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Biomedical subjects

C Hulme

Publications and source records attributed to C Hulme.

At least 19 recordsLinked to original sources
PubMed2000

Oscillator-based memory for serial order.

A computational model of human memory for serial order is described (OSCillator-based Associative Recall [OSCAR]). In the model, successive list items become associated to successive states of a dynamic learning-context signal. Retrieval involves reinstatement of the learning context, successive states of which cue successive recalls. The model provides an integrated account of both item memory and order memory and allows the hierarchical representation of temporal order information. The model accounts for a wide range of serial order memory data, including differential item and order memory, transposition gradients, item similarity effects, the effects of item lag and separation in judgments of relative and absolute recency, probed serial recall data, distinctiveness effects, grouping effects at various temporal resolutions, longer term memory for serial order, list length effects, and the effects of vocabulary size on serial recall.

Association↗
PubMed1999

New 4-point pharmacophore method for molecular similarity and diversity applications: overview of the method and applications, including a novel approach to the design of combinatorial libraries containing privileged substructures.

A new 4-point pharmacophore method for molecular similarity and diversity that rapidly calculates all potential pharmacophores/pharmacophoric shapes for a molecule or a protein site is described. The method, an extension to the ChemDiverse/Chem-X software (Oxford Molecular, Oxford, England), has also been customized to enable a new internally referenced measure of pharmacophore diversity. The "privileged" substructure concept for the design of high-affinity ligands is presented, and an example of this new method is described for the design of combinatorial libraries for 7-transmembrane G-protein-coupled receptor targets, where "privileged" substructures are used as special features to internally reference the pharmacophoric shapes. Up to 7 features and 15 distance ranges are considered, giving up to 350 million potential 4-point 3D pharmacophores/molecule. The resultant pharmacophore "key" ("fingerprint") serves as a powerful measure for diversity or similarity, calculable for both a ligand and a protein site, and provides a consistent frame of reference for comparing molecules, sets of molecules, and protein sites. Explicit "on-the-fly" conformational sampling is performed for a molecule to enable the calculation of all geometries accessible for all combinations of four features (i.e., 4-point pharmacophores) at any desired sampling resolution. For a protein site, complementary site points to groups displayed in the site are generated and all combinations of four site points are considered. In this paper we report (i) the details of our customized implementation of the method and its modification to systematically measure 4-point pharmacophores relative to a "special" substructure of interest present in the molecules under study; (ii) comparisons of 3- and 4-point pharmacophore methods, highlighting the much increased resolution of the 4-point method; (iii) applications of the 4-point potential pharmacophore descriptors as a new measure of molecular similarity and diversity and for the design of focused/biased combinatorial libraries.

Binding Sites↗
PubMed1999

Phonemes, rhymes, and intelligence as predictors of children's responsiveness to remedial reading instruction: evidence from a longitudinal intervention study.

We present an analysis of data from a longitudinal intervention study with 7-year-old poor readers (Hatcher, Hulme, & Ellis, 1994). A battery of cognitive and phonological tasks administered before the intervention began revealed five separate factors: Phoneme Manipulation, Rhyme, Verbal Ability, Nonverbal Ability and Phonological Memory. We assessed the extent to which these factors were predictive of children's responsiveness to the teaching interventions they received. For reading accuracy, Verbal Ability, Nonverbal Ability, Phonological Memory, and Rhyme made no significant contribution to predicting responsiveness to teaching, while Phoneme Manipulation was a very strong predictor. However for reading comprehension, Verbal ability (but not nonverbal ability) made an additional unique contribution to predicting responsiveness to teaching. The results are discussed in the context of current theories of the role of intelligence and phonological skills in learning to read.

Aptitude Tests↗
PubMed1999

Phonological and semantic processes influence beginning readers' ability to learn to read words.

Children (4 to 6 years of age) were taught to associate printed 3- or 4-letter abbreviations, or cues, with spoken words (e.g., bfr for beaver). All but 1 of the letters in the cue corresponded to phonemes in the spoken target word. Two types of cues were constructed: phonetic cues, in which the medial letter was phonetically similar to the target word, and control cues, in which the central phoneme was phonetically dissimilar. In Experiment 1, children learned the phonetic cues better than the control cues, and learning correlated with measures of phonological skill and knowledge of the meanings of the words taught. In Experiment 2, the target words differed on a semantic variable-imageability-and learning was influenced by both the phonetic properties of the cue and the imageability of the words used.

