28 research outputs found

    Improve in-depth immunological risk assessment to optimize genetic-compatibility and clinical outcomes in child and adolescent recipients of parental donor kidney transplants: protocol for the INCEPTION study.

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    BACKGROUND: Parental donor kidney transplantation is the most common treatment option for children and adolescents with kidney failure. Emerging data from observational studies have reported improved short- and medium-term allograft outcomes in recipients of paternal compared to maternal donors. The INCEPTION study aims to identify potential differences in immunological compatibility between maternal and paternal donor kidneys and ascertain how this affects kidney allograft outcomes in children and adolescents with kidney failure. METHODS: This longitudinal observational study will recruit kidney transplant recipients aged ≤18 years who have received a parental donor kidney transplant across 4 countries (Australia, New Zealand, United Kingdom and the Netherlands) between 1990 and 2020. High resolution human leukocyte antigen (HLA) typing of both recipients and corresponding parental donors will be undertaken, to provide an in-depth assessment of immunological compatibility. The primary outcome is a composite of de novo donor-specific anti-HLA antibody (DSA), biopsy-proven acute rejection or allograft loss up to 60-months post-transplantation. Secondary outcomes are de novo DSA, biopsy-proven acute rejection, acute or chronic antibody mediated rejection or Chronic Allograft Damage Index (CADI) score of > 1 on allograft biopsy post-transplant, allograft function, proteinuria and allograft loss. Using principal component analysis and Cox proportional hazards regression modelling, we will determine the associations between defined sets of immunological and clinical parameters that may identify risk stratification for the primary and secondary outcome measures among young people accepting a parental donor kidney for transplantation. This study design will allow us to specifically investigate the relative importance of accepting a maternal compared to paternal donor, for families deciding on the best option for donation. DISCUSSION: The INCEPTION study findings will explore potentially differential immunological risks of maternal and paternal donor kidneys for transplantation among children and adolescents. Our study will provide the evidence base underpinning the selection of parental donor in order to achieve the best projected long-term kidney transplant and overall health outcomes for children and adolescents, a recognized vulnerable population. TRIAL REGISTRATION: The INCEPTION study has been registered with the Australian New Zealand Clinical Trials Registry, with the trial registration number of ACTRN12620000911998 (14th September 2020)

    Design and implementation of the international genetics and translational research in transplantation network

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    Concept and design of a genome-wide association genotyping array tailored for transplantation-specific studies

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    Background: In addition to HLA genetic incompatibility, non-HLA difference between donor and recipients of transplantation leading to allograft rejection are now becoming evident. We aimed to create a unique genome-wide platform to facilitate genomic research studies in transplant-related studies. We designed a genome-wide genotyping tool based on the most recent human genomic reference datasets, and included customization for known and potentially relevant metabolic and pharmacological loci relevant to transplantation. Methods: We describe here the design and implementation of a customized genome-wide genotyping array, the ‘TxArray’, comprising approximately 782,000 markers with tailored content for deeper capture of variants across HLA, KIR, pharmacogenomic, and metabolic loci important in transplantation. To test concordance and genotyping quality, we genotyped 85 HapMap samples on the array, including eight trios. Results: We show low Mendelian error rates and high concordance rates for HapMap samples (average parent-parent-child heritability of 0.997, and concordance of 0.996). We performed genotype imputation across autosomal regions, masking directly genotyped SNPs to assess imputation accuracy and report an accuracy of >0.962 for directly genotyped SNPs. We demonstrate much higher capture of the natural killer cell immunoglobulin-like receptor (KIR) region versus comparable platforms. Overall, we show that the genotyping quality and coverage of the TxArray is very high when compared to reference samples and to other genome-wide genotyping platforms. Conclusions: We have designed a comprehensive genome-wide genotyping tool which enables accurate association testing and imputation of ungenotyped SNPs, facilitating powerful and cost-effective large-scale genotyping of transplant-related studies. Electronic supplementary material The online version of this article (doi:10.1186/s13073-015-0211-x) contains supplementary material, which is available to authorized users

    Concept and design of a genome-wide association genotyping array tailored for transplantation-specific studies

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    Proceedings of the Virtual 3rd UK Implementation Science Research Conference : Virtual conference. 16 and 17 July 2020.

