Push-Pull Control of Motor Output

Inhibition usually decreases input–output excitability of neurons. If, however, inhibition is coupled to excitation in a push–pull fashion, where inhibition decreases as excitation increases, neuron excitability can be increased. Although the presence of push–pull organization has been demonstrated in single cells, its functional impact on neural processing depends on its effect on the system level. We studied push–pull in the motor output stage of the feline spinal cord, a system that allows independent control of inhibitory and excitatory components. Push–pull organization was clearly present in ankle extensor motoneurons, producing increased peak-to-peak modulation of synaptic currents. The effect at the system level was equally strong. Independent control of the inhibitory component showed that the stronger the background of inhibition, the greater the peak force production. This illustrates the paradox at the heart of push–pull organization: increased force output can be achieved by increasing background inhibition to provide greater disinhibition

Fires in the Rough: A Close Examination of the Fire Hazards in the Rural-Urban Fringe in Kelowna, B.C.

Fire hazards in the rural-urban fringe have been a cause of concern for several decades. During the hot, dry summer months, risks for fires increase dramatically. This is due in part to the low level of maintenance in these areas when compared to their urban counterparts, as well as the issues of weather, lack of adherence to policy regarding environmental management, and the emergency response of the region. These issues have been thoroughly investigated using a deep literature review using peer reviewed articles, newspaper articles, regional data from statistics Canada, and this paper includes an examination of wildfire events in the Kelowna area, exploring the potential improvements from the perspectives of management, policy, and individual responsibility. We found that the probability of fires occurring is greater in the rural- urban fringe, the response time by regional district is slower, and there is a greater susceptibility of the landscape to hazardous weather conditions. In conclusion, the social and physical characteristics of the rural-urban fringe in Kelowna promote an environment that is particularly vulnerable to wildfires, and the city is continuing to improve land-use patterns in the area to ensure a decrease risk of fire hazards

Sexual well-being and diurnal cortisol after prostate cancer treatment.

Sexual dysfunction and psychological distress are common after prostate cancer. Research has not examined the role of neuroendocrine markers of stress (e.g. cortisol). This study examines whether sexual functioning or sexual bother is associated with diurnal cortisol. Men treated for prostate cancer completed the University of California-Los Angeles Prostate Cancer Index and provided saliva samples four times daily for cortisol assessment. Higher sexual bother, but not sexual functioning, was associated with steeper cortisol slope. Better sexual functioning, and not sexual bother, was significantly associated with the cortisol awakening response. Assessment of stress and stress-reducing interventions might be warranted in sexual rehabilitation after prostate cancer

Response and Resistance to Paradox-Breaking BRAF Inhibitor in Melanomas

FDA-approved BRAF inhibitors produce high response rates and improve overall survival in patients with BRAF V600E/K-mutant melanoma, but are linked to pathologies associated with paradoxical ERK1/2 activation in wild-type BRAF cells. To overcome this limitation, a next-generation paradox-breaking RAF inhibitor (PLX8394) has been designed. Here, we show that by using a quantitative reporter assay, PLX8394 rapidly suppressed ERK1/2 reporter activity and growth of mutant BRAF melanoma xenografts. Ex vivo treatment of xenografts and use of a patient-derived explant system (PDeX) revealed that PLX8394 suppressed ERK1/2 signaling and elicited apoptosis more effectively than the FDA-approved BRAF inhibitor, vemurafenib. Furthermore, PLX8394 was efficacious against vemurafenibresistant BRAF splice variant-expressing tumors and reduced splice variant homodimerization. Importantly, PLX8394 did not induce paradoxical activation of ERK1/2 in wild-type BRAF cell lines or PDeX. Continued in vivo dosing of xenografts with PLX8394 led to the development of acquired resistance via ERK1/2 reactivation through heterogeneous mechanisms; however, resistant cells were found to have differential sensitivity to ERK1/2 inhibitor. These findings highlight the efficacy of a paradox-breaking selective BRAF inhibitor and the use of PDeX system to test the efficacy of therapeutic agents. © 2017 American Association for Cancer Research

