GH/IGF-1 axis in a large cohort of ß-thalassemia major adult patients: a cross-sectional study.

PURPOSE: GH deficit (GHD) could represent an endocrine issue in ß-Thalassemia Major (ßTM) patients. GH/IGF-1 axis has not been extensively explored in ßTM adults, so far. We aim to assess GHD and IGF-1 deficiency prevalence in ßTM adult population, focusing on the relationship with liver disease. METHODS: Cross-sectional multi-centre study conducted on 81 adult ßTM patients (44 males, mean age 41 ± 8 years) on transfusion and chelation therapy. GHD was investigated by GHRH + arginine test. IGF-1 levels, routine biochemical exams, Fibroscan, Hepatic Magnetic Resonance Imaging (MRI) and pituitary MRI were collected. RESULTS: Eighteen patients were affected by GHD and 63 were not (nGHD) according to GHRH + arginine test, while basal GH levels did not differ. GHD was associated with a higher BMI and a worse lipid profile (p < 0.05). No significant differences were observed regarding liver function between the two groups. Pituitary MRI scan was normal except for one case of empty sella. The 94.4% and 93.6% of GHD and nGHD, respectively, presented lower IGF-1 levels than the reference range, and mean IGF-1 SDS was significantly lower in GHD patients. CONCLUSION: GHD is frequent in adult ßTM patients and is associated with higher BMI and worse lipid profile. nGHD patients present lower IGF-1 levels as well. There was no relationship between IGF-1 levels and liver disease. Further, multicentric studies with larger cohorts and standardized diagnostic protocols are needed.

Pharmacogenetics and induction/consolidation therapy toxicities in acute lymphoblastic leukemia patients treated with AIEOP-BFM ALL 2000 protocol.

Drug-related toxicities represent an important clinical concern in chemotherapy, genetic variants could help tailoring treatment to patient. A pharmacogenetic multicentric study was performed on 508 pediatric acute lymphoblastic leukemia patients treated with AIEOP-BFM 2000 protocol: 28 variants were genotyped by VeraCode and Taqman technologies, deletions of GST-M1 and GST-T1 by multiplex PCR. Toxicities were derived from a central database: 251 patients (49.4%) experienced at least one gastrointestinal (GI) or hepatic (HEP) or neurological (NEU) grade III/IV episode during the remission induction phase: GI occurred in 63 patients (12.4%); HEP in 204 (40.2%) and NEU in 44 (8.7%). Logistic regression model adjusted for sex, risk and treatment phase revealed that ITPA rs1127354 homozygous mutated patients showed an increased risk of severe GI and NEU. ABCC1 rs246240 and ADORA2A rs2236624 homozygous mutated genotypes were associated to NEU and HEP, respectively. These three variants could be putative predictive markers for chemotherapy-related toxicities in AIEOP-BFM protocols.

Experimental Evidence for Static Charge Density Waves in Iron Oxypnictides.

In this Letter we report high-resolution synchrotron x-ray powder diffraction and transmission electron microscope analysis of Mn-substituted LaFeAsO samples, demonstrating that a static incommensurate modulated structure develops across the low-temperature orthorhombic phase, whose modulation wave vector depends on the Mn content. The incommensurate structural distortion is likely originating from a charge-density-wave instability, a periodic modulation of the density of conduction electrons associated with a modulation of the atomic positions. Our results add a new component in the physics of Fe-based superconductors, indicating that the density wave ordering is charge driven.

Lymphocytes subsets reference values in childhood.

Immunophenotyping of blood lymphocyte subsets and activation markers is a basic tool in the diagnostic process of primary immunodeficiency diseases, its use becoming more and more widespread as the knowledge about these illnesses increases. However, the availability of reliable reference values, which need to be age-matched for the pediatric population, is a pre-requisite for the reliable interpretation of immunophenotyping data. Aim of this study is to analyze the lymphocyte subsets and activation markers distribution in children aged 0-18 years referring to the University Hospital of Padova and to create age-matched reference values expressed by percentiles, thus providing a valuable guideline for the interpretation of the immunophenotype.

High-performance Fe(Se,Te) films on chemical CeO2-based buffer layers.

