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1.
Nature ; 2024 Jun 05.
Article En | MEDLINE | ID: mdl-38839966

Introducing the concept of topology has revolutionized materials classification, leading to the discovery of topological insulators and Dirac-Weyl semimetals1-3. One of the most fundamental theories underpinning topological materials is the Su-Schrieffer-Heeger (SSH) model4,5, which was developed in 1979-decades before the recognition of topological insulators-to describe conducting polymers. Distinct from the vast majority of known topological insulators with two and three dimensions1-3, the SSH model predicts a one-dimensional analogue of topological insulators, which hosts topological bound states at the endpoints of a chain4-8. To establish this unique and pivotal state, it is crucial to identify the low-energy excitations stemming from bound states, but this has remained unknown in solids because of the absence of suitable platforms. Here we report unusual electronic states that support the emergent bound states in elemental tellurium, the single helix of which was recently proposed to realize an extended version of the SSH chain9,10. Using spin- and angle-resolved photoemission spectroscopy with a micro-focused beam, we have shown spin-polarized in-gap states confined to the edges of the (0001) surface. Our density functional theory calculations indicate that these states are attributed to the interacting bound states originating from the one-dimensional array of SSH tellurium chains. Helices in solids offer a promising experimental platform for investigating exotic properties associated with the SSH chain and exploring topological phases through dimensionality control.

2.
ESMO Open ; 9(4): 102975, 2024 Apr.
Article En | MEDLINE | ID: mdl-38520847

BACKGROUND: Efficacy of necitumumab [recombinant human monoclonal antibody that blocks the ligand binding epidermal growth factor receptor (EGFR)] in patients with squamous (SQ) non-small-cell lung cancer (NSCLC) has been confirmed in two randomized clinical trials (SQUIRE and JFCM). This study evaluated the association between efficacy and initial skin toxicity with necitumumab treatment by analyzing pooled data from two clinical trials (SQUIRE and JFCM). MATERIALS AND METHODS: Data of 635 patients with SQ-NSCLC (intent-to-treat population) treated with necitumumab plus gemcitabine and cisplatin (N + GC) were pooled from two clinical trials (SQUIRE and JFCM). The relationship between skin toxicities developed by the end of the second cycle and efficacy was evaluated. Efficacy endpoints included overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Univariate and multivariate analyses were carried out for these endpoints. RESULTS: OS and ORR were associated with skin toxicity, whereas PFS was not. Patients with grade ≥2 or grade 1 skin toxicity had significantly longer OS compared to patients without skin toxicity (grade 0) in the N + GC group [median = 15.0 (grade ≥2); 12.7 (grade 1); 9.4 (grade 0) months; hazard ratio (HR) = 0.51 (grade ≥2 to grade 0); 95% confidence interval (CI) 0.40-0.64, P < 0.001 and HR = 0.64 (grade 1 to grade 0); 95% CI 0.52-0.80, P < 0.001]. In multivariate analysis, OS was significantly associated with skin toxicity. CONCLUSIONS: A significant association was found between necitumumab-induced skin toxicity and efficacy. These results are consistent with the previously reported association between other EGFR inhibitors-induced skin toxicity and efficacy.


Antibodies, Monoclonal, Humanized , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Male , Female , Middle Aged , Aged , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/pharmacology , Antibodies, Monoclonal, Humanized/adverse effects , Randomized Controlled Trials as Topic , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Gemcitabine , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/pathology , Deoxycytidine/analogs & derivatives , Deoxycytidine/therapeutic use , Cisplatin/therapeutic use , Cisplatin/pharmacology , Cisplatin/adverse effects , Aged, 80 and over
3.
Sci Rep ; 14(1): 2573, 2024 Feb 09.
Article En | MEDLINE | ID: mdl-38336981

