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 $T$ does not exceed some finite value $T_c$. At the same time, it can be also proven that at high enough $T$ 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, $T<T_c$, 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

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 &gt;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 &lt; .0001). ORR was 26.2% for TRAM vs 6.2% for SOC (OR 5.4; 95% CI, 2.39-12.21; P&lt; .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 &gt;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