An internally validated prediction model for critical COVID-19 infection and intensive care unit admission in symptomatic pregnant women.

BACKGROUND: Pregnant women are at an increased risk of mortality and morbidity owing to COVID-19. Many studies have reported on the association of COVID-19 with pregnancy-specific adverse outcomes, but prediction models utilizing large cohorts of pregnant women are still lacking for estimating the risk of maternal morbidity and other adverse events. OBJECTIVE: The main aim of this study was to develop a prediction model to quantify the risk of progression to critical COVID-19 and intensive care unit admission in pregnant women with symptomatic infection. STUDY DESIGN: This was a multicenter retrospective cohort study including 8 hospitals from 4 countries (the United Kingdom, Austria, Greece, and Turkey). The data extraction was from February 2020 until May 2021. Included were consecutive pregnant and early postpartum women (within 10 days of birth); reverse transcriptase polymerase chain reaction confirmed SARS-CoV-2 infection. The primary outcome was progression to critical illness requiring intensive care. The secondary outcomes included maternal death, preeclampsia, and stillbirth. The association between the primary outcome and 12 candidate predictors having a known association with severe COVID-19 in pregnancy was analyzed with log-binomial mixed-effects regression and reported as adjusted risk ratios. All the potential predictors were evaluated in 1 model and only the baseline factors in another. The predictive accuracy was assessed by the area under the receiver operating characteristic curves. RESULTS: Of the 793 pregnant women who were positive for SARS-CoV-2 and were symptomatic, 44 (5.5%) were admitted to intensive care, of whom 10 died (1.3%). The 'mini-COvid Maternal Intensive Therapy' model included the following demographic and clinical variables available at disease onset: maternal age (adjusted risk ratio, 1.45; 95% confidence interval, 1.07-1.95; P=.015); body mass index (adjusted risk ratio, 1.34; 95% confidence interval, 1.06-1.66; P=.010); and diagnosis in the third trimester of pregnancy (adjusted risk ratio, 3.64; 95% confidence interval, 1.78-8.46; P=.001). The optimism-adjusted area under the receiver operating characteristic curve was 0.73. The 'full-COvid Maternal Intensive Therapy' model included body mass index (adjusted risk ratio, 1.39; 95% confidence interval, 1.07-1.95; P=.015), lower respiratory symptoms (adjusted risk ratio, 5.11; 95% confidence interval, 1.81-21.4; P=.007), neutrophil to lymphocyte ratio (adjusted risk ratio, 1.62; 95% confidence interval, 1.36-1.89; P<.001); and serum C-reactive protein (adjusted risk ratio, 1.30; 95% confidence interval, 1.15-1.44; P<.001), with an optimism-adjusted area under the receiver operating characteristic curve of 0.85. Neither model showed signs of a poor fit. Categorization as high-risk by either model was associated with a shorter diagnosis to intensive care unit admission interval (log-rank test P<.001, both), higher maternal death (5.2% vs 0.2%; P<.001), and preeclampsia (5.7% vs 1.0%; P<.001). A spreadsheet calculator is available for risk estimation. CONCLUSION: At presentation with symptomatic COVID-19, pregnant and recently postpartum women can be stratified into high- and low-risk for progression to critical disease, even where resources are limited. This can support the nature and place of care. These models also highlight the independent risk for severe disease associated with obesity and should further emphasize that even in the absence of other comorbidities, vaccination is particularly important for these women. Finally, the model also provides useful information for policy makers when prioritizing national vaccination programs to quickly protect those at the highest risk of critical and fatal COVID-19.

The Gestational Effects of Maternal Appetite Axis Molecules on Fetal Growth, Metabolism and Long-Term Metabolic Health: A Systematic Review.

Increased maternal food intake is considered a normal pregnancy adjustment. However, the overavailability of nutrients may lead to dysregulated fetal development and increased adiposity, with long-lasting effects on offspring in later life. Several gut-hormone molecules regulate maternal appetite, with both their orexigenic and anorectic effects being in a state of sensitive equilibrium. The aim of this manuscript is to systematically review literature on the effects of maternal gut-hormone molecules on fetal growth and metabolism, birth weight and the later metabolic health of offspring. Maternal serum ghrelin, leptin, IGF-1 and GLP-1 appear to influence fetal growth; however, a lack of consistent and strong correlations of maternal appetite axis hormones with birth weight and the concomitant correlation with fetal and birth waist circumference may suggest that these molecules primarily mediate fetal energy deposition mechanisms, preparing the fetus for survival after birth. Dysregulated intrauterine environments seem to have detrimental, sex-dependent effects on fetal energy stores, affecting not only fetal growth, fat mass deposition and birth weight, but also future metabolic and endocrine wellbeing of offspring.

