Effect of hyperglycaemic conditions on the response of human periodontal ligament fibroblasts to mechanical stretching

Objectives: The aim of the present study was to investigate the impact of high glucose concentration on the response of human periodontal ligament fibroblasts (PDLFs) to cyclic tensile strain. Materials and methods: Human PDLFs were incubated under normal or high glucose conditions, and then were subjected to cyclic tensile stretching (8 per cent extension, 1 Hz). Gene expression was determined by quantitative real-time polymerase chain reaction. Intracellular reactive oxygen species (ROS) were determined by the 2',7'-dichlorofluorescein-diacetate assay, activation of mitogen-activated protein kinase (MAPK) was monitored by western analysis and osteoblastic differentiation was estimated with Alizarin Red-S staining. Results: Cyclic tensile stretching of PDLF leads to an immediate activation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), as well as to the increased expression of the transcription factor c-fos, known to regulate many osteogenesis-related genes. At later time points, the alkaline phosphatase and osteopontin genes were also upregulated. Hyperglycaemic conditions inhibited these effects. High glucose conditions were unable to increase ROS levels, but they increased the medium's osmolality. Finally, increase of osmolality mimics the inhibitory effect of hyperglycaemia on MAPK activation, c-fos and osteoblast-specific gene markers' upregulation, as well as osteogenic differentiation capacity. Conclusion: Our findings indicate that under high glucose conditions, human PDLFs fail to adequately respond to mechanical deformation, while their strain-elicited osteoblast differentiation ability is deteriorated. The aforementioned effects are most probably mediated by the increased osmolality under hyperglycaemic conditions

Community resilience to climate change: an evidence review

The concept of community resilience to climate change in the UK has a diverse range of meanings and associated activities. This review of evidence and practice explores this varied and contested field to build the evidence base and help support the development of community resilience to climate change. The report shows: •the variety of actions being carried out across the UK that can be classed as improving resilience of communities to climate change; •the barriers and facilitators to improving resilience to climate change for communities; •the value of a framework to understand resilience of communities to climate change that emphasises existing capacities of communities, engagement and empowerment of citizens, and multi-level governance; and •examples of innovative actions to improve resilience of communities to climate change with a focus on four case studies, which are further explored in a separate report

Reproducibility of computed tomography angiography data analysis using semiautomated plaque quantification software: Implications for the design of longitudinal studies

Reproducibility of the quantitative assessment of atherosclerosis by computed tomography coronary angiography (CTCA) is paramount for the design of longitudinal studies. The purpose of this study was to assess the inter- and intra-observer reproducibility using semiautomated CT plaque analysis software in symptomatic individuals. CTCA was performed in 10 symptomatic patients after percutaneous treatment of the culprit lesions and was repeated after 3 years. The plaque quantitative analysis was performed in untreated vessels with mild-tomoderate atherosclerosis and included geometrical and compositional characteristics using semiautomated CT plaque analysis software. A total of 945 matched crosssections from 21 segments were analyzed independently by a second reviewer to assess inter-observer variability; the first observer repeated all the analyses after 3 months to assess intra-observer variability. The observer variability was also compared to the absolute plaque changes detected over time. Agreement was evaluated by Bland-Altman analysis and co

Computed tomography coronary angiography accuracy in women and men at low to intermediate risk of coronary artery disease

Objectives To investigate the diagnostic accuracy of CT coronary angiography (CTCA) in women at low to intermediate pre-test probability of coronary artery disease (CAD) compared with men. Methods In this retrospective study we included symptomatic patients with low to intermediate risk who underwent both invasive coronary angiography and CTCA. Exclusion criteria were previous revascularisation or myocardial infarction. The pre-test probability of CAD was estimated using the Duke risk score. Thresholds of less than 30 % and 30-90 % were used for determining low and intermediate risk, respectively. The diagnostic accuracy of CTCA in detecting obstructive CAD (≥50 % lumen diameter narrowing) was calculated on patient level. P<0.05 was considered significant. Results A total of 570 patients (46 % women [262/570]) were included and stratified as low (women 73 % [80/109]) and intermediate risk (women 39 % [182/461]). Sensitivity, specificity, PPV and NPV were not significantly different in and between women and men at low and intermediate risk. For women vs. me

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Σχεδίαση ολοκληρωμένου ενισχυτή ισχύος συχνότητας λειτουργίας 5GHz σε 90nm CMOS τεχνολογία

