The role of coronary artery calcification score in clinical practice

<p>Abstract</p> <p>Background</p> <p>Coronary artery calcification (CAC) measured by electron-beam computed tomography (EBCT) has been well studied in the prediction of coronary artery disease (CAD). We sought to evaluate the impact of the CAC score in the diagnostic process immediately after its introduction in a large tertiary referral centre.</p> <p>Methods</p> <p>598 patients with no history of CAD who underwent EBCT for evaluation of CAD were retrospectively included into the study. Ischemia detection test results (exercise stress test, single photon emission computed tomography or ST segment analysis on 24 hours ECG detection), as well as the results of coronary angiography (CAG) were collected.</p> <p>Results</p> <p>The mean age of the patients was 55 ± 11 years (57% male). Patients were divided according to CAC scores; group A < 10, B 10 – 99, C 100 – 399 and D ≥ 400 (304, 135, 89 and 70 patients respectively). Ischemia detection tests were performed in 531 (89%) patients; negative ischemia results were found in 362 patients (183 in group A, 87 in B, 58 in C, 34 in D). Eighty-eight percent of the patients in group D underwent CAG despite negative ischemia test results, against 6% in group A, 16% in group B and 29% in group C. A positive ischemia test was found in 74 patients (25 in group A, 17 in B, 16 in C, 16 in D). In group D 88% (N = 14) of the patients with a positive ischemia test were referred for CAG, whereas 38 – 47% in group A-C.</p> <p>Conclusion</p> <p>Our study showed that patients with a high CAC score are more often referred for CAG. The CAC scores can be used as an aid in daily cardiology practice to determine further decision making.</p

Report on the sixth blind test of organic crystal structure prediction methods.

