Showing papers by "University of Leicester published in 1995"

Consensus methods for medical and health services research.

Abstract: Health providers face the problem of trying to make decisions in situations where there is insufficient information and also where there is an overload of (often contradictory) information. Statistical methods such as meta-analysis have been developed to summarise and to resolve inconsistencies in study findings—where information is available in an appropriate form. Consensus methods provide another means of synthesising information, but are liable to use a wider range of information than is common in statistical methods, and where published information is inadequate or non-existent these methods provide a means of harnessing the insights of appropriate experts to enable decisions to be made. Two consensus methods commonly adopted in medical, nursing, and health services research—the Delphi process and the nominal group technique (also known as the expert panel)—are described, together with the most appropriate situations for using them; an outline of the process involved in undertaking a study using each method is supplemented by illustrations of the authors' work. Key methodological issues in using the methods are discussed, along with the distinct contribution of consensus methods as aids to decision making, both in clinical practice and in health service development. This is the sixth in a series of seven articles describing non-quantitative techniquesand showing their value in health research Quantitative methods such as meta-analysis have been developed to provide statistical overviews of the results of clinical trials and to resolve inconsistencies in the results of published studies. Consensus methods are another means of dealing with conflicting scientific evidence. They allow a wider range of study types to be considered than is usual in statistical reviews. In addition they allow a greater role for the qualitative assessment of evidence (box 1). These methods, unlike those described in the other papers in this series, are primarily concerned with deriving quantitative estimates through qualitative …

Reaching the parts other methods cannot reach: an introduction to qualitative methods in health and health services research.

Abstract: Qualitative research methods have a long history in the social sciences and deserve to be an essential component in health and health services research. Qualitative and quantitative approaches to research tend to be portrayed as antithetical; the aim of this series of papers is to show the value of a range of qualitative techniques and how they can complement quantitative research. Medical advances, increasing specialisation, rising patient expectations, and the sheer size and diversity of health service provision mean that today's health professionals work in an increasingly complex arena. The wide range of research questions generated by this complexity has encouraged the search for new ways of conducting research. The rapid expansion of research on and about health and health services, and the relatively recent demarcation of a distinct field of “health services research” depend heavily on doctors and other health professionals being investigators, participants, and peer reviewers. Yet some of the most important questions in health services concern the organisation and culture of those who provide health care, such as why the findings of randomised controlled trials are often difficult to apply in day to day clinical practice. The social science methods appropriate to studying such phenomena are very different from the methods familiar to many health professionals. Although the more qualitative approaches found in certain of the social sciences may seem alien alongside the experimental, quantitative methods used in clinical and biomedical research, they should be an essential component of health services research--not just because they enable us to access areas not amenable to quantitative research, such as lay and professional health beliefs, but also because qualitative description is a prerequisite of good quantitative research, particularly in areas that have received little previous investigation. A good example of this is the study of the social consequences of the …

Phototyping: comprehensive DNA typing for HLA-A, B, C, DRB1, DRB3, DRB4, DRB5 & DQB1 by PCR with 144 primer mixes utilizing sequence-specific primers (PCR-SSP)

Abstract: We have developed a single DNA typing method which uses 144 sequence-specific primer (SSP) reactions to simultaneously detect all known HLA-A, B, C, DRB1, DRB3, DRB4, DRB5 and DQB1 specificities in an allele specific or group specific manner using the same method, reagents, PCR parameters and protocols for all loci. The results from this integrated class I & II method can be visualized on a single photographic or electronic image and hence is described as "Phototyping". Phototyping has an overall resolution greater than or equivalent to good serology and results can be obtained in under 3 hours making the method suitable for genotyping potential cadaver donor peripheral blood without serological backup. This in turn produces the potential for reducing cold ischaemia times in renal transplantation as well as the application of prospective matching to cardiac and liver transplantation. The method has capacity to detect new alleles, for example, novel amplification patterns suggestive of 4 new HLA-B alleles have been detected. The Phototyping set has been used as the sole method of HLA typing for over 1010 individuals. Phototyping is not problem-free; deviations from the standard protocol, poor quality DNA and unsuitable PCR machines can result in individual PCR failures or in incorrect assignment of antigens. Approximately 5% of genotypes were repeated (either partially or fully) because of incomplete or equivocal results.

