727 research outputs found
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
Mixed Supervision of Histopathology Improves Prostate Cancer Classification from MRI
Non-invasive prostate cancer detection from MRI has the potential to
revolutionize patient care by providing early detection of
clinically-significant disease (ISUP grade group >= 2), but has thus far shown
limited positive predictive value. To address this, we present an MRI-based
deep learning method for predicting clinically significant prostate cancer
applicable to a patient population with subsequent ground truth biopsy results
ranging from benign pathology to ISUP grade group~5. Specifically, we
demonstrate that mixed supervision via diverse histopathological ground truth
improves classification performance despite the cost of reduced concordance
with image-based segmentation. That is, where prior approaches have utilized
pathology results as ground truth derived from targeted biopsies and
whole-mount prostatectomy to strongly supervise the localization of clinically
significant cancer, our approach also utilizes weak supervision signals
extracted from nontargeted systematic biopsies with regional localization to
improve overall performance. Our key innovation is performing regression by
distribution rather than simply by value, enabling use of additional pathology
findings traditionally ignored by deep learning strategies. We evaluated our
model on a dataset of 973 (testing n=160) multi-parametric prostate MRI exams
collected at UCSF from 2015-2018 followed by MRI/ultrasound fusion (targeted)
biopsy and systematic (nontargeted) biopsy of the prostate gland, demonstrating
that deep networks trained with mixed supervision of histopathology can
significantly exceed the performance of the Prostate Imaging-Reporting and Data
System (PI-RADS) clinical standard for prostate MRI interpretation
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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
Isolation of Flow and Nonflow Correlations by Two- and Four-Particle Cumulant Measurements of Azimuthal Harmonics in 200 GeV Au+Au Collisions
A data-driven method was applied to measurements of Au+Au collisions at
200 GeV made with the STAR detector at RHIC to isolate
pseudorapidity distance -dependent and -independent
correlations by using two- and four-particle azimuthal cumulant measurements.
We identified a component of the correlation that is -independent,
which is likely dominated by anisotropic flow and flow fluctuations. It was
also found to be independent of within the measured range of
pseudorapidity . The relative flow fluctuation was found to be for particles of transverse momentum
less than GeV/. The -dependent part may be attributed to
nonflow correlations, and is found to be relative to the
flow of the measured second harmonic cumulant at
Population structure and linkage disequilibrium unravelled in tetraploid potato
Association mapping is considered to be an important alternative strategy for the identification of quantitative trait loci (QTL) as compared to traditional QTL mapping. A necessary prerequisite for association analysis to succeed is detailed information regarding hidden population structure and the extent of linkage disequilibrium. A collection of 430 tetraploid potato cultivars, comprising two association panels, has been analysed with 41 AFLP® and 53 SSR primer combinations yielding 3364 AFLP fragments and 653 microsatellite alleles, respectively. Polymorphism information content values and detected number of alleles for the SSRs studied illustrate that commercial potato germplasm seems to be equally diverse as Latin American landrace material. Genome-wide linkage disequilibrium (LD)—reported for the first time for tetraploid potato—was observed up to approximately 5 cM using r2 higher than 0.1 as a criterion for significant LD. Within-group LD, however, stretched on average twice as far when compared to overall LD. A Bayesian approach, a distance-based hierarchical clustering approach as well as principal coordinate analysis were adopted to enquire into population structure. Groups differing in year of market release and market segment (starch, processing industry and fresh consumption) were repeatedly detected. The observation of LD up to 5 cM is promising because the required marker density is not likely to disable the possibilities for association mapping research in tetraploid potato. Population structure appeared to be weak, but strong enough to demand careful modelling of genetic relationships in subsequent marker-trait association analyses. There seems to be a good chance that linkage-based marker-trait associations can be identified at moderate marker densities
Observation of charge asymmetry dependence of pion elliptic flow and the possible chiral magnetic wave in heavy-ion collisions
We present measurements of and elliptic flow, , at
midrapidity in Au+Au collisions at 200, 62.4, 39, 27,
19.6, 11.5 and 7.7 GeV, as a function of event-by-event charge asymmetry,
, based on data from the STAR experiment at RHIC. We find that
() elliptic flow linearly increases (decreases) with charge asymmetry
for most centrality bins at and higher.
At , the slope of the difference of
between and as a function of 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
Charged-to-neutral correlation at forward rapidity in Au+Au collisions at =200 GeV
Event-by-event fluctuations of the ratio of inclusive charged to photon
multiplicities at forward rapidity in Au+Au collision at =200
GeV have been studied. Dominant contribution to such fluctuations is expected
to come from correlated production of charged and neutral pions. We search for
evidences of dynamical fluctuations of different physical origins. Observables
constructed out of moments of multiplicities are used as measures of
fluctuations. Mixed events and model calculations are used as baselines.
Results are compared to the dynamical net-charge fluctuations measured in the
same acceptance. A non-zero statistically significant signal of dynamical
fluctuations is observed in excess to the model prediction when charged
particles and photons are measured in the same acceptance. We find that, unlike
dynamical net-charge fluctuation, charge-neutral fluctuation is not dominated
by correlation due to particle decay. Results are compared to the expectations
based on the generic production mechanism of pions due to isospin symmetry, for
which no significant (<1%) deviation is observed.Comment: 14 pages, 6 figure
Observation of Transverse Spin-Dependent Azimuthal Correlations of Charged Pion Pairs in at GeV
We report the observation of transverse polarization-dependent azimuthal
correlations in charged pion pair production with the STAR experiment in
collisions at RHIC. These correlations directly probe quark
transversity distributions. We measure signals in excess of five standard
deviations at high transverse momenta, at high pseudorapidities eta>0.5, and
for pair masses around the mass of the rho-meson. This is the first direct
transversity measurement in p+p collisions. Comparing the results to data from
lepton-nucleon scattering will test the universality of these spin-dependent
quantities.Comment: 11 pages, 5 figures, 15 tables. Submitted to PR
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