Cytogenetic complexity in chronic lymphocytic leukemia: definitions, associations, and clinical impact.

Recent evidence suggests that complex karyotype (CK) defined by the presence of ≥3 chromosomal aberrations (structural and/or numerical) identified by using chromosome-banding analysis (CBA) may be relevant for treatment decision-making in chronic lymphocytic leukemia (CLL). However, many challenges toward the routine clinical application of CBA remain. In a retrospective study of 5290 patients with available CBA data, we explored both clinicobiological associations and the clinical impact of CK in CLL. We found that patients with ≥5 abnormalities, defined as high-CK, exhibit uniformly dismal clinical outcomes, independently of clinical stage, TP53 aberrations (deletion of chromosome 17p and/or TP53 mutations [TP53abs]), and the expression of somatically hypermutated (M-CLL) or unmutated immunoglobulin heavy variable genes. Thus, they contrasted with CK cases with 3 or 4 aberrations (low-CK and intermediate-CK, respectively) who followed aggressive disease courses only in the presence of TP53abs. At the other end of the spectrum, patients with CK and +12,+19 displayed an exceptionally indolent profile. Building upon CK, TP53abs, and immunoglobulin heavy variable gene somatic hypermutation status, we propose a novel hierarchical model in which patients with high-CK exhibit the worst prognosis, whereas those with mutated CLL lacking CK or TP53abs, as well as CK with +12,+19, show the longest overall survival. Thus, CK should not be axiomatically considered unfavorable in CLL, representing a heterogeneous group with variable clinical behavior. High-CK with ≥5 chromosomal aberrations emerges as prognostically adverse, independent of other biomarkers. Prospective clinical validation is warranted before ultimately incorporating high-CK in risk stratification of CLL.

Aspirin versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia.

BACKGROUND: Preterm preeclampsia is an important cause of maternal and perinatal death and complications. It is uncertain whether the intake of low-dose aspirin during pregnancy reduces the risk of preterm preeclampsia. METHODS: In this multicenter, double-blind, placebo-controlled trial, we randomly assigned 1776 women with singleton pregnancies who were at high risk for preterm preeclampsia to receive aspirin, at a dose of 150 mg per day, or placebo from 11 to 14 weeks of gestation until 36 weeks of gestation. The primary outcome was delivery with preeclampsia before 37 weeks of gestation. The analysis was performed according to the intention-to-treat principle. RESULTS: A total of 152 women withdrew consent during the trial, and 4 were lost to follow up, which left 798 participants in the aspirin group and 822 in the placebo group. Preterm preeclampsia occurred in 13 participants (1.6%) in the aspirin group, as compared with 35 (4.3%) in the placebo group (odds ratio in the aspirin group, 0.38; 95% confidence interval, 0.20 to 0.74; P=0.004). Results were materially unchanged in a sensitivity analysis that took into account participants who had withdrawn or were lost to follow-up. Adherence was good, with a reported intake of 85% or more of the required number of tablets in 79.9% of the participants. There were no significant between-group differences in the incidence of neonatal adverse outcomes or other adverse events. CONCLUSIONS: Treatment with low-dose aspirin in women at high risk for preterm preeclampsia resulted in a lower incidence of this diagnosis than placebo. (Funded by the European Union Seventh Framework Program and the Fetal Medicine Foundation; EudraCT number, 2013-003778-29 ; Current Controlled Trials number, ISRCTN13633058 .).

Aspirin for Evidence-Based Preeclampsia Prevention trial: effect of aspirin on length of stay in the neonatal intensive care unit.

