Introduction of new myeloma therapies offers new options for patients refractory to immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs). In this multicenter study, patients with relapsed ...multiple myeloma, who have received at least three prior lines of therapy, are refractory to both an IMiD (lenalidomide or pomalidomide) and a PI (bortezomib or carfilzomib), and have been exposed to an alkylating agent were identified. The time patients met the above criteria was defined as time zero (T
). Five hundred and forty-three patients diagnosed between 2006 and 2014 were enrolled in this study. Median age at T
was 62 years (range 31-87); 61% were males. The median duration between diagnosis and T
was 3.1 years. The median number of lines of therapy before T
was 4 (range 3-13). The median overall survival (OS) from T
for the entire cohort was 13 (95% confidence interval (CI) 11, 15) months. At least one regimen recorded after T
in 462 (85%) patients, with a median (95% CI) progression-free survival and OS from T
of 5 (4, 6), and 15.2 (13, 17) months, respectively. The study provides the expected outcome of relapsed multiple myeloma that is refractory to a PI and an IMiD, a benchmark for comparison of new therapies being evaluated.
Giant Piezoelectricity on Si for Hyperactive MEMS Baek, S. H.; Park, J.; Kim, D. M. ...
Science (American Association for the Advancement of Science),
11/2011, Letnik:
334, Številka:
6058
Journal Article
Recenzirano
Microelectromechanical systems (MEMS) incorporating active piezoelectric layers offer integrated actuation, sensing, and transduction. The broad implementation of such active MEMS has long been ...constrained by the inability to integrate materials with giant piezoelectric response, such as Pb(MG 1/3 Nb 2/3 )O₃-PbTiO₃ (PMN-PT). We synthesized high-quality PMN-PT epitaxial thin films on vicinal (001) Si wafers with the use of an epitaxial (001) SrTiO₃ template layer with superior piezoelectric coefficients (e 31,f = -27 ± 3 coulombs per square meter) and figures of merit for piezoelectric energy-harvesting systems. We have incorporated these heterostructures into microcantilevers that are actuated with extremely low drive voltage due to thin-film piezoelectric properties that rival bulk PMN-PT single crystals. These epitaxial heterostructures exhibit very large electromechanical coupling for ultrasound medical imaging, microfluidic control, mechanical sensing, and energy harvesting.
We conducted a systemic evaluation to describe the effect of minimal residual disease (MRD) kinetics on long-term allogeneic transplantation outcome by analyzing 95 adult transplants with ...Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL) who received first-line two courses of imatinib-based chemotherapy (median follow-up 5 years). MRD monitoring was centrally evaluated by real-time quantitative PCR (4.5 log sensitivity). After the first course of imatinib-based chemotherapy, 33 patients (34.7%) achieved at least major molecular response. On the basis of MRD kinetics by the end of two courses of imatinib-based chemotherapy, we stratified entire patients into four subgroups: early-stable molecular responders (EMRs, n=33), late molecular responders (LMRs, n=35), intermediate molecular responders (IMRs, n=9) and poor molecular responders (PMRs, n=18). Multivariate analysis showed that the most powerful factor affecting long-term transplantation outcome was MRD kinetics. Compared with EMRs, IMRs or PMRs had significantly higher risk of treatment failure in terms of relapse and disease-free survival (DFS). LMRs had a tendency toward a lower DFS. Quantitative monitoring of MRD kinetics during the first-line imatinib-based chemotherapy course is useful in identifying subgroups of Ph-positive ALL transplants at a high risk of relapse.
Observational studies and randomized controlled trials have yielded inconsistent findings about the association between the use of acid-suppressive drugs and the risk of pneumonia. We performed a ...systematic review and meta-analysis to summarize this association.
We searched three electronic databases (MEDLINE PubMed, Embase and the Cochrane Library) from inception to Aug. 28, 2009. Two evaluators independently extracted data. Because of heterogeneity, we used random-effects meta-analysis to obtain pooled estimates of effect.
We identified 31 studies: five case-control studies, three cohort studies and 23 randomized controlled trials. A meta-analysis of the eight observational studies showed that the overall risk of pneumonia was higher among people using proton pump inhibitors (adjusted odds ratio OR 1.27, 95% confidence interval CI 1.11-1.46, I(2) 90.5%) and histamine(2) receptor antagonists (adjusted OR 1.22, 95% CI 1.09-1.36, I(2) 0.0%). In the randomized controlled trials, use of histamine(2) receptor antagonists was associated with an elevated risk of hospital-acquired pneumonia (relative risk 1.22, 95% CI 1.01-1.48, I(2) 30.6%).
Use of a proton pump inhibitor or histamine(2) receptor antagonist may be associated with an increased risk of both community- and hospital-acquired pneumonia. Given these potential adverse effects, clinicians should use caution in prescribing acid-suppressive drugs for patients at risk.
To investigate the risk factors for acute GVHD (aGVHD), based on NIH consensus criteria (NCC), we evaluated 775 patients who underwent allogeneic transplantation. Of them, 346 patients developed ...aGVHD by NCC, in whom we also analyzed factors affecting aGVHD-specific survival. The cumulative incidence of aGVHD was 44.7%, consisting of classic aGVHD (n=320) and late-onset (n=26). Multivariate analyses revealed that younger age (P=0.015), unrelated donors (P=0.004) and acute leukemia compared with other hematologic malignancies (P=0.005) were significant risk factors for aGVHD, whereas PBSCs showed no association (P=0.720). Multivariate analyses, with only aGVHD patients, revealed that late-onset aGVHD had superior aGVHD-specific survival to classic aGVHD (P=0.044), and identified the association of visceral organ involvement (P=0.002), severity of aGVHD at onset (P=0.035) and advanced disease status (P<0.001) with inferior aGVHD-specific survival. In conclusion, this study demonstrates the risk and prognostic factors for aGVHD by NCC with some differences with the previous reports that were based on old criteria. The difference in the risk factors according to different criteria will give insights about the pathophysiology of GVHD. The better prognosis of late-onset aGVHD than of classic aGVHD raises the necessity for prospective trials with a large cohort focusing on the onset time.
