Theorising Indigenous Sociology: Australian perspectives

Indigenous social issues are a topic of regular media interest, but there is scope for much work to be done by Australian sociologists to provide new ways of understanding these issues. The contested terrain of the field, the need for new concepts and frameworks, debates about the possibilities for an Indigenous sociology, and the call for a specifically Australian approach, are some of the challenges and dilemmas for the field. A growing, but small group of Australian sociologist are responding to these dilemmas through a range of interesting and innovative theoretical approaches. To provide an opportunity to explore these developments and to encourage greater collaboration with other researchers in the field a two-day workshop was co-hosted by the Australian Sociological Association (TASA) Sociology of Indigenous Issues Thematic Group and the Department of Sociology and Social Policy at the University of Sydney. The workshop organisers were Dr Deirdre Howard-Wagner (University of Sydney), Dr Daphne Habibis (University of Tasmania) and Dr Theresa Petray (James Cook University). This double blind refereed edited workshop collection consists of six 3000 word full papers from the 18 papers presented at a two-day workshop held at the University of Sydney on Thursday 19 July and Friday 20 July 2012

Whole Genome Sequencing Progress in Medical Application

At present, there are still a lot of diseases pathogenesis not clear, but making use of a new generation of sequencing technology to organisms conduct whole genome sequencing, which for the pathogenesis of many diseases provide a new theoretical basis. So, Which aspects the whole genome sequencing in medical use? In this article, I got through reading the whole genome sequencing of research papers about abroad nearly five years finding that the whole genome sequencing could be widely used in genetic disease, tumor, infectious diseases, infectious epidemic, judge the individual susceptibility to disease, the diagnosis and treatment of a variety of diseases such as biological evolution. This paper reviewed the whole genome sequencing progress in medical application from a genetic disease, tumor, infectious diseases, infectious epidemic, determine the individual susceptibility and biological evolution

Nuclear and Metabolic Quantification for Enhanced Ductal Carcinoma In Situ Risk Stratification

Ductal carcinoma in situ (DCIS) is currently considered an early and localized form of ductal breast cancer stemming from the epithelial ductal cells. These lesions are largely heterogenous, categorized by their morphologies, amount of necrosis, and stromal changes. Even though 10-year mortality rate for DCIS is 1-2.6% while that of early invasive breast cancer is 7-10%. Yet, current recommended treatment for DCIS is breast-conserving surgery and radiation or mastectomy – the same treatment regimen recommended for early invasive breast cancer. This assumes that all DCIS will progress to invasive breast cancer if left untreated. However, mounting evidence indicates that a significant number of DCIS would remain indolence and never progress to invasive cancer. Current risk stratification is based on grade and hormone receptor (estrogen and progesterone) status. While the underlying mechanisms for DCIS to invasive cancer progression are not well understood, an improvement in the quantification of cellular morphology, the extracellular matrix and the metabolism modification of the tumor microenvironment could provide a more accurate and objective prognostication and treatment recommendations. DCIS is currently graded manually by a surgical pathologist using a representative number of areas on the slide. This risks grading bias between different pathologists. By using an automated software to measure quantifiable attributes such as nuclear density, size, and degree of variation of all areas of DCIS on the slide, we can have a more uniform and objective scoring system that would have minimal bias and variation. In addition, we will quantify heterogeneity of collagen arrangement, collagen fiber profile in the stroma as well as the metabolic modifications in the tumor microenvironment of “low risk” vs “high risk” DCIS to determine factors that could provide us with a better prognostication system.https://digitalcommons.unmc.edu/surp2022/1032/thumbnail.jp

p38 mitogen-activated protein kinase activation during platelet storage: Consequences for platelet recovery and hemostatic function in vivo

Platelets undergo several modifications during storage that reduce their posttransfusion survival and functionality. One important feature of these changes, which are known as platelet storage lesion, is the shedding of the surface glycoproteins GPIb-α and GPV. We recently demonstrated that tumor necrosis factor-α converting enzyme (TACE/ADAM17) mediates mitochondrial injury-induced shedding of adhesion receptors and that TACE activity correlates with reduced posttransfusion survival of these cells. We now confirm that TACE mediates receptor shedding and clearance of platelets stored for 16 hours at 37°C or 22°C. We further demonstrate that both storage and mitochondrial injury lead to the phosphorylation of p38 mitogen-activated kinase (MAPK) in platelets and that TACE-mediated receptor shedding from mouse and human platelets requires p38 MAP kinase signaling. Protein kinase C, extracellular regulated-signal kinase MAPK, and caspases were not involved in TACE activation. Both inhibition of p38 MAPK and inactivation of TACE during platelet storage led to a markedly improved posttransfusion recovery and hemostatic function of platelets in mice. p38 MAPK inhibitors had only minor effects on the aggregation of fresh platelets under static or flow conditions in vitro. In summary, our data suggest that inhibition of p38 MAPK or TACE during storage may significantly improve the quality of stored platelets

Promoting Smoke-free Multi-unit Affordable Housing in North Carolina Through a Health Communication Campaign

