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A Harding

Publications and source records attributed to A Harding.

At least 19 recordsLinked to original sources
PubMed2003

The left human speech-processing cortex is thinner but longer than the right.

We present histological data from 21 post-mortem, adult human cases that indicate the neocortex on the left planum temporale (secondary auditory cortex) is thinner but longer than that on the right side. The volumes of the left and right regions are approximately equal. Thus, the left planum temporale cortex is long and thin and the right short and thick. The present data fit excellently with previous studies of the volume, surface area, cytoarchitectonics, and neuronal structures of these areas. From these studies we suggest that the hemispheric differences arise from a so-called "balloon model" of cortical development. In this the cortex is extended and stretched by white matter growth. The stretching is greater on the left side, leaving greater distances between neuronal columns and more tangentially (to the pial surface) oriented dendrites on that side. This difference in fine structure can result in more independent activity of individual columns on the left, and could be an anatomical factor in the usual dominance of the left hemisphere for speech perception (Seldon, 1982, 1985).

Journal Article↗
PubMed2003

A reconstruction algorithm for coherent scatter computed tomography based on filtered back-projection.

Coherent scatter computed tomography (CSCT) is a reconstructive x-ray imaging technique that yields the spatially resolved coherent-scatter form factor of the investigated object. Reconstruction from coherently scattered x-rays is commonly done using algebraic reconstruction techniques (ART). In this paper, we propose an alternative approach based on filtered back-projection. For the first time, a three-dimensional (3D) filtered back-projection technique using curved 3D back-projection lines is applied to two-dimensional coherent scatter projection data. The proposed algorithm is tested with simulated projection data as well as with projection data acquired with a demonstrator setup similar to a multi-line CT scanner geometry. While yielding comparable image quality as ART reconstruction, the modified 3D filtered back-projection algorithm is about two orders of magnitude faster. In contrast to iterative reconstruction schemes, it has the advantage that subfield-of-view reconstruction becomes feasible. This allows a selective reconstruction of the coherent-scatter form factor for a region of interest. The proposed modified 3D filtered back-projection algorithm is a powerful reconstruction technique to be implemented in a CSCT scanning system. This method gives coherent scatter CT the potential of becoming a competitive modality for medical imaging or nondestructive testing.

Algorithms↗
PubMed2002

Consensus neuropathological diagnosis of common dementia syndromes: testing and standardising the use of multiple diagnostic criteria.

The aim of this study was to assess the variation between neuropathologists in the diagnosis of common dementia syndromes when multiple published protocols are applied. Fourteen out of 18 Australian neuropathologists participated in diagnosing 20 cases (16 cases of dementia, 4 age-matched controls) using consensus diagnostic methods. Diagnostic criteria, clinical synopses and slides from multiple brain regions were sent to participants who were asked for case diagnoses. Diagnostic sensitivity, specificity, predictive value, accuracy and variability were determined using percentage agreement and kappa statistics. Using CERAD criteria, there was a high inter-rater agreement for cases with probable and definite Alzheimer's disease but low agreement for cases with possible Alzheimer's disease. Braak staging and the application of criteria for dementia with Lewy bodies also resulted in high inter-rater agreement. There was poor agreement for the diagnosis of frontotemporal dementia and for identifying small vessel disease. Participants rarely diagnosed more than one disease in any case. To improve efficiency when applying multiple diagnostic criteria, several simplifications were proposed and tested on 5 of the original 20 cases. Inter-rater reliability for the diagnosis of Alzheimer's disease and dementia with Lewy bodies significantly improved. Further development of simple and accurate methods to identify small vessel lesions and diagnose frontotemporal dementia is warranted.

Alzheimer Disease↗
PubMed2001

Right medial thalamic lesion causes isolated retrograde amnesia.

