SIMULATIONS OF FISHING EFFECTS ON THE SOUTHERN BENGUELA FISH COMMUNITY USING AN INDIVIDUAL-BASED MODEL: LEARNING FROM A COMPARISON WITH ECOSIM

By applying an individual-based model (OSMOSE) to the southern Benguela ecosystem, a multispecies analysis is proposed, complementary to that provided by the application of ECOPATH/ECOSIM models. To reconstruct marine foodwebs, OSMOSE is based on the hypothesis that predation is a size-structured process. In all, 12 fish species, chosen for their importance in terms of biomass and catches, are explicitly modelled. Growth, reproduction and mortality parameters are required to model their dynamics and trophic interactions. Maps of mean spatial distribution of the species are compiled from published literature. Taking into account the spatial component is necessary because spatial co-occurrence determines potential interactions between predatory fish and prey fish of suitable size. To explore ecosystem effects of fishing, different fishing scenarios, previously examined using ECOSIM, are simulated using the OSMOSE model. They explore the effects of targeting fish species in the southern Benguela considered to be predators (Cape hake Merluccius capensis and M. paradoxus) or prey (anchovy Engraulis encrasicolus, sardine Sardinops sagax, round herring Etrumeus whiteheadi). Simulation results are compared and are generally consistent with those obtained using an ECOSIM model. This cross-validation appears to be a promising means of evaluating the robustness of model outputs, when separate validation of marine ecosystem models are still difficult to perform.Afr. J. mar. Sci. 26: 95–11

Using Uppaal for the secure and optimal control of AGV fleets

The design and realization of an on line control system for automated guided vehicles (AGV) is addressed. A synthesis method is proposed based on the use of the model checking tool for timed automata Uppaal. This system has to route the vehicles while ensuring the system safeness, a good coordination between vehicles and the optimization of performance criteria.This problem is like synthesizing a Ramadge and Wonham supervisor combined with routing and optimizing functions, that is an ongoing problem within the supervisory control theory. The proposed concepts are validated through a software tool suite based on Uppaal in order to generate optimal traces and interact with an AGV system emulated with Arena

Peripheral Sensitization Increases Opioid Receptor Expression And Activation By Crotalphine In Rats

