This study was performed to investigate the prevalence, clinical characteristics, and treatment response according to BRCA1 and BRCA2 (BRCA) mutations in Korean patients with epithelial ovarian ...cancer (EOC). Two‐hundred and ninety‐eight Korean women diagnosed with high‐grade serous and/or endometrioid EOC from 2010 to 2015 were tested for germline and 86 specimens for somatic BRCA mutations, regardless of the family history. Clinical characteristics including survival outcomes were compared in patients with and without BRCA mutations (NCT02963688). A total of 43 different germline BRCA mutations were identified in 78 patients among 298 patients (26.2%). Somatic BRCA mutations were identified in 11 (12.8%) patients among patients without germline BRCA mutations. Haplotype analysis demonstrated no founder mutations in our Korean patient cohort. Insignificant differences in age at diagnosis, primary site, and residual disease after surgery were observed between patients with and without BRCA mutations. In multivariate analysis for overall survival (OS), the presence of BRCA mutation was significantly associated with OS (P = .049) in addition to platinum sensitivity (P < .001), indicating it is an independent prognostic factor for survival regardless of platinum sensitivity to first‐line chemotherapy. In addition, a higher response rate to subsequent chemotherapy after recurrence was observed in EOC patients with BRCA mutations resulting in better OS. In the current study, the prevalence of BRCA mutations in Korean patients with EOC was higher than previously reported in other ethnic groups. We demonstrated characteristics and treatment response in Korean EOC patients with BRCA mutations. These findings may provide valuable information to be considered in future clinical trials including Asian patients.
A total of 43 different germline BRCA mutations were identified in 78 patients among 298 patients (26.2%). Somatic BRCA mutations were identified in 11 (12.8%) patients among patients without germline BRCA mutations. BRCA mutation is an independent prognostic factor for survival regardless of platinum sensitivity to first‐line chemotherapy. A higher response rate to subsequent chemotherapy after recurrence was observed in patients with BRCA mutation, resulting in better overall survival in these patients.
Satellite altimeter sea surface heights, in combination with Argo ocean temperature and salinity observations, provide an independent measure of global mean ocean mass (GMOM) change. Over the period ...January 2005 to April 2020, GMOM rates observed by the Gravity Recovery and Climate Experiment (GRACE) and GRACE Follow‐On (GFO) range from 1.88 ± 0.10 to 2.63 ± 0.10 mm/year, compared to 2.85 ± 0.37 mm/year from Altimeter‐Argo. Over much of the GRACE era, GRACE GMOM estimates agree well with Altimeter‐Argo over a broadband of frequencies. However, during the late stage of the GRACE mission (after August 2016) and into the GFO era, differences between GRACE/GFO and Altimeter‐Argo GMOM estimates become substantially larger and systematic, which may be related to the single accelerometer mode of operation during late‐stage GRACE and GFO missions and/or errors of Argo and altimeter data.
Key Points
GRACE/GFO‐derived global ocean mass change agrees generally well with Altimeter‐Argo estimates at seasonal and long‐term scales
The GRACE/GFO and Altimeter‐Argo GMOM differences become substantially larger and systematic during the late‐stage GRACE and GFO periods
The discrepancy is likely related to the single accelerometer mode of the late‐stage GRACE and GFO and/or errors of Argo and altimeter data
Pazopanib is an oral, multikinase inhibitor of vascular endothelial growth factor receptor (VEGFR) -1/-2/-3, platelet-derived growth factor receptor (PDGFR) -α/-β, and c-Kit. Preclinical and clinical ...studies support VEGFR and PDGFR as targets for advanced ovarian cancer treatment. This study evaluated the role of pazopanib maintenance therapy in patients with ovarian cancer whose disease did not progress during first-line chemotherapy.
Nine hundred forty patients with histologically confirmed cancer of the ovary, fallopian tube, or peritoneum, International Federation Gynecology Obstetrics (FIGO) stages II-IV, no evidence of progression after primary therapy consisting of surgery and at least five cycles of platinum-taxane chemotherapy were randomized 1:1 to receive pazopanib 800 mg once per day or placebo for up to 24 months. The primary end point was progression-free survival by RECIST 1.0 assessed by the investigators.
Maintenance pazopanib prolonged progression-free survival compared with placebo (hazard ratio HR, 0.77; 95% CI, 0.64 to 0.91; P = .0021; median, 17.9 v 12.3 months, respectively). Interim survival analysis based on events in 35.6% of the population did not show any significant difference. Grade 3 or 4 adverse events of hypertension (30.8%), neutropenia (9.9%), liver-related toxicity (9.4%), diarrhea (8.2%), fatigue (2.7%), thrombocytopenia (2.5%), and palmar-plantar erythrodysesthesia (1.9%) were significantly higher in the pazopanib arm. Treatment discontinuation related to adverse events was higher among patients treated with pazopanib (33.3%) compared with placebo (5.6%).
