Second-Generation Tyrosine Kinase Inhibitor Discontinuation in Chronic Myeloid Leukemia Patients with Stable Deep Molecular Response: A Systematic Review and a Meta-Analysis.

The treatment with 2nd-generation tyrosine kinase inhibitors (2G-TKIs), namely, dasatinib and nilotinib, has been reported to have faster and deeper responses in newly diagnosed chronic phase-chronic myeloid leukemia (CP-CML) patients as compared with imatinab. A number of studies on the discontinuation of 2G-TKIs have been conducted and recently published. A meta-analysis was conducted in this study to assess the rate of treatment-free remission (TFR) rate as well as the long-term safety of 2G-TKI discontinuation in CML patients with stable deep molecular response (DMR). 517 patients were recruited in 5 single-armed, prospective cohort studies. The overall weighted mean TFR rate at the follow-up of 12 months reached 57% (95% CI 51-64%; I 2 = 56.4%). The weighted mean TFR rate at the 24-month follow-up was 53% (95% CI 47-60%; I 2 = 47.1%). The loss of TFR was primarily concentrated in the first 12 months. 96.5% of patients, having restarted TKI therapy after a molecular relapse, achieved major molecular response (MMR) rapidly. There were four deaths at the two-year follow-up. As suggested from the results of the final study, 2G-TKI discontinuation in CML patients with stable DMR was reported to be feasible. Relapsed patients were retreated with 2G-TKI, and over 95% of patients could reach MMR. Almost no deaths occurred due to adverse events in two years after discontinuation, and more than half of the patients could maintain a TFR.

Low-loss GaOx-core/SiO2-cladding planar waveguides on Si substrate.

The unique properties of gallium oxide (GaOx) have drawn increasing interest as a material suitable for high-power electronic and optical applications. Herein, we report the demonstration of low-loss GaOx-core/SiO2-cladding waveguides on Si substrate. We present the fabrication process and annealing treatments of the waveguide devices, and we characterize the corresponding effects on optical transmission for 3 common wavelengths: 633 nm, 1064 nm, and 1550 nm. The best propagation loss achieved for these wavelengths is measured to be -0.4±0.1dB/cm, -0.3±0.2dB/cm, and -2.4±0.5dB/cm, respectively. We discuss the major waveguide loss mechanisms, followed by results of pump and probe experiments using visible/IR wavelengths for waveguides treated under various post-fabrication annealing conditions. We also show nonlinear measurements for a 250 fs laser beam to offer additional insights into the loss mechanisms, which are consistent with the linear optical transmission performances. High waveguide laser-induced damage threshold (LIDT) of >2.5J/cm2 is measured at this pulse width, making GaOx a potential candidate for high-power integrated photonic devices.

A Meta-Analysis on the Relationship Between Hair Dye and the Incidence of Non-Hodgkin's Lymphoma.

BACKGROUND: Epidemiologic studies have suggested hair dye to be a risk factor for many cancers. However, previous studies on the association between the personal use of hair dye and risk of non-Hodgkin's lymphoma (NHL) have been inconclusive. METHODS: The PubMed, Embase, Cochrane Library, and Web of Science databases, as well as the references cited in included studies, were searched for relevant studies up to February 10, 2015. Odds ratios (OR) with 95% confidence intervals (CI) were applied to assess the strength of the association. Publication bias was evaluated using a funnel plot by Egger's and Begg's tests. RESULTS: A total of 16 studies were included in the analysis, including 13 case-control studies and 3 cohort studies. The present meta-analysis results revealed that the risk of NHL in a high population of hair dye users was 14% (OR 1.14, 95% CI 1.01-1.29). Furthermore, individuals who used more than 20 pack-years of hair dye had increased risk of NHL. CONCLUSION: The outcomes indicate that hair dye use increases the risk of NHL, especially for females. Hence, people who frequently use hair dyes or have been using hair dyes for more than 20 years should minimize their exposure to hair dye products to prevent the risk of NHL.

Design of a tapered slot waveguide dielectric laser accelerator for sub-relativistic electrons.

We propose a dielectric laser accelerator design based on a tapered slot waveguide structure for sub-relativistic electron acceleration. This tapering scheme allows for straightforward tuning of the phase velocity of the accelerating field along the propagation direction, which is necessary for maintaining synchronization with electrons as their velocities increase. Furthermore, the non-resonant nature of this design allows for better tolerance to experimental errors. We also introduce a method to design this continuously tapered structure based on the eikonal approximation, and give a working example based on realistic experimental parameters.

Phase-dependent laser acceleration of electrons with symmetrically driven silicon dual pillar gratings.

We present the demonstration of phase-dependent laser acceleration and deflection of electrons using a symmetrically driven silicon dual pillar grating structure. We show that exciting an evanescent inverse Smith-Purcell mode on each side of a dual pillar grating can produce hyperbolic cosine acceleration and hyperbolic sine deflection modes, depending on the relative excitation phase of each side. Our devices accelerate sub-relativistic 99.0 keV kinetic energy electrons by 3.0 keV over a 15 µm distance with accelerating gradients of 200 MeV/m with 40 nJ, 300 fs, 1940 nm pulses from an optical parametric amplifier. These results represent a significant step towards making practical dielectric laser accelerators for ultrafast, medical, and high-energy applications.

miR-139 acts as a tumor suppressor in T-cell acute lymphoblastic leukemia by targeting CX chemokine receptor 4.

