Development and pilot evaluation of a personalized decision support intervention for low risk prostate cancer patients.

ObjectivesDevelopment and pilot evaluation of a personalized decision support intervention to help men with early-stage prostate cancer choose among active surveillance, surgery, and radiation.MethodsWe developed a decision aid featuring long-term survival and side effects data, based on focus group input and stakeholder endorsement. We trained premedical students to administer the intervention to newly diagnosed men with low-risk prostate cancer seen at the University of California, San Francisco. Before the intervention, and after the consultation with a urologist, we administered the Decision Quality Instrument for Prostate Cancer (DQI-PC). We hypothesized increases in two knowledge items from the DQI-PC: How many men diagnosed with early-stage prostate cancer will eventually die of prostate cancer? How much would waiting 3 months to make a treatment decision affect chances of survival? Correct answers were: "Most will die of something else" and "A little or not at all."ResultsThe development phase involved 6 patients, 1 family member, 2 physicians, and 5 other health care providers. In our pilot test, 57 men consented, and 44 received the decision support intervention and completed knowledge surveys at both timepoints. Regarding the two knowledge items of interest, before the intervention, 35/56 (63%) answered both correctly, compared to 36/44 (82%) after the medical consultation (P = .04 by chi-square test).ConclusionsThe intervention was associated with increased patient knowledge. Data from this pilot have guided the development of a larger scale randomized clinical trial to improve decision quality in men with prostate cancer being treated in community settings

Incomplete inhibition of phosphorylation of 4E-BP1 as a mechanism of primary resistance to ATP-competitive mTOR inhibitors

The mammalian target of rapamycin (mTOR) regulates cell growth by integrating nutrient and growth factor signaling and is strongly implicated in cancer. But mTOR is not an oncogene, and which tumors will be resistant or sensitive to new ATP-competitive mTOR inhibitors now in clinical trials remains unknown. We screened a panel of over 600 human cancer cell lines to identify markers of resistance and sensitivity to the mTOR inhibitor PP242. RAS and PIK3CA mutations were the most significant genetic markers for resistance and sensitivity to PP242, respectively; colon origin was the most significant marker for resistance based on tissue type. Among colon cancer cell lines, those with KRAS mutations were most resistant to PP242, while those without KRAS mutations most sensitive. Surprisingly, cell lines with co-mutation of PIK3CA and KRAS had intermediate sensitivity. Immunoblot analysis of the signaling targets downstream of mTOR revealed that the degree of cellular growth inhibition induced by PP242 was correlated with inhibition of phosphorylation of the translational repressor 4E-BP1, but not ribosomal protein S6. In a tumor growth inhibition trial of PP242 in patient-derived colon cancer xenografts, resistance to PP242 induced inhibition of 4E-BP1 phosphorylation and xenograft growth was again observed in KRAS mutant tumors without PIK3CA co-mutation, compared to KRAS WT controls. We show that, in the absence of PIK3CA co-mutation, KRAS mutations are associated with resistance to PP242 and that this is specifically linked to changes in the level of phosphorylation of 4E-BP1

Optimal interdependence between networks for the evolution of cooperation

Recent research has identified interactions between networks as crucial for the outcome of evolutionary games taking place on them. While the consensus is that interdependence does promote cooperation by means of organizational complexity and enhanced reciprocity that is out of reach on isolated networks, we here address the question just how much interdependence there should be. Intuitively, one might assume the more the better. However, we show that in fact only an intermediate density of sufficiently strong interactions between networks warrants an optimal resolution of social dilemmas. This is due to an intricate interplay between the heterogeneity that causes an asymmetric strategy flow because of the additional links between the networks, and the independent formation of cooperative patterns on each individual network. Presented results are robust to variations of the strategy updating rule, the topology of interdependent networks, and the governing social dilemma, thus suggesting a high degree of universality

Observation of charge asymmetry dependence of pion elliptic flow and the possible chiral magnetic wave in heavy-ion collisions

We present measurements of $\pi^-$ and $\pi^+$ elliptic flow, $v_2$, at midrapidity in Au+Au collisions at $\sqrt{s_{_{\rm NN}}} =$ 200, 62.4, 39, 27, 19.6, 11.5 and 7.7 GeV, as a function of event-by-event charge asymmetry, $A_{ch}$, based on data from the STAR experiment at RHIC. We find that $\pi^-$ ($\pi^+$) elliptic flow linearly increases (decreases) with charge asymmetry for most centrality bins at $\sqrt{s_{_{\rm NN}}} = \text{27 GeV}$ and higher. At $\sqrt{s_{_{\rm NN}}} = \text{200 GeV}$, the slope of the difference of $v_2$ between $\pi^-$ and $\pi^+$ as a function of $A_{ch}$ exhibits a centrality dependence, which is qualitatively similar to calculations that incorporate a chiral magnetic wave effect. Similar centrality dependence is also observed at lower energies.Comment: 6 pages, 4 figure

Centrality and transverse momentum dependence of elliptic flow of multi-strange hadrons and ϕ\phi meson in Au+Au collisions at sNN\sqrt{s_{NN}} = 200 GeV

We present high precision measurements of elliptic flow near midrapidity ($|y|<1.0$) for multi-strange hadrons and $\phi$ meson as a function of centrality and transverse momentum in Au+Au collisions at center of mass energy $\sqrt{s_{NN}}=$ 200 GeV. We observe that the transverse momentum dependence of $\phi$ and $\Omega$ $v_{2}$ is similar to that of $\pi$ and $p$, respectively, which may indicate that the heavier strange quark flows as strongly as the lighter up and down quarks. This observation constitutes a clear piece of evidence for the development of partonic collectivity in heavy-ion collisions at the top RHIC energy. Number of constituent quark scaling is found to hold within statistical uncertainty for both 0-30$\%$ and 30-80$\%$ collision centrality. There is an indication of the breakdown of previously observed mass ordering between $\phi$ and proton $v_{2}$ at low transverse momentum in the 0-30$\%$ centrality range, possibly indicating late hadronic interactions affecting the proton $v_{2}$.Comment: 7 pages and 4 figures, Accepted for publication in Physical Review Letter

Beam Energy Dependence of the Third Harmonic of Azimuthal Correlations in Au+Au Collisions at RHIC

We present results from a harmonic decomposition of two-particle azimuthal correlations measured with the STAR detector in Au+Au collisions for energies ranging from $\sqrt{s_{NN}}=7.7$ GeV to 200 GeV. The third harmonic $v_3^2\{2\}=\langle \cos3(\phi_1-\phi_2)\rangle$, where $\phi_1-\phi_2$ is the angular difference in azimuth, is studied as a function of the pseudorapidity difference between particle pairs $\Delta\eta = \eta_1-\eta_2$. Non-zero {\vthree} is directly related to the previously observed large-$\Delta\eta$ narrow-$\Delta\phi$ ridge correlations and has been shown in models to be sensitive to the existence of a low viscosity Quark Gluon Plasma (QGP) phase. For sufficiently central collisions, $v_3^2\{2\}$ persist down to an energy of 7.7 GeV suggesting that QGP may be created even in these low energy collisions. In peripheral collisions at these low energies however, $v_3^2\{2\}$ is consistent with zero. When scaled by pseudorapidity density of charged particle multiplicity per participating nucleon pair, $v_3^2\{2\}$ for central collisions shows a minimum near {\snn}$=20$ GeV.Comment: 7 pages, 4 figures, for submission to Phys. Rev. Let