator deferoxamine. In humans, a polymorphism for haptoglobin associated with increased cardiovascular disease is also characterized by increased lesional iron. Heme oxygenase 1 (HO1) is an important component of the system for mobilization of iron from macrophages. Human HO1 promoter polymorphisms causing weaker upregulation of the enzyme are associated with increased cardiovascular disease and increased serum ferritin. Increased cardiovascular disease associated with inflammation may be in part caused by elevated hepcidin levels that promote retention of iron within plaque macrophages. Defective retention of iron within arterial macrophages in genetic hemochromatosis may explain why there is little evidence of increased atherosclerosis in this disorder despite systemic iron overload. The reviewed findings support the concept that arterial plaque iron is a modifiable risk factor for atherogenesis

A three-group study, internet-based, face-to-face based and standard- management after acute whiplash associated disorders (WAD) – choosing the most efficient and cost-effective treatment: study protocol of a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>The management of Whiplash Associated Disorders is one of the most complicated challenges with high expenses for the health care system and society. There are still no general guidelines or scientific documentation to unequivocally support any single treatment for acute care following whiplash injury.</p> <p>The main purpose of this study is to try a new behavioural medicine intervention strategy at acute phase aimed to reduce the number of patients who have persistent problems after the whiplash injury. The goal is also to identify which of three different interventions that is most cost-effective for patients with Whiplash Associated Disorders. In this study we are controlling for two factors. First, the effect of behavioural medicine approach is compared with standard care. Second, the manner in which the behavioural medicine treatment is administered, Internet or face-to-face, is evaluated in it's effectiveness and cost-effectiveness.</p> <p>Methods/Design</p> <p>The study is a randomized, prospective, experimental three-group study with analyses of cost-effectiveness up to two-years follow-up. <it>Internet – based programme </it>and <it>face-to-face group treatment programme </it>are compared to <it>standard-treatment </it>only. Patient follow-ups take place three, six, twelve and 24 months, that is, short-term as well as long-term effects are evaluated. Patients will be enrolled via the emergency ward during the first week after the accident.</p> <p>Discussion</p> <p>This new self-help management will concentrate to those psychosocial factors that are shown to be predictive in long-term problems in Whiplash Associated Disorders, i.e. the importance of self-efficacy, fear of movement, and the significance of catastrophizing as a coping strategy for restoring and sustaining activities of daily life. Within the framework of this project, we will develop, broaden and evaluate current physical therapy treatment methods for acute Whiplash Associated Disorders. The project will contribute to the creation of a cost-effective behavioural medicine approach to management of acute Whiplash Associated Disorders. The results of this study will answer an important question; on what extent and how should these patients be treated at acute stage and how much does the best management cost.</p> <p>Trial registration number</p> <p>Current Controlled Trials ISRCTN61531337</p

A chemical survey of exoplanets with ARIEL

Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Perspectives in immunotherapy: meeting report from the Immunotherapy Bridge (29-30 November, 2017, Naples, Italy)

Immunotherapy represents the third important wave in the history of the systemic treatment of cancer after chemotherapy and targeted therapy and is now established as a potent and effective treatment option across several cancer types. The clinical success of anti-cytotoxic T-lymphocyte-associated antigen (CTLA)-4, first, and anti-programmed death (PD)-1/PD-ligand (L)1 agents in melanoma and other cancers a few years later, has encouraged increasing focus on the development of other immunotherapies (e.g. monoclonal antibodies with other immune targets, adoptive cell transfer, and vaccines), with over 3000 immuno-oncology trials ongoing, involving hundreds of research institutes across the globe. The potential use of these different immunotherapeutic options in various combinations with one another and with other treatment modalities is an area of particular promise. The third Immunotherapy Bridge meeting (29-30 November, 2017, Naples, Italy) focused on recent advances in immunotherapy across various cancer types and is summarised in this report

