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1.
Phys Rev Lett ; 132(23): 236201, 2024 Jun 07.
Article de Anglais | MEDLINE | ID: mdl-38905683

RÉSUMÉ

We consider spin injection driven by nonequilibrium chiral phonons from a chiral insulator into an adjacent metal. Phonon-spin conversion arises from the coupling of the electron spin with the microrotation associated with chiral phonons. We derive a microscopic formula for the spin injection rate at a metal-insulator interface. Our results clearly illustrate the microscopic origin of spin current generation by chiral phonons and may lead to a breakthrough in the development of spintronic devices without heavy elements.

2.
Nature ; 631(8019): 54-59, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38839966

RÉSUMÉ

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.

3.
ESMO Open ; 9(4): 102975, 2024 Apr.
Article de Anglais | MEDLINE | ID: mdl-38520847

RÉSUMÉ

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.


Sujet(s)
Anticorps monoclonaux humanisés , Carcinome pulmonaire non à petites cellules , Tumeurs du poumon , Humains , Carcinome pulmonaire non à petites cellules/traitement médicamenteux , Carcinome pulmonaire non à petites cellules/anatomopathologie , Tumeurs du poumon/traitement médicamenteux , Tumeurs du poumon/anatomopathologie , Mâle , Femelle , Adulte d'âge moyen , Sujet âgé , Anticorps monoclonaux humanisés/usage thérapeutique , Anticorps monoclonaux humanisés/pharmacologie , Anticorps monoclonaux humanisés/effets indésirables , Essais contrôlés randomisés comme sujet , Adulte , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Protocoles de polychimiothérapie antinéoplasique/pharmacologie , Protocoles de polychimiothérapie antinéoplasique/effets indésirables , , Carcinome épidermoïde/traitement médicamenteux , Carcinome épidermoïde/anatomopathologie , Désoxycytidine/analogues et dérivés , Désoxycytidine/usage thérapeutique , Cisplatine/usage thérapeutique , Cisplatine/pharmacologie , Cisplatine/effets indésirables , Sujet âgé de 80 ans ou plus
4.
Radiography (Lond) ; 29(5): 838-844, 2023 08.
Article de Anglais | MEDLINE | ID: mdl-37393738

RÉSUMÉ

INTRODUCTION: No study has investigated scan parameters in head and neck dual layer dual-energy computed tomography (DL-DECT). This study aimed to select the appropriate scan parameters in head and neck imaging by evaluating the scan parameter effects on the accuracies of CT numbers and conduct iodine quantification in DL-DECT. METHODS: A multi-energy phantom was scanned using a dual layer CT (DLCT) scanner. Reference materials of iodine, blood, calcium, and adipose were used. A helical scan was performed by using reference and several protocols. Iodine density and virtual monochromatic images (VMIs) at the energy of 50, 70, and 100 keV were reconstructed. The iodine concentrations and CT numbers in each protocol were measured. Moreover, the absolute percentage errors (APEs) of iodine quantifications and CT numbers (reference vs. each protocol) were compared. Equivalence was observed when APEs between reference and each protocol was within 5%. Statistical analysis was performed using appropriate software. RESULTS: The APEs between the high-tube-voltage and reference protocol were 23.7, 14.0, 8.8, and 8.1% for iodine reference materials with concentrations equal to 2, 5, 10, and 15 mg/ml, respectively. At 50 keV, APEs between the high-tube-voltage and reference protocols were greater than 5% except for calcium and adipose. At 100 keV, APEs between the high-tube-voltage and reference protocols were greater than 5% except for blood and calcium. CONCLUSIONS: The high-tube-voltage protocol improved the accuracies of the measurement for iodine quantification and CT numbers. Additionally, the scanning parameters except for tube voltage had no effect on accuracies of iodine quantitation and CT numbers in the DLCT scanner. IMPLICATIONS FOR PRACTICE: The use of the high-tube-voltage protocol will be recommended for more accurate material decomposition in head and neck DL-DECT.


