Objective: To determine the extent to which nephrology journals recommend and require reporting guideline adherence and clinical trial registration.
Background: Despite a rising disease burden, research published on chronic kidney disease (CKD) and the field of nephrology has failed to keep pace and is limited. To improve the quality of research in the field of nephrology, reporting guidelines have been developed to minimize such deficits in research quality.
Importance: Chemotherapy agents are typically initially tested in their most promising indications; however, following initial US FDA approval, new clinical trials are often initiated in less promising indications where patients experience a worse burden-benefit ratio. The current literature on the burden-benefit profile of lenvatinib in non-FDA-approved indications is lacking.
Objective: This study aimed to evaluate published clinical trials of lenvatinib in order to determine the burden-benefit profile for patients over time.
Reduction or complete loss of traits is a common occurrence throughout evolutionary history. In spite of this, numerous questions remain about why and how trait loss has occurred. Cave animals are an excellent system in which these questions can be answered, as multiple traits, including eyes and pigmentation, have been repeatedly reduced or lost across populations of cave species.
View Article and Find Full Text PDFPhys Rev E Stat Nonlin Soft Matter Phys
July 2012
Synchronized oscillations of large numbers of central neurons are believed to be important for a wide variety of cognitive functions, including long-term memory recall and spatial navigation. It is therefore plausible that evolution has optimized the biophysical properties of central neurons in some way for synchronized oscillations to occur. Here, we use computational models to investigate the relationships between the presumably genetically determined parameters of stellate cells in layer II of the entorhinal cortex and the ability of coupled populations of these cells to synchronize their intrinsic oscillations: in particular, we calculate the time it takes circuits of two or three cells with initially randomly distributed phases to synchronize their oscillations to within one action potential width, and the metabolic energy they consume in doing so.
View Article and Find Full Text PDFPhys Rev E Stat Nonlin Soft Matter Phys
August 2010
We report on a theoretical study showing that the leak conductance density, G{L} , in the squid giant axon appears to be optimal for the action potential firing frequency. More precisely, the standard assumption that the leak current is composed of chloride ions leads to the result that the experimental value for G{L} is very close to the optimal value in the Hodgkin-Huxley model, which minimizes the absolute refractory period of the action potential, thereby maximizing the maximum firing frequency under stimulation by sharp, brief input current spikes to one end of the axon. The measured value of G{L} also appears to be close to optimal for the frequency of repetitive firing caused by a constant current input to one end of the axon, especially when temperature variations are taken into account.
View Article and Find Full Text PDFWith the goal of understanding the intricate behavior and dynamics of collections of neurons, we present superconducting circuits containing Josephson junctions that model biologically realistic neurons. These "Josephson junction neurons" reproduce many characteristic behaviors of biological neurons such as action potentials, refractory periods, and firing thresholds. They can be coupled together in ways that mimic electrical and chemical synapses.
View Article and Find Full Text PDFThe action potential of the unmyelinated nerve is metabolically expensive. Using the energetic cost per unit length for the biophysically modeled action potential of the squid giant axon, we analyze this cost and identify one possible optimization. The energetic cost arising from an action potential is divided into three separate components: 1) the depolarization of the rising phase; 2) the hyperpolarization of the falling phase; and 3) the largest component, the overlapping of positive and negative currents, which has no electrical effect.
View Article and Find Full Text PDFWe obtain very stringent bounds on the possible cold dark matter, baryon, and neutrino isocurvature contributions to the primordial fluctuations in the Universe, using recent cosmic microwave background and large scale structure data. Neglecting the possible effects of spatial curvature, tensor perturbations, and reionization, we perform a Bayesian likelihood analysis with nine free parameters, and find that the amplitude of the isocurvature component cannot be larger than about 31% for the cold dark matter mode, 91% for the baryon mode, 76% for the neutrino density mode, and 60% for the neutrino velocity mode, at 2sigma, for uncorrelated models. For correlated adiabatic and isocurvature components, the fraction could be slightly larger.
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