SARS-CoV-2 infection predicts larger infarct volume in patients with acute ischemic stroke

Background and purpose: Acute ischemic stroke (AIS) is a fearful complication of Coronavirus Disease-2019 (COVID-19). Aims of this study were to compare clinical/radiological characteristics, endothelial and coagulation dysfunction between acute ischemic stroke (AIS) patients with and without COVID-19 and to investigate if and how the SARS-CoV-2 spike protein (SP) was implicated in triggering platelet activation. Methods: We enrolled AIS patients with COVID-19 within 12 h from onset and compared them with an age- and sex-matched cohort of AIS controls without COVID-19. Neuroimaging studies were performed within 24 h. Blood samples were collected in a subset of 10 patients. Results: Of 39 AIS patients, 22 had COVID-19 and 17 did not. Admission levels of Factor VIII and von Willebrand factor antigen were significantly higher in COVID-19 patients and positively correlated with the infarct volume. In multivariate linear regression analyses, COVID-19 was an independent predictor of infarct volume (B 20.318, Beta 0.576, 95%CI 6.077-34.559; p = 0.011). SP was found in serum of 2 of the 10 examined COVID-19 patients. Platelets from healthy donors showed a similar degree of procoagulant activation induced by COVID-19 and non-COVID-19 patients' sera. The anti-SP and anti-FcγRIIA blocking antibodies had no effect in modulating platelet activity in both groups. Conclusions: SARS-CoV-2 infection seems to play a major role in endothelium activation and infarct volume extension during AIS

A through-life costing methodology for use in product-service-systems

Availability-based contracts which provide customers with the use of assets such as machines, ships, aircraft platforms or subsystems like engines and avionics are increasingly offered as an alternative to the purchase of an asset and separate support contracts. The cost of servicing a durable product can be addressed by Through-life Costing (TLC). Providers of advanced services are now concerned with the cost of delivering outcomes that meet customer requirements using combinations of assets and activities via a Product Service System (PSS). This paper addresses the question: To what extent are the current approaches to TLC methodologically appropriate for costing the provision of advanced services, particularly availability, through a PSS? A novel methodology for TLC is outlined addressing the challenges of PSS cost assessment with regard to 'what?' (cost object), 'why/to what extent?' (scope and boundaries), and 'how?' (computations). The research provides clarity for those seeking to cost availability in a performance-orientated contractual setting and provides insight to the measures that may be associated with it. In particular, a reductionist approach that focuses on one cost object at a time is not appropriate for a PSS. Costing an advanced service delivered through a PSS is a problem of attributing the value of means to the economic activities carried out for specific ends to be achieved. Cost results from the interplay between monetary and non-monetary metrics, and uncertainties thereof. Whilst seeking to ensure generality of the findings, the application of TLC examined here is limited to a military aircraft platform and subsystems. © 2014 Elsevier B.V. All rights reserved

The AGILE Mission

AGILE is an Italian Space Agency mission dedicated to observing the gamma-ray Universe. The AGILE's very innovative instrumentation for the first time combines a gamma-ray imager (sensitive in the energy range 30 MeV-50 GeV), a hard X-ray imager (sensitive in the range 18-60 keV), a calorimeter (sensitive in the range 350 keV-100 MeV), and an anticoincidence system. AGILE was successfully launched on 2007 April 23 from the Indian base of Sriharikota and was inserted in an equatorial orbit with very low particle background. Aims. AGILE provides crucial data for the study of active galactic nuclei, gamma-ray bursts, pulsars, unidentified gamma-ray sources, galactic compact objects, supernova remnants, TeV sources, and fundamental physics by microsecond timing. Methods. An optimal sky angular positioning (reaching 0.1 degrees in gamma- rays and 1-2 arcmin in hard X-rays) and very large fields of view (2.5 sr and 1 sr, respectively) are obtained by the use of Silicon detectors integrated in a very compact instrument. Results. AGILE surveyed the gamma- ray sky and detected many Galactic and extragalactic sources during the first months of observations. Particular emphasis is given to multifrequency observation programs of extragalactic and galactic objects. Conclusions. AGILE is a successful high-energy gamma-ray mission that reached its nominal scientific performance. The AGILE Cycle-1 pointing program started on 2007 December 1, and is open to the international community through a Guest Observer Program

The FLUXNET2015 dataset and the ONEFlux processing pipeline for eddy covariance data

