Randomized controlled trials of maternal-fetal surgery: a challenge to clinical equipoise.

This article focuses on maternal-fetal surgery (MFS) and on the concept of clinical equipoise that is a widely accepted requirement for conducting randomized controlled trials (RCT). There are at least three reasons why equipoise is unsuitable for MFS. First, the concept is based on a misconception about the nature of clinical research and the status of research subjects. Second, given that it is not clear who the research subject/s in MFS is/are, if clinical equipoise is to be used as a criterion to test the ethical appropriateness of RCT, its meaning should be unambiguous. Third, because of the multidisciplinary character of MFS, it is not clear who should be in equipoise. As a result, we lack an adequate criterion for the ethical review of MFS protocols. In our account, which is based on Chervenak and McCullough's seminal work in the field of obstetric ethics, equipoise is abandoned. and RCT involving MFS can be ethically initiated when a multidisciplinary ethics review board (ERB), having an evidence-based assessment of the risks involved, is convinced that the value of answering the research hypothesis, for the sake of the health interests of future pregnant women carrying fetuses with certain congenital birth defects, justifies the actual risks research participants might suffer within a set limit of low/manageable.

Swine manure treatment technologies as drivers for circular economy in agribusiness: A techno-economic and life cycle assessment approach.

Anaerobic digestion has been employed as a technology capable of adding value to waste coupled with environmental impact mitigation. However, many issues need to be elucidated to ensure the systems viability based on this technology. In this sense, the present study evaluated technically, environmentally, and economically, four configurations of swine waste treatment systems focused on the promotion of decarbonization and circularity of the swine chain. For this, a reference plant, based on a compact treatment process named SISTRATES® (Portuguese acronym for swine effluent treatment system) was adopted to serve as a model for comparison and validation. The results showed the importance of prioritization of the energy recuperation routes through anaerobic digestion, providing increased economic benefits and minimizing environmental damage. Thus, the SISTRATES® configuration was the one that presented the best designs in a circular context, maximizing the recovery of energy and nutrients, along with the reduction of greenhouse gas emissions, ensuring the sustainability of the pig production chain.

When referring physicians and researchers disagree on equipoise: the TOTAL trial experience.

OBJECTIVE: In this article, we reflect on whether randomized controlled trials (RCTs) are adequate for the clinical evaluation of maternal-fetal surgery for congenital diaphragmatic hernia (CDH), focusing on the role of patients' preferences in the setting up of research protocols, on the requirement of equipoise and on the concept of therapeutic misconception (TM). METHOD: We describe the conception and setting up of the tracheal occlusion (TO) to accelerate lung growth trial and analyze the ethical dilemmas faced by the research team during that time. RESULTS: Depending on the view adopted regarding the scope of equipoise, there are two ways of dealing with patient's preferences concerning fetoscopic endoluminal TO and expectant management during pregnancy for CDH. CONCLUSION: The solution adopted for fetoscopic endoluminal tracheal occlusion (FETO) is justified by the extended period of time it has been available to patients before the start of the RCT. Strong patient and referring physician preferences do not entail a right to have FETO, since it is a procedure of yet unproven efficacy and safety. In the future, to avoid the dilemmas posed by the TM and in name of the right of future generations of patients to have access to treatment of proven safety and efficacy, researchers must be able to plan RCT in due time.

Homogenization method for microscopic characterization of the composite magnetoelectric multiferroics.