BACKGROUND: Preeclampsia is a major pregnancy complication with adverse short- and long-term implications for both the mother and baby. Screening for preeclampsia at 11-13 weeks' gestation by a combination of maternal demographic characteristics and medical history with measurements of biomarkers can identify about 75% of women who develop preterm preeclampsia with delivery at <37 weeks' gestation and 90% of those with early preeclampsia at <32 weeks, at a screen-positive rate of 10%. A recent trial (Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence-Based Preeclampsia Prevention) has reported that in women identified by first-trimester screening as being at high risk for preeclampsia, use of aspirin (150 mg/d from the first to the third trimester), compared to placebo, reduced the incidence of preterm preeclampsia, which was the primary outcome, by 62% (95% confidence interval, 26-80%) and the incidence of early preeclampsia by 89% (95% confidence interval, 53-97%). The surprising finding of the trial was that despite the reduction in preeclampsia the incidence of admission to the neonatal intensive care unit, which was one of the secondary outcomes, was not significantly affected (odds ratio, 0.93; 95% confidence interval, 0.62-1.40). OBJECTIVE: We sought to examine the effect of prophylactic use of aspirin during pregnancy in women at high risk of preeclampsia on length of stay in the neonatal intensive care unit. STUDY DESIGN: This was a secondary analysis of data from the Aspirin for Evidence-Based Preeclampsia Prevention trial to assess evidence of differences in the effect of aspirin on length of stay in neonatal intensive care. Bootstrapping was used for the comparison of mean length of stay between the aspirin and placebo groups. Logistic regression was used to assess treatment effects on stay in the neonatal intensive care unit. RESULTS: In the trial there were 1620 participants and 1571 neonates were liveborn. The total length of stay in neonatal intensive care was substantially longer in the placebo than aspirin group (1696 vs 531 days). This is a reflection of significantly shorter mean lengths of stay in babies admitted to the neonatal intensive care unit from the aspirin than the placebo group (11.1 vs 31.4 days), a reduction of 20.3 days (95% confidence interval, 7.0-38.6; P = .008). Neonatal intensive care of babies born at <32 weeks' gestation contributed 1856 (83.3%) of the total of 2227 days in intensive care across both treatment arms. These occurred in 9 (1.2%) of the 777 livebirths in the aspirin group and in 23 (2.9%) of 794 in the placebo group (odds ratio, 0.42; 95% confidence interval, 0.19-0.93; P = .033). Overall, in the whole population, including 0 lengths of stay for those not admitted to the neonatal intensive care unit, the mean length of stay was longer in the placebo than aspirin group (2.06 vs 0.66 days; reduction of 1.4 days; 95% confidence interval, 0.45-2.81; P = .014). This corresponds to a reduction in length of stay of 68% (95% confidence interval, 20-86%). CONCLUSION: In pregnancies at high risk of preeclampsia administration of aspirin reduces the length of stay in the neonatal intensive care unit by about 70%. This reduction could essentially be attributed to a decrease in the rate of births at <32 weeks' gestation, mainly because of prevention of early preeclampsia. The findings have implications for both short- and long-term health care costs as well as infant survival and handicap.

Using Electroencephalogram-Extracted Nonlinear Complexity and Wavelet-Extracted Power Rhythm Features during the Performance of Demanding Cognitive Tasks (Aristotle's Syllogisms) in Optimally Classifying Patients with Anorexia Nervosa.

Anorexia nervosa is associated with impaired cognitive flexibility and central coherence, i.e., the ability to provide an overview of complex information. Therefore, the aim of the present study was to evaluate EEG features elicited from patients with anorexia nervosa and healthy controls during mental tasks (valid and invalid Aristotelian syllogisms and paradoxes). Particularly, we examined the combination of the most significant syllogisms with selected features (relative power of the time-frequency domain and wavelet-estimated EEG-specific waves, Higuchi fractal dimension (HFD), and information-oriented approximate entropy (AppEn)). We found that alpha, beta, gamma, theta waves, and AppEn are the most suitable measures, which, when combined with specific syllogisms, form a powerful tool for efficiently classifying healthy subjects and patients with AN. We assessed the performance of triadic combinations of "feature-classifier-syllogism" via machine learning techniques in correctly classifying new subjects in these two groups. The following triads attain the best classifications: (a) "AppEn-invalid-ensemble BT classifier" (accuracy 83.3%), (b) "Higuchi FD-valid-linear discriminant" (accuracy 75%), (c) "alpha amplitude-valid-SVM" (accuracy 83.3%), (d) "alpha RP-paradox-ensemble BT" (accuracy 85%), (e) "beta RP-valid-ensemble" (accuracy 85%), (f) "gamma RP-valid-SVM" (accuracy 85%), and (g) "theta RP-valid-KNN" (accuracy 80%). Our findings suggest that anorexia nervosa has a specific information-processing style across reasoning tasks in the brain as measured via EEG activity. Our findings also contribute to further supporting the view that entropy-oriented, i.e., information-based features (the AppEn measure used in this study) are promising diagnostic tools (biomarkers) in clinical applications related to medical classification problems. Furthermore, the main EEG-specific frequency waves are extremely enhanced and become powerful classification tools when combined with Aristotle's syllogisms.

