Model estimation of cerebral hemodynamics between blood flow and volume changes: A data-based modeling approach

It is well known that there is a dynamic relationship between cerebral blood flow (CBF) and cerebral blood volume (CBV). With increasing applications of functional MRI, where the blood oxygen-level-dependent signals are recorded, the understanding and accurate modeling of the hemodynamic relationship between CBF and CBV becomes increasingly important. This study presents an empirical and data-based modeling framework for model identification from CBF and CBV experimental data. It is shown that the relationship between the changes in CBF and CBV can be described using a parsimonious autoregressive with exogenous input model structure. It is observed that neither the ordinary least-squares (LS) method nor the classical total least-squares (TLS) method can produce accurate estimates from the original noisy CBF and CBV data. A regularized total least-squares (RTLS) method is thus introduced and extended to solve such an error-in-the-variables problem. Quantitative results show that the RTLS method works very well on the noisy CBF and CBV data. Finally, a combination of RTLS with a filtering method can lead to a parsimonious but very effective model that can characterize the relationship between the changes in CBF and CBV.

A model of the dynamic relationship between blood flow and volume changes during brain activation

The temporal relationship between changes in cerebral blood flow (CBF) and cerebral blood volume (CBV) is important in the biophysical modeling and interpretation of the hemodynamic response to activation, particularly in the context of magnetic resonance imaging and the blood oxygen level-dependent signal. Grubb et al. (1974) measured the steady state relationship between changes in CBV and CBF after hypercapnic challenge. The relationship CBV proportional to CBFPhi has been used extensively in the literature. Two similar models, the Balloon (Buxton et al., 1998) and the Windkessel (Mandeville et al., 1999), have been proposed to describe the temporal dynamics of changes in CBV with respect to changes in CBF. In this study, a dynamic model extending the Windkessel model by incorporating delayed compliance is presented. The extended model is better able to capture the dynamics of CBV changes after changes in CBF, particularly in the return-to-baseline stages of the response.

The life history legacy of evolutionary body size change in carnivores

We estimate the body sizes of direct ancestors of extant carnivores, and examine selected aspects of life history as a function not only of species' current size, but also of recent changes in size. Carnivore species that have undergone marked recent evolutionary size change show life history characteristics typically associated with species closer to the ancestral body size. Thus, phyletic giants tend to mature earlier and have larger litters of smaller offspring at shorter intervals than do species of the same body size that are not phyletic giants. Phyletic dwarfs, by contrast, have slower life histories than nondwarf species of the same body size. We discuss two possible mechanisms for the legacy of recent size change: lag (in which life history variables cannot evolve as quickly as body size, leading to species having the 'wrong' life history for their body size) and body size optimization (in which life history and hence body size evolve in response to changes in energy availability); at present, we cannot distinguish between these alternatives. Our finding that recent body size changes help explain residual variation around life history allometries shows that a more dynamic view of character change enables comparative studies to make more precise predictions about species traits in the context of their evolutionary background.

Alternatives to linear analysis of energy balance data from lactating dairy cows

The current energy requirements system used in the United Kingdom for lactating dairy cows utilizes key parameters such as metabolizable energy intake (MEI) at maintenance (MEm), the efficiency of utilization of MEI for 1) maintenance, 2) milk production (k(l)), 3) growth (k(g)), and the efficiency of utilization of body stores for milk production (k(t)). Traditionally, these have been determined using linear regression methods to analyze energy balance data from calorimetry experiments. Many studies have highlighted a number of concerns over current energy feeding systems particularly in relation to these key parameters, and the linear models used for analyzing. Therefore, a database containing 652 dairy cow observations was assembled from calorimetry studies in the United Kingdom. Five functions for analyzing energy balance data were considered: straight line, two diminishing returns functions, (the Mitscherlich and the rectangular hyperbola), and two sigmoidal functions (the logistic and the Gompertz). Meta-analysis of the data was conducted to estimate k(g) and k(t). Values of 0.83 to 0.86 and 0.66 to 0.69 were obtained for k(g) and k(t) using all the functions (with standard errors of 0.028 and 0.027), respectively, which were considerably different from previous reports of 0.60 to 0.75 for k(g) and 0.82 to 0.84 for k(t). Using the estimated values of k(g) and k(t), the data were corrected to allow for body tissue changes. Based on the definition of k(l) as the derivative of the ratio of milk energy derived from MEI to MEI directed towards milk production, MEm and k(l) were determined. Meta-analysis of the pooled data showed that the average k(l) ranged from 0.50 to 0.58 and MEm ranged between 0.34 and 0.64 MJ/kg of BW0.75 per day. Although the constrained Mitscherlich fitted the data as good as the straight line, more observations at high energy intakes (above 2.4 MJ/kg of BW0.75 per day) are required to determine conclusively whether milk energy is related to MEI linearly or not.

