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This article describes a study in which 53 teachers participating in arts-based professional development courses and workshops gained a profound understanding of the role of the arts in education and an appreciation for the powerful role the arts can play in pedagogy and social justice. The findings of study demonstrate how arts-based instructional approaches contributed to the teachers' perceptions about the importance of students' active engagement in the learning process (i.e., the importance of student voice) and the role of higher-order thinking in providing all children the possibility of success in learning. We discuss how the described study was based on action research and how the participants' perspectives were discerned from their writings using document analysis.

In this article, the authors describe the outcomes of a Continuing Professional Development (CPD) course that offered a pedagogical innovation called "Imagination Quest." This CPD course was a part of a 2-year project entitled Teaching to Reach Potential. Participants were all from Montgomery County (Maryland) Public Schools' (MCPS') Program of Assessment, Diagnosis, and Instruction (PADI) schools, an Early Recognition of Potential program whose goal is to identify and nurture potential abilities among those elementary school students most frequently overlooked because of socio-economic, cultural, and/or linguistic differences so that some of them might move on into programs of giftedness and talent. Teachers of PADI students must be willing to acquire and utilize a variety of innovative instructional strategies that recognize learning differences in order to nurture and challenge each and every one of these young people. The CPD course methodology, "Imagination Quest" (IQ), offered this pedagogical innovation. "Imagination Quest" is a performing and visual arts-based teaching and learning model whose purpose is to provide host school teachers with innovative arts-based instructional tools and strategies that can be applied to their existing curriculum and personal pedagogy, that link to learner outcomes in content areas and in the arts, and that foster gains in their students' academic achievement. (Contains 2 tables and 4 endnotes.)

Aims: Preclinical studies of MR309, a selective sigma‐1 receptor (σ1R) antagonist, support a potential role in treating neuropathic pain. We report 2 studies that provide insight into the pharmacokinetics (PK) and brain σ1R binding of MR309. Methods: Steady‐state PK of MR309 (400 mg once daily and 200 mg twice‐daily [BID] for 10 days; EudraCT 2015–001818‐99 [PK study]) and the relationship between MR309 plasma exposure and brain σ1R occupancy (EudraCT 2017–000670‐11 [positron emission tomography study]) were investigated in healthy volunteers. Positron emission tomography using the σ1R ligand [11C]SA4503 was conducted at baseline, and 2 and 8 hours after a single dose of MR309 (200–800 mg). The relationship between brain σ1R occupancy and MR309 exposure was explored using data‐driven model fitting. Results: MR309 was well tolerated, brain σ1R occupancy ranged between 30.5 and 74.9% following single‐dose MR309 (n = 7). MR309 BID provided a plasma PK profile with less fluctuation than once daily dosing (n = 16). MR309 200 mg BID yielded average steady state plasma concentrations between 2000 and 4000 ng/mL in the PK study, which corresponded to an estimated brain σ1R occupancy of 59–74%. Conclusion: MR309 200 mg BID dose was below the 75% σ1R occupancy threshold expected to elicit maximal antinociceptive effect as observed in neuropathic pain models. Further investigations of MR309 for neuropathic pain will require higher brain σ1R occupancy, and establish the optimal dose by elucidating the clinical impact of a broad range of brain σ1R occupancy across different neuropathic pain indications. [ABSTRACT FROM AUTHOR]

Mitochondrial complex I (MC-I) is an essential regulator of brain bioenergetics and can be quantified in the brain using PET radioligand 18F-BCPP-EF. Here we evaluate the test–retest reproducibility of 18F-BCPP-EF in humans, and assess the use of a non-invasive quantification method (standardised uptake value ratio – SUVR). Thirty healthy volunteers had a 90-min dynamic 18F-BCPP-EF scan with arterial blood sampling, five of which received a second scan to be included in the test–retest analysis. Time-activity curves (TAC) were analysed using multilinear analysis 1 (MA1) and the two-tissue compartment model (2TC) to estimate volumes of distribution (VT). Regional SUVR-1 values were calculated from the 70 to 90-min TAC data using the centrum semiovale as a pseudo reference region, and compared to kinetic analysis-derived outcome measures. The mean absolute test–retest variability of VT ranged from 12% to 18% across regions. Both DVR-1and SUVR-1 had improved test–retest variability in the range 2%–7%. SUVR-1 was highly correlated with DVR-1 (r2 = 0.97, n = 30). In conclusion, 18F-BCPP-EF has suitable test–retest reproducibility and can be used to quantify MC-I in clinical studies. [ABSTRACT FROM AUTHOR]