Pervasive retrograde amnesia without anterograde memory impairment has rarely been described as a consequence of circumscribed brain damage. We report this phenomenon in a 33 yr-old, right-handed man (JG) in association with the extension in the right thalamus of a previously small, bilateral thalamic lesion. JG presented with a dense amnesia for autobiographical material more than a few years old, with some sparing of recent memories. Furthermore, he was completely unable to recognise famous people or world events. Many other aspects of semantic knowledge were intact and there was no evidence of general intellectual impairment, executive dysfunction or loss of visual imagery. Magnetic resonance imaging revealed an acute lesion in the right thalamus and two small, symmetrical, bilateral non-acute thalamic lesions. Follow-up neuropsychological assessment indicated a stable pattern of impaired retrograde and spared anterograde memory over 18 months and psychiatric assessments yielded no evidence of confabulation, malingering or other symptoms to suggest psychogenic amnesia. JG's profile indicates that the division of declarative memory into just two categories - episodic and semantic - is inadequate. Rather, his case adds to the growing body evidence to suggest that world knowledge pertaining to people and events is stored or accessed similarly to autobiographical information and differently from other types of more general factual knowledge. We hypothesize that the right mediodorsal thalamic nucleus and immediately surrounding regions comprise the central processing mechanism referred to by McClelland (Revue Neurologique, 150 (1994) 570) and Markowitsch (Brain Research Review, 21 (1995) 117) as responsible for inducing and co-ordinating the recall of these sorts of cortically stored memory engrams.

Adult↗
PubMed2001

GTP-dependent segregation of H-ras from lipid rafts is required for biological activity.

Different sites of plasma membrane attachment may underlie functional differences between isoforms of Ras. Here we show that palmitoylation and farnesylation targets H-ras to lipid rafts and caveolae, but that the interaction of H-ras with these membrane subdomains is dynamic. GTP-loading redistributes H-ras from rafts into bulk plasma membrane by a mechanism that requires the adjacent hypervariable region of H-ras. Release of H-ras-GTP from rafts is necessary for efficient activation of Raf. By contrast, K-ras is located outside rafts irrespective of bound nucleotide. Our studies identify a novel protein determinant that is required for H-ras function, and show that the GTP/GDP state of H-ras determines its lateral segregation on the plasma membrane.

Animals↗
PubMed2000

Psychiatrists' experience and views regarding St John's Wort and 'alternative' treatments.

OBJECTIVE: This study aims to ascertain the experience and views of psychiatrists in relation to St John's Wort and alternative treatments generally. METHOD: A questionnaire was posted to all members of the Royal Australian and New Zealand College of Psychiatrists living in Australia or New Zealand. RESULTS: Of the 1910 mailed questionnaires, 862 (45%) were returned. Eighty per cent of respondents had patients who had used the herb. Side-effects and drug interactions were reported by 28% and 8% respectively of these psychiatrists. Some adverse events were described as serious. Psychiatrist attitudes about St John's Wort and alternative treatments were positive overall and psychiatrists seemed willing to recommend St John's Wort despite limited evidence of its usefulness. CONCLUSIONS: Psychiatrists in Australia and New Zealand regularly manage patients who take St John's Wort and a considerable number actually recommend the treatment. However, they also report side-effects and drug interactions. Psychiatrists should routinely enquire about their patients' use of alternative treatments, be mindful of possible side-effects and in particular be aware of the dangers of combining St John's Wort with other psychotropics.

Adult↗
PubMed2000

Degeneration of anterior thalamic nuclei differentiates alcoholics with amnesia.

The specific neural substrate underlying the amnesia in alcoholic Korsakoff's psychosis is poorly defined because of the considerable brain damage found in many non-amnesic alcoholics, particularly those with Wernicke's encephalopathy. Using operational criteria to identify alcoholics with and without Korsakoff's psychosis, we have shown that many of the cortical and subcortical regions involved in the encoding and retrieval of episodic memory are either unaffected (hippocampus) or damaged to the same extent (prefrontal cortex and the cholinergic basal forebrain) in both amnesic and non-amnesic alcoholics. In the present study we analysed the diencephalic regions involved in episodic memory to determine the neural substrate for the amnesia observed in alcoholic Korsakoff's psychosis. The number of neurons in spaced serial sections containing the hypothalamic mamillary nuclei and the anterior and mediodorsal thalamic nuclei was estimated using unbiased stereological techniques. Neurodegeneration of the hypothalamic mamillary nuclei and the mediodorsal thalamic nuclei was substantial in both non-amnesic and amnesic alcoholics with Wernicke's encephalopathy. However, neuronal loss in the anterior thalamic nuclei was found consistently only in alcoholic Korsakoff's psychosis. This is the first demonstration of a differentiating lesion in alcoholic Korsakoff's psychosis and supports previous evidence that degeneration of thalamic relays are important in this memory disorder.

