Clinical trials of post-mastectomy radiotherapy (PMRT) for early invasive breast cancer (EIBC) have included few older women. This study examined whether the association between overall survival or ...breast cancer-specific survival (BCSS) and receipt of PMRT for EIBC altered with age.
The study used patient-level linked cancer registration, routine hospital and radiotherapy data for England and Wales. It included 31 243 women aged ≥50 years diagnosed between 2014 and 2018 with low- (T1-2N0), intermediate- (T3N0/T1-2N1) or high-risk (T1-2N2/T3N1-2) EIBC who received a mastectomy within 12 months from diagnosis. Patterns of survival were analysed using a landmark approach. Associations between overall survival/BCSS and PMRT in each risk group were analysed with flexible parametric survival models, which included patient and tumour factors; whether the association between PMRT and overall survival/BCSS varied by age was assessed using interaction terms.
Among 4711 women with high-risk EIBC, 86% had PMRT. Five-year overall survival was 70.5% and BCSS was 79.3%. Receipt of PMRT was associated with improved overall survival adjusted hazard ratio (aHR) 0.75, 95% confidence interval 0.64–0.87 and BCSS (aHR 0.78, 95% confidence interval 0.65–0.95) compared with women who did not have PMRT; associations did not vary by age (overall survival, P-value for interaction term = 0.141; BCSS, P = 0.077). Among 10 814 women with intermediate-risk EIBC, 59% had PMRT; 5-year overall survival was 78.4% and BCSS was 88.0%. No association was found between overall survival (aHR 1.01, 95% confidence interval 0.92–1.11) or BCSS (aHR 1.16, 95% confidence interval 1.01–1.32) and PMRT. There was statistical evidence of a small change in the association with age for overall survival (P = 0.007), although differences in relative survival were minimal, but not for BCSS (P = 0.362).
The association between PMRT and overall survival/BCSS does not appear to be modified by age among women with high- or intermediate-risk EIBC and, thus, treatment recommendations should not be modified on the basis of age alone.
•Assessed if the association between PMRT and 5-year OS and BCSS changed with age among women aged 50+ years with EIBC.•Women stratified into three groups based on recurrence risk: low (T1-2N0), intermediate (T1-2N1/T3N0) high (T1-2N2/T3N1-2).•PMRT associated with improved survival for women in the high-risk group, but not in the low- or intermediate-risk groups.•Found no evidence that the association between OS/BCSS and PMRT varied by age among women in any of the three risk groups.
We propose a novel method to characterize the temporal duration and shape of femtosecond x-ray pulses in a free-electron laser (FEL) by measuring the time-resolved electron-beam energy loss and ...energy spread induced by the FEL process, with a transverse radio-frequency deflector located after the undulator. Its merits are simplicity, high resolution, wide diagnostic range, and non-invasive to user operation. When the system is applied to the Linac Coherent Light Source, the first hard x-ray free-electron laser in the world, it can provide single-shot measurements on the electron beam and x-ray pulses with a resolution on the order of 1-2 femtoseconds rms.
Summary
Introduction
This study investigates the benefits of using multiplex reverse transcriptase‐PCR (RT‐PCR) in addition to standard karyotyping during the initial evaluation of acute leukemia.
...Methods
A total of 1114 consecutive specimens from patients with acute leukemia were tested using a commercial multiplex RT‐PCR kit (HemaVision, DNA Diagnostic). NPM1 and CEBPA mutations were selectively tested in acute myeloid leukemia (AML) patients with multiplex RT‐PCR negativity.
Results
In specimens with optimal cytogenetics, the frequency of recurrent translocations was 31.3%, and cryptic translocations were detected in 2.1% of samples. The concordance rate between karyotyping and multiplex RT‐PCR was 97.5%. In addition to the established functions, we demonstrated the additional benefits of multiplex RT‐PCR, including successful molecular characterization, even in cytogenetically suboptimal specimens (5.7%); detection of submicroscopic aberrations (1.0%); detection of rare but potentially significant translocations or variants (2.5%); selection of AML candidates for mutation analysis (68.3%); and finally exclusion of recurrent translocations in patients with acute lymphoblastic leukemia or mixed phenotype acute leukemia (22.5%).
Conclusion
We reconfirmed the accuracy and reliability of multiplex RT‐PCR for diagnosing acute leukemia and demonstrated additional advantages of this system for the initial evaluation of acute leukemia. Thus, multiplex RT‐PCR is worth considering in diagnostic testing of acute leukemias.
