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Rodríguez Carmona, Manuela. "C & T Projects." Comunicació educativa, no. 27 (September 29, 2015): 47. http://dx.doi.org/10.17345/comeduc201447-54.
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<p>La interacció, l’expressió i la creativitat esdevenen un fil conductor que possibilita la manifestació de la identitat pròpia, el valor d’aquestes particularitats en relació amb la societat i amb un mateix. El desenvolupament de la creativitat porta a una autoestima equilibrada, a una consciència personal en un ambient de llibertat expressiva, de seguretat, on mostrar-se, on explorar, des de la pròpia forma de ser, veure i percebre el món. En aquest article es presenta C & T (Cinema and Theatre) Projects, una proposta educativa destinada al desenvolupament creatiu d’infants i joves a través de l’expressivitat.</p>
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Pak, Marjorie. "Head movement and allomorphy in children's negative questions." Proceedings of the Linguistic Society of America 3, no. 1 (March 3, 2018): 33. http://dx.doi.org/10.3765/plsa.v3i1.4321.
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English-speaking preschoolers occasionally produce negative questions with a ‘doubled’ auxiliary (e.g. Why did you didn’t know?). These 2AuxQs apparently involve a failure to raise [NEG n’t] to C (cf. Why didn’t you know?). I analyze 2AuxQs as the product of two independent errors: a planning error (raising T-to-C without raising Neg-to-T first) and an allomorphy error (overgeneralization of ‑n’t). The planning error results from lack of practice: serial head-movement is relatively uncommon in English, and true Neg-to-T-to-C may be rarer than appearances suggest. In e.g. Why don’t we play, ok?, -n’t is not interpreted within TP—and strikingly, 2AuxQs are unattested here.
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Norquist, Kay. "G/C/T Review: Children's Learning in the “Zone of Proximal Development”." G/C/T 8, no. 3 (May 1985): 54. http://dx.doi.org/10.1177/107621758500800334.
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Ndari, Susianty selaras, Chandrawaty Chandrawaty, Imam Mujtaba, and Mafaza Conita Ananto. "Children's Outdoor Activities and Parenting Style in Children's Social Skill." JPUD - Jurnal Pendidikan Usia Dini 13, no. 2 (November 30, 2019): 217–31. http://dx.doi.org/10.21009/jpud.132.02.
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Physical activity is very important for early childhood, especially outdoor activities that add a lot of new experiences. This study aims to check the relationship of children's outdoor activities and parenting styles and children's social skills. The participants are 125 parents of early childhood who attend kindergarten. The research method is a descriptive study using the relational screening model. The results showed that there was a relationship between outside play and parenting style on the social skills of children in their childhood. Democratic parenting styles are found to promote children's social skills, while authoritative parenting styles have a negative correlation with interpersonal skills, the ability to express verbally, self-control, listening skills, emotional management and adaptation to change. In the sub-dimensions of anger management and adaptation to changing skills is a significant difference between authoritative parenting styles and not permissive parenting with children's social skills.
Keywords: Early Childhood Social skills, Outdoor Activities, Parenting Styles
Reference:
Azlina, W., & S., Z. A. (2012). A Pilot Study: The Impact of Outdoor Play Spaces on Kindergarten Children. Procedia - Social and Behavioral Sciences, 38(December 2010), 275–283. https://doi.org/10.1016/j.sbspro.2012.03.349
Bento, G., & Dias, G. (2017). The importance of outdoor play for young childrenʼs healthy development. Porto Biomedical Journal, 2(5), 157–160. https://doi.org/10.1016/j.pbj.2017.03.003
Beyer, K., Bizub, J., Szabo, A., Heller, B., Kistner, A., Shawgo, E., & Zetts, C. (2015). Development and validation of the attitudes toward outdoor play scales for children. Social Science and Medicine, 133, 253–260. https://doi.org/10.1016/j.socscimed.2014.10.033
Boxberger, K., & Reimers, A. K. (2019). Parental correlates of outdoor play in boys and girls aged 0 to 12—A systematic review. International Journal of Environmental Research and Public Health, 16(2). https://doi.org/10.3390/ijerph16020190
Coleman, W. L., & Lindsay, R. L. (1992). Interpersonal disabilities: Social skill deficits in older children and adolescents: Their description, assessment, and management. Pediatric Clinics of North America, 39(3), 551–567. https://doi.org/10.1016/S0031-3955(16)38344-4
Cui, M., Janhonen-Abruquah, H., Darling, C. A., Carlos Chavez, F. L., & Palojoki, P. (2019). Helicopter Parenting and Young Adults’ Well-Being: A Comparison Between United States and Finland. Cross-Cultural Research, 53(4), 410–427. https://doi.org/10.1177/1069397118802253
Fjørtoft, I., & Sageie, J. (2000). The natural environment as a playground for children. Landscape description and analyses of a natural playscape. Landscape and Urban Planning, 48(1–2), 83–97. https://doi.org/10.1016/S0169-2046(00)00045-1
Ghanbari-Azarneir, S., Anbari, S., Hosseini, S.-B., & Yazdanfar, S.-A. (2015). Identification of Child-friendly Environments in Poor Neighborhoods. Procedia - Social and Behavioral Sciences, 201(February), 19–29. https://doi.org/10.1016/j.sbspro.2015.08.114
Giedd, J. N. (2012). The Digital Revolution and Adolescent Brain Evolution. Journal of Adolescent Health, 51(2), 101–105. https://doi.org/10.1016/j.jadohealth.2012.06.002
Hinkley, T., Brown, H., Carson, V., & Teychenne, M. (2018). Cross sectional associations of screen time and outdoor play with social skills in preschool children. PLoS ONE, 13(4), 1–15. https://doi.org/10.1371
Johnson, J. E., & Christie, J. F. (2009). Play and digital media. Computers in the Schools, 26(4), 284–289. https://doi.org/10.1080/07380560903360202
Junot, A., Paquet, Y., & Martin-Krumm, C. (2017). Passion for outdoor activities and environmental behaviors: A look at emotions related to passionate activities. Journal of Environmental Psychology, 53, 177–184. https://doi.org/10.1016/j.jenvp.2017.07.011
Kemple, K. M., Oh, J. H., Kenney, E., & Smith-Bonahue, T. (2016). The Power of Outdoor Play and Play in Natural Environments. Childhood Education, 92(6), 446–454. https://doi.org/10.1080/00094056.2016.1251793
Kol, S. (2016). The Effects of the Parenting Styles on Social Skills of Children Aged 5-6. Malaysian Online Journal of Educational Sciences, 4(2), 49–58.
Kozina, Z., Repko, O., Kozin, S., Kostyrko, A., Yermakova, T., & Goncharenko, V. (2016). Motor skills formation technique in 6 to 7-year-old children based on their psychological and physical features (Rock climbing as an example). Journal of Physical Education and Sport, 16(3), 866–874. https://doi.org/10.7752/jpes.2016.03137
Larson, L. R., Szczytko, R., Bowers, E. P., Stephens, L. E., Stevenson, K. T., & Floyd, M. F. (2019). Outdoor Time, Screen Time, and Connection to Nature: Troubling Trends Among Rural Youth? Environment and Behavior, 51(8), 966–991. https://doi.org/10.1177/0013916518806686
Lindsey, G., Maraj, M., & Kuan, S. C. (2001). Access, Equity, and Urban Greenways: An Exploratory Investigation. Professional Geographer, 53(3), 332–346. https://doi.org/10.1111/0033-0124.00288
Louv, R. (2008). Last child in the woods: Saving our children from nature-deficit disorder. Chapel Hill, NC: Algonquin Books.
Maynard, T., & Waters, J. (2007). Learning in the outdoor environment: A missed opportunity? Early Years, 27(3), 255–265. https://doi.org/10.1080/09575140701594400
Moreland, A. D., & McRae-Clark, A. (2018). Parenting outcomes of parenting interventions in integrated substance-use treatment programs: A systematic review. Journal of Substance Abuse Treatment, 89(August 2017), 52–59. https://doi.org/10.1016/j.jsat.2018.03.005
Moriguchi, Y., Zelazo, P. D., & Chevalier, N. (2016). Development of Executive Function During Childhood. https://doi.org/10.3389/978-2-88919-800-9
Mullenbach, L. E., Andrejewski, R. G., & Mowen, A. J. (2019). Connecting children to nature through residential outdoor environmental education. Environmental Education Research, 25(3), 365–374. https://doi.org/10.1080/13504622.2018.1458215
Norðdahl, K., & Einarsdóttir, J. (2015). Children’s views and preferences regarding their outdoor environment. Journal of Adventure Education and Outdoor Learning, 15(2), 152–167. https://doi.org/10.1080/14729679.2014.896746
Pinquart, M. (2016). Associations of Parenting Styles and Dimensions with Academic Achievement in Children and Adolescents: A Meta-analysis. Educational Psychology Review, 28(3), 475–493. https://doi.org/10.1007/s10648-015-9338-y
Riany, Y. E., Cuskelly, M., & Meredith, P. (2016). Cultural Beliefs about Autism in Indonesia. International Journal of Disability, Development and Education, 63(6), 623–640. https://doi.org/10.1080/1034912X.2016.1142069
Riany, Y. E., Meredith, P., & Cuskelly, M. (2017). Understanding the Influence of Traditional Cultural Values on Indonesian Parenting. Marriage and Family Review, 53(3), 207–226. https://doi.org/10.1080/01494929.2016.1157561
Saltali, N. D., & Arslan, E. (2012). Parent ’ s Attitudes as a Predictor of Preschoolers ’ Social Competence and Introverted Behavior. Elementary Education Online, 11(3), 729–737.
Schoeppe, S., Vandelanotte, C., Bere, E., Lien, N., Verloigne, M., Kovács, É., … Van Lippevelde, W. (2017). The influence of parental modelling on children’s physical activity and screen time: Does it differ by gender? European Journal of Public Health, 27(1), 152–157. https://doi.org/10.1093/eurpub/ckw182
Shi, Y. (2017). Explore Children’s Outdoor Play Spaces of Community Areas in High-density Cities in China: Wuhan as an Example. Procedia Engineering, 198(September 2016), 654–682. https://doi.org/10.1016/j.proeng.2017.07.118
Strasburger, V. C., Jordan, A. B., & Donnerstein, E. (2012). Children, Adolescents, and the Media:. Health Effects. Pediatric Clinics of North America, 59(3), 533–587. https://doi.org/10.1016/j.pcl.2012.03.025
Victoria J. Rideout, Foehr, M. A. U. G., & Roberts, D. F. (2010). GENERATION M2 Media in the Lives of 8- to 18-Year-Olds. In Theresa Boston (Ed.), Henry J. Kaiser Family Foundation. Boston: Henry J. Kaiser Family Foundation.
Wang, S. hua, Zhang, Y., & Baillargeon, R. (2016). Young infants view physically possible support events as unexpected: New evidence for rule learning. Cognition, 157, 100–105. https://doi.org/10.1016/j.cognition.2016.08.021
Waters, J., & Rekers, A. (2019). Young Children ’ s Outdoor Play-Based Learning. 1–7.
Webster-Stratton, C., Reid, J., & Hammond, M. (2001). Social skills and problem-solving training for children with early-onset conduct problems: Who benefits? Journal of Child Psychology and Psychiatry and Allied Disciplines, 42(7), 943–952. Retrieved from http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=emed5&NEWS=N&AN=2001380196
Wilkie, H. J., Standage, M., Gillison, F. B., Cumming, S. P., & Katzmarzyk, P. T. (2018). The home electronic media environment and parental safety concerns: relationships with outdoor time after school and over the weekend among 9-11 year old children. BMC Public Health, 18(1), 456. https://doi.org/10.1186/s12889-018-5382-0
Zajenkowska, A., Jankowski, K. S., Lawrence, C., & Zajenkowski, M. (2013). Personality and individual differences in responses to aggression triggering events among prisoners and non-prisoners. Personality and Individual Differences, 55(8), 947–951. https://doi.org/10.1016/j.paid.2013.07.467
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McKEE, CECILE, and DANA McDANIEL. "Multiple influences on children's language performance." Journal of Child Language 31, no. 2 (May 2004): 489–92. http://dx.doi.org/10.1017/s0305000904006130.
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Our commentary concerns the Competing Factors Model (CFM). As Drozd says, the CFM is fictitious and without proponents. (See also McDaniel, 2001.) But we will argue that something like it is necessary to our field. Everyone recognizes multiple influences on language performance, even C&T. Most important, recognizing these factors does not require a denial of the grammar's existence or even of its dominance.
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DONDERS, JACQUES. "Performance discrepancies between the Children's Category Test (CCT) and the California Verbal Learning Test–Children's (CVLT–C) Version in the standardization sample." Journal of the International Neuropsychological Society 4, no. 3 (May 1998): 242–46. http://dx.doi.org/10.1017/s1355617798002422.
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Standardization data for the Children's Category Test (CCT) and California Verbal Learning Test–Children's Version (CVLT–C) were used to evaluate covariances and statistically significant discrepancies between the T scores of those instruments, as well as the base rate of specific discrepancies. The results indicate that the CCT and CVLT–C share only a limited amount of common variance and that statistically significant discrepancies between the respective T scores are actually quite common. It is suggested that evaluation of the potential clinical significance of a discrepancy between the obtained results of these two instruments in individual cases should include consideration of the presented base rates. (JINS, 1998, 4, 242–246.)
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Sri Wahyuni, Siti Fadilah, and Adolf Bastian. "Children's independence Skills Analysis at Low Socioeconomic Environment." JPUD - Jurnal Pendidikan Usia Dini 14, no. 2 (November 30, 2020): 303–12. http://dx.doi.org/10.21009/jpud.142.08.
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Research suggests that child independence is more popular in countries with greater wealth and a higher percentage of the educated population. Various research implications expect children's independence and compliance to increase over time in developing countries. This study aims to describe the independence of early childhood who comes from low-income families or at low socioeconomic environment. Using quantitative descriptive, data collection techniques are carried out through a questionnaire. The study population was 30 respondents from the ECE institution who were included in the list of low-income families in 2018, using an area sampling technique. Overall, the teacher stated that all indicators of dependence on children from low-income families had reached the high category, which was 75%. The implication of further research is that aspects of independence in physical abilities, self-confidence, responsibility, discipline, sociability, sharing, and independence in terms of emotional control in early childhood can develop better in a low socio-economic environment.
