Environmental capacity in the East Midlands: an evidence base fit for purpose

This report relates to the initial study into the measurement of Environmental Capacity within the East Midlands Region considering what indicators/measures of Environmental Capacity can be put into place in the near future within the region and what are the aspirations regarding longer term indicators / measures of Environmental Capacity in the region. The study involved in depth interviews with relevant employees from local authorities and other key agencies within the region covering the current data collected/used in monitoring and the possible link to the monitoring of Environmental Capacity as well as the interviewees' awareness of and attitudes towards Environmental Capacity as a monitoring tool

Hypomethylation of CYP2E1 and DUSP22 Promoters Associated With Disease Activity and Erosive Disease Among Rheumatoid Arthritis Patients.

OBJECTIVE:Epigenetic modifications have previously been associated with rheumatoid arthritis (RA). In this study, we aimed to determine whether differential DNA methylation in peripheral blood cell subpopulations is associated with any of 4 clinical outcomes among RA patients. METHODS:Peripheral blood samples were obtained from 63 patients in the University of California, San Francisco RA cohort (all satisfied the American College of Rheumatology classification criteria; 57 were seropositive for rheumatoid factor and/or anti-cyclic citrullinated protein). Fluorescence-activated cell sorting was used to separate the cells into 4 immune cell subpopulations (CD14+ monocytes, CD19+ B cells, CD4+ naive T cells, and CD4+ memory T cells) per individual, and 229 epigenome-wide DNA methylation profiles were generated using Illumina HumanMethylation450 BeadChips. Differentially methylated positions and regions associated with the Clinical Disease Activity Index score, erosive disease, RA Articular Damage score, Sharp score, medication at time of blood draw, smoking status, and disease duration were identified using robust regression models and empirical Bayes variance estimators. RESULTS:Differential methylation of CpG sites associated with clinical outcomes was observed in all 4 cell types. Hypomethylated regions in the CYP2E1 and DUSP22 gene promoters were associated with active and erosive disease, respectively. Pathway analyses suggested that the biologic mechanisms underlying each clinical outcome are cell type-specific. Evidence of independent effects on DNA methylation from smoking, medication use, and disease duration were also identified. CONCLUSION:Methylation signatures specific to RA clinical outcomes may have utility as biomarkers or predictors of exposure, disease progression, and disease severity

Rheumatoid Arthritis Naive T Cells Share Hypermethylation Sites With Synoviocytes.

ObjectiveTo determine whether differentially methylated CpGs in synovium-derived fibroblast-like synoviocytes (FLS) of patients with rheumatoid arthritis (RA) were also differentially methylated in RA peripheral blood (PB) samples.MethodsFor this study, 371 genome-wide DNA methylation profiles were measured using Illumina HumanMethylation450 BeadChips in PB samples from 63 patients with RA and 31 unaffected control subjects, specifically in the cell subsets of CD14+ monocytes, CD19+ B cells, CD4+ memory T cells, and CD4+ naive T cells.ResultsOf 5,532 hypermethylated FLS candidate CpGs, 1,056 were hypermethylated in CD4+ naive T cells from RA PB compared to control PB. In analyses of a second set of CpG candidates based on single-nucleotide polymorphisms from a genome-wide association study of RA, 1 significantly hypermethylated CpG in CD4+ memory T cells and 18 significant CpGs (6 hypomethylated, 12 hypermethylated) in CD4+ naive T cells were found. A prediction score based on the hypermethylated FLS candidates had an area under the curve of 0.73 for association with RA case status, which compared favorably to the association of RA with the HLA-DRB1 shared epitope risk allele and with a validated RA genetic risk score.ConclusionFLS-representative DNA methylation signatures derived from the PB may prove to be valuable biomarkers for the risk of RA or for disease status

Evaluation of global fire simulations in CMIP6 Earth system models

Fire is the primary form of terrestrial ecosystem disturbance on a global scale and an important Earth system process. Most Earth system models (ESMs) have incorporated fire modeling, with 19 out of them submitting model outputs of fire-related variables to the Coupled Model Intercomparison Project Phase 6 (CMIP6). This study provides the first comprehensive evaluation of CMIP6 historical fire simulations by comparing them with multiple satellite-based products and charcoal-based historical reconstructions. Our results show that most CMIP6 models simulate the present-day global burned area and fire carbon emissions within the range of satellite-based products. They also capture the major features of observed spatial patterns and seasonal cycles, the relationship of fires with precipitation and population density, and the influence of El Niño-Southern Oscillation (ENSO) on the interannual variability of tropical fires. Regional fire carbon emissions simulated by the CMIP6 models from 1850 to 2010 generally align with the charcoal-based reconstructions, although there are regional mismatches, such as in southern South America and eastern temperate North America prior to the 1910s and in temperate North America, eastern boreal North America, Europe, and boreal Asia since the 1980s. The CMIP6 simulations have addressed three critical issues identified in the CMIP5: (1) the simulated global burned area less than half of the observations, (2) the failure to reproduce the high burned area fraction observed in Africa, and (3) the weak fire seasonal variability. Furthermore, the CMIP6 models exhibit improved accuracy in capturing the observed relationship between fires and both climatic and socioeconomic drivers, and better align with the historical long-term trends indicated by charcoal-based reconstructions in most regions worldwide. However, the CMIP6 models still fail to reproduce the decline in global burned area and fire carbon emissions observed over the past two decades, mainly attributed to an underestimation of anthropogenic fire suppression, and the spring peak in fires in the Northern Hemisphere mid-latitudes, mainly due to an underestimation of crop fires. In addition, the model underestimates the fire sensitivity to wet-dry conditions, indicating the need to improve fuel wetness estimation. Based on these findings, we present specific guidance for fire scheme development and suggest the post-processing methodology for using CMIP6 multi-model outputs to generate reliable fire projection products

25 years of epidermal stem cell research.