Analysis of Variance↗
PubMed1999

Benzofuran based PDE4 inhibitors.

Replacement of the 3,4-dialkoxyphenyl substructure common to a number of PDE4 inhibitors with a 2-alkyl-7-methoxybenzofuran unit is described. This substitution can result in either enhancement or substantial reductions in PDE4 inhibitory activity depending on the system to which it is applied. An in vitro SAR study of a potent series of 4-(2-heteroaryl-ethyl)-benzoiurans 26 is also presented.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1999

Think before you speak: pauses, memory search, and trace redintegration processes in verbal memory span.

Immediate memory span and speed of memory search were assessed for words and nonwords of short and long spoken duration. Memory span was substantially greater for words than for nonwords and for short than for long items, though speed of memory search was unaffected by either length or lexicality. An analysis of the temporal pattern of responses in the memory span task indicated that inter-item pauses were longer between nonwords than words but that these pause durations were unaffected by item length. A model of verbal short-term memory span is described in which trace selection from a short-term store and the redintegration (restoration) of degraded phonological traces both occur in the pauses between saying successive items. Both trace selection and trace redintegration appear to play important roles in accounting for individual differences in memory span.

Adolescent↗
PubMed1998

Orally active indole N-oxide PDE4 inhibitors.

This communication describes the synthesis and in vitro and in vivo evaluation of a novel potent series of phosphodiesterase type (IV) (PDE4) inhibitors. Several of the compounds presented possess low nanomolar IC50's for PDE4 inhibition and excellent in vivo activity for inhibition of TNF-alpha levels in LPS challenged mice (mouse endotoxemia model). Emesis studies (dog) and efficacy in a SCW arthritis model for the most potent PDE4 inhibitors are presented.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1998

The synthesis and biological evaluation of a novel series of indole PDE4 inhibitors I.

This communication describes the synthesis and in vitro evaluation of a novel potent series of phosphodiesterase type (IV) (PDE4) inhibitors. The compounds described contain an indole moiety which replaces the 'rolipram-like' 3-methoxy-4-cyclopentoxy motif. Several of the compounds presented possess low nanomolar IC50's for PDEIV inhibition. In vivo activities determined from measurement of serum TNF-alpha levels in LPS challenged mice (mouse endotoxemia model) are also reported.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1998

Segmentation, not rhyming, predicts early progress in learning to read.

We present a longitudinal study of children in the first 2 years of learning to read. A battery of tests of phonological skills administered when the children were prereaders identified two distinct and relatively independent factors, Rhyming (defined by measures of rhyme detection and rhyme production) and Segmentation (defined by measures of phoneme identification and phoneme deletion). Segmentation was strongly correlated with attainment in reading and spelling at the end of the first year at school, while Rhyming was not. In addition, letter name knowledge predicted both reading and spelling skill and showed an interactive effect with children's segmentation skills. By the end of the second year of school, however, rhyming had started to exert a predictive effect on spelling, but not on reading. The results are discussed in the context of current theories of the role of phonological skills in learning to read.

Achievement↗
PubMed1998

Segmentation does predict early progress in learning to read better than rhyme: A reply to bryant

In our recent paper (Muter, Hulme, Snowling, & Taylor, 1997) we argued that measures of segmentation were better predictors of early progress in learning to read than were measures of rhyme. Bryant (1998, this issue), in his comment on our paper, has argued that this conclusion is flawed because the instructions used in our rhyme detection measure included the phrase "rhymes with or sounds like." We present new data showing that the instructions used do not have the effect Bryant claims: asking children which word "rhymes with" or which word "rhymes with or sounds like" a target word produces identical patterns of responses. We argue that Bryant's new measure derived from our data simply reflects children's global sensitivity to the similarity in sound between different words and that this measure provides no convincing support for his conclusion that sensitivity to onset and rime is a predictor of children's success in learning to read. We conclude that the data in our paper, as well as other recent evidence, support the view that measures of phonemic segmentation are better predictors of early reading skills than are measures of onset-rime sensitivity. Copyright 1998 Academic Press.

