Wearable sensors to measure the influence of sonic seasoning on wine consumers in a live context: a preliminary proof-of-concept study.

BACKGROUND: Any action capable of creating expectations about product quality would be able to modulate experienced pleasantness. In this context, during the 2022 edition of the Internet Festival (Pisa, Italy) a 'social experiment' was promoted to set up an affordable and reliable methodology based on wearable sensors to measure the emotions aroused in a live context on consumers by different kinds of wines. Therefore, five wines (two faulty ones and three high-quality samples) were proposed to 50 non-selected consumers in an arousing context with live jazz music as background. Both explicit (questionnaires) and two different approaches for implicit methods (electrocardiogram (ECG) recorded by wearable sensors vs. smartphones), the latter performed on a subgroup of 16, to measure the emotions aroused by wines and music were utilized synergistically. RESULTS: According to our findings: (i) wine undoubtedly generates a significant emotional response on consumers; (ii) this answer is multifaceted and attributable to the quality level of the wine tasted. In fact, all things being equal, while drinking wine even untrained consumers can perfectly recognize good wines compared to products of lower quality; (iii) high-quality wines are able to induce a spectrum of positive emotions, as observed by the analysis of ECG signals, especially when they are coupled with background music. CONCLUSION: The framework has certainly played to the advantage of good-quality wines, fostering their positive emotional characteristics on the palate even of some less experienced consumers, thanks to a dragging effect towards a positive mood generated by the surrounding conditions (good music in a beautiful location). © 2024 Society of Chemical Industry.

Deficits in emotion recognition and processing in children with high callous-unemotional traits: the role of the MAOA gene.

Children with high Callous-Unemotional (CU) traits show deficits in recognizing and processing facial expressions. Alterations in emotion recognition have been linked to a higher synaptic concentration of monoaminergic neurotransmitters. The current study investigated the relationship between the MAOA-Low-activity alleles and the ability to recognize and process facial expressions in 97 male children (8-12 years old) diagnosed with disruptive behavior disorder. Participants completed a computerized emotion-recognition task while an eye-tracking system recorded the number (Fixation Count, FC) and length (Fixation Duration, FD) of fixations to the eye region of the emotional stimuli. Children with high CU traits exhibited lower scores in recognition of sadness and anger, and lower FC and FD for sadness and fear than children with low CU traits. Children carrying the MAOA-Low-activity alleles displayed lower FD for sadness, and FD and FC for fear than those carrying the MAOA-High-activity alleles. These genetic effects appeared even stronger in children with CU traits. Moderation analysis revealed that CU traits were associated with lower FC and FD for fear, and lower FD for sadness, probably due to the MAOA-Low-activity alleles. Our findings, although to be replicated, suggest MAOA-Low-activity alleles as potential genetic biomarkers to identify CU children in need of training focused on emotion processing.

Taste the emotions: pilot for a novel, sensors-based approach to emotional analysis during coffee tasting.

BACKGROUND: Coffee is a natural drink with important properties for the human body and mind, capable of delivering energy and strong emotions, thus being appreciated since ancient times. The qualitative and quantitative assessment of the coffee properties is normally performed by trained panelists, though relying on standardized questionnaires, with possible biases arising. In this study, for the first time in the scientific literature, we applied a technology-based approach, based on the use of wearable sensors, to study the implicit emotional responses of a small cohort of experienced coffee judges, thus taking this chance to assess the feasibility of this approach in such a scenario. The merging of different technologies for capturing biomedical signals, including electrocardiogram, galvanic skin response, and electroencephalogram, was therefore adopted to retrieve results in terms of the relationships between implicit (i.e. psychophysiological) and explicit (i.e. derived from questionnaires) measurements. RESULTS: Significant correlations were obtained between biomedical signals and data from the questionnaires within all the sensory domains (olfaction, vision, taste) investigated, particularly concerning autonomic-related features. CONCLUSIONS: The results obtained confirmed the viability of this new approach in the psychophysical and emotional assessment in coffee tasting judges, paving the way for a new perspective into the universe of coffee quality assessment panels, eventually transferable to broader scale investigations, somewhat dealing with consumer satisfaction and neuromarketing at large. © 2023 Society of Chemical Industry.

Wearable Sensors to Evaluate Autonomic Response to Olfactory Stimulation: The Influence of Short, Intensive Sensory Training.

