211 research outputs found
Radical Access: Textiles and Museums
This presentation discusses recent initiatives at Glenbow and Nickle Galleries that endeavor to provide new, radical levels of access to textile collections as a means to build community and affect creativity. While locking textiles away in environmentally controlled rooms and minimizing handling are useful methods for preservation, they are less effective in building vibrant communities or creating future relevance form museum collections. This paper, building on Hemmingâs post-colonial textile theory, as well as Onciulâs theories on decolonizing engagement, challenge the apparent dichotomy between access and preservation. It argues that preservation without radical access, without shared community meaning making, without respecting the inherent kinship of museum textiles, is unattainable. This apparent stalemate is a relic of museumsâ colonial past where institutional priorities have tended to exclude consideration of source communitiesâ needs. With textile collections, their physical well-being has been prioritized over their ongoing relationships with cultural groups. The concept of radicalizing access is an approach that both the Nickle Galleries and Glenbow are exploring in order to transform their relationships with the communities they serve. Schmidt will discuss how Glenbow is taking responsibility for previously stripping culture from Indigenous people and how connecting community members with textile collections is affecting reconciliation. A recent project involves connecting Indigenous foster children with textiles, enhancing their awareness and experience of Indigenous Culture. Hardy will discuss ongoing teaching efforts with the Nickleâs Afghan textiles, enhancing awareness of refugeeâs experiences of war. Other initiatives involve connecting artists and the Nickleâs textile collections, fostering new creative research. Both sets of examples illustrate how radical access can shift the balance of power between museums and source communities and enable shared meaning making or abrogating that right-enhancing the relevance and ongoing preservation of textiles and communities of textile users
Starting out right : early education and looked after children
Looked after children (LAC) are those for whom the state assumes parental responsibility because the adults caring for them â usually the birth parent/s â are no longer able to. In England, 60 per cent of LAC enter care following abuse or neglect. The majority of LAC are placed with a foster carer, either a registered foster parent or âkinship careâ with a relative or friend. The number of LAC in England has been rising steadily in recent years, reaching 70,440 in 2016. Just under one fifth of these children (12,860) were under the age of compulsory schooling. The research evidence is conclusive on the link between early adversity and poorer outcomes. Looked after children are at risk of poorer cognitive, socio-emotional and academic outcomes and are almost ten times more likely than their peers to have a statement of special educational needs or an education, health and care plan. In England, the starkest differences are seen towards the end of schooling, with only 18 per cent of LAC achieving five GSCEs at grade C or above, compared to 64 per cent of children not in care. However, research suggests that the gap between LAC and their non-looked-after peers emerges well before school-age. There is also strong evidence that attending early years provision can help disadvantaged children catch up with their peers, with the benefits both more significant and more sustained if provision is of good quality. Given that many LAC are from disadvantaged homes, there is a good reason to believe that the same applies for this vulnerable group. In England, all three and four-year-old children are entitled to a free part-time âearly educationâ place within an early years setting, with take-up rates of more than 90 per cent within the general population. Recent policy initiatives such as free early education for disadvantaged two-year-olds (for which all LAC are eligible) and the early years âpupil premiumâ for disadvantaged children offer huge potential to improve access to - and the quality of â early education for LAC. However at present not enough is known to ensure that these benefits translate into improved outcomes. This exploratory study aimed to address this gap, and explore the current situation in England
Multinational Experiences in Reducing and Preventing the Use of Restraint and Seclusion
Restraint and seclusion (R/S) have been used in many countries and across service sectors for centuries. With the recent and increasing recognition of the harm associated with these procedures, efforts have been made to reduce and prevent R/S. Following a scathing media exposé in 1998 and congressional scrutiny, the United States began a national effort to reduce and prevent R/S use. With federal impetus and funding, an evidence-based practice, the Six Core Strategies1 to Prevent Conflict, Violence and the Use of Seclusion and Restraint, was developed. This model was widely and successfully implemented in a number of U.S. states and is being adopted by other countries, including Finland, Australia, and the United Kingdom. Recently, the first cluster randomized controlled study of the Six Core Strategies in Finland provided the first evidence-based data of the safety and effectiveness of a coercion prevention methodology. Preliminary findings of some of the international efforts are discussed. Reduction in R/S use and other positive outcomes are also reported
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Interspecies differences in protein expression do not impact the spatiotemporal regulation of glycoprotein VI mediated activation
Background
Accurate protein quantification is a vital prerequisite for generating meaningful predictions when using systems biology approaches, a method that is increasingly being used to unravel the complexities of sub cellular interactions and as part of the drug discovery process. Quantitative proteomics, flow cytometry and western blotting have been extensively used to define human platelet protein copy numbers, yet for mouse platelets, a model widely used for platelet research, evidence is largely limited to a single proteomic dataset in which the total amount of proteins were generally comparatively higher than those found in human platelets.
