Efficacy of subsequent chemotherapy for patients with BRCA1/2-mutated recurrent epithelial ovarian cancer progressing on olaparib versus placebo maintenance: post-hoc analyses of the SOLO2/ENGOT Ov-21 trial.

BACKGROUND: In the SOLO2 trial (ENGOT Ov-21; NCT01874353), maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer (PSROC) and BRCA mutation significantly improved progression-free survival (PFS) and prolonged overall survival (OS). Following disease progression on olaparib, efficacy of subsequent chemotherapy remains unknown. PATIENTS AND METHODS: We conducted a post-hoc hypothesis-generating analysis of SOLO2 data to determine the efficacy of different chemotherapy regimens following RECIST disease progression in patients who received olaparib or placebo. We evaluated time to second progression (TTSP) calculated from the date of RECIST progression to the next progression/death. RESULTS: The study population comprised 147 patients who received chemotherapy as their first subsequent treatment after RECIST progression. Of these, 69 (47%) and 78 (53%) were originally randomized to placebo and olaparib arms, respectively. In the placebo-treated cohort, 27/69 and 42/69 received non-platinum and platinum-based chemotherapy, respectively, compared with 24/78 and 54/78, respectively, in the olaparib-treated cohort. Among patients treated with chemotherapy (N = 147), TTSP was significantly longer in the placebo than in the olaparib arm: 12.1 versus 6.9 months [hazard ratio (HR) 2.17, 95% confidence interval (CI) 1.47-3.19]. Similar result was obtained on multivariable analysis adjusting for prognostic factors at RECIST progression (HR 2.13, 95% CI 1.41-3.22). Among patients treated with platinum-based chemotherapy (n = 96), TTSP was significantly longer in the placebo arm: 14.3 versus 7.0 months (HR 2.89, 95% CI 1.73-4.82). Conversely, among patients treated with non-platinum-based chemotherapy (n = 51), the TTSP was comparable in the placebo and olaparib arms: 8.3 versus 6.0 months (HR 1.58, 95% CI 0.86-2.90). CONCLUSIONS: Following progression from maintenance olaparib in the recurrent setting, the efficacy of platinum-based subsequent chemotherapy seems to be reduced in BRCA1/2-mutated patients with PSROC compared to patients not previously receiving poly (ADP-ribose) polymerase inhibitors (PARPi). The optimal strategy for patients who relapse after PARPi is an area of ongoing research.

Experimental Observation and Spin Texture of Dirac Node Arcs in Tetradymite Topological Metals.

We report the observation of a nontrivial spin texture in Dirac node arcs, i.e., novel topological objects formed when Dirac cones of massless particles extend along an open one-dimensional line in momentum space. We find that such states are present in all the compounds of the tetradymite M_{2}Te_{2}X family (M=Ti, Zr, or Hf and X=P or As) regardless of the weak or strong character of the topological invariant. The Dirac node arcs in tetradymites are thus the simplest possible textbook example of a type-I Dirac system with a single spin-polarized node arc.

Bulk Fermi Surfaces of the Dirac Type-II Semimetallic Candidates MAl_{3} (Where M=V, Nb, and Ta).

We report a de Haas-van Alphen (dHvA) effect study on the Dirac type-II semimetallic candidates MAl_{3} (where, M=V, Nb and Ta). The angular dependence of their Fermi surface (FS) cross-sectional areas reveals a remarkably good agreement with our first-principles calculations. Therefore, dHvA supports the existence of tilted Dirac cones with Dirac type-II nodes located at 100, 230 and 250 meV above the Fermi level ϵ_{F} for VAl_{3}, NbAl_{3} and TaAl_{3} respectively, in agreement with the prediction of broken Lorentz invariance in these compounds. However, for all three compounds we find that the cyclotron orbits on their FSs, including an orbit nearly enclosing the Dirac type-II node, yield trivial Berry phases. We explain this via an analysis of the Berry phase where the position of this orbit, relative to the Dirac node, is adjusted within the error implied by the small disagreement between our calculations and the experiments. We suggest that a very small amount of doping could displace ϵ_{F} to produce topologically nontrivial orbits encircling their Dirac node(s).

Effect of Hg, As and Pb on biomass production, photosynthetic rate, nutrients uptake and phytochelatin induction in Pfaffia glomerata.

Plantlets of Pfaffia glomerata (Spreng.) were exposed for 28 days to three different metal/metalloid (Hg, Pb and As) with different levels (Hg 1; As 25, 50, 100 and Pb 100 and 400 µM) to analyze the possible phytochelatin initiation and affects on growth and photosynthetic pigments vis-à-vis metal accumulation potential of plants. The plantlets showed significant Hg, As and Pb accumulation in roots (150, 1267.67 and 2129 µg g(-1) DW respectively); however, a low root to shoot metal translocation was observed. It was interesting to note that all tested macronutrient (Mg, K, Ca) was higher in shoots and just opposite in case of micronutrients (Cu, Fe, Zn), was recorded highest in roots. The growth of plantlets (analyzed in terms of length and dry weight) was negatively affected by various metal treatments. In addition, the level of photosynthetic pigments alters significantly in response to all metal/metalloid treatment. In response to all tested metal/metalloids in plants only As induced phytochelatins (PC2, PC3 and PC4) in roots, and in shoots, GSH was observed in all tested metal/metalloids. In conclusion, P. glomerata plantlets could not cooperatively induce phytochelatins under any of Hg and Pb levels.

Nutritional status of children in two districts of the mountain region of Nepal.

BACKGROUND: Nutritional status is a prime indicator of health. Generally, three anthropometric indicators are often used to assess nutritional status during childhood and adolescence: underweight (weight-for-age), stunting (height- for-age) and thinness (BMI-for-age). Malnutrition in children is a major public health problem in many developing countries. This study was conducted to assess nutritional status among children attending health camps in two mountainous districts in Nepal. METHODS: Five hundred and seventy five children below 15 years of age attending the medical camp in Humla and Mugu districts in October 2011 were assessed for nutritional status. For children less than five years, weight for age, weight for height and height for age as per WHO classification, and for children between five to 15 years age specific values of height, weight and Body Mass Index (BMI) were calculated. RESULTS: In Humla district, 28.2% children were undernourished, 8.8% wasted and 22.4% stunted in less than five years. In the same age group, 31.7% children were undernourished, 9.4% wasted and 29.4% stunted in Mugu district. In the age group five to 15 years, thinness was seen in 22.4% and 29.4% children in Humla and Mugu respectively. CONCLUSIONS: Malnutrition (underweight, stunting, wasting and thinness) still constitutes a major health problem among Nepalese children, particularly in mountainous regions.

Confinement resonances in photoionization of Xe@C60+.

Experimental evidence is presented for confinement resonances associated with photoabsorption by a Xe atom in a C60 cage. The giant 4d resonance in photoionization of Xe is predicted to be redistributed into four components due to multipath interference of photoelectron waves reflected by the cage. The measurements were made in the photon energy range 60-150 eV by merging a beam of synchrotron radiation with a mass/charge selected Xe@C60+ ion beam. The phenomenon was observed in the Xe@C(58)(3+) product ion channel. [corrected]