Motor System-Dependent Effects of Amygdala and Ventral Striatum Lesions on Explore-Exploit Behaviors.

Deciding whether to forego immediate rewards or explore new opportunities is a key component of flexible behavior and is critical for the survival of the species. Although previous studies have shown that different cortical and subcortical areas, including the amygdala and ventral striatum (VS), are implicated in representing the immediate (exploitative) and future (explorative) value of choices, the effect of the motor system used to make choices has not been examined. Here, we tested male rhesus macaques with amygdala or VS lesions on two versions of a three-arm bandit task where choices were registered with either a saccade or an arm movement. In both tasks we presented the monkeys with explore-exploit tradeoffs by periodically replacing familiar options with novel options that had unknown reward probabilities. We found that monkeys explored more with saccades but showed better learning with arm movements. VS lesions caused the monkeys to be more explorative with arm movements and less explorative with saccades, although this may have been due to an overall decrease in performance. VS lesions affected the monkeys' ability to learn novel stimulus-reward associations in both tasks, while after amygdala lesions this effect was stronger when choices were made with saccades. Further, on average, VS and amygdala lesions reduced the monkeys' ability to choose better options only when choices were made with a saccade. These results show that learning reward value associations to manage explore-exploit behaviors is motor system dependent and they further define the contributions of amygdala and VS to reinforcement learning.

The connectivity of the human frontal pole cortex, and a theory of its involvement in exploit versus explore.

The frontal pole is implicated in humans in whether to exploit resources versus explore alternatives. Effective connectivity, functional connectivity, and tractography were measured between six human frontal pole regions and for comparison 13 dorsolateral and dorsal prefrontal cortex regions, and the 360 cortical regions in the Human Connectome Project Multi-modal-parcellation atlas in 171 HCP participants. The frontal pole regions have effective connectivity with Dorsolateral Prefrontal Cortex regions, the Dorsal Prefrontal Cortex, both implicated in working memory; and with the orbitofrontal and anterior cingulate cortex reward/non-reward system. There is also connectivity with temporal lobe, inferior parietal, and posterior cingulate regions. Given this new connectivity evidence, and evidence from activations and damage, it is proposed that the frontal pole cortex contains autoassociation attractor networks that are normally stable in a short-term memory state, and maintain stability in the other prefrontal networks during stable exploitation of goals and strategies. However, if an input from the orbitofrontal or anterior cingulate cortex that expected reward, non-reward, or punishment is received, this destabilizes the frontal pole and thereby other prefrontal networks to enable exploration of competing alternative goals and strategies. The frontal pole connectivity with reward systems may be key in exploit versus explore.

Mice exhibit stochastic and efficient action switching during probabilistic decision making.

In probabilistic and nonstationary environments, individuals must use internal and external cues to flexibly make decisions that lead to desirable outcomes. To gain insight into the process by which animals choose between actions, we trained mice in a task with time-varying reward probabilities. In our implementation of such a two-armed bandit task, thirsty mice use information about recent action and action­outcome histories to choose between two ports that deliver water probabilistically. Here we comprehensively modeled choice behavior in this task, including the trial-to-trial changes in port selection, i.e., action switching behavior. We find that mouse behavior is, at times, deterministic and, at others, apparently stochastic. The behavior deviates from that of a theoretically optimal agent performing Bayesian inference in a hidden Markov model (HMM). We formulate a set of models based on logistic regression, reinforcement learning, and sticky Bayesian inference that we demonstrate are mathematically equivalent and that accurately describe mouse behavior. The switching behavior of mice in the task is captured in each model by a stochastic action policy, a history-dependent representation of action value, and a tendency to repeat actions despite incoming evidence. The models parsimoniously capture behavior across different environmental conditionals by varying the stickiness parameter, and like the mice, they achieve nearly maximal reward rates. These results indicate that mouse behavior reaches near-maximal performance with reduced action switching and can be described by a set of equivalent models with a small number of relatively fixed parameters.

