Seroprotection rate, mean fold increase, seroconversion rate: which parameter adequately expresses seroresponse to influenza vaccination?

Serological parameters intend to describe antibody response to influenza vaccine in a population. However, there is uncertainty about the mathematical appropriateness and the biological or clinical meaning of conventionally used parameters. Theoretical considerations and exploration of a data-set of 16 studies with an inactivated (subunit) influenza vaccine involving 1176 adult subjects suggest the following conclusions. In a population seronegative before vaccination, the post-vaccination geometric mean titre (post-GMT) is a meaningful immunological parameter adequately expressing antibody response after vaccination. The related protection rate (PR) is a good surrogate parameter for protection provided by a given vaccine, thus relevant to public health. However, in a population partially seropositive before vaccination (due to previous exposition to influenza antigens), the same parameters may, under certain conditions, seriously overestimate the antibody response, as they do not account for the pre-vaccination state. Conventional attempts to address pre-vaccination antibody are associated with either loss of information (exclusion of seropositive subjects) or incomplete control of pre-vaccination state (mean fold increase (MFI), response rate (RR)). Although not devoid of theoretical limitations (heteroscedasticity), correction of post-GMT and PR by linear regression appears to provide better estimates of antibody response and vaccine immunogenicity.     

Effort—reward imbalance,heart rate,and heart rate variability: the cardiovascular risk in young finns study

Background: Work stress indicated by effort—reward imbalance is hypothesized to cause autonomic arousal, which, if prolonged or frequent, could contribute to cardiovascular pathology. However, only limited empirical evidence on this mechanism is available. Purpose: This study examined associations between effort-reward imbalance, heart rate (HR), and heart rate variability (HRV). Method: The participants were 457 women and 406 men (mean age 32.3 years) derived from the population-based Young Finns Study. Effort—reward imbalance was defined as the ratio between effort and reward, higher efforts compared to rewards indicating greater imbalance. Results: In age-adjusted regression models, higher effort-reward imbalance was associated with lower HRV, and lower reward was associated with higher HR among women. These associations were not attenuated after additional adjustments for demographic characteristics and coronary risk factors. No significant associations of effort—reward imbalance or its components with HR and HRV were found in men. Conclusion: Our finding of lower HRV and higher HR in young healthy women with high effort—reward imbalance and low rewards provides evidence of a potential mechanism that may link effort-reward imbalance to the development of coronary heart disease (CHD) in women.     

Oxygen uptake-heart rate relationship in élite wheelchair racers

The American College of Sports Medicine (ACSM) recommends that, as a general rule for health purposes, individuals should exercise at 40%–85% of their maximal oxygen uptakes. Moreover, it has been suggested that 55%–90% of the maximal heart rate may be used as an alternative estimate of these percentage maximal oxygen uptake values. The present study examined the relationship between percentage peak heart rate (% HR_peak) and percentage peak oxygen uptake (% ) during steady-state incremental intensity wheelchair propulsion of 16 élite, male wheelchair racers (WR). Oxygen uptake was determined during each submaximal exercise stage and heart rate (HR) was continuously monitored. The was subsequently determined using a separate protocol. Linear regression equations of % HR_peak versus % for each participant included % HR_peak values corresponding to 40%, 60%, 80% and 85% . The linear regression equation, derived as the group mean of the slope and intercept terms determined for each individual, was: . The group mean of the individual correlation coefficients for the relationship was 0.99. The values of % HR_peak for each of the % values below 85% were significantly greater (P<0.01) than those suggested by the ACSM. This suggests that the ACSM guidelines below 85% , based on % HR_peak, may underestimate the relative exercise intensity (i.e. % ) in the WR population. However, in élite level WR, % HR_peak can be recommended as an alternative estimate of % at wheelchair propulsion intensities of 85% or more. Electronic Publication     

Estimation of maximal heart rate using the relationship between heart rate variability and exercise intensity in 40–67 years old men

