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Biomedical subjects

M Crowder

Publications and source records attributed to M Crowder.

17 recordsLinked to original sources
PubMed2000

Control and statistical analysis of in vitro reporter gene assays.

The use of in vitro gene reporter assays is becoming increasingly widespread in biology and particularly in drug metabolism, where the need for rapid screening of novel compounds is a driving factor. There is, however, little standardization of technique in the control of such assays, nor in the interpretation of results. This leads to confusion in the literature, with the possibility of a single piece of data being interpreted by several different methods, potentially giving vastly differing results. We have developed a reporter gene assay methodology that controls for many biological and experimental variables in the system and allows the application of a mathematical model to determine statistical significance between groups. Use of this methodology, we feel, allows an accurate and reproducible method of analyzing in vitro reporter gene assay data and increases its value as a biological tool.

Animals↗
PubMed1998

Common genetic determinants of halothane and isoflurane potencies in Caenorhabditis elegans.

BACKGROUND: Genetics provides a way to evaluate anesthetic action simultaneously at the molecular and behavioral levels. Results from strains that differ in anesthetic sensitivity have been mixed in their support of unitary theories of anesthesia. Here the authors use the previously demonstrated large variation of halothane sensitivities in Caenorhabditis elegans recombinant inbred strains to assess the similarities of the determinants of halothane action with those of another volatile anesthetic, isoflurane. METHODS: The recombinant inbred strains, constructed from two evolutionarily distinct C. elegans lineages, were phenotyped. A coordination assay on agar quantified the sensitivity to the volatile anesthetics; median effective concentrations (EC50s) were calculated by nonlinear regression of concentration-response data and were correlated between the drugs for those strains tested in common. Genetic loci were identified by statistical association between EC50s and chromosomal markers. RESULTS: The recombinant inbred strains varied dramatically in sensitivity to halothane and isoflurane, with a 10-fold range in EC50s. Heritability estimates for each drug were imprecise but altogether high (49-80%). Halothane and isoflurane EC50s were significantly correlated (r=0.71, P < 10(-9)). Genetic loci controlling sensitivity were found for both volatile anesthetics; the most significant determinant colocalized on chromosome V. A smaller recombinant inbred strain study of ethanol-induced immobility segregated different genetic effects that did not correlate with sensitivity to either halothane or isoflurane. CONCLUSIONS: The genetic determinants driving the large variation in anesthetic sensitivity in these C. elegans recombinant inbred strains are very similar for halothane and isoflurane sensitivity.

Anesthetics, Inhalation↗
PubMed1997

A test for independence of competing risks with discrete failure times.

The identifiability problem in Competing Risks is well known. In particular, it implies that independent action or otherwise of the risks cannot be inferred from data alone. However, Crowder (1996) showed that, in the case of purely discrete failure times, an inference can be made. An algebraic criterion was derived which bears essentially on the independence in question. The condition was presented in a theoretical setting but it was pointed out that the quantities involved can be estimated from data and that, therefore, there is the potential to develop practical tests for the hypothesis of independence. It is the purpose of this paper to construct such a test.

Catheterization↗
PubMed1996

On assessing independence of competing risks when failure times are discrete.

The traditional approach to modelling for Competing Risks, via a multivariate distribution of latent failure times, is very natural for many applications but suffers from a well-documented problem of identifiability. However, the demonstrations of this problem in the literature apply to essentially continuous latent failure times where any atoms of probability in their distributions are not too intrusive. It is shown in this paper that for discrete failure times the classic results on the identifiability problem concerning the existence of equivalent independent risks are incomplete.

Equipment Failure↗
PubMed1995

Analysis of fracture toughness data.

In studies of the fracture toughness of irradiated weld metal, specimens are subjected to an increasing load. The test on any one specimen might be terminated by choice or because the specimen ruptures. Prior to termination, ductile tearing might or might not have occurred. The situation is thus basically one of competing risks, with different types of termination, but there are additional features. The major purpose of statistical analysis is to estimate probabilities concerning the values of "toughness" and crack length. The analysis has been based on a model developed for the joint survivor function of these quantities.

Humans↗
PubMed1986

Bowel function measurements of individuals with different eating patterns.

Bowel function was assessed in 51 subjects: 10 women and seven men who habitually consumed an omnivorous, vegetarian, or vegan diet. The subjects on these diets had a mean intake of fibre of 23 g, 37 g, and 47 g respectively. Mean transit times were variable and not significantly different between the groups. Vegans, however, had a greater frequency of defecation and passed softer stools. All measurements of bowel function were significantly correlated with total dietary fibre. As dietary fibre increased mean transit time decreased, stool frequency increased and the stools became softer. Men produced a greater quantity of softer, less formed faeces than women. During the luteal phase of the menstrual cycle women excreted harder stools and had a significantly longer mean transit time. The finding that mean transit time was more highly correlated with faecal form than any of the other bowel function measurements could be of practical importance.

