Artificial intelligence-based radiomics on computed tomography of lumbar spine in subjects with fragility vertebral fractures.

PURPOSE: There is emerging evidence that radiomics analyses can improve detection of skeletal fragility. In this cross-sectional study, we evaluated radiomics features (RFs) on computed tomography (CT) images of the lumbar spine in subjects with or without fragility vertebral fractures (VFs). METHODS: Two-hundred-forty consecutive individuals (mean age 60.4 ± 15.4, 130 males) were evaluated by radiomics analyses on opportunistic lumbar spine CT. VFs were diagnosed in 58 subjects by morphometric approach on CT or XR-ray spine (D4-L4) images. DXA measurement of bone mineral density (BMD) was performed on 17 subjects with VFs. RESULTS: Twenty RFs were used to develop the machine learning model reaching 0.839 and 0.789 of AUROC in the train and test datasets, respectively. After correction for age, VFs were significantly associated with RFs obtained from non-fractured vertebrae indicating altered trabecular microarchitecture, such as low-gray level zone emphasis (LGLZE) [odds ratio (OR) 1.675, 95% confidence interval (CI) 1.215-2.310], gray level non-uniformity (GLN) (OR 1.403, 95% CI 1.023-1.924) and neighboring gray-tone difference matrix (NGTDM) contrast (OR 0.692, 95% CI 0.493-0.971). Noteworthy, no significant differences in LGLZE (p = 0.94), GLN (p = 0.40) and NGDTM contrast (p = 0.54) were found between fractured subjects with BMD T score < - 2.5 SD and those in whom VFs developed in absence of densitometric diagnosis of osteoporosis. CONCLUSIONS: Artificial intelligence-based analyses on spine CT images identified RFs associated with fragility VFs. Future studies are needed to test the predictive value of RFs on opportunistic CT scans in identifying subjects with primary and secondary osteoporosis at high risk of fracture.

Yersinia pestis: the Natural History of Plague.

The Gram-negative bacterium Yersinia pestis is responsible for deadly plague, a zoonotic disease established in stable foci in the Americas, Africa, and Eurasia. Its persistence in the environment relies on the subtle balance between Y. pestis-contaminated soils, burrowing and nonburrowing mammals exhibiting variable degrees of plague susceptibility, and their associated fleas. Transmission from one host to another relies mainly on infected flea bites, inducing typical painful, enlarged lymph nodes referred to as buboes, followed by septicemic dissemination of the pathogen. In contrast, droplet inhalation after close contact with infected mammals induces primary pneumonic plague. Finally, the rarely reported consumption of contaminated raw meat causes pharyngeal and gastrointestinal plague. Point-of-care diagnosis, early antibiotic treatment, and confinement measures contribute to outbreak control despite residual mortality. Mandatory primary prevention relies on the active surveillance of established plague foci and ectoparasite control. Plague is acknowledged to have infected human populations for at least 5,000 years in Eurasia. Y. pestis genomes recovered from affected archaeological sites have suggested clonal evolution from a common ancestor shared with the closely related enteric pathogen Yersinia pseudotuberculosis and have indicated that ymt gene acquisition during the Bronze Age conferred Y. pestis with ectoparasite transmissibility while maintaining its enteric transmissibility. Three historic pandemics, starting in 541 AD and continuing until today, have been described. At present, the third pandemic has become largely quiescent, with hundreds of human cases being reported mainly in a few impoverished African countries, where zoonotic plague is mostly transmitted to people by rodent-associated flea bites.

The central autonomic network at rest: Uncovering functional MRI correlates of time-varying autonomic outflow.

Peripheral measures of autonomic nervous system (ANS) activity at rest have been extensively employed as putative biomarkers of autonomic cardiac control. However, a comprehensive characterization of the brain-based central autonomic network (CAN) sustaining cardiovascular oscillations at rest is missing, limiting the interpretability of these ANS measures as biomarkers of cardiac control. We evaluated combined cardiac and fMRI data from 34 healthy subjects from the Human Connectome Project to detect brain areas functionally linked to cardiovagal modulation at rest. Specifically, we combined voxel-wise fMRI analysis with instantaneous heartbeat and spectral estimates obtained from inhomogeneous linear point-process models. We found exclusively negative associations between cardiac parasympathetic activity at rest and a widespread network including bilateral anterior insulae, right dorsal middle and left posterior insula, right parietal operculum, bilateral medial dorsal and ventrolateral posterior thalamic nuclei, anterior and posterior mid-cingulate cortex, medial frontal gyrus/pre-supplementary motor area. Conversely, we found only positive associations between instantaneous heart rate and brain activity in areas including frontopolar cortex, dorsomedial prefrontal cortex, anterior, middle and posterior cingulate cortices, superior frontal gyrus, and precuneus. Taken together, our data suggests a much wider involvement of diverse brain areas in the CAN at rest than previously thought, which could reflect a differential (both spatially and directionally) CAN activation according to the underlying task. Our insight into CAN activity at rest also allows the investigation of its impairment in clinical populations in which task-based fMRI is difficult to obtain (e.g., comatose patients or infants).