Tuning of magnetization or electrical polarization using external fields other than their corresponding conjugate fields (i.e., magnetic field for the former or electric field for the latter response) attracts renewed interest due to its potential for applications. The magnetoelectric effect in multiferroic 1-3 composite composed of alternating magnetic and ferroelectric layers operating in linear regime consequent to external biasing fields is simulated and analysed theoretically. Two-scale homogenization procedure to arrive at the equilibrium overall physical properties of magnetoelectric multiferroic composite is formulated using variational analysis. This procedure is extended to quantify the underlying local (microscopic) electric, magnetic and elastic fields and thereby compute local distribution of stresses and strains, electrical and magnetic potentials, the electric and magnetic fields as well as the equivalent von Mises stresses. The computational model is implemented by modifying the software POSTMAT (material postprocessing). Computed local stress/strain profiles and the von Mises stresses consequent to biasing electrical and magnetic fields provide insightful information related to the magnetostriction and the ensuing electrical and magnetic polarization. Average polarization and magnetization against magnetic and electric fields respectively are computed and found to be in reasonable limits of the experimental results on similar composite systems. The homogenization model covers multiferroics and its composites regardless of crystallographic symmetry (with the caveat of assuming an ideal and semi-coherent interface connecting the constituent phases) and offer computational efficiency besides unveiling the nature of the underlying microscopic field characteristics.

Solutions for maximum coupling in multiferroic magnetoelectric composites by material design.

Electrical control of magnetization offers an extra degree of freedom in materials possessing both electric and magnetic dipole moments. A stochastic optimization combined with homogenization is applied for the solution for maximum magnetoelectric (ME) coupling coefficient α of a laminar ME composite with the thickness and orientation of ferroelectric phase as design variables. Simulated annealing with a generalized Monte Carlo scheme is used for optimization problem. Optimal microstructure with single and poly-crystalline configurations that enhances the overall α is identified. It is found that juxtaposing a preferentially oriented ferroelectric material with a ferromagnetic ferrite into a composite would result in manifold increase in magnetoelectric coupling. The interface shear strains are found to be richly contributing to the ME coupling. The preferential orientation of the ferroelectric phase in the optimal ME composite laminate is demonstrated using the optimal pole figure analyses.

[The need for uncertainty in clinical research. Equipoise]. / De noodzaak van onzekerheid in klinisch onderzoek. Equipoise.

When a randomized controlled trial (RCT) that has potentially therapeutic benefits for research subjects is conducted, the line between treatment and research is often difficult to draw. However, in order to protect the well-being and rights of prospective research subjects and to ensure that they are not subjected to harmful and pointless research, the distinction between normal care and scientific research must be thoroughly explained. There has to be clear-cut 'equipoise', i.e. uncertainty in physician, patient and investigator regarding the outcome of the study. Strong patient preference for the experimental arm of an RCT does not entail a right to have access to it, as by definition it represents an option of unproven safety or efficacy (equipoise). Only in a therapeutic context do patients have the right to receive the best available care and a right to discuss their treatment preferences with their physicians. A careful informed consent procedure that clarifies the differences between research and therapy, and that emphasizes the experimental nature of trial arms, should be in place prior to randomization.

Numerical modeling of bone tissue adaptation--a hierarchical approach for bone apparent density and trabecular structure.

In this work, a three-dimensional model for bone remodeling is presented, taking into account the hierarchical structure of bone. The process of bone tissue adaptation is mathematically described with respect to functional demands, both mechanical and biological, to obtain the bone apparent density distribution (at the macroscale) and the trabecular structure (at the microscale). At global scale bone is assumed as a continuum material characterized by equivalent (homogenized) mechanical properties. At local scale a periodic cellular material model approaches bone trabecular anisotropy as well as bone surface area density. For each scale there is a material distribution problem governed by density-based design variables which at the global level can be identified with bone relative density. In order to show the potential of the model, a three-dimensional example of the proximal femur illustrates the distribution of bone apparent density as well as microstructural designs characterizing both anisotropy and bone surface area density. The bone apparent density numerical results show a good agreement with Dual-energy X-ray Absorptiometry (DXA) exams. The material symmetry distributions obtained are comparable to real bone microstructures depending on the local stress field. Furthermore, the compact bone porosity is modeled giving a transversal isotropic behavior close to the experimental data. Since, some computed microstructures have no permeability one concludes that bone tissue arrangement is not a simple stiffness maximization issue but biological factors also play an important role.