Positive surgical margins in nephron-sparing surgery; the great unknown

There is a currently a general trend towards organ-preserving surgery, and urology is no exception. Specifically, nephron-sparing surgery (NSS) has gained general acceptance for T1a renal cell carcinoma (guidelines recommendations). Moreover T1b, T2 and even T3 stage tumors have been included on the nephron sparing list at some centers. An unresolved issue is that of positive surgical margins (PSM), not only their detection but also the implications for follow up and treatment. This paper highlights data available on risk factors for PSM, their clinical relevance, and possible therapeutic consequences. From the surgeon’s viewpoint, NSS is a daring and risky surgical procedure. Urological guidelines stress the importance of NSS, and thus the trend is moving in that direction. Unresolved, however, is the problem of PSM. Trifecta, MIC, and pentafecta are applicable concepts which attempt to define the optimal endpoint of NSS, but further elaboration is necessary. Specifically, research needs to focus less on the concept of definitive margins and more on their identification and avoidance. Although some studies suggest that PSMs do not influence overall survival rate, the basic idea of preserving tissue that is not cancerous leads to further medical, social, and psychological considerations

From Imitation to Collusion: Long-run Learning in a Low-Information Environment

We study long-run learning in an experimental Cournot game with no explicit information about the payoff function. Subjects see only the quantities and payoffs of each oligopolist after every period. In line with theoretical predictions and previous experimental findings, duopolies and triopolies both reach highly competitive levels, with price approaching marginal cost within 50 periods. Using the new ConG software, we extend the horizon to 1,200 periods, far beyond that previously investigated. Already after 100 periods we observe a qualitative change in behavior, and quantity choices start to drop. Without pausing at the Cournot-Nash level quantities continue to drop, eventually reaching almost fully collusive levels in duopolies and often reaching deep into collusive territory for triopolies. Fitted models of individual adjustment suggest that subjects switch from imitation of the most profitable rival to other behavior that, intentionally or otherwise, facilitates collusion via effective punishment and forgiveness. Remarkably, subjects never learn the best-reply correspondence of the one-shot game. Our results suggest a new explanation for the emergence of cooperation

How to tell if your cloud files are vulnerable to drive crashes

This paper presents a new challenge--verifying that a remote server is storing a file in a fault-tolerant manner, i.e., such that it can survive hard-drive failures. We describe an approach called the Remote Assessment of Fault Tolerance (RAFT). The key technique in a RAFT is to measure the time taken for a server to respond to a read request for a collection of file blocks. The larger the number of hard drives across which a file is distributed, the faster the read-request response. Erasure codes also play an important role in our solution. We describe a theoretical framework for RAFTs and offer experimental evidence that RAFTs can work in practice in several settings of interest

Drug Repurposing: Far Beyond New Targets for Old Drugs

Repurposing drugs requires finding novel therapeutic indications compared to the ones for which they were already approved. This is an increasingly utilized strategy for finding novel medicines, one that capitalizes on previous investments while derisking clinical activities. This approach is of interest primarily because we continue to face significant gaps in the drug–target interactions matrix and to accumulate safety and efficacy data during clinical studies. Collecting and making publicly available as much data as possible on the target profile of drugs offer opportunities for drug repurposing, but may limit the commercial applications by patent applications. Certain clinical applications may be more feasible for repurposing than others because of marked differences in side effect tolerance. Other factors that ought to be considered when assessing drug repurposing opportunities include relevance to the disease in question and the intellectual property landscape. These activities go far beyond the identification of new targets for old drugs

Evaluation of a Bayesian inference network for ligand-based virtual screening

Background Bayesian inference networks enable the computation of the probability that an event will occur. They have been used previously to rank textual documents in order of decreasing relevance to a user-defined query. Here, we modify the approach to enable a Bayesian inference network to be used for chemical similarity searching, where a database is ranked in order of decreasing probability of bioactivity. Results Bayesian inference networks were implemented using two different types of network and four different types of belief function. Experiments with the MDDR and WOMBAT databases show that a Bayesian inference network can be used to provide effective ligand-based screening, especially when the active molecules being sought have a high degree of structural homogeneity; in such cases, the network substantially out-performs a conventional, Tanimoto-based similarity searching system. However, the effectiveness of the network is much less when structurally heterogeneous sets of actives are being sought. Conclusion A Bayesian inference network provides an interesting alternative to existing tools for ligand-based virtual screening

