Model metadata summary report for the Ipswich-Sudbury LithoFrame 10-50 Model

This report is the published product of a regional GSI3D model of the Ipswich-Sudbury area of southern east Anglia and north Essex. The model was assembled between 2001-07 concurrently with surveying of the area by S.J. Mathers with a modelling contribution to the TL sheets by A. Benha

The long-term dynamics of invasive signal crayfish forcing of fluvial sediment supply via riverbank burrowing

Animals are important drivers of sediment dynamics. Invasive signal crayfish (Pacifastacus leniusculus) have been shown to supply sediment to rivers by burrowing into riverbanks. Burrowing directly transfers excavated sediment into the river and also has an additional indirect affect by promoting riverbank failure. While previous research has isolated burrow densities at a point in time, rates of burrow construction and of burrow loss due to erosion are unknown, which introduces uncertainty into estimates of how much sediment burrows contribute to rivers. Here we report results from a 5-year study that evaluated the temporal dynamics of crayfish populations, rates of burrow loss due to erosion, and the mass of sediment directly supplied to rivers by burrow excavation. At ten reaches across five lowland streams in England, we estimated the mass of sediment displaced by 1861 new and previously constructed burrows. Both crayfish and burrow densities were variable over time, suggesting that burrows contribute temporally variable amounts of fine sediment to riverine systems. 42 % of observed burrows were constructed within the previous 365 days, and individual burrows lasted on average 461 days. Applying this to comparable historical data, an average of 2.0 t km−1 a−1 of sediment was excavated to construct burrows in the study reaches, which is eight times more than estimated in previous studies. Whilst total burrow densities in each year were not consistently correlated with contemporary crayfish densities, the mass of sediment excavated over the prior year was strongly correlated with contemporary crayfish densities. Current fine sediment management practices are largely aimed at controlling fine sediment delivery, predominately from agricultural activities, but biotic burrowing into riverbanks may represent an important and overlooked source of fine sediment supply. Incorporation of biotic processes in sediment dynamics would improve the accuracy of fluvial sediment budgets and enhance the knowledge base underpinning effective fine-sediment management practices

DNA methylation of ESR-1 and N-33 in colorectal mucosa of patients with Ulcerative Colitis (UC)

Introduction: Epigenetic marking such as DNA methylation influence gene transcription and chromosomal stability and may also be affected by environmental exposures. Few studies exist on alteration in DNA methylation profiles (genomic and gene specific methylation) in patients with Ulcerative Colitis (UC) and none assessing its relationship with lifestyle exposures. Aims & Methods: To assess genomic methylation and promoter methylation of the ESR-1 (oestrogen receptor - 1) and N-33 (tumour suppressor candidate-3) genes in the macroscopically normal mucosa of UC patients as well as to investigate effects of anthropometric and lifestyle exposures on DNA methylation. Sixty eight subjects were recruited (24 UC and 44 age and sex matched controls). Colorectal mucosal biopsies were obtained and DNA was extracted. Genomic DNA methylation was quantified using the tritium-labelled cytosine extension assay (3[H] dCTP) whilst gene specific methylation was quantified using the COBRA method. Results: The methylation level of both ESR-1 and N-33 genes were significantly higher in UC subjects compared with controls (7.9% vs 5.9%; p = 0.015 and 66% vs 9.3%; p < 0.001 respectively). There was no detectable difference in global DNA methylation between patients with UC and age and sex matched controls. No associations between indices of DNA methylation and anthropometric measures or smoking patterns were detected. Conclusions: For the first time, we have shown increased methylation in the promoter regions of the putative tumour suppressor gene N-33 in macroscopically normal mucosa of patients with UC. In addition, we have confirmed that methylation of ESR-1 promoter is higher in UC patients compared with age and sex matched controls. These findings suggests that, inactivation through methylation of the putative tumour suppressor genes N-33 and ESR-1, may not be associated with colorectal carcinogenesis in UC

Evaluation of the Graduate Leader Fund: Factors relating to quality: findings from the baseline study

This is the final version of the report. Available from the Department for Education via the link in this record.

