Social Affordances of Mixed Reality Learning Environments: A case from the Science through Technology Enhanced Play project (STEP)

We describe the design of the Science through Technology Enhanced Play (STEP) project. In STEP, we explore the potential for dramatic play—a form of activity that is particularly familiar to early elementary students—to promote meaningful inquiry about scientific concepts. We report on the first round of design experiments conducted with 120 first and second grade students who investigated how and why different states of matter have different properties. Pre-post analyses indicate that the majority of students learned the content and demonstrate how the affordances of the socio-technical system promoted the transition from individual observation to collective inquiry, how play as the root activity provided agency within that inquiry, and how the teacher and the social norms of the classroom reinforced these productive social processes

Geochemical Signature of Mesozoic Volcanic and Granitic Rocks in Madina Regency Area, North Sumatra, Indonesia, and Its Tectonic Implication

Http://dx.doi.org/10.17014/ijog.vol4no2.20094Five samples consisting of two Permian-Triassic basalts, two Triassic-Jurassic granitic rocks, and a Miocene andesite were collected from the Madina Regency area in North Sumatra that is regionally situated on the West Sumatra Block. Previous authors have proposed three different scenarios for the geological setting of West Sumatra Permian Plutonic-Volcanic Belt, namely an island-arc, subduction related continental margin arc, and continental break-up. Petrographic analysis of the Mesozoic basaltic samples indicates that they are island-arcs in origin; however their trace element spider diagram patterns (Rock/MORB ratio) also show the character of back-arc marginal basin, besides the island-arc. Furthermore, their REE spider diagram patterns (Rock/ Chondrite ratio) clearly reveal that they were actually generated in a back-arc marginal basin tectonic setting. Meanwhile, the two Mesozoic granitic rocks and the Miocene andesite reflect the character of an active continental margin. Their spider diagram patterns show a significant enrichment on incompat- ible elements, usually derived from fluids of the subducted slab beneath the subduction zone. The high enrichment on Th makes their plots on Ta/Yb versus Th/Yb diagram are shifted to outside the active continental margin field. Although the volcanic-plutonic products represent different ages, their La/Ce ratio leads to a probability that they have been derived from the same magma sources. This study offers another different scenario for the geological setting of West Sumatra Permian Plutonic-Volcanic Belt, where the magmatic activities started in a back-arc marginal basin tectonic setting during the Permian-Triassic time and changed to an active continental margin during Triassic to Miocene. The data are collected through petrographic and chemical analyses for major, trace, and REE includ- ing literature studies

Natural Polysaccharides as Preventive and Therapeutic Horizon for Neurodegenerative Diseases

Neurodegenerative diseases are a serious and widespread global public health burden amongst aging populations. The total estimated worldwide global cost of dementia was US$818 billion in 2015 and has been projected to rise to 2 trillion US$ by 2030. While advances have been made to understand different neurodegenerative disease mechanisms, effective therapeutic strategies do not generally exist. Several drugs have been proposed in the last two decades for the treatment of different types of neurodegenerative diseases, with little therapeutic benefit, and often with severe adverse and side effects. Thus, the search for novel drugs with higher efficacy and fewer drawbacks is an ongoing challenge in the treatment of neurodegenerative disease. Several natural compounds including polysaccharides have demonstrated neuroprotective and even therapeutic effects. Natural polysaccharides are widely distributed in plants, animals, algae, bacterial and fungal species, and have received considerable attention for their wide-ranging bioactivity, including their antioxidant, anti-neuroinflammatory, anticholinesterase and anti-amyloidogenic effects. In this review, we summarize different mechanisms involved in neurodegenerative diseases and the neuroprotective effects of natural polysaccharides, highlighting their potential role in the prevention and therapy of neurodegenerative disease

Structure Guided Design of Potent and Selective Ponatinib-Based Hybrid Inhibitors for RIPK1

SummaryRIPK1 and RIPK3, two closely related RIPK family members, have emerged as important regulators of pathologic cell death and inflammation. In the current work, we report that the Bcr-Abl inhibitor and anti-leukemia agent ponatinib is also a first-in-class dual inhibitor of RIPK1 and RIPK3. Ponatinib potently inhibited multiple paradigms of RIPK1- and RIPK3-dependent cell death and inflammatory tumor necrosis factor alpha (TNF-α) gene transcription. We further describe design strategies that utilize the ponatinib scaffold to develop two classes of inhibitors (CS and PN series), each with greatly improved selectivity for RIPK1. In particular, we detail the development of PN10, a highly potent and selective “hybrid” RIPK1 inhibitor, capturing the best properties of two different allosteric RIPK1 inhibitors, ponatinib and necrostatin-1. Finally, we show that RIPK1 inhibitors from both classes are powerful blockers of TNF-induced injury in vivo. Altogether, these findings outline promising candidate molecules and design approaches for targeting RIPK1- and RIPK3-driven inflammatory pathologies

An evaluation of the effectiveness of self-management interventions for people with type 2 diabetes after an acute coronary syndrome: a systematic review.

