Osteoporosis is a disease characterized by impairment of bone microarchitecture that causes high socioeconomic impacts in the world because of fractures and hospitalizations. Although dual-energy ...X-ray absorptiometry (DXA) is the gold standard for diagnosing the disease, access to DXA in developing countries is still limited due to its high cost, being present only in specialized hospitals. In this paper, we analyze the performance of Osseus, a low-cost portable device based on electromagnetic waves that measures the attenuation of the signal that crosses the medial phalanx of a patient's middle finger and was developed for osteoporosis screening. The analysis is carried out by predicting changes in bone mineral density using Osseus measurements and additional common risk factors used as input features to a set of supervised classification models, while the results from DXA are taken as target (real) values during the training of the machine learning algorithms. The dataset consisted of 505 patients who underwent osteoporosis screening with both devices (DXA and Osseus), of whom 21.8% were healthy and 78.2% had low bone mineral density or osteoporosis. A cross-validation with k-fold = 5 was considered in model training, while 20% of the whole dataset was used for testing. The obtained performance of the best model (Random Forest) presented a sensitivity of 0.853, a specificity of 0.879, and an F1 of 0.859. Since the Random Forest (RF) algorithm allows some interpretability of its results (through the impurity check), we were able to identify the most important variables in the classification of osteoporosis. The results showed that the most important variables were age, body mass index, and the signal attenuation provided by Osseus. The RF model, when used together with Osseus measurements, is effective in screening patients and facilitates the early diagnosis of osteoporosis. The main advantages of such early screening are the reduction of costs associated with exams, surgeries, treatments, and hospitalizations, as well as improved quality of life for patients.
Evolutionary branching occurs when a population with a unimodal phenotype distribution diversifies into a multimodally distributed population consisting of two or more strains. Branching results from ...frequency-dependent selection, which is caused by interactions between individuals. For example, a population performing a social task may diversify into a cooperator strain and a defector strain. Branching can also occur in multi-dimensional phenotype spaces, such as when two tasks are performed simultaneously. In such cases, the strains may diverge in different directions: possible outcomes include division of labor (with each population performing one of the tasks) or the diversification into a strain that performs both tasks and another that performs neither. Here we show that the shape of the population's phenotypic distribution plays a role in determining the direction of branching. Furthermore, we show that the shape of the distribution is, in turn, contingent on the direction of approach to the evolutionary branching point. This results in a distribution-selection feedback that is not captured in analytical models of evolutionary branching, which assume monomorphic populations. Finally, we show that this feedback can influence long-term evolutionary dynamics and promote the evolution of division of labor.
•Carbendazim (1–2mg/L) elicited developmental anomalies in zebrafish embryos.•Biochemical effects were detected at concentrations above 0.04mg/L.•Locomotor assay was extremely sensitive, detecting ...effects at 0.00016mg/L.•Results highlight the potential of behavioural endpoints in ecotoxicology.
Carbendazim is a widely used broad spectrum benzimidazole fungicide; however, its effects to non-target aquatic organisms are poorly studied. The aim of this study was to investigate the toxic effects of carbendazim to zebrafish early life stages at several levels of biological organization, including developmental, biochemical and behavioural levels. The embryo assay was done following the OECD guideline 236 and using a concentration range between 1.1 and 1.8mg/L. Lethal and developmental endpoints such as hatching, edemas, malformations, heart beat rate, body growth and delays were assessed in a 96h exposure. A sub-teratogenic range (from 0.16 to 500μg/L) was then used to assess effects at biochemical and behavioural levels. Biochemical markers included cholinesterase (ChE), glutathione-S-transferase (GST), lactate dehydrogenase (LDH) and catalase (CAT) and were assessed at 96h. The locomotor behaviour was assessed using an automated video tracking system at 120h.