Sujet(s)
Hominidae , Iode , Humains , Animaux , Iode/analyse , Calcium/analyse , Japon , Tomodensitométrie/méthodes , Hôpitaux
6.
J Intellect Disabil Res ; 67(7): 640-654, 2023 07.
Article de Anglais | MEDLINE | ID: mdl-37066677

RÉSUMÉ

BACKGROUND: Individuals with Down syndrome (DS) exhibit deficits in static and dynamic balance abilities and maladaptive functions. This study aimed to determine the effectiveness of dance movement therapy (DMT) group intervention in individuals with DS. METHODS: The 31 participating individuals with DS, aged 5-29 years, were randomly divided into intervention (n = 16) and control (n = 15) groups. Posturography was used for static balance measurement, timed up and go test for dynamic balance measurement and the Achenbach System of Empirically Based Assessment (ASEBA) questionnaire for adaptive function and behavioural problem measurement in participants before and after the DMT interventions. The intervention group underwent 60-min DMT intervention once a week for 10 times, while the control group had usual daily activities. RESULTS: The results revealed a statistically significant difference and large effect sizes in dynamic balance [(f(1, 29) = 4.52, P = 0.04, ηp 2 = 0.14)] in the intervention group compared with the control group. There were no statistically significant differences in static balance and ASEBA scores between the groups. CONCLUSIONS: This study found that the DMT interventions helped to improve the dynamic balance in individuals with DS.


Sujet(s)
Thérapie par la danse , Syndrome de Down , Humains , Thérapie par la danse/méthodes , Équilibre postural , Projets pilotes , Syndrome de Down/thérapie , Études ergonomiques
7.
Radiography (Lond) ; 29(3): 557-563, 2023 05.
Article de Anglais | MEDLINE | ID: mdl-36965243

RÉSUMÉ

INTRODUCTION: Dual-energy computed tomography (DECT) can generate virtual non-contrast (VNC) images. Herein, we sought to improve the accuracy of VNC images by identifying the optimal slope of contrast media (SCM) for VNC-image generation based on the iodine concentration and subject's body size. METHODS: We used DECT to scan a multi-energy phantom including four iodine concentration rods (15, 10, 5, and 2 mg/mL), and 240 VNC images (eight SCM ranging from 0.49 to 0.56 × three body sizes × ten scans) that were generated by three-material decomposition. The CT number of each iodine and solid water rod part was measured in each VNC image. The difference in the CT number between the iodine and the solid water rod part was calculated and compared using paired t-test or repeated measures ANOVA. RESULTS: The SCM that achieved an absolute value of the difference in CT number of <5.0 Hounsfield units (HU) for all body sizes simultaneously was greater at lower iodine concentration (SCM of 0.5, 0.51, and 0.53 at 10, 5, and 2 mg/mL iodine, respectively). At an iodine concentration of 15 mg/mL, no SCM achieved an absolute difference of <5.0 HU in CT number for all body sizes simultaneously. At all iodine concentrations, the SCM achieving the minimal difference in the CT number increased with the increase in body size. CONCLUSION: By adjusting the SCM according to the iodine concentration and body size, it is possible to generate VNC images with an accuracy of <5.0 HU. IMPLICATIONS FOR PRACTICE: Improving the accuracy of VNC images minimizing incomplete iodine subtraction would make it possible to replace true non-contrast (TNC) images with VNC images and reduce the radiation dose.


Sujet(s)
Iode , Tomodensitométrie , Humains , Tomodensitométrie/méthodes , Reproductibilité des résultats , Fantômes en imagerie
8.
Radiography (Lond) ; 29(1): 240-246, 2023 01.
Article de Anglais | MEDLINE | ID: mdl-36608378

