The time is ripe for robopsychology.

As robotic applications become increasingly diverse, more domains of human lives are being involved, now also extending to educational, therapeutic, and social situations, with a trend to even more complex interactions. This diversity generates new research questions that need to be met with an adequate infrastructure of psychological methods and theory. In this review, we illustrate the current lack of a sub-discipline in psychology to systematically study the psychological corollaries of living in societies where the application of robotic and artificial intelligence (AI) technologies is becoming increasingly common. We thus propose that organized efforts be made toward recognition of robopsychology as a sub-discipline so that the field of psychology moves away from isolated publications of robot- and AI-related topics to a body of knowledge that is able to meet the demands for change, as the world is preparing for the Fourth Industrial Revolution. We propose a definition of robopsychology that not only covers the study of the effects of robots on human behavior, but also of robots and AI themselves, as well as acknowledging how this sub-discipline may eventually be fundamentally changed through robots and AI. In this sense, our definition mirrors an already existing definition of the field of robophilosophy.

Analysis of Phonetic Balance in Standard English Passages.

Purpose A common way of eliciting speech from individuals is by using passages of written language that are intended to be read aloud. Read passages afford the opportunity for increased control over the phonetic properties of elicited speech, of which phonetic balance is an often-noted example. No comprehensive analysis of the phonetic balance of read passages has been reported in the literature. The present article provides a quantitative comparison of the phonetic balance of widely used passages in English. Method Assessment of phonetic balance is carried out by comparing the distribution of phonemes in several passages to distributions consistent with typical spoken English. Data regarding the distribution of phonemes in spoken American English are aggregated from the published literature and large speech corpora. Phoneme distributions are compared using Spearman rank order correlation coefficient to quantify similarities of phoneme counts in those sources. Results Correlations between phoneme distributions in read passages and aggregated material representative of spoken American English ranged from .70 to .89. Correlations between phoneme counts from all passages, literature sources, and corpus sources ranged from .55 to .99. All correlations were statistically significant at the Bonferroni-adjusted level. Conclusions Passages considered in the present work provide high, but not ideal, phonetic balance. Space exists for the creation of new passages that more closely match the phoneme distributions observed in spoken American English. The Caterpillar provided the best phonetic balance, but phoneme distributions in all considered materials were highly similar to each other.

Stakeholder engagement in methodological research: Development of a clinical decision support tool.

INTRODUCTION: Shared patient-clinician decision-making is central to choosing between medical treatments. Decision support tools can have an important role to play in these decisions. We developed a decision support tool for deciding between nonsurgical treatment and surgical total knee replacement for patients with severe knee osteoarthritis. The tool aims to provide likely outcomes of alternative treatments based on predictive models using patient-specific characteristics. To make those models relevant to patients with knee osteoarthritis and their clinicians, we involved patients, family members, patient advocates, clinicians, and researchers as stakeholders in creating the models. METHODS: Stakeholders were recruited through local arthritis research, advocacy, and clinical organizations. After being provided with brief methodological education sessions, stakeholder views were solicited through quarterly patient or clinician stakeholder panel meetings and incorporated into all aspects of the project. RESULTS: Participating in each aspect of the research from determining the outcomes of interest to providing input on the design of the user interface displaying outcome predications, 86% (12/14) of stakeholders remained engaged throughout the project. Stakeholder engagement ensured that the prediction models that form the basis of the Knee Osteoarthritis Mathematical Equipoise Tool and its user interface were relevant for patient-clinician shared decision-making. CONCLUSIONS: Methodological research has the opportunity to benefit from stakeholder engagement by ensuring that the perspectives of those most impacted by the results are involved in study design and conduct. While additional planning and investments in maintaining stakeholder knowledge and trust may be needed, they are offset by the valuable insights gained.

Assessment of speech and fine motor coordination in children with autism spectrum disorder.