Carbendazim (96h-LC50 of 1.75mg/L) elicited several developmental anomalies in zebrafish embryos with EC50 values ranging from 0.85 to 1.6mg/L. ChE, GST and LDH activities were increased at concentrations equal or above 4μg/L. The locomotor assay showed to be extremely sensitive, detecting effects in time that larvae spent swimming at concentrations of 0.16μg/L and thus, being several orders of magnitude more sensitive that developmental parameters or lethality. These are ecological relevant concentrations and highlight the potential of behavioural endpoints as early warning signs for environmental stress. Further studies should focus on understanding how the behavioural disturbances measured in these types of studies translate into fitness impairment at the adult stage.
Cognitive human error and recent cognitive taxonomy on human error causes of software defects support the intuitive idea that, for instance, mental overload, attention slips, and working memory ...overload are important human causes for software bugs. In this paper, we approach the EEG as a reliable surrogate to MRI-based reference of the programmer's cognitive state to be used in situations where heavy imaging techniques are infeasible. The idea is to use EEG biomarkers to validate other less intrusive physiological measures, that can be easily recorded by wearable devices and useful in the assessment of the developer's cognitive state during software development tasks. Herein, our EEG study, with the support of fMRI, presents an extensive and systematic analysis by inspecting metrics and extracting relevant information about the most robust features, best EEG channels and the best hemodynamic time delay in the context of software development tasks. From the EEG-fMRI similarity analysis performed, we found significant correlations between a subset of EEG features and the Insula region of the brain, which has been reported as a region highly related to high cognitive tasks, such as software development tasks. We concluded that despite a clear inter-subject variability of the best EEG features and hemodynamic time delay used, the most robust and predominant EEG features, across all the subjects, are related to the Hjorth parameter Activity and Total Power features, from the EEG channels F4, FC4 and C4, and considering in most of the cases a hemodynamic time delay of 4 seconds used on the hemodynamic response function. These findings should be taken into account in future EEG-fMRI studies in the context of software debugging.
Electrocardiogram (ECG) recordings, lasting hours before epileptic seizures, have been studied in the search for evidence of the existence of a preictal interval that follows a normal ECG trace and ...precedes the seizure's clinical manifestation. The preictal interval has not yet been clinically parametrized. Furthermore, the duration of this interval varies for seizures both among patients and from the same patient. In this study, we performed a heart rate variability (HRV) analysis to investigate the discriminative power of the features of HRV in the identification of the preictal interval. HRV information extracted from the linear time and frequency domains as well as from nonlinear dynamics were analysed. We inspected data from 238 temporal lobe seizures recorded from 41 patients with drug-resistant epilepsy from the EPILEPSIAE database. Unsupervised methods were applied to the HRV feature dataset, thus leading to a new perspective in preictal interval characterization. Distinguishable preictal behaviour was exhibited by 41% of the seizures and 90% of the patients. Half of the preictal intervals were identified in the 40 min before seizure onset. The results demonstrate the potential of applying clustering methods to HRV features to deepen the current understanding of the preictal state.
Ultra-short-term HRV features assess minor autonomous nervous system variations such as variations resulting from cognitive stress peaks during demanding tasks. Several studies compare ...ultra-short-term and short-term HRV measurements to investigate their reliability. However, existing experiments are conducted in low cognitively demanding environments. In this paper, we propose to evaluate these measurements’ reliability under cognitively demanding tasks using a near real-life setting. For this purpose, we selected 31 HRV features, extracted from data collected from 21 programmers performing code comprehension, and compared them across 18 different time frames, ranging from 3 min to 10 s. Statistical significance and correlation tests were performed between the features extracted using the larger window (3 min) and the same features extracted with the other 17 time frames. We paired these analyses with Bland–Altman plots to inspect how the extraction window size affects the HRV features. The main results show 13 features that presented at least 50% correlation when using 60-second windows. The HF and mNN features achieved around 50% correlation using a 30-second window. The 30-second window was the smallest time frame considered to have reliable measurements. Furthermore, the mNN feature proved to be quite robust to the shortening of the time resolution.
