Allometric Approach Research Articles

Estimation of tree biomass and carbon stock in the Tangkoko Nature Reserve, North Sulawesi

The objective of this study is to tree biomass and forest carbon stocks contained in the Tangkoko Nature Reserve (TNR) of North Sulawesi. Phylogenetic diversity was analysed based on tree species composition weighted by aboveground biomass. A stratified systematic sampling was used in the study across transect lines. Field measurements follow the method described in the SNI 7724:2019 on ground-based forest carbon accounting. Based on allometric approach, this study produces a quantity of 255.45 Mg.ha−1 of total biomass estimation consisting of 201.14 Mg.ha−1 AGB and 54.31 Mg.ha−1 BGB. A standard approach of C-stock calculation (i.e. 47% of tree biomass and 50% of soil organic biomass) results in quantities of 94.53 and 27.15 Mg.ha−1 respectively). The importance of species traits for biomass estimation should be considered by initiatives in reforestation for carbon offsetting.

Key Anthropometric Variables Associated With Front-Crawl Swimming Performance in Youth Swimmers: An Allometric Approach.

Sammoud, S, Negra, Y, Chaabene, H, Bouguezzi, R, Attia, A, Granacher, U, Younes, H, and Nevill, AM. Key anthropometric variables associated with front-crawl swimming performance in youth swimmers: an allometric approach. J Strength Cond Res 37(6): 1259-1263, 2023-This study aimed to establish key anthropometric characteristics (e.g., optimal body height, limb-segment length, and girth/breadth ratios) related to 100-m front-crawl performance in young swimmers. In total, 74 swimmers (boys [ n = 41; age: 18.1 ± 3.5 years]; girls [ n = 33; age: 15.9 ± 3.1 years]) participated in this study. We adopted a multiplicative allometric log-linear regression model to identify key anthropometric characteristics associated with 100-m front-crawl swimming performance. The main outcomes indicated that length ratio = ([height/leg length]), foot length and ankle girth, biacromial breadth, and % of body fat were associated with 100-m front-crawl mean swimming speed performance. These findings highlight the importance of assessing anthropometric characteristics in young front-crawl swimmers for talent identification and development.

Forest carbon stock and biomass estimation in West Central India using two allometric models

The west central Indian forest ecosystems strongly contribute to livelihood of local human communities as well as climate change mitigation. However, due to the lack of accurate biomass equations and predictive tools, the contribution of these forests towards carbon stock and sequestration remains poorly recognized. At present due to some developmental and mining activities these forests face huge anthropogenic pressure.Therefore, the objective of the present study was to estimate the biomass and carbon stock of forest tree species of west central India to provide baseline information. It will also be useful for measuring the changes after the intervention as well as for future management and conservation.The non-destructive allometric equation approach was adopted to estimate the biomass, carbon stock and carbon dioxide equivalent from total 28 plots of 0.1 ha at seven sites of dry deciduous forests of west central India. In the present study, the results of biomass and carbon stock were calculated by employing two different allometric models.The model with tree diameter and wood specific gravity gave higher estimations of total plant biomass (123.39 – 65.86 Mg ha−1) and carbon stock (58.61—31.28 Mg ha−1) as compared with model having only tree diameter (108.84 – 55.91 Mg ha−1) and (51.70 -26.55 Mg ha−1), respectively.We conclude that the allometric model with tree diameter and wood specific gravity was found best suited for these forests. The results also showed the positive relation between tree diversity, basal area and aboveground biomass and carbon stock.

Allometric analysis of sexual dimorphism and morphological variation in two chromosome races of the Sceloporus grammicus complex (Squamata: Phrynosomatidae) from Mexico

Sexual dimorphism is a widespread feature in the Animal Kingdom. In lizards of the Sceloporus grammicus complex, studies of sexual dimorphism that analyze the allometric trajectories of body traits remain unexplored. Here we investigate sexual dimorphism in key phenotypic traits, including body size (snout-vent length, SVL) as well as head length (HL), head width (HW), and forearm length (FL). We use an allometric approach to detect differences in scale relationships among body parts in the S. grammicus complex in Mexico. We focus on two chromosomal races within this complex, F5 (2n = 34) and FM2 (2n = 46). In the complex, we found that males are larger than females in all morphological variables, and this pattern was confirmed in both races. We determined negative allometric trajectories (SVLvs.HL and HW), isometry (SVLvs.FL) and intersexual differences in the slopes of the SVLvs.HL and HW; the males showed steeper slopes. Thus, the growth of the head is more pronounced in males than females. Additionally, we found between-race differences in these trajectories (SVLvs.FL) and in all morphological variables (F5 lizards are larger than those of the FM2 race), which correlate with their chromosomal divergence. We discuss biological implications of our findings in relation to sexual selection and natural selection.