RÉSUMÉ

INTRODUCTION: Dual-energy subtraction (DES) imaging can obtain chest radiographs with high contrast between nodules and healthy lung tissue, and evaluating of chest radiography and evaluating exposure conditions is crucial to obtain a high-quality diagnostic image. This study aimed to investigate the effect of the dose allocation ratio of entrance surface dose (ESD) between high- and low-energy projection in low-contrast resolution of soft-tissue images for two-shot DES imaging in digital radiography using a contrast-detail phantom (CD phantom). METHODS: A custom-made phantom mimicking a human chest that combined a CD phantom, polymethylmethacrylate square plate, and an aluminum plate (1-3 mm) was used. The tube voltage was 120 kVp (high-energy) and 60 kVp (low-energy). The ESD was changed from 0.1 to 0.5 mGy in 0.1 mGy increments. Dose allocation ratio of ESD between 120 kVp and 60 kVp projection was set at 1:1, 1:2, 1:3, and 2:1. Inverse image quality figure (IQFinv) was calculated from the custom-made phantom images. RESULTS: When the total ESD and aluminum thickness were constant, no significant difference in IQFinv was observed under most conditions of varied dose allocation ratio. Similarly, when the total ESD and the dose allocation ratio were constant, there was no significant difference in IQFinv based on the aluminum plate thickness. CONCLUSION: Using IQFinv to evaluate the quality of the two-shot DES image suggested that dose allocation ratio did not have a significant effect on low-contrast resolution of soft-tissue images. IMPLICATIONS FOR PRACTICE: The present results provide useful information for determining exposure conditions for two-shot DES imaging.


Sujet(s)
Aluminium , Radiographie thoracique , Humains , Radiographie thoracique/méthodes , Amélioration d'image radiographique/méthodes , Radiographie , Poumon
9.
Environ Toxicol Chem ; 42(2): 449-462, 2023 02.
Article de Anglais | MEDLINE | ID: mdl-36484737

RÉSUMÉ

Dissolved copper (Cu) can contribute to toxicity in aquatic systems impacted by acid mine drainage (AMD), and its bioavailability is influenced by aqueous complexation with organic ligands that predominantly include fulvic acids (FAs). Because the geochemical fractionation of FAs that accompanies sorption to hydrous aluminum oxides (HAOs) and hydrous iron oxides (HFOs) can alter Cu complexation with FA, we investigated FAs isolated from three categories of water (pristine, AMD, and in situ-fractionated mixtures of pristine and AMD collected at stream confluences) in three mining-impacted alpine watersheds in central Colorado, USA. We also conducted geochemical fractionation of field-collected FAs and Suwannee River FAs by precipitating HAOs and HFOs in the laboratory. Spectral properties of the FAs (e.g., UV-VIS absorbance) were altered by geochemical fractionation, and in acute toxicity tests with an aquatic invertebrate (Daphnia magna) Cu was more toxic in the presence of in situ- and laboratory-fractionated FAs (median effect concentration [EC50] 19-50 µg Cu L-1 ) than in the presence of nonfractionated FAs (EC50 48-146 µg Cu L-1 ). After adjusting for the strain-specific sensitivity of our D. magna, we improved the accuracy of Biotic Ligand Model predictions of Cu EC50 values for AMD-related FAs by using an "effective dissolved organic carbon" based on spectral properties that account for among-FA differences in protectiveness against Cu toxicity. However, some differences remained between predicted and measured EC50 values, especially for FAs from AMD-related waters that might contain important metal-binding moieties not accounted for by our measured spectral indices. Environ Toxicol Chem 2023;42:449-462. © 2022 SETAC.


Sujet(s)
Cuivre , Polluants chimiques de l'eau , Animaux , Cuivre/toxicité , Cuivre/composition chimique , Daphnia , Benzopyranes , Eau , Ligands , Polluants chimiques de l'eau/composition chimique
10.
Environ Sci Process Impacts ; 24(12): 2419-2436, 2022 Dec 14.
Article de Anglais | MEDLINE | ID: mdl-36377918

