Typography for children with reading difficulties: preferences for type in reading books

For children with developmental dyslexia the already challenging task of learning to read is made harder by difficulties with phonological processing and perceptual distortions. As a result, these children may be less motivated to practise their literacy skills. This is problematic in that literacy can only be gained through constant and continued exposure to reading scenarios, and children who are unmotivated to practise are unlikely to develop into fluent readers. Children are active in choosing the books they read and it is therefore important to understand how the typography in those books influences their choice. Research with typically developing children has shown that they have clear opinions about the typography in their reading materials and that these opinions are likely to influence their motivation to read particular books. However, it cannot be assumed that children with reading difficulties read and respond to texts in the same way as children who do not struggle. Through case-studies of three children with reading difficulties, preferences for the typography in their reading books is examined. Looking at elements of typesetting such as spacing and size shows that this group of children is aware of differences in typography and that they have preferences for how their reading books are typeset. These children showed a preference for books that resembled those that their peers are reading rather than those that would, by typographic convention, be considered easier to read. This study is part of ongoing research into the development of alternative materials for teaching literacy skills to children with dyslexia.

A practical approach to a multi-level analysis with a sparse binary outcome within a large surgical trial

Objectives: To assess the potential source of variation that surgeon may add to patient outcome in a clinical trial of surgical procedures. Methods: Two large (n = 1380) parallel multicentre randomized surgical trials were undertaken to compare laparoscopically assisted hysterectomy with conventional methods of abdominal and vaginal hysterectomy; involving 43 surgeons. The primary end point of the trial was the occurrence of at least one major complication. Patients were nested within surgeons giving the data set a hierarchical structure. A total of 10% of patients had at least one major complication, that is, a sparse binary outcome variable. A linear mixed logistic regression model (with logit link function) was used to model the probability of a major complication, with surgeon fitted as a random effect. Models were fitted using the method of maximum likelihood in SAS((R)). Results: There were many convergence problems. These were resolved using a variety of approaches including; treating all effects as fixed for the initial model building; modelling the variance of a parameter on a logarithmic scale and centring of continuous covariates. The initial model building process indicated no significant 'type of operation' across surgeon interaction effect in either trial, the 'type of operation' term was highly significant in the abdominal trial, and the 'surgeon' term was not significant in either trial. Conclusions: The analysis did not find a surgeon effect but it is difficult to conclude that there was not a difference between surgeons. The statistical test may have lacked sufficient power, the variance estimates were small with large standard errors, indicating that the precision of the variance estimates may be questionable.

Control of human immunodeficiency virus type-1 protease activity in insect cells expressing Gag-Pol rescues assembly of immature but not mature virus-like particles

Expression of human immunodeficiency virus type 1 (HIV-1) Gag protein in insect cells using baculovirus vectors leads to the abundant production of virus-like particles (VLPs) that represent the immature form of the virus. When Gag-Pol is included, however, VLP production is abolished, a result attributed to premature protease activation degrading the intracellular pool of Gag precursor before particle assembly can occur. As large-scale synthesis of mature noninfectious VLPs would be useful, we have sought to control HIV protease activity in insect cells to give a balance of Gag and Gag-Pol that is compatible with mature particle formation. We show here that intermediate levels of protease activity in insect cells can be attained through site-directed mutagenesis of the protease and through antiprotease drug treatment. However, despite Gag cleavage patterns that mimicked those seen in mammalian cells, VLP synthesis exhibited an essentially all-or-none response in which VLP synthesis occurred but was immature or failed completely. Our data are consistent with a requirement for specific cellular factors in addition to the correct ratio of Gag and Gag-Pol for assembly of mature retrovirus particles in heterologous cell types. (C) 2003 Elsevier Science (USA). All rights reserved.

Development of novel brush-type chiral stationary phases based on terpenoid selectors: HPLC evaluation and theoretical investigation of enantioselective binding interactions

