PubMed Health⌕ Search

Biomedical subjects

D Naylor

Publications and source records attributed to D Naylor.

At least 19 recordsLinked to original sources

Synapse-specific contribution of the variation of transmitter concentration to the decay of inhibitory postsynaptic currents.

Synaptic transmission is characterized by a remarkable trial-to-trial variability in the postsynaptic response, influencing the way in which information is processed in neuronal networks. This variability may originate from the probabilistic nature of quantal transmitter release, from the stochastic behavior of the receptors, or from the fluctuation of the transmitter concentration in the cleft. We combined nonstationary noise analysis and modeling techniques to estimate the contribution of transmitter fluctuation to miniature inhibitory postsynaptic current (mIPSC) variability. A substantial variability (approximately 30%) in mIPSC decay was found in all cell types studied (neocortical layer2/3 pyramidal cells, granule cells of the olfactory bulb, and interneurons of the cerebellar molecular layer). This large variability was not solely the consequence of the expression of multiple types of GABA(A) receptors, as a similar mIPSC decay variability was observed in cerebellar interneurons that express only a single type (alpha(1)beta(2)gamma(2)) of GABA(A) receptor. At large synapses on these cells, all variance in mIPSC decay could be accounted for by the stochastic behavior of approximately 36 pS channels, consistent with the conductance of alpha(1)beta(2)gamma(2) GABA(A) receptors at physiological temperatures. In contrast, at small synapses, a significant amount of variability in the synaptic cleft GABA transient had to be present to account for the additional variance in IPSC decay over that produced by stochastic channel openings. Thus, our results suggest a synapse-specific contribution of the variation of the spatiotemporal profile of GABA to the decay of IPSCs.

Animals↗

In the queue for coronary artery bypass grafting: patients' perceptions of risk and 'maximal acceptable waiting time'.

OBJECTIVES: To elicit patients' maximal acceptable waiting times (MAWT) for non-urgent coronary artery bypass grafting (CABG), and to determine if MAWT is related to prior expectations of waiting times, symptom burden, expected relief, or perceived risks of myocardial infarction while waiting. METHODS: Seventy-two patients on an elective CABG waiting list chose between two hypothetical but plausible options: a 1-month wait with 2% risk of surgical mortality, and a 6-month wait with 1% risk of surgical mortality. Waiting time in the 6-month option was varied up if respondents chose the 6-month/lower risk option, and down if they chose the 1-month/higher risk option, until the MAWT switch point was reached. Patients also reported their expected waiting time, perceived risks of myocardial infarction while waiting, current function, expected functional improvement and the value of that improvement. RESULTS: Only 17 (24%) patients chose the 6-month/1% risk option, while 55 (76%) chose the 1-month/2% risk option. The median MAWT was 2 months; scores ranged from 1 to 12 months (with two outliers). Many perceived high cumulative risks of myocardial infarction if waiting for 1 (upper quartile, > or = 1.45%) or 6 (upper quartile, > or = 10%) months. However, MAWT scores were related only to expected waiting time (r = 0.47; P < 0.0001). CONCLUSIONS: Most patients reject waiting 6 months for elective CABG, even if offered along with a halving in surgical mortality (from 2% to 1%). Intolerance for further delay seems to be determined primarily by patients' attachment to their scheduled surgical dates. Many also have severely inflated perceptions of their risk of myocardial infarction in the queue. These results suggest a need for interventions to modify patients' inaccurate risk perceptions, particularly if a scheduled surgical date must be deferred.

Adult↗

A comparison of statistical learning methods on the Gusto database.

We apply a battery of modern, adaptive non-linear learning methods to a large real database of cardiac patient data. We use each method to predict 30 day mortality from a large number of potential risk factors, and we compare their performances. We find that none of the methods could outperform a relatively simple logistic regression model previously developed for this problem.

Databases as Topic↗

Socio-economic status and visits to physicians by adults in Ontario, Canada.

OBJECTIVES: To examine the association between socio-economic status, need for medical care and visits to physicians in a universal health insurance system. METHODS: Cross-sectional analysis of the 1990 Ontario Health Survey, a population-based survey utilizing a multi-stage, randomized cluster sample. The analysis considered only those respondents who were 16 years of age or older from the province of Ontario, Canada: 21,272 males and 24,738 females. RESULTS: There was no difference by education or income in persons having made at least one visit to a general practitioner in the previous year. High income persons were less likely to have made six or more visits to a general practitioner--odds ratio (OR) = 0.67, 95% CI = 0.52, 0.87 for men; OR = 0.66, 95% CI = 0.58, 0.75 for women--but more likely to have made at least one visit to a specialist--OR = 1.42, 95% CI = 1.15, 1.76 for men; OR = 1.25, 95% CI = 1.07, 1.45 for women. A person's need for medical care was the most important determinant of a physician visit. CONCLUSIONS: Self-reported visits to general practitioners in Canada are strongly influenced by a person's need for medical care and are appropriately related to socio-economic status. However, there is a residual association between higher socio-economic levels and greater use of specialist services.

