Most reports on chronic myeloid leukaemia (CML) treatment with tyrosine kinase inhibitors (TKIs) focus on efficacy, particularly on molecular response and outcome. In contrast, adverse events (AEs) ...are often reported as infrequent, minor, tolerable and manageable, but they are increasingly important as therapy is potentially lifelong and multiple TKIs are available. For this reason, the European LeukemiaNet panel for CML management recommendations presents an exhaustive and critical summary of AEs emerging during CML treatment, to assist their understanding, management and prevention. There are five major conclusions. First, the main purpose of CML treatment is the antileukemic effect. Suboptimal management of AEs must not compromise this first objective. Second, most patients will have AEs, usually early, mostly mild to moderate, and which will resolve spontaneously or are easily controlled by simple means. Third, reduction or interruption of treatment must only be done if optimal management of the AE cannot be accomplished in other ways, and frequent monitoring is needed to detect resolution of the AE as early as possible. Fourth, attention must be given to comorbidities and drug interactions, and to new events unrelated to TKIs that are inevitable during such a prolonged treatment. Fifth, some TKI-related AEs have emerged which were not predicted or detected in earlier studies, maybe because of suboptimal attention to or absence from the preclinical data. Overall, imatinib has demonstrated a good long-term safety profile, though recent findings suggest underestimation of symptom severity by physicians. Second and third generation TKIs have shown higher response rates, but have been associated with unexpected problems, some of which could be irreversible. We hope these recommendations will help to minimise adverse events, and we believe that an optimal management of them will be rewarded by better TKI compliance and thus better CML outcomes, together with better quality of life.
Ferroelectric Control of Spin Polarization Garcia, V; Bibes, M; Bocher, L ...
Science (American Association for the Advancement of Science),
02/2010, Letnik:
327, Številka:
5969
Journal Article
Recenzirano
Odprti dostop
A current drawback of spintronics is the large power that is usually required for magnetic writing, in contrast with nanoelectronics, which relies on "zero-current," gate-controlled operations. ...Efforts have been made to control the spin-relaxation rate, the Curie temperature, or the magnetic anisotropy with a gate voltage, but these effects are usually small and volatile. We used ferroelectric tunnel junctions with ferromagnetic electrodes to demonstrate local, large, and nonvolatile control of carrier spin polarization by electrically switching ferroelectric polarization. Our results represent a giant type of interfacial magnetoelectric coupling and suggest a low-power approach for spin-based information control.
Dengue is a public health problem that presents complexity in its dissemination. The physical means of spreading and the dynamics of the spread between municipalities need to be analyzed to guide ...effective public policies to combat this problem.
This study uses timing varying graph methods (TVG) to construct a correlation network between occurrences of reported cases of dengue between cities in the state of Bahia-Brazil. The topological network indices of all cities were correlated with dengue incidence using Spearman correlation. A randomization test was used to estimate the significance value of the correlation.
The correlation network presented a complex behavior with a heavy-tail distribution of the network edges weight. The randomization test exhibit a significant correlation (P < 0.0001) between the degree of each municipality in the network and the incidence of dengue in each municipality.
The hypothesis of the existence of a correlation between the occurrences of reported cases of dengue between different municipalities in the state of Bahia was validated. The significant correlation between the node degree and incidence, indicates that municipalities with high incidence are also responsible for the spread of the disease in the state. The method proposed suggests a new tool in epidemiological control strategy.
Ubiquicidin (UBI)/ribosomal protein S30 (RS30) is an intracellular protein with antimicrobial activities against various pathogens. UBI (29–41) and UBI (31–38) are two crucial peptides derived from ...Ubiquicidin, which have shown potential as infection imaging probes. Here, we report the interactions of UBI-derived peptides with anionic and zwitterionic phospholipid membranes. Our isothermal titration calorimetry results show that both peptides selectively interact with the anionic phospholipid membrane (a model bacterial membrane) and reside mainly on the membrane surface. The interaction of UBI-derived peptides with the anionic phospholipid membrane is exothermic and driven by both enthalpy (ΔH) and entropy (ΔS), with the entropic term TΔS being greater than ΔH. This large entropic term can be a result of the aggregation of the anionic vesicles, which is confirmed by dynamic light scattering (DLS) measurements. DLS data show that vesicle aggregation is enhanced with increasing peptide-to-lipid molar ratios (P/L) and is found to be more pronounced in the case of UBI (29–41). DLS results are found to be consistent with independent transmission measurements. To study the effects of UBI-derived peptides on the microscopic dynamics of the model bacterial membrane, quasielastic neutron scattering (QENS) measurements have been carried out. The QENS results show that both peptides restrict the lateral motion of the lipid within the leaflet. UBI (29–41) acts as a stronger stiffening agent, hindering the lateral diffusion of lipids more efficiently than UBI (31–38). To our knowledge, this is the first report illustrating the mechanism of interaction of UBI-derived peptides with model membranes. This study also has implications for the improvement and design of antimicrobial peptide-based infection imaging probes.