Timing of Hot Spot—Related Volcanism and the Breakup of Madagascar and India

Abstract: Widespread basalts and rhyolites were erupted in Madagascar during the Late Cretaceous. These are considered to be related to the Marion hot spot and the breakup of Madagascar and Greater India. Seventeen argon-40/argon-39 age determinations reveal that volcanic rocks and dikes from the 1500-kilometer-long rifted eastern margin of Madagascar were emplaced rapidly (mean age = 87.6 ± 0.6 million years ago) and that the entire duration of Cretaceous volcanism on the island was no more than 6 million years. The evidence suggests that the thick lava pile at Volcan de l'Androy in the south of the island marks the focal point of the Marion hot spot at 88 million years ago and that this mantle plume was instrumental in causing continental breakup.

A protein catalytic framework with an N-terminal nucleophile is capable of self-activation

Abstract: The crystal structures of three amidohydrolases have been determined recently: glutamine PRPP amidotransferase (GAT), penicillin acylase, and the proteasome. These enzymes use the side chain of the amino-terminal residue, incorporated in a beta-sheet, as the nucleophile in the catalytic attack at the carbonyl carbon. The nucleophile is cysteine in GAT, serine in penicillin acylase, and threonine in the proteasome. Here we show that all three enzymes share an unusual fold in which the nucleophile and other catalytic groups occupy equivalent sites. This fold provides both the capacity for nucleophilic attack and the possibility of autocatalytic processing. We suggest the name Ntn (N-terminal nucleophile) hydrolases for this structural superfamily of enzymes which appear to be evolutionarily related but which have diverged beyond any recognizable sequence similarity.

Modulation by mu-opioid agonists of guanosine-5'-O-(3-[35S]thio)triphosphate binding to membranes from human neuroblastoma SH-SY5Y cells

Abstract: The ability of mu-opioid agonists to activate G proteins has been demonstrated by studying the binding of the GTP analogue guanosine-5'-O-(3-[35S]thio)triphosphate ([35S]GTP gamma S) to membranes from the human neuroblastoma SH-SY5Y cell line. The potent opioid agonist fentanyl caused an approximate doubling of basal [35S]GTP gamma S binding in a naloxone-sensitive manner, confirming this to be an opioid receptor-mediated process. The presence of GDP was necessary to observe this effect. Pretreatment of the cells with pertussis toxin (100 ng/ml, for 24 hr) completely prevented the fentanyl-stimulated increase in [35S]GTP gamma S binding and lowered the basal binding of [35S]GTP gamma S. These latter data suggest an involvement of Gi and/or Go proteins and their activation by added membrane-bound receptors even in the absence of agonist. The order of potency of a series of opioid agonists in stimulating the binding of [35S]GTP gamma S was buprenorphine > cyclazocine = levallorphan > nalorphine > [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAMGO) > fentanyl > morphine > pentazocine. DAMGO, fentanyl, and morphine were full agonists but the remaining compounds showed decreasing levels of intrinsic activity in the order buprenorphine > pentazocine > cyclazocine = nalorphine > levallorphan. The opioid antagonist naloxone was without effect. Under the conditions of the [35S]GTP gamma S assay, binding of agonists was to a high affinity site, indicating that a high agonist affinity state of the mu-opioid receptor is responsible for the observed stimulation of [35S]GTP gamma S binding. The level of [35S]GTP gamma S binding (597 fmol/mg of protein) stimulated by DAMGO was 2-fold greater than the maximal number of mu-opioid agonist binding sites (Bmax) determined using [3H]DAMGO (254 fmol/mg of protein). The opioid agonist-mediated stimulation of [35S]GTP gamma S binding in SH-SY5Y cell membranes thus provides a "functional" measure of agonist occupation of mu-opioid receptors and offers a simple method for the determination of efficacy and intrinsic activity of mu-opioid agonists.