Adolescent↗

Alanine scan and N-methyl amide derivatives of Ac-bombesin[7-14]. Development of a proposed binding conformation at the neuromedin B (NMB) and gastrin releasing peptide (GRP) receptors.

Alanine and N-methylation scans together with molecular modelling were implemented in order to propose a binding conformation of the minimum active fragment of bombesin (BB), Ac-BB[7-14], to the gastrin releasing peptide (GRP) and neuromedin B (NMB) receptors. These data are also used to critically evaluate the previously proposed binding conformations such as alpha-helix and antiparallel beta-sheets. This shows that the previously reported conformations do not satisfy the experimental data. A new binding conformation of Ac-BB[7-14] is proposed consisting of three consecutive gamma-turns followed by a bend and finishing with two gamma-turns. This low energy conformation (analogous to a fragment of thymidylate synthase, 2TSC) of bombesin stabilized by five internal hydrogen bonds, and with the side chains of residues Trp8 and Leu13 held on the same side of the peptide, is in agreement with the experimentally observed data. This and the results of molecular modelling may aid in the synthesis of conformationally restricted high affinity bombesin analogues and/or high affinity template-based GRP or NMB receptor agonists and antagonists.

Amides↗

Quantitative structure-activity relationships (QSARs) of N-terminus fragments of NK1 tachykinin antagonists: a comparison of classical QSARs and three-dimensional QSARs from similarity matrices.

The ability of three-dimensional quantitative structure-activity relationships (QSARs) derived from classical QSAR descriptors and similarity indices to rationalize the activity of 28 N-terminus fragments of tachykinin NK1 receptor antagonists was examined. Two different types of analyses, partial least squares and multiple regression, were performed in order to check the robustness of each derived model. The models derived using classical QSAR descriptors lacked accurate quantitative and predictive abilities to describe the nature of the receptor-inhibitor interaction. However models derived using 3D QSAR descriptors based on similarity indices were both robust and significantly predictive. The best model was obtained through the statistical analysis of molecular field similarity indices (n = 28, r2 = 0.846, r(cv)2 = 0.737, s = 0.987, PRESS = 7.102) suggesting that electronic and size-related properties are the most relevant in explaining the affinity data of the training set. The overall quality and predictive ability of the models applied to the test set appear to be very high, since the predicted affinities of three test compounds agree with the experimentally determined affinities obtained subsequently within the experimental error of the binding data.

Carbamates↗

MAMBAs: a real-time graphics environment for QSAR.

MAMBAs (Multivariate Analysis Methods in Biomechanistic Activity Studies) is an integrated workstation-based graphics program designed for the investigation of quantitative structure activity relationships (QSAR). It combines many of the commonly used statistical techniques with an extensive database of substituent constants, a variety of molecular and substituent property calculations and detailed graphics-based table and graph editors. Graphical representations of standard substituent generation and optimization techniques are also included. These are all utilized within a state-of-the-art real-time graphics environment.

Computer Graphics↗

Neural network feature detector for real-time video signal processing.

The application of artificial neural networks to real-time image processing tasks requires the use of dedicated, high performance hardware. A linear array processor called HANNIBAL has been developed which implements the backpropagation neural learning algorithm on-chip. This paper considers the design of a complete neural system which integrates HANNIBAL into an existing image processing environment. The goals for the design of the system have been set partly by the primary application, namely feature recognition, but mainly by the desire for a flexible, high performance hardware tool for the study and evaluation of range of neural image processing applications.

Algorithms↗

Unexpected dystocia secondary to a fetal sacrococcygeal teratoma: a successful outcome.

Sacrococcygeal teratoma is a rare cause of dystocia. With recent advances in perinatal care, particularly the increasing use of maternal ultrasound, it is unlikely that unexpected dystocia secondary to this tumor will be seen by many physicians. Recent reports of this type of dystocia are rare and infant mortality secondary to it is high. However, if and when encountered, such dystocia need not imply a bad prognosis for either mother or infant. This is a report of successful management of one case as well as a presentation of recently reported cases and recommendations for management.

Adult↗

Allocation of health care resources: a challenge for the medical profession.

If current limitations on health care funding continue, medical practitioners will face increasing pressure to conserve scarce resources and to participate in the allocation of funds. This article discusses the ethical and economic aspects of the physician's role and briefly reviews some efficiency measures that might mitigate the effects of rationing of health care services.

Canada↗

Reducing distress in pediatric cardiac catheterization.

To examine the efficacy of rehearsal in reducing distress in 3- to 6-year-old children undergoing diagnostic cardiac catheterization, 40 children were assigned randomly to the rehearsal preparation procedure or to usual preparation. The rehearsal program involved the use of behavioral rehearsal in the catheterization laboratory, manuals to explain the procedure to the parents, and coloring books to provide parents and children with a vicarious experience of catheterization. Rehearsed patients cried, yelled for mother, complained of pain less, and showed lower rates of motor activity than did control patients. Rehearsed patients also showed less overt regressive, aggressive, and anxiety behaviors at home following the catheterization than did controls. Parents in the rehearsed group showed less anxiety following the catheterization, and negative reactions in children correlated significantly with parental anxiety. Participants' reactions were uniformly more positive in the rehearsed than in the control patients.

Anxiety↗