Μη διαθέσιμη περίληψηNot available summarizatio

Σχεδίαση ενισχυτών διαγωγιμότητας χαμηλής κατανάλωσης για υψηλά επίπεδα ιονίζουσας ακτινοβολίας και θέματα υλοποίησης εξειδικευμένου 65nm CMOS τεχνολογίας Κιτ σχεδίασης

Summarization: Microelectronic system components intended for space, aeronautic, military, nuclear physics and biomedical applications should exhibit radiation hardness, the ability to withstand damages caused by high levels of ionizing radiation. The increasing demand for higher system performance and the availability of advanced CMOS technologies are responsible for the shift towards the use of commercial foundry CMOS processes for such applications. In high energy physics (HEP) experiments, such as the High-Luminosity Large Hadron Collider (HL-LHC) at CERN, ultra high Total Ionizing Dose (TID) levels up to 1 Grad(SiO2) are expected, where many components such as particle detectors are designed in bulk silicon CMOS. However, a key concern is the impact of TID on CMOS device performance. In this work, the system integration of a dedicated 65 nm CMOS TID-Process Design Kit developed for CERN is presented, accounting for effects of 100, 200 and 500 Mrad(SiO2), established for TID experiments carried out at three temperatures (-30°C, 0°C and 25°C) for standard-layout MOSTs and Enclosed-Gate MOSTs. The scope of this work is to provide insight in the way high TID phenomena affect low power analog CMOS design, as well as to show the effectiveness of inversion-level based techniques for radiation hardened design. In that direction, two operational transconductance amplifiers (OTAs) are designed and selected criteria are used for bench-marking their performance, such as gain bandwidth (GBW), phase margin (PM), slew rate (SR) and power dissipation (PD).Περίληψη: Μικροηλεκτρονικά συστήματα που χρησιμοποιούνται σε αεροδιαστημικές, στρατιωτικές, πυρηνικής φυσικής και εφαρμογές βιοϊατρικής πρέπει να έχουν την δυνατότητα να αντέξουν τις συνέπειες της υψηλής ιονίζουσας ακτινοβολίας. Η στροφή στη χρήση εμπορικά διαθέσιμων CMOS processes για τέτοιου είδους εφαρμογές οφείλεται στη συνεχή ζήτηση για συστήματα υψηλών επιδόσεων και τη διαθεσιμότητα εξελιγμένων CMOS τεχνολογιών. Στα πειράματα υψηλών ενεργειών, όπως το High-Luminosity Large Hadron Collider (HL-LHC) του CERN, όπου μέρη των συστημάτων του, όπως οι ανιχνευτές σωματιδίων, κατασκευάζονται με bulk CMOS τεχνολογίες, αναμένονται εξαιρετικά υψηλά επίπεδα Total Ionizing Dose (TID) (έως 1 Grad(SiO2)). Συνεπώς, μεγάλο ενδιαφέρον παρουσιάζει ο αντίκτυπος των υψηλών TID στην απόδοση των CMOS διατάξεων. Σε αυτή την εργασία παρουσιάζεται η ενσωμάτωση ενός εξειδικευμένου 65 nm CMOS TID-Process Design Kit που αναπτύχθηκε για το CERN για να καλύπτει πειράματα σε 100, 200 and 500 Mrad(SiO2) και θερμοκρασίες -30°C, 0°C and 25°C για standard-layout και Enclosed-Gate MOSTs. Ο σκοπός της εργασίας είναι να μελετηθεί η επίδραση των υψηλών TID στην χαμηλής ισχύος αναλογική CMOS σχεδίαση όπως επίσης και την αποτελεσματικότητα των τεχνικών βασισμένων στα επίπεδα αναστροφής για radiation hardened σχεδίαση. Για το σκοπό αυτό, σχεδιάστηκαν δύο ενισχυτές διαγωγιμότητας (OTAs) και επιλέχθηκαν συγκεκριμένα κριτήρια, όπως gain bandwidth (GBW), phase margin (PM), slew rate (SR) και power dissipation (PD)) για την αξιολόγηση της απόδοσης τους

Forward and Reverse Operation of Enclosed-Gate MOSFETs and Sensitivity to High Total Ionizing Dose

Frond-end electronics at the High Luminosity-Large Hadron Collider (HL-LHC) at CERN, will be exposed to ten-fold radiation doses. The use of enclosed gate (EG) MOSFETs of 65 nm Bulk CMOS process, is considered to be a viable solution in order to suppress performance degradation effects that occur after high TID exposure. The present paper presents a detailed analysis of the functionality of EG MOSFETs operating under high TID, taking into accountspecific layout characteristics