A Novel Modality Enables New Evidence-Based Individual Risk Stratification That Can Potentially Lead to Decisive Management and Treatment Decisions in Prostate Cancer.

A key step in providing management/treatment options to men with suspected prostate cancer (PCa) is categorizing the risk in terms of the presence of benign, low-risk, intermediate-risk, or high-risk disease. Our novel modality brings new evidence, based on the long-known hallmark characteristic of PCa-decreased zinc (Zn), which is the most direct metabolic sign of malignancy and its aggressiveness. To date, this approach has not been adopted for clinical use for a number of reasons that are described in this article, and which have been addressed by our approach. Zn has to be measured on fresh samples, prior to fixating in formalin; therefore, samples have to be scanned during the biopsy session. As Zn depletion occurs in the glands where the tumors develop, estimation of the glands' levels in the scanned tissue, along with their compactness, are essential for accurate diagnosis. Combined with the Zn depletion, this facilitates a reliable assessment of disease aggressiveness. Data gathered in the clinical study described here indicate that, in addition to improving the biopsy quality by real-time interactive guidance, a malignancy score can now be established for the entire prostate, allowing higher granularity personalized risk stratification and more decisive treatment decisions for all PCa patients.

Inhibition of return in the archer fish.

Inhibition of return is the inhibitory tagging of recently attended locations or objects. It was previously suggested that inhibition of return is a foraging facilitator in visual search. Inhibition of return was first discovered in humans and was demonstrated also in monkeys, yet it has never been demonstrated in non-primates. Here we report the presence of inhibition of return in the archer fish, which shoots down prey on overhanging vegetation, using squirts of water spouted from its mouth. Moreover, we find similar attentional effects for fish as for human participants. Our results show that the generation of inhibition of return does not require a fully developed cortex and strengthen the view that inhibition of return functions as a foraging facilitator.

On the phase behavior of binary mixtures of nanoparticles.

The assembly of mixtures of nanoparticles with different properties into a binary nanoparticle superlattice (BNSL) provides a route to fabricate novel classes of materials with properties emerging from the choice of the building blocks. The common theoretical approach based on the hard-spheres model predicts crystallization of only a few metastable binary superstructures (NaCl, AlB2 or the AB13). Recently [Shevchenko, E. V.; Talapin, D. V.; O'Brien, S.; Murray, C. B. Nature 2006; 439, 55.)], it has been demonstrated that with the use of a combination of semiconducting, metallic, and magnetic nanoparticles, a variety of novel BNSL structures were formed, where at least 10 were low density structures that have not been previously reported. While some of the structures can be explained by the addition of electrostatic interactions, it is clear that at the nanometer scale one needs to consider other influences, such as van der Waals forces, steric effects, etc. Motivated by those experiments, we study, using Monte Carlo simulations, the phase behavior of binary mixtures of nanoparticles interacting via a combination of hard-core electrostatics and van der Waals forces. We include a tuning parameter that can be used to balance between electrostatic and dispersion interactions and study the phase behavior as a function of the different charges and size ratios of the nanoparticles. The results indicate that at the nanoscale, both electrostatic and dispersion interactions are necessary to explain the experimental observed BNSL structures.

Visual acuity in the archerfish: behavior, anatomy, and neurophysiology.

Archerfish are known for their remarkable behavior of shooting water jets at prey hanging on vegetation above water. Motivated by the fish's capacity to knock down small prey as high as two meters above water level, we studied the role of the retina in facilitating their excellent visual acuity. First, we show behaviorally that archerfish (Toxotes jaculatrix) can detect visual structures with a minimum angle of resolution in the range of 0.075°-0.15°. Then, combining eye movement measurements with a ray tracing method, we show that the image of a target on the retina coincides with the area centralis at the ventro-temporal retina. Moving down to retinal neural circuits, we then examine the ratio by which retinal ganglion cells multiplex visual information from the photoreceptors. Measuring the anatomical densities of both cell types in the area centralis, we found photoreceptor spacing to be 5.8 µm, which supports a minimum angle of resolution as low as 0.073°. Similarly, the average spacing of the ganglion cells was 5.7 µm. Based on electrophysiological measurements we found the smallest receptive fields of ganglion cells in that area to be in the range of 8-16 µm, which translates to an angular width of 0.1°-0.2°. These findings indicate that retinal ganglion cells in the area centralis stream information to the brain at a comparable resolution with which it is sampled by the photoreceptors. Thus, the archerfish can be used as an animal model for studying how visual details are streamed to the brain by retinal output.