A potential vulnerability locus for schizophrenia on chromosome 6p24–22: evidence for genetic heterogeneity

Abstract: In 265 Irish pedigrees, with linkage analysis we find evidence for a vulnerability locus for schizophrenia in region 6p24-22 The greatest lod score, assuming locus heterogeneity, is 351 (P = 00002) with D6S296 Another test, the C test, also supported linkage, the strongest results being obtained with D6S296 (P = 000001), D6S274 (P = 0004) and D6S285 (P = 0006) Non-parametric analysis yielded suggestive, but substantially weaker, findings This locus appears to influence the vulnerability to schizophrenia in roughly 15 to 30% of our pedigrees Evidence for linkage was maximal using an intermediate phenotypic definition and declined when this definition was narrowed or was broadened to include other psychiatric disorders

Geochemical Evidence for Subduction Fluxes, Mantle Melting and Fractional Crystallization Beneath the South Sandwich Island Arc

Abstract: The volcanoes of the South Sandwich island arc follow three distinct series: low-K tholeiitic (followed by Zavodovski, Candlemas, Vindication, Montagu and Bristol), tholeiitic (followed by Visokoi, Sounders and Bellinghausen) and calcalkaline (followed by Ltskov, Freezland and part of Cook and Thule). Flux calculations indicate that the percentage contribution of the subduction component to the mantle source of all three series varies from undetectable (e.g. Zr) through small (e.g. Nd=20%) and moderate (e.g. La, Ce, Sr = 50-80%) to dominant (e.g. Pb, K, Ba, Rb, Cs >90%) with little change along the arc. Isotope systematics (Pb, Nd, Sr) show that this subduction component obtains a greater contribution from altered oceanic crust than from pelagic sediment. Elements for which the subduction contribution is small show that the mantle is already depleted relative to N-MORB mantle (equivalent to loss of an ~2-5% melt fraction) before melting beneath the arc. After addition of the subduction component, dynamic melting of this depleted mantle then causes the variationsin K that distinguish the three series. The estimated degree of partial melting (~20%) is slightly greater than that beneath ocean ridges, though geothermometry suggests that the primary magma temperature (~1225°C) is similar to that of primary MORB. About half of the melting may be attributed to volatile addition, and half to decompression. Dynamic melting involving three-dimensional, two-phase flow may be needed to explain fully the inter-island variations.

A lunar occultation and direct imaging survey of multiplicity in the Ophiuchus and Taurus star-forming regions

Abstract: We present an IR lunar occultation and direct imaging search for companions in the Ophiuchus star-forming region and update a similar search of the Taurus region. The search is sensitive to companions in the angular separation range 0.005-10 sec. In Ophiuchus, we surveyed 35 young star targets; this sample contains at least 10 binaries, two triples, and one quadruple. Ten of the companion stars are newly discovered. In Taurus, the survey now includes 47 systems among which there are at least 22 binaries and four triples. Only two companion stars are newly identified because there is strong overlap with prior work. All the triples and quadruple are hierarchical. The observed binary frequency in Ophiuchus, in the 3-1400 AU range of separations, is at least 1.1 +/- 0.3 that of the nearby solar-like stars. This value is a lower bound because we make no corrections for incompleteness. In Taurus, in the same range of separations, the observed binary frequency is at least 1.6 +/- 0.3 that of the nearby solar-like stars. This value extends Ghez et al.'s (1993) and Leinert's et al.'s (1993) determination of an excess binary frequency to 3 AU separation. We used the weak-line T Tauri star/T Tauri star (WT/TT) type and the K-L color index to distinguish between systems with and without inner disks. We find no convincing difference in the binary frequency or distribution of separations of the systems with and without inner disks. The 1.3 mm continuum emission of the single systems exceeds that of the multiples suggesting that their extensive outer disks are more massive. The specific angular momenta of the binaries overlap those of molecular cloud cores measured by Goodman et al. (1993).

