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Showing papers by "Newcastle University published in 1995"


Journal ArticleDOI
TL;DR: A review of the medical records of over 14 000 admissions to 28 hospitals in New South Wales and South Australia revealed that 16.6% of these admissions were associated with an “adverse event”, which resulted in disability or a longer hospital stay for the patient and was caused by health care management.
Abstract: A review of the medical records of over 14,000 admissions to 28 hospitals in New South Wales and South Australia revealed that 16.6% of these admissions were associated with an "adverse event", which resulted in disability or a longer hospital stay for the patient and was caused by health care management; 51% of the adverse events were considered preventable. In 77.1% the disability had resolved within 12 months, but in 13.7% the disability was permanent and in 4.9% the patient died.

2,197 citations


Journal ArticleDOI
01 Jan 1995-Carbon
TL;DR: In this paper, X-ray photoelectron spectroscopy (XPS) was used to investigate the fate of nitrogen functional forms present in a lignite and its chars, derived from the model compounds acridine, carbazole and polyacrylonitrile (PAN).

1,792 citations


Journal ArticleDOI
21 Jul 1995-Science
TL;DR: The ternary complex factor (TCF) subfamily of ETS-domain transcription factors bind with serum response factor (SRF) to the serum response element (SRE) and mediate increased gene expression and integrates MAP kinase signaling pathways in vivo to coordinate biological responses to different extracellular stimuli.
Abstract: The ternary complex factor (TCF) subfamily of ETS-domain transcription factors bind with serum response factor (SRF) to the serum response element (SRE) and mediate increased gene expression. The TCF protein Elk-1 is phosphorylated by the JNK and ERK groups of mitogen-activated protein (MAP) kinases causing increased DNA binding, ternary complex formation, and transcriptional activation. Activated SRE-dependent gene expression is induced by JNK in cells treated with interleukin-1 and by ERK after treatment with phorbol ester. The Elk-1 transcription factor therefore integrates MAP kinase signaling pathways in vivo to coordinate biological responses to different extracellular stimuli.

962 citations


Journal ArticleDOI
TL;DR: The findings suggest that in humans, as in other mammals, the MC1R is a control point in the regulation of pigmentation phenotype and, more importantly, that variations in this protein are associated with a poor tanning response.
Abstract: Melanin pigmentation protects the skin from the damaging effects of ultraviolet radiation (UVR). There are two types of melanin, the red phaeomelanin and the black eumelanin, both of which are present in human skin. Eumelanin is photoprotective whereas phaeomelanin, because of its potential to generate free radicals in response to UVR, may contribute to UV-induced skin damage. Individuals with red hair have a predominance of phaeomelain in hair and skin and/or a reduced ability to produce eumelanin, which may explain why they fail to tan and are at risk from UVR. In mammals the relative proportions of phaeomelanin and eumelanin are regulated by melanocyte stimulating hormone (MSH), which acts via its receptor (MC1R), on melanocytes, to increase the synthesis of eumelanin and the product of the agouti locus which antagonises this action. In mice, mutations at either the MC1R gene or agouti affect the pattern of melanogenesis resulting in changes in coat colour. We now report the presence of MC1R gene sequence variants in humans. These were found in over 80% of individuals with red hair and/or fair skin that tans poorly but in fewer than 20% of individuals with brown or black hair and in less than 4% of those who showed a good tanning response. Our findings suggest that in humans, as in other mammals, the MC1R is a control point in the regulation of pigmentation phenotype and, more importantly, that variations in this protein are associated with a poor tanning response.