Purpose: GSK2647544 is a potent and specific inhibitor of lipoprotein-associated phospholipase A2 (Lp-PLA2), which was in development as a potential treatment for Alzheimer's disease (AD). In order to refine therapeutic dose predictions and confirm brain penetration, a radiolabelled form of the inhibitor, [18F]GSK2647544, was manufactured for use in a positron emission tomography (PET) biodistribution study.Procedures: [18F]GSK2647544 was produced using a novel, copper iodide (Cu(I)) mediated, [18F]trifluoromethylation methodology. Healthy male subjects (n = 4, age range 34-42) received an oral dose of unlabelled GSK2647544 (100 mg) and after 2 h an intravenous (iv) injection of [18F]GSK2647544 (average injected activity and mass were 106 ± 47 MBq and 179 ± 55 μg, respectively) followed by dynamic PET scans for 120 min. Defined regions of interest (ROI) throughout the brain were used to obtain regional time-activity curves (TACs) and compartmental modelling analysis used to estimate the primary outcome measure, whole brain volume of distribution (VT). Secondary PK and safety endpoints were also recorded.Results: PET dynamic data were successfully obtained from all four subjects and there were no clinically significant variations of the safety endpoints. Inspection of the TACs indicated a relatively homogenous uptake of [18F]GSK2647544 across all the ROIs examined. The mean whole brain VT was 0.56 (95 % CI, 0.41-0.72). Secondary PK parameters, Cmax (geometric mean) and Tmax (median), were 354 ng/ml and 1.4 h, respectively. Metabolism of GSK2647544 was relatively consistent across subjects, with 20-40 % of the parent compound [18F]GSK2647544 present after 120 min.Conclusions: The study provides evidence that GSK2647544 is able to cross the blood brain barrier in healthy male subjects leading to a measurable brain exposure. The administered doses of GSK2647544 were well tolerated. Exploratory modelling suggested that a twice-daily dose of 102 mg, at steady state, would provide ~80 % trough inhibition of brain Lp-PLA2 activity.Trial Registration: Clintrials.gov: NCT01924858. [ABSTRACT FROM AUTHOR]

The article focuses on the story of two brothers, William John Bankes and Ralph Bankes, who were collectors and half of their 3000 volumes are from the seventeenth-century collection.

Background: A number of pathophysiological mechanisms are associated with neurodegeneration, including synaptic dysfunction and/or loss. Novel radiotracers which enable the quantification of synaptic proteins in vivo have not previously been explored in frontotemporal dementia (FTD). We used [11C]UCB‐J PET to measure the density of synaptic vesicle protein 2A (SV2A) in FTD. Method: Six participants with behavioural variant FTD (mean age 61.8, SD 5.4) and 17 cognitively normal participants (63.7, 12.5) underwent 90‐minute dynamic acquisition PET scans following injection of [11C]UCB‐J, with metabolite corrected arterial input function. Thirteen regions of interest (ROIs) were defined on individual MR images using the CIC anatomical atlas. Regional density was evaluated using the regional VT normalised to the VT in the centrum semiovale (DVR‐1). Groups were compared using Mann‐Whitney tests with Bonferroni correction for multiple comparisons. W‐scores were computed from the 17 controls, with age and gender as covariates, to compare the magnitude of group differences in regional volumes versus [11C]UCB‐J distribution. Volumes were expressed as a percentage of total intracranial volume. A w‐score of <‐1.65 was considered abnormal. Result: We found significant reductions in regional density of SV2A in FTD compared to controls in multiple cortical and subcortical regions: frontal, temporal, parietal, insula, anterior cingulate and posterior cingulate cortices (all 0.001), as well as the hippocampus, amygdala, thalamus and cerebellum (all 0.001). The w‐score analysis revealed significant reductions in SV2A density in FTD in all 13 ROIs, with the greatest reduction in the anterior cingulate (‐4.2), and in volume in 8 ROIs, with the greatest reduction in the temporal lobe (‐6.4). The magnitude of SV2A density loss was greater than the magnitude of volume loss in most ROIs (9/13), and there was more variability in the reduction in volume than there was in SV2A density (SD range [11C]UCB‐J 0.7‐2.1, volume 1.4‐3.9). Conclusion: Significant reductions in [11C]UCB‐J distribution indicate reduced synaptic density in disease‐relevant regions in FTD, which surpass reductions in volume. This suggests that [11C]UCB‐J PET imaging could be a sensitive biomarker of synaptic dysfunction in FTD, with future studies focused on its relationship with symptoms and whether it becomes abnormal before symptom onset. [ABSTRACT FROM AUTHOR]

The article focuses on the World Wide Fund for Nature of South Africa has commissioned The Green House to develop a system dynamics model to explore the workings of a shift of freight between road and rail for the greenhouse gas emission mitigation. Topics discussed include impact of mitigation measures on costs, reliability and resulting decision-making in freight transport, its impacts on job creation, emissions and water use and warehousing cost depends on the punctuality of fleets.

Positron emission tomography (PET) targeting the 18 kDa translocator protein (TSPO) is used to quantify neuroinflammation. Translocator protein is expressed throughout the brain, and therefore a classical reference region approach cannot be used to estimate binding potential (BPND). Here, we used blockade of the TSPO radioligand [11C]PBR28 with the TSPO ligand XBD173, to determine the non-displaceable volume of distribution (VND), and hence estimate the BPND. A total of 26 healthy volunteers, 16 high-affinity binders (HABs) and 10 mixed affinity binders (MABs) underwent a [11C]PBR28 PET scan with arterial sampling. Six of the HABs received oral XBD173 (10 to 90 mg), 2 hours before a repeat scan. In XBD173-dosed subjects, VND was estimated via the occupancy plot. Values of BPND for all subjects were calculated using this VND estimate. Total volume of distribution (VT) of MABs (2.94±0.31) was lower than VT of HABs (4.33±0.29) (P<0.005). There was dose-dependent occupancy of TSPO by XBD173 (ED50=0.34±0.13 mg/kg). The occupancy plot provided a VND estimate of 1.98 (1.69, 2.26). Based on these VND estimates, BPND for HABs is approximately twice that of MABs, consistent with predictions from in vitro data. Our estimates of [11C]PBR28 VND and hence BPND in the healthy human brain are consistent with in vitro predictions. XBD173 blockade provides a practical means of estimating VND for TSPO targeting radioligands. [ABSTRACT FROM AUTHOR]