RÉSUMÉ

Municipalities in central Oklahoma, U.S.A. increasingly rely on water drawn from the Central Oklahoma Aquifer (COA) as surface water resources have not grown in proportion to population and current water demands. However, water drawn from certain regions of the COA frequently contains elevated levels of naturally occurring hexavalent chromium. Rock samples from the Norman Arsenic Test Hole Core (NATHC) were investigated to identify the mineralogic host(s) of Cr and mechanisms of Cr(VI) release via bulk mineralogy and chemistry measurements, selective chemical extractions, and microscale elemental analyses. Results demonstrate most COA Cr is contained in Fe oxides and clays as isomorphic substitutions for Fe(III). Analyses of regional groundwater data, including hierarchical clustering methods and GIS, demonstrate the most intense Cr(VI) occurrence is linked to cation exchange with Na-clays at depth. Cation exchange allows dissolution of Mn-bearing dolomite, which in turn produces Mn oxides in otherwise dolomite-saturated groundwaters. Mn oxides in turn are known to oxidize Cr(III) to Cr(VI). In general, co-occurrence of Mn-bearing carbonates and exchangeable clays in any aquifer, particularly those with Cr(III) present in iron oxide cements, serve as ingredients for groundwater occurrences of oxidizable trace metals.


Sujet(s)
Nappe phréatique , Polluants chimiques de l'eau , Composés du fer III , Argile , Solubilité , Polluants chimiques de l'eau/analyse , Nappe phréatique/analyse , Chrome/analyse , Oxydes , Eau/analyse , Cations , Coenzyme A/analyse
11.
J Nutr Health Aging ; 26(6): 621-627, 2022.
Article de Anglais | MEDLINE | ID: mdl-35718872

RÉSUMÉ

OBJECTIVES: Extending healthy life expectancy (HALE), defined as the average number of years that a person can expect to live in "full health" by taking into account years lived in less than full health due to disease and/or injury, is a common topic worldwide. This study aims to clarify the relationships between the Mediterranean diet score (MDS) and life expectancy (LE) and HALE globally using publicly available international data. SETTING: Analyses were conducted on 130 countries with populations of 1 million or more for which all data were available. Individual countries were scored from 0 to 9 to indicate adherence to the Mediterranean diet according to the MDS scoring method. The supply of vegetables, legumes, fruits and nuts, cereals, fish, and olive oil per 1,000 kcal per country was calculated based on the Food and Agriculture Organization Corporate Statistical Database, with a score of 1 for above the median and 0 for below. The same method was used to calculate scores of presumed detrimental components (meat and dairy), with consumption below the median given a value of 1, and consumption above the median given a value of 0. For ethanol, a score of 1 was given for 10g to 50 g of consumption. We investigated the cross-sectional associations between the MDS and LE and HALE at birth in 2009, and the longitudinal associations between the MDS in 2009 and LE and HALE between 2009 and 2019, controlling for covariates at baseline using linear mixed models. RESULTS: In the cross-sectional analysis, the MDS was significantly positively associated with LE (ß=0.906 [95% confidence interval, 0.065-1.747], p=0.037) and HALE (ß=0.875 [0.207-1.544], p=0.011) after controlling for all covariates. The longitudinal analysis also revealed significantly positive associations between the MDS and LE (0.621 [0.063-1.178], p=0.030) and HALE (0.694 [0.227-1.161], p=0.004) after controlling for all covariates. CONCLUSION: The present study, based on an analysis using 10 years of international data, showed that countries with a higher MDS showed a positive association with HALE.


Sujet(s)
Régime méditerranéen , Animaux , Études transversales , Espérance de vie en bonne santé , Humains , Espérance de vie , Modèles linéaires
12.
Placenta ; 123: 12-23, 2022 06 01.
Article de Anglais | MEDLINE | ID: mdl-35512490

