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Research from cognitive science and geoscience education has shown that sketching can improve spatial thinking skills and facilitate solving spatially complex problems. Yet sketching is rarely implemented in introductory geosciences courses, due to time needed to grade sketches and lack of materials that incorporate cognitive science research. Here, we report a design-centered, collaborative effort, between geoscientists, cognitive scientists, and artificial intelligence (AI) researchers, to characterize spatial learning challenges in geoscience and to design sketch activities that use a sketch-understanding program, CogSketch. We developed 26 CogSketch worksheets that use cognitive science-based principles to scaffold problem solving of spatially complex geoscience problems and report observations of an implementation in an introductory geoscience course where students used CogSketch or human-graded paper worksheets. Overall, this research highlights the principles of interdisciplinary design between cognitive scientists, geoscientists, and AI researchers that can inform the collaborative design process for others aiming to develop effective educational materials.

Glioblastoma is the most common and most aggressive primary brain tumour. Standard of care consists of surgical resection followed by radiotherapy and concomitant and maintenance temozolomide (temozolomide/radiotherapy→temozolomide). Corticosteroids are commonly used perioperatively to control cerebral oedema and are frequently continued throughout subsequent treatment, notably radiotherapy, for amelioration of side effects. The effects of corticosteroids such as dexamethasone on cell growth in glioma models and on patient survival have remained controversial. We performed a retrospective analysis of glioblastoma patient cohorts to determine the prognostic role of steroid administration. A disease-relevant mouse model of glioblastoma was used to characterize the effects of dexamethasone on tumour cell proliferation and death, and to identify gene signatures associated with these effects. A murine anti-VEGFA antibody was used in parallel as an alternative for oedema control. We applied the dexamethasone-induced gene signature to The Cancer Genome Atlas glioblastoma dataset to explore the association of dexamethasone exposure with outcome. Mouse experiments were used to validate the effects of dexamethasone on survival in vivo Retrospective clinical analyses identified corticosteroid use during radiotherapy as an independent indicator of shorter survival in three independent patient cohorts. A dexamethasone-associated gene expression signature correlated with shorter survival in The Cancer Genome Atlas patient dataset. In glioma-bearing mice, dexamethasone pretreatment decreased tumour cell proliferation without affecting tumour cell viability, but reduced survival when combined with radiotherapy. Conversely, anti-VEGFA antibody decreased proliferation and increased tumour cell death, but did not affect survival when combined with radiotherapy. Clinical and mouse experimental data suggest that corticosteroids may decrease the effectiveness of treatment and shorten survival in glioblastoma. Dexamethasone-induced anti-proliferative effects may confer protection from radiotherapy- and chemotherapy-induced genotoxic stress. This study highlights the importance of identifying alternative agents such as vascular endothelial growth factor antagonists for managing oedema in glioblastoma patients. Beyond the established adverse effect profile of protracted corticosteroid use, this analysis substantiates the request for prudent and restricted use of corticosteroids in glioblastoma.

Functional magnetic resonance imaging studies have reported reduced activation in parietotemporal and occipitotemporal areas in adults and children with developmental dyslexia compared to controls during reading and reading related tasks. These patterns of regionally reduced activation have been linked to behavioral impairments of reading-related processes (e.g., phonological skills and rapid automatized naming). The observed functional and behavioral differences in individuals with developmental dyslexia have been complemented by reports of reduced gray matter in left parietotemporal, occipitotemporal areas, fusiform and lingual gyrus and the cerebellum. An important question for education is whether these neural differences are present before reading is taught. Developmental dyslexia can only be diagnosed after formal reading education starts. However, here we investigate whether the previously detected gray matter alterations in adults and children with developmental dyslexia can already be observed in a small group of pre-reading children with a family-history of developmental dyslexia compared to age and IQ-matched children without a family-history (N = 20/mean age: 5:9 years; age range 5:1-6:5 years). Voxel-based morphometry revealed significantly reduced gray matter volume indices for pre-reading children with, compared to children without, a family-history of developmental dyslexia in left occipitotemporal, bilateral parietotemporal regions, left fusiform gyrus and right lingual gyrus. Gray matter volume indices in left hemispheric occipitotemporal and parietotemporal regions of interest also correlated positively with rapid automatized naming. No differences between the two groups were observed in frontal and cerebellar regions. This discovery in a small group of children suggests that previously described functional and structural alterations in developmental dyslexia may not be due to experience-dependent brain changes but may be present at birth or develop in early childhood prior to reading onset. Further studies using larger sample sizes and longitudinal analyses are needed in order to determine whether the identified structural alterations may be utilized as structural markers for the early identification of children at risk, which may prevent the negative clinical, social and psychological outcome of developmental dyslexia.

