Longitudinal Heterogeneity Research Articles

Application of Person‐Centered Analytic Methodology in Longitudinal Research: Exemplars From the Women's Health Initiative Clinical Trial Data

Despite the variety of available analytic methods, longitudinal research in nursing has been dominated by use of a variable-centered analytic approach. The purpose of this article is to present the utility of person-centered methodology using a large cohort of American women 65 and older enrolled in the Women's Health Initiative Clinical Trial (N = 19,891). Four distinct trajectories of energy/fatigue scores were identified. Levels of fatigue were closely linked to age, socio-demographic factors, comorbidities, health behaviors, and poor sleep quality. These findings were consistent regardless of the methodological framework. Finally, we demonstrated that energy/fatigue levels predicted future hospitalization in non-disabled elderly. Person-centered methods provide unique opportunities to explore and statistically model the effects of longitudinal heterogeneity within a population.

Longitudinal heterogeneity of arterial remodeling and endothelial shear stress in human coronary artery plaques and their effects on the natural history of atherosclerosis

Purpose: Expansive remodeling (ER) and low endothelial shear stress (ESS) critically determine the natural history of atherosclerosis, but they have only been investigated in a cross-sectional arterial axis. In this study, we assessed the longitudinal variation of remodeling and ESS along the length of individual plaques in human coronary arteries and their relation to subsequent plaque growth. Methods: We performed 3D coronary reconstruction by angiography/IVUS at baseline and at 6-10 months follow-up as part of the PREDICTION Study. In discrete baseline plaques (max thickness >0.5 mm, length 9 to 30 mm), we assessed arterial remodeling and ESS (using computational fluid dynamics) in 3mm-long segments. Plaque growth was evaluated in the same locations at follow-up. Results: In 313 arteries from 220 patients, 371 plaques (average length 16.6±0.4 mm) were identified. Of these plaques, 237 (63.9%) had evidence of remodeling while the remaining 134 (36.1%) showed no remodeling. The vast majority of remodeled plaques (93.2%) displayed heterogeneous remodeling patterns along their length: 52 plaques (23.5%) exhibited two remodeling patterns, 14 (6.3%) exhibited three remodeling patterns and 155 plaques (70.1%) showed a combination of one remodeling pattern in some areas of the plaque with absence of remodeling elsewhere (p<0.001). Of plaques with homogeneous remodeling, 18.8% had Excessive ER, 6.2% Compensatory ER, 12.5% Inadequate ER and 62.5% Constrictive remodeling (p<0.05). Similarly, 75.7% of all plaques demonstrated heterogeneous ESS profiles along their length: 20 plaques (7.1%) exhibited both low and high ESS, 79 (28.1%) both low and moderate ESS, 67 (23.8%) both moderate and high ESS; and 115 plaques (40.9%) showed all three ESS patterns (p<0.001). Of plaques with homogeneous ESS, 40% had low ESS, 20% moderate ESS and 40% high ESS. Segments with Excessive ER were associated with low ESS while constrictively remodeled segments with high ESS (p<0.001). Plaque growth at follow-up was primarily evident in segments with baseline low ESS (OR 1.4, 95% CI 1.1-1.7, p<0.05). Conclusions: Arterial remodeling and ESS patterns are not homogeneously distributed along the length of individual coronary plaques, but show significant longitudinal heterogeneity. Since Excessive ER is related to low ESS and subsequent plaque growth, the detailed characterization of remodeling and ESS profiles along the longitudinal aspect of lesions may enhance early identification of highest-risk plaques.

Longitudinal Dispersion in River Flows Characterized by Random Large-Scale Bed Irregularities: First-Order Analytical Solution

AbstractA stochastic Lagrangian approach is proposed for the analytical derivation of a longitudinal dispersion coefficient that accounts for both transverse and longitudinal flow field variability in straight-axis open channels characterized by longitudinal large-scale bed heterogeneity, that is, by longitudinal bed irregularities over a wide range of representative lengths, from the simple grain roughness to large undulations (up to order of kilometers), possibly related to topographical discontinuities or to extended and inhomogeneous depositional processes carried out by natural or anthropogenic agents. The resulting dimensionless expression, involving the average Chezy coefficient and the ratios of river width and longitudinal heterogeneity correlation length to the average flow depth, is obtained at the first order in the depth fluctuations as a time-dependent function given by the sum of three distinct components. The first main component is related to the transverse velocity distribution and would...

