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Understanding and treating human diseases require valid animal models. Leveraging the genetic diversity in rhesus macaque populations across eight primate centers in the United States, we conduct targeted-sequencing on 1845 individuals for 374 genes linked to inherited human retinal and neurodevelopmental diseases. We identify over 47,000 single nucleotide variants, a substantial proportion of which are shared with human populations. By combining rhesus and human allele frequencies with established variant prediction methods, we develop a machine learning-based score that outperforms established methods in predicting missense variant pathogenicity. Remarkably, we find a marked number of loss-of-function variants and putative deleterious variants, which may lead to the development of rhesus disease models. Through phenotyping of macaques carrying a pathogenic OPA1:p.A8S variant, we identify a genetic model of autosomal dominant optic atrophy. Finally, we present a public website housing variant and genotype data from over two thousand rhesus macaques.

Nontuberculous mycobacteria (NTM) infections are increasing globally and have thus become pathogens of substantial public health concern (1). However, because of scarce public health reporting, little is known about epidemiologic [...]

PurposeWe sought to define the role of Wwtr1 in murine ocular structure and function and determine the role of mechanotransduction in Fuchs' endothelial corneal dystrophy (FECD), with emphasis on interactions between corneal endothelial cells (CEnCs) and Descemet's membrane (DM).MethodsA Wwtr1 deficient mouse colony was established, and advanced ocular imaging, atomic force microscope (AFM), and histology/immunofluorescence were performed. Corneal endothelial wound healing was assessed using cryoinjury and phototherapeutic keratectomy in Wwtr1 deficient mice. Expression of WWTR1/TAZ was determined in the corneal endothelium from normal and FECD-affected patients; WWTR1 was screened for coding sequence variants in this FECD cohort.ResultsMice deficient in Wwtr1 had reduced CEnC density, abnormal CEnC morphology, softer DM, and thinner corneas versus wildtype controls by 2 months of age. Additionally, CEnCs had altered expression and localization of Na/K-ATPase and ZO-1. Further, Wwtr1 deficient mice had impaired CEnC wound healing. The WWTR1 transcript was highly expressed in healthy human CEnCs comparable to other genes implicated in FECD pathogenesis. Although WWTR1 mRNA expression was comparable between healthy and FECD-affected patients, WWTR1/TAZ protein concentrations were higher and localized to the nucleus surrounding guttae. No genetic associations were found in WWTR1 and FECD in a patient cohort compared to controls.ConclusionsThere are common phenotypic abnormalities seen between Wwtr1 deficient and FECD-affected patients, suggesting that Wwtr1 deficient mice could function as a murine model of late-onset FECD. Despite the lack of a genetic association between FECD and WWTR1, aberrant WWTR1/TAZ protein subcellular localization and degradation may play critical roles in the pathogenesis of FECD.

BACKGROUND: Currently available semiautomated insulin-delivery systems require individualized insulin regimens for the initialization of therapy and meal doses based on carbohydrate counting for routine operation. In contrast, the bionic pancreas is initialized only on the basis of body weight, makes all dose decisions and delivers insulin autonomously, and uses meal announcements without carbohydrate counting. METHODS: In this 13-week, multicenter, randomized trial, we randomly assigned in a 2:1 ratio persons at least 6 years of age with type 1 diabetes either to receive bionic pancreas treatment with insulin aspart or insulin lispro or to receive standard care (defined as any insulin-delivery method with unblinded, real-time continuous glucose monitoring). The primary outcome was the glycated hemoglobin level at 13 weeks. The key secondary outcome was the percentage of time that the glucose level as assessed by continuous glucose monitoring was below 54 mg per deciliter; the prespecified noninferiority limit for this outcome was 1 percentage point. Safety was also assessed. RESULTS: A total of 219 participants 6 to 79 years of age were assigned to the bionic-pancreas group, and 107 to the standard-care group. The glycated hemoglobin level decreased from 7.9% to 7.3% in the bionic-pancreas group and did not change (was at 7.7% at both time points) in the standard-care group (mean adjusted difference at 13 weeks, -0.5 percentage points; 95% confidence interval [CI], -0.6 to -0.3; P

