Perspectives on the revised Ghent criteria for the diagnosis of Marfan syndrome

Three international nosologies have been proposed for the diagnosis of Marfan syndrome (MFS): the Berlin nosology in 1988; the Ghent nosology in 1996 (Ghent-1); and the revised Ghent nosology in 2010 (Ghent-2). We reviewed the literature and discussed the challenges and concepts of diagnosing MFS in adults. Ghent-1 proposed more stringent clinical criteria, which led to the confirmation of MFS in only 32%-53% of patients formerly diagnosed with MFS according to the Berlin nosology. Conversely, both the Ghent-1 and Ghent-2 nosologies diagnosed MFS, and both yielded similar frequencies of MFS in persons with a causative FBN1 mutation (90% for Ghent-1 versus 92% for Ghent-2) and in persons not having a causative FBN1 mutation (15% versus 13%). Quality criteria for diagnostic methods include objectivity, reliability, and validity. However, the nosology-based diagnosis of MFS lacks a diagnostic reference standard and, hence, quality criteria such as sensitivity, specificity, or accuracy cannot be assessed. Medical utility of diagnosis implies congruency with the historical criteria of MFS, as well as with information about the etiology, pathogenesis, diagnostic triggers, prognostic triggers, and potential complications of MFS. In addition, social and psychological utilities of diagnostic criteria include acceptance by patients, patient organizations, clinicians and scientists, practicability, costs, and the reduction of anxiety. Since the utility of a diagnosis or exclusion of MFS is context-dependent, prioritization of utilities is a strategic decision in the process of nosology development. Screening tests for MFS should be used to identify persons with MFS. To confirm the diagnosis of MFS, Ghent-1 and Ghent-2 perform similarly, but Ghent-2 is easier to use. To maximize the utility of the diagnostic criteria of MFS, a fair and transparent process of nosology development is essential

Systolic and Hyper-Systolic Algorithms for the Gravitational N-Body Problem, with an Application to Brownian Motion

A systolic algorithm rhythmically computes and passes data through a network of processors. We investigate the performance of systolic algorithms for implementing the gravitational N-body problem on distributed-memory computers. Systolic algorithms minimize memory requirements by distributing the particles between processors. We show that the performance of systolic routines can be greatly enhanced by the use of non-blocking communication, which allows particle coordinates to be communicated at the same time that force calculations are being carried out. Hyper-systolic algorithms reduce the communication complexity at the expense of increased memory demands. As an example of an application requiring large N, we use the systolic algorithm to carry out direct-summation simulations using 10^6 particles of the Brownian motion of the supermassive black hole at the center of the Milky Way galaxy. We predict a 3D random velocity of 0.4 km/s for the black hole.Comment: 33 pages, 10 postscript figure

Mitral valve prolapse syndrome and MASS phenotype: stability of aortic dilatation but progression of mitral valve prolapse

AbstractBackgroundMitral valve prolapse syndrome (MVPS) and MASS phenotype (MASS) are Marfan-like syndromes that exhibit aortic dilatation and mitral valve prolapse. Unlike in Marfan syndrome (MFS), the presence of ectopia lentis and aortic aneurysm preclude diagnosis of MVPS and MASS. However, it is unclear whether aortic dilatation and mitral valve prolapse remain stable in MVPS or MASS or whether they progress like in MFS.MethodsThis retrospective longitudinal observational study examines clinical characteristics and long-term prognosis of 44 adults with MVPS or MASS (18 men, 26 women aged 38±17years) as compared with 81 adults with Marfan syndrome (MFS) with similar age and sex distribution. The age at final contact was 42±15years with mean follow-up of 66±49months.ResultsAt baseline, ectopia lentis and aortic sinus aneurysm were absent in MVPS and MASS, and systemic scores defined by the revised Ghent nosology were lower than in MFS (all P<.001). Unlike in MFS, no individual with MVPS and MASS developed aortic complications (P<.001). In contrast, the incidence of endocarditis (P=.292), heart failure (P=.644), and mitral valve surgery (P=.140) was similar in all syndromes. Cox regression analysis identified increased LV end-diastolic (P=.013), moderate MVR (P=.019) and flail MV leaflet (P=.017) as independent predictors of mitral valve surgery.ConclusionsThe study provides evidence that MVPS and MASS are Marfan-like syndromes with stability of aortic dilatation but with progression of mitral valve prolapse. Echocardiographic characteristics of mitral valve disease rather than the type of syndrome, predict clinical progression of mitral valve prolapse

Stellar Processes Near the Massive Black Hole in the Galactic Center

A massive black hole resides in the center of most, perhaps all galaxies. The one in the center of our home galaxy, the Milky Way, provides a uniquely accessible laboratory for studying in detail the connections and interactions between a massive black hole and the stellar system in which it grows; for investigating the effects of extreme density, velocity and tidal fields on stars; and for using stars to probe the central dark mass and probe post-Newtonian gravity in the weak- and strong-field limits. Recent results, open questions and future prospects are reviewed in the wider context of the theoretical framework and physical processes that underlie them. Contents: [1] Introduction (1.1) Astrophysical context (1.2) Science questions (1.3) Scope and connections to related topics [2] Observational overview: Stars in the Galactic center (2.1) The central 100 parsecs (2.2) The central parsec [3] Stellar dynamics at extreme densities (3.1) Physical processes and scales (3.2) The stellar cusp in the Galactic center (3.3) Mass segregation (3.4) Stellar Collisions [4] Probing the dark mass with stellar dynamics (4.1) Weighing and pinpointing the dark mass (4.2) Constraints on non-BH dark mass alternatives (4.3) Limits on MBH binarity (4.4) High-velocity runaway stars [5] Probing post-Newtonian gravity near the MBH (5.1) Relativistic orbital effects (5.2) Gravitational lensing [6] Strong star-MBH interactions (6.1) Tidal disruption (6.2) Dissipative interactions with the MBH [7] The riddle of the young stars (7.1) The difficulties of forming or importing stars near a MBH (7.2) Proposed solutions (7.3) Feeding the MBH with stellar winds [8] Outlook (8.1) Progress report (8.2) Future directionsComment: Invited review article, to appear in Physics Reports. 101 p