Pazopanib maintenance therapy provided a median improvement of 5.6 months (HR, 0.77) in progression-free survival in patients with advanced ovarian cancer who have not progressed after first-line chemotherapy. Overall survival data to this point did not suggest any benefit. Additional analysis should help to identify subgroups of patients in whom improved efficacy may balance toxicity (NCT00866697).
This study introduces graphited nanodiamond (G-ND) as an environmentally friendly, easy-to-regenerate, and cost-effective alternative catalyst to activate persulfate (i.e., peroxymonosulfate (PMS) ...and peroxydisulfate (PDS)) and oxidize organic compounds in water. The G-ND was found to be superior for persulfate activation to other benchmark carbon materials such as graphite, graphene, fullerene, and carbon nanotubes. The G-ND/persulfate showed selective reactivity toward phenolic compounds and some pharmaceuticals, and the degradation kinetics were not inhibited by the presence of oxidant scavengers and natural organic matter. These results indicate that radical intermediates such as sulfate radical anion and hydroxyl radical are not majorly responsible for this persulfate-driven oxidation of organic compounds. The findings from linear sweep voltammetry, thermogravimetric analysis, Fourier transform infrared spectroscopy, and electron paramagnetic resonance spectroscopy analyses suggest that the both persulfate and phenol effectively bind to G-ND surface and are likely to form charge transfer complex, in which G-ND plays a critical role in mediating facile electron transfer from phenol to persulfate.
Abstract
Single atom catalysts have been found to exhibit superior selectivity over nanoparticulate catalysts for catalytic reactions such as hydrogenation due to their single-site nature. However, ...improved selectively is often accompanied by loss of activity and slow kinetics. Here we demonstrate that neighboring Pd single atom catalysts retain the high selectivity merit of sparsely isolated single atom catalysts, while the cooperative interactions between neighboring atoms greatly enhance the activity for hydrogenation of carbon-halogen bonds. Experimental results and computational calculations suggest that neighboring Pd atoms work in synergy to lower the energy of key meta-stable reactions steps, i.e., initial water desorption and final hydrogenated product desorption. The placement of neighboring Pd atoms also contribute to nearly exclusive hydrogenation of carbon-chlorine bond without altering any other bonds in organohalogens. The promising hydrogenation performance achieved by neighboring single atoms sheds light on a new approach for manipulating the activity and selectivity of single atom catalysts that are increasingly studied in multiple applications.
Nanoscale catalysts that can enable Fenton-like chemistry and produce reactive radicals from hydrogen peroxide activation have been extensively studied in order to overcome the limitations of ...homogeneous Fenton processes. Despite several advantageous features, limitation in mass transfer of short-lived radical species is an inherent drawback of the heterogeneous system. Here, we present a mechanistic foundation for the way spatial confinement of Fenton chemistry at the nanoscale can significantly enhance the kinetics of radical-mediated oxidation reactionspollutant degradation in particular. We synthesized a series of Fe3O4-functionalized nanoreactors with precise pore dimensions, based on an anodized aluminum oxide template, to enable quantitative analysis of nanoconfinement effects. Combined with computational simulation of spatial distribution of radicals, we found that hydroxyl radical concentration was strongly dependent on the distance from the surface of Fenton catalysts. This distance dependency significantly influences the gross reaction kinetics and accounts for the observed nanoconfinement effects. We further found that a length scale below 25 nm is critical to avoid the limitation of short-lived species diffusion and achieve kinetics that are orders of magnitude faster than those obtained in a batch suspension of heterogeneous catalysts. These findings suggest a new strategy to develop an innovative heterogeneous catalytic system with the most effective use of hydroxyl radicals in oxidation treatment scenarios.
