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Number-recognition tasks, such as the how-many task, involve set-to-word mapping, and number-creation tasks, such as the give-n task, entail word-to-set mapping. The present study involved comparing sixty 3-year-olds' performance on the two tasks with collections of one to three items over three time points about 3 weeks apart. Inconsistent with the sparse evidence indicating equivalent task performance, an omnibus test indicated that success differed significantly by task (and set size but not by time). A follow-up analysis indicated that the hypothesis that success emerges first on the how-many task was, in general, significantly superior to the hypothesis of simultaneous development. It further indicated the how-many-first hypothesis was superior to a give-n-first hypothesis for sets of three. A theoretical implication is that set-to-word mapping appears to develop before word-to-set mapping, especially in the case of three. A methodological implication is that the give-n task may underestimate a key aspect of children's cardinal understanding of small numbers. Another is that the traditional give-n task, which requires checking an initial response by one-to-one counting, confounds pre-counting and counting competencies.

To mediate critical host-microbe interactions in the human small intestine, Paneth cells constitutively produce abundant levels of α-defensins and other antimicrobials. We report that the expression profile of these antimicrobials is dramatically askew in human small intestinal organoids (enteroids) as compared to that in paired tissue from which they are derived, with a reduction of α-defensins to nearly undetectable levels. Murine enteroids, however, recapitulate the expression profile of Paneth cell α-defensins seen in tissue. WNT/TCF signaling has been found to be instrumental in the regulation of α-defensins, yet in human enteroids exogenous stimulation of WNT signaling appears insufficient to rescue α-defensin expression. By stark contrast, forkhead box O (FOXO) inhibitor AS1842856 induced the expression of α-defensin mRNA in enteroids by >100,000-fold, restoring DEFA5 and DEFA6 to levels comparable to those found in primary human tissue. These results newly identify FOXO signaling as a pathway of biological and potentially therapeutic relevance for the regulation of human Paneth cell α-defensins in health and disease.

Abstract Purpose To report a case series of patients with uveitic glaucoma who were treated with micropulse transscleral cyclophotocoagulation (mpCPC). Methods This retrospective case series consists of patients from the University of Colorado Sue Anschutz-Rodgers Eye Center from 2015 to 2020 who were diagnosed with uveitic glaucoma. Information collected includes demographic data, type of uveitis, glaucoma severity, and prior glaucoma surgeries. Pre- and postoperative best corrected visual acuity, intraocular pressure (IOP), glaucoma medications, degree of inflammation, and uveitis therapies were included up to 36 months postoperatively. Surgical success was defined as an IOP reduction of 30% with achievement of IOP goal using the same number of glaucoma medications or less at 6 months or 1 year. Uveitis success was defined as the absence of persistent anterior uveitis at 3 months. Results Six patients and seven eyes with uveitic glaucoma underwent mpCPC. Types of uveitis included idiopathic anterior uveitis, HLA-B27-associated anterior uveitis, varicella zoster virus anterior uveitis, juvenile idiopathic arthritis-associated chronic anterior uveitis, lichen planus-associated intermediate uveitis, and sarcoidosis-associated panuveitis. Two of six eyes (33.3%) at 6 months and three of five eyes (60%) at 1 year achieved surgical success. Around 6 months postoperatively, two out of seven eyes (28.6%) required Ahmed glaucoma valve placement (n = 1) or repeat mpCPC (n = 1). One eye (14.3%) required phacoemulsification with goniotomy followed by an Ahmed glaucoma valve 18 months after mpCPC. There were no cases of persistent anterior uveitis, hypotony, or phthisis after mpCPC in this cohort. Conclusions Micropulse transscleral cyclophotocoagulation may safely reduce intraocular pressure in some patients with uveitic glaucoma without exacerbation of intraocular inflammation. Multiple treatments may be required to achieve longer-term success.

Abstract Background Regulations put in place to protect the privacy of individuals receiving substance use disorder (SUD) treatment have resulted in an unintended consequence of siloed SUD treatment and referral information outside of the integrated electronic health record (EHR). Recent revisions to these regulations have opened the door to data integration, which creates opportunities for enhanced patient care and more efficient workflows. We report on the experience of one safety-net hospital system integrating SUD treatment data into the EHR. Methods SUD treatment and referral information was integrated from siloed systems into the EHR through the implementation of a referral order, treatment episode definition, and referral and episode-related tools for addiction therapists and other clinicians. Integration was evaluated by monitoring SUD treatment episode characteristics, patient characteristics, referral linkage, and treatment episode retention before and after integration. Satisfaction of end-users with the new tools was evaluated through a survey of addiction therapists. Results After integration, three more SUD treatment programs were represented in the EHR. This increased the number of patients that could be tracked as initiating SUD treatment by 250%, from 562 before to 1,411 after integration. After integration, overall referral linkage declined (74% vs. 48%) and treatment episode retention at 90-days was higher (45% vs. 74%). Addiction therapists appreciated the efficiency of having all SUD treatment information in the EHR but did not find that the tools provided a large time savings shortly after integration. Conclusions Integration of SUD treatment program data into the EHR facilitated both care coordination in patient treatment and quality improvement initiatives for treatment programs. Referral linkage and retention rates were likely modified by a broader capture of patients and changed outcome definition criteria. Greater preparatory workflow analysis may decrease initial end-user burden. Integration of siloed data, made possible given revised regulations, is essential to an efficient hub-and-spoke model of care, which must standardize and coordinate patient care across multiple clinics and departments.