The 1000IBD project: multi-omics data of 1000 inflammatory bowel disease patients; data release 1.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic complex disease of the gastrointestinal tract. Patients with IBD can experience a wide range of symptoms, but the pathophysiological mechanisms that cause these individual differences in clinical presentation remain largely unknown. In consequence, IBD is currently classified into subtypes using clinical characteristics. If we are to develop a more targeted treatment approach, molecular subtypes of IBD need to be discovered that can be used as new drug targets. To achieve this, we need multiple layers of molecular data generated from the same IBD patients. CONSTRUCTION AND CONTENT: We initiated the 1000IBD project ( https://1000ibd.org ) to prospectively follow more than 1000 IBD patients from the Northern provinces of the Netherlands. For these patients, we have collected a uniquely large number of phenotypes and generated multi-omics profiles. To date, 1215 participants have been enrolled in the project and enrolment is on-going. Phenotype data collected for these participants includes information on dietary and environmental factors, drug responses and adverse drug events. Genome information has been generated using genotyping (ImmunoChip, Global Screening Array and HumanExomeChip) and sequencing (whole exome sequencing and targeted resequencing of IBD susceptibility loci), transcriptome information generated using RNA-sequencing of intestinal biopsies and microbiome information generated using both sequencing of the 16S rRNA gene and whole genome shotgun metagenomic sequencing. UTILITY AND DISCUSSION: All molecular data generated within the 1000IBD project will be shared on the European Genome-Phenome Archive ( https://ega-archive.org , accession no: EGAS00001002702). The first data release, detailed in this announcement and released simultaneously with this publication, will contain basic phenotypes for 1215 participants, genotypes of 314 participants and gut microbiome data from stool samples (315 participants) and biopsies (107 participants) generated by tag sequencing the 16S gene. Future releases will comprise many more additional phenotypes and -omics data layers. 1000IBD data can be used by other researchers as a replication cohort, a dataset to test new software tools, or a dataset for applying new statistical models. CONCLUSIONS: We report on the establishment and future development of the 1000IBD project: the first comprehensive multi-omics dataset aimed at discovering IBD biomarker profiles and treatment targets.

Correction to: The 1000IBD project: multi-omics data of 1000 inflammatory bowel disease patients; data release 1.

Following publication of the original article [1], the authors.

Late sodium current blocker GS967 inhibits persistent currents induced by familial hemiplegic migraine type 3 mutations of the SCN1A gene.

BACKGROUND: Familial hemiplegic migraine (FHM) is a group of genetic migraine, associated with hemiparesis and aura. Three causative different genes have been identified, all of which are involved in membrane ion transport. Among these, SCN1A encodes the voltage-gated Na+ channel Nav1.1, and FHM caused by mutations of SCN1A is named FHM3. For 7 of the 12 known FHM3-causing SCNA1 mutations functional consequences have been investigated, and even if gain of function effect seems to be a predominant phenotype, for several mutations conflicting results have been obtained and the available data do not reveal a univocal FHM3 pathomechanism. METHODS: To obtain a more complete picture, here, we characterized by patch clamp approach the remaining 5 mutations (Q1489H, I1498M, F1499 L, M1500 V, F1661 L) in heterologous expression systems. RESULTS: With the exception of I1498M, all mutants exhibited the same current density as WT and exhibited a shift of the steady state inactivation to more positive voltages, an accelerated recovery from inactivation, and an increase of the persistent current, revealing that most FHM3 mutations induce a gain of function. We also determined the effect of GS967, a late Na+ current blocker, on the above mentioned mutants as well as on previously characterized ones (L1649Q, L1670 W, F1774S). GS967 inhibited persistent currents of all SCNA1 FMH3-related mutants and dramatically slowed the recovery from fast inactivation of WT and mutants, consistent with the hypothesis that GS967 specifically binds to and thereby stabilizes the fast inactivated state. Simulation of neuronal firing showed that enhanced persistent currents cause an increase of ionic fluxes during action potential repolarization and consequent accumulation of K+ and/or exhaustion of neuronal energy resources. In silico application of GS967 largely reduced net ionic currents in neurons without impairing excitability. CONCLUSION: In conclusion, late Na+ current blockers appear a promising specific pharmacological treatment of FHM3.