Objectives
To investigate the functional implications of discrepancies between levels of mouse and human proteins in the GPVI signalling pathway using a systems pharmacology model of GPVI
Methods
The protein copy number of mouse platelet receptors was determined using flow cytometry. The Virtual Platelet, a mathematical model of Glycoprotein VI (GPVI) signalling, was used to determine the consequences of protein copy number differences observed between human and mouse platelets.
Results and conclusion
Despite the small size of mouse platelets compared to human platelets they possessed a greater density of surface receptors alongside a higher concentration of intracellular signalling proteins. Surprisingly the predicted temporal profile of Syk activity was similar in both species with predictions supported experimentally. Super resolution microscopy demonstrates that the spatial distribution of Syk is similar between species, suggesting that the spatial distribution of receptors and signalling molecules in activated platelets, rather than their copy number, is important for signalling pathway regulation
Microglia-synapse engulfment via PtdSer-TREM2 ameliorates neuronal hyperactivity in Alzheimer's disease models
Neuronal hyperactivity is a key feature of early stages of Alzheimer's disease (AD). Genetic studies in AD support that microglia act as potential cellular drivers of disease risk, but the molecular determinants of microglia-synapse engulfment associated with neuronal hyperactivity in AD are unclear. Here, using super-resolution microscopy, 3D-live imaging of co-cultures, and in vivo imaging of lipids in genetic models, we found that spines become hyperactive upon AÎČ oligomer stimulation and externalize phosphatidylserine (ePtdSer), a canonical "eat-me" signal. These apoptotic-like spines are targeted by microglia for engulfment via TREM2 leading to amelioration of AÎČ oligomer-induced synaptic hyperactivity. We also show the in vivo relevance of ePtdSer-TREM2 signaling in microglia-synapse engulfment in the hAPP NL-F knock-in mouse model of AD. Higher levels of apoptotic-like synapses in mice as well as humans that carry TREM2 loss-of-function variants were also observed. Our work supports that microglia remove hyperactive ePtdSer+ synapses in AÎČ-relevant context and suggest a potential beneficial role for microglia in the earliest stages of AD
Choice of faecal immunochemical test matters: Comparison of OC-Sensor and HM-JACKarc, in the assessment of patients at high risk of colorectal cancer
Objectives: Currently NICE recommends the use of faecal immunochemical test (FIT) at faecal haemoglobin concentrations (f-Hb) of 10 Όg Hb/g faeces to stratify for colorectal cancer (CRC) risk in symptomatic populations. This f-Hb cut-off is advised across all analysers, despite the fact that a direct comparison of analyser performance, in a clinical setting, has not been performed.Methods: Two specimen collection devices (OC-Sensor, OC-S; HM-JACKarc, HM-J) were sent to 914 consecutive individuals referred for follow up due to their increased risk of CRC. Agreement of f-Hb around cut-offs of 4, 10 and 150 ”g Hb/g faeces and CRC detection rates were assessed. Two OC-S devices were sent to a further 114 individuals, for within test comparisons.Results: 732 (80.1%) individuals correctly completed and returned two different FIT devices, with 38 (5.2%) CRCs detected. Median f-Hb for individuals diagnosed with and without CRC were 258.5 and 1.8 ”g Hb/g faeces for OC-S and 318.1 and 1.0 ”g Hb/g faeces for HM-J respectively.Correlation of f-Hb results between OC-S/HM-J over the full range was rho=0.74, p[less than]0.001. Using a f-Hb of 4Όg Hb/g faeces for both tests found an agreement of 88.1%, at 10Όg Hb/g faeces 91.7% and at 150Όg Hb/g faeces 96.3%.114 individuals completed and returned two OC-S devices; correlation across the full range was rho=0.98, p[less than]0.001.Conclusion: We found large variations in f-Hb when different FIT devices were used, but a smaller variation when the same FIT device was used. Our data suggest that analyser-specific f-Hb cut-offs are applied with regard to clinical decision making, especially at lower f-Hb
Faecal immunochemical testing and blood tests for prioritization of urgent colorectal cancer referrals in symptomatic patients: a 2-year evaluation
