f(Q, T) gravity Xu, Yixin; Li, Guangjie; Harko, Tiberiu ...
The European physical journal. C, Particles and fields,
08/2019, Letnik:
79, Številka:
8
Journal Article
Recenzirano
Odprti dostop
We propose an extension of the symmetric teleparallel gravity, in which the gravitational action
L
is given by an arbitrary function
f
of the non-metricity
Q
and of the trace of the ...matter-energy-momentum tensor
T
, so that
L
=
f
(
Q
,
T
)
. The field equations of the theory are obtained by varying the gravitational action with respect to both metric and connection. The covariant divergence of the field equations is obtained, with the geometry–matter coupling leading to the nonconservation of the energy-momentum tensor. We investigate the cosmological implications of the theory, and we obtain the cosmological evolution equations for a flat, homogeneous and isotropic geometry, which generalize the Friedmann equations of general relativity. We consider several cosmological models by imposing some simple functional forms of the function
f
(
Q
,
T
), corresponding to additive expressions of
f
(
Q
,
T
) of the form
f
(
Q
,
T
)
=
α
Q
+
β
T
,
f
(
Q
,
T
)
=
α
Q
n
+
1
+
β
T
, and
f
(
Q
,
T
)
=
-
α
Q
-
β
T
2
. The Hubble function, the deceleration parameter, and the matter-energy density are obtained as a function of the redshift by using analytical and numerical techniques. For all considered cases the Universe experiences an accelerating expansion, ending with a de Sitter type evolution. The theoretical predictions are also compared with the results of the standard
Λ
CDM model.
We consider an
f
(
Q
,
T
) type gravity model in which the scalar non-metricity
Q
α
μ
ν
of the space-time is expressed in its standard Weyl form, and it is fully determined by a vector field
w
μ
. ...The field equations of the theory are obtained under the assumption of the vanishing of the total scalar curvature, a condition which is added into the gravitational action via a Lagrange multiplier. The gravitational field equations are obtained from a variational principle, and they explicitly depend on the scalar nonmetricity and on the Lagrange multiplier. The covariant divergence of the matter energy-momentum tensor is also determined, and it follows that the nonmetricity-matter coupling leads to the nonconservation of the energy and momentum. The energy and momentum balance equations are explicitly calculated, and the expressions of the energy source term and of the extra force are found. We investigate the cosmological implications of the theory, and we obtain the cosmological evolution equations for a flat, homogeneous and isotropic geometry, which generalize the Friedmann equations of standard general relativity. We consider several cosmological models by imposing some simple functional forms of the function
f
(
Q
,
T
), and we compare the predictions of the theory with the standard
Λ
CDM model.
Cisplatin-based adjuvant chemotherapy is the standard of care for patients with resected stage II–IIIA non-small-cell lung cancer (NSCLC). RADIANT and SELECT trial data suggest patients with ...EGFR-mutant stage IB–IIIA resected NSCLC could benefit from adjuvant EGFR tyrosine kinase inhibitor treatment. We aimed to compare the efficacy of adjuvant gefitinib versus vinorelbine plus cisplatin in patients with completely resected EGFR-mutant stage II–IIIA (N1–N2) NSCLC.
We did a randomised, open-label, phase 3 trial at 27 centres in China. We enrolled patients aged 18–75 years with completely resected (R0), stage II–IIIA (N1–N2), EGFR-mutant (exon 19 deletion or exon 21 Leu858Arg) NSCLC. Patients were stratified by N stage and EGFR mutation status and randomised (1:1) by Pocock and Simon minimisation with a random element to either gefitinib (250 mg once daily) for 24 months or intravenous vinorelbine (25 mg/m2 on days 1 and 8) plus intravenous cisplatin (75 mg/m2 on day 1) every 3 weeks for four cycles. The primary endpoint was disease-free survival in the intention-to-treat population, which comprised all randomised patients; the safety population included all randomised patients who received at least one dose of study medication. Enrolment to the study is closed but survival follow-up is ongoing. The study is registered with ClinicalTrials.gov, number NCT01405079.
Between Sept 19, 2011, and April 24, 2014, 483 patients were screened and 222 patients were randomised, 111 to gefitinib and 111 to vinorelbine plus cisplatin. Median follow-up was 36·5 months (IQR 23·8–44·8). Median disease-free survival was significantly longer with gefitinib (28·7 months 95% CI 24·9–32·5) than with vinorelbine plus cisplatin (18·0 months 13·6–22·3; hazard ratio HR 0·60, 95% CI 0·42–0·87; p=0·0054). In the safety population, the most commonly reported grade 3 or worse adverse events in the gefitinib group (n=106) were raised alanine aminotransferase and asparate aminotransferase (two 2% patients with each event vs none with vinorelbine plus cisplatin). In the vinorelbine plus cisplatin group (n=87), the most frequently reported grade 3 or worse adverse events were neutropenia (30 34% patients vs none with gefitinib), leucopenia (14 16% vs none), and vomiting (eight 9% vs none). Serious adverse events were reported for seven (7%) patients who received gefitinib and 20 (23%) patients who received vinorelbine plus cisplatin. No interstitial lung disease was noted with gefitinib. No deaths were treatment related.