Interpretative modelling of a geological cross section from boreholes: sources of uncertainty and their quantification

We conducted a designed experiment to quantify sources of uncertainty in geologists' interpretations of a geological cross section. A group of 28 geologists participated in the experiment. Each interpreted borehole record included up to three Palaeogene bedrock units, including the target unit for the experiment: the London Clay. The set of boreholes was divided into batches from which validation boreholes had been withheld; as a result, we obtained 129 point comparisons between the interpreted elevation of the base of the London Clay and its observed elevation in a borehole not used for that particular interpretation. Analysis of the results showed good general agreement between the observed and interpreted elevations, with no evidence of systematic bias. Between-site variation of the interpretation error was spatially correlated, and the variance appeared to be stationary. The between-geologist component of variance was smaller overall, and depended on the distance to the nearest borehole. There was also evidence that the between-geologist variance depends on the degree of experience of the individual. We used the statistical model of interpretation error to compute confidence intervals for any one interpretation of the base of the London Clay on the cross section, and to provide uncertainty measures for decision support in a hypothetical route-planning process. The statistical model could also be used to quantify error propagation in a full 3-D geological model produced from interpreted cross sections

Model metadata report summary report for the Colchester Lithoframe 10-50 model

This report is the published product of a regional GSI3D model of the Colchester area of southern East Anglia and north Essex. The model was assembled between 2006-08 concurrently with surveying of the parts of the area within the Colchester and Brightlingsea 1:50 000 mapsheets (BGS, 2010) by S.J. Mathers, the TL92 sheet was appended in 2011

National evaluation of the neighbourhood nurseries: integrated report

Report description: The NNI was launched in 2001 to provide high quality childcare in the most disadvantaged neighbourhoods of England, to help parents into employment, reduce child poverty and boost children’s development. By 2005 45,000 new childcare places had been created in approximately 1,400 neighbourhood nurseries. This report brings together the findings of the four individual strands of the National Evaluation of Neighbourhood Nurseries Initiative as shown above and makes a number of recommendations. The report shows the rationale for the government’s strategy in targeting disadvantaged neighbourhoods and in focusing on high quality childcare to provide the link between raising parental employment and income and improving children’s life chances

Safety and efficacy of dimethyl fumarate in ALS: randomised controlled study

Objective Neuroinflammation is an important pathogenic mechanism in amyotrophic lateral sclerosis (ALS), with regulatory T cells (Tregs) mediating a slower rate of disease progression. Dimethyl fumarate enhances Treg levels and suppresses pro-inflammatory T cells. The present study assessed the safety and efficacy of dimethyl fumarate in ALS. Methods Phase-2, double-blind, placebo-controlled randomised clinical trial recruited participants from May 1, 2018 to September 25, 2019, across six Australian sites. Participants were randomised (2:1 ratio) to dimethyl fumarate (480 mg/day) or matching placebo, completing visits at screening, baseline, weeks 12, 24 and 36. The primary efficacy endpoint was a change in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) at week 36. Secondary outcome measures included survival, neurophysiological index (NI), respiratory function, urinary neurotrophin-receptor p75 and quality of life. Results A total of 107 participants were randomised to dimethyl fumarate (n = 72) or placebo (n = 35). ALSFRS-R score was not significantly different at week 36 (−1.12 [−3.75 to 1.52, p = 0.41]). Dimethyl fumarate was associated with a reduced NI decline week 36 (differences in the least-squares mean: (0.84 [−0.51 to 2.22, p = 0.22]). There were no significant differences in other secondary outcome measures. Safety profiles were comparable between groups. Interpretation Dimethyl fumarate, in combination with riluzole, was safe and well-tolerated in ALS. There was no significant improvement in the primary endpoint. The trial provides class I evidence for safety and lack of efficacy of dimethyl fumarate in ALS