The characteristics of millisecond pulsar emission: I. Spectra, pulse shapes and the beaming fraction

We have monitored a large sample of millisecond pulsars using the 100-m Effelsberg radio telescope in order to compare their radio emission properties to the slowly rotating population. With some notable exceptions, our findings suggest that the two groups of objects share many common properties. A comparison of the spectral indices between samples of normal and millisecond pulsars demonstrates that millisecond pulsar spectra are not significantly different from those of normal pulsars. There is evidence, however, that millisecond pulsars are slightly less luminous and less efficient radio emitters compared to normal pulsars. We confirm recent suggestions that a diversity exists among the luminosities of millisecond pulsars with the isolated millisecond pulsars being less luminous than the binary millisecond pulsars. There are indications that old millisecond pulsars exhibit somewhat flatter spectra than the presumably younger ones. We present evidence that millisecond pulsar profiles are only marginally more complex than those found among the normal pulsar population. Moreover, the development of the profiles with frequency is rather slow, suggesting very compact magnetospheres. The profile development seems to anti-correlate with the companion mass and the spin period, again suggesting that the amount of mass transfer in a binary system might directly influence the emission properties. The angular radius of radio beams of millisecond pulsars does not follow the scaling predicted from a canonical pulsar model which is applicable for normal pulsars. Instead they are systematically smaller. The smaller inferred luminosity and narrower emission beams will need to be considered in future calculations of the birth-rate of the Galactic population.Comment: 40 pages, 14 figures, accepted for publication in Ap

T-2 toxin induced Salmonella Typhimurium intoxication results in decreased Salmonella numbers in the cecum contents of pigs, despite marked effects on Salmonella-host cell interactions

The mycotoxin T-2 toxin and Salmonella Typhimurium infections pose a significant threat to human and animal health. Interactions between both agents may result in a different outcome of the infection. Therefore, the aim of the presented study was to investigate the effects of low and relevant concentrations of T-2 toxin on the course of a Salmonella Typhimurium infection in pigs. We showed that the presence of 15 and 83 μg T-2 toxin per kg feed significantly decreased the amount of Salmonella Typhimurium bacteria present in the cecum contents, and a tendency to a reduced colonization of the jejunum, ileum, cecum, colon and colon contents was noticed. In vitro, proteomic analysis of porcine enterocytes revealed that a very low concentration of T-2 toxin (5 ng/mL) affects the protein expression of mitochondrial, endoplasmatic reticulum and cytoskeleton associated proteins, proteins involved in protein synthesis and folding, RNA synthesis, mitogen-activated protein kinase signaling and regulatory processes. Similarly low concentrations (1-100 ng/mL) promoted the susceptibility of porcine macrophages and intestinal epithelial cells to Salmonella Typhimurium invasion, in a SPI-1 independent manner. Furthermore, T-2 toxin (1-5 ng/mL) promoted the translocation of Salmonella Typhimurium over an intestinal porcine epithelial cell monolayer. Although these findings may seem in favour of Salmonella Typhimurium, microarray analysis showed that T-2 toxin (5 ng/mL) causes an intoxication of Salmonella Typhimurium, represented by a reduced motility and a downregulation of metabolic and Salmonella Pathogenicity Island 1 genes. This study demonstrates marked interactions of T-2 toxin with Salmonella Typhimurium pathogenesis, resulting in bacterial intoxication

European hydrogen train the trainer framework for responders: Outcomes of the HyResponder project

HyResponder is a European Hydrogen Train the Trainer programme for responders. This paper describes the key outputs of the project and the steps taken to develop and implement a long-term sustainable train the trainer programme in hydrogen safety for responders across Europe and beyond. This FCH2 JU (now Clean Hydrogen Joint Undertaking) funded project has built on the successful outcomes of the previous HyResponse project. HyResponder has developed further and updated educational, operational, and virtual reality training for trainers of responders to reflect the state-of-the-art in hydrogen safety, including liquid hydrogen, and expand the programme across Europe and specifically within the 10 countries represented directly within the project consortium: Austria, Belgium, the Czech Republic, France, Germany, Italy, Norway, Spain, Switzerland, and the United Kingdom. For the first time, four levels of educational materials from fire fighter through to specialist have been developed. The digital training resources are available on the e-Platform (https://hyresponder.eu/e-platform/). The revised European Emergency Response Guide is now available to all stakeholders. The resources are intended to be used to support national training programs. They are available in 8 languages: Czech, Dutch, English, French, German, Italian, Norwegian and Spanish. Through the HyResponder activities, trainers from across Europe have undertaken joint actions which are in turn being used to inform the delivery of regional and national training both within and beyond the project. The established pan-European network of trainers is shaping the future in the important for inherently safer deployment of hydrogen systems and infrastructure across Europe and enhancing the reach and impact of the programme