Divergent heritages? UNESCO and the cultural heritage of landscapes in the UK and Japan

With climate change, many cultural landscapes will be lost or permanently altered. One approach to managing this is through international designation, through UNESCO, and the focus that it provides. National designations such as National Park status also offer a set of strategies for managing and adapting. This paper explores landscape designations in Japan and the UK focusing on the UNESCO World Heritage List. It is suggested that the UK’s dualistic governmental structures for landscapes prioritise some attributes over others. This is examined through the recent inscription of the Lake District as a World Heritage Property and counterpointed through looking at the recent Landscape Review also known as the Glover Report. A case study on a Japanese approach to landscape designation is explored to suggest alternative approaches. Both country’s relationship with international designation is discussed. Methodologies and theoretical approaches are examined with the conclusion that landscape change and loss are dealt with in Japan differently and arguably more effectively

Multi-organ spatial stratification of 3-D dose distributions improves risk prediction of long-term self-reported severe symptoms in oropharyngeal cancer patients receiving radiotherapy:development of a pre-treatment decision support tool

PURPOSE: Identify Oropharyngeal cancer (OPC) patients at high-risk of developing long-term severe radiation-associated symptoms using dose volume histograms for organs-at-risk, via unsupervised clustering.MATERIAL AND METHODS: All patients were treated using radiation therapy for OPC. Dose-volume histograms of organs-at-risk were extracted from patients' treatment plans. Symptom ratings were collected via the MD Anderson Symptom Inventory (MDASI) given weekly during, and 6 months post-treatment. Drymouth, trouble swallowing, mucus, and vocal dysfunction were selected for analysis in this study. Patient stratifications were obtained by applying Bayesian Mixture Models with three components to patient's dose histograms for relevant organs. The clusters with the highest total mean doses were translated into dose thresholds using rule mining. Patient stratifications were compared against Tumor staging information using multivariate likelihood ratio tests. Model performance for prediction of moderate/severe symptoms at 6 months was compared against normal tissue complication probability (NTCP) models using cross-validation.RESULTS: A total of 349 patients were included for long-term symptom prediction. High-risk clusters were significantly correlated with outcomes for severe late drymouth (p &lt;.0001, OR = 2.94), swallow (p = .002, OR = 5.13), mucus (p = .001, OR = 3.18), and voice (p = .009, OR = 8.99). Simplified clusters were also correlated with late severe symptoms for drymouth (p &lt;.001, OR = 2.77), swallow (p = .01, OR = 3.63), mucus (p = .01, OR = 2.37), and voice (p &lt;.001, OR = 19.75). Proposed cluster stratifications show better performance than NTCP models for severe drymouth (AUC.598 vs.559, MCC.143 vs.062), swallow (AUC.631 vs.561, MCC.20 vs -.030), mucus (AUC.596 vs.492, MCC.164 vs -.041), and voice (AUC.681 vs.555, MCC.181 vs -.019). Simplified dose thresholds also show better performance than baseline models for predicting late severe ratings for all symptoms.CONCLUSION: Our results show that leveraging the 3-D dose histograms from radiation therapy plan improves stratification of patients according to their risk of experiencing long-term severe radiation associated symptoms, beyond existing NTPC models. Our rule-based method can approximate our stratifications with minimal loss of accuracy and can proactively identify risk factors for radiation-associated toxicity.</p

Genome-wide association identifies ATOH7 as a major gene determining human optic disc size

Optic nerve assessment is important for many blinding diseases, with cup-to-disc ratio (CDR) assessments commonly used in both diagnosis and progression monitoring of glaucoma patients. Optic disc, cup, rim area and CDR measurements all show substantial variation between human populations and high heritability estimates within populations. To identify loci underlying these quantitative traits, we performed a genome-wide association study in two Australian twin cohorts and identified rs3858145, P = 6.2 × 10−10, near the ATOH7 gene as associated with the mean disc area. ATOH7 is known from studies in model organisms to play a key role in retinal ganglion cell formation. The association with rs3858145 was replicated in a cohort of UK twins, with a meta-analysis of the combined data yielding P = 3.4 × 10−10. Imputation further increased the evidence for association for several SNPs in and around ATOH7 (P = 1.3 × 10−10 to 4.3 × 10−11, top SNP rs1900004). The meta-analysis also provided suggestive evidence for association for the cup area at rs690037, P = 1.5 × 10−7, in the gene RFTN1. Direct sequencing of ATOH7 in 12 patients with optic nerve hypoplasia, one of the leading causes of blindness in children, revealed two novel non-synonymous mutations (Arg65Gly, Ala47Thr) which were not found in 90 unrelated controls (combined Fisher's exact P = 0.0136). Furthermore, the Arg65Gly variant was found to have very low frequency (0.00066) in an additional set of 672 controls

The Origins of King's Lynn? Control of Wealth on the Wash prior to the Norman Conquest

THIS PAPER investigates the archaeology and history of 'productive' sites, estate centres and towns between A.D. 600 and 1100 in north-western East Anglia. Whilst it concentrates on a specific sub-region (NW. Norfolk), an argument is developed on the nature of the relationship between archaeological assemblages and administrative structures that can be applied more widely for this period. In particular, the nature of 'productive' sites is discussed, and it is suggested that these places were centres of estate administration and tax collection. The later history of 'productive' sites in western Norfolk is then examined, focusing on the effect that the Viking wars and subsequent (short-lived) Danish rule may have had on them. How this background may have affected the decision by Herbert de Losinga (first Bishop of Norwich) to site a priory, port and new town at Lynn is then explore

Sutton Hoo and long-distance contacts

This article looks at the importance of long-distance connections between the English kingdoms and the eastern Mediterranean in the sixth to eighth centurie

PhD

dissertationThe central nervous system gives rise to an extraordinary number of different cell types. Understanding the process of cell fate specification whereby these cells are generated is a fundamental challenge for developmental biologists. I n particular, this dissertation is focused on deciphering the molecular mechanisms that lead to the generation of retinal ganglion cells and understanding how the basic helix-loop-helix (bHLH) transcription factor Xath5 influences this process. Towards this aim, we took two approaches. First, we investigated the mechanisms by which Xath5 influences retinal ganglion cell genesis. Specifically, the retinal ganglion cell specific POUhomeodomain transcription factor XBrn3d was identified, and it was shown that Xath5 can directly induce the expression of this factor. This suggests that Xath5 is able to bias cells to adopt the retinal ganglion cell fate in part by coupling to retinal ganglion cell specific factors. Second, we sought to identify the regulatory mechanisms that determine the spatial and temporal pattern of Xath5 expression in vivo. Us ing transgenic Xenopus laevis embryos to perform in vivo promoter analysis, two promoters were identified in the 5'genomic region of the Xath5a locus. Within the proximal promoter region, two highly conserved E-box binding sites were identified, which, in the context of this proximal promoter, are necessary for retinal expression of a transgene. This indicates that Xath5 expression is likely regulated in part by auto- or cross-regulation with other bHLH factors. Collectively, these results enhance our understanding of retinal ganglion cell genesis by placing Xath5 in a molecular context and contributing to our knowledge of the mechanisms by which Xath5 influences the retinal ganglion cell fate