The FLUXNET2015 dataset provides ecosystem-scale data on CO2, water, and energy exchange between the biosphere and the atmosphere, and other meteorological and biological measurements, from 212 sites around the globe (over 1500 site-years, up to and including year 2014). These sites, independently managed and operated, voluntarily contributed their data to create global datasets. Data were quality controlled and processed using uniform methods, to improve consistency and intercomparability across sites. The dataset is already being used in a number of applications, including ecophysiology studies, remote sensing studies, and development of ecosystem and Earth system models. FLUXNET2015 includes derived-data products, such as gap-filled time series, ecosystem respiration and photosynthetic uptake estimates, estimation of uncertainties, and metadata about the measurements, presented for the first time in this paper. In addition, 206 of these sites are for the first time distributed under a Creative Commons (CC-BY 4.0) license. This paper details this enhanced dataset and the processing methods, now made available as open-source codes, making the dataset more accessible, transparent, and reproducible.Peer reviewe

Study of the B−→Λc+Λˉc−K−B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} decay

The decay $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ is studied in proton-proton collisions at a center-of-mass energy of $\sqrt{s}=13$ TeV using data corresponding to an integrated luminosity of 5 $\mathrm{fb}^{-1}$ collected by the LHCb experiment. In the $\Lambda_{c}^+ K^{-}$ system, the $\Xi_{c}(2930)^{0}$ state observed at the BaBar and Belle experiments is resolved into two narrower states, $\Xi_{c}(2923)^{0}$ and $\Xi_{c}(2939)^{0}$, whose masses and widths are measured to be $$m(\Xi_{c}(2923)^{0}) = 2924.5 \pm 0.4 \pm 1.1 \,\mathrm{MeV}, \\ m(\Xi_{c}(2939)^{0}) = 2938.5 \pm 0.9 \pm 2.3 \,\mathrm{MeV}, \\ \Gamma(\Xi_{c}(2923)^{0}) = \phantom{000}4.8 \pm 0.9 \pm 1.5 \,\mathrm{MeV},\\ \Gamma(\Xi_{c}(2939)^{0}) = \phantom{00}11.0 \pm 1.9 \pm 7.5 \,\mathrm{MeV},$$ where the first uncertainties are statistical and the second systematic. The results are consistent with a previous LHCb measurement using a prompt $\Lambda_{c}^{+} K^{-}$ sample. Evidence of a new $\Xi_{c}(2880)^{0}$ state is found with a local significance of $3.8\,\sigma$, whose mass and width are measured to be $2881.8 \pm 3.1 \pm 8.5\,\mathrm{MeV}$ and $12.4 \pm 5.3 \pm 5.8 \,\mathrm{MeV}$, respectively. In addition, evidence of a new decay mode $\Xi_{c}(2790)^{0} \to \Lambda_{c}^{+} K^{-}$ is found with a significance of $3.7\,\sigma$. The relative branching fraction of $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ with respect to the $B^{-} \to D^{+} D^{-} K^{-}$ decay is measured to be $2.36 \pm 0.11 \pm 0.22 \pm 0.25$, where the first uncertainty is statistical, the second systematic and the third originates from the branching fractions of charm hadron decays.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-028.html (LHCb public pages

Measurement of the ratios of branching fractions R(D∗)\mathcal{R}(D^{*}) and R(D0)\mathcal{R}(D^{0})

The ratios of branching fractions $\mathcal{R}(D^{*})\equiv\mathcal{B}(\bar{B}\to D^{*}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(\bar{B}\to D^{*}\mu^{-}\bar{\nu}_{\mu})$ and $\mathcal{R}(D^{0})\equiv\mathcal{B}(B^{-}\to D^{0}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(B^{-}\to D^{0}\mu^{-}\bar{\nu}_{\mu})$ are measured, assuming isospin symmetry, using a sample of proton-proton collision data corresponding to 3.0 fb${ }^{-1}$ of integrated luminosity recorded by the LHCb experiment during 2011 and 2012. The tau lepton is identified in the decay mode $\tau^{-}\to\mu^{-}\nu_{\tau}\bar{\nu}_{\mu}$. The measured values are $\mathcal{R}(D^{*})=0.281\pm0.018\pm0.024$ and $\mathcal{R}(D^{0})=0.441\pm0.060\pm0.066$, where the first uncertainty is statistical and the second is systematic. The correlation between these measurements is $\rho=-0.43$. Results are consistent with the current average of these quantities and are at a combined 1.9 standard deviations from the predictions based on lepton flavor universality in the Standard Model.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-039.html (LHCb public pages

