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We evaluated the effects of a discrimination training procedure for establishing praise as a reinforcer for three children with autism spectrum disorder. After establishing two praise words as discriminative stimuli and two nonsense words as S-deltas, we evaluated whether the stimuli then functioned as reinforcers by presenting each stimulus as a consequence for a new response. The results demonstrated that previously neutral praise words functioned as reinforcers and nonsense words did not. As in previous studies on establishing reinforcers, the effects were transitory, and praise words did not continue to function as reinforcers after repeated exposure without discrimination training. Recommendations are provided for future research and maintaining reinforcement effects.

Abstract A novel model called PyIRI was recently developed. It constructs the ionospheric electron density for the entire day and on the entire global grid in one computation, which has a very low computational overhead. PyIRI introduced a novel approach to the computation of the global and diurnal functions and their matrix multiplication with Consultative Committee on International Radio (CCIR) coefficients or the International Union of Radio Science (URSI) coefficients, that enabled this global approach for the density specification. Since the International Reference Ionosphere‐based Real‐Time Assimilative Model (IRTAM) produces coefficients in a similar format as CCIR/URSI coefficients, the PyIRI computational approach was extended to work with IRTAM coefficients. This technical note describes the PyIRTAM software and provides usage examples. The PyIRTAM tool is made publicly available through PyPI and GitHub.

The adoption, of human excreta compost improves soil health and yields of crops. It also supports baobab cultivation, livelihoods, nutrition, and incomes, in a healthy sanitary safe environment. This study examines the farmers’ adoption perception of human excreta compost from the Urine Diversion Dry Toilets (UDDT). It links the compost to the cultivation of early maturing baobab seedlings. It used a random sampling to select 139 respondents from 230 households in 6 communities of Adaklu. We test for the differences between the characteristics of the participants interested in adopting and those with no interest to adopt the two technologies. The study also used a probit model to investigate the influence of the characteristics of the households on the adoption perception of two technologies. The results show that significant differences exist in the ages, cereal, roots, and tuber cultivation as well as the perception of features of baobab seedlings, between the individuals willing to adopt the compost or not. Contrarily, significant differences exist between the age, sex, farm size, cereals, root, and tuber cultivation, as well as the features of the new baobab seedlings between adopters and non-adopters. The probit model results show that years of farming experience, farm size, multiple uses of the baobab and its early fruiting nature exert positive effects on the adoption of the two technologies. Contrarily, the younger people are more likely to accept the technologies more than older ones. Also, formal education is also likely to lead to low adoption of the technologies. Besides, as the male respondents are more likely to adopt the baobab cultivation than the females, larger households could also adopt the compost than the smaller ones. The paper concludes that these factors influence the adoption perception of the respondents and, therefore, recommends that these factors should be considered in promoting the compost and the early maturing baobab seedling adoption.

Studies employing multiple-schedule arrangements to bring social approaches (e.g., requesting attention, raising hand) under stimulus control have commonly used correlated contrived, continuous stimuli with at least one condition (e.g., displaying a green stimulus when attention is available and a red stimulus when it is not). Although imposing these correlates may have advantages for teaching, it may be impractical or stigmatizing to use them indefinitely in a learner's natural environment. The purpose of the current study was to extend previous research by using rules as naturalistic schedule correlates in a multiple-schedule arrangement. We evaluated the effects of multiple schedules with spoken rules (naturalistic, noncontinuous correlates) and a written rule (contrived, continuous correlate) on social approaches in three classrooms with adolescents with a variety of special education classifications. Social approaches decreased quickly during independent work periods and remained below criterion for all participants, with a novel teacher, when the written rule was removed, and during maintenance probes. Social validity assessments with the participants and special education teachers indicated high acceptability.

Summary: Why aggressive traits evolve in some species but not in others is poorly understood. We modeled the population dynamics of the extinct Mauritius dodo and Rodrigues solitaire to examine divergent pathways in the evolution of aggression. Whereas the dodo conformed to island syndrome predictions of tameness, its sister-taxon the solitaire evolved strong sexual dimorphism and aggressive traits. We computed rates of change in island size from sea level modeling and connected island size change to population dynamics by integrating a Hawk-Dove game theory model for territory competition with a population model. We find that the rapid rate of decrease in island size likely was an important trigger for the onset of aggressive behavior and that aggressive behavior becomes fixed if a tipping point is reached where island size falls below a critical threshold.