Measurement of the Ge 70 (n,γ) cross section up to 300 keV at the CERN n-TOF facility

©2019 American Physical Society.Neutron capture data on intermediate mass nuclei are of key importance to nucleosynthesis in the weak component of the slow neutron capture processes, which occurs in massive stars. The (n,γ) cross section on Ge70, which is mainly produced in the s process, was measured at the neutron time-of-flight facility n-TOF at CERN. Resonance capture kernels were determined up to 40 keV neutron energy and average cross sections up to 300 keV. Stellar cross sections were calculated from kT=5 keV to kT=100 keV and are in very good agreement with a previous measurement by Walter and Beer (1985) and recent evaluations. Average cross sections are in agreement with Walter and Beer (1985) over most of the neutron energy range covered, while they are systematically smaller for neutron energies above 150 keV. We have calculated isotopic abundances produced in s-process environments in a 25 solar mass star for two initial metallicities (below solar and close to solar). While the low metallicity model reproduces best the solar system germanium isotopic abundances, the close to solar model shows a good global match to solar system abundances in the range of mass numbers A=60-80.Peer reviewedFinal Published versio

New measurement of the 242Pu(n,γ) cross section at n-TOF-EAR1 for MOX fuels : Preliminary results in the RRR

The spent fuel of current nuclear reactors contains fissile plutonium isotopes that can be combined with 238U to make mixed oxide (MOX) fuel. In this way the Pu from spent fuel is used in a new reactor cycle, contributing to the long-term sustainability of nuclear energy. The use of MOX fuels in thermal and fast reactors requires accurate capture and fission cross sections. For the particular case of 242Pu, the previous neutron capture cross section measurements were made in the 70's, providing an uncertainty of about 35% in the keV region. In this context, the Nuclear Energy Agency recommends in its "High Priority Request List" and its report WPEC-26 that the capture cross section of 242Pu should be measured with an accuracy of at least 7-12% in the neutron energy range between 500 eV and 500 keV. This work presents a brief description of the measurement performed at n-TOF-EAR1, the data reduction process and the first ToF capture measurement on this isotope in the last 40 years, providing preliminary individual resonance parameters beyond the current energy limits in the evaluations, as well as a preliminary set of average resonance parameters

Characterization of the n-TOF EAR-2 neutron beam

The experimental area 2 (EAR-2) at CERNs neutron time-of-flight facility (n-TOF), which is operational since 2014, is designed and built as a short-distance complement to the experimental area 1 (EAR-1). The Parallel Plate Avalanche Counter (PPAC) monitor experiment was performed to characterize the beam prole and the shape of the neutron 'ux at EAR-2. The prompt γ-flash which is used for calibrating the time-of-flight at EAR-1 is not seen by PPAC at EAR-2, shedding light on the physical origin of this γ-flash

Optimality of mutation and selection in germinal centers

The population dynamics theory of B cells in a typical germinal center could play an important role in revealing how affinity maturation is achieved. However, the existing models encountered some conflicts with experiments. To resolve these conflicts, we present a coarse-grained model to calculate the B cell population development in affinity maturation, which allows a comprehensive analysis of its parameter space to look for optimal values of mutation rate, selection strength, and initial antibody-antigen binding level that maximize the affinity improvement. With these optimized parameters, the model is compatible with the experimental observations such as the ~100-fold affinity improvements, the number of mutations, the hypermutation rate, and the "all or none" phenomenon. Moreover, we study the reasons behind the optimal parameters. The optimal mutation rate, in agreement with the hypermutation rate in vivo, results from a tradeoff between accumulating enough beneficial mutations and avoiding too many deleterious or lethal mutations. The optimal selection strength evolves as a balance between the need for affinity improvement and the requirement to pass the population bottleneck. These findings point to the conclusion that germinal centers have been optimized by evolution to generate strong affinity antibodies effectively and rapidly. In addition, we study the enhancement of affinity improvement due to B cell migration between germinal centers. These results could enhance our understandings to the functions of germinal centers.Comment: 5 figures in main text, and 4 figures in Supplementary Informatio