RÉSUMÉ

INTRODUCTION: The effect of SARS-CoV-2 severity or the trimester of infection in pregnant mothers, placentas, and infants is not fully understood. METHODS: A retrospective, observational cohort study in Chapel Hill, NC of 115 mothers with SARS-CoV-2 and singleton pregnancies from December 1, 2019 to May 31, 2021 via chart review to document the infants' weight, length, head circumference, survival, congenital abnormalities, hearing loss, maternal complications, and placental pathology classified by the Amsterdam criteria. RESULTS: Of the 115 mothers, 85.2% were asymptomatic (n = 37) or had mild (n = 61) symptoms, 13.0% had moderate (n = 9) or severe (n = 6) COVID-19, and 1.74% (n = 2) did not have symptoms recorded. Moderate and severe maternal infections were associated with increased C-section, premature delivery, infant NICU admission, and were more likely to occur in Type 1 (p = 0.0055) and Type 2 (p = 0.0285) diabetic mothers. Only one infant (0.870%) became infected with SARS-CoV-2, which was not via the placenta. Most placentas (n = 63, 54.8%) did not show specific histologic findings; however, a subset showed mild maternal vascular malperfusion (n = 26, 22.6%) and/or mild microscopic ascending intrauterine infection (n = 28, 24.3%). The infants had no identifiable congenital abnormalities, and all infants and mothers survived. DISCUSSION: Most mothers and their infants had a routine clinical course; however, moderate and severe COVID-19 maternal infections were associated with pregnancy complications and premature delivery. Mothers with pre-existing, non-gestational diabetes were at greatest risk of developing moderate or severe COVID-19. The placental injury patterns of maternal vascular malperfusion and/or microscopic ascending intrauterine infection were not associated with maternal COVID-19 severity.


Sujet(s)
COVID-19 , Complications infectieuses de la grossesse , Naissance prématurée , Femelle , Humains , Immunoglobuline G , Nourrisson , Transmission verticale de maladie infectieuse , Mères , Placenta/anatomopathologie , Grossesse , Complications infectieuses de la grossesse/anatomopathologie , Naissance prématurée/épidémiologie , Naissance prématurée/anatomopathologie , Études rétrospectives , SARS-CoV-2
13.
Nat Commun ; 13(1): 1213, 2022 03 08.
Article de Anglais | MEDLINE | ID: mdl-35260556

RÉSUMÉ

V/A-ATPase is a motor protein that shares a common rotary catalytic mechanism with FoF1 ATP synthase. When powered by ATP hydrolysis, the V1 domain rotates the central rotor against the A3B3 hexamer, composed of three catalytic AB dimers adopting different conformations (ABopen, ABsemi, and ABclosed). Here, we report the atomic models of 18 catalytic intermediates of the V1 domain of V/A-ATPase under different reaction conditions, determined by single particle cryo-EM. The models reveal that the rotor does not rotate immediately after binding of ATP to the V1. Instead, three events proceed simultaneously with the 120˚ rotation of the shaft: hydrolysis of ATP in ABsemi, zipper movement in ABopen by the binding ATP, and unzipper movement in ABclosed with release of both ADP and Pi. This indicates the unidirectional rotation of V/A-ATPase by a ratchet-like mechanism owing to ATP hydrolysis in ABsemi, rather than the power stroke model proposed previously for F1-ATPase.


Sujet(s)
Adenosine triphosphatases , Adénosine triphosphate , Adenosine triphosphatases/métabolisme , Adénosine triphosphate/métabolisme , Hydrolyse , Modèles moléculaires , Proton-Translocating ATPases/métabolisme , Rotation
14.
Phys Rev Lett ; 128(1): 017701, 2022 Jan 07.
Article de Anglais | MEDLINE | ID: mdl-35061474

RÉSUMÉ

We propose a nanoscale rotor embedded between two ferromagnetic electrodes that is driven by spin injection. The spin-rotation coupling allows this nanorotor to continuously receive angular momentum from an injected spin under steady current flow between ferromagnetic electrodes in an antiparallel magnetization configuration. We develop a quantum theory of this angular-momentum transfer and show that a relaxation process from a precession state into a sleeping top state is crucial for the efficient driving of the nanorotor by solving the master equation. Our work clarifies a general strategy for efficient driving of a nanorotor.

15.
Phys Rev Lett ; 127(11): 119902, 2021 Sep 10.
Article de Anglais | MEDLINE | ID: mdl-34558959

RÉSUMÉ

This corrects the article DOI: 10.1103/PhysRevLett.120.037201.