In the last few decades, while the sensory evaluation of edible products has been leveraged to make strategic decisions about many domains, the traditional descriptive analysis performed by a skilled sensory panel has been seen to be too complex and time-consuming for the industry needs, making it largely unsustainable in most cases. In this context, the study of the effectiveness of different methods for sensory training on panel performances represents a new trend in research activity. With this purpose, wearable sensors are applied to study physiological signals (ECG and skin conductance) concerned with the emotions in a cohort of volunteers undergoing a short, two-day (16 h) sensory training period related to wine tasting. The results were compared with a previous study based on a conventional three-month (65 h) period of sensory training. According to what was previously reported for long panel training, it was seen that even short, intensive sensory training modulated the ANS activity toward a less sympathetically mediated response as soon as odorous compounds become familiar. A large-scale application of shorter formative courses in this domain appears possible without reducing the effectiveness of the training, thus leading to money saving for academia and scientific societies, and challenging dropout rates that might affect longer courses.

A randomized controlled trial into the effects of probiotics on electroencephalography in preschoolers with autism.

LAY ABSTRACT: This study investigates the effects of a probiotic on preschoolers' brain electrical activity with autism spectrum disorder. Autism is a disorder with an increasing prevalence characterized by an enormous individual, family, and social cost. Although the etiology of autism spectrum disorder is unknown, an interaction between genetic and environmental factors is implicated, converging in altered brain synaptogenesis and, therefore, connectivity. Besides deepening the knowledge on the resting brain electrical activity that characterizes this disorder, this study allows analyzing the positive central effects of a 6-month therapy with a probiotic through a randomized, double-blind placebo-controlled study and the correlations between electroencephalography activity and biochemical and clinical parameters. In subjects treated with probiotics, we observed a decrease of power in frontopolar regions in beta and gamma bands, and increased coherence in the same bands together with a shift in frontal asymmetry, which suggests a modification toward a typical brain activity. Electroencephalography measures were significantly correlated with clinical and biochemical measures. These findings support the importance of further investigations on probiotics' benefits in autism spectrum disorder to better elucidate mechanistic links between probiotics supplementation and changes in brain activity.

Horticultural Therapy May Reduce Psychological and Physiological Stress in Adolescents with Anorexia Nervosa: A Pilot Study.

Studies in psychiatric populations have found a positive effect of Horticultural therapy (HCT) on reductions in stress levels. The main objective of the present pilot study was to evaluate the impact of the addition of HCT to conventional clinical treatment (Treatment as Usual, TaU) in a sample of six female adolescents with anorexia nervosa restricting type (AN-R), as compared to six AN-R patients, matched for sex and age, under TaU only. This is a prospective, non-profit, pilot study on patients with a previous diagnosis of AN-R and BMI < 16, recruited in 2020 in clinical settings. At enrolment (T0) and after treatment completion (TF), psychiatric assessment was performed. At T0, all the patients underwent: baseline electrocardiogram acquisition with a wearable chest strap for recording heart rate and its variability; skin conductance registration and thermal mapping of the individual's face. An olfactory identification test was administered both to evaluate the olfactory sensoriality and to assess the induced stress. One-way analyses of variance (ANOVAs) were performed to analyze modifications in clinical and physiological variables, considering time (T0, TF) as a within-subjects factor and group (experimental vs. control) as between-subjects factors. When the ANOVA was significant, post hoc analysis was performed by Paired Sample T-tests. Only in the HCT group, stress response levels, as measured by the biological parameters, improved over time. The body uneasiness level and the affective problem measures displayed a significant improvement in the HCT subjects. HCT seems to have a positive influence on stress levels in AN-R.

High-Risk Siblings without Autism: Insights from a Clinical and Eye-Tracking Study.