The terpenoid chiral selectors dehydroabietic acid, 12,14-dinitrodehydroabietic acid and friedelin have been covalently linked to silica gel yielding three chiral stationary phases CSP 1, CSP 2 and CSP 3, respectively. The enantiodiscriminating capability of each one of these phases was evaluated by HPLC with four families of chiral aromatic compounds composed of alcohols, amines, phenylalanine and tryptophan amino acid derivatives and beta-lactams. The CSP 3 phase, containing a selector with a large friedelane backbone is particularly suitable for resolving free alcohols and their derivatives bearing fluorine substituents, while CSP 2 with a dehydroabietic architecture is the only phase that efficiently discriminates 1, 1'-binaphthol atropisomers. CSP 3 also gives efficient resolution of the free amines. All three phases resolve well the racemates of N-trifluoracetyl and N-3,5-dinitrobenzoyl phenylalanine amino acid ester derivatives. Good enantioseparation of beta-lactams and N-benzoyl tryptophan amino acid derivatives was achieved on CSP 1. In order to understand the structural factors that govern the chiral molecular recognition ability of these phases, molecular dynamics simulations were carried out in the gas phase with binary diastereomeric complexes formed by the selectors of CSP 1 and CSP 2 and several amino acid derivatives. Decomposition of molecular mechanics energies shows that van der Waals interactions dominate the formation of the diastereomeric transient complexes while the electrostatic binding interactions are primarily responsible for the enantioselective binding of the (R)- and (S)-analytes. Analysis of the hydrogen bonds shows that electrostatic interactions are mainly associated with the formation of N-(HO)-O-...=C enantio selective hydrogen bonds between the amide binding sites from the selectors and the carbonyl groups of the analytes. The role of mobile phase polarity, a mixture of n-hexane and propan-2-ol in different ratios, was also evaluated through molecular dynamics simulations in explicit solvent. (c) 2006 Elsevier Ltd. All rights reserved.

Effects of resistant starch type III polymorphs on human colon microbiota and short chain fatty acids in human gut models

This study probed the possible effects of type III resistant starch (RS) crystalline polymorphism on RS fermentability by human gut microbiota and the short chain fatty acids production in vitro. Human fecal pH-controlled batch cultures showed RS induces an ecological shift in the colonic microbiota with polymorph B inducing Bifidobacterium spp. and polymorph A inducing Atopobium spp. Interestingly, polymorph B also induced higher butyrate production to levels of 0.79 mM. In addition, human gut simulation demonstrated that polymorph B promotes the growth of bifidobacteria in the proximal part of the colon and double their relative proportion in the microbiota in the distal colon. These findings suggest that RS polymorph B may promote large bowel health. While the findings are limited by study constraints, they do raise the possibility of using different thermal processing to delineate differences in the prebiotic capabilities of RS, especially its butryrogenicity in the human colon.

The printed page

In the year 1702 two books were published, in Oxford and Paris, that can now be seen as defining the presses that produced them. In Paris, the Imprimerie Royale issued the Médailles sur les principaux évènements du règne de Louis le Grand, a large folio of text and plates intended to glorify the regime of Louis XIV. In Oxford, the first, large format volume of Clarendon’s The history of the rebellion appeared; painstakingly edited at Christ Church, it brought prestige and profit to the University. Both were considerable statements of publishing intent in graphic form: both were sumptuous, and both used types and decorations reserved to their respective presses. But the French book points the way to future developments in typography, particularly in the design of type, while the Oxford book is a summation of the past, and its types and page design would be abandoned by the Oxford press in little more than thirty years. Tracing the printed pages of Oxford books from the late sixteenth to the mid-eighteenth century shows changes that parallel wider developments in English and European typography, but from a distinctly Oxford perspective.

Wind-direction effects on urban-type flows

Practically all extant work on flows over obstacle arrays, whether laboratory experiments or numerical modelling, is for cases where the oncoming wind is normal to salient faces of the obstacles. In the field, however, this is rarely the case. Here, simulations of flows at various directions over arrays of cubes representing typical urban canopy regions are presented and discussed. The computations are of both direct numerical simulation and large-eddy simulation type. Attention is concentrated on the differences in the mean flow within the canopy region arising from the different wind directions and the consequent effects on global properties such as the total surface drag, which can change very significantly—by up to a factor of three in some circumstances. It is shown that for a given Reynolds number the typical viscous forces are generally a rather larger fraction of the pressure forces (principally the drag) for non-normal than for normal wind directions and that, dependent on the surface morphology, the average flow direction deep within the canopy can be largely independent of the oncoming wind direction. Even for regular arrays of regular obstacles, a wind direction not normal to the obstacle faces can in general generate a lateral lift force (in the direction normal to the oncoming flow). The results demonstrate this and it is shown how computations in a finite domain with the oncoming flow generated by an appropriate forcing term (e.g. a pressure gradient) then lead inevitably to an oncoming wind direction aloft that is not aligned with the forcing term vector.

Expression of type 1 fimbriae (SEF 21) of Salmonella enterica serotype Enteritidis in the early colonisation of the rat intestine

The involvement of type 1 fimbriae in colonisation of the rat gastrointestinal tract in vivo was investigated with Salmonella enterica serotype Enteritidis LA5 and a mutant of LA5 denoted EAV3 unable to elaborate type 1 fimbriae (SEF 21), Rats were given a single dose of LA5 or EAV3 or a 1:1 mixture of both, LA5 was found in higher numbers in the stomach and small intestine than EAV3 at 6 h after infection with a single strain, but not after 6 days, LA5 did not out-compete EAV3 when the strains were administered together. Indeed, after 6 and 21 days, EAV3 was found in the distal small intestine and large intestine in far higher numbers than LA5. These findings suggest that SEF 21 have an important role(s) in the early stages of infection in vivo, However, SEF 21 expression may disadvantage the pathogen in the longer term as indicated by EAV3 out-competing LA5 in the gut at 21 days.