A three-compartment model of the hemodynamic response and oxygen delivery to brain

We describe a mathematical model linking changes in cerebral blood flow, blood volume and the blood oxygenation state in response to stimulation. The model has three compartments to take into account the fact that the cerebral blood flow and volume as measured concurrently using laser Doppler flowmetry and optical imaging spectroscopy have contributions from the arterial, capillary as well as the venous compartments of the vasculature. It is an extension to previous one-compartment hemodynamic models which assume that the measured blood volume changes are from the venous compartment only. An important assumption of the model is that the tissue oxygen concentration is a time varying state variable of the system and is driven by the changes in metabolic demand resulting from changes in neural activity. The model takes into account the pre-capillary oxygen diffusion by flexibly allowing the saturation of the arterial compartment to be less than unity. Simulations are used to explore the sensitivity of the model and to optimise the parameters for experimental data. We conclude that the three-compartment model was better than the one-compartment model at capturing the hemodynamics of the response to changes in neural activation following stimulation.

Fundamental insights into ontogenetic growth from theory and fish

The fundamental features of growth may be universal, because growth trajectories of most animals are very similar, but a unified mechanistic theory of growth remains elusive. Still needed is a synthetic explanation for how and why growth rates vary as body size changes, both within individuals over their ontogeny and between populations and species over their evolution. Here we use Bertalanffy growth equations to characterize growth of ray-finned fishes in terms of two parameters, the growth rate coefficient, K, and final body mass, m∞. We derive two alternative empirically testable hypotheses and test them by analyzing data from FishBase. Across 576 species, which vary in size at maturity by almost nine orders of magnitude, K scaled as m_∞^(-0.23). This supports our first hypothesis that growth rate scales as m_∞^(-0.25) as predicted by metabolic scaling theory; it implies that species which grow to larger mature sizes grow faster as juveniles. Within fish species, however, K scaled as m_∞^(-0.35). This supports our second hypothesis which predicts that growth rate scales as m_∞^(-0.33) when all juveniles grow at the same rate. The unexpected disparity between across- and within-species scaling challenges existing theoretical interpretations. We suggest that the similar ontogenetic programs of closely related populations constrain growth to m_∞^(-0.33) scaling, but as species diverge over evolutionary time they evolve the near-optimal m_∞^(-0.25) scaling predicted by metabolic scaling theory. Our findings have important practical implications because fish supply essential protein in human diets, and sustainable yields from wild harvests and aquaculture depend on growth rates.

Visceral tissue mass and rumen volume in dairy cows during the transition from late gestation to early lactation

The objectives were to measure the effects of transition and supplemental barley or rumen-protected protein on visceral tissue mass in dairy cows and the effects of transition and barley on rumen volume and liquid turnover. Cows were individually fed a grass silage-based gestation ration to meet energy and protein requirements for body weight stasis beginning 6 wk before expected calving. A corn silage-based lactation ration was individually fed ad libitum after calving. In the visceral mass study, 36 cows were randomly assigned to one of 3 dietary treatments: basal ration or basal ration plus either 800 g dry matter (DM) of barley meal per day or 750 g DM of rumen-protected soybean protein per day. Cows were slaughtered at 21 and 7 d before expected calving date or at 10 and 22 d postpartum. Visceral mass and rumen papillae characteristics were measured. Diets had little effect on visceral mass. The mass of the reticulo-rumen, small intestine, large intestine, and liver was, or tended to be, greater at 22 d postpartum but not at 10 d postpartum before DM intake had increased. Rumen papillae mass increased at 10 d postpartum, perhaps in response to increased concentrates. Mesenteric fat decreased after calving, reflecting body fat mobilization. Ten rumen-cannulated cows were fed the basal gestation ration alone or supplemented with 880 g of barley meal DM. Rumen volumes and liquid dilution rates were measured at 17 and 8 d before calving and at 10, 20, and 31 d postpartum. Feeding barley had no effects. After calving, rumen DM volume and liquid dilution rate increased, but liquid volume did not increase. Changes in gastrointestinal and liver mass during transition were apparently a consequence of changes in DM intake and nutrient supply and not initiation of lactation per se.

