9 research outputs found

    Learning together for and with the Martuwarra Fitzroy River

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    Co-production across scientific and Indigenous knowledge systems has become a cornerstone of research to enhance knowledge, practice, ethics, and foster sustainability transformations. However, the profound differences in world views and the complex and contested histories of nation-state colonisation on Indigenous territories, highlight both opportunities and risks for Indigenous people when engaging with knowledge co-production. This paper investigates the conditions under which knowledge co-production can lead to improved Indigenous adaptive environmental planning and management among remote land-attached Indigenous peoples through a case study with ten Traditional Owner groups in the Martuwarra (Fitzroy River) Catchment in Western Australia’s Kimberley region. The research team built a 3D map of the river and used it, together with an interactive table-top projector, to bring together both scientific and Indigenous spatial knowledge. Participatory influence mapping, aligned with Traditional Owner priorities to achieve cultural governance and management planning goals set out in the Fitzroy River Declaration, investigated power relations. An analytical framework, examining underlying mechanisms of social learning, knowledge promotion and enhancing influence, based on different theories of change, was applied to unpack the immediate outcomes from these activities. The analysis identified that knowledge co-production activities improved the accessibility of the knowledge, the experiences of the knowledge users, strengthened collective identity and partnerships, and strengthened Indigenous-led institutions. The focus on cultural governance and management planning goals in the Fitzroy River Declaration enabled the activities to directly affect key drivers of Indigenous adaptive environmental planning and management—the Indigenous-led institutions. The nation-state arrangements also gave some support to local learning and decision-making through a key Indigenous institution, Martuwarra Fitzroy River Council. Knowledge co-production with remote land-attached Indigenous peoples can improve adaptive environmental planning and management where it fosters learning together, is grounded in the Indigenous-led institutions and addresses their priorities

    Inhibition of prostate cancer cell growth by activated eosinophils

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    BACKGROUND. Host Immune response to prostate cancer primarily involves the CTL and NK effector cells. Recent immunotherapeutic strategies incorporating cytokine genes into the tumor cell and/or dendritic cells have had encouraging results. In this study, we describe the inhibitory activity of a third potential effector cell, the eosinophil, against DU 145 and PC-3 prostate tumor cells growth in vitro. METHODS. Subconfluent monolayer cultures of DU 145 and PC-3 cells were incubated with peripheral blood eosinophils from allergic or asthmatic individuals and also with eosinophil cultured supernatants. Newly established eosinophil cell lines were also studied. After harvesting, the plates were washed and stained with Hematoxylin/eosin (H/E) then photographed. The combination of monolayer cell growth inhibition and colony formation inhibition assays were used to evaluate eosinophil inhibitory activity. In the colony formation inhibition assay one hundred cells per well in 6-well plates were incubated overnight, after which peripheral blood eosinophils, conditioned media and cytokines, IL-4 and TNF-α were added. The plates were harvested after 10 days incubation period. Colonies were stained and counted. RESULTS. Hypo- and hyperdense peripheral blood eosinophils from allergic and asthmatic individuals as well as eosinophil cell lines established from these subpopulations inhibited both DU 145 and PC-3 cell growth at 58-78% and 10-38%, respectively. IL-5 up-regulated eosinophil cell line activity by 21-24%. The conditioned media which contained the released mediators of activated eosinophils were potent in their actions on both DU 145 and PC-3, inhibiting colony formation by as much as 90-100%. CONCLUSION. These results clearly demonstrate the inhibitory potential of activated eosinophils and their released soup of mediators and therefore support the hypothesis that eosinophils may participate in host response to prostate cancer together with CTLs and NK cells. Furthermore, this study offers insights into possible strategies for enhancing eosinophilic activity in prostate cancer. © 2003 Wiley-Liss, Inc

    Electronic health records identify timely trends in childhood mental health conditions