929 citations


Journal ArticleDOI
TL;DR: The MADS-box family of transcription factors has been defined on the basis of primary sequence similarity amongst numerous proteins from a diverse range of eukaryotic organisms including yeasts, plants, insects, amphibians and mammals and the name refers to four of the originally identified members: MCM1, AG, DEFA and SRF.
Abstract: The MADS-box family of transcription factors has been defined on the basis of primary sequence similarity amongst numerous proteins from a diverse range of eukaryotic organisms including yeasts, plants, insects, amphibians and mammals. The MADS-box is a conserved motif found within the DNA-binding domains of these proteins and the name refers to four of the originally identified members: MCM1, AG, DEFA and SRF. Several proteins within this family have significant biological roles. For example, the human serum-response factor (SRF) is involved in co-ordinating transcription of the protooncogene c-fos, whilst MCM1 is central to the transcriptional control of cell-type specific genes and the pheromone response in the yeast Saccharomyces cerevisiae. The RSRF/MEF2 proteins comprise a sub-family of this class of transcription factors which are key components in muscle-specific gene regulation. Moreover, in plants, MADS-box proteins such as AG, DEFA and GLO play fundamental roles during flower development. The MADS-box is a contiguous conserved sequence of 56 amino acids, of which 9 are identical in all family members described so far. Several members have been shown to form dimers and consequently two functional regions within the MADS-box have been defined. The N-terminal half is the major determinant of DNA-binding specificity whilst the C-terminal half is necessary for dimerisation. This organisation allows the potential formation of numerous proteins, with subtly different DNA-binding specificities, from a limited number of genes by heterodimerisation between different MADS-box proteins. The majority of MADS-box proteins bind similar sites based on the consensus sequence CC(A/T)6GG although each protein apparently possesses a distinct binding specificity. Moreover, several MADS-box proteins specifically recruit other transcription factors into multi-component regulatory complexes. Such interactions with other proteins appears to be a common theme within this family and play a pivotal role in the regulation of target genes.

849 citations


Journal Article
TL;DR: Monoclonal antibodies revealed that p21WAF1/CIP1 expression followed radiation-induced DNA damage in human skin in a pattern consistent with its regulation by p53, and escape from this regulation may be a critical feature of neoplastic transformation.
Abstract: The p53-regulated gene product p21WAF1/CIP1 is the prototype of a family of small proteins that negatively regulate the cell cycle. To learn more about p21WAF1/CIP1 regulation in vivo, monoclonal antibodies were developed for immunohistochemistry. These revealed that p21WAF1/CIP1 expression followed radiation-induced DNA damage in human skin in a pattern consistent with its regulation by p53. A detailed comparison of the human, rat, and mouse p21WAF1/CIP1 promoter sequences revealed that this induction was probably mediated by conserved p53-binding sites upstream of the transcription start site. In unirradiated tissues, p21WAF1/CIP1 expression was apparently independent of p53 and was observed in a variety of cell types. Moreover, there was a striking compartmentalization of p21WAF1/CIP1 expression throughout the gastrointestinal tract that correlated with proliferation rather than differentiation. As epithelial cells migrated up the crypts, the Ki67-expressing proliferating compartment near the crypt base ended abruptly, with the coincident appearance of a nonproliferating compartment expressing p21WAF1/CIP1. In colonic neoplasms, this distinct compartmentalization was largely abrogated. Cell cycle inhibitors are thus subject to precise topological control, and escape from this regulation may be a critical feature of neoplastic transformation.

595 citations


Journal ArticleDOI
09 Nov 1995-Nature
TL;DR: It is shown that floating head is the zebrafish homologue of Xnot, a homeobox gene expressed in the amphibian organizer and notochord, and it is proposed that flh regulates notochords precursor cell fate.
Abstract: The notochord is a midline mesodermal structure with an essential patterning function in all vertebrate embryos. Zebrafish floating head (flh) mutants lack a notochord, but develop with prechordal plate and other mesodermal derivatives, indicating that flh functions specifically in notochord development. We show that floating head is the zebrafish homologue of Xnot, a homeobox gene expressed in the amphibian organizer and notochord. We propose that flh regulates notochord precursor cell fate.

471 citations


Journal ArticleDOI
TL;DR: In the presence of continuing high alcohol consumption the above histological features identified those at high risk of disease progression, and patients with these features should be counselled intensively regarding their alcohol consumption.

