Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways

It is of considerable translational importance whether depression is a form or a consequence of sickness behavior. Sickness behavior is a behavioral complex induced by infections and immune trauma and mediated by pro-inflammatory cytokines. It is an adaptive response that enhances recovery by conserving energy to combat acute inflammation. There are considerable phenomenological similarities between sickness behavior and depression, for example, behavioral inhibition, anorexia and weight loss, and melancholic (anhedonia), physio-somatic (fatigue, hyperalgesia, malaise), anxiety and neurocognitive symptoms. In clinical depression, however, a transition occurs to sensitization of immuno-inflammatory pathways, progressive damage by oxidative and nitrosative stress to lipids, proteins, and DNA, and autoimmune responses directed against self-epitopes. The latter mechanisms are the substrate of a neuroprogressive process, whereby multiple depressive episodes cause neural tissue damage and consequent functional and cognitive sequelae. Thus, shared immuno-inflammatory pathways underpin the physiology of sickness behavior and the pathophysiology of clinical depression explaining their partially overlapping phenomenology. Inflammation may provoke a Janus-faced response with a good, acute side, generating protective inflammation through sickness behavior and a bad, chronic side, for example, clinical depression, a lifelong disorder with positive feedback loops between (neuro)inflammation and (neuro)degenerative processes following less well defined triggers

Circulating endothelial cells in oncology: pitfalls and promises

Adequate blood supply is a prerequisite in the pathogenesis of solid malignancies. As a result, depriving a tumour from its oxygen and nutrients, either by preventing the formation of new vessels, or by disrupting vessels already present in the tumour, appears to be an effective treatment modality in oncology. Given the mechanism by which these agents exert their anti-tumour activity together with the crucial role of tumour vasculature in the pathogenesis of tumours, there is a great need for markers properly reflecting its impact. Circulating endothelial cells (CEC), which are thought to derive from damaged vasculature, may be such a marker. Appropriate enumeration of these cells appears to be a technical challenge. Nevertheless, first studies using validated CEC assays have shown that CEC numbers in patients with advanced malignancies are elevated compared to healthy controls making CEC a potential tool for among other establishing prognosis and therapy-induced effects. In this review, we will address the possible clinical applications of CEC detection in oncology, as well as the pitfalls encountered in this process

The Gaia-ESO Survey: open clusters in Gaia-DR1 A way forward to stellar age calibration