Aged↗
PubMed2000

"Make or buy" decisions in the production of health care goods and services: new insights from institutional economics and organizational theory.

A central theme of recent health care reforms has been a redefinition of the roles of the state and private providers. With a view to helping governments to arrive at more rational "make or buy" decisions on health care goods and services, we propose a conceptual framework in which a combination of institutional economics and organizational theory is used to examine the core production activities in the health sector. Empirical evidence from actual production modalities is also taken into consideration. We conclude that most inputs for the health sector, with the exception of human resources and knowledge, can be efficiently produced by and bought from the private sector. In the health services of low-income countries most dispersed production forms, e.g. ambulatory care, are already provided by the private sector (non-profit and for-profit). These valuable resources are often ignored by the public sector. The problems of measurability and contestability associated with expensive, complex and concentrated production forms such as hospital care require a stronger regulatory environment and skilled contracting mechanisms before governments can rely on obtaining these services from the private sector. Subsidiary activities within the production process can often be unbundled and outsourced.

Decision Making↗
PubMed1999

Interactions of c-Raf-1 with phosphatidylserine and 14-3-3.

Activation of Raf-1 occurs at the plasma membrane. We recently showed that 14-3-3 must be complexed with Raf-1 for efficient recruitment to the plasma membrane and activation by Ras, but that 14-3-3 is completely displaced from Raf-1 following plasma membrane binding. We show here that the Raf-1 zinc finger is not absolutely required for 14-3-3 binding but is required to stabilize the interaction between Raf-1 and 14-3-3. Incubation of Raf-1 with phosphatidylserine, an inner plasma membrane phospholipid, results in removal of 14-3-3 and an increase in Raf-1 kinase activity, whereas removal of 14-3-3 from Raf-1 using specific phosphopeptides substantially reduces Raf-1 basal kinase activity. Displacement of 14-3-3 from activated Raf-1 by phosphopeptides has no effect on kinase activity if Raf-1 is first removed from solution, but completely eradicates kinase activity of soluble activated Raf-1. These results suggest a mechanism for the removal of 14-3-3 from Raf-1 at the plasma membrane and show that removal of 14-3-3 from Raf-1 has markedly different effects depending on experimental conditions.

14-3-3 Proteins↗
PubMed1999

Dominant-negative caveolin inhibits H-Ras function by disrupting cholesterol-rich plasma membrane domains.

The plasma membrane pits known as caveolae have been implicated both in cholesterol homeostasis and in signal transduction. CavDGV and CavKSY, two dominant-negative amino-terminal truncation mutants of caveolin, the major structural protein of caveolae, significantly inhibited caveola-mediated SV40 infection, and were assayed for effects on Ras function. We find that CavDGV completely blocked Raf activation mediated by H-Ras, but not that mediated by K-Ras. Strikingly, the inhibitory effect of CavDGV on H-Ras signalling was completely reversed by replenishing cell membranes with cholesterol and was mimicked by cyclodextrin treatment, which depletes membrane cholesterol. These results provide a crucial link between the cholesterol-trafficking role of caveolin and its postulated role in signal transduction through cholesterol-rich surface domains. They also provide direct evidence that H-Ras and K-Ras, which are targeted to the plasma membrane by different carboxy-terminal anchors, operate in functionally distinct microdomains of the plasma membrane.

3T3 Cells↗
PubMed1998

Characterization of 12 microsatellite loci of the human MHC in a panel of reference cell lines.

The human genome contains a large number of interspersed microsatellite repeats which exhibit a high degree of polymorphism and are inherited in a Mendelian fashion, making them extremely useful genetic markers. Several microsatellites have been described in the HLA region, but allele nomenclature, a set of broadly distributed controls, and typing methods have not been standardized, which has resulted in discrepant microsatellite data between laboratories. In this report we present a detailed protocol for genotyping microsatellites using a semi-automated fluorescence-based method. Twelve microsatellites within or near the major histocompatibility complex (MHC) were typed in the 10th International Histocompatibility Workshop homozygous typing cell lines (HTCs) and alleles were designated based on size. All loci were sequenced in two HTCs providing some information on the level of complexity of the repeat sequence. A comparison of allele size obtained by genotyping versus that obtained by direct sequencing showed minor discrepancies in some cases, but these were not unexpected given the technical differences in the methodologies. Fluorescence-based typing of microsatellites in the MHC described herein is highly efficient, accurate, and reproducible, and will allow comparison of results between laboratories.