The fabrication of a Fe-based coated conductor (CC) becomes possible when Fe(Se,Te) is grown as an epitaxial film on a metallic oriented substrate. Thanks to the material's low structural anisotropy, less strict requirements on the template microstructure allow for the design of a simplified CC architecture with respect to the REBCO multi-layered layout. This design, though, still requires a buffer layer to promote the oriented growth of the superconducting film and avoid diffusion from the metallic template. In this work, Fe(Se,Te) films are grown on chemically-deposited, CeO2-based buffer layers via pulsed laser deposition, and excellent properties are obtained when a Fe(Se,Te) seed layer is used. Among all the employed characterization techniques, transmission electron microscopy proved essential to determine the actual effect of the seed layer on the final film properties. Also, systematic investigation of the full current transport properties J(θ, H, T) is carried out: Fe(Se,Te) samples are obtained with sharp superconducting transitions around 16 K and critical current densities exceeding 1 MA cm-2 at 4.2 K in self-field. The in-field and angular behavior of the sample are in line with data from the literature. These results are the demonstration of the feasibility of a Fe-based CC, with all the relative advantages concerning process simplification and cost reduction.

Retention of the tetragonal to orthorhombic structural transition in F-substituted SmFeAsO: a new phase diagram for SmFeAs(O(1-x)F(x)).

In this Letter we propose a new phase diagram for the SmFeAs(O(1-x)F(x)) system, based on careful analysis of synchrotron powder diffraction data, SQUID, and muon spin rotation measurements. The tetragonal to orthorhombic structural transition is slightly affected by F content and is retained for the superconducting samples, even at optimal doping. These findings relate the AFM transition on a different ground with respect to the structural one and suggests that orbital ordering could be the driving force for symmetry breaking.

Correlated trends of coexisting magnetism and superconductivity in optimally electron-doped oxypnictides.

We report on the recovery of the short-range static magnetic order and on the concomitant degradation of the superconducting state in optimally F-doped SmFe(1-x)Ru(x)AsO(0.85)F(0.15) for 0.1≤x≲0.5. The two reduced order parameters coexist within nanometer-size domains in the FeAs layers and eventually disappear around a common critical threshold x(c)~0.6. Superconductivity and magnetism are shown to be closely related to two distinct well-defined local electronic environments of the FeAs layers. The two transition temperatures, controlled by the isoelectronic and diamagnetic Ru substitution, scale with the volume fraction of the corresponding environments. This fact indicates that superconductivity is assisted by magnetic fluctuations, which are frozen whenever a short-range static order appears, and totally vanish above the magnetic dilution threshold x(c).

Mn-induced Fermi-surface reconstruction in the SmFeAsO parent compound.

The electronic ground state of iron-based materials is unusually sensitive to electronic correlations. Among others, its delicate balance is profoundly affected by the insertion of magnetic impurities in the FeAs layers. Here, we address the effects of Fe-to-Mn substitution in the non-superconducting Sm-1111 pnictide parent compound via a comparative study of SmFe[Formula: see text]Mn[Formula: see text]AsO samples with [Formula: see text] 0.05 and 0.10. Magnetization, Hall effect, and muon-spin spectroscopy data provide a coherent picture, indicating a weakening of the commensurate Fe spin-density-wave (SDW) order, as shown by the lowering of the SDW transition temperature [Formula: see text] with increasing Mn content, and the unexpected appearance of another magnetic order, occurring at [Formula: see text] and 20 K for [Formula: see text] and 0.10, respectively. We attribute the new magnetic transition at [Formula: see text], occurring well inside the SDW phase, to a reorganization of the Fermi surface due to Fe-to-Mn substitutions. These give rise to enhanced magnetic fluctuations along the incommensurate wavevector [Formula: see text], further increased by the RKKY interactions among Mn impurities.

Suppression of the critical temperature of superconducting NdFeAs(OF) single crystals by Kondo-like defect sites induced by alpha-particle irradiation.

We report the effect of alpha-particle irradiation on the reduction of the critical temperature T{c} of a NdFeAs(OF) single crystal. Our data indicate that irradiation defects cause both nonmagnetic and magnetic scattering, resulting in the Kondo-like excess resistance Delta rho(T) proportional to lnT over 2 decades in temperatures above T{c}. The critical density of magnetic irradiation defects which suppresses T{c} is found to be much higher than those for cuprates and multiband BCS superconductors. We suggest that such anomalously weak pair breaking by irradiation defects indicates that magnetic scattering in pnictides is coupled with pairing interactions mediated by spin fluctuations.

Mn substitution effect on the local structure of La(Fe1-x Mn x )AsO studied by temperature dependent x-ray absorption measurements.

