ALBERT

Description: BACKGROUND: The diagnosis of BCR-ABL negative chronic myeloproliferative disorders (CMPD) according to WHO/PVSG criteria may be difficult. The V617F mutation has been reported in 65–97% of patients with polycythemia vera (PV), 23–57% with essential thrombocythemia (ET) and 35–57% with idiopathic myelofibrosis (IM). The value of JAK2 mutation in unclassifiable CMPD, idiopathic erythrocytosis (IE) and idiopathic thrombocythosis (IT) is unknown. AIMS: We wished to evaluate the utility of the V617F screening in patients with known or suspected myeloproliferative diseases. METHODS: We applied the screening assay for JAK2V617F described by Baxter (Lancet2005;365) in 84 patients from our Clinical Department with a previous or suspected diagnosis of CMPD (retrospective and prospective cohort study). The variables were obtained from clinical records and the diagnosis were made according to WHO or PVSG criteria when was possible. There was: 14 cases of PV, 34 of ET, 14 of unclassifiable CMPD, 3 of IM, 13 of IT and 6 of secondary disorders. RESULTS: The V617F screening was positive in 11/14 (79 %) of PV, 14/34 (41 %) of ET, 10/14 (71%) of unclassifiable CMPD, 3/3 IM, 1/13 (8%) of IT and 0/6 secondary disorders. At diagnosis, patients with mutation had significantly higher leucocyte and neutrophil counts and hemoglobin, hematocrit and LDH level. No significant interaction was noted between V617F mutation and the clinical data (gender, rates of transformation, splenomegaly, thrombosis and hemorrhage). The unclassifiable CMPD group was compared with the ET and PV groups. The unclassifiable CMPD group compared with the ET group showed a lower platelet count, a higher HCT level, and a higher frequency of JAK2 mutation. CONCLUSIONS: In case of suspected CMPD the JAK2 mutation screening seems to be useful . Some patients with IT had the mutation and these patients may represent an early phase of ET. According to the literature the V617F mutation was associated with some laboratory parameters but we don’t find significant clinical associations. The JAK2 mutation is frequent in the unclassifiable CMPD and these patients had clinical features similar to the PV group. The WHO or PVSG criteria should be changed to incorporate the JAK2 screening to reach a higher sensibility.

Description: Foam rubber experiments simulating unilaterally propagating strike-slip earthquakes provide a means to explore the sensitivity of near-fault ground motions to rupture geometry. Subsurface accelerometers on the model fault plane show rupture propagation that approaches a limiting velocity close to the Rayleigh velocity. The slip-velocity waveform at depth is cracklike (slip duration of the order of narrower fault dimension W divided by S-wave speed beta ). Surface accelerometers record near-fault ground motion enhanced along strike by rupture-induced directivity. Most experimental features (initiation time, shape, duration and absolute amplitude of acceleration pulses) are successfully reproduced by a 3D spontaneous-rupture numerical model of the experiments. Numerical- and experimental-model acceleration pulses show similar decay with distance away from the fault, and fault-normal components in both models show similar, large amplitude growth with distance along fault strike. This forward directivity effect is also evident in response spectra: the fault-normal spectral response peak (at period approximately W/3beta ) increases approximately sixfold along strike, on average, in the experiments, with similar increase (about fivefold) in the corresponding numerical simulation. The experimental- and numerical-model response spectra agree with an empirical directivity model for natural earthquakes at long periods (near approximately W/beta ), and both overpredict shorter-period empirical directivity effects, with the amount of overprediction increasing systematically with diminishing period. We attribute this difference to rupture- and wavefront incoherence in natural earthquakes, due to fault-zone heterogeneities in stress, frictional resistance, and elastic properties present in the Earth but absent or minimal in the experimental and numerical models. Rupture-front incoherence is an important component of source models for ground-motion prediction, but finding an effective kinematic parameterization may be challenging.