Assembling more O2 uptake responses: is it possible to merely stack the repeated transitions?

Kinetic parameters for pulmonary O2 uptake at exercise onset are estimated by non-linear regression on repeated responses assembled together. The native data contain the information, thus the "stacking" of the responses should provide correct values and uncertainties. Kinetic parameters and corresponding uncertainties (computed from the asymptotic standard errors; ASE) were estimated on 10(4) simulated noisy responses (with time constant τ=25s), repeated 10 times and assembled over an increasing number of repetitions (Nr) by "stacking" or ensemble averaging the responses processed to obtain 1s bins ("1-s-bins"). Independent of the assembling method, the average estimated τ amounted to ∼25.05 s. Independent of Nr, the "1-s-bins" and the "stacking" yielded an ASE/SD ratio for τ amounting to ∼0.52 and ∼0.98, respectively, resulting in a probability of including τ=25s within the estimated uncertainty from an individual kinetics amounting to ∼70% and >94% for the "1-s-bins" and the "stacking", respectively. In conclusion, the "stacking" allowed obtaining, also for individual kinetics, coherent estimated parameters and associated uncertainties.

Confidence intervals for the parameters estimated from simulated O2 uptake kinetics: effects of different data treatments.

The behaviour of pulmonary O2 uptake following a moderate-intensity step exercise increment is usually described by a first brief increase, followed by a second exponential time course reaching the new steady state (phase II). The parameters describing the phase II kinetics are investigated by applying different data treatments to the acquired O2 uptake data to reduce the effects of their noise before running a non-linear regression procedure. The effects of different data treatments (nothing, resampling at various time intervals or averaging of more repetitions) on the precision and/or accuracy of the kinetics parameters estimated by non-linear regression with a simple mono-exponential model were investigated by artificially generating 10(5) simulated responses with average breath duration of 3.5 s. The simulations showed that, whatever the explored data treatment, the average estimated parameters were close to the theoretical ones. Nevertheless, in all the explored conditions, the non-linear regression provided narrower asymptotic confidence intervals than the real ones. In particular, when the responses were resampled at 1 s time intervals, the width of the asymptotic confidence interval for the time constant was 50% of the real one, even after the averaging of more repetitions. The reasons for this discrepancy were investigated further, allowing us to identify some methods to obtain the correct confidence interval of the O2 uptake kinetics parameters. The simplest method to obtain an asymptotic confidence interval close to the real one is to average more responses resampled to a time interval slightly longer than the average breath duration.

Evaluation of clinical and clinical chemical parameters in periparturient cows.

Certain blood parameters and clinical symptoms have been connected with milk fever and a hypocalcemic condition in the cow. The present study intended to establish a mutual connection between relevant blood parameters and potentially valuable background information about the cow and its observed clinical symptoms at calving. Two veterinarians were summoned within 12 h of parturition of 201 cows, distributed among 41 Danish commercial herds. Cows were at different parity levels (2 to 10) and breeds and management differed broadly among herds. A blood sample was taken from the vena jugularis or the tail vein and was subsequently analyzed in the laboratory. Furthermore, 13 different clinical symptoms were recorded as categorical data. We investigated associations among the data obtained. We assessed an interpretative model for actual blood calcium level with blood parameters and background knowledge of the animals. We established a path analysis using background knowledge, blood parameters, and results of clinical examinations to uncover causal connections among the variables. Twenty-six percent of the animals were diagnosed as having milk fever and subsequent blood analyses revealed a high frequency of hypocalcemia within the general range from 0.69 to 2.73 mmol of Ca per liter. Rectal temperature, inorganic blood phosphate, and potassium were all directly correlated with blood calcium, while glucose, lactate, and magnesium were inversely associated with calcium. Blood osteocalcin was significantly lower in hypocalcemic animals, indicating that de novo synthesis of bone was arrested during hypocalcemia. A mixed effect linear interpretative model explained 75% of the variation in blood calcium. Clinical symptoms like mood, appetite, muscle shivering, rumen motility, and paresis were individually correlated with blood calcium and were thereby predictive of hypocalcemia. The path analysis showed the central role of calcium in affecting the clinical symptoms. However, several other factors contributed to hypocalcemia.

Applications of likelihood asymptotics for nonlinear regression in herbicide bioassays.

Dose-response models are intensively used in herbicide bioassays. Despite recent advancements in the development of new herbicides, statistical analyses are commonly based on asymptotic approximations that are sometimes poor. This paper presents the use of recent results in higher order asymptotics for likelihood-based inference in nonlinear regression. The methods presented provide accurate approximation for the distribution of test statistics and for prediction limits. Analyses of the fit and measures of detection limits of the bioassays are considered, and the potential of the methods is illustrated by examples with real data.

Protein binding in deactivation of ferrylmyoglobin by chlorogenate and ascorbate.

Kinetics of reduction of iron(IV) in ferrylmyoglobin by chlorogenate in neutral or moderately acidic aqueous solutions (0.16 M NaCl) to yield metmyoglobin was studied using stopped flow absorption spectroscopy. The reaction occurs by direct bimolecular electron transfer with (2.7 +/- 0.3) x 10(3) M(-)(1).s(-)(1) at 25.0 degrees C (DeltaH( )(#) = 59 +/- 6 kJ.mol(-)(1), DeltaS(#) = 15 +/- 22 J. mol(-)(1).K(-)(1)) for protonated ferrylmyoglobin (pK(a) = 4.95) and with 216 +/- 50 M(-)(1).s(-)(1) (DeltaH( )(#) = 73 +/- 8 kJ. mol(-)(1), DeltaS( )(#) = 41 +/- 30 J.mol(-)(1).K(-)(1)) for nonprotonated ferrylmyoglobin in parallel with reduction of a chlorogenate/ferrylmyoglobin complex by a second chlorogenate molecule with (8.6 +/- 1.1) x 10(2) M(-)(1).s(-)(1) (DeltaH( )(#) = 74 +/- 8 kJ.mol(-)(1), DeltaS( )(#) = 59 +/- 28 J.mol(-)(1).K(-)(1)) for protonated ferrylmyoglobin and with 61 +/- 9 M(-)(1).s(-)(1) (DeltaH( )(#) = 82 +/- 12 kJ.mol(-)(1), DeltaS( )(#) = 63 +/- 41 J. mol(-)(1).K(-)(1)) for nonprotonated ferrylmyoglobin. Previously published data on ascorbate reduction of ferrylmyoglobin are reevaluated according to a similar mechanism. For both protonated and nonprotonated ferrylmyoglobin the binding constant of chlorogenate is approximately 300 M(-)(1), and the modulation of ferrylmyoglobin as an oxidant by chlorogenate (or ascorbate) leads to a novel antioxidant interaction for reduction of ferrylmyoglobin by ascorbate in mixtures with chlorogenate.