Keywords: Early Childhood, Independence skills, low-socioeconomic environment
References
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Amini, M. (2018). Parental Involvement in Improving Independence in Early Childhood. Advances in Social Science, Education and Humanities Research (ASSEHR), 169(Icece 2017), 190–192. https://doi.org/10.2991/icece-17.2018.48
Blair, C., & Diamond, A. (2008). Biological processes in prevention and intervention: The promotion of self-regulation as a means of preventing school failure. Development and Psychopathology, 20(3), 899–911. https://doi.org/10.1017/S0954579408000436
Blair, C., & Raver, C. C. (2015). School Readiness and Self-Regulation: A Developmental Psychobiological Approach. Annual Reviews Psychology, 3(66), 711–731. https://doi.org/10.1146/annurev-psych-010814-015221.School
Bridgett, D. J., Burt, N. M., Edwards, E. S., & Deater-deckard, K. (2015). Supplemental Material for Intergenerational Transmission of Self-Regulation: A Multidisciplinary Review and Integrative Conceptual Framework. Psychological Bulletin, 141(3), 602–654. https://doi.org/10.1037/a0038662.supp
Brophy-Herb, H. E., Stansbury, K., Bocknek, E., & Horodynski, M. A. (2012). Modeling maternal emotion-related socialization behaviors in a low-income sample: Relations with toddlers’ self-regulation. Early Childhood Research Quarterly, 27(3), 352–364. https://doi.org/10.1016/j.ecresq.2011.11.005
Buckner, J. C., Mezzacappa, E., & Beardslee, W. R. (2009). Self-Regulation and Its Relations to Adaptive Functioning in Low Income Youths. American Journal of Orthopsychiatry, 79(1), 19–30. https://doi.org/10.1037/a0014796
Charilaos, Z., Anastasia, C., Artemis, G., & Dimitrios, S. (2018). The Relationship Between Performance of Neuromuscular Junction and Social Skills (Co-Operation, Interaction, Independence). European Journal of Physical Education and Sport Science, 4(12), 1–20. https://doi.org/10.5281/zenodo.1455997
Cirino, P. T., Miciak, J., Gerst, E., Barnes, M. A., Vaughn, S., Child, A., Huston-Warren, E., Coelho, V., Cadima, J., Pinto, A. I., Guimarães, C., Dark-Freudeman, A., West, R. L., Eisenberg, N., Sulik, M. J., Huh, Y., Reigeluth, C. M., Kim, S., Holloway, S. D., … Cheah, C. S. L. (2018). Attachment and self-regulation. Personality and Social Psychology Bulletin,16(2), 450–467. https://doi.org/10.1177/0022219415618497
Eisenberg, N., Valiente, C., & Eggum, N. D. (2010). Self-regulation and school readiness. Early Education and Development, 21(5), 681–698. https://doi.org/10.1080/10409289.2010.497451
Ellis, B. J., Boyce, W. T., Belsky, J., Bakermans-Kranenburg, M. J., & Van Ijzendoorn, M. H. (2011). Differential susceptibility to the environment: An evolutionary- neurodevelopmental theory. Development and Psychopathology, 23(1), 7–28. https://doi.org/10.1017/S0954579410000611
Evans, G. W., & Kim, P. (2013). Childhood Poverty, Chronic Stress, Self-Regulation, and Coping. Child Development Perspectives, 7(1), 43–48. https://doi.org/10.1111/cdep.12013
Fay-Stammbach, T., Hawes, D. J., & Meredith, P. (2014). Parenting Influences on Executive Function in Early Childhood: A Review. Child Development Perspectives, 8(4), 258–264. https://doi.org/10.1111/cdep.12095
Havighurst, S. S., Wilson, K. R., Harley, A. E., Prior, M. R., & Kehoe, C. (2010). Tuning in to Kids: Improving emotion socialization practices in parents of preschool children-findings from a community trial. Journal of Child Psychology and Psychiatry and Allied Disciplines. https://doi.org/10.1111/j.1469-7610.2010.02303.x
Jimenez-Gomez, C., Haggerty, K., & Topçuoǧlu, B. (2020). Wearable activity schedules to promote independence in young children. Journal of Applied Behavior Analysis, 9999(9999), 1–20. https://doi.org/10.1002/jaba.756
Julian, M. M., Leung, C. Y. Y., Rosenblum, K. L., LeBourgeois, M. K., Lumeng, J. C., Kaciroti, N., & Miller, A. L. (2019). Parenting and Toddler Self-Regulation in Low-Income Families: What Does Sleep Have to do with it? Infant Ment Health J., 40(4), 479–495. https://doi.org/doi:10.1002/imhj.21783
Kaya, İ., & Deniz, M. E. (2020). The effects of life skills education program on problem behaviors and social skills of 4-year-old preschoolers. Elementary Education Online, 19(2), 612–623. https://doi.org/10.17051/ilkonline.2020.692983
Lengua, L. J., Moran, L., Zalewski, M., Ruberry, E., Kiff, C., & Thompson, S. (2015). Relations of Growth in Effortful Control to Family Income, Cumulative Risk, and Adjustment in Preschool-age Children. Journal of Abnormal Child Psychology,43(4), 705–720. https://doi.org/10.1007/s10802-014-9941-2
Meylia, K. N., Siswati, T., Paramashanti, B. A., & Hati, F. S. (2020). Fine motor, gross motor, and social independence skills among stunted and non-stunted children. Early Child Development and Care, 0(0), 1–8. https://doi.org/10.1080/03004430.2020.1739028
Nahar, B., Hossain, M., Mahfuz, M., Islam, M. M., Hossain, M. I., Murray-Kolb, L. E., Seidman, J. C., & Ahmed, T. (2020). Early childhood development and stunting: Findings from the MAL-ED birth cohort study in Bangladesh. Maternal and Child Nutrition, 16(1). https://doi.org/10.1111/mcn.12864
Park, H., & Lau, A. S. (2016). Socioeconomic Status and Parenting Priorities: Child Independence and Obedience Around the World. Journal of Marriage and Family, 78(1), 43–59. https://doi.org/10.1111/jomf.12247
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Spangler, Matthew. "Artist's Statement: Adapting T. C. Boyle's novelThe Tortilla Curtainand Subsequent Production by the San Diego Repertory Theatre." Text and Performance Quarterly 33, no. 2 (April 2013): 151–67. http://dx.doi.org/10.1080/10462937.2013.769061.
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Bachman, Betty. "The Development of a Sustainable, Community-Supported Children's Bereavement Camp." OMEGA - Journal of Death and Dying 67, no. 1-2 (August 2013): 21–35. http://dx.doi.org/10.2190/om.67.1-2.c.
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This article describes the creation and development of a sustainable, community-supported children's bereavement camp. Numerous grief camps were examined prior to the project development. The project development was guided by the S.M.A.R.T. (S—Strategic/specific; M—Measurable; A—Achievable/attainable; R—Realistic; and T—Time-framed) stratagem to direct steps toward the development of the bereavement camp. Outcome measures included program participation, as well as evaluations completed by campers, family members, and volunteers. Camp attendance continues to grow, with 48 children the first year and an average of 65 the following 3 years. According to post-evaluation surveys, campers were able to integrate back into school with a decrease in stress and an increase in their ability to verbalize their grief, share feelings and begin to trust others. One child “got her sparkle back” according to her grandmother. Several campers commented that camp allowed them to see themselves as normal children. The goal of Camp Healing Hearts was that campers would laugh again, and they are.
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Hayashi, Robert James, Stuart S. Winter, Kimberly P. Dunsmore, Meenakshi Devidas, Brent Wood, Michelle L. Hermiston, David T. Teachey, et al. "Children's Oncology Group (COG) AALL0434: Successful Disease Control without Cranial Radiation in Newly Diagnosed T Lymphoblastic Lymphoma (T-LL)." Blood 132, Supplement 1 (November 29, 2018): 1000. http://dx.doi.org/10.1182/blood-2018-99-113481.
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Abstract Background: COG AALL0434 evaluated the safety and efficacy of a multi agent chemotherapy backbone containing Capizzi based methotrexate/pegaspargase in newly diagnosed T-LL patients. High-risk patients were randomized to receive the COG augmented BFM (ABFM) regimen with or without Nelarabine. This was part of a larger trial including T-Lymphoblastic Leukemia (T-ALL) patients featuring a 2 x 2 pseudo-factorial randomization at the end of induction using the COG ABFM regimen with a randomization of Capizzi MTX/pegaspargase (C-MTX) verses high dose MTX and a randomization with or without Nelarabine (Nel). Methods: AALL0434 enrolled 277 patients with T-LL (2010-2014). Patients were assigned to two risk categories based upon the degree of bone marrow involvement at diagnosis: (≥1%, High Risk, <1% Standard Risk), and the ability to achieve at least a partial response at the end of induction. Patients with prior steroid treatment were assigned to the high risk group. Both groups were treated using the ABFM C-MTX regimen. High-risk patients were randomized to receive or not receive six, 5-day courses of Nel 650 mg/m2/day. No patients received prophylactic cranial radiation and CNS3 patients were ineligible. Response criteria included, Complete Response (CR): disappearance, Complete Response unconfirmed (CRu): >75% reduction, Partial Response (PR): >50% reduction, of all measurable disease, all without new lesions. Results: At the end of induction, 98.9% of the evaluable patients achieved at least a partial response (30.7% CR, 34.7% CRu, 33.5% PR). For all T-LL patients, the 4-year event free survival (EFS) and overall survival (OS) were 87.0 +/- 2.1% and 90.0+/-1.8%. The 4-year Disease Free Survival (DFS) from end of induction was 90.0+/- 2.1%. There was no difference in DFS observed between the high risk and standard risk groups, (p=0.25) or by treatment regimen (p=0.31). Nel did not show an advantage for high-risk T-LL patients, with 4-year DFS 85.0 +/- 5.6% with Nel (N=60) vs 89.0 +/- 4.7% without Nel (N=58) (p=0.28). Neither stage nor tumor response at the end of four weeks of induction therapy resulted in differences in EFS (p= 0.34 and p= 0.22, respectively). Minimal detectable disease (MDD) of the bone marrow at diagnosis (<0.1%, 0.1-0.99%, >1.0%), used to establish the risk assignment for this trial, failed to demonstrate thresholds at diagnosis that resulted in differences in EFS (p=0.27). Relapse involving the CNS only occurred in 4 patients (1.4%). Overall toxicity and neurotoxicity was acceptable and not significantly different than that experienced from the ALL cohort. There was one observed second malignancy and 5 deaths not from progressive disease. Conclusion: COG AALL0434 produced excellent outcomes in one of the largest trials ever conducted for patients with newly diagnosed T-LL. The COG ABFM regimen with C-MTX provides excellent disease control regardless of stage, or the degree of disease involvement of the bone marrow at diagnosis. Nelarabine did not show an improvement in the outcome, although the trial was underpowered to address this specific question. Disclosures Teachey: Amgen: Consultancy; La Roche: Consultancy. Bollard:Torque: Honoraria, Membership on an entity's Board of Directors or advisory committees; Cellectis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Neximmune: Honoraria, Membership on an entity's Board of Directors or advisory committees.
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DROZD, KENNETH F. "Learnability and linguistic performance." Journal of Child Language 31, no. 2 (May 2004): 431–57. http://dx.doi.org/10.1017/s0305000904006051.
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Crain, S. & Thornton, R. Investigations in Universal Grammar. Cambridge: MIT, 1998.Stephen Crain (C) & Rosalind Thornton (T) have garnered a well-deserved reputation for their unwavering commitment to language learnability as a constraint not only on theories of child language and language development but also on experimental design and the interpretation of experimental findings. In his well-known defense of children's early knowledge of syntactic constraints, Crain (1991) argued for the widely-held position that the best solution to the learnability problem is to assume that grammatical knowledge which cannot be learned on the basis of experience is specified in advance as part of the human biological endowment for language in the form of a UNIVERSALGRAMMAR (UG) (Chomsky, 1965). With respect to experimental design, C&T have strongly maintained that even young children know UG constraints but perform poorly in some experiments-due to the extralinguistic demands associated with experimental tasks, particularly those involved in presupposition accommodation and complex response planning. C&T specifically design their experiments to reduce the impact of extralinguistic demands on children's linguistic performance while at the same time providing felicitous environments for adultlike performance.
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Maxwell, Desmond. "New Lamps for Old: The Theatre of Tom Murphy." Theatre Research International 15, no. 1 (1990): 57–66. http://dx.doi.org/10.1017/s0307883300009524.
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(i) A vision and a sense of placeTom Murphy has responded with some incredulity to an interviewer's suggestion that he has written plays ‘about emigration’. The subject figures in some of the plays; Michael, returned from the exile his tales embroider (Conversations on a Homecoming);, the Carneys, immigrants in Coventry, making a precarious sanctuary of violence (A Whistle in the Dark); John Joe's unsettling meditations on departure from and attachment to his small town (The Fooleen, revised as A Crucial Week in the Life of a Grocer's Assistant). These are, on the face of it, situations familiar enough in the Irish dramatic tradition, from Padraic Colum's The Land (1905) and T. C. Murray's Birthright (1910). Murphy is not, however – nor, indeed, were Colum and Murray – evoking distresses measurable by newspaper editorials or the documentation of government reports. The literal emigrations are made to paraphrase emigrations of the self, interior journeys arrivine: at a goal or losing their way.
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THEAKSTON, ANNA L. "The Modularity Matching model: a solution to the problem of performance limitations in production?" Journal of Child Language 31, no. 2 (May 2004): 508–11. http://dx.doi.org/10.1017/s030500090400618x.