Abstract Prey must balance resource acquisition with predator avoidance for survival and reproduction. To reduce risk of predation, prey may avoid areas with high predator use, but if they are unable to due to resource acquisition requirements, they may instead change their habitat use or movement speed to mitigate predation risk. Prey risk response may depend on spatially or temporally varying forage availability as well as seasonal variation in prey vulnerability and availability of alternate foods for predators. To quantify how prey respond to spatial and temporal variation in risk of brown bear predation, we examined Roosevelt elk (Cervus canadensis roosevelti) spatiotemporal behavior responses to brown bear (Ursus arctos) habitat use on Afognak and Raspberry islands, Alaska, using Global Positioning System location data during elk parturition (20 May–15 June), summer (16 June–20 September), and autumn (21 September–10 November). During parturition and summer, elk used forest and shrub landcover in areas of higher brown bear probability of use. During parturition, elk used areas with lower forage productivity in areas of higher bear probability of use, and movement speed decreased with higher bear probability of use, especially in shrub landcover. During summer, elk used areas with higher forage productivity in areas of higher brown bear probability of use. During autumn, elk were less likely to use areas with higher bear habitat probability of use across landcover categories and forage productivity. During summer and autumn, elk movement speed increased with higher brown bear probability of use. Elk behavioral response to risk of brown bear predation could increase energy expenditure and decrease their ability to acquire forage, therefore negatively impacting survival and reproduction with spatiotemporal variation in risk response potentially amplifying these impacts.

Abstract Sigma-2-ligands (S2L) are characterized by high binding affinities to their cognate sigma-2 receptor, overexpressed in rapidly proliferating tumor cells. As such, S2L were developed as imaging probes (ISO1) or as cancer therapeutics, alone (SV119 [C6], SW43 [C10]) and as delivery vehicles for cytotoxic drug cargoes (C6-Erastin, C10-SMAC). However, the exact mechanism of S2L-induced cytotoxicity remains to be fully elucidated. A series of high-affinity S2L were evaluated regarding their cytotoxicity profiles across cancer cell lines. While C6 and C10 displayed distinct cytotoxicities, C0 and ISO1 were essentially non-toxic. Confocal microscopy and lipidomics analysis in cellular and mouse models revealed that C10 induced increases in intralysosomal free cholesterol and in cholesterol esters, suggestive of unaltered intracellular cholesterol trafficking. Cytotoxicity was caused by cholesterol excess, a phenomenon that contrasts the effects of NPC1 inhibition. RNA-sequencing revealed gene clusters involved in cholesterol homeostasis and ER stress response exclusively by cytotoxic S2L. ER stress markers were confirmed by qPCR and their targeted modulation inhibited or enhanced cytotoxicity of C10 in a predicted manner. Moreover, C10 increased sterol regulatory element-binding protein 2 (SREBP2) and low-density lipoprotein receptor (LDLR), both found to be pro-survival factors activated by ER stress. Furthermore, inhibition of downstream processes of the adaptive response to S2L with simvastatin resulted in synergistic treatment outcomes in combination with C10. Of note, the S2L conjugates retained the ER stress response of the parental ligands, indicative of cholesterol homeostasis being involved in the overall cytotoxicity of the drug conjugates. Based on these findings, we conclude that S2L-mediated cell death is due to free cholesterol accumulation that leads to ER stress. Consequently, the cytotoxic profiles of S2L drug conjugates are proposed to be enhanced via concurrent ER stress inducers or simvastatin, strategies that could be instrumental on the path toward tumor eradication.