593. Population Pharmacokinetic Model Development for Epetraborole and Mycobacterium avium Complex (MAC) Lung Disease Patients Using Data from Phase 1 and 2 Studies

593. Population Pharmacokinetic Model Development for Epetraborole and <i>Mycobacterium avium</i> Complex (MAC) Lung Disease Patients Using Data from Phase 1 and 2 Studies

Translational Approach for Predicting Human Pharmacokinetics of Engineered Therapeutic Monoclonal Antibodies with Increased FcRn-Binding Mutations.

Recently, increasing FcRn binding by Fc engineering has become a promising approach for prolonging the half-life of therapeutic monoclonal antibodies (mAbs). This study is the first to investigate the optimization of an allometric scaling approach for engineered mAbs based on cynomolgus monkey data to predict human pharmacokinetics. Linear two-compartmental model parameters (clearance [CL]; volume of distribution in the central compartment [Vc]; inter-compartmental clearance [Q]; volume of distribution in the peripheral compartment [Vp]) after the intravenous (IV) injection of engineered mAbs (M252Y/S254T/T256E or M428L/N434S mutations) in cynomolgus monkeys and humans were collected from published data. We explored the optimal exponent for allometric scaling to predict parameters in humans based on cynomolgus monkey data. Moreover, the plasma concentration-time profile of engineered mAbs after IV injection in humans was predicted using parameters estimated based on an optimized exponent. For engineered mAbs, a significant positive correlation between cynomolgus monkeys and humans was observed for CL, but not for other parameters. Whereas conventional exponents (CL: 0.8, Q: 0.75, Vc: 1.0, Vp: 0.95) previously established for normal mAbs showed poor prediction accuracy for CL and Q of engineered mAbs, the newly optimized exponents (CL: 0.55, Q: 0.6, Vc: 0.95, Vp: 0.95) achieved superior predictability for engineered mAbs. Moreover, the optimized exponents accurately predicted plasma mAb concentration-time profiles after IV injection of engineered mAbs in humans. We found that engineered mAbs require specially optimized exponents to accurately predict pharmacokinetic parameters and plasma concentration-time profiles after IV injections in humans based on cynomolgus monkey data. This optimized approach can contribute to a more accurate prediction of human pharmacokinetics in the development of engineered mAbs.

Interspecies normalization of dose-response relationship for adeno-associated virus-mediated haemophilia gene therapy-Application to human dose prediction.

The aim of this study is to develop an approach to predict human dose-response relationship and first-in-human (FIH) dose for adeno-associated virus (AAV)-mediated haemophilia gene therapy. Preclinical dose-response relationships of 7 AAV vectors were normalized to a species-invariant scale using an exponent of 0.25, and the normalized dose-response relationship was then used for FIH dose prediction. The performance of this dose-response normalization approach for FIH dose prediction was compared to that of direct body weight-based dose (vg/kg) conversion and allometric scaling approaches. A power regression analysis of normalized factor VIII (FVIII) or factor IX (FIX) showed a moderate-to-strong correlation between FVIII or FIX and vector dose across 3 species (R2 ranged 0.59 to 0.89), indicating it was feasible to normalize dose-response in multiple species to a species-invariant scale. When the mean values of normalized FVIII or FIX at each dose level were used for regression, the R2 values of the 7 vectors were improved to be >0.84. The FIH doses predicted by the 3 approaches were ranked as allometric scaling > dose-response normalization > direct vg/kg conversion for all vectors except for rAAV2-hAAT-FIX and scAAV2/8-LP1-hFIXco. Among the 7 vectors, dose-response normalization, direct vg/kg conversion and allometric scaling generated accurate FIH dose predictions for 2, 2 and 3 vectors, respectively. This study first demonstrated that it is feasible to normalize dose-response relationship of AAV-mediated haemophilia gene therapy in multiple species to a species-invariant scale. The normalized dose-response relationship from preclinical species was successfully extrapolated to patients for FIH dose prediction.