MicroRNAs (miRNAs) act as tumor regulators in T-cell acute lymphoblastic leukemia (T-ALL). However, the molecular mechanisms by which miRNA-139 (miR-139) regulates T-ALL remain unclear. In this study, we found that miR-139 was lowly expressed whereas C-X-C chemokine receptor type 4 (CXCR4) was highly expressed in T-ALL cell lines and patient samples. The T-ALL patients simultaneously with high levels of CXCR4 and low expression of miR-139 possessed poor prognosis. Moreover, the introduction of miR-139 inhibited T-ALL cell proliferation and invasion in vitro and suppressed tumor growth and lung metastasis in vivo. CXCR4 was identified as a direct target of miR-139. The suppressive effects of miR-139 were mimicked and counteracted by CXCR4 depletion and overexpression, respectively. Overall, the miR-139/CXCR4 axis plays an important role in T-ALL carcinogenesis.

Relationship between cigarette smoking and risk of chronic myeloid leukaemia: a meta-analysis of epidemiological studies.

OBJECTIVE: Previous epidemiologic studies that have been reported on the association between cigarette smoking and risk of chronic myeloid leukaemia (CML) have remained controversial. A comprehensive meta-analysis was performed to evaluate smoking as a potential relationship factor and incidence of CML. METHODS: Systematic literatures collected from articles published before August 2015 were searched from PubMed, EMBASE and the Cochrane Library. A total of 10 studies (nine case-controls and one cohort) met inclusion criteria of this meta-analysis. Odds ratios (ORs) with 95% confidence interval (CI) were calculated to assess the strength of the association between cigarette smoking and risk of CML in this study. Quality assessments were performed on the studies with the Newcastle-Ottawa Scale. I2 index was used to evaluate heterogeneity. Finally, publication bias was assessed through funnel plots and Begger's test. RESULTS: No significant association was observed between ever-smokers and CML when compared among non-smokers (OR = 1.13, 95% CI: 0.99-1.29) or between subgroups stratified by smoking history, gender, geographical region, study design and source of patients. Our results demonstrate that this association was stronger in individuals who smoked <20 cigarettes/day (OR = 1.72, 95% CI: 1.06-2.79) vs. individuals who smoked >20 cigarettes/day (OR = 1.24, 95% CI: 0.55-2.81). Moreover, cumulative smoking of <15, 15-30 and >30 pack-years was associated with ORs of 1.22, 1.32 and 1.39, respectively (P < 0.001, for trend). CONCLUSION: This meta-analysis suggests that smoking may significantly increase the risk of CML in a dose-dependent manner. However, additional well-designed, prospective cohort studies are required to verify these findings and identify other risk factors associated with CML.

Transverse and longitudinal characterization of electron beams using interaction with optical near-fields.

We demonstrate an experimental technique for both transverse and longitudinal characterization of bunched femtosecond free electron beams. The operation principle is based on monitoring of the current of electrons that obtained an energy gain during the interaction with the synchronized optical near-field wave excited by femtosecond laser pulses. The synchronous accelerating/decelerating fields confined to the surface of a silicon nanostructure are characterized using a highly focused sub-relativistic electron beam. Here the transverse spatial resolution of 450 nm and femtosecond temporal resolution of 480 fs (sub-optical-cycle temporal regime is briefly discussed) achievable by this technique are demonstrated.

Dielectric laser acceleration of sub-100 keV electrons with silicon dual-pillar grating structures.

We present the demonstration of high-gradient laser acceleration and deflection of electrons with silicon dual-pillar grating structures using both evanescent inverse Smith-Purcell modes and coupled modes. Our devices accelerate subrelativistic 86.5 and 96.3 keV electrons by 2.05 keV over 5.6 µm distance for accelerating gradients of 370 MeV/m with a 3 nJ mode-locked Ti:sapphire laser. We also show that dual pillars can produce uniform accelerating gradients with a coupled-mode field profile. These results represent a significant step toward making practical dielectric laser accelerators for ultrafast, medical, and high-energy applications.

Bias-dependence of luminescent coupling efficiency in multijunction solar cells.

In this work, we demonstrate an improved method to simulate the characteristics of multijunction solar cell by introducing a bias-dependent luminescent coupling efficiency. The standard two-diode equivalent-circuit model with constant luminescent coupling efficiency has limited accuracy because it does not include the recombination current from photogenerated carriers. Therefore, we propose an alternative analytical method with bias-dependent luminescent coupling efficiency to model multijunction cell behavior. We show that there is a noticeable difference in the J-V characteristics and cell performance generated by simulations with a constant vs. bias-dependent coupling efficiency. The results indicate that introducing a bias-dependent coupling efficiency produces more accurate modeling of multijunction cell behavior under real operating conditions.

Automatic Dent-landmark detection in 3-D CBCT dental volumes.

Orthodontic craniometric landmarks provide critical information in oral and maxillofacial imaging diagnosis and treatment planning. The Dent-landmark, defined as the odontoid process of the epistropheus, is one of the key landmarks to construct the midsagittal reference plane. In this paper, we propose a learning-based approach to automatically detect the Dent-landmark in the 3D cone-beam computed tomography (CBCT) dental data. Specifically, a detector is learned using the random forest with sampled context features. Furthermore, we use spacial prior to build a constrained search space other than use the full three dimensional space. The proposed method has been evaluated on a dataset containing 73 CBCT dental volumes and yields promising results.