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There is increasing interest in the therapeutic potential of psilocybin. In rodents, the serotonin precursor, 5-hydroxytryptophan (5-HTP) and psilocybin induce a characteristic 5-HT2A receptor (5-HT2AR)-mediated head twitch response (HTR), which is correlated with the human psychedelic trip. We examined the role of other serotonergic receptors and the trace amine -associated receptor 1 (TAAR1) in modulating 5-HTP- and psilocybin-induced HTR. Male C57BL/6J mice (11 weeks, ~30 g) were administered 5-HTP, 50–250 mg/kg i.p., 200 mg/kg i.p. after pretreatment with 5-HT/TAAR1 receptor modulators, psilocybin 0.1–25.6 mg/kg i.p. or 4.4 mg/kg i.p., immediately preceded by 5-HT/TAAR1 receptor modulators. HTR was assessed in a custom-built magnetometer. 5-HTP and psilocybin induced a dose-dependent increase in the frequency of HTR over 20 min with attenuation by the 5-HT2AR antagonist, M100907, and the 5-HT1AR agonist, 8-OH-DPAT. The 5-HT2CR antagonist, RS-102221, enhanced HTR at lower doses but reduced it at higher doses. The TAAR1 antagonist, EPPTB, reduced 5-HTP- but not psilocybin-induced HTR. We have confirmed the key role of 5-HT2AR in HTR, an inhibitory effect of 5-HT1AR, a bimodal contribution of 5-HT2CR and a role of TAAR1 in modulating HTR induced by 5-HTP. Compounds that modulate psychedelic-induced HTR have important potential in the emerging therapeutic use of these compounds.

Educators aim to equip students with learning strategies they can apply when approaching new problems on their own. Teaching design-thinking strategies may support this goal. A first test would show that the strategies are good for learning and that students spontaneously transfer them beyond classroom instruction. To examine this, we introduce choice-based assessments (CBAs). CBAs measure how people learn when there is minimal guidance and they must make decisions as independent learners. Here, sixth-grade students completed multiple design activities that emphasized either seeking constructive criticism or exploring a space of alternatives. Afterward, they completed the CBAs, which measured strategy transfer. Results showed that lower-achieving students benefitted most from instruction, exhibiting a relative increase in their use of design-thinking strategies. In addition, strategy choices correlated with prior achievement measures and appeared to mediate performance in and learning from the CBAs. The choices to use the two strategies themselves were not correlated, which indicates that they are not subsets of a larger construct, such as growth mindset. In sum, CBAs enabled a double demonstration: design-thinking strategies may improve learning and problem solving, and design-thinking instruction may improve the likelihood of lower-achieving students choosing to use effective strategies in novel settings that require new learning.

Decreases in children's anger reactivity because of the onset of their autonomous use of strategies characterizes the prevailing model of the development of emotion regulation in early childhood (Kopp, 1989). There is, however, limited evidence of the varied pathways that mark this development and their proposed antecedents and consequences. This study used a person-centered approach to identify such pathways, antecedents, and outcomes. A sample of 120 children from economically strained rural and semirural households were observed while waiting to open a gift at ages 24, 36, and 48 months. Multitrajectory modeling of children's anger expressions and strategy use yielded three subgroups. As they aged, typically developing children's strategy use (calm bids and focused distraction) increased while anger expressions decreased. Later developing children, though initially elevated in anger expression and low in strategy use, demonstrated marked growth across indicators and did not differ from typically developing children at 48 months. At-risk children, despite developing calm bidding skills, did not display longitudinal self-distraction increases or anger expression declines. Some predicted antecedents (12–24 month child language skills and language-capitalizing parenting practices) and outcomes (age 5 years externalizing behavior) differentiated pathways. Findings illustrate how indicator-specific departures from typical pathways signal risk for behavior problems and point to pathway-specific intervention opportunities.

The increasing number of emerging adults with diabetes (EAWD) being cared for in adult health care settings requires a better understanding of the needs of EAWD and their interactions with adult health care providers (HCPs). This article describes findings from interviews with endocrinologists and diabetes nurses from a safety-net health care system to investigate HCPs' perspectives regarding influences on EAWD self-management and HCP interactions with EAWD. HCPs frequently perceived lower EAWD engagement in diabetes management, which was complicated by barriers such as the emotional burden of diabetes, busy lives and multiple responsibilities, and limited access to resources; however, HCPs valued the role of information and communication at visits in tailoring care for EAWD. Measures to tailor care should address the psychosocial burden related to the life stage goals and priorities of EAWD, identification of resources for EAWD and HCPs, and further elucidation of effective self-management guidance and communication strategies to support EAWD in safety-net settings.

Nocturnal enuresis is a prevalent and challenging problem in children and young adults with sickle cell disease (SCD). Limited progress has been made in elucidating etiology and pathophysiology of nocturnal enuresis in individuals with SCD. Among adults with SCD ages 18-20 years, approximately 9% report nocturnal enuresis. Nocturnal enuresis contributes to decreased health related quality of life in people with SCD, resulting in low self-esteem and sometimes social isolation. Postulated non-mutually exclusive causes of nocturnal enuresis in individuals with SCD include hyposthenuria leading to nocturnal polyuria, decreased bladder capacity or nocturnal bladder overactivity, increased arousal thresholds, and sleep disordered breathing. No evidence-based therapy for nocturnal enuresis in SCD exists. This review is focused on describing the natural history, postulated causes and a rational approach to the evaluation and management of nocturnal enuresis in children and adults with SCD.

