The Jet and the Supernova in GRB990712

The optical light curve of the afterglow following the gamma-ray burst GRB990712 is re-examined. Recently published polarization measurements of that source require a collimated outflow geometry that in turn predicts a break in the light curve. We show that the V-band light curve is consistent with such a break and that the post-break light curve evolution is dominated by a supernova contribution

Polymer-coated bioactive glass S53P4 increases VEGF and TNF expression in an induced membrane model in vivo

The two-stage induced-membrane technique for treatment of large bone defects has become popular among orthopedic surgeons. In the first operation, the bone defect is filled with poly(methyl methacrylate) (PMMA), which is intended to produce a membrane around the implant. In the second operation, PMMA is replaced with autograft or allograft bone. Bioactive glasses (BAGs) are bone substitutes with bone-stimulating and angiogenetic properties. The aim of our study was to evaluate the inductive vascular capacity of BAG-S53P4 and poly(lactide-co-glycolide) (PLGA)-coated BAG-S53P4 for potential use as bone substitutes in a single-stage induced-membrane technique. Sintered porous rods of BAG-S53P4, PLGA-coated BAG-S53P4 and PMMA were implanted in the femur of 36 rabbits for 2, 4 and 8 weeks. The expression of vascular endothelial growth factor (VEGF) and tumor necrosis factor alpha (TNF) in the induced membranes of implanted materials was analyzed with real-time quantitative polymerase chain reaction and compared with histology. Both uncoated BAG-S53P4 and PLGA-coated BAG-S53P4 increase expression of VEGF and TNF, resulting in higher amounts of capillary beds, compared with the lower expression of VEGF and less capillary beads observed for negative control and PMMA samples. A significantly higher expression of VEGF was observed for PLGA-coated BAG-S53P4 than for PMMA at 8 weeks (p <0.036). VEGF and TNF expression in the induced membrane of BAG-S53P4 and PLGA-coated BAG-S53P4 is equal or superior to PMMA, the "gold standard" material used in the induced-membrane technique. Furthermore, the VEGF and TNF expression for PLGA-coated BAG-S53P4 increased during follow-up.Peer reviewe

S53P4 bioactive glass scaffolds induce BMP expression and integrative bone formation in a critical-sized diaphysis defect treated with a single-staged induced membrane technique

Surgical management of critical-sized diaphyseal defects involves multiple challenges, and up to 10% result in delayed or non-union. The two-staged induced membrane technique is successfully used to treat these defects, but it is limited by the need of several procedures and bone graft. Repeated procedures increase costs and morbidity, while grafts are subject to donor-site complications and scarce availability. To transform this two-staged technique into one graft-independent procedure, we developed amorphous porous scaffolds sintered from the clinically used bioactive glass S53P4. This work constitutes the first evaluation of such scaffolds in vivo in a critical-sized diaphyseal defect in the weight-bearing rabbit femur. We provide important knowledge and prospects for future development of sintered S53P4 scaffolds as a bone substitute. Critical-sized diaphysis defects are complicated by inherent sub-optimal healing conditions. The two staged induced membrane technique has been used to treat these challenging defects since the 1980 & rsquo;s. It involves temporary implantation of a membrane-inducing spacer and subsequent bone graft defect filling. A single-staged, graft-independent technique would reduce both socio-economic costs and patient morbidity. Our aim was to enable such single-staged approach through development of a strong bioactive glass scaffold that could replace both the spacer and the graft filling. We constructed amorphous porous scaffolds of the clinically used bioactive glass S53P4 and evaluated them in vivo using a critical sized defect model in the weight-bearing femur diaphysis of New Zealand White rabbits. S53P4 scaffolds and standard polymethylmethacrylate spacers were implanted for 2, 4, and 8 weeks. Induced membranes were confirmed histologically, and their osteostimulative activity was evaluated through RT-qPCR of bone morphogenic protein 2, 4, and 7 (BMPs). Bone formation and osseointegration were examined using histology, scanning electron microscopy, energy-dispersive X-ray analysis, and micro-computed tomography imaging. Scaffold integration, defect union and osteosynthesis were assessed manually and with X-ray projections. We demonstrated that S53P4 scaffolds induce osteostimulative membranes and produce osseointegrative new bone formation throughout the scaffolds. We also demonstrated successful stable scaffold integration with early defect union at 8 weeks postoperative in critical-sized segmental diaphyseal defects with implanted sintered amorphous S53P4 scaffolds. This study presents important considerations for future research and the potential of the S53P4 bioactive glass as a bone substitute in large diaphyseal defects. Statement of significance Surgical management of critical-sized diaphyseal defects involves multiple challenges, and up to 10% result in delayed or non-union. The two-staged induced membrane technique is successfully used to treat these defects, but it is limited by the need of several procedures and bone graft. Repeated procedures increase costs and morbidity, while grafts are subject to donor-site complications and scarce availability. To transform this two-staged technique into one graft-independent procedure, we developed amorphous porous scaffolds sintered from the clinically used bioactive glass S53P4. This work constitutes the first evaluation of such scaffolds in vivo in a critical-sized diaphyseal defect in the weight-bearing rabbit femur. We provide important knowledge and prospects for future development of sintered S53P4 scaffolds as a bone substitute. (c) 2021 The Author(s). Published by Elsevier Ltd on behalf of Acta Materialia Inc. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )Peer reviewe