Environmental variation at the onset of independent foraging affects full-grown body mass in the red fox

The period following the withdrawal of parental care has been highlighted as a key developmental period for juveniles. One reason for this is that juveniles cannot forage as competently as adults, potentially placing them at greater risk from environmentally-induced changes in food availability. However, no study has examined this topic. Using a long-term dataset on red foxes (Vulpes vulpes), we examined (i) dietary changes that occurred in the one-month period following the attainment of nutritional independence, (ii) diet composition in relation to climatic variation, and (iii) the effect of climatic variation on subsequent full-grown mass. Diet at nutritional independence contained increased quantities of easy-to-catch food items (earthworms and insects) when compared with pre-independence. Interannual variation in the volume of rainfall at nutritional independence was positively correlated to the proportion of earthworms in cub diet. Pre-independence cub mass and rainfall immediately following nutritional independence explained a significant proportion of variance in full-grown mass, with environmental variation affecting full-grown mass of the entire cohorts. Thus, weather-mediated availability of easy-to-catch food items at a key developmental stage has lifelong implications for the development of juvenile foxes by affecting full-grown mass, which in turn appears to be an important component of individual reproductive potential.

Changes in fat, fat-free mass and body water in human normal pregnancy

Measurements of body weight, total body water and total body potassium (40K) were made serially on three occasions during pregnancy and once post partum in 27 normal pregnant women. Skinfold thickness and fat cell diameter were also measured. A model of body composition was formulated to permit the estimation of changes in fat, lean tissue and water content of the maternal body. Total maternal body fat increased during pregnancy, reaching a peak towards the end of the second trimester before diminishing. Serial measurements of fat cell diameter showed poor correlation, whilst total body fat calculated from skinfold thickness correlated well with our estimated values for total body fat in pregnancy.

Variation in genes related to hepatic lipid metabolism and changes in waist circumference and body weight.

We analysed single nucleotide polymorphisms (SNPs) tagging the genetic variability of six candidate genes (ATF6, FABP1, LPIN2, LPIN3, MLXIPL and MTTP) involved in the regulation of hepatic lipid metabolism, an important regulatory site of energy balance for associations with body mass index (BMI) and changes in weight and waist circumference. We also investigated effect modification by sex and dietary intake. Data of 6,287 individuals participating in the European prospective investigation into cancer and nutrition were included in the analyses. Data on weight and waist circumference were followed up for 6.9 ± 2.5 years. Association of 69 tagSNPs with baseline BMI and annual changes in weight as well as waist circumference were investigated using linear regression analysis. Interactions with sex, GI and intake of carbohydrates, fat as well as saturated, monounsaturated and polyunsaturated fatty acids were examined by including multiplicative SNP-covariate terms into the regression model. Neither baseline BMI nor annual weight or waist circumference changes were significantly associated with variation in the selected genes in the entire study population after correction for multiple testing. One SNP (rs1164) in LPIN2 appeared to be significantly interacting with sex (p = 0.0003) and was associated with greater annual weight gain in men (56.8 ± 23.7 g/year per allele, p = 0.02) than in women (-25.5 ± 19.8 g/year per allele, p = 0.2). With respect to gene-nutrient interaction, we could not detect any significant interactions when accounting for multiple testing. Therefore, out of our six candidate genes, LPIN2 may be considered as a candidate for further studies.

A high-order arbitrarily unstructured finite-volume model of the global atmosphere: tests solving the shallow-water equations

Simulations of the global atmosphere for weather and climate forecasting require fast and accurate solutions and so operational models use high-order finite differences on regular structured grids. This precludes the use of local refinement; techniques allowing local refinement are either expensive (eg. high-order finite element techniques) or have reduced accuracy at changes in resolution (eg. unstructured finite-volume with linear differencing). We present solutions of the shallow-water equations for westerly flow over a mid-latitude mountain from a finite-volume model written using OpenFOAM. A second/third-order accurate differencing scheme is applied on arbitrarily unstructured meshes made up of various shapes and refinement patterns. The results are as accurate as equivalent resolution spectral methods. Using lower order differencing reduces accuracy at a refinement pattern which allows errors from refinement of the mountain to accumulate and reduces the global accuracy over a 15 day simulation. We have therefore introduced a scheme which fits a 2D cubic polynomial approximately on a stencil around each cell. Using this scheme means that refinement of the mountain improves the accuracy after a 15 day simulation. This is a more severe test of local mesh refinement for global simulations than has been presented but a realistic test if these techniques are to be used operationally. These efficient, high-order schemes may make it possible for local mesh refinement to be used by weather and climate forecast models.