Diversity and carbon storage across the tropical forest biome

Tropical forests are global centres of biodiversity and carbon storage. Many tropical countries aspire to protect forest to fulfil biodiversity and climate mitigation policy targets, but the conservation strategies needed to achieve these two functions depend critically on the tropical forest tree diversity-carbon storage relationship. Assessing this relationship is challenging due to the scarcity of inventories where carbon stocks in aboveground biomass and species identifications have been simultaneously and robustly quantified. Here, we compile a unique pan-tropical dataset of 360 plots located in structurally intact old-growth closed-canopy forest, surveyed using standardised methods, allowing a multi-scale evaluation of diversity-carbon relationships in tropical forests. Diversity-carbon relationships among all plots at 1 ha scale across the tropics are absent, and within continents are either weak (Asia) or absent (Amazonia, Africa). A weak positive relationship is detectable within 1 ha plots, indicating that diversity effects in tropical forests may be scale dependent. The absence of clear diversity-carbon relationships at scales relevant to conservation planning means that carbon-centred conservation strategies will inevitably miss many high diversity ecosystems. As tropical forests can have any combination of tree diversity and carbon stocks both require explicit consideration when optimising policies to manage tropical carbon and biodiversity.Additional co-authors: Kofi Affum-Baffoe, Shin-ichiro Aiba, Everton Cristo de Almeida, Edmar Almeida de Oliveira, Patricia Alvarez-Loayza, Esteban Álvarez Dávila, Ana Andrade, Luiz E. O. C. Aragão, Peter Ashton, Gerardo A. Aymard C., Timothy R. Baker, Michael Balinga, Lindsay F. Banin, Christopher Baraloto, Jean-Francois Bastin, Nicholas Berry, Jan Bogaert, Damien Bonal, Frans Bongers, Roel Brienen, José Luís C. Camargo, Carlos Cerón, Victor Chama Moscoso, Eric Chezeaux, Connie J. Clark, Álvaro Cogollo Pacheco, James A. Comiskey, Fernando Cornejo Valverde, Eurídice N. Honorio Coronado, Greta Dargie, Stuart J. Davies, Charles De Canniere, Marie Noel Djuikouo K., Jean-Louis Doucet, Terry L. Erwin, Javier Silva Espejo, Corneille E. N. Ewango, Sophie Fauset, Ted R. Feldpausch, Rafael Herrera, Martin Gilpin, Emanuel Gloor, Jefferson S. Hall, David J. Harris, Terese B. Hart, Kuswata Kartawinata, Lip Khoon Kho, Kanehiro Kitayama, Susan G. W. Laurance, William F. Laurance, Miguel E. Leal, Thomas Lovejoy, Jon C. Lovett, Faustin Mpanya Lukasu, Jean-Remy Makana, Yadvinder Malhi, Leandro Maracahipes, Beatriz S. Marimon, Ben Hur Marimon Junior, Andrew R. Marshall, Paulo S. Morandi, John Tshibamba Mukendi, Jaques Mukinzi, Reuben Nilus, Percy Núñez Vargas, Nadir C. Pallqui Camacho, Guido Pardo, Marielos Peña-Claros, Pascal Pétronelli, Georgia C. Pickavance, Axel Dalberg Poulsen, John R. Poulsen, Richard B. Primack, Hari Priyadi, Carlos A. Quesada, Jan Reitsma, Maxime Réjou-Méchain, Zorayda Restrepo, Ervan Rutishauser, Kamariah Abu Salim, Rafael P. Salomão, Ismayadi Samsoedin, Douglas Sheil, Rodrigo Sierra, Marcos Silveira, J. W. Ferry Slik, Lisa Steel, Hermann Taedoumg, Sylvester Tan, John W. Terborgh, Sean C. Thomas, Marisol Toledo, Peter M. Umunay, Luis Valenzuela Gamarra, Ima Célia Guimarães Vieira, Vincent A. Vos, Ophelia Wang, Simon Willcock & Lise Zemagh

Black gold: trustworthiness in artistic research (seen from the sidelines of arts and health)

Rigour plays a central role in contemporary research culture. But how appropriate a concept is it to think, perform, and make judgements with on what is trustworthy and excellent in artistic research and its neighbouring field of arts and health? The historical meanings of rigour suggest severity and rigidity: straight lines, austere habits, privations. As a word, rigour has a mixed ancestry – French, Latin, Middle English. Some of its earliest uses coincide with a feudal system of government in Europe, with rigge [verb] meaning to plough a straight line in a narrow strip, and rig [verb] to provide a straight ridge to a house. Rig [noun] a derivation of ridge, was used in England five hundred years ago of human and animal backbones, perhaps reflecting everyday physical burdens. Rigours [noun] conveyed the meting out of un-cautioned punishments and cruelty. While the temperament of rigour might be appropriate for research that follows pre-set norms and standards of repeatability, its use to judge what is trustworthy in artistic research is questionable. Though artistic researchers need to understand the rigour concept, by contrast, artistic research as a kind of ‘thinking through making’ (Ravetz, 2011, 159; Ingold, 2013, 6), places value on improvisation, chance encounter, unforeseen admixture and the in- and outward- folding of process, affect and material. Once it is accepted that poiesis is part of the research process (Ingold, 2013; Haraway, 2016), it becomes apparent that artistic research cannot easily accommodate straight backed rigour