A ‘Boscastle-type’ quasi-stationary convective system over the UK Southwest Peninsula

An investigation is presented of a quasi-stationary convective system (QSCS) which occurred over the UK Southwest Peninsula on 21 July 2010. This system was remarkably similar in its location and structure to one which caused devastating flash flooding in the coastal village of Boscastle, Cornwall on 16 August 2004. However, in the 2010 case rainfall accumulations were around four times smaller and no flooding was recorded. The more extreme nature of the Boscastle case is shown to be related to three factors: (1) higher rain rates, associated with a warmer and moister tropospheric column and deeper convective clouds; (2) a more stationary system, due to slower evolution of the large-scale flow; and (3) distribution of the heaviest precipitation over fewer river catchments. Overall, however, the synoptic setting of the two events was broadly similar, suggesting that such conditions favour the development of QSCSs over the Southwest Peninsula. A numerical simulation of the July 2010 event was performed using a 1.5-km grid length configuration of the Met Office Unified Model. This reveals that convection was repeatedly initiated through lifting of low-level air parcels along a quasi-stationary coastal convergence line. Sensitivity tests are used to show that this convergence line was a sea breeze front which temporarily stalled along the coastline due to the retarding influence of an offshore-directed background wind component. Several deficiencies are noted in the 1.5-km model’s representation of the storm system, including delayed convective initiation; however, significant improvements are observed when the grid length is reduced to 500 m. These result in part from an improved representation of the convergence line, which enhances the associated low-level ascent allowing air parcels to more readily reach their level of free convection. The implications of this finding for forecasting convective precipitation are discussed.

Large-scale surface mass balance of ice sheets from a comprehensive atmospheric model

The surface mass balance for Greenland and Antarctica has been calculated using model data from an AMIP-type experiment for the period 1979–2001 using the ECHAM5 spectral transform model at different triangular truncations. There is a significant reduction in the calculated ablation for the highest model resolution, T319 with an equivalent grid distance of ca 40 km. As a consequence the T319 model has a positive surface mass balance for both ice sheets during the period. For Greenland, the models at lower resolution, T106 and T63, on the other hand, have a much stronger ablation leading to a negative surface mass balance. Calculations have also been undertaken for a climate change experiment using the IPCC scenario A1B, with a T213 resolution (corresponding to a grid distance of some 60 km) and comparing two 30-year periods from the end of the twentieth century and the end of the twenty-first century, respectively. For Greenland there is change of 495 km3/year, going from a positive to a negative surface mass balance corresponding to a sea level rise of 1.4 mm/year. For Antarctica there is an increase in the positive surface mass balance of 285 km3/year corresponding to a sea level fall by 0.8 mm/year. The surface mass balance changes of the two ice sheets lead to a sea level rise of 7 cm at the end of this century compared to end of the twentieth century. Other possible mass losses such as due to changes in the calving of icebergs are not considered. It appears that such changes must increase significantly, and several times more than the surface mass balance changes, if the ice sheets are to make a major contribution to sea level rise this century. The model calculations indicate large inter-annual variations in all relevant parameters making it impossible to identify robust trends from the examined periods at the end of the twentieth century. The calculated inter-annual variations are similar in magnitude to observations. The 30-year trend in SMB at the end of the twenty-first century is significant. The increase in precipitation on the ice sheets follows closely the Clausius-Clapeyron relation and is the main reason for the increase in the surface mass balance of Antarctica. On Greenland precipitation in the form of snow is gradually starting to decrease and cannot compensate for the increase in ablation. Another factor is the proportionally higher temperature increase on Greenland leading to a larger ablation. It follows that a modest increase in temperature will not be sufficient to compensate for the increase in accumulation, but this will change when temperature increases go beyond any critical limit. Calculations show that such a limit for Greenland might well be passed during this century. For Antarctica this will take much longer and probably well into following centuries.

Simulation of hurricane-type vortices in a general circulation model

A study of intense hurricane-type vortices in the ECMWF operational model is reported. These vortices develop around day 4 in the forecast and occur in the tropical belt in areas and at times where intense tropical cyclones normally occur. The frequency resembles that observed over most tropical regions with a pronounced maximum in the western North Pacific. The life time of the vortices and their 3-dimensional structure agree in some fundamental way with observations although, because of the resolution, the systems are less intense than the observed ones. The general large-scale conditions for active and inactive cyclone periods are discussed. The model cyclones are sensitive to the sea-surface temperature and do not develop with sea surface temperatures lower than 28–29°C. The dynamical conditions favouring cyclone development are characterized by intense large-scale divergence in the upper troposphere. Cyclogenesis appears to take place when these conditions are found outside the equatorial zone and over oceans where the water is sufficiently warm.

