41 research outputs found

    3R- Reach, Recruit, Reform: Working with the Grand Rapids Community to Meet the Volunteer Needs of the Heartside Gleaning Initiative

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    The purpose of this project is to address the volunteer needs of the Heartside Gleaning Initiative, a nonprofit organization founded by Grand Valley State University professor Lisa Sisson. The mission of the Heartside Gleaning Initiative is to “empower the Heartside community to become healthier through nutrition education and improving accessibility of healthy foods” (Heartside, 2014). Members of the Heartside Gleaning Initiative are currently working to give people living in the Heartside community of Grand Rapids access to fresh produce. Volunteers glean the produce from local farmers at the Fulton Street Farmers Market and then deliver it to shelters in the Heartside neighborhood. This work is also a part of a larger goal to fight the national issue of food insecurity, which affects millions of people living in the United States. For this project, our group chose to focus on volunteer recruitment. Volunteers are the backbone of the Heartside Gleaning Initiative and a necessary component for the work being done. We have begun to work with several Grand Rapids schools and local churches in the Heartside neighborhood to generate awareness about the initiative and to try and fill this need for volunteers. The organization specifically needs a core group of four to five volunteers who can consistently work with the initiative. Though we have generated interest among community members to volunteer for a weekend, we struggled to establish this core group of leaders. This proved to be our biggest challenge with the project, and finding a group of leaders will continue to be a task for the initiative in the future, though we have several suggestions that may help their efforts. The final goal for this project was to provide the Heartside Gleaning Initiative with recruitment materials. We recreated a pamphlet for the organization to give to potential volunteers. It includes information about the goals and the mission of the organization and contact information. It can be used to generate awareness and knowledge about the Heartside Gleaning Initiative. We also provided the organization with a list of the local churches and schools with interested members. We hope the initiative will be able to use these materials to continue to recruit a stable group of volunteers

    NADPH Oxidase Limits Innate Immune Responses in the Lungs in Mice

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    Background: Chronic granulomatous disease (CGD), an inherited disorder of the NADPH oxidase in which phagocytes are defective in generating superoxide anion and downstream reactive oxidant intermediates (ROIs), is characterized by recurrent bacterial and fungal infections and by excessive inflammation (e.g., inflammatory bowel disease). The mechanisms by which NADPH oxidase regulates inflammation are not well understood. Methodology/Principal Findings: We found that NADPH oxidase restrains inflammation by modulating redox-sensitive innate immune pathways. When challenged with either intratracheal zymosan or LPS, NADPH oxidase-deficient p47phox-/- mice and gp91phox-deficient mice developed exaggerated and progressive lung inflammation, augmented NF-kB activation, and elevated downstream pro-inflammatory cytokines (TNF-α, IL-17, and G-CSF) compared to wildtype mice. Replacement of functional NADPH oxidase in bone marrow-derived cells restored the normal lung inflammatory response. Studies in vivo and in isolated macrophages demonstrated that in the absence of functional NADPH oxidase, zymosan failed to activate Nrf2, a key redox-sensitive anti-inflammatory regulator. The triterpenoid, CDDO-Im, activated Nrf2 independently of NADPH oxidase and reduced zymosan-induced lung inflammation in CGD mice. Consistent with these findings, zymosan-treated peripheral blood mononuclear cells from X-linked CGD patients showed impaired Nrf2 activity and increased NF-kB activation. Conclusions/Significance: These studies support a model in which NADPH oxidase-dependent, redox-mediated signaling is critical for termination of lung inflammation and suggest new potential therapeutic targets for CGD

    Early experience of COVID-19 vaccination in adults with systemic rheumatic diseases : Results from the COVID-19 Global Rheumatology Alliance Vaccine Survey