Inflammation enhances the peripheral analgesic efficacy of opioid drugs, but the mechanisms involved in this phenomenon have not been fully elucidated. Crotalphine (CRP), a peptide that was first isolated from South American rattlesnake C.d. terrificus venom, induces a potent and long-lasting anti-nociceptive effect that is mediated by the activation of peripheral opioid receptors. Because the high efficacy of CRP is only observed in the presence of inflammation, we aimed to elucidate the mechanisms involved in the CRP anti-nociceptive effect induced by inflammation. Using real-time RT-PCR, western blot analysis and ELISA assays, we demonstrate that the intraplantar injection of prostaglandin E2 (PGE2) increases the mRNA and protein levels of the μ- and κ-opioid receptors in the dorsal root ganglia (DRG) and paw tissue of rats within 3 h of the injection. Using conformation state-sensitive antibodies that recognize activated opioid receptors, we show that PGE 2, alone does not increase the activation of these opioid receptors but that in the presence of PGE2, the activation of specific opioid receptors by CRP and selective μ- and κ-opioid receptor agonists (positive controls) increases. Furthermore, PGE2 down-regulated the expression and activation of the δ-opioid receptor. CRP increased the level of activated mitogen-activated protein kinases in cultured DRG neurons, and this increase was dependent on the activation of protein kinase Cζ. This CRP effect was much more prominent when the cells were pretreated with PGE 2. These results indicate that the expression and activation of peripheral opioid receptors by opioid-like drugs can be up- or down-regulated in the presence of an acute injury and that acute tissue injury enhances the efficacy of peripheral opioids. © 2014 Zambelli et al.93Stein, C., Peripheral mechanisms of opioid analgesia (1993) Anesth Analg, 76, pp. 182-191Obara, I., Parkitna, J.R., Korostynski, M., Makuch, W., Kaminska, D., Local peripheral opioid effects and expression of opioid genes in the spinal cord and dorsal root ganglia in neuropathic and inflammatory pain (2009) Pain, 141, pp. 283-291Puehler, W., Zollner, C., Brack, A., Shaqura, M.A., Krause, H., Schafer, M., Stein, C., Rapid upregulation of mu opioid receptor mRNA in dorsal root ganglia in response to peripheral inflammation depends on neuronal conduction (2004) Neuroscience, 129 (2), pp. 473-479. , DOI 10.1016/j.neuroscience.2004.06.086, PII S030645220400627XMaekawa, K., Minami, M., Masuda, T., Satoh, M., Expression of mu- and kappa-, but not delta-, opioid receptor mRNAs is enhanced in the spinal dorsal horn of the arthritic rats (1996) Pain, 64 (2), pp. 365-371. , DOI 10.1016/0304-3959(95)00132-8Cahill, C.M., Morinville, A., Hoffert, C., O'Donnell, D., Beaudet, A., Up-regulation and trafficking of delta opioid receptor in a model of chronic inflammation: Implications for pain control (2003) Pain, 101 (1-2), pp. 199-208. , DOI 10.1016/S0304-3959(02)00333-0Hassan, A.H.S., Ableitner, A., Stein, C., Herz, A., Inflammation of the rat paw enhances axonal transport of opioid receptors in the sciatic nerve and increases their density in the inflamed tissue (1993) Neuroscience, 55 (1), pp. 185-195. , DOI 10.1016/0306-4522(93)90465-RZollner, C., Shaqura, M.A., Bopaiah, C.P., Mousa, S., Stein, C., Schafer, M., Painful inflammation-induced increase in mu-opioid receptor binding and G-protein coupling in primary afferent neurons (2003) Molecular Pharmacology, 64 (2), pp. 202-210. , DOI 10.1124/mol.64.2.202Shaqura, M.A., Zollner, C., Mousa, S.A., Stein, C., Schafer, M., Characterization of mu Opioid Receptor Binding and G Protein Coupling in Rat Hypothalamus, Spinal Cord, and Primary Afferent Neurons during Inflammatory Pain (2004) Journal of Pharmacology and Experimental Therapeutics, 308 (2), pp. 712-718. , DOI 10.1124/jpet.103.057257Antonijevic, I., Mousa, S.A., Schafer, M., Stein, C., Perineurial defect and peripheral opioid analgesia in inflammation (1995) J Neurosci, 15, pp. 165-172Mousa, S.A., Zhang, Q., Sitte, N., Ji, R.-R., Stein, C., beta-endorphin-containing memory-cells and mu-opioid receptors undergo transport to peripheral inflamed tissue (2001) Journal of Neuroimmunology, 115 (1-2), pp. 71-78. , DOI 10.1016/S0165-5728(01)00271-5, PII S0165572801002715Konno, K., Picolo, G., Gutierrez, V.P., Brigatte, P., Zambelli, V.O., Crotalphine, a novel potent analgesic peptide from the venom of the South American rattlesnake Crotalus durissus terrificus (2008) PeptidesGutierrez, V.P., Zambelli, V.O., Picolo, G., Chacur, M., Sampaio, S.C., The peripheral L-arginine-nitric oxide-cyclic GMP pathway and ATP-sensitive K channels are involved in the antinociceptive effect of crotalphine on neuropathic pain in rats Behav Pharmacol, 23, pp. 14-24Gutierrez, V.P., Konno, K., Chacur, M., Sampaio, S.C., Picolo, G., Crotalphine induces potent antinociception in neuropathic pain by acting at peripheral opioid receptors (2008) Eur J Pharmacol, 594, pp. 84-92Granados-Soto, V., Rufino, M.D.O., Gomes, L.L.D., Ferreira, S.H., Evidence for the involvement of the nitric oxide-cGMP pathway in the antinociception of morphine in the formalin tests (1997) European Journal of Pharmacology, 340 (2-3), pp. 177-180. , DOI 10.1016/S0014-2999(97)01399-X, PII