Predictive saccade in the absence of smooth pursuit: interception of moving targets in the archer fish.

Interception of fast-moving targets is a demanding task many animals solve. To handle it successfully, mammals employ both saccadic and smooth pursuit eye movements in order to confine the target to their area centralis. But how can non-mammalian vertebrates, which lack smooth pursuit, intercept moving targets? We studied this question by exploring eye movement strategies employed by archer fish, an animal that possesses an area centralis, lacks smooth pursuit eye movements, but can intercept moving targets by shooting jets of water at them. We tracked the gaze direction of fish during interception of moving targets and found that they employ saccadic eye movements based on prediction of target position when it is hit. The fish fixates on the target's initial position for ∼0.2 s from the onset of its motion, a time period used to predict whether a shot can be made before the projection of the target exits the area centralis. If the prediction indicates otherwise, the fish performs a saccade that overshoots the center of gaze beyond the present target projection on the retina, such that after the saccade the moving target remains inside the area centralis long enough to prepare and perform a shot. These results add to the growing body of knowledge on biological target tracking and may shed light on the mechanism underlying this behavior in other animals with no neural system for the generation of smooth pursuit eye movements.

Coding "what" and "when" in the Archer fish retina.

Traditionally, the information content of the neural response is quantified using statistics of the responses relative to stimulus onset time with the assumption that the brain uses onset time to infer stimulus identity. However, stimulus onset time must also be estimated by the brain, making the utility of such an approach questionable. How can stimulus onset be estimated from the neural responses with sufficient accuracy to ensure reliable stimulus identification? We address this question using the framework of colour coding by the archer fish retinal ganglion cell. We found that stimulus identity, "what", can be estimated from the responses of best single cells with an accuracy comparable to that of the animal's psychophysical estimation. However, to extract this information, an accurate estimation of stimulus onset is essential. We show that stimulus onset time, "when", can be estimated using a linear-nonlinear readout mechanism that requires the response of a population of 100 cells. Thus, stimulus onset time can be estimated using a relatively simple readout. However, large nerve cell populations are required to achieve sufficient accuracy.

Measuring and tracking eye movements of a behaving archer fish by real-time stereo vision.

The archer fish (Toxotes chatareus) exhibits unique visual behavior in that it is able to aim at and shoot down with a squirt of water insects resting on the foliage above water level and then feed on them. This extreme behavior requires excellent visual acuity, learning, and tight synchronization between the visual system and body motion. This behavior also raises many important questions, such as the fish's ability to compensate for air-water refraction and the neural mechanisms underlying target acquisition. While many such questions remain open, significant insights towards solving them can be obtained by tracking the eye and body movements of freely behaving fish. Unfortunately, existing tracking methods suffer from either a high level of invasiveness or low resolution. Here, we present a video-based eye tracking method for accurately and remotely measuring the eye and body movements of a freely moving behaving fish. Based on a stereo vision system and a unique triangulation method that corrects for air-glass-water refraction, we are able to measure a full three-dimensional pose of the fish eye and body with high temporal and spatial resolution. Our method, being generic, can be applied to studying the behavior of marine animals in general. We demonstrate how data collected by our method may be used to show that the hunting behavior of the archer fish is composed of surfacing concomitant with rotating the body around the direction of the fish's fixed gaze towards the target, until the snout reaches in the correct shooting position at water level.