To detect and track structural changes in atomic nuclei, the systematic study of nuclear levels with firm spin-parity assignments is important. While linear polarization measurements have been applied to determine the electromagnetic character of gamma-ray transitions, the applicable range is strongly limited due to the low efficiency of the detection system. The multi-layer Cadmium-Telluride (CdTe) Compton camera can be a state-of-the-art gamma-ray polarimeter for nuclear spectroscopy with the high position sensitivity and the detection efficiency. We demonstrated the capability to operate this detector as a reliable gamma-ray polarimeter by using polarized 847-keV gamma rays produced by the [Formula: see text]([Formula: see text]) reaction. By combining the experimental data and simulated calculations, the modulation curve for the gamma ray was successfully obtained. A remarkably high polarization sensitivity was achieved, compatible with a reasonable detection efficiency. Based on the obtained results, a possible future gamma-ray polarimetery is discussed.

4.
Ann Oncol ; 35(1): 77-90, 2024 Jan.
Article En | MEDLINE | ID: mdl-37879444

BACKGROUND: Amivantamab plus carboplatin-pemetrexed (chemotherapy) with and without lazertinib demonstrated antitumor activity in patients with refractory epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) in phase I studies. These combinations were evaluated in a global phase III trial. PATIENTS AND METHODS: A total of 657 patients with EGFR-mutated (exon 19 deletions or L858R) locally advanced or metastatic NSCLC after disease progression on osimertinib were randomized 2 : 2 : 1 to receive amivantamab-lazertinib-chemotherapy, chemotherapy, or amivantamab-chemotherapy. The dual primary endpoints were progression-free survival (PFS) of amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy. During the study, hematologic toxicities observed in the amivantamab-lazertinib-chemotherapy arm necessitated a regimen change to start lazertinib after carboplatin completion. RESULTS: All baseline characteristics were well balanced across the three arms, including by history of brain metastases and prior brain radiation. PFS was significantly longer for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy [hazard ratio (HR) for disease progression or death 0.48 and 0.44, respectively; P < 0.001 for both; median of 6.3 and 8.3 versus 4.2 months, respectively]. Consistent PFS results were seen by investigator assessment (HR for disease progression or death 0.41 and 0.38 for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy, respectively; P < 0.001 for both; median of 8.2 and 8.3 versus 4.2 months, respectively). Objective response rate was significantly higher for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy (64% and 63% versus 36%, respectively; P < 0.001 for both). Median intracranial PFS was 12.5 and 12.8 versus 8.3 months for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy (HR for intracranial disease progression or death 0.55 and 0.58, respectively). Predominant adverse events (AEs) in the amivantamab-containing regimens were hematologic, EGFR-, and MET-related toxicities. Amivantamab-chemotherapy had lower rates of hematologic AEs than amivantamab-lazertinib-chemotherapy. CONCLUSIONS: Amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy improved PFS and intracranial PFS versus chemotherapy in a population with limited options after disease progression on osimertinib. Longer follow-up is needed for the modified amivantamab-lazertinib-chemotherapy regimen.


Acrylamides , Aniline Compounds , Antibodies, Bispecific , Carcinoma, Non-Small-Cell Lung , Indoles , Lung Neoplasms , Morpholines , Pyrazoles , Pyrimidines , Humans , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/adverse effects , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Disease Progression , ErbB Receptors/genetics , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Mutation , Protein Kinase Inhibitors/therapeutic use
5.
Nat Commun ; 14(1): 7396, 2023 Nov 17.
Article En | MEDLINE | ID: mdl-37978297

Antiferromagnetic (AF) topological materials offer a fertile ground to explore a variety of quantum phenomena such as axion magnetoelectric dynamics and chiral Majorana fermions. To realize such intriguing states, it is essential to establish a direct link between electronic states and topology in the AF phase, whereas this has been challenging because of the lack of a suitable materials platform. Here we report the experimental realization of the AF topological-insulator phase in NdBi. By using micro-focused angle-resolved photoemission spectroscopy, we discovered contrasting surface electronic states for two types of AF domains; the surface having the out-of-plane component in the AF-ordering vector displays Dirac-cone states with a gigantic energy gap, whereas the surface parallel to the AF-ordering vector hosts gapless Dirac states despite the time-reversal-symmetry breaking. The present results establish an essential role of combined symmetry to protect massless Dirac fermions under the presence of AF order and widen opportunities to realize exotic phenomena utilizing AF topological materials.

