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Swath altimetry is likely to revolutionize our ability to monitor and forecast ocean dynamics. To meet the requirements of the EU Copernicus Marine Service, a constellation of two wide-swath altimeters is envisioned for the long-term (post-2030) evolution of the Copernicus Sentinel 3 topography mission. A series of observing system simulation experiments (OSSEs) is carried out to quantify the expected performances. The OSSEs use a state-of-the-art high-resolution (1/12∘) global ocean data assimilation system similar to the one used operationally by the Copernicus Marine Service. Flying a constellation of two wide-swath altimeters will provide a major improvement of our capabilities to monitor and forecast the oceans. Compared to the present situation with three nadir altimeters flying simultaneously, the sea surface height (SSH) analysis and 7 d forecast error are globally reduced by about 50 % in the OSSEs. With two wide-swath altimeters, the quality of SSH 7 d forecasts is equivalent to the quality of SSH analysis errors from three nadir altimeters. Our understanding of ocean currents is also greatly improved (30 % improvements at the surface and 50 % at 300 m depth). The resolution capabilities will be drastically improved and will be closer to 100 km wavelength compared to about 250 km today. Flying a constellation of two wide-swath altimeters thus looks to be a very promising solution for the long-term evolution of the Sentinel 3 constellation and the Copernicus Marine Service.

Canada has the longest coastline in the world and includes diverse ocean environments, from the frozen waters of the Canadian Arctic Archipelago to the confluence region of Labrador and Gulf Stream waters on the east coast. There is a strong need for a pan-Canadian operational regional ocean prediction capacity covering all Canadian coastal areas in support of marine activities including emergency response, search and rescue, and safe navigation in ice-infested waters. Here we present the first pan-Canadian operational regional ocean analysis system developed as part of the Regional Ice Ocean Prediction System version 2 (RIOPSv2) running in operations at the Canadian Centre for Meteorological and Environmental Prediction (CCMEP). The RIOPSv2 domain extends from 26∘ N in the Atlantic Ocean through the Arctic Ocean to 44∘ N in the Pacific Ocean, with a model grid resolution that varies between 3 and 8 km. RIOPSv2 includes a multivariate data assimilation system based on a reduced-order extended Kalman filter together with a 3D-Var bias correction system for water mass properties. The analysis system assimilates satellite observations of sea level anomaly and sea surface temperature, as well as in situ temperature and salinity measurements. Background model error is specified in terms of seasonally varying model anomalies from a 10-year forced model integration, allowing inhomogeneous anisotropic multivariate error covariances. A novel online tidal harmonic analysis method is introduced that uses a sliding-window approach to reduce numerical costs and allow for the time-varying harmonic constants necessary in seasonally ice-infested waters. Compared to the Global Ice Ocean Prediction System (GIOPS) running at CCMEP, RIOPSv2 also includes a spatial filtering of model fields as part of the observation operator for sea surface temperature (SST). In addition to the tidal harmonic analysis, the observation operator for sea level anomaly (SLA) is also modified to remove the inverse barometer effect due to the application of atmospheric pressure forcing fields. RIOPSv2 is compared to GIOPS and shown to provide similar innovation statistics over a 3-year evaluation period. Specific improvements are found near the Gulf Stream for all model fields due to the higher model grid resolution, with smaller root mean squared (rms) innovations for RIOPSv2 of about 5 cm for SLA and 0.5 ∘C for SST. Verification against along-track satellite observations demonstrates the improved representation of mesoscale features in RIOPSv2 compared to GIOPS, with increased correlations of SLA (0.83 compared to 0.73) and reduced rms differences (12 cm compared to 14 cm). While the RIOPSv2 grid resolution is 3 times higher than GIOPS, the power spectral density of surface kinetic energy provides an indication that the effective resolution of RIOPSv2 is roughly double that of the global system (35 km compared to 66 km). Observations made as part of the Year of Polar Prediction (2017–2019) provide a rare glimpse at errors in Arctic water mass properties and show average salinity biases over the upper 500 m of 0.3–0.4 psu in the eastern Beaufort Sea in RIOPSv2.