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In his review of Crain & Thornton's (C&T) (1998) ‘Investigations in Universal Grammar’ (IUG), Drozd raises the question of how models of children's linguistic competence relate to their linguistic performance. He highlights the use of processing limitations (PLs) to explain children's non-adultlike performance in most models of acquisition that adopt a Universal Grammar (UG) framework. Although the Modularity Matching (MM) model claims to avoid the need for performance-based constraints by assuming that children and adults operate with the same processing resources, Drozd argues that the model lacks predictive power.
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Cao, Shunwang, Yanhua Sha, Peifeng Ke, Tingting Li, Weixi Yuan, and Xianzhang Huang. "Deafness Gene Mutations in Newborns in the Foshan Area of South China With Bloodspot-Based Genetic Screening Tests." American Journal of Audiology 29, no. 2 (June 8, 2020): 165–69. http://dx.doi.org/10.1044/2020_aja-19-00094.
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Purpose The aim of this study was to determine the rate of deafness gene mutations in the Foshan area of South China. Method We enrolled the infants delivered in Foshan Maternity and Children's Healthcare Hospital. Deafness gene mutation was detected by HibriMax method. Our study tested 47,538 newborns within 3 days after birth, including 13 sites in four genes: GJB2 (c.35 del G, c.176 del 16, c.235 del C, c.299 del AT, c.155 del TCTG), GJB3 (c.583 C>T), SLC26A4 (c.2168 A>G, c.919-2 A>G, c.1299 C>T), and mtDNA 12S rRNA (m.1555 A>G, m.1494 C>T, m.12201 T>C, m.7445 A>G). The birth condition of infants was collected, including sex, low or high birth weight, twins, and premature delivery. Results In a total of 47,538 newborns, 1,415 were positively identified with deafness gene mutations. The total rate of the deafness gene mutation was 2.976%. The carrier rates of GJB2 (c.35 del G, c.176 del 16, c.235 del C, c.299 del AT, c.155 del TCTG), GJB3 (c.583 C>T), SLC26A4 (c.2168 A>G, c.919-2 A>G, c.1299 C>T), and mtDNA 12S rRNA (m.1555 A>G, m.1494 C>T, m.12201 T>C, m.7445 A>G) mutations were 0.000%, 0.048%, 1.422%, 0.185%, 0.000%, 0.076%, 0.116%, 0.755%, 0.160%, 0.187%, 0.021%, 0.000%, and 0.006%, respectively. Conclusions Our study showed that the c.235 del C GJB2 mutation was the leading deafness-related mutation in the Foshan area of South China. Deafness gene mutations screening in newborns detected by bloodspot-based genetic screening tests can help the diagnosis of newborn congenital hearing loss.
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Hebestreit, H., O. Bar-Or, C. McKinty, M. Riddell, and P. Zehr. "Climate-related corrections for improved estimation of energy expenditure from heart rate in children." Journal of Applied Physiology 79, no. 1 (July 1, 1995): 47–54. http://dx.doi.org/10.1152/jappl.1995.79.1.47.
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The purpose of this study was to determine the relationship between children's heart rate (HR) and climatic heat stress at several O2 uptake (Vo2) levels and to construct equations and nomograms for an improved estimation of energy expenditure (EE) from HR monitoring. On four occasions 12 boys and 8 girls (8–11 yr) cycled for 5 min each at 35, 55, and 75% of peak Vo2 (random order), with rest periods in between, in a climatic chamber. The randomly assigned conditions were 22 degrees C dry bulb temperature, 50% relative humidity (RH); 28 degrees C, 55% RH; 32 degrees C, 52% RH; or 35 degrees C, 58% RH. HR and Vo2 were determined during the final 2 min of rest and exercise bouts. HR measured at a dry bulb temperature (T) (HRmeas) was then related to a HR at 22 degrees C that would have been expected to occur at an identical Vo2 (HRcalc22) by using individual 22 degrees C HR-Vo2 regression lines. HRcalc22 could be estimated from HRmeas.[1.175032-(0.007956.T)], with a mean error of prediction for the entire group < 1.5 beats/min for each temperature. The following conclusions were drawn: 1) children's HR at a given Vo2 increases linearly with ambient temperature at 22–35 degrees C, 50–60% RH; and 2) HR can be corrected for the influence of climate in groups of children resting and exercising at the above conditions, thereby reducing the error of estimating EE from HR.
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de Schonen, Scania, and Christine Deruelle. "Visual field asymmetries for pattern processing are present in infancy. A comment on T. Hatta's study on children's performances." Neuropsychologia 29, no. 4 (January 1991): 335–37. http://dx.doi.org/10.1016/0028-3932(91)90047-c.
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Winter, Stuart S., Meenakshi Devidas, Si Chen, Barbara Asselin, William L. Carroll, Brent L. Wood, Natia Esiashvili, et al. "Capizzi-Style Methotrexate with Pegasparagase (C-MTX) Is Superior to High-Dose Methotrexate (HDMTX) in T-Lineage Acute Lymphoblastic Leukemia (T-ALL): Results from Children's Oncology Group (COG) AALL0434." Blood 126, no. 23 (December 3, 2015): 794. http://dx.doi.org/10.1182/blood.v126.23.794.794.
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Abstract Early intensification with MTX is a key component of most treatment regimens used for children, adolescents and young adults with ALL. We have previously shown that HDMTX is superior to C-MTX in B-ALL in COG Study AALL0232. Because there are differences in sensitivity to MTX and pegaspargase (PEG-ASNase) between B- and T-ALL that might affect outcome, we conducted a front-line, Phase III study for patients with T-ALL. COG AALL0434 was a 2 x 2 pseudo-factorial randomization comparing the COG augmented BFM (ABFM) regimen with C-MTX without leucovorin rescue to ABFM with HDMTX plus leucovorin rescue in T-ALL, and randomizing patients with T-ALL and T-lymphoblastic lymphoma to therapy with/without six, five-day courses of nelarabine. Study subjects with T-ALL received either block of MTX therapy during the 8-week Interim Maintenance (IM) phase; those with CNS3 status were non-randomly assigned to receive HDMTX. The T-ALL patients all received prophylactic (1200 cGy) or therapeutic (1800 cGy for CNS3) cranial irradiation (cXRT), except for the ~10% with low-risk T-ALL (NCI standard risk, CNS1 without extramedullary disease, and Day 29 minimal residual disease <0.1%), who did not receive cXRT. AALL0434 accrued 1,895 study subjects between 2007 and 2014. One thousand thirty-one T-ALL subjects without CNS3 status were randomized to receive ABFM with C-MTX or HDMTX. Subjects randomized to C-MTX (n= 518) received cXRT during Consolidation (Week 4 of protocol therapy), while subjects randomized to HDMTX (n=513) received cXRT during Delayed Intensification (DI) Week 26 of protocol therapy. The 4-year disease-free survival rates (DFS) were 89.3% (SE 1.5%) overall and 92.5% (SE 1.8%) for the C-MTX regimen vs. 86.1% (SE 2.4%) for the HDMTX regimen (p = 0.0173) (Figure 1). Interim monitoring resulted in the early release of efficacy results showing that C-MTX is superior to HDMTX, but data for the nelarabine randomization (n = 659) have not yet matured enough to assess its impact. The C-MTX regimen had 11 relapses; 7 without CNS, and 4 with CNS involvement, all occurring after Week 21 in DI phase therapy. In contrast, among those randomized to HDMTX, there were 24 relapses, 14 without CNS and 10 with CNS involvement, 6 with CNS before delivery of HDMTX and cXRT. This result is directly opposite to what we observed in B-ALL (Larsen et al, ASCO 2011), emphasizing the different biology and treatment sensitivities of B- and T-ALL. The reasons for these differences are uncertain, but may be related to different sensitivities to MTX with/without leucovorin rescue, differences in PEG-ASNase scheduling, or near universal use of cXRT in AALL0434 with different timings of cXRT administration between study arms. In conclusion, AALL0434 produced a 4-year DFS rate of 89.3% (SE 1.5%) in children, adolescents, and young adults with T-ALL, and established that ABFM with C-MTX was superior to ABFM plus HDMTX. Figure 1. Figure 1. Disclosures Hunger: Bristol-Myers Squibb: Employment; Jazz Pharmaceuticals; Sigma Tau Pharmaceuticals; Erytech: Honoraria.
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Elsiņa, Inese, and Guna Svence. "CHANGES OF MIDDLE CHILDHOOD STUDENTS’ EMOTIONAL AWARENESS IN SOCIAL COMPETENCE AND AWARENESS INTERVENTION GROUP FOR CHILDREN." SOCIETY. INTEGRATION. EDUCATION. Proceedings of the International Scientific Conference 1 (May 26, 2016): 331. http://dx.doi.org/10.17770/sie2016vol1.1530.
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Emotion awareness (EA) is the cornerstone of emotional intelligence, an essential prerequisite for the development of children's social competence. Recent scientific studies have shown that EA has a number of positive psychological outcomes. The main objective of the study was to develop and implement the EA and social competence intervention program for children (N=19, boys n=8 and girls n=11, age8 -9, M=8,05, SD=0,23) and compare the indicators of EA of middle childhood students before and after the realization of the author's program. Additional purpose of the study was the approbation of The Levels of Emotional Awareness Scale for Children (LEAS-C; Bajgar&Lane, 2003) by analysis of its psychometric indicators. In total 13 sessions were carried out during the school year 2013/2014 - from the beginning of November, 2013 until the end of May, 2014. LEAS-C (Bajgar&Lane, 2003) and Children's Personality Questionnaire (CPQ, Porter & Cattel, 1975), observations, interviews, content analysis were used. The study results show the effectiveness of intervention programs, namely, it was found that there was a statistically significant difference between the EA level of children before and after the intervention program (SELF t=- 2,99, p=0,008, OTHER t=- 3,78, p=0,001, TOTAL t=- 3,58 (p=0,002<0,05). The level of EA increased and the quality of emotional vocabulary improved after the intervention program. The LEAS-C version in Latvian language of showed high internal consistency scores and high Inter-Rater Reliability between the two encoders. The paper also carries out detailed analysis of indicators of construct validity.
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Zhang, Hao, Ming Pei Xu, Zuo Qing Dong, Shao Hua Liu, and Ai Jun Yang. "Does using outpatient room air for bleomycin foam preparation increase the risk of infection?" Phlebology: The Journal of Venous Disease 35, no. 8 (April 20, 2020): 583–88. http://dx.doi.org/10.1177/0268355520919267.
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Objective To evaluate whether the risk of infections is increased with the use of air from outpatient rooms to prepare bleomycin foam. Methods Settling plates were adopted to collect bacteria from outpatient room air, operating theatre air, human serum albumin, bleomycin solution and bleomycin foam prepared with both outpatient room and operating theatre air. The plates were placed in an incubator at 37°C for 48 h, and the number of bacterial colonies was recorded using colony-forming units. The results were analysed by the t-test. A retrospective study was then performed to evaluate the outpatient safety of bleomycin foam. Results The number of colony-forming units in the bleomycin foam produced using both operating and outpatient room air was very low, with no statistic difference. No infection cases were reported in clinical evaluation. Conclusion Using the air from outpatient treatment rooms for bleomycin foam preparation does not increase the risk of infections.
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Bhatia, Smita, Mark D. Krailo, Zhengjia Chen, Laura Burden, Frederic B. Askin, Paul S. Dickman, Holcombe E. Grier, et al. "Therapy-related myelodysplasia and acute myeloid leukemia after Ewing sarcoma and primitive neuroectodermal tumor of bone: a report from the Children's Oncology Group." Blood 109, no. 1 (September 19, 2006): 46–51. http://dx.doi.org/10.1182/blood-2006-01-023101.
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Abstract This study describes the magnitude of risk of therapy-related myelodysplasia and acute myeloid leukemia (t-MDS/AML) in 578 individuals diagnosed with Ewing sarcoma and enrolled on Children's Oncology Group therapeutic protocol, INT-0091. Between 1988 and 1992, patients with or without metastatic disease were randomized to receive doxorubicin, vincristine, cyclophosphamide, and dactinomycin (regimen A) or these 4 drugs alternating with etoposide and ifosfamide (regimen B). Between 1992 and 1994, patients with metastatic disease were nonrandomly assigned to receive high-intensity therapy (regimen C: regimen B therapy with higher doses of doxorubicin, cyclophosphamide, and ifosfamide). Median age at diagnosis of Ewing sarcoma was 12 years, and median length of follow-up, 8 years. Eleven patients developed t-MDS/AML, resulting in a cumulative incidence of 2% at 5 years. While patients treated on regimens A and B were at a low risk for development of t-MDS/AML (cumulative incidence: 0.4% and 0.9% at 5 years, respectively), patients treated on regimen C were at a 16-fold increased risk of developing t-MDS/AML (cumulative incidence: 11% at 5 years), when compared with those treated on regimen A. Increasing exposure to ifosfamide from 90 to 140 g/m2, cyclophosphamide from 9.6 to 17.6 g/m2, and doxorubicin from 375 to 450 mg/m2 increased the risk of t-MDS/AML significantly.
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Yufiarti, Yufiarti, Edwita, and Suharti. "Health Promotion Program (JUMSIH); To Enhance Children's Clean and Healthy Living Knowledge." JPUD - Jurnal Pendidikan Usia Dini 13, no. 2 (December 13, 2019): 341–55. http://dx.doi.org/10.21009/jpud.132.10.
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Knowledge about clean and healthy life in children needs to be given early to shape behavior in everyday life. Knowledge about healthy living can be provided at school through various learning programs. This study aims to find the effectiveness of health promotion programs (JUMSIH) to increase children's knowledge about clean and healthy living. The research method is a pre-experimental one-shot case study design. The respondents of this study were 68 students aged 7-8 years. The results showed that the JUMSIH program can help children have knowledge about healthy living. Based on data analysis, n = 15 generally obtained scores above 2.6. It was concluded that healthy living skills are often performed by students such as hand washing, bathing, and toothbrush behavior which are basic skills for children to be able to live healthy lives. Suggestions for further research which is the development of various programs to increase awareness of clean and healthy living from an early age.