Reviewing explore/exploit decision-making as a transdiagnostic target for psychosis, depression, and anxiety.

In many everyday decisions, individuals choose between trialling something novel or something they know well. Deciding when to try a new option or stick with an option that is already known to you, known as the "explore/exploit" dilemma, is an important feature of cognition that characterises a range of decision-making contexts encountered by humans. Recent evidence has suggested preferences in explore/exploit biases are associated with psychopathology, although this has typically been examined within individual disorders. The current review examined whether explore/exploit decision-making represents a promising transdiagnostic target for psychosis, depression, and anxiety. A systematic search of academic databases was conducted, yielding a total of 29 studies. Studies examining psychosis were mostly consistent in showing that individuals with psychosis explored more compared with individuals without psychosis. The literature on anxiety and depression was more heterogenous; some studies found that anxiety and depression were associated with more exploration, whereas other studies demonstrated reduced exploration in anxiety and depression. However, examining a subset of studies that employed case-control methods, there was some evidence that both anxiety and depression also were associated with increased exploration. Due to the heterogeneity across the literature, we suggest that there is insufficient evidence to conclude whether explore/exploit decision-making is a transdiagnostic target for psychosis, depression, and anxiety. However, alongside our advisory groups of lived experience advisors, we suggest that this context of decision-making is a promising candidate that merits further investigation using well-powered, longitudinal designs. Such work also should examine whether biases in explore/exploit choices are amenable to intervention.

Developmental differences in children and adults' enforcement of explore versus exploit search strategies in the United States and Turkey.

Across development, as children acquire a deeper understanding of their environment, they explore less and take advantage, or "exploit," what they already know. Here, we test whether children also enforce exploration-oriented search behaviors onto others. Specifically, we ask whether children are more likely to encourage a search agent to explore versus exploit their environment, and whether this pattern varies across childhood (between 3 and 6 years). We also ask whether this pattern differs between children and adults, and generalizes across two different sociocultural contexts-Turkey and the United States-that differ on dimensions that might relate to children's decisions about exploration (e.g., curiosity-focused educational practices, attitudes toward uncertainty avoidance). Participants (N = 358) watched an agent search for rewards and were asked at various points whether the agent should "stay" (exploit) in their current location, or "go" (explore) to a new location. At all points in the experiment, children enforced exploration significantly more often than adults. Early in the agent's search, children in the US enforced exploration more often than children in Turkey; later in the search, younger children (from both sociocultural contexts) were more likely to continue enforcing exploration compared to older children. These findings highlight that children are not only highly exploratory themselves, but also enforce exploration onto others-underscoring the central role that exploration plays in driving early cognitive development across diverse sociocultural contexts. RESEARCH HIGHLIGHTS: The current study examined developmental and cross-cultural differences in children and adults' enforcement of explore-exploit search strategies. Children in the US and Turkey enforced exploration more than adults, who enforced exploitation more often; results were generally consistent across cultures with small differences. Mirroring developmental changes in children's own search behavior; the tendency to enforce exploration decreased between 3- to 6-years of age. Findings underscore the central role of an "exploration mindset" in children's early decision-making-even when exploration has no direct benefits to the child themselves.

The explore/exploit trade-off: An ecologically valid and translational framework that can advance mechanistic understanding of eating disorders.

