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

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

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

The London Basin superficial and bedrock LithoFrame 50 Model

This report describes the methodology and datasets used in the construction of the 1:50 000 resolution superficial and bedrock geological model of the London Basin. The London Basin study area was divided into twelve 20 x 20 km tiles, with construction of the first tiles beginning in 2006 and completion of the combined model in 2014. This time period coincided with the ongoing development of GSI3D software which was used to construct much of the model. The GSI3D software was used to calculate a rockhead (base Quaternary and Anthropocene) surface that was then used as a capping surface for the modelling of the bedrock geology in the GOCAD® software. The model complements the corresponding DiGMapGB-50 tiles of the area and consists of about 80 modelled geological units, comprising mass movement (landslip), artificial, superficial, and bedrock. This report supersedes an earlier report detailing the construction of the superficial part of this model (Burke et al. 2013). A glossary of technical terms used is included at the end of this report

A Systematic Review of Dental Disease in Patients Undergoing Cancer Therapy

Introduction: The purpose of this systematic review was to evaluate the literature and update our current understanding of the impact of present cancer therapies on the dental apparatus (teeth and periodontium) since the 1989 NIH Development Consensus Conference on the Oral Compli­cations of Cancer Therapies. Review Method: A systematic literature search was con­ducted with assistance from a research librarian in the databases MEDLINE/PubMed and EMBASE for articles published between 1 January 1990 and 31 December 2008. Each study was independently assessed by two reviewers. Taking into account predetermined quality measures, a weighted prevalence was calculated for the prevalence of dental caries, severe gingival disease, and dental infection. Data on DMFT/dmft, DMFS/dmfs, plaque, and gingival indexes were also gathered. The level of evidence, recommendation, and guideline (if possible) were given for published preventive and management strategies. Results: Sixty-four published papers between 1990 and 2008 were reviewed. The weighted overall prevalence of dental caries was 28.1%. The overall DMFT for patients who were post-antineoplastic therapy was 9.19 (SD, 7.98; n=457). The overall plaque index for patients who were post­antineoplastic therapy was 1.38 (SD, 0.25; n=189). The GI for patients who were post-chemotherapy was 1.02 (SD, 0.15; n=162). The weighted prevalence of dental infections/ abscess during chemotherapy was reported in three studies and was 5.8%. Conclusions: Patients who were post-radiotherapy had the highest DMFT. The use of fluoride products and chlorhex­idine rinses are beneficial in patients who are post-radiotherapy. There continues to be lack of clinical studies on the extent and severity of dental disease that are associated with infectious complications during cancer therapy