EXPLAIN Fragile-X: an explorative, longitudinal study on the characterization, treatment pathways, and patient-related outcomes of Fragile X Syndrome

BACKGROUND: Fragile X syndrome (FXS), caused by a mutation of the FMR1 gene on the X chromosome, is the most common inherited form of intellectual disability and autism spectrum disorders. Comprehensive data are lacking, however, on the characteristics and management patients with FXS in Germany. METHODS/DESIGN: EXPLAIN is a prospective, observational, longitudinal registry with a non-probability sampling approach. It collects data on patient characteristics, therapeutic interventions, psychosocial parameters (including those of family members and caregivers), quality of life of caregiver and patient, caregiver burden, and health economic parameters, such as hospitalisation time. It is designed to include data from 300 patients in ambulatory care from about 50 centres that employ psychiatrists, paediatricians, neurologists, and other relevant specialists, in Germany. The study was initiated in March, 2013. Patients will be followed for at least two years. DISCUSSION: The registry is expected to provide much-needed data on the characteristics and management of patients with FXS in Germany. It will also allow comparisons with other countries, and will enable gap analyses based on current guidelines for management of these patients. TRIAL REGISTRATION: The ClinicalTrials.gov identifier is NCT01711606

A 0535+26: an X-ray/Optical Tour

We compiled X-ray and Optical observations of the accreting X-ray binary system A 0535+262 since its discovery in 1975, that will allow us to shed light on the unpredictable behavior of this binary system. We present the data in terms of the Be-disk interaction with the neutron star companion. In addition, we show recent results from the continuous monitoring of this source by the Gamma-ray Burst Monitor(GBM), on board the Fermi observatory, since its launch in 2008 June 11.Comment: 4 pages, 5 figures, Conference proceeding of "Astrophysics of Neutron Stars 2010 - a conference in honor of M. Ali Alpar", 2-6 August 2010, Cesme, Izmir, Turke

Characterization, treatment patterns, and patient-related outcomes of patients with Fragile X syndrome in Germany: final results of the observational EXPLAIN-FXS study

BACKGROUND: As data on the phenotype, characteristics and management of patients with Fragile X Syndrome (FXS) are limited, we aimed to collect such data in Germany in experienced centres involved in the treatment of such patients. METHODS: EXPLAIN-FXS is a prospective observational (non-interventional) study (registry) performed between April 2013 and January 2016 at 18 sites in Germany. Requirements for patient participation included confirmed diagnosis of FXS by genetic testing (>200 CGG repeats) and written informed consent. Patients were followed for up to 2 years. RESULTS: Seventy-five patients (84.0 % males, mean age 16.7 +/- 14.5 years, ranging from 2 - 82 years) were analysed. The mean 6-item score, determined according to Giangreco (J Pediatr 129:611-614, 1996), was 6.9 +/- 2.5 points. At least one neurological finding each was noted in 53 patients (69.7 %). Specifically, ataxia was noted in 5 patients (6.6 %), lack of fine motor skills in 40 patients, (52.6 %), muscle tonus disorder in 4 patients (5.3 %), and other neurological disorders in 39 patients (51.3 %). Spasticity was not noted in any patient. Seizures were reported in 6 patients (8.1 %), anxiety disorders in 22 patients (30.1 %), depression in 7 patients (9.6 %), ADHD/ADD in 36 patients (49.3 %), impairment of social behavior in 39 patients (53.4 %), and other comorbidities in 23 patients (31.5 %). The mean Aberrant Behaviour Checklist Community Edition (ABC-C) score on behavioral symptoms, obtained in 71 patients at first documentation, was 48.4 +/- 27.8 (median 45.0, range 5-115). The mean visual analogue scale (VAS) score, obtained in 59 patients at first documentation, was 84.9 +/- 14.6 points (median 90; range 50 - 100). CONCLUSIONS: This report describes the largest cohort of patients with FXS in Europe. The reported observations indicate a substantial burden of disease for patients and their caregivers. Based on these observations, an early expert psychiatric diagnosis is recommended for suspected FXS patients. Further recommendations include multimodal and multi-professional management that is tailored to the individual patient's needs