The impact of forthcoming wide-swath altimetry missions on the ocean analysis and forecasting system was investigated by means of OSSEs (observing system simulation experiments). These experiments were performed with a regional data assimilation system, implemented in the Iberian–Biscay–Ireland (IBI) region, at 1∕12° resolution using simulated observations derived from a fully eddy-resolving free simulation at 1∕36° resolution over the same region. The objective of the experiments was to assess the ability of different satellite constellations to constrain the ocean analyses and forecasts, considering both along-track altimeters and future wide-swath missions; consequently, the capability of the data assimilation techniques used in the Mercator Ocean operational system to effectively combine the different kinds of measurements was also investigated. These assessments were carried out as part of a European Space Agency (ESA) study on the potential role of wide-swath altimetry in future versions of the European Union Copernicus programme. The impact of future wide-swath altimetry data is evident for investigating the reliability of sea level values in OSSEs. The most significant results were obtained when looking at the sensitivity of the system to wide-swath instrumental error: considering a constellation of three nadir and two accurate (small instrumental error) wide-swath altimeters, the error in ocean analysis was reduced by up to 50 % compared to conventional altimeters. Investigating the impact of the repetitivity of the future measurements, the results showed that two wide-swath missions had a major impact on sea-level forecasting – increasing the accuracy over the entire time window of the 5-day forecasts – compared with a single wide-swath instrument. A spectral analysis underlined that the contributions of wide-swath altimetry data observed in ocean analyses and forecast statistics were mainly due to the more accurate resolution, compared with along-track data, of ocean variability at spatial scales smaller than 100 km. Considering the ocean currents, the results confirmed that the information provided by wide-swath measurements at the surface is propagated down the water column and has a considerable impact (30 %) on ocean currents (up to a depth of 300 m), compared with the present constellation of altimeters. The ocean analysis and forecasting systems used here are those currently used by the Copernicus Marine Environment and Monitoring Service (CMEMS) to provide operational services and ocean reanalysis. The results obtained in the OSSEs considering along-track altimeters were consistent with those derived from real data (observing system experiments, OSEs). OSSEs can also be used to assess the potential of new observing systems, and in this study the results showed that future constellations of altimeters will have a major impact on constraining the CMEMS ocean analysis and forecasting systems and their applications.

Since 19 October 2016, and in the framework of Copernicus Marine Environment Monitoring Service (CMEMS), Mercator Ocean has delivered real-time daily services (weekly analyses and daily 10-day forecasts) with a new global 1∕12° high-resolution (eddy-resolving) monitoring and forecasting system. The model component is the NEMO platform driven at the surface by the IFS ECMWF atmospheric analyses and forecasts. Observations are assimilated by means of a reduced-order Kalman filter with a three-dimensional multivariate modal decomposition of the background error. Along-track altimeter data, satellite sea surface temperature, sea ice concentration, and in situ temperature and salinity vertical profiles are jointly assimilated to estimate the initial conditions for numerical ocean forecasting. A 3D-VAR scheme provides a correction for the slowly evolving large-scale biases in temperature and salinity.This paper describes the recent updates applied to the system and discusses the importance of fine tuning an ocean monitoring and forecasting system. It details more particularly the impact of the initialization, the correction of precipitation, the assimilation of climatological temperature and salinity in the deep ocean, the construction of the background error covariance and the adaptive tuning of observation error on increasing the realism of the analysis and forecasts.The scientific assessment of the ocean estimations are illustrated with diagnostics over some particular years, assorted with time series over the time period 2007–2016. The overall impact of the integration of all updates on the product quality is also discussed, highlighting a gain in performance and reliability of the current global monitoring and forecasting system compared to its previous version.