Background Excess nitrogen (N) loading to coastal ecosystems impairs estuarine water quality. Land management decisions made within estuarine watersheds have a direct impact on downstream N delivery. Natural features within watersheds can act as landscape sinks for N, such as wetlands, streams and ponds that transform dissolved N into gaseous N, effectively removing it from the aquatic system. Identifying and evaluating these landscape sinks and their spatial relationship to N sources can help managers understand the effects of alternative decisions on downstream resources. Methods The N-Sink approach uses widely available GIS data to identify landscape sinks within HUC-12 (or larger) catchments, estimate their N removal potential and map the effect of those sinks on N movement through the catchment. Static maps are produced to visualize N removal efficiency, transport and delivery, the latter in the form of an index. The R package nsink was developed to facilitate data acquisition, processing and visualization. Results nsink creates static maps for a specific HUC-12, or users can visit the University of Connecticut website to explore previously mapped areas. Users can investigate specific flowpaths interactively by clicking on any location within the catchment. A flowpath is generated with a table describing N removal along each segment. We describe the motivation behind developing nsink, discuss implementation in R, and present two use case examples. nsink is available from https://github.com/USEPA/nsink. Conclusions N-Sink is a decision support tool created for local decision-makers and NGOs to facilitate better understanding of the relationship between land use and downstream N delivery. Local decision-makers that have prioritized N mitigation in their long-term planning can use nsink to better understand the potential impact of proposed development projects, zoning variances, and land acquisition or restoration. nsink also allows resource economists to investigate the tradeoffs among different, often costly, N reduction strategies.

Although reformers have embraced learning trajectories (LT, also called learning progressions) as an important tool for improving mathematics education, the efficacy and assumptions of LT-based instruction are largely unproven. The aim of a recently completed research project was to fill this void. Fulfilling this aim was more challenging than many supporters of LT-based instruction might imagine. A total of 10 experiments were untaken, of which 5 demonstrated that LT-based instruction was significantly more efficacious than a counterfactual involving either a Teach-to-Target/Skip-Level approach (Assumption 1) or the same unordered activities (Assumption 2). The results of the remaining studies were non-significant either for theoretical (2) or methodological (3) reasons. In the five indicating LTs' efficacy, we found that some LTs consists of levels that are facilitative conditions for the next higher level and, thus, may be helpful but perhaps not necessary for the subsequent level.

Abstract Introduction The annulus fibrosus (AF) of the Intervertebral disc (IVD) is composed of concentric lamellae of helically wound collagen fibers. Understanding the spatial variation of collagen fiber orientations in these lamellae, and the resulting material anisotropy, is crucial to predicting the mechanical behavior of the complete IVD. Methods This study builds on a prior model predicated on path‐independent displacement of fiber endpoints during vertebral body growth to predict a complete, three‐dimensional annulus fibrosus fiber network from a small number of subject‐independent input parameters and vertebral endplate topographies obtained from clinical imaging. To evaluate the model, it was first fit to mid‐plane fiber orientations obtained using polarized light microscopy in a population of bovine caudal discs for which computed tomography images vertebral endplates were also available. Additionally, the model was used to predict the trajectories based on human lumbar disc geometries and results were compared to previously reported data. Finally, the model was employed to investigate potential disc‐related variations in fiber angle distributions. Results The model was able to accurately predict experimentally measured fiber distributions in both bovine and human discs using only endplate topography and three input parameters. Critically, the model recapitulated previously observed asymmetry between the inclinations of right‐ and left‐handed fibers in the posterolateral aspect of the human AF. Level to level variation of disc height and aspect ratio in the human lumbar spine was predicted to affect absolute values of fiber inclination, but not this asymmetry. Conclusion Taken together these results suggest that patient‐specific distributions of AF fiber orientation may be readily incorporated into computational models of the spine using only disc geometry and a small number of subject‐independent parameters.