S53P4 bioactive glass scaffolds induce BMP expression and integrative bone formation in a critical-sized diaphysis defect treated with a single-stage d induce d membrane technique

Surgical management of critical-sized diaphyseal defects involves multiple challenges, and up to 10% result in delayed or non-union. The two-staged induced membrane technique is successfully used to treat these defects, but it is limited by the need of several procedures and bone graft. Repeated procedures increase costs and morbidity, while grafts are subject to donor-site complications and scarce availability. To transform this two-staged technique into one graft-independent procedure, we developed amorphous porous scaffolds sintered from the clinically used bioactive glass S53P4. This work constitutes the first evaluation of such scaffolds in vivo in a critical-sized diaphyseal defect in the weight-bearing rabbit femur. We provide important knowledge and prospects for future development of sintered S53P4 scaffolds as a bone substitute. Critical-sized diaphysis defects are complicated by inherent sub-optimal healing conditions. The two staged induced membrane technique has been used to treat these challenging defects since the 1980 & rsquo;s. It involves temporary implantation of a membrane-inducing spacer and subsequent bone graft defect filling. A single-staged, graft-independent technique would reduce both socio-economic costs and patient morbidity. Our aim was to enable such single-staged approach through development of a strong bioactive glass scaffold that could replace both the spacer and the graft filling. We constructed amorphous porous scaffolds of the clinically used bioactive glass S53P4 and evaluated them in vivo using a critical sized defect model in the weight-bearing femur diaphysis of New Zealand White rabbits. S53P4 scaffolds and standard polymethylmethacrylate spacers were implanted for 2, 4, and 8 weeks. Induced membranes were confirmed histologically, and their osteostimulative activity was evaluated through RT-qPCR of bone morphogenic protein 2, 4, and 7 (BMPs). Bone formation and osseointegration were examined using histology, scanning electron microscopy, energy-dispersive X-ray analysis, and micro-computed tomography imaging. Scaffold integration, defect union and osteosynthesis were assessed manually and with X-ray projections. We demonstrated that S53P4 scaffolds induce osteostimulative membranes and produce osseointegrative new bone formation throughout the scaffolds. We also demonstrated successful stable scaffold integration with early defect union at 8 weeks postoperative in critical-sized segmental diaphyseal defects with implanted sintered amorphous S53P4 scaffolds. This study presents important considerations for future research and the potential of the S53P4 bioactive glass as a bone substitute in large diaphyseal defects. Statement of significance Surgical management of critical-sized diaphyseal defects involves multiple challenges, and up to 10% result in delayed or non-union. The two-staged induced membrane technique is successfully used to treat these defects, but it is limited by the need of several procedures and bone graft. Repeated procedures increase costs and morbidity, while grafts are subject to donor-site complications and scarce availability. To transform this two-staged technique into one graft-independent procedure, we developed amorphous porous scaffolds sintered from the clinically used bioactive glass S53P4. This work constitutes the first evaluation of such scaffolds in vivo in a critical-sized diaphyseal defect in the weight-bearing rabbit femur. We provide important knowledge and prospects for future development of sintered S53P4 scaffolds as a bone substitute. (c) 2021 The Author(s). Published by Elsevier Ltd on behalf of Acta Materialia Inc. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )Peer reviewe