Longitudinal heterogeneity of coronary artery distensibility in plaques related to acute coronary syndrome

How coronary distensibility contributes to stable or unstable clinical manifestations remains obscure. We postulated that the heterogeneous plaque distensibility is associated with unstable clinical presentations in patients with acute coronary syndrome (ACS). Seventeen and 19 ACS-related and -unrelated lesions, respectively, were visualized using intravascular ultrasound imaging with simultaneous intracoronary pressure recording. Systolic and diastolic lumen cross-sectional areas were measured at the lesion site and at five evenly spaced sites between the proximal and distal reference sites. The coronary distensibility index and stiffness index β were calculated for each site and averaged for each coronary segment. Maximal distensibility index, standard deviation and the difference between maximal and minimal distensibility indices within each segment were significantly higher in the ACS-related than -unrelated plaques (5.6 ± 2.3 vs. 3.7 ± 1.8, p < 0.001, 2.1 ± 0.9 vs. 1.1 ± 0.6, p < 0.001 and 5.3 ± 2.3 vs. 2.8 ± 1.5, p < 0.001, respectively). Moreover, the difference in the distensibility index between the lesion site of ACS-related plaques and the immediate proximal site was significantly larger (2.88 ± 2.35 vs. 1.17 ± 1.44, p = 0.022) than that in ACS-unrelated plaques. Coronary artery distensibility is longitudinally more heterogeneous in ACS-related than-unrelated plaques, especially between the lesion and the immediate proximal site.

Eutrophication and retention time affecting spatial heterogeneity in a tropical reservoir

Longitudinal heterogeneity in reservoirs is especially related to increase in sedimentation and water transparency along the river/dam axis. Consequently, primary production tends to reach higher values in intermediate regions where there is a balance between the availability of the main resources (light and nutrients) suitable for phytoplankton growth. Many factors such as reservoir morphometry, retention time, thermal stratification and geographical location can affect the boundaries between these regions. The tropical Funil Reservoir (Brazil), despite a low retention time, has experienced severe eutrophication in recent decades, with persistent cyanobacteria blooms. During the course of 1 year, samples were collected at four stations along the reservoir (fluvial, intermediate and lentic compartments) to evaluate if spatial heterogeneity could affect the occurrence and distribution of these blooms along the reservoir. Although the reservoir has a short annual retention time (mean 41.5 days), the typical zonation pattern was observed for the main abiotic variables and phytoplankton abundance. However, higher biomass occurred in the lentic compartment rather than in the intermediate zone. Despite the peculiar heterogeneity in total biomass, the phytoplankton composition and seasonal variability were very similar along the entire reservoir, with a few marked differences only in the fluvial zone. Phytoplankton total biomass in Funil Reservoir was high, even in periods of lower seasonal retention time (around 15 days), and was especially related to high input of nutrients. Moreover, retention time directly affects the spatial heterogeneity of phytoplankton biomass, since strong variability was only observed during the cold–dry season, corresponding to periods of longer retention time (around 80 days). While high availability of nutrients promoted high cyanobacterial biomass in the entire system, the few periods of heterogeneous spatiality seemed to be related to changes in retention time.

Functional effect of longitudinal heterogeneity in constricted airways before and after lung expansion