6.
Phys Rev Lett ; 130(17): 173001, 2023 Apr 28.
Article En | MEDLINE | ID: mdl-37172243

To test bound-state quantum electrodynamics (BSQED) in the strong-field regime, we have performed high precision x-ray spectroscopy of the 5g-4f and 5f- 4d transitions (BSQED contribution of 2.4 and 5.2 eV, respectively) of muonic neon atoms in the low-pressure gas phase without bound electrons. Muonic atoms have been recently proposed as an alternative to few-electron high-Z ions for BSQED tests by focusing on circular Rydberg states where nuclear contributions are negligibly small. We determined the 5g_{9/2}- 4f_{7/2} transition energy to be 6297.08±0.04(stat)±0.13(syst) eV using superconducting transition-edge sensor microcalorimeters (5.2-5.5 eV FWHM resolution), which agrees well with the most advanced BSQED theoretical prediction of 6297.26 eV.

10.
Int J Life Cycle Assess ; 28(2): 146-155, 2023.
Article En | MEDLINE | ID: mdl-36685326

Goal and theoretical commentary: A number of recent life cycle assessment (LCA) studies have concluded that animal-sourced foods should be restricted-or even avoided-within the human diet due to their relatively high environmental impacts (particularly those from ruminants) compared with other protein-rich foods (mainly protein-rich plant foods). From a nutritional point of view, however, issues such as broad nutrient bioavailability, amino acid balances, digestibility and even non-protein nutrient density (e.g., micronutrients) need to be accounted for before making such recommendations to the global population. This is especially important given the contribution of animal sourced foods to nutrient adequacy in the global South and vulnerable populations of high-income countries (e.g., children, women of reproductive age and elderly). Often, however, LCAs simplify this reality by using 'protein' as a functional unit in their models and basing their analyses on generic nutritional requirements. Even if a 'nutritional functional unit' (nFU) is utilised, it is unlikely to consider the complexities of amino acid composition and subsequent protein accretion. The discussion herein focuses on nutritional LCA (nLCA), particularly on the usefulness of nFUs such as 'protein,' and whether protein quality should be considered when adopting the nutrient as an (n)FU. Further, a novel and informative case study is provided to demonstrate the strengths and weaknesses of protein-quality adjustment. Case study methods: To complement current discussions, we present an exploratory virtual experiment to determine how Digestible Indispensable Amino Acid Scores (DIAAS) might play a role in nLCA development by correcting for amino acid quality and digestibility. DIAAS is a scoring mechanism which considers the limiting indispensable amino acids (IAAs) within an IAA balance of a given food (or meal) and provides a percentage contribution relative to recommended daily intakes for IAA and subsequent protein anabolism; for clarity, we focus only on single food items (4 × animal-based products and 4 × plant-based products) in the current case exemplar. Further, we take beef as a sensitivity analysis example (which we particularly recommend when considering IAA complementarity at the meal-level) to elucidate how various cuts of the same intermediary product could affect the interpretation of nLCA results of the end-product(s). Recommendations: First, we provide a list of suggestions which are intended to (a) assist with deciding whether protein-quality correction is necessary for a specific research question and (b) acknowledge additional uncertainties by providing mitigating opportunities to avoid misinterpretation (or worse, dis-interpretation) of protein-focused nLCA studies. We conclude that as relevant (primary) data availability from supply chain 'gatekeepers' (e.g., international agri-food distributors and processors) becomes more prevalent, detailed consideration of IAA provision of contrasting protein sources needs to be acknowledged-ideally quantitatively with DIAAS being one example-in nLCA studies utilising protein as a nFU. We also contend that future nLCA studies should discuss the complementarity of amino acid balances at the meal-level, as a minimum, rather than the product level when assessing protein metabolic responses of consumers. Additionally, a broader set of nutrients should ideally be included when evaluating "protein-rich foods" which provide nutrients that extend beyond amino acids, which is of particular importance when exploring dietary-level nLCA.