Large interindividual variation in maximal heart rate (HR_max) may not be accounted for by age alone. In order to evaluate a novel method in the prediction of HR_max, this study examined the profile of HR variability (HRV) during exercise in 40–67 years old men (n = 74). R–R intervals were recorded during supine rest and during a graded exercise test by cycle ergometry until exhaustion. A third-degree polynomial function was fitted to the HRV data recorded during exercise to represent the HRV profile of each subject. The instantaneous beat-to-beat R–R interval variability (SD1), high (HF) and low frequency power decreased between all consecutive exercise intensities (P < 0.033). The relationship between HR_max and a variable illustrating the declining rate of HF (HR_HF50%) was stronger (r = 0.50, P < 0.001) than between HR_max and age (r = −0.36, P < 0.01). The regression analysis showed that a more accurate estimation of HR_max was attained when HRV was used in the equation in addition to age: HR_max = 160.633–0.603(age) + 0.441(HR_HF50%) (SEE = 9.8 bpm vs. 11.6 bpm in the equation based on age alone). The decline of HRV during incremental exercise seems to be useful for accurate estimation of maximal heart rate.     

Could heart rate play a role in pericardial inflammation?

Purpose and medical hypothesis: Rest is usually recommended in acute pericarditis, as it could help to lower heart rate (HR) and contribute to limit "mechanical inflammation". Whether HR on admission could be correlated and perhaps participate to inflammation has not been reported. Methods: Between March 2007 and February 2010, we conducted a retrospective study on all patients admitted to our center for acute pericarditis. Diagnosis criteria included two of the following ones: typical chest pain, friction rub, pericardial effusion on cardiac echography, or typical electrocardiogram (ECG) findings. Primary endpoint was biology: CRP on admission, on days 1, 2, 3, and especially peak. Results: We included 73 patients. Median age was 38years (interquartiles 28-51) and median hospitalization duration was 2.0days (1.5-3.0). Median heart rate was 88.0beats per minute (bpm) on admission (interquartiles 76.0-100.0) and 72.0 on discharge (65.0-80.0). Heart rate on admission was significantly correlated with CRP peak (p<0.001), independently of temperature on admission, hospitalization duration and age. Recurrences occurred within 1month in 32% of patients. Heart rate on hospital discharge was correlated with recurrence, independently of age. Conclusion: In acute pericarditis, heart rate on admission is independently correlated with CRP levels and heart rate on discharge seems to be independently correlated to recurrence. This could suggest a link between heart rate and pericardial inflammation.     

Does motor activity during psychophysiological paradigms confound the quantification and interpretation of heart rate and heart rate variability measures in young children?

Respiratory sinus arrhythmia (RSA), heart period, and motor activity were monitored in preschoolers during a variety of tasks varying in required movement. The data analyses indicate: (1) that when activity increases during tasks, there are synchronous decreases in heart period and RSA; (2) that correlations between changes in RSA and heart period are related to activity only during exercise when there is a major demand for increased metabolic resources; and (3) that the covariation among the variables within each condition is low except during exercise. These findings suggest that the slight increases in motor activity (i.e., hand movements) often required in attention demanding psychophysiological protocols are not related to RSA and heart period responses. However, when tasks necessitate large increases in motor activity (e.g., exercise), the decreases in heart period and RSA are related to the change in motor activity.     

Does preprocessing change nonlinear measures of heart rate variability?

This work investigated if methods used to produce a uniformly sampled heart rate variability (HRV) time series significantly change the deterministic signature underlying the dynamics of such signals and some nonlinear measures of HRV. Two methods of preprocessing were used: the convolution of inverse interval function values with a rectangular window and the cubic polynomial interpolation. The HRV time series were obtained from 33 Wistar rats submitted to autonomic blockade protocols and from 17 healthy adults. The analysis of determinism was carried out by the method of surrogate data sets and nonlinear autoregressive moving average modelling and prediction. The scaling exponents , ₁ and ₂ derived from the detrended fluctuation analysis were calculated from raw HRV time series and respective preprocessed signals. It was shown that the technique of cubic interpolation of HRV time series did not significantly change any nonlinear characteristic studied in this work, while the method of convolution only affected the ₁ index. The results suggested that preprocessed time series may be used to study HRV in the field of nonlinear dynamics.     

