Security Council Resolution 808: A Step Toward a Permanent International Court for the Prosecution of International Crimes and Human Rights Violations

This comment examines the difficulties involved in implementing Resolution 808, and also its contribution to the development of a permanent international criminal court (hereinafter ICC ). The comment begins with an overview of Security Council Resolution 808. The comment next considers the factors that have stopped previous attempts to create an ICC. Finally, the author proposes that a permanent ICC could and should be implemented and that the earlier difficulties in establishing such a tribunal have been overcome

Dynamic Changes in White Matter Abnormalities Correlate With Late Improvement and Deterioration Following TBI: A Diffusion Tensor Imaging Study.

OBJECTIVE: Traumatic brain injury (TBI) is not a single insult with monophasic resolution, but a chronic disease, with dynamic processes that remain active for years. We aimed to assess patient trajectories over the entire disease narrative, from ictus to late outcome. METHODS: Twelve patients with moderate-to-severe TBI underwent magnetic resonance imaging in the acute phase (within 1 week of injury) and twice in the chronic phase of injury (median 7 and 21 months), with some undergoing imaging at up to 2 additional time points. Longitudinal imaging changes were assessed using structural volumetry, deterministic tractography, voxel-based diffusion tensor analysis, and region of interest analyses (including corpus callosum, parasagittal white matter, and thalamus). Imaging changes were related to behavior. RESULTS: Changes in structural volumes, fractional anisotropy, and mean diffusivity continued for months to years postictus. Changes in diffusion tensor imaging were driven by increases in both axial and radial diffusivity except for the earliest time point, and were associated with changes in reaction time and performance in a visual memory and learning task (paired associates learning). Dynamic structural changes after TBI can be detected using diffusion tensor imaging and could explain changes in behavior. CONCLUSIONS: These data can provide further insight into early and late pathophysiology, and begin to provide a framework that allows magnetic resonance imaging to be used as an imaging biomarker of therapy response. Knowledge of the temporal pattern of changes in TBI patient populations also provides a contextual framework for assessing imaging changes in individuals at any given time point

Australian utility weights for the EORTC QLU-C10D, a multi-attribute utility instrument derived from the cancer-specific quality of life questionnaire, EORTC QLQ-C30

Background: The EORTC QLU-C10D is a new multi-attribute utility instrument derived from the widely-used cancer-specific quality of life questionnaire, EORTC QLQ-C30. The QLU-C10D contains ten dimensions (Physical, Role, Social and Emotional Functioning; Pain, Fatigue, Sleep, Appetite, Nausea, Bowel Problems), each with 4 levels. To be used in cost-utility analysis, country-specific valuation sets are required. Objective: To provide Australian utility weights for the QLU-C10D. Methods: An Australian online panel was quota sampled to ensure population representativeness by sex and age (≥18y). Participants completed a discrete choice experiment (DCE) consisting of 16 choice-pairs. Each pair comprised two QLU-C10D health states plus life expectancy. Data were analysed using conditional logistic regression, parameterised to fit the quality-adjusted life-year framework. Utility weights were calculated as the ratio of each QOL dimension-level coefficient to the coefficient on life expectancy. Results: 1979 panel members opted-in, 1904 (96%) completed at least one choice-pair, and 1846 (93%) completed all 16 choice-pairs. Dimension weights were generally monotonic: poorer levels within each dimension were generally associated with greater utility decrements. The dimensions that impacted most on choice were, in order, Physical Functioning, Pain, Role Functioning and Emotional Functioning. Oncology-relevant dimensions with moderate impact were Nausea and Bowel Problems. Fatigue, Trouble Sleeping and Appetite had relatively small impact. The value of the worst health state was -0.096, somewhat worse than death. Conclusions: This study provides the first country-specific value set for the QLU-C10D, which can facilitate cost-utility analyses when applied to data collected with the EORTC QLQ-C30, prospectively and retrospectively

From basic mechanisms to clinical applications in heart protection, new players in cardiovascular diseases and cardiac theranostics: meeting report from the third international symposium on "New frontiers in cardiovascular research"

In this meeting report, particularly addressing the topic of protection of the cardiovascular system from ischemia/reperfusion injury, highlights are presented that relate to conditioning strategies of the heart with respect to molecular mechanisms and outcome in patients' cohorts, the influence of co-morbidities and medications, as well as the contribution of innate immune reactions in cardioprotection. Moreover, developmental or systems biology approaches bear great potential in systematically uncovering unexpected components involved in ischemia-reperfusion injury or heart regeneration. Based on the characterization of particular platelet integrins, mitochondrial redox-linked proteins, or lipid-diol compounds in cardiovascular diseases, their targeting by newly developed theranostics and technologies opens new avenues for diagnosis and therapy of myocardial infarction to improve the patients' outcome

The rise and fall of the king : the correlation between FO Aquarii's low states and the White Dwarf's Spindown

The intermediate polar FO Aquarii experienced its first-reported low-accretion states in 2016, 2017, and 2018. We establish that these low states occurred shortly after the system's white dwarf (WD) began spinning down, after having spent a quarter-century spinning up. FO Aquarii is the only intermediate polar whose period derivative has undergone a sign change, and it has now done so twice. By combining our spin-pulse timings with previous data, we determine that the WD's spin period has varied quasi-sinusoidally since the system's discovery, and an extrapolation predicts that the white dwarf was spinning down during newly discovered low states in photographic plates from 1964, 1965, and 1974. Thus, FO Aquarii's low states appear to occur exclusively during epochs of spindown. Additionally, our time-series photometry of the 2016-18 low states reveals that the mode of accretion is extremely sensitive to the accretion rate; when the system is fainter than V~14.0, the accretion onto the WD is largely stream-fed, but when it is brighter, it is almost exclusively disk-fed. The system's grazing eclipse remained detectable throughout all observations, confirming the uninterrupted presence of a disk-like structure, regardless of the accretion state. Our observations are consistent with theoretical predictions that during the low states, the accretion disk dissipates into a ring of diamagnetic blobs. Finally, a new XMM-Newton observation from 2017 indicates that the system's anomalously soft X-ray spectrum and diminished X-ray luminosity in the wake of the 2016 low state appear to be long-lasting changes compared to pre-2016 observations.peer-reviewe

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

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 submissions, 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