A 0535+26 in the August/September 2005 outburst observed by RXTE and INTEGRAL

In this Letter we present results from INTEGRAL and RXTE observations of the spectral and timing behavior of the High Mass X-ray Binary A 0535+26 during its August/September 2005 normal (type I) outburst with an average flux F(5-100keV)~400mCrab. The search for cyclotron resonance scattering features (fundamental and harmonic) is one major focus of the paper. Our analysis is based on data from INTEGRAL and RXTE Target of Opportunity Observations performed during the outburst. The pulse period is determined. X-ray pulse profiles in different energy ranges are analyzed. The broad band INTEGRAL and RXTE pulse phase averaged X-ray spectra are studied. The evolution of the fundamental cyclotron line at different luminosities is analyzed. The pulse period P is measured to be 103.39315(5)s at MJD 53614.5137. Two absorption features are detected in the phase averaged spectra at E_1~45keV and E_2~100keV. These can be interpreted as the fundamental cyclotron resonance scattering feature and its first harmonic and therefore the magnetic field can be estimated to be B~4x10^12G.Comment: 4 pages, 5 figures, accepted for publication in A&A Letter

Peculiar outburst of A 0535+26 observed with INTEGRAL, RXTE and Suzaku

A normal outburst of the Be/X-ray binary system A0535+26 has taken place in August 2009. It is the fourth in a series of normal outbursts that have occured around the periastron passage of the source, but is unusual by starting at an earlier orbital phase and by presenting a peculiar double-peaked light curve. A first "flare" (lasting about 9 days from MJD 55043 on) reached a flux of 440 mCrab. The flux then decreased to less than 220 mCrab, and increased again reaching 440 mCrab around the periastron at MJD 55057. Target of Opportunity observations have been performed with INTEGRAL, RXTE and Suzaku. First results of these observations are presented, with special emphasis on the cyclotron lines present in the X-ray spectrum of the source, as well as in the pulse period and energy dependent pulse profiles of the source.Comment: 6 pages, Accepted for publication on PoS, Proceedings of "The Extreme sky: Sampling the Universe above 10 keV", held in Otranto (Italy) in October 200

The INTEGRAL view of the Soft Gamma-ray Repeater SGR 1806-20

We present the results obtained by INTEGRAL on the Soft-Gamma Ray Repeater SGR 1806-20. In particular we report on the temporal and spectral properties of the bursts detected during a moderately active period of the source in September and October 2003 and on the search for quiescent emission.Comment: To appear in the proceedings (ESA-SP) of the 5th INTEGRAL Workshop, "The INTEGRAL UNIVERSE", Munich, 16-20 February 200

Two years of INTEGRAL monitoring of GRS 1915+105 Part 1: multiwavelength coverage with INTEGRAL, RXTE, and the Ryle radio Telescope

(Abridged) We report the results of monitoring observations of the Galactic microquasar GRS 1915+105 performed simultaneously with INTEGRAL and RXTE Ryle . We present the results of the whole \integral campaign, report the sources that are detected and their fluxes and identify the classes of variability in which GRS 1915+105 is found. The accretion ejection connections are studied in a model independent manner through the source light curves, hardness ratio, and color color diagrams. During a period of steady ``hard'' X-ray state (the so-called class chi) we observe a steady radio flux. We then turn to 3 particular observations during which we observe several types of soft X-ray dips and spikes cycles, followed by radio flares. During these observations GRS 1915+105 is in the so-called nu, lambda, and beta classes of variability. The observation of ejections during class lambda are the first ever reported. We generalize the fact that a (non-major) discrete ejection always occurs, in GRS 1915+105, as a response to an X-ray sequence composed of a spectrally hard X-ray dip terminated by an X-ray spike marking the disappearance of the hard X-ray emission above 18 keV. We also identify the trigger of the ejection as this X-ray spike. A possible correlation between the amplitude of the radio flare and the duration of the X-ray dip is found in our data. In this case the X-ray dips prior to ejections could be seen as the time during which the source accumulates energy and material that is ejected later.Comment: 17 pages, 14 figures. Accepted for publication in ApJ, scheduled for the March 20, 2008, vol676 issue. Table 3 has been degrade