Joint attention (JA)-the human ability to coordinate our attention with that of other people-is impaired in the early stage of Autism Spectrum Disorder (ASD). However, little is known about the JA skills in the younger siblings of children with ASD who do not develop ASD at 36 months of age [high-risk (HR)-noASD]. In order to advance our understanding of this topic, a prospective multicenter observational study was conducted with three groups of toddlers (age range: 18-33 months): 17 with ASD, 19 with HR-noASD and 16 with typical development (TD). All subjects underwent a comprehensive clinical assessment and an eye-tracking experiment with pre-recorded stimuli in which the visual patterns during two tasks eliciting initiating joint attention (IJA) were measured. Specifically, fixations, transitions and alternating gaze were analyzed. Clinical evaluation revealed that HR-noASD subjects had lower non-verbal cognitive skills than TD children, while similar levels of restricted and repetitive behaviors and better social communication skills were detected in comparison with ASD children. Eye-tracking paradigms indicated that HR-noASD toddlers had visual patterns resembling TD in terms of target-object-to-face gaze alternations, while their looking behaviors were similar to ASD toddlers regarding not-target-object-to-face gaze alternations. This study indicated that high-risk, unaffected siblings displayed a shared profile of IJA-eye-tracking measures with both ASD patients and TD controls, providing new insights into the characterization of social attention in this group of toddlers.

Music Modulates Autonomic Nervous System Activity in Human Fetuses.

Context: Fetal Autonomic Nervous sysTem Evaluation (FANTE) is a non-invasive tool that evaluates the autonomic nervous system activity in a fetus. Autonomic nervous system maturation and development during prenatal life are pivotal for the survival and neuropsychiatric development of the baby. Objective: Aim of the study is to evaluate the effect of music stimulation on fetal heart rate and specific parameters linked to ANS activity, in particular fetal heart rate variability. Methods: Thirty-two women between the 32nd and 38th week with a singleton uncomplicated pregnancy were recruited. All FANTE data collections were acquired using a 10-derivation electrocardiograph placed on the maternal abdomen. In each session (5 min basal, 10 min with music stimulus, and 5 min post-stimulus), FANTE was registered. The music stimulus was "Clair de lune" Debussy, played through headphones on the mother's abdomen (CTR: 31927). Results: Music does not change the mean value of fetal heart rate. However, indices of total fetal heart rate variability statistically increase (RRsd p = 0.037, ANNsd p = 0.039, SD2 p = 0.019) during music stimulation in comparison to the basal phase. Heart rate variability increase depends mainly on the activation of parasympathetic branches (CVI p = 0.013), meanwhile, no significant changes from basal to stimulation phase were observed for indices of sympathetic activity. All the parameters of heart rate variability and parasympathetic activity remained activated in the post-stimulus phase compared to the stimulus phase. In the post-stimulus phase, sympathetic activity resulted in a significant reduction (LFn p = 0.037). Conclusion: Music can influence the basal activity of the fetal autonomic nervous system, enhancing heart rate variability, without changing fetal heart rate mean value. Music is enabled to induce a relaxation state in a near-to-term fetus, mediated by parasympathetic activation and by a parallel sympathetic inhibition.

Parenting practices moderate the link between attention to the eyes and callous unemotional traits in children with Disruptive Behavior Disorder: An eye-tracking study.

Callous-unemotional (CU) traits are associated with gaze pattern deficits in youths, though it has not yet been explored if environmental factors could influence this relationship. Since parenting can influence both CU traits and children's emotion processing, the current study sought to test whether parenting moderated the relation between gaze pattern deficits and CU traits in a sample of children with Disruptive Behavior Disorder. The sample included 92 boys (aged 7-12 years) with Conduct Disorder (N = 12) and Oppositional Defiant Disorder (N = 80). All children completed a task, during which they were presented with 24 images depicting happy, sad, fearful, disgusted, angry, and neutral facial expressions. Gaze pattern has been recorded throughout the task with an eye-tracker. Positive parenting moderated the association between CU traits and first fixation duration to the eyes of facial expressions depicting negative emotions. Negative parenting moderated the association between CU traits and fixation count and fixation duration to the eyes of negative emotions. Negative parenting along with reduced attention to emotional cues (i.e., eyes) may identify a group of youths with Disruptive Behavior Disorder diagnosis at risk for severe outcomes.

A Machine Learning Application to Predict Early Lung Involvement in Scleroderma: A Feasibility Evaluation.