Cardiac surgery for ergotamine-induced multivalvular heart disease.

Ergotamine is used to abort or prevent vascular headache. Valvular heart disease as an adverse effect of long-term ergotamine therapy has been rarely reported in the English literature, with only a few cases published. It is hypothesized that ergot-derived agents stimulate serotonergic receptors (5-HT2B), causing proliferation of myofibroblasts, with subsequent thickening of valve leaflets and chords. This case presentation aims at increasing clinicians' awareness of this potential complication.

Assessing temporal variability of lake turbidity and trophic state of European lakes using open data repositories.

Water turbidity is one of the more important water quality parameters that is strictly linked with the productivity of the lake and is commonly used as an indicator of the trophic state. However, limited field data availability across wide geographic gradients may hinder the conduction of large scale longitudinal studies. In this study, time series of lake turbidity and trophic state index (TSI) between 2002 and 2012 were obtained from the Copernicus Lake Water products to create a large longitudinal dataset of lake variables for 22 European lakes. The dataset was combined with estimates of nutrient concentrations and surface water temperature obtained from the Hydrological Predictions for the Environment (HYPE) and ERA5-Land data repositories, that were used as environmental predictors. Hence, the validity of the lake water quality parameters was tested by a) exploring their spatial and temporal variability and b) identifying associations with the environmental predictors. For this purpose, seasonal Mann-Kendall tests were applied to find significant inter-annual trends of turbidity and TSI for each lake, and generalized additive models (GAMs) were employed to identify the main parameters that shape their temporal dynamics. Although we did not find significant inter-annual changes, our findings highlighted the strong influence of seasonality and surface water temperature in defining the temporal variability patterns in most of the lakes. In addition, the importance of nutrients varied among lakes as several lakes exhibited narrow nutrient gradients reflecting relatively stable nutrient conditions during the examined period. Other lake intrinsic factors, such as local climate and biotic interactions, are important drivers of shaping turbidity and nutrient dynamics. This study highlighted the usefulness of combining lake data from large repositories in conducting large scale spatial studies as a valuable asset for future lake research and management purposes.

Fertility status in childhood cancer survivors of hematological malignancies: a systematic review.

Stunning advances in treatment modalities implemented in children with hematological malignancies have led to 5-year overall survival rates exceeding 85%. However, this growing population of long-term survivors has raised significant concerns about their fertility status throughout adulthood, while specific treatment- and non-treatment-related factors appear to possibly affect fertility through distinct mechanisms. We aimed to comprehensively review the published literature on the association between treatment-related factors and risk of impaired fertility in childhood hematological cancer survivors. We searched PubMed up to March 2021 to identify eligible studies published during the last two decades. A narrative synthesis of the results was performed, although no meta-analysis was feasible due to the small number of studies and the large heterogeneity of evidence. Five studies on 2020 survivors of childhood leukemia were deemed eligible. The qualitative data synthesis showed significant fertility deficits in survivors treated with cranial radiotherapy and chemotherapy for childhood leukemia. Two studies examined biochemical measures of reduced ovarian reserve, providing some evidence that the levels of anti-Müllerian hormone can be used as a proxy for diminished ovarian reserve. The current findings should facilitate the delivery of age- and gender-appropriate interventions to optimize reproductive outcomes in childhood hematological cancer survivors.

Yolk sac diameter in early pregnancy in maternal diabetes mellitus.