Two voltage-dependent K+ conductances with complementary functions in postsynaptic integration at a central auditory synapse

Abstract: The medial nucleus of the trapezoid body (MNTB) relays auditory information important for sound source localization. MNTB neurons faithfully preserve the temporal patterning of action potentials (APs) occurring in their single giant input synapse, even at high frequencies. The aim of this work was to examine the postsynaptic potassium conductances that shape the transfer of auditory information across this glutamatergic synapse. We used whole cell patch techniques to record from MNTB neurons in thin slices of rat brainstem. Two types of potassium conductance were found which had a strong influence on an MNTB neuron's postsynaptic response. A small low voltage threshold current, Id, limited the response during each EPSP to a single brief AP. Id was specifically blocked by dendrotoxin (DTX), resulting in additional APs during the tail end of the EPSP. Thus DTX degraded the temporal fidelity of synaptic transmission, since one presynaptic AP then led to several postsynaptic APs. A second conductance was a fast delayed rectifier with a high voltage activation threshold, that rapidly repolarised APs and thus facilitated high frequency AP responses. Together, these two conductances allow high frequency auditory information to be passed accurately across the MNTB relay synapse and separately, such conductances may perform analogous functions elsewhere in the nervous system.

Satisfying solutions? A review of some unresolved issues in the measurement of patient satisfaction

Abstract: The measurement of patient satisfaction has been encouraged by a growing consumer orientation in health care, especially since it yields information about consumers' views in a form which can be used for comparison and monitoring. However, drawing on literature from a variety of sources, this paper suggests that there remain several unresolved issues relating to the measurement of satisfaction, and some serious questions about the validity of the concept. It is argued that current approaches to measuring satisfaction may not be grounded in the values and experiences of patients; therefore satisfaction surveys could be denying patients the opportunity to have their opinions included in the planning and evaluation of health care services.

Neuronal Ca2+ stores : activation and function

Abstract: The intracellular concentration of free Ca2+ ([Ca2+]i) displays complex fluctuations in response to a variety of stimuli, and acts as a pluripotent signal for many neuronal functions. It is well established that various 'metabotropic' neurotransmitter receptors can mediate the mobilization of Ca2+ stores via actions of inositol-polyphosphate second messengers, and more recent evidence suggests that 'ionotropic' receptor-mediated Ca2+ signals in neurones might also involve release of Ca2+ from intracellular stores. These two mechanisms of release of Ca2+ enable considerable temporal and spatial complexity of increases in the [Ca2+]i via multiple interactions at the level of intracellular-receptor activation. The complexity of Ca2+ signalling that is elicited via these interconnecting pathways might underlie mechanisms that are central to information transfer and integration within neuronal compartments.

Angiotensin II Increases Vascular Permeability Factor Gene Expression by Human Vascular Smooth Muscle Cells

Abstract: Angiotensin II (Ang II) has been implicated in the pathogenesis of the vascular injury associated with hypertension and diabetes mellitus. Increased vascular permeability is an important early manifestation of endothelial dysfunction and the pathogenesis of atherosclerosis. How Ang II contributes to endothelial dysfunction and promotes an increase in vascular permeability is unknown but is classically attributed to its pressor actions. We demonstrate that human vascular smooth muscle cells express abundant mRNA for vascular permeability/endothelial growth factor. Vascular permeability factor is a 34- to 42-kD glycoprotein that markedly increases vascular endothelial permeability and is a potent endothelial mitogen. Ang II potently induced a concentration-dependent (maximal, 10(-7) mol/L) and time-dependent increase in vascular permeability factor mRNA expression by human vascular smooth muscle cells that was maximal after 3 hours and diminished by 24 hours. Ang II-induced vascular permeability factor mRNA expression by human vascular smooth muscle cells was inhibited by the specific Ang II receptor antagonist losartan (DuP 753), confirming that this is an Ang II receptor subtype 1-mediated event. These results describe a new action of Ang II on human vascular smooth muscle, notably the induction of vascular permeability factor mRNA expression. The wide spectrum and potent activity of vascular permeability factor suggest a novel mechanism whereby Ang II could locally and directly influence the permeability, growth, and function of the vascular endothelium independent of changes in hemodynamics.