S001429999701399XSachs, D., Cunha, F.Q., Ferreira, S.H., Peripheral analgesic blockade of hypernociception: Activation of arginine/NO/cGMP/protein kinase G/ATP-sensitive K+ channel pathway (2004) Proceedings of the National Academy of Sciences of the United States of America, 101 (10), pp. 3680-3685. , DOI 10.1073/pnas.0308382101Pacheco, D.F., Reis, G.M.L., Francischi, J.N., Castro, M.S.A., Perez, A.C., Duarte, I.D.G., delta-Opioid receptor agonist SNC80 elicits peripheral antinociception via delta1 and delta2 receptors and activation of the L-arginine/nitric oxide/cyclic GMP pathway (2005) Life Sciences, 78 (1), pp. 54-60. , DOI 10.1016/j.lfs.2005.04.032, PII S0024320505006697Amarante, L.H., Duarte, I.D.G., The kappa-opioid agonist (+/-)-bremazocine elicits peripheral antinociception by activation of the L-arginine/nitric oxide/cyclic GMP pathway (2002) European Journal of Pharmacology, 454 (1), pp. 19-23. , DOI 10.1016/S0014-2999(02)02275-6, PII S0014299902022756Cunha, T.M., Roman-Campos, D., Lotufo, C.M., Duarte, H.L., Souza, G.R., Morphine peripheral analgesia depends on activation of the PI3Kgamma/AKT/nNOS/NO/KATP signaling pathway Proc Natl Acad Sci U S A, 107, pp. 4442-4447Law, B.K., Waltner-Law, M.E., Entingh, A.J., Chytil, A., Aakre, M.E., Norgaard, P., Moses, H.L., Salicylate-induced growth arrest is associated with inhibition of p70s6k and down-regulation of c-Myc, cyclin D1, cyclin A, and proliferating cell nuclear antigen (2000) Journal of Biological Chemistry, 275 (49), pp. 38261-38267. , DOI 10.1074/jbc.M005545200Belcheva, M.M., Clark, A.L., Haas, P.D., Serna, J.S., Hahn, J.W., Kiss, A., Coscia, C.J., Mu and kappa opioid receptors activate ERK/MAPK via different protein kinase C isoforms and secondary messengers in astrocytes (2005) Journal of Biological Chemistry, 280 (30), pp. 27662-27669. , DOI 10.1074/jbc.M502593200Connor, M., Christie, M.J., Opioid receptor signalling mechanisms (1999) Clinical and Experimental Pharmacology and Physiology, 26 (7), pp. 493-499. , DOI 10.1046/j.1440-1681.1999.03049.xZimmermann, M., Ethical guidelines for investigations of experimental pain in conscious animals (1983) Pain, 16, pp. 109-110Picolo, G., Giorgi, R., Bernardi, M.M., Cury, Y., The antinociceptive effect of Crotalus durissus terrificus snake venom is mainly due to a supraspinally integrated response (1998) Toxicon, 36 (1), pp. 223-227. , DOI 10.1016/S0041-0101(97)00048-2, PII S0041010197000482Von Banchet, G.S., Scholze, A., Schaible, H.-G., Prostaglandin E2 increases the expression of the neurokinin1 receptor in adult sensory neurones in culture: A novel role of prostaglandins (2003) British Journal of Pharmacology, 139 (3), pp. 672-680Picolo, G., Giorgi, R., Cury, Y., delta-Opioid receptors and nitric oxide mediate the analgesic effect of Crotalus durissus terrificus snake venom (2000) European Journal of Pharmacology, 391 (1-2), pp. 55-62. , DOI 10.1016/S0014-2999(99)00934-6, PII S0014299999009346Gendron, L., Pintar, J.E., Chavkin, C., Essential role of mu opioid receptor in the regulation of delta opioid receptor-mediated antihyperalgesia (2007) Neuroscience, 150 (4), pp. 807-817. , DOI 10.1016/j.neuroscience.2007.09.060, PII S0306452207012365Lomas, L.M., Barrett, A.C., Terner, J.M., Lysle, D.T., Picker, M.J., Sex differences in the potency of kappa opioids and mixed-action opioids administered systemically and at the site of inflammation against capsaicin-induced hyperalgesia in rats (2007) Psychopharmacology, 191 (2), pp. 273-285. , DOI 10.1007/s00213-006-0663-1Ji, Y., Murphy, A.Z., Traub, R.J., Estrogen modulation of morphine analgesia of visceral pain in female rats is supraspinally and peripherally mediated (2007) J Pain, 8, pp. 494-502. , JPicolo, G., Cury, Y., Peripheral neuronal nitric oxide synthase activity mediates the antinociceptive effect of Crotalus durissus terrificus snake venom, a delta- and kappa-opioid receptor agonist (2004) Life Sciences, 75 (5), pp. 559-573. , DOI 10.1016/S0024-3205(04)00292-9, PII S0024320504002929Randall, L.O., Selitto, J.J., A method for measurement of analgesia activity on inflamed tissue (1957) Arch Inst Pharmacodyn, 111, pp. 209-219Bradford, M.M., A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding (1976) Anal Biochem, 72, pp. 248-254Gupta, A., Decaillot, F.M., Gomes, I., Tkalych, O., Heimann, A.S., Conformation state sensitive antibodies to G-protein coupled receptors (2006) J Biol ChemCunha, T.M., Souza, G.R., Domingues, A.C., Carreira, E.U., Lotufo, C.M., Stimulation of peripheral Kappa opioid receptors inhibits inflammatory hyperalgesia via activation of the PI3Kgamma/AKT/nNOS/NO signaling pathway Mol Pain, 8, p. 10Bruchas, M.R., Chavkin, C., Kinase cascades and ligand-directed signaling at the kappa opioid receptor Psychopharmacology, 210, pp. 137-147. , BerlBerra, E., Diaz-Meco, M.T., Dominguez, I., Municio, M.M., Sanz, L., Lozano, J., Chapkin, R.S., Moscat, J., Protein kinase C zeta isoform is critical for mitogenic signal transduction (1993) Cell, 74 (3), pp. 555-563Kwong, K., Lee, L.