The interaction of light with metallic nanostructures produces a collective excitation of electrons at the metal surface, also known as surface plasmons. These collective excitations lead to ...resonances that enable the confinement of light in deep-subwavelength regions, thereby leading to large near-field enhancements. The simulation of plasmon resonances presents notable challenges. From the modeling perspective, the realistic behavior of conduction-band electrons in metallic nanostructures is not captured by Maxwell's equations, thus requiring additional modeling. From the simulation perspective, the disparity in length scales stemming from the extreme field localization demands efficient and accurate numerical methods.
In this paper, we develop the hybridizable discontinuous Galerkin (HDG) method to solve Maxwell's equations augmented with the hydrodynamic model for the conduction-band electrons in noble metals. This method enables the efficient simulation of plasmonic nanostructures while accounting for the nonlocal interactions between electrons and the incident light. We introduce a novel postprocessing scheme to recover superconvergent solutions and demonstrate the convergence of the proposed HDG method for the simulation of a 2D gold nanowire and a 3D periodic annular nanogap structure. The results of the hydrodynamic model are compared to those of a simplified local response model, showing that differences between them can be significant at the nanoscale.
•Formulation and implementation details of the hydrodynamic model for metals using HDG.•Novel postprocessing strategy to recover solutions with superconvergent properties.•Solve linear systems with reduced number of degrees of freedom.•Simulate interaction of 3d nanogaps with mm-long wavelengths.•Nonlocal effects become predominant in nanometric geometries at low THz frequencies.
Paclitaxel is currently only available as an intravenous (i.v.) formulation. DHP107 is a novel oral formulation of lipid ingredients and paclitaxel. DHP107 demonstrated comparable efficacy, safety, ...and pharmacokinetics to i.v. paclitaxel as a second-line therapy in patients with advanced gastric cancer (AGC). DREAM is a multicenter, open-label, prospective, randomized phase III study of patients with histologically/cytologically confirmed, unresectable/recurrent AGC after first-line therapy failure.
Patients were randomized 1:1 to DHP107 (200mg/m2 orally twice daily days 1, 8, 15 every 4weeks) or i.v. paclitaxel (175mg/m2 day 1 every 3weeks). Patients were stratified by Eastern Cooperative Oncology Group performance status, disease status, and prior treatment; response was assessed (Response Evaluation Criteria in Solid Tumors) every 6weeks. Primary end point: non-inferiority of progression-free survival (PFS); secondary end points: overall response rate (ORR), overall survival (OS), and safety. For the efficacy analysis, sequential tests for non-inferiority were carried out, first with a non-inferiority margin of 1.48, then with a margin of 1.25.
Baseline characteristics were balanced in the 236 randomized patients (n=118 per arm). Median PFS (per-protocol) was 3.0 (95% CI 1.7–4.0) months for DHP107 and 2.6 (95% CI 1.8–2.8) months for paclitaxel (hazard ratio HR=0.85; 95% CI 0.64–1.13). A sensitivity analysis on PFS using independent central review showed similar results (HR=0.93; 95% CI 0.70–1.24). Median OS (full analysis set) was 9.7 (95% CI 7.1−11.5) months for DHP107 versus 8.9 (95% CI 7.1–12.2) months for paclitaxel (HR=1.04; 95% CI 0.76–1.41). ORR was 17.8% for DHP107 (CR 4.2%; PR 13.6%) versus 25.4% for paclitaxel (CR 3.4%; PR 22.0%). Nausea, vomiting, diarrhea, and mucositis were more common with DHP107; peripheral neuropathy was more common with paclitaxel. There were only few Grade≥3 adverse events, most commonly neutropenia (42% versus 53%); febrile neutropenia was reported infrequently (5.9% versus 2.5%). No hypersensitivity reactions occurred with DHP107 (paclitaxel 2.5%).
DHP107 as a second-line treatment of AGC was non-inferior to paclitaxel for PFS; other efficacy and safety parameters were comparable. DHP107 is the first oral paclitaxel with proven efficacy/safety for the treatment of AGC.
NCT01839773.
