PlantSimLab - a modeling and simulation web tool for plant biologists.

BACKGROUND: At the molecular level, nonlinear networks of heterogeneous molecules control many biological processes, so that systems biology provides a valuable approach in this field, building on the integration of experimental biology with mathematical modeling. One of the biggest challenges to making this integration a reality is that many life scientists do not possess the mathematical expertise needed to build and manipulate mathematical models well enough to use them as tools for hypothesis generation. Available modeling software packages often assume some modeling expertise. There is a need for software tools that are easy to use and intuitive for experimentalists. RESULTS: This paper introduces PlantSimLab, a web-based application developed to allow plant biologists to construct dynamic mathematical models of molecular networks, interrogate them in a manner similar to what is done in the laboratory, and use them as a tool for biological hypothesis generation. It is designed to be used by experimentalists, without direct assistance from mathematical modelers. CONCLUSIONS: Mathematical modeling techniques are a useful tool for analyzing complex biological systems, and there is a need for accessible, efficient analysis tools within the biological community. PlantSimLab enables users to build, validate, and use intuitive qualitative dynamic computer models, with a graphical user interface that does not require mathematical modeling expertise. It makes analysis of complex models accessible to a larger community, as it is platform-independent and does not require extensive mathematical expertise.

Inhibition or Stimulation of Autophagy Affects Early Formation of Lipofuscin-Like Autofluorescence in the Retinal Pigment Epithelium Cell.

The accumulation of lipofuscin in the retinal pigment epithelium (RPE) is dependent on the effectiveness of photoreceptor outer segment material degradation. This study explored the role of autophagy in the fate of RPE lipofuscin degradation. After seven days of feeding with either native or modified rod outer segments, ARPE-19 cells were treated with enhancers or inhibitors of autophagy and the autofluorescence was detected by fluorescence-activated cell sorting. Supplementation with different types of rod outer segments increased lipofuscin-like autofluorescence (LLAF) after the inhibition of autophagy, while the induction of autophagy (e.g., application of rapamycin) decreased LLAF. The effects of autophagy induction were further confirmed by Western blotting, which showed the conversion of LC3-I to LC3-II, and by immunofluorescence microscopy, which detected the lysosomal activity of the autophagy inducers. We also monitored LLAF after the application of several autophagy inhibitors by RNA-interference and confocal microscopy. The results showed that, in general, the inhibition of the autophagy-related proteins resulted in an increase in LLAF when cells were fed with rod outer segments, which further confirms the effect of autophagy in the fate of RPE lipofuscin degradation. These results emphasize the complex role of autophagy in modulating RPE autofluorescence and confirm the possibility of the pharmacological clearance of RPE lipofuscin by small molecules.

Brain activation differences in schizophrenia during context-dependent processing of saccade tasks.

BACKGROUND: Brain function in schizophrenia has been probed using saccade paradigms and functional magnetic resonance imaging, but little information exists about how changing task context impacts saccade related brain activation and behavioral performance. We recruited schizophrenia and comparison subjects to perform saccade tasks in differing contexts: (1) two single task runs (anti- or pro-saccades alternating with fixation) and (2) one dual task run (antisaccades alternating with prosaccades). RESULTS: Context-dependent differences in saccade circuitry were evaluated using ROI analyses. Distinction between anti- and pro-saccade activation across contexts (single versus dual task) suggests that the schizophrenia group did not respond to context in the same way as the comparison group. CONCLUSIONS: Further investigation of context processing effects on brain activation and saccade performance measures informs models of cognitive deficits in the disorder and enhances understanding of antisaccades as a potential endophenotype for schizophrenia.

Resynchronising returns to service in anoestrous dairy cows in the South Island of New Zealand.