438 citations


Journal ArticleDOI
TL;DR: This work has shown that in the absence of the retentive outer membrane, components carrying out functions within the gram-positive cell envelope must somehow be tethered in order to prevent their loss into the growth environment.
Abstract: Our view of the complexity of the Gram-positive bacterial cell envelope has altered considerably in recent years, with the recognition of the presence of a variety of proteins retained by different mechanisms. Lipoproteins, i.e., proteins containing lipid covalently linked to an N-terminal cysteine residue, have been extensively studied in gram-negative bacteria (7), but examples from gram-positive species have only quite recently been recognized (Table 1). Despite its thickness, the peptidoglycan layer of gram-positive bacteria remains a relatively porous structure. Thus, in the absence of the retentive outer membrane, components carrying out functions within the gram-positive cell envelope must somehow be tethered in order to prevent their loss into the growth environment. The lipidated N terminus is presumed to anchor lipoproteins into the outer leaflet of the cell membrane, and lipoproteins can be compared topographically to the other major class of macroamphiphiles present in the gram-positive cell envelope, the lipoteichoic acids and lipoglycans (65). Several approaches can be used to identify lipoproteins: (i) metabolic labelling with radiolabelled fatty acid, usually palmitic acid; (ii) interference with protein processing by the antibiotic globomycin, which inhibits lipoprotein processing by signal peptidase II; and (iii) presence of a conserved consensus sequence within prelipoprotein signal peptides, which is thought to direct processing of the prelipoprotein to form the mature acylated protein (6, 7, 71). The last has become the standard method for recognition of putative lipoproteins, but it must be stressed that relatively few lipoprotein structures have yet been the subjects of rigorous chemical analysis.

431 citations


Journal ArticleDOI
TL;DR: The authors discusses the policy alternatives that might be mobilized to reverse the centralizing forces unleashed by the pursuit of neo-liberal policies in the European Union, highlighting the limitations of contemporary versions of the managed economy model, and explores the significance of an emerging model of development rooted in socioeconomics, and stressing the powers of associationism.
Abstract: This article, focusing on regional development issues, discusses thepolicy alternatives that might be mobilized to reverse the centralizing forces unleashed by the pursuit of neo-liberal policies in the European Union. It highlights the limitations of contemporary versions of the managed economy model, and explores the significance of anemerging model of development rooted in socioeconomics, and stressing the powers of ‘associationism’. While broadly sympathizing with this third way-in between market and hierarchy - as a basis for generating economic success, the article goes on to argue that questions of social equity and political democracy remain unresolved by the associationist agenda.

349 citations


Journal ArticleDOI
TL;DR: The role of free radical mechanisms as a contributory factor to motor neuron injury in the common sporadic form of motor neuron disease requires urgent exploration, particularly as this may provide an avenue for therapy aimed at retarding pathological progression as mentioned in this paper.
Abstract: The recent discovery that defects in the gene encoding copper-zinc superoxide dismutase (SOD1) are associated with some cases of familial motor neuron disease has heightened interest in the possibility that free radical mechanisms may contribute to selective motor neuron injury. Sporadic and familial motor neuron diseases are clinically and pathologically very similar and may share common pathophysiological mechanisms. Thus the role of free radical mechanisms as a contributory factor to motor neuron injury in the common sporadic form of motor neuron disease requires urgent exploration, particularly as this may provide an avenue for therapy aimed at retarding pathological progression. We investigated oxidative damage to proteins in the lumbar spinal cord by quantifying the protein carbonyl level from 19 patients with sporadic motor neuron disease, 8 neurologically normal control subjects, and 11 neurological disease control subjects, most of whom had slowly progressive neurodegenerative disease. In sporadic motor neuron disease the mean protein carbonyl level in the spinal cord was increased by 119% (p < 0.02) compared to normal control subjects and by 88% (p < 0.04) compared to the neurological disease control subjects. These data contribute to the emerging evidence that oxidative damage may play a contributory role in the neuronal death in sporadic motor neuron disease. This mechanism may be particularly important in a subset of patients with motor neuron disease.

Journal ArticleDOI
TL;DR: In this paper, the effects of altering the method of eliciting willingness to pay (WTP) responses are analyzed. And the authors conclude that respondents experience significant uncertainty in answering open-ended questions and may exhibit free-riding or strategic overbidding tendencies (although this is less certain).