11.
Br Poult Sci ; 64(1): 47-55, 2023 Feb.
Article En | MEDLINE | ID: mdl-36129068

1. This study assessed 1) the effects of Paracoccus carotinifaciens supplementation containing high astaxanthin levels on egg production performance and quality, 2) dynamics of carotenoids levels in the egg yolk and 3) taste of astaxanthin-rich egg yolk.2. Laying hens were fed diets containing different levels of P. carotinifaciens-derived astaxanthin (ASX; 0, 2, 4, 8, or 16 ppm) for 28 d (experiment 1) or a diet containing 16 ppm astaxanthin for 28 d followed by a 0 ppm astaxanthin diet for 28 days (experiment 2).3. Production performance, egg quality and egg yolk carotenoid levels were examined in experiment 1 (Ex1) and the dynamics of egg yolk carotenoid levels and egg yolk taste in experiment 2 (Ex2).4. ASX supplementation did not affect production performance or egg quality. ASX levels in the egg yolk became saturated after seven days of 16 ppm supplementation and decreased to less than one-tenth of the saturated levels seven days after supplementation cessation. Supplementation with 16 ppm ASX for 28 d did not affect egg yolk taste.5. Supplementation resulted in the production of ASX-rich eggs for a brief period without affecting production performance, egg quality or taste. Understanding the time taken for the incorporation of ASX into egg yolks is beneficial for value-added egg production and may help in minimising supplementation costs.


Chickens , Ovum , Female , Animals , Egg Yolk , Diet/veterinary , Carotenoids , Dietary Supplements/analysis , Animal Feed/analysis , Eggs/analysis
12.
Science ; 379(6634): eabn8671, 2023 Feb 24.
Article En | MEDLINE | ID: mdl-36137011

Samples of the carbonaceous asteroid Ryugu were brought to Earth by the Hayabusa2 spacecraft. We analyzed 17 Ryugu samples measuring 1 to 8 millimeters. Carbon dioxide-bearing water inclusions are present within a pyrrhotite crystal, indicating that Ryugu's parent asteroid formed in the outer Solar System. The samples contain low abundances of materials that formed at high temperatures, such as chondrules and calcium- and aluminum-rich inclusions. The samples are rich in phyllosilicates and carbonates, which formed through aqueous alteration reactions at low temperature, high pH, and water/rock ratios of <1 (by mass). Less altered fragments contain olivine, pyroxene, amorphous silicates, calcite, and phosphide. Numerical simulations, based on the mineralogical and physical properties of the samples, indicate that Ryugu's parent body formed ~2 million years after the beginning of Solar System formation.

13.
Food Energy Secur ; 12(4): e480, 2023 Jul.
Article En | MEDLINE | ID: mdl-38439909

Rothamsted Research (RRes) is the world's oldest agricultural research centre, notable for the development of the first synthetic fertilizer (superphosphate) and long-term farming experiments (LTEs) spanning over 170 years. In 2015, RRes recruited several life cycle assessment (LCA) experts and began adopting the method to utilize high resolution agronomical data covering livestock (primarily ruminants), grassland/forage productivity and quality, and arable systems established on its North Wyke Farm Platform (NWFP) and the LTEs. The NWFP is a UK 'National Bioscience Research Infrastructure' (NBRI) developed for informing and testing systems science utilising high-resolution data to determine whether it is possible to produce nutritious food sustainably. Thanks largely to the multidisciplinary knowledge at RRes, and its collaborators, its LCA Team has been at the forefront of methodological advances during a 6-year Institute Strategic Programme (ISP) 'Soil-to-Nutrition' (S2N). While S2N investigated the co-benefits and trade-offs of new mechanistic understanding of efficient nutrient use across scales from pot to landscape, this commentary specifically synthesizes progress in incorporating human nutrition in the context of environmental footprinting, known as 'nutritional LCA' (nLCA). We conclude our commentary with a brief discussion on future pathways of exploration and methodological developments covering various activities along entire agri-food supply-chains.