Magnetic Fields of Accreting X-Ray Pulsars with the Rossi X-Ray Timing Explorer

Using a consistent set of models, we parameterized the X-ray spectra of all accreting pulsars in the Rossi X-ray Timing Explorer database which exhibit Cyclotron Resonance Scattering Features (CRSFs, or cyclotron lines). These sources in our sample are Her X-1, 4U 0115+63, Cen X-3, 4U 1626-67, XTE J1946-274, Vela X-1, 4U 1907+09, 4U 1538-52, GX 301-2, and 4U 0352+309 (X Per). We searched for correlations among the spectral parameters, concentrating on how the cyclotron line energy relates to the continuum and therefore how the neutron star B-field influences the X-Ray emission. As expected, we found a correlation between the CRSF energy and the spectral cutoff energy. However, with our consistent set of fits we found that the relationship is more complex than what has been reported previously. Also, we found that not only does the width of the cyclotron line correlate with the energy (as suggested by theory), but that the width scaled by the energy correlates with the depth of the feature. We discuss the implications of these results, including the possibility that accretion directly affects the relative alignment of the neutron star spin and dipole axes. Lastly, we comment on the current state of fitting phenomenological models to spectra in the RXTE/BeppoSAX era and the need for better theoretical models of the X-Ray continua of accreting pulsars.Comment: 36 Pages, 9 Figures, 9 Tables, ApJ in pres

The pre-outburst flare of the A 0535+26 August/September 2005 outburst

We study the spectral and temporal behavior of the High Mass X-ray Binary A 0535+26 during a `pre-outburst flare' which took place ~5 d before the peak of a normal (type I) outburst in August/September 2005. We compare the studied behavior with that observed during the outburst. We analyse RXTE observations that monitored A 0535+26 during the outburst. We complete spectral and timing analyses of the data. We study the evolution of the pulse period, present energy-dependent pulse profiles both at the initial pre-outburst flare and close to outburst maximum, and measure how the cyclotron resonance-scattering feature (hereafter CRSF) evolves. We present three main results: a constant period P=103.3960(5)s is measured until periastron passage, followed by a spin-up with a decreasing period derivative of Pdot=(-1.69+/-0.04)x10^(-8)s/s at MJD 53618, and P remains constant again at the end of the main outburst. The spin-up provides evidence for the existence of an accretion disk during the normal outburst. We measure a CRSF energy of Ecyc~50kev during the pre-outburst flare, and Ecyc~46kev during the main outburst. The pulse shape, which varies significantly during both pre-outburst flare and main outburst, evolves strongly with photon energy.Comment: 4 pages, 4 figures, accepted for publication in A&A Letters. To be published in parallel to Postnov et al. 200

Small-world networks: Evidence for a crossover picture

Watts and Strogatz [Nature 393, 440 (1998)] have recently introduced a model for disordered networks and reported that, even for very small values of the disorder $p$ in the links, the network behaves as a small-world. Here, we test the hypothesis that the appearance of small-world behavior is not a phase-transition but a crossover phenomenon which depends both on the network size $n$ and on the degree of disorder $p$. We propose that the average distance $\ell$ between any two vertices of the network is a scaling function of $n / n^*$. The crossover size $n^*$ above which the network behaves as a small-world is shown to scale as $n^*(p \ll 1) \sim p^{-\tau}$ with $\tau \approx 2/3$.Comment: 5 pages, 5 postscript figures (1 in color), Latex/Revtex/multicols/epsf. Accepted for publication in Physical Review Letter