AIMS: To investigate the possible association between maternal diabetes mellitus and increased yolk sac diameter (YSD). METHODS: We searched the Early Pregnancy Unit database to identify singleton pregnancies with measurements of embryonic crown-rump length (CRL) and YSD at 6-10 weeks of gestation and subsequent delivery of phenotypically normal neonates. We compared the YSD in patients with pre-gestational and gestational diabetes with those who were unaffected by diabetes. RESULTS: A total of 3,686 cases were identified including 43 (1.2%) with type 1 diabetes, 31 (0.8%) with type 2 diabetes and 71 (1.9%) who subsequently developed gestational diabetes. The measured YSD in both the diabetic and non-diabetic groups were expressed as differences from the expected normal mean for CRL (Δ values). There were no significant differences in ΔYSD between the groups. The median (IQR) ΔYSD was 0.01 (-0.33 to 0.37) mm in the unaffected group, 0.01 (-0.35 to 0.51) mm in type 1 diabetes, -0.02 (-3.44 to 0.27) mm in type 2 diabetes and 0.01 (-0.28 to 0.35) mm in gestational diabetes. CONCLUSION: After exclusion of miscarriages and embryopathies, pre-gestational and gestational diabetes are not associated with altered YSD.

Trends of lake temperature, mixing depth and ice cover thickness of European lakes during the last four decades.

Lakes are particularly vulnerable ecosystems to global warming. Surface temperature of most lakes in the world has significantly increased. Here, we analysed time-series of water temperature, mixing-depth, and ice depth of 51 European lakes over the last four decades. We used data of surface temperature, total layer water temperature, mix-layer temperature, mix-layer depth, and ice cover depth obtained from the ERA5-Land reanalysis dataset. Our main objectives were a) to identify significant changes of the examined variables that have occurred from 1981 to 2019 and b) to assess the variability of changes in relation with geographical and lake morphological gradients. To this end, time series analysis was conducted using generalized additive models (GAMs). In addition, we quantified the magnitude of change by estimating the Sen's slopes for each variable and then we examined the variability of these slopes to geographical and lake morphological parameters using GAMs. Our results confirmed that water temperature parameters (surface, total-layer and mix-layer temperature) have significantly increased for all lakes during the last four decades. We also found significant changes of the mixing depth for 14 lakes. In addition, the lake ice depth has significantly decreased in all fifteen lakes of the subarctic climate region. Finally, we showed that the Sen's slopes depend on the geographic coordinates and the elevation of the lakes, whereas lake morphometry (e.g. depth) has a smaller effect on the magnitude of changes. These findings hint that lake ecosystems of Europe have substantially changed over the last forty years and urge the need to take precautionary measures to prevent future implications for the freshwater biota.

Ultrasonographic prediction of early miscarriage.

BACKGROUND: The aim of this retrospective study was to assess the value of maternal history and ultrasound scan findings at 6-10 weeks for predicting early miscarriage. METHODS: Embryonic crown-rump length (CRL), heart rate (HR), gestational sac diameter (GSD) and yolk sac diameter (YSD) were compared in two groups of women with singleton pregnancies attending an early pregnancy unit. In the first group the initial scan demonstrated a live embryo but in a subsequent visit the scan showed a dead embryo, complete or incomplete miscarriage. In the second group with a live embryo there was subsequent live birth of a normal neonate. RESULTS: There were 729 pregnancies with miscarriage and 4698 with normal outcome. Logistic regression analysis demonstrated that in the prediction of miscarriage the risk was higher in women of African racial origin [odds ratio (OR) 1.62], cigarette smokers (OR 1.91) and those with vaginal bleeding (OR 2.03) and increased with maternal age (OR 1.05) and YSD (OR 1.88) and was inversely related to CRL (OR 0.79), HR (OR 0.96) and GSD (OR 0.84). At false-positive rate of 30%, the detection rate of miscarriage in screening by vaginal bleeding was 45%, 53% by the addition of maternal history factors and 85.7% by the addition of ultrasound findings. CONCLUSIONS: In early pregnancy a prediction of miscarriage can be provided by a combination of maternal characteristics and ultrasound findings and the estimated risk can be used to rationalize follow-up. Our multivariate model requires prospective evaluation in a new sample population.

