In this article, 3 views of the relation between various forms of phonological awareness (detection of rhyme and alliteration and detection of phonemes) and children's reading were tested. These are (a) that the experience of learning to read leads to phoneme awareness and that neither of these is connected to awareness of rhyme, (b) that sensitivity to rhyme leads to awareness of phonemes, which in turn affects reading, and (c) that rhyme makes a direct contribution to reading that is independent of the connection between reading and phoneme awareness. The results from a longitudinal study that monitored the phonological awareness and progress in reading and spelling of 65 children from the ages of 4 years 7 months to 6 years 7 months produced strong support for a combination of the 2nd and 3rd models and none at all for the 1 st model. This research was supported by a grant from the Medical Research Council.We are grateful for the help of Terezinha Carraher who read and commented on an earlier version of the article. We would like to thank the teachers and staff of local primary and first schools for letting us visit the children in our project at school.

Methylglyoxal is a toxic electrophile. In Escherichia coli cells, the principal route of methylglyoxal production is from dihydroxyacetone phosphate by the action of methylglyoxal synthase. The toxicity of methylglyoxal is believed to be due to its ability to interact with the nucleophilic centres of macromolecules such as DNA. Bacteria possess an array of detoxification pathways for methylglyoxal. In E. coli, glutathione-based detoxification is central to survival of exposure to methylglyoxal. The glutathione-dependent glyoxalase I-II pathway is the primary route of methylglyoxal detoxification, and the glutathione conjugates formed can activate the KefB and KefC potassium channels. The activation of these channels leads to a lowering of the intracellular pH of the bacterial cell, which protects against the toxic effects of electrophiles. In addition to the KefB and KefC systems, E. coli cells are equipped with a number of independent protective mechanisms whose purpose appears to be directed at ensuring the integrity of the DNA. A model of how these protective mechanisms function will be presented. The production of methylglyoxal by cells is a paradox that can be resolved by assigning an important role in adaptation to conditions of nutrient imbalance. Analysis of a methylglyoxal synthase-deficient mutant provides evidence that methylglyoxal production is required to allow growth under certain environmental conditions. The production of methylglyoxal may represent a high-risk strategy that facilitates adaptation, but which on failure leads to cell death. New strategies for antibacterial therapy may be based on undermining the detoxification and defence mechanisms coupled with deregulation of methylglyoxal synthesis.

Nursery rhymes are an almost universal part of young English-speaking children's lives. We have already established that there are strong links between children's early knowledge of nursery rhymes at 3;3 and their developing phonological skills over the next year and a quarter. Since such skills are known to be related to children's success in learning to read, this result suggests the hypothesis that acquaintance with nursery rhymes might also affect children's reading. We now report longitudinal data from a group of 64 children from the age of 3;4 to 6;3 which support this hypothesis. There is a strong relation between early knowledge of nursery rhymes and success in reading and spelling over the next three years even after differences in social background, I.Q and the children's phonological skills at the start of the project are taken into account. This raises the question of how nursery rhymes have such an effect. Our answer is that knowledge of nursery rhymes enhances children's phonological sensitivity which in turn helps them to learn to read. This paper presents further analyses which support the idea of this path from nursery rhymes to reading. Nursery rhymes are related to the child's subsequent sensitivity to rhyme and phonemes. Moreover the connection between knowledge of nursery rhymes and reading and spelling ability disappears when controls are made for differences in these subsequent phonological skills.

There has been a growth in students with dyslexia attending university. These students commonly rate writing as one of their greatest problem areas. Our research set out to describe the effects of dyslexia on the writing skills of students compared to age-matched peers and a spelling-skill-matched group. Generally, the texts of the students with dyslexia were poorer than age controls but not poorer than the spelling-skill controls. However, there were no major differences in "higher order" skills such as ideas and organization with the chronological age controls, only in "lower order" transcription skills such as spelling and handwriting fluency. The students with dyslexia made more spelling errors in their essays than one would predict given their dictated spelling skills.

SummaryThe glyoxalase I gene (gloA) of Escherichia coli has been cloned and used to create a null mutant. Cells overexpressing glyoxalase I exhibit enhanced tolerance of methylglyoxal (MG) and exhibit elevated rates of detoxification, although the increase is not stoichiometric with the change in enzyme activity. Potassium efflux via KefB is also enhanced in the overexpressing strain. Analysis of the physiology of the mutant has revealed that growth and viability are quite normal, unless the cell is challenged with MG either added exogenously or synthesized by the cells. The mutant strain has a low rate of detoxification of MG, and cells rapidly lose viability when exposed to this electrophile. Activation of KefB and KefC is diminished in the absence of functional glyoxalase I. These data suggest that the glutathione-dependent glyoxalase I is the dominant detoxification pathway for MG in E. coli and that the product of glyoxalase I activity, S-lactoylglutathione, is the activator of KefB and KefC.