Uncertainty Monitoring by Young Children in a Computerized Task

Adult humans show sophisticated metacognitive abilities, including the ability to monitor uncertainty. Unfortunately, most measures of uncertainty monitoring are limited to use with adults due to their general complexity and dependence on explicit verbalization. However, recent research with nonhuman animals has successfully developed measures of uncertainty monitoring that are simple and do not require explicit verbalization. The purpose of this study was to investigate metacognition in young children using uncertainty monitoring tests developed for nonhumans. Children judged whether stimuli were more pink or blue—stimuli nearest the pink-blue midpoint were the most uncertain and the most difficult to classify. Children also had an option to acknowledge difficulty and gain the necessary information for correct classification. As predicted, children most often asked for help on the most difficult stimuli. This result confirms that some metacognitive abilities appear early in cognitive development. The tasks of animal metacognition research clearly have substantial utility for exploring the early developmental roots of human metacognition

An Unsettling Outcome: Why the Florida Supreme Court Was Wrong to Ban All Settlement Evidence in \u3ci\u3eSaleeby v Rocky Elson Construction, Inc.\u3c/i\u3e, 3 So. 3d 1078 (Fla. 2009)

It is rare that a court as sophisticated as the Florida Supreme Court casually makes a fundamental mistake in an important area of the law. Unfortunately, Saleeby v. Rocky Elson Construction, Inc., 3 So. 3d 1078 (Fla. 2009) represents one of these unusual instances. The Court was faced with a simple question: may evidence pertaining to a prior settlement be offered at trial when it is relevant to something other than liability or the invalidity or amount of the pending claim. The universal answer under both federal law and the law of other states is yes, as long as the probative value of the evidence outweighs its prejudicial impact. In Saleeby, the Florida Supreme Court held that the answer is a resounding “no.” The result could be a miscarriage of justice – for instance, in a case in which a witness’s testimony is effectively “purchased” through an overly generous settlement, but the fact-finder will be prevented by the Saleeby holding from finding this out

Monkeys (Macaca mulatta and Cebus apella) and Human Adults and Children (Homo sapiens) Enumerate and Compare Subsets of Moving Stimuli Based on Numerosity

Two monkey species (Macaca mulatta and Cebus apella) and human children and adults judged the numerousness of two subsets of moving stimuli on a computer screen. Two sets of colored dots that varied in number and size were intermixed in an array in which all dots moved in random directions and speeds. Participants had to indicate which dot color was more numerous within the array. All species performed at high and comparable levels, including on trials in which the subset with the larger number of items had a smaller total area of coloration. This indicated a similarity across species to use the number of items in the subsets, and not dimensions such as area or volume, to guide decision making. Discrimination performance was constrained by the ratio between the subsets, consistent with other reports of numerousness judgments of stationary stimuli. These results indicate a similarity in numerical estimation ability for moving stimuli across primate species, and this capacity may be necessary for naturally occurring experiences in which moving stimuli must be summed

An Unsettling Outcome: Why the Florida Supreme Court Was Wrong to Ban All Settlement Evidence in \u3ci\u3eSaleeby v Rocky Elson Construction, Inc.\u3c/i\u3e, 3 So. 3d 1078 (Fla. 2009)

It is rare that a court as sophisticated as the Florida Supreme Court casually makes a fundamental mistake in an important area of the law. Unfortunately, Saleeby v. Rocky Elson Construction, Inc., 3 So. 3d 1078 (Fla. 2009) represents one of these unusual instances. The Court was faced with a simple question: may evidence pertaining to a prior settlement be offered at trial when it is relevant to something other than liability or the invalidity or amount of the pending claim. The universal answer under both federal law and the law of other states is yes, as long as the probative value of the evidence outweighs its prejudicial impact. In Saleeby, the Florida Supreme Court held that the answer is a resounding “no.” The result could be a miscarriage of justice – for instance, in a case in which a witness’s testimony is effectively “purchased” through an overly generous settlement, but the fact-finder will be prevented by the Saleeby holding from finding this out