BACKGROUND: Type 2 diabetes is highly prevalent in patients with acute coronary syndrome and impacts negatively on health outcomes and self-management. Both conditions share similar risk factors. However, there is insufficient evidence on the effectiveness of combined interventions to promote self-management behaviour for people with diabetes and cardiac problems. Identifying critical features of successful interventions will inform future integrated self-management programmes for patients with both conditions. OBJECTIVES: To assess the evidence on the effectiveness of existing interventions to promote self-management behaviour for patients presenting with acute coronary syndrome and type 2 diabetes in secondary care settings and postdischarge. DESIGN: We searched MEDLINE, PubMed, CINAHL Plus, PsycInfo, Cochrane Library and AMED for randomised controlled trials published between January 2005-December 2014. The search was performed using the following search terms of 'acute coronary syndrome', 'type 2 diabetes' and 'self-management intervention' and their substitutes combined. RESULTS: Of 4275 articles that were retrieved, only four trials met all the inclusion criteria (population, intervention, comparison and outcome) and were analysed. Overall, the results show that providing combined interventions for patients with both conditions including educational sessions supported by multimedia or telecommunication technologies was partially successful in promoting self-management behaviours. Implementation of these combined interventions during patient's hospitalisation and postdischarge was feasible. Intervention group subjects reported a significant improvement in self-efficacy, level of knowledge, glycated haemoglobin, blood pressure and fasting glucose test. However, there are many threats have been noticed around internal validity of included studies that could compromise the conclusions drawn. CONCLUSION: With limited research in this area, there was no final evidence to support effectiveness of combined interventions to promote self-management behaviour for patients with type 2 diabetes and acute coronary syndrome. Sufficiently powered, good quality, well-conducted and reported randomised controlled trials are required.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1111/jocn.1348

Inflammatory Signaling by NOD-RIPK2 Is Inhibited by Clinically Relevant Type II Kinase Inhibitors

Summary RIPK2 mediates pro-inflammatory signaling from the bacterial sensors NOD1 and NOD2, and is an emerging therapeutic target in autoimmune and inflammatory diseases. We observed that cellular RIPK2 can be potently inhibited by type II inhibitors that displace the kinase activation segment, whereas ATP-competitive type I inhibition was only poorly effective. The most potent RIPK2 inhibitors were the US Food and Drug Administration-approved drugs ponatinib and regorafenib. Their mechanism of action was independent of NOD2 interaction and involved loss of downstream kinase activation as evidenced by lack of RIPK2 autophosphorylation. Notably, these molecules also blocked RIPK2 ubiquitination and, consequently, inflammatory nuclear factor κB signaling. In monocytes, the inhibitors selectively blocked NOD-dependent tumor necrosis factor production without affecting lipopolysaccharide-dependent pathways. We also determined the first crystal structure of RIPK2 bound to ponatinib, and identified an allosteric site for inhibitor development. These results highlight the potential for type II inhibitors to treat indications of RIPK2 activation as well as inflammation-associated cancers

Azimuthal anisotropy of charged jet production in root s(NN)=2.76 TeV Pb-Pb collisions

We present measurements of the azimuthal dependence of charged jet production in central and semi-central root s(NN) = 2.76 TeV Pb-Pb collisions with respect to the second harmonic event plane, quantified as nu(ch)(2) (jet). Jet finding is performed employing the anti-k(T) algorithm with a resolution parameter R = 0.2 using charged tracks from the ALICE tracking system. The contribution of the azimuthal anisotropy of the underlying event is taken into account event-by-event. The remaining (statistical) region-to-region fluctuations are removed on an ensemble basis by unfolding the jet spectra for different event plane orientations independently. Significant non-zero nu(ch)(2) (jet) is observed in semi-central collisions (30-50% centrality) for 20 <p(T)(ch) (jet) <90 GeV/c. The azimuthal dependence of the charged jet production is similar to the dependence observed for jets comprising both charged and neutral fragments, and compatible with measurements of the nu(2) of single charged particles at high p(T). Good agreement between the data and predictions from JEWEL, an event generator simulating parton shower evolution in the presence of a dense QCD medium, is found in semi-central collisions. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