SummaryBackgroundThe American Academy of Pediatrics recommends a permissive hypoxaemic target for an oxygen saturation of 90% for children with bronchiolitis, which is consistent with the WHO recommendations for targets in children with lower respiratory tract infections. No evidence exists to support this threshold. We aimed to assess whether the 90% or higher target for management of oxygen supplementation was equivalent to a normoxic 94% or higher target for infants admitted to hospital with viral bronchiolitis.MethodsWe did a parallel-group, randomised, controlled, equivalence trial of infants aged 6 weeks to 12 months of age with physician-diagnosed bronchiolitis newly admitted into eight paediatric hospital units in the UK (the Bronchiolitis of Infancy Discharge Study [BIDS]). A central computer randomly allocated (1:1) infants, in varying length blocks of four and six and without stratification, to be clipped to standard oximeters (patients treated with oxygen if pulse oxygen saturation [SpO2] <94%) or modified oximeters (displayed a measured value of 90% as 94%, therefore oxygen not given until SpO2 <90%). All parents, clinical staff, and outcome assessors were masked to allocation. The primary outcome was time to resolution of cough (prespecified equivalence limits of plus or minus 2 days) in the intention-to-treat population. This trial is registered with ISRCTN, number ISRCTN28405428.FindingsBetween Oct 3, and March 30, 2012, and Oct 1, and March 29, 2013, we randomly assigned 308 infants to standard oximeters and 307 infants to modified oximeters. Cough resolved by 15·0 days (median) in both groups (95% CI for difference −1 to 2) and so oxygen thresholds were equivalent. We recorded 35 serious adverse events in 32 infants in the standard care group and 25 serious adverse events in 24 infants in the modified care group. In the standard care group, eight infants transferred to a high-dependency unit, 23 were readmitted, and one had a prolonged hospital stay. In the modified care group, 12 infants were transferred to a high-dependency unit and 12 were readmitted to hospital. Recorded adverse events did not differ significantly.InterpretationManagement of infants with bronchiolitis to an oxygen saturation target of 90% or higher is as safe and clinically effective as one of 94% or higher. Future research should assess the benefits and risks of different oxygen saturation targets in acute respiratory infection in older children, particularly in developing nations where resources are scarce.FundingNational Institute for Health Research, Health Technology Assessment programme.

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It has been shown that there is a strong relation between children's phonological skills and the progress that they make in reading. But there is some uncertainty whether this is a specific connection or whether it is just a byproduct of variations in general language ability. We report evidence from a longitudinal study showing that the relation between children's sensitivity to rhyme and alliteration and their success in reading is highly specific and cannot be accounted for in terms of general language ability. In this study measures were taken of a group of children's linguistic and metalinguistic skills when they were 3 and 4 years old. The linguistic measures were of the children's vocabulary, their receptive and expressive use of grammar, and their ability to imitate sentences. The metalinguistic measures were of their ability to detect rhyme and alliteration and of their awareness of syntax. Two to three years later, when the children were 6;7, we measured their progress in reading and spelling. The children's rhyme and alliteration scores were related to their reading two years later even after controls for differences in linguistic skills and also for differences in intelligence and in social background. The other metalinguistic task -syntax awareness -did not predict reading after these controls. Awareness of rhyme, we argue, makes a distinctive contribution to reading by helping children to form spelling categories.Preschool children are reasonably good at producing rhymes and at detecting whether words rhyme or not (Chukovsky, 1963;Dowker, 1989;Lenel & Cantor, 1981;MacLean, Bryant, & Bradley, 1987). Their ability to do so is interesting for two reasons. First, it demonstrates that preschool children can analyze the constituent sounds in words. If they understand that cat and hat rhyme, they recognize that these two words have a speech segment -the rime /at/ -in common.The second reason why young children's rhyming abilities deserve attention is that there is a powerful connection between these abilities and the progress that children make later on when they learn to read and write. The performance of 3-, 4-, and 5-year-old children, who cannot yet read, in tests of sensitivity to rhyme and alliteration predicts their success in learning to read over the next three to four years even after controls for differences in