A major house dust mite allergen disrupts the immunoglobulin E network by selectively cleaving CD23: innate protection by antiproteases

Abstract: Asthma is a chronic life-threatening disease of worldwide importance. Although allergic asthma and related atopic conditions correlate strongly with immune sensitization to house dust mites, it is unclear why antigens from mites provoke such powerful allergic immune responses. We have characterized the protease activity of Der p I, the group I protease allergen of the house dust mite Dermatophagoides pteronyssinus, and here report that it cleaves the low-affinity immunoglobulin (Ig) E Fc receptor (CD23) from the surface of human B lymphocytes. Der p I selectively cleaves CD23 and has no effect on the expression of any other B cell surface molecules tested. We speculate that this loss of cell surface CD23 from IgE-secreting B cells may promote and enhance IgE immune responses by ablating an important feedback inhibitory mechanism that normally limits IgE synthesis. Furthermore, since soluble CD23 is reported to promote IgE production, fragments of CD23 released by Der p I may directly enhance the synthesis of IgE. alpha 1-Antiprotease, a pulmonary antiprotease, is also shown to inhibit the cleavage of CD23 by Der p I. This may be significant in the etiopathogenesis of asthma, because other indoor pollutants associated with asthma are known to potently inhibit this antiprotease. These data suggest that the proteolytic activity of Der p I, the group I allergen of the house dust mite D. pteronyssinus, is mechanistically linked to the potent allergenicity of house dust mites. Furthermore, inhibition of Der p I by alpha 1-antiprotease suggests a mechanism by which confounding factors, such as tobacco smoke, may act as a risk factor for allergic asthma.

The role of hyaluronan in tumour neovascularization (review).

Abstract: Tumour growth and metastasis are totally dependant upon neovascularization. The target cell for tumour neovascularization is the blood-vessel endothelial cell, and specific angiogenic molecules produced or induced by the tumour are believed to initiate the process. In this report, we review one of these angiogenic molecules, the glycosaminoglycan hyaluronan (HA), which appears to have differing roles in neovascularization depending on its molecular mass. High-molecular-mass HA is anti-angiogenic whereas oligosaccharides of HA, of specific size, actively stimulate endothelial-cell proliferation and migration, 2 of the key events associated with neovascularization, and induce angiogenesis in vivo. We provide details of the action of HA oligosaccharides on endothelial cells, from binding to cell-surface receptors, through activation of signal transduction pathways and gene expression to protein synthesis, cell proliferation and cell migration. We also suggest a model to account for HA of differing molecular mass being present, at different locations, within a single tumour and how this HA aids both general tumour growth and tumour metastasis.

Interferon expression in the pancreases of patients with type I diabetes.

Abstract: We have used a reverse transcriptase-polymerase chain reaction (RT-PCR) protocol to examine the expression of cytokines in the pancreases and islets of patients with type I diabetes. We detect a significant increase in the level of expression of interferon (IFN)-alpha in the pancreases of the diabetic patients as compared with the control pancreases. In contrast, IFN-beta was detected at comparable levels in both groups, while IFN-gamma was detected in three of four control pancreases and one of four pancreases from the diabetic individuals. The IFN-alpha cDNAs generated by the RT-PCR were cloned and sequenced to determine which alpha-subtypes were being expressed. We found that the repertoire of subtypes was quite limited in any one individual (diabetic or not), although each individual was different with respect to the pattern of subtypes expressed. We also examined these pancreases for the expression of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-2, IL-4, and IL-6. We found no detectable expression of TNF-alpha or IL-2 in any pancreases, and the expression of the other cytokines was variable, with no pattern emerging from the comparison of the diabetic and nondiabetic individuals. We conclude that, of the cytokines examined, only IFN-alpha was significantly increased in the diabetic patients, a result that is consistent with the possibility that this cytokine is directly involved in the development of type I diabetes.

