Shaping and Dilating the Fitness Landscape for Parameter Estimation in Stochastic Biochemical Models

The parameter estimation (PE) of biochemical reactions is one of the most challenging tasks in systems biology given the pivotal role of these kinetic constants in driving the behavior of biochemical systems. PE is a non-convex, multi-modal, and non-separable optimization problem with an unknown fitness landscape; moreover, the quantities of the biochemical species appearing in the system can be low, making biological noise a non-negligible phenomenon and mandating the use of stochastic simulation. Finally, the values of the kinetic parameters typically follow a log-uniform distribution; thus, the optimal solutions are situated in the lowest orders of magnitude of the search space. In this work, we further elaborate on a novel approach to address the PE problem based on a combination of adaptive swarm intelligence and dilation functions (DFs). DFs require prior knowledge of the characteristics of the fitness landscape; therefore, we leverage an alternative solution to evolve optimal DFs. On top of this approach, we introduce surrogate Fourier modeling to simplify the PE, by producing a smoother version of the fitness landscape that excludes the high frequency components of the fitness function. Our results show that the PE exploiting evolved DFs has a performance comparable with that of the PE run with a custom DF. Moreover, surrogate Fourier modeling allows for improving the convergence speed. Finally, we discuss some open problems related to the scalability of our methodology

Effects of vibration direction and pressing force on finger vibrotactile perception and force control

This paper reports about the effects of vibration direction and finger-pressing force on vibrotactile perception, with the goal of improving the effectiveness of haptic feedback on interactive surfaces. An experiment was conducted to assess the sensitivity to normal or tangential vibration at 250 Hz of a finger exerting constant pressing forces of 0.5 or 4.9 N. Results show that perception thresholds for normal vibration depend on the applied pressing force, significantly decreasing for the stronger force level. Conversely, perception thresholds for tangential vibrations are independent of the applied force, and approximately equal the lowest thresholds measured for normal vibration

Tools and Methods for Human Robot Collaboration: Case Studies at i-LABS

The collaboration among humans and machines is one of the most relevant topics in the Industry 4.0 paradigm. Collaborative robotics owes part of the enormous impact it has had in small and medium size enterprises to its innate vocation for close cooperation between human operators and robots. The i-Labs laboratory, which is introduced in this paper, developed some case studies in this sense involving different technologies at different abstraction levels to analyse the feasibility of human-robot interaction in common, yet challenging, application scenarios. The ergonomics of the processes, safety of operators, as well as effectiveness of the cooperation are some of the aspects under investigation with the main objective of drawing to these issues the attention from industries who could benefit from them

Respiratory muscle training in patients recovering recent open cardio-thoracic surgery: a randomized-controlled trial.

Objectives- To evaluate the clinical efficacy and feasibility of an expiratory muscle training (EMT) device (Respilift™) applied to patients recovering from recent open cardio-thoracic surgery (CTS). Design- Prospective, double-blind, 14-day randomised-controlled trial. Participants and setting- 60 inpatients recovering from recent CTS and early admitted to a pulmonary rehabilitation program. Interventions- Chest physiotherapy plus EMT with a resistive load of 30 cm H2O for active group and chest physiotherapy plus EMT with a sham load for control group. Measures- Changes in maximal expiratory pressure (MEP) was considered as primary outcome, while maximal inspiratory pressures (MIP), dynamic and static lung volumes, oxygenation, perceived symptoms of dyspnoea, thoracic pain and well being (evaluated by visual analogic scale-VAS) and general health status were considered secondary outcomes. Results- All outcomes recorded showed significant improvements in both groups; however, the change of MEP (+34.2 mmHg, p<0.001 and +26.1%, p<0.001 for absolute and % of predicted, respectively) was significantly higher in Active group. Also VAS-dyspnoea improved faster and more significantly (p<0.05) at day 12 and 14 in Active group when compared with Control. The drop out rate was 6%, without differences between groups. Conclusions- In patients recovering from recent CTS specific EMT by Respilift™ is feasible and effective

Use of artificial intelligence to automatically predict the optimal patient-specific inversion time for late gadolinium enhancement imaging. Tool development and clinical validation

Introduction With the worldwide diffusion of cardiac magnetic resonance (CMR), demand on image quality has grown. CMR late gadolinium enhancement (LGE) imaging provides critical diagnostic and prognostic information, and guides management. The identification of optimal Inversion Time (TI), a time-sensitive parameter closely linked to contrast kinetics, is pivotal for correct myocardium nulling. However, determining the optimal TI can be challenging in some diseases and for less experienced operators. Purpose To develop and test an artificial intelligence tool to automatically predict the personalised optimal TI in LGE imaging. Methods The tool, named THAITI, consists of a Random Forest regression model. It considers, as input parameters, patient-specific TI determinants (age, gender, weight, height, kidney function, heart rate) and CMR scan-specific TI determinants (B0, contrast type and dose, time elapsed from contrast injection). THAITI was trained on 219 patients (3585 images) with mixed conditions who underwent CMR (1.5T; Gadobutrol; averaged, MOCO, free-breathing true-FISP IR [1]) for clinical reasons. The dataset was split with a 90–10 policy: 90% of data for training, and 10% for testing. THAITI’s hyperparameters were optimised by embedding k-fold cross validation into an evolutionary computation algorithm, and the best performing model was finally evaluated on the test set. A graphical user interface was also developed. Clinical validation was performed on 55 consecutive patients, randomised to experimental (THAITI-set TI) vs control (operator-set TI) group. Image quality was assessed blindly by 2 independent experienced operators by a 4-points Likert scale, and by means of the contrast/enhancement ratio (CER) (i.e., signal intensity of enhanced/remote myocardium ratio). Results In the testing set, the TI predicted by THAITI differed from the ground truth by ≥ 5ms in 16% of cases. At clinical validation, myocardial nulling quality did not differ between the experimental vs the control group either by CER or visual assessment, with an overall "optimal" or "good" nulling in 96% vs 93%, respectively. Conclusions Using main determinants of contrast kinetics, THAITI efficiently predicted the optimal TI for CMR-LGE imaging. The tool works as a stand-alone on laptops/mobile devices, not requiring adjunctive scanner technology and thus has great potential for diffusion, including in small or recently opened CMR services, and in low-resource settings. Additional development is ongoing to increase generalisability (multi-vendor, multi-sequence, multi-contrast) and to test its potential to further improve CMR-LGE image quality and reduce the need for repeated imaging for inexperienced operators. Figure 1. Top: THAITI interface. Bottom: examples of experimental group CMR-LGE imaging. Table 1. Control vs experimental group. Data expressed as absolute number (%), mean ± SD, median [IQR]. ⧧ T-test; * Chi-square