Measuring performance on the Healthcare Access and Quality Index for 195 countries and territories and selected subnational locations: A systematic analysis from the Global Burden of Disease Study 2016

Background: A key component of achieving universal health coverage is ensuring that all populations have access to quality health care. Examining where gains have occurred or progress has faltered across and within countries is crucial to guiding decisions and strategies for future improvement. We used the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) to assess personal health-care access and quality with the Healthcare Access and Quality (HAQ) Index for 195 countries and territories, as well as subnational locations in seven countries, from 1990 to 2016. Methods Drawing from established methods and updated estimates from GBD 2016, we used 32 causes from which death should not occur in the presence of effective care to approximate personal health-care access and quality by location and over time. To better isolate potential effects of personal health-care access and quality from underlying risk factor patterns, we risk-standardised cause-specific deaths due to non-cancers by location-year, replacing the local joint exposure of environmental and behavioural risks with the global level of exposure. Supported by the expansion of cancer registry data in GBD 2016, we used mortality-to-incidence ratios for cancers instead of risk-standardised death rates to provide a stronger signal of the effects of personal health care and access on cancer survival. We transformed each cause to a scale of 0-100, with 0 as the first percentile (worst) observed between 1990 and 2016, and 100 as the 99th percentile (best); we set these thresholds at the country level, and then applied them to subnational locations. We applied a principal components analysis to construct the HAQ Index using all scaled cause values, providing an overall score of 0-100 of personal health-care access and quality by location over time. We then compared HAQ Index levels and trends by quintiles on the Socio-demographic Index (SDI), a summary measure of overall development. As derived from the broader GBD study and other data sources, we examined relationships between national HAQ Index scores and potential correlates of performance, such as total health spending per capita. Findings In 2016, HAQ Index performance spanned from a high of 97\ub71 (95% UI 95\ub78-98\ub71) in Iceland, followed by 96\ub76 (94\ub79-97\ub79) in Norway and 96\ub71 (94\ub75-97\ub73) in the Netherlands, to values as low as 18\ub76 (13\ub71-24\ub74) in the Central African Republic, 19\ub70 (14\ub73-23\ub77) in Somalia, and 23\ub74 (20\ub72-26\ub78) in Guinea-Bissau. The pace of progress achieved between 1990 and 2016 varied, with markedly faster improvements occurring between 2000 and 2016 for many countries in sub-Saharan Africa and southeast Asia, whereas several countries in Latin America and elsewhere saw progress stagnate after experiencing considerable advances in the HAQ Index between 1990 and 2000. Striking subnational disparities emerged in personal health-care access and quality, with China and India having particularly large gaps between locations with the highest and lowest scores in 2016. In China, performance ranged from 91\ub75 (89\ub71-93\ub76) in Beijing to 48\ub70 (43\ub74-53\ub72) in Tibet (a 43\ub75-point difference), while India saw a 30\ub78-point disparity, from 64\ub78 (59\ub76-68\ub78) in Goa to 34\ub70 (30\ub73-38\ub71) in Assam. Japan recorded the smallest range in subnational HAQ performance in 2016 (a 4\ub78-point difference), whereas differences between subnational locations with the highest and lowest HAQ Index values were more than two times as high for the USA and three times as high for England. State-level gaps in the HAQ Index in Mexico somewhat narrowed from 1990 to 2016 (from a 20\ub79-point to 17\ub70-point difference), whereas in Brazil, disparities slightly increased across states during this time (a 17\ub72-point to 20\ub74-point difference). Performance on the HAQ Index showed strong linkages to overall development, with high and high-middle SDI countries generally having higher scores and faster gains for non-communicable diseases. Nonetheless, countries across the development spectrum saw substantial gains in some key health service areas from 2000 to 2016, most notably vaccine-preventable diseases. Overall, national performance on the HAQ Index was positively associated with higher levels of total health spending per capita, as well as health systems inputs, but these relationships were quite heterogeneous, particularly among low-to-middle SDI countries. Interpretation GBD 2016 provides a more detailed understanding of past success and current challenges in improving personal health-care access and quality worldwide. Despite substantial gains since 2000, many low-SDI and middle- SDI countries face considerable challenges unless heightened policy action and investments focus on advancing access to and quality of health care across key health services, especially non-communicable diseases. Stagnating or minimal improvements experienced by several low-middle to high-middle SDI countries could reflect the complexities of re-orienting both primary and secondary health-care services beyond the more limited foci of the Millennium Development Goals. Alongside initiatives to strengthen public health programmes, the pursuit of universal health coverage hinges upon improving both access and quality worldwide, and thus requires adopting a more comprehensive view-and subsequent provision-of quality health care for all populations