Energy Systems Contribution in the Running-based Anaerobic Sprint Test.

The aims of the present study were to verify the contributions of the energy systems during repeated sprints with a short recovery time and the associations of the time- and power-performance of repeated sprints with energetic contributions and aerobic and anaerobic variables. 13 healthy men performed the running-based anaerobic sprint test (RAST) followed by an incremental protocol for lactate minimum intensity determination. During the RAST, the net energy system was estimated using the oxygen consumption and the blood lactate responses. The relative contributions of oxidative phosphorylation, glycolytic, and phosphagen pathways were 38, 34, and 28%, respectively. The contribution of the oxidative pathway increased significantly during RAST especially from the third sprint, at the same time that power- and time-performances decreases significantly. The phosphagen pathway was associated with power-performance (peak power=432±107 W, r=0.65; mean power=325±80 W, r=0.65; minimum power=241±77 W, r=0.57; force impulse=1 846±478 N·s, r=0.74; p<0.05). The time-performance (total time=37.9±2.5 s; best time=5.7±0.4 s; mean time=6.3±0.4 s; worst time=7.0±0.6 s) was significantly correlated with the oxidative phosphorylation pathway (0.57+0.65; p<0.05) and glycolytic pathway (0.57+<+r>0.58; p<0.05). The oxidative pathway appears to play an important role in better recovery between sprints, and the continued use of the glycolytic metabolic pathway seems to decrease sprint performances. Finally, the phosphagen pathway was linked to power production/maintenance.

A prospective cohort study of endometriosis and subsequent risk of infertility.

STUDY QUESTION: Is there a temporal relationship between endometriosis and infertility? SUMMARY ANSWER: Endometriosis is associated with a higher risk of subsequent infertility, but only among women age <35 years. WHAT IS KNOWN ALREADY: Endometriosis is the most commonly observed gynecologic pathology among infertile women undergoing laparoscopic examination. Whether endometriosis is a cause of infertility or an incidental discovery during the infertility examination is unknown. STUDY DESIGN, SIZE, DURATION: This study included data collected from 58 427 married premenopausal female nurses <40 years of age from 1989 to 2005, who are participants of the Nurses' Health Study II prospective cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS: Our exposure was laparoscopically confirmed endometriosis. Multivariate Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for infertility risk (defined as attempting to conceive for >12 months) among women with and without endometriosis. MAIN RESULTS AND THE ROLE OF CHANCE: We identified 4612 incident cases of infertility due to any cause over 362 219 person-years of follow-up. Compared with women without a history of endometriosis, women with endometriosis had an age-adjusted 2-fold increased risk of incident infertility (HR = 2.12, 95% CI = 1.76-2.56) that attenuated slightly after accounting for parity. The relationship with endometriosis was only observed among women <35 years of age (multivariate HR <35 years = 1.77, 95% CI = 1.46-2.14; multivariate HR 35-39 years = 1.20, 95% CI = 0.94-1.53; P-interaction = 0.008). Risk of primary versus secondary infertility was similar subsequent to endometriosis diagnosis. Among women with primary infertility, 50% became parous after the endometriosis diagnosis, and among all women with endometriosis, 83% were parous by age 40 years. LIMITATIONS, REASONS FOR CAUTION: We did not have information on participants' intentions to conceive, but by restricting the analytic population to married women we increased the likelihood that pregnancies were planned (and therefore infertility would be recognized). Women in our cohort with undiagnosed asymptomatic endometriosis will be misclassified as unexposed. However, the small proportion of these women are diluted among the >50 000 women accurately classified as endometriosis-free, minimizing the impact of exposure misclassification on the effect estimates. WIDER IMPLICATIONS OF THE FINDINGS: This study supports a temporal association between endometriosis and infertility risk. Our prospective analysis indicates a possible detection bias in previous studies, with our findings suggesting that the infertility risk posed by endometriosis is about half the estimates observed in cross-sectional analyses. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the National Institutes of Health (grant numbers: UM1 CA176726, HD52473, HD57210, T32DK007703, T32HD060454, K01DK103720). We have no competing interests to declare.