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    Funding Information: Competing interests SES has received funding from the Vasculitis Foundation and the Vasculitis Clinical Research Consortium unrelated to this work. JL has received research grant funding from Pfizer unrelated to this work. ES is a Board Member of the Canadian Arthritis Patient Alliance, a patient run, volunteer-based organisation whose activities are primarily supported by independent grants from pharmaceutical companies. MP was supported by a Rheumatology Research Foundation Scientist Development grant. DA-R is a Scientific Advisor for GlaxoSmithKilne unrelated to this work. FB reports personal fees from Boehringer, Bone Therapeutics, Expanscience, Galapagos, Gilead, GSK, Merck Sereno, MSD, Nordic, Novartis, Pfizer, Regulaxis, Roche, Sandoz, Sanofi, Servier, UCB, Peptinov, TRB Chemedica and 4P Pharma outside of the submitted work. No funding relevant to this manuscript. RC: speakers bureau for Janssen, Roche, Sanofi, AbbVie. KD reports no COI-unpaid volunteer president of the Autoinflammatory Alliance. Any grants or funding from pharma is received by the non-profit organisation only. CLH received funding under a sponsored research agreement unrelated to the data in the paper from Vifor Pharmaceuticals. LeK has received a research grant from Lilly unrelated to this work. AHJK participated in consulting, advisory board or speaker's bureau for Alexion Pharmaceuticals, Aurinia Pharmaceuticals, Annexon Biosciences, Exagen Diagnostics and GlaxoSmithKilne and received funding under a sponsored research agreement unrelated to the data in the paper from GlaxoSmithKline. JSingh has received consultant fees from Crealta/ Horizon, Medisys, Fidia, PK Med, Two Labs, Adept Field Solutions, Clinical Care Options, Clearview Healthcare Partners, Putnam Associates, Focus Forward, Navigant Consulting, Spherix, MedIQ, Jupiter Life Science, UBM, Trio Health, Medscape, WebMD and Practice Point Communications; and the National Institutes of Health and the American College of Rheumatology. JSingh owns stock options in TPT Global Tech, Vaxart Pharmaceuticals and Charlotte’s Web Holdings. JSingh previously owned stock options in Amarin, Viking and Moderna Pharmaceuticals. JSingh is on the speaker’s bureau of Simply Speaking. JSingh is a member of the executive of Outcomes Measures in Rheumatology (OMERACT), an organisation that develops outcome measures in rheumatology and receives arms-length funding from eight companies. JSingh serves on the FDA Arthritis Advisory Committee. JSingh is the chair of the Veterans Affairs Rheumatology Field Advisory Committee. JSingh is the editor and the Director of the University of Alabama at Birmingham (UAB) Cochrane Musculoskeletal Group Satellite Center on Network Meta-analysis. NSingh is supported by funding from the Rheumatology Research Foundation Investigator Award and the American Heart Association. MFU-G has received research support from Pfizer and Janssen, unrelated to this work. SB reports personal fees from Novartis, AbbVie, Pfizer and Horizon Pharma, outside the submitted work. RG reports personal fees from AbbVie New Zealand, Cornerstones, Janssen New Zealand and personal fees and non-financial support Pfizer New Zealand (all <US$10 000) outside the submitted work. PMM reports personal fees from AbbVie, Eli Lilly, Janssen, Novartis, Pfizer and UCB, grants and personal fees from Orphazyme, outside the submitted work. PCR reports personal fees from AbbVie, Gilead, Lilly and Roche, grants and personal fees from Novartis, UCB Pharma, Janssen and Pfizer and non-financial support from BMS, outside the submitted work. PS reports honoraria from Social media editor for @ACR_Journals, outside the submitted work. ZSW reports grants from NIH, BMS and Principia/ Sanofi and personal fees from Viela Bio and MedPace, outside the submitted work. JY reports personal fees from Pfizer and Eli Lilly, and grants and personal fees from AstraZeneca, outside the submitted work. MJL reports grants from American College of Rheumatology, during the conduct of the study and consulting fees from AbbVie, Amgen, Actelion, Boehringer Ingelheim, BMS, Celgene, Gilead, J&J, Mallinckrodt, Novartis, Pfizer, Roche, Sandoz, Sanofi, Sobi and UCB, outside the submitted work. LGR was supported by the Intramural Research Program of the National Institute of Environmental Health Sciences (NIEHS; ZIAES101074) of the National Institutes of Health. JH reports grants from Childhood Arthritis and Rheumatology Research Alliance (CARRA) and Rheumatology Research Alliance, and personal fees from Novartis, Pfizer and Biogen, outside the submitted work. JSimard received research grant funding from the National Institutes of Health unrelated to this work (NIAMS: R01 AR077103 and NIAID R01 AI154533). JSparks has performed consultancy for AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Inova Diagnostics, Optum and Pfizer unrelated to this work. Funding Information: Funding This study was supported by the European Alliance of Associations for Rheumatology and American College of Rheumatology Research and Education Foundation. Dr. Lisa Rider's involvement was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences. Publisher Copyright: © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.Background. We describe the early experiences of adults with systemic rheumatic disease who received the COVID-19 vaccine. Methods From 2 April to 30 April 2021, we conducted an online, international survey of adults with systemic rheumatic disease who received COVID-19 vaccination. We collected patient-reported data on clinician communication, beliefs and intent about discontinuing disease-modifying antirheumatic drugs (DMARDs) around the time of vaccination, and patient-reported adverse events after vaccination. Results We analysed 2860 adults with systemic rheumatic diseases who received COVID-19 vaccination (mean age 55.3 years, 86.7% female, 86.3% white). Types of COVID-19 vaccines were Pfizer-BioNTech (53.2%), Oxford/AstraZeneca (22.6%), Moderna (21.3%), Janssen/Johnson & Johnson (1.7%) and others (1.2%). The most common rheumatic disease was rheumatoid arthritis (42.3%), and 81.2% of respondents were on a DMARD. The majority (81.9%) reported communicating with clinicians about vaccination. Most (66.9%) were willing to temporarily discontinue DMARDs to improve vaccine efficacy, although many (44.3%) were concerned about rheumatic disease flares. After vaccination, the most reported patient-reported adverse events were fatigue/somnolence (33.4%), headache (27.7%), muscle/joint pains (22.8%) and fever/chills (19.9%). Rheumatic disease flares that required medication changes occurred in 4.6%. Conclusion. Among adults with systemic rheumatic disease who received COVID-19 vaccination, patient-reported adverse events were typical of those reported in the general population. Most patients were willing to temporarily discontinue DMARDs to improve vaccine efficacy. The relatively low frequency of rheumatic disease flare requiring medications was reassuring.publishersversionPeer reviewe

