Pulmonary arterial hypertension registries: past, present and into the future

Registries have greatly contributed to knowledge about PAH epidemiology, risk factors, prognosis and treatment. Future registries face unique challenges but may benefit from integration of multiple data sources and capitalising on “Big Data” opportunitiesConflict of interest: J. Weatherald reports grants, personal fees and non-financial support from Janssen Inc. and Actelion, personal fees and non-financial support from Bayer, personal fees from Novartis, and grants from Alberta Lung Association, Canadian Vascular Network, European Respiratory Society and Canadian Thoracic Society, outside the submitted work. Conflict of interest: A. Reis reports grants, personal fees and non-financial support from Janssen Inc. and Actelion, outside the submitted work. Conflict of interest: O. Sitbon reports grants, personal fees and non-financial support from Actelion Pharmaceuticals, Bayer and Merck, grants from GlaxoSmithKline, grants, and personal fees from United Therapeutics and Gossamer Bio, outside the submitted work. Conflict of interest: M. Humbert reports personal fees from Actelion and Merck, and grants and personal fees from Bayer, GSK and United Therapeutics, outside the submitted work.info:eu-repo/semantics/publishedVersio

Delirium in older patients undergoing aortic valve replacement: incidence, predictors, and cognitive prognosis.

Transcatheter aortic valve replacement is increasingly performed in frail older patients who were previously ineligible for a standard surgical procedure. The objectives of this study are to determine delirium incidence, predictors, and relationship with cognitive performance at 3-month follow-up in older patients undergoing aortic valve replacement (AVR). Patients (N = 93) aged 70 years and older, undergoing transcatheter (TAVR, N = 66) or surgical (SAVR, N = 27) aortic valve replacement in an academic medical center were enrolled in this prospective cohort study. Delirium was assessed using the Confusion Assessment Method (CAM) on postoperative days 1, 2, 3, and 7. Data on patients' socio-demographics, functional status (including instrumental activities of daily living (IADL), and surgical risk scores (including Society of Thoracic Surgeons (STS) risk score), were collected at baseline. Cognitive status was assessed with the Mini-Mental Status Exam (MMSE) and the Clock Drawing Test (CDT) at baseline and 3 months after AVR. Delirium occurred in 21 (23%) patients, within the first three postoperative days in 95% (20/21) of the cases. Delirium incidence was lower in TAVR (13/66 = 20%) than SAVR (8/27 = 30%) patients, but this difference was not statistically significant (p = .298). Patients with delirium had lower baseline cognitive performance (median MMSE score 27.0 ± 3.0 vs 28.0 ± 3.0, p = .029), lower performance in IADL (7.0 vs 8.0, p = .038), and higher STS risk scores (4.7 ± 2.7 vs 2.9 ± 2.3, p = .020). In multivariate analyses, patients with intermediate (score > 3 to ≤8) and high (score > 8) STS risk scores had 4.3 (95%CI 1.2-15.1, p = .025) and 16.5 (95%CI 2.0-138.2, p = .010), respectively, higher odds of incident delirium compared to patients with low (score ≤ 3) STS risk scores. At 3-month follow-up (N = 77), patients with delirium still had lower MMSE score (27.0 ± 8.0 vs 28.0 ± 2.0, p = .007) but this difference did not remain significant once adjusting for baseline MMSE (β-coefficient 1.11, 95%CI [- 3.03-0.80], p = .248). Delirium occurred in about one in five older patients undergoing AVR, almost essentially within the first three postoperative days. Beside cognitive performance, STS risk score could enhance the identification of high-risk older patients to better target preventative interventions

Interference between magnetic field and cavity modes in an extended Josephson junction