INTEGRAL observations of the field of the BL Lacertae object S5~0716+714

We have performed observations of the blazar S5 0716+714 with INTEGRAL on 2-6 April 2004. In the first months of 2004, the source had increased steadily in optical brightness and had undergone two outbursts. During the latter, occurred in March, it reached the extreme level of R = 12.1 mag, which triggered our INTEGRAL program. The target has been detected with IBIS/ISGRI up to 60 keV, with a flux of ~3 x 10e-11 erg/s/cm2 in the 30-60 keV interval, a factor of ~2 higher than observed by the BeppoSAX PDS in October 2000. In the field of S5 0716+714 we have also detected the Flat Spectrum Radio Quasar S5 0836+710 and the two Seyfert galaxies Mkn 3 and Mkn 6. Their IBIS/ISGRI spectra are rather flat, albeit consistent with those measured by BeppoSAX. In the spectrum of Mkn 3 we find some evidence of a break between ~60 and ~100 keV, reminiscent of the high energy cut-offs observed in other Seyfert galaxies. This is the first report of INTEGRAL spectra of weak Active Galactic Nuclei.Comment: 5 pages, 5 figures, in press in A&

The Hardness-Intensity Diagram of Cygnus X-3: Revisiting the Radio/X-Ray States

Cygnus X-3 is one of the brightest X-ray and radio sources in the Galaxy, and is well known for its erratic behaviour in X-rays as well as in the radio, occasionally producing major radio flares associated with relativistic ejections. However, even after many years of observations in various wavelength bands Cyg X-3 still eludes clear physical understanding. Studying different emission bands simultaneously in microquasars has proved to be a fruitful approach towards understanding these systems, especially by shedding light on the accretion disc/jet connection. We continue this legacy by constructing a hardness-intensity diagram (HID) from archival Rossi X-ray Timing Explorer data and linking simultaneous radio observations to it. We find that surprisingly Cyg X-3 sketches a similar shape in the HID to that seen in other transient black hole X-ray binaries during outburst but with distinct differences. Together with the results of this analysis and previous studies of Cyg X-3 we conclude that the X-ray states can be assigned to six distinct states. This categorization relies heavily on the simultaneous radio observations and we identify one new X-ray state, the hypersoft state, similar to the ultrasoft state, which is associated to the quenched radio state during which there is no or very faint radio emission. Recent observations of GeV flux observed from Cyg X-3 (Tavani et al. 2009; Fermi LAT Collaboration et al. 2009) during a soft X-ray and/or radio quenched state at the onset of a major radio flare hint that a very energetic process is at work during this time, which is also when the hypersoft X-ray state is observed. In addition, Cyg X-3 shows flaring with a wide range of hardness.Comment: 17 pages, 9 figures, accepted for publication in MNRA

AGILE observation of a gamma-ray flare from the blazar 3C 279

Context. We report the detection by the AGILE satellite of an intense gamma-ray flare from the gamma-ray source 3EG J1255-0549, associated to the Flat Spectrum Radio Quasar 3C 279, during the AGILE pointings towards the Virgo Region on 2007 July 9-13. Aims. The simultaneous optical, X-ray and gamma-ray covering allows us to study the spectral energy distribution (SED) and the theoretical models relative to the flaring episode of mid-July. Methods. AGILE observed the source during its Science Performance Verification Phase with its two co-aligned imagers: the Gamma- Ray Imaging Detector (GRID) and the hard X-ray imager (Super-AGILE) sensitive in the 30 MeV - 50 GeV and 18 - 60 keV respectively. During the AGILE observation the source was monitored simultaneously in optical band by the REM telescope and in the X-ray band by the Swift satellite through 4 ToO observations. Results. During 2007 July 9-13 July 2007, AGILE-GRID detected gamma-ray emission from 3C 279, with the source at ~2 deg from the center of the Field of View, with an average flux of (210+-38) 10^-8 ph cm^-2 s^-1 for energy above 100 MeV. No emission was detected by Super-AGILE, with a 3-sigma upper limit of 10 mCrab. During the observation lasted about 4 days no significative gamma-ray flux variation was observed. Conclusions. The Spectral Energy Distribution is modelled with a homogeneous one-zone Synchrotron Self Compton emission plus the contributions by external Compton scattering of direct disk radiation and, to a lesser extent, by external Compton scattering of photons from the Broad Line Region.Comment: Accepted for publication in Astronomy and Astrophysic

The establishment and utility of Sweha-Reg: a Swedish population-based registry to understand hereditary angioedema

