Representativeness of samples from general practice lists in epidemiological studies: case-control study

Ethical constraints often prevent epidemiological studies from evaluating the impact of non-participation. Particular problems may arise when subjects fail to respond to an approach by researchers or when they cannot be contacted because of inaccurate contact details or a doctor's refusal to give permission for their patient to be approached. If these subjects differ from those subjects who agree or decline to participate then the validity and generalisability of the study may be compromised. We investigated these issues in a case-control study of acute leukaemia in England

Studies in the acridine series

In the Annual Reports on the Progress of Chemistry for 1918 under the heading "chromoisomerism" the following passage may be found: but it seems tine to protest against one halfpennyworth of practice to this intolerable deal of theory, and to demand something more than assertion in proof of the constitutional formulae which are drawn up so lavishly." It is fairly clear that the reviewer is referring principally to Hantzsch who originated the term "chromoisomeric" to describe compounds which exist in two or more solid modifications with distinctly different colours. Hantzsch (1) supposed that all such cases are to be explained in terms of isomerism and he proposed many structures.Hantzsch, however, was right in looking for an explanation and his reviewers were wrong where they dismissed the phenomena as being "merely polymorphism" (2). Polymorphism perhaps; but where, as in some cases, the colour change is pronounced - say from green to red - this is hardly a sufficient explanation.In the sequel the purely descriptive term polychromism will be used,in place of Hantzsch's "chromoisomerism'' to avoid the implication that isomerism is necessarily involved.We know that electronic absorption is not exclusively a function of molecular structure; it may be affected by the polar environment of the molecule and also by more specific intermolecular forces such as hydrogen bonding or charge transfer interaction. A crystal lattice may be regarded as a structure of intermolecular interactions; to change the lattice is to change these interactions and, in so far as some of these may influence light absorption, to change the colour.But the problem remains. If there is no difference in the structure or conformation of the molecules in Lifferent polychromic states then there must be a difference in one or other of those forms of intermolecular interaction which can have a significant effect on colour and it should be possible to specify which of these is involved.Most polychromic organic compounds for which no evident explanation in terms of isomerism exists, are either salts or aromatic nitro -compounds (usually polynitro-compounds and usually phenols or amines). The origin of polychromism in these cases has not been fully established, but it may well be that comparatively recent work on charge transfer phenomena will provide at least a partial answer. Charge transfer might be expected to occur in the solid state with both of these classes of compounds.It is well known that aromatic polynitro-compounds can form coloured molecular compounds with aromatic hydrocarbons, amines,phenols etc. The formation of such compounds has been attributed to charge transfer interaction between the components one of which must be a Lewis acid (e.g. a nitro - compound) and the other á Lewis base (e.g. an aromatic hydrocarbon or amine) (3 a - e).This type of interaction gives rise to a new absorption band, which has been called the charge transfer spectrum, in the visible or near ultra -violet regions. It appears to be due to the occurrence of electronic transitions between rather than within molecules. Charge transfer spectra are always broad and without fine structure. This is probably due (3a) to the weakness of the charge transfer bonding (2 - 4 K.cals. /mole (4)) allowing thermal vibration to provide a considerable range of displacements and orientations between the interacting groups. If the energy required for these intermolecular transitions does indeed depend upon the orientation of the interacting groups in the crystal - and this seems probable - then the colour of the solid will be a function of crystal structure. Thus where a compound, which shows charge transfer interaction in the solid, is polymorphic it will in general be polychromie.This charge transfer hypothesis for polychromism must be regarded as a more modern version of a theory put forward by Pfeiffer (8) as early as 1915 in terms of residual valency. He proposed that the orange and yellow forms of nitromethoxystilbenes result from the orientations A and B respectively in the solids.No work appears to have been done in order to decide whether charge transfer can occur in organic salts: its occurrence in inorganic salts appears to be very common. It is too early therefore to judge whether an extension of the charge transfer idea to cover the numerous cases of polychromism in organic salts is justifiable. A purely electrostatic theory has been proposed by Lucas and Kemp (9) to explain the polychromism of organic and inorganic salts. Their general conclusion is that the electronic absorption of an ion in a crystal lattice will depend on its electrostatic environment, created by the surrounding ions of opposite charge, and that this will depend on the crystal structure.Although at present it is not possible to decide which, if any, of these theories is true, one thing is clear: where a compound exists in more than one differently coloured solid form it is not possible to conclude directly from this that different molecular structures must be assigned to these forms. On the other hand a knowledge of the general classes of compounds which show polychromism and an appreciation of the factors which may influence light absorption in a crystal will help in deciding, in specific cases, whether it is worth looking for an explanation in terms of isomerism. For example if the compound in question is a salt or a polynitrocompound, or indeed if it is a betaine or contains both Lewis acid and Lewis base functions, any "isomeric" theory will be somewhat unconvincing. But the converse also is true.According to Kehrmann and Matusinsky (10) 2- hydroxy5- phenylacridine crystallises from hot benzene as fine yellow needles with a melting point of 264 °C. On crystallising slowly from cold benzene red prisms are obtained which may be converted to the yellow form by heating at 135 °C. The red modification is formed from the yellow slowly on standing and rapidly by crushing and powdering. From these observations it was concluded that the yellow is the form stable at higher temperatures and the red the lower temperature stable form.In view of the difference of more than 100 °C between the melting points of the two forms and in view of their strong difference in colour, Kehrmann suggested that this was a case of tautomerism between the structures.Neither argument is very convincing and the great ease with which the red modification can be formed from the yellow would seem to weigh heavily in favour of an explanation in terms of polymorphism. But if this example is considered in the context of polychromism in general and in the light of work carried out more recently by John (11) and by Albert and Short (12) on the tautomerism of analogous compounds, Kehrmann's theory becomes distinctly more probable.In the first place 2- hydroxy- 5- phenylacridine does not fall into any of the general classes of polychromic compounds: 8. this appears to be the only published example of a polychromic free acridine (although polychromism in acridine salts is very common). On the other hand John has studied a group of 2- hydroxy -phenazine derivatives.This compound exists in a yellow and a deep violet modification,these colours corresponding to the colours of the 0- Methyl and N- Methyl derivatives respectively. In solution 1:3:4 trimethyl- 2- hyäroxyphenazine is present as an equilibrium mixture of the structures(IIIa) and (IIIb). John concluded that the yellow and violet modifications were to be identified with (IIIa) and (IIIb) respectively. In this case however interconversion between the solids can only be brought about by recrystallising from solution or by heating to 135 °C at which temperature sublimation can be seen to occur.Albert and Short (12) have shown that 2- hydroxyacridine also is tautomeric (although not polychromic) existing in solution as an equilibrium mixture of lactim and lactam structures analogous to (I) and (II). Here the lactim structure is yellow and the lactam structure red.Kehrmann and P+iatusinsky's theory might now seem to be so reasonable as to be hardly worth questioning. But there remains one difficulty: the yellow crystals of 2- hydroxy- 5- phenylacridine can be converted to the red modification simply by rub-uing. If this is a tautomeric change it occurs with remarkable facility.It was therefore decided to investigate more thoroughly the colour changes of 2- hydroxy -5- phenylacridine

