[Show abstract][Hide abstract] ABSTRACT: A full Bayesian approach based on ODE-penalized B-splines and penalized Gaussian mixture is proposed to jointly estimate ODE-parameters, state function and error distribution from the observation of some state functions involved in systems of affine differential equations. Simulations inspired by pharmacokinetic studies show that the proposed method provides com-parable results to the method based on the standard ODE-penalized B-spline approach (i.e. with the Gaussian error distribution assumption) and outperforms the standard ODE-penalized B-splines when the distribution is not Gaussian. This methodology is illustrated on the Theo-phylline dataset.
Journal of Applied Statistics 12/2014; 41(12). · 0.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Nonlinear (systems of) ordinary differential equations (ODEs) are common
tools in the analysis of complex one-dimensional dynamic systems. In this paper
we propose a smoothing approach regularized by a quasilinearized ODE-based
penalty in order to approximate the state functions and estimate the parameters
defining nonlinear differential systems from noisy data. Within the
quasilinearized spline based framework, the estimation process reduces to a
conditionally linear problem for the optimization of the spline coefficients.
Furthermore, standard ODE compliance parameter(s) selection criteria are easily
applicable and conditions on the state function(s) can be eventually imposed
using soft or hard constraints. The approach is illustrated on real and
[Show abstract][Hide abstract] ABSTRACT: Differential equations (DEs) are commonly used to describe dynamic systems
evolving in one (ordinary differential equations or ODEs) or in more than one
dimensions (partial differential equations or PDEs). In real data applications
the parameters involved in the DE models are usually unknown and need to be
estimated from the available measurements together with the state function. In
this paper, we present frequentist and Bayesian approaches for the joint
estimation of the parameters and of the state functions involved in PDEs. We
also propose two strategies to include differential (initial and/or boundary)
conditions in the estimation procedure. We evaluate the performances of the
proposed strategy on simulated and real data applications.
[Show abstract][Hide abstract] ABSTRACT: STUDY QUESTION: Can a vitrification protocol using an ethylene glycol/dimethyl sulphoxide-based solution and a cryopin successfully cryopreserve baboon ovarian tissue? SUMMARY ANSWER: Our results show that baboon ovarian tissue can be successfully cryopreserved with our vitrification protocol. WHAT IS KNOWN ALREADY: Non-human primates have already been used as an animal model to test vitrification protocols for human ovarian tissue cryopreservation. STUDY DESIGN, SIZE, DURATION: Ovarian biopsies from five adult baboons were vitrified, warmed and autografted for 5 months. PARTICIPANTS/MATERIALS, SETTING, METHODS: After grafting, follicle survival, growth and function and also the quality of stromal tissue were assessed histologically and by immunohistochemistry. The influence of the vitrification procedure on the cooling rate was evaluated by a computer model. MAIN RESULTS: After vitrification, warming and long-term grafting, follicles were able to grow and maintain their function, as illustrated by Ki67, anti-Müllerian hormone (AMH) and growth differentiation factor-9 (GDF-9) immunostaining. Corpora lutea were also observed, evidencing successful ovulation in all the animals. Stromal tissue quality did not appear to be negatively affected by our cryopreservation procedure, as demonstrated by vascularization and proportions of fibrotic areas, which were similar to those found in fresh ungrafted ovarian tissue. LIMITATIONS, REASONS FOR CAUTION: Despite our promising findings, before applying this technique in a clinical setting, we need to validate it by achieving pregnancies. WIDER IMPLICATIONS OF THE FINDINGS: In addition to encouraging results obtained with our vitrification procedure for non-human ovarian tissue, this study also showed, for the first time, expression of AMH and GDF-9 in ovarian follicles. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grants from the Fonds National de la Recherche Scientifique de Belgique (grant Télévie No. 7.4507.10, grant 3.4.590.08 awarded to Marie-Madeleine Dolmans), Fonds Spéciaux de Recherche, Fondation St Luc, Foundation Against Cancer, and Department of Mechanical Engineering at Louisiana State University (support to Ram Devireddy), and donations from Mr Pietro Ferrero, Baron Frère and Viscount Philippe de Spoelberch. None of the authors has any competing interests to declare.
[Show abstract][Hide abstract] ABSTRACT: To assess the efficiency of two vitrification protocols to cryopreserve human preantral follicles with the use of a xenografting model.
Gynecology research unit in a university hospital.
Ovarian biopsies were obtained from seven women aged 30-41 years.
Ovarian tissue fragments were subjected to one of three cryopreservation protocols (slow freezing, vitrification protocol 1, and vitrification protocol 2) and xenografted for 1 week to nude mice.
The number of morphologically normal follicles after cryopreservation and grafting and fibrotic surface area were determined by histologic analysis. Apoptosis was assessed by the TUNEL method. Morphometric analysis of TUNEL-positive surface area also was performed. Follicle proliferation was evaluated by immunohistochemistry.
After xenografting, a difference was observed between the cryopreservation procedures applied. According to TUNEL analysis, both vitrification protocols showed better preservation of preantral follicles than the conventional freezing method. Moreover, histologic evaluation showed a significantly higher proportion of primordial follicles in vitrified (protocol 2)-warmed ovarian tissue than in frozen-thawed tissue. The proportion of growing follicles and fibrotic surface area was similar in all groups.
Vitrification procedures appeared to preserve not only the morphology and survival of preantral follicles after 1 week of xenografting, but also their ability to resume folliculogenesis. In addition, vitrification protocol 2 had a positive impact on the quiescent state of primordial follicles after xenografting.
Fertility and sterility 08/2012; 98(5):1291-1298.e2. · 3.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: For women diagnosed with leukemia, transplantation of cryopreserved ovarian tissue after disease remission is not advisable. Therefore, to restore fertility in these patients, we aim to develop a biodegradable artificial ovary that offers an environment where isolated follicles and ovarian cells (OCs) can survive and grow. Four NMRI mice were ovariectomized and their ovaries used to isolate OCs. Groups of 50,000 OCs were embedded in an alginate-matrigel matrix for further fixation (fresh controls), one week of in vitro culture (IVC) or heterotopic autografting. OC proliferation (Ki67), apoptosis (TUNEL), scaffold degradation, vessel formation (CD34) and inflammation (CD45) were analyzed. Ki67-positive OCs were found in 2.3%, 9.0% and 15.5% cells of cases in fresh, IVC and grafted beads respectively, while cells were TUNEL-positive in 0%, 1.5% and 6.9% of cases. After IVC or grafting, the beads degraded, losing their original round aspect, and infiltrating blood capillaries could be observed in the grafted beads. CD34-positive cells and 22% CD45-positive cells were found around and inside the matrix. In conclusion, our results demonstrate that an alginate-based matrix is a promising proposition to graft isolated OCs. After transplantation, this matrix was able to degrade, allowed vascularization and elicited a low inflammatory response.
[Show abstract][Hide abstract] ABSTRACT: Dierential equation models with observational errors are used in modeling complex ex- periments in chemical engineering, pharmacokinetics and other sciences. Current methods for the parameter and functional estimations in models dened