Anorexia nervosa and reproduction: connecting brain to gonads

Anorexia nervosa (AN) is a psychiatric disorder that predominantly affects young women and is characterized by low caloric intake and a major dissatisfaction with one’s body image. It is often overlooked and, while patients and family seek medical help, emaciation and nutritional misbalances may become extreme and potentially life threatening. Among the many somatic complications, an accumulation of early endocrine adaptations occurs, leading to functional amenorrhea and impaired reproduction as a result of dysfunction of the hypothalamic-pituitary-ovarian axis. Even though these conditions are reversible, long-term consequences may affect the fertility of women with AN and can lead to maternal and fetal complications during pregnancy and birth. This review presents the clinical particularities of reproduction in the context of AN, along with the possible pathophysiological mechanisms involved

Evaluation of Image Registration Accuracy for Tumor and Organs at Risk in the Thorax for Compliance With TG 132 Recommendations

Purpose To evaluate accuracy for 2 deformable image registration methods (in-house B-spline and MIM freeform) using image pairs exhibiting changes in patient orientation and lung volume and to assess the appropriateness of registration accuracy tolerances proposed by the American Association of Physicists in Medicine Task Group 132 under such challenging conditions via assessment by expert observers. Methods and Materials Four-dimensional computed tomography scans for 12 patients with lung cancer were acquired with patients in prone and supine positions. Tumor and organs at risk were delineated by a physician on all data sets: supine inhale (SI), supine exhale, prone inhale, and prone exhale. The SI image was registered to the other images using both registration methods. All SI contours were propagated using the resulting transformations and compared with physician delineations using Dice similarity coefficient, mean distance to agreement, and Hausdorff distance. Additionally, propagated contours were anonymized along with ground-truth contours and rated for quality by physician-observers. Results Averaged across all patients, the accuracy metrics investigated remained within tolerances recommended by Task Group 132 (Dice similarity coefficient \u3e0.8, mean distance to agreement \u3c3 \u3emm). MIM performed better with both complex (vertebrae) and low-contrast (esophagus) structures, whereas the in-house method performed better with lungs (whole and individual lobes). Accuracy metrics worsened but remained within tolerances when propagating from supine to prone; however, the Jacobian determinant contained regions with negative values, indicating localized nonphysiologic deformations. For MIM and in-house registrations, 50% and 43.8%, respectively, of propagated contours were rated acceptable as is and 8.2% and 11.0% as clinically unacceptable. Conclusions The deformable image registration methods performed reliably and met recommended tolerances despite anatomically challenging cases exceeding typical interfraction variability. However, additional quality assurance measures are necessary for complex applications (eg, dose propagation). Human review rather than unsupervised implementation should always be part of the clinical registration workflow

Closed-loop effects in cardiovascular clinical decision support

We have recently seen impressive methodological developments in quantitative cardiovascular physiology and pathophysiology, with novel mathematical models for the mechanical and electrophysiological processes of the heart, and fluid dynamical models to describe the pressure and flow distribution in the blood vessel network. This allows us to gain deeper insight into the state of a variety of serious cardiovascular diseases. The majority of recent research studies have focused on the forward problem: developing flexible mathematical models and robust numerical simulation procedures to match characteristics of physiological target data, and the inverse problem: inferring model parameters from cardiac physiological data with reliable uncertainty quantification. However, when connecting mathematical model predictions and statistical inference to the clinical decision process, new challenges arise. This paper briefly discusses the complications that potentially result from closed-loop effects, and the model extensions that are required to reduce the ensuing bias

Between a chicken and a grape: estimating the number of human genes

The number of genes in the human genome is still an estimate

Dynamical behavior and influence of stochastic noise on certain generalized Boolean networks

This study considers a simple Boolean network with N nodes, each node’s state at time t being determined by a certain number of parent nodes. The network is analyzed when the connectivity k is fixed or variable. Making use of a Boolean rule that is a generalization of Rule 22 of elementary cellular automata, a generalized formula for providing the probability of finding a node in state 1 at a time t is determined. We show typical behaviors of the iterations, and we study the dynamics of the network through Lyapunov exponents, bifurcation diagrams, and fixed point analysis. We conclude that the network may exhibit stability or chaos depending on the underlying parameters. In general high connectivity is associated with a convergence to zero of the probability of finding a node in state 1 at time t. We also study analytically and numerically the dynamics of the network under a stochastic noise procedure. We show that under a smaller probability of disturbing the nodes through the noise procedure the system tends to exhibit more nodes in the same state. For many parameter combinations there is no critical value of the noise parameter below which the network remains organized and above which it behaves randomly

Auditory, graphical and haptic contact cues for a reach, grasp, and place task in an augmented environment