This is a chronicle of concepts in the field of epidermal stem cell biology and a historic look at their development over time. The past 25 years have seen the evolution of epidermal stem cell science, from first fundamental studies to a sophisticated science. The study of epithelial stem cell biology was aided by the ability to visualize the distribution of stem cells and their progeny through lineage analysis studies. The excellent progress we have made in understanding epidermal stem cell biology is discussed in this article. The challenges we still face in understanding epidermal stem cells include defining molecular markers for stem and progenitor sub-populations, determining the locations and contributions of the different stem cell niches, and mapping regulatory pathways of epidermal stem cell proliferation and differentiation. However, our rapidly evolving understanding of epidermal stem cells has many potential uses that promise to translate into improved patient therapy

Appropriate Osteoporosis Treatment by Family Physicians inResponse to FRAX vs CAROC Reporting: Results Froma Randomized Controlled Trial

© 2014 The International Society for Clinical Densitometry. Canadian guidelines recommend either the FRAX or the Canadian Association of Radiologists and Osteoporosis Canada (CAROC) fracture risk assessment tools to report 10-yr fracture risk as low (20%). It is unknown whether one reporting system is more effective in helping family physicians (FPs) identify individuals who require treatment. Individuals ≥50yr old with a distal radius fracture and no previous osteoporosis diagnosis or treatment were recruited. Participants underwent a dual-energy x-ray absorptiometry scan and answered questions about fracture risk factors. Participants\u27 FPs were randomized to receive either a FRAX report or the standard CAROC-derived bone mineral density report currently used by the institution. Only the FRAX report included statements regarding treatment recommendations. Within 3 mo, all participants were asked about follow-up care by their FP, and treatment recommendations were compared with anosteoporosis specialist. Sixty participants were enrolled (31 to FRAX and 29 to CAROC). Kappa statistics of agreement in treatment recommendation were 0.64 for FRAX and 0.32 for bone mineral density. The FRAX report was preferred by FPs and resulted in better postfracture follow-up and treatment that agreed more closely with a specialist. Either the clear statement of fracture risk or the specific statement of treatment recommendations on the FRAX report may have supported FPs to make better treatment decisions

The multiplicity of self: neuropsychological evidence and its implications for the self as a construct in psychological research

This paper examines the issue ofwhat the self is by reviewing neuropsychological research,which converges on the idea that the selfmay be more complex and differentiated than previous treatments of the topic have suggested. Although some aspects of self-knowledge such as episodic recollection may be compromised in individuals, other aspects—for instance, semantic trait summaries—appear largely intact. Taken together, these findings support the idea that the self is not a single, unified entity. Rather, it is a set of interrelated, functionally independent systems. Implications for understanding the self in various areas of psychological research—e.g., neuroimaging, autism, amnesia, Alzheimer’s disease, and mirror self-recognition—are discussed in brief

The dispositionalist deity: how God creates laws and why theists should care

How does God govern the world? For many theists “laws of nature” play a vital role. But what are these laws, metaphysically speaking? I shall argue that laws of nature are not external to the objects they govern, but instead should be thought of as reducible to internal features of properties. Recent work in metaphysics and philosophy of science has revived a dispositionalist conception of nature, according to which nature is not passive, but active and dynamic. Disposition theorists see particulars as being internally powerful rather than being governed by external laws of nature, making external laws in effect ontologically otiose. I will argue that theists should prefer a dispositionalist ontology, since it leads them toward the theory of concurrentism in divine conservation, rather than occasionalism, and revives the distinction between internal and external teleology. God on this view does not govern the world through external laws of nature, but rather through internal aspects of powerful properties

A review of the distribution of particulate trace elements in urban terrestrial environments and its application to considerations of risk

We review the evolution, state of the art and future lines of research on the sources, transport pathways, and sinks of particulate trace elements in urban terrestrial environments to include the atmosphere, soils, and street and indoor dusts. Such studies reveal reductions in the emissions of some elements of historical concern such as Pb, with interest consequently focusing on other toxic trace elements such as As, Cd, Hg, Zn, and Cu. While establishment of levels of these elements is important in assessing the potential impacts of human society on the urban environment, it is also necessary to apply this knowledge in conjunction with information on the toxicity of those trace elements and the degree of exposure of human receptors to an assessment of whether such contamination represents a real risk to the city’s inhabitants and therefore how this risk can be addressed