Autism Spectrum Disorder (ASD) is a developmental disorder characterized by difficulty in communication, which includes a high incidence of speech production errors. We hypothesize that these errors are partly due to underlying deficits in motor coordination and control, which are also manifested in degraded fine motor control of facial expressions and purposeful hand movements. In this pilot study, we computed correlations of acoustic, video, and handwriting time-series derived from five children with ASD and five children with neurotypical development during speech and handwriting tasks. These correlations and eigenvalues derived from the correlations act as a proxy for motor coordination across articulatory, laryngeal, and respiratory speech production systems and for fine motor skills. We utilized features derived from these correlations to discriminate between children with and without ASD. Eigenvalues derived from these correlations highlighted differences in complexity of coordination across speech subsystems and during handwriting, and helped discriminate between the two subject groups. These results suggest differences in coupling within speech production and fine motor skill systems in children with ASD. Our long-term goal is to create a platform assessing motor coordination in children with ASD in order to track progress from speech and motor interventions administered by clinicians.

The use of patient-specific equipoise to support shared decision-making for clinical care and enrollment into clinical trials.

BACKGROUND: To enhance enrollment into randomized clinical trials (RCTs), we proposed electronic health record-based clinical decision support for patient-clinician shared decision-making about care and RCT enrollment, based on "mathematical equipoise." OBJECTIVES: As an example, we created the Knee Osteoarthritis Mathematical Equipoise Tool (KOMET) to determine the presence of patient-specific equipoise between treatments for the choice between total knee replacement (TKR) and nonsurgical treatment of advanced knee osteoarthritis. METHODS: With input from patients and clinicians about important pain and physical function treatment outcomes, we created a database from non-RCT sources of knee osteoarthritis outcomes. We then developed multivariable linear regression models that predict 1-year individual-patient knee pain and physical function outcomes for TKR and for nonsurgical treatment. These predictions allowed detecting mathematical equipoise between these two options for patients eligible for TKR. Decision support software was developed to graphically illustrate, for a given patient, the degree of overlap of pain and functional outcomes between the treatments and was pilot tested for usability, responsiveness, and as support for shared decision-making. RESULTS: The KOMET predictive regression model for knee pain had four patient-specific variables, and an r 2 value of 0.32, and the model for physical functioning included six patient-specific variables, and an r 2 of 0.34. These models were incorporated into prototype KOMET decision support software and pilot tested in clinics, and were generally well received. CONCLUSIONS: Use of predictive models and mathematical equipoise may help discern patient-specific equipoise to support shared decision-making for selecting between alternative treatments and considering enrollment into an RCT.

Effects of cranberry extracts on gene expression in THP-1 cells.

Cranberry contains high levels of nutrients and bioactive molecules that have health-promoting properties. The purpose of the present studies was to determine if cranberry extracts (CEs) contain phytochemicals that exert anti-inflammatory effects. The human monocytic cell line THP-1 was treated with two CEs (CE and 90MX) and subsequently challenged with Lipopolysaccharides (LPS). Tumor necrosis factor α (TNF α) expression was decreased in the CE-treated cells, indicative of an anti-inflammatory effect. Gene expression microarrays identified several immune-related genes that were responsive to CEs including interferon-induced protein with tetratricopeptide repeats 1 and 3 (IFIT 1 and 3), macrophage scavenger receptor 1 (MSR1) and colony-stimulating factor 2 (CSF2). In addition, in the CE-treated cells, metallothionein 1F and other metal-responsive genes were induced. Taken together, this data indicates that CEs contain bioactive components that have anti-inflammatory effects and may protect cells from oxidative damage.

Regulation of inflammatory and lipid metabolism genes by eicosapentaenoic acid-rich oil.

Omega-3-PUFAs, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), are associated with prevention of various aspects of metabolic syndrome. In the present studies, the effects of oil rich in EPA on gene expression and activation of nuclear receptors was examined and compared with other ω3-PUFAs. The EPA-rich oil (EO) altered the expression of FA metabolism genes in THP-1 cells, including stearoyl CoA desaturase (SCD) and FA desaturase-1 and -2 (FASDS1 and -2). Other ω3-PUFAs resulted in a similar gene expression response for a subset of genes involved in lipid metabolism and inflammation. In reporter assays, EO activated human peroxisome proliferator-activated receptor α (PPARα) and PPARß/γ with minimal effects on PPARγ, liver X receptor, retinoid X receptor, farnesoid X receptor, and retinoid acid receptor γ (RARγ); these effects were similar to that observed for purified EPA. When serum from a 6 week clinical intervention with dietary supplements containing olive oil (control), DHA, or two levels of EPA were applied to THP-1 cells, the expression of SCD and FADS2 decreased in the cells treated with serum from the ω3-PUFA-supplemented individuals. Taken together, these studies indicate regulation of gene expression by EO that is consistent with treating aspects of dyslipidemia and inflammation.