Adjuvant gefitinib led to significantly longer disease-free survival compared with that for vinorelbine plus cisplatin in patients with completely resected stage II–IIIA (N1–N2) EGFR-mutant NSCLC. Based on the superior disease-free survival, reduced toxicity, and improved quality of life, adjuvant gefitinib could be a potential treatment option compared with adjuvant chemotherapy in these patients. However, the duration of benefit with gefitinib after 24 months might be limited and overall survival data are not yet mature.
Guangdong Provincial Key Laboratory of Lung Cancer Translational Medicine; National Health and Family Planning Commission of People's Republic of China; Guangzhou Science and Technology Bureau; AstraZeneca China.
The ADJUVANT study reported the comparative superiority of adjuvant gefitinib over chemotherapy in disease-free survival of resected EGFR-mutant stage II-IIIA non-small cell lung cancer (NSCLC). ...However, not all patients experienced favorable clinical outcomes with tyrosine kinase inhibitors (TKI), raising the necessity for further biomarker assessment. In this work, by comprehensive genomic profiling of 171 tumor tissues from the ADJUVANT trial, five predictive biomarkers are identified (TP53 exon4/5 mutations, RB1 alterations, and copy number gains of NKX2-1, CDK4, and MYC). Then we integrate them into the Multiple-gene INdex to Evaluate the Relative benefit of Various Adjuvant therapies (MINERVA) score, which categorizes patients into three subgroups with relative disease-free survival and overall survival benefits from either adjuvant gefitinib or chemotherapy (Highly TKI-Preferable, TKI-Preferable, and Chemotherapy-Preferable groups). This study demonstrates that predictive genomic signatures could potentially stratify resected EGFR-mutant NSCLC patients and provide precise guidance towards future personalized adjuvant therapy.
ADJUVANT-CTONG1104 (ClinicalTrials.gov identifier: NCT01405079), a randomized phase III trial, showed that adjuvant gefitinib treatment significantly improved disease-free survival (DFS) versus ...vinorelbine plus cisplatin (VP) in patients with epidermal growth factor receptor (
) mutation-positive resected stage II-IIIA (N1-N2) non-small-cell lung cancer (NSCLC). Here, we report the final overall survival (OS) results.
From September 2011 to April 2014, 222 patients from 27 sites were randomly assigned 1:1 to adjuvant gefitinib (n = 111) or VP (n = 111). Patients with resected stage II-IIIA (N1-N2) NSCLC and
-activating mutation were enrolled, receiving gefitinib for 24 months or VP every 3 weeks for four cycles. The primary end point was DFS (intention-to-treat ITT population). Secondary end points included OS, 3-, 5-year (y) DFS rates, and 5-year OS rate. Post hoc analysis was conducted for subsequent therapy data.
Median follow-up was 80.0 months. Median OS (ITT) was 75.5 and 62.8 months with gefitinib and VP, respectively (hazard ratio HR, 0.92; 95% CI, 0.62 to 1.36;
= .674); respective 5-year OS rates were 53.2% and 51.2% (
= .784). Subsequent therapy was administered upon progression in 68.4% and 73.6% of patients receiving gefitinib and VP, respectively. Subsequent targeted therapy contributed most to OS (HR, 0.23; 95% CI, 0.14 to 0.38) compared with no subsequent therapy. Updated 3y DFS rates were 39.6% and 32. 5% with gefitinib and VP (
= .316) and 5y DFS rates were 22. 6% and 23.2% (
= .928), respectively.
Adjuvant therapy with gefitinib in patients with early-stage NSCLC and
mutation demonstrated improved DFS over standard of care chemotherapy. Although this DFS advantage did not translate to a significant OS difference, OS with adjuvant gefitinib was one of the longest observed in this patient group compared with historic data.
Aim
Climate change is expected to have important effects on plant phenology and carbon storage, with further shifts predicted in the future. Therefore, we proposed the community carbon accumulation ...rate (CAR) from the start of the growing season (SOS) to the peak of the growing season (POS) to fill the gap that the dynamic interactions between plant phenology and plant carbon research.
Location
Tibetan Plateau.
Major taxa
Alpine grassland plants.
Time period
2015.
Methods
We conducted a transect survey across grasslands to measure community aboveground net primary production and carbon concentration. Additionally, phenology indicator data (SOS and POS) were extracted from the Global Inventory Modeling and Mapping Studies (GIMMS) normalized difference vegetation index version 3 database. Next, we used ‘changepoint’ analysis to detect the patterns of CARs, and performed linear regression and one‐way ANOVA to explore the variability of CARs in response to the environmental factors. Ultimately, the total effects of environmental factors on CARs were illustrated by a structural equation model.