Journal ArticleDOI
TL;DR: It is shown that Jadassohn–Lewandowsky PC is caused by a heterozygous missense mutation in the helix initiation peptide of K16 (Leu130Pro), and the known expression patterns of these keratins in epidermal structures correlates with the specific abnormalities observed in each form of PC.
Abstract: Pachyonychia congenita (PC) is a group of autosomal dominant disorders characterized by dystrophic nails and other ectodermal aberrations A gene for Jackson–Lawler PC was recently mapped to the type I keratin cluster on 17q Here, we show that a heterozygous missense mutation in the helix initiation motif of K17 (Asn92Asp) co–segregates with the disease in this kindred We also show that Jadassohn–Lewandowsky PC is caused by a heterozygous missense mutation in the helix initiation peptide of K16 (Leu130Pro) The known expression patterns of these keratins in epidermal structures correlates with the specific abnormalities observed in each form of PC

Journal ArticleDOI
TL;DR: In this article, the authors analyze the decision by teachers to leave the profession and affirm the importance of relative earnings in the tenure and turnover decisions of teachers, using an econometric modeling approach used yields important insights into the appropriateness of adopting a flexible, semiparametric specification of the duration dependence structure and of the unobserved heterogeneity distribution in duration models.
Abstract: In this paper, the authors analyze the decision by teachers to leave the profession. Their results affirm the importance of relative earnings in the tenure and turnover decisions of teachers. The econometric modeling approach used yields important insights into the appropriateness of adopting a flexible, semiparametric specification of the duration dependence structure and of the unobserved heterogeneity distribution in duration models. Copyright 1995 by Royal Economic Society.

Journal ArticleDOI
TL;DR: The identification of a subgroup of MND patients with high CSF glutamate levels may be important in evaluating the clinical response to antiglutamate therapeutic agents.

Journal ArticleDOI
TL;DR: In vitro fermentations with inocula made from human faeces and from rat caecal contents gave similar results and there was a close correspondence between the data obtained in the present experiment and those previously published in in vivo studies in the rat.
Abstract: Five European laboratories tested a simple in vitro batch system for dietary fibre fermentation studies. The inoculum was composed of fresh human faeces mixed with a carbonate-phosphate buffer complex supplemented with trace elements and urea. Five dietary fibre sources (cellulose, sugarbeet fibre, soyabean fibre, maize bran and pectin) were used by each laboratory on three occasions to determine pH, residual non-starch polysaccharides (NSP) and short-chain fatty acid production during fermentation. Cellulose and maize bran degradabilities were very low (7.2(SE 10.8) and 6.2 (SE 9.1)% respectively after 24 h), whereas pectin and soyabean fibre were highly degraded (97.4 (SE 4.4) and 91.1 (SE 3.4)% respectively after 24 h). Sugarbeet fibre exhibited an intermediate level of degradability (59.5 (SE 14.9)%). Short-chain fatty acid production was closely related to NSP degradation (r 0.99). Although each variable was ranked similarly by all laboratories, some differences occurred with respect to absolute values. However, the adaptation of donors to the experimental substrates was not an influential factor. Interlaboratory differences could be reduced either by adding less substrate during incubations or using less-diluted inocula. In vitro fermentations with inocula made from human faeces and from rat caecal contents gave similar results. There was a close correspondence between the data obtained in the present experiment and those previously published in in vivo studies in the rat using the same fibres. The in vitro batch system tested during the present study provides a rapid means of obtaining quantitative estimates of the fermentation and the estimation of the energy content of new sources of dietary fibre.

Journal ArticleDOI
11 Nov 1995-BMJ
TL;DR: A pronounced improvement in the population lipid profile in Mauritius was probably related to a change in the saturated fat content of a widely used cooking oil.
Abstract: Objective: To study changes in the prevalence of risk factors for cardiovascular disease after a five year population-wide intervention programme promoting a healthy lifestyle in a developing country. Design: Cross sectional cluster surveys in 1987 and 1992. Methodology included a two hour 75 g oral glucose tolerance test, measurement of body mass index, waist:hip ratio, basal lipid concentrations, and blood pressure; and a lifestyle questionnaire. Setting: Mauritius, in the Indian Ocean. Subjects: All adults aged 25-74 years residing in geographically defined clusters. Main outcome measures: Age standardised prevalence of categorical disease and risk factor conditions and mean levels and frequency distributions of continuous variables. Results: Response rates were 86.2% (5080/5892) in 1987 and 89.5% (5162/5770) in 1992. Significant decreases were found in the prevalence of hypertension (15.0% to 12.1% in men and 12.4% to 10.9% in women); cigarette smoking (58.2% to 47.2% and 6.9% to 3.7% respectively); and heavy alcohol consumption (38.2% to 14.4% and 2.6% to 0.6% respectively). Moderate leisure physical activity increased from 16.9% to 22.1% in men and from 1.3% to 2.7% in women. Mean population serum total cholesterol concentration fell appreciably from 5.5 mmol/l to 4.7 mmol/l (P Conclusions: Lifestyle intervention projects can be implemented and have positive effects in developing countries. A pronounced improvement in the population lipid profile in Mauritius was probably related to a change in the saturated fat content of a widely used cooking oil.