Measurement of fetal heart rate variability on an electronic monitor using a prototype electronic ruler.

OBJECTIVE: To develop a prototype electronic ruler for assessment of fetal heart rate (FHR) variability on an electronic monitor and test its reliability and accuracy. STUDY DESIGN: A prototype electronic ruler was designed and developed for assessment of FHR variability on electronic monitors. The electronic ruler consisted of horizontal bands that were sized and colored to embed the four FHR variability categories. The reliability and accuracy of using the electronic ruler to assess FHR variability was studied with expert clinicians. RESULTS: Intrarater and interrater reliability was moderate for both the electronic ruler and paper strips. The amplitude measurement accuracy of expert variability assessment compared with a gold standard was significantly improved (p < 0.001) with the electronic ruler versus paper strips. The accuracy of subjects' FHR variability category responses compared with the gold standard revealed no significant difference (p = 0.50) using either display type. CONCLUSION: Performance of the electronic ruler was equivalent to paper strips, which may aid assessment of variability on electronic monitors as paper strips become less prevalent.

Alpha-linolenic acid increases cholesterol efflux in macrophage-derived foam cells by decreasing stearoyl CoA desaturase 1 expression: evidence for a farnesoid-X-receptor mechanism of action.

Increased cholesterol efflux from macrophage-derived foam cells (MDFCs) is an important protective mechanism to decrease lipid load in the atherosclerotic plaque. Dietary alpha-linolenic acid (ALA), an omega-3 polyunsaturated fatty acid (PUFA), decreases circulating cholesterol, but its role in cholesterol efflux has not been extensively studied. Stearoyl CoA desaturase 1 (SCD1) is the rate-limiting enzyme in the synthesis of monounsaturated fatty acids (MUFAs). Endogenous MUFAs are preferentially incorporated into triglycerides, phospholipids and cholesteryl ester, which are abundant in atherosclerotic plaque. This study investigated the mechanisms by which ALA regulated SCD1 and subsequent effect on cholesterol storage and transport in MDFCs. Small interfering RNA (siRNA) also was applied to modify SCD1 expression in foam cells. Alpha-linolenic acid treatment and SCD1 siRNA significantly decreased SCD1 expression in MDFCs. The reduction of SCD1 was accompanied with increased cholesterol efflux and decreased intracellular cholesterol storage within these cells. Alpha-linolenic acid activated the nuclear receptor farnesoid-X-receptor, which in turn increased its target gene small heterodimer partner (SHP) expression, and decreased liver-X-receptor dependent sterol regulatory element binding protein 1c transcription, ultimately resulting in repressed SCD1 expression. In conclusion, repression of SCD1 by ALA favorably increased cholesterol efflux and decreased cholesterol accumulation in foam cells. This may be one mechanism by which dietary omega-3 PUFAs promote atherosclerosis regression.

Regulation of peroxisome proliferator-activated receptor-alpha by MDM2.

Peroxisome proliferator-activated receptor-alpha (PPARalpha) belongs to the nuclear receptor (NR) family of transcription factors and regulates lipid and glucose metabolism. Like other NRs, the regulation of gene expression by PPARalpha depends on cofactor recruitment to the transcription complex and multiple protein-protein interactions. In this study, Murine Double Minute 2 (MDM2), an E3 ubiquitin ligase, is identified as a PPARalpha-interacting protein that regulates PPARalpha transcriptional activity. MDM2 modulated the transcriptional activity of PPARalpha and PPARbeta/delta, but not PPARgamma in reporter assays. Knockdown of MDM2 by small interfering RNA in rat hepatoma cells inhibited ligand-induced mRNA levels of several PPARalpha target genes involved in lipid metabolism. MDM2 associated with PPARalpha on target gene promoters, and this association increased in response to Wy14,643 treatment. MDM2 interacted with PPARalpha and this interaction occurred with the A/B domain of PPARalpha. Coexpression of MDM2 increased PPARalpha ubiquitination and the E3 ubiquitin ligase activity of MDM2 affected PPARalpha protein expression and transcriptional activity. MDM2 expression was decreased in response to clofibrate in wild-type (WT), but not in PPARalpha null mice, indicating a PPARalpha-dependent regulation. These studies identify a role for MDM2 in regulating PPARalpha-mediated pathways of lipid metabolism.