Journal Article↗
PubMed1997

Segmentation, not rhyming, predicts early progress in learning to read.

We present a longitudinal study of children in the first two years of learning to read. A battery of tests of phonological skills administered when the children were prereaders identified two distinct and relatively independent factors, Rhyming (defined by measures of rhyme detection and rhyme production) and Segmentation (defined by measures of phoneme identification and phoneme deletion). Segmentation was strongly correlated with attainment in reading and spelling at the end of the first year at school, though Rhyming was not. In addition, letter name knowledge predicted both reading and spelling skill and showed an interactive effect with children's segmentation skills. By the end of the second year of school, however, rhyming had started to exert a predictive effect of spelling, but not on reading. The results are discussed in the context of current theories of the role of phonological skills in learning to read.

Achievement↗
PubMed1997

Word-frequency effects on short-term memory tasks: evidence for a redintegration process in immediate serial recall.

Four experiments investigated the mechanisms responsible for the advantage enjoyed by high-frequency words in short-term memory tasks. Experiment 1 demonstrated effects of word frequency on memory span that were independent of differences in speech rate. Experiments 2 and 3 showed that word frequency has an increasing effect on serial recall across serial positions, but Experiment 4 showed that this effect was abolished for backward recall. A model that includes a redintegration process that operates to "clean up" decayed short-term memory traces is proposed, and the multinomial processing tree model described by R. Schweickert (1993) is used to provide a quantitative fit to data from Experiments 2, 3, and 4.

Adult↗
PubMed1997

Social drinking and laughter.

Pairs of observers monitored drinking and laughter in groups of social drinkers (N = 56). A significant correlation of .27 was found between units of alcohol consumed and laughter scores.

Adolescent↗
PubMed1996

The Automatic Activation of Sound-Letter Knowledge: An Alternative Interpretation of Analogy and Priming Effects in Early Spelling Development

This paper presents two experiments investigating 6-year-old children's use of analogy in spelling. In Experiment 1, children make analogies between a visible clue word and a similar sounding target word. Analogies are made to the same extent regardless of whether the clue and target share a rime unit, a consonant vowel (CV) or a vowel but are not made when only common letters are shared. A second experiment investigates children's spelling by analogy when the clue word is not visible. Again, an equal number of analogies are made between words sharing a rime unit, a CV or a vowel. From the earliest stages of learning to spell, children benefit from drawing analogies (at the level of individual phonemes) with words that they know. These findings are related to recent connectionist models of the development of reading and spelling skills.

Journal Article↗
PubMed1996

The remediation of clumsiness. I: An evaluation of Laszlo's kinaesthetic approach.

The effectiveness of a kinaesthetic training programme proposed by Laszlo for children with movement difficulties was evaluated by comparing two groups of 10 'clumsy' children matched pairwise on age, IQ and sex as well as degree of kinaesthetic and motor impairment. Tests of kinaesthetic ability, using the Parameter Estimation by Sequential Testing (PEST) procedure, and motor competence administered before and after treatment revealed an improvement in both groups on all measures but no differential effect of the training programme. Immediately after training, the changes we obtained in motor performance were confined to balance skills but, at follow up, 3 months later, changes in manual and ball skills were also evident. This unusual pattern of change requires replication. Our findings forced us to consider the possibility that any effect of Laszlo's recommended training programme had been obscured by our use of the PEST procedure, which had in itself facilitated motor learning.

Case-Control Studies↗
PubMed1996

The remediation of clumsiness. II. Is kinaesthesis the answer?

The paper reports the second of two studies designed to evaluate the effectiveness of the Kinaesthetic Training Programme (Laszlo and Bairstow, 1985) for children with movement difficulties. Three groups of 12 children were matched on age, IQ and sex as well as degree of kinaesthetic and motor impairment. One group received the Laszlo training, another received a training programme designed to avoid explicit reference to kinaesthesis and the third group received no training. Children receiving no intervention failed to show a change in performance. By contrast, the motor competence of both groups of treated children improved significantly. There was no advantage for the Laszlo trained group. It seems that in designing a remediation programme for clumsy children, the way that training is presented is as important as its actual content.

Activities of Daily Living↗