The sixth blind test of organic crystal structure prediction (CSP) methods has been held, with five target systems: a small nearly rigid molecule, a polymorphic former drug candidate, a chloride salt hydrate, a co-crystal and a bulky flexible molecule. This blind test has seen substantial growth in the number of participants, with the broad range of prediction methods giving a unique insight into the state of the art in the field. Significant progress has been seen in treating flexible molecules, usage of hierarchical approaches to ranking structures, the application of density-functional approximations, and the establishment of new workflows and `best practices' for performing CSP calculations. All of the targets, apart from a single potentially disordered Z' = 2 polymorph of the drug candidate, were predicted by at least one submission. Despite many remaining challenges, it is clear that CSP methods are becoming more applicable to a wider range of real systems, including salts, hydrates and larger flexible molecules. The results also highlight the potential for CSP calculations to complement and augment experimental studies of organic solid forms.The organisers and participants are very grateful to the crystallographers who supplied the candidate structures: Dr. Peter Horton (XXII), Dr. Brian Samas (XXIII), Prof. Bruce Foxman (XXIV), and Prof. Kraig Wheeler (XXV and XXVI). We are also grateful to Dr. Emma Sharp and colleagues at Johnson Matthey (Pharmorphix) for the polymorph screening of XXVI, as well as numerous colleagues at the CCDC for assistance in organising the blind test. Submission 2: We acknowledge Dr. Oliver Korb for numerous useful discussions. Submission 3: The Day group acknowledge the use of the IRIDIS High Performance Computing Facility, and associated support services at the University of Southampton, in the completion of this work. We acknowledge funding from the EPSRC (grants EP/J01110X/1 and EP/K018132/1) and the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC through grant agreements n. 307358 (ERC-stG- 2012-ANGLE) and n. 321156 (ERC-AG-PE5-ROBOT). Submission 4: I am grateful to Mikhail Kuzminskii for calculations of molecular structures on Gaussian 98 program in the Institute of Organic Chemistry RAS. The Russian Foundation for Basic Research is acknowledged for financial support (14-03-01091). Submission 5: Toine Schreurs provided computer facilities and assistance. I am grateful to Matthew Habgood at AWE company for providing a travel grant. Submission 6: We would like to acknowledge support of this work by GlaxoSmithKline, Merck, and Vertex. Submission 7: The research was financially supported by the VIDI Research Program 700.10.427, which is financed by The Netherlands Organisation for Scientific Research (NWO), and the European Research Council (ERC-2010-StG, grant agreement n. 259510-KISMOL). We acknowledge the support of the Foundation for Fundamental Research on Matter (FOM). Supercomputer facilities were provided by the National Computing Facilities Foundation (NCF). Submission 8: Computer resources were provided by the Center for High Performance Computing at the University of Utah and the Extreme Science and Engineering Discovery Environment (XSEDE), supported by NSF grant number ACI-1053575. MBF and GIP acknowledge the support from the University of Buenos Aires and the Argentinian Research Council. Submission 9: We thank Dr. Bouke van Eijck for his valuable advice on our predicted structure of XXV. We thank the promotion office for TUT programs on advanced simulation engineering (ADSIM), the leading program for training brain information architects (BRAIN), and the information and media center (IMC) at Toyohashi University of Technology for the use of the TUT supercomputer systems and application software. We also thank the ACCMS at Kyoto University for the use of their supercomputer. In addition, we wish to thank financial supports from Conflex Corp. and Ministry of Education, Culture, Sports, Science and Technology. Submission 12: We thank Leslie Leiserowitz from the Weizmann Institute of Science and Geoffrey Hutchinson from the University of Pittsburgh for helpful discussions. We thank Adam Scovel at the Argonne Leadership Computing Facility (ALCF) for technical support. Work at Tulane University was funded by the Louisiana Board of Regents Award # LEQSF(2014-17)-RD-A-10 “Toward Crystal Engineering from First Principles”, by the NSF award # EPS-1003897 “The Louisiana Alliance for Simulation-Guided Materials Applications (LA-SiGMA)”, and by the Tulane Committee on Research Summer Fellowship. Work at the Technical University of Munich was supported by the Solar Technologies Go Hybrid initiative of the State of Bavaria, Germany. Computer time was provided by the Argonne Leadership Computing Facility (ALCF), which is supported by the Office of Science of the U.S. Department of Energy under contract DE-AC02-06CH11357. Submission 13: This work would not have been possible without funding from Khalifa University’s College of Engineering. I would like to acknowledge Prof. Robert Bennell and Prof. Bayan Sharif for supporting me in acquiring the resources needed to carry out this research. Dr. Louise Price is thanked for her guidance on the use of DMACRYS and NEIGHCRYS during the course of this research. She is also thanked for useful discussions and numerous e-mail exchanges concerning the blind test. Prof. Sarah Price is acknowledged for her support and guidance over many years and for providing access to DMACRYS and NEIGHCRYS. Submission 15: The work was supported by the United Kingdom’s Engineering and Physical Sciences Research Council (EPSRC) (EP/J003840/1, EP/J014958/1) and was made possible through access to computational resources and support from the High Performance Computing Cluster at Imperial College London. We are grateful to Professor Sarah L. Price for supplying the DMACRYS code for use within CrystalOptimizer, and to her and her research group for support with DMACRYS and feedback on CrystalPredictor and CrystalOptimizer. Submission 16: R. J. N. acknowledges financial support from the Engineering and Physical Sciences Research Council (EPSRC) of the U.K. [EP/J017639/1]. R. J. N. and C. J. P. acknowledge use of the Archer facilities of the U.K.’s national high-performance computing service (for which access was obtained via the UKCP consortium [EP/K014560/1]). C. J. P. also acknowledges a Leadership Fellowship Grant [EP/K013688/1]. B. M. acknowledges Robinson College, Cambridge, and the Cambridge Philosophical Society for a Henslow Research Fellowship. Submission 17: The work at the University of Delaware was supported by the Army Research Office under Grant W911NF-13-1- 0387 and by the National Science Foundation Grant CHE-1152899. The work at the University of Silesia was supported by the Polish National Science Centre Grant No. DEC-2012/05/B/ST4/00086. Submission 18: We would like to thank Constantinos Pantelides, Claire Adjiman and Isaac Sugden of Imperial College for their support of our use of CrystalPredictor and CrystalOptimizer in this and Submission 19. The CSP work of the group is supported by EPSRC, though grant ESPRC EP/K039229/1, and Eli Lilly. The PhD students support: RKH by a joint UCL Max-Planck Society Magdeburg Impact studentship, REW by a UCL Impact studentship; LI by the Cambridge Crystallographic Data Centre and the M3S Centre for Doctoral Training (EPSRC EP/G036675/1). Submission 19: The potential generation work at the University of Delaware was supported by the Army Research Office under Grant W911NF-13-1-0387 and by the National Science Foundation Grant CHE-1152899. Submission 20: The work at New York University was supported, in part, by the U.S. Army Research Laboratory and the U.S. Army Research Office under contract/grant number W911NF-13-1-0387 (MET and LV) and, in part, by the Materials Research Science and Engineering Center (MRSEC) program of the National Science Foundation under Award Number DMR-1420073 (MET and ES). The work at the University of Delaware was supported by the U.S. Army Research Laboratory and the U.S. Army Research Office under contract/grant number W911NF-13-1- 0387 and by the National Science Foundation Grant CHE-1152899. Submission 21: We thank the National Science Foundation (DMR-1231586), the Government of Russian Federation (Grant No. 14.A12.31.0003), the Foreign Talents Introduction and Academic Exchange Program (No. B08040) and the Russian Science Foundation, project no. 14-43-00052, base organization Photochemistry Center of the Russian Academy of Sciences. Calculations were performed on the Rurik supercomputer at Moscow Institute of Physics and Technology. Submission 22: The computational results presented have been achieved in part using the Vienna Scientific Cluster (VSC). Submission 24: The potential generation work at the University of Delaware was supported by the Army Research Office under Grant W911NF-13-1-0387 and by the National Science Foundation Grant CHE-1152899. Submission 25: J.H. and A.T. acknowledge the support from the Deutsche Forschungsgemeinschaft under the program DFG-SPP 1807. H-Y.K., R.A.D., and R.C. acknowledge support from the Department of Energy (DOE) under Grant Nos. DE-SC0008626. This research used resources of the Argonne Leadership Computing Facility at Argonne National Laboratory, which is supported by the Office of Science of the U.S. Department of Energy under Contract No. DE-AC02-06CH11357. This research used resources of the National Energy Research Scientific Computing Center, which is supported by the Office of Science of the U.S. Department of Energy under Contract No. DEAC02-05CH11231. Additional computational resources were provided by the Terascale Infrastructure for Groundbreaking Research in Science and Engineering (TIGRESS) High Performance Computing Center and Visualization Laboratory at Princeton University.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1107/S2052520616007447