First-in-Patient Dose Prediction for Adeno-Associated Virus-Mediated Hemophilia Gene Therapy Using Allometric Scaling.

In this study, the author compared the performance of two allometric scaling approaches and body-weight-based dose conversion approach for first-in-patient (FIP) dose prediction for adeno-associated virus (AAV)-mediated hemophilia gene therapy using preclinical and clinical efficacy data of nine AAV vectors. In general, body-weight-based direct conversion of effective doses in monkeys or dogs was more likely to underestimate FIP dose but worked for one bioengineered vector with a high transduction efficiency specifically in humans. In contrast, allometric scaling between gene efficiency factor (log GEF) and body weight (log W) was likely to overestimate FIP dose but worked for two vectors with capsid-specific T-cell responses in patients. The third approach, allometric scaling between log GEF and W-0.25 was appropriate for FIP dose prediction in the absence of T-cell responses to AAV vectors or a dramatic difference in vector transduction efficiency between animals and humans.

Tailored Torsion and Bending‐Resistant Avian‐Inspired Structures

The escalating demand for torsion‐ and bending‐resistant structures paired with the need for more efficient use of materials and geometries, have led to novel bio‐inspired ingenious solutions. However, lessons from Nature could be as inspiring as they are puzzling: plants and animals offer an enormous range of promising but hierarchically complex configurations. Avian bones are prominent candidates for addressing the torsional and bending issue. They present a unique intertwining of simple components: helicoidal ridges and crisscrossing struts, able to bear flexural and twisting actions of winds. Here, it is set how to harmonically move from the natural to the engineering level to formalize and analyze the biological phenomena under controlled design conditions. The effect of ridges and struts is isolated and combined toward tailored torsion and bending‐resistant arrangements. Then the biological level is revisited to extrapolate the avian allometric design approach and is translated into multiscale lightweight structures at the engineering level. This study exploits the complexity of Nature and the scalability that characterizes the evolutionary design of bird bones through the design and fabrication versatility allowed by additive manufacturing technologies. This paves the way for exploring the transferability of the proposed solution at multiple engineering scales.

Current Approaches for Predicting Human PK for Small Molecule Development Candidates: Findings from the IQ Human PK Prediction Working Group Survey.

Accurate prediction of human clearance (CL) and volume of distribution at steady state (Vd,ss) for small molecule drug candidates is an essential component of assessing likely efficacious dose and clinical safety margins. In 2021, the IQ Consortium Human PK Prediction Working Group undertook a survey of IQ member companies to understand the current PK prediction methods being used to estimate these parameters across the pharmaceutical industry. The survey revealed a heterogeneity in approaches being used across the industry (e.g., the use of allometric approaches, differing incorporation of binding terms, and inconsistent use of empirical correction factors for in vitro-in vivo extrapolation, IVIVE), which could lead to different PK predictions with the same input data. Member companies expressed an interest in improving human PK predictions by identifying the most appropriate compound-class specific methods, as determined by physiochemical properties and knowledge of CL pathways. Furthermore, there was consensus that increased understanding of the uncertainty inherent to the compound class-dependent prediction would be invaluable in aiding communication of human PK and dose uncertainty at the time of candidate nomination for development. The human PK Prediction Working Group is utilizing these survey findings to help interrogate clinical IV datasets from across the IQ consortium member companies to understand PK prediction accuracy and uncertainty from preclinical datasets.