•GEM concentrations not causing perceived developmental effects significantly impaired behavioral endpoints.•Selection of eleutheroembryos stages is highly relevant in swimming behavior ...assessment.•Behavioral endpoints are recommended for toxicity screening due to their high sensitivity.•Fish acute toxicity (FET) test and behavior emphasize the need to study GEM effects in fish.
Pharmaceuticals are emerging contaminants as their worldwide consumption increases. Fibrates such as gemfibrozil (GEM) are used in human medicine to reduce blood concentrations of cholesterol and triacylglycerol and also are some of the most frequently reported pharmaceuticals in waste waters and surface waters. Despite some studies have already demonstrated the negative impact in physiological and/or reproductive endpoints in adult fish, data on survival and behavioral effects in fish larvae are lacking. This study aimed to assess the effects of GEM on zebrafish eleutheroembryo development and locomotor behavior. A fish embryo toxicity (FET) test was undertaken to evaluate GEM acute toxicity by exposing embryos to 0, 6.58, 9.87, 14.81, 22.22, 33.33 and 50mg/L. Developmental endpoints such as hatching success, edemas and malformations were recorded. A second test was undertaken by exposing embryos to 0, 1.5, 3 and 6mg/L in order to evaluate the effects of GEM on 120 and 144h post fertilization (hpf) larvae locomotor activity by video tracking, using a Zebrabox® (Viewpoint, France) device. From the data recorded, several parameters such as total swimming distance (TSD) and total swimming time (TST) in each 120s integration time were calculated. Data showed that this compound has a moderate toxic effect on fish embryo development, affecting both survival and hatching success with a calculated 96h LC50 of 11.01mg/L and no effects at the developmental level at 6mg/L. GEM seems to impair locomotor activity, even at concentrations where developmental abnormalities were unperceived, at concentrations as low as 1.5mg/L. Both TSD and TST were sensitive to GEM exposure. These effects do not seem to be independent of the developmental stage as 120hpf larvae seem to present a development bias with repercussions in locomotor behavior. This study highlights the need to include behavioral endpoints in ecotoxicological assays as this seems to be a more sensitive endpoint often disregarded.
Blood pressure (BP) surrogates, such as pulse transit time (PTT) or pulse arrival time (PAT), have been intensively explored with the goal of achieving cuffless, continuous, and accurate BP ...inference. In order to estimate BP, a one-point calibration strategy between PAT and BP is typically used. Recent research focuses on advanced calibration procedures exploiting the cuff inflation process to improve calibration robustness by active and controlled modulation of peripheral PAT, as measured via plethysmograph (PPG) and electrocardiogram (ECG) combination. Such methods require a detailed understanding of the mechanisms behind the vasculature's response to cuff inflation; for this, a model has recently been developed to infer the PAT-BP calibration from measured cuff-induced vasculature changes. The model, while promising, is still preliminary and only partially validated; in-depth analysis and further developments are still needed. Therefore, this work aims to improve our understanding of the cuff-vasculature interaction in this model; we seek to define potential opportunities and to highlight which aspects may require further study. We compare model behaviors with clinical data samples based on a set of observable characteristics relevant for BP inference and calibration. It is found that the observed behaviors are qualitatively well represented with the current simulation model and complexity, with limitations regarding the prediction of the onset of the distal arm dynamics and behavior changes at high cuff pressures. Additionally, a sensitivity analysis of the model's parameter space is conducted to show the factors that influence the characteristics of its observable outputs. It was revealed that easily controllable experimental variables, such as lateral cuff length and inflation rate, have a significant impact on cuff-induced vasculature changes. An interesting dependency between systemic BP and cuff-induced distal PTT change is also found, revealing opportunities for improved methods for BP surrogate calibration. However, validation via patient data shows that this relation does not hold for all patients, indicating required model improvements to be validated in follow up studies. These results provide promising directions to improve the calibration process featuring cuff inflation towards accurate and robust non-invasive blood pressure estimation.
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