Hydrogen peroxide does not function downstream of salicylic acid in the induction of PR protein expression

Abstract: The roles of salicylic acid (SA) and H2O2 in the induction of PR proteins in tobacco have been examined. Studies were conducted on wild-type tobacco and plants engineered to express a bacterial salicylate hydroxylase capable of metabolizing SA to catechol (SH-L plants). Wild-type and PR-1a-GUS-transformed plants express PR-1a following challenge with Pseudomonas syringae pathovar syringae, SA or 2,6-dichloro-isonicotinic acid (INA). In contrast, SH-L plants failed to respond to SA but did express PR-1a following INA treatment. H2O2 and the irreversible catalase inhibitor 3-amino-1,2,4-triazole (3-AT) were found to be weak inducers of PR-1a expression (relative to SA) in wild-type tobacco but were unable to induce PR-1a in SH-L plants, suggesting that the action of these compounds depends upon the accumulation of SA. A model has been proposed suggesting that SA binds to and inhibits a catalase inducing an increase in H2O2 leading to PR protein expression. Catalase activity has been measured in tobacco and no significant changes in activity following infection with P. syringae pv. syringae were detected. Furthermore, inhibition of catalase activity in vitro in plant extracts requires pre-incubation and only occurs at SA concentrations above 250 microM. Leaf disks preincubated with 1 mM SA do accumulate SA to these levels and PR-1a is efficiently induced but there is no apparent inhibition of catalase activity. It is also shown that a SA-responsive gene, PR-1a, and a H2O2-sensitive gene, AoPR-1, are both relatively insensitive to 3-AT suggesting that induction of these genes is unlikely to be due entirely to inhibition of an endogenous catalase.

Pre- and postsynaptic glutamate receptors at a giant excitatory synapse in rat auditory brainstem slices.

Abstract: 1. Whole-cell patch recordings were used to examine the EPSC generated by the calyx of Held in neurones of the medial nucleus of the trapezoid body (MNTB). Each neurone receives a somatic input from a single calyx (giant synapse). 2. A slow NMDA receptor-mediated EPSC peaked in 10 ms and decayed as a double exponential with time constants of 44 and 147 ms. A fast EPSC had a mean rise time of 356 microseconds (at 25 degrees C), while the decay was described by a double exponential with time constants of 0.70 and 3.43 ms. 3. Cyclothiazide slowed the decay of the fast EPSC, indicating that it is mediated by AMPA receptors. The slower time constant was slowed to a greater extent than the faster time constant. Cyclothiazide potentiated EPSC amplitude, partly by a presynaptic mechanism. 4. The metabotropic glutamate receptor (mGluR) agonists, 1S,3S-ACPD, 1S,3R-ACPD and L-2-amino-4-phosphonobutyrate (L-AP4) reversibly depressed EPSC amplitude. A dose-response curve for 1S,3S-ACPD gave an EC50 of 7 microM and a Hill coefficient of 1.2. 5. Analysis of the coefficient of variation ratio showed that the above mGluR agonists acted presynaptically to reduce the probability of transmitter release. Adenosine and baclofen also depressed transmission by a presynaptic mechanism. 6. alpha-Methyl-4-carboxyphenylglycine (MCPG; 0.5-1 mM) did not antagonize the effects of 1S,3S-ACPD, while high concentrations of L-2-amino-3-phosphonopropionic acid (L-AP3; 1 mM) and 4-carboxy-3-hydroxyphenyglycine (4C3HPG; 500 microM) depressed transmission. 7. There was a power relationship between [Ca2+]o and EPSC amplitude with co-operativity values ranging from 1.5 to 3.4. 8. The mechanism by which mGluRs modulate transmitter release appeared to be independent of presynaptic Ca2+ or K+ currents, since ACPD caused no change in the level of paired-pulse facilitation or the duration of the presynaptic action potential (observed by direct recording from the terminal), indicating that the presynaptic mGluR transduction mechanism may be coupled to part of the exocytotic machinery. 9. Our data are not consistent with the presence at the calyx of Held of any one known mGluR subtype. Comparison of the time course and pharmacology of the fast EPSC with data from cloned AMPA receptors is consistent with the idea that GluR-Do subunits dominate the postsynaptic channels.