Should heart rate variability be “corrected” for heart rate? Biological,quantitative, and interpretive considerations

Metrics of heart period variability are widely used in the behavioral and biomedical sciences, although somewhat confusingly labeled as heart rate variability (HRV). Despite their wide use, HRV metrics are usually analyzed and interpreted without reference to prevailing levels of cardiac chronotropic state (i.e., mean heart rate or mean heart period). This isolated treatment of HRV metrics is nontrivial. All HRV metrics routinely used in the literature exhibit a known and positive relationship with the mean duration of the interval between two beats (heart period): as the heart period increases, so does its variability. This raises the question of whether HRV metrics should be “corrected” for the mean heart period (or its inverse, the heart rate). Here, we outline biological, quantitative, and interpretive issues engendered by this question. We provide arguments that HRV is neither uniformly nor simply a surrogate for heart period. We also identify knowledge gaps that remain to be satisfactorily addressed with respect to assumptions underlying existing HRV correction approaches. In doing so, we aim to stimulate further progress toward the rigorous use and disciplined interpretation of HRV. We close with provisional guidance on HRV reporting that acknowledges the complex interplay between the mean and variability of the heart period.     

Physiological studies on trematodes — Fasciola gigantica rate of oxygen consumption

Summary 1. The Q _O ² of adult F. gigantica has been compared with F. hepatica.2. The oxygen consumption of the experimental parasite has been found to be very low.3. There is a marked difference in Q _O ² values of the whole and minced parasite.     

Can the cerebral metabolic rate of oxygen be estimated with near-infrared spectroscopy?

We have measured the changes in oxy-haemoglobin and deoxy-haemoglobin in the adult human brain during a brief finger tapping exercise using near-infrared spectroscopy (NIRS). The cerebral metabolic rate of oxygen (CMRO2) can be estimated from these NIRS data provided certain model assumptions. The change in CMRO2 is related to changes in the total haemoglobin concentration, deoxy-haemoglobin concentration and blood flow. As NIRS does not provide a measure of dynamic changes in blood flow during brain activation, we relied on a Windkessel model that relates dynamic blood volume and flow changes, which has been used previously for estimating CMRO2 from functional magnetic resonance imaging (fMRI) data. Because of the partial volume effect we are unable to quantify the absolute changes in the local brain haemoglobin concentrations with NIRS and thus are unable to obtain an estimate of the absolute CMRO2 change. An absolute estimate is also confounded by uncertainty in the flow-volume relationship. However, the ratio of the flow change to the CMRO2 change is relatively insensitive to these uncertainties. For the linger tapping task, we estimate a most probable flow-consumption ratio ranging from 1.5 to 3 in agreement with previous findings presented in the literature, although we cannot exclude the possibility that there is no CMRO2 change. The large range in the ratio arises from the large number of model parameters that must be estimated from the data. A more precise estimate of the flow-consumption ratio will require better estimates of the model parameters or flow information, as can be provided by combining NIRS with fMRI.     

Heart rate variability in children with aortic valve stenosis – a pilot study

Introduction

The aim of our prospective study was to evaluate heart rate variability (HRV) in children with aortic valve stenosis (AS) and its relationship with left ventricular mass and peak transaortic valve pressure gradient (PG).

Material and methods

Sixty children with AS divided into 3 groups according to their PG and 60 healthy controls were studied. Holter ECG monitoring with time domain HRV analysis was performed. Left ventricular mass was calculated by echocardiography.