Adolescent↗
PubMed1985

Assessment of the hot-plate antinociceptive test in mice. A new method for the statistical treatment of graded data.

The use of graded data from hot-plate antinociceptive tests is complicated by the problem of how to treat responses that are greater than the cut-off time. This paper describes a statistical procedure for analysis of antinociceptive data that circumvents this problem. The method is based upon the likelihood function and the data is assumed to follow a Weibull distribution. The technique can be implemented with the use of a computer and provides a more comprehensive assessment of antinociceptive data.

Analgesics↗
PubMed1985

Dietary fibre intakes of individuals with different eating patterns.

This study was undertaken to provide evidence of the variation in the diet necessary to incorporate a high fibre content. Food intakes were measured for seven days by 51 subjects who were either omnivores, vegetarians or vegans. Omnivores consumed the least fibre (23 g), vegetarians significantly more (37 g) and vegans the most (47 g). Men had higher intakes (44 g) than women (30.5 g). Vegans ate the most cereal fibre, but high intake of fibre by both vegetarian groups were due to their preference for unrefined foods, particularly bread. Higher intakes of vegetable fibre by both vegetarian groups were due to high consumption of pulses. Total dietary fibre was significantly related to cereal fibre. As the percentage of fibre increased, the percentage of energy derived from protein decreased. Fat contributed less energy (34 per cent) to the vegan than to the omnivore diet (41 per cent). This study showed that high fibre intake can be achieved on an omnivorous diet and the observation that high fibre diets are possible when the energy content is low, is of relevance to slimming regimes.

Adolescent↗
PubMed1977

Transitional care: a new approach to aftercare.

The transitional-care program incorporates the principles of behavior modification and group and family therapy in order to help recently discharged psychiatric patients maintain the positive changes that occurred in the hospital. Patients meet for approximately three hours a week, for up to 12 weeks, with nursing staff who worked with them while they were hospitalized. Each patient has an individual treatment program and goals, and during meetings with his team he discusses his progress and problems in meeting those goals. Staff members encourage patients to accept responsibility for each other and not to become too dependent on them. The program has been successful in preventing rehospitalization.

Adolescent↗
PubMed1975

The effect of weather on some infectious diseases.

For several years the Royal College of General Practitioners has been collecting data supplied by local doctors throughout Britain on some infectious diseases seen in their practices. We describe a method of computerisation of this information and statistical analyses. We are investigating the influence of external factors such as climate on the infectiousness of some diseases. A model is fitted involving a non homogeneous two-state Markov chain whose transition probabilities are governed by the explanatory data.

Adolescent↗
PubMedDate not supplied

An analysis of resistance times to infection under treatment.

A general model is proposed for the time taken by a subject to catch an infectious disease when there may be treatment intervention during the exposure time. Particular specifications are then made in order to apply the model to some recent data on the infectivity of whooping cough within the family.

Child↗
PubMedDate not supplied

Interactions between anticholinesterase poisoning and opioid analgesia and locomotion in mice.

Interactions between anticholinesterases and opioid drugs on antinociception and locomotor behaviour have been studied in the mouse. The anticholinesterase di-isopropylfluorophosphate (DFP) (1 mg/kg), pyridostigmine (1 mg/kg) and neostigmine (200 micrograms/kg) or drugs used to treat anticholinesterase poisoning (atropine, pralidoxime and diazepam) were not antinociceptive. DFP, at doses which produced marked neurotoxicity (2 mg/kg), produced antinociception which was not mediated by opioid receptors. The antinociceptive effects of alfentanil, but not fentanyl or morphine, were potentiated by DFP, whereas pyridostigmine and neostigmine were without effect. The potentiating activity of DFP was unaffected by atropine, pralidoxime and diazepam. DFP (1 mg/kg) produced a small degree of hypolocomotion whilst atropine and pralidoxime produced marked hyperlocomotion. Diazepam alone and with DFP, atropine, pralidoxime or opioid drugs produced marked motor incapacitation. Hyperlocomotion induced by morphine and alfentanil was reduced by DFP but fentanyl hyperlocomotion was unaffected. Treatment of DFP toxicity with atropine and pralidoxime reversed the effects on alfentanil locomotion but failed to alter DFP's action upon morphine or fentanyl locomotion. Atropine and pralidoxime treatment alone did not affect fentanyl hyperlocomotion, attenuated alfentanil hyperlocomotion and produced marked hypolocomotion in morphine-treated mice. Opioids and anticholinesterases do not exhibit common interactions and their effects are dependent on both opioid, anticholinesterase and the behaviour studied.

Alfentanil↗