Icotinib has been previously shown to be non-inferior to gefitinib in non-selected advanced non-small-cell lung cancer patients when given as second- or further-line treatment. In this open-label, ...randomized, phase 3 CONVINCE trial, we assessed the efficacy and safety of first-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance in lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) mutation.
Eligible participants were adults with stage IIIB/IV lung adenocarcinoma and exon 19/21 EGFR mutations. Participants were randomly allocated (1 : 1) to receive oral icotinib or 3-week cycle of cisplatin plus pemetrexed for up to four cycles; non-progressive patients after four cycles were maintained with pemetrexed until disease progression or intolerable toxicity. The primary end point was progression-free survival (PFS) assessed by independent response evaluation committee. Other end points included overall survival (OS) and safety.
Between January 2013 and August 2014, 296 patients were randomized, and 285 patients were treated (148 to icotinib, 137 to chemotherapy). Independent response evaluation committee-assessed PFS was significantly longer in the icotinib group (11.2 versus 7.9 months; hazard ratio, 0.61, 95% confidence interval 0.43-0.87; P = 0.006). No significant difference for OS was observed between treatments in the overall population or in EGFR-mutated subgroups (exon 19 Del/21 L858R). The most common grade 3 or 4 adverse events (AEs) in the icotinib group were rash (14.8%) and diarrhea (7.4%), compared with nausea (45.9%), vomiting (29.2%), and neutropenia (10.9%) in the chemotherapy group. AEs (79.1% versus 94.2%; P < 0.001) and treatment-related AEs (54.1% versus 90.5%; P < 0.001) were significantly fewer in the icotinib group than in the chemotherapy group.
First-line icotinib significantly improves PFS of advanced lung adenocarcinoma patients with EGFR mutation with a tolerable and manageable safety profile. Icotinib should be considered as a first-line treatment for this patient population.
ABO incompatibility is no longer considered a contraindication for adult living donor liver transplantation (ALDLT) due to various strategies to overcome the ABO blood group barrier. We report the ...largest single‐center experience of ABO‐incompatible (ABOi) ALDLT in 235 adult patients. The desensitization protocol included a single dose of rituximab and total plasma exchange. In addition, local graft infusion therapy, cyclophosphamide, or splenectomy was used for a certain time period, but these treatments were eventually discontinued due to adverse events. There were three cases (1.3%) of in‐hospital mortality. The cumulative 3‐year graft and patient survival rates were 89.2% and 92.3%, respectively, and were comparable to those of the ABO‐compatible group (n = 1301). Despite promising survival outcomes, 17 patients (7.2%) experienced antibody‐mediated rejection that manifested as diffuse intrahepatic biliary stricture; six cases required retransplantation, and three patients died. ABOi ALDLT is a feasible method for expanding a living liver donor pool, but the efficacy of the desensitization protocol in targeting B cell immunity should be optimized.
This article presents the clinical results of ABO‐incompatible adult living donor liver transplantation in a single institution.
To identify and appraise empirical studies on publication and related biases published since 1998; to assess methods to deal with publication and related biases; and to examine, in a random sample of ...published systematic reviews, measures taken to prevent, reduce and detect dissemination bias.
The main literature search, in August 2008, covered the Cochrane Methodology Register Database, MEDLINE, EMBASE, AMED and CINAHL. In May 2009, PubMed, PsycINFO and OpenSIGLE were also searched. Reference lists of retrieved studies were also examined.
In Part I, studies were classified as evidence or method studies and data were extracted according to types of dissemination bias or methods for dealing with it. Evidence from empirical studies was summarised narratively. In Part II, 300 systematic reviews were randomly selected from MEDLINE and the methods used to deal with publication and related biases were assessed.
Studies with significant or positive results were more likely to be published than those with non-significant or negative results, thereby confirming findings from a previous HTA report. There was convincing evidence that outcome reporting bias exists and has an impact on the pooled summary in systematic reviews. Studies with significant results tended to be published earlier than studies with non-significant results, and empirical evidence suggests that published studies tended to report a greater treatment effect than those from the grey literature. Exclusion of non-English-language studies appeared to result in a high risk of bias in some areas of research such as complementary and alternative medicine. In a few cases, publication and related biases had a potentially detrimental impact on patients or resource use. Publication bias can be prevented before a literature review (e.g. by prospective registration of trials), or detected during a literature review (e.g. by locating unpublished studies, funnel plot and related tests, sensitivity analysis modelling), or its impact can be minimised after a literature review (e.g. by confirmatory large-scale trials, updating the systematic review). The interpretation of funnel plot and related statistical tests, often used to assess publication bias, was often too simplistic and likely misleading. More sophisticated modelling methods have not been widely used. Compared with systematic reviews published in 1996, recent reviews of health-care interventions were more likely to locate and include non-English-language studies and grey literature or unpublished studies, and to test for publication bias.
