Frequent, quantitative bone planar scintigraphy for determination of bone anabolism in growing mice

Background To provide insight into bone turnover, quantitative measurements of bone remodeling are required. Radionuclide studies are widely used in clinical care, but have been rarely used in the exploration of the bone in preclinical studies. We describe a bone planar scintigraphy method for frequent assessment of bone activity in mice across the growing period. Since repeated venous radiotracer injections are hardly feasible in mice, we investigated the subcutaneous route. Methods Repeated 99mTc-hydroxymethylene diphosphonate (HMDP) tracer bone planar scintigraphy studies of the knee region and µCT to measure femur growth rate were performed in eight mice between week 6 and week 27 of life, i.e., during their growth period. Three independent investigators assessed the regions of interest (ROI). An index was calculated based on the counts in knees ROI (normalized by pixels and seconds), corrected for the activity administered, the decay between administration and imaging, and individual weights. Results A total of 93 scintigraphy studies and 85 µCT were performed. Repeated subcutaneous tracer injections were well tolerated and allowed for adequate radionuclide studies. Mean scintigraphic indexes in the knees ROI decreased from 87.4 ± 2.6 × 10−6 counts s−1 pixel−1 MBq−1 g−1 at week 6 to 15.0 ± 3.3 × 10−6 counts s−1 pixel−1 MBq−1 g−1 at week 27. The time constant of the fitted exponential decay was equal to 23.5 days. As control mean femur length assessed by µCT increased from 12.2 ± 0.8 mm at week 6 to 15.8 ± 0.2 mm at week 22. The time constant of the fitted Gompertz law was equal to 26.7 days. A correlation index of −0.97 was found between femur growth and decrease of bone tracer activity count between week 6 and 24. Conclusion This methodological study demonstrates the potential of repeated bone planar scintigraphy in growing mice, with subcutaneous route for tracer administration, for quantitative assessment of bone remodeling.

Non-Homogeneous Tumor Growth and Its Implications for Radiotherapy: A Phenomenological Approach

Tumor regrowth and heterogeneity are important clinical parameters during radiotherapy, and the probability of treatment benefit critically depends on the tumor progression pattern in the interval between the fractional irradiation treatments. We propose an analytic, easy-to-use method to take into account clonal subpopulations with different specific growth rates and radiation resistances. The different strain regrowth effects, as described by Gompertz law, require a dose-boost to reproduce the survival probability of the corresponding homogeneous system and for uniform irradiation. However, the estimate of the survival fraction for a tumor with a hypoxic subpopulation is more reliable when there is a slow specific regrowth rate and when the dependence on the oxygen enhancement ratio of radiotherapy is consistently taken into account. The approach is discussed for non-linear two-population dynamics for breast cancer and can be easily generalized to a larger number of components and different tumor phenotypes.

Modified leaky competing accumulator model of decision making with multiple alternatives: the Lie-algebraic approach

In this communication, based upon the stochastic Gompertz law of population growth, we have reformulated the Leaky Competing Accumulator (LCA) model with multiple alternatives such that the positive-definiteness of evidence accumulation is automatically satisfied. By exploiting the Lie symmetry of the backward Kolmogorov equation (or Fokker–Planck equation) assoicated with the modified model and applying the Wei–Norman theorem, we have succeeded in deriving the N-dimensional joint probability density function (p.d.f.) and marginal p.d.f. for each alternative in closed form. With this joint p.d.f., a likelihood function can be constructed and thus model-fitting procedures become feasible. We have also demonstrated that the calibration of model parameters based upon the Monte Carlo simulated time series is indeed both efficient and accurate. Moreover, it should be noted that the proposed Lie-algebraic approach can also be applied to tackle the modified LCA model with time-varying parameters.

Gompertz Law in Clean Foam Coalescence

Clean foams tend to age with time through sequential coalescence events. This study evaluates aging dynamics in clean foams by measuring bubble populations from coalescence simulation experiments and adopting biological population dynamics analysis. The population dynamics of bubbles in clean foams during coalescence show that the mortality rates of individual bubbles change exponentially with time, regardless of initial simulation conditions, consistent with the Gompertz mortality law commonly observed in biological aging. This result would be beneficial in understanding the aging dynamics of clean foams.

Frequent, Quantitative Bone Planar Scintigraphy for Determination of Bone Anabolism in Growing Mice

BackgroundTo provide insight into bone turnover, quantitative measurements of bone remodeling are required. Radionuclide studies are widely used in clinical care, but have been rarely used in the exploration of the bone in preclinical studies. We describe a bone planar scintigraphy method for frequent assessment of bone activity in mice across the growing period. Since repeated venous radiotracer injections are hardly feasible in mice, we investigated the subcutaneous route.MethodsRepeated phosphonate tracer bone planar scintigraphy studies of the knee region and μCT to measure femur growth rate were performed in eight mice between week 6 and week 27 of life, i.e. during their growth period. Three independent investigators assessed the regions of interest (ROI). An index was calculated based on the counts in knees ROI (normalized by pixels and seconds), corrected for the activity administered, the decay between administration and imaging, and individual weights.ResultsA total of 97 scintigraphy studies and 90 μCT were performed. Repeated subcutaneous tracer injections were well tolerated and allowed for adequate radionuclide studies. Mean scintigraphic indexes in the knees ROI decreased from 87.4 ± 13.0x10-6 counts.s-1.pixel-1.MBq-1.g-1 at week 6 to 13.1 ± 3.9x10-6 counts.s-1.pixel-1.MBq-1.g-1 at week 27. The time constant of the fitted exponential decay was equal to 23.6 days. Mean femur length assessed by μCT increased from 12.2 ± 0.8 mm at week 6 to 15.8 ± 0.2 mm at week 24. The time constant of the fitted Gompertz law was equal to 26.7 days.ConclusionThis study demonstrates the potential of repeated bone planar scintigraphy in growing mice, with subcutaneous route for tracer administration, for quantitative assessment of bone remodeling.

Data analysis on Coronavirus spreading by macroscopic growth laws

To evaluate the effectiveness of the containment on the epidemic spreading of the new Coronavirus disease 2019, we carry on an analysis of the time evolution of the infection in a selected number of different Countries, by considering well-known macroscopic growth laws, the Gompertz law, and the logistic law. We also propose here a generalization of Gompertz law. Our data analysis permits an evaluation of the maximum number of infected individuals. The daily data must be compared with the obtained fits, to verify if the spreading is under control. From our analysis, it appears that the spreading reached saturation in China, due to the strong containment policy of the national government. In Singapore a large growth rate, recently observed, suggests the start of a new strong spreading. For South Korea and Italy, instead, the next data on new infections will be crucial to understand if the saturation will be reached for lower or higher numbers of infected individuals.

Effects of Cholesterol in Stress-Related Neuronal Death—A Statistical Analysis Perspective

The association between plasma cholesterol levels and the development of dementia continues to be an important topic of discussion in the scientific community, while the results in the literature vary significantly. We study the effect of reducing oxidized neuronal cholesterol on the lipid raft structure of plasma membrane. The levels of plasma membrane cholesterol were reduced by treating the intact cells with methyl-ß-cyclodextrin (MßCD). The relationship between the cell viability with varying levels of MßCD was then examined. The viability curves are well described by a modified form of the empirical Gompertz law of mortality. A detailed statistical analysis is performed on the fitting results, showing that increasing MßCD concentration has a minor, rather than significant, effect on the cellular viability. In particular, the dependence of viability on MßCD concentration was found to be characterized by a ~25% increase per 1 μM of MßCD concentration.