The explore/exploit trade-off is a decision-making process that is conserved across species and balances exploring unfamiliar choices of unknown value with choosing familiar options of known value to maximize reward. This framework is rooted in behavioral ecology and has traditionally been used to study maladaptive versus adaptive non-human animal foraging behavior. Researchers have begun to recognize the potential utility of understanding human decision-making and psychopathology through the explore/exploit trade-off. In this article, we propose that explore/exploit trade-off holds promise for advancing our mechanistic understanding of decision-making processes that confer vulnerability for and maintain eating pathology due to its neurodevelopmental bases, conservation across species, and ability to be mathematically modeled. We present a model for how suboptimal explore/exploit decision-making can promote disordered eating and present recommendations for future research applying this framework to eating pathology. Taken together, the explore/exploit trade-off provides a translational framework for expanding etiologic and maintenance models of eating pathology, given developmental changes in explore/exploit decision-making that coincide in time with the emergence of eating pathology and evidence of biased explore/exploit decision-making in psychopathology. Additionally, understanding explore/exploit decision-making in eating disorders may improve knowledge of their underlying pathophysiology, informing targeted clinical interventions such as neuromodulation and pharmacotherapy. PUBLIC SIGNIFICANCE STATEMENT: The explore/exploit trade-off is a cross-species decision-making process whereby organisms choose between a known option with a known reward or sampling unfamiliar options. We hypothesize that imbalanced explore/exploit decision-making can promote disordered eating and present preliminary data. We propose that explore/exploit trade-off has significant potential to advance understanding of the neurocognitive and neurodevelopmental mechanisms of eating pathology, which could ultimately guide revisions of etiologic models and inform novel interventions.

El balance entre explorar y explotar es un proceso de toma de decisiones que se conserva a través de las especies y equilibra la exploración de opciones desconocidas de valor desconocido con la elección de opciones familiares de valor conocido para maximizar la recompensa. Este marco está arraigado en la ecología del comportamiento y tradicionalmente se ha utilizado para estudiar el comportamiento de forrajeo no adaptativo versus adaptativo en animales no humanos. Los investigadores han comenzado a reconocer la utilidad potencial de entender la toma de decisiones humanas y la psicopatología a través del balance entre explorar y explotar. En este artículo, proponemos que el balance entre explorar y explotar ofrece promesas para avanzar en nuestra comprensión mecanicista de los procesos de toma de decisiones que confieren vulnerabilidad y mantienen la patología alimentaria debido a sus bases neurodesarrolladoras, su conservación a través de las especies y su capacidad de ser modelado matemáticamente. Presentamos un modelo de cómo la toma de decisiones subóptima entre explorar y explotar puede promover la alimentación disfuncional y presentamos recomendaciones para futuras investigaciones que apliquen este marco a la patología alimentaria. En conjunto, el balance entre explorar y explotar proporciona un marco translacional para expandir los modelos etiológicos y de mantenimiento de la patología alimentaria, dadas los cambios en el desarrollo de la toma de decisiones entre explorar y explotar que coinciden en el tiempo con la aparición de la patología alimentaria y la evidencia de una toma de decisiones entre explorar y explotar sesgada en la psicopatología. Además, comprender la toma de decisiones entre explorar y explotar en los trastornos alimentarios puede mejorar el conocimiento de su fisiopatología subyacente, informando intervenciones clínicas dirigidas como la neuromodulación y la farmacoterapia.

What Does the Frontopolar Cortex Contribute to Goal-Directed Cognition and Action?

Understanding the unique functions of different subregions of primate prefrontal cortex has been a longstanding goal in cognitive neuroscience. Yet, the anatomy and function of one of its largest subregions (the frontopolar cortex) remain enigmatic and underspecified. Our Society for Neuroscience minisymposium Primate Frontopolar Cortex: From Circuits to Complex Behaviors will comprise a range of new anatomic and functional approaches that have helped to clarify the basic circuit anatomy of the frontal pole, its functional involvement during performance of cognitively demanding behavioral paradigms in monkeys and humans, and its clinical potential as a target for noninvasive brain stimulation in patients with brain disorders. This review consolidates knowledge about the anatomy and connectivity of frontopolar cortex and provides an integrative summary of its function in primates. We aim to answer the question: what, if anything, does frontopolar cortex contribute to goal-directed cognition and action?

A One-Shot Shift from Explore to Exploit in Monkey Prefrontal Cortex.

