39 research outputs found
Enhancing preschoolers' executive functions through embedding cognitive activities in shared book reading
Given evidence that early executive functioning sets the stage for a broad range of subsequent
outcomes, researchers have sought to identify ways to foster these cognitive capacities. An
increasingly common approach involves computerized ‘brain training’ programs, yet there are
questions about whether these are well suited for fostering the early development of executive
functions (EFs). The current series of studies sought to design, develop, and provide evidence for the
efficacy of embedding cognitive activities in a commonplace activity – shared reading of a children’s
book. The book, Quincey Quokka’s Quest, required children to control their thinking and behaviour to
help the story’s main character through a series of obstacles. The first study investigated effects of
reading with embedded cognitive activities in individual and group contexts on young children’s
executive functions (EFs). The second study compared reading with embedded cognitive activities
against a more-active control condition (dialogic reading) that similarly engaged children in the
reading process yet lacked clear engagement of EFs. The third study sought to investigate whether the
effect of reading the story with embedded EF activities changed across differing doses of the
intervention and whether effects persisted 2 months post-intervention. Findings provide converging
evidence of intervention effects on working memory and shifting in as little as 3 weeks (compared to
more traditional reading) and maintenance of these gains 2 months later. This suggests the efficacy of
embedding cognitive activities in the context of everyday activities, thereby extending the range of
users and contexts in which this approach can be used
Providing alcohol-related screening and brief interventions to adolescents through health care systems: Obstacles and solutions
Duncan Clark and Howard Moss identify obstacles to alcohol-related screening and treatment for adolescents and propose policy solutions
Climatic and geographic predictors of life history variation in Eastern Massasauga (Sistrurus catenatus): A range-wide synthesis
Elucidating how life history traits vary geographically is important to understanding variation in population dynamics. Because many aspects of ectotherm life history are climate-dependent, geographic variation in climate is expected to have a large impact on population dynamics through effects on annual survival, body size, growth rate, age at first reproduction, size-fecundity relationship, and reproductive frequency. The Eastern Massasauga (Sistrurus catenatus) is a small, imperiled North American rattlesnake with a distribution centered on the Great Lakes region, where lake effects strongly influence local conditions. To address Eastern Massasauga life history data gaps, we compiled data from 47 study sites representing 38 counties across the range. We used multimodel inference and general linear models with geographic coordinates and annual climate normals as explanatory variables to clarify patterns of variation in life history traits. We found strong evidence for geographic variation in six of nine life history variables. Adult female snout-vent length and neonate mass increased with increasing mean annual precipitation. Litter size decreased with increasing mean temperature, and the size-fecundity relationship and growth prior to first hibernation both increased with increasing latitude. The proportion of gravid females also increased with increasing latitude, but this relationship may be the result of geographically varying detection bias. Our results provide insights into ectotherm life history variation and fill critical data gaps, which will inform Eastern Massasauga conservation efforts by improving biological realism for models of population viability and climate change
Antitumor Activity of MEDI3726 (ADCT-401), a Pyrrolobenzodiazepine Antibody-drug Conjugate Targeting PSMA, in Pre-clinical Models of Prostate Cancer
Prostate specific membrane antigen (PSMA) is a membrane bound glutamate carboxypeptidase that is highly expressed in nearly all prostate cancers with the highest expression in metastatic castration-resistant prostate cancer (mCRPC). The prevalence of increased surface expression and constitutive internalization of PSMA make it an attractive target for an antibody-drug conjugate (ADC) approach to treating patients with mCRPC. MEDI3726 (previously known as ADCT-401) is an ADC consisting of an engineered version of the anti-PSMA antibody J591 site-specifically conjugated to the pyrrolobenzodiazepine (PBD) dimer tesirine. MEDI3726 specifically binds the extracellular domain of PSMA and, once internalized, releases the PBD dimer to crosslink DNA and trigger cell death. In vitro, MEDI3726 demonstrated potent and specific cytotoxicity in a panel of PSMA-positive prostate cancer cell lines, consistent with internalization and DNA interstrand crosslinking. In vivo, MEDI3726 showed robust antitumor activity against the LNCaP and the castration-resistant CWR22Rv1 prostate cancer cell line xenografts. MEDI3726 also demonstrated durable antitumor activity in the PSMA-positive human prostate cancer patient-derived xenograft (PDX) LuCaP models. This activity correlated with increased phosphorylated Histone H2AX in tumor xenografts treated with MEDI3726. MEDI3726 is being evaluated in a Phase 1 clinical trial as a treatment for patients with metastatic castrate-resistant prostate cancer (NCT02991911)