Progress report on the geology of 1:50k sheet 64W (Newtonmore)

This report describes the results of solid geology fieldwork in 1:50 000 sheet 64W (Newtonmore) resulting from the 2002 summer mapping season. A full revision of the solid geology at 1:10 000 scale was completed in the north-western part of the sheet (Sheet NN69SE) while rapid mapping/reconnaissance of the solid geology has been carried out in the remaining 85% of the sheet area The superficial geology of the sheet has been completely revised and will be described in a separate report. The north-western part of the sheet contains the transition from the deeper water graded sandy and silty turbidite deposits of the Corrieyairack Subgroup upwards (and south-eastwards) into the shallow water sand-dominated deposits of the Strathtummel Subgroup. East of the A9 trunk road, the Gaick region is confirmed as a single lithostratigraphical package in the Strathtummel Subgroup recording shallow water depositional conditions, greatly thickened by D2 recumbent folding. Axial surfaces of these folds dip gently east overall with gently east plunging to subhorizontal fold axes. Axial traces are generally N-S trending. The main regional (biotite) schistosity is axial planar to these folds and locally, can be seen clearly deforming an earlier bedding near-parallel biotite fabric. The available evidence for stratigraphical younging is limited to a few well-washed river sections but shows that regional facing is always to the south in S2 across the Gaick region. No large-scale F1 folds are recognised with the exception of those at Crubenmore on the A9. Minor undulations of the main regional fabric mean that the sheet dip varies between gently north to gently east across open upright north-east-plunging folds, in marked contrast to the conspicuous pattern of reclined, north-west verging D3 folds deforming the main regional (S2) schistosity in Glen Truim and farther north-west. There appear to be no other major fold sets across this part of the Gaick region The Drummochter Dome thus takes the form of a stack of recumbent D2 folds, modified by steep zones to the north-west (Geal CharnOssian Steep Belt) and south-east (Tummel Steep belt and correlatives). The pattern of early recumbent folds and later steep belts is similar to that seen in the higher structural levels south of the Boundary Slide which include the Tay Nappe

Self-replication and evolution of DNA crystals

Is it possible to create a simple physical system that is capable of replicating itself? Can such a system evolve interesting behaviors, thus allowing it to adapt to a wide range of environments? This paper presents a design for such a replicator constructed exclusively from synthetic DNA. The basis for the replicator is crystal growth: information is stored in the spatial arrangement of monomers and copied from layer to layer by templating. Replication is achieved by fragmentation of crystals, which produces new crystals that carry the same information. Crystal replication avoids intrinsic problems associated with template-directed mechanisms for replication of one-dimensional polymers. A key innovation of our work is that by using programmable DNA tiles as the crystal monomers, we can design crystal growth processes that apply interesting selective pressures to the evolving sequences. While evolution requires that copying occur with high accuracy, we show how to adapt error-correction techniques from algorithmic self-assembly to lower the replication error rate as much as is required