Since December 2010, the MyOcean global analysis and forecasting system has consisted of the Mercator Océan NEMO global 1/4° configuration with a 1/12° nested model over the Atlantic and the Mediterranean. The open boundary data for the nested configuration come from the global 1/4° configuration at 20° S and 80° N. The data are assimilated by means of a reduced-order Kalman filter with a 3-D multivariate modal decomposition of the forecast error. It includes an adaptive-error estimate and a localization algorithm. A 3-D-Var scheme provides a correction for the slowly evolving large-scale biases in temperature and salinity. Altimeter data, satellite sea surface temperature and in situ temperature and salinity vertical profiles are jointly assimilated to estimate the initial conditions for numerical ocean forecasting. In addition to the quality control performed by data producers, the system carries out a proper quality control on temperature and salinity vertical profiles in order to minimise the risk of erroneous observed profiles being assimilated in the model. This paper describes the recent systems used by Mercator Océan and the validation procedure applied to current MyOcean systems as well as systems under development. The paper shows how refinements or adjustments to the system during the validation procedure affect its quality. Additionally, we show that quality checks (in situ, drifters) and data sources (satellite sea surface temperature) have as great an impact as the system design (model physics and assimilation parameters). The results of the scientific assessment are illustrated with diagnostics over the year 2010 mainly, assorted with time series over the 2007–2011 period. The validation procedure demonstrates the accuracy of MyOcean global products, whose quality is stable over time. All monitoring systems are close to altimetric observations with a forecast RMS difference of 7 cm. The update of the mean dynamic topography corrects local biases in the Indonesian Throughflow and in the western tropical Pacific. This improves also the subsurface currents at the Equator. The global systems give an accurate description of water masses almost everywhere. Between 0 and 500 m, departures from in situ observations rarely exceed 1 °C and 0.2 psu. The assimilation of an improved sea surface temperature product aims to better represent the sea ice concentration and the sea ice edge. The systems under development are still suffering from a drift which can only be detected by means of a 5-yr hindcast, preventing us from upgrading them in real time. This emphasizes the need to pursue research while building future systems for MyOcean2 forecasting.

XPC plays an important role in the nuclear exicision repair pathways. Here the authors show that in addition, XPC plays a role in transcription regulation by interacting with KAT2A and E2F1 and recruiting the ATAC coactivator complex to promoters.

The thrombotic microangiopathy is a syndrome characterized by the combination of mechanical hemolytic anemia, peripheral thrombocytopenia, and organ failure of variable severity. In addition to the idiopathic form, several cases are identified as secondary to pregnancy, infections, disease systems, organ transplants, and cancer. Other forms are secondary to drugs including antimitotics. We report the case of a patient followed for acute myelogenous leukemia. She received induction chemotherapy combining daunorubicin and cytarabine, complicated by thrombotic thrombocytopenic purpura.

Objective: The purpose of our study was to assess the diagnostic performance of 18 F-FDG PET-CT for large vessel involvement in patients with suspected giant cells arteritis (GCA) and a negative temporal artery biopsy (TAB)., Methods: We conducted a retrospective study in a cohort of patients with suspected GCA and negative TAB who underwent an 18 F-FDG PET-CT. Ten vascular segments were studied using a visual score and a semi-quantitative method based on SUVmax ratio with respect to liver uptake. The diagnosis of GCA was established during a mean follow-up of 42 months, based on the presence of clinical symptoms, laboratory results, and imaging data compatible with GCA, good response to corticosteroid therapy, and no differential diagnosis after a follow-up of at least 18 months., Results: We included 63 patients (30 men and 33 women, aged 67 ± 12 years). 18 F-FDG PET-CT showed large vessel involvement in 22 patients, 14 of whom were finally diagnosed with GCA. Forty-one patients were 18 F-FDG PET-CT negative, 9 of whom were finally diagnosed with GCA. Overall, 18 F-FDG uptake by large vessel yielded 61% sensitivity, 80% specificity, 64% positive predictive value, 78% negative predictive value, and 73% diagnostic accuracy. A significant number of patients were treated by corticosteroids before 18 F-FDG PET-CT. However, corticosteroid therapy did not impact significantly the diagnostic performance, although there was a trend to a lower sensitivity in patients receiving corticosteroid therapy for more than 3 days., Conclusions: 18 F-FDG PET-CT is a useful imaging technique to assess large vessel involvement in patients with suspected GCA and negative TAB.