PurposeTo define the normal range of central corneal thickness (CCT) and corneal endothelial cell density (ECD) in rhesus macaques (Macaca mulatta) and the effects of age, body weight, sex, and intraocular pressure (IOP) on these parameters.MethodsOphthalmic examinations were performed on 144 rhesus macaques without anterior segment pathology. The CCT was measured via ultrasound pachymetry (USP) and specular microscopy, and the ECD was semiautomatically and manually counted using specular microscopy. Rebound tonometry was used to measure IOP. Linear regression and mixed-effects linear regression models were used to evaluate the effects of age, body weight, sex, and IOP on CCT and ECD.ResultsWe included 98 females and 46 males with an age range of 0.2 to 29.4 years. The mean CCT by USP and specular microscopy were 483 ± 39 and 463 ± 33 µm, respectively, and were statistically different (P < 0.001). The ECDs were 2717 ± 423 and 2747 ± 438 cells/mm2 by semiautomated and manual analysis, respectively. Corneal endothelial degeneration was identified in one aged rhesus macaque.ConclusionsThe mean USP and specular microscopy CCT values differed significantly, whereas the semiautomatic and manual ECD did not. The CCT was associated with the IOP and sex, whereas the ECD was associated with body weight and age (P < 0.05). As in humans, corneal disease in rhesus macaques is uncommon.Translational relevanceEstablishing reference values is fundamental to use rhesus macaques as a model for corneal disease or to identify toxicity in studies of ocular drugs or devices.

Research shows that students benefit when they explain their mathematical reasoning (e.g., Booth et al., 2015); however, not all students will do this on their own without being prompted (Berthold, Eysink, & Renkl, 2009). Self-explanation prompts are questions posed to a student that encourage the student to explain what they have learned (Rittle-Johnson, Loehr, & Durkin, 2017). While self-explanation prompts can be used in a variety of ways in the classroom, this article will focus on the use of these prompts conjoined with worked-examples; in such cases, students are asked to study a worked-example--an example of a potential solution to a mathematics problem that is already completed--and are then prompted to explain the reasoning behind the procedure used to solve the problem (see Figure 1 for an example). These worked-examples and self-explanation prompts are presented to students in the form of a worksheet, with the expectation that students will explain the reasoning of others through their writing. This task is suggested as an alternative type of classroom activity that teachers could use rather than a string of traditional practice problems. This article provides instructions for creating and revising your own self-explanation prompts for your students. It then describes how these prompts are aligned with the Australian Curriculum: Mathematics (Australian Curriculum, Assessment & Reporting Authority [ACARA], n.d.), the benefits of using self-explanation prompts paired with worked-examples, and teachers' perspectives on using this tool. [This article was published in "Australian Primary Mathematics Classroom" (EJ1288974).]

Fraction knowledge and algebraic skill are closely linked. Algebra is a gatekeeper for advanced courses (Booth & Newton, 2012; Brown & Quinn, 2007). This study uses the person-centered approach of latent profile analysis to examine individual differences in middle schoolers' (N = 350) algebra performance at the end of the year (EOY). The relative importance of a range of fraction skills is considered in predicting the likelihood of displaying a particular profile of EOY algebra knowledge, measured by feature knowledge, equation encoding, equation solving, and word-problem skills. Notably, fraction number line estimation did not predict algebra performance on any of the four measures. Fraction arithmetic at the beginning of the year is most predictive of displaying the highest performing EOY algebra profile.

Recent studies have established that students knowledge about fractions is predictive of their readiness, performance, andlearning in Algebra (Booth & Newton, 2012; Booth, Newton, & Twiss-Garrity, 2013). However, it is yet unknown whetherthe relationship between fractions and algebra is causal; that is, would improving students’ knowledge of fractions causeimprovements in their ability to perform in and learn Algebra? The present study examines the impact of improvingfraction computation and fraction magnitude knowledge in real world classrooms on middle school students’ learningof key concepts and problem-solving techniques in Algebra. Individual differences in the impact of improved fractionknowledge will also be investigated and discussed.

Scientific writing is a rewarding, challenging, and necessary part of research. Building skills in scientific writing is critical in graduate student training and provides the foundation for scientific communication at all professional levels. Despite the importance of writing in research, this skill remains a barrier to success for many students. We have developed a practical approach to minimize scientific writing barriers using student-driven, peer-exchange in combination with concrete project goals and dedicated writing group times for a graduate Scientific Writing course. Course topics were drawn from self-identified student challenge areas and presented using in-class activities and discussion. Students selected their semester-long project on which to work, including research proposals, thesis chapters, and manuscripts. Students exchanged two rounds of peer review that provided overview comments and detailed editorial feedback. At each stage of their project, students built on their previous work in response to peer and instructor feedback. All students made progress on their individual projects and the majority improved their skills in at least one challenge area. This student-directed approach to scientific writing offers an opportunity to empower students to improve their writing skills with an emphasis on establishing consistent writing habits that will benefit students throughout their professional careers. [ABSTRACT FROM AUTHOR]

