Meta-analysis of epigenome-wide association studies in newborns and children show widespread sex differences in blood DNA methylation

Publisher Copyright: © 2022 The AuthorsBackground: Among children, sex-specific differences in disease prevalence, age of onset, and susceptibility have been observed in health conditions including asthma, immune response, metabolic health, some pediatric and adult cancers, and psychiatric disorders. Epigenetic modifications such as DNA methylation may play a role in the sexual differences observed in diseases and other physiological traits. Methods: We performed a meta-analysis of the association of sex and cord blood DNA methylation at over 450,000 CpG sites in 8438 newborns from 17 cohorts participating in the Pregnancy And Childhood Epigenetics (PACE) Consortium. We also examined associations of child sex with DNA methylation in older children ages 5.5–10 years from 8 cohorts (n = 4268). Results: In newborn blood, sex was associated at Bonferroni level significance with differences in DNA methylation at 46,979 autosomal CpG sites (p < 1.3 × 10−7) after adjusting for white blood cell proportions and batch. Most of those sites had lower methylation levels in males than in females. Of the differentially methylated CpG sites identified in newborn blood, 68% (31,727) met look-up level significance (p < 1.1 × 10−6) in older children and had methylation differences in the same direction. Conclusions: This is a large-scale meta-analysis examining sex differences in DNA methylation in newborns and older children. Expanding upon previous studies, we replicated previous findings and identified additional autosomal sites with sex-specific differences in DNA methylation. Differentially methylated sites were enriched in genes involved in cancer, psychiatric disorders, and cardiovascular phenotypes.Peer reviewe

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Thermodynamic analysis of the ternary mixture R152a/R125/R32 with the Peng-Robinson equation of state

106 σ.Σε αυτή τη διπλωματική εργασία δοκιμάστηκε το μοντέλο καταστατικής εξίσωσης Peng-Robinson για τα υπέρθερμα αέρια μίγματα R407b και R152a / R125 / R32 με κατά μάζα σύσταση 48 / 18 / 34. Το δεύτερο είναι ένα νέο μίγμα με πολύ μικρή επίδραση στο περιβάλλον σε σχέση με τα σημερινά ψυκτικά μέσα και από πρόσφατες μελέτες φαίνεται ικανό να αντικαταστήσει το R22. Με σκοπό τον προσδιορισμό των θερμοφυσικών ιδιοτήτων του νέου αερίου στην περιοχή λειτουργίας δημιουργήθηκε υπολογιστικός κώδικας στη γλώσσα προγραμματισμού java. Επιλέχθηκε να μελετηθούν η πίεση, η εντροπία, η ενθαλπία, η ειδική θερμοχωρητικότητα υπό σταθερό όγκο, η ειδική θερμοχωρητικότητα υπό σταθερή πίεση, ο λόγος ειδικών θερμοχωρητικοτήτων, οι ισεντροπικοί συντελεστές, ο συντελεστής συμπιεστότητας και η ταχύτητα ήχου. Το εύρος θερμοκρασίας ορίστηκε 240,15 Κ - 481,05 Κ και το εύρος όγκου 0,006 m3/kg – 0,6 m3/kg. Για κάθε μέγεθος εκπονήθηκε διάγραμμα συναρτήσει της θερμοκρασίας και της πίεσης. Στη συνέχεια πραγματοποιήθηκε συγκριτική ανάλυση των αποτελεσμάτων με στοιχεία που αντλήθηκαν από το πρόγραμμα REFPROP της NIST και υπολογίστηκαν τα σχετικά σφάλματα. Για τον εύκολο προσδιορισμό των σφαλμάτων δημιουργήθηκαν τα αντίστοιχα διαγράμματα των ιδιοτήτων που παρουσιάζουν μεγάλες αποκλίσεις. Η εργασία καταλήγει με το συμπέρασμα ότι το μοντέλο της Peng-Robinson περιγράφει ικανοποιητικά όλα τα υπό εξέταση μεγέθη εκτός από τις ειδικές θερμοχωρητικότητες υπό σταθερό όγκο και σταθερή πίεση. Γι’ αυτές τις δύο μεταβλητές εμφανίζονται υψηλές αποκλίσεις για μεγάλη περιοχή θερμοκρασιών και όγκων, οι οποίες καθιστούν ακατάλληλη τη χρήση του μοντέλου αυτού.This thesis applies the Peng-Robinson equation of state (EoS) for the superheated gas mixture R407b and R152a / R125 / R32 with a mass ratio 48 / 18 / 34. The last mentioned gas is a new blend with little impact on the environment in comparison to current refrigerants and from recent studies it seems to have an ideal potential to be a drop-in replacement of R22. With the aim to investigate the thermophysical characteristics of this new mixture in the operating region, a computer code has been developed with the java programming language. The selected properties were pressure, entropy, enthalpy, specific heat capacity at constant volume, specific heat capacity at constant pressure, ratio of specific heat capacities, compressibility factor and speed of sound. The range of temperature was set from 240,15 Κ to 481,05 Κ and the range of volume from 0,006 m3/kg to 0,6 m3/kg. The diagrams of every variable were produced as a function of temperature and pressure. Afterwards, a comparative analysis was performed using the REFPROP program of NIST to estimate the relative errors of the calculations. For the easy determination of the errors the corresponding diagrams of the properties with high deviations were created and presented. Finally, this work concludes that the Peng-Robinson EoS simulates with adequacy the performance of all characteristics studied except for the specific heat capacities. For these two variables high deviations were measured in a large range of temperature and volume, which indicates that this type of equation of state is unsuitable.Εύα Α. Παππ