Heat and desiccation are the predominant factors affecting inactivation of Bacillus licheniformis and Bacillus thuringiensis spores during simulated composting.

AIMS: The suitability of composting for disposal of livestock mortalities due to Bacillus anthracis was assessed by measuring viability of surrogate spores from two strains each of Bacillus licheniformis and Bacillus thuringiensis after a heating cycle modelled on a cattle composting study. METHODS AND RESULTS: Sporulation was attempted from 10 to 37°C, but poor yields at lower temperatures resulted in 25, 30 and 37°C being selected to generate sufficient spores (8 log10  CFU ml(-1) ) for experiments. Spores were inoculated into 3 g autoclaved dried-ground compost rehydrated with 6 ml water or silica beads in a factorial design for each strain, sporulation temperature, matrix and sampling day (0, 25, 50, 100, 150). Maximum incubation temperature was 62°C, but spores were maintained at ≥55°C for 78 of 150 days. Although significant differences existed among Bacillus strains and sporulation temperatures, numbers of viable spores after 150 days averaged 1·3 log10  CFU g(-1) , a 5·2 log10 reduction from day 0. CONCLUSIONS: Spore inactivation was likely due to heat and desiccation as matrices were autoclaved prior to incubation, negating impacts of microflora. SIGNIFICANCE AND IMPACT OF STUDY: Results support composting for disposal of anthrax mortalities, provided long-term thermophillic heating is achieved. Due to limited sporulation at 10°C, livestock mortalities from anthrax at this or lower ambient temperatures would likely be of lower risk for disease transmission.

The Hoff circuit test is more specific than an incremental treadmill test to assess endurance with the ball in youth soccer players.

The assessment of aerobic endurance is important for training prescription in soccer, and is usually measured by straight running without the ball on a track or treadmill. Due to the ball control and technical demands during a specific soccer test, the running speeds are likely to be lower compared to a continuous incremental test. The aim of the present study was to compare the heart rate (HR), rating of perceived exertion (RPE) and speeds corresponding to 2.0 mmol∙L(-1), 3.5 mmol∙L(-1), lactate threshold (Dmax method) and peak lactate determined in the laboratory and in the Hoff circuit soccer-specific test. Sixteen soccer players (16±1 years) underwent two incremental tests (laboratory and Hoff circuit tests). The speeds were significantly higher in the treadmill test than on the Hoff circuit (2.0 mmol∙L(-1): 9.5±1.2 and 8.1±1.0 km∙h(-1); 3.5 mmol∙L(-1): 12.0±1.2 and 10.2±1.1 km∙h(-1); Dmax: 11.4±1.4 and 9.3±0.4 km∙h(-1); peak lactate: 14.9±1.6 and 10.9±0.8 km∙h(-1)). The HR corresponding to 3.5 mmol∙L-1 was significantly higher on the Hoff circuit compared to the laboratory test (187.5±18.0 and 178.2±17.6 bpm, respectively; P <0.001), while the RPE at the last incremental stage was lower on the Hoff circuit (P < 0.01). The speeds during the Hoff specific soccer test and the HR corresponding to 2.0 mmol∙L(-1), 3.5 mmol∙L(-1) and Dmax/threshold were different compared with the laboratory test. The present study shows that it is possible to assess submaximal endurance related variables specifically in soccer players.

Genes of detoxification are important modulators of hereditary medullary thyroid carcinoma risk.

