We perform a systematic investigation of along-strike rupture directivity of 70 earthquakes (3.0 ≤ M
w ≤ 6.1) of the 2009 L'Aquila seismic sequence by analysing azimuthal variations of broad-band ...seismograms recorded in the distance range 60 km < R < 230 km. We use reference spectra of events with little directivity (similar to the empirical Green's function method) to deconvolve propagation-site effects and focus on source properties. A directivity index (0 ≤ I
DIR ≤ 1) calculated for each earthquake quantifies the spectral separation above the corner frequency of the target event at opposite along-strike directions. A large number (73 per cent) of events including the M
w 6.1 main shock show high (>0.7) I
DIR values indicating predominantly unilateral rupture propagation. The preferred rupture propagation direction is generally to the southeast with no dependence on the earthquake magnitude or occurrence time. Events on two main faults (L'Aquila and Campotosto) show somewhat different behaviour. Almost all earthquakes on the L'Aquila fault have strong unilateral directivity to the southeast, whereas earthquakes on the Campotosto fault show more diverse behaviour. However, there is a predominance of unilateral ruptures (14 out of 22) also on the Campotosto fault, and the few (five) earthquakes with ruptures to the northwest are limited to the most northwestern segment of the fault. The spectral results are consistent with time-domain analysis when the latter samples adequately the frequency band above corner frequency. The preferred rupture direction may be produced at least in part by a velocity contrast across the fault. The results provide important input for estimates of seismic motion and physics of earthquake ruptures.
KM3NeT will be a network of deep-sea neutrino telescopes in the Mediterranean Sea. The KM3NeT/ARCA detector, to be installed at the Capo Passero site (Italy), is optimised for the detection of ...high-energy neutrinos of cosmic origin. Thanks to its geographical location on the Northern hemisphere, KM3NeT/ARCA can observe upgoing neutrinos from most of the Galactic Plane, including the Galactic Centre. Given its effective area and excellent pointing resolution, KM3NeT/ARCA will measure or significantly constrain the neutrino flux from potential astrophysical neutrino sources. At the same time, it will test flux predictions based on gamma-ray measurements and the assumption that the gamma-ray flux is of hadronic origin. Assuming this scenario, discovery potentials and sensitivities for a selected list of Galactic sources and to generic point sources with an E−2 spectrum are presented. These spectra are assumed to be time independent. The results indicate that an observation with 3σ significance is possible in about six years of operation for the most intense sources, such as Supernovae Remnants RX J1713.7-3946 and Vela Jr. If no signal will be found during this time, the fraction of the gamma-ray flux coming from hadronic processes can be constrained to be below 50% for these two objects.
Nowadays, different treatment options are available for an extending list of lysosomal storage diseases (LSDs). Hematopoietic stem cell transplantation (HSCT) can benefit selected subsets of patients ...with some LSDs, but results have been poor in several other disorders, including metachromatic leukodystrophy (MLD), outlining the need for innovative therapeutic approaches in this field. Enzyme replacement therapy has been developed recently for MLD, and a Phase I/II trial is ongoing. However, the blood-brain barrier limits the access of the recombinant product to the nervous tissues. Autologous hematopoietic stem/progenitor cells can be genetically modified to constitutively express supra-physiological levels of arylsulfatase-A and may become a quantitatively more effective source of functional enzyme than normal donor cells when transplanted in patients with MLD, thus possibly overcoming the limits of HSCT. Moreover, autologous transplantation might be associated with a significantly reduced transplant-related morbidity and TRM avoiding the risk of GVHD. Therefore, such a gene therapy strategy could represent a significant advance in comparison to conventional allogeneic HSCT.
The treatment with recombinant human growth hormone in patients affected by Mucopolysaccharidoses (MPS) is considered whenever a concurrent diagnosis of growth hormone deficiency is demonstrated. The ...short- and long-term effects of recombinant human growth hormone in this selected cohort is still debated, given the natural progression of disease-related skeletal malformations and the paucity of treated patients reported in literature. The presented case series provides detailed information about the response to recombinant growth hormone in MPS patients diagnosed with growth hormone deficiency.