Keywords: Clean and healthy life Knowledge, Early Childhood, Health Promotion Program (JUMSIH)
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Kutny, Matthew A., Todd A. Alonzo, Robert B. Gerbing, Kristen Miller, Phoenix Ho, Nyla A. Heerema, Beverly Lange, Alan S. Gamis, and Soheil Meshinchi. "RUNX1 Mutations in Pediatric AML: A Report From the Children's Oncology Group." Blood 114, no. 22 (November 20, 2009): 2614. http://dx.doi.org/10.1182/blood.v114.22.2614.2614.
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Abstract Abstract 2614 Poster Board II-590 The RUNX1 gene (previously AML1) encodes the alpha subunit of core binding factor (CBFα), which is implicated in normal and malignant hematopoiesis. Translocations involving RUNX1 have been associated with favorable prognosis in acute leukemias (e.g., t(8;21) in AML and t(12;21) in ALL). Point mutations of RUNX1 have been identified in exon 3 and exon 8 of the RUNX1 gene in a subset of AML patients and are most closely associated with MDS associated AML and AML subtype M0. We evaluated the prevalence and prognostic significance of RUNX1 mutations in pediatric patients with de novo AML treated on pediatric AML trials CCG-2941 and CCG-2961. Initial evaluation of exon 3 and exon 8 of the RUNX1 gene was conducted on a cohort of 100 randomly selected patient specimens. In this initial analysis, we identified 4 missense mutations of exon 3 that caused a change in codon 56. No exon 8 mutations were identified. Subsequent molecular genotyping of the remaining 484 patient specimens were limited to exon 3. Of the 584 diagnostic specimens tested, a missense mutation of exon 3 was detected in 19 patients (3.3%). All detected mutations occurred at nucleotide 167 (T to C) causing a leucine to serine substitution at codon 56 (L56S). Additionally, two patients had a synonymous mutation (G to A at nucleotide 183, P61P) and were considered wild type. Demographics, laboratory characteristics and clinical outcome were compared between those with and without RUNX1 mutations. There was no significant difference with regard to age, gender or race between these groups. Those with RUNX1 mutations had a significantly lower prevalence of organomegaly (16% vs. 42%, p=0.02) and significantly higher rate of extramedullary disease (chloroma 26% vs. 10%, p=0.04). There was no significant difference in association with other known cytogenetic abnormalities or risk groupings (standard, low, or high risk grouping on these studies). t(8;21) translocations were detected in 22% of those with RUNX1 mutations compared to 16% in those without mutation (p=0.6), and there was no RUNX1 mutation detected in patients with inv(16). Of the 85 patients with FLT3/ITD, NPM1 or CEBPA mutations, only 3 patients had a concomitant RUNX1 mutation (2 with FLT3/ITD and 1 with NPM1 mutation). Remission induction rate was compared between patients with and without RUNX1 mutations. Those with RUNX1 mutations had a similar CR rate to those without mutations (89% vs. 79%, p=0.4). Overall survival from remission for patients with and without RUNX1 mutation was 39 ± 25% and 60 ± 5% respectively (p=0.1) with a corresponding disease-free survival of 34 ± 24% vs. 49 ± 5% (p=0.25). RUNX1 mutations may represent a biologically distinct group that presents in 3.3% of pediatric AML patients across different morphologic and cytogenetic populations. Alterations of RUNX1 affect signal transduction pathways and may be exploited in defining a population for directed and risk based therapy. Disclosures: No relevant conflicts of interest to declare.
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Chrzanowska-Kluczewska, Elzbieta. "Humorous nonsense and multimodality in British and American children's poetry." European Journal of Humour Research 5, no. 3 (November 21, 2017): 25. http://dx.doi.org/10.7592/ejhr2017.5.3.kluczewska.
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Nonsense and humour are two cognitive and linguistic phenomena that frequently overlap. The focus of this article falls on chosen instances of humorous nonsense poetry, targeted at English-speaking children, which contains verbal and visual modes of expression. Formal sources of nonsense-creation in natural language can be several, among others semantic anomaly, syntactic ill-formedness and structural ambiguity, phonetic and graphological experimentation. The interplay of nonsense with the visuality of the text in children's poetry assumes three distinct forms: 1) visual poems, 2) multimodal texts,, where illustrations, often nonensical and funny in themselves, support the verbal text, and 3) texts based on the phonetic play. Examples will be drawn from the classics of the Anglophone children's poetry: Mother Goose, the Victorian classics L. Carroll and E. Lear, 20th-c. British and American poets - L. Hughes, e.e. cummings, T. Hughes, J. Agard, as well as the Polish-British pair W. Graniczewski and R. Shindler. In all the poems to be analyzed multimodality has an important role to play in the creation and strengthening of the effect of humorous bisociation/incongruity. A tight intertwining of the phonetic, semantic and visual layers in such texts becomes an additional challenge for their translators. The theoretical keystone for our considerations remains H. Bergson's study Laughter (1900/2008), which deftly combines the Superiority, the Incongruity and the Release Theory of Modern Humour Studies. Bergson rightly links the sources and effects of the nonsensical and the comic to the notion of game/play and to the idea of dream-like illusion they create.
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Xie, Chengzhi, Holly Edwards, Lisa Polin, Hui Zhou, Xuanlin Wang, Song Yang, Salvatore B. LoGrasso, et al. "Synergistic Antileukemic Interactions Between Valproic Acid and Cytarabine: A Potential Means to Improve the Treatment of Pediatric Acute Myeloid Leukemia." Blood 114, no. 22 (November 20, 2009): 2084. http://dx.doi.org/10.1182/blood.v114.22.2084.2084.
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Abstract Abstract 2084 Poster Board II-61 Acute myeloid leukemia (AML) accounts for one fourth of acute leukemias in children, but it is responsible for more than half of the leukemia deaths in this patient population. In contrast to the tremendous success in the treatment of acute lymphoblastic leukemia over the last three decades, resulting in a >80% cure rate, improvements in AML therapy have been limited. Resistance to cytarabine (ara-C), the most active drug in the treatment of AML, is a major cause of treatment failure in this disease. Therefore, new therapies for children with AML need to be developed to overcome drug resistance, decrease relapse rate, and reduce short- and long-term adverse effects of treatment. Histone deacetylase inhibitors (HDACIs) possess antitumor activity and are currently being tested in clinical trials for the treatment of a variety of different cancers. Valproic acid (VPA), an FDA-licensed drug for treating both children and adults with epilepsy, also acts as an HDACI and can induce apoptosis in leukemic cells but not normal cells. In this study, we hypothesized that VPA synergizes with ara-C in antileukemic activity by inducing apoptosis in AML cells. To model this concept and to provide the basis for future clinical studies, we examined the effects of VPA on sensitivities to ara-C in 8 AML cell lines derived from patients (4 were children) with different subtypes of AML and in AML blasts collected at the time of diagnosis from 10 children with de novo AML treated at Children's Hospital of Michigan. We demonstrated synergistic antileukemic interactions between ara-C and VPA in all of the AML cell lines and additive to synergistic antileukemic interactions between the two drugs in the patient samples by standard isobolograms and calculation of combination indexes. It is interesting to note that MV4-11 [which harbors t(4;11)] and Kasumi-1 [which harbors t(8;21)] cells were substantially more sensitive to VPA than the other AML cell lines. Analogous to the Kasumi-1 cells, diagnostic blasts from t(8;21) AML cases (n=4) were significantly more sensitive to VPA than blasts from non-t(8;21) AML cases (n=6) (mean VPA IC50 0.51 mM vs 1.95 mM, p=0.0095) and showed median 53.9-fold increased ara-C sensitivities when combined with VPA at concentrations of 0.5 mM or lower. By contrast, non-t(8;21) AML blasts only showed median 2.1-fold increased ara-C sensitivities when combined with 0.5 mM VPA (p=0.048). In a pilot experiment, treatment of SCID mice with K562 xenograft tumors with combined Palmo-ara-C and VPA resulted in a 31% T/C and a 0.8 gross log cell kill compared to treatments with Palmo-ara-C (67% T/C) or VPA alone (100% T/C), establishing unambiguous in vivo synergy. Real-time RT-PCR analyses revealed changes in transcript levels for hENT1 and cytidine deaminase in Kasumi-1 cells post VPA and ara-C treatment alone or in combination. However, these changes would antagonize ara-C sensitivity in Kasumi-1 cells, suggesting that the effects of VPA or ara-C alone or in combination on expression of genes related to ara-C transport and metabolism do not contribute to the observed synergistic effects in AML cells. Interestingly, ara-C and VPA co-treatment resulted in synergistic induction of apoptosis and S-phase arrest in Kasumi-1 cells determined by flow cytometry analysis with annexin V and PI staining. The synergy between ara-C and VPA in induction of apoptosis in Kasumi-1 cells was accompanied by synergistic activation of caspase-3, induction of both total and acetylated p53 (ac-p53), and release of the active form of Bax determined by caspase-3 assays, co-immunoprecipitation, and Western blotting. Collectively, these results suggest that VPA enhances ara-C sensitivity in Kasumi-1 cells most likely by modulating levels of total and ac-p53 proteins and then release of the active form of Bax to trigger apoptosis. Based on our laboratory results, VPA has been incorporated into a treatment arm for high risk AML patients enrolled in the St. Jude Children's Research Hospital (SJCRH) clinical trial AML08: “A Randomized Trial of Clofarabine Plus Cytarabine Versus Conventional Induction Therapy and of Natural Killer Cell Transplantation Versus Conventional Consolidation Therapy in Patients with Newly Diagnosed Acute Myeloid Leukemia”. The results of our study provide compelling evidence to support the use of VPA in combination with ara-C in clinical trials for treating different risk groups of pediatric AML. Disclosures: No relevant conflicts of interest to declare.
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BROOKS, PATRICIA J. "Grammatical competence is not a psychologically valid construct." Journal of Child Language 31, no. 2 (May 2004): 467–70. http://dx.doi.org/10.1017/s0305000904006087.
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It is not unusual for developmental psychologists to become frustrated with the theory of universal grammar (UG), whose proponents have tended to dismiss most research on children's language production and comprehension as irrelevant to explaining how human languages are acquired. This is because children's actual linguistic behaviour is presumed to reflect factors besides their grammatical competence, rendering most methods of sampling linguistic behaviour unsuitable for evaluating UG theory. This means, in practice, that UG proponents do not view performance errors as evidence against their hypothesis that grammatical knowledge is largely innate. When children perform at ceiling on a given task, this is usually taken as proof of their adultlike grammatical competence, while poor performance is dismissed as due to research design flaws or limitations in information processing capacities (e.g. working memory). Crain & Thornton (1998) attempt to eliminate what they consider to be post hoc processing accounts of children's linguistic behaviour by arguing, counter to Chomsky (1965) and many others, that children and adults share identical language processing mechanisms, and that linguistic performance directly reflects grammatical competence. Therefore, if UG principles are available from an early age, child and adult performance should be the same when tasks are properly constructed to avoid extra-linguistic demand characteristics (excepting adult–child differences predicted by parameter-setting or maturational models). It should not be surprising then that some psycholinguists, such as Drozd (target article), would find C&T to be misguided with respect to these issues, because children's linguistic behaviour surely differs from adults' in seemingly unpredictable ways.
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Insani, Asri, Yufiarti, and Elindra Yetti. "Parental Involvement and Mothers' Employment on Children's Independence During Covid-19 Pandemics." JPUD - Jurnal Pendidikan Usia Dini 15, no. 1 (April 30, 2021): 22–40. http://dx.doi.org/10.21009/jpud.151.02.
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The pandemic that occurred this year created conditions that changed the activities of parents and children, the role of parents working outside the home often led to a lack of parental involvement in child development, especially the development of independence. The conditions of the Covid-19 pandemic have caused parents and children to be in one place at the same time. This study aims to determine the effect of parental involvement and maternal employment status on the independence of children aged 7-8 years in the Covid-19 pandemic situation. This quantitative research uses a comparative causal ex-post facto design, with groups of working mothers and groups of non-working mothers. The sample of each group was 60 people who were randomly selected. The findings of the study with the calculation of the two-way ANOVA test obtained the value of Fo = 4.616> F table = 3.92 or with p-value = 0.034 <α = 0.05, indicating that there is an interaction between parental involvement and maternal employment status on children's independence, and Based on the results of hypothesis testing, there is no effect of parental involvement and mother's work status on the independence of the child even though there are differences in the average results of children's independence.
Keywords: Children's Independence, Parental Involvement and Mothers' Employment
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Schorin, M. A., S. Blattner, R. D. Gelber, N. J. Tarbell, M. Donnelly, V. Dalton, H. J. Cohen, and S. E. Sallan. "Treatment of childhood acute lymphoblastic leukemia: results of Dana-Farber Cancer Institute/Children's Hospital Acute Lymphoblastic Leukemia Consortium Protocol 85-01." Journal of Clinical Oncology 12, no. 4 (April 1994): 740–47. http://dx.doi.org/10.1200/jco.1994.12.4.740.
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PURPOSE The goals of this treatment program were as follows: to improve event-free survival (EFS) rates for high-risk (HR) patients by increasing the intensity of induction treatment; to improve EFS rates for infants by adding a special postinduction intensification; to treat the CNS using cranial irradiation doses that were lower than in our historic control group; and to confirm our previously obtained good results for children with T-cell disease. PATIENTS AND METHODS Two hundred twenty children with acute lymphoblastic leukemia (ALL) from all risk groups, including infants and patients with T-cell disease, were treated between 1985 and 1987 with multiagent chemotherapy and cranial irradiation. RESULTS The 7-year EFS rate (+/- SE) for all 220 patients was 78% +/- 3% at a median follow-up duration of 6.2 years, 89% +/- 4% for the 82 patients classified as standard risk (SR), and 72% +/- 4% for the remaining 138 patients classified as HR and very high risk (VHR). Eleven infants had an EFS rate of 55% +/- 15% that might be attributable to treatment with high doses of methotrexate and cytarabine (ara-c). Twenty children with T-cell disease had an EFS rate of 70% +/- 10%. CNS leukemia relapse (isolated or combined with bone marrow) occurred in four of 82 SR patients who received 18 Gy of cranial irradiation and four of 138 HR and VHR patients who received 24 Gy. CONCLUSION This protocol, which featured early intensive treatment including asparaginase, doxorubicin, and cranial irradiation, provided good long-term disease control for children with ALL.
