Long-term clinical and economic outcomes in previously untreated paediatric patients with severe haemophilia A : A nationwide real-world study with 700 person-years

AimFor previously untreated patients (PUPs) with severe haemophilia A in Finland for the past 2 decades, the standard practice has been to start early primary prophylaxis. We evaluated the long-term clinical outcomes and costs of treatment with high-dose prophylaxis in PUPs from birth to adolescence, including immune tolerance induction (ITI). MethodsFrom the medical records of all PUPs born between June 1994 and May 2013 in Finland, we retrospectively extracted data on clinical outcomes and healthcare use. Using linear mixed models, we analysed longitudinal clinical outcome data. To analyse skewed cost data, including zero costs, we applied hurdle regression. ResultsAll 62 patients received early regular prophylaxis; totally, they have had treatment for nearly 700 patient-years. The median age of starting home treatment was 1.1years. The mean (SD) annual treatment costs (Europerkg) were 4391Euro (3852). For ages 1-3, ITI comprised over half of the costs; in other groups, prophylactic FVIII treatment dominated. With these high costs, however, clinical outcomes were desirable; median (IQR) ABR was low at 0.19 (0.07-0.46) and so was AJBR at 0.06 (0-0.24). Thirteen (21%) patients developed a clinically significant inhibitor, 10 (16%) with a high titre. All ITIs were successful. The mean costs for ITI were 383448Euro (259085). The expected ITI payback period was 1.81 (95% CI 0.62-12.12) years. ConclusionsEarly high-dose prophylaxis leads to excellent long-term clinical outcomes, and early childhood ITI therapy seems to turn cost-neutral generally already in 2years.Peer reviewe

Physical parameters of a relativistic jet at very high redshift: the case of the blazar J1430+4204

Context. The high-redshift (z = 4.72) blazar J1430+4204 produced a major radio outburst in 2005. Such outbursts are usually associated with the emergence of a new component in the inner radio jet. Aims. We searched for possible changes in the radio structure on milli-arcsecond angular scales, to determine physical parameters that characterise the relativistic jet ejected from the centre of this source. Methods. We analysed 15-GHz radio interferometric images obtained with the Very Long Baseline Array (VLBA) before and after the peak of the outburst. Results. We did not identify any significant new jet component over a period of 569 days. We estimated the Doppler factor, the Lorentz factor, and the apparent transverse speed of a putative jet component using three different methods. The likely small jet angle to the line of sight and our values of the apparent transverse speed are consistent with not detecting a new jet feature.Comment: (6 pages, 4 figures) accepted for publication in Astronomy and Astrophysic

37 GHz observations of a large sample of BL Lacertae objects

We present 37 GHz data obtained at Metsahovi Radio Observatory in 2001 December - 2005 April for a large sample of BL Lacertae objects. We also report the mean variability indices and radio spectral indices in frequency intervals 5 - 37 GHz and 37 - 90 GHz. Approximately 34 % of the sample was detected at 37 GHz, 136 BL Lacertae objects in all. A large majority of the detected sources were low-energy BL Lacs (LBLs). The variability index values of the sample were diverse, the mean fractional variability of the sample being \Delta S_2 = 0.31. The spectral indices also varied widely, but the average radio spectrum of the sample sources is flat. Our observations show that many of the high-energy BL Lacs (HBL), which are usually considered radio-quiet, can at times be detected at 37 GHz.Comment: 12 pages, 5 figures + 5 tables. Published in Astronomical Journa

Cooper Pair Splitting by Means of Graphene Quantum Dots

A split Cooper pair is a natural source for entangled electrons which is a basic ingredient for quantum information in the solid state. We report an experiment on a superconductor-graphene double quantum dot (QD) system, in which we observe Cooper pair splitting (CPS) up to a CPS efficiency of ∼10%. With bias on both QDs, we are able to detect a positive conductance correlation across the two distinctly decoupled QDs. Furthermore, with bias only on one QD, CPS and elastic cotunneling can be distinguished by tuning the energy levels of the QDs to be asymmetric or symmetric with respect to the Fermi level in the superconductor.Peer reviewe

INTEGRAL observations of the blazar Mrk 421 in outburst (Results of a multi-wavelength campaign)

We report the results of a multi-wavelength campaign on the blazar Mrk 421 during outburst. We observed four strong flares at X-ray energies that were not seen at other wavelengths (partially because of missing data). From the fastest rise in the X-rays, an upper limit could be derived on the extension of the emission region. A time lag between high-energy and low-energy X-rays was observed, which allowed an estimation of the magnetic-field strength. The spectral analysis of the X-rays revealed a slight spectral hardening of the low-energy (3 - 43 keV) spectral index. The hardness-ratio analysis of the Swift-XRT (0.2 - 10 keV) data indicated a small correlation with the intensity; i. e., a hard-to-soft evolution was observed. At the energies of IBIS/ISGRI (20 - 150 keV), such correlations are less obvious. A multiwavelength spectrum was composed and the X-ray and bolometric luminosities are calculated.Comment: 15 pages, 18 figures; accepted by Astronomy & Astrophysic

Planck intermediate results XXIII : Galactic plane emission components derived from Planck with ancillary data