The prevalence of overweight and obesity is increasing worldwide, and the evidence base for a link between obesity and cancer is growing. In the United States, approximately 85,000 new cancer cases per year are related to obesity. Recent research has found that as the body mass index increases by 5 kg/m2, cancer mortality increases by 10%. Additionally, studies of patients who have had bariatric surgery for weight loss report reductions in cancer incidence and mortality, particularly for women. The goal of this review is to provide an update of recent research, with a focus on epidemiologic studies on the link between obesity and cancer. In addition, we will briefly review hypothesized mechanisms underlying the relationship between obesity and cancer. High priorities for future research involve additional work on the underlying mechanisms, and trials to examine the effect of lifestyle behavior change and weight loss interventions on cancer and intermediate biomarkers.

Computational modeling of sketch understanding is interesting both scientifically and for creating systems that interact with people more naturally. Scientifically, understanding sketches requires modeling aspects of visual processing, spatial representations, and conceptual knowledge in an integrated way. Software that can understand sketches is starting to be used in classrooms, and it could have a potentially revolutionary impact as the models and technologies become more advanced. This paper looks at one such effort, Sketch Worksheets, which have been used in multiple classroom experiments already, with students ranging from elementary school to college. Sketch Worksheets are a software equivalent of pencil and paper worksheets commonly found in classrooms, but they provide on-the-spot feedback based on what students draw. They are built on the CogSketch platform, which provides qualitative visual and spatial representations and analogical processing based on computational models of human cognition. This paper explores three issues. First, we examine how research from cognitive science and artificial intelligence, combined with the constraints of creating new kinds of educational software, led to the representations and processing in CogSketch. Second, we examine how these capabilities have been used in Sketch Worksheets, drawing upon experiments with fifth-grade students in biology and college students in engineering design and in geoscience. Finally, we examine some open issues in sketch understanding that need to be addressed to better model high-level aspects of vision, and for sketch understanding systems to reach their full potential for supporting education.

Serious dermatologic adverse events such as erythema multiforme (EM) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) have been reported in patients receiving antiepileptic drugs (AEDs) and cranial radiotherapy (RT). Given the frequency of AED-associated rashes and the infrequency of serious dermatologic adverse events after cranial RT, we sought to further assess the prevalence of cutaneous eruptions in patients receiving an AED before and after cranial RT. We reviewed medical records of patients taking AEDs while undergoing RT for a high-grade glioma and recorded demographic, disease, and treatment parameters, as well as the development of rashes. Rashes were found in 19 % of patients taking AEDs. Phenytoin was most commonly implicated (93 %) in rash formation compared with other AEDs (P < 0.0001), both before and during RT. Most rashes (76 %) occurred before starting RT (P < 0.0001). However, of those during RT, most were associated with phenytoin compared with other AEDs (P = 0.002). One case of SJS was noted in a patient receiving phenytoin prior to RT. While rashes were slightly less prevalent in patients receiving temozolomide compared with those not receiving temozolomide (3.4 vs 4.8 %), this difference was not statistically significant (P = 0.65). Rashes are relatively common in patients receiving AEDs, with the highest incidence associated with phenytoin. However, the risk of serious dermatologic events is low. There did not appear to be an association between the receipt of cranial radiotherapy and the development of AED-associated rash with phenytoin or other AEDs.