    Prolonged COVID-19 symptom duration in people with systemic autoimmune rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance Vaccine Survey

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    OBJECTIVE: We investigated prolonged COVID-19 symptom duration, defined as lasting 28 days or longer, among people with systemic autoimmune rheumatic diseases (SARDs). METHODS: We analysed data from the COVID-19 Global Rheumatology Alliance Vaccine Survey (2 April 2021-15 October 2021) to identify people with SARDs reporting test-confirmed COVID-19. Participants reported COVID-19 severity and symptom duration, sociodemographics and clinical characteristics. We reported the proportion experiencing prolonged symptom duration and investigated associations with baseline characteristics using logistic regression. RESULTS: We identified 441 respondents with SARDs and COVID-19 (mean age 48.2 years, 83.7% female, 39.5% rheumatoid arthritis). The median COVID-19 symptom duration was 15 days (IQR 7, 25). Overall, 107 (24.2%) respondents had prolonged symptom duration (≥28 days); 42/429 (9.8%) reported symptoms lasting ≥90 days. Factors associated with higher odds of prolonged symptom duration included: hospitalisation for COVID-19 vs not hospitalised and mild acute symptoms (age-adjusted OR (aOR) 6.49, 95% CI 3.03 to 14.1), comorbidity count (aOR 1.11 per comorbidity, 95% CI 1.02 to 1.21) and osteoarthritis (aOR 2.11, 95% CI 1.01 to 4.27). COVID-19 onset in 2021 vs June 2020 or earlier was associated with lower odds of prolonged symptom duration (aOR 0.42, 95% CI 0.21 to 0.81). CONCLUSION: Most people with SARDs had complete symptom resolution by day 15 after COVID-19 onset. However, about 1 in 4 experienced COVID-19 symptom duration 28 days or longer; 1 in 10 experienced symptoms 90 days or longer. Future studies are needed to investigate the possible relationships between immunomodulating medications, SARD type/flare, vaccine doses and novel viral variants with prolonged COVID-19 symptoms and other postacute sequelae of COVID-19 among people with SARDs