Valutazione angiografica e ruolo di endotelina-1 ed ossido nitrico nel no-reflow phenomenon in pazienti con ictus ischemico acuto da occlusione dei grossi vasi trattati con successo con trombectomia meccanica

Background. Futile recanalization (FR), defined as a 90-day mRS 3-6 despite successful recanalization, account for 29% to 60% of large vessel occlusion (LVO) acute ischemic stroke (AIS) treated with mechanical thrombectomy (MT). Failure of early neurological improvement (fENI) describes patients successfully recanalized but not clinically improving at 24-hours or at 7-days. No-reflow phenomenon (NRP) is a possible cause of FR and fENI, described in animal models and myocardial infarction as deficient microvascular reperfusion. Evidence of NRP in AIS patients is scarce. Proposed determinants of NRP include vasoactive agents such as Endothelin-1 (ET-1) and Nitric oxide (NO), possibly involved in microvascular disfunction of NRP. Aim of our research was to define NRP in AIS from LVO of the anterior circulation treated with MT with successful recanalization. STUDY 1. Methods. We retrospectively analyzed 185 post-interventional digital subtraction angiographies (DSA) of anterior circulation LVO AIS patients treated with MT. We created a score, called modified capillary index score (mCIS), dividing middle cerebral artery territory in three segments. For each segment we gave 2 points if the capillary blush was present without any delay, 1 if delayed and 0 if absent. We used ROC curve to define mCIS≤3 as cut-off and marker of NRP. The primary endpoint was to identify a marker of NRP on post interventional DSA and to test whether this marker may predict FR and fENI. Secondary endpoint was to search a correlation between NRP, lesion volume and hemorrhagic transformation. Results. NRP was present in 35.1% of patients. NRP predicted fENI at 24h (aOR2.617, 95%CI1.192–5.745, p=0.016) and at 7 days (aOR4.601, 95%CI1.636–12.936, p=0.004), but not FR. Moreover, NRP predicted hemorrhagic transformation (aOR2.444, 95%CI 1.266–4.717, p=0.008). Discussion. NRP is poorly investigated in AIS. We identified an angiographic score able to identify NRP in AIS patients. Our angiographic marker was able to predict early outcome and hemorrhagic transformation of the ischemic lesion. STUDY 2. Methods. We prospectively enrolled 61 patients with AIS from LVO of the anterior circulation, successfully treated with MT. Patients were divided in groups according to the presence of NRP, as defined in study1. Peripheral venous blood samples were taken to dose ET-1 and NO at admission, after 24 and 48 hours. When technically possible, intracranial arterial blood samples, before and after recanalization, were taken. Primary endpoint was to test the association between ET-1 and NO levels and NRP. Secondary endpoint was to explore the association between ET-1 and NO levels and clinical outcome. Results. NRP Patients showed lower pre-MT intracranial levels of NO (9.60 µM ±2.80 vs 18.58 µM ±5.92, p=0.004) but the association was not confirmed at logistic regression (aOR0.561, 95%CI 0.297–1.061, p=0.075). Mean peripheral NO levels at 48 hours were 20.46 µM ±7.08 in the NRP group and 14.00 µM ± 8.06 in the no-NRP group (p=0.084). fENI at 24h was associated to lower serum NO levels at 24h (aOR1.19, 95%CI 1.014–1.213, p=0.023). Discussion. Our study tried to explore the role of ET-1 and NO in NRP. The trend to lower pre-MT levels of NO, might be the consequence of a reduced activity of the endothelial isoform of nitric oxide synthase (NOS). The increased values of NO at 24h in NRP patients might be due to the activation of the neuronal NOS. NO rather than ET-1 seems to have a major role in NRP. Conclusion. Reperfusion of main arteries in AIS from LVO is not always sufficient to ensure clinical improvement, a possible cause might be deficient microvascular reperfusion. We identified a marker of NRP in AIS patients, which could represent a useful tool to study this poorly recognized condition. Furthermore, we outlined a possible role of NO in NRP. Our data may contribute to future research studying NRP pathophysiology and possibly treatment.Background. Futile recanalization (FR), defined as a 90-day mRS 3-6 despite successful recanalization, account for 29% to 60% of large vessel occlusion (LVO) acute ischemic stroke (AIS) treated with mechanical thrombectomy (MT). Failure of early neurological improvement (fENI) describes patients successfully recanalized but not clinically improving at 24-hours