AIMS: To investigate the effect of targeted resynchronisation of cows treated for non-observed oestrus before the planned start of mating (PSM), that were not detected in oestrus or pregnant 23 days after treatment (phantom cows), on the proportion pregnant at 42 days after PSM and the end of mating. METHODS: Farm staff from eight herds in two regions of the South Island of New Zealand identified 1,819 cows not showing oestrus by 10 days before PSM. These cows were treated with intravaginal progesterone for 7 days, and I/M gonadorelin 10 days and 1 day before PSM. Three days before PSM they were injected with cloprostenol and equine chorionic gonadotrophin, with fixed time artificial insemination (FTAI) at PSM. By 23 days after PSM, 1,218 cows had not returned to oestrus. Of these, 161 cows confirmed not pregnant by transrectal ultrasonography were randomly assigned to no treatment (control group; n=74) or were resynchronised 25 days after PSM using the same treatment programme as above, with FTAI 35 days after PSM (n=87). All cows that returned to oestrus were artificially inseminated until 42 days after PSM, when natural mating was used. All cows were examined using transrectal ultrasonography 80 to 90 days after PSM to confirm conception dates. RESULTS: Of the 1,819 anoestrous cows treated before PSM, 526 (29 (95% CI=23.1-34.0)%) had not been observed in oestrus by 23 days after PSM and had not conceived, so were diagnosed as phantoms cows. For resynchronised cows, 42/87 (48 (95% CI=37.8-58.8)%) were pregnant by 42 days after PSM compared to 21/74 (28 (95% CI=18.1-38.7)%) control cows (p=0.009). At the end of mating 58/87 (67 (95% CI=56.6-76.7)%) cows in the resynchronised group were pregnant and 46/74 (62 (95% CI=50.9-73.2)%) in the control group (p=0.554). The hazard of conception from 21 to 42 days after PSM was 1.9 (95% CI=1.07-3.12) times greater for resynchronised than control cows (p=0.026). CONCLUSION: In cows not observed in oestrus and treated before PSM, resynchronisation increased the proportion pregnant by 42 days after PSM. CLINICAL RELEVANCE: The benefit of resynchronisation depends on the number of anoestrous cows before PSM and the number of phantom cows after PSM. However at the herd-level it is likely that providing advice to reduce the known risk factors for cows not being observed in oestrus before the PSM may well be more cost effective than identifying and treating a sub-population of phantom cows.

Microbes bind complement inhibitor factor H via a common site.

To cause infections microbes need to evade host defense systems, one of these being the evolutionarily old and important arm of innate immunity, the alternative pathway of complement. It can attack all kinds of targets and is tightly controlled in plasma and on host cells by plasma complement regulator factor H (FH). FH binds simultaneously to host cell surface structures such as heparin or glycosaminoglycans via domain 20 and to the main complement opsonin C3b via domain 19. Many pathogenic microbes protect themselves from complement by recruiting host FH. We analyzed how and why different microbes bind FH via domains 19-20 (FH19-20). We used a selection of FH19-20 point mutants to reveal the binding sites of several microbial proteins and whole microbes (Haemophilus influenzae, Bordetella pertussis, Pseudomonas aeruginosa, Streptococcus pneumonia, Candida albicans, Borrelia burgdorferi, and Borrelia hermsii). We show that all studied microbes use the same binding region located on one side of domain 20. Binding of FH to the microbial proteins was inhibited with heparin showing that the common microbial binding site overlaps with the heparin site needed for efficient binding of FH to host cells. Surprisingly, the microbial proteins enhanced binding of FH19-20 to C3b and down-regulation of complement activation. We show that this is caused by formation of a tripartite complex between the microbial protein, FH, and C3b. In this study we reveal that seven microbes representing different phyla utilize a common binding site on the domain 20 of FH for complement evasion. Binding via this site not only mimics the glycosaminoglycans of the host cells, but also enhances function of FH on the microbial surfaces via the novel mechanism of tripartite complex formation. This is a unique example of convergent evolution resulting in enhanced immune evasion of important pathogens via utilization of a "superevasion site."