The growth patterns of 4 MPS female patients (current age: 11.7-14.3 years) treated with recombinant human growth hormone due to growth hormone deficiency have been retrospectively analyzed. Two patients, diagnosed with MPS IH, had undergone haematopoietic stem cell transplantation at an early age; the remaining two patients were affected by MPS IV and VI and were treated with enzyme replacement therapy. 4/4 patients presented with a progressive growth deceleration before the diagnosis of growth hormone deficiency was confirmed. This trend was initially reverted by a remarkable increase in height velocity after the start of recombinant growth hormone. We recorded an average increase in height velocity z-score of + 4.23 ± 2.9 and + 4.55 ± 0.96 respectively after 6 and 12 months of treatment. After the first 12-24 months, growth showed a deceleration in all the patients. While in a girl with MPS IH recombinant human growth hormone was discontinued due to a lack in clinical efficacy, 3/4 patients grew at a stable pace, tracking the height centile achieved after the cited initial increase in height velocity. Furthermore, mineral bone density assessed via bone densitometry, showed a remarkable increase in the two patients who were tested before and after starting treatment.
Recombinant human growth hormone appears to have effectively reverted the growth deceleration experienced by MPS patients diagnosed with growth hormone deficiency, at least during the first 12-24 months of treatment.
Hurler's syndrome (HS), the most severe form of mucopolysaccharidosis type-I, causes progressive deterioration of the central nervous system and death in childhood. Allogeneic stem cell ...transplantation (SCT) before the age of 2 years halts disease progression. Graft failure limits the success of SCT. We analyzed data on HS patients transplanted in Europe to identify the risk factors for graft failure. We compared outcomes in 146 HS patients transplanted with various conditioning regimens and grafts. Patients were transplanted between 1994 and 2004 and registered to the European Blood and Marrow Transplantation database. Risk factor analysis was performed using logistic regression. 'Survival' and 'alive and engrafted'-rate after first SCT was 85 and 56%, respectively. In multivariable analysis, T-cell depletion (odds ratio (OR) 0.18; 95% confidence interval (CI) 0.04-0.71; P=0.02) and reduced-intensity conditioning (OR 0.08; 95% CI 0.02-0.39; P=0.002) were the risk factors for graft failure. Busulfan targeting protected against graft failure (OR 5.76; 95% CI 1.20-27.54; P=0.028). No difference was noted between cell sources used (bone marrow, peripheral blood stem cells or cord blood (CB)); however, significantly more patients who received CB transplants had full-donor chimerism (OR 9.31; 95% CI 1.06-82.03; P=0.044). These outcomes may impact the safety/efficacy of SCT for 'inborn-errors of metabolism' at large. CB increased the likelihood of sustained engraftment associated with normal enzyme levels and could therefore be considered as a preferential cell source in SCT for 'inborn errors of metabolism'.
Ambient noise measurements performed on the western flank of Mt. Etna are analyzed to infer the occurrence of directional amplification effects in fault zones. The data were recorded along short ...(<500 m) profiles crossing the Ragalna Fault System. Ambient noise records were processed to compute the horizontal-to-vertical noise spectral ratio as a function of frequency and direction of motion. Wavefield polarization was investigated in the time–frequency domain as well. Peaks of the spectral ratios generally fall in the frequency band 1.0–6.0 Hz pointing out directional amplifications that are also confirmed by the results of the time–frequency analysis, the largest amplification occurring with high angle to the fault strike. A variation of the frequency of the spectral peak is observed between the two sides of the fault, possibly related to a damage fault asymmetry. Measurements performed several kilometers away from the fault zone do not show behavior that is as systematic as in the fault zone, and this suggests that the observed directional effects can be ascribed to the fault fabric. We relate the polarization effect to compliance anisotropy in the fault zone, where the presence of predominantly oriented fractures makes the normal component of ground motion larger than the transversal one. In order to test the direction and the type of fractures that are expected in the fault zone, we modeled the brittle deformation pattern of the investigated fault. Theoretical results are in good agreement with field observations of the fracture strike.
