Getting to Know Harlan: A New Approach to Judicial Biography? Book Review: The Republic According to John Marshall Harlan. by Linda Przybyszewski

Book review: The Republic According to John Marshall Harlan. By Linda Przybyszewski. University of North Carolina Press. 1999. Pp. xii, 286. Reviewed by: James A. Thomso

Prologue to Power: Selecting Supreme Court Justices

Review of God Save This Honorable Court: How the Choice of Supreme Court Justices Shapes Our History, by Laurence A. Tribe (Random House, 1985)

A community approach to road safety education using practical training methods : the Drumchapel project

Research shows that practical training methods, in which children receive guided experience of solving traffic problems in realistic traffic situations, are amongst the most effective in improving children's pedestrian competence. However, practical training is both time consuming and labour intensive, making it difficult to capitalise on the strengths of the method. The report describes a solution to this problem by adopting a community participation approach in which local volunteers carried out all roadside training, working in co-operation with schools and project staff. The project took place in an area of Glasgow known for its exceptionally high child pedestrian accident rate

Children's perception of safety and danger on the road

This study investigates the ability of children between 5 and 11 years to select safe places to cross the street. The children were presented with situations which were either extremely safe or manifestly dangerous and were asked to correctly identify these. In other cases, they were asked to choose for themselves routes across the road which they thought would be safe. The tasks were presented in various ways: by means of a table-top simulation on which traffic scenarios had been contrived; by means of photographs of road situations; and by taking the children to real-world sites in the streets near their schools. All the experiments showed a similar pattern of results. Five- and 7-year olds exhibited very poor skill in identifying dangerous road-crossing sites. Their judgements relied exclusively on the visible presence of cars in the vicinity. Other factors such as blind summits, obscuring obstacles or complex junctions were never recognized as threatening situations. They also showed an unwillingness to make detours when planning their own routes, even where the direct route was manifestly dangerous. Nine-year-olds showed a higher level of ability and 11-year -olds showed quite good skill in these judgements. No sex differences were apparent. These results suggest that young children up to about 9 years must often be at considerable risk as they do not have the ability to recognize a location as dangerous, even if they know the mechanics of the Green Cross Code. The implications for road safety education are discussed

The influence of MRI scan position on patients with oropharyngeal cancer undergoing radical radiotherapy

<p>Background: The purpose of this study was to demonstrate how magnetic resonance imaging (MRI) patient position protocols influence registration quality in patients with oropharyngeal cancer undergoing radical radiotherapy and the consequences for gross tumour volume (GTV) definition and radiotherapy planning.</p> <p>Methods and materials: Twenty-two oropharyngeal patients underwent a computed tomography (CT), a diagnostic MRI (MRID) and an MRI in the radiotherapy position within an immobilization mask (MRIRT). Clinicians delineated the GTV on the CT viewing the MRID separately (GTVC); on the CT registered to MRID (GTVD) and on the CT registered to MRIRT (GTVRT). Planning target volumes (PTVs) were denoted similarly. Registration quality was assessed by measuring disparity between structures in the three set-ups. Volumetric modulated arc therapy (VMAT) radiotherapy planning was performed for PTVC, PTVD and PTVRT. To determine the dose received by the reference PTVRT, we optimized for PTVC and PTVD while calculating the dose to PTVRT. Statistical significance was determined using the two-tailed Mann–Whitney or two-tailed paired student t-tests.</p> <p>Results: A significant improvement in registration accuracy was found between CT and MRIRT versus the MRID measuring distances from the centre of structures (geometric mean error of 2.2 mm versus 6.6 mm). The mean GTVC (44.1 cm3) was significantly larger than GTVD (33.7 cm3, p value = 0.027) or GTVRT (30.5 cm3, p value = 0.014). When optimizing the VMAT plans for PTVC and investigating the mean dose to PTVRT neither the dose to 99% (58.8%) nor 95% of the PTV (84.7%) were found to meet the required clinical dose constraints of 90% and 95% respectively. Similarly, when optimizing for PTVD the mean dose to PTVRT did not meet clinical dose constraints for 99% (14.9%) nor 95% of the PTV (66.2%). Only by optimizing for PTVRT were all clinical dose constraints achieved.</p> <p>Conclusions: When oropharyngeal patients MRI scans are performed in the radiotherapy position there are significant improvements in CT-MR image registration, target definition and PTV dose coverage.</p&gt