Journal ArticleDOI
TL;DR: A rapid assay which, for the first time, detects the 13kb Xba I gene deletion allele by the use of long-PCR technology and will improve the scientific and clinical use of CYP2D6 genotyping.
Abstract: The cytochrome P450 enzyme debrisoquine 4-hydroxylase metabolizes many different classes of commonly used drugs, such as antidepressants and neuroleptics. Deficient hydroxylation of debrisoquine, known as the poor metabolizer (PM) phenotype, affects 5- 10% of Caucasians and may lead to adverse react

Journal ArticleDOI
TL;DR: There is substantial evidence that tributyltin (TBT) contamination has decreased following the introduction of legislation prohibiting the use of TBT-based paints on vessels less than 25 m in length as mentioned in this paper.

Journal ArticleDOI
TL;DR: In this article, three influential accounts of economic change are examined and are found to be overwhelmingly concerned with identifying new orders, paradigms, or modes of accumulation: regulation theory, flexible specialization, and networks.
Abstract: Declarations of societal shift, economic transition, and the dawning of a new era have now become commonplace in social science, particularly in the analysis of economic forms. In this paper, three influential accounts of economic change are examined and are found to be overwhelmingly concerned with identifying new orders, paradigms, or modes of accumulation. First, regulation theory is described. Although this perspective is valuable in its focus upon institutional ensembles and interrelations, it lapses all too easily into structuralism; that is, these institutional ensembles can be explained by their structural ‘coupling’ to the mode of production and the mode of regulation. Second, flexible specialization is considered. Here again the explanation of new industrial forms is distinguished from their description by the use of ‘ideal types’. These types define the contours of the new era. Last, networks are also identified as the dominant organizational form of the post-Fordist era. The argument proposed ...

Journal ArticleDOI
TL;DR: In this article, the effect of multiple factor interaction in the coagulation of turbid water with Moringa oleifera was investigated using the results of experimental runs involving varying initial turbidity.

Journal Article
07 Sep 1995-Oncogene
TL;DR: The observations indicate that, in a subset of breast cancers, aberrant cyclin D1 expression is a contributory factor to tumorigenesis and in association with EGFR or pRB expression, identify those tumours which may require more aggressive therapy.
Abstract: Cyclin D1 plays a critical role in the timing of the initiation of DNA synthesis in the normal cell cycle of mammalian cells Deregulated expression of this protein has been seen in a variety of tumours either as a result of gene amplification or chromosomal translocation, in breast cancer and B cell malignancies respectively In order to determine the role this putative oncoprotein plays in breast cancer, we have applied a new monoclonal antibody, recently produced in our laboratory, in an immunohistochemical study of 93 primary breast carcinomas We show that approximately 28% of the cases displayed enhanced expression of the cyclin D1 protein Furthermore, either cyclin D1, cyclin D3, or both, were expressed in 69% of cases, suggesting that overexpression of any one member of this family may relieve cancer cells of their mitogenic stimulatory requirement In addition, we show that those patients whose breast cancers co-express cyclin D1 with either epidermal growth factor receptor (EGFR) or the retinoblastoma protein (pRB) have a significantly poorer prognosis in comparison to those expressing cyclin D1 alone Our observations indicate that, in a subset of breast cancers, aberrant cyclin D1 expression is a contributory factor to tumorigenesis and in association with EGFR or pRB expression, identify those tumours which may require more aggressive therapy

