An Extended and More Sensitive Search for Periodicities in RXTE/ASM X-ray Light Curves

We present the results of a systematic search in approximately 14 years of Rossi X-ray Timing Explorer All-Sky Monitor data for evidence of periodicities not reported by Wen et al. (2006). Two variations of the commonly used Fourier analysis search method have been employed to achieve significant improvements in sensitivity. The use of these methods and the accumulation of additional data have resulted in the detection of the signatures of the orbital periods of eight low-mass X-ray binary systems and of ten high-mass X-ray binaries not listed in the tables of Wen et al.Comment: 20 pages, 22 figures, in emulateapj format; submitted to ApJ

High accuracy power spectra including baryonic physics in dynamical Dark Energy models

The next generation mass probes will obtain information on non--linear power spectra P(k,z) and their evolution, allowing us to investigate the nature of Dark Energy. To exploit such data we need high precision simulations, extending at least up to scales of k 10 h/Mpc, where the effects of baryons can no longer be neglected. In this paper, we present a series of large scale hydrodynamical simulations for LCDM and dynamical Dark Energy (dDE) models, in which the equation of state parameter is z-dependent. The simulations include gas cooling, star formation and Supernovae feedback. They closely approximate the observed star formation rate and the observationally derived star/Dark Matter mass ratio in collapsed systems. Baryon dynamics cause spectral shifts exceeding 1% at k > 2-3 h/Mpc compared to pure n-body simulations in the LCDM simulations. This agrees with previous studies, although we find a smaller effect (~50%) on the power spectrum amplitude at higher k's. dDE exhibits similar behavior, even though the dDE simulations produce ~20% less stars than the analogous LCDM cosmologies. Finally, we show that the technique introduced in Casarini et al. to obtain spectra for any $w(z)$ cosmology from constant-w models at any redshift still holds when gas physics is taken into account. While this relieves the need to explore the entire functional space of dark energy state equations, we illustrate a severe risk that future data analysis could lead to misinterpretation of the DE state equation.Comment: 12 pages, 13 figures, minor changes to match the accepted version, MNRAS in pres

Therapeutic efficacy of microtube-embedded chondroitinase ABC in a canine clinical model of spinal cord injury

Many hundreds of thousands of people around the world are living with the long-term consequences of spinal cord injury and they need effective new therapies. Laboratory research in experimental animals has identified a large number of potentially translatable interventions but transition to the clinic is not straightforward. Further evidence of efficacy in more clinically-relevant lesions is required to gain sufficient confidence to commence human clinical trials. Of the many therapeutic candidates currently available, intraspinally applied chondroitinase ABC has particularly well documented efficacy in experimental animals. In this study we measured the effects of this intervention in a double-blinded randomized controlled trial in a cohort of dogs with naturally-occurring severe chronic spinal cord injuries that model the condition in humans. First, we collected baseline data on a series of outcomes: forelimb-hindlimb coordination (the prespecified primary outcome measure), skin sensitivity along the back, somatosensory evoked and transcranial magnetic motor evoked potentials and cystometry in 60 dogs with thoracolumbar lesions. Dogs were then randomized 1:1 to receive intraspinal injections of heat-stabilized, lipid microtube-embedded chondroitinase ABC or sham injections consisting of needle puncture of the skin. Outcome data were measured at 1, 3 and 6 months after intervention; skin sensitivity was also measured 24 h after injection (or sham). Forelimb-hindlimb coordination was affected by neither time nor chondroitinase treatment alone but there was a significant interaction between these variables such that coordination between forelimb and hindlimb stepping improved during the 6-month follow-up period in the chondroitinase-treated animals by a mean of 23%, but did not change in controls. Three dogs (10%) in the chondroitinase group also recovered the ability to ambulate without assistance. Sensitivity of the dorsal skin increased at 24 h after intervention in both groups but subsequently decreased to normal levels. Cystometry identified a non-significant improvement of bladder compliance at 1 month in the chondroitinase-injected dogs but this did not persist. There were no overall differences between groups in detection of sensory evoked potentials. Our results strongly support a beneficial effect of intraspinal injection of chondroitinase ABC on spinal cord function in this highly clinically-relevant model of chronic severe spinal cord injury. There was no evidence of long-term adverse effects associated with this intervention. We therefore conclude that this study provides strong evidence in support of initiation of clinical trials of chondroitinase ABC in humans with chronic spinal cord injury

Retreatment with brentuximab vedotin in patients with CD30-positive hematologic malignancies