Challenges of optimizing glycaemic control in children with Type 1 diabetes: a qualitative study of parents' experiences and views.

AIMS: To explore the difficulties parents encounter in trying to achieve clinically recommended blood glucose levels and how they could be better supported to optimize their child's glycaemic control. METHODS: In-depth interviews were conducted with 54 parents of children with Type 1 diabetes (≤ 12 years). Data were analysed thematically. RESULTS: Parents described being reluctant and finding it difficult to keep their child's blood glucose levels consistently within clinically recommended ranges. As well as worrying about their child's ability to detect/report hypoglycaemia, parents highlighted a multitude of factors that had an impact on their child's blood glucose levels and over which they could exercise little control. These included: leaving their child with other caregivers who could not be trusted to detect hypoglycaemia; difficulties remotely monitoring and regulating their child's food consumption and activity; and physical and social changes accompanying childhood development. Most parents used two sets of blood glucose targets, with clinically recommended targets employed when their child was in their immediate care and higher targets when in the care of others. Parents described health professionals as lacking understanding of the difficulties they encountered keeping blood glucose within target ranges and needing more empathetic, tailored and realistic advice. CONCLUSION: It is not parents' fear of hypoglycaemia in isolation that leads to decisions to raise their child's blood glucose but, rather, parental fear in conjunction with other factors and considerations. Hence, to improve diabetes management in children, these factors may need to be addressed; for instance, by training others in diabetes management and using new technologies. Changes to consultations are also recommended.

Light-dependent phosphorylation of Bardet-Biedl syndrome 5 in photoreceptor cells modulates its interaction with arrestin1.

Arrestins are dynamic proteins that move between cell compartments triggered by stimulation of G-protein-coupled receptors. Even more dynamically in vertebrate photoreceptors, arrestin1 (Arr1) moves between the inner and outer segments according to the light conditions. Previous studies have shown that the light-driven translocation of Arr1 in rod photoreceptors is initiated by rhodopsin through a phospholipase C/protein kinase C (PKC) signaling cascade. The purpose of this study is to identify the PKC substrate that regulates the translocation of Arr1. Mass spectrometry was used to identify the primary phosphorylated proteins in extracts prepared from PKC-stimulated mouse eye cups, confirming the finding with in vitro phosphorylation assays. Our results show that Bardet-Biedl syndrome 5 (BBS5) is the principal protein phosphorylated either by phorbol ester stimulation or by light stimulation of PKC. Via immunoprecipitation of BBS5 in rod outer segments, Arr1 was pulled down; phosphorylation of BBS5 reduced this co-precipitation of Arr1. Immunofluorescence and immunoelectron microscopy showed that BBS5 principally localizes along the axonemes of rods and cones, but also in photoreceptor inner segments, and synaptic regions. Our principal findings in this study are threefold. First, we demonstrate that BBS5 is post-translationally regulated by phosphorylation via PKC, an event that is triggered by light in photoreceptor cells. Second, we find a direct interaction between BBS5 and Arr1, an interaction that is modulated by phosphorylation of BBS5. Finally, we show that BBS5 is distributed along the photoreceptor axoneme, co-localizing with Arr1 in the dark. These findings suggest a role for BBS5 in regulating light-dependent translocation of Arr1 and a model describing its role in Arr1 translocation is proposed.

A multifaceted pharmacist intervention to improve antihypertensive adherence: a cluster-randomized, controlled trial (HAPPy trial).