Temporal variations in English Populations of a forest insect pest, the green spruce aphid (Elatobium abietinum), associated with the North Atlantic Oscillation and global warming

Based on an exceptionally long modern ecological dataset (41 years), it has been possible to show that warm weather in England associated with a positive North Atlantic Oscillation (NAO) index causes the spring migration of the green spruce aphid (Elatobium abietinum), a pest species of spruce trees (Picea) to start earlier, continue for longer and contain more aphids. An upward trend in the NAO index during the period 1966-2006 is associated with an increasing population size of E. abietinum. It is important to understand the mechanisms behind the population fluctuations, because this aphid causes considerable damage to Picea plantations. Present day weather associated fluctuations in forest insect pests may be useful analogues in understanding past pest outbreaks in forests

Intellectual functioning in clinically confirmed fetal valproate syndrome

Background: An increased risk of impaired intelligence (IQ) has been documented in valproate-exposed children, but investigations have not previously focused on those with a clinical diagnosis of Fetal Valproate Syndrome (FVS). Methods: This cross sectional observational study recruited individuals with a diagnosis of FVS and completed standardized assessments of intellectual abilities making comparisons to a normative comparison group. Both mean difference (MD) and prevalence of scores below the lower average range were analyzed. Results: The mean full-scale IQ in 31 individuals with FVS (mean age 14.97; range 6–27 years) was 19 points lower (19.55, 95% CI −24.94 to 14.15), and IQ scores <70 were present in 26%. The mean differences for verbal comprehension (21.07, 95% CI −25.84 to −16.29), working memory (19.77, 95% CI −25.00 to −14.55) and processing speed (16.87, 95% CI −22.24 to −11.50) performances were poorer than expected with the mean differences over one standard deviation from the comparison group. Sixty one percent of cases demonstrated disproportionately lower verbal comprehension ability. There were no significant group differences for IQ in high vs. moderate dose valproate or mono vs. polytherapy. There were no differences in IQ between those with and those without a major congenital malformation. The requirement for educational intervention was high at 74%. Conclusion: Intellectual difficulties are a central feature of FVS and are more severe in their presentation in individuals with a diagnosis of valproate embryopathy. Individuals with FVS who present with the characteristic facial presentation should be considered at high risk of cognitive difficulties regardless of the dose of valproate exposure or the presence of a major congenital malformation

Electron Spin Injection at a Schottky Contact

We investigate theoretically electrical spin injection at a Schottky contact between a spin-polarized electrode and a non-magnetic semiconductor. Current and electron density spin-polarizations are discussed as functions of barrier energy and semiconductor doping density. The effect of a spin-dependent interface resistance that results from a tunneling region at the contact/semiconductor interface is described. The model can serve as a guide for designing spin-injection experiments with regard to the interface properties and device structure.Comment: 4 pages, 4 figure

High-Energy Aspects of Solar Flares: Overview of the Volume

In this introductory chapter, we provide a brief summary of the successes and remaining challenges in understanding the solar flare phenomenon and its attendant implications for particle acceleration mechanisms in astrophysical plasmas. We also provide a brief overview of the contents of the other chapters in this volume, with particular reference to the well-observed flare of 2002 July 23Comment: This is the introductory article for a monograph on the physics of solar flares, inspired by RHESSI observations. The individual articles are to appear in Space Science Reviews (2011

The geochemistry of sea-bed sediments of the United Kingdom Continental Shelf : the North Sea, Hebrides and West Shetland shelves, and the Malin-Hebrides sea area

The sea area around the United Kingdom is used for a wide range of human activities all of which have a significant impact on the marine environment. The naturally-occurring concentrations of chemical elements in sea-bed sediments may be enhanced by contaminants introduced by input from rivers and the atmosphere and by more localised sources arising from shipping operations, exploitation of oil and gas, and by direct discharges from drainage systems, sewage outfalls, effluents from industry and waste' disposal at sea. It is therefore important to identify components of sea-floor sediments which are due to the rocks or older sediments from which they are derived, and those which are introduced into the environment. This report presents regional geochemical data for a variety of sediment types occurring in a wide range of environments. Samples have been collected offshore of the eastern coast of the UK where major river systems which drain heavily populated and industrialised catchment areas, such as the Thames, Humber and Tyne, flow into the North Sea, and on the shelf west of Scotland where man's activities have had much less impact. The data presented here provide a baseline for chemical element concentrations in sea-bed sediments against which future work may be assessed. It should therefore be of significance to a diverse range of interests including pollution control, fishing, natural resources, nature conservation, shipping, tourism, recreation, and waste disposal management. In addition the information will be of use to geologists in identifying the source of sea-bed sediments and the underlying glacial deposits