CONTEXT: Different inherited profiles of genes involved in cellular mechanisms of activation and detoxification of carcinogenic products can provide specific protection or determine the risk for cancer. Low-penetrance polymorphic genes related to the biotransformation of environmental toxins have been associated with susceptibility to and the phenotype of, human tumours. OBJECTIVE: To investigate the role of germline inheritance of polymorphisms in CYP1A2*F, CYP1A1 m1, GSTP1, NAT2 and TP53 genes in hereditary medullary thyroid carcinoma (HMTC) patients. DESIGN: This study was developed in University of Campinas (Unicamp). PATIENTS: We studied 132 patients with HMTC, 88 first-degree relatives of HMTC patients and 575 control individuals. MEASUREMENTS: All patients with MTC and their relatives were sequenced for the RET gene and five genes were genotyped using TaqMan(®) system. RESULTS: We observed that the inheritance of CYP1A2*F (OR = 2·10; 95% CI = 1·11-3·97; P = 0·022), GSTP1 (OR = 4·41; 95% CI = 2·47-7·88; P < 0·001) and NAT2 (OR = 2·54; 95% CI = 1·16-5·58; P = 0·020) variants increased the risk for HMTC. In addition, multiple regression analysis showed that the inheritance of GSTP1 polymorphisms was associated with the diagnosis in older patients (B = 8·0229; 95% IC = ± 5·5735; P = 0·0054). Concerning the group of HTMC relatives, CYP1A2*F (OR = 2:40; 95% CI = 1·19-4·86; P = 0·015), CYP1A1 m1 (OR = 2·79; 95% CI = 1:04-7·51; P = 0·042), GSTP1 (OR = 2·86; 95% IC = 1·53-5·32; P < 0·001) and NAT2 (OR = 2·25; 95% IC = 1·20-4·22; P = 0·012) were associated with HMTC risk. CONCLUSIONS: We have demonstrated that the inheritance of specific genes determining the individual response to environmental toxins may contribute to the risk and phenotypic variability that exists in patients with HMTC. Moreover, we identified a group at risk in relatives of HMTC patients.

The impact of healthy pregnancy on features of heart rate variability and pulse wave morphology derived from wrist-worn photoplethysmography.

Due to the association between dysfunctional maternal autonomic regulation and pregnancy complications, tracking non-invasive features of autonomic regulation derived from wrist-worn photoplethysmography (PPG) measurements may allow for the early detection of deteriorations in maternal health. However, even though a plethora of these features-specifically, features describing heart rate variability (HRV) and the morphology of the PPG waveform (morphological features)-exist in the literature, it is unclear which of these may be valuable for tracking maternal health. As an initial step towards clarity, we compute comprehensive sets of HRV and morphological features from nighttime PPG measurements. From these, using logistic regression and stepwise forward feature elimination, we identify the features that best differentiate healthy pregnant women from non-pregnant women, since these likely capture physiological adaptations necessary for sustaining healthy pregnancy. Overall, morphological features were more valuable for discriminating between pregnant and non-pregnant women than HRV features (area under the receiver operating characteristics curve of 0.825 and 0.74, respectively), with the systolic pulse wave deterioration being the most valuable single feature, followed by mean heart rate (HR). Additionally, we stratified the analysis by sleep stages and found that using features calculated only from periods of deep sleep enhanced the differences between the two groups. In conclusion, we postulate that in addition to HRV features, morphological features may also be useful in tracking maternal health and suggest specific features to be included in future research concerning maternal health.

Regulation of innate immunity by the nucleotide pathway in children with idiopathic nephrotic syndrome.

Activation of the oxidative burst and failure of CD4(+) CD25(+) cell regulation have been implicated in idiopathic nephrotic syndrome (iNS). The intimate mechanism is, however, unknown and requires specifically focused studies. We investigated reactive oxygen species (ROS) generation [di-chlorofluorescein-diacetate (DCFDA)] fluorescence assay and the regulatory adenosine 5'-triphosphate (ATP) pathways in the blood of 41 children with iNS, utilizing several agonists and antagonists of nucleotide/nucleoside receptors, including the addition of soluble apyrase. The CD4(+) CD25(+) CD39(+) /CD73(+) expression was determined in vivo in parallel during disease activity. Overall, we found that the percentage of CD39(+) CD4(+) CD25(+) was reduced markedly in iNS by 80% (3·43±0·04% versus 13·14±0·07% of total lymphocytes, P<0·001). In these patients, reactive oxygen species (ROS) generation by polymorphonuclear neutrophils (PMN) at rest was a function of apyrase (CD39) expressed by CD4(+) CD25(+) , with higher rates in patients with very low CD39(+) CD4(+) CD25(+) levels (<7·5%). Addition of apyrase reduced ROS generation by 40% in both iNS and controls and was mainly effective in patients. The quota of ROS surviving ATP elimination was higher still in iNS. In vitro studies to limit ROS generation with adenosine analogues (2'-chloroadenosine and 5'-N-ethylcarboxamidoadenosine) produced minor effects. At variance, antagonizing ATP efflux with carbenoxolone or by antagonizing ATP effects (Brilliant Blue G, KN62 and A437089) reduced ROS generation comparable to apyrase. These results confirm a key role of ATP in the regulation of innate immunity and minimize the effect of adenosine. Decreased CD39(+) CD4(+) CD25(+) expression in iNS highlights an impairment of ATP degradation in this pathology. However, high ROS surviving ATP consumption implies a major role of other regulatory pathways.