WHAT IS KNOWN AND OBJECTIVES: About half of all patients taking antihypertensives discontinue treatment by 12 months. There is potential for substantial health gains at both individual and population levels through improved treatment adherence. The objective was to evaluate a community pharmacist intervention to improve adherence with antihypertensive medicines with a view to improving blood pressure (BP) control. DESIGN: prospective, non-blinded, cluster-randomized, controlled trial. PARTICIPANTS: adults with primary hypertension who obtained antihypertensives in the previous 6 months. Patients with poor refill adherence were preferentially identified with the help of a purpose-built software application. INTERVENTION: package comprising BP monitor; training on BP self-monitoring; motivational interviewing; medication use review; prescription refill reminders. FOLLOW-UP: six months. PRIMARY OUTCOME: change in proportion self-reporting medication adherence. Secondary outcome: BP changes. RESULTS: Participants (n = 395; intervention - 207; control - 188) had a mean age of 66.7 years; 51.1% were males. The proportion of adherent participants increased in both groups but was not significantly different between groups [57·2% to 63·6% (control) vs. 60·0% to 73·5% (intervention), P = 0·23]. The mean reduction in systolic BP was significantly greater in the intervention group (10·0 mmHg vs. 4·6 mmHg; P = 0·05). The proportion of patients who were non-adherent at baseline and adherent at 6 months was 22·6% (95%CI 5·1-40·0%) higher in the intervention group (61·8% vs. 39·2%, P = 0·007). Among participants with baseline BP above target, reduction of systolic BP was significantly greater in the intervention group [by 7·2 mmHg (95%CI 1·6-12·8 mmHg); (P = 0·01)]. Among participants non-adherent at baseline and above target BP, the proportion reporting adherence at 6 months was significantly greater in the intervention group [56·8% vs. 35·9%, P = 0·039). WHAT IS NEW AND CONCLUSION: This community pharmacist intervention resulted in improved adherence to antihypertensive medication and reduced systolic BP.

Geographic and temporal trends in pediatric and young adult brain tumors in Kentucky, 1995-2019.

INTRODUCTION: Pediatric and young adult brain tumors (PYBT) account for a large share of cancer-related morbidity and mortality among children in the United States, but their etiology is not well understood. Previous research suggests the Appalachian region of Kentucky has high rates of PYBT. This study explored PYBT incidence over 25 years in Kentucky to identify geographic and temporal trends and generate hypotheses for future research. METHODS: The Kentucky Cancer Registry contributed data on all PYBT diagnosed among those aged 0-29 during years 1995-2019. Age- and sex-adjusted spatio-temporal scan statistics-one for each type of PYBT, and one for all types-comprised the primary analysis. These results were mapped along with environmental and occupational data. RESULTS: Findings indicated that north-central Kentucky and the Appalachian region experienced higher rates of some PYBT. High rates of astrocytomas were clustered in a north-south strip of central Kentucky toward the end of the study period, while high rates of other specified types of intracranial and intraspinal neoplasms were significantly clustered in eastern Kentucky. The area where these clusters overlapped, in north-central Kentucky, had significantly higher rates of PYBT generally. DISCUSSION: This study demonstrates north-central Kentucky and the Appalachian region experienced higher PYBT risk than the rest of the state. These regions are home to some of Kentucky's signature industries, which should be examined in further research. Future population-based and individual-level studies of genetic factors are needed to explore how the occupations of parents, as well as prenatal and childhood exposures to pesticides and air pollutants, impact PYBT incidence.

Formation of lipofuscin-like material in the RPE Cell by different components of rod outer segments.

