1,020 research outputs found
Modelling soil erosion and transport in the Burrishoole catchment, Newport, Co. Mayo, Ireland
The Burrishoole catchment is situated in County Mayo, on the northwest coast of the Republic of Ireland. Much of the catchment is covered by blanket peat that, in many areas, has become heavily eroded in recent years. This is thought to be due, primarily, to the adverse effects of forestry and agricultural activities in the area. Such activities include ploughing, drainage, the planting and harvesting of trees, and sheep farming, all of which are potentially damaging to such a sensitive landscape if not managed carefully. This article examines the sediment yield and hydrology of the Burrishoole catchment. Flow and sediment concentrations were measured at 8-hourly intervals from 5 February 2001 to 8 November 2001 with an automatic sampler and separate flow gauge, and hourly averages were recorded between 4 July 2002 and 6 September 2002 using an automatic river monitoring system [ARMS]. The authors describe the GIS-based model of soil erosion and transport that was applied to the Burrishoole catchment during this study. The results of these analyses were compared, in a qualitative manner, with the aerial photography available for the Burrishoole catchment to see whether areas that were predicted to contribute large proportions of eroded material to the drainage network corresponded with areas where peat erosion could be identified through photo-interpretation
Modelling soil erosion and transport in the Burrishoole catchment, Newport, Co. Mayo, Ireland
The Burrishoole catchment is situated in County Mayo, on the northwestcoast of the Republic of Ireland. Much of the catchment is covered byblanket peat that, in many areas, has become heavily eroded in recent years(Fig. 1). This is thought to be due, primarily, to the adverse effects offorestry and agricultural activities in the area. Such activities includeploughing, drainage, the planting and harvesting of trees, and sheepfarming, all of which are potentially damaging to such a sensitivelandscape if not managed carefully
Anti-PD-1 monoclonal antibody MEDI0680 in a phase I study of patients with advanced solid malignancies.
BACKGROUND: The safety, efficacy, pharmacokinetics, and pharmacodynamics of the anti-programmed cell death-1 antibody MEDI0680 were evaluated in a phase I, multicenter, dose-escalation study in advanced solid malignancies.
METHODS: MEDI0680 was administered intravenously once every 2 weeks (Q2W) or once every 3 weeks at 0.1, 0.5, 2.5, 10 or 20âmg/kg. Two cohorts received 20âmg/kg once a week for 2 or 4âweeks, then 20âmg/kg Q2W. All were treated for 12âmonths or until progression. The primary endpoint was safety. Secondary endpoints were efficacy and pharmacokinetics. Exploratory endpoints included pharmacodynamics.
RESULTS: Fifty-eight patients were treated. Median age was 62.5âyears and 81% were male. Most had kidney cancer (nâ=â36) or melanoma (nâ=â9). There were no dose-limiting toxicities. Treatment-related adverse events occurred in 83% and were gradeââ„â3 in 21%. Objective clinical responses occurred in 8/58 patients (14%): 5 with kidney cancer, including 1 with a complete response, and 3 with melanoma. The relationship between dose and serum levels was predictable and linear, with apparent receptor saturation at 10âmg/kg Q2W and all 20âmg/kg cohorts.
CONCLUSIONS: MEDI0680 induced peripheral T-cell proliferation and increased plasma IFNÎł and associated chemokines regardless of clinical response. CD8+ T-cell tumor infiltration and tumoral gene expression of IFNG, CD8A, CXCL9, and granzyme K (GZMK) were also increased following MEDI0680 administration.
TRIAL REGISTRATION: NCT02013804 ; date of registration December 12, 2013
Implementing health research through academic and clinical partnerships : a realistic evaluation of the Collaborations for Leadership in Applied Health Research and Care (CLAHRC)
Background: The English National Health Service has made a major investment in nine partnerships between
higher education institutions and local health services called Collaborations for Leadership in Applied Health
Research and Care (CLAHRC). They have been funded to increase capacity and capability to produce and
implement research through sustained interactions between academics and health services. CLAHRCs provide a
natural âtest bedâ for exploring questions about research implementation within a partnership model of delivery.