14.
Rev Sci Instrum ; 93(12): 123512, 2022 Dec 01.
Article En | MEDLINE | ID: mdl-36586891

A double-chord ion Doppler spectroscopy (IDS) system was developed to measure the ion temperature and flow velocity of field-reversed configuration (FRC) plasmas in the FRC amplification via a translation-collisional merging (FAT-CM) device. Adopting a Czerny-Turner mount monochromator and 16-channel photomultiplier tube array, the developed IDS system achieves high wavelength resolution and fast time response. In addition, two vertically aligned optical paths share the optical system up to the monochromator and then branch just before the detector, successfully reducing crosstalk to <1%. The Doppler broadening was measured at two measurement points in the FAT-CM device, simultaneously, and ion temperatures of ∼50 eV were measured. Toroidal spin-up from 7 to 15 km/s and a steady flow velocity of ∼10 km/s were estimated from the Doppler shift obtained by the developed system. The observation of the toroidal flow velocity and the spatial profile of the ion temperature of the FRC plasma in the FAT-CM device were realized. These spectroscopic diagnostic's double chord capabilities will aid in understanding and improving the FRC plasmas.

15.
Rev Sci Instrum ; 93(10): 103526, 2022 Oct 01.
Article En | MEDLINE | ID: mdl-36319347

Visualization of the collisional merging formation process of field-reversed configuration (FRC) has been attempted. In the collisional merging formation process, two initial FRC-like plasmoids are accelerated toward each other by a magnetic pressure gradient. The relative speed of the collision reaches several times the typical ion sonic speed and Alfvénic speed. The magnetic structure of the initial-FRCs is disrupted in the collision process, but the FRC-like magnetic structure is reformed in ∼30 µs after the collision. Magnetic reconnection should occur in this process; however, general theoretical models in magnetohydrodynamics approximation cannot be applied to this process because of the high-beta nature of FRC and super-Alfvénic/sonic relative speed. In this work, the spectroscopic observation of the collisional merging FRC formation was conducted to evaluate the timescale and geometry of merging. A slight amount of tracer element (e.g., helium) was mixed into one of two initial-FRCs. Mixing of the tracer did not cause serious adverse effects on the performance of the initial-FRC in the collision and merging processes. The collision and merging processes were visualized successfully and observed using a fast-framing camera with a bandpass filter. The timescale of merging and the outflow speed in the collisional merging process of FRCs were optically evaluated for the first time.

16.
Rev Sci Instrum ; 93(10): 103520, 2022 Oct 01.
Article En | MEDLINE | ID: mdl-36319387

A visible light tomographic imaging system has been developed for the collisional merging experiment of field-reversed configurations (FRCs) on the FRC Amplification via Translation-Collisional Merging device at Nihon University. Two FRCs formed by field-reversed theta-pinch translate at super-Alfvénic velocity and collide with each other. The translation and collision processes are completed in 20-30 µs, and a single FRC is reformed in ∼70 µs. To study these translation and collisional merging processes, the tomographic system, including fast response tomographic cameras and a reconstruction method assuming a Rigid-Rotor (RR) model, is developed. The developed tomographic cameras simply consist of 16 channels of multi-anode photomultipliers, a band-pass filter, a slit, and a cylindrical lens, which expands the viewing angle. Because the viewing angle is limited by the size of the viewports of the metal chamber, the iterative method assuming the RR model has been applied to reconstruct tomographic images from a small number of projections. The developed tomographic imaging system can estimate the behavior of FRCs. Four cameras are installed in the two cross sections near the collision point. The radial shift of each translated FRC can be calculated by this system. Details of the developed tomographic camera system and RR reconstruction method are reported.