The effect of consumption volume on profile and liking of oral nutritional supplements of varied sweetness: sequential profiling and boredom tests

Oral nutrition supplements (ONS) are routinely prescribed to those with, or at risk of, malnutrition. Previous research identified poor compliance due to taste and sweetness. This paper investigates taste and hedonic liking of ONS, of varying sweetness and metallic levels, over consumption volume; an important consideration as patients are prescribed large volumes of ONS daily. A sequential descriptive profile was developed to determine the perception of sensory attributes over repeat consumption of ONS. Changes in liking of ONS following repeat consumption were characterised by a boredom test. Certain flavour (metallic taste, soya milk flavour) and mouthfeel (mouthdrying, mouthcoating) attributes built up over increased consumption volume (p 0.002). Hedonic liking data from two cohorts, healthy older volunteers (n = 32, median age 73) and patients (n = 28, median age 85), suggested such build-up was disliked. Efforts made to improve the palatability of ONS must take account of the build up of taste and mouthfeel characteristics over increased consumption volume.

Changes in light intensity during the rearing period can influence egg production in domestic fowl

1. A total of 240 Shaver White and 240 ISA Brown pullets that had been reared in multi-bird cages on a 10-h photoperiod, and maintained at a light intensity of 3 or 25 lux, or changed from 3 to 25 lux or from 25 to 3 lux at 9 or 16 weeks of age, were moved into individual-bird cages at 20 weeks and transferred to 15-h photoperiods at 25 lux. 2. In both breeds, birds transferred from 3 to 25 lux at 16 or 20 weeks laid significantly more eggs than birds maintained on the brighter intensity from one day or increased to it at 9 weeks. 3. Mean egg weight, shell deformation, albumen height, feed intake and body weight gain in lay were not significantly affected by the light intensity treatments during the rearing period. There was, however, a small, but significant, negative correlation of egg numbers with mean egg weight, although this only partially explained the difference in egg numbers. The differences in egg production were unrelated to rate of sexual maturation.

Changes in light intensity can influence age at sexual maturity in domestic pullets

1. Shaver White and ISA Brown pullets were reared to 140 d in groups of 8 in cages on a 10-h photoperiod of incandescent light and maintained at an illuminance of 3 or 25 lux, or transferred from 3 to 25 lux or from 25 to 3 lux at 63 or 112 d of age. 2. There was no significant difference in sexual maturity, measured as eggs per 100 bird.d at 139 and 140 d, for ISA Brown maintained on 3 or 25 lux, but Shaver White pullets exposed to constant 3 lux matured significantly later than those maintained on 25 lux. 3. In Shaver Whites, sexual maturity was significantly delayed by an increase from 3 to 25 lux at 63 and 112 d, and advanced by a decrease from 25 to 3 lux at 112 d. Sexual maturity of ISA Browns was not significantly affected by a change in illuminance at 63 or 112 d, though responses were in the same direction as for Shaver Whites. 4. In both breeds, total feed consumed to 112 d was higher for birds on 3 lux than 25 lux, but lower between 112 d and 140 d when birds on 25 lux underwent rapid sexual development. In both breeds, body weight at 63 d was higher for birds exposed to 3 lux than 25 lux, but body weight gain thereafter was similar for the two light intensities. 5. In both breeds, plasma luteinising hormone (LH) concentration at 63 and 112 d was lower in birds maintained on 3 lux than 25 lux. At 63 and 112 d, transfers from 25 to 3 lux depressed, whereas transfers from 3 to 25 lux at 63 d, but not at 112 d, increased plasma LH. 6. Advances or delays in sexual maturity induced by changes in illuminance were not correlated with differences in feed intake, body weight gain, or with changes in plasma LH. 7. One possible explanation for the inverse relationship between the direction of change in illuminance at 63 and 112 d in pullets exposed to a 10-h photoperiod and the age at which they became sexually mature is that changes in light intensity and/or spectral composition affect the entrainment of the circadian rhythm of photoinducibility, to effect a phase shift in the photoinducible phase and/or the responsiveness of phototransduction pathways.