Junggar, Turfan and Alakol basins as Late Permian to ?Early Triassic extensional structures in a sinistral shear zone in the Altaid orogenic collage, Central Asia

Abstract: The Junggar, Turfan and Alakol basins in northwestern China and Kazakhstan formed as Late Permian to ?Early Triassic extensional structures in a broad sinistral shear zone between large strike-slip faults that separate two main domains of the Altaid orogenic collage. This extension was in response to an inferred large (> l000 km) sinistral motion of the East European craton with respect to the Angaran craton during this time. Deformation associated with the formation of the basins was taken up in part by counter-clockwise rotations of crustal blocks with respect to the Altaid orogenic collage and to the Angaran craton. This event is the only important phase of extension in a region otherwise dominated by compressional tectonics throughout the Phanerozoic. The basement rocks of these basins formed by Altaid subduction–accretion through the latter half of the Palaeozoic and the region was subsequently thrown into compression again during the Mesozoic Cimmeride and Cenozoic Alpide evolution.

Climate and the distribution of Fallopia japonica: use of an introduced species to test the predictive capacity of response surfaces

Abstract: . The relationship between present climate and the distribution in Europe of the aggressively invasive exotic Fallopia japonica is described by fitting a response surface based on three bioclimatic variables: mean temperature of the coldest month, the annual temperature sum > 5 °C, and the ratio of actual to potential evapotranspiration. The close fit between the observed and simulated distributions suggests that the species' European distribution is climatically determined. The response surface also provides a simulation of the extent of the area of native distribution of F. japonica in Southeast Asia that is generally accurate, confirming the robustness of the static correlative model upon which it is based. Simulations of the potential distribution of F. japonica under two alternative 2 x CO2 climate change scenarios indicate the likelihood of considerable spread into higher latitudes and possible eventual exclusion of the species from central Europe. However, despite the robustness of the response surface with present-day climate, the reliability of these simulations as forecasts is likely to be limited because no account is taken of the direct effects of CO2 and their interaction with the species' physiological responses to climate. Similarly, no account is taken of the potential impact of interactions with ‘new’ species as ecosystems change in composition in response to climate change. Nevertheless, the simulations indicate both the possible magnitude of the impacts of forecast climate changes and the regions that may be susceptible to invasion by F. japonica.

The Role of Pneumolysin and Autolysin in the Pathology of Pneumonia and Septicemia in Mice Infected with a Type 2 Pneumococcus

Abstract: Mice were infected intranasally with a serotype 2 pneumococcus, a pneumolysin-negative derivative (PLN-A), or an autolysin-negative derivative (AL-2). Numbers of wild type pneumococci were seen in the lung from approximately 12 h after infection and were first detected in the blood around this time. Immunofluorescent staining of lung sections showed that pneumolysin was produced in vivo. Pneumococcal infection resulted in alteration of the composition of the blood but not the bone marrow. Some of the hematologic changes did not occur after PLN-A. PLN-A had a slower growth rate in the lung and bacteremia was delayed. AL-2 was rapidly cleared from the lungs and was not detected in the blood. These events paralleled the pattern of histology in the lung, with the severity of inflammation reduced with PLN-A and no inflammation or hematologic changes with AL-2.