Allometric Models to Estimate Carbon Content in Arecaceae Based on Seven Species of Neotropical Palms

We present allometric models for estimating total carbon content and above ground carbon (AGC) for the Arecaceae family, and for seven abundant neotropical palm species: the canopy speciesSocratea exorrhiza(n= 10) andIriartea deltoidea(n= 10), the sub-canopy palmEuterpe precatoria(n= 10), and the understory speciesAsterogyne martiana(n= 15),Prestoea decurrens(n= 10),Geonoma interrupta(n= 10), andChamaedorea tepejilote(n= 22). Understanding the allometry of functional groups such as palms is critical for improving carbon stocks estimates in tropical forests and determining how allometric differences affect species functional diversity. The research was carried out in the tropical rainforests of the Caribbean slope of Costa Rica. We harvested 87 palms of a wide range of sizes, and separated them into roots, stems, and leaves, measured their fresh and dry biomass, and calculated their carbon content, tissue density, and dry mass fraction (dmf). Our general palm model estimating total carbon content based on these seven species and 87 samples accounted for 92% of the variation across species. We generated a similar model to estimate AGC and explained 91% of the variation. We compared our AGC model with two models used to estimate palm carbon content:Goodman et al. (2013)’s andChave et al. (2014)’s models and found that all three converged on the estimation of AGC although our model was the most parsimonious because it achieved the same efficiency with only two variables, stem diameter and stem height. To improve the accuracy of allometric models we need to incorporate more species, a greater diversity of growth forms, a wider range of sizes, a larger sample size, and more diversity of habitats dominated by palms. Estimating carbon content using allometric approaches could benefit from more consistency in data collection across plant groups.

Population Pharmacokinetic Model of AST-001, L-Isomer of Serine, Combining Endogenous Production and Exogenous Administration in Healthy Subjects.

AST-001 is an L-isomer of serine that has protective effects on neurological disorders. This study aimed to establish a population pharmacokinetic (PK) model of AST-001 in healthy Korean to further propose a fixed-dose regimen in pediatrics. The model was constructed using 648 plasma concentrations from 24 healthy subjects, including baseline endogenous levels during 24 h and concentrations after a single dose of 10, 20, and 30 g of AST-001. For the simulation, an empirical allometric power model was applied to the apparent clearance and volume of distribution with body weight. The PK characteristics of AST-001 after oral administration were well described by a two-compartment model with zero-order absorption and linear elimination. The endogenous production of AST-001 was well explained by continuous zero-order production at a rate of 0.287 g/h. The simulation results suggested that 2 g, 4 g, 7 g, 10 g, and 14 g twice-daily regimens for the respective groups of 10–14 kg, 15–24 kg, 25–37 kg, 38–51 kg, 52–60 kg were adequate to achieve sufficient exposure to AST-001. The current population PK model well described both observed endogenous production and exogenous administration of AST-001 in healthy subjects. Using the allometric scaling approach, we suggested an optimal fixed-dose regimen with five weight ranges in pediatrics for the upcoming phase 2 trial.

Gross motor coordination and their relationship with body mass and physical activity level during growth in Children aged 8-11 years old: a longitudinal and allometric approach.

BackgroundGross motor coordination (GMC) is fundamental to the harmonious development of physical skills during the growth of children. This research aimed to explore the developmental changes in GMC during childhood, having controlled for the differences in children’s body size and shape using a longitudinal, allometric scaling methodology.MethodsA total of 104 children from North-East Italy of third-fourth- and fifth-grade students and each participant were tested for three consequently years. Subjects performed the short version of korperkoordinationstest fur kinder (KTK3) and the anthropometric characteristics were simultaneously collected. The physical activity questionnaire (PAQ-C) was used to evaluate the weekly physical engagement.ResultsOntogenetic multiplicative models suggested nonlinear associations with GMC across the children’s developmental years. Linear physique was a significant predictor associated with the development of GMC across time. PAQ-C was significantly associated with GMC from 8 to 13 years old.ConclusionGrowth does not respect linear trends. A greater lean body mass could be assessed as a reliable predictor of GMC in children. The crucial period of life to improve the GMC is 8–10 years, while stabilization becomes evident from 10 to 13 years.

Cross-sectional associations of body size indicators and lifestyle behaviors with cardiorespiratory fitness among adolescents: an allometric approach

Cross-sectional associations of body size indicators and lifestyle behaviors with cardiorespiratory fitness among adolescents: an allometric approach

Population Pharmacokinetics of Nifurtimox in Adult and Pediatric Patients With Chagas Disease