The KM3NeT research infrastructure is under construction in the Mediterranean Sea. It consists of two water Cherenkov neutrino detectors, ARCA and ORCA, aimed at neutrino astrophysics and oscillation ...research, respectively. Instrumenting a large volume of sea water with Formula omitted optical modules comprising a total of Formula omitted photomultiplier tubes, KM3NeT will achieve sensitivity to Formula omitted neutrinos from Galactic and near-Galactic core-collapse supernovae through the observation of coincident hits in photomultipliers above the background. In this paper, the sensitivity of KM3NeT to a supernova explosion is estimated from detailed analyses of background data from the first KM3NeT detection units and simulations of the neutrino signal. The KM3NeT observational horizon (for a Formula omitted discovery) covers essentially the Milky-Way and for the most optimistic model, extends to the Small Magellanic Cloud ( Formula omitted). Detailed studies of the time profile of the neutrino signal allow assessment of the KM3NeT capability to determine the arrival time of the neutrino burst with a few milliseconds precision for sources up to 5-8 kpc away, and detecting the peculiar signature of the standing accretion shock instability if the core-collapse supernova explosion happens closer than 3-5 kpc, depending on the progenitor mass. KM3NeT's capability to measure the neutrino flux spectral parameters is also presented.
SUMMARY
We investigate shear wave polarization in the Hayward fault zone near Niles Canyon, Fremont, CA. Waveforms of 12 earthquakes recorded by a seven‐accelerometer seismic array around the fault ...are analysed to clarify directional site effects in the fault damage zone. The analysis is performed in the frequency domain through H/V spectral ratios with horizontal components rotated from 0° to 180°, and in the time domain using the eigenvectors and eigenvalues of the covariance matrix method employing three component records. The near‐fault ground motion tends to be polarized in the horizontal plane. At two on‐fault stations where the local strike is N160°, ground motion polarization is oriented N88 ± 19° and N83 ± 32°, respectively. At a third on‐fault station, the motion is more complex with horizontal polarization varying in different frequency bands. However, a polarization of N86 ± 7°, similar to the results at the other two on‐fault stations, is found in the frequency band 6–8 Hz. The predominantly high‐angle polarization from the fault strike at the Hayward Fault is consistent with similar results at the Parkfield section of the San Andreas Fault and the Val d’Agri area (a Quaternary extensional basin) in Italy. In all these cases, comparisons of the observed polarization directions with models of fracture orientation based on the fault movement indicate that the dominant horizontal polarization is near‐orthogonal to the orientation of the expected predominant cracking direction. The results help to develop improved connections between fault mechanics and near‐fault ground motion.
Haematopoietic cell transplantation (HCT) can benefit some selected subsets of patients with lysosomal diseases. Results had been impressive in children with MPS I-H, but poor in other disorders. ...Careful, multidisciplinary decision-making regarding whether to recommend HCT and how to provide optimal pre- and post-HCT care has proven essential to increase the likelihood of a good outcome.
Progressive multifocal leukoencephalopathy (PML) associated with polyomavirus JC (JCV) infection has been reported to be usually fatal in allogeneic hematopoietic SCT (HSCT) recipients. We present ...the case of a 19-year-old HSCT patient diagnosed with JCV-associated PML after prolonged immunosuppression for severe GVHD. No short-term neurological improvement was observed after antiviral treatment and discontinuation of immunosuppressive therapy. Donor-derived JCV Ag-specific CTLs were generated in vitro after stimulation with 15-mer peptides derived from VP1 and large T viral proteins. After adoptive CTL infusion, virus-specific cytotoxic cells were shown in the peripheral blood, JCV-DNA was cleared in the cerebrospinal fluid and the patient showed remarkable improvement. Adoptive T-lymphocyte therapy with JCV-specific CTLs was feasible and had no side effects. This case suggests that adoptive transfer of JCV-targeted CTLs may contribute to restore JCV-specific immune competence and control PML in transplanted patients.
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