Heterogeneity in narrowing among individual airways is an important contributor to airway hyperresponsiveness. This paper investigates the contribution of longitudinal heterogeneity (the variability along the airway in cross-sectional area and shape) to airway resistance (R(aw)). We analyzed chest high-resolution computed tomography scans of 8 asthmatic (AS) and 9 nonasthmatic (NA) subjects before and after methacholine (MCh) challenge, and after lung expansion to total lung capacity. In each subject, R(aw) was calculated for 35 defined central airways with >2 mm diameter. Ignoring the area variability and noncircular shape results in an underestimation of R(aw) (%U(total)) that was substantial in some airways (∼50%) but generally small (median <6%). The average contribution of the underestimation of R(aw) caused by longitudinal heterogeneity in the area (%U(area)) to %U(total) was 36%, while the rest was due to the noncircularity of the shape (%U(shape)). After MCh challenge, %U(area) increased in AS and NA (P < 0.05). A lung volume increase to TLC reduced %U(total) and %U(area) in both AS and NA (P < 0.0001, except for %U(total) in AS with P < 0.01). Only in NA, %U(shape) had a significant reduction after increasing lung volume to TLC (P < 0.005). %U(area) was highly correlated, but not identical to the mean-normalized longitudinal heterogeneity in the cross-sectional area [CV(2)(A)] and %U(shape) to the average eccentricity of the elliptical shape. This study demonstrates that R(aw) calculated assuming a cylindrical shape and derived from an average area along its length may, in some airways, substantially underestimate R(aw). The observed changes in underestimations of R(aw) with the increase in lung volume to total lung capacity may be consistent with, and contribute in part to, the differences in effects of deep inhalations in airway function between AS and NA subjects.

An ultrastructural and biochemical analysis of collagen in rat peripheral nerves: the relationship between fibril diameter and mechanical properties

Mechanical features are distributed heterogeneously within nerve tissue, with compliance increased at articulations. This study explored whether differences in stiffness between joint regions (JRs) and non-joint regions (NJRs) of rat median and sciatic nerves were related to localised variation in collagen content or fibril diameter. There was no significant difference in the amount of collagen detected by biochemical assay in JRs and NJRs of either nerve. Ultrastructural analysis showed collagen fibril diameter ranges of 20-80 nm in the endoneurium and perineurium and 30-130 nm in the epineurium. In the median nerve, but not the sciatic nerve, there were significantly smaller fibrils in JRs compared to NJRs. This corresponded to a greater number density of fibrils in JRs compared to NJRs in the epineurium and endoneurium of the median nerve. We report the presence therefore of a population of thinner collagen fibrils in the JR of the median nerve that corresponds to the location of increased compliance in this tissue, suggesting that localised variation in collagen fibril diameter contributes to the longitudinal heterogeneity of tensile properties in this nerve.

Non-uniform distribution of strain during stretch of relaxed skeletal muscle fibers from rat soleus muscle.

Tension and regional average sarcomere length (L(s)) behavior were examined during repeated stretches of single, permeabilized, relaxed muscle fibers isolated from the soleus muscles of rats. We tested the hypothesis that during stretches of single permeabilized fibers, the global fiber strain is distributed non-uniformly along the length of a relaxed fiber in a repeatable pattern. Each fiber was subjected to eight constant-velocity stretch and release cycles with a strain of 32% and strain rate of 54% s(-1). Stretch-release cycles were separated by a 4.5 min interval. Throughout each stretch-release cycle, sarcomere lengths were measured using a laser diffraction technique in which 20 contiguous sectors along the entire length of a fiber segment were scanned within 2 ms. The results revealed that: (1) the imposed length change was not distributed uniformly along the fiber, (2) the first stretch-release cycle differed from subsequent cycles in passive tension and in the distribution of global fiber strain, and (3) a characteristic "signature" for the L(s) response emerged after cycle 3. The findings support the conclusions that longitudinal heterogeneity exists in the passive stiffness of individual muscle fibers and that preconditioning of fibers with stretch-release cycles produces a stable pattern of sarcomere strains.

Longitudinal heterogeneity of sediment characteristics during southwest monsoon season in hyper-eutrophic Krishnagiri reservoir, India

Krishnagiri reservoir is a hyper-eutrophicated reservoir located in Krishnagiri district which is one of the drought-prone districts in Tamil Nadu, India. The reservoir water is being used for various purposes such as irrigation, drinking, fish rearing, livestock rearing, and recreation. Since there is no an evidence of investigation on bottom sediments in Krishnagiri reservoir, the present study was carried out during southwest monsoon season in 2008. This study examined the physical and chemical characteristics of the bottom sediments such as composition, redox potential, moisture content, organic carbon, organic matter, total phosphorus, and total iron at 15 locations in the reservoir. Phosphorus fractionation study was carried out to find out different fractions such as loosely adsorbed phosphorous, iron and aluminium-bound phosphorus, calcium-bound phosphorous, and organic phosphorous. Results indicated that there was spatial variation in the composition of sediments and low values of redox potential. The significant positive correlation exists between the organic carbon and organic phosphorus concentration. The lacustrine zone of the reservoir showed high accumulation of total phosphorus and total iron when compared to riverine and transition zones. This study concludes an allogenic origin of majority of inorganic phosphorus in the reservoir during the study period and this might have been derived from the catchment during the erosion process. The high concentration of surface sediment phosphorus clearly indicates a greater threat of eutrophication in Krishnagiri reservoir.