Assessing an Automatic Procedure of Extraction of Physiological Parameters from Skin using Video Photoplethysmography.

Video Photoplethysmography (vPPG) allows for estimation of blood volume pulse (BVP) from the skin by means of a video camera recording at high frequency rate. The estimation procedure presents several drawbacks in its application to real world conditions, such as light changes or movements that often generate artifacts in the extracted BVP waveform. In addition, the process requires a skin segmentation algorithm to distinguish skin pixels from the background. To date, even the most refined skin segmentation algorithms still need a manual definition that could lead to incorrect pixel classification, and consequently to a decrease in the signal-to-noise ratio (SNR). We here propose a fully autonomic procedure able to extract BVP from video recordings of the skin in real world conditions.The experimental protocol is designed to record the signals of interest and to evaluate changes in the Autonomic Nervous System modulation of the heart during a baseline condition and a controlled breathing phase. Video recordings are gathered from 4 young healthy subjects (age: 21±1 years). vPPG signals are processed in order to extract the BVP waveform, and a peak detection algorithm detects pulse wave peaks that are then used to compute specific measures of heart rate variability (HRV).The procedure is successfully validated by comparing the extracted HRV measures against those extracted using a finger photoplethysmograph (fPPG) using three different skin segmentation algorithms from BVP signals.

A 2,000-year-old specimen with intraerythrocytic Bartonella quintana.

Photogrammetry and cascading microscopy investigations of dental pulp specimens collected from 2,000-year-old individuals buried in a Roman necropolis in Besançon, France, revealed unprecedented preserved tissular and cellular morphology. Photogrammetry yielded 3-D images of the smallest archaeological human remains ever recovered. Optical microscopy examinations after standard haematoxylin-phloxine-saffron staining and anti-glycophorin A immunohistochemistry exposed dental pulp cells, in addition erythrocytes were visualised by electron microscopy, which indicated the ancient dental pulp trapped a blood drop. Fluorescence in situ hybridisation applied on red blood cells revealed the louse-borne pathogen Bartonella quintana, a finding confirmed by polymerase chain reaction assays. Through paleohistology and paleocytology, we demonstrate that the ancient dental pulp preserved intact blood cells at the time of the individual's death, offering an unprecedented opportunity to engage in direct and indirect tests to diagnose pathogens in ancient buried individuals.

Resting State Neural Correlates of Cardiac Sympathetic Dynamics in Healthy Subjects.

Recent advances in functional Magnetic Resonance Imaging (fMRI) research have uncovered the existence of the central autonomic network (CAN), which comprises brain regions whose activity correlates with autonomic nervous system dynamics. By exploiting the spectral paradigm of heartbeat dynamics, cortical and sub-cortical areas functionally linked to vagal activity have been identified. However, due to methodological limitations, functional neural correlates of cardiac sympathetic dynamics remain uncharacterized. To this extent, we exploit the high spatiotemporal resolution of fMRI data from the Human Connectome Project to study the CAN activity by correlating a recently proposed instantaneous characterization of sympathetic activity (the sympathetic activity index - SAI) from heartbeat dynamics. SAI estimates are embedded into the probabilistic modeling of inhomogeneous point-processes, and are derived from a combination of disentangling coefficients linked to the orthonormal Laguerre functions. By analyzing resting state recordings from 34 young healthy people, we obtain positive correlations between instantaneous SAI estimates and a number of brain regions including frontal pole, insular cortex, frontal and temporal gyri, lateral occipital cortex, paracingulate and cingulate gyri, precuneus and temporal fusiform cortices, as well as thalamus, caudate nucleus, putamen, brain-stem, hippocampus, amygdala, and nucleus accumbens. Our findings significantly extend current knowledge on the CAN, opening new avenues in the characterization of healthy and pathological states in humans.