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Yang, Jun, Heng Xu, Cheng Cheng, Meenakshi Devidas, Deqing Pei, Yiping Fan, Wenjian Yang, et al. "ARID5B Genetic Polymorphisms Contribute to Racial Disparities In Childhood Acute Lymphoblastic Leukemia: A Children's Oncology Group Study." Blood 116, no. 21 (November 19, 2010): 8. http://dx.doi.org/10.1182/blood.v116.21.8.8.
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Abstract Abstract 8 Acute lymphoblastic leukemia (ALL) is the most common type of cancer in children. Substantial racial differences exist not only in the risk of developing childhood ALL, but also in the outcome of ALL therapy, e.g. children with Hispanic ethnic background exhibit the highest incidence of ALL and the lowest survival rate among major racial/ethnic groups in the US. Although both genetic and non-genetic factors are thought to be important, the exact cause(s) of such racial disparities remains largely unknown. Taking a genome-wide approach, we previously identified single nucleotide polymorphisms (SNPs) in the ARID5B gene that are strongly associated with ALL risk in whites (e.g. rs10821936, P=1.4×10-15, Nat. Genet. 2009, 41:1001), which was independently replicated in several studies (Nat. Genet. 2009, 41:1006; Blood 2010 115:1765). Interestingly, the ALL risk allele (allele C) at the ARID5B SNP is also associated with ALL risk in black children, but is much less prevalent in blacks than whites (allele C frequency, 18% in blacks and 34% in whites), providing a genetic basis for the lower risk of ALL in black children (Leukemia 2010 24:894). In this study, we evaluated the contribution of ARID5B genetic variations to the disparities in ALL incidence and outcome between Hispanic and white children. To identify genetic variations associated with ALL in each population, we first compared genotype frequencies at 51 ARID5B SNPs between ALL cases and ancestry-matched controls, i.e., between 330 Hispanic children with ALL and 134 Hispanic controls; and between 978 white children with ALL and 1,046 white controls. After adjusting genetic ancestry to control for population stratification, we observed that 10 of 51 ARID5B SNPs were significantly associated with ALL in both populations, and 6 and 10 SNPs were significant only in whites and Hispanics, respectively. In both race groups, the strongest association was observed at rs10821936 (P= 8.3×10-20 in whites and P=3.7×10-8 in Hispanics). Interestingly, the frequency of the ALL risk allele (allele C) at rs10821936 was higher in Hispanics (43%) than in whites (33%), consistent with the higher incidence of ALL in Hispanics. In fact, for all 10 SNPs significant in both populations, the risk alleles were consistently more common in Hispanics than whites and conferred greater risk of ALL (higher odds ratios in Hispanics than whites). Additionally, we performed forward selection-based multivariate analyses in each population in which ARID5B SNPs compete against each other on the basis of independent associations with ALL. In whites, rs10821936 was the first and only SNP that entered the multivariate model, suggesting a single causal variant at the ARID5B locus tagged by this SNP. In contrast, in Hispanics, 3 ARID5B SNPs were independently associated with ALL in the multivariate model even after adjusting for genotype at rs10821936. Moreover, these 3 ARID5B SNPs were located in linkage disequilibrium blocks distinct from that tagged by rs10821936, arguing for multiple possible causal variants in the ARID5B gene in Hispanics. Finally, we tested whether ARID5B polymorphisms are related to treatment outcome in 1,605 children enrolled on the COG P9904 and P9905 studies. Of 26 ARID5B SNPs associated with ALL risk, 5 were also associated ALL relapse (P<0.05), with the alleles related to disease risk always linked to poorer treatment outcomes. For instance, the T allele at rs6479778 was more frequent in ALL cases than in healthy controls (P=0.0029 in whites and P=0.0031 in Hispanics), and patients carrying the T allele also exhibited an increased risk of ALL relapse (P=1.3×10-4). Because the T allele is more common in Hispanics (24%) than whites (14%), this polymorphism is likely to contribute to the racial differences in both disease risk and treatment outcome of ALL. In conclusion, our results indicate that genetic polymorphisms in the ARID5B gene are important determinants of racial disparities in childhood ALL. Disclosures: Relling: St. Jude Children's Research Hospital: Employment, Patents & Royalties; Enzon Pharmaceuticals: Research Funding.
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Rafiee, Roya, Soheil Meshinchi, and Jatinder K. Lamba. "ABCB1 rs1045642 C>T Change Is Associated with AML Cell Line Sensitivity to Calicheamicin." Blood 132, Supplement 1 (November 29, 2018): 1364. http://dx.doi.org/10.1182/blood-2018-99-119648.
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Abstract Introduction: Gemtuzumab ozogamicin (GO), a CD33-antibody conjugated to DNA damaging cytotoxin-calicheamcin is a re-emerging and promising drug in AML treatment. Promising results from multiple clinical trials demonstrated GO improved outcomes in both adult and pediatric patients with most pronounced effect in favorable-risk cytogenetics. In light of these results GO was reapproved for treatment of AML by FDA in Sep 2017. Given the anticipated increase in GO use post approval, it is very timely to understand mechanisms contributing to differences in patient response. Calicheamicin releases intracellularly and causes DNA strand breaks which leads to apoptosis and cell death. The anti-leukemic effects of GO are thus entirely due to calicheamicin-induced DNA damage. Given that calicheamicin is a substrate of drug transporter ABCB1 (Pgp1), genetic polymorphisms in ABCB1 can impact the intra-cellular accumulation of calicheamicin and thus clinical outcome. Our group have recently shown that ABCB1 synonymous SNP rs1045642 C>T (also well known as 3435C>T) is associated with clinical outcome in children with AML trial, now we report the results of the in vitro evaluation of impact of ABCB1 SNP on calicheamicin mediated cell cytotoxicity. Methods: To understand differences in in vitro calicheamicin toxicity mediated by ABCB1 variation, HL-60 cells with low native ABCB1 expression were transfected with expression plasmid of ABCB1*1 (rs1045642-C and also WT for other two other SNPs in ABCB1) (WT Plasmid), and rs1045642-T. Cells were harvested 48 hours' post-transfection and treated with 40nM calicheamicin for 24 hours. Posttreatment cell were stained with permeant nuclear stain (NucRed® 647 Live Invitrogen) that emits bright far-red fluorescence upon binding to DNA in live cells. One-hour after incubation with the dye, calicheamicin toxicity was assessed by checking cell viability using flow cytometry (BDTM LSR II) and Nikon fluoresce microscope for additional visualization. Results: As shown in Figure 1a, our previous data show rs1045642 a synonymous coding change in ABCB1, in patients treated with GO presence of variant allele (CT/TT) is associated with significantly improved outcome as compared to patients with CC genotype (risk of relapse CC=45±10%, CT=30±7% TT=28±10%, CC vs. CT/TT p=0.007). Consistent with these results we observe significant decrease in cell viability with transfection with ABCB1-rs1045642/3435T as compared to the ABCB1-rs1045642/3435-C (P < 0.05) expression constructs. These results indicate that higher levels of calicheamicin toxicity in ABCB1-3435T transfected cells as opposed to cells transfected with the WT plasmid (Figure 1b and c) probably due to impact of T allele on ABCB1 levels. rs1045642-T allele has been shown to be associated with lower ABCB1 expression in several studies and with higher expression in one study. Hofmeyer et al has previously inked TT genotype of rs1045642 with lower expression and activity of ABCB1 which is consistent with our observation with respect to calicheamicin. Although more work is required to establish the clear relationship between ABCB1 genotypes and calicheamicin efflux, our results suggest that presence of ABCB1- low expressing rs1045642 TT genotype might be resulting in lower-efflux and thus higher intracellular abundance of calicheamicin in leukemic cells which in turn makes cells more sensitive to calicheamicin. Acknowledgments: Funding support from R21CA155524 and Children's Oncology group Disclosures No relevant conflicts of interest to declare.
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Bang, Hye-Young, Meghan Clayards, and Heather Goad. "Compensatory Strategies in the Developmental Patterns of English /s/: Gender and Vowel Context Effects." Journal of Speech, Language, and Hearing Research 60, no. 3 (March 2017): 571–91. http://dx.doi.org/10.1044/2016_jslhr-l-15-0381.
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Purpose The developmental trajectory of English /s/ was investigated to determine the extent to which children's speech productions are acoustically fine-grained. Given the hypothesis that young children have adultlike phonetic knowledge of /s/, the following were examined: (a) whether this knowledge manifests itself in acoustic spectra that match the gender-specific patterns of adults, (b) whether vowel context affects the spectra of /s/ in adults and children similarly, and (c) whether children adopt compensatory production strategies to match adult acoustic targets. Method Several acoustic variables were measured from word-initial /s/ (and /t/) and the following vowel in the productions of children aged 2 to 5 years and adult controls using 2 sets of corpora from the Paidologos database. Results Gender-specific patterns in the spectral distribution of /s/ were found. Acoustically, more canonical /s/ was produced before vowels with higher F 1 (i.e., lower vowels) in children, a context where lingual articulation is challenging. Measures of breathiness and vowel intrinsic F 0 provide evidence that children use a compensatory aerodynamic mechanism to achieve their acoustic targets in articulatorily challenging contexts. Conclusion Together, these results provide evidence that children's phonetic knowledge is acoustically detailed and gender specified and that speech production goals are acoustically oriented at early stages of speech development.
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KIM, YOUNG-SUK. "Phonological awareness and literacy skills in Korean: An examination of the unique role of body-coda units." Applied Psycholinguistics 28, no. 1 (January 2007): 69–94. http://dx.doi.org/10.1017/s014271640707004x.
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This study examines a salient intrasyllabic phonological unit in Korean, the body-coda unit, its role in literacy skills in Korean, and a possible source of the salience of body-coda units in the spoken language. Data were collected from Korean-speaking, monolingual beginning readers (41 kindergarteners, 40 first graders). The results indicate that body-coda boundary (e.g.,ca-t) is more salient than onset–rime boundary (e.g.,c-at) for Korean children and show that children's body-coda awareness is an important predictor of word decoding and spelling in Korean. Furthermore, the analysis of phonological neighbors and frequency of syllable types suggests that a phonotactic feature in Korean, the frequency of consonant–verb syllable type, may be a possible source of the saliency of the body-coda intrasyllabic division for Korean children.
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Ham, Suchang, and Hanyi Lee. "The influence of mothers' health beliefs and attitudes on prevention of infectious diseases on preventive health behaviors of late school-aged children." Journal of Korean Academic Society of Nursing Education 27, no. 3 (August 31, 2021): 287–97. http://dx.doi.org/10.5977/jkasne.2021.27.3.287.
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Purpose: The purpose of this study was to examine the differences in preventive health behaviors of school-age children according to their mothers' health beliefs and attitudes toward the prevention of infectious diseases. Methods: This study was conducted with 121 pairs of 4th to 6th grade elementary school children and their mothers from October 13 to October 30, 2020. The collected data were analyzed using descriptive analysis, an independent t-test, a one-way ANOVA, Sheffé’s test, Pearson’s correlation coefficient analysis and a multiple linear regression.Result: The mean and SD of mother's health belief in preventing infectious diseases was 3.58±0.41, the mean and SD of mother's attitude toward preventing infectious diseases was 3.39±0.38, and the mean and SD of late school-age children's preventive health behavior was 3.52±0.37. The multiple linear regression results show that the children's vaccination behavior was influenced by their mothers’ perceived benefits in preventing infectious diseases. In addition, the child's vitamin C and vegetable consumption was influenced by the mother's perceived susceptibility in preventing infectious diseases, and the child's mask-wearing behavior was influenced by the mother's perceived seriousness in preventing infectious diseases. Conclusion: In order to improve the health behavior of school-aged children, programs or education are required to enhance the health beliefs and attitudes of their mothers, who were shown to affect the preventive health behavior of their children.
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Hobbs, Christopher J. "It Hurts You Inside: Children Talking About Smacking. C. Willow & T. Hyder. London: National Children's Bureau, 1998. pp. 106. £13.00 (non-members of NCB); £8.50 (NCB members) (pb)." Child Psychology and Psychiatry Review 4, no. 4 (November 1999): 190–93. http://dx.doi.org/10.1017/s1360641799252057.
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Li, Shiyong, and Glen Lew. "Is B-Lineage Acute Lymphoblastic Leukemia With a Mature Phenotype and L1 Morphology a Precursor B-Lymphoblastic Leukemia/Lymphoma or Burkitt Leukemia/Lymphoma?" Archives of Pathology & Laboratory Medicine 127, no. 10 (October 1, 2003): 1340–44. http://dx.doi.org/10.5858/2003-127-1340-iballw.
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Abstract Context.—B-lineage acute lymphoblastic leukemia (ALL) with a mature phenotype and L1 morphology is a rare condition that may pose a diagnostic and management challenge. Objective.—To report our experience with 2 such unusual cases of pediatric B-lineage ALL. Design.—Morphologic, immunophenotypic, and cytogenetic features of the leukemic blast cells were reviewed in conjunction with clinical and other laboratory findings. Results.—The leukemic blast cells in both cases were small to medium with scant basophilic cytoplasm and several small inconspicuous nucleoli, characteristic of L1 lymphoblasts. Immunophenotypically, they were positive for CD19, CD22, and low-density CD20, with expression of surface immunoglobulin λ light chain. They were negative for immature (CD34 and terminal deoxynucleotidyl transferase), myeloid, and T-cell–associated markers. Conventional cytogenetic and fluorescent in situ hybridization studies failed to demonstrate chromosomal translocations involving the c-myc gene. Both patients were treated with Children's Cancer Group ALL protocols and had good responses. Conclusions.—B-lineage ALL with a mature phenotype, L1 morphology, and absent chromosomal translocations involving the c-myc gene is best classified and managed as precursor B-lymphoblastic leukemia/lymphoma instead of Burkitt leukemia/lymphoma.
