18 research outputs found
Metal-insulator transition in a weakly interacting many-electron system with localized single-particle states
We consider low-temperature behavior of weakly interacting electrons in
disordered conductors in the regime when all single-particle eigenstates are
localized by the quenched disorder. We prove that in the absence of coupling of
the electrons to any external bath dc electrical conductivity exactly vanishes
as long as the temperatute does not exceed some finite value . At the
same time, it can be also proven that at high enough the conductivity is
finite. These two statements imply that the system undergoes a finite
temperature Metal-to-Insulator transition, which can be viewed as Anderson-like
localization of many-body wave functions in the Fock space. Metallic and
insulating states are not different from each other by any spatial or discrete
symmetries. We formulate the effective Hamiltonian description of the system at
low energies (of the order of the level spacing in the single-particle
localization volume). In the metallic phase quantum Boltzmann equation is
valid, allowing to find the kinetic coefficients. In the insulating phase,
, we use Feynmann diagram technique to determine the probability
distribution function for quantum-mechanical transition rates. The probability
of an escape rate from a given quantum state to be finite turns out to vanish
in every order of the perturbation theory in electron-electron interaction.
Thus, electron-electron interaction alone is unable to cause the relaxation and
establish the thermal equilibrium. As soon as some weak coupling to a bath is
turned on, conductivity becomes finite even in the insulating phase
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Gastrointestinal adjuvant chemotherapy regimens improve survival outcomes in women with mucinous ovarian cancer
A randomized phase II/III study to assess the efficacy of trametinib in patients with recurrent or progressive low-grade serous ovarian or peritoneal cancer
Background:
Low-grade serous carcinoma of the ovary/peritoneum (LGSOC) is a rare subtype, accounting for 5-10% of all serous cancers, and is characterized by alterations in the MAPK pathway, relative chemoresistance, and prolonged overall survival (OS) compared to high-grade serous carcinoma. NRG Oncology in the US and the National Cancer Research Network (NCRN) in the UK collaborated on a phase II/III trial to assess the efficacy of a MEK inhibitor trametinib (TRAM) compared to physician’s choice standard of care (SOC) in recurrent LGSOC.
Methods:
Patients (pts) were randomized 1:1 to receive either TRAM 2 mg daily or 1 of 5 SOC options (weekly paclitaxel, PLD, topotecan, letrozole, or tamoxifen) until disease progression. Pts who progressed on SOC were allowed to crossover to TRAM. The primary objective tested the progression-free survival (PFS) superiority of TRAM vs SOC. Secondary objectives included toxicity, QoL, and objective response rate (ORR) by RECIST 1.1. Exploratory objectives were OS and PFS and ORR after crossover. PFS and OS curves were estimated using the Kaplan-Meier method and compared by a 1-sided, α = 0.025 log-rank test.
Results:
260 pts (48.1% had >3 prior lines of therapy) were enrolled between Feb 2014 and Apr 2018. Median follow-up was 31.4 months (mo). PFS was significantly improved for TRAM compared to SOC (median, 13.0 vs 7.2 mo; HR 0.48; 95% CI, 0.36-0.64; P < .0001). ORR was 26.2% for TRAM vs 6.2% for SOC (OR 5.4; 95% CI, 2.39-12.21; P< .0001). Response duration for TRAM was significantly better than for SOC (median, 13.63 mo; 95% CI, 8.08-18.76; vs 5.88 mo; 95% CI, 2.76-12.19). Preliminary analysis of QoL patient reported outcomes shows no significant therapy effects. Main Grade >3 AE in TRAM vs SOC were hematologic toxicity (13.4% vs 9.4%), GI toxicity (27.6% vs 29%), skin toxicity (15% vs 3.9%), and vascular toxicity (18.9% vs 8.6%). Median OS for TRAM vs SOC was 37.0 mo (95% CI, 30.3-NE) vs 29.2 mo (95% CI, 23.5-51.6) (HR 0.75; 95% CI, 0.51-1.11). For 88 pts who crossed over to TRAM, median PFS = 10.8 mo (95% CI, 7.3-12.0), and ORR = 15% (95% CI, 0.07-0.22).
Conclusions:
Compared to physician’s choice SOC, TRAM was associated with significantly improved PFS and ORR in women with recurrent LGSOC