The stabilizing effect of resting egg banks of the Daphnia longispina species complex for longitudinal taxon heterogeneity in long and narrow reservoirs

We compared the spatial distribution of taxa from the Daphnia longispina complex (D. longispina, D. galeata, D. cucullata, and their hybrids) in the active water column community and in resting egg banks in five long narrow reservoirs in the Czech Republic (Central Europe). In each reservoir, we sampled at both ends of the longitudinal gradient: in the inflow region and at the dam. Ephippia abundance in the sediments significantly increased in the downstream direction, reflecting differences in the sedimentation regime and Daphnia population size. Similarly to the active zooplankton community, in which D. cucullata and D. longispina tended to occur at opposite ends of the reservoirs, Daphnia species and interspecific hybrids in resting eggs revealed a spatially diversified pattern; however, we observed some differences in taxon distributions between sediments and water columns. High relative abundances of hybrid genotypes (up to 16% of resting eggs, and 74% of Daphnia in the water column) confirm that interspecific hybridization is frequent in these reservoirs, and some hybrids are successful in competition with the parental taxa. We assume that the spatial heterogeneity of Daphnia taxonomic composition in reservoirs, being affected by the seasonal selection of taxa within the mixed reservoir species pool, is substantially strengthened by the presence of spatially heterogeneous egg banks.

Recovery of biochemical functionality in polluted flood-plain soils: The role of microhabitat differentiation through revegetation and rehabilitation of the river dynamics

Soil biogeochemical functions in flood-plains are controlled mainly by interactions between river flooding dynamics and vegetation change. This generates a pattern of landscape cross-sectional and longitudinal heterogeneity in texture, microtopography and plant cover. Agricultural uses restrain such mechanisms, eliminating the mosaic of soil environments and vegetation patches in natural flood-plains. The ecological restoration performed in ca. 5000 ha of agricultural lands in the Guadiamar river basin (SW Spain), affected by the Aználcollar mine spill in 1998 (Cd, Cu, Pb and Zn-rich pyritic sludge), has focused on the re-creation of those controlling mechanisms (enhancement of the natural river flooding dynamics and patchy afforestation). We have studied temporal trends, and the role of specific habitats differentiation in the river terraces, on the recovery of the soil biochemical status in the emerging ecosystems. During 2000–2004, the geometric mean of enzyme activities (dehydrogenase, β-glucosidase, urease, arylsulfatase, acid and alkaline phosphatase) increased three-fold in the most-impacted, coarser textured, upper-watershed soils; and by six-fold in less polluted, loamy soils at the mid-watershed. In 2005, sampling was stratified by microhabitats at two representative watershed sections. Vegetation cover-type and transport/sedimentation processes are the main driving forces increasing both the mean value and intra-site spatial heterogeneity of soil properties (especially enzyme activities) in reclaimed areas. In the wet season, soil enzyme activity under adult trees (holm-oaks and Eucaliptus), and in spots where silt and plant residues had accumulated during previous floodings, was more than 50% higher than in bare areas. However, activities were strongly inhibited in eroded areas where pollutant residues appeared in the surface. Woody patches and the grassy matrix of revegetated areas showed distinctive soil N features. Specific plant species effects were observed, such as a generally high enzymatic activity in soils under Tamarix gallica.

Modélisation de la fiabilité structurale des réseaux enterrés dans un environnement hétérogène

ABSTRACT The reliability of buried pipes from the point of view of their longitudinal behavior was studied, in order to analyze the consequences of the longitudinal heterogeneity of the geotechnic conditions on the mechanical behavior of the elements of the network. The spatial variability of the soil is modelled within the framework of the random fields theory, local rigidity being defined by a random variable with its average, its coefficient of variation and its spatial organization, by means of a correlation length. The reliability of the system is analyzed in terms of forces in the pipes (mainly bending moments, which are compared with the ultimate moments of the cross-sections) and in terms of displacements (misalignment, compared with the threshold values, prejudicial with a good hydraulic operation of the system).

