The association between in-stent neoatherosclerosis and native coronary artery disease progression: a long-term angiographic and optical coherence tomography cohort study

Aims The purpose of the present study was to investigate the relationship between in-stent neoatherosclerosis (NA) and native atherosclerosis progression of untreated coronary segments. Methods and results In-stent NA was assessed by optical coherence tomography (OCT) among patients included in the SIRTAX-LATE OCT study 5 years after drug-eluting stent (DES) (sirolimus-eluting and paclitaxel-eluting stents) implantation. Neoatherosclerosis was defined as the presence of fibroatheroma or fibrocalcific plaque within the neointima of stented segments with a longitudinal extension >1.0 mm. Atherosclerosis progression in untreated native coronary segments was evaluated by serial quantitative coronary angiography (QCA). The change in minimal lumen diameter (MLD) was serially assessed within matched segments at baseline and 5-year angiographic follow-up. The key clinical endpoint was non-target lesion (non-TL) revascularization throughout 5 years. A total of 88 patients with 88 lesions were available for OCT analysis 5 years after DES implantation. In-stent NA was observed in 16% of lesions with the majority of plaques being fibroatheromas (11.4%) followed by fibrocalcific plaques (5.7%). A total of 704 non-TL segments were serially evaluated by QCA. Between baseline and 5-year follow-up, the reduction in MLD was significantly more pronounced in patients with NA (−0.25 mm, 95% CI −0.36 to −0.17 mm) when compared with patients without NA (−0.13 mm, 95% CI −0.17 to −0.10 mm, P = 0.002). Similarly, non-TL revascularization was more frequent in patients with NA (78.6%) when compared with patients without NA (44.6%, P = 0.028) throughout 5 years. Conclusions In-stent NA is more common among patients with angiographic and clinical evidence of native atherosclerosis progression suggesting similar pathophysiological mechanisms. SIRTAX trial is registered at http://www.clinicaltrials.gov/ct2/show/NCT0061708

Destabilization of the thermohaline circulation by transient perturbations to the hydrological cycle

We reconsider the problem of the stability of the thermohaline circulation as described by a two-dimensional Boussinesq model with mixed boundary conditions. We determine how the stability properties of the system depend on the intensity of the hydrological cycle. We define a two-dimensional parameters' space descriptive of the hydrology of the system and determine, by considering suitable quasi-static perturbations, a bounded region where multiple equilibria of the system are realized. We then focus on how the response of the system to finite-amplitude surface freshwater forcings depends on their rate of increase. We show that it is possible to define a robust separation between slow and fast regimes of forcing. Such separation is obtained by singling out an estimate of the critical growth rate for the anomalous forcing, which can be related to the characteristic advective time scale of the system.Comment: 37 pages, 8 figures, submitted to Clim. Dy

Das Triftprojekt : ein Überblick zu Projekt, Ökologie und Partizipation

Mit der Realisierung des Triftprojekts kann ein wesentlicher Beitrag zur erfolgreichen Umsetzung der schweizerischen Energiewende geleistet werden. Neben einer Erhöhung der Energieproduktion um 145 GWh/a kann künftig die Flexibilität der Stromproduktion erhöht und insbesondere ein Grossteil der Stromproduktion im Winter erfolgen. Allerdings sind mit dieser energiepolitischen Verbesserung sowohl gewässerökologische als auch terrestrische Beeinträchtigungen verbunden. Die umfangreichen und sehr detaillierten ökologischen Untersuchungen bildeten eine hervorragende Ausgangsbasis zur Beurteilung des Projekts und eine sachliche Diskussion. Im Rahmen eines gut strukturierten Begleitprozesses hatten alle relevanten Stakeholder die Möglichkeit, sich aktiv in die Diskussionen und Lösungsfindung einzubringen. Die Diskussionen im Begleitprozess verliefen sehr offen und lösungsorientiert. Mit zwei von allen Seiten anerkannten Bewertungsmethoden wurden die ökologischen Beeinträchtigungen und die Aufwertungsmassnahmen sowohl für aquatische als auch für terrestrische Lebensräume objektiv bilanziert. Nach rund drei Jahren Verhandlungen wurde schliesslich für alle relevanten ökologischen und technischen Aspekte eine Lösung gefunden und wurden die Konzessionsunterlagen im Herbst 2017 eingereicht

Cerebral regional tissue Oxygen Saturation to Guide Oxygen Delivery in preterm neonates during immediate transition after birth (COSGOD III): an investigator-initiated, randomized, multi-center, multi-national, clinical trial on additional cerebral tissue oxygen saturation monitoring combined with defined treatment guidelines versus standard monitoring and treatment as usual in premature infants during immediate transition: study protocol for a randomized controlled trial

Background: Transition immediately after birth is a complex physiological process. The neonate has to establish sufficient ventilation to ensure significant changes from intra-uterine to extra-uterine circulation. If hypoxia or bradycardia or both occur, as commonly happens during immediate transition in preterm neonates, cerebral hypoxia–ischemia may cause perinatal brain injury. The primary objective of the COSGOD phase III trial is to investigate whether it is possible to increase survival without cerebral injury in preterm neonates of less than 32 weeks o

The IXPE View of GRB 221009A

We present the IXPE observation of GRB 221009A, which includes upper limits on the linear polarization degree of both prompt and afterglow emission in the soft X-ray energy band. GRB 221009A is an exceptionally bright gamma-ray burst (GRB) that reached Earth on 2022 October 9 after traveling through the dust of the Milky Way. The Imaging X-ray Polarimetry Explorer (IXPE) pointed at GRB 221009A on October 11 to observe, for the first time, the 2–8 keV X-ray polarization of a GRB afterglow. We set an upper limit to the polarization degree of the afterglow emission of 13.8% at a 99% confidence level. This result provides constraints on the jet opening angle and the viewing angle of the GRB, or alternatively, other properties of the emission region. Additionally, IXPE captured halo-rings of dust-scattered photons that are echoes of the GRB prompt emission. The 99% confidence level upper limit to the prompt polarization degree depends on the background model assumption, and it ranges between ∼55% and ∼82%. This single IXPE pointing provides both the first assessment of X-ray polarization of a GRB afterglow and the first GRB study with polarization observations of both the prompt and afterglow phases

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Visual Pattern Recognition with on On-Chip Learning: Towards a Fully Neuromorphic Approach

We present a spiking neural network (SNN) for visual pattern recognition with on-chip learning on neuromorphic hardware. We show how this network can learn simple visual patterns composed of horizontal and vertical bars sensed by a Dynamic Vision Sensor, using a local spike-based plasticity rule. During recognition, the network classifies the pattern's identity while at the same time estimating its location and scale. We build on previous work that used learning with neuromorphic hardware in the loop and demonstrate that the proposed network can properly operate with on-chip learning, demonstrating a complete neuromorphic pattern learning and recognition setup. Our results show that the network is robust against noise on the input (no accuracy drop when adding 130% noise) and against up to 20% noise in the neuron parameters