Biomedical subjects

N T Longford

Publications and source records attributed to N T Longford.

8 recordsLinked to original sources

PubMed2002

Effects of fatigue on the torque-velocity relation in muscle.

BACKGROUND: The extent to which fatigue is related to the velocity of shortening is still not fully understood. OBJECTIVES: To examine the effects of fatigue induced by maximal intensity exercise at different velocities on subsequent torque-velocity relations in muscle. METHODS: Ten men (mean (SD) age 25 (3) years; stature 1.78 (0.34) m; body mass 80.6 (14.5) kg) provided written informed consent and, over a five day period in a randomised manner, performed 16 fatiguing bouts of maximal intensity exercise on an isokinetic dynamometer each followed by one repetition maximum action. Concentric peak torque of the preferred leg was assessed at angular velocities of 0.52, 1.05, 2.09, and 3.14 rad/s. Mechanical work performed for all fatiguing bouts was held at 3050-3150 J. After a 45 second rest, a maximum effort was performed at one of the preset velocities. As a baseline, dependent variables of peak torque (N.m), angle of peak torque (rad), and mean torque (N.m) were measured at each velocity. An analysis of covariance was used to compare torque-velocity relations, and one factor, within subject analyses of variance with repeated measures investigated differences from baseline. RESULTS: Torque-velocity relations for all dependent variables did not differ (p>0.05). Similarly, angles at which peak torque occurred were not velocity dependent and did not differ from baseline and subsequent exercise measures (p>0.05). Generally, fatiguing exercise at low velocities led to reductions in peak and mean torque in subsequent exercise at higher velocities (p<0.05). CONCLUSIONS: Torque-velocity relations fundamentally remain intact after fatigue induced at any velocity, although the magnitude changes. The results suggest that the greater decline in torque during subsequent exercise at high velocities could be due to greater exhaustion of fatigue sensitive type II fibres, whereas low velocity subsequent exercise is less affected because of the greater use of type I fibres.

Adult↗

PubMed2001

Synthetic estimators with moderating influence: the carry-over in cross-over trials revisited.

A general approach to combining alternative estimators of a parameter is described and applied to the analysis of 2x2 cross-over trials in which the treatment effect is of principal interest and carry-over is a nuisance feature. The approach requires prior information about the carry-over. Although modest information is sufficient, more information is rewarded by greater efficiency. The combination, or synthetic, estimator exhibits a moderating influence: its mean squared error is a flat function of the carry-over effect in the range of its feasible values, and for the largest feasible carry-over effect it is superior to either of the originally considered estimators. An extension of the approach is outlined and two other applications in medical research discussed. Although the method can be regarded as Bayesian in spirit, we focus on its resampling (frequentist) properties.

Biometry↗

PubMed2001

Multilevel analysis with messy data.

This paper reviews applications of the method of multiple imputation to dealing with multilevel data that have several kinds of imperfections. These are classified into two broad categories: missing values and imprecise measurement (corrupted recording). The role of the model describing the data imperfections is emphasized. With multiple imputation, these imperfections and information about the processes underlying them can be taken into account. The inferences drawn exploit all the collected information and appropriately reflect the information contained in the data.

Algorithms↗

PubMed1999

Selection bias and treatment heterogeneity in clinical trials.

A common perception about many commercially available medical treatments is that they are effective for every patient having the relevant indication and that developers have provided the regulatory authorities with evidence of such a property. We show that the standard of evidence is much lower and that the standard is appropriate only when the treatment effects are almost constant. We discuss the implications on the design and analysis of clinical trials if the standards were made to correspond with the common perception. We conclude that the evidence of positive mean treatment effect should be accompanied by evidence of limited dispersion of the effects and by a sensitivity analysis that explores the impact of the selection bias in recruitment.

Clinical Trials as Topic↗

PubMed1999

Influence of exercise and menstrual cycle phase on plasma homocyst(e)ine levels in young women--a prospective study.