    SARS-CoV-2 breakthrough infections among vaccinated individuals with rheumatic disease : Results from the COVID-19 Global Rheumatology Alliance provider registry

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    Funding Information: members of the COVID-19 Global Rheumatology Alliance and do not necessarily represent the views of the American College of Rheumatology (ACR), EULAR, the UK National Health Service (NHS), the National Institute for Health Research (NIHR), the UK Department of Health or any other organisation. Competing interests KLH reports she has received non-personal speaker’s fees from AbbVie and grant income from BMS, UCB and Pfizer, all unrelated to this manuscript; KLH is supported by the NIHR Manchester Biomedical Research Centre. LG reports personal consultant fees from AbbVie, Amgen, BMS, Biogen, Celgene, Gilead, Janssen, Lilly, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis and UCB, and grants from Amgen, Lilly, Janssen, Pfizer, Sandoz, Sanofi and Galapagos, all unrelated to this manuscript. AS reports research grants from a consortium of 14 companies (among them AbbVie, BMS, Celltrion, Fresenius Funding Information: Kabi, Gilead/Galapagos, Lilly, Mylan/Viatris, Hexal, MSD, Pfizer, Roche, Samsung, Sanofi-Aventis and UCB) supporting the German RABBIT register and personal fees from lectures for AbbVie, MSD, Roche, BMS, Lilly and Pfizer, all unrelated to this manuscript. LC has not received fees or personal grants from any laboratory, but her institute works by contract for laboratories among other institutions, such as AbbVie Spain, Eisai, Gebro Pharma, Merck Sharp & Dohme España, Novartis Farmaceutica, Pfizer, Roche Farma, Sanofi-Aventis, Astellas Pharma, Actelion Pharmaceuticals España, Grünenthal and UCB Pharma. EF-M reports personal consultant fees from Boehringer Ingelheim Portugal and that LPCDR received support for specific activities: grants from AbbVie, Novartis, Janssen-Cilag, Lilly Portugal, Sanofi, Grünenthal, MSD, Celgene, Medac, Pharmakern and GAfPA; grants and non-financial support from Pfizer; and non-financial support from Grünenthal, outside the submitted work. IB reports personal consultant fees from AbbVie, Novartis, Pfizer and Janssen, all unrelated to this manuscript. JZ reports speaker fees from AbbVie, Novartis and Janssen/Johnson & Johnson, all unrelated to this manuscript. GR-C reports personal consultant fees from Eli Lilly and Novartis, all unrelated to this manuscript. JS is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant numbers: R01 AR077607, P30 AR070253 and P30 AR072577), and the R Bruce and Joan M Mickey Research Scholar Fund. JS has received research support from Amgen and Bristol Myers Squibb and performed consultancy for Bristol Myers Squibb, Gilead, Inova, Janssen and Optum, unrelated to this work. LW receives speaker’s bureau fees from Aurinia Pharma, unrelated to this manuscript. SB reports no competing interests related to this work. He reports non-branded consulting fees for AbbVie, Horizon and Novartis (all <10000).MGMhasnocompetinginterestsrelatedtothiswork.SheservesasapatientconsultantforBMS,BIJNJandAurinia(all<10 000). MGM has no competing interests related to this work. She serves as a patient consultant for BMS, BI JNJ and Aurinia (all <10 000). RG reports no competing interests related to this work. Outside of this work she reports personal and/or speaking fees from AbbVie, Janssen, Novartis, Pfizer and Cornerstones and travel assistance from Pfizer (all <10000).JHreportsnocompetinginterestsrelatedtothiswork.HeissupportedbygrantsfromtheRheumatologyResearchFoundationandhassalarysupportfromtheChildhoodArthritisandRheumatologyResearchAlliance.HehasperformedconsultingforNovartis,SobiandBiogen,allunrelatedtothiswork(<10 000). JH reports no competing interests related to this work. He is supported by grants from the Rheumatology Research Foundation and has salary support from the Childhood Arthritis and Rheumatology Research Alliance. He has performed consulting for Novartis, Sobi and Biogen, all unrelated to this work (<10 000). ESi reports