A vertically aligned nanotube array of titanium oxide was fabricated on the surface of titanium substrate by anodization. The nanotubes were then treated with NaOH solution to make them bioactive, ...and to induce growth of hydroxyapatite (bone-like calcium phosphate) in a simulated body fluid. It is shown that the presence of TiO
2 nanotubes induces the growth of a “nano-inspired nanostructure”, i.e., extremely fine-scale (∼8
nm feature) nanofibers of bioactive sodium titanate structure on the top edge of the ∼15
nm thick nanotube wall. During the subsequent in-vitro immersion in a simulated body fluid, the nano-scale sodium titanate, in turn, induced the nucleation and growth nano-dimensioned hydroxyapatite (HAp) phase. The kinetics of HAp formation is significantly accelerated by the presence of the nanostructures. Such TiO
2 nanotube arrays and associated nanostructures can be useful as a well-adhered bioactive surface layer on Ti implant metals for orthopaedic and dental implants, as well as for photocatalysts and other sensor applications.
Summary
This systematic review was performed to compare the diagnostic accuracy of vertebral fracture assessment (VFA) with that of spinal radiography for identification of vertebral fractures (VFs). ...VFA appeared to have moderate sensitivity and high specificity for detecting VFs when compared with spinal radiography.
Introduction
VFs are recognized as the hallmark of osteoporosis, and a previous VF increases the risk of a future fracture. Therefore, the timely detection of VFs is important for prevention of further fractures. This systematic review examined the diagnostic accuracy of VFA using dual X-ray absorptiometry (DXA) to identify VFs.
Methods
We searched for potentially relevant studies using electronic databases, including Ovid-Medline, Ovid-EMBASE, Cochrane library, and four Korean databases, from their inception to May 2013. We compared the diagnostic accuracy of VFA with that of spinal radiography for detection of VFs by analyzing the sensitivity and specificity using a 2 × 2 contingency table. Subgroup analyses were also performed on studies with a low risk of bias and applicability.
Results
Twelve studies were analyzed for the diagnostic accuracy of VFA. The sensitivity and specificity were 0.70–0.93 and 0.95–1.00, respectively, analyzed on a per-vertebra basis, and 0.65–1.00 and 0.74–1.00 on a per-patient basis. The sensitivity and specificity of five studies in subgroups with a low risk of bias in the intervention test were 0.70–0.84 and 0.96–0.99, respectively. In studies with a low risk of bias in the patient selection, those based on a per-vertebra basis in three studies were 0.70–0.93 and 0.96–1.00, respectively.
Conclusions
VFA had moderate sensitivity and high specificity for detecting VF when compared with spinal radiography. However, the present findings are insufficient to assess whether spinal radiography should be replaced by VFA.
Abstract
Funding Acknowledgements
Type of funding sources: None.
Objectives
Conflicting results regarding sex-based differences in the outcomes of out-of-hospital cardiac arrest (OHCA) patients have ...been reported. Furthermore, no study has examined whether differences in in-hospital interventions and courses are driven by sex differences. This study evaluated the effect of sex on the in-hospital course of these patients as well as the survival rates and long-term neurological outcomes of comatose OHCA patients treated with targeted temperature management (TTM).
Methods
We retrospectively analyzed the Korean Hypothermia Network prospective registry composed of data collected from 22 hospitals in Korea between October 2015 and December 2018. To evaluate the effect of sex on patient outcomes, we created various multivariate logistic regression models including baseline characteristics, resuscitation, and in-hospital care variables with an interaction term (age × sex). We also performed a stratified analysis of different age groups (less than 50 years of age and older). Regarding the difference in in-hospital courses, we compared daily total and SOFA sub-scores between the sexes and analyzed whether the decision regarding early cardiac interventions and limitations in in-hospital care were associated with sex.
Results
Among 1339 patients included in the study, 952 were men and 387 were women. There were no differences in age or modified comorbidity index values between the gender groups. Women were more likely to experience cardiac arrest at home and unwitnessed arrests, whereas men were more likely to have shockable initial rhythm, cardiac cause arrest, and ST-segment elevation myocardial infarction (STEMI) on initial electrocardiography and undergo early coronary interventions. The rate of survival to discharge was similar, but men showed better 6-month neurological outcomes. After adjusting for confounders, the male sex was not associated with survival to discharge or good 6-month neurological outcomes. There was no association between sex and outcome in patients of reproductive age and no interaction between age and sex. Regarding the in-hospital course, the daily total and SOFA sub-scores were similar in both sexes. The adjusted effect of sex was not associated with the clinician’s decision to perform early cardiac interventions. The decision to discontinue life-sustaining treatment was determined by poor prognostic factors, not by sex.