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    Abstract Background Electronic health records (EHRs) data provide an opportunity to collect patient information rapidly, efficiently and at scale. National collaborative research networks, such as PEDSnet, aggregate EHRs data across institutions, enabling rapid identification of pediatric disease cohorts and generating new knowledge for medical conditions. To date, aggregation of EHR data has had limited applications in advancing our understanding of mental health (MH) conditions, in part due to the limited research in clinical informatics, necessary for the translation of EHR data to child mental health research. Methods In this cohort study, a comprehensive EHR-based typology was developed by an interdisciplinary team, with expertise in informatics and child and adolescent psychiatry, to query aggregated, standardized EHR data for the full spectrum of MH conditions (disorders/symptoms and exposure to adverse childhood experiences (ACEs), across 13 years (2010–2023), from 9 PEDSnet centers. Patients with and without MH disorders/symptoms (without ACEs), were compared by age, gender, race/ethnicity, insurance, and chronic physical conditions. Patients with ACEs alone were compared with those that also had MH disorders/symptoms. Prevalence estimates for patients with 1+ disorder/symptoms and for specific disorders/symptoms and exposure to ACEs were calculated, as well as risk for developing MH disorder/symptoms. Results The EHR study data set included 7,852,081 patients < 21 years of age, of which 52.1% were male. Of this group, 1,552,726 (19.8%), without exposure to ACEs, had a lifetime MH disorders/symptoms, 56.5% being male. Annual prevalence estimates of MH disorders/symptoms (without exposure to ACEs) rose from 10.6% to 2010 to 15.1% in 2023, a 44% relative increase, peaking to 15.4% in 2019, prior to the Covid-19 pandemic. MH categories with the largest increases between 2010 and 2023 were exposure to ACEs (1.7, 95% CI 1.6–1.8), anxiety disorders (2.8, 95% CI 2.8–2.9), eating/feeding disorders (2.1, 95% CI 2.1–2.2), gender dysphoria/sexual dysfunction (43.6, 95% CI 35.8–53.0), and intentional self-harm/suicidality (3.3, 95% CI 3.2–3.5). White youths had the highest rates in most categories, except for disruptive behavior disorders, elimination disorders, psychotic disorders, and standalone symptoms which Black youths had higher rates. Median age of detection was 8.1 years (IQR 3.5–13.5) with all standalone symptoms recorded earlier than the corresponding MH disorder categories. Conclusions These results support EHRs’ capability in capturing the full spectrum of MH disorders/symptoms and exposure to ACEs, identifying the proportion of patients and groups at risk, and detecting trends throughout a 13-year period that included the Covid-19 pandemic. Standardized EHR data, which capture MH conditions is critical for health systems to examine past and current trends for future surveillance. Our publicly available EHR-mental health typology codes can be used in other studies to further advance research in this area

    Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus

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    Coats plus is a highly pleiotropic disorder particularly affecting the eye, brain, bone and gastrointestinal tract. Here, we show that Coats plus results from mutations in CTC1, encoding conserved telomere maintenance component 1, a member of the mammalian homolog of the yeast heterotrimeric CST telomeric capping complex. Consistent with the observation of shortened telomeres in an Arabidopsis CTC1 mutant and the phenotypic overlap of Coats plus with the telomeric maintenance disorders comprising dyskeratosis congenita, we observed shortened telomeres in three individuals with Coats plus and an increase in spontaneous ?H2AX-positive cells in cell lines derived from two affected individuals. CTC1 is also a subunit of the ?-accessory factor (AAF) complex, stimulating the activity of DNA polymerase-? primase, the only enzyme known to initiate DNA replication in eukaryotic cells. Thus, CTC1 may have a function in DNA metabolism that is necessary for but not specific to telomeric integrity.<br/

    Coronal Heating as Determined by the Solar Flare Frequency Distribution Obtained by Aggregating Case Studies

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    Flare frequency distributions represent a key approach to addressing one of the largest problems in solar and stellar physics: determining the mechanism that counter-intuitively heats coronae to temperatures that are orders of magnitude hotter than the corresponding photospheres. It is widely accepted that the magnetic field is responsible for the heating, but there are two competing mechanisms that could explain it: nanoflares or Alfv\'en waves. To date, neither can be directly observed. Nanoflares are, by definition, extremely small, but their aggregate energy release could represent a substantial heating mechanism, presuming they are sufficiently abundant. One way to test this presumption is via the flare frequency distribution, which describes how often flares of various energies occur. If the slope of the power law fitting the flare frequency distribution is above a critical threshold, α=2\alpha=2 as established in prior literature, then there should be a sufficient abundance of nanoflares to explain coronal heating. We performed >>600 case studies of solar flares, made possible by an unprecedented number of data analysts via three semesters of an undergraduate physics laboratory course. This allowed us to include two crucial, but nontrivial, analysis methods: pre-flare baseline subtraction and computation of the flare energy, which requires determining flare start and stop times. We aggregated the results of these analyses into a statistical study to determine that α=1.63±0.03\alpha = 1.63 \pm 0.03. This is below the critical threshold, suggesting that Alfv\'en waves are an important driver of coronal heating.Comment: 1,002 authors, 14 pages, 4 figures, 3 tables, published by The Astrophysical Journal on 2023-05-09, volume 948, page 7
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