How quantizable matter gravitates: a practitioner's guide

We present the practical step-by-step procedure for constructing canonical gravitational dynamics and kinematics directly from any previously specified quantizable classical matter dynamics, and then illustrate the application of this recipe by way of two completely worked case studies. Following the same procedure, any phenomenological proposal for fundamental matter dynamics must be supplemented with a suitable gravity theory providing the coefficients and kinematical interpretation of the matter equations, before any of the two theories can be meaningfully compared to experimental data.Comment: 45 pages, no figure

Gravitational dynamics for all tensorial spacetimes carrying predictive, interpretable and quantizable matter

Only a severely restricted class of tensor fields can provide classical spacetime geometries, namely those that can carry matter field equations that are predictive, interpretable and quantizable. These three conditions on matter translate into three corresponding algebraic conditions on the underlying tensorial geometry, namely to be hyperbolic, time-orientable and energy-distinguishing. Lorentzian metrics, on which general relativity and the standard model of particle physics are built, present just the simplest tensorial spacetime geometry satisfying these conditions. The problem of finding gravitational dynamics---for the general tensorial spacetime geometries satisfying the above minimum requirements---is reformulated in this paper as a system of linear partial differential equations, in the sense that their solutions yield the actions governing the corresponding spacetime geometry. Thus the search for modified gravitational dynamics is reduced to a clear mathematical task.Comment: 47 pages, no figures, minor update

Validation of the revised IPSS at transplant in patients with myelodysplastic syndrome/transformed acute myelogenous leukemia receiving allogeneic stem cell transplantation

The International Prognostic Scoring System has been revised (IPSS-R) to predict prognosis of patients with myelodysplastic syndromes at diagnosis. To validate the use of the IPSS-R assesse

Impact of the revised International Prognostic Scoring System, cytogenetics and monosomal karyotype on outcome after allogeneic stem cell transplantation for myelodysplastic syndromes and secondary acute myeloid leukemia evolving from myelodysplastic syndromes : a retrospective multicenter study of the European Society of Blood and Marrow Transplantation

The aim of this study was to determine the impact of the revised 5-group International Prognostic Scoring System cytogenetic classification on outcome after allogeneic stem cell transplantation in patients with myelodysplastic syndromes or secondary acute myeloid leukemia who were reported to the European Society for Blood and Marrow Transplantation database. A total of 903 patients had sufficient cytogenetic information available at stem cell transplantation to be classified according to the 5-group classification. Poor and very poor risk according to this classification was an independent predictor of shorter relapse-free survival (hazard ratio 1.40 and 2.14), overall survival (hazard ratio 1.38 and 2.14), and significantly higher cumulative incidence of relapse (hazard ratio 1.64 and 2.76), compared to patients with very good, good or intermediate risk. When comparing the predictive performance of a series of Cox models both for relapse-free survival and for overall survival, a model with simplified 5-group cytogenetics (merging very good, good and intermediate cytogenetics) performed best. Furthermore, monosomal karyotype is an additional negative predictor for outcome within patients of the poor, but not the very poor risk group of the 5-group classification. The revised International Prognostic Scoring System cytogenetic classification allows patients with myelodysplastic syndromes to be separated into three groups with clearly different outcomes after stem cell transplantation. Poor and very poor risk cytogenetics were strong predictors of poor patient outcome. The new cytogenetic classification added value to prediction of patient outcome compared to prediction models using only traditional risk factors or the 3-group International Prognostic Scoring System cytogenetic classification.Peer reviewe

Effectiveness and safety of opicapone in Parkinson’s disease patients with motor fluctuations: the OPTIPARK open-label study