Recipients of extended‐criteria donor (ECD) kidneys have poorer long‐term outcomes compared to standard‐criteria donor kidney recipients. We report 3‐year outcomes from a randomized, phase III study ...in recipients of de novo ECD kidneys (n = 543) assigned (1:1:1) to either a more intensive (MI) or less intensive (LI) belatacept regimen, or cyclosporine. Three hundred twenty‐three patients completed treatment by year 3. Patient survival with a functioning graft was comparable between groups (80% in MI, 82% in LI, 80% in cyclosporine). Mean calculated GFR (cGFR) was 11 mL/min higher in belatacept‐treated versus cyclosporine‐treated patients (42.7 in MI, 42.2 in LI, 31.5 mL/min in cyclosporine). More cyclosporine‐treated patients (44%) progressed to GFR <30 mL/min (chronic kidney disease CKD stage 4/5) than belatacept‐treated patients (27–30%). Acute rejection rates were similar between groups. Posttransplant lymphoproliferative disorder (PTLD) occurrence was higher in belatacept‐treated patients (two in MI, three in LI), most of which occurred during the first 18 months; four additional cases (3 in LI, 1 in cyclosporine) occurred after 3 years. Tuberculosis was reported in two MI, four LI and no cyclosporine patients. In conclusion, at 3 years after transplantation, immunosuppression with belatacept resulted in similar patient survival, graft survival and acute rejection, with better renal function compared with cyclosporine. As previously reported, PTLD and tuberculosis were the principal safety findings associated with belatacept in this study population.
Three‐year results from the BENEFIT‐EXT study confirm the durability of the renal function benefits of belatacept over time compared to cyclosporine, while providing comparable 3‐year patient/graft survival and balancing risks associated with belatacept in recipients of extended criteria donor kidneys.
An acoustic metamaterial made of a two-dimensional (2D) periodic array of multi-resonant acoustic scatterers is analyzed both experimentally and theoretically. The building blocks consist of a ...combination of elastic beams of low-density polyethylene foam (LDPF) with cavities of known area. Elastic resonances of the beams and acoustic resonances of the cavities can be excited by sound producing several attenuation peaks in the low frequency range. Due to this behavior the periodic array with long wavelength multi-resonant structural units can be classified as a locally multi-resonant acoustic metamaterial (LMRAM) with strong dispersion of its effective properties.The results presented in this paper could be used to design effective tunable acoustic filters for the low frequency range.
► We design a sonic crystal with resonant scatterers presenting elastic and cavity resonances. ► The system has theoretically and experimentally analyzed. ► We characterize the Sonic Crystal as a locally multi-resonant acoustic metamaterial. ► Changing the geometry of the scatterers the propagation properties can be tuned.
Broadband acoustic attenuation produced by a three dimensional (3D) locally resonant sonic crystal (LRSC), exploiting both the multiple coupled resonances and the Bragg band gaps, is numerically and ...experimentally reported in this work. The LRSC is made of square cross-section scatterers arranged on a square lattice and periodically incorporating both quarter-wavelength and Helmholtz resonators along their heights. Local resonators of different types are combined with the periodicity of the system generating multiple coupled resonances at low frequencies and opening Bragg band gaps respectively. This twofold coupling produces a strong broadband attenuation: a large insertion loss (IL), with an average value of 16.8 dB, covering three and a half octaves from 350 Hz to 5000 Hz with a LRSC of 30 cm width. This frequency band corresponds to one of the several railway noise sources (rolling noise, traction auxiliaries, etc.). A simplified 2D LRSC is finally analyzed numerically in a real train-track configuration, showing the efficiency of the proposed design to attenuate the railway rolling noise.
During neonatal development, sensory cortices generate spontaneous activity patterns shaped by both sensory experience and intrinsic influences. How these patterns contribute to the assembly of ...neuronal circuits is not clearly understood. Using longitudinal in vivo calcium imaging in un-anesthetized mouse pups, we show that spatially segregated functional assemblies composed of interneurons and pyramidal cells are prominent in the somatosensory cortex by postnatal day (P) 7. Both reduction of GABA release and synaptic inputs onto pyramidal cells erode the emergence of functional topography, leading to increased network synchrony. This aberrant pattern effectively blocks interneuron apoptosis, causing increased survival of parvalbumin and somatostatin interneurons. Furthermore, the effect of GABA on apoptosis is mediated by inputs from medial ganglionic eminence (MGE)-derived but not caudal ganglionic eminence (CGE)-derived interneurons. These findings indicate that immature MGE interneurons are fundamental for shaping GABA-driven activity patterns that balance the number of interneurons integrating into maturing cortical networks.
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•GABA limits MGE-cIN participation in synchronous network events during development•Synaptic GABA regulates the emergence of interneuron-pyramidal cell assemblies•GABAergic restriction of pyramidal cell activity is required for MGE-cIN apoptosis•GABAAγ2-containing GABAA receptors are essential for interneuron apoptosis
Duan, Che, Chu et al. use genetic tools and in vivo imaging to show that cortical GABAergic signaling restricts functional assemblies and enables developmental apoptosis of MGE interneurons, balancing the number of interneurons integrating into maturing cortical networks.
Multiferroic materials possess two or more ferroic orders but have not been exploited in devices owing to the scarcity of room-temperature examples. Those that are ferromagnetic and ferroelectric ...have potential applications in multi-state data storage if the ferroic orders switch independently, or in electric-field controlled spintronics if the magnetoelectric coupling is strong. Future applications could also exploit toroidal moments and optical effects that arise from the simultaneous breaking of time-reversal and space-inversion symmetries. Here, we use soft X-ray resonant magnetic scattering and piezoresponse force microscopy to reveal that, at the interface with Fe or Co, ultrathin films of the archetypal ferroelectric BaTiO simultaneously possess a magnetization and a polarization that are both spontaneous and hysteretic at room temperature. Ab initio calculations of realistic interface structures provide insight into the origin of the induced moments and bring support to this new approach for creating room-temperature multiferroics. PUBLICATION ABSTRACT
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