A reinforcement learning theory for homeostatic regulation

Reinforcement learning models address animal’s behavioral adaptation to its changing “external” environment, and are based on the assumption that Pavlovian, habitual and goal-directed responses seek to maximize reward acquisition. Negative-feedback models of homeostatic regulation, on the other hand, are concerned with behavioral adaptation in response to the “internal” state of the animal, and assume that animals’ behavioral objective is to minimize deviations of some key physiological variables from their hypothetical setpoints. Building upon the drive-reduction theory of reward, we propose a new analytical framework that integrates learning and regulatory systems, such that the two seemingly unrelated objectives of reward maximization and physiological-stability prove to be identi- cal. The proposed theory shows behavioral adaptation to both internal and external states in a disciplined way. We further show that the proposed framework allows for a unified explanation of some behavioral pattern like motivational sensitivity of different associative learning mechanism, anticipatory responses, interaction among competing motivational systems, and risk aversion

Factors influencing verbal intelligence and spoken language in children with phenylketonuria

Objectives: To determine verbal intelligence and spoken language of children with phenylketonuria and to study the effect of age at diagnosis and phenylalanine plasma level on these abilities. Design: Cross-sectional. Setting: Children with phenylketonuria were recruited from pediatric hospitals in 2012. Normal control subjects were recruited from kindergartens in Tehran. Participants: 30 phenylketonuria and 42 control subjects aged 4- 6.5 years. Skills were compared between 3 phenylketonuria groups categorized by age at diagnosis/treatment, and between the phenylketonuria and control groups. Main outcome measures: Scores on Wechsler Preschool and Primary Scale of Intelligence for verbal and total intelligence, and Test of Language Development-Primary, third edition for spoken language, listening, speaking, semantics, syntax, and organization. Results: The performance of control subjects was significantly better than that of early-treated subjects for all composite quotients from Test of Language Development and verbal intelligence (P >0.001). Early-treated subjects scored significantly higher than the two groups of late-treated subjects for spoken language (P =0.01), speaking (P =0.04), syntax (P =0.02), and verbal intelligence (P =0.019). There was a negative correlation between phenylalanine level and verbal intelligence (r= �0.79) in early-treated subjects and between phenylalanine level and spoken language (r= �0.71), organization (r= �0.82) and semantics (r= �0.82) for late-treated subjects diagnosed before the age one year. Conclusion: The study confirmed that diagnosis of newborns and control of blood phenylalanine concentration improves verbal intelligence and spoken language scores in phenylketonuria subjects. © 2015, Indian Academy of Pediatrics

MicroRNA-129-1 acts as tumour suppressor and induces cell cycle arrest of GBM cancer cells through targeting IGF2BP3 and MAPK1

Background MicroRNA-129-1 (miR-129-1) seems to behave as a tumour suppressor since its decreased expression is associated with different tumours such as glioblastoma multiforme (GBM). GBM is the most common form of brain tumours originating from glial cells. The impact of miR-129-1 downregulation on GBM pathogenesis has yet to be elucidated. Methods MiR-129-1 was overexpressed in GBM cells, and its effect on proliferation was investigated by cell cycle assay. MiR-129-1 predicted targets (CDK6, IGF1, HDAC2, IGF2BP3 and MAPK1) were also evaluated by western blot and luciferase assay. Results Restoration of miR-129-1 reduced cell proliferation and induced G1 accumulation, significantly. Several functional assays confirmed IGF2BP3, MAPK1 and CDK6 as targets of miR-129-1. Despite the fact that IGF1 expression can be suppressed by miR-129-1, through 30-untranslated region complementary sequence, we could not find any association between IGF1 expression and GBM. MiR-129-1 expression inversely correlates with CDK6, IGF2BP3 and MAPK1 in primary clinical samples. Conclusion This is the first study to propose miR129-1 as a negative regulator of IGF2BP3 and MAPK1 and also a cell cycle arrest inducer in GBM cells. Our data suggests miR-129-1 as a potential tumour suppressor and presents a rationale for the use of miR-129-1 as a novel strategy to improve treatment response in GBM