The mechanisms that control the natural rate of lipofuscin accumulation in the retinal pigment epithelial (RPE) cell and its stability over time are not well understood. Similarly, the contributions of retinoids, phospholipids and oxidation to the rate of accumulation of lipofuscin are uncertain. The experiments in this study were conducted to explore the individual contribution of rod outer segments (ROS) components to lipofuscin formation and its accumulation and stability over time. During the period of 14 days incubation of ROS, lipofuscin-like autofluorescence (LLAF) determined at two wavelengths (530 and 585 nm) by fluorescence-activated cell sorting (FACS) was measured from RPE cells. The autofluorescence increased in an exponential manner with a strong linear component between days 1 and 7. The magnitude of the increase was larger in cells incubated with 4-hydroxynonenal (HNE-ROS) compared with cells incubated with either bleached or unbleached ROS, but with a different spectral profile. A small (10-15%) decrease in LLAF was observed after stopping the ROS feeding for 14 days. The phagocytosis rate of HNE-ROS was higher than that of either bleached or unbleached ROS during the first 24 h of supplementation. Among the different ROS components, the increase of LLAF was highest in cells incubated with all-trans-retinal. Surprisingly, incubation with 11-cis-retinal and 9-cis-retinal also resulted in strong LLAF increase, comparable to the increase induced by all-trans-retinal. Supplementation with liposomes containing phosphatidylethanolamine (22: 6-PE) and phosphatidylcholine (18:1-PC) also increased LLAF, while incubation with opsin had little effect. Cells incubated with retinoids demonstrated strong dose-dependence in LLAF increase, and the magnitude of the increase was 2-3 times higher at 585 nm compared to 530 nm, while cells incubated with liposomes showed little dose-dependence and similar increase at both wavelengths. Very little difference in LLAF was noted between cells incubated with either unbleached or bleached ROS under any conditions. In summary, results from this study suggest that supplementation with various ROS components can lead to an increase in LLAF, although the autofluorescence generated by the different classes of components has distinct spectral profiles, where the autofluorescence induced by retinoids results in a spectral profile closest to the one observed from human lipofuscin. Future fluorescence characterization of LLAF in vitro would benefit from an analysis of multiple wavelengths to better match the spectral characteristics of lipofuscin in vivo.

Uveitis-associated epitopes of retinal antigens are pathogenic in the humanized mouse model of uveitis and identify autoaggressive T cells.

Noninfectious uveitis is a leading cause of blindness and thought to involve autoimmune T cell responses to retinal proteins (e.g., retinal arrestin [soluble-Ag (S-Ag)]). There are no known biomarkers for the disease. Susceptibility is associated with HLA, but little is known about susceptible class II alleles or the potentially pathogenic epitopes that they present. Using a humanized HLA-transgenic mouse model of S-Ag-induced autoimmune uveitis, we identified several susceptible and resistant alleles of HLA-DR and -DQ genes and defined pathogenic epitopes of S-Ag presented by the susceptible alleles. The sequences of these epitopes overlap with some previously identified peptides of S-Ag ("M" and "N"), known to elicit memory responses in lymphocytes of uveitis patients. HLA-DR-restricted, S-Ag-specific CD4(+) T cells could be detected in blood and draining lymph nodes of uveitic mice with HLA class II tetramers and transferred the disease to healthy mice. Importantly, tetramer-positive cells were detected in peripheral blood of a uveitis patient. To our knowledge, these findings provide the first tangible evidence that an autoimmune response to retina is causally involved in pathogenesis of human uveitis, demonstrating the feasibility of identifying and isolating retinal Ag-specific T cells from uveitis patients and may facilitate their development as biomarkers for the disease.

Representations of Complexity: How Nature Appears in Our Theories.

In science we study processes in the material world. The way these processes operate can be discovered by conducting experiments that activate them, and findings from such experiments can lead to functional complexity theories of how the material processes work. The results of a good functional theory will agree with experimental measurements, but the theory may not incorporate in its algorithmic workings a representation of the material processes themselves. Nevertheless, the algorithmic operation of a good functional theory may be said to make contact with material reality by incorporating the emergent computations the material processes carry out. These points are illustrated in the experimental analysis of behavior by considering an evolutionary theory of behavior dynamics, the algorithmic operation of which does not correspond to material features of the physical world, but the functional output of which agrees quantitatively and qualitatively with findings from a large body of research with live organisms.

Creating and Studying the Behavior of Artificial Organisms Animated by an Evolutionary Theory of Behavior Dynamics.