Geochemical structure of the Hawaiian plume: Sr, Nd, and Os isotopes in the 2.8 km HSDP‐2 section of Mauna Kea volcano

Sr, Nd, and Os isotopic measurements were made on 110 Mauna Kea lava and hyaloclastite samples from the drillcore retrieved from the second phase of the Hawaii Scientific Drilling Project (HSDP‐2). The samples come from depths of 255 to 3098 meters below sea level, span an age range from 200 to about 550‐600 kyr, and represent an ordered record of the lava output from Mauna Kea volcano as it drifted a distance of about 40 km over the magma‐producing region of the Hawaiian hot spot. The deepest (oldest) samples represent the time when Mauna Kea was closest to the center of the melting region of the Hawaiian plume. The Sr and Os isotopic ratios in HSDP‐2 lavas show only subtle isotopic shifts over the ∼400 kyr history represented by the core. Neodymium isotopes (ɛNd values) increase systematically with decreasing age from an average value of nearly +6.5 to an average value of +7.5. This small change corresponds to subtle shifts in 87Sr/86Sr and 187Os/188Os isotope ratios, with small shifts of ɛHf, a large shift in 208Pb/204Pb and 208Pb/207Pb values, and with a very large shift in He isotope ratios from R/RA values of about 7–8 to values as high as 25. When Mauna Kea was closest to the plume core, the magma source did not have primitive characteristics for Nd, Sr, Pb, Hf, and Os isotopes but did have variable amounts of “primitive” helium. The systematic shifts in Nd, Hf, Pb, and He isotopes are consistent with radial isotopic zoning within the melting region of the plume. The melting region constitutes only the innermost, highest‐temperature part of the thermally anomalous plume mantle. The different ranges of values observed for each isotopic system, and comparison of Mauna Kea lavas with those of Mauna Loa, suggest that the axial region of the plume, which has a radius of ∼20 km, is a mixture of recycled subducted components and primitive lower mantle materials, recently combined during the formational stages of the plume at the base of the mantle. The proportions of recycled and primitive components are not constant, and this requires there be longitudinal (vertical) heterogeneity within the core of the plume. The remainder of the plume, outside this plume “core zone,” is less heterogeneous but distinct from upper mantle as represented by mid‐ocean ridge basalt (MORB). The plume structure may provide a detailed view of mantle isotopic composition near the core‐mantle boundary.

Changes in the spectral and chemical properties of a water mass passing through extensive macrophyte beds in a large fluvial lake (Lake Saint-Pierre, Québec, Canada)

Large fluvial lakes, as part of river corridors, are recognized as spatially heterogeneous ecosystems. Due to their shallowness, the littoral zone of these lakes occupies a large proportion of their surface and is extensively covered by macrophytes that are known to affect their physical, chemical and biological environments in various ways. This study documents the small-scale (5 km) bio-optical variations associated with the longitudinal passage of a water mass through macrophyte beds during their maximal growth season. The utilization of a 2D hydrodynamic model allowed us to establish hydrological connectivity between stations within the beds, and thus to identify longitudinal heterogeneity along the macrophyte beds. Significant changes in the inherent properties of the water were observed along the upstream-downstream gradient. Due to their effects on hydrodynamics, macrophytes were responsible for a decrease in particles and dissolved organic carbon (DOC) resulting in an increasing penetration depth of ultraviolet (UV) and photosynthetically active radiation (PAR). Along the transect, chromophoric dissolved organic matter (CDOM) decreased more rapidly than DOC resulting in a decrease of the CDOM to DOC ratio. The observed changes in the DOC pool may be explained by the constant input of non-chromophoric DOC from macrophyte leachates and exudation within the bed and/or the photochemical and microbial degradation of CDOM. The implication of such small-scale heterogeneity on Lake Saint-Pierre productivity is discussed.