Aims: There is a need to increase representation of diverse older adults in health‐related qualitative research to better understand and improve chronic disease care over the lifespan. Our aim was to elicit perspectives about research recruitment among a diverse sample of older adults with diabetes participating in a qualitative study. Methods: Older adults with diabetes and caregivers were recruited through purposive sampling for semi‐structured interviews focused on diabetes self care. Six questions were used to explore recruitment strategies and recommendations for engaging older adults in research. We analysed interview transcripts using descriptive analysis to identify themes related to engaging older adults in research studies. Results: Seventeen older adults with diabetes and three caregivers participated (N = 20). Descriptive analysis revealed four themes: (1) Recruitment of older adults requires varied strategies to overcome barriers to engagement and participation; (2) Building and leveraging personal relationships is central to successful recruitment; (3) Transparent communication about the research process and value of the study is needed to inform and motivate older adults to participate; and (4) Research offers a connection to a broader community: sharing, learning and helping others. Conclusions: We found four main themes related to the complexity of recruiting older adults for research studies. These insights may inform more effective, equitable and inclusive recruitment efforts targeted at older adults in the future. [ABSTRACT FROM AUTHOR]

OBJECTIVE We characterized the receipt of diabetes specialty care and management services among older adults with diabetes. RESEARCH DESIGN AND METHODS Using a 20% random sample of fee-for-service Medicare beneficiaries aged ≥65 years, we analyzed cohorts of type 1 diabetes (T1D) or type 2 diabetes (T2D) with history of severe hypoglycemia (HoH), and all other T2D annually from 2015 to 2019. Outcomes were receipt of office-based endocrinology care, diabetes education, outpatient diabetes health services, excluding those provided in primary care, and any of the aforementioned services. RESULTS In the T1D cohort, receipt of endocrinology care and any service increased from 25.9% and 29.2% in 2015 to 32.7% and 37.4% in 2019, respectively. In the T2D with HoH cohort, receipt of endocrinology care and any service was 13.9% and 16.4% in 2015, with minimal increases. Age, race/ethnicity, residential setting, and income were associated with receiving care. CONCLUSIONS These findings suggest that many older adults may not receive specialty diabetes care and underscore health disparities. [ABSTRACT FROM AUTHOR]

Numerical magnitude knowledge is related to current math abilities and predictive of future math learning. However, this relationship has previously been shown only for knowledge of positive magnitudes; the present study is the first, to our knowledge, to examine the connection between magnitude knowledge and math ability with negative integers. In the current study, 8th Grade Algebra I students (n = 154) were given assessments of their algebra and negative sign knowledge and 2 number line tasks, an all negative (-10,000 to 0) and a bidirectional scale (-1,000 to 1,000) as part of a pretest and posttest surrounding their unit on 2-step equation solving. Results show that students' negative sign and numerical magnitude knowledge are associated with their current, or pretest, algebra performance. However, only negative magnitude knowledge from the bidirectional number line was predictive of improvement in students' overall algebra knowledge. These findings illustrate differences between knowledge of positive and negative magnitudes and provide support for the integrated theory of numerical development.

This study explores primary school aged children's perspectives and experiences of their Emotional Literacy Support Assistant (ELSA) support. Thematic analysis was employed to analyse qualitative data from semi-structured interviews with 12 Key Stage 2 participants, who had had a minimum of one month's ongoing ELSA support. Four core themes were identified: positive relationships, unique qualities, facilitates skill development, and positive impact. The findings suggest the importance of a positive therapeutic relationship with an ELSA, and that children value ELSAs teaching specific individualised coping strategies in particular. The findings may also be pertinent to practitioners outside of ELSA related work, highlighting the importance of listening to children of all ages and employing alternative methods, such as drawing, to support them in sharing their views. Since the evidence base for ELSA support is limited, this study contributes children's views to this area, and should be used to inform future research.

An abundance of empirical evidence has amassed supporting the effectiveness of having students explain why correctproblem solutions are correct (Aleven & Koedinger, 2002; Hilbert, Renkl, Kessler, & Reiss, 2008) as well as why incor-rect problem solutions are incorrect (Durkin & Rittle-Johnson, 2012; Grosse & Renkl, 2006). However, despite strongtheoretical background for the approaches (e.g., Sweller, 1999; Siegler, 2002) and the growing amount of empirical ev-idence collected in real-world classrooms for students in middle school and above (e.g., Adams et al., 2014; Booth etal, 2015) it is yet unknown whether prompting self-explanation of correct and incorrect examples could be effectivelytranslated for elementary school mathematics classroom. In this project, we worked with elementary school teachers andmathematics coaches to construct developmentally appropriate worked-example assignments for 4th graders; the presentstudy tests the effectiveness of these collaboratively developed assignments for different topics in ethnically diverse 4thgrade classrooms.