INTRODUCTION: Systemic sclerosis (SSc) is a systemic immune-mediated disease, featuring fibrosis of the skin and organs, and has the greatest mortality among rheumatic diseases. The nervous system involvement has recently been demonstrated, although actual lung involvement is considered the leading cause of death in SSc and, therefore, should be diagnosed early. Pulmonary function tests are not sensitive enough to be used for screening purposes, thus they should be flanked by other clinical examinations; however, this would lead to a risk of overtesting, with considerable costs for the health system and an unnecessary burden for the patients. To this extent, Machine Learning (ML) algorithms could represent a useful add-on to the current clinical practice for diagnostic purposes and could help retrieve the most useful exams to be carried out for diagnostic purposes. METHOD: Here, we retrospectively collected high resolution computed tomography, pulmonary function tests, esophageal pH impedance tests, esophageal manometry and reflux disease questionnaires of 38 patients with SSc, applying, with R, different supervised ML algorithms, including lasso, ridge, elastic net, classification and regression trees (CART) and random forest to estimate the most important predictors for pulmonary involvement from such data. RESULTS: In terms of performance, the random forest algorithm outperformed the other classifiers, with an estimated root-mean-square error (RMSE) of 0.810. However, this algorithm was seen to be computationally intensive, leaving room for the usefulness of other classifiers when a shorter response time is needed. CONCLUSIONS: Despite the notably small sample size, that could have prevented obtaining fully reliable data, the powerful tools available for ML can be useful for predicting early lung involvement in SSc patients. The use of predictors coming from spirometry and pH impedentiometry together might perform optimally for predicting early lung involvement in SSc.

Heartbeat-Evoked Cortical Potential during Sleep and Interoceptive Sensitivity: A Matter of Hypnotizability.

Individuals with different hypnotizability display different interoceptive sensitivity/awareness (IS) and accuracy (IA), likely sustained by morphofunctional differences in interoception-related brain regions and, thus, possibly also observable during sleep. We investigated the heartbeat-evoked cortical potential amplitude (HEP) during sleep, its association with IS, and the role of hypnotizability in such association. We performed a retrospective analysis of polysomnographic recordings of 39 healthy volunteers. Participants completed the Multidimensional Assessment of Interoceptive Awareness (MAIA), measuring IS and IA, and underwent hypnotic assessment via the Stanford Hypnotic Susceptibility Scale, form A. The amplitude of the early and late HEP components was computed at EEG frontal and central sites. In both regions, the early HEP component was larger in N3 than in N2 and REM, with no difference between N2 and REM. Greater HEP amplitude at frontal than at central sites was found for the late HEP component. HEP amplitudes were not influenced by the autonomic state assessed by heart rate variability in the frequency and time domains. We report for the first time a positive correlation between the central late HEP component and MAIA dimensions, which became non-significant after removing the effects of hypnotizability. Our findings indicate that hypnotizability sustains the correlation between IS and HEP amplitude during sleep.

Wearable Sensors for Assessing the Role of Olfactory Training on the Autonomic Response to Olfactory Stimulation.

Wearable sensors are nowadays largely employed to assess physiological signals derived from the human body without representing a burden in terms of obtrusiveness. One of the most intriguing fields of application for such systems include the assessment of physiological responses to sensory stimuli. In this specific regard, it is not yet known which are the main psychophysiological drivers of olfactory-related pleasantness, as the current literature has demonstrated the relationship between odor familiarity and odor valence, but has not clarified the consequentiality between the two domains. Here, we enrolled a group of university students to whom olfactory training lasting 3 months was administered. Thanks to the analysis of electrocardiogram (ECG) and galvanic skin response (GSR) signals at the beginning and at the end of the training period, we observed different autonomic responses, with higher parasympathetically-mediated response at the end of the period with respect to the first evaluation. This possibly suggests that an increased familiarity to the proposed stimuli would lead to a higher tendency towards relaxation. Such results could suggest potential applications to other domains, including personalized treatments based on odors and foods in neuropsychiatric and eating disorders.

Healthy aging: the INTECMAN project.

Aging is associated not only with the reduction of psychophysical and sensory capacities but also with different types of neurodegenerative disorders up to dementia manifestations. Aging in health and self-sufficiency is strictly dependent on the prevention and correction of factors that may determine reduction of psychophysical capacities (e.g., cardiovascular, locomotor and neurodegenerative ones). To reach this goal, due to the dynamics of social and family changes and to the aging of the population, health professionals can be supported by technologies which provide noninvasive monitoring of physiologic parameters and rely on telemedicine, both instruments of support and care for better aging in the home setting. The authors, starting from the initial idea of a personalized monitoring of different psychophysical variables, defined a pilot study to assess the role of a 12-month individually tailored lifestyle counseling on parameters of mild cognitive impairment in a group of elderly subjects. Data derived from the applied approach appeared promising and may open the road to the possible implementation of individual counseling, based on multiparametric non-obtrusive technologies which take into consideration both psychological and physical aspects, to be followed in the home environment.