-Y., Prostaglandin E2 potentiates a TTX-resistant sodium current in rat capsaicin-sensitive vagal pulmonary sensory neurones (2005) Journal of Physiology, 564 (2), pp. 437-450. , DOI 10.1113/jphysiol.2004.078725Southall, M.D., Vasko, M.R., Prostaglandin receptor subtypes, EP3C and EP4, mediate the prostaglandin E2-induced cAMP production and sensitization of sensory neurons (2001) J Biol Chem, 276, pp. 16083-16091Ferreira, S.H., Lorenzetti, B.B., Prostaglandin hyperalgesia, IV: A metabolic process (1981) Prostaglandins, 21, pp. 789-792Stein, C., Millan, M.J., Shippenberg, T.S., Peter, K., Herz, A., Peripheral opioid receptors mediating antinociception in inflammation. Evidence for involvement of mu, delta and kappa receptors (1989) Journal of Pharmacology and Experimental Therapeutics, 248 (3), pp. 1269-1275Mousa, S.A., Machelska, H., Schafer, M., Stein, C., Immunohistochemical localization of endomorphin-1 and endomorphin-2 in immune cells and spinal cord in a model of inflammatory pain (2002) Journal of Neuroimmunology, 126 (1-2), pp. 5-15. , DOI 10.1016/S0165-5728(02)00049-8, PII S0165572802000498Furst, S., Riba, P., Friedmann, T., Timar, J., Al-Khrasani, M., Obara, I., Makuch, W., Schmidhammer, H., Peripheral versus central antinociceptive actions of 6-amino acid-substituted derivatives of 14-O-methyloxymorphone in acute and inflammatory pain in the rat (2005) Journal of Pharmacology and Experimental Therapeutics, 312 (2), pp. 609-618. , DOI 10.1124/jpet.104.075176Nunez, S., Lee, J.-S., Zhang, Y., Bai, G., Ro, J.Y., Role of peripheral mu-opioid receptors in inflammatory orofacial muscle pain (2007) Neuroscience, 146 (3), pp. 1346-1354. , DOI 10.1016/j.neuroscience.2007.02.024, PII S030645220700173XSchafer, M., Imai, Y., Uhl, G.R., Stein, C., Inflammation enhances peripheral mu-opioid receptor-mediated analgesia, but not mu-opioid receptor transcription in dorsal root ganglia (1995) Eur J Pharmacol, 279, pp. 165-169Zhou, L., Zhang, Q., Stein, C., Schafer, M., Contribution of opioid receptors on primary afferent versus sympathetic neurons to peripheral opioid analgesia (1998) Journal of Pharmacology and Experimental Therapeutics, 286 (2), pp. 1000-1006Lecat, S., Bucher, B., Mely, Y., Galzi, J.-L., Mutations in the extracellular amino-terminal domain of the NK2 neurokinin receptor abolish cAMP signaling but preserve intracellular calcium responses (2002) Journal of Biological Chemistry, 277 (44), pp. 42034-42048. , DOI 10.1074/jbc.M203606200Decaillot, F.M., Befort, K., Filliol, D., Yue, S.Y., Walker, P., Kieffer, B.L., Opioid receptor random mutagenesis reveals a mechanism for G protein-coupled receptor activation (2003) Nature Structural Biology, 10 (8), pp. 629-636. , DOI 10.1038/nsb950Selley, D.E., Breivogel, C.S., Childers, S.R., Modification of G protein-coupled functions by low-pH pretreatment of membranes from NG108-15 cells: Increase in opioid agonist efficacy by decreased inactivation of G proteins (1993) Molecular Pharmacology, 44 (4), pp. 731-741Belcheva, M.M., Vogel, Z., Ignatova, E., Avidor-Reiss, T., Zippel, R., Levy, R., Young, E.C., Coscia, C.J., Opioid modulation of extracellular signal-regulated protein kinase activity is ras-dependent and involves G(betagamma) subunits (1998) Journal of Neurochemistry, 70 (2), pp. 635-645Bohn, L.M., Belcheva, M.M., Coscia, C.J., Mitogenic signaling via endogenous kappa-opioid receptors in C6 glioma cells: Evidence for the involvement of protein kinase C and the mitogen- activated protein kinase signaling cascade (2000) Journal of Neurochemistry, 74 (2), pp. 564-573. , DOI 10.1046/j.1471-4159.2000.740564.xBruchas, M.R., Macey, T.A., Lowe, J.D., Chavkin, C., Kappa opioid receptor activation of p38 MAPK is GRK3- and arrestin-dependent in neurons and astrocytes (2006) Journal of Biological Chemistry, 281 (26), pp. 18081-18089. , http://www.jbc.org/cgi/reprint/281/26/18081, DOI 10.1074/jbc.M513640200Sweatt, J.D., Mitogen-activated protein kinases in synaptic plasticity and memory (2004) Curr Opin Neurobiol, 14, pp. 311-317Thomas, G.M., Huganir, R.L., MAPK cascade signalling and synaptic plasticity (2004) Nature Reviews Neuroscience, 5 (3), pp. 173-183Carlezon Jr., W.A., Duman, R.S., Nestler, E.J., The many faces of CREB (2005) Trends in Neurosciences, 28 (8), pp. 436-445. , DOI 10.1016/j.tins.2005.06.005, PII S016622360500158XBruchas, M.R., Xu, M., Chavkin, C., Repeated swim stress induces kappa opioid-mediated activation of extracellular signal-regulated kinase 1/2 (2008) Neuroreport, 19, pp. 1417-1422Kreibich, A.S., Blendy, J.A., cAMP response element-binding protein is required for stress but not cocaine-induced reinstatement (2004) Journal of Neuroscience, 24 (30), pp. 6686-6692. , DOI 10.1523/JNEUROSCI.1706-04.2004Bruchas, M.R., Yang, T., Schreiber, S., DeFino, M., Kwan, S.C., Li, S., Chavkin, C., Long-acting kappa opioid antagonists disrupt receptor signaling and produce noncompetitive effects by activating c-Jun N-terminal kinase (2007) Journal of Biological Chemistry, 282 (41), pp. 29803-29811. , http://www.jbc.org/cgi/reprint/282/41/29803, DOI 10.1074/jbc.M705540200Melief, E.J., Miyatake, M., Bruchas, M.R., Chavkin, C., Ligand-directed c-Jun N-terminal kinase activation disrupts opioid receptor signaling (2010) Proc Natl Acad Sci U S A, 107, pp. 11608-11613Velazquez, K.T., Mohammad, H., Sweitzer, S.M., Protein kinase C in pain: Involvement of multiple isoforms (2007) Pharmacological Research, 55 (6), pp. 578-589. , DOI 10.1016/j.phrs.2007.04.006, PII S104366180700084