Background The efficacy and safety of opicapone, a once-daily catechol-O-methyltransferase inhibitor, have been established in two large randomized, placebo-controlled, multinational pivotal trials. Still, clinical evidence from routine practice is needed to complement the data from the pivotal trials. Methods OPTIPARK (NCT02847442) was a prospective, open-label, single-arm trial conducted in Germany and the UK under clinical practice conditions. Patients with Parkinson’s disease and motor fluctuations were treated with opicapone 50 mg for 3 (Germany) or 6 (UK) months in addition to their current levodopa and other antiparkinsonian treatments. The primary endpoint was the Clinician’s Global Impression of Change (CGI-C) after 3 months. Secondary assessments included Patient Global Impressions of Change (PGI-C), the Unified Parkinson’s Disease Rating Scale (UPDRS), Parkinson’s Disease Questionnaire (PDQ-8), and the Non-Motor Symptoms Scale (NMSS). Safety assessments included evaluation of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Results Of the 506 patients enrolled, 495 (97.8%) took at least one dose of opicapone. Of these, 393 (79.4%) patients completed 3 months of treatment. Overall, 71.3 and 76.9% of patients experienced any improvement on CGI-C and PGI-C after 3 months, respectively (full analysis set). At 6 months, for UK subgroup only (n = 95), 85.3% of patients were judged by investigators as improved since commencing treatment. UPDRS scores at 3 months showed statistically significant improvements in activities of daily living during OFF (mean ± SD change from baseline: − 3.0 ± 4.6, p < 0.0001) and motor scores during ON (− 4.6 ± 8.1, p < 0.0001). The mean ± SD improvements of − 3.4 ± 12.8 points for PDQ-8 and -6.8 ± 19.7 points for NMSS were statistically significant versus baseline (both p < 0.0001). Most of TEAEs (94.8% of events) were of mild or moderate intensity. TEAEs considered to be at least possibly related to opicapone were reported for 45.1% of patients, with dyskinesia (11.5%) and dry mouth (6.5%) being the most frequently reported. Serious TEAEs considered at least possibly related to opicapone were reported for 1.4% of patients. Conclusions Opicapone 50 mg was effective and generally well-tolerated in PD patients with motor fluctuations treated in clinical practice. Trial registration Registered in July 2016 at clinicaltrials.gov (NCT02847442)

Gravity actions from matter actions

Ausgehend von der Forderung, dass die Dynamik klassischer Materiefelder auf einer glatten Mannigfaltigkeit prädiktiv und quantisierbar sein muss, leiten wir einen Satz von „Mastergleichungen“ her, deren Lösungen die Dynamik (in Form einer Lagrangedichte) der den Materiegleichungen zugrundeliegenden Geometrie beschreiben. Es gelingt also das physikalische Problem der Suche nach geeigneten Gravitationsdynamiken für eine beliebige tensorielle Raumzeitgeometrie, die physikalische Materie tragen kann, in die bloß noch mathematische Frage nach der Lösung eines Systems von linearen partiellen Differentialgleichungen zu reformulieren. Dieses Ergebnis fußt auf der Einsicht, dass die Forderung nach der Prädiktivität und Quantisierbarkeit einer Materietheorie zunächst die möglichen Klassen der zugrundeliegenden Raumzeitgeometrien auf solche beschränkt, die bi-hyperbolisch sind und die Unterscheidung von positiven und negativen Energien zulassen. Gleichzeitig stellen solche Materietheorien bereits alle kinematischen Strukturen zur Verfügung, die nötig sind, um die Dynamik der Geometrie als Anfangswertproblem zu formulieren. Die Mastergleichungen stellen dann einen Ausdruck dafür dar, dass die Lagrangefunktion der Gravitationsdynamik, die die zeitliche Entwicklung von geometrischen Anfangsdaten beschreibt, eine Darstellung der Hyperflächendeformationsalgebra sein muss, welche sich ausgehend von der Dynamik der Materietheorie direkt berechnen lässt. Wir geben eine allgemeine Vorgehensweise an, mit der sich die Mastergleichungen für eine beliebige tensorielle Raumzeitgeometrie herleiten lassen und illustrieren dieses Verfahren anhand von vier physikalisch relevanten Beispielen. Die Arbeit wird abgerundet durch ein Studium von Energie-Impuls-Tensoren von Materie auf tensoriellen Raumzeiten.Starting from classical matter dynamics on a smooth manifold that are required to be predictive and quantizable, we derive a set of `gravitational master equations'' that determine the Lagrangian describing the dynamics of the geometry on which the matter dynamics are defined. We thus convert the physical problem of finding admissible gravitational dynamics for any tensorial geometry that can support physical matter equations into the clear mathematical task of solving a system of linear partial differential equations. This result builds on the insight that predictive and quantizable matter dynamics, on the one hand, restrict the class of admissible spacetime geometries to those that are bi-hyperbolic and energy-distinguishing, and, on the other hand, provide the necessary kinematical structure needed to formulate spacetime geometry dynamics as an initial value problem. The gravitational master equations then express the fact that the Lagrangian of the gravitational dynamics must arise as a representation of the algebra of hypersurface deformations---which can be calculated from the kinematical structure imprinted on the geometry by the matter field dynamics---on a suitable geometric phase space. We provide a general prescription of how to obtain the gravitational master equations for any candidate geometry and illustrate our procedure by way of four instructive examples. We solve the master equations for metric geometry supporting Maxwell theory, finding Einstein-Hilbert dynamics as the unique solution, and for a non-trivial composite geometry supporting modified Dirac dynamics. We also discuss generalized energy-momentum tensors of matter fields and their role as sources of the gravitational dynamics obtained from the gravitational master equations