Nifurtimox (LAMPIT) has been used for decades for the treatment of Chagas disease, a chronic and potentially life-threatening disease caused by the parasite Trypanosoma cruzi. The pharmacokinetic (PK) information on nifurtimox in humans derived from controlled clinical studies is very limited. The objective was to investigate and compare the population PK of nifurtimox in adult and pediatric patients with Chagas disease to confirm the clinical dosing regimen in children, which was based on allometric approaches using the concept that a dose-equivalent exposure would reach equivalent antiparasitic efficacy as in adults. The resulting adult model adequately described the PK in adults. Significant predictors of the availability in PK were food intake, tablet formulation (fast- vs slow-dissolution tablet), study, and body weight. As the resulting adult model could not adequately predict the sparse sampled pediatric patient data, these data were analyzed separately to derive exposure estimates for comparison with adult exposure. In the population PK model for pediatric patients, significant covariates were body weight and age. As compared to adults, children aged >2 years were estimated to have 50.6% higher apparent clearance. No hints of dose nonlinearity were observed in a dose range of 30 to 240 mg single dose in adults and 15 to 300 mg 3 times daily (8-20 mg/kg) in children. Altogether, this study retroactively showed that the current mg/kg dosing regimen in children reached similar exposure as in adults receiving an 8 mg/kg total daily dose.

An allometric model-based approach for estimating biomass in seven Indian bamboo species in western Himalayan foothills, India

The rapid growth rate, high biomass production, and annual harvesting make bamboo a suitable species for commercial production. Allometric equations for many broadleaf and conifer tree species are available. However, knowledge of biomass production and allometric equations of bamboos is limited. This study aims to develop species- specific allometric models for predicting biomass and synthetic height values as a proxy variable for seven bamboo species in Himalayan foothills. Two power form-based allometric models were used to predict aboveground and culm biomass using diameter at breast height (D) alone and D combined with culm height (H) as an independent variable. This study also extended to establishing an H–D allometric model that can be used to generate synthetic H values as a proxy to missing H. In the seven bamboo species studied, among three major biomass components (culm, branch and foliage), culm is the most important component with the highest share (69.56–78.71%). The distribution of percentage (%) share of culm, branch and foliage to above-ground fresh weight varies significantly between different bamboo species. D. hamiltonii has the highest productivity for above-ground biomass components. Ratio of dry to fresh weight of seven bamboo species was estimated for culm, branch, foliage and above-ground biomass to convert fresh weight to dry weight.

Measuring plant biomass remotely using drones in arid landscapes.

Measurement of variation in plant biomass is essential for answering many ecological and evolutionary questions. Quantitative estimates require plant destruction for laboratory analyses, while field studies use allometric approaches based on simple measurement of plant dimensions.We estimated the biomass of individual shrub‐sized plants, using a low‐cost unmanned aerial system (drone), enabling rapid data collection and non‐destructive sampling. We compared volume measurement (a surrogate for biomass) and sampling time, from the simple dimension measurements and drone, to accurate laboratory‐derived biomass weights. We focused on three Australian plant species which are ecologically important to their terrestrial and floodplain ecosystems: porcupine grass Triodia scariosa, Queensland bluebush Chenopodium auricomum, and lignum Duma florulenta.Estimated volume from the drone was more accurate than simple dimension measurements for porcupine grass and Queensland bluebush, compared to estimates from laboratory analyses but, not for lignum. The latter had a sparse canopy, with thin branches, few vestigial leaves and a similar color to the ground. Data collection and analysis consistently required more time for the drone method than the simple dimension measurements, but this would improve with automation.The drone method promises considerable potential for some plant species, allowing data to be collected over large spatial scales and, in time series, increasing opportunities to answer complex ecological and evolutionary questions and monitor the state of ecosystems and plant populations.

A PBPK Model of Ternary Cyclodextrin Complex of ST-246 Was Built to Achieve a Reasonable IV Infusion Regimen for the Treatment of Human Severe Smallpox.