Alleles↗
PubMed1998

Exercise before puberty may confer residual benefits in bone density in adulthood: studies in active prepubertal and retired female gymnasts.

Exercise during growth may contribute to the prevention of osteoporosis by increasing peak bone mineral density (BMD). However, exercise during puberty may be associated with primary amenorrhea and low peak BMD, while exercise after puberty may be associated with secondary amenorrhea and bone loss. As growth before puberty is relatively sex hormone independent, are the prepubertal years the time during which exercise results in higher BMD? Are any benefits retained in adulthood? We measured areal BMD (g/cm2) by dual-energy X-ray absorptiometry in 45 active prepubertal female gymnasts aged 10.4 +/- 0.3 years (mean +/- SEM), 36 retired female gymnasts aged 25.0 +/- 0.9 years, and 50 controls. The results were expressed as a standardized deviation (SD) or Z score adjusted for bone age in prepubertal gymnasts and chronological age in retired gymnasts. In the cross-sectional analyses, areal BMD in the active prepubertal gymnasts was 0.7-1.9 SD higher at the weight-bearing sites than the predicted mean in controls (p < 0.01). The Z scores increased as the duration of training increased (r = 0.32-0.48, p ranging between <0.04 and <0.002). During 12 months, the increase in areal BMD (g/cm2/year) of the total body, spine, and legs in the active prepubertal gymnasts was 30-85% greater than in prepubertal controls (all p < 0.05). In the retired gymnasts, the areal BMD was 0.5-1.5 SD higher than the predicted mean in controls at all sites, except the skull (p ranging between <0.06 and <0.0001). There was no diminution across the 20 years since retirement (mean 8 +/- 1 years), despite the lower frequency and intensity of exercise. The prepubertal years are likely to be an opportune time for exercise to increase bone density. As residual benefits are maintained into adulthood, exercise before puberty may reduce fracture risk after menopause.

Adolescent↗
PubMed1998

The development and role of the Read Codes.

Produced and maintained by Britain's National Health Service, the Read Codes are a comprehensive, controlled clinical vocabulary. Here's a look at how the codes evolved, their use in the NHS, and the continual process of aligning the system with the needs of its users.

Abstracting and Indexing↗
PubMed1996

Cleft palate speech dissected: a review of current knowledge and analysis.

In this review, normal speech and its development is described and compared with the patterns typical of cleft palate speech. Attention is drawn to the importance of measuring and analysing these factors adequately for research and audit purposes, and the need for agreed parameters for reporting outcomes.

Child↗
PubMed1996

Characteristics of cleft palate speech.

In recent years, interest in the nature of cleft palate speech and the influences on speech quality has increased. This overview of contemporary research reveals new perspectives on cleft palate speech development and the phonological consequences of early articulatory constraints. Cleft palate speech is perceived as the result of the synthesis between physical, physiological, cognitive and linguistic development. Developmental influences on cleft palate speech are considered in the context of early vocalisations of cleft and non-cleft children, followed by an examination of the literature on the development of babble, the emergence of early words and consonant development in children born with cleft palate. Speech development is then discussed from a phonological perspective interpreting reported characteristics as 'cleft-type developmental processes', for example, lack of target stabilisation; compensatory articulations; active/passive strategies; and systematic sound preference. Given these influences on speech development the extent to which cleft palate speech should be regarded as an 'articulatory disorder' has been reconsidered. Descriptions and interpretations of nasal resonance, nasal emission, and nasal turbulence are followed by discussion of articulatory errors in place and manner and patterns of change in cleft palate speech. Finally, some of the available evidence on speech in relation to structural imperfections, such as unrepaired clefts, velopharyngeal insufficiency, oro-nasal fistulae, dental and occlusal deviations, and open-mouth posture is summarised briefly. These new perspectives aim to facilitate more effective clinical management and to provide indications for future research.

Child, Preschool↗