Prediction of outcome in dichorionic twin pregnancies at 6-10 weeks' gestation.

OBJECTIVE: The objective of the study was to predict the outcome of dichorionic (DC) twin pregnancies at 6-10 weeks' gestation from intertwin discordance in crown-rump length (CRL), heart rate (HR), and gestational sac diameter (GSD). STUDY DESIGN: Intertwin discordance in CRL, HR, and GSD, was compared in 3 groups of DC twin pregnancies with 2 live embryos at 6-10 weeks. In one group, there were 2 live births (n = 174), in another 1 live birth (n = 24), and in a third group there were no live births (n = 33). Regression analysis was used to determine the predictors of outcome. RESULTS: Significant contributors to the prediction of 1 intrauterine death were discordance in CRL and GSD. The only predictor of 2 deaths was discordance in CRL. Detection rates of screening for single or double death, at 10% false-positive rate, were 79.2% and 27.3%, respectively. CONCLUSION: In DC twins, intertwin discordance in CRL and GSD at 6-10 weeks can predict outcome.

Perinatal outcome of appropriate-weight fetuses with decelerating growth.

INTRODUCTION: To assess the perinatal outcome of fetuses dropping by ≥50 estimated fetal weight (EFW) centiles between the second and third trimester. METHODS: Singleton pregnancies progressing after 32 + 0 weeks, who had their second- and third-trimester scans at our institutions were enrolled in the study. The perinatal outcome of AGA fetuses crossing more than 50 centiles was compared to that of fetuses with FGR, small for gestational age (SGA) and nondecelerating appropriate for gestational age (AGA). The primary perinatal outcomes were perinatal death, neonatal intensive care (NICU) admission and emergency cesarean section (CS). The rates of these outcomes were compared between the four groups and regression analysis was performed to account for maternal and fetal confounders. RESULTS: Our analysis included 4394 cases. Compared to nondecelerating SGA, fetuses crossing ≥50 centiles had higher rates of NICU admission (odds ratio [OR] 1.8, 95% confidence interval [CI] CI 1.1-3.1) and perinatal death (OR 3.8, 95%CI 1.3-11.4). Regression analysis showed that significant independent predictors for NICU admission included maternal age, gestational age at birth and FGR (area under the curve [AUC] 0.851), whereas significant predictors for perinatal death included maternal age, gestational age at birth, decelerating growth ≥50 centiles, conception through ART and third-trimester CPR centile (AUC 0.801). CONCLUSION: AGA fetuses that cross >50 EFW centiles between the second and third trimester are at increased risk of adverse perinatal outcome and it seems advisable that they are followed up as typical FGR cases.

Complexity analysis of the brain activity in Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD) due to cognitive loads/demands induced by Aristotle's type of syllogism/reasoning. A Power Spectral Density and multiscale entropy (MSE) analysis.