Involvement of formyl peptide receptors in the stimulatory effect of crotoxin on macrophages co-cultivated with tumour cells

Crotoxin (CTX) is the main neurotoxic component of Crotalus durissus terrificus snake venom. It inhibits tumour growth and modulates the function of macrophages, which are essential cells in the tumour microenvironment. the present study investigated the effect of CTX on the secretory activity of monocultured macrophages and macrophages co-cultivated with LLC-WRC 256 cells. the effect of the macrophage secretory activities on tumour cell proliferation was also evaluated. Macrophages pre-treated with CTX (0.3 mu g/mL) for 2 h were co-cultivated with LLC-WRC 256 cells, and the secretory activity of the macrophages was determined after 12, 24 and 48 h. the co-cultivation of CTX-treated macrophages with the tumour cells caused a 20% reduction in tumour cell proliferation. the production of both H2O2 and NO was increased by 41% and 29% after 24 or 48 h of co-cultivation, respectively, compared to the values for the co-cultures of macrophages of control. the level of secreted IL-1 beta increased by 3.7- and 3.2-fold after 12 h and 24 h of co-cultivation, respectively. Moreover, an increased level of LXA(4) (25%) was observed after 24 h of co-cultivation, and a 2.3- and 2.1-fold increased level of 15-epi-LXA(4) was observed after 24 h and 48 h, respectively. Boc-2, a selective antagonist of formyl peptide receptors, blocked both the stimulatory effect of CTX on the macrophage secretory activity and the inhibitory effect of these cells on tumour cell proliferation. Taken together, these results indicate that CTX enhanced the secretory activity of macrophages, which may contribute to the antitumour activity of these cells, and that activation of formyl peptide receptors appears to play a major role in this effect. (C) 2013 Elsevier B.V. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)PAPInstituto Nacional de Ciencia e Tecnologia em ToxinasButantan Inst, Lab Pathophysiol, BR-05503900 São Paulo, BrazilUniversidade Federal de São Paulo, Lab Inflammat & Vasc Pharmacol, BR-09913030 Diadema, SP, BrazilUniv São Paulo, Fac Med, BR-01246000 São Paulo, BrazilUniv São Paulo, Inst Biomed Sci, Dept Anat, BR-05508900 São Paulo, BrazilUniv São Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05508900 São Paulo, BrazilButantan Inst, Special Lab Pain & Signaling, BR-05503900 São Paulo, BrazilUniversidade Federal de São Paulo, Lab Inflammat & Vasc Pharmacol, BR-09913030 Diadema, SP, BrazilFAPESP: 09/52330-9Instituto Nacional de Ciencia e Tecnologia em Toxinas: INCTTOX 2008/57898-0Web of Scienc