Pelvic floor dysfunction and polycystic ovary syndrome

Objectives: To compare the prevalence of pelvic floor muscle dysfunction (PFMD) in patients with and without polycystic ovary syndrome (PCOS); to test PFMD in women with different PCOS phenotypes. Methods: This was a case-control study of 202 women who were recruited in an infertility clinic in Hormozgan, Iran: PCOS (n=103) and control groups who were healthy women whose husbands were diagnosed with male infertility (n=99). According to the presence or absence of menstrual dysfunction (M), hyperandrogenism (HA) and polycystic ovaries on ultrasonoghraphy (PCO), patients with PCOS were divided into three phenotypes: HA+PCO, M+PCO and M+HA+PCO. PFMD was assessed by the Pelvic Floor Distress Inventory-20 (PFDI-20. Results: The reported PFMD symptoms were higher in PCOS (P=0.05) than the non-PCOS group. The mean PFDI score in the HA+M+PCO was higher compared to other phenotypes, although the difference did not reach significance level (P>0.05). The mean LH level was higher in HA+M+PCO than the two other phenotypes. There was a significant positive correlation between LH level and PFDI score (P<0.04). Conclusion: The findings suggest that a high level of LH may cause PFMD. Further studies are needed to determine the precise role of LH levels and potential treatment options in women with PCOS and PFMD. Keywords: polycystic ovary syndrome, pelvic floor distress inventory, pelvic floor muscle dysfunctio

Doppler echocardiographic indices in aortic coarctation: A comparison of profiles before and after stenting

Background: Diagnosis of aortic coarctation is important as it is a difficult condition to evaluate, especially in adults. A Doppler echocardiographic index could provide a simple tool to evaluate coarctation. This study was performed to compare Doppler echocardiographic profiles before and after stenting and to assess the diagnostic value of a complete list of echocardiographic indices for detecting aortic coarctation. Methods: This prospective study was conducted on 23 patients with a diagnosis of aortic coarctation based on angiography. Echocardiographic assessment was done twice for all patients before and after stenting. Each time, two-dimensional and Doppler echocardiographic imaging modalities were performed and complete lists of indices were recorded for each case. After comparing the values of indices before and after stenting, diagnostic values of each index were calculated in order to diagnose significant coarctation. Results: Twenty-three patients, including 16 males and seven females with a mean age of 26.14 ± 10.17 years, were enrolled in this study. Except for the mean velocity and mean pressure gradient of the abdominal aorta, the values of the other indices of the abdominal/descending aorta showed enough change after stenting to indicate significant diagnostic accuracy for detecting aortic coarctation. The velocity-time integral and the pressure half-time were among the indices with the highest accuracy rates for this purpose (all p < 0.001). Conclusion: Post-stenting echocardiographic profiles could provide a reliable reference value of the normal aortic haemodynamics as a unique identification of each patient and it is presumed that these indices could be used as reliable indicators of response to treatment

Retrospective model-based inference guides model-free credit assignment

An extensive reinforcement learning literature shows that organisms assign credit efficiently, even under conditions of state uncertainty. However, little is known about credit-assignment when state uncertainty is subsequently resolved. Here, we address this problem within the framework of an interaction between model-free (MF) and model-based (MB) control systems. We present and support experimentally a theory of MB retrospective-inference. Within this framework, a MB system resolves uncertainty that prevailed when actions were taken thus guiding an MF credit-assignment. Using a task in which there was initial uncertainty about the lotteries that were chosen, we found that when participants’ momentary uncertainty about which lottery had generated an outcome was resolved by provision of subsequent information, participants preferentially assigned credit within a MF system to the lottery they retrospectively inferred was responsible for this outcome. These findings extend our knowledge about the range of MB functions and the scope of system interactions

TVOCs and BTEX concentrations in the air of south pars special economic energy zone