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    The auction = 爱的拍卖

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    Failure to escape a marriage proposal from her longtime partner, Gloria is forced to choose contentment over ambition. The Restaurant transforms into the auction where the bids represents the ambitions Gloria have for her life. We follow Gloria's decisions as the auction goes on, revealing her true desires.Bachelor of Fine Arts in Digital Filmmakin

    Linking Language & Well-Being: Transforming Teaching at the Intersection of Hawaiian Places, Practices, Values, and Language

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    “Transforming Teaching” reports on year 1 of a 2-year DR-K12, NSF funded professional development (PD) research project asking if transforming STEM instruction to intersect with Native Hawaiian culture supports underrepresented Native Hawaiian students’ interest and learning in STEM (NCES, 2011). The project design applies theories of structure and agency (Sewell, 1992) and cultural funds of knowledge (Moll, Amanti, Neff, & Gonzalez, 1992) to explicitly intersect Hawaiian and western knowledge and culture. Teachers researched their ahupua‘a for cultural, historical, and STEM resources relevant to place-based lessons for their students and communities because place-based knowledge of diverse topographies and ecosystems was critical to Hawaiian sustainability, well-being, and identity. Educational innovations e.g., a database of Hawaiian language newspaper articles, the Institute for Hawaiian Language Research and Translation and the Hawai‘i Dept. of Education’s adoption of Next Generation Science Standards provide new resources for designing STEAM curricula (inclusive of arts) through the lenses of culture and place. Nā Hopena A‘o (HIDOE, 2015), six general learner outcomes reflecting Hawaiian values provided assessments associated with belonging, responsibility, excellence, aloha, total wellbeing and Hawai‘i. Data sources include student surveys, teachers’ reflective writings, lessons, student work, and assessments guided by Na Hopena A‘o. Lessons on native and invasive species and sustainability show 4-8th graders learned key Hawaiian and technical terms, understood and critiqued the impact of humans and invasive species on Hawaiian ecosystems, and recognized values underlying sustainability. Surveys applying Nā Hopena A’o showed the great majority of 6th and 7th graders in two O‘ahu schools reported their learning activities led to positive outcomes. In a 4th grade class where 22 students identified their ethnicities, the 6 Native Hawaiian students were more interested in taking STEM and Hawaiian culture/language courses, more concerned about invasive species and culturally important plant and animals, but less able to connect school and family activities than their non-Hawaiian peers. However, students generally agreed (n=14) that science should be taught “outdoors” “to be more interesting.” Findings suggest place-based PD explicitly integrating Western and Hawaiian STEM systems contributes to equity in STEM education and well-being of children in Hawaii’s schools. Further research with a second cohort of teachers will expand grades and numbers of students surveyed to refine first year findings and guide future PD oriented to transforming teachers’ practices towards equitable STEM education and greater sense of well-being for Native Hawaiians, the largest ethnic group in Hawai‘i’s K-12 schools. References: Hawai‘i State Department of Education (2015, Nov.). Nā Hopena A‘o Statements. Retrieved from www.hawaiipublicschools.org/DOE%20Forms/NaHopenaAoE3.pdf Moll, L.C., Amanti, C., Neff, D., & Gonzalez, N. (1992). Funds of Knowledge for Teaching: Using a Qualitative Approach to Connect Homes and Classrooms. Theory into Practice, Qualitative Issues in Educational Research, 31, 2, 132-141. National Center for Education Statistics (2011, Dec.). Comparing the Achievement Patterns of Native Hawaiian and Non-Native Hawaiian Grade 8 Students in Reading and Math. Retrieved from http://ies.ed.gov/ncee/edlabs/regions/pacific/pdf/REL_2012120.pdf Sewell, W. Jr. (1992). A Theory of Structure: Duality, Agency, and Transformation. American Journal of Sociology, 98, 1, 1-29

    Corrigendum to “A multicenter retrospective study of calcineurin inhibitors in nephrotic syndrome secondary to podocyte gene variants.”

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    DOI of original article: https://doi.org/10.1016/j.kint.2023.02.022 The authors regret to report that Hee Gyung Kang, Department of Pediatrics, Seoul National University Children's Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea, inadvertently was not included in the list of authors of the published article. The collaborator was removed from the Acknowledgments. This has been corrected in the article online. The authors would like to apologize for any inconvenience caused.</p
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