Measuring performance on the Healthcare Access and Quality Index for 195 countries and territories and selected subnational locations: A systematic analysis from the Global Burden of Disease Study 2016

Copyright © 2018 The Author(s). Published by Elsevier Ltd. Background A key component of achieving universal health coverage is ensuring that all populations have access to quality health care. Examining where gains have occurred or progress has faltered across and within countries is crucial to guiding decisions and strategies for future improvement. We used the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) to assess personal health-care access and quality with the Healthcare Access and Quality (HAQ) Index for 195 countries and territories, as well as subnational locations in seven countries, from 1990 to 2016. Methods Drawing from established methods and updated estimates from GBD 2016, we used 32 causes from which death should not occur in the presence of effective care to approximate personal health-care access and quality by location and over time. To better isolate potential effects of personal health-care access and quality from underlying risk factor patterns, we risk-standardised cause-specific deaths due to non-cancers by location-year, replacing the local joint exposure of environmental and behavioural risks with the global level of exposure. Supported by the expansion of cancer registry data in GBD 2016, we used mortality-to-incidence ratios for cancers instead of risk-standardised death rates to provide a stronger signal of the effects of personal health care and access on cancer survival. We transformed each cause to a scale of 0-100, with 0 as the first percentile (worst) observed between 1990 and 2016, and 100 as the 99th percentile (best); we set these thresholds at the country level, and then applied them to subnational locations. We applied a principal components analysis to construct the HAQ Index using all scaled cause values, providing an overall score of 0-100 of personal health-care access and quality by location over time. We then compared HAQ Index levels and trends by quintiles on the Socio-demographic Index (SDI), a summary measure of overall development. As derived from the broader GBD study and other data sources, we examined relationships between national HAQ Index scores and potential correlates of performance, such as total health spending per capita. Findings In 2016, HAQ Index performance spanned from a high of 97·1 (95% UI 95·8-98·1) in Iceland, followed by 96·6 (94·9-97·9) in Norway and 96·1 (94·5-97·3) in the Netherlands, to values as low as 18·6 (13·1-24·4) in the Central African Republic, 19·0 (14·3-23·7) in Somalia, and 23·4 (20·2-26·8) in Guinea-Bissau. The pace of progress achieved between 1990 and 2016 varied, with markedly faster improvements occurring between 2000 and 2016 for many countries in sub-Saharan Africa and southeast Asia, whereas several countries in Latin America and elsewhere saw progress stagnate after experiencing considerable advances in the HAQ Index between 1990 and 2000. Striking subnational disparities emerged in personal health-care access and quality, with China and India having particularly large gaps between locations with the highest and lowest scores in 2016. In China, performance ranged from 91·5 (89·1-93·6) in Beijing to 48·0 (43·4-53·2) in Tibet (a 43·5-point difference), while India saw a 30·8-point disparity, from 64·8 (59·6-68·8) in Goa to 34·0 (30·3-38·1) in Assam. Japan recorded the smallest range in subnational HAQ performance in 2016 (a 4·8-point difference), whereas differences between subnational locations with the highest and lowest HAQ Index values were more than two times as high for the USA and three times as high for England. State-level gaps in the HAQ Index in Mexico somewhat narrowed from 1990 to 2016 (from a 20·9-point to 17·0-point difference), whereas in Brazil, disparities slightly increased across states during this time (a 17·2-point to 20·4-point difference). Performance on the HAQ Index showed strong linkages to overall development, with high and high-middle SDI countries generally having higher scores and faster gains for non-communicable diseases. Nonetheless, countries across the development spectrum saw substantial gains in some key health service areas from 2000 to 2016, most notably vaccine-preventable diseases. Overall, national performance on the HAQ Index was positively associated with higher levels of total health spending per capita, as well as health systems inputs, but these relationships were quite heterogeneous, particularly among low-to-middle SDI countries. Interpretation GBD 2016 provides a more detailed understanding of past success and current challenges in improving personal health-care access and quality worldwide. Despite substantial gains since 2000, many low-SDI and middle- SDI countries face considerable challenges unless heightened policy action and investments focus on advancing access to and quality of health care across key health services, especially non-communicable diseases. Stagnating or minimal improvements experienced by several low-middle to high-middle SDI countries could reflect the complexities of re-orienting both primary and secondary health-care services beyond the more limited foci of the Millennium Development Goals. Alongside initiatives to strengthen public health programmes, the pursuit of universal health coverage hinges upon improving both access and quality worldwide, and thus requires adopting a more comprehensive view - and subsequent provision - of quality health care for all populations