non-financial support from Canadian Arthritis Patient Alliance, outside the submitted work. PS reports personal fees from the American College of Rheumatology/Wiley Publishing, outside the submitted work. ZW reports grant support from Bristol Myers Squibb and Principia/Sanofi and performed consultancy for Viela Bio and MedPace, outside the submitted work. His work is supported by grants from the National Institutes of Health. PMM has received consulting/speaker’s fees from AbbVie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this study. PMM is supported by the National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre (BRC). PCR reports no competing interests related to this work. Outside of this work PCR reports personal fees from AbbVie, Atom Bioscience, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, Kukdong, Novartis, UCB, Roche and Pfizer; meeting attendance support from BMS, Pfizer and UCB; and grant funding from Janssen, Novartis, Pfizer and UCB Pharma (all <$10 000). JY reports no competing interests related to this work. Her work is supported by grants from the National Institutes of Health (K24 AR074534 and P30 AR070155). Outside of this work, she has received research grants or performed consulting for Gilead, BMS Foundation, Pfizer, Aurinia and AstraZeneca. Funding Information: Twitter Jean Liew @rheum_cat, Loreto Carmona @carmona_loreto, Pedro M Machado @pedrommcmachado and Philip C Robinson @philipcrobinson Contributors All authors contributed to the study design, data collection, interpretation of results and review/approval of the final submitted manuscript. JL and MG are guarantors for this manuscript. Funding MG reports grants from the National Institutes of Health, NIAMS, outside the submitted work. KLH is supported by the NIHR Manchester Biomedical Research Centre. JS is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant numbers: R01 AR077607, P30 AR070253 and P30 AR072577), and the R Bruce and Joan M Mickey Research Scholar Fund. JH is supported by grants from the Rheumatology Research Foundation. ZW is supported by grants from the National Institutes of Health. PMM is supported by the National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre (BRC). JY is supported by grants from the National Institutes of Health (K24 AR074534 and P30 AR070155). Publisher Copyright: ©Objective. While COVID-19 vaccination prevents severe infections, poor immunogenicity in immunocompromised people threatens vaccine effectiveness. We analysed the clinical characteristics of patients with rheumatic disease who developed breakthrough COVID-19 after vaccination against SARS-CoV-2.  Methods. We included people partially or fully vaccinated against SARS-CoV-2 who developed COVID-19 between 5 January and 30 September 2021 and were reported to the Global Rheumatology Alliance registry. Breakthrough infections were defined as occurring ≥14 days after completion of the vaccination series, specifically 14 days after the second dose in a two-dose series or 14 days after a single-dose vaccine. We analysed patients' demographic and clinical characteristics and COVID-19 symptoms and outcomes. Results SARS-CoV-2 infection was reported in 197 partially or fully vaccinated people with rheumatic disease (mean age 54 years, 77% female, 56% white). The majority (n=140/197, 71%) received messenger RNA vaccines. Among the fully vaccinated (n=87), infection occurred a mean of 112 (±60) days after the second vaccine dose. Among those fully vaccinated and hospitalised (n=22, age range 36-83 years), nine had used B cell-depleting therapy (BCDT), with six as monotherapy, at the time of vaccination. Three were on mycophenolate. The majority (n=14/22, 64%) were not taking systemic glucocorticoids. Eight patients had pre-existing lung disease and five patients died. Conclusion. More than half of fully vaccinated individuals with breakthrough infections requiring hospitalisation were on BCDT or mycophenolate. Further risk mitigation strategies are likely needed to protect this selected high-risk population.publishersversionPeer reviewe