Conclusions
The findings suggested that men had more favorable 6-month survivals and good neurological outcomes compared to women since they had more favorable resuscitation variables. However, after adjusting for confounders, there was no difference between the sexes. This result was consistent with the data in patients of reproductive age. The results regarding in-hospital course showed that daily patient severity scores, early cardiac interventions, resource consumption, and the rates of withdrawal/withholding of in-hospital care were similar in men and women.
Summary Surveillance of healthcare-associated infection has been associated with a reduction in surgical site infection (SSI). Our aim was to evaluate the Korean Nosocomial Infection Surveillance ...System (KONIS) in order to assess its effects on SSI since it was introduced. SSI data after gastrectomy, total hip arthroplasty (THA), and total knee arthroplasty (TKA) between 2008 and 2012 were analysed. The pooled incidence of SSI was calculated for each year; the same analyses were also conducted from hospitals that had participated in KONIS for at least three consecutive years. Standardized SSI rates for each year were calculated by adjusting for SSI risk factors. SSI trends were analysed using the Cochran‒Armitage test. The SSI rate following gastrectomy was 3.12% (522/16,918). There was a significant trend of decreased crude SSI rates over five years. This trend was also evident in analysis of hospitals that had participated for more than three years. The SSI rate for THA was 2.05% (157/7656), which decreased significantly from 2008 to 2012. The risk factors for SSI after THA included the National Nosocomial Infections Surveillance risk index, trauma, reoperation, and age (60–69 years). The SSI rate for TKA was 1.90% (152/7648), which also decreased significantly during a period of five years. However, the risk-adjusted analysis of SSI did not show a significant decrease for all surgical procedures. In conclusion, the SSI incidence of gastrectomy and prosthetic joint replacement declined over five years as a result of active surveillance by KONIS.
Lactic acid bacteria (LAB) are beneficial micro-organisms that have been associated with several probiotic effects in both humans and animals. Here, using proteome analysis, we investigate the ...antitumour effects of cell-bound exopolysaccharides (cb-EPS) isolated from Lactobacillus acidophilus 606 on colon cancer cells and explore the proteins critical for their antitumour activity. cb-EPS inhibited the proliferation of HT-29 colon cancer cells by directly affecting cell morphology and not the cell cycle. Using two-dimensional polyacrylamide gel electrophoresis coupled with matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF/MS) and immunoblot analysis, we found that cb-EPS dramatically induced Beclin-1 and GRP78, and affected Bcl-2 and Bak regulation. The results of this study indicate that cb-EPS are antitumourigenic against HT-29 colon cancer cells and that this activity is because of the activation of autophagic cell death promoted directly by the induction of Beclin-1 and GRP78, as well as indirectly through the induction of Bcl-2 and Bak. These results may contribute to understanding the novel mechanisms by which probiotic bacteria induce tumour cell death via autophagy.
Summary
Background
A novel potassium‐competitive acid blocker, DWP14012, is in clinical development as a potential alternative to proton pump inhibitors for the treatment of acid‐related diseases.
...Aims
To evaluate the safety, tolerability, pharmacodynamics and pharmacokinetics of DWP14012 in humans.
Methods
A randomised, double‐blind, double‐dummy, placebo‐ and active‐controlled, single‐ and multiple‐ascending dose (SAD and MAD, respectively) study was conducted in healthy male subjects without Helicobacter pylori infection. Subjects randomly received a single oral dose of 10‐320 mg DWP14012, esomeprazole (active comparator) or placebo in the SAD study (n = 72) and once daily doses of 20‐160 mg DWP14012, esomeprazole or placebo for 7 days in the MAD study (n = 48; 8:2:2). Tolerability was evaluated using a microRNA‐122 assay. Pharmacodynamics were evaluated through 24‐hour gastric pH monitoring, and pharmacokinetics were evaluated plasma and urine DWP14012 concentrations.