Background: Secondhand smoke exposure causes 50,000 deaths each year in adult nonsmokers in the United States. In multi-unit housing (e.g. apartments and condominiums), secondhand smoke moves through hallways, air ducts, and small spaces between units, contaminating the air in both smokers' and nonsmokers' units. The presence of secondhand smoke is of particular concern for low-income individuals residing in public housing and affordable housing, where there are higher rates of smoking and secondhand smoke exposure. Smoke-free policies in housing offer health benefits for both tenants and housing operators, including reduced risk of fire, and reduced maintenance and turnover costs for property owners. The 2012-2013 Capstone team partnered with the Tobacco Prevention and Control Branch (TPCB) to promote adoption of smoke-free policies among multi-unit affordable housing (MUAH) operators in North Carolina (NC), building on the work of the previous Capstone team. The 2011-2012 Capstone team surveyed NC tenants, housing managers, and owners regarding facilitators, motivators, and barriers to implementing smoke-free policies and created an online toolkit of materials and resources for housing operators who are interested in implementing smoke-free policies in their properties. Building off of these efforts, the 2012-2013 Capstone team designed a health communication campaign with two goals: 1) to decrease perceived barriers and increase perceived benefits to implementing smoke-free policies among MUAH operators who are contemplating policy adoption, and 2) to increase use of the online toolkit. Methods: We conducted interviews with MUAH operators and organizations to identify preferred and feasible communication channels and to collect narratives from MUAH operators who have implemented smoke-free policies. Based on a literature review and these formative research findings, we created health communication materials that included case studies and thematic content for the online toolkit, newsletter blurbs for housing organization e-newsletters, and a fact sheet to be disseminated at housing conferences. We then created plans for implementing and evaluating the health communication campaign. Finally, we pre-tested the fact sheet with an online survey sent to MUAH operators. Discussion: The Capstone team's work increased Capstone team members' skills in developing health communication campaigns and has important implications for TPCB, the state of North Carolina, and for the field of smoke-free housing. Our work contributed to TPCB's overall mission of promoting smoke-free environments and to TPCB's efforts to engage and build relationships with housing stakeholders, such as MUAH owners and managers. Our work also generated discussion and interest about smoke-free policies among MUAH operators and housing organizations. Smoke-free policies are relatively new to the housing industry, and smoke-free housing advocates around the country work to promote policies and share best practices and information. Our hope is that the health communication campaign will influence additional MUAH operators to adopt smoke-free policies, which will ultimately reduce secondhand smoke exposure among affordable housing residents in NC. Finally, we hope that the health communication materials and comprehensive approach to gathering and sharing operators' experiences will contribute to the growing literature regarding smoke-free multi-unit housing and will serve as a model for smoke-free policy advocates in other states.Master of Public Healt

Identification of Melatonin-Regulated Genes in the Ovine Pituitary Pars Tuberalis, a Target Site for Seasonal Hormone Control

The pars tuberalis (PT) of the pituitary gland expresses a high density of melatonin (MEL) receptors and is believed to regulate seasonal physiology by decoding changes in nocturnal melatonin secretion. Circadian clock genes are known to be expressed in the PT in response to the decline (Per1) and onset (Cry1) of MEL secretion, but to date little is known of other molecular changes in this key MEL target site. To identify transcriptional pathways that may be involved in the diurnal and photoperiod-transduction mechanism, we performed a whole genome transcriptome analysis using PT RNA isolated from sheep culled at three time points over the 24-h cycle under either long or short photoperiods. Our results reveal 153 transcripts where expression differs between photoperiods at the light-dark transition and 54 transcripts where expression level was more globally altered by photoperiod (all time points combined). Cry1 induction at night was associated with up-regulation of genes coding for NeuroD1 (neurogenic differentiation factor 1), Pbef / Nampt (nicotinamide phosphoribosyltransferase) , Hif1α (hypoxia-inducible factor-1α), and Kcnq5 (K channel) and down-regulation of Rorβ, a key clock gene regulator. Using in situ hybridization, we confirmed day-night differences in expression for Pbef / Nampt, NeuroD1, and Rorβ in the PT. Treatment of sheep with MEL increased PT expression for Cry1, Pbef / Nampt, NeuroD1, and Hif1α, but not Kcnq5. Our data thus reveal a cluster of Cry1-associated genes that are acutely responsive to MEL and novel transcriptional pathways involved in MEL action in the PT

HLA-DRB3/4/5 Matching Improves Outcome of Unrelated Hematopoietic Stem Cell Transplantation