The evolutionary theory of behavior dynamics (ETBD) is a complexity theory, which means that it is stated in the form of simple low-level rules, the repeated operation of which generates high-level outcomes that can be compared to data. The low-level rules of the theory implement Darwinian processes of selection, reproduction, and mutation. This tutorial is an introduction to the ETBD for a general audience, and illustrates how the theory is used to animate artificial organisms that can behave continuously in any experimental environment. Extensive research has shown that the theory generates behavior in artificial organisms that is indistinguishable in qualitative and quantitative detail from the behavior of live organisms in a wide variety of experimental environments. An overview and summary of this supporting evidence is provided. The theory may be understood to be computationally equivalent to the biological nervous system, which means that the algorithmic operation of the theory and the material operation of the nervous system give the same answers. The applied relevance of the theory is also discussed, including the creation of artificial organisms with various forms of psychopathology that can be used to study clinical problems and their treatment. Finally, possible future directions are discussed, such as the extension of the theory to behavior in a two-dimensional grid world.

A test of the evolutionary theory's account of punishment superimposed on single-alternative schedules.

A test of the evolutionary theory was conducted by replicating Bradshaw et al.'s (1977, 1978, 1979) experiments in which human participants worked on single-alternative variable-interval (VI) schedules of reinforcement under three punishment conditions: no punishment, superimposed VI punishment, and superimposed variable-ratio (VR) punishment. Artificial organisms (AOs) animated by the theory worked in the same environments. Four principal findings were reported for the human participants: (1) their behavior was well described by an hyperbola in all conditions, (2) the asymptote of the hyperbola under VI punishment was equal to the asymptote in the absence of punishment, but the asymptote under VR punishment was lower than the asymptote in the absence of punishment, (3) the parameter in the denominator of the hyperbola was larger under both VI and VR punishment than in the absence of punishment, and (4) response suppression under punishment was greater at lower than at higher reinforcement frequencies. These four outcomes were also observed in the behavior of the AOs working in the same environments, thereby confirming the theory's first-order predictions about the effects of punishment on single-alternative responding.

Emotional scene processing in biotypes of psychosis.

Social-emotional deficits in psychosis may be indexed by deviations in emotional scene processing, but event-related potential (ERP) studies indicate such deviations may not map cleanly to diagnostic categories. Neurobiologically defined psychosis subgroups offer an alternative that may better capture neurophysiological correlates of social-emotional deficits. The current study investigates emotional scene-elicited ERPs in Biotypes of psychosis in a large (N = 622), well-characterized sample. Electroencephalography was recorded in healthy persons (N = 129), Biotype-1 (N = 195), Biotype-2 (N = 131), and Biotype-3 (N = 167) psychosis cases. ERPs were measured from posterior and centroparietal scalp locations. Neural responses to emotional scenes were compared between healthy and psychosis groups. Multivariate group discrimination analyses resulted in two composite variates that differentiated groups. The first variate displayed large differences between low-cognition (Biotype-1, Biotype-2) and intact-cognition groups (Biotype-3, healthy persons). The second indicated a small-to-moderate distinction of Biotypes-2 and -3 from Biotype-1 and healthy persons. Two multivariate correlations were identified indicating associations between 1) self-reported emotional experience and generalized cognition and 2) socio-occupational functioning and late-stage emotional processing. Psychosis Biotypes displayed emotional processing deficits not apparent in DSM psychosis subgroups. Future translational research may benefit from exploring emotional scene processing in such neurobiologically-defined psychosis groups.

Empirical Matching, Matching Theory, and an Evolutionary Theory of Behavior Dynamics in Clinical Application.