OBJECTIVE: We aim to investigate whether EEG dynamics differ in adults with ASD (Autism Spectrum Disorders), ADHD (attention-deficit/hyperactivity disorder), compared with healthy subjects during the performance of an innovative cognitive task: Aristotle's valid and invalid syllogisms. We follow the Neuroanatomical differences type of criterion in assessing the results of our study in supporting or not the dual-process theory of Kahneman, 2011) (Systems I & II of thinking). METHOD: We recorded EEGs from 14 scalp electrodes in 30 adults with ADHD, 30 with ASD and 24 healthy, normal subjects. The subjects were exposed in a set of innovative cognitive tasks (inducing varying cognitive loads), the Aristotle's four types of syllogism mentioned above. The multiscale entropy (MSE), a nonlinear information-theoretic measure or tool was computed to extract features that quantify the complexity of the EEG. RESULTS: The dynamics of the curves of the grand average of MSE values of the ADHD and ASD participants was significantly in higher levels for the majority of time scales, than the healthy subjects over a number of brain regions (electrodes locations), during the performance of both valid and invalid types of syllogism. This result is seemingly not in accordance of the broadly accepted 'theory' of complexity loss in 'pathological' subjects, but actually this is not the case as explained in the text. ADHD subjects are engaged in System II of thinking, for both Valid and Invalid syllogism, ASD and Control in System I for valid and invalid syllogism, respectively. A surprising and 'provocative' result of this paper, as shown in the next sections, is that the Complexity-variability of ASD and ADHD subjects, when they face Aristotle's types of syllogisms, is higher than that of the control subjects. An explanation is suggested as described in the text. Also, in the case of invalid type of Aristotelian syllogisms, the linguistic and visuo-spatial systems are both engaged ONLY in the temporal and occipital regions of the brain, respectively, of ADHD subjects. In the case of valid type, both above systems are engaged in the temporal and occipital regions of the brain, respectively, of both ASD and ADHD subjects, while in the control subjects only the visuo-spatial type is engaged (Goel et al., 2000; Knauff, 2007). CONCLUSION: Based on the results of the analysis described in this work, the differences in the EEG complexity between the three groups of participants lead to the conclusion that cortical information processing is changed in ASD and ADHD adults, therefore their level of cortical activation may be insufficient to meet the peculiar cognitive demand of Aristotle's reasoning. SIGNIFICANCE: The present paper suggest that MSE, is a powerful and efficient nonlinear measure in detecting neural dysfunctions in adults with ASD and ADHD characteristics, when they are called on to perform in a very demanding as well as innovative set of cognitive tasks, that can be considered as a new diagnostic 'benchmark' in helping detecting more effectively such type of disorders. A linear measure alone, as the typical PSD, is not capable in making such a distinction. The work contributes in shedding light on the neural mechanisms of syllogism/reasoning of Aristotelian type, as well as toward understanding how humans reason logically and why 'pathological' subjects deviate from the norms of formal logic.

Differences in Performance of ASD and ADHD Subjects Facing Cognitive Loads in an Innovative Reasoning Experiment.

We aim to investigate whether EEG dynamics differ in adults with ASD (Autism Spectrum Disorders) and ADHD (attention-deficit/hyperactivity disorder) compared with healthy subjects during the performance of an innovative cognitive task, Aristotle's valid and invalid syllogisms, and how these differences correlate with brain regions and behavioral data for each subject. We recorded EEGs from 14 scalp electrodes (channels) in 21 adults with ADHD, 21 with ASD, and 21 healthy, normal subjects. The subjects were exposed in a set of innovative cognitive tasks (inducing varying cognitive loads), Aristotle's two types of syllogism mentioned above. A set of 39 questions were given to participants related to valid-invalid syllogisms as well as a separate set of questionnaires, in order to collect a number of demographic and behavioral data, with the aim of detecting shared information with values of a feature extracted from EEG, the multiscale entropy (MSE), in the 14 channels ('brain regions'). MSE, a nonlinear information-theoretic measure of complexity, was computed to extract a feature that quantifies the complexity of the EEG. Behavior-Partial Least Squares Correlation, PLSC, is the method to detect the correlation between two sets of data, brain, and behavioral measures. -PLSC, a variant of PLSC, was applied to build a functional connectivity of the brain regions involved in the reasoning tasks. Graph-theoretic measures were used to quantify the complexity of the functional networks. Based on the results of the analysis described in this work, a mixed 14 × 2 × 3 ANOVA showed significant main effects of group factor and brain region* syllogism factor, as well as a significant brain region* group interaction. There are significant differences between the means of MSE (complexity) values at the 14 channels of the members of the 'pathological' groups of participants, i.e., between ASD and ADHD, while the difference in means of MSE between both ASD and ADHD and that of the control group is not significant. In conclusion, the valid-invalid type of syllogism generates significantly different complexity values, MSE, between ASD and ADHD. The complexity of activated brain regions of ASD participants increased significantly when switching from a valid to an invalid syllogism, indicating the need for more resources to 'face' the task escalating difficulty in ASD subjects. This increase is not so evident in both ADHD and control. Statistically significant differences were found also in the behavioral response of ASD and ADHD, compared with those of control subjects, based on the principal brain and behavior saliences extracted by PLSC. Specifically, two behavioral measures, the emotional state and the degree of confidence of participants in answering questions in Aristotle's valid-invalid syllogisms, and one demographic variable, age, statistically and significantly discriminate the three groups' ASD. The seed-PLC generated functional connectivity networks for ASD, ADHD, and control, were 'projected' on the regions of the Default Mode Network (DMN), the 'reference' connectivity, of which the structural changes were found significant in distinguishing the three groups. The contribution of this work lies in the examination of the relationship between brain activity and behavioral responses of healthy and 'pathological' participants in the case of cognitive reasoning of the type of Aristotle's valid and invalid syllogisms, using PLSC, a machine learning approach combined with MSE, a nonlinear method of extracting a feature based on EEGs that captures a broad spectrum of EEGs linear and nonlinear characteristics. The results seem promising in adopting this type of reasoning, in the future, after further enhancements and experimental tests, as a supplementary instrument towards examining the differences in brain activity and behavioral responses of ASD and ADHD patients. The application of the combination of these two methods, after further elaboration and testing as new and complementary to the existing ones, may be considered as a tool of analysis in helping detecting more effectively such types of disorders.