Journal ArticleDOI
KJ Belton1, Steff Lewis1, S Payne1, Rawlins1, SM Wood1 
TL;DR: Attitudes of doctors to the Committee on Safety of Medicines' (CSM) adverse drug reaction (ADR) reporting scheme were investigated in order to assess their understanding of the purposes of the scheme and to identify reasons for failing to report suspected adverse drug reactions.
Abstract: 1. Attitudes of doctors to the Committee on Safety of Medicines' (CSM) adverse drug reaction (ADR) reporting scheme were investigated in order to assess their understanding of the purposes of the scheme and to identify reasons for failing to report suspected adverse drug reactions. 2. A postal questionnaire and letter of invitation were sent to 500 doctors who were randomly selected from the 1992 Medical Directory. A reminder letter and a second copy of the questionnaire were sent to non-responders after 4 weeks. 3. 284 (57%) responded to the questionnaire. Of these, 179 (63%) stated that they had previously reported an ADR to the CSM or a pharmaceutical manufacturer. 77% of general practitioners stated that they had reported one or more ADRs compared with 55% of hospital doctors. 4. Reasons for under-reporting included lack of time, lack of report forms and the misconception that absolute confidence in the diagnosis of an adverse reaction was important in the decision to send in a report. 5. An investigation of seven commonly proposed reasons for under-reporting showed that on the whole they did not apply. 6. Most doctors knew the types of reactions that the Committee on Safety of Medicines seeks reports for but only 38% knew the precise meaning of the Committee on Safety of Medicines' black triangle symbol. There also seemed to be confusion about some of the purposes of the adverse drug reaction reporting scheme. 7. The number of reporting doctors is much higher than has previously been estimated.(ABSTRACT TRUNCATED AT 250 WORDS)

Journal ArticleDOI
TL;DR: The incidence of de-novo breast cancer arising in women receiving immunosuppressive therapy after kidney or heart transplantation is examined, and observations raise the possibility of therapeutic manipulation of specific immune mechanisms that promote tumour growth.

Journal ArticleDOI
TL;DR: In this article, preliminary investigations into the possible use of Moringa oleifera seed suspension for softening of hardwater are presented, which is due to adsorption with the adsoration isotherm approximating to the Langmuir type, and conversion of soluble hardness-causing ions to insoluble products by precipitation reactions.

Journal ArticleDOI
TL;DR: The natural history of thyroid associated ophthalmopathy is poorly documented and it is widely thought that many cases improve spontaneously with time, but is also a critical factor when assessing the effects of different treatments.
Abstract: Summary BACKGROUND The natural history of thyroid associated ophthalmopathy is poorly documented, although It is widely thought that many cases Improve spontaneously with time. This has Important Implications in the management of patients and is also a critical factor when assessing the effects of different treatments. OBJECTIVE To document the natural history of thyroid associated ophthalmopathy, 59 patients were studied longitudinally and the severity of eye disease documented at regular Intervals. METHODS Fifty-nine patients with thyroid associated ophthalmopathy who had not received Immunosuppressive or surgical treatment for their eye disease, were recruited from a combined thyroid-eye clinic. They were assessed at presentation and at 3–6-monthly Intervals for a median of 12 months. The eyes were assessed by separate and objective measurements relating to the status of the eyelids, cornea, extraocular muscles, proptosis and optic nerve function. In addition, a scoring system based on the above measurements was used to grade the overall severity of eye disease. RESULTS Thirteen patients (22%) Improved substantially, 25 patients (42·4%) showed minor Improvement, 13 patients (22%) did not change, and 8 patients (13·5%) deteriorated progressively, to the extent that Immunosuppressive treatment was considered to be necessary. CONCLUSIONS A significant proportion of patients with thyroid associated ophthalmopathy (64·4% in the present series) Improve spontaneously so serial assessment plays an Important part in deciding which patients require Immunosuppressive treatment. These findings also support the view that clinical trials designed to test the efficacy of new treatments in thyroid associated ophthalmopathy should be scrupulously controlled to allow for the natural tendency towards remission.