16.
Phys Rev Lett ; 127(8): 086802, 2021 Aug 20.
Article de Anglais | MEDLINE | ID: mdl-34477427

RÉSUMÉ

We report the preparation and readout of multielectron high-spin states, a three-electron quartet, and a four-electron quintet, in a gate-defined GaAs/AlGaAs single quantum dot using spin filtering by quantum Hall edge states coupled to the dot. The readout scheme consists of mapping from multielectron to two-electron spin states and a subsequent two-electron spin readout, thus obviating the need to resolve dense multielectron energy levels. Using this technique, we measure the relaxations of the high-spin states and find them to be an order of magnitude faster than those of low-spin states. Numerical calculations of spin relaxation rates using the exact diagonalization method agree with the experiment. The technique developed here offers a new tool for the study and application of high-spin states in quantum dots.

17.
Ann Oncol ; 32(11): 1434-1441, 2021 11.
Article de Anglais | MEDLINE | ID: mdl-34391895

RÉSUMÉ

BACKGROUND: The severity of oxaliplatin (L-OHP)-induced peripheral sensory neuropathy (PSN) exhibits substantial interpatient variability, and some patients suffer from long-term, persisting PSN. To identify single-nucleotide polymorphisms (SNPs) predicting L-OHP-induced PSN using a genome-wide association study (GWAS) approach. PATIENTS AND METHODS: A large prospective GWAS including 1379 patients with stage II/III colon cancer who received L-OHP-based adjuvant chemotherapy (mFOLFOX6/CAPOX) under the phase II (JOIN/JFMC41) or the phase III (ACHIVE/JFMC47) trial. Firstly, GWAS comparison of worst grade PSN (grade 0/1 versus 2/3) was carried out. Next, to minimize the impact of ambiguity in PSN grading, extreme PSN phenotypes were selected and analyzed by GWAS. SNPs that could predict time to recovery from PSN were also evaluated. In addition, SNPs associated with L-OHP-induced allergic reactions (AR) and time to disease recurrence were explored. RESULTS: No SNPs exceeded the genome-wide significance (P < 5.0 × 10-8) in either GWAS comparison of worst grade PSN, extreme PSN phenotypes, or time to recovery from PSN. An association study focusing on AR or time to disease recurrence also failed to reveal any significant SNPs. CONCLUSION: Our results highlight the challenges of utilizing SNPs for predicting susceptibility to L-OHP-induced PSN in daily clinical practice.


Sujet(s)
Tumeurs du côlon , Étude d'association pangénomique , Protocoles de polychimiothérapie antinéoplasique , Traitement médicamenteux adjuvant , Essais cliniques de phase II comme sujet , Essais cliniques de phase III comme sujet , Tumeurs du côlon/traitement médicamenteux , Tumeurs du côlon/génétique , Fluorouracil/usage thérapeutique , Humains , Récidive tumorale locale , Oxaliplatine/effets indésirables , Études prospectives
18.
ESMO Open ; 6(3): 100146, 2021 06.
Article de Anglais | MEDLINE | ID: mdl-33984677

RÉSUMÉ

BACKGROUND: Recent advances in adjuvant chemotherapy for early colon cancer have widened physicians' recommendations on the regimen and duration (3 or 6 months) of the treatment. We conducted this prospective study to evaluate whether the 12-gene recurrence score (12-RS) assay affected physicians' recommendations on adjuvant treatment selection. PATIENTS AND METHODS: Patients with stage IIIA/IIIB or stage II colon cancer were enrolled. After the patients discussed adjuvant treatment with their treating physicians, the physicians filled in the questionnaire before assay indicating the treatment recommendation. When the 12-RS assay results were available, the physicians again filled in the questionnaire after assay. The primary endpoint was the rate of change in treatment recommendations from before to after the assay, with a threshold rate of change being 20%. Patients with stage IIIA/B to II were enrolled in a ratio of 2 : 1. RESULTS: Overall, the treatment recommendations changed in 40% of cases after obtaining 12-RS assay results. Recommendations were changed in 45% (80/178; 95% confidence interval, 37% to 53%; P < 0.001) and 30% (29/97; 95% confidence interval, 21% to 40%; P < 0.001) of patients with stage IIIA/B and II colon cancer, respectively. Patients with stage IIIA/B cancer had significantly more change than those with stage II cancer (P = 0.0148). From before to after the 12-RS assay, the percentage of patients whose physicians reported being confident in their treatment recommendations significantly increased from 54% to 81% in stage IIIA/B (P < 0.001) and from 65% to 83% in stage II (P < 0.001). CONCLUSION: Our study confirmed the usefulness of the 12-RS assay in aiding the physician-patient decision-making process for tailoring adjuvant chemotherapy for stage IIIA/B colon cancer.