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Voigt, Andrew P., Lisa Eidenschink Brodersen, Robert B. Gerbing, Andrew J. Menssen, Betsy A. Hirsch, Susana C. Raimondi, Alan S. Gamis, Todd A. Alonzo, Soheil Meshinchi, and Michael R. Loken. "Recurrent Genetic Abnormalities Are Reflected in Phenotype at Diagnosis in Pediatric Acute Myeloid Leukemia: A Report from the Children's Oncology Group Protocol AAML0531." Blood 126, no. 23 (December 3, 2015): 1377. http://dx.doi.org/10.1182/blood.v126.23.1377.1377.
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Abstract Background: Acute myeloid leukemia (AML) is a heterogeneous disease with high genomic and phenotypic complexity. Although a relationship between phenotype and t(15;17) is recognized, the effect of other genotypic abnormalities on phenotype remains to be elucidated. Objective: To explore the relationships between genotypic and phenotypic abnormalities in diagnostic specimens in pediatric AML. Methods: Of 1022 newly diagnosed pediatric patients with de novo AML enrolled on protocol AAML0531, 769 satisfied three criteria for this study: (1) submission of a blood or bone marrow sample for multidimensional flow cytometry (MDF) at diagnosis, (2) consent to blood bank specimen testing and (3) leukemia comprising >10% of non-erythroid cells by MDF. The diagnostic AML tumor population was identified by gating on CD45 vs log-SSC. A fifteen-dimensional immunophenotypic expression profile (IEP) was defined by computing mean fluorescent intensities, antigen intensity coefficient of variations, and light scatter characteristics of each leukemia without analyst imposed cut-offs. Unsupervised hierarchical clustering was performed to mathematically cluster patients with similar IEPs. The underlying karyotypic and mutational profile of each patient was compared to the IEPs to identify clusters of patients with relationships between phenotype and identifiable genetic abnormalities. Supervised bagged tree-based models were used to quantify the importance of each cell-surface antigen in identifying these clusters. Levene's test was used to assess the homogeneity of mean cell-surface antigen expression for important markers. Results: Analysis of hierarchical clustering results revealed 7 immunophenotypic clusters (A-G) of patients with relationships between IEP and 4 common genetic abnormalities (Figure 1). Cluster A and Cluster B were both strongly associated with the t(8;21) karyotype (Figure 1). 54/62 patients in Cluster A (87%) and 24/26 patients in Cluster B (92%) were positive for t(8;21). The most important cell-surface antigens in identifying patients with the Cluster A associated phenotype were dim CD33, expression of CD56, expression of CD34 and expression of HLA-DR. The mean antigen expression of these markers was significantly more homogenous for patients in Cluster A compared to all other patients for CD33 (p = 0.02), CD34 (p < 0.01) and HLA-DR (p<0.01). Mean expression of CD56 was notably more heterogeneous (p = 0.40) but positive in 91% of patients in this cluster. The most important cell-surface antigens in identifying the Cluster B associated phenotype were dim CD13, expression of CD34, expression of HLA-DR and dim CD33. The mean expression of these markers was significantly more homogeneous for patients in Cluster B compared to all other patients (all p values <0.01). In contrast to Cluster A, CD56 MFIs were negative for patients in Cluster B. Collectively, 72% of all patients with t(8;21) segregated into Cluster A (50%) or Cluster B (22%). Cluster C was strongly associated with chromosome 16 abnormalities (Figure 1). Of patients in this cluster, 50/55 (91%) were positive for inv(16)/t(16;16). The mean high-expression of CD13 was the most important antigen in identifying patients with this phenotype, and patients in Cluster C had more consistent mean CD13 expression compared to all other patients (p<0.01). 53% of all patients with chromosome 16 abnormalities comprised this cluster. Cluster D was strongly associated with 11q23 abnormalities (Figure 1). Of patients in this cluster, 105/135 (78%) were positive for 11q23 translocations. The most discriminating markers in identifying these patients were dim-to-negative CD34 and dim-to-negative CD117. 69% of all patients with 11q23 abnormalities comprised this cluster. Clusters E, F and G were associated with FLT3 ITD mutations (Figure 1). Of patients in these clusters, 44%, 49% and 53% were positive for FLT3 ITD mutations. Cumulatively, 63% of all patients with FLT3 ITD mutations were grouped into one of these three clusters. Conclusion: Hierarchical clustering algorithms identify IEPs associated with common genetic abnormalities in pediatric AML, providing insight into the consistent dysregulation of cell-surface gene product expression in patients with common genetic abnormalities. Further analysis may reveal that IEPs can identify patients otherwise classified as good or standard risk that will have a poor outcome. Disclosures Voigt: Hematologics Inc.: Employment. Brodersen:Hematologics Inc.: Employment. Menssen:Hematologics Inc.: Employment. Loken:Hematologics Inc.: Equity Ownership.
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Liang, Der-Cherng, Lee-Yung Shih, Chao-Ping Yang, Iou-Jih Hung, Tang-Her Jaing, Hsi-Che Liu, Ting-Chi Yeh, et al. "Cooperation of Gene Mutations Including Class I, Class II and Tumor Suppressor Genes In Childhood Acute Myeloid Leukemia and Their Impacts on Survivals." Blood 116, no. 21 (November 19, 2010): 2713. http://dx.doi.org/10.1182/blood.v116.21.2713.2713.
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Abstract Abstract 2713 Background. The cooperation of gene mutations, especially their impacts on survivals of childhood acute myeloid leukemia (AML) has not been well known. Aims. Our aims were (1) to study the frequency of each gene mutation in childhood AML, (2) to study the impact of each gene mutation on the treatment outcome, and (3) to examine the cooperativity of gene mutations. Materials and Methods. From Feb. 1996 to Jan. 2010, bone marrow samples at diagnosis from 198 children with AML at Chang Gung Children's Hospital, Taoyuan and Mackay Memorial Hospital, Taipei, were analyzed for gene mutations including FLT3-ITD, FLT3-TKD (D835), c-KIT, cFMS, JAK 2V617F, NRAS, KRAS, PTPN11 (Class I mutations), RUNX1, CEBPα, NPM1 (Class II mutations), WT1 and P53 (tumor suppressor genes). The subtypes included: t(8;21) 19.9%, inv(16) 8.9%, t(15;17) 8.4%, t(9;11) 5.2%, t(10;11) 2.6%, trisomy 21 4.2%, intermediate-risk group 40.3% (including 13 patients with other MLL translocations), and poor-risk group 11.0% (including 7 patients with complex chromosomal abnormalities and 4 patients with MLL-PTD). Results. FLT3-ITD occurred in 15.0% of patients, FLT3-TKD 7.2%, c-KIT 11.5%, c-FMS 2.9%, JAK2V617F 3.3%, NRAS 9.1%, KRAS 7.7%, PTPN11 3.3%, RUNX1 2.7%, CEBPα 7.9%, NPM1 4.1%, WT1 3.9% and P53 1.7%. Taken together, 52.5% of patients had Class I gene mutations, 13.1% had Class II gene mutations, and 5.1% had WT1 or P53 mutations. In all, 59.1% of patients had Class I, Class II or tumor suppressor gene mutations. Only one patient (0.5 %) had gene mutations involving all Class I, Class II and tumor suppressor genes. Ninety-eight patients, who were treated with Taiwan Pediatric Oncology Group (TPOG) APL protocols (for acute promyelocytic leukemia) and TPOG 97A protocol (for other AML) (Liang et al, Leukemia 2006), were analyzed for survivals. In patients with t(8;21), the 5-year event-free survival (EFS) was 66±12%; 71±17% for patients with c-KIT mutations and 50±35% for the 2 patients with JAK2V617F. In patients with inv(16), the EFS of 70±15% seemed to be compromised (60±22%) for those with c-KIT mutations. In patients with t(15;17), the EFS of 78±11% was not compromised by FLT3-ITD or FLT3-TKD mutations. In patients with t(9;11), the EFS of 64% seemed to be compromised (50±35%) in the 2 patients with FLT3-TKD mutations. In 3 patients with t(10;11), no gene mutations were found. In trisomy 21, the EFS of 75±22% seemed to be compromised (50±35%) in the 2 patients with CEBPα mutations. Of the 5 patients with complex chromosomal abnormalities, the only one patient carrying RUNX1 survived. Of the 3 patients with MLL-PTD having an EFS of 33±27%, one each patient with c-FMS or WT1 mutation died. The only one patient who had all Class I, Class II and tumor suppressor gene mutations (FLT3-TKD+ CEBPα+ WT1) died in induction therapy. Two of the other 4 patients who had 3 mutations acrossing 2 classes had EFS of 6 and 10 months, respectively. Conclusions. Our study on a large cohort of pediatric AML patients revealed that 59.1% patients had at least one gene mutation. That 3 of 5 patients who had 3 gene mutations soon failed suggested that gene mutations, especially in 3 combinations, might compromise the survival. Further study on more patients is warranted to explore more of the prognostic significance of cooperating gene mutations in pediatric AML. (Supported by grants MMH-E-98009, NSC 96–2314-B-195-006-MY3, NHRI-EX-96-9434SI and DOH99-TD-C-111-006.) Disclosures: No relevant conflicts of interest to declare.
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Pangestuti, Retno, Anissa Lestari Kadiyono, Surya Cahyadi, and Hendriati Agustiani. "A Modifying the Instrument of Self-Regulation in Early Childhood Assessment." JPUD - Jurnal Pendidikan Usia Dini 13, no. 1 (April 30, 2019): 114–27. http://dx.doi.org/10.21009/10.21009/jpud.131.09.
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Self-regulation for pre-school children is very important to support children’s adjustments in all situations and conditions. The current problem is the instrument of self-regulation is more focused on regulation in learning which is not suitable for young children. This study aims to examine the validity and reliability of Preschool Self-Regulation Assessment (PSRA) in Indonesia by modifying several children self-regulation theories. The instrument was translated from English into Indonesian and it retranslated into the native language by linguists. The questions, then, were validated through a process of professional judgment and cognitive de-briefing. The study was carried out to 179 children aged 6 to 7 years old. Data were analyzed by using confirmatory factor analysis (CFA). It showed that there are 5 dimensions of children's self-regulation, namely: attentional focus, behavioral control, self-motivated, self-autonomy and emotional control. The result showed that the five-dimensional model is agreed with the data and prove to measure children’s self-regulation. Cronbach’s alpha coefficient value was 0.899, indicating high scale reliability. Thus, the pre-school children’s self-regulation assessment has well psychometric for further use.
Keywords: Children’s self-regulation, Confirmatory Factor Analysis, Construct validation, Pre-school self-regulation assessment, Reliability
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Basargina, E. N., M. K. Umarova, K. V. Savostyanov, Yu V. Derevnina, and I. E. Smirnov. "THE FREQUENCY OF THROMBOTIC COMPLICATIONS AND FEATURES OF GENOTYPES OF POLYMORPHIC MARKERS OF HEMOSTASIS GENES IN CHILDREN WITH NONCOMPACT CARDIOMYOPATHY." Russian Pediatric Journal 20, no. 3 (April 30, 2019): 139–44. http://dx.doi.org/10.18821/1560-9561-2017-20-3-139-144.
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Noncompaction cardiomyopathy (NCMP) is characterized by the anomalous myocardium structure and various types of cardiac remodeling, in some cases it is accompanied by thrombotic complications. Preconditions for thrombosis in the disease are unknown, as also there are differences in thrombosis rates between NCMP and other cardiomyopathies, similarly accompanied by the chronic heart failure and analogous remodeling phenotypes. Aim of study is to reveal the difference in the rate of thrombosis in NCMP and dilated cardiomyopathies (DCMP) in children, and to define differences in the frequency of different genotypes of polymorphic markers in an array of hemostasis genes in the two cardiomyopathies. Methods. There was executed a prospective-retrospective cohort study, included patients from the Cardiac Department of the National Scientific and Practical Center of Children's Health from October 2011 to May 2015. The presence of NCMP was established by echocardiography, alleles and genotypes of polymorphic markers of hemostasis and folate cycle genes were determined by polymerase chain reaction in real-time mode. Results. Thrombotic complications in NCMP children were observed more often than in DCMP cases. There were no differences between NCMP and DCMC patients in the frequency of the polymorphic markers c.1691G>A of the F5 gene (p=0.61) , c.20210G>A of the F2 gene (p=1.0) , c.1565T> C of the ITGB3 gene (p=0.32) , 5G(-675)4G of PLANH1 gene (p=0,52) , G(-455)A of FGB gene (p=0.82) , c.677C>T of MTHFR gene (p=0.11). Conclusion Thrombotic complications in NCMP children occur rather more often than in DCMP cases, studied polymorphic markers of the hemostasis and folate cycle genes do not cause this difference, and this requires continuation of the study.
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Georgescu, Nicolae. "The history of orthopedics and traumatology in Iasi." Jurnalul de Chirurgie 17, no. 1 (April 20, 2021): 56–62. http://dx.doi.org/10.7438/jsurg.2021.01.08.