Context. Determination and calibration of the ages of stars, which heavily rely on stellar evolutionary models, are very challenging, while representing a crucial aspect in many astrophysical areas. Aims. We describe the methodologies that, taking advantage of Gaia-DR1 and the Gaia-ESO Survey data, enable the comparison of observed open star cluster sequences with stellar evolutionary models. The final, long-term goal is the exploitation of open clusters as age calibrators. Methods. We perform a homogeneous analysis of eight open clusters using the Gaia-DR1 TGAS catalogue for bright members and information from the Gaia-ESO Survey for fainter stars. Cluster membership probabilities for the Gaia-ESO Survey targets are derived based on several spectroscopic tracers. The Gaia-ESO Survey also provides the cluster chemical composition. We obtain cluster parallaxes using two methods. The first one relies on the astrometric selection of a sample of bona fide members, while the other one fits the parallax distribution of a larger sample of TGAS sources. Ages and reddening values are recovered through a Bayesian analysis using the 2MASS magnitudes and three sets of standard models. Lithium depletion boundary (LDB) ages are also determined using literature observations and the same models employed for the Bayesian analysis. Results. For all but one cluster, parallaxes derived by us agree with those presented in Gaia Collaboration (2017, A&A, 601, A19), while a discrepancy is found for NGC 2516; we provide evidence supporting our own determination. Inferred cluster ages are robust against models and are generally consistent with literature values. Conclusions. The systematic parallax errors inherent in the Gaia DR1 data presently limit the precision of our results. Nevertheless, we have been able to place these eight clusters onto the same age scale for the first time, with good agreement between isochronal and LDB ages where there is overlap. Our approach appears promising and demonstrates the potential of combining Gaia and ground-based spectroscopic datasets.Based on data products from observations made with ESO Telescopes at the La Silla Paranal Observatory under programme IDs 188.B-3002, 193.B.0936, and 197.B-1074. These data products have been processed by the Cambridge Astronomy Survey Unit (CASU) at the Institute of Astronomy, University of Cambridge, and by the FLAMES/UVES reduction team at INAF/Osservatorio Astrofisico di Arcetri. These data have been obtained from the Gaia-ESO Survey Data Archive, prepared and hosted by the Wide Field Astronomy Unit, Institute for Astronomy, University of Edinburgh, which is funded by the UK Science and Technology Facilities Council. This work has made use of data from the European Space Agency (ESA) mission Gaia (http://www.cosmos.esa.int/gaia), processed by the Gaia Data Processing and Analysis Consortium (DPAC, http://www.cosmos.esa.int/web/gaia/dpac/consortium). Funding for the DPAC has been provided by national institutions, in particular the institutions participating in the Gaia Multilateral Agreement. This research was made possible through the use of the AAVSO Photometric All-Sky Survey (APASS), funded by the Robert Martin Ayers Sciences Fundation. This research has made use of the SIMBAD and VizieR databases, operated at CDS, Strasbourg, France. This research has made use of NASA’s Astrophysics Data System. This work was partly supported by the European Union FP7 programme through ERC grant number 320360 and by the Leverhulme Trust through grant RPG-2012-541. We acknowledge the support from INAF and Ministero dell’ Istruzione, dell’ Università’ e della Ricerca (MIUR) in the form of the grant “Premiale VLT 2012” and by PRIN-INAF 2014. The results presented here benefit from discussions held during the Gaia-ESO Survey workshops and conferences supported by the ESF (European Science Foundation) through the GREAT Research Network Programme. E.T., P.G.P.M. and S.D. acknowledge PRA Universitá di Pisa 2016 (Stelle di piccola massa: le pietre miliari dell’archeologia galattica, PI: S. Degl’Innocenti) and INFN (Iniziativa specifica TAsP). M.T.C. acknowledge the financial support from the Spanish Ministerio de Economía y Competitividad, through grant AYA2016-75931. U.H. acknowledges support from the Swedish National Space Board (SNSB/Rymdstyrelsen)

Compressed representation of a partially defined integer function over multiple arguments

In OLAP (OnLine Analitical Processing) data are analysed in an n-dimensional cube. The cube may be represented as a partially defined function over n arguments. Considering that often the function is not defined everywhere, we ask: is there a known way of representing the function or the points in which it is defined, in a more compact manner than the trivial one

Poly(ethylmethacrylate-co-diethylaminoethyl acrylate) coating improves endothelial re-population, bio-mechanical and anti-thrombogenic properties of decellularized carotid arteries for blood vessel replacement

Decellularized vascular scaffolds are promising materials for vessel replacements. However, despite the natural origin of decellularized vessels, issues such as biomechanical incompatibility, immunogenicity risks and the hazards of thrombus formation, still need to be addressed. In this study, we coated decellularized vessels obtained from porcine carotid arteries with poly (ethylmethacrylate-co-diethylaminoethylacrylate) (8g7) with the purpose of improving endothelial coverage and minimizing platelet attachment while enhancing the mechanical properties of the decellularized vascular scaffolds. The polymer facilitated binding of endothelial cells (ECs) with high affinity and also induced endothelial cell capillary tube formation. In addition, platelets showed reduced adhesion on the polymer under flow conditions. Moreover, the coating of the decellularized arteries improved biomechanical properties by increasing its tensile strength and load. In addition, after 5 days in culture, ECs seeded on the luminal surface of 8g7-coated decellularized arteries showed good regeneration of the endothelium. Overall, this study shows that polymer coating of decellularized vessels provides a new strategy to improve re-endothelialization of vascular grafts, maintaining or enhancing mechanical properties while reducing the risk of thrombogenesis. These results could have potential applications in improving tissue-engineered vascular grafts for cardiovascular therapies with small caliber vessels