This protocol describes an externally funded evaluation that focuses on implementation mechanisms and
processes within three CLAHRCs. It seeks to uncover what works, for whom, how, and in what circumstances.
Design and methods: This study is a longitudinal three-phase, multi-method realistic evaluation, which
deliberately aims to explore the boundaries around knowledge use in context. The evaluation funder wishes to see
it conducted for the process of learning, not for judging performance. The study is underpinned by a conceptual
framework that combines the Promoting Action on Research Implementation in Health Services and Knowledge to
Action frameworks to reflect the complexities of implementation. Three participating CLARHCS will provide indepth
comparative case studies of research implementation using multiple data collection methods including
interviews, observation, documents, and publicly available data to test and refine hypotheses over four rounds of
data collection. We will test the wider applicability of emerging findings with a wider community using an
interpretative forum.
Discussion: The idea that collaboration between academics and services might lead to more applicable health
research that is actually used in practice is theoretically and intuitively appealing; however the evidence for it is
limited. Our evaluation is designed to capture the processes and impacts of collaborative approaches for
implementing research, and therefore should contribute to the evidence base about an increasingly popular (e.g.,
Mode two, integrated knowledge transfer, interactive research), but poorly understood approach to knowledge
translation. Additionally we hope to develop approaches for evaluating implementation processes and impacts
particularly with respect to integrated stakeholder involvement
A multi-targeted approach to suppress tumor-promoting inflammation
Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-ÎșB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes
The state of the Martian climate
60°N was +2.0°C, relative to the 1981â2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes
Diagnostic accuracy of cyst fluid amphiregulin in pancreatic cysts
<p>Abstract</p> <p>Background</p> <p>Accurate tests to diagnose adenocarcinoma and high-grade dysplasia among mucinous pancreatic cysts are clinically needed. This study evaluated the diagnostic utility of amphiregulin (AREG) as a pancreatic cyst fluid biomarker to differentiate non-mucinous, benign mucinous, and malignant mucinous cysts.</p> <p>Methods</p> <p>A single-center retrospective study to evaluate AREG levels in pancreatic cyst fluid by ELISA from 33 patients with a histological gold standard was performed.</p> <p>Results</p> <p>Among the cyst fluid samples, the median (IQR) AREG levels for non-mucinous (n = 6), benign mucinous (n = 15), and cancerous cysts (n = 15) were 85 pg/ml (47-168), 63 pg/ml (30-847), and 986 pg/ml (417-3160), respectively. A significant difference between benign mucinous and malignant mucinous cysts was observed (<it>p </it>= 0.025). AREG levels greater than 300 pg/ml possessed a diagnostic accuracy for cancer or high-grade dysplasia of 78% (sensitivity 83%, specificity 73%).</p> <p>Conclusion</p> <p>Cyst fluid AREG levels are significantly higher in cancerous and high-grade dysplastic cysts compared to benign mucinous cysts. Thus AREG exhibits potential clinical utility in the evaluation of pancreatic cysts.</p
The role of Indigenous peoples and local communities in effective and equitable conservation
Debate about what proportion of the Earth to protect often overshadows the question of how nature should be conserved and by whom. We present a systematic review and narrative synthesis of 169 publications investigating how different forms of governance influence conservation outcomes, paying particular attention to the role played by Indigenous peoples and local communities. We find a stark contrast between the outcomes produced by externally controlled conservation, and those produced by locally controlled efforts. Crucially, most studies presenting positive outcomes for both well-being and conservation come from cases where Indigenous peoples and local communities play a central role, such as when they have substantial influence over decision making or when local institutions regulating tenure form a recognized part of governance. In contrast, when interventions are controlled by external organizations and involve strategies to change local practices and supersede customary institutions, they tend to result in relatively ineffective conservation at the same time as producing negative social outcomes. Our findings suggest that equitable conservation, which empowers and supports the environmental stewardship of Indigenous peoples and local