Dissemination of research findings is likely to be a biased process, although the actual impact of such bias depends on specific circumstances. The prospective registration of clinical trials and the endorsement of reporting guidelines may reduce research dissemination bias in clinical research. In systematic reviews, measures can be taken to minimise the impact of dissemination bias by systematically searching for and including relevant studies that are difficult to access. Statistical methods can be useful for sensitivity analyses. Further research is needed to develop methods for qualitatively assessing the risk of publication bias in systematic reviews, and to evaluate the effect of prospective registration of studies, open access policy and improved publication guidelines.
A transparent heater is produced from single‐walled carbon nanotubes (SWCNTs) with a high thermal conductivity. A transparent conducting SWCNT film is fabricated on glass or polymer substrates by ...using a vacuum infiltration method. SWCNT films with a transparency of 65–97 % and a sheet resistance of 230–3500 Ω square–1 are demonstated. These films are good candidates for many applications that require transparent film heaters.
In this paper, for the first time we demonstrate that horizontally stacked gate-all-around (GAA) Nanosheet structure is a good candidate for the replacement of FinFET at the 5nm technology node and ...beyond. It offers increased W eff per active footprint and better performance compared to FinFET, and with a less complex patterning strategy, leveraging EUV lithography. Good electrostatics are reported at L g =12nm and aggressive 44/48nm CPP (Contacted Poly Pitch) ground rules. We demonstrate work function metal (WFM) replacement and multiple threshold voltages, compatible with aggressive sheet to sheet spacing for wide stacked sheets. Stiction of sheets in long-channel devices is eliminated. Dielectric isolation is shown on standard bulk substrate for sub-sheet leakage control. Wrap-around contact (WAC) is evaluated for extrinsic resistance reduction.
A feeding trial was conducted to investigate the effects of different levels of calcium (Ca) on growth and tissue mineralization in Japanese seabass, Lateolabrax japonicus. Six experimental diets ...were formulated to contain different levels of Ca (2.9, 4.2, 6.5, 7.9, 10.2 and 31.0 g kg−1) from dietary ingredients and Ca‐lactate·5H2O. The diets were fed to three triplicate groups of Japanese seabass (initial weight, 12.5 ± 0.0 g) for 56 days. Dietary Ca had no significant effect on survival or feed efficiency; however, the highest Ca (31.0 g kg−1) diet significantly reduced weight gain, feeding rate and whole‐body and muscle protein and lipid contents, as well as serum Ca concentration and alkaline phosphatase activity. A significant reduction in vertebral Ca, P, Zn, Fe and Mn contents and scale Ca, P, Mg and Mn contents was observed in Japanese seabass as dietary Ca level increased. Deformed fish were primarily found in the 2.9 and 31.0 g Ca kg−1 groups, indicating that these fish had poor bone mineralization.
The interplay between hydrogen and nanovoids, despite long being recognized as a central factor in hydrogen-induced damage in structural materials, remains poorly understood. Here, focusing on ...tungsten as a model body-centred cubic system, we explicitly demonstrate sequential adsorption of hydrogen adatoms on Wigner-Seitz squares of nanovoids with distinct energy levels. Interaction between hydrogen adatoms on nanovoid surfaces is shown to be dominated by pairwise power-law repulsion. We establish a predictive model for quantitative determination of the configurations and energetics of hydrogen adatoms in nanovoids. This model, combined with the equation of states of hydrogen gas, enables the prediction of hydrogen molecule formation in nanovoids. Multiscale simulations, performed based on our model, show good agreement with recent thermal desorption experiments. This work clarifies fundamental physics and provides a full-scale predictive model for hydrogen trapping and bubbling in nanovoids, offering long-sought mechanistic insights that are crucial for understanding hydrogen-induced damage in structural materials.
Overview of nuclear data production system at RAON Ham, C.; Tshoo, K.; Lee, S. ...
