Spatiotemporal response integration across the neural receptive field (RF) is a general feature of sensory coding and has an important role in shaping responses to naturalistic stimuli. In the primary somatosensory cortex of the rat vibrissa pathway, such integration across the vibrissa array strongly shapes the coding of spatiotemporally distributed deflections. Using a spatiotemporal paired-pulse paradigm, this study revealed that fundamentally different types of pairwise interactions have similar qualitative behavior but that the magnitude, latency, and precision of the neural responses depend on the specific RF components being engaged. In all cases, however, increase in the suppression of response magnitude accompanied a lengthening of latency and a decrease in response precision. Furthermore, nonlinear interactions evoked by stimulation of multiple RF subregions strongly influence both response magnitude and timing to more complex sequences. Despite their complexity, such response interactions are highly predictable from elementary pairwise interactions. To understand the functional role of spatiotemporal interactions in coding, we developed a response model that incorporated the experimentally measured modulations in response magnitude, latency, and precision induced by cross-vibrissa interactions. Simulations of a simplified textural discrimination task indicate that spatiotemporal interactions enhance discrimination under certain stimulus time scales. This improvement follows from a nonlinear response property that acts to restore the neural response in the face of suppression. Together, the present findings highlight the role of response integration in shaping single-cell responses and provide predictions about how changes in response parameters influence coding accuracy.

BackgroundHyperglycemia following solid organ transplant is common among patients without pre-existing diabetes mellitus (DM). Post-transplant hyperglycemia can occur once or multiple times, which if continued, causes new-onset diabetes after transplantation (NODAT).ObjectiveTo study if the first and recurrent incidence of hyperglycemia are affected differently by immunosuppressive regimens, demographic and medical-related risk factors, and inpatient hyperglycemic conditions (i.e., an emphasis on the time course of post-transplant complications).MethodsWe conducted a retrospective analysis of 407 patients who underwent kidney transplantation at Mayo Clinic Arizona. Among these, there were 292 patients with no signs of DM prior to transplant. For this category of patients, we evaluated the impact of (1) immunosuppressive drugs (e.g., tacrolimus, sirolimus, and steroid), (2) demographic and medical-related risk factors, and (3) inpatient hyperglycemic conditions on the first and recurrent incidence of hyperglycemia in one year post-transplant. We employed two versions of Cox regression analyses: (1) a time-dependent model to analyze the recurrent cases of hyperglycemia and (2) a time-independent model to analyze the first incidence of hyperglycemia.ResultsAge (P = 0.018), HDL cholesterol (P = 0.010), and the average trough level of tacrolimus (P<0.0001) are significant risk factors associated with the first incidence of hyperglycemia, while age (P<0.0001), non-White race (P = 0.002), BMI (P = 0.002), HDL cholesterol (P = 0.003), uric acid (P = 0.012), and using steroid (P = 0.007) are the significant risk factors for the recurrent cases of hyperglycemia.DiscussionThis study draws attention to the importance of analyzing the risk factors associated with a disease (specially a chronic one) with respect to both its first and recurrent incidence, as well as carefully differentiating these two perspectives: a fact that is currently overlooked in the literature.

During behavior, rats and other rodents use their facial vibrissae to actively explore surfaces through whisking and head/body movement, resulting in complex sensory inputs that vary over a large range of angular velocities and temporal scales. How these complex sensory inputs manifest in the patterns of cortical firing events that ultimately form the perceptual experience is not well understood. Through single-unit cortical recordings of layer 4 neurons in S1 of the anesthetized rat, we systematically quantified the interactions between instantaneous velocity and timing of vibrissa motion, finding a strong interaction between angular velocity and timing of contacts on the tens of milliseconds time scale. From the quantification of these joint tuning properties, a detailed nonlinear encoding model was formulated that was highly predictive of firing probabilityandtimingcharacteristicsofthesparsecorticalrepresentationofcomplexpatternedtactileinputs.WithinaBayesianframework,the encoding model was then used to decode tactile patterns under simple transformations of the stimulus along dimensions of velocity and timing, as a demonstration of the lower bound of the idealized perceptual capabilities of the animal.