The local structure of La(Fe1-x Mn x )AsO has been investigated using temperature dependent Fe K-edge extended x-ray absorption fine structure (EXAFS) measurements. The EXAFS data reveal distinct behavior of Fe-As and Fe-Fe atomic displacements with a clear boundary between x ⩽ 0.02 and x > 0.02. The Fe-As bondlength shows a gradual thermal expansion while the Fe-Fe bond manifests a temperature dependent anomaly at ∼180 K for x > 0.02. It is interesting to find characteristically different nature of Fe-As and Fe-Fe bondlengths shown by the temperature dependent mean square relative displacements. Indeed, the Fe-As bond, stiffer than that of the Fe-Fe, gets softer for x ⩽ 0.02 and hardly shows any change for x > 0.02. On the other hand, Fe-Fe bond tends to be stiffer for x ⩽ 0.02 followed by a substantial softening for x > 0.02. Such a distinction has been seen also in the As K-edge x-ray absorption near edge structure, probing local geometry around As atom together with the valence electronic structure. The results suggest that local atomic displacements by Mn substitution inducing increased iron local magnetic moment that should be the main reason for its dramatic effect in iron-based superconductors.

In-plane and out-of-plane properties of a BaFe2As2 single crystal.

Anisotropy of transport and magnetic properties of parent compounds of iron based superconductors is a key ingredient of superconductivity. In this work, we investigate in-plane and out-of-plane properties, namely thermal, electric, thermoelectric transport and magnetic susceptibility in a high quality BaFe2As2 single crystal of the 122 parent compound, using a combined experimental and theoretical approach. Combining the ab initio calculation of the band structure and the measured in-plane and out-of-plane resistivity, we evaluate the scattering rates which turn out to be strongly anisotropic and determined by spin excitations in the antiferromagnetic state. The observed anisotropy of thermal conductivity is discussed in terms of anisotropy of sound velocities which we estimate to be [Formula: see text]. Remarkably, we find that thermal conductivity is characterized by a sizeable electronic contribution at low temperature, which is ascribed to the high purity of our crystal.

Genotypic characterization of common acute lymphoblastic leukemia may improve the phenotypic classification.

The reactivity of five anti-B monoclonal antibodies (McAb)-OKB2 (CD24), B4 (CD19), Leu12 (CD19), BA1 (CD24), B1 (CD20)--as well as the presence of cytoplasmic immunoglobulins (CyIg) were assessed in 100 cases of common acute lymphoblastic leukemia (cALL) at presentation (TdT+, J5 [CD10]+, HLA-Dr+). All cases studied revealed one or more B-cell related markers and a hierarchy in their expression was documented: OKB2 was positive in all cases tested (100%), B4 was expressed in 96.4% of cases, Leu12 in 95.8%, BA1 in 94.9%, B1 in 18.3%, and CyIg in 23%. Further evidence of the B-cell origin of cALL was obtained by molecular analyses at the DNA level which demonstrated the presence of an Ig heavy chain gene rearrangement in all 37 cases assessed, while 37.8% showed a light chain gene reorganization. A genomic subclassification of cALL demonstrated that the majority of cases showed an immature molecular configuration with one (8.1%) or both (54.1%) Ig heavy chain alleles rearranged and a germ-line configuration of the light chain genes; 27% revealed a heavy chain gene involvement and one k allele rearranged. Only four cases (10.8%) showed a more mature configuration with both k alleles rearranged or a gamma chain gene involvement. This study confirms that cALL is characterized by the proliferation of immature B-lineage-committed elements and indicates that the leukemic cells are blocked at different levels of B-differentiation which may be recognized with the use of multiple phenotypic or genotypic B-cell-related markers.

Molecular characterization of Ph' + hybrid acute leukemia.

The configuration of the immunoglobulin heavy chain (IgH), T-cell receptor (TcR) beta and gamma chain regions, and the major breakpoint cluster region (M-bcr) genes were analysed in four cases of Ph' + acute leukemia (AL). Monoclonal rearrangements of the IgH region were detected in three cases exhibiting two phenotypically distinct cell populations (i.e. one lymphoid and one myeloid. In one of these cases, identical genetic events were observed by molecular analysis of FACS separated blasts. Multi-lineage rearrangements involving also the TcR gamma gene were observed in a biphenotypic AL showing co-expression of markers. The lack of rearrangements within the M-bcr gene, together with demonstration in one case of the Ph' + AL specific p190 protein product, pointed against the occurrence of chronic myeloid leukemias presenting in blastic transformation. Our results imply that such cases are to be considered as true AL and should therefore be included in the definition of hybrid AL.