Spectral gap for Glauber type dynamics for a special class of potentials

We consider an equilibrium birth and death type process for a particle system in infinite volume, the latter is described by the space of all locally finite point configurations on Rd. These Glauber type dynamics are Markov processes constructed for pre-given reversible measures. A representation for the ``carré du champ'' and ``second carré du champ'' for the associate infinitesimal generators L are calculated in infinite volume and for a large class of functions in a generalized sense. The corresponding coercivity identity is derived and explicit sufficient conditions for the appearance and bounds for the size of the spectral gap of L are given. These techniques are applied to Glauber dynamics associated to Gibbs measure and conditions are derived extending all previous known results and, in particular, potentials with negative parts can now be treated. The high temperature regime is extended essentially and potentials with non-trivial negative part can be included. Furthermore, a special class of potentials is defined for which the size of the spectral gap is as least as large as for the free system and, surprisingly, the spectral gap is independent of the activity. This type of potentials should not show any phase transition for a given temperature at any activity.

A Wiener-Hopf type factorization for the exponential functional of Levy processes

For a Lévy process ξ=(ξt)t≥0 drifting to −∞, we define the so-called exponential functional as follows: Formula Under mild conditions on ξ, we show that the following factorization of exponential functionals: Formula holds, where × stands for the product of independent random variables, H− is the descending ladder height process of ξ and Y is a spectrally positive Lévy process with a negative mean constructed from its ascending ladder height process. As a by-product, we generate an integral or power series representation for the law of Iξ for a large class of Lévy processes with two-sided jumps and also derive some new distributional properties. The proof of our main result relies on a fine Markovian study of a class of generalized Ornstein–Uhlenbeck processes, which is itself of independent interest. We use and refine an alternative approach of studying the stationary measure of a Markov process which avoids some technicalities and difficulties that appear in the classical method of employing the generator of the dual Markov process.

Progress in the genetics of common obesity and type 2 diabetes

The prevalence of obesity and diabetes, which are heritable traits that arise from the interactions of multiple genes and lifestyle factors, continues to rise worldwide, causing serious health problems and imposing a substantial economic burden on societies. For the past 15 years, candidate gene and genome-wide linkage studies have been the main genetic epidemiological approaches to identify genetic loci for obesity and diabetes, yet progress has been slow and success limited. The genome-wide association approach, which has become available in recent years, has dramatically changed the pace of gene discoveries. Genome-wide association is a hypothesis-generating approach that aims to identify new loci associated with the disease or trait of interest. So far, three waves of large-scale genome-wide association studies have identified 19 loci for common obesity and 18 for common type 2 diabetes. Although the combined contribution of these loci to the variation in obesity and diabetes risk is small and their predictive value is typically low, these recently identified loci are set to substantially improve our insights into the pathophysiology of obesity and diabetes. This will require integration of genetic epidemiological methods with functional genomics and proteomics. However, the use of these novel insights for genetic screening and personalised treatment lies some way off in the future.

Activation of glycoprotein VI (GPVI) and C-type lectin-like receptor-2 (CLEC-2) underlies platelet activation by diesel exhaust particles and other charged/hydrophobic ligands

Platelets are activated by a range of stimuli that share little or no resemblance in structure to each other or to recognized ligands, including diesel exhaust particles (DEP), small peptides [4N1-1, Champs (computed helical anti-membrane proteins), LSARLAF (Leu-Ser-Ala-Arg-Leu-Ala-Phe)], proteins (histones) and large polysaccharides (fucoidan, dextran sulfate). This miscellaneous group stimulate aggregation of human and mouse platelets through the glycoprotein VI (GPVI)-FcR γ-chain complex and/or C-type lectin-like receptor-2 (CLEC-2) as shown using platelets from mice deficient in either or both of these receptors. In addition, all of these ligands stimulate tyrosine phosphorylation in GPVI/CLEC-2-double-deficient platelets, indicating that they bind to additional surface receptors, although only in the case of dextran sulfate does this lead to activation. DEP, fucoidan and dextran sulfate, but not the other agonists, activate GPVI and CLEC-2 in transfected cell lines as shown using a sensitive reporter assay confirming a direct interaction with the two receptors. We conclude that this miscellaneous group of ligands bind to multiple proteins on the cell surface including GPVI and/or CLEC-2, inducing activation. These results have pathophysiological significance in a variety of conditions that involve exposure to activating charged/hydrophobic agents.