CORAL PHOTOBIOLOGY STUDIED WITH A NEW IMAGING PULSE AMPLITUDE MODULATED FLUOROMETER1

A new high‐resolution imaging fluorometer (Imaging‐PAM) was used to identify heterogeneity of photosynthetic activity across the surface of corals. Three species were examined: Acropora nobilis Dana (branching), Goniastrea australiensis Edwards &amp; Haime (massive), and Pavona decussata Dana (plate). Images of fluorescence parameters (F, Fm′, effective quantum yield, optimal quantum yield, electron transport rate, relative photosynthetic rate, and non‐photochemical quenching) allowed heterogeneity to be detected in terms of position on colony and indicated that the photosynthetic activity of polyp and coenosarc tissues responded differently to changing light for all three species. The Imaging‐PAM offers a special routine, with which images of PAR absorption (absorptivity) are obtained. In this way, for the first time it has become possible to derive images of the relative photosynthesis rate. Polyps had a lower PAR absorptivity than coenosarc tissue for A. nobilis and P. decussata, whereas G. australiensis showed the opposite pattern. Acropora nobilis showed heterogeneity along the longitudinal axis of the branch, which could be differentiated from the effect of variations in illumination across the rugose and curved surface. Diel changes were apparent and influenced the longitudinal heterogeneity along the A. nobilis branch. Images were also obtained showing the degree of photoinhibition caused by high‐light stress across a coral surface at a hitherto unobtainable level of resolution.

Fluorescence imaging application: effect of leaf age on seagrass photokinetics

We used the Imaging-PAM fluorometer to map spatial variability of photosynthesis in three seagrass species, Halophila ovalis, Zostera capricorni and Posidonia australis. Photosynthesis was described by relative photosynthetic rate (PS/50), effective quantum yield (Φ PSII), non-photochemical quenching (NPQ and qN), electron transport rate (ETR) and leaf absorptivity. Photosynthetic patterns were linked to leaf age and light climate but patterns were not consistent across species. Longitudinal heterogeneity in photosynthesis was apparent along the leaves of all three species while lateral spatial heterogeneity was found only across Z. capricorni and H. ovalis leaves. Age of leaf tissue, determined by longitudinal location on the leaf, strongly influenced photosynthetic activity of Z. capricorni and P. australis. A comparison of H. ovalis leaves of differing maturity demonstrated the influence of leaf age on photosynthetic activity, yet a comparison of Z. capricorni leaves of differing maturity showed no leaf-age effects. Variations in stress-induced changes across a seagrass leaf can be used to identify areas or particular regions of the leaf, which are more susceptible to photodamage. Clear evidence of substantial within-leaf heterogeneity in photosynthetic activity (i.e., a two-fold variation in half saturation constant along a leaf of P. australis) has serious implications for use of small sections of leaf for photosynthetic incubations (such as O 2 or single-point chlorophyll a fluorescence measurements).

Peripheral nerves in the rat exhibit localized heterogeneity of tensile properties during limb movement.

Peripheral nerves in the limbs stretch to accommodate changes in length during normal movement. The aim of this study was to determine how stretch is distributed along the nerve relative to local variations in mechanical properties. Deformation (strain) in joint and non-joint regions of rat median and sciatic nerves was measured in situ during limb movement using optical image analysis. In each nerve the strain was significantly greater in the joint rather than the non-joint regions (2-fold in the median nerve, 5- to 10-fold in the sciatic). In addition, this difference in strain was conserved in the median nerve ex vivo, demonstrating an in-built longitudinal heterogeneity of mechanical properties. Tensile testing of isolated samples of joint and non-joint regions of both nerves showed that joint regions were less stiff (more compliant) than their non-joint counterparts with joint: non-joint stiffness ratios of 0.5 +/- 0.07 in the median nerve, and 0.8 +/- 0.02 in the sciatic. However, no structural differences identified at the light microscope level in fascicular/non-fascicular tissue architecture between these two nerve regions could explain the observed tensile heterogeneity. This identification of localized functional heterogeneity in tensile properties is particularly important in understanding normal dynamic nerve physiology, provides clues to why peripheral nerve repair outcomes are variable, and suggests potential novel therapeutic targets.