Results
Our results indicated that three CAR patterns were detected, which are low‐CAR (0.15 g/m2/day), medium‐CAR (0.31 g/m2/day) and high‐CAR (0.84 g/m2/day) patterns. We found that the availabilities of water and heat mediated CARs by regulating soil nutrition variability, and that drought climate and insufficient soil resources co‐constrained the community CAR at long time‐scales. In contrast, high CAR could be explained by more water and heat availability via either direct or indirect effects on soil moisture and soil nutrients.
Main conclusions
Our findings highlight that water and heat availability are critical driving factors in ecological carbon accumulation processes undergoing climate change. Meanwhile, the vegetative phenology also has important effect on carbon accumulation. Consequently, we propose incorporating the dynamic interactions between plant phenology and plant carbon into the ecological carbon cycle model to improve our understanding of resource utilization and survival strategies of plants under environmental change.
Competitive proteome profiling is a powerful approach for the identification of targets of small molecules. This approach usually employs an inhibitor-derived probe or a cysteine-reactive probe such ...as an IA-alkyne in a comparison between inhibitor-treated and untreated samples, thus enabling distinction between genuine targets and nonspecific labeling. We have developed an active probe derived from an EGFR inhibitor, afatinib, and a cysteine reactive probe, an alkyne-containing α,β-unsaturated amide, to compare their characterization of cellular targets. In both approaches, myosin heavy chain 9 (MYH9) was identified as an off-target. Subsequent functional validation experiments suggested that MYH9 might be involved in the function of afatinib.
The atmospheric CO2 concentration continues a rapid increase to its current record high value of 416 ppm for the time being. It calls for advanced CO2 capture technologies. One of the attractive ...technologies is physical adsorption‐based separation, which shows easy regeneration and high cycle stability, and thus reduced energy penalties and cost. The extensive research on this topic is evidenced by the growing body of scientific and technical literature. The progress spans from the innovation of novel porous adsorbents to practical separation practices. Major CO2 capture materials include the most widely used industrially relevant porous carbons, zeolites, activated alumina, mesoporous silica, and the newly emerging metal‐organic frameworks (MOFs) and covalent‐organic framework (COFs). The key intrinsic properties such as pore structure, surface chemistry, preferable adsorption sites, and other structural features that would affect CO2 capture capacity, selectivity, and recyclability are first discussed. The industrial relevant variables such as particle size of adsorbents, the mechanical strength, adsorption heat management, and other technological advances are equally important, even more crucial when scaling up from bench and pilot‐scale to demonstration and commercial scale. Therefore, we aim to bring a full picture of the adsorption‐based CO2 separation technologies, from adsorbent design, intrinsic property evaluation to performance assessment not only under ideal equilibrium conditions but also in realistic pressure swing adsorption processes.
Divide and conquer: This Review discusses the recent advances in adsorption‐based CO2 separation technology, from porous materials synthesis, adsorbents’ intrinsic property evaluation to performance assessments not only in view of the ideal equilibrium conditions but also in critically practical perspective.
Adjuvant gefitinib therapy prolonged disease-free survival in patients with resected early-stage EGFR-mutation positive NSCLC in the ADJUVANT study (CTONG 1104). However, treatment failure patterns ...after gefitinib therapy are less well characterized.
Overall, 222 stage N1–N2, EGFR-mutant NSCLC patients received gefitinib or vinorelbine plus cisplatin (VP) treatment. Tumor recurrences or metastases occurring during follow-up were defined as treatment failure; sites and data of first treatment failure were recorded. A post hoc analysis of treatment failure patterns which was estimated by Kaplan-Meier and hazard rate curves in modified intention-to-treat patients was conducted.
There were 114 recurrences and 10 deaths before recurrence across 124 progression events. Spatial distribution analysis showed that the first metastasis site was most frequently the central nervous system in the gefitinib group (29 of 106 27.4%), extracranial metastases were most frequent in the VP group (32 of 87 36.8%). Temporal distribution analysis showed lower tumor recurrence with gefitinib than with VP 0 to 21 months post-surgery. However, recurrence with gefitinib showed a constant rate of increase 12 months post-surgery. The first peak of extracranial metastasis appeared during 9 to 15 months with VP and 24 to 30 months with gefitinib. The highest peak for central nervous system metastases post-surgery occurred after 12 to 18 months with VP and 24 to 36 months with gefitinib.
Adjuvant gefitinib showed advantages over VP chemotherapy in treatment failure patterns especially in extracranial metastasis. Adjuvant tyrosine kinas inhibitors may be considered as a treatment option in resected stage N1–N2 EGFR-mutant NSCLC but longer duration should be explored.
PDF