<p>Abstract</p> <p>Background</p> <p>The importance of acquiring comprehensive epidemiological and clinical data on hereditary angioedema has increasingly caught the attention of physicians and scientists around the world. The development of networks and creation of comprehensive policies to improve care of people suffering from rare diseases, such as hereditary angioedema, is a stated top priority of the European Union.</p> <p>Hereditary angioedema is a rare disease, that it may be life-threatening. Although the exact prevalence is unknown, current estimates suggest that it is 1/10,000–1/150,000 individuals. The low prevalence requires combined efforts to gain accurate epidemiological data on the disease and so give us tools to reduce morbidity and mortality, and improve quality of life of sufferers.</p> <p>Methods</p> <p>Sweha-Reg is a population-based registry of hereditary angioedema in Sweden with the objectives of providing epidemiological data, and so creates a framework for the study of this disease. The registry contains individual-based data on diagnoses, treatments and outcomes.</p> <p>Conclusion</p> <p>The present manuscript seeks to raise awareness of the existence of Sweha-Reg to stimulate the international collaboration of registries. A synthesis of data from similar registries across several countries is required to approach an inclusive course understanding of HAE.</p

The correlated optical and radio variability of BL Lacertae. WEBT data analysis 1994-2005

Since 1997, BL Lacertae has undergone a phase of high optical activity, with the occurrence of several prominent outbursts. Starting from 1999, the Whole Earth Blazar Telescope (WEBT) consortium has organized various multifrequency campaigns on this blazar, collecting tens of thousands of data points. One of the main issues in the study of this huge dataset has been the search for correlations between the optical and radio flux variations, and for possible periodicities in the light curves. The analysis of the data assembled during the first four campaigns (comprising also archival data to cover the period 1968-2003) revealed a fair optical-radio correlation in 1994-2003, with a delay of the hard radio events of ~100 days. Moreover, various statistical methods suggested the existence of a radio periodicity of ~8 years. In 2004 the WEBT started a new campaign to extend the dataset to the most recent observing seasons, in order to possibly confirm and better understand the previous results. In this campaign we have collected and assembled about 11000 new optical observations from twenty telescopes, plus near-IR and radio data at various frequencies. Here, we perform a correlation analysis on the long-term R-band and radio light curves. In general, we confirm the ~100-day delay of the hard radio events with respect to the optical ones, even if longer (~200-300 days) time lags are also found in particular periods. The radio quasi-periodicity is confirmed too, but the "period" seems to progressively lengthen from 7.4 to 9.3 years in the last three cycles. The optical and radio behaviour in the last forty years suggests a scenario where geometric effects play a major role. In particular, the alternation of enhanced and suppressed optical activity (accompanied by hard and soft radio events, respectively) canComment: 6 pages, 4 figure

Another look at the BL Lacertae flux and spectral variability

The GLAST-AGILE Support Program (GASP) of the Whole Earth Blazar Telescope (WEBT) monitored BL Lacertae in 2008-2009 at radio, near-IR, and optical frequencies. During this period, high-energy observations were performed by XMM-Newton, Swift, and Fermi. We analyse these data with particular attention to the calibration of Swift UV data, and apply a helical jet model to interpret the source broad-band variability. The GASP-WEBT observations show an optical flare in 2008 February-March, and oscillations of several tenths of mag on a few-day time scale afterwards. The radio flux is only mildly variable. The UV data from both XMM-Newton and Swift seem to confirm a UV excess that is likely caused by thermal emission from the accretion disc. The X-ray data from XMM-Newton indicate a strongly concave spectrum, as well as moderate flux variability on an hour time scale. The Swift X-ray data reveal fast (interday) flux changes, not correlated with those observed at lower energies. We compare the spectral energy distribution (SED) corresponding to the 2008 low-brightness state, which was characterised by a synchrotron dominance, to the 1997 outburst state, where the inverse-Compton emission was prevailing. A fit with an inhomogeneous helical jet model suggests that two synchrotron components are at work with their self inverse-Compton emission. Most likely, they represent the radiation from two distinct emitting regions in the jet. We show that the difference between the source SEDs in 2008 and 1997 can be explained in terms of pure geometrical variations. The outburst state occurred when the jet-emitting regions were better aligned with the line of sight, producing an increase of the Doppler beaming factor. Our analysis demonstrates that the jet geometry can play an extremely important role in the BL Lacertae flux and spectral variability.Comment: 12 pages, 10 figures, accepted for publication in A&