Since c-Met has an important role in the development of cancer, it is considered as an attractive target for cancer therapy. Although molecular mechanisms for oncogenic property of c-Met have been ...actively investigated, regulatory elements for c-Met endocytosis and its effect on c-Met signaling remain unclear. In this study, we identified a pivotal endocytic motif in c-Met and tested it for selective modulation of HGF-induced c-Met response. Using various chimeric constructs with the cytoplasmic tail of c-Met, we were able to demonstrate that a dileucine motif located in the C-terminus of c-Met acts to regulate its endocytosis. Synthetic peptide Ant-3S, consisting of antennapedia-derived protein transduction domain (designated as Ant) and c-Met-derived 16 amino-acids (designated as 3S, spanning amino-acids 1378 to 1393), rapidly moved into cancer cells and disrupted c-Met trafficking. Importantly, an extension of c-Met retention time on the membrane by Ant-3S peptide significantly decreased phosphorylation-dependent c-Met signal transduction. Additionally, the peptide effectively inhibited HGF-induced cell growth, scattering and migration. The underlying molecular mechanism for these observations has been investigated and revealed that the dileucine motif interacts with endocytic machinery, including adaptin β and caveolin-1, for sustained and enhanced signal transduction. Finally, Ant-3S peptide specifically blocked internalization of interleukin-2 receptor α-subunit/3S chimeric protein, but not the other receptors, including Glut4, Glut8 and transferrin receptor. Such results indicate the presence of a selective endocytic assembly for c-Met. It also suggests a potential for c-Met-specific anti-cancer therapy using the identified endocytic motif in this study.
Amyloid β, the major constituent of the senile plaques in the brains of patients with Alzheimer’s disease, is cytotoxic to neurons and has a central role in the pathogenesis of the disease. We have ...previously demonstrated that potent antioxidants idebenone and α-tocopherol prevent learning and memory impairment in rats which received a continuous intracerebroventricular infusion of amyloid β, suggesting a role for oxidative stress in amyloid β-induced learning and memory impairment. To test the hypothesis, in the present study, we investigated alterations in the immunoreactivity of endogenous antioxidant systems such as mitochondrial Mn–superoxide dismutase, glutathione, glutathione peroxidase and glutathione-S-transferase following the continuous intracerebroventricular infusion of amyloid β for 2 weeks. The infusion of amyloid β (1–42) resulted in a significant reduction of the immunoreactivity of these antioxidant substances in such brain areas as the hippocampus, parietal cortex, piriform cortex, substantia nigra and thalamus although the same treatment with amyloid β (40–1) had little effect. The alterations induced by amyloid β (1–42) were not uniform, but rather specific for each immunoreactive substance in a brain region-dependent manner.
These results demonstrate a cytological effect of oxidative stress induced by amyloid β (1–42) infusion. Furthermore, our findings may indicate a heterogeneous susceptibility to the oxidative stress produced by amyloid β.
One of the least documented and understood aspects of gamma-ray bursts (GRBs) is the rise phase of the optical light curve. The Ultra-Fast Flash Observatory (UFFO) is an effort to address this ...question through extraordinary opportunities presented by a series of space missions including a small spacecraft observatory. The UFFO is equipped with a fast-response Slewing Mirror Telescope (SMT) that uses a rapidly moving mirror or mirror array to redirect the optical beam rather than slewing the entire spacecraft to aim the optical instrument at the GRB position. The UFFO will probe the early optical rise of GRBs with sub-second response, for the first time, opening a completely new frontier in GRBs and transient studies. Its fast response measurements of the optical emission of dozens of GRBs each year will provide unique probes of the burst mechanism and test the prospect of GRBs as a new standard candle, potentially opening up the z > 10 universe. For the first time we employ a motorized slewing stage in SMT that can point to the event within 1 s after the x-ray trigger provided by the UFFO Burst Alert and Trigger Telescope. These two scientific instruments comprise the UFFO-pathfinder payload, which will be placed onboard the Lomonosov satellite and launched in 2013. The UFFO-pathfinder is the first step of our long-term program of space instruments for rapid-response GRB observations. We describe early photon science, our soon-to-be-launched UFFO-pathfinder hardware and mission, and our next planned mission, the UFFO-100.
APEX (Agricultural Policy/Environmental eXtender) is an oft-used agroecosystem model but has limited use in groundwater-driven watersheds due to a simplistic representation of groundwater processes. ...This paper presents the linkage of APEX and the groundwater flow model MODFLOW into a single modeling code. The mapping of recharge, groundwater head, and groundwater-surface water interactions are handled internally via subroutines. The APEX-MODFLOW model is applied to three watersheds in the United States for testing code accuracy and hydrologic state variables and fluxes: the Animas River Watershed, Colorado and New Mexico (3543 km2); the Price River Watershed, Utah (4886 km2); and the Middle Bosque River Watershed, Texas (470 km2). Whereas the hydrology of the Animas River and Price River watersheds is driven by snowmelt and spring runoff, the hydrology of the Middle Bosque River Watershed is driven by summer thunderstorms. The model can be used for scenario analysis in groundwater-driven watersheds.
•New integrated hydrologic model links APEX model to MODFLOW model.•Model passes recharge, water table elevation, and gw-sw flux rates internally.•APEX-MODFLOW applied to three watersheds in Utah, Colorado, and Texas, USA.•Model results show importance of including physically based groundwater flow.
Lasing via a phase retardation defect mode is reported for the first time. The Figure shows the far‐field pattern of laser emission realized by inserting an anisotropic nematic liquid crystal (LC) ...defect layer between polymer cholesteric LC layers. The system mimics the cuticle of Plusiotis resplendens, a beetle, using the birefringence of the anisotropic layer to achieve reflectance greater than the 50 % provided by simple cholesteric LC photonic bandgaps.
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