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In Iasi, Orthopedics-Traumatology later appeared as a distinct specialty. In a first stage, orthopedics developed in surgical clinics - the period of surgical clinics (1879-1970). In each surgical clinic there were surgeons who dedicated themselves to orthopedic pathology: Radu Dimitrie, Theodor Căpățînă (Surgery I), Filimon Cicerone, Eusebiu Neagoe, Iulian Grădinaru (Surgery II), Paul Trosc (Surgery III). In 1967, at the Charity Hospital, two surgical services were carried out: The Surgery and Children's Orthopedic Clinic (Th. Economu) and the Osteoarticular Tuberculosis Clinic (A. Berneaga). Also, this year, 1970, in Iasi, the construction of a new medical unit will be completed - the Children's Hospital where the Clinic of Pediatric Surgery and Orthopedics will be moved. The Charity Hospital is disbanded and the Emergency Clinical Hospital will be established on the site of the former establishment. A second period begins - the transition period (1970-1983) - characterized by the search for optimal solutions, which involved changes and temporary until the establishment of orthopedic clinics. The newly established unit, the Emergency Clinical Hospital, was designed to include three departments: General Surgery IV (I. Jitaru), Medical Clinic (G. Popa) and an Orthopedics and Traumatology Clinic (conf. Gh. Floareș). This clinic treated all surgical pathology of orthopedics, traumatology and had didactic activity with fourth year students. The Orthopedics-Traumatology Department had 40 beds. There is also an Orthopedics-Traumatology department, with 40 beds, located in the Dr. C. I. Parhon Hospital run first by A. Berneaga and then by P. Trosc. Dimitrie Radu, Iulian Grădinaru and G. Herescu worked in this department. A new Recovery Hospital appears in Iasi. The new hospital also has an Orthopedics-Traumatology department (with 111 beds) where the orthopedics department will be transferred from Parhon Hospital. In 1983, Professor Gh. Floareș opted to move the clinic from the Emergency Hospital to the new Rehabilitation Hospital. At the Emergency Hospital there remains an Orthopedics-Traumatology Department staffed by a single doctor - Nicolae Georgescu who will develop a new team, which also have teaching activity: T. Cozma, L. Stratan, P. Sîrbu, Ovidiu Alexa, Paul Corlaci, Cezar Popescu. There are eight resident doctors (Elena Glod, Luminița Lăbușcă, Victor Pencu, G. Ghinoiu, C. Nanu, T. Bunescu, R. Malancea, L. Pacu). During this period (1992-1996) a basic A.O. course was organized in Iași. internationally, on which occasion many orthopedists are persuaded to routinely use modern means of osteosynthesis. Two more doctors come in this clinic: B. Puha, R. Asaftei, D. Cionca and A. Ciubara. After 1989, the ATOM was born: The Association of Traumatologists and Orthopedists of Moldova, congresses and postgraduate courses are organized. In 2012 the Orthopedic Clinic moved to the St. Spiridon Emergency Clinical Hospital (Prof. Ovidiu Alexa). The orthopedic clinic at the Recovery Hospital treats chronic osteoarticular pathology (prof Paul Sirbu).
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Goldman, S., J. C. Lynch, L. Harrison, and M. S. Cairo. "A prospective trial of prophylaxis and treatment (P+T) of acute tumor lysis syndrome (ATLS) with rasburicase (R) and nonalkaline hydration in children and adolescents (C+A) with intermediate- (Group B) and high-risk (Group C) mature B-NHL: A Children's Oncology Group report." Journal of Clinical Oncology 28, no. 15_suppl (May 20, 2010): 9572. http://dx.doi.org/10.1200/jco.2010.28.15_suppl.9572.
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Turney, Danielle. "It Hurts You Inside: Children Talk About Smacking, by C. Willow and T. Hyder, National Children's Bureau Enterprises in association with Save the Children, London, 1998. ISBN 190099044X (Pbk), �8.50 NCB members, �13 non-members." Child Abuse Review 9, no. 6 (2000): 450–51. http://dx.doi.org/10.1002/1099-0852(200011/12)9:6<450::aid-car645>3.0.co;2-q.
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Liu, Shuguang, Chao Gao, Ruidong Zhang, Xiaoxi Zhao, Lei Cui, Weijing Li, Huyong Zheng, and Zhigang Li. "Germline Genetic Variations in Methotrexate Candidate Genes Are Associated with Pharmacokinetics and Outcome in Pediatric Acute Lymphoblastic Leukemia in China." Blood 128, no. 22 (December 2, 2016): 1595. http://dx.doi.org/10.1182/blood.v128.22.1595.1595.
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Abstract BackgroundMethotrexate (MTX) is a key chemotherapeutic agent in the treatment of pediatric acute lymphoblastic leukemia (ALL). Nevertheless, MTX can cause severe adverse effects and toxicities. The aim of the present study was to identify genetic polymorphisms in candidate genes of the MTX pathway associated with MTX pharmacokinetics, toxicity, and outcome in ALL in China. MethodsThree hundred and twenty-two Chinese children with ALL in the standard-risk and medium-risk treatment branches from the Beijing Children's Hospital-2003 and Chinese Childhood Leukemia Group-2008 protocols were enrolled in this study. Sequenom MassARRAY was used to genotype 12 single nucleotide polymorphisms (SNPs) in 4 candidate genes of the MTX/folate pathway. A total of 1268 high-dose MTX (HD-MTX) courses were analyzed. The plasma MTX levels were evaluated at 48 h after the first dose of HD-MTX infusion. Oral mucositis during the consolidation therapy period was recorded. Results No polymorphism was associated with clinical features, prednisone response, and minimal residual disease (MRD) at day 33 and 78. Long-term outcome was better in SLCO1B1 rs4149056 T and TC allele carriers than patients with C allele (5-year RFS 92.3±1.6% vs. 27.8±23.2%,P<0.0001), in ABCB1 rs1128503 T and TC allele carriers than patients with C allele (92.7±1.6% vs. 78.2±6.9%, P=0.020), and in SCL19A1 rs2838958 AG and G allele carries than patients with A allele (93.9±1.6% vs. 83.0±4.2%, P =0.010). Multiple Cox regression analyses revealed an association of MRD at day 33 (hazard ratio 3.356; P=0.018), MRD at day 78 (hazard ratio 2.843; P=0.034), and SLCO1B1 rs4149056 (hazard ratio 8.073; P=0.002) with RFS in the study population. As to MTX pharmacokinetics, ABCB1 rs1128503 showed a significant association with serum MTX levels (P=0.004). SNPs (rs3788200, rs1131596, rs1051266) of the SLC19A1 gene were also associated with the plasma levels of MTX (P=0.003, 0.004, and 0.003, respectively). No association was found between oral mucositis with any polymorphism. Conclusions Genetic variations substantially influence the kinetics and response to HD-MTX therapy in childhood ALL. Disclosures No relevant conflicts of interest to declare.
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Kim, Sun Young, Alexander Ing, Kristin Clemenz, Kai Lee Yap, Sherif M. Badawy, Robert I. Liem, Alexis A. Thompson, and A. Kyle Mack. "Probably Pathogenic KMT2D Variants Presenting with Cytopenias and Primary Immune Deficiency." Blood 134, Supplement_1 (November 13, 2019): 2334. http://dx.doi.org/10.1182/blood-2019-131468.
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Background The mutations in KMT2D gene are well known to be associated with Kabuki syndrome. Up to date, 1,027 different germline KMT2D variants have been reported in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/?term=KMT2D%5Bgene%5D), and among them, 365 variants (35.5%) are classified as uncertain significance and 53 (5.2%) are assigned to conflicting interpretations. This means about 40% of KMTD2 variants still need further evaluation to figure out whether they are 'pathogenic' or 'likely pathogenic'. Currently, the problem with the respect to the interpretation of variants is that they are prone to be reported as variants of unknown significance (VUS) without further study if the KMT2D variants have not been clinically described and reported previously. And in the clinical field, the KMT2D variants interpreted as VUS most likely do not get paid attention by the clinicians and can be easily ignored without further testing. Recently, Hadjadj et al.1 brought up the criteria 'probably pathogenic' variants which include the minor allele frequency less than 0.01 in the general population, and in Silico algorithms predicts the pathogenicity of missense variants. The authors found these 'probably pathogenic' variants were not significantly different from 'pathogenic' mutations in Evans syndrome in terms of clinical manifestations. Hypothesis and objective We hypothesized that there could be 'probably pathogenic' KMT2D variants which have been reported as VUS in patients with hematologic cytopenias and primary immune deficiency and we sought to find these 'probably pathogenic' variants for further evaluation to figure out their pathogenicity. Methods We analyzed the next generation sequencing data performed on patients with hematologic cytopenias and primary immune deficiency at the Ann and Robert H. Lurie Children's Hospital from March 2017 to May 2019. This primary immune deficiency (PID) panel analyzes 290 genes and the clinical manifestations of the patients were compared with the previous reports published regarding the KMT2D pathogenic mutations. We reviewed not only the online PubMed resource, but the websites well known for gene analysis were also used as references (https://www.ncbi.nlm.nih.gov/clinvar/, http://exac.broadinstitute.org/, http://genetics.bwh.harvard.edu/pph2/, http://provean.jcvi.org/index.php, https://sift.bii.a-star.edu.sg/, etc). Results Among 52 patients who had a PID panel ordered, 10 patients (19.2%) were found to have KMT2D variants. Among them, 4 variants (7.6%) were polymorphisms (c.7705G>A, p.Gly2569Ser; c.11849A>G, p.Gln3950Arg; c.1408C>T, p.Pro470Ser; c.2506C>A, p.Ile238Val) and 6 (11.5%) 'probably pathogenic' KMT2D variants were newly identified. Novel heterozygous KMT2D variants, previously reported as VUS: c.15341A>C, p.His5114Pro; c.10640G>A, p.Arg3547; c.6902C>T, p.Pro2301Leu; c.7328G>T, p.Arg2443Leu; c.15694A>G, p.I5232V; c.7001G>A, p.R2334Q were identified in patients who presented with various clinical manifestations known to be associated with KMT2D mutations which are neutropenia, anemia, thrombocytopenia, cardiac anomaly, urogenital anomaly, primary immune deficiency, variable degrees of mental retardation and distinctive facial features that include arched eyebrows, long eyelashes, elongated eyelids with lower lids that turn out, prominent ears, a flat tip of the nose, and a downward slant to the mouth. Further parental testing revealed one of them was a novel de novo mutation which was reclassified as 'likely pathogenic', 4 variants were inherited from mother or father and parental testing was not done for 1 patient. Conclusion We concluded that the mutational gene analysis should be correlated with patients' clinical manifestations. The second look analysis of the 'probably pathogenic' variants reported as VUS to figure out the clinical meaning would be important in terms of diagnosis and treatment of patients in the future. Further evaluation regarding family history and gene analysis would be necessary as well as further downstream pathway studies to confirm the pathogenicity of the 'probably pathogenic' KMT2D variants. References 1. Jérôme Hadjadj, Nathalie Aladjidi, Helder Fernandes, et al. Pediatric Evans syndrome is associated with a high frequency of potentially damaging variants in immune genes, Blood 2019 134:9-21. Disclosures Thompson: Baxalta: Research Funding; Novartis: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; bluebird bio, Inc.: Consultancy, Research Funding.
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Ahmed, Shariq, Arshi Naz, Hamideh Yadegari, Julia Driesen, Tahir Shamsi, Nisar Ahmed, Shahla Tariq, et al. "Molecular Genetics Analysis of Von Williebrand Disease: Studies in Cohort Pakistani Patients." Blood 126, no. 23 (December 3, 2015): 4689. http://dx.doi.org/10.1182/blood.v126.23.4689.4689.
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Abstract Introduction: Von Willebrand disease (VWD) type III is the second most common inherited bleeding disorder in Pakistan. It is caused by severe quantitative deficiency of plasma Von Willebrand factor (VWF). Absence of VWF increases the severity of disease and is caused by homozygous/ compound heterozygous mutations in Von Willebrand factor gene. Objective: The aim of study is to characterize molecular genetics of Von Willebrand type III in Pakistani population. Setting: NIBD & BMT Karachi, Chughtais lab, Children's Hospital Lahore, PAEC Islamabad and HMC Peshawar. Material And Method: In this cohort study of Von Willebrand disease (VWD) type III, Blood samples of 48 unrelated patients of type III VWD were collected in National Institute Of Blood Disease & Bone Marrow Transplant (NIBD) Karachi, Chughtais lab, Children's Hospital Lahore, PAEC Islamabad and HMC Peshawar. Genomic DNA was extracted from peripheral blood by QIAamp DNA Blood mini kit (Qiagen) and Exon specific PCR was done for VWF gene and Direct gene sequenced on automated ABI-3130 Genetic Analyzer (Applied Biosystems). Sequence Variations in VWF were checked on ISTH-SSC VWD homepage (http://www.vwf.group.shef.ac.uk/), Ensemble genome browser (http://www.ensembl.org/), VWFdb hemobase and biobase biological database (http://www.hgmd.cf.ac.uk/ac/index.php). We have adopted the nomenclature for numbering amino acids of Human genome variation society (HGVS). Statistics analysis was done SPSSv17. Results: Sequence analysis detected mutations in 46 (95.83%) out of 48 samples. VWD type III has led to identification of 28 cases (60.8%) homozygous and 18 (39.1%) were compound heterozygous. We have indentified total 31 Mutations distributed as 17 missense mutations (54%), 7 nonsense mutations (22%) 2 small deletions (6%) , 2 insertion mutations (6%) and 3 splice site mutations (9%).19 of these were newly mutations in this cohort study.. Further method multiplex ligation dependent probe amplification (MLPA) is needed for detection of large deletions in two patients. Nonsense c.3931C>T, p.Q1311*was founder mutation in Pakistani patients. Conclusion: In cohort study, missense mutations are detected as common in among patients and most of the mutations identified in this cohort were homozygous due to Consanguinity in the family of the patients. Disclosures Oldenburg: SOBI: Consultancy.
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Asmawati, Luluk, and Sholeh Hidayat. "Parenting E-book: Coping Early Childhood Education Problems During Learning from Home." JPUD - Jurnal Pendidikan Usia Dini 14, no. 2 (November 30, 2020): 332–40. http://dx.doi.org/10.21009/jpud.142.11.
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During COVID-19, early-childhood school closings led to higher levels of stress in parents when compared to childless adults. In addition, lack of time to prepare, as well as mental-health problems, worry, and stress in parenting, may have hampered parents' ability to support their children's educational needs. The research aims to solve the problem of early childhood parenting during learning from home and improve the quality of early childhood parenting. The research method uses the research and development stage of the Borg & Gall model. Participants are mothers who have children aged 5-6 years. The data collection technique was done through expert validation and effectiveness testing with a quasi-experimental design. The data analysis used paired t-test statistical analysis. The findings show that the validity of the results of the material expert's test is 96%, and the media expert's test is 94% in the very good category. The effectiveness test based on the pre-test and post-test results showed that Sig. (2-tailed) <0,05 (α), which means that the parenting e-book media significantly increases mothers' understanding of parenting well-being practices in early childhood. The implications of this multimedia-based anyflip e-book can be downloaded via gadgets, android, laptop, practical, easy to read and repeated to accompany childcare activities from home.
