Ian Wood

The completion of whole genome sequencing projects has provided the genetic instructions of life. However, whereas the identification of gene coding regions has progressed, the mapping of transcriptional regulatory motifs has moved more slowly. To understand how distinct expression profiles can be established and maintained, a greater understanding of these sequences and their trans-acting factors is required. Herein we have used a combined in silico and biochemical approach to identify binding sites [repressor element 1/neuron-restrictive silencer element (RE1/NRSE)] and potential target genes of RE1 silencing transcription factor/neuron-restrictive silencing factor (REST/NRSF) within the human, mouse, and Fugu rubripes genomes. We have used this genome-wide analysis to identify 1,892 human, 1,894 mouse, and 554 Fugu RE1/NRSEs and present their location and gene linkages in a searchable database. Furthermore, we identified an in vivo hierarchy in which distinct subsets of RE1/NRSEs interact with endogenous levels of REST/NRSF, whereas others function as bona fide transcriptional control elements only in the presence of elevated levels of REST/NRSF. These data show that individual RE1/NRSE sites interact differentially with REST/NRSF within a particular cell type. This combined bioinformatic and biochemical approach serves to illustrate the selective manner in which a transcription factor interacts with its potential binding sites and regulates target genes. In addition, this approach provides a unique whole-genome map for a given transcription factor-binding site implicated in establishing specific patterns of neuronal gene expression.

This book investigates the ways in which literacy was important in early mediaeval Europe, and examines the context of literacy, its uses, levels, and distribution, in a number of different early mediaeval societies between c. 400 and c. 1000. The studies, by leading scholars in the field, set out to provide the factual basis from which assessments of the significance of literacy in the early mediaeval world can be made, as well as analysing the significance of literacy, its implications, and its consequences for the societies in which we observe it. In all cases, the studies represent recent research and bring evidence such as the recent archaeological discoveries at San Vincenzo al Volturno to the subject. They provide fascinating insight into the attitudes of early mediaeval societies towards the written word and the degree to which these attitudes were formed. This period is shown as fundamental for the subsequent uses of literacy in mediaeval and modern Europe.

Modern Europe has been seen as having its origins in the Fall of the Roman Empire and the Barbarian Invasions of the fourth, fifth, and sixth centuries. As a result, the period has been drawn into a series of discourses that are more concerned with the eighteenth, nineteenth and twentieth centuries than with the distant past. During the Ancien Regime the Franks were discussed as providing a key to the social structure of the Age. During the Risorgimento the Lombards were thought to present a model of the oppression of Italy by occupying forces. The early Germanic peoples were also drawn in to debates about the frontiers of Germany at the time of Unification and of the First and Second World Wars. The early Church has been an inspiration for Christian revival. The historical writing about the Fall of Rome and the early Middle Ages has thus been influenced by social, political and religious debate concerned with modern European problems, but at the same time the history of the end of Antiquity and the early Middle Ages has had considerable influence on notions of class, race, religion, nation, and on Europe.

OBJECTIVE: To provide an update on glycaemic control in European patients with type 2 diabetes based on data from the nine-country, cross-sectional PANORAMA study (NCT00916513). DESIGN: Post-hoc analysis to report the number of patients achieving/not achieving glycaemic goal (HbA(1c) <7%). PATIENTS: Patients were randomly or consecutively selected from physician practices in nine countries. Eligible patients were aged ≥40 years, diagnosed with type 2 diabetes >1 year prior to study entry, and had an available medical record of >1 year. MEASUREMENTS: All data were collected at a single visit, including HbA1c measurement using a common device (A1CNow). Bivariate and multivariate analyses were used to investigate factors associated with not reaching glycaemic goal. RESULTS: Of 5817 patients enrolled (aged 65·9 ± 10·4 years, 53·7% male), 37·4% had an HbA(1c) ≥7%; (range 25·9% in The Netherlands to 52·0% in Turkey). In adjusted multivariate analyses, higher individual glycaemic target, younger age, poor physician-reported patient adherence to lifestyle/medication, longer diabetes duration, increasing treatment regimen complexity and physician-reported patient's unwillingness to intensify treatment were associated with not achieving goal. However, bivariate analyses also found gender, socioeconomic factors, body mass index, rate of complications and hypoglycaemia to be associated with not achieving goal. CONCLUSIONS: In PANORAMA, 37·4% of patients enrolled were not at glycaemic goal. Factors relating to patient characteristics, physician selection of individualized HbA1c target and diabetes itself (longer duration, more complex treatment) were strongly associated with not achieving goal. Further studies are warranted to explore these associations and evaluate strategies for improving glycaemic control.