Nuclear instruments & methods in physics research. Section B, Beam interactions with materials and atoms,
August 2023, 2023-08-00, Letnik:
541
Journal Article
Recenzirano
Nuclear Data Production System (NDPS), a fast neutron facility for nuclear science and applications, was constructed at the Rare Isotope Accelerator complex for ON-line experiments (RAON) in Korea. ...NDPS is designed to provide both white and quasi-monoenergetic neutrons using 98 MeV deuteron and 20 – 83 MeV proton beams with thick graphite and thin lithium targets, respectively. Neutron energy is determined by employing the Time-Of-Flight (TOF) technique, along with a pulsed deuteron (or proton) beam with a repetition rate of less than 200 kHz. Fast neutrons are produced in the target room and are guided to the TOF room through a 4 m long neutron collimator consisting of iron and 5% borated polyethylene. The neutron beam is monitored using a parallel plate avalanche counter (PPAC) and a micro-mesh gaseous (MICROMEGAS) detector installed in the TOF room, so as to measure the energy and the position of neutrons.
Abstract Purpose Combined hepatocellular carcinoma (HCC) and cholangiocellular carcinoma (CCC) is a rare pair of intrahepatic malignancies. Differential diagnosis among combined HCC-CCC, HCC, or CCC ...can be difficult; thus malignancies other than ordinary HCC are occasionally encountered unexpectedly in explanted liver specimens. The present study analyzed the long-term outcomes of liver transplantation (OLT) among patients with HCC-CCC. Methods Between January 1999 and December 2009, we performed 2137 adult OLT at our institution including 15 cases of pathologically confirmed HCC-CCC, who all underwent OLT with a pretransplant diagnosis of HCC. We reviewed retrospectively the medical records of these 15 patients. Results Their mean age was 58.9 ± 7.2 years. The median preoperative alpha-fetoprotein level was 32.6 ng/mL. Fourteen patients underwent living donor and one deceased donor OLT. The Milan criteria were met in 12 cases. A single tumor was identified in 8 and multiple lesions in 7 patients. The maximal tumor diameter was 2.9 ± 1.7 cm. Seven patients experienced tumor recurrences: including 6 within the first 12 months. All of the patients who experienced recurrences died at a median 4 months after that diagnosis. The overall patient survival rates were 66.7% at 1 year and 60.0% at 3 and 5 years. Disease-free patient survival rates were 60.0% at 1 year and 53.3% at 3 and 5 years. Conclusions Patients with combined HCC-CCC showed a high rate of early recurrences, particularly within the first year.
In the KATHERINE study (NCT01772472), patients with residual invasive early breast cancer (EBC) after neoadjuvant chemotherapy (NACT) plus human epidermal growth factor receptor 2 (HER2)-targeted ...therapy had a 50% reduction in risk of recurrence or death with adjuvant trastuzumab emtansine (T-DM1) versus trastuzumab. Here, we present additional exploratory safety and efficacy analyses.
KATHERINE enrolled HER2-positive EBC patients with residual invasive disease in the breast/axilla at surgery after NACT containing a taxane (± anthracycline, ± platinum) and trastuzumab (± pertuzumab). Patients were randomized to adjuvant T-DM1 (n = 743) or trastuzumab (n = 743) for 14 cycles. The primary endpoint was invasive disease-free survival (IDFS).
The incidence of peripheral neuropathy (PN) was similar regardless of neoadjuvant taxane type. Irrespective of treatment arm, baseline PN was associated with longer PN duration (median, 105-109 days longer) and lower resolution rate (∼65% versus ∼82%). Prior platinum therapy was associated with more grade 3-4 thrombocytopenia in the T-DM1 arm (13.5% versus 3.8%), but there was no grade ≥3 hemorrhage in these patients. Risk of recurrence or death was decreased with T-DM1 versus trastuzumab in patients who received anthracycline-based NACT hazard ratio (HR) = 0.51; 95% confidence interval (CI): 0.38-0.67, non-anthracycline-based NACT (HR = 0.43; 95% CI: 0.22-0.82), presented with cT1, cN0 tumors (0 versus 6 IDFS events), or had particularly high-risk tumors (HRs ranged from 0.43 to 0.72). The central nervous system (CNS) was more often the site of first recurrence in the T-DM1 arm (5.9% versus 4.3%), but T-DM1 was not associated with a difference in overall risk of CNS recurrence.
T-DM1 provides clinical benefit across patient subgroups, including small tumors and particularly high-risk tumors and does not increase the overall risk of CNS recurrence. NACT type had a minimal impact on safety.
•Baseline PN was associated with longer on-study PN and a lower resolution rate in both study arms.•Prior platinum was associated with more grade 3-4 thrombocytopenia with T-DM1, but not with more grade ≥3 hemorrhage.•IDFS benefit with T-DM1 versus trastuzumab was similar irrespective of neoadjuvant therapy containing anthracyclines.•T-DM1 was not associated with an increased overall risk of CNS recurrence.•The T-DM1 IDFS benefit was maintained in high-risk tumors defined by operable status, nodal involvement, and HR status.
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