Coronary Artery Plaque Characterization from CCTA Scans Using Deep Learning and Radiomics

Assessing coronary artery plaque segments in coronary CT angiography scans is an important task to improve patient management and clinical outcomes, as it can help to decide whether invasive investigation and treatment are necessary. In this work, we present three machine learning approaches capable of performing this task. The first approach is based on radiomics, where a plaque segmentation is used to calculate various shape-, intensity- and texture-based features under different image transformations. A second approach is based on deep learning and relies on centerline extraction as sole prerequisite. In the third approach, we fuse the deep learning approach with radiomic features. On our data the methods reached similar scores as simulated fractional flow reserve (FFR) measurements, which - in contrast to our methods - requires an exact segmentation of the whole coronary tree and often time-consuming manual interaction. In literature, the performance of simulated FFR reaches an AUC between 0.79–0.93 predicting an abnormal invasive FFR that demands revascularization. The radiomics approach achieves an AUC of 0.84, the deep learning approach 0.86 and the combined method 0.88 for predicting the revascularization decision directly. While all three proposed methods can be determined within seconds, the FFR simulation typically takes several minutes. Provided representative training data in sufficient quantities, we believe that the presented methods can be used to create systems for fully automatic non-invasive risk assessment for a variety of adverse cardiac events

Clinical risk factors and atherosclerotic plaque extent to define risk for major events in patients without obstructive coronary artery disease: the long-term coronary computed tomography angiography CONFIRM registry.