An experiment was conducted to investigate how performance of a reach, grasp and place task was influenced by added auditory and graphical cues. The cues were presented at points in the task, specifically when making contact for grasping or placing the object, and were presented in single or in combined modalities. Haptic feedback was present always during physical interaction with the object. The auditory and graphical cues provided enhanced feedback about making contact between hand and object and between object and table. Also, the task was performed with or without vision of hand. Movements were slower without vision of hand. Providing auditory cues clearly facilitated performance, while graphical contact cues had no additional effect. Implications are discussed for various uses of auditory displays in virtual environments

Androgenic alopecia; the risk–benefit ratio of Finasteride

Finasteride is currently approved and largely used as a therapeutic option for androgenetic alopecia. Apparently a safe drug and effective at the onset of its application, several concerns have since appeared over the years regarding the frequency and magnitude of finasteride adverse effects, which in some cases appear irreversible even after drug termination. This paper discusses the use of finasteride for androgenic alopecia from two distinct perspectives. On the one hand, androgenic alopecia is a condition that especially affects a person’s self-image and esteem, aspects that are subjectively-constructed and thus relative and changeable. On the other hand, this condition involves a multifactorial etiology, with androgens being only partly responsible. Because androgens have important and unique physiological roles within the body, any procedure that results in androgenic suppression should be advised with caution. Furthermore, adverse effects induced by finasteride are neither fully documented nor easily treated. Finally, as alternative therapeutic approaches (such as topical finasteride) become available, the oral administration of finasteride for androgenic alopecia should, in our opinion, be reevaluated. Due to such concerns, a detailed and informed discussion should take place with patients considering therapy with finasteride for androgenic alopecia

Parameter Inference in the Pulmonary Circulation of Mice

This study focuses on parameter inference in a pulmonary blood cir- culation model for mice. It utilises a fluid dynamics network model that takes selected parameter values and aims to mimic features of the pulmonary haemody- namics under normal physiological and pathological conditions. This is of medical relevance as it allows monitoring of the progression of pulmonary hypertension. Constraint nonlinear optimization is successfully used to learn the parameter values

A computational survey of candidate exonic splicing enhancer motifs in the model plant Arabidopsis thaliana

Algorithmic approaches to splice site prediction have relied mainly on the consensus patterns found at the boundaries between protein coding and non-coding regions. However exonic splicing enhancers have been shown to enhance the utilization of nearby splice sites. We have developed a new computational technique to identify significantly conserved motifs involved in splice site regulation. First, 84 putative exonic splicing enhancer hexamers are identified in Arabidopsis thaliana. Then a Gibbs sampling program called ELPH was used to locate conserved motifs represented by these hexamers in exonic regions near splice sites in confirmed genes. Oligomers containing 35 of these motifs have been shown experimentally to induce significant inclusion of A. thaliana exons. Second, integration of our regulatory motifs into two different splice site recognition programs significantly improved the ability of the software to correctly predict splice sites in a large database of confirmed genes. We have released GeneSplicerESE, the improved splice site recognition code, as open source software. Our results show that the use of the ESE motifs consistently improves splice site prediction accuracy.https://doi.org/10.1186/1471-2105-8-15

Characterization of Respiration-Induced Motion in Prone Versus Supine Patient Positioning for Thoracic Radiation Therapy

Purpose Variations in the breathing characteristics, both on short term (intrafraction) and long term (interfraction) time scales, may adversely affect the radiation therapy process at all stages when treating lung tumors. Prone position has been shown to improve consistency (ie, reduced intrafraction variability) and reproducibility (ie, reduced interfraction variability) of the respiratory pattern with respect to breathing amplitude and period as a result of natural abdominal compression, with no active involvement required from the patient. The next natural step in investigating breathing-induced changes is to evaluate motion amplitude changes between prone and supine targets or organs at risk, which is the purpose of the present study. Methods and Materials Patients with lung cancer received repeat helical 4-dimensional computed tomography scans, one prone and one supine, during the same radiation therapy simulation session. In the maximum-inhale and maximum-exhale phases, all thoracic structures were delineated by an expert radiation oncologist. Geometric centroid trajectories of delineated structures were compared between patient orientations. Motion amplitude was measured as the magnitude of difference in structure centroid position between inhale and exhale. Results Amplitude of organ motion was larger when the patient was in the prone position compared with supine for all structures except the lower left lobe and left lung as a whole. Across all 12 patients, significant differences in mean motion amplitude between orientations were identified for the right lung (3.0 mm, P = .01), T2 (0.5 mm, P = .01) and T12 (2.1 mm, P \u3c .001) vertebrae, the middle third of the esophagus (4.0 mm, P = .03), and the lung tumor (1.7 mm, P = .02). Conclusions Respiration-induced thoracic organ motion was quantified in the prone position and compared with that of the supine position for 12 patients with thoracic lesions. The prone position induced larger organ motion compared with supine, particularly for the lung tumor, likely requiring increases in planning margins compared with supine