Plasma total homocysteine (tHcy) has been identified as an independent risk factor for cardiovascular diseases (CVD). The difference in tHcy between the sexes has most often been related to the sex hormones, but also to a higher muscle mass in men. The purpose of this study was to assess the effects of acute exercise, brief exhaustive training, and menstrual cycle phase on circulating plasma tHcy concentrations. Fifteen untrained eumenorrheic women (mean age [+/-SD]: 18.7+/-0.4 yr, body fat: 25.8+/-3.4%, VO2max: 43.8+/-2.3 ml x kg(-1) x min(-1)) volunteered for the present study, which covered two menstrual cycles. During the second cycle the subjects participated in two exhaustive 5-day training programs on a cycle ergometer: one in the follicular (FPh) and one in the luteal phase (LPh). Pre- and posttraining plasma tHcy and total estrogen (E) responses were determined in blood samples obtained immediately before, during and immediately after incremental exercise to exhaustion. tHcy levels showed a large between-subject variation, but differences between FPh and LPh levels were consistent (P=0.063). Mean tHcy levels at rest were 9.44+/-1.65 micromol/L and 8.93+/-1.71 micromol/L during the FPh and LPh, respectively. Brief exhaustive training did not elicit any changes in plasma tHcy concentrations, although posttraining LPh E levels were lower (P<0.01). Overall, the differences between FPh and LPh values for tHcy and E were attenuated by training. Acute exercise increased plasma tHcy concentrations (P<0.001). At exhaustion, tHcy levels increased by 17% and 16% during the FPh and LPh, respectively. This was also significantly above tHcy levels at submaximal exercise (P=0.044). After a short period of training tHcy levels did not increase as much during acute exercise as they did before training; however, the increments were still significant (P=0.048). In conclusion, acute exercise in women produces significant increases in plasma tHcy concentrations, whereas brief exhaustive training does not significantly alter plasma tHcy levels. Our findings also suggest that plasma tHcy concentrations are menstrual cycle phase-dependent and that there is a close association between estrogen status and tHcy levels.

Adolescent↗

PubMed1994

Empirical Bayes methods for estimating hospital-specific mortality rates.

We present alternative methods for estimating hospital-level mortality rates to those used by the Health Care Finance Administration for Medicare patients. We use an empirical Bayes model to represent the different sources of variation in observed hospital-specific mortality rates and we use a logistic regression model to adjust for severity differences (in patient mix) across hospitals. In addition to providing a principled derivation of a standard error for the commonly used estimator, our fully model-based formulation produces much more accurate estimates and resolves the severe problem of multiple comparisons that arises when extreme estimates are used to identify exceptional hospitals. We estimate models for each of four disease conditions using the national Medicare mortality data base which does not contain patient severity descriptors, and mortality data from national samples which do include patient severity descriptors. We find substantial between-hospital variation in the unadjusted death rates from the national data base. Mortality rates differ substantially with patient severity in our models, but the sample sizes are too small to yield reliable estimates of the between-hospital variation in adjusted mortality rates.

Bayes Theorem↗

PubMedDate not supplied

Statistics versus statistical science in the regulatory process.

This paper reviews the established practice of providing evidence to regulatory authorities about the claimed properties (such as efficacy and safety) of new pharmaceutical products. The established conventions and procedures are contrasted with scientific concepts and principles. The following issues are discussed: (a) recruitment of subjects and its connection to treatment heterogeneity; (b) the measurement process and the handling of missing data; (c) data transformation and the use of generalized linear models; (d) model selection and model checking; (e) the 'cult of the single trial' and the use of prior information; and (f) hypothesis testing and the P-value culture.

Area Under Curve↗

PubMedDate not supplied

Gender differences in the relationship between alcohol consumption and drink problems are largely accounted for by body water.

It is widely reported that women drink less and have a lower prevalence of drink problems than men, but the gender differences in the relationship between level of drinking and drink problems have rarely been investigated quantitatively. This paper reports results from the Medical Research Council National Survey of Health and Development (the 1946 British Cohort) when the subjects were 43 years old. Using 7-day recall for alcohol consumption and CAGE scores of 2, 3 or 4 for drink problems, it was found that the prevalence of drink problems increased with level of alcohol consumption. Women were more likely than men to report drink problems at the same level of alcohol consumption. However, this gender difference was largely accounted for by individual differences in weight of body water. Beer accounted for the excess of men's drinking over women's and the proportion of alcohol consumed as beer was inversely related to drink problems. Eighty per cent of women and 52% of men who had drink problems in the past year reported drinking less than an average of 3 U (women) or 4 U (men) a day in the past week. As drinking levels in women begin to approach those in men, rates of drink problems in women are likely to overtake those in men because of women's greater physiological sensitivity to the effects of alcohol.

Adult↗