Stroke Awareness in Luxemburg: Deficit concerning Symptoms and Risk Factors

Background Awareness of stroke risk factors is important for stroke prevention. Knowledge of stroke symptoms and awareness regarding the necessity of seeking urgent stroke treatment are vital to provide rapid admission to a stroke unit. Data on this specific knowledge in Luxemburg are lacking. METHODS We investigated 420 patients from the Department of Neurology and their relatives using a questionnaire. There were 44% men and 56% women; 25% were immigrants and 75% Luxemburgish nationals; 13% already had had a stroke or transient ischemic attack (TIA); and the mean age was 55 years ranging from 18 to 87 years. Results A total of 88% of participants knew that a stroke occurs in the head/brain. In all, 10% of participants did not know any symptom of a stroke. The most frequently quoted symptoms (>15%) were paralysis/weakness (36%), speech disorders (32%), cranial nerve deficit (16%), vertigo (15%), and visual disorders (15%). Sensory deficits were mentioned by only 4% of patients. Known risk factors (>15%) were smoking (40%), hypertension (32%), alcohol (32%), poor nutrition (28%), high cholesterol (26%), stress (23%), and lack of exercise (19%). Age (4%), diabetes (6%), carotid stenosis (2%), and heart disease (1%) were less frequently known. In all, 11% of participants did not know any risk factor of a stroke. A total of 89% of participants would correctly call the 112 (emergency phone number). The following groups were better informed: Luxemburgish nationals, younger people, and participants with higher education level. Stroke/TIA patients were better informed concerning stroke symptoms, but unfortunately not concerning how to react in the case of a stroke. There was no relevant gender difference. Discussion Although most of the participants knew what to do in the case of a stroke, they did not know the relevant stroke symptoms and risk factors. Future campaigns should therefore focus on risk factors and symptoms, and should address immigrants, elderly persons, less-educated persons, and patients who had already suffered a stroke/TIA

Principle and perspectives of hydrogen production through biocatalyzed electrolysis

Biocatalyzed electrolysis is a novel biological hydrogen production process with the potential to efficiently convert a wide range of dissolved organic materials in wastewaters. Even substrates formerly regarded to be unsuitable for hydrogen production due to the endothermic nature of the involved conversion reactions can be converted with this technology. Biocatalyzed electrolysis achieves this by utilizing electrochemically active micro-organisms that are capable of generating electrical current from the oxidation of organic matter. When this biological anode is coupled to a proton reducing cathode by means of a power supply, hydrogen is generated. In the biocatalyzed electrolysis experiments presented in this article acetate is used as a model compound. In theory, biocatalyzed electrolysis of acetate requires applied voltages that can be as low as 0.14V, while hydrogen production by means of conventional water electrolysis, in practice, requires applied voltages well above 1.6V. At an applied voltage of 0.5V the biocatalyzed electrolysis setup used in this study, produces approximately 0.02m3 H2/m3 reactor liquid volume/day from acetate at an overall efficiency of 53±3.5%. This performance was mainly limited by the current design of the system, diffusional loss of hydrogen from the cathode to the anode chamber and high overpotentials associated with the cathode reaction. In this article we show that optimization of the process will allow future volumetric hydrogen production rates above 10m3 H2/m3 reactor liquid volume/day at overall efficiencies exceeding 90% and applied voltages as low as 0.3–0.4V. In the future, this will make biocatalyzed electrolysis an attractive technology for hydrogen production from a wide variety of wastewaters.