Heartbeat Dynamics Analysis under Cold-Pressure Test using Wavelet p-Leader Non-Gaussian Multiscale Expansions.

Multiscale and multifractal (MF) analyses have been proven an effective tool for the characterisation of heartbeat dynamics in physiological and pathological conditions. However, pre-processing methods for the unevenly sampled heartbeat interval series are known to affect the estimation of MF properties. In this study, we employ a recently proposed method based on wavelet p-leaders MF spectra to estimate MF properties from cardiovascular variability series, which are also pre-processed through an inhomogeneous point-process modelling. Particularly, we exploit a non-Gaussian multiscale expansion to study changes in heartbeat dynamics as a response to a sympathetic elicitation given by the cold-pressor test. By comparing MF estimates from raw heartbeat series and the point-process model, results suggest that the proposed modelling provides features statistically discerning between stress and resting condition at different time scales. These findings contribute to a comprehensive characterization of autonomic nervous system activity on cardiovascular control during cold-pressor elicitation.

Characterizing autonomic response to arousing visual-auditory multi-modal task in Autism Spectrum Disorder (ASD).

Sensory abnormalities are widespread in Autism Spectrum Disorder (ASD). However, their definition is still quite subjective and vague. Here we propose a novel approach for characterization of Autonomic Nervous System responses to sensory stimulation based on electrocardiogram (ECG) assessment. In particular, we develop a preliminary study where autonomic responses of both autistic (ASD = 5) and neurotypical (NT = 5) participants have been evaluated in terms of changes in responsiveness to repeated stimuli. Autonomic control has been estimated via high-frequency heart rate variability (HF-HRV) and low-frequency HRV (LF-HRV). Results show significant differences among groups for the HRV measures (p value = 0.0158), supported by expected changes of HF (p value = 0.0079) and LF (p value = 0.0079) trends over stimulations. We thus conclude that an overall decrease in autonomic arousal can give important insights for devising new habituation metrics in NT and ASD individuals.

Identification and Tracking of Physiological Parameters from Skin using Video Photoplethysmography.

In recent years, there has been a growing interest in video Photoplethysmography (vPPG), a technique able to estimate cardiovascular parameters from video recordings of the skin. Despite the growing interest in vPPG technology, there are still problems in extracting the correct waveform of blood volume pulse, mainly due to real world artifacts, such as changes in light condition and movement artifacts. Another important issue is the correct definition of skin against background. Therefore, we propose an algorithm of skin detection that is able to recognize skin pixels solid to variations of luminosity. We recorded the signals of interest during an experimental protocol designed to provide thermal stimulation and observe the resulting Autonomic Nervous System changes. Experimental data were gathered from 10 young healthy subjects (age: 21±2 years). Video recordings are processed using a band-pass filter and then an automatic algorithm of peak detection is applied to detect the pulse wave peaks, then used to estimate heart rate variability (HRV). The efficiency and stability of the algorithm are compared against finger-PPG waveforms. Preliminary results show an overall statistical agreement between time and frequency domain indexes. However, further efforts are required to improve the estimation of frequency components, particularly during rest.

Quantification of Different Regulatory Pathways Contributing to Heartbeat Dynamics during Multiple Stimuli: a Proof of the Concept.

The dynamical interplay between brain and heart is mediated by several feedback mechanisms including the central autonomic network and baroreflex loop at a peripheral level, also for a short-term regulation. State of the art focused on the characterization of each regulatory pathway through a single stressor elicitation. However, no studies targeted the actual quantification of different mediating routes leading to the generation of heartbeat dynamics, particularly in case of combined exogenous stimuli. In this study, we propose a new approach based on computational modeling to quantify the contribution of multiple concurrent stimuli in modulating cardiovascular dynamics. In this preliminary attempt, the model estimates the high-frequency power of heartbeat dynamics, and derives disentangling coefficients quantifying the effect of multiple elicitations. Model evaluation is performed on healthy rate variability (HRV) series from fourteen healthy subjects undergoing physical (tilt-table) and mental stressors (aritmetics), as well as their combined administration. Results indicate that, at a group-wise level, in base of concurrent physical and mental elicitations, the physical stressor contributes for the 85% of the resulting heartbeat dynamics. These findings are in agreement with the current knowledge on heartbeat regulatory systems, providing valuable perspectives on the quantification of underlying generative mechanisms of HRV.