Sujet(s)
Tumeurs du côlon , Récidive tumorale locale , Dosage biologique , Traitement médicamenteux adjuvant , Tumeurs du côlon/traitement médicamenteux , Tumeurs du côlon/génétique , Humains , Récidive tumorale locale/traitement médicamenteux , Récidive tumorale locale/génétique , Études prospectives
19.
ESMO Open ; 6(3): 100115, 2021 06.
Article de Anglais | MEDLINE | ID: mdl-33984681

RÉSUMÉ

BACKGROUND: FLAURA, the prospective trial of osimertinib as a first-line therapy compared with first-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), did not show superior survival benefit for osimertinib in either the subgroup of Asians or the subgroup with the L858R mutation. In addition, the superiority of osimertinib compared with second-generation EGFR-TKI is thus far unclear. PATIENTS AND METHODS: We reviewed the clinical data of all consecutive patients who were treated with osimertinib or afatinib as first-line therapy between May 2016 and October 2019 from 15 institutions in Japan. We defined the groups based on first-line EGFR-TKI as the afatinib group and the osimertinib group. Outcomes included time to discontinuation of any EGFR-TKI (TD-TKI), overall survival (OS), and time to treatment failure, with propensity score analysis carried out as an exploratory analysis in the survival and subgroup analyses. RESULTS: A total of 554 patients were enrolled. Data on 326 patients in the osimertinib group, and 224 patients in the afatinib group were analyzed. TD-TKI adjusted by propensity score in the afatinib and osimertinib groups was 18.6 months (95% confidence interval 15.8 to 22.0) and 20.5 months (95% confidence interval 13.8 to not reached), respectively, without significant difference (P = 0.204). OS adjusted by propensity score favored the afatinib group with a significant difference (P = 0.018). Subgroup analysis with propensity score showed that patients with L858R and without brain metastasis had superior survival benefit with afatinib compared with osimertinib (P < 0.001). CONCLUSIONS: TD-TKI in the afatinib group was not significantly prolonged compared with the osimertinib group in the practical data. In the exploratory analysis of patients with L858R-mutated non-small-cell lung cancer without brain metastasis, afatinib showed more benefit in OS over osimertinib.


Sujet(s)
Carcinome pulmonaire non à petites cellules , Tumeurs du poumon , Acrylamides , Afatinib/usage thérapeutique , Dérivés de l'aniline , Protocoles de polychimiothérapie antinéoplasique , Carcinome pulmonaire non à petites cellules/traitement médicamenteux , Carcinome pulmonaire non à petites cellules/génétique , Études de cohortes , Récepteurs ErbB/génétique , Humains , Tumeurs du poumon/traitement médicamenteux , Tumeurs du poumon/génétique , Études prospectives
20.
Phys Rev Lett ; 126(12): 121801, 2021 Mar 26.
Article de Anglais | MEDLINE | ID: mdl-33834796

RÉSUMÉ

The rare decay K_{L}→π^{0}νν[over ¯] was studied with the dataset taken at the J-PARC KOTO experiment in 2016, 2017, and 2018. With a single event sensitivity of (7.20±0.05_{stat}±0.66_{syst})×10^{-10}, three candidate events were observed in the signal region. After unveiling them, contaminations from K^{±} and scattered K_{L} decays were studied, and the total number of background events was estimated to be 1.22±0.26. We conclude that the number of observed events is statistically consistent with the background expectation. For this dataset, we set an upper limit of 4.9×10^{-9} on the branching fraction of K_{L}→π^{0}νν[over ¯] at the 90% confidence level.

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