Spin-orbit coupling results in technologically-crucial phenomena underlying magnetic devices like magnetic memories and energy-efficient motors. In heavy element materials, the strength of spin-orbit ...coupling becomes large to affect the overall electronic nature and induces novel states such as topological insulators and spin-orbit-integrated Mott states. Here we report an unprecedented charge-ordering cascade in IrTe2 without the loss of metallicity, which involves localized spin-orbit Mott states with diamagnetic Ir(4+)-Ir(4+) dimers. The cascade in cooling, uncompensated in heating, consists of first order-type consecutive transitions from a pure Ir(3+) phase to Ir(3+)-Ir(4+) charge-ordered phases, which originate from Ir 5d to Te 5p charge transfer involving anionic polymeric bond breaking. Considering that the system exhibits superconductivity with suppression of the charge order by doping, analogously to cuprates, these results provide a new electronic paradigm of localized charge-ordered states interacting with itinerant electrons through large spin-orbit coupling.
An unusual conductance sequenceEffects of correlations between electrons are enhanced in systems of reduced dimensions. The two-dimensional interface between two oxide materials, lanthanum aluminate ...(LaAlO3) and strontium titanate (SrTiO3), exhibits magnetism and superconductivity. In even lower-dimensional systems fabricated in similar heterostructures, electrons can pair without going superconducting. Briggeman et al. have now observed another exotic effect in LaAlO3/SrTiO3 waveguides: At certain magnetic fields, the conductance in these one-dimensional systems exhibits steps of an unconventional sequence. To understand the experimental data, the researchers used a model that accounted for interactions between electrons and found that the phenomenology was consistent with the formation of a series of correlated phases characterized by bound states of three or more electrons.Science, this issue p. 769One-dimensional electronic systems can support exotic collective phases because of the enhanced role of electron correlations. We describe the experimental observation of a series of quantized conductance steps within strongly interacting electron waveguides formed at the lanthanum aluminate–strontium titanate (LaAlO3/SrTiO3) interface. The waveguide conductance follows a characteristic sequence within Pascal’s triangle: (1, 3, 6, 10, 15, …) ⋅ e2/h, where e is the electron charge and h is the Planck constant. This behavior is consistent with the existence of a family of degenerate quantum liquids formed from bound states of n = 2, 3, 4, … electrons. Our experimental setup could provide a setting for solid-state analogs of a wide range of composite fermionic phases.
Using in situ high-resolution synchrotron x-ray scattering, the Curie temperature TC has been determined for ultrathin c-axis epitaxial PbTiO3 films on conducting substrates (SrRuO3 on SrTiO3), with ...surfaces exposed to a controlled vapor environment. The suppression of TC was relatively small, even for the thinnest film (1.2 nm). We observe that 180 degrees stripe domains do not form, indicating that the depolarizing field is compensated by free charge at both interfaces. This is confirmed by ab initio calculations that find polar ground states in the presence of ionic adsorbates.
•We demonstrated gallium nitride (GaN) based negative capacitance field-effect transistors (NCFETs) that achieve steep switching operation.•Ferroelectric phase characteristics were successfully ...demonstrated using a 10 nm thick undoped-HfO2 ferroelectric thin film fabricated through atomic layer deposition.•The HfO2 metal-ferroelectric-metal (MFM) capacitor was connected in series with the gate electrode of a recessed normally-off AlGaN/GaN MOS-HFET.•The forward/reverse subthreshold slopes were dramatically reduced from 104/105 to 22/23 mV/dec.
We demonstrated gallium nitride (GaN) based negative capacitance field-effect transistors (NCFETs) that achieve steep switching operation. Ferroelectric phase characteristics were successfully demonstrated using a 10 nm thick undoped-HfO2 ferroelectric thin film fabricated through atomic layer deposition. The HfO2 metal-ferroelectric-metal (MFM) capacitor was connected in series with the gate electrode of a recessed normally-off AlGaN/GaN MOS-HFET. The forward/reverse subthreshold slopes were dramatically reduced from 104/105 to 22/23 mV/dec.
Background
In allogeneic stem cell transplantation (allo‐SCT), reduced‐intensity conditioning (RIC) is known for producing less regimen‐related toxicity. However, whether or not RIC reduces the risk ...for infection and infection‐related mortality (IRM) remains controversial.
Methods
We retrospectively analyzed infectious episodes and IRMs after allo‐SCTs by time period and by the intensity of the conditioning regimen (RIC n = 81 vs. myeloablative conditioning, MAC n = 150).
Results
The cumulative incidence of any kind of infection was lower in the RIC group through the entire period (72% vs. 87%; P = 0.007). The onset of infections was deferred in the RIC group as compared with the MAC group (P = 0.012). Bacteremia occurred less frequently in the RIC group through the entire period (5% vs. 14%; P = 0.044). However, the incidences of cytomegalovirus reactivation and disease, herpes zoster, virus‐associated hemorrhagic cystitis, and invasive fungal infection were not different between the two groups. Furthermore, there was no difference in relapse‐free survival and IRM between the two conditioning regimens.
Conclusion
Careful monitoring and appropriate preventive/therapeutic strategies for infectious complications, comparable to those for allo‐SCT recipients with MAC, should also be applied to those with RIC, especially after engraftment.
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