Modern treat-to-target management of rheumatoid arthritis (RA) involves titration of drug therapy to achieve remission, requiring close monitoring of disease activity through frequent clinical assessments. Accelerometry offers a novel method for continuous remote monitoring of RA activity by capturing fluctuations in mobility, sedentary behaviours, physical activity and sleep patterns over prolonged periods without the expense, inconvenience and environmental impact of extra hospital visits. We aimed to (a) assess the feasibility, usability and acceptability of wearable devices in patients with active RA; (b) investigate the multivariate relationships within the dataset; and (c) explore the robustness of accelerometry outcomes to downsampling to facilitate future prolonged monitoring. Eleven people with active RA newly starting an arthritis drug completed clinical assessments at 4-week intervals for 12 weeks. Participants wore an Axivity AX6 wrist device (sampling frequency 100 Hz) for 7 days after each clinical assessment. Measures of macro gait (volume, pattern and variability), micro gait (pace, rhythm, variability, asymmetry and postural control of walking), sedentary behaviour (standing, sitting and lying) and physical activity (moderate to vigorous physical activity [MVPA], sustained inactive bouts [SIBs]) and sleep outcomes (sleep duration, wake up after sleep onset, number of awakenings) were recorded. Feasibility, usability and acceptability of wearable devices were assessed using Rabinovich’s questionnaire, principal component (PC) analysis was used to investigate the multivariate relationships within the dataset, and Bland–Altman plots (bias and Limits of Agreement) and Intraclass Correlation Coefficient (ICC) were used to test the robustness of outcomes sampled at 100 Hz versus downsampled at 50 Hz and 25 Hz. Wearable devices obtained high feasibility, usability and acceptability scores among participants. Macro gait outcomes and MVPA (first PC) and micro gait outcomes and number of SIBs (second PC) exhibited the strongest loadings, with these first two PCs accounting for 40% of the variance of the dataset. Furthermore, these device metrics were robust to downsampling, showing good to excellent agreements (ICC ≥ 0.75). We identified two main domains of mobility, physical activity and sleep outcomes of people with RA: micro gait outcomes plus MVPA and micro gait outcomes plus number of SIBs. Combined with the high usability and acceptability of wearable devices and the robustness of outcomes to downsampling, our real-world data supports the feasibility of accelerometry for prolonged remote monitoring of RA disease activity.

Abstract ANCHOR is a novel assimilative model developed at the U.S. Naval Research Laboratory, which was designed for rapid assimilative runs. ANCHOR uses recently developed PyIRI model for the background and for the formation of the background covariance matrix. It only takes a few minutes for ANCHOR to complete the data assimilation (DA) for one day, including data pre‐processing and model set up. ANCHOR extracts ionospheric parameters from radio occultation (RO) and ionosonde data using PyIRI formalism and assimilates them as point measurements into maps of the background parameters using a Kalman Filter approach. This paper introduces the ANCHOR algorithm, discusses its coordinate system and background, explains the background covariance formation, discusses the extraction of the ionospheric parameters from the data and the assimilation process, and, finally, shows the results of the observing system simulation experiment with synthetic data simulated using the SAMI3 model. ANCHOR reduces the root mean square errors in the analysis by more than a half for all of the ionospheric parameters in comparison to the background. Finally, this paper discusses advantages and limitations of the parametrized ionospheric DA, highlighting the avenues for its future improvement.

Background Patients may prefer percutaneous coronary intervention (PCI) over coronary artery bypass graft (CABG) surgery, despite heart team recommendations. The outcomes in such patients have not been examined. We sought to examine the results of PCI in patients who were recommended for but declined CABG. Methods and Results Consecutive patients with stable ischemic heart disease and unprotected left main or 3‐vessel disease or Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery score >22 who underwent PCI after heart team review between 2013 and 2020 were included. Patients were categorized into 3 groups according to heart team recommendations on the basis of appropriate use criteria: (1) PCI‐recommended; (2) CABG‐eligible but refused CABG (CABG‐refusal); and (3) CABG‐ineligible. The primary end point was the composite of death, myocardial infarction, or stroke at 1 year. The study included 3687 patients undergoing PCI (PCI‐recommended, n=1718 [46.6%]), CABG‐refusal (n=1595 [43.3%]), and CABG‐ineligible (n=374 [10.1%]). Clinical and procedural risk increased across the 3 groups, with the highest comorbidity burden in CABG‐ineligible patients. Composite events within 1 year after PCI occurred in 55 (4.1%), 91 (7.0%), and 41 (14.8%) of patients in the PCI‐recommended, CABG‐refusal, and CABG‐ineligible groups, respectively. After multivariable adjustment, the risk of the primary composite outcome was significantly higher in the CABG‐refusal (hazard ratio [HR], 1.67 [95% CI, 1.08–3.56]; P=0.02) and CABG‐ineligible patients (HR, 3.26 [95% CI, 1.28–3.65]; P=0.004) groups compared with the reference PCI‐recommended group, driven by increased death and stroke. Conclusions Cardiovascular event rates after PCI were significantly higher in patients with multivessel disease who declined or were ineligible for CABG. Our findings provide real‐world data to inform shared decision‐making discussions.

Argumentation is an important component of scientific education (Osborne, 2010). However, how students create and evaluate competing arguments in scientific investigations is a complex construct, which presents significant challenges for assessment. We engaged 349 middle and high school students in a virtual scientific investigation based on an authentic problem involving the ecosystem of Yellowstone National Park. Students evaluated three possible causes for vegetation loss in Lamar Valley: tourism, global warming, and killing wolves. Students compared their responses to individual claims to formulate a final decision. The authors developed a coding system to assess student arguments and analysed how students changed their evaluations across the investigation. Four distinct levels of responses reveal the range of student decision making and patterns that have implications for instruction and assessment. Few student evaluations explained both merits and weaknesses of claims.