Regulation of peroxisome proliferator-activated receptors by e6-associated protein.

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors (NRs) that regulate genes involved in lipid and glucose metabolism. PPAR activity is regulated by interactions with cofactors and of interest are cofactors with ubiquitin ligase activity. The E6-associated protein (E6-AP) is an E3 ubiquitin ligase that affects the activity of other NRs, although its effects on PPARs have not been examined. E6-AP inhibited the ligand-independent transcriptional activity of PPARalpha and PPARbeta, with marginal effects on PPARgamma, and decreased basal mRNA levels of PPARalpha target genes. Inhibition of PPARalpha activity required the ubiquitin ligase function of E6-AP, but occurred in a proteasome-independent manner. PPARalpha interacted with E6-AP, and in mice treated with PPARalpha agonist clofibrate, mRNA and protein levels of E6-AP were increased in wildtype, but not in PPARalpha null mice, indicating a PPARalpha-dependent regulation. These studies suggest coordinate regulation of E6-AP and PPARalpha, and contribute to our understanding of the role of PPARs in cellular metabolism.

Examination of Ligand-Dependent Coactivator Recruitment by Peroxisome Proliferator-Activated Receptor-alpha (PPARalpha).

The ligand-dependent recruitment of coactivators to peroxisome proliferator-activated receptor-alpha (PPARalpha) was examined. PPAR-binding protein (PBP), PPARgamma coactivator-1alpha (PGC-1alpha), steroid receptor coactivator-1 (SRC-1), and CBP/p300-interacting transactivator with ED-rich tail 2 (CITED2) affected PPARalpha activity in the presence of Wy-14,643. The effects on PPARalpha activity in light of increased or decreased expression of these coactivators were qualitatively different depending on the ligand examined. Diminished expression of PGC-1alpha, SRC-1, or PBP by RNAi plasmids affected natural or synthetic agonist activity whereas only Wy-14,643 was affected by decreased PGC-1alpha. The interaction of PPARalpha with an LXXLL-containing peptide library showed ligand-specific patterns, indicative of differences in conformational change. The association of coactivators to PPARalpha occurs predominantly via the carboxyl-terminus and mutating (456)LHPLL to (456)LHPAA resulted in a dominant-negative construct. This research confirms that coactivator recruitment to PPARalpha is ligand-dependent and that selective receptor modulators (SRMs) of this important protein are likely.

Comprehensive analysis of gene expression in rat and human hepatoma cells exposed to the peroxisome proliferator WY14,643.

Peroxisome proliferators (PPs) are an important class of chemicals that act as hepatic tumor promoters in laboratory rodents. The key target for PPs is the nuclear receptor peroxisome proliferator-activated receptor-alpha (PPARalpha) and these chemicals cause cancer by altering the expression of a subset of genes involved in cell growth regulation. The purpose of the present study was to utilize high-density gene expression arrays to examine the genes regulated by the potent PP Wy14,643 (50 microM, 6 h) in both rat (FaO) and human (HepG2) hepatoma cells. Treatment of FaO cells, but not HepG2, revealed the expected fatty acid catabolism genes. However, a larger than expected number of protein kinases, phosphatases, and signaling molecules were also affected exclusively in the FaO cells, including MAPK-phosphatase 1 (MKP-1), Janus-activated kinases 1 and 2 (JAK1 and 2), and glycogen synthetase kinase alpha and beta (GSKalpha and beta). The mRNA accumulation of these genes as well as the protein level for GSK3alpha, JAK1, and JAK2 and MKP-1 activity was corroborated. Due to the importance of MKP-1 in cell signaling, this induction was examined further and was found to be controlled, at least in part, at the level of the gene's promoter. Interestingly, overexpression of MKP-1 in turn affected the constitutive activity of PPARalpha. Taken together, the gene expression arrays revealed an important subset of PP-regulated genes to be kinases and phosphatases. These enzymes not only would affect growth factor signaling and cell cycle control but also could represent feedback control mechanisms and modulate the activity of PPARalpha.