Increased local delivery of antagomir therapeutics to the rodent myocardium using ultrasound and microbubbles

Recent developments in microRNA (miRNA) research have identified these as important mediators in the pathophysiological response upon myocardial infarction (MI). Specific miRNAs can inhibit the translation of entire groups of mRNAs, which are involved in specific processes in the pathophysiology after MI, e.g. the fibrotic, apoptotic or angiogenic response. By modulating miRNAs in the heart, these processes can be tuned to improve cardiac function. Antagomirs are effective miRNA-inhibitors, but have a low myocardial specificity and cardiac antagomir treatment therefore requires high doses, which causes side effects. In the present study, ultrasound-triggered microbubble destruction (UTMD) was studied to increase specific delivery of antagomir to the myocardium. Healthy control mice were treated with UTMD and sacrificed at 30min, 24h and 48h, after which antagomir delivery in the heart was analyzed, both qualitatively and quantitatively. Additionally, potential harmful effects of treatment were analyzed by monitoring ECG, analyzing neutrophil invasion and cell death in the heart, and measuring troponin I after treatment. Finally, UTMD was tested for delivery of antagomir in a model of ischemia-reperfusion (I/R) injury. We found that UTMD can significantly increase local antagomir delivery to the non-ischemic heart with modest side-effects like neutrophil invasion without causing apoptosis. Delivered antagomirs enter cardiomyocytes within 30min after treatment and remains there for at least 48h. Interestingly, after I/R injury antagomir already readily enters the infarcted zone and we observed no additional benefit of UTMD for antagomir delivery. This study is the first to explore cardiac antagomir delivery using UTMD. In addition, it is the first to study tissue distribution of short RNA based therapeutics (~22 base pairs) at both the cellular and organ levels after UTMD to the heart in general. In summary, UTMD provides a myocardial delivery strategy for non-vascular permeable cardiac conditions later in the I/R response or chronic conditions like cardiac hypertrophy

The Role of Virulence Proteins in Protection Conferred by Bordetella pertussis Outer Membrane Vesicle Vaccines

The limited protective immunity induced by acellular pertussis vaccines demands development of novel vaccines that induce broader and longer-lived immunity. In this study, we investigated the protective capacity of outer membrane vesicle pertussis vaccines (omvPV) with different antigenic composition in mice to gain insight into which antigens contribute to protection. We showed that total depletion of virulence factors (bvg(-) mode) in omvPV led to diminished protection despite the presence of high antibody levels. Antibody profiling revealed overlap in humoral responses induced by vaccines in bvg(-) and bvg(+) mode, but the potentially protective responses in the bvg(+) vaccine were mainly directed against virulence-associated outer membrane proteins (virOMPs) such as BrkA and Vag8. However, deletion of either BrkA or Vag8 in our outer membrane vesicle vaccines did not affect the level of protection. In addition, the vaccine-induced immunity profile, which encompasses broad antibody and mixed T-helper 1, 2 and 17 responses, was not changed. We conclude that the presence of multiple virOMPs in omvPV is crucial for protection against Bordetella pertussis. This protective immunity does not depend on individual proteins, as their absence or low abundance can be compensated for by other virOMPs

To love and play: Testing the association of adult playfulness with the relationship personality and relationship satisfaction

It is hypothesized that playfulness in adults is positively associated with relationship satisfaction and that specific types of attachment and love are related with this trait. Findings, based on two samples of adults that are currently in a relationship (N = 161 and 598), show that playfulness is positively associated with relationship satisfaction—albeit low in effect size. Playfulness shares about 17 % overlapping variance with different types of love and attachment; particularly, Seduction, low Market Orientation, Attachment, and Love were predictive for playfulness. While gender differences only played a minor role it was shown that playfulness mediates about 5.7 % of the gender differences in the inclination to Sexuality. Overall, findings are in the expected direction. The discussion highlights the importance of considering multidimensional measures for playfulness and satisfaction and gives future research directions