Results
DWP14012 was generally well tolerated. The liver toxicity of DWP14012 was not higher than that of placebo after multiple oral administrations. DWP14012 showed rapid and sustained suppression of gastric acid secretion for 24 hours after dosing. Clear dose‐response and exposure‐response relationships were observed. Plasma concentrations of DWP14012 increased in a dose‐proportional manner in the MAD study, whereas in the SAD study, DWP14012 did not significantly accumulate in the plasma.
Conclusions
DWP14012 was well tolerated, and showed a rapid and long‐lasting gastric acid suppression effect in healthy subjects. These results justify further investigation of DWP14012 in patients with acid‐related disorders.
Linked ContentThis article is linked to Sachs et al paper. To view this article visit https://doi.org/10.1111/apt.14864.
Adjuvant chemotherapy and chemoradiotherapy are some of the standards of care for gastric cancer (GC). The Adjuvant chemoRadioTherapy In Stomach Tumors (ARTIST) 2 trial compares two adjuvant ...chemotherapy regimens and chemoradiotherapy in patients with D2-resected, stage II or III, node-positive GC.
The ARTIST 2 compared, in a 1:1:1 ratio, three adjuvant regimens: oral S-1 (40-60 mg twice daily 4 weeks on/2 weeks off) for 1 year, S-1 (2 weeks on/1 week off) plus oxaliplatin 130 mg/m2 every 3 weeks (SOX) for 6 months, and SOX plus chemoradiotherapy 45 Gy (SOXRT). Randomization was stratified according to surgery type (total or subtotal gastrectomy), pathologic stage (II or III), and Lauren histologic classification (diffuse or intestinal/mixed). The primary endpoint was disease-free survival (DFS) at 3 years; a reduction of 33% in the hazard ratio (HR) for DFS with SOX or SOXRT, when compared with S-1, was considered clinically meaningful. The trial is registered at clinicaltrials.gov (NCT0176146).
A total of 546 patients were recruited between February 2013 and January 2018 with 182, 181, and 183 patients in the S-1, SOX, and SOXRT arms, respectively. Median follow-up period was 47 months, with 178 DFS events observed. Estimated 3-year DFS rates were 64.8%, 74.3%, and 72.8% in the S-1, SOX, and SOXRT arms, respectively. HR for DFS in the control arm (S-1) was shorter than that in the SOX and SOXRT arms: S-1 versus SOX, 0.692 (P = 0.042) and S-1 versus SOXRT, 0.724 (P = 0.074). No difference in DFS was found between SOX and SOXRT (HR 0.971; P = 0.879). Adverse events were as anticipated in each arm, and were generally well-tolerated and manageable.
In patients with curatively D2-resected, stage II/III, node-positive GC, adjuvant SOX or SOXRT was effective in prolonging DFS, when compared with S-1 monotherapy. The addition of radiotherapy to SOX did not significantly reduce the rate of recurrence after D2 gastrectomy.
•In patients with curatively D2-resected, stage II/III, node-positive GC, adjuvant SOX or SOXRT was effective in prolonging DFS, when compared with S-1 monotherapy.•The addition of radiotherapy to chemotherapy did not significantly reduce the rate of recurrence after D2 gastrectomy.•DFS between patients treated with adjuvant chemotherapy and chemoradiotherapy was similar across all subgroups, including Lauren classification.
Abstract
This study uses H
i
image data from the Widefield ASKAP L-band Legacy All-sky Blind surveY (WALLABY) pilot survey with the Australian Square Kilometre Array Pathfinder (ASKAP) telescope, ...covering the Hydra cluster out to 2.5
r
200
. We present the projected phase–space distribution of H
i
-detected galaxies in Hydra, and identify that nearly two-thirds of the galaxies within
1.25
r
200
may be in the early stages of ram pressure stripping. More than half of these may be only weakly stripped, with the ratio of strippable H
i
(i.e., where the galactic restoring force is lower than the ram pressure in the disk) mass fraction (over total H
i
mass) distributed uniformly below 90%. Consequently, the H
i
mass is expected to decrease by only a few 0.1 dex after the currently strippable portion of H
i
in these systems has been stripped. A more detailed look at the subset of galaxies that are spatially resolved by WALLABY observations shows that, while it typically takes less than 200 Myr for ram pressure stripping to remove the currently strippable portion of H
i
, it may take more than 600 Myr to significantly change the total H
i
mass. Our results provide new clues to understanding the different rates of H
i
depletion and star formation quenching in cluster galaxies.
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