An extended Josephson junction consists of two superconducting electrodes that are separated by an insulator and it is therefore also a microwave cavity. The superconducting phase difference across the junction determines the supercurrent as well as its spatial distribution. Both, an external magnetic field and a resonant cavity intrafield produce a spatial modification of the superconducting phase along the junction. The interplay between these two effects leads to interference in the critical current of the junction and allows us to continuously tune the coupling strength between the first cavity mode and the Josephson phase from 1 to -0.5. This enables static and dynamic control over the junction in the ultra-strong coupling regime.Comment: 4 pages, 3 figure

Dry-season length and runoff control annual variability in stream DOC dynamics in a small, shallowgroundwater-dominated agricultural watershed

International audienceAs a phenomenon integrating climate conditions and hydrological control of the connection betweenstreams and terrestrial dissolved organic carbon (DOC) sources, groundwater dynamics controlpatterns of stream DOC characteristics (concentrations and fluxes). Influence of intra-annualvariations in groundwater level, discharge and climatic factors on DOC concentrations and fluxeswere assessed over 13 years at the headwater watershed of Kervidy-Naizin (5 km²) in westernFrance. Four seasonal periods were delineated within each year according to groundwaterfluctuations (A: rewetting, B: high flow, C: recession, and D: drought). Annual and seasonal baseflow vs stormflow DOC concentrations were defined based on daily hydrograph readings. Highinter-annual variability of annual DOC fluxes (5.4-39.5 kg.ha-1.yr-1) indicates that several years ofdata are required to encompass variations in water flux to evaluate the actual DOC export capacity ofa watershed. Inter-annual variability of mean annual DOC concentrations was much lower (4.9-7.5mg C.l-1), with concentrations decreasing within each year from ca. 9.2 mg C.l-1 in A to ca. 3.0 mgC.l-1 in C. This indicates an intra-annual pattern of stream DOC concentrations controlled by DOCsource characteristics and groundwater dynamics very similar across years. Partial least squareregressions combined with multiple linear regressions showed that the dry season characteristics(length and drawdown) determine the mean annual DOC concentration while annual runoffdetermines the annual flux. Antagonistic mechanisms of production-accumulation and dilution depletioncombined with an unlimited DOC supply from riparian wetland soils can mitigate theresponse of stream concentrations to global changes and climatic variations

Absence of influence of gender and BMPR2 mutation type on clinical phenotypes of pulmonary arterial hypertension

<p>Abstract</p> <p>Background</p> <p>Previous studies indicate that patients with pulmonary arterial hypertension (PAH) carrying a mutation in the bone morphogenetic protein receptor type 2 (<it>BMPR2</it>) gene, develop the disease 10 years earlier than non-carriers, and have a more severe hemodynamic compromise at diagnosis. A recent report has suggested that this may only be the case for females and that patients with missense mutations in <it>BMPR2 </it>gene have more severe disease than patients with truncating mutations.</p> <p>Methods</p> <p>We reviewed data from all patients with PAH considered as idiopathic and patients with a family history of PAH, who underwent genetic counselling in the French PAH network between January, 1^st2004 and April, 1^st2010. We compared clinical, functional, and hemodynamic characteristics between carriers and non-carriers of a <it>BMPR2 </it>mutation, according to gender or <it>BMPR2 </it>mutation type.</p> <p>Results</p> <p>PAH patients carrying a <it>BMPR2 </it>mutation (n = 115) were significantly younger at diagnosis than non-carriers (n = 267) (35.8 ± 15.4 and 47.5 ± 16.2 respectively, p < 0.0001). The presence of a <it>BMPR2 </it>mutation was associated with a younger age at diagnosis in females (36.4 ± 14.9 in <it>BMPR2 </it>mutation carriers and 47.4 ± 15.8 in non-carriers, p < 0.0001), and males (34.6 ± 16.8 in <it>BMPR2 </it>mutation carriers and 47.8 ± 17.1 in non-carriers, p < 0.0001). <it>BMPR2 </it>mutation carriers had a more severe hemodynamic compromise at diagnosis, but this was not influenced by gender. No differences in survival and time to death or lung transplantation were found in male and female PAH patients carrying a <it>BMPR2 </it>mutation. No differences were observed in clinical outcomes according to the type of <it>BMPR2 </it>mutations (missense, truncating, large rearrangement or splice defect).</p> <p>Conclusion</p> <p>When compared to non-carriers, <it>BMPR2 </it>mutation carriers from the French PAH network are younger at diagnosis and present with a more severe hemodynamic compromise, irrespective of gender. Moreover, <it>BMPR2 </it>mutation type had no influence on clinical phenotypes in our patient population.</p