This article provides an overview of highlights from 60 years of basic research on choice that are relevant to the assessment and treatment of clinical problems. The quantitative relations developed in this research provide useful information about a variety of clinical problems including aggressive, antisocial, and delinquent behavior, attention-deficit/hyperactivity disorder (ADHD), bipolar disorder, chronic pain syndrome, intellectual disabilities, pedophilia, and self-injurious behavior. A recent development in this field is an evolutionary theory of behavior dynamics that is used to animate artificial organisms (AOs). The behavior of AOs animated by the theory has been shown to conform to the quantitative relations that have been developed in the choice literature over the years, which means that the theory generates these relations as emergent outcomes, and therefore provides a theoretical basis for them. The theory has also been used to create AOs that exhibit specific psychopathological behavior, the assessment and treatment of which has been studied virtually. This modeling of psychopathological behavior has contributed to our understanding of the nature and treatment of the problems in humans.

Evolutionary theory prediction: Response rate as a joint function of reinforcement rate and reinforcer magnitude.

Artificial organisms (AOs) animated by an evolutionary theory of behavior dynamics (ETBD) worked on concurrent interval schedules with a standard reinforcer magnitude on 1 alternative and a range of reinforcer magnitudes on the other. The reinforcer magnitudes on the second alternative were hedonically scaled using the generalized matching law. The AOs then worked on single interval schedules that arranged various combinations of the scaled reinforcer magnitudes and a range of nominal schedule values. This produced bivariate response rate data to which 5 candidate equations were fitted. One equation was found to provide the best description of the bivariate data in terms of percentage of variance accounted for, information criterion value, and residual profile. This equation consisted of 2 factors, 1 entailing the scaled magnitude, 1 entailing the obtained reinforcement rate, and both expressed in the form of exponentiated hyperbolas. The theory's prediction of the bivariate equation, along with additional predictions of the theory, were tested on data from an experiment in which rats pressed levers for various concentrations of sucrose pellets. The bivariate equation predicted by the theory was confirmed, as were all the additional predictions of the theory that could be tested on this data set.

Modeling Subtypes of Automatically Reinforced Self-Injurious Behavior with the Evolutionary Theory of Behavior Dynamics.

The subtypes of automatically reinforced self-injurious behavior (ASIB) delineated by Hagopian and colleagues (Hagopian et al., 2015; 2017) demonstrated how functional-analysis (FA) outcomes may predict the efficacy of various treatments. However, the mechanisms underlying the different patterns of responding obtained during FAs and corresponding differences in treatment efficacy have remained unclear. A central cause of this lack of clarity is that some proposed mechanisms, such as differences in the reinforcing efficacy of the products of ASIB, are difficult to manipulate. One solution may be to model subtypes of ASIB using mathematical models of behavior in which all aspects of the behavior can be controlled. In the current study, we used the evolutionary theory of behavior dynamics (ETBD; McDowell, 2019) to model the subtypes of ASIB, evaluate predictions of treatment efficacy, and replicate recent research aiming to test explanations for subtype differences. Implications for future research related to ASIB are discussed.

Methodological improvements to a Procedure for Rapidly Establishing Steady-State Behavior.

We performed three experiments to improve the quality and retention of data obtained from a Procedure for Rapidly Establishing Steady-State Behavior (PRESS-B; Klapes et al., 2020). In Experiment 1, 120 participants worked on nine concurrent random-interval random-interval (conc RI RI) schedules and were assigned to four conditions of varying changeover delay (COD) length. The 0.5-s COD condition group exhibited the fewest instances of exclusive reinforcer acquisition. Importantly, this group did not differ in generalized matching law (GML) fit quality from the other groups. In Experiment 2, 60 participants worked on nine conc RI RI schedules with a wider range of scheduled reinforcement rate ratios than was used in Experiment 1. Participants showed dramatic reductions in exclusive reinforcer acquisition. Experiment 3 entailed a replication of Experiment 2 wherein blackout periods were implemented between the schedule presentations and each schedule remained in operation until at least one reinforcer was acquired on each alternative. GML fit quality was slightly more consistent in Experiment 3 than in the previous experiments. Thus, these results suggest that future PRESS-B studies should implement a shorter COD, a wider and richer scheduled reinforcement rate ratio range, and brief blackouts between schedule presentations for optimal data quality and retention.