What type of general practice do patients prefer? Exploration of practice characteristics influencing patient satisfaction

Abstract: BACKGROUND: General practice is currently experiencing a large number of developments. Studies of patient satisfaction are required to guide the changes that many general practitioners are introducing. AIM: A study set out to examine the characteristics of general practices that influence patient satisfaction. METHOD: In 1991-92, a surgery satisfaction questionnaire of demonstrated reliability and validity was administered to 220 patients in each of 89 general practices. A further questionnaire completed by a member of practice staff collected information about practice characteristics including total list size, number, age and sex of practice partners, training status, fundholding status, presence of a practice manager and whether there was a personal list system. Stepwise multiple regression analyses were undertaken to identify those practice characteristics that influenced patient satisfaction. RESULTS: The mean of the response rates of patients completing questionnaires in each practice was 82%. An increasing total list size of patients registered with practices was associated with decreasing levels of general satisfaction and decreased satisfaction with accessibility, availability, continuity of care, medical care and premises. The presence of a personal list system was associated with increased levels of general satisfaction and increased satisfaction with accessibility, availability, continuity of care and medical care. Training practices were associated with decreased levels of general satisfaction and decreased satisfaction with availability and continuity of care. CONCLUSION: The patients of practices in this study preferred smaller practices, non-training practices and practices that had personal list systems. Practice organization should be reviewed in order to ensure that the trend towards larger practices that provide a wider range of services does not lead to a decline in patient satisfaction. General practitioners should have personal list systems and consider the creation of several personal teams within the practice consisting of small numbers of doctors, receptionists and practice nurses.

Modelling the Errors in Areal Interpolation between Zonal Systems by Monte Carlo Simulation

Abstract: Areal interpolation involves the transfer of data (often socioeconomic statistics and especially population data) from one zonation of a region to another, where the two zonations are geographically incompatible. This process is inevitably imprecise and is subject to a number of possible errors depending on the assumptions inherent in the methods used. Previous analysts have had only limited information with which to compare the results of interpolation and so assess the errors. In this paper a Monte Carlo simulation method based on modifiable areal units is employed. This allows multiple interpolations of population to be conducted from a single set of source zones to numerous sets of target zones. The properties of the full error distribution associated with a particular interpolation model can then be examined. The method based on dasymetric mapping consistently gave the highest accuracy of those tested, whereas the areal weighting method gave the lowest. More important than the results presented is th...

The Average X-Ray/Gamma-Ray Spectra of Seyfert Galaxies From Ginga and OSSE and the Origin of the Cosmic X-Ray Background

Abstract: We have obtained the first average 2-500 keV spectra of Seyfert galaxies, using the data from Ginga and Compton Gamma-Ray Observatory's (CGRO) Oriented Scintillation Spectrometer Experiment (OSSE). Our sample contains three classes of objects with markedly different spectra: radio-quiet Seyfert 1's and 2's, and radio-loud Seyfert 1's. The average radio-quiet Seyfert 1 spectrum is well-fitted by a power law continuum with the energy spectral index alpha approximately equals 0.9, a Compton reflection component corresponding to a approximately 2 pi covering solid angle, and ionized absorption. There is a high-energy cutoff in the incident power law continuum: the e-folding energy is E(sub c) approximately equals 0.6(sup +0.8 sub -0.3) MeV. The simplest model that describes this spectrum is Comptonization in a relativistic optically-thin thermal corona above the surface of an accretion disk. Radio-quiet Seyfert 2's show strong netural absorption, and there is an indication that their X-ray power laws are intrinsically harder. Finally, the radio-loud Seyfert spectrum has alpha approximately equals 0.7, moderate neutral absorption E(sub C) = 0.4(sup +0.7 sub -0.2) MeV, and no or little Compton reflection. This is incompatible with the radio-quiet Seyfert 1 spectrum, and probably indicating that the X-rays are beamed away from the accretion disk in these objects. The average spectra of Seyferts integrated over redshift with a power-law evolution can explain the hard X-ray spectrum of the cosmic background.