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Background: Population pharmacokinetic (PK) studies of busulfan in children have shown that individualized model-based algorithms provide improved targeted busulfan therapy when compared with conventional dose guidelines. The adoption of population PK models into routine clinical practice has been hampered by the tendency of pharmacologists to develop complex models too impractical for clinicians to use. The authors aimed to develop a population PK model for busulfan in children that can reliably achieve therapeutic exposure (concentration at steady state) and implement a simple model-based tool for the initial dosing of busulfan in children undergoing hematopoietic cell transplantation. Patients and Methods: Model development was conducted using retrospective data available in 90 pediatric and young adult patients who had undergone hematopoietic cell transplantation with busulfan conditioning. Busulfan drug levels and potential covariates influencing drug exposure were analyzed using the nonlinear mixed effects modeling software, NONMEM. The final population PK model was implemented into a clinician-friendly Microsoft Excel-based tool and used to recommend initial doses of busulfan in a group of 21 pediatric patients prospectively dosed based on the population PK model. Results: Modeling of busulfan time-concentration data indicates that busulfan clearance displays nonlinearity in children, decreasing up to approximately 20% between the concentrations of 250-2000 ng/mL. Important patient-specific covariates found to significantly impact busulfan clearance were actual body weight and age. The percentage of individuals achieving a therapeutic concentration at steady state was significantly higher in subjects receiving initial doses based on the population PK model (81%) than in historical controls dosed on conventional guidelines (52%) (P = 0.02). Conclusions: When compared with the conventional dosing guidelines, the model-based algorithm demonstrates significant improvement for providing targeted busulfan therapy in children and young adults.

The NASA/IPAC Teacher Archive Research Program (NITARP) provides a year-long authentic astronomy research project by partnering a research astronomer with small groups of educators. NITARP has worked with a total of 103 educators since 2005. In this paper, surveys are explored that were obtained from 74 different educators, at up to four waypoints during the course of 13 months, from the class of 2010 through the class of 2017; those surveys reveal how educator participants describe the major changes and outcomes in themselves fostered by NITARP. Three-quarters of the educators self-report some or major changes in their understanding of the nature of science. The program provides educators with experience collaborating with astronomers and other educators, and forges a strong link to the astronomical research community; the NITARP community of practice encourages and reinforces these linkages. During the experience, educators get comfortable with learning complex new concepts, with ~40% noting in their surveys that their approach to learning has changed. Educators are provided opportunities for professional growth; at least 12% have changed career paths substantially in part due to the program, and 14% report that the experience was "life changing." At least 60% express a desire to include richer, more authentic science activities in their classrooms. This work illuminates what benefits the program brings to its participants; the NITARP approach could be mirrored in similar professional development programs in other STEM subjects.

[This paper is part of the Focused Collection on Astronomy Education Research.] The NASA/IPAC Teacher Archive Research Program (NITARP) partners small groups of educators with a research astronomer for a year-long authentic research project. This program aligns well with the characteristics of high-quality professional development (PD) programs and has worked with a total of 103 educators since 2005. In this paper, surveys were explored that were obtained from 74 different educators, at up to four waypoints during the course of 13 months, incorporating data from the class of 2010 through the class of 2017. This paper investigates how participating teachers describe their motivations for participating in NITARP as evidenced in these feedback forms. Analysis of self-reported data allows a mapping onto a continuum ranging from more inward focused to more outward focused; there is a shift from more inward-focused responses to more outward-focused responses. This insight into teacher motivations has implications for how the educators might be supported during their year with the program. This work provides a new way of parametrizing why educators participate in PD programs that require a considerable investment of time. NITARP, since it has many qualities of successful PD, serves as a model for similar PD programs in other STEM subjects. Likewise, the analysis method might also be useful to similarly evaluate other PD programs.

The article discusses the potential use of tazarotene and bexarotene as therapeutic agents for multiple sulfatase deficiency (MSD), an ultra-rare neurodegenerative lysosomal disorder. MSD is caused by mutations in the SUMF1 gene, resulting in impaired function of the formylglycine-generating enzyme (FGE) and reduced activity of cellular sulfatases. The researchers conducted a high-throughput screening assay and found that tazarotene and bexarotene increased sulfatase activities, improved cellular markers of disease, and normalized lysosomal size and position in MSD patient-derived cells. These findings suggest that these drugs could be repurposed as a therapy for MSD patients. [Extracted from the article]

There is convincing evidence that targeting self-efficacy is an effective means of increasing physical activity. However, evidence concerning which are the most effective techniques for changing self-efficacy and thereby physical activity is lacking. The present review aims to estimate the association between specific intervention techniques used in physical activity interventions and change obtained in both self-efficacy and physical activity behaviour. A systematic search yielded 27 physical activity intervention studies for "healthy" adults that reported self-efficacy and physical activity data. A small, yet significant (P less than 0.01) effect of the interventions was found on change in self-efficacy and physical activity (d = 0.16 and 0.21, respectively). When a technique was associated with a change in effect sizes for self-efficacy, it also tended to be associated with a change (r[subscript s] = 0.690, P less than 0.001) in effect size for physical activity. Moderator analyses found that "action planning", "provide instruction" and "reinforcing effort towards behaviour" were associated with significantly higher levels of both self-efficacy and physical activity. "Relapse prevention" and "setting graded tasks" were associated with significantly lower self-efficacy and physical activity levels. This meta-analysis provides evidence for which psychological techniques are most effective for changing self-efficacy and physical activity.