Analysis of Bernoulli beams with 3D stochastic heterogeneity

The behavior of stochastically heterogeneous beams, composed of isotropic sub-elements of randomly distributed stiffness is studied. Cross sectional as well as longitudinal heterogeneity are included. Average displacements, reaction forces and their statistical variance are found analytically by a functional perturbation method. Ratio of sub-element to beam characteristic size is not negligible and the use of an equivalent homogeneous structure with the classical effective material properties is not sufficient. The major aim is to study the relation between various microstructure properties (grain size, shape, modulus, statistical correlation lengths etc.) and the overall behavior of linear elastic Bernoulli beams. For the statically determinate case, only cross sectional 2D microstructure statistics is found to affect the elastic response, so that an equal average displacement can be achieved by an equivalent, non-isotropic homogeneous beam. For the indeterminate case, the average values of macro properties are affected by the 3D morphological features. Therefore, the proper equivalent homogeneous beam has to include non-local elastic properties. A simple reciprocal relation, connecting two separate loading systems is found, relating their external forces and displacement statistical variances. Morphological parameters, like two point probability moments, used in the final results are derived analytically, and their physical interpretations are discussed.

Gluconeogenesis from glutamine and lactate in the isolated humanrenal proximal tubule: longitudinal heterogeneity and lack of response to adrenaline

Recent studies in vivo have suggested that, in humans in the postabsorptive state, the kidneys contribute a significant fraction of systemic gluconeogenesis, and that the stimulation of renal gluconeogenesis may fully explain the increase in systemic gluconeogenesis during adrenaline infusion. Given the potential importance of human renal gluconeogenesis in various physiological and pathophysiological situations, we have conducted a study in vitro to further characterize this metabolic process and its regulation. For this, successive segments (S1, S2 and S3) of human proximal tubules were dissected and incubated with physiological concentrations of glutamine or lactate, two potential gluconeogenic substrates that are taken up by the human kidney in vivo, and glucose production was measured. The effects of adrenaline, noradrenaline and cAMP, a well established stimulator of gluconeogenesis in animal kidney tubules, were also studied in suspensions of human renal proximal tubules. The results indicate that the three successive segments have about the same capacity to synthesize glucose from glutamine; by contrast, the S2 and S3 segments synthesize more glucose from lactate than the S1 segment. In the S2 and S3 segments, lactate appears to be a better gluconeogenic precursor than glutamine. The addition of cAMP, but not of adrenaline or noradrenaline, led to the stimulation of gluconeogenesis from lactate and glutamine by human proximal tubules. These results indicate that, in the human kidney in vivo, lactate might be the main gluconeogenic precursor, and that the stimulation of renal gluconeogenesis observed in vivo upon adrenaline infusion may result from an indirect action on the renal proximal tubule.

Gluconeogenesis from glutamine and lactate in the isolated human renal proximal tubule: longitudinal heterogeneity and lack of response to adrenaline.

Recent studies in vivo have suggested that, in humans in the postabsorptive state, the kidneys contribute a significant fraction of systemic gluconeogenesis, and that the stimulation of renal gluconeogenesis may fully explain the increase in systemic gluconeogenesis during adrenaline infusion. Given the potential importance of human renal gluconeogenesis in various physiological and pathophysiological situations, we have conducted a study in vitro to further characterize this metabolic process and its regulation. For this, successive segments (S1, S2 and S3) of human proximal tubules were dissected and incubated with physiological concentrations of glutamine or lactate, two potential gluconeogenic substrates that are taken up by the human kidney in vivo, and glucose production was measured. The effects of adrenaline, noradrenaline and cAMP, a well established stimulator of gluconeogenesis in animal kidney tubules, were also studied in suspensions of human renal proximal tubules. The results indicate that the three successive segments have about the same capacity to synthesize glucose from glutamine; by contrast, the S2 and S3 segments synthesize more glucose from lactate than the S1 segment. In the S2 and S3 segments, lactate appears to be a better gluconeogenic precursor than glutamine. The addition of cAMP, but not of adrenaline or noradrenaline, led to the stimulation of gluconeogenesis from lactate and glutamine by human proximal tubules. These results indicate that, in the human kidney in vivo, lactate might be the main gluconeogenic precursor, and that the stimulation of renal gluconeogenesis observed in vivo upon adrenaline infusion may result from an indirect action on the renal proximal tubule.