Valproic acid (VA) is an antiepileptic drug (AED) and histone deacetylase (HDAC) inhibitor taken by patients with glioblastoma (GB) to manage seizures, and it can modulate the biologic effects of radiation therapy (RT). We investigated whether VA use during RT for GB was associated with overall survival (OS).Medical records of 544 adults with GB were retrospectively reviewed. Analyses were performed to determine the association of Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA) class, seizure history, and concurrent temozolomide (TMZ) and AED use during RT with OS.Seizures before the end of RT were noted in 217 (40%) patients, and 403 (74%) were taking an AED during RT; 29 (7%) were taking VA. Median OS in patients taking VA was 16.9 months (vs 13.6 months taking another AED, P=.16). Among patients taking an AED during RT, OS was associated with VA (P=.047; hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.27-1.07), and RTOG RPA class (P.0001; HR, 1.49; 95% CI, 1.37-1.61). Of the 5 most common AEDs, only VA was associated with OS. Median OS of patients receiving VA and TMZ during RT was 23.9 months (vs 15.2 months for patients taking another AED, P=.26). When the analysis was restricted to patients who received concurrent TMZ, VA use was marginally associated with OS (P=.057; HR, 0.54; 95% CI, -0.09 to 1.17), independently of RTOG RPA class and seizure history.VA use during RT for GB was associated with improved OS, independently of RTOG RPA, seizure history, and concurrent TMZ use. Further studies of treatment that combines HDAC inhibitors and RT are warranted.

Survival of elderly patients with glioblastoma (GBM) is poor, but improves with tumor resection and radiotherapy (RT). Concurrent temozolomide (TMZ) chemotherapy during RT improves the survival of younger patients with GBM, but the benefit in elderly patients is unclear. Medical records of patients ≥65 years old with primary GBM, histologically confirmed at Memorial Sloan-Kettering Cancer Center and treated with RT, were reviewed. Survival was associated with patient (age, performance status), tumor (single or multiple), and treatment (extent of surgery, RT field, technique, fractionation and use of concurrent TMZ) characteristics in a multivariable Cox regression model. Grade ≥3 hematologic toxicity rates were compared to reported rates in younger patients. Median age of the 291 patients studied was 71 years. Longer survival was associated with younger age, tumor resection, and concomitant TMZ and RT (p < 0.01). Concurrent TMZ and RT improved median survival of patients with favorable prognostic factors from 12 to 21 months and from 10 to 13 months in patients 65–70 and ≥71 years old, respectively. Concomitant TMZ and RT increased the 2 year OS rate from 14 to 41 % and from 5 to 24 % in patients 65–70 and ≥71 years old, respectively. Grade 3–4 thrombocytopenia was significantly more frequent in the present cohort. Survival of elderly patients with GBM may be prolonged with the use of concomitant TMZ during RT. An ongoing randomized study will determine the benefit of this approach in a prospective fashion.