BackgroundA novel pathway incorporating faecal immunochemical testing (FIT) for rapid colorectal cancer diagnosis (RCCD) was introduced in 2017. This paper reports on the service evaluation after 2 years of pathway implementation.MethodsThe RCCD protocol was based on FIT, blood results and symptoms to stratify adult patients in primary care. Two-week-wait (2WW) investigation was indicated for patients with rectal bleeding, rectal mass and faecal haemoglobin (fHb) level of 10 ”g Hb/g faeces or above or 4 ”g Hb/g faeces or more in the presence of anaemia, low ferritin or thrombocytosis, in all other symptom groups. Patients with 100 ”g Hb/g faeces or above had expedited investigation . A retrospective audit of colorectal cancer detected between 2017 and 2019 was conducted, fHb thresholds were reviewed and critically assessed for cancer diagnoses.ResultsIn 2 years, 14788 FIT tests were dispatched with 13361 (90.4 per cent) completed returns. Overall, fHb was less than 4 ”g Hb/g faeces in 9208 results (68.9 per cent), 4â9.9 ”g Hb/g in 1583 (11.8 per cent), 10â99.9 ”g Hb/g in 1850 (13.8 per cent) and 100 ”g Hb/g faeces or above in 720 (5.4 per cent). During follow-up (median 10.4 months), 227 colorectal cancers were diagnosed. The cancer detection rate was 0.1 per cent in patients with fHb below 4 ”g Hb/g faeces, 0.6 per cent in those with fHb 4â9.9 ”g Hb/g faeces, 3.3 per cent for fHb 10â99.9 ”g Hb/g faeces and 20.7 per cent for fHb 100 ”g Hb/g faeces or above. The detection rate in the cohort with 10â19.9 ”g Hb/g faeces was 1.4 per cent, below the National Institute for Health and Care Excellence threshold for urgent referral. The colorectal cancer rate in patients with fHb below 20 ”g Hb/g faeces was less than 0.3 per cent.ConclusionUse of FIT to "rule out" urgent referral from primary care misses a small number of cases. The threshold for referral may be adjusted with blood results to improve stratification
A recurrent mitochondrial p.Trp22Arg NDUFB3 variant causes a distinctive facial appearance, short stature and a mild biochemical and clinical phenotype
Background Isolated Complex I deficiency is the most common paediatric mitochondrial disease presentation, associated with poor prognosis and high mortality. Complex I comprises 44 structural subunits with at least 10 ancillary proteins; mutations in 29 of these have so far been associated with mitochondrial disease but there are limited genotype-phenotype correlations to guide clinicians to the correct genetic diagnosis.
Methods Patients were analysed by whole-exome sequencing, targeted capture or candidate gene sequencing. Clinical phenotyping of affected individuals was performed.
Results We identified a cohort of 10 patients from 8 families (7 families are of unrelated Irish ancestry) all of whom have short stature (C, p.Trp22Arg NDUFB3 variant. Two sibs presented with primary short stature without obvious metabolic dysfunction. Analysis of skeletal muscle from three patients confirmed a defect in Complex I assembly.
Conclusions Our report highlights that the long-term prognosis related to the p.Trp22Arg NDUFB3 mutation can be good, even for some patients presenting in acute metabolic crisis with evidence of an isolated Complex I deficiency in muscle. Recognition of the distinctive facial featuresâparticularly when associated with markers of mitochondrial dysfunction and/or Irish ancestryâshould suggest screening for the p.Trp22Arg NDUFB3 mutation to establish a genetic diagnosis, circumventing the requirement of muscle biopsy to direct genetic investigations
Genome-wide association meta-analyses to identify common genetic variants associated with hallux valgus in Caucasian and African Americans
Objective Hallux valgus (HV) affects âŒ36% of Caucasian adults. Although considered highly heritable, the underlying genetic determinants are unclear. We conducted the first genome-wide association study (GWAS) aimed to identify genetic variants associated with HV.
Methods HV was assessed in three Caucasian cohorts (n=2263, n=915 and n=1231 participants, respectively). In each cohort, a GWAS was conducted using 2.5â
M imputed SNPs. Mixed-effect regression with the additive genetic model adjusted for age, sex, weight and within-family correlations was used for both sex-specific and combined analyses. To combine GWAS results across cohorts, fixed-effect inverse-variance meta-analyses were used. Following meta-analyses, top-associated findings were also examined in an African American cohort (n=327).
Results The proportion of HV variance explained by genome-wide genotyped SNPs was 50% in men and 48% in women. A higher proportion of genetic determinants of HV were sex specific. The most significantly associated SNP in men was rs9675316 located on chr17q23-a24 near the AXIN2 gene (p=0.000000546Ă10â7); the most significantly associated SNP in women was rs7996797 located on chr13q14.1-q14.2 near the ESD gene (p=0.000000721Ă10â7). Genome-wide significant SNP-by-sex interaction was found for SNP rs1563374 located on chr11p15.1 near the MRGPRX3 gene (interaction p value =0.0000000041Ă10â9). The association signals diminished when combining men and women.