Abstract The International Reference Ionosphere (IRI) model is widely used in the ionospheric community and considered the gold standard for empirical ionospheric models. The development of this model was initiated in the late 1960s using the FORTRAN language; for its programming approach, the model outputs were calculated separately for each given geographic location and time stamp. The Consultative Committee on International Radio (CCIR) and International Union of Radio Science (URSI) coefficients provide the skeleton of the IRI model, as they define the global distribution of the maximum useable ionospheric frequency foF2 and the propagation factor M(3,000)F2. At the U.S. Naval Research Laboratory, a novel Python tool was developed that enables global runs of the IRI model with significantly lower computational overhead. This was made possible through the Python rebuild of the core IRI component (which calculates ionospheric critical frequency using the CCIR or URSI coefficients), taking advantage of NumPy matrix multiplication instead of using cyclic addition. This paper explains in detail this new approach and introduces all components of the PyIRI package.

Children with autism spectrum disorder (ASD) often have difficulty with personal hygiene skills, such as toothbrushing, yet there is a dearth of studies in this area demonstrating experimental control. We used a multiple-probe-across-participants design to evaluate the effectiveness of a treatment package that consisted of a picture activity schedule and a progressive prompt-delay procedure to teach toothbrushing to three children with ASD. Independent toothbrushing increased once the treatment package was introduced and maintained after treatment withdrawal. Treatment goals, procedures, and outcomes were socially accepted by parents, teachers, and graduate students. The results add to previous research by experimentally demonstrating a treatment package resulting in independent toothbrushing. These effects maintained following schedule removal and generalized to a novel setting. Future research is also discussed in applications of picture activity schedules when teaching independence with additional personal hygiene skills.

Abstract Species distribution models (SDMs) are widely applied to understand the processes governing spatial and temporal variation in species abundance and distribution but often do not account for measurement errors such as false negatives and false positives. We describe unmarked, a package for the freely available and open‐source R software that provides a complete workflow for modelling species distribution and abundance while explicitly accounting for measurement errors. Here we focus on recent advances in unmarked functionality to support multi‐species, multi‐state, and multi‐season data, as well as support for fitting models with random effects. For illustration, we present an analysis of Acadian Flycatcher Empidonax virescens abundance on Roanoke River National Wildlife Refuge, North Carolina, USA, over 18 years. We found that Acadian Flycatcher abundance was initially greater in hardwood plantation habitat relative to bottomland hardwood forest along river levees but that abundance declined over time in both habitats. We plan for unmarked development to keep pace with advances in hierarchical modelling in ecology, including better handling of continuous‐time data from camera trap and automated recording units and integrated models for multiple data streams.

Lung tumor-promoting environmental exposures and γherpesvirus infections are associated with Type 17 inflammation. To test the effect of γherpesvirus infection in promoting lung tumorigenesis, we infected mutant K-Ras-expressing (K-RasLA1) mice with the murine γherpesvirus MHV68 via oropharyngeal aspiration. After 7 weeks, the infected mice displayed a more than 2-fold increase in lung tumors relative to their K-RasLA1 uninfected littermates. Assessment of cytokines in the lung revealed that expression of Type 17 cytokines (Il-6, Cxcl1, Csf3) peaked at day 7 post-infection. These observations correlated with the post-infection appearance of known immune mediators of tumor promotion via IL-17A in the lungs of tumor-bearing mice. Surprisingly, Cd84, an immune cell marker mRNA, did not increase in MHV68-infected wild-type mice lacking lung tumors. Csf3 and Cxcl1 protein levels increased more in the lungs of infected K-RasLA1 mice relative to infected wild-type littermates. Flow cytometric and transcriptomic analyses indicated that the infected K-RasLA1 mice had increased Ly6Gdim/Ly6Chi immune cells in the lung relative to levels seen in uninfected control K-RasLA1 mice. Selective methylation of adenosines (m6A modification) in immune-cell-enriched mRNAs appeared to correlate with inflammatory infiltrates in the lung. These observations implicate γherpesvirus infection in lung tumor promotion and selective accumulation of immune cells in the lung that appears to be associated with m6A modification of mRNAs in those cells.