Under pressure: Response urgency modulates striatal and insula activity during decision-making under risk

When deciding whether to bet in situations that involve potential monetary loss or gain (mixed gambles), a subjective sense of pressure can influence the evaluation of the expected utility associated with each choice option. Here, we explored how gambling decisions, their psychophysiological and neural counterparts are modulated by an induced sense of urgency to respond. Urgency influenced decision times and evoked heart rate responses, interacting with the expected value of each gamble. Using functional MRI, we observed that this interaction was associated with changes in the activity of the striatum, a critical region for both reward and choice selection, and within the insula, a region implicated as the substrate of affective feelings arising from interoceptive signals which influence motivational behavior. Our findings bridge current psychophysiological and neurobiological models of value representation and action-programming, identifying the striatum and insular cortex as the key substrates of decision-making under risk and urgency

Heart rate variability: Measurement and emerging use in critical care medicine

Variation in the time interval between consecutive R wave peaks of the QRS complex has long been recognised. Measurement of this RR interval is used to derive heart rate variability. Heart rate variability is thought to reflect modulation of automaticity of the sinus node by the sympathetic and parasympathetic components of the autonomic nervous system. The clinical application of heart rate variability in determining prognosis post myocardial infarction and the risk of sudden cardiac death is well recognised. More recently, analysis of heart rate variability has found utility in predicting foetal deterioration, deterioration due to sepsis and impending multiorgan dysfunction syndrome in critically unwell adults. Moreover, reductions in heart rate variability have been associated with increased mortality in patients admitted to the intensive care unit. It is hypothesised that heart rate variability reflects and quantifies the neural regulation of organ systems such as the cardiovascular and respiratory systems. In disease states, it is thought that there is an ‘uncoupling’ of organ systems, leading to alterations in ‘inter-organ communication’ and a clinically detectable reduction in heart rate variability. Despite the increasing evidence of the utility of measuring heart rate variability, there remains debate as to the methodology that best represents clinically relevant outcomes. With continuing advances in technology, our understanding of the physiology responsible for heart rate variability evolves. In this article, we review the current understanding of the physiological basis of heart rate variability and the methods available for its measurement. Finally, we review the emerging use of heart rate variability analysis in intensive care medicine and conditions in which heart rate variability has shown promise as a potential physiomarker of disease

Systematically Debugging IoT Control System Correctness for Building Automation

ABSTRACT Advances and standards in Internet of Things (IoT) have simplified the realization of building automation. However, non-expert IoT users still lack tools that can help them to ensure the underlying control system correctness: userprogrammable logics match the user intention. In fact, nonexpert IoT users lack the necessary know-how of domain experts. This paper presents our experience in running a building automation service based on the Salus framework. Complementing efforts that simply verify the IoT control system correctness, Salus takes novel steps to tackle practical challenges in automated debugging of identified policy violations, for non-expert IoT users. First, Salus leverages formal methods to localize faulty user-programmable logics. Second, to debug these identified faults, Salus selectively transforms the control system logics into a set of parameterized equations, which can then be solved by popular model checking tools or SMT (Satisfiability Modulo Theories) solvers. Through office deployments, user studies, and public datasets, we demonstrate the usefulness of Salus in systematically debugging the correctness of IoT control systems for building automation

Potentiation of Anticancer Drugs: Effects of Pentoxifylline on Neoplastic Cells

The drug efflux activity of P-glycoprotein (P-gp, a product of the mdr1 gene, ABCB1 member of ABC transporter family) represents a mechanism by which tumor cells escape death induced by chemotherapeutics. In this study, we investigated the mechanisms involved in the effects of pentoxifylline (PTX) on P-gp-mediated multidrug resistance (MDR) in mouse leukemia L1210/VCR cells. Parental sensitive mouse leukemia cells L1210, and multidrug-resistant cells, L1210/VCR, which are characterized by the overexpression of P-gp, were used as experimental models. The cells were exposed to 100 μmol/L PTX in the presence or absence of 1.2 μmol/L vincristine (VCR). Western blot analysis indicated a downregulation of P-gp protein expression when multidrug-resistant L1210/VCR cells were exposed to PTX. The effects of PTX on the sensitization of L1210/VCR cells to VCR correlate with the stimulation of apoptosis detected by Annexin V/propidium iodide apoptosis necrosis kit and proteolytic activation of both caspase-3 and caspase-9 monitored by Western blot analysis. Higher release of matrix metalloproteinases (MMPs), especially MMP-2, which could be attenuated by PTX, was found in L1210/VCR than in L1210 cells by gelatin zymography in electrophoretic gel. Exposure of resistant cells to PTX increased the content of phosphorylated Akt kinase. In contrast, the presence of VCR eliminated the effects of PTX on Akt kinase phosphorylation. Taken together, we conclude that PTX induces the sensitization of multidrug-resistant cells to VCR via downregulation of P-gp, stimulation of apoptosis and reduction of MMPs released from drug-resistant L1210/VCR cells. These facts bring new insights into the mechanisms of PTX action on cancer cells

When the Choice Is Ours: Context and Agency Modulate the Neural Bases of Decision-Making

The option to choose between several courses of action is often associated with the feeling of being in control. Yet, in certain situations, one may prefer to decline such agency and instead leave the choice to others. In the present functional magnetic resonance imaging (fMRI) study, we provide evidence that the neural processes involved in decision-making are modulated not only by who controls our choice options (agency), but also by whether we have a say in who is in control (context). The fMRI results are noteworthy in that they reveal specific contributions of the anterior frontomedian cortex (viz. BA 10) and the rostral cingulate zone (RCZ) in decision-making processes. The RCZ is engaged when conditions clearly present us with the most choice options. BA 10 is engaged in particular when the choice is completely ours, as well as when it is completely up to others to choose for us which in turn gives rise to an attribution of control to oneself or someone else, respectively. After all, it does not only matter whether we have any options to choose from, but also who decides on that