Objective: To compare cardiac sympathetic adrenergic nerve activity in patients with narcolepsy type 1 (NT1) and controls using 123 I-MIBG myocardial scintigraphy, and to determine the clinical and neurophysiological variables associated with 123 I-MIBG scintigraphy results in NT1., Methods: Fifty-six NT1 patients and 91 controls without neurological diseases underwent a cardiac scintigraphy. MIBG uptake was quantified by delayed heart/mediastinum (H/M) ratio. Clinical, neurophysiological and biological determinants of a low H/M were assessed in NT1., Results: MIBG uptake did not differ between NT1 and controls in crude and adjusted associations. Five patients had low MIBG uptake (<1.42, first decile of controls), often with advanced age, cardiovascular (CV) diseases, stimulants intake, and REM sleep behavior disorder. Patients with H/M <1.62 (lowest tertile) were older, with higher BMI, microarousal index and CV comorbidities. A three-fold increase of phasic/tonic REM sleep motor activities was found in those patients, confirmed in a subanalysis of 40 drug-free patients. No association was found with CSF hypocretin levels., Conclusion: A direct measure of the heart adrenergic nerve activity revealed no sympathetic denervation in NT1., Significance: Our results indicate normal cardiac sympathetic innervation in NT1. However, few patients with low MIBG uptake also presented CV comorbidities and REM sleep motor deregulation, potentially at high CV risk, requiring a careful follow-up., (Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

The pathophysiology of rapid eye movement sleep behavior disorder (RBD) associated with narcolepsy type 1 (NT1) is still poorly understood, potentially distinct from idiopathic RBD (iRBD), but may share affected common pathways. We investigated whether MIBG cardiac uptake differs between iRBD and NT1 comorbid with RBD. Thirty-four patients with NT1-RBD and 15 patients with iRBD underwent MIBG cardiac scintigraphy. MIBG uptake was measured by calculating the early and delayed heart to mediastinum (H/M) ratios. A delayed H/M ratio lower than 1.46 was considered abnormal based on a population of 78 subjects without neurological or cardiac diseases. Patients with iRBD were older, had an older RBD onset age and higher REM sleep phasic and tonic muscular activities than NT1-RBD. Lower delayed and early H/M ratios were associated with iRBD, but not with NT1-RBD, in crude and adjusted associations. The delayed H/M ratio differed between iRBD and controls, after adjustment, but not between patients with NT1-RBD and controls. In conclusion, the MIBG cardiac uptake difference between NT1-RBD and iRBD supports the hypothesis of different processes involved in RBD pathogenesis, providing for the first time a cardiac biomarker to differentiate those disorders.

Background: Myocardial salvage is an important surrogate endpoint to estimate the impact of treatments in patients with ST-segment elevation myocardial infarction (STEMI)., Aim: The aim of this study was to evaluate the correlation between cardiac sympathetic denervation area assessed by single-photon emission computed tomography (SPECT) using iodine-123-meta-iodobenzylguanidine (I-MIBG) and myocardial area at risk (AAR) assessed by cardiac magnetic resonance (CMR) (gold standard)., Patients and Methods: A total of 35 postprimary reperfusion STEMI patients were enrolled prospectively to undergo SPECT using I-MIBG (evaluates cardiac sympathetic denervation) and thallium-201 (evaluates myocardial necrosis), and to undergo CMR imaging using T2-weighted spin-echo turbo inversion recovery for AAR and postgadolinium T1-weighted phase sensitive inversion recovery for scar assessment., Results: I-MIBG imaging showed a wider denervated area (51.1±16.0% of left ventricular area) in comparison with the necrosis area on thallium-201 imaging (16.1±14.4% of left ventricular area, P<0.0001). CMR and SPECT provided similar evaluation of the transmural necrosis (P=0.10) with a good correlation (R=0.86, P<0.0001). AAR on CMR was not different compared with the denervated area (P=0.23) and was adequately correlated (R=0.56, P=0.0002). Myocardial salvage evaluated by SPECT imaging (mismatch denervated but viable myocardium) was significantly higher than by CMR (P=0.02)., Conclusion: In patients with STEMI, I-MIBG SPECT, assessing cardiac sympathetic denervation may precisely evaluate the AAR, providing an alternative to CMR for AAR assessment.