This paper describes the data release of the Sloan Digital Sky Survey-II (SDSS-II) Supernova Survey conducted between 2005 and 2007. Light curves, spectra, classifications, and ancillary data are presented for 10,258 variable and transient sources discovered through repeat ugriz imaging of SDSS Stripe 82, a 300 deg2 area along the celestial equator. This data release is comprised of all transient sources brighter than r 22.5 mag with no history of variability prior to 2004. Dedicated spectroscopic observations were performed on a subset of 889 transients, as well as spectra for thousands of transient host galaxies using the SDSS-III BOSS spectrographs. Photometric classifications are provided for the candidates with good multi-color light curves that were not observed spectroscopically, using host galaxy redshift information when available. From these observations, 4607 transients are either spectroscopically confirmed, or likely to be, supernovae, making this the largest sample of supernova candidates ever compiled. We present a new method for SN host-galaxy identification and derive host-galaxy properties including stellar masses, star formation rates, and the average stellar population ages from our SDSS multi-band photometry. We derive SALT2 distance moduli for a total of 1364 SN Ia with spectroscopic redshifts as well as photometric redshifts for a further 624 purely photometric SN Ia candidates. Using the spectroscopically confirmed subset of the three-year SDSS-II SN Ia sample and assuming a flat ΛCDM cosmology, we determine M = 0.315 0.093 (statistical error only) and detect a non-zero cosmological constant at 5.7 .

Synergistic learning combining computational thinking (CT) and STEM has proven to be an effective method for advancing learning and understanding in a number of STEM domains and simultaneously helping students develop important CT concepts and practices. We adopt a design-based approach to develop, evaluate, and refine our Collaborative, Computational STEM (C2STEM) learning environment. The system adopts a novel paradigm that combines visual model building with a domain-specific modeling language (DSML) to scaffold learning of high school physics using a computational modeling approach. In this paper, we discuss the design principles that guided the development of our open-ended learning environment (OELE) using a learning-by-modeling and evidence-centered approach for curriculum and assessment design. Students learn by building models that describe the motion of objects, and their learning is supported by scaffolded tasks and embedded formative assessments that introduce them to physics and CT concepts. We have also developed preparation for future learning (PFL) assessments to study students’ abilities to generalize and apply CT and science concepts and practices across problem solving tasks and domains. We use mixed quantitative and qualitative analysis methods to analyze student learning during a semester-long study run in a high school physics classroom. We document some of the lessons learned from this study and discuss directions for future work.

MicroRNAs are small noncoding RNAs that recognize and bind to partially complementary sites in the 3′ untranslated regions of target genes in animals and, by unknown mechanisms, regulate protein production of the target transcript 1 , 2 , 3 . Different combinations of microRNAs are expressed in different cell types and may coordinately regulate cell-specific target genes. Here, we present PicTar, a computational method for identifying common targets of microRNAs. Statistical tests using genome-wide alignments of eight vertebrate genomes, PicTar's ability to specifically recover published microRNA targets, and experimental validation of seven predicted targets suggest that PicTar has an excellent success rate in predicting targets for single microRNAs and for combinations of microRNAs. We find that vertebrate microRNAs target, on average, roughly 200 transcripts each. Furthermore, our results suggest widespread coordinate control executed by microRNAs. In particular, we experimentally validate common regulation of Mtpn by miR-375 , miR-124 and let-7b and thus provide evidence for coordinate microRNA control in mammals.

Background: While the number of emerging adults with diabetes (EAWD) increases, health outcomes among EAWD remain suboptimal with frequent rates of poor glycemic control. Interventions are needed to facilitate age-appropriate care for EAWD. Event history calendars (EHC) have been used to facilitate patient provider communication and contextualized care. The purpose of this study was to investigate perspectives of EAWD and healthcare providers regarding diabetes self-management influences and EAWD-provider diabetes visit interactions and to develop an EHC tailored for EAWD diabetes care visits. Methods: The study used a mixed method exploratory sequential design. Focus groups and interviews with EAWD and interviews with healthcare providers from a public healthcare system were conducted to identify influences on self-management as well as perspectives on current and desired interactions with diabetes providers. Qualitative findings were used to inform EHC development. In quantitative follow up, EAWD and providers reviewed the EHC for content validity, feasibility, and utility for clinical use, including cognitive benefits for EAWD and communication benefits for EAWD and providers.Results: EAWD and providers both identified intrapersonal, interpersonal, and structural influences on diabetes self-management. Both EAWD and providers described psychological burden complicated by life stage tasks and responsibilities associated with emerging adulthood as well as resource barriers to optimal management. Providers perceived lack of EAWD engagement as a challenge to EAWD care. Both EAWD and providers perceived that additional value could be gained from EAWD-provider interactions and valued the importance of the EAWD-provider relationship in care. The EHC was well received by EAWD and providers in regard to feasibility and utility. EHC topics rated as highly relevant by both EAWD and providers included diabetes supplies, medications, physical activity, stress, and diet. Several other EHC topics may require additional review, and feasibility could be improved with revision.Conclusions: EAWD and providers value tailored, contextualized information for diabetes care. With additional assessment and development, an EAWD specific EHC may provide a feasible tool to improve diabetes care and communication for EAWD at diabetes visits.