17.
Radiat Prot Dosimetry ; 198(13-15): 1104-1108, 2022 Sep 09.
Article En | MEDLINE | ID: mdl-36083763

Significant quantities of radionuclides were released into the environment due to the 2011 TEPCO's FDNPS accident. Radiocaesium is the most important radionuclide for assessment of radiation dose, and small amounts of 90Sr and very long-lived radionuclide of 129I were also released into the environment. Spinach, potato and brown rice were collected from Fukushima, neighboring prefectures and reference areas of negligible deposition in 2018 and 2019. The activity concentration of 137Cs in crops in Hamadori (coastal side) was relatively higher than other areas. The activity concentration of 90Sr in the crops showed a similar range among four areas in Fukushima, and they were similar level of those collected throughout Japan. The activity concentration of 129I in the crops collected from Hamadori was higher than other Fukushima areas. However, the activity ratio of 129I/137Cs was lower by five to seven orders of magnitude. Internal radiation doses of radiocaesium for adult males from ingestion of local crops collected from Hamadori were 0.0046 mSv, and that of 129I were 0.00000045 mSv in 2019.


Fukushima Nuclear Accident , Radiation Monitoring , Cesium Radioisotopes/analysis , Crops, Agricultural , Iodine Radioisotopes , Japan , Radiation Dosage , Strontium Radioisotopes
18.
Clin Oncol (R Coll Radiol) ; 34(12): e505-e514, 2022 12.
Article En | MEDLINE | ID: mdl-35654667

AIMS: Although palliative radiotherapy for gastric cancer may improve some symptoms, it may also have a negative impact due to its toxicity. We investigated whether symptoms improved after radiotherapy with adjustment for the Palliative Prognostic Index (PPI) considering that patients with limited survival tend to experience deterioration of symptoms. MATERIALS AND METHODS: This study was an exploratory analysis of the Japanese Radiation Oncology Study Group study (JROSG 17-3). We assessed six symptom scores (nausea, anorexia, fatigue, shortness of breath, pain at the irradiated area and distress) at registration and 2, 4 and 8 weeks thereafter. We tested whether symptoms linearly improved after adjusting for the baseline PPI. Shared parameter models were used to adjust for potential bias in missing data. RESULTS: The present study analysed all 55 patients enrolled in JROSG 17-3. With time from registration as the only explanatory variable in the model, a significant linear decrease was observed in shortness of breath, pain and distress (slopes, -0.26, -0.22 and -0.19, respectively). Given that the interaction terms (i.e. PPI × time) were not significantly associated with symptom scores in any of the six symptoms, only PPI was included as the main effect in the final multivariable models. After adjusting for the PPI, shortness of breath, pain and distress significantly improved (slope, -0.25, -0.19 and -0.17; P < 0.001, 0.002 and 0.047, respectively). An improvement in fatigue and distress was observed only in patients treated with a biologically effective dose ≤14.4 Gy. CONCLUSION: Shortness of breath, pain and distress improved after radiotherapy. Moreover, a higher PPI was significantly associated with higher symptom scores at all time points, including baseline. In contrast, PPI did not seem to influence the improvement of these symptoms. Regardless of the expected survival, patients receiving radiotherapy for gastric cancer can expect an improvement in shortness of breath, pain and distress over 8 weeks. Multiple-fraction radiotherapy might hamper the improvement in fatigue and distress by its toxicity or treatment burden.