BACKGROUND: Brentuximab vedotin is a CD30-directed antibody-drug conjugate. Retreatment with brentuximab vedotin monotherapy was investigated in patients with CD30-positive Hodgkin lymphoma (HL) or systemic anaplastic large cell lymphoma (ALCL) who relapsed after achieving complete or partial remission (CR or PR) with initial brentuximab vedotin therapy in a previous study (ClinicalTrials.gov NCT00947856). METHODS: Twenty-one patients with HL and 8 patients with systemic ALCL were retreated; 3 patients with systemic ALCL were retreated twice. Patients generally received brentuximab vedotin 1.8 mg/kg intravenously approximately every 3 weeks over 30 minutes as an outpatient infusion. The primary objectives of this study were to assess safety and to estimate antitumor activity of brentuximab vedotin retreatment. RESULTS: The objective response rate was 60% (30% CR) in HL patients and 88% (63% CR) in systemic ALCL patients. The estimated median duration of response for patients with an objective response was 9.5 months (range, 0.0+ to 28.0+ months) at the time of study closure. Of the 19 patients with objective response, 7 patients had not had an event of disease progression or death at the time of study closure; duration of response for these patients ranged from 3.5 to 28 months. Of the 11 patients with CR, 45% had response durations of over 1 year. Adverse events (AEs) occurring in ≥25% of patients during the retreatment period were generally similar in type and frequency to those observed in the pivotal trials of brentuximab vedotin monotherapy, with the exception of peripheral neuropathy, which is known to have a cumulative effect. Grade 3 or higher events were observed in 48% of patients; these were generally transient and managed by dose modifications or delays. Deaths due to AEs occurred in 3 HL patients; none were considered to be related to brentuximab vedotin retreatment. DISCUSSION: With the exception of a higher rate of peripheral motor neuropathy, retreatment with brentuximab vedotin was associated with similar side effects seen in the pivotal trials. CONCLUSIONS: Retreatment with brentuximab vedotin monotherapy is associated with response rates in 68% (39% CR) of patients with relapsed HL and systemic ALCL. TRIAL REGISTRATION: United States registry and results database ClinicalTrials.gov NCT00947856

First Results from Fermi GBM Earth Occultation Monitoring: Observations of Soft Gamma-Ray Sources Above 100 keV

The NaI and BGO detectors on the Gamma-ray Burst Monitor (GBM) on Fermi are now being used for long-term monitoring of the hard X-ray/low energy gamma-ray sky. Using the Earth occultation technique as demonstrated previously by the BATSE instrument on the Compton Gamma-Ray Observatory, GBM can be used to produce multiband light curves and spectra for known sources and transient outbursts in the 8 keV to 1 MeV energy range with its NaI detectors and up to 40 MeV with its BGO detectors. Over 85% of the sky is viewed every orbit, and the precession of the Fermi orbit allows the entire sky to be viewed every ~26 days with sensitivity exceeding that of BATSE at energies below ~25 keV and above ~1.5 MeV. We briefly describe the technique and present preliminary results using the NaI detectors after the first two years of observations at energies above 100 keV. Eight sources are detected with a significance greater than 7 sigma: the Crab, Cyg X-1, SWIFT J1753.5-0127, 1E 1740-29, Cen A, GRS 1915+105, and the transient sources XTE J1752-223 and GX 339-4. Two of the sources, the Crab and Cyg X-1, have also been detected above 300 keV.Comment: 13 pages, 9 figures, submitted to Ap

Grey and white matter correlates of recent and remote autobiographical memory retrieval:Insights from the dementias

The capacity to remember self-referential past events relies on the integrity of a distributed neural network. Controversy exists, however, regarding the involvement of specific brain structures for the retrieval of recently experienced versus more distant events. Here, we explored how characteristic patterns of atrophy in neurodegenerative disorders differentially disrupt remote versus recent autobiographical memory. Eleven behavioural-variant frontotemporal dementia, 10 semantic dementia, 15 Alzheimer's disease patients and 14 healthy older Controls completed the Autobiographical Interview. All patient groups displayed significant remote memory impairments relative to Controls. Similarly, recent period retrieval was significantly compromised in behavioural-variant frontotemporal dementia and Alzheimer's disease, yet semantic dementia patients scored in line with Controls. Voxel-based morphometry and diffusion tensor imaging analyses, for all participants combined, were conducted to investigate grey and white matter correlates of remote and recent autobiographical memory retrieval. Neural correlates common to both recent and remote time periods were identified, including the hippocampus, medial prefrontal, and frontopolar cortices, and the forceps minor and left hippocampal portion of the cingulum bundle. Regions exclusively implicated in each time period were also identified. The integrity of the anterior temporal cortices was related to the retrieval of remote memories, whereas the posterior cingulate cortex emerged as a structure significantly associated with recent autobiographical memory retrieval. This study represents the first investigation of the grey and white matter correlates of remote and recent autobiographical memory retrieval in neurodegenerative disorders. Our findings demonstrate the importance of core brain structures, including the medial prefrontal cortex and hippocampus, irrespective of time period, and point towards the contribution of discrete regions in mediating successful retrieval of distant versus recently experienced events