Extreme melting at Greenland's largest floating ice tongue

The 79° North Glacier (Nioghalvfjerdsbrae, 79NG) is one of three remaining glaciers with a floating tongue in Greenland. Although the glacier has been considered exceptionally stable in the past, earlier studies have shown that the ice tongue has thinned in recent decades. By conducting high-resolution ground-based and airborne radar measurements in conjunction with satellite remote-sensing observations, we find significant changes in the geometry of 79NG. In the vicinity of the grounding line, a 500 m high subglacial channel has grown since ∼ 2010 and has caused surface lowering of up to 7.6 m a−1. Our results show extreme basal melt rates exceeding 150 m a−1 over a period of 17 d within a distance of 5 km from the grounding line, where the ice has thinned by 32 % since 1998. We find a heterogeneous distribution of melt rates, likely due to variability in water column thickness and channelization of the ice base. Time series of melt rates show a decrease in basal melting since 2018, indicating an inflow of colder water into the cavity below 79NG. We discuss the processes that have led to the changes in geometry and conclude that the inflow of warm ocean currents has led to the extensive thinning of 79NG's floating ice tongue near the grounding line over the last 2 decades. In contrast, we hypothesize that the growth of the channel results from increased subglacial discharge due to a considerably enlarged area of summer surface melt due to the warming of the atmosphere.</p

Loss of human Scribble cooperates with H-Ras to promote cell invasion through deregulation of MAPK signalling

Activating mutations in genes of the Ras-mitogen-activated protein kinase (MAPK) pathway occur in approximately 30% of all human cancers; however, mutation of Ras alone is rarely sufficient to induce tumour development. Scribble is a polarity regulator recently isolated from a Drosophila screen for events that cooperate with Ras mutation to promote tumour progression and cell invasion. In mammals, Scribble regulates directed cell migration and wound healing in vivo; however, no role has been identified for mammalian Scribble in oncogenic transformation. Here we show that in human epithelial cells expressing oncogenic Ras or Raf, loss of Scribble promotes invasion of cells through extracellular matrix in an organotypic culture system. Further, we show that the mechanism by which this occurs is in the regulation of MAPK signalling by Scribble. The suppression of MAPK signalling is a highly conserved function of Scribble as it also prevents Raf-mediated defects in Drosophila wing development. Our data identify Scribble as an important mediator of MAPK signalling and provide a molecular basis for the observation that Scribble expression is decreased in many invasive human cancers. © 2008 Macmillan Publishers Limited All rights reserved

Exact and explicit probability densities for one-sided Levy stable distributions

We study functions g_{\alpha}(x) which are one-sided, heavy-tailed Levy stable probability distributions of index \alpha, 0< \alpha <1, of fundamental importance in random systems, for anomalous diffusion and fractional kinetics. We furnish exact and explicit expression for g_{\alpha}(x), 0 \leq x < \infty, satisfying \int_{0}^{\infty} exp(-p x) g_{\alpha}(x) dx = exp(-p^{\alpha}), p>0, for all \alpha = l/k < 1, with k and l positive integers. We reproduce all the known results given by k\leq 4 and present many new exact solutions for k > 4, all expressed in terms of known functions. This will allow a 'fine-tuning' of \alpha in order to adapt g_{\alpha}(x) to a given experimental situation.Comment: 4 pages, 3 figures and 1 tabl