Within the last decade there has been an increase in the use of structural and functional magnetic resonance imaging (fMRI) to investigate the neural basis of human perception, cognition and behavior 1, 2. Moreover, this non-invasive imaging method has grown into a tool for clinicians and researchers to explore typical and atypical brain development. Although advances in neuroimaging tools and techniques are apparent, (f)MRI in young pediatric populations remains relatively infrequent 2. Practical as well as technical challenges when imaging children present clinicians and research teams with a unique set of problems 3, 2. To name just a few, the child participants are challenged by a need for motivation, alertness and cooperation. Anxiety may be an additional factor to be addressed. Researchers or clinicians need to consider time constraints, movement restriction, scanner background noise and unfamiliarity with the MR scanner environment2,4-10. A progressive use of functional and structural neuroimaging in younger age groups, however, could further add to our understanding of brain development. As an example, several research groups are currently working towards early detection of developmental disorders, potentially even before children present associated behavioral characteristics e.g.11. Various strategies and techniques have been reported as a means to ensure comfort and cooperation of young children during neuroimaging sessions. Play therapy 12, behavioral approaches 13, 14,15, 16-18 and simulation 19, the use of mock scanner areas 20,21, basic relaxation 22 and a combination of these techniques 23 have all been shown to improve the participant's compliance and thus MRI data quality. Even more importantly, these strategies have proven to increase the comfort of families and children involved 12. One of the main advances of such techniques for the clinical practice is the possibility of avoiding sedation or general anesthesia (GA) as a way to manage children's compliance during MR imaging sessions 19,20. In the current video report, we present a pediatric neuroimaging protocol with guidelines and procedures that have proven to be successful to date in young children.

Statins are a class of drugs that inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMGcoA) reductase, a critical enzyme in the mevalonate pathway. Several reports document that statins may prevent different human cancers. However, whether or not statins can prevent cancer is controversial due to discordant results. One possible explanation for these conflicting conclusions is that only some tumors or specific statins may be effective. Here, we demonstrate in an in vivo transgenic model in which atorvastatin reverses and prevents the onset of MYC-induced lymphomagenesis, but fails to reverse or prevent tumorigenesis in the presence of constitutively activated K-Ras (G12D). Using phosphoprotein fluorescence-activated cell sorter (FACS) analysis, atorvastatin treatment was found to result in the inactivation of the Ras and ERK1/2 signaling pathways associated with the dephosphorylation and inactivation of MYC. Correspondingly, tumors with a constitutively activated K-Ras (G12D) did not exhibit dephosphorylation of ERK1/2 and MYC. Atorvastatin's effects on MYC were specific to the inhibition of HMGcoA reductase, as treatment with mevalonate, the product of HMG-CoA reductase activity, abrogated these effects and inhibited the ability of atorvastatin to reverse or suppress tumorigenesis. Also, RNAi directed at HMGcoA reductase was sufficient to abrogate the neoplastic properties of MYC-induced tumors. Thus, atorvastatin, by inhibiting HMGcoA reductase, induces changes in phosphoprotein signaling that in turn prevent MYC-induced lymphomagenesis.

Evidence of reduced P3b amplitudes in chronic alcoholics and individuals at risk for developing alcoholism suggest that the P3b may be an endophenotypic marker for alcoholism. If this is the case, then long-term abstinent alcoholics (LTAAs) should exhibit reduced P3b amplitudes. Thus far, P3b studies on chronic alcoholics have focused primarily on samples with relatively short-term abstinence (less than 15 months). This study examines the amplitude and latency of the P3b and P3a event-related brain electrical components in LTAAs compared with normal controls (NCs) and whether these measures are related to alcohol use and other subject variables.Electroencephalographs (EEGs) were recorded on 48 LTAAs (mean abstinence=6.7 years) compared with 48 age-matched and gender-matched NCs during a visual P300 experiment consisting of standard, target, and rare nontarget conditions. This paradigm elicited the P3b (target condition) and the P3a (rare nontarget condition) components.Long-term abstinent alcoholics had reduced P3b amplitudes and increased P3b latencies in comparison with NCs. Long-term abstinent alcoholics also exhibited delayed P3a components, but no P3a amplitude reductions. Alcohol use variables, a family history of alcohol problems, and the duration of alcohol abstinence were not associated with any amplitude or latency variables.Even after very prolonged abstinence, reduced P3b amplitudes are present in chronic alcoholics and are not associated with any family history or alcohol use variables. These results provide equivocal support for reduced P3b amplitude being an endophenotypic marker for alcoholism, but are also consistent with P3b being affected by a threshold of alcohol abuse, with the effect not resolving over long periods of abstinence.