Successful treatment of secondary acute myeloid leukemia relapsing after allogeneic bone marrow transplantation with donor lymphocyte infusion failed to prevent recurrence of primary disease: a case report.

We report a case of therapy-related secondary acute myeloid leukemia occurring in a patient during treatment for anaplastic large cell lymphoma. In spite of response to induction chemotherapy and prompt bone marrow transplantation from his matched sister, the patient experienced an early leukemia relapse within 3 months of the transplant. Treatment with oral etoposide for 3 weeks followed by donor lymphocyte infusion achieved a 7-month remission from leukemia without any further treatment. Unfortunately, the patient suffered a recurrence of the primary anaplastic large cell lymphoma that was treated by resuming chemotherapy and local radiotherapy. The patient died 20 months after DLI, still in CR for his leukemia, due to ALCL progression.

Cytogenetic t(11;17)(q13;q21) in a pediatric ependymoma. Is 11q13 a recurring breakpoint in ependymomas?

Cytogenetic studies on a supratentorial ependymoma from a 1-year-old boy showed a t(11;17)(q13;q21). This is the second ependymoma reported with a rearrangement at 11q13; to our knowledge the 11q13 is the first recurring breakpoint reported in ependymoma.

The role of immunophenotype in acute lymphoblastic leukemia of infant age.

The prognosis of acute lymphoblastic leukemia in infants is still significantly worse than that of older children. This is thought to be due to both clinical and biological factors, such as high white blood cell (WBC) counts at diagnosis, irregular or immature phenotypes, and molecular and cytogenetical abnormalities. In order to focus the significance of immunophenotypic analysis, we have reviewed the immunophenotypic studies of 145 infants under 18 months of age treated at the AIEOP centers from 1984 to 1992. Children have been divided in three age groups of six months each; WBC count at diagnosis has been evaluated both as mean values and within different categories (< 10.10(9)/L, > 100.10(9)/L). These have been studied in correlation with immunophenotype and with the expression of single, specific markers. A significant correlation has been found between young age, high WBC count and immature phenotypes. Common ALL was more frequent in older children and showed lower WBC counts. Moreover, event-free survival was significantly better in older children with WBC count < 100.00/mm3, with CD10+, MyAg- ALL. Therefore, we suggest that immunophenotypic analysis is still an important prognostic factor and can be usefully used, together with simple clinical data, to plan therapy for ALL in infants.

Crossover between magnetism and superconductivity in LaFeAsO with low H-doping level.

By making a systematic study of the hydrogen-doped LaFeAsO system by means of dc resistivity, dc magnetometry, and muon-spin spectroscopy, we addressed the question of universality of the phase diagram of rare-earth-1111 pnictides. In many respects, the behaviour of LaFeAsO(1-x)H(x) resembles that of its widely studied F-doped counterpart, with H(-) realizing a similar (or better) electron doping in the LaO planes. In an x = 0.01 sample we found a long-range spin-density wave (SDW) order with TN = 119 K, while at x = 0.05 the SDW establishes only at 38 K and, below Tc = 10 K, it coexists at a nanoscopic scale with bulk superconductivity. Unlike the abrupt magnetic-superconducting transition found in the La-1111 compound, the presence of a crossover region makes the H-doped system qualitatively similar to other Sm-1111, Ce-1111, and Nd-1111 families.

Study of the electronic and magnetic properties as a function of isoelectronic substitution in SmFe(1-x)RuxAsO0.85F0.15.

We have studied the electronic and magnetic properties of SmFe(1-x)RuxAsO0.85F0.15 (x = 0, 0.05, 0.25, 0.33, 0.5) by high-resolution x-ray absorption and x-ray emission spectroscopy. The local Fe magnetic moment (µ) tends to decrease for a small Ru substitution, but it shows a clear increase with further substitution. It appears that impurity scattering prevails in reducing the µ with small Ru substitution due to an extended Ru d-band. A nanoscale phase separation, that decouples the FeAs layers from the spacer layers, drives the increase of µ at higher Ru substitution. The results provide important information on nanoscale phase separation due to isoelectronic substitution in the active layers of iron-based 1111-superconductors and its effect on the local magnetic properties.