Results

Mean values of all HRV parameters were statistically significantly lower (p < 0.001) in children with AS than in controls (respectively: SDNN 127.8 ±28.2 ms; 162.6 ±38.0 ms, SDNN day 99.7 ±26.6 ms; 134.1 ±36.1 ms, SDNN night 99.9 ±32.8 ms; 123.4 ±45.7 ms, SDANN 112.2 ±27.7 ms; 142.4 ±34.6, SDNNi 62.2 ±16.2 ms; 75.9 ±21.6, RMSSD 39.6 ±12.1 ms; 50.3 ±16.7 ms, rMSSD day 33.6 ±10.9 ms; 43.1 ±14.7 ms, rMSSD night 49.8 ±18.1 ms; 64.4 ±24.9 ms, pNN50 16.4 ±9.5%; 23.5 ±11.7%, pNN50 day 12.0 ±8.5%; 18.4 ±10.7%, pNN50 night; 26.5 ±14.8%; 36.4 ±17.4%. No significant differences between the mean values of HRV parameters in children with different PG and with and without myocardial hypertrophy were found. In children with AS and ventricular arrhythmia SDNN day was significantly lower (p < 0.05) compared to patients without arrhythmia (94.9 ±22.1 ms vs. 109.3 ±22.5 ms).

Conclusions

In children with AS the balance of the autonomic nervous systemic disturbed which manifests in an increase in sympathetic and decrease in parasympathetic activity. Transaortic valve pressure gradient and myocardial hypertrophy do not influence the HRV. The SDNN reduction during the day period may indicate the risk of ventricular arrhythmia in children with AS.     

Effect of β-adrenoblockers on heart rate variability in awake and narcotized rats

In narcotized rats, β-adrenoceptor blockers changed all parameters of heart rate variability indicating up-regulation of parasympathetic activity and down-regulation of the sympathetic one. In immobilized awake rats, the temporal and geometrical parameters varied similarly, while spectral analysis indicated possible activation of other neurohumoral mechanisms against the background of β-blocker treatment. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 144, No. 10, pp. 372–264, October, 2007     

Automated detection of perinatal hypoxia using time–frequency-based heart rate variability features

Perinatal hypoxia is a cause of cerebral injury in foetuses and neonates. Detection of foetal hypoxia during labour based on the pattern recognition of heart rate signals suffers from high observer variability and low specificity. We describe a new automated hypoxia detection method using time–frequency analysis of heart rate variability (HRV) signals. This approach uses features extracted from the instantaneous frequency and instantaneous amplitude of HRV signal components as well as features based on matrix decomposition of the signals’ time–frequency distributions using singular value decomposition and non-negative matrix factorization. The classification between hypoxia and non-hypoxia data is performed using a support vector machine classifier. The proposed method is tested on a dataset obtained from a newborn piglet model with a controlled hypoxic insult. The chosen HRV features show strong performance compared to conventional spectral features and other existing methods of hypoxia detection with a sensitivity 93.3 %, specificity 98.3 % and accuracy 95.8 %. The high predictive value of this approach to detecting hypoxia is a substantial step towards developing a more accurate and reliable hypoxia detection method for use in human foetal monitoring.     

Optimum two-stage designs in case–control association studies using false discovery rate

Genetic association studies using case–control designs are often done to identify loci associated with disease susceptibility. These studies are often expensive to perform, due to a large number of genetic markers. Several types of two-stage designs are proposed and used from the point of cost effectiveness. We proposed to control the false discovery rate for multiple-testing correction in two-stage designs, using optimal sample sizes and criteria for selecting markers associated with a disease in each stage to minimize the cost of genotyping. The expected power and cost of two-stage designs were compared with those of one-stage designs, under the assumptions that the genetic markers are independent and total sample size is fixed. The results showed that the proposed two-stage procedure usually reduced the cost of genotyping by 40–60%, with a power similar to that of the one-stage designs. In addition, the sample size and selection criteria, which are optimized parameters, are defined as a function of a prior probability that marker–disease association is true. So, the effects of mis-specification of a prior probability on efficiency were also considered.Aya Kuchiba and Noriko Y. Tanaka have contributed equally to this study.