Radiation Oncology , Stomach Neoplasms , Humans , Prognosis , Stomach Neoplasms/complications , Stomach Neoplasms/radiotherapy , Palliative Care , Fatigue/etiology , Pain/etiology , Pain/radiotherapy , Pain/diagnosis , Dyspnea/etiology , Dyspnea/radiotherapy
19.
Ann Oncol ; 33(9): 959-967, 2022 09.
Article En | MEDLINE | ID: mdl-35688358

BACKGROUND: Prognosis of advanced gastrointestinal stromal tumors (GIST) refractory to tyrosine kinase inhibitors (TKIs) is poor. This randomized, placebo-controlled, phase III trial evaluated the efficacy and safety of pimitespib, a novel heat shock protein 90 inhibitor, in advanced GIST refractory to standard TKIs. PATIENTS AND METHODS: Patients with histologically confirmed GIST refractory to imatinib, sunitinib, and regorafenib were randomized 2 : 1 to oral pimitespib 160 mg/day or placebo for 5 consecutive days per week in 21-day cycles. Following disease progression by blinded central radiological review (BCRR), cross-over to open-label pimitespib was permitted. The primary endpoint was progression-free survival (PFS) by BCRR in the full analysis set. Secondary endpoints included overall survival (OS) adjusted using the rank-preserving structural failure time (RPSFT) method to reduce the expected confounding impact of cross-over. RESULTS: From 31 October 2018 to 30 April 2020, 86 patients were randomized to pimitespib (n = 58) or placebo (n = 28). Median PFS was 2.8 months [95% confidence interval (CI) 1.6-2.9 months] with pimitespib versus 1.4 months (0.9-1.8 months) with placebo [hazard ratio (HR) 0.51 (95% CI 0.30-0.87); one-sided P = 0.006]. Pimitespib showed an improvement in cross-over-adjusted OS compared with placebo [HR 0.42 (0.21-0.85), one-sided P = 0.007]. Seventeen (60.7%) patients receiving placebo crossed-over to pimitespib; median PFS after cross-over was 2.7 months (95% CI 0.7-4.1 months). The most common (≥30%) treatment-related adverse events (AEs) with pimitespib were diarrhea (74.1%) and decreased appetite (31.0%); the most common (≥10%) grade ≥3 treatment-related AE was diarrhea (13.8%). Treatment-related AEs leading to pimitespib discontinuation occurred in three (5.2%) patients. CONCLUSIONS: Pimitespib significantly improved PFS and cross-over-adjusted OS compared with placebo and had an acceptable safety profile in patients with advanced GIST refractory to standard TKIs.


Antineoplastic Agents , Gastrointestinal Stromal Tumors , Antineoplastic Agents/adverse effects , Diarrhea/chemically induced , Double-Blind Method , Gastrointestinal Stromal Tumors/drug therapy , Gastrointestinal Stromal Tumors/pathology , Humans , Imatinib Mesylate/therapeutic use , Indoles , Pyrroles
20.
Eur J Prosthodont Restor Dent ; 30(4): 262-266, 2022 Nov 30.
Article En | MEDLINE | ID: mdl-35333011

PURPOSE/AIM: To evaluate the effect of different veneering liquids used for modeling on microhardness, fracture toughness and biaxial flexural strength of a glass-veneering ceramic. MATERIAL AND METHODS: The manufacturer recommended modeling liquid (ML), distilled water (DW), isopropyl alcohol (IA), 0.5% (P05), 1% (P1), and 2% (P2) polyethylene glycol solutions were mixed with feldspathic ceramic powder to form disc-shaped samples (n=20, 15 mm × 1.2 mm). After sintering, samples were mirror-polished and subjected to Vickers indentation (n=5) for measurement of microhardness and fracture toughness. The remaining 15 samples from each group were subjected to biaxial flexural strength. Data were subjected to one-way ANOVA and Weibull analysis. RESULTS: The microhardness was affected by veneering liquid (p=0.002): DW promoted higher microhardness values than ML and IA. Fracture toughness (p=0.301) and flexural strength (p=0.930) were not affected by the veneering liquid but Weibull parameters were affected. All groups presented surface pores under high magnification. CONCLUSION: Even though the use of DW led to higher values of surface microhardness than the ML, all obtained values are inside the range of enamel microhardness values reported in the literature. Such parameters may affect antagonist wear and should be reported in clinical trials.


Dental Porcelain , Dental Veneers , Water , Materials Testing , Surface Properties , Pliability , Ceramics , Zirconium , Dental Stress Analysis
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