ST-246 is an oral drug against pathogenic orthopoxvirus infections. An intravenous formulation is required for some critical patients. A ternary complex of ST-246/meglumine/hydroxypropyl-β-cyclodextrin with well-improved solubility was successfully developed in our institute. The aim of this study was to achieve a reasonable intravenous infusion regimen of this novel formulation by a robust PBPK model based on preclinical pharmacokinetic studies. The pharmacokinetics of ST-246 after intravenous injection at different doses in rats, dogs, and monkeys were conducted to obtain clearances. The clearance of humans was generated by using the allometric scaling approach. Tissue distribution of ST-246 was conducted in rats to obtain tissue partition coefficients (K p ). The PBPK model of the rat was first built using in vivo clearance and K p combined with in vitro physicochemical properties, unbound fraction, and cyclodextrin effect parameters of ST-246. Then the PBPK model was transferred to a dog and monkey and validated simultaneously. Finally, pharmacokinetic profiles after IV infusion at different dosages utilizing the human PBPK model were compared to the observed oral PK profile of ST-246 at therapeutic dosage (600 mg). The mechanistic PBPK model described the animal PK behaviors of ST-246 via intravenous injection and infusion with fold errors within 1.2. It appeared that 6h-IV infusion at 5 mg/kg BID produced similar Cmax and AUC as oral administration at 600 mg. A PBPK model of ST-246 was built to achieve a reasonable regimen of IV infusion for the treatment of severe smallpox, which will facilitate the clinical translation of this novel formulation.

A new protocol for estimation of woody aboveground biomass in disturbance-prone ecosystems

Almost one third of global drylands are open forests and savannas, which are typically shaped by frequent natural disturbances such as wildfire and herbivory. Studies on ecosystem functions and services of woody vegetation require robust estimates of aboveground biomass (AGB). However, most methods have been developed for comparatively undisturbed forest ecosystems. As they are not tailored to accurately quantify AGB of small and irregular growth forms, their application on these growth forms may lead to unreliable or even biased AGB estimates in disturbance-prone dryland ecosystems. Moreover, these methods cannot quantify AGB losses caused by disturbance agents. Here we propose a methodology to estimate individual- and stand-level woody AGB in disturbance-prone ecosystems. It consists of flexible field sampling routines and estimation workflows for six growth classes, delineated by size and damage criteria. It also comprises a detailed damage assessment, harnessing the ecological archive of woody growth for past disturbances. Based on large inventories collected along steep gradients of elephant disturbances in African dryland ecosystems, we compared the AGB estimates generated with our proposed method against estimates from a less adapted forest inventory method. We evaluated the necessary stepwise procedures of method adaptation and analyzed each step’s effect on stand-level AGB estimation. We further explored additional advantages of our proposed method with regard to disturbance impact quantification. Results indicate that a majority of growth forms and individuals in savanna vegetation could only be assessed if methods of AGB estimation were adapted to the conditions of a disturbance-prone ecosystem. Furthermore, our damage assessment demonstrated that one third to half of all woody AGB was lost to disturbances. Consequently, less adapted methods may be insufficient and are likely to render inaccurate AGB estimations. Our proposed method has the potential to accurately quantify woody AGB in disturbance-prone ecosystems, as well as AGB losses. Our method is more time consuming than conventional allometric approaches, yet it can cover sufficient areas within reasonable timespans, and can also be easily adapted to alternative sampling schemes.

DallphinAtoM: Physiologically based pharmacokinetics software predicting human PK parameters based on physicochemical properties, in vitro and animal in vivo data

Background and objectivesIn silico experiments and simulations using physiologically based pharmacokinetic (PBPK) and allometric approaches have played an important role in pharmaceutical research and drug development. These methods integrate diverse data from preclinical and clinical development, and have been widely applied to in vitro-in vivo extrapolation (IVIVE) of absorption, distribution, metabolism, and excretion (ADME). MethodsTo develop a user-friendly open tool predicting human PK, we assessed various references on PBPK and allometric methods published so far. They were integrated into a software system named “DallphinAtoM” (Drugs with ALLometry and PHysiology Inside-Animal to huMan), which has a user-friendly platform that can handle complex PBPK models and allometric models with a relatively small amount of essential information of the drug. The models of DallphinAtoM support the integration of data gained during the nonclinical development phase, enable translation from animal to human, and allow the prediction of concentration-time profiles with predicted PK parameters. ResultsWe presented two illustrative applications using DallphinAtoM: (1) human PK simulation of an orally administered drug using PBPK method; and (2) simulation of intravenous infusion following a two-compartment model using the allometric scaling method. ConclusionsWe conclude that this is a straightforward and transparent tool allowing fast and reliable human PK simulation based on the latest knowledge on biochemical processes and physiology and provides valuable information for decision making during the early-phase drug development.