communities represents the primary pathway to effective long-term conservation of biodiversity, particularly when upheld in wider law and policy. Whether for protected areas in biodiversity hotspots or restoration of highly modified ecosystems, whether involving highly traditional or diverse and dynamic local communities, conservation can become more effective through an increased focus on governance type and quality, and fostering solutions that reinforce the role, capacity, and rights of Indigenous peoples and local communities. We detail how to enact progressive governance transitions through recommendations for conservation policy, with immediate relevance for how to achieve the next decadeâs conservation targets under the UN Convention on Biological Diversity
Sub-Telomere Directed Gene Expression during Initiation of Invasive Aspergillosis
Aspergillus fumigatus is a common mould whose spores are a
component of the normal airborne flora. Immune dysfunction permits developmental
growth of inhaled spores in the human lung causing aspergillosis, a significant
threat to human health in the form of allergic, and life-threatening invasive
infections. The success of A. fumigatus as a pathogen is unique
among close phylogenetic relatives and is poorly characterised at the molecular
level. Recent genome sequencing of several Aspergillus species
provides an exceptional opportunity to analyse fungal virulence attributes
within a genomic and evolutionary context. To identify genes preferentially
expressed during adaptation to the mammalian host niche, we generated multiple
gene expression profiles from minute samplings of A. fumigatus
germlings during initiation of murine infection. They reveal a highly
co-ordinated A. fumigatus gene expression programme, governing
metabolic and physiological adaptation, which allows the organism to prosper
within the mammalian niche. As functions of phylogenetic conservation and
genetic locus, 28% and 30%, respectively, of the
A. fumigatus subtelomeric and lineage-specific gene
repertoires are induced relative to laboratory culture, and physically clustered
genes including loci directing pseurotin, gliotoxin and siderophore biosyntheses
are a prominent feature. Locationally biased A. fumigatus gene
expression is not prompted by in vitro iron limitation, acid,
alkaline, anaerobic or oxidative stress. However, subtelomeric gene expression
is favoured following ex vivo neutrophil exposure and in
comparative analyses of richly and poorly nourished laboratory cultured
germlings. We found remarkable concordance between the A.
fumigatus host-adaptation transcriptome and those resulting from
in vitro iron depletion, alkaline shift, nitrogen
starvation and loss of the methyltransferase LaeA. This first transcriptional
snapshot of a fungal genome during initiation of mammalian infection provides
the global perspective required to direct much-needed diagnostic and therapeutic
strategies and reveals genome organisation and subtelomeric diversity as
potential driving forces in the evolution of pathogenicity in the genus
Aspergillus
52 Genetic Loci Influencing Myocardial Mass.
BACKGROUND: Myocardial mass is a key determinant of cardiac muscle function and hypertrophy. Myocardial depolarization leading to cardiac muscle contraction is reflected by the amplitude and duration of the QRS complex on the electrocardiogram (ECG). Abnormal QRS amplitude or duration reflect changes in myocardial mass and conduction, and are associated with increased risk of heart failure and death. OBJECTIVES: This meta-analysis sought to gain insights into the genetic determinants of myocardial mass. METHODS: We carried out a genome-wide association meta-analysis of 4 QRS traits in up to 73,518 individuals of European ancestry, followed by extensive biological and functional assessment. RESULTS: We identified 52 genomic loci, of which 32 are novel, that are reliably associated with 1 or more QRS phenotypes at p < 1 à 10(-8). These loci are enriched in regions of open chromatin, histone modifications, and transcription factor binding, suggesting that they represent regions of the genome that are actively transcribed in the human heart. Pathway analyses provided evidence that these loci play a role in cardiac hypertrophy. We further highlighted 67 candidate genes at the identified loci that are preferentially expressed in cardiac tissue and associated with cardiac abnormalities in Drosophila melanogaster and Mus musculus. We validated the regulatory function of a novel variant in the SCN5A/SCN10A locus in vitro and in vivo. CONCLUSIONS: Taken together, our findings provide new insights into genes and biological pathways controlling myocardial mass and may help identify novel therapeutic targets
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