cold season were higher than those in warm season. High concentrations of Benzene in cold and warm seasons were used to identify areas of high exposure risk.survey TVOCs and BTEX in the air of South Pars Special Economic Energy Zone in 2014. Materials and methods: In a cross-sectional study sampling and analysis was done by NIOSH 1501 method. The study was carried out in 336 activated carbon tubes and personal sampling pump in 6 sampling stations during one year. The compounds were extracted by solvent carbon disulfide and analyzed using Gas Chromatography- Flame Ionization Detector (GC-FID). Data analysis was performed in SPSS Ver.18 applying Kruskal-Wallis, Fligner test and ANOVA. Results: The mean concentrations of TVOCs and TBTEX were 229.34 and 31.23 µg/m3 in cold season and 212.19 and 29.89 µg/m3 in warm season, respectively. The mean concentrations of Benzene in all stations were 11.72 µg/m3 which were higher than the threshold levels recommended by Iranian Clean Air Act and US Environmental Protection Agency (USEPA). The ANOVA results showed a significant difference between the concentration of pollutants and hour, month and sampling stations (P&lt;0.05), but no significant difference was found between the concentration of pollutants and seasons (P&gt;0.05). Conclusion: The concentrations of measured pollutants in cold season were higher than those in warm season. High concentrations of Benzene in cold and warm seasons were used to identify areas of high exposure risk. © 2016, AMazandaran University of Medical Sciences. All rights reserved

Takayasu's arteritis associated with Crohn's disease: a case report

<p>Abstract</p> <p>Introduction</p> <p>The simultaneous presence of Takayasu's arteritis and Crohn's disease in a patient seems to be rare. To our knowledge, no patient with the combination of Crohn's disease and Takayasu's arteritis has been reported from our region.</p> <p>Case presentation</p> <p>Herein we present the case of a 22-year-old Iranian woman previously diagnosed as Crohn's disease and who had subsequently developed Takayasu's arteritis.</p> <p>Conclusion</p> <p>Clinical suspicion, proper imaging, and consideration of the differential diagnosis are important for the correct diagnosis and management of patients with this coincidence.</p

Electroosmotic flow of biorheological micropolar fluids through microfluidic channels

An analysis is presented in this work to assess the influence of micropolar nature of fluids in fully developed flow induced by electrokinetically driven peristaltic pumping through a parallel plate microchannel. The walls of the channel are assumed as sinusoidal wavy to analyze the peristaltic flow nature. We consider that the wavelength of the wall motion is much larger as compared to the channel width to validate the lubrication theory. To simplify the Poisson Boltzmann equation, we also use the Debye-Hückel linearization (i.e. wall zeta potential ≤ 25mV). We consider governing equation for micropolar fluid in absence of body force and couple effects however external electric field is employed. The solutions for axial velocity, spin velocity, flow rate, pressure rise and stream functions subjected to given physical boundary conditions are computed. The effects of pertinent parameters like Debye length and Helmholtz-Smoluchowski velocity which characterize the EDL phenomenon and external electric field, coupling number and micropolar parameter which characterize the micropolar fluid behavior, on peristaltic pumping are discussed through the illustrations. The results show that peristaltic pumping may alter by applying external electric fields. This model can be used to design and engineer the peristalsis-lab-on-chip and micro peristaltic syringe pumps for biomedical applications

Valence-dependent influence of serotonin depletion on model-based choice strategy.

Human decision-making arises from both reflective and reflexive mechanisms, which underpin goal-directed and habitual behavioural control. Computationally, these two systems of behavioural control have been described by different learning algorithms, model-based and model-free learning, respectively. Here, we investigated the effect of diminished serotonin (5-hydroxytryptamine) neurotransmission using dietary tryptophan depletion (TD) in healthy volunteers on the performance of a two-stage decision-making task, which allows discrimination between model-free and model-based behavioural strategies. A novel version of the task was used, which not only examined choice balance for monetary reward but also for punishment (monetary loss). TD impaired goal-directed (model-based) behaviour in the reward condition, but promoted it under punishment. This effect on appetitive and aversive goal-directed behaviour is likely mediated by alteration of the average reward representation produced by TD, which is consistent with previous studies. Overall, the major implication of this study is that serotonin differentially affects goal-directed learning as a function of affective valence. These findings are relevant for a further understanding of psychiatric disorders associated with breakdown of goal-directed behavioural control such as obsessive-compulsive disorders or addictions.This research was funded by Wellcome Trust Grants awarded to VV (Intermediate WT Fellowship) and Programme Grant (089589/Z/09/Z) awarded to TWR, BJE, ACR, JWD and BJS. It was conducted at the Behavioural and Clinical Neuroscience Institute, which is supported by a joint award from the Medical Research Council and Wellcome Trust (G00001354). YW was supported by the Fyssen Foundation. SP is supported by Marie Curie Intra-European Fellowship (FP7-People-2012-IEF).This is the final version of the article. It first appeared from NPG via http://dx.doi.org/10.1038/mp.2015.4