Experimental study on the interlaminar fracture properties of carbon fibre reinforced polymer composites with a single embedded toughened film

In this study, two types of single polymer films have been inserted in a composite laminate to examine their toughening effects on mechanical properties. The first is a thermoplastic polyurethane (PU) film, and the second is an adhesive epoxy film featuring a polyester net. The laminates were manufactured either using a co-curing (CC) process or a secondary bonding (SB) process used for the epoxy film. Mode I and mode II interlaminar fracture toughness were measured for laminates manufactured by both processes and compared with the corresponding reference laminate toughness. A significant increase in both mode I and mode II toughness resulted when introducing a single PU film, approximately 290% and 50%, respectively. Similarly, the epoxy film improved the interlaminar fracture properties; the CC process produced an increase of 175% for mode II toughness, while the SB adhesive film showed an increase of 75% for mode II toughness

Meta-analysis of epigenome-wide association studies in newborns and children show widespread sex differences in blood DNA methylation

Background: Among children, sex-specific differences in disease prevalence, age of onset, and susceptibility have been observed in health conditions including asthma, immune response, metabolic health, some pediatric and adult cancers, and psychiatric disorders. Epigenetic modifications such as DNA methylation may play a role in the sexual differences observed in diseases and other physiological traits. Methods: We performed a meta-analysis of the association of sex and cord blood DNA methylation at over 450,000 CpG sites in 8438 newborns from 17 cohorts participating in the Pregnancy And Childhood Epigenetics (PACE) Consortium. We also examined associations of child sex with DNA methylation in older children ages 5.5–10 years from 8 cohorts (n = 4268). Results: In newborn blood, sex was associated at Bonferroni level significance with differences in DNA methylation at 46,979 autosomal CpG sites (p \u3c 1.3 × 10−7) after adjusting for white blood cell proportions and batch. Most of those sites had lower methylation levels in males than in females. Of the differentially methylated CpG sites identified in newborn blood, 68% (31,727) met look-up level significance (p \u3c 1.1 × 10−6) in older children and had methylation differences in the same direction. Conclusions: This is a large-scale meta-analysis examining sex differences in DNA methylation in newborns and older children. Expanding upon previous studies, we replicated previous findings and identified additional autosomal sites with sex-specific differences in DNA methylation. Differentially methylated sites were enriched in genes involved in cancer, psychiatric disorders, and cardiovascular phenotypes