Conclusions The findings suggest that the potential pathophysiological mechanisms of HV are complex and strongly underlined by sex-specific interactions. The identified genetic variants imply contribution of biological pathways observed in osteoarthritis as well as new pathways, influencing skeletal development and inflammation
Ecological Survey of Tauranga Harbour
This report summarises the results of biological and physical data collected from a broad scale intertidal survey of Tauranga Harbour conducted between December 2011 and February 2012. The survey was designed to understand more fully the role of various anthropogenic stressors on the ecology of the harbour. The research was conducted as part of the Manaaki Taha Moana (MTM) programme. The wider research project aims to restore and enhance coastal ecosystems and their services of importance to iwi/hapƫ, by working with iwi to improve knowledge of these ecosystems and the degradation processes that affect them.
In this report we assess the health of macrofaunal benthic communities (bottom-dwelling animals) as well as trends in sediments, nutrients and contaminants. The results indicate that the sites identified as most impacted were generally located in the upper reaches of estuaries in some of the locations least exposed to wind, waves and currents. In addition, the biological community composition characterising sites with different sediment textures, nutrient and contaminant loadings were found to vary. Sediments within Tauranga Harbour were predominantly sandy with the percentage of mud within a similar range as measured for other New Zealand estuaries. The exceptions included Te Puna Estuary and Apata Estuary, which experience higher rates of sedimentation.
Heavy metal contamination in sediments is often highly correlated with the percentage of mud content due to the adherence of chemicals to fine sediments and/or organic content. It is, therefore, not surprising that heavy metal concentrations were also highest in the depositional inner areas of the harbour, such as Te Puna Estuary. The heavy metal contaminant levels within Tauranga were well below relevant guideline thresholds and lower than concentrations measured in many other estuaries in New Zealand and overseas. Although the three metals recorded were found to be highly correlated, zinc levels tended to be closer to guideline thresholds for possible biological effects.
Sediment nutrient concentrations in the harbour tended to decline with distance from the inner harbour and associated rivers. Te Puna Estuary showed comparatively high nitrogen and phosphorus loadings. Comparison of sediment nutrient concentrations with other New Zealand estuaries indicates that the Tauranga Harbour sits within a range typical for slightly to moderately enriched estuaries. Although total phosphorus was low compared with other estuaries, total N:P ratios suggest Tauranga Harbour is still limited by nitrogen.
We developed a BHM using statistical ordination techniques to identify key stressors affecting the âhealthâ of macrofaunal communities. Sediments, nutrients and heavy metals were identified as key âstressorsâ, i.e. variables affecting the ecology of the harbour. Therefore, three multivariate models were developed based on the variability in community composition using canonical analysis of principal coordinates (CAP). The ecological assemblages generally reflected gradients of stress or pollution very well. However, the CAP models for sedimentation and contamination performed best. In general, the multivariate models were found to be more sensitive to changing ecological health than simple univariate measures (abundance, species diversity, evenness and Shannon-Wiener diversity). This finding has also been reported in the literature where univariate measures based on abundance and diversity were only able to detect significant differences between the most and least disturbed sites, but were not able to differentiate between smaller relative changes in ecological health. Hence univariate measures were less sensitive to smaller degradative changes in community composition. For Tauranga Harbour, ordination models based on community composition appear to be a more sensitive measure of âhealthâ along an ecological gradient and should enable long term degradative change from multiple disturbances to be assessed. This BHM approach can be used as a management or monitoring tool where sites are repeatedly sampled over time and tracked to determine whether the communities are moving towards a more healthy or unhealthy state.
The key species at âhealthyâ and âimpactedâ sites as determined from the CAP models were also identified. Species at âimpactedâ sites can be considered to be tolerant to the stressor (i.e. sediment, nutrients or contaminants), while species with high abundances at only âhealthyâ sites are sensitive to increasing stressors. We developed species response models for 20 taxa. Although the type of response differed by taxa and stressor, variation in the abundance of most of the taxa modelled was most likely to be better predicted by sedimentation. Unimodal responses were almost always observed in response to nutrients, while declines or skewed unimodal responses were most often observed in response to sedimentation and metals.
The results from this study are consistent with models of macrofaunal species occurrence with respect to sediment mud content developed across a range of New Zealand estuaries by Thrush et al. (2003). Within this report we extend this analysis by also developing models of macrofaunal species occurrence with respect to nutrient and contaminants loadings. Ultimately such statistical models provide a tool to forecast the distribution and abundance of species associated with habitat changes in sediments, nutrients and metals.
In conclusion, Tauranga Harbour is a predominantly sandy harbour with slight to moderate enrichment and low levels of heavy metal contaminants. Sites identified as most impacted by elevated sediments, heavy metal contaminants and nutrients were generally located in the upper reaches of estuaries in some of the least exposed locations. To some extent, this reflects the natural progression of an estuary from land to sea; however, the rates of accumulation of sediments and nutrients have been accelerated as a result of anthropogenic land-based activities. Sediments and contaminants were found to explain the largest variance in benthic communities. Species response models suggest that taxa were either sensitive to elevated sediments, nutrients loading or contamination at all levels, or sensitive to these stressors beyond a critical point
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