The HLA-DRB3/4/5 loci are closely linked to the HLA-DRB1 gene. Mismatches in these loci occur with a frequency of about 8%–12% in otherwise 10/10 HLA-matched transplant pairs. There is preliminary evidence that these disparities may associate with increased acute graft-versus-host disease (GvHD) rates. The aim of this study was to analyze a large cohort of German patients and their donors for HLA-DRB3/4/5 compatibility and to correlate the HLA-DRB3/4/5 matching status with the outcome of unrelated hematopoietic stem cell transplantation (uHSCT). To this end, 3,410 patients and their respective donors were HLA-DRB3/4/5 and HLA-DPB1 typed by amplicon-based nextgeneration sequencing (NGS). All patients included received their first allogeneic transplant for malignant hematologic diseases between 2000 and 2014. Mismatches in the antigen recognition domain (ARD) of HLA-DRB3/4/5 genes were correlated with clinical outcome. HLA-DRB3/4/5 incompatibility was seen in 12.5% (n = 296) and 17.8% (n = 185) of the 10/10 and 9/10 HLA-matched cases, respectively. HLA-DRB3/4/5 mismatches in the ARD associated with a worse overall survival (OS), as shown in univariate (5-year OS: 46.1% vs. 39.8%, log-rank p = 0.038) and multivariate analyses [hazard ratio (HR) 1.25, 95% CI 1.02–1.54, p = 0.034] in the otherwise 10/10 HLAmatched subgroup. The worse outcome was mainly driven by a significantly higher nonrelapse mortality (HR 1.35, 95% CI 1.05–1.73, p = 0.017). In the 9/10 HLA-matched cases, the effect was not statistically significant. Our study results suggest that mismatches within the ARD of HLA-DRB3/4/5 genes significantly impact the outcome of otherwise fully matched uHSCT and support their consideration upon donor selection in the future

HLA-DRB3/4/5 Matching Improves Outcome of Unrelated Hematopoietic Stem Cell Transplantation

The HLA-DRB3/4/5 loci are closely linked to the HLA-DRB1 gene. Mismatches in these loci occur with a frequency of about 8%–12% in otherwise 10/10 HLA-matched transplant pairs. There is preliminary evidence that these disparities may associate with increased acute graft-versus-host disease (GvHD) rates. The aim of this study was to analyze a large cohort of German patients and their donors for HLA-DRB3/4/5 compatibility and to correlate the HLA-DRB3/4/5 matching status with the outcome of unrelated hematopoietic stem cell transplantation (uHSCT). To this end, 3,410 patients and their respective donors were HLA-DRB3/4/5 and HLA-DPB1 typed by amplicon-based nextgeneration sequencing (NGS). All patients included received their first allogeneic transplant for malignant hematologic diseases between 2000 and 2014. Mismatches in the antigen recognition domain (ARD) of HLA-DRB3/4/5 genes were correlated with clinical outcome. HLA-DRB3/4/5 incompatibility was seen in 12.5% (n = 296) and 17.8% (n = 185) of the 10/10 and 9/10 HLA-matched cases, respectively. HLA-DRB3/4/5 mismatches in the ARD associated with a worse overall survival (OS), as shown in univariate (5-year OS: 46.1% vs. 39.8%, log-rank p = 0.038) and multivariate analyses [hazard ratio (HR) 1.25, 95% CI 1.02–1.54, p = 0.034] in the otherwise 10/10 HLAmatched subgroup. The worse outcome was mainly driven by a significantly higher nonrelapse mortality (HR 1.35, 95% CI 1.05–1.73, p = 0.017). In the 9/10 HLA-matched cases, the effect was not statistically significant. Our study results suggest that mismatches within the ARD of HLA-DRB3/4/5 genes significantly impact the outcome of otherwise fully matched uHSCT and support their consideration upon donor selection in the future

The Human Leukocyte Antigen-DPB1 Degree of Compatibility Is Determined by Its Expression Level and Mismatch Permissiveness: A German Multicenter Analysis

T-cell epitope matching according to the TCE3 algorithm classifies HLA-DPB1 mismatches in permissive and non-permissive. This classification has been shown to be predictive for mortality and acute GvHD (aGvHD) events in large international cohorts. We retrospectively genotyped HLA-DPB1 in 3523 patients transplanted in Germany between 2000 and 2014 and in their unrelated donors using an Illumina amplicon-NGS based assay. Aim of the study was to evaluate DP-compatibility beyond the established TCE3 algorithm by assessing the combined effect of several DP-mismatch parameters on post-transplant outcome. We implemented an extended DP-mismatch assessment model where TCE3, DP allotype expression with respect to rs9277534, mismatch vector and number of mismatches were conjointly taken into consideration. In this model, non-permissive HLA-DPB1 mismatches showed significantly increased aGvHD risk if they were accompanied by two HLA-DPB1 mismatches in GvH direction (HR: 1.46) or one mismatched highly expressed patient allotype (HR: 1.53). As previously reported, non-permissive HLA-DPB1 mismatches associated with a significantly higher risk of aGvHD and non-relapse mortality (HR 1.36 and 1.21, respectively), which in turn translated into worse GvHD and relapse free survival (HR 1.13). Effects on GvL and GvHD appeared strongest in GvH-directed non-permissive mismatches. Our study results support the consideration of additional HLA-DPB1 mismatch parameters along with the established TCE3 matching algorithm for refinement of future donor selection. In particular, our findings suggest that DP non-permissiveness associated with two HLA-DPB1 mismatches or at least on highly expressed mismatched patient allotype should be avoided