Fertility-sparing treatment (FST) might be considered an option for reproductive patients with low-risk endometrial cancer (EC). On the other hand, the matching rates between preoperative assessment ...and postoperative pathology in low-risk EC patients are not high enough. We aimed to predict the postoperative pathology depending on preoperative myometrial invasion (MI) and grade in low-risk EC patients to help extend the current criteria for FST. This ancillary study (KGOG 2015S) of Korean Gynecologic Oncology Group 2015, a prospective, multicenter study included patients with no MI or MI <1/2 on preoperative MRI and endometrioid adenocarcinoma and grade 1 or 2 on endometrial biopsy. Among the eligible patients, Groups 1-4 were defined with no MI and grade 1, no MI and grade 2, MI <1/2 and grade 1, and MI <1/2 and grade 2, respectively. New prediction models using machine learning were developed. Among 251 eligible patients, Groups 1-4 included 106, 41, 74, and 30 patients, respectively. The new prediction models showed superior prediction values to those from conventional analysis. In the new prediction models, the best NPV, sensitivity, and AUC of preoperative each group to predict postoperative each group were as follows: 87.2%, 71.6%, and 0.732 (Group 1); 97.6%, 78.6%, and 0.656 (Group 2); 71.3%, 78.6% and 0.588 (Group 3); 91.8%, 64.9%, and 0.676% (Group 4). In low-risk EC patients, the prediction of postoperative pathology was ineffective, but the new prediction models provided a better prediction.
Systematic pelvic and paraaortic lymphadenectomy has been widely used in the surgical treatment of patients with advanced ovarian cancer, although supporting evidence from randomized clinical trials ...has been limited.
We intraoperatively randomly assigned patients with newly diagnosed advanced ovarian cancer (International Federation of Gynecology and Obstetrics stage IIB through IV) who had undergone macroscopically complete resection and had normal lymph nodes both before and during surgery to either undergo or not undergo lymphadenectomy. All centers had to qualify with regard to surgical skills before participation in the trial. The primary end point was overall survival.
A total of 647 patients underwent randomization from December 2008 through January 2012, were assigned to undergo lymphadenectomy (323 patients) or not undergo lymphadenectomy (324), and were included in the analysis. Among patients who underwent lymphadenectomy, the median number of removed nodes was 57 (35 pelvic and 22 paraaortic nodes). The median overall survival was 69.2 months in the no-lymphadenectomy group and 65.5 months in the lymphadenectomy group (hazard ratio for death in the lymphadenectomy group, 1.06; 95% confidence interval CI, 0.83 to 1.34; P = 0.65), and median progression-free survival was 25.5 months in both groups (hazard ratio for progression or death in the lymphadenectomy group, 1.11; 95% CI, 0.92 to 1.34; P = 0.29). Serious postoperative complications occurred more frequently in the lymphadenectomy group (e.g., incidence of repeat laparotomy, 12.4% vs. 6.5% P = 0.01; mortality within 60 days after surgery, 3.1% vs. 0.9% P = 0.049).
Systematic pelvic and paraaortic lymphadenectomy in patients with advanced ovarian cancer who had undergone intraabdominal macroscopically complete resection and had normal lymph nodes both before and during surgery was not associated with longer overall or progression-free survival than no lymphadenectomy and was associated with a higher incidence of postoperative complications. (Funded by Deutsche Forschungsgemeinschaft and the Austrian Science Fund; LION ClinicalTrials.gov number, NCT00712218.).
Climate model estimates show significant groundwater depletion during the 20th century, consistent with global mean sea level (GMSL) budget analysis. However, prior to the Argo float era, in the ...early 2000’s, there is little information about steric sea level contributions to GMSL, making the role of groundwater depletion in this period less certain. We show that a useful constraint is found in observed polar motion (PM). In the period 1993–2010, we find that predicted PM excitation trends estimated from various sources of surface mass loads and the estimated glacial isostatic adjustment agree very well with the observed. Among many contributors to the PM excitation trend, groundwater storage changes are estimated to be the second largest (4.36 cm/yr) toward 64.16°E. Neglecting groundwater effects, the predicted trend differs significantly from the observed. PM observations may also provide a tool for studying historical continental scale water storage variations.
Plain Language Summary
Melting of polar ice sheets and mountain glaciers has been understood as a main cause of sea level rise associated with contemporary climate warming. It has been proposed that an important anthropogenic contribution is sea level rise due to groundwater depletion resulting from irrigation. A climate model estimate for the period 1993–2010 gives total groundwater depletion of 2,150 GTon, equivalent to global sea level rise of 6.24 mm. However, direct observational evidence supporting this estimate has been lacking. In this study, we show that the model estimate of water redistribution from aquifers to the oceans would result in a drift of Earth's rotational pole, about 78.48 cm toward 64.16°E. In combination with other well‐understood sources of water redistribution, such as melting of polar ice sheets and mountain glaciers, good agreement with PM observations serves as an independent confirmation of the groundwater depletion model estimate.
Key Points
Earth's pole has drifted toward 64.16°E at a speed of 4.36 cm/yr during 1993–2010 due to groundwater depletion and resulting sea level rise
Including groundwater depletion effects, the estimated drift of Earth's rotational pole agrees remarkably well with observations
PDF