Background: Dual-isotope 201 Tl/ 123 I-MIBG SPECT can assess trigger zones (dysfunctions in the autonomic nervous system located in areas of viable myocardium) that are substrate for ventricular arrhythmias after STEMI. This study evaluated the necessity of delayed acquisition and scatter correction for dual-isotope 201 Tl/ 123 I-MIBG SPECT studies with a CZT camera to identify trigger zones after revascularization in patients with STEMI in routine clinical settings., Methods: Sixty-nine patients were prospectively enrolled after revascularization to undergo 201 Tl/ 123 I-MIBG SPECT using a CZT camera (Discovery NM 530c, GE). The first acquisition was a single thallium study (before MIBG administration); the second and the third were early and late dual-isotope studies. We compared the scatter-uncorrected and scatter-corrected (TEW method) thallium studies with the results of magnetic resonance imaging or transthoracic echography (reference standard) to diagnose myocardial necrosis., Results: Summed rest scores (SRS) were significantly higher in the delayed MIBG studies than the early MIBG studies. SRS and necrosis surface were significantly higher in the delayed thallium studies with scatter correction than without scatter correction, leading to less trigger zone diagnosis for the scatter-corrected studies. Compared with the scatter-uncorrected studies, the late thallium scatter-corrected studies provided the best diagnostic values for myocardial necrosis assessment., Conclusions: Delayed acquisitions and scatter-corrected dual-isotope 201 Tl/ 123 I-MIBG SPECT acquisitions provide an improved evaluation of trigger zones in routine clinical settings after revascularization for STEMI.

Objective: The purpose of this study was to compare computed tomography (CT)-based attenuation correction (AC) using a hybrid single photon emission computed tomography (SPECT)-CT system and quantitative analysis of wall thickening using gated SPECT with regard to the diagnostic accuracy of myocardial perfusion imaging., Materials and Methods: We prospectively included 70 patients with low prevalence of acute coronary artery disease who underwent a myocardial stress-rest SPECT study. Interpretation was based on supine nongated SPECT data with (AC) or without (NC) CT-based attenuation correction, and on gated SPECT data without attenuation correction (GNC). The scintigraphic diagnosis was obtained using standard automated quantitative analysis software and compared with a 23±14 months' clinical follow-up for 57 patients or with the results of a coronary angiography for 13 patients., Results: The sensitivity, specificity, and overall accuracy were, respectively, 77, 60, and 63% for NC SPECT, 67, 81, and 79% for AC SPECT, and 69, 98, and 93% for GNC SPECT. The initial diagnosis was modified in about one-third of the cases for both AC and GNC, this rate being independent of any clinical parameter (including BMI) except sex (two to four times more artifact correction in men)., Conclusion: Its widespread availability, cost effectiveness, safety in terms of radiation exposure, and ability to significantly improve myocardial perfusion imaging specificity and accuracy make gated SPECT a self-sufficient modality for coronary artery disease screening and follow-up, whereas CT-AC should be discussed on a case-by-case basis.

Purpose: A higher prevalence of cardiovascular risk factors (CRFs) in HIV-infected patients, together with chronic infection and treatments, has resulted in an increased risk of silent myocardial ischaemia (SMI). The objective of this study was to evaluate whether myocardial SPECT should be used for screening HIV-infected patients with no clinical symptoms of coronary artery disease., Methods: The prevalence of SMI detected by myocardial SPECT was determined in 94 HIV-infected patients with a normal clinical cardiovascular examination in relation to anthropomorphic parameters, CRFs, inflammatory and HIV infection status, and treatment., Results: Coronary artery disease was detected in nine patients (eight with ischaemia, one with myocardial infarction), corresponding to 9.6 % positivity. All but two of the scintigraphic diagnoses of ischaemia were confirmed by coronarography. Univariate analysis revealed that the overall number of CRFs and the combination of gender and age were associated with a diagnosis of SMI (p < 0.05). According to multivariate analysis, the only independent parameter significantly associated with the scintigraphic diagnosis of SMI was the combination of gender and age (p = 0.01). All the positive myocardial SPECT scans were in men older than 52 years with at least two other CRFs. In this subpopulation of 47 patients, the prevalence of SMI detected by myocardial SPECT reached 19.2 %., Conclusion: In male HIV-infected patients older than 52 years and with at least two other CRFs, screening for SMI using myocardial SPECT was about four times more likely to be positive than in the general population. This may motivate physicians to advise these patients to undergo more systematic screening for SMI using this technique.