AimsIn patients without obstructive coronary artery disease (CAD), we examined the prognostic value of risk factors and atherosclerotic extent.Methods and resultsPatients from the long-term CONFIRM registry without prior CAD and without obstructive (≥50%) stenosis were included. Within the groups of normal coronary computed tomography angiography (CCTA) (N = 1849) and non-obstructive CAD (N = 1698), the prognostic value of traditional clinical risk factors and atherosclerotic extent (segment involvement score, SIS) was assessed with Cox models. Major adverse cardiac events (MACE) were defined as all-cause mortality, non-fatal myocardial infarction, or late revascularization. In total, 3547 patients were included (age 57.9 ± 12.1 years, 57.8% male), experiencing 460 MACE during 5.4 years of follow-up. Age, body mass index, hypertension, and diabetes were the clinical variables associated with increased MACE risk, but the magnitude of risk was higher for CCTA defined atherosclerotic extent; adjusted hazard ratio (HR) for SIS >5 was 3.4 (95% confidence interval [CI] 2.3-4.9) while HR for diabetes and hypertension were 1.7 (95% CI 1.3-2.2) and 1.4 (95% CI 1.1-1.7), respectively. Exclusion of revascularization as endpoint did not modify the results. In normal CCTA, presence of ≥1 traditional risk factors did not worsen prognosis (log-rank P = 0.248), while it did in non-obstructive CAD (log-rank P = 0.025). Adjusted for SIS, hypertension and diabetes predicted MACE risk in non-obstructive CAD, while diabetes did not increase risk in absence of CAD (P-interaction = 0.004).ConclusionAmong patients without obstructive CAD, the extent of CAD provides more prognostic information for MACE than traditional cardiovascular risk factors. An interaction was observed between risk factors and CAD burden, suggesting synergistic effects of both

Coronary atherosclerosis scoring with semiquantitative CCTA risk scores for prediction of major adverse cardiac events: Propensity score-based analysis of diabetic and non-diabetic patients.

AIMS:We aimed to compare semiquantitative coronary computed tomography angiography (CCTA) risk scores - which score presence, extent, composition, stenosis and/or location of coronary artery disease (CAD) - and their prognostic value between patients with and without diabetes mellitus (DM). Risk scores derived from general chest-pain populations are often challenging to apply in DM patients, because of numerous confounders. METHODS:Out of a combined cohort from the Leiden University Medical Center and the CONFIRM registry with 5-year follow-up data, we performed a secondary analysis in diabetic patients with suspected CAD who were clinically referred for CCTA. A total of 732 DM patients was 1:1 propensity-matched with 732 non-DM patients by age, sex and cardiovascular risk factors. A subset of 7 semiquantitative CCTA risk scores was compared between groups: 1) any stenosis ≥50%, 2) any stenosis ≥70%, 3) stenosis-severity component of the coronary artery disease-reporting and data system (CAD-RADS), 4) segment involvement score (SIS), 5) segment stenosis score (SSS), 6) CT-adapted Leaman score (CT-LeSc), and 7) Leiden CCTA risk score. Cox-regression analysis was performed to assess the association between the scores and the primary endpoint of all-cause death and non-fatal myocardial infarction. Also, area under the receiver-operating characteristics curves were compared to evaluate discriminatory ability. RESULTS:A total of 1,464 DM and non-DM patients (mean age 58 ± 12 years, 40% women) underwent CCTA and 155 (11%) events were documented after median follow-up of 5.1 years. In DM patients, the 7 semiquantitative CCTA risk scores were significantly more prevalent or higher as compared to non-DM patients (p ≤ 0.022). All scores were independently associated with the primary endpoint in both patients with and without DM (p ≤ 0.020), with non-significant interaction between the scores and diabetes (interaction p ≥ 0.109). Discriminatory ability of the Leiden CCTA risk score in DM patients was significantly better than any stenosis ≥50% and ≥70% (p = 0.003 and p = 0.007, respectively), but comparable to the CAD-RADS, SIS, SSS and CT-LeSc that also focus on the extent of CAD (p ≥ 0.265). CONCLUSION:Coronary atherosclerosis scoring with semiquantitative CCTA risk scores incorporating the total extent of CAD discriminate major adverse cardiac events well, and might be useful for risk stratification of patients with DM beyond the binary evaluation of obstructive stenosis alone

The impact of Oportunidades on human capital and income distribution in Mexico: A top-down/bottom-up approach

This paper sets a computable general equilibrium model for the Mexican economy and a behavioural microsimulation model for Mexico's Oportunidades social transfers, and links the models in a bi-directional and iterative way. The model results suggest that partial equilibrium analysis may underestimate the effects of the program. Extending the coverage of the program leads to a significant increase in school attendance, which lowers labour supply and increases the equilibrium wages of the children who remain at work. The general equilibrium effect indirectly reduces income inequality and poverty at the national level

The global cardiovascular magnetic resonance registry (GCMR) of the society for cardiovascular magnetic resonance (SCMR): its goals, rationale, data infrastructure, and current developments

GCMR received seed funding from SCMR (SCMR_GRANT_001) for the development and maintenance of GCMR websites and database infrastructure