Effects of Probiotic Supplementation on Gastrointestinal, Sensory and Core Symptoms in Autism Spectrum Disorders: A Randomized Controlled Trial.

The microbiota-gut-brain axis has been recently recognized as a key modulator of neuropsychiatric health. In this framework, probiotics (recently named "psychobiotics") may modulate brain activity and function, possibly improving the behavioral profiles of children with Autism Spectrum Disorder (ASD). We evaluated the effects of probiotics on autism in a double-blind randomized, placebo-controlled trial of 85 preschoolers with ASD (mean age, 4.2 years; 84% boys). Participants were randomly assigned to probiotics (De Simone Formulation) (n=42) or placebo (n=43) for six months. Sixty-three (74%) children completed the trial. No differences between groups were detected on the primary outcome measure, the Total Autism Diagnostic Observation Schedule - Calibrated Severity Score (ADOS-CSS). An exploratory secondary analysis on subgroups of children with or without Gastrointestinal Symptoms (GI group, n= 30; NGI group, n=55) revealed in the NGI group treated with probiotics a significant decline in ADOS scores as compared to that in the placebo group, with a mean reduction of 0.81 in Total ADOS CSS and of 1.14 in Social-Affect ADOS CSS over six months. In the GI group treated with probiotics we found greater improvements in some GI symptoms, adaptive functioning, and sensory profiles than in the GI group treated with placebo. These results suggest potentially positive effects of probiotics on core autism symptoms in a subset of ASD children independent of the specific intermediation of the probiotic effect on GI symptoms. Further studies are warranted to replicate and extend these promising findings on a wider population with subsets of ASD patients which share targets of intervention on the microbiota-gut-brain axis. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT02708901.

Electronic Nose as a Novel Method for Diagnosing Cancer: A Systematic Review.

Cancer is fast becoming the most important cause of death worldwide, its mortality being mostly caused by late or wrong diagnosis. Novel strategies have been developed to identify early signs of cancer in a minimally obtrusive way, including the Electronic Nose (E-Nose) technology, user-friendly, cost- and time-saving alternative to classical approaches. This systematic review, conducted under the PRISMA guidelines, identified 60 articles directly dealing with the E-Nose application in cancer research published up to 31 January 2020. Among these works, the vast majority reported successful E-Nose use for diagnosing Lung Cancer, showing promising results especially when employing the Aeonose tool, discriminating subjects with Lung Cancer from controls in more than 80% of individuals, in most studies. In order to tailor the main limitations of the proposed approach, including the application of the protocol to advanced stage of cancer, sample heterogeneity and massive confounders, future studies should be conducted on early stage patients, and on larger cohorts, as to better characterize the specific breathprint associated with the various subtypes of cancer. This would ultimately lead to a better and faster diagnosis and to earlier treatment, possibly reducing the burden associated to such conditions.

Rich at risk: socio-economic drivers of COVID-19 pandemic spread.

COVID-19, the novel coronavirus affecting the most part of worldwide countries since early 2020, is fast increasing its prevalence around the world, representing a significant emergency for the population and the health systems at large. While proper treatments are being developed, in-depth studies concerning its way of diffusion are necessary, in order to understand how the virus is actually spreading, through the investigation on some socio-economic indicators for the various countries in the world, retrieved through open-access data publicly available. The correlation analysis displayed significant relationships between COVID-19 incidence with several of such indicators, including the Gross Domestic Product per capita and the number of flights per capita, whereas mortality is mainly related to the main age of the population. All such data displayed an interesting mean to understand the way the virus has diffused worldwide, possibly representing the basis for future preventive measures to effectively challenge a new COVID-19 pandemic wave, but also other, similar pandemics.

"Mom Let's Go to the Dentist!" Preliminary Feasibility of a Tailored Dental Intervention for Children with Autism Spectrum Disorder in the Italian Public Health Service.