Two dimensional polymer-embedded quasi-distributed FBG pressure sensor for biomedical applications.

We report on the development of a flexible 2D optical fiber-based pressure sensing surface suitable for biomedical applications. The sensor comprises of highly-sensitive Fiber Bragg Grating elements embedded in a thin polymer sheet to form a 2x2 cm(2) sensing pad with a minimal thickness of 2.5mm, while it is easily expandable in order to be used as a building block for larger surface sensors. The fabricated pad sensor was combined with a low physical dimension commercially available interrogation unit to enhance the portability features of the complete sensing system. Sensor mechanical properties allow for matching human skin behavior, while its operational performance exhibited a maximum fractional pressure sensitivity of 12 MPa(-1) with a spatial resolution of 1x1cm(2) and demonstrated no hysteresis and real time operation. These attractive operational and mechanical properties meet the requirements of various biomedical applications with respect to human skin pressure measurements, including amputee sockets, shoe sensors, wearable sensors, wheelchair seating-system sensors, hospital-bed monitoring sensors.

Normal ranges of embryonic length, embryonic heart rate, gestational sac diameter and yolk sac diameter at 6-10 weeks.

OBJECTIVES: To construct normal ranges for embryonic crown-rump length (CRL), heart rate (HR), gestational sac diameter (GSD) and yolk sac diameter (YSD) at 6-10 weeks of gestation. METHODS: We examined 4,698 singleton pregnancies with ultrasound measurements of CRL, HR, GSD and YSD at 6-10 weeks and CRL at 11-13 weeks resulting in the live birth after 36 weeks of phenotypically normal neonates with birth weight above the 5th centile. Gestational age was derived from CRL at the 11- to 13-week scan using the formula of Robinson and Fleming. Regression analysis was used to establish normal ranges of CRL, fetal HR, GSD and YSD with gestation, and fetal HR, GSD and YSD with CRL. RESULTS: At 6-10 weeks there were significant quadratic associations between CRL, GSD, YSD and gestation and between HR, GSD, YSD and CRL, and a cubic association between HR and gestation. The estimated gestation from CRL was the same as that of Robinson and Fleming for a CRL of 10.2-36.5 mm, but the formula of Robinson and Fleming underestimated the gestation by 1 day for a CRL 7.4-10.2 mm and this increased to 9 days for a CRL of 1 mm. CONCLUSION: This study established normal ranges for early pregnancy biometry.

Deep Sequencing Identified Dysregulated Circulating MicroRNAs in Late Onset Preeclampsia.

BACKGROUND/AIM: To characterize global microRNA (miRNA) expression profile in the first trimester maternal plasma of women who subsequently develop late-onset preeclampsia (LOPE) compared to uncomplicated pregnancies. MATERIALS AND METHODS: Five first trimester plasma samples from women who developed LOPE and 5 controls were analyzed using next generation sequencing technology (NGS) followed by target prediction, Gene Ontology analysis and pathway identification. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed for confirmation in an independent cohort of 12 LOPE cases and 12 controls. RESULTS: miR-23b-5p and miR-99b-5p were down-regulated by >1.5 fold in LOPE complicated pregnancies (p value <0.05) compared to controls. Target prediction showed that the major targets of these miRNAs are associated with glycometabolism and immune response. CONCLUSION: miR-23b-5p and miR-99b-5p are possibly implicated in the pathogenic mechanisms leading to the induction of LOPE and may serve as candidate non-invasive biomarkers for early prediction and prevention.