Developing safe route planing strategies in young child pedestrians

This paper identifies deficiencies in young children's route planning strategies in traffic contexts and reviews intervention programs relating to this ability. Evidence concerning age-related changes shows that only a small proportion of children aged 5 years are able to construct safe routes to a destination, with the proportion increasing steadily through the middle childhood years. Intervention programs utilizing pre-test/post-test comparisons and no-treatment controls show that 5-year-olds' abilities can be improved dramatically. Longer term stability of such improvements is also assessed. Intervention programs tailored for use with groups of young children and for use by parents from socio-economically deprived areas of Glasgow, Scotland, are also evaluated

Study of diffusion weighted MRI as a predictive biomarker of response during radiotherapy for high and intermediate risk squamous cell cancer of the oropharynx: The MeRInO study

Introduction and background: A significant proportion of patients with intermediate and high risk squamous cell cancer of the oropharynx (OPSCC) continue to relapse locally despite radical chemoradiotherapy (CRT). The toxicity of the current combination of intensified dose per fraction radiotherapy and platinum based chemotherapy limits further uniform intensification. If a predictive biomarker for outcomes from CRT can be identified during treatment then individualised and adaptive treatment strategies may be employed. Methods/design: The MeRInO study is a prospective observational imaging study of patients with intermediate and high risk, locally advanced OPSCC receiving radical RT or concurrent CRT Patients undergo diffusion weighted MRI prior to treatment (MRI_1) and during the third week of RT (MRI_2). Apparent diffusion coefficient (ADC) measurements will be made on each scan for previously specified target lesions (primary and lymph nodes) and change in ADC calculated. Patients will be followed up and disease status for each target lesion noted. The primary aim of the MeRInO study is to determine the threshold change in ADC from baseline to week 3 of RT that may identify the sub-group of non-responders during treatment. Discussion: The use of DW-MRI as a predictive biomarker during RT for SCC H&N is in its infancy but studies to date have found that response to treatment may indeed be predicted by comparison of DW-MRI carried out before and during treatment. However, previous studies have included all sub-sites and biological sub-types. Establishing ADC thresholds that predict for local failure is an essential step towards using DW-MRI to improve the therapeutic ratio in treating SCC H&N. This would be done most robustly in a specific H&N sub-site and in sub-types with similar biological behaviour. The MeRInO study will help establish these thresholds in OPSCC

Vascular changes in diabetic retinopathy-a longitudinal study in the Nile rat.

Diabetic retinopathy is the most common microvascular complication of diabetes and is a major cause of blindness, but an understanding of the pathogenesis of the disease has been hampered by a lack of accurate animal models. Here, we explore the dynamics of retinal cellular changes in the Nile rat (Arvicanthis niloticus), a carbohydrate-sensitive model for type 2 diabetes. The early retinal changes in diabetic Nile rats included increased acellular capillaries and loss of pericytes that correlated linearly with the duration of diabetes. These vascular changes occurred in the presence of microglial infiltration but in the absence of retinal ganglion cell loss. After a prolonged duration of diabetes, the Nile rat also exhibits a spectrum of retinal lesions commonly seen in the human condition including vascular leakage, capillary non-perfusion, and neovascularization. Our longitudinal study documents a range and progression of retinal lesions in the diabetic Nile rat remarkably similar to those observed in human diabetic retinopathy, and suggests that this model will be valuable in identifying new therapeutic strategies

DNA methylation affects nuclear organization, histone modifications, and linker histone binding but not chromatin compaction

DNA methylation has been implicated in chromatin condensation and nuclear organization, especially at sites of constitutive heterochromatin. How this is mediated has not been clear. In this study, using mutant mouse embryonic stem cells completely lacking in DNA methylation, we show that DNA methylation affects nuclear organization and nucleosome structure but not chromatin compaction. In the absence of DNA methylation, there is increased nuclear clustering of pericentric heterochromatin and extensive changes in primary chromatin structure. Global levels of histone H3 methylation and acetylation are altered, and there is a decrease in the mobility of linker histones. However, the compaction of both bulk chromatin and heterochromatin, as assayed by nuclease digestion and sucrose gradient sedimentation, is unaltered by the loss of DNA methylation. This study shows how the complete loss of a major epigenetic mark can have an impact on unexpected levels of chromatin structure and nuclear organization and provides evidence for a novel link between DNA methylation and linker histones in the regulation of chromatin structure