Keywords: Anyflip E-book, Early Childhood, Parenting
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Yi, Joanna S., Tiffany Chambers, Kelly D. Getz, Tamara P. Miller, Evanette Burrows, Marla Daves, Philip J. Lupo, et al. "Transient Elevations in Markers of Hepatic Function during Pediatric Acute Lymphoblastic Leukemia Treatment Are Common but Do Not Influence Outcomes: A Study of 805 Patients from the Learn Consortium." Blood 134, Supplement_1 (November 13, 2019): 3814. http://dx.doi.org/10.1182/blood-2019-123992.
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Introduction: Hepatotoxicity is a frequent and challenging adverse event in children with acute lymphoblastic leukemia (ALL), but patient factors that are predictive of hepatotoxicity are not well understood. We leveraged a data repository jointly developed by two pediatric oncology centers within the Leukemia Electronic Abstraction of Records [LEARN] Consortium to assess the landscape and determinants of liver dysfunction throughout ALL therapy in patients who were risk-stratified to receive either standard- or high-intensity treatment blocks. Methods: The subjects were children ages 1-21 years who were treated for ALL between 2006-2014 at either Children's Hospital of Philadelphia or Texas Children's Hospital. Demographics, disease-related data, and every laboratory value collected during treatment were obtained by targeted manual abstraction and extensive semi-automated extraction of patient electronic medical record (EMR) data. To reduce cohort heterogeneity, we excluded patients who received non-standard ALL therapies. Patients were categorized as receiving either standard-intensity or high-intensity treatment for their first three blocks of therapy (Induction, Consolidation, Interim Maintenance 1 [IM1]) based on chemotherapeutic agents delivered in those blocks. Differences in laboratory value-determined hepatoxicity were then analyzed based on this categorization for all remaining phases of therapy. Hepatic lab values (AST [SGOT], ALT [SGPT], total bilirubin [t. bili], and conjugated bilirubin [c. bili]) were first normalized to the age-based upper limit of normal (ULN), and the median value was then determined. A multivariate mixed-effects linear regression model with random effects was used to identify differences in the treatment group medians and the following covariates: age, race/ethnicity, sex, BMI, and ALL immunophenotype. Laboratory values were classified by the CTCAE v5.0 grading system, with grade ≥ 3 considered 'elevated.' Results: 805 pediatric ALL patients were included in the analysis, representing 114,095 hepatic lab values (Table 1). Less than 10% of patients had elevated lab values at diagnosis. Throughout treatment, the majority of lab values fell within 1-2x ULN for age for both standard- and high-intensity treatment groups (Fig. 1a-d). The median hepatic lab values for the high-intensity group were slightly higher than the standard risk group across all treatment phases, and this difference was most consistently significant in Consolidation and Delayed Intensification. Among the four hepatic labs that were assessed, ALT had the most significant deviation above normal (up to 30x ULN, Fig 1a). Patients were more likely to have elevated transaminases during maintenance than prior to maintenance (Fig. 1e). Similarly, but to a lesser degree, patients were more likely to have elevated t. or c. bili during maintenance than prior to maintenance. Age, race, and BMI were correlated with elevated hepatic labs, with Hispanic and/or overweight patients more likely to have elevations in 3 or more phases of therapy (Table 2). However, no hepatic lab abnormalities were correlated with either overall or relapse-free survival. Conclusions: This is the first comprehensive study of measures of hepatotoxicity in a large and uniformly-treated cohort of pediatric ALL. While significantly elevated hepatic labs are rare at diagnosis, they are common during ALL treatment and are seen more commonly in maintenance than in prior phases. Patients who are overweight and/or Hispanic are more likely to experience grade 3 or higher hepatoxicity. We observed no relationship between hepatotoxicity and relapse or survival. Further studies are ongoing to delineate the temporal correlation of liver function and chemotherapy dosing and administration. Disclosures No relevant conflicts of interest to declare.
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Kim, Benjamin, Zachary A. Hing, Andrew Wu, Tal Schiller, Evi B. Struble, David Liuwantara, Pamela H. Kempert, et al. "Single-Nucleotide Variations Defining Previously Unreported ADAMTS13 Haplotypes Are Associated With Differential Expression and Activity Of The VWF-Cleaving Protease In a Salvadoran Congenital Thrombotic Thrombocytopenic Purpura Family." Blood 122, no. 21 (November 15, 2013): 2319. http://dx.doi.org/10.1182/blood.v122.21.2319.2319.
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Abstract Background Although autosomal recessive hematologic disorders are individually rare and difficult to ascertain, studies involving one or more homozygous affected children and their unaffected heterozygous parents have led to expanded understanding of known and discovery of previously unknown processes. The son and daughter of two Salvadoran parents were diagnosed with congenital thrombotic thrombocytopenic purpura (cTTP) at 6 and 2 years of age, respectively, after presenting with fever, respiratory symptoms, hemolytic anemia, and thrombocytopenia and being found to have ADAMTS13 activities <1% without neutralizing IgG antibodies. They remain without long-term neurologic or renal sequelae following prophylactic infusions of fresh plasma (10 mL/kg every 2.5-weeks). The purpose of this study was to characterize and correlate single-nucleotide variations (SNVs) in each parent's, non-mutant ADAMTS13 allele with its mRNA and protein expression, activity, and enzyme kinetics. Methods Prior to a plasma infusion, blood samples were collected from the children and parents. Genomic DNA was isolated for polymerase chain reaction (PCR), and direct Sanger sequencing of all ADAMTS13 exons and flanking intronic segments was performed; all variants identified were confirmed by bidirectional sequencing of a second, independently generated amplicon. Total RNA was isolated and the steady-state level of ADAMTS13 mRNA was measured using a quantitative real-time PCR (q-RT-PCR)-based assay. ADAMTS13 was characterized enzymatically using the fluorogenic FRETS-VWF73 substrate and antigenically by ELISA. Results Both children were found to be homozygous and parents to be heterozygous for the previously described, cTTP-causing ADAMTS13 single-base-substitution mutation 20506C>T, a missense mutation that encodes cDNA-nucleotide 2518 (c.2518C>T) and ADAMTS13 residue 692 (692Arg>Cys [692R>C]) (Fig. A). As expected, the children's ADAMTS13 antigen and activity levels were undetectable, although notably, steady-state levels of the ADAMTS13 mRNA were >2.5-fold higher in the daughter than in the son. The re-sequenced regions of the ADAMTS13 loci segregating within this family contained 26 additional SNVs, seven of which were nonsynonymous (ns) including two previously unreported ns-SNVs: 27852C>T (c.3362C>T; 972Arg>Trp) and 33325G>A (c.3733G>A; 1096Arg>His) (Fig. A, left panel). The parents' genotypes differed at nine positions, including three ns-SNVs, creating two distinct, non-mutant haplotypes (designated I and III) at the gene, mRNA and protein levels. The q-RT-PCR assay revealed >4-fold higher steady-state mRNA levels in the father compared to the mother (p<0.001; Fig. B). Plasma ADAMTS13 activity and antigen levels were ∼2-fold greater in the father than in the mother (p=0.00164 and p=0.0633, respectively), but the specific activities of these structurally distinct ADAMTS13 proteins were notably almost identical (253.5 vs. 256.2 U/μg). Moreover, initial velocity kinetic analysis using the Michelis-Menten equation demonstrated that the Vmax of the father's ADAMTS13 was twice that of the mother's (1.4 vs. 0.7; p < 0.0001) while its affinity for substrate was one-third that of her ADAMTS13 (Km = 0.3 vs. 0.1; p = 0.0585). Discussion We capitalized on the fortuitous finding of children with complete homozygosity across ancestrally-related ADAMTS13 alleles harboring a null-type, loss-of-function mutation, as this enabled the substantially different levels of gene expression and function observed in the parents to be attributed to their two previously unreported, SNV-based, ADAMTS13 haplotypes. Additional investigation at the molecular, biochemical, cellular, and organismal levels will be necessary to determine which of the myriad potential individual SNV- and/or haplotype-based mechanisms are responsible for the observed parental differences in circulating ADAMTS13 antigen and activity. Disclosures: Kim: Haplomics, Inc.: Membership on an entity’s Board of Directors or advisory committees; Baxter: Honoraria. Marder:Baxter: Research Funding. Howard:Haplomics, Inc.: Equity Ownership, Membership on an entity’s Board of Directors or advisory committees; Baxter: Research Funding.
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King, Michael. "Children's Sexual Encounters with Adults. By C. K. Li, D. L. West and T. P. Woodhouse London: Duckworth. 1990. 343 pp. £39.95. - Child Sexual Abuse in Northern Ireland. By The Research Team. Northern Ireland: Greystone Books. 1990. 188 pp. £18.00." British Journal of Psychiatry 158, no. 5 (May 1991): 728. http://dx.doi.org/10.1192/s0007125000024089.
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Aftandilian, Catherine, Kathleen M. Sakamoto, Kara L. Davis, Gary Van Houten Dahl, and Norman J. Lacayo. "Chromatin Remodeling Therapy and Capizzi Methotrexate in Treatment-Related MDS/AML." Blood 132, Supplement 1 (November 29, 2018): 5222. http://dx.doi.org/10.1182/blood-2018-99-110481.
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Abstract Treatment-related myelodysplastic syndrome/acute myeloid leukemia (t-MDS/t-AML) is a devastating complication for pediatric patients with osteosarcoma. Even with intensive chemotherapy, overall survival ranges from 10-26%. These regimens cause significant morbidity, poor quality of life and increased toxicity, at times precluding the ultimate goal of hematopoietic cell transplant (HCT). Chromatin remodeling therapy with decitabine and vorinostat has shown some promise in adults with relapsed/refractory AML and MDS. The synergistic combination of methotrexate and asparaginase, also referred to as 'Capizzi methotrexate', is not generally part of upfront treatment for AML but does have some activity in relapsed/refractory disease. Using this rationale, we report the use of this combination regimen in 2 children with t-AML where chromatin remodeling therapy with subsequent Capizzi methotrexate successfully bridged both patients to HCT. Patients were treated at Lucile Packard Children's Hospital Stanford between 2010 and 2018 for osteosarcoma and subsequently for t-AML. An overview of the treatments used is described in Table 1. An adolescent female was treated for metastatic osteosarcoma. She developed an isolated pulmonary recurrence 5 months after completing therapy. She underwent resection of her pulmonary nodule and then was enrolled on a clinical trial. Four months later, she developed another pulmonary recurrence. At this time, she began treatment with ifosfamide and etoposide. After the sixth cycle, she was noted to have blasts in her blood, and a bone marrow evaluation confirmed t-MDS. Cytogenetics were negative for deletion of 5q, 7q or MLL rearrangement. Repeat bone marrow evaluation two months later revealed progression to t-AML. She initially received 5 days of high dose cytarabine without response and was then transitioned to Treatments A and B. Bone marrow evaluation on day 30 of Treatment B showed morphologic remission with 11% MRD. She underwent Treatment C and then proceeded to a matched sibling HCT. She had no detectable osteosarcoma at the time of her transplant. The patient remained in remission from t-AML but subsequently died from recurrent osteosarcoma more than 2 years after HCT. An adolescent male was treated for non-metastatic osteosarcoma of the left distal femur with methotrexate, adriamycin, cisplatin, ifosfamide and etoposide. Six years after completing treatment, he developed weight loss, epistaxis and pancytopenia. Bone marrow aspiration revealed a hypercellular marrow with 18% blasts, increased marrow fibrosis and cytogenetics with a complex del(7q)/+8 clone, consistent with t-MDS. He received Treatment B, and a bone marrow evaluation on day 25 showed a hemodilute specimen with MRD <0.1%. He then received vincristine and methotrexate on day 35 followed by erwinia on day 36. Repeat bone marrow evaluation on day 42 again showed a hypocellular marrow with MRD of <0.1%. He went on to receive another cycle of vincristine and methotrexate followed by days 1 through 5 of Treatment B. Bone marrow evaluation on day 29 showed a hypocellular marrow with insufficient viable cells for MRD analysis. The patient received an alpha/beta T cell depleted haploidentical transplant. He remains in morphologic remission with no evidence of disease more than 3 months after HCT. Treatment-related MDS/AML remains a devastating complication of osteosarcoma treatment with no standard treatment. The two cases presented here demonstrated good response to a novel combination of therapy with decitabine/vorinostat followed by Capizzi methotrexate. Given the significant toxicity associated with most regimens for t-MDS/t-AML, this regimen should be considered when first line salvage chemotherapy has failed. The precise regimen as well as the optimal number of cycles prior to stem cell transplant should be evaluated in the context of a clinical trial. Disclosures No relevant conflicts of interest to declare.
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AKHTAR, NAMEERA. "Nativist versus constructivist goals in studying child language." Journal of Child Language 31, no. 2 (May 2004): 459–62. http://dx.doi.org/10.1017/s0305000904006063.
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Crain & Thornton (1998: 5) are admirably clear in stating the aims of their research programme: they ‘hope to convince a greater number of students and researchers in child language of the correctness of the Innateness Hypothesis and the theory of Universal Grammar’. As Drozd notes, however, their assumptions under Modularity Matching ‘set the stage for a research programme unlike those typically adopted by developmental psycholinguists’. Whereas C&T are avowedly committed to the continuity assumption (clearly preferring ‘special nativism’ over ‘general nativism’; O'Grady, 1997), constructivists are more interested in the question of how children ‘get from here to there’ (Tomasello, 2003) – that is, from immature levels of language comprehension and use to adultlike levels (and, it is important to note that adultlike levels are not always characterized in generativist terms). Most constructivists are also committed to studying the relations between language development and other simultaneously developing social and cognitive skills (Clark, 2003), whereas nativists tend to be interested in ‘pure’ linguistic ability uncontaminated by nonlinguistic influences. The main goal of nativists then is to verify a specific theory of linguistic competence that suggests that linguistic knowledge is innate and modular and to account for children's linguistic development in terms of UG, whereas the main goal for constructivists is to account for development (change) in the child's language system (beginning from perhaps no predetermined linguistic knowledge) and how it relates to other aspects of development. It is this fundamental difference in goals that makes one quite pessimistic that constructivist and nativist researchers in syntactic development can learn anything from one another; they are simply engaged in separate tasks.