Journal ArticleDOI
22 Jul 1995-BMJ
TL;DR: The assessment of a health practice and the development of a policy for the use of that practice is the final step in a long process that begins with a research idea and ends in actual changes in people's health.
Abstract: #### Summary points The assessment of a health practice and the development of a policy for the use of that practice is the final step in a long process that begins with a research idea and ends in actual changes in people's health. All the accumulated research, development, and experience is converted into practical recommendations that largely determine what happens to a patient. In this pivotal position the design of a policy deserves whatever effort is required to ensure that all the proceeding work is put to the best effect1 There is an explosion of interest in guidelines, reflected in a vivid debate ranging from “the best thing since sliced bread” to cries of “cookbook medicine” and fears of constraint on clinical freedom.2 3 4 5 6 7 8 Furthermore, the Department of Health has introduced an initiative to encourage the adoption of evidence based guidelines within purchaser-provider contracts,9 10 and a review of the effectiveness of clinical guidelines has recently been published.11 The subject of guidelines is complex. Even for enthusiasts, ensuring that guidelines are effective by addressing each part of the complex chain of development, dissemination, implementation, and evaluation (fig 1) can be a daunting task. There are an increasing number of publications on the subject--for example, on the details of guideline development and effectiveness.1 12 13 14 15 16 In particular, the seminal work of Grimshaw and Russell has led to a …

Journal ArticleDOI
TL;DR: Focal injections of the anterograde tracer biocytin were made into physiologically identified loci of the CNIC and the spatial organisation of the labeled fibres was revealed with computer‐assisted threedimensional (3‐D) reconstruction.
Abstract: We present a comprehensive description of the local (intrinsic and commissural) connections in the central nucleus of the inferior colliculi (CNICs) in guinea pig. Focal injections of the anterograde tracer biocytin were made into physiologically identified loci of the CNIC and the spatial organisation of the labeled fibres was revealed with computer-assisted threedimensional (3-D) reconstruction. The intrinsic fibres form a series of V-shaped laminar plexuses composed of fibres bearing both terminal and en passant boutons. Each laminar plexus has a central wing located in the CNIC that extends into the dorsal cortex and an external wing located in the external cortex. The edge where the two wings intersect delimits the lateral border of the central nucleus with the external cortex. The density of labeled terminals was consistently lower in the cortices than in the CNIC. The laminar plexus connects points of similar frequency within the CNIC. Seen in 3-D, the location, orientation, shape, and area of the laminar plexus vary as a function of best frequency. The commissural fibres ending in the contralateral IC to the injection also form a laminar plexus which is symmetrical to the ipsilateral plexus. Electrolytic lesions placed in the contralateral IC at sites with best frequencies corresponding to those of the injection coincided with the terminals of the commissural fibres in most instances. Possible patterns for the organisation of these connections (point-to-point and diverging) are discussed. Three systems of peripheral axons to the laminar plexus are described: parallel, oblique, and perpendicular to the central wing. The novel parallel system has terminals in both ICs that run parallel to the central wing. It might constitute the anatomical basis for across-frequency interactions. The oblique and perpendicular systems are fibres of passage projecting to the commissure and brachium of the IC, respectively. © 1995 Wiley-Liss, Inc.

Journal ArticleDOI
TL;DR: Histological examination of bleached tissues from the reef corals subjected to increased seawater temperatures and possibly increased irradiance in the field revealed a reduction in zooxanthellae density between 50 and 90% compared with the zooxanhellae complement of normally-coloured corals.
Abstract: Histological examination of bleached tissues from the reef corals Goniastrea aspera, G. retiformis, Favites abdita, Coeloseris mayeri, Goniopora pandoraensis, and Galaxea fascicularis subjected to increased seawater temperatures and possibly increased irradiance in the field, revealed a reduction in zooxanthellae density between 50 and 90% (depending on species) compared with the zooxanthellae complement of normally-coloured corals. The study revealed a number of cellular mechanisms which would result in reduced zooxanthellae densities in bleached corals. These included degeneration of zooxanthellae in situ, release of zooxanthellae from mesenterial filaments and, for two species in an advanced state of bleaching, release of algae within host cells which became detached from the endoderm. The existence of a number of cellular mechanisms of zooxanthellae loss in naturally-bleached tissues contrasts with previous descriptions of a single predominant mechanism of zooxanthellae release in laboratory simulations, and highlights the importance of complementing laboratory studies with relevant field observations.

Journal ArticleDOI
TL;DR: An algorithm is presented which estimates a “risk surface” from a set of point-referenced events, which is adaptive, in the sense that parameters which control the surface estimation are adjusted over geographic space, allowing for local variations in point pattern characteristics.