Problem definition: Organ-transplanted patients typically receive high amounts of immunosuppressive drugs (e.g., tacrolimus) as a mechanism to reduce their risk of organ rejection. However, because of the diabetogenic effect of these drugs, this practice exposes them to a greater risk of new-onset diabetes after transplantation (NODAT), and hence, becoming insulin dependent. We study and develop effective medication management strategies to address the common conundrum of balancing the risk of organ rejection versus that of NODAT. Academic/practical relevance: Our research contributes to the healthcare operations management literature by developing a robust stochastic decision-making framework that allows for incorporating (1) false-positive and false-negative errors of medical tests, (2) inevitable estimation errors when data sets are used, (3) variability among physician’ attitudes toward ambiguous outcomes, and (4) dynamic and patient risk-profile-dependent progression of health conditions. Methodology: We apply an ambiguous partially observable Markov decision process (APOMDP) approach where dynamic optimization with respect to a “cloud” of possible models allows us to make decisions that are robust to potential misspecifications of risks. Results: We first provide various structural results that facilitate characterizing the optimal medication policies. Utilizing a clinical data set, we then compare the performance of the optimal medication policies obtained from our APOMDP model with the policies currently used in the medical practice. We observe that, in one year after transplant, our proposed policies can improve the life expectancy of each patient up to 4.58%, while reducing the medical expenditures up to 11.57%. Managerial implications: Balancing the risks of organ rejection and diabetes complications and considering factors such as physicians’ attitudes toward ambiguous outcomes, partial observability of medical tests, and patient-specific risk factors are shown to result in more cost-effective strategies for management of post-transplant medications compared with the current medical practice. Finally, simultaneous management of medications can facilitate the care coordination process between transplantation/nephrology and endocrinology departments of a hospital that are typically in charge of administering such medications.

Sensory systems must form stable representations of the external environment in the presence of self-induced variations in sensory signals. It is also possible that the variations themselves may provide useful information about self-motion relative to the external environment. Rats have been shown to be capable of fine texture discrimination and object localization based on palpation by facial vibrissae, or whiskers, alone. During behavior, the facial vibrissae brush against objects and undergo deflection patterns that are influenced both by the surface features of the objects and by the animal's own motion. The extent to which behavioral variability shapes the sensory inputs to this pathway is unknown. Using high-resolution, high-speed videography of unconstrained rats running on a linear track, we measured several behavioral variables including running speed, distance to the track wall, and head angle, as well as the proximal vibrissa deflections while the distal portions of the vibrissae were in contact with periodic gratings. The measured deflections, which serve as the sensory input to this pathway, were strongly modulated both by the properties of the gratings and the trial-to-trial variations in head-motion and locomotion. Using presumed internal knowledge of locomotion and head-rotation, gratings were classified using short-duration trials (<150 ms) from high-frequency vibrissa motion, and the continuous trajectory of the animal's own motion through the track was decoded from the low frequency content. Together, these results suggest that rats have simultaneous access to low- and high-frequency information about their environment, which has been shown to be parsed into different processing streams that are likely important for accurate object localization and texture coding.

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The current opioid epidemic has killed more than 446,000 Americans over the past two decades. Despite the magnitude of the crisis, little is known to what degree the misalignment of incentives among stakeholders due to competing interests has contributed to the current situation. In this study, we explore evidence in the literature for the working hypothesis that misalignment rooted in the cost, quality, or access to care can be a significant contributor to the opioid epidemic. The review identified several problems that can contribute to incentive misalignment by compromising the triple aims (cost, quality, and access) in this epidemic. Some of these issues include the inefficacy of conventional payment mechanisms in providing incentives for providers, practice guidelines in pain management that are not easily implementable across different medical specialties, barriers in adopting multi-modal pain management strategies, low capacity of providers/treatments to address opioid/substance use disorders, the complexity of addressing the co-occurrence of chronic pain and opioid use disorders, and patients’ non-adherence to opioid substitution treatments. In discussing these issues, we also shed light on factors that can facilitate the alignment of incentives among stakeholders to effectively address the current crisis.

In nature, several species use flexible probes to actively explore their environment and acquire important sensory information, such as surface topology, texture, and water or air flow velocity. For example, rats and other rodents have an array of facial vibrissae (or whiskers) with which they gather tactile information about the external world. The complex mechanisms by which mechanical deformations of the probe lead to neuronal activity in the animal's nervous system are still far from being completely understood. This is due to the intricacy of the deformation mechanics of the flexible sensors, the processes responsible for transforming the deformation to electrical activity, and the subsequent representation of the sensory information by the nervous system. Understanding how these mechanosensory signals are transduced and extracted by the nervous system promises great insight into biological function, and has novel technological applications. To understand the mechanical aspect of sensory transduction, here we monitored the deformation of a rat's vibrissa as it strikes rigid objects with different topologies (surface features) during locomotion, using high-speed videography. Motivated by our observations, we developed detailed numerical models to study the mechanics of such flexible probes. Our findings elucidate how active sensation with vibrissae might provide sensory information and in addition have direct implications for several technological areas. To put this in perspective, we propose strategies in which flexible probes can be used to characterize surface topology at high speeds, which is a desirable feature in several technological applications such as memory retrieval.