    Expansion of the human μ-opioid receptor gene architecture: novel functional variants

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    The μ-opioid receptor (OPRM1) is the principal receptor target for both endogenous and exogenous opioid analgesics. There are substantial individual differences in human responses to painful stimuli and to opiate drugs that are attributed to genetic variations in OPRM1. In searching for new functional variants, we employed comparative genome analysis and obtained evidence for the existence of an expanded human OPRM1 gene locus with new promoters, alternative exons and regulatory elements. Examination of polymorphisms within the human OPRM1 gene locus identified strong association between single nucleotide polymorphism (SNP) rs563649 and individual variations in pain perception. SNP rs563649 is located within a structurally conserved internal ribosome entry site (IRES) in the 5′-UTR of a novel exon 13-containing OPRM1 isoforms (MOR-1K) and affects both mRNA levels and translation efficiency of these variants. Furthermore, rs563649 exhibits very strong linkage disequilibrium throughout the entire OPRM1 gene locus and thus affects the functional contribution of the corresponding haplotype that includes other functional OPRM1 SNPs. Our results provide evidence for an essential role for MOR-1K isoforms in nociceptive signaling and suggest that genetic variations in alternative OPRM1 isoforms may contribute to individual differences in opiate responses

    Cultivation and sequencing of rumen microbiome members from the Hungate1000 Collection

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    Productivity of ruminant livestock depends on the rumen microbiota, which ferment indigestible plant polysaccharides into nutrients used for growth. Understanding the functions carried out by the rumen microbiota is important for reducing greenhouse gas production by ruminants and for developing biofuels from lignocellulose. We present 410 cultured bacteria and archaea, together with their reference genomes, representing every cultivated rumen-associated archaeal and bacterial family. We evaluate polysaccharide degradation, short-chain fatty acid production and methanogenesis pathways, and assign specific taxa to functions. A total of 336 organisms were present in available rumen metagenomic data sets, and 134 were present in human gut microbiome data sets. Comparison with the human microbiome revealed rumen-specific enrichment for genes encoding de novo synthesis of vitamin B12, ongoing evolution by gene loss and potential vertical inheritance of the rumen microbiome based on underrepresentation of markers of environmental stress. We estimate that our Hungate genome resource represents ?75% of the genus-level bacterial and archaeal taxa present in the rumen.publishersversionPeer reviewe

    Pathways to success: AIME\u27s educational mentoring model

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    The Australian Indigenous Mentoring Experience (AIME) is a structured educational mentoring program provided for Indigenous students to access throughout their high school experience. The program is designed to support students to complete high school and transition into university, further education and training or employment at the same rate as every Australian child, effectively closing the gap on educational outcomes. To better understand the impact of the program, AIME has developed a research partnership with a team of researchers from the University of Wollongong (UOW) and the University of Technology, Sydney (UTS). Comprising researchers with experience in qualitative and quantitative approaches, this research has grown from a small UOW internally funded project, to a large national project. This collaborative research partnership has already spanned five years and has produced several theorised academic papers, based on both qualitative and quantitative research that describes the AIME program and its merits (Bodkin-Andrews et al. 2013; O\u27Shea et al. 2013; Kervin et al. 2014; O\u27Shea et al. 2014; Harwood et al. 2015). Findings from the research to date have reported the success of the AIME program in engaging Indigenous young people in education (Bodkin-Andrews et al. 2013) as well as described the novel ways that the AIME program reorients the focus on aspirations to one of \u27recognition of aspirations\u27 (Harwood et al. 2014). Further analysis continues to be conducted, including the outcomes of an AIME national survey in 2014 and a paper currently under review that explains the different pedagogy used in the AIME program (McMahon et al, under review). All research activities through this partnership are aligned with protocols for research with Indigenous Australians, as described by the Australian Institute of Aboriginal and Torres Strait Islander Studies. We work collaboratively to discuss, plan and develop research projects and we have adapted data analyses approaches so we can engage in-group analysis so that a range of perspectives and epistemologies are able to be applied the collected data
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