Children with autism spectrum disorder (ASD) show worse oral health than their peers. Their access to health services is, at present, inadequate: few high-quality interventions have been designed and implemented to improve their care procedures so far. The purpose of this study is to describe an experience of dental care supported by Information and Communication Technologies (ICT), for children with ASD in a public health service. In our study, 59 children (mean age 9.9 years; SD = 5.43) participated in the MyDentist project. It integrates classic dental care techniques with new practices for desensitization and fear control, delivered through an enhanced customized ICT-based intervention aiming at familiarizing the child with ASD with the medical setting and procedures. Two questionnaires were filled out by parents to describe the acceptability of the MyDentist experience for their children. Significant results were shown from T0 (before initiating MyDentist) to T1 (after 6 months of the MyDentist experience) regarding improved oral hygiene and cooperation during dental treatments. Families positively assessed the use of ICT support. In conclusion, the project demonstrated acceptability by parents, suggesting that public health dental care and prevention can be successfully implemented without resorting to costly pharmacological interventions (with potential side effects), taking better care of children's health.

Behavioral and Autonomic Responses in Treating Children with High-Functioning Autism Spectrum Disorder: Clinical and Phenomenological Insights from Two Case Reports.

In this study, we aimed to evaluate the process applied in subjects with Autism Spectrum Disorder (ASD) to elaborate and communicate their experiences of daily life activities, as well as to assess the autonomic nervous system response that subtend such a process. This procedure was evaluated for the first time in two eight-year-old girls with high-functioning ASDs. The subjects performed six months of training, based on the cognitive-motivational-individualized (c.m.i.®) approach, which mainly consisted in building domestic procedures and re-elaborating acquired experiences through drawing or the use of icons made by the children. Together with behavioral observations, the response of the autonomic nervous system during such re-elaboration was recorded. A change in communicative and interactive competences was observed, moving from a condition of spontaneity to one in which the girls were engaged in relating their experiences to a parent. Autonomic response highlighted how, in communicating their own experiences, they achieved a state of cognitive activation, which enabled a greater communicative and emotional connection with the interlocutor. This is a proof-of-concept study on the application of the c.m.i.®, which needs to be extensively validated in the clinical setting.

EYES Are The Window to the Mind: Eye-Tracking Technology as a Novel Approach to Study Clinical Characteristics of ADHD.

In recent years, the study of eye movements has increasingly become a window into neurological function and processes. This paper reports data about applications of eye-tracking technology in the field of neurodevelopmental disorders, especially in studying the clinical characteristics of ADHD. These studies indicated that eye-tracking approach represents a non-invasive methodology to test specific domains, such as attention networks and inhibition control, in an objectively and reliable way in youths. Although the studies results are still not conclusive, eye-tracking represents a potential valid support for clinicians in identifying specific biomarkers to orient ADHD diagnosis and the best intervention strategies.

A feasibility study on non-invasive fetal ECG to evaluate prenatal autonomic nervous system activity.

BACKGROUND: Maturity of the autonomic nervous system (ANS) is of paramount importance for fetal adaptation to extrauterine life and for early neurological development. Markers of ANS maturity, such as electrophysiological heart rate parameters, are of interest as tools to determine prenatal fetal maturity. The available technology, fetal magnetocardiography is expensive and not suitable for clinical use. Detection of fetal electrocardiographic signals using traditional ECG leads on the maternal abdomen may be brought to the bedside, but is technically challenging. Our group has recently developed an innovative system consisting of a standard ECG with external leads applied on the maternal abdomen coupled with a software that extracts the fetal heart signal from the maternal noise. OBJECTIVE: To validate the use of this innovative non-invasive system to detect fetal ECG (fECG) and its ability to detect changes in electrophysiological fetal cardiac parameters associated with ANS maturation. STUDY DESIGN: we recruited 50 pregnant women between 24 and 41 weeks and they received non-invasive recording of fECG. RESULTS: fECG was measurable at all gestational ages. Fetal heart rate variability (RR interval) and other associated parameters, such as low and high frequency increased with gestational age, particularly up to the 31st week. CONCLUSIONS: This study shows that non-invasive fECG is feasible throughout a broad range of gestational ages and allows detecting electrophysiological parameters of the fetal heart that may be used a surrogate of ANS maturity. Technological implementation of this system and its further exploitation may generate new tool to estimate fetal maturity.