Planck data when combined with ancillary data provide a unique opportunity to separate the diffuse emission components of the inner Galaxy. The purpose of the paper is to elucidate the morphology of the various emission components in the strong star-formation region lying inside the solar radius and to clarify the relationship between the various components. The region of the Galactic plane covered is 1 = 300 degrees -> 0 degrees -> 60 degrees where star-formation is highest and the emission is strong enough to make meaningful component separation. The latitude widths in this longitude range lie between 1 and 2, which correspond to FWHM z-widths of 100-200 pc at a typical distance of 6 kpc. The four emission components studied here are synchrotron, free-free, anomalous microwave emission (AME), and thermal (vibrational) dust emission. These components are identified by constructing spectral energy distributions (SEDs) at positions along the Galactic plane using the wide frequency coverage of Planck (28.4-857 GHz) in combination with low-frequency radio data at 0.408-2.3 GHz plus WMAP data at 23-94 GHz, along with far-infrared (FIR) data from COBE-DIRBE and IRAS. The free-free component is determined from radio recombination line (RRL) data. AME is found to be comparable in brightness to the free-free emission on the Galactic plane in the frequency range 20-40 GHz with a width in latitude similar to that of the thermal dust; it comprises 45 +/- 1% of the total 28.4 GHz emission in the longitude range 1 = 300 degrees -> 0 degrees -> 60 degrees. The free-free component is the narrowest, reflecting the fact that it is produced by current star-formation as traced by the narrow distribution of OB stars. It is the dominant emission on the plane between 60 and 100 GHz. RRLs from this ionized gas are used to assess its distance, leading to a free-free z-width of FWHM approximate to 100 pc. The narrow synchrotron component has a low-frequency brightness spectral index beta(synch) approximate to -2.7 that is similar to the broad synchrotron component indicating that they are both populated by the cosmic ray electrons of the same spectral index. The width of this narrow synchrotron component is significantly larger than that of the other three components, suggesting that it is generated in an assembly of older supernova remnants that have expanded to sizes of order 150 pc in 3 x 10(5) yr; pulsars of a similar age have a similar spread in latitude. The thermal dust is identified in the SEDs with average parameters of T-dust = 20.4 +/- 0.4 K, beta(FIR) = 1.94 +/- 0.03 (>353 GHz), and beta(mm) = 1.67 +/- 0.02 (Peer reviewe

The milliarcsecond-scale jet of PKS 0735+178 during quiescence

We present polarimetric 5 GHz to 43 GHz VLBI observations of the BL Lacertae object PKS 0735+178, spanning March 1996 to May 2000. Comparison with previous and later observations suggests that the overall kinematic and structural properties of the jet are greatly influenced by its activity. Time intervals of enhanced activity, as reported before 1993 and after 2000 by other studies, are followed by highly superluminal motion along a rectilinear jet. In contrast the less active state in which we performed our observations, shows subluminal or slow superluminal jet features propagating through a twisted jet with two sharp bends of about 90 deg. within the innermost three-milliarcsecond jet structure. Proper motion estimates from the data presented here allow us to constrain the jet viewing angle to values < 9 deg., and the bulk Lorentz factor to be between 2 and 4.Comment: 11 pages, 12 figures. Accepted for publication in A&

Emission from Hot Dust in the Infrared Spectra of Gamma-ray Bright Blazars

A possible source of $\gamma$-ray photons observed from the jets of blazars is inverse Compton scattering by relativistic electrons of infrared seed photons from a hot, dusty torus in the nucleus. We use observations from the Spitzer Space Telescope to search for signatures of such dust in the infrared spectra of four $\gamma$-ray bright blazars, the quasars 4C 21.35, CTA102, and PKS 1510$-$089, and the BL Lacertae object ON231. The spectral energy distribution (SED) of 4C 21.35 contains a prominent infrared excess indicative of dust emission. After subtracting a non-thermal component with a power-law spectrum, we fit a dust model to the residual SED. The model consists of a blackbody with temperature $\sim1200$ K, plus a much weaker optically thin component at $\sim660$ K. The total luminosity of the thermal dust emission is $7.9\pm0.2 \times 10^{45}$ erg s$^{-1}$. If the dust lies in an equatorial torus, the density of IR photons from the torus is sufficient to explain the $\gamma$-ray flux from 4C 21.35 as long as the scattering occurs within a few parsecs of the central engine. We also report a tentative detection of dust in the quasar CTA102, in which the luminosity of the infrared excess is $7 \pm 2 \times 10^{45}$ erg s$^{-1}$. However, in CTA102 the far-IR spectra are too noisy to detect the $10 \mu$m silicate feature. Upper limits to the luminosity from thermal emission from dust in PKS 1510-089, and ON231, are, $2.3\times10^{45}$, and $6.6\times10^{43}$ erg s$^{-1}$, respectively. These upper limits do not rule out the possibility of inverse Compton up-scattering of IR photons to $\gamma$-ray energies in these two sources. The estimated covering factor of the hot dust in 4C 21.35, 22%, is similar to that of non-blazar quasars; however, 4C 21.35 is deficient in cooler dust.Comment: 23 Pages, 5 Figures, 2 Tables, 1 Machine Readable Table. Accepted to Ap