Railway Systems and the 'Universal Good of the State': Technologies of Government in the 19th-Century Papal State

Informed by Foucault’s concept of governmentality, the paper focuses on nineteenth-century General Commissariat for the Railroad Industry in the Papal State. Unlike in liberal States, where government intervention in the affairs of railway companies was limited, the pressing need to reinforce the Pope’s pastoral power, strengthen the bond between the believers and the Holy See and ensure equity and the efficiency of the new infrastructure meant that the Commissariat acted as a governmental centre of calculation. Accounting technologies in the form of budgets, cost accounting systems and penetrating audits enabled the government to intervene in the operations of private railway companies. The study analyses the role of accounting and auditing practices in the pursuit of non-liberal goals in an industry which is traditionally perceived as critical to the development of a liberal economy, one in which accounting was traditionally used to maintain investors’ confidence in the capitalist system

Multiscale multifactorial approaches for engineering tendon substitutes

The physiology of tendons and the continuous strains experienced daily make tendons very prone to injury. Excessive and prolonged loading forces and aging also contribute to the onset and progression of tendon injuries, and conventional treatments have limited efficacy in restoring tendon biomechanics. Tissue engineering and regenerative medicine (TERM) approaches hold the promise to provide therapeutic solutions for injured or damaged tendons despite the challenging cues of tendon niche and the lack of tendon-specific factors to guide cellular responses and tackle regeneration. The roots of engineering tendon substitutes lay in multifactorial approaches from adequate stem cells sources and environmental stimuli to the construction of multiscale 3D scaffolding systems. To achieve such advanced tendon substitutes, incremental strategies have been pursued to more closely recreate the native tendon requirements providing structural as well as physical and chemical cues combined with biochemical and mechanical stimuli to instruct cell behavior in 3D architectures, pursuing mechanically competent constructs with adequate maturation before implantation.Authors acknowledge the project “Accelerating tissue engineering and personalized medicine discoveries by the integration of key enabling nanotechnologies, marinederived biomaterials and stem cells,” supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). Authors acknowledge the H2020 Achilles Twinning Project No. 810850, and also the European Research Council CoG MagTendon No. 772817, and the FCT Project MagTT PTDC/CTM-CTM/ 29930/2017 (POCI-01-0145-FEDER-29930

Effect of simplifications of bone and components inclination on the elastohydrodynamic lubrication modeling of metal-on-metal hip resurfacing prosthesis

It is important to study the lubrication mechanism of metal-on-metal hip resurfacing prosthesis in order to understand its overall tribological performance, thereby minimize the wear particles. Previous elastohydrodynamic lubrication studies of metal-on-metal hip resurfacing prosthesis neglected the effects of the orientations of the cup and head. Simplified pelvic and femoral bone models were also adopted for the previous studies. These simplifications may lead to unrealistic predictions. For the first time, an elastohydrodynamic lubrication model was developed and solved for a full metal-onmetal hip resurfacing arthroplasty. The effects of the orientations of components and the realistic bones on the lubrication performance of metal-on-metal hip resurfacing prosthesis were investigated by comparing the full model with simplified models. It was found that the orientation of the head played a very important role in the prediction of pressure distributions and film profiles of the metal-on-metal hip resurfacing prosthesis. The inclination of the hemispherical cup up to 45 had no appreciable effect on the lubrication performance of the metal-on-metal hip resurfacing prosthesis. Moreover, the combined effect of material properties and structures of bones was negligible. Future studies should focus on higher inclination angles, smaller coverage angle and microseparation related to the occurrences of edge loading. © IMechE 2012