Dark blood ischemic LGE segmentation using a deep learning approach

The extent of ischemic scar detected by Cardiac Magnetic Resonance (CMR) with late gadolinium enhancement (LGE) is linked with long-term prognosis, but scar quantification is time-consuming. Deep Learning (DL) approaches appear promising in CMR segmentation. Purpose: To train and apply a deep learning approach to dark blood (DB) CMR-LGE for ischemic scar segmentation, comparing results to 4-Standard Deviation (4-SD) semi-automated method. Methods: We trained and validated a dual neural network infrastructure on a dataset of DB-LGE short-axis stacks, acquired at 1.5T from 33 patients with ischemic scar. The DL architectures were an evolution of the U-Net Convolutional Neural Network (CNN), using data augmentation to increase generalization. The CNNs worked together to identify and segment 1) the myocardium and 2) areas of LGE. The first CNN simultaneously cropped the region of interest (RoI) according to the bounding box of the heart and calculated the area of myocardium. The cropped RoI was then processed by the second CNN, which identified the overall LGE area. The extent of scar was calculated as the ratio of the two areas. For comparison, endo- and epi-cardial borders were manually contoured and scars segmented by a 4-SD technique with a validated software. Results: The two U-Net networks were implemented with two free and open-source software library for machine learning. We performed 5-fold cross-validation over a dataset of 108 and 385 labelled CMR images of the myocardium and scar, respectively. We obtained high performance (&gt; ∼0.85) as measured by the Intersection over Union metric (IoU) on the training sets, in the case of scar segmentation. With regards to heart recognition, the performance was lower (&gt; ∼0.7), although improved (∼ 0.75) by detecting the cardiac area instead of heart boundaries. On the validation set, performances oscillated between 0.8 and 0.85 for scar tissue recognition, and dropped to ∼0.7 for myocardium segmentation. We believe that underrepresented samples and noise might be affecting the overall performances, so that additional data might be beneficial. Figure1: examples of heart segmentation (upper left panel: training; upper right panel: validation) and of scar segmentation (lower left panel: training; lower right panel: validation). Conclusion: Our CNNs show promising results in automatically segmenting LV and quantify ischemic scars on DB-LGE-CMR images. The performances of our method can further improve by expanding the data set used for the training. If implemented in a clinical routine, this process can speed up the CMR analysis process and aid in the clinical decision-making

Evaluation of Plant and Fungal Extracts for Their Potential Antigingivitis and Anticaries Activity

The link between diet and health has lead to the promotion of functional foods which can enhance health. In this study, the oral health benefits of a number of food homogenates and high molecular mass and low molecular mass fractions were investigated. A comprehensive range of assays were performed to assess the action of these foods on the development of gingivitis and caries using bacterial species associated with these diseases. Both antigingivitis and anticaries effects were investigated by assays examining the prevention of biofilm formation and coaggregation, disruption of preexisting biofilms, and the foods' antibacterial effects. Assays investigating interactions with gingival epithelial cells and cytokine production were carried out to assess the foods' anti- gingivitis properties. Anti-caries properties such as interactions with hydroxyapatite, disruption of signal transduction, and the inhibition of acid production were investigated. The mushroom and chicory homogenates and low molecular mass fractions show promise as anti-caries and anti-gingivitis agents, and further testing and clinical trials will need to be performed to evaluate their true effectiveness in humans

Management of pediatric post-infectious neurological syndromes

BackgroundPost-Infectious Neurological Syndromes (PINS) are heterogeneous neurological disorders with post or para-infectious onset. PINS diagnosis is complex, mainly related to the absence of any recognized guidelines and a univocal definition.Aim of the studyTo elaborate a diagnostic guide for PINS.Materials and methodsWe retrospectively analysed patients younger than 14years old admitted to Bambino GesU Children's Hospital in Rome for PINS from December 2005 to March 2018. Scientific literature using PubMed as research platform was analysed: the key words "Post-Infectious Neurological Syndromes" were used.ResultsA polysymptomatic presentation occurred in a percentage of 88% of the children. Motor signs and visual disturbances the most observed symptoms/signs were the most detached, followed by fever, speech disturbances, sleepiness, headache and bradipsychism. Blood investigations are compatible with inflammation, as a prodromal illnesses was documented in most cases. Normal cerebral spinal fluid (CSF) characteristics has been found in the majority of the study population. Magnetic resonance imaging (MRI) was positive for demyelinating lesions. Antibiotics, acyclovir and steroids have been given as treatment.DiscussionWe suggest diagnostic criteria for diagnosis of PINS, considering the following parameters: neurological symptoms, timing of disease onset, blood and CSF laboratory tests, MRI imaging.ConclusionsWe propose criteria to guide clinician to diagnose PINS as definitive, probable or possible. Further studies are required to validate diagnostic criteria