Much animal learning is slow, with cumulative changes in behavior driven by reward prediction errors. When the abstract structure of a problem is known, however, both animals and formal learning models can rapidly attach new items to their roles within this structure, sometimes in a single trial. Frontal cortex is likely to play a key role in this process. To examine information seeking and use in a known problem structure, we trained monkeys in an explore/exploit task, requiring the animal first to test objects for their association with reward, then, once rewarded objects were found, to reselect them on further trials for further rewards. Many cells in the frontal cortex showed an explore/exploit preference aligned with one-shot learning in the monkeys' behavior: the population switched from an explore state to an exploit state after a single trial of learning but partially maintained the explore state if an error indicated that learning had failed. Binary switch from explore to exploit was not explained by continuous changes linked to expectancy or prediction error. Explore/exploit preferences were independent for two stages of the trial: object selection and receipt of feedback. Within an established task structure, frontal activity may control the separate processes of explore and exploit, switching in one trial between the two.SIGNIFICANCE STATEMENT Much animal learning is slow, with cumulative changes in behavior driven by reward prediction errors. When the abstract structure a problem is known, however, both animals and formal learning models can rapidly attach new items to their roles within this structure. To address transitions in neural activity during one-shot learning, we trained monkeys in an explore/exploit task using familiar objects and a highly familiar task structure. When learning was rapid, many frontal neurons showed a binary, one-shot switch between explore and exploit. Within an established task structure, frontal activity may control the separate operations of exploring alternative objects to establish their current role, then exploiting this knowledge for further reward.

Computational mechanisms underpinning greater exploratory behaviour in excess weight relative to healthy weight adolescents.

Obesity in adolescence is associated with cognitive changes that lead to difficulties in shifting unhealthy habits in favour of alternative healthy behaviours, similar to addictive behaviours. An outstanding question is whether this shift in goal-directed behaviour is driven by over-exploitation or over-exploration of rewarding outcomes. Here, we addressed this question by comparing explore/exploit behaviour on the Iowa Gambling Task in 43 adolescents with excess weight against 38 adolescents with healthy weight. We computationally modelled both exploitation behaviour (e.g., reinforcement sensitivity and inverse decay parameters), and explorative behaviour (e.g., maximum directed exploration value). We found that overall, adolescents with excess weight displayed more behavioural exploration than their healthy-weight counterparts - specifically, demonstrating greater overall switching behaviour. Computational models revealed that this behaviour was driven by a higher maximum directed exploration value in the excess-weight group (U = 520.00, p = .005, BF10 = 5.11). Importantly, however, we found substantial evidence that groups did not differ in reinforcement sensitivity (U = 867.00, p = .641, BF10 = 0.30). Overall, our study demonstrates a preference for exploratory behaviour in adolescents with excess weight, independent of sensitivity to reward. This pattern could potentially underpin an intrinsic desire to explore energy-dense unhealthy foods - an as-yet untapped mechanism that could be targeted in future treatments of obesity in adolescents.

Computational models of exploration and exploitation characterise onset and efficacy of treatment in methamphetamine use disorder.

People with Methamphetamine Use Disorder (PwMUD) spend substantial time and resources on substance use, which hinders their ability to explore alternate reinforcers. Gold-standard behavioural treatments attempt to remedy this by encouraging action towards non-drug reinforcers, but substance use often persists. We aimed to unravel the mechanistic drivers of this behaviour by applying a computational model of explore/exploit behaviour to decision-making data (Iowa Gambling Task) from 106 PwMUD and 48 controls. We then examined the longitudinal link between explore/exploit mechanisms and changes in methamphetamine use 6 weeks later. Exploitation parameters included reinforcement sensitivity and inverse decay (i.e., number of past outcomes used to guide choices). Exploration parameters included maximum directed exploration value (i.e., value of trying novel actions). The Timeline Follow Back measured changes in methamphetamine use. Compared to controls, PwMUD showed deficits in exploitative decision-making, characterised by reduced reinforcement sensitivity, U = 3065, p = 0.009, and less use of previous choice outcomes, U = 3062, p = 0.010. This was accompanied by a behavioural pattern of frequent shifting between choices, which appeared consistent with random exploration. Furthermore, PwMUD with greater reductions of methamphetamine use at 6 weeks had increased directed exploration (ß = 0.22, p = 0.045); greater use of past choice outcomes (ß = -0.39, p = 0.002) and greater choice consistency (ß = -0.39, p = 0.002). Therefore, limited computational exploitation and increased behavioural exploration characterise PwMUD's presentation to treatment, while increased directed exploration, use of past choice outcomes and choice consistency predict greater reductions of methamphetamine use.

Efficient team structures in an open-ended cooperative creativity experiment.

Creativity is progressively acknowledged as the main driver for progress in all sectors of humankind's activities: arts, science, technology, business, and social policies. Nowadays, many creative processes rely on many actors collectively contributing to an outcome. The same is true when groups of people collaborate in the solution of a complex problem. Despite the critical importance of collective actions in human endeavors, few works have tackled this topic extensively and quantitatively. Here we report about an experimental setting to single out some of the key determinants of efficient teams committed to an open-ended creative task. In this experiment, dynamically forming teams were challenged to create several artworks using LEGO bricks. The growth rate of the artworks, the dynamical network of social interactions, and the interaction patterns between the participants and the artworks were monitored in parallel. The experiment revealed that larger working teams are building at faster rates and that higher commitment leads to higher growth rates. Even more importantly, there exists an optimal number of weak ties in the social network of creators that maximizes the growth rate. Finally, the presence of influencers within the working team dramatically enhances the building efficiency. The generality of the approach makes it suitable for application in very different settings, both physical and online, whenever a creative collective outcome is required.

Primate Orbitofrontal Cortex Codes Information Relevant for Managing Explore-Exploit Tradeoffs.

Reinforcement learning (RL) refers to the behavioral process of learning to obtain reward and avoid punishment. An important component of RL is managing explore-exploit tradeoffs, which refers to the problem of choosing between exploiting options with known values and exploring unfamiliar options. We examined correlates of this tradeoff, as well as other RL related variables, in orbitofrontal cortex (OFC) while three male monkeys performed a three-armed bandit learning task. During the task, novel choice options periodically replaced familiar options. The values of the novel options were unknown, and the monkeys had to explore them to see if they were better than other currently available options. The identity of the chosen stimulus and the reward outcome were strongly encoded in the responses of single OFC neurons. These two variables define the states and state transitions in our model that are relevant to decision-making. The chosen value of the option and the relative value of exploring that option were encoded at intermediate levels. We also found that OFC value coding was stimulus specific, as opposed to coding value independent of the identity of the option. The location of the option and the value of the current environment were encoded at low levels. Therefore, we found encoding of the variables relevant to learning and managing explore-exploit tradeoffs in OFC. These results are consistent with findings in the ventral striatum and amygdala and show that this monosynaptically connected network plays an important role in learning based on the immediate and future consequences of choices.SIGNIFICANCE STATEMENT Orbitofrontal cortex (OFC) has been implicated in representing the expected values of choices. Here we extend these results and show that OFC also encodes information relevant to managing explore-exploit tradeoffs. Specifically, OFC encodes an exploration bonus, which characterizes the relative value of exploring novel choice options. OFC also strongly encodes the identity of the chosen stimulus, and reward outcomes, which are necessary for computing the value of novel and familiar options.

Increasing the gradient of energetic cost does not initiate adaptation in human walking.

When in a new situation, the nervous system may benefit from adapting its control policy. In determining whether or not to initiate this adaptation, the nervous system may rely on some features of the new situation. Here, we tested whether one such feature is salient cost savings. We changed cost saliency by manipulating the gradient of participants' energetic cost landscape during walking. We hypothesized that steeper gradients would cause participants to spontaneously adapt their step frequency to lower costs. To manipulate the gradient, a mechatronic system applied controlled fore-aft forces to the waist of participants as a function of their step frequency as they walked on a treadmill. These forces increased the energetic cost of walking at high step frequencies and reduced it at low step frequencies. We successfully created three cost landscapes of increasing gradients, where the natural variability in participants' step frequency provided cost changes of 3.6% (shallow), 7.2% (intermediate), and 10.2% (steep). Participants did not spontaneously initiate adaptation in response to any of the gradients. Using metronome-guided walking-a previously established protocol for eliciting initiation of adaptation-participants next experienced a step frequency with a lower cost. Participants then adapted by -1.41 ± 0.81 (P = 0.007) normalized units away from their originally preferred step frequency obtaining cost savings of 4.80% ± 3.12%. That participants would adapt under some conditions, but not in response to steeper cost gradients, suggests that the nervous system does not solely rely on the gradient of energetic cost to initiate adaptation in novel situations.NEW & NOTEWORTHY People can adapt to novel conditions but often require cues to initiate the adaptation. Using a mechatronic system to reshape energetic cost gradients during treadmill walking, we tested whether the nervous system can use information present in the cost gradient to spontaneously initiate adaptation. We found that our participants did not spontaneously initiate adaptation even in the steepest gradient. The nervous system does not rely solely on the cost gradient when initiating adaptation.

Effect of noise on the electrocardiographic parameters.

PURPOSE: Noise, defined as any sound that is unpleasant, is one of the most important environmental problems. Prolonged exposure to noise has been shown to be associated with the development of cardiovascular diseases. No study investigated the effect of noise on surface electrocardiography (ECG). AIMS: The aim of our study is to investigate the effect of noise on surface ECG parameters including P-wave dispersion (PWD), QT intervals, corrected QT interval (QTc), T-wave peak to end (Tp-e) interval, and Tp-e/QT and Tp-e/QTc ratios. METHODS: A total of 51 people working in the textile factory affected by the noise and 43 volunteers without any disease and who were not exposed to noise were included in this study. The average noise level in the textile factory was 112 dB. A 12-lead ECG was obtained from all individuals. PR interval, PWD, QRS duration, QT interval, QTc interval, Tp-e interval, and Tp-e/QT and Tp-e/QTc ratios were calculated for all individuals. RESULTS: The noise group had significantly increased PWD [35 (28-40) vs. 28 (22-36) p = 0.029], QT interval ( 373.5 ± 27.3 vs. 359.3 ± 2.74, p = 0.001), QTc interval [(409 ± 21 vs. 403 ± 13 p = 0.045)], Tp-e interval [(90.6 ± 6.0 vs. 83.5 ± 7.3 p < 0.001)], Tp-e/QT [(0.24 ± 0.03 vs. 0.23 ± 0.02, p = 0.015)] and Tp-e/QTc [(0.22 ± 0.02 vs. 0.21 ± 0.02 p < 0.001)] compared to control group. Also, duration of working was positively correlated with PWD (r = 0.468, p = 0.001) and Tp-e/QTc ratio (r = 0.328, p = 0.019). In multiple linear regression linear regression analysis, noise was the independent predictor of both PWD (ß = 0.244, p = 0.032) and Tp-e/QTc (ß = 0.319, p = 0.003) CONCLUSION: We showed that noise significantly increased PWD, QT and Tp-e interval measurements. Also, noise was the independent predictor for both PWD and Tp-e/QTc.

Regulation of vocal precision by noradrenergic modulation of a motor nucleus.

Recent theories of norepinephrine (NE) function suggest that NE modulates the transition between stereotyped, goal-directed behavior and more variable, exploratory behaviors that facilitate learning and adaptation. We provide evidence for context-dependent switching by NE that is analogous to this explore/exploit strategy in the vocal system of the zebra finch (Taeniopygia guttata). Stimulation of the locus coeruleus, the major source of NE in the brain, decreases song trial-to-trial variability, transforming the variable, exploratory "undirected" song into song that resembles the more stereotyped, exploitative "directed" song that males sing to females. This behavioral switch is mediated by NE acting directly on a cortical motor nucleus that integrates inputs from a premotor cortical nucleus and a basal ganglia circuit necessary for vocal motor learning. These findings suggest that NE can act directly on the motor system to influence the transition between exploratory and exploitative behavioral strategies.NEW & NOTEWORTHY Norepinephrine (NE) function is often implicated in regulating arousal levels. Recent theory suggests that the noradrenergic system also regulates the optimization of behavior with respect to reward maximization by controlling a switch between exploration and exploitation of the specific actions that yield greatest utility. We show in the songbird that NE can act directly on a cortical motor area and cause a switch between exploratory and exploitative behavior.

Variants in STAT4 Associated With Cure of Chronic HBV Infection in HBeAg-positive Patients Treated With Pegylated Interferon-alpha.

BACKGROUND & AIMS: Variants in STAT4 (rs7574865) have been associated with seroconversion to hepatitis B e antigen (HBeAg) and reduction in levels of hepatitis B virus (HBV) DNA in patients with chronic infection treated with interferon alpha (IFNA). We evaluated the associations among rs7574865, loss of HB surface antigen (HBsAg, a marker of functional cure of HBV infection), and response to treatment with pegylated IFNA (PegIFN) or nucleos(t)ide analogues (NUCs) in HBeAg-positive patients with chronic HBV infection. METHODS: We performed a retrospective analysis of 1823 HBeAg-positive patients with chronic HBV infection (954 patients treated with PegIFN and 869 patients treated with NUCs) included in 4 phase-4 multicenter randomized controlled trials. The Cochran-Armitage trend test was used to evaluate the association of rs7574865 genotype with combined response (CR, defined as HBeAg seroconversion and HBV DNA level <2000 IU/mL) and loss of HBsAg at week 72, for patients given PegIFN, or week 104, for patients given NUCs. RESULTS: We found a significant association between rs7574865 genotype and CR (P = .004) and loss of HBsAg (P = .037) in patients treated with PegIFN. In patients with HBV genotype B infection, 43.6% of those with rs7574865 TT achieved a CR, compared to patients with rs7574865 GG (20.5%), and 7.7% had loss of HBsAg, compared to 1.9% of patients with rs7574865 GG. However, in patients treated with NUCs, we found no association of rs7574865 genotype with CR (P = .811) or loss of HBsAg (P=.439). CONCLUSIONS: In a retrospective analysis of data from 4 clinical trials, we found rs7574865 in STAT4 to be associated with functional cure of chronic HBV infection by PegIFN treatment, but not NUCs treatment, in HBeAg-positive patients with HBV genotype B infection.

[An study on the incidence of heat stroke and explore it's prediction model in Pudong New Area of Shanghai from 2013-2017].

Objective: To know the incidence of heat stroke and explore it's prediction model in Pudong New Area of Shanghai. Methods: An epidemiological investigation was conducted on heat stroke cases in Pudong New Area of Shanghai from 2013 to 2017. Daily temperature data during this period were collected to explore it's influence. Results: 246 heat stroke cases were reported and investigated, 70.3% (173/246) of them were male. 170 cases are severe heat stroke, accounting for 69.1%. 28 patients died, accounting for 11.4% of all cases of heat stroke, and 16.5% (28/170) of severe heat stroke cases. Thermoplegia (56.5%, 96/170) was the most popular type among severe heat stroke cases. Heat prostration, heat cramps and mixed type account for 17.1% (29/170) , 12.4% (21/170) and 14.0% (24/170) respectively. Scatter plot and linear regression demonstrated that there was a significant linear relation between number of high temperature days and number of heat stroke cases (P<0.01) . And the prediction model is: Predictive number of annual heat stroke cases=ß×Number of annual high temperature days+Intercept. Leave-one-out cross validation result shows that the predictive number of annual heat stroke cases from 2013 to 2017 were 85.7%, 90.9%, 83.3%, 91.9 and 84.3% respectively. Conclusion: There was a significant linear relation between number of high temperature days and number of heat stroke cases in Pudong New Area. The related work arrangement for heat stroke prevention could be well planed according to the prediction model.

Learning and choosing in an uncertain world: An investigation of the explore-exploit dilemma in static and dynamic environments.

How do people solve the explore-exploit trade-off in a changing environment? In this paper we present experimental evidence from an "observe or bet" task, in which people have to determine when to engage in information-seeking behavior and when to switch to reward-taking actions. In particular we focus on the comparison between people's behavior in a changing environment and their behavior in an unchanging one. Our experimental work is motivated by rational analysis of the problem that makes strong predictions about information search and reward seeking in static and changeable environments. Our results show a striking agreement between human behavior and the optimal policy, but also highlight a number of systematic differences. In particular, we find that while people often employ suboptimal strategies the first time they encounter the learning problem, most people are able to approximate the correct strategy after minimal experience. In order to describe both the manner in which people's choices are similar to but slightly different from an optimal standard, we introduce four process models for the observe or bet task and evaluate them as potential theories of human behavior.

Children Use Teachers' Beliefs About Their Abilities to Calibrate Explore-Exploit Decisions.

Models of the explore-exploit problem have explained how children's decision making is weighed by a bias for information (directed exploration), randomness, and generalization. These behaviors are often tested in domains where a choice to explore (or exploit) is guaranteed to reveal an outcome. An often overlooked but critical component of the assessment of explore-exploit decisions lies in the expected success of taking actions in the first place-and, crucially, how such decisions might be carried out when learning from others. Here, we examine how children consider an informal teacher's beliefs about the child's competence when deciding how difficult a task they want to pursue. We present a simple model of this problem that predicts that while learners should follow the recommendation of an accurate teacher, they should exploit easier games when a teacher overestimates their abilities, and explore harder games when she underestimates them. We tested these predictions in two experiments with adults (Experiment 1) and 6- to 8-year-old children (Experiment 2). In our task, participants' performance on a picture-matching game was either overestimated, underestimated, or accurately represented by a confederate (the "Teacher"), who then presented three new matching games of varying assessed difficulty (too easy, too hard, just right) at varying potential reward (low, medium, high). In line with our model's predictions, we found that both adults and children calibrated their choices to the teacher's representation of their competence. That is, to maximize expected reward, when she underestimated them, participants chose games the teacher evaluated as being too hard for them; when she overestimated them, they chose games she evaluated as being too easy; and when she was accurate, they chose games she assessed as being just right. This work provides insight into the early-emerging ability to calibrate explore-exploit decisions to others' knowledge when learning in informal pedagogical contexts.

The Role of HBx Protein in Diseases Beyond the Liver.

HBX gene is essential for HBV replication, evading the surveillance of the immune system by integrating its sequence into the human genome. It also exists stably in human cells by inhibiting the expression and activity of mismatch repair-related pathway genes. Previous reviews have comprehensively summarized the role of HBx in liver-related diseases. Our article complements the summary of research on HBx in diseases other than liver disease. Through a comprehensive literature search and reading, we found that HBx is expressed in the kidney, placenta, lung and other organs of HBV-infected patients, and is closely related to the occurrence and development of diseases such as nephritis, diffuse large B-cell lymphoma, and gastric cancer. However, in the clinical treatment of these diseases, HBV infection and the role of HBx have not attracted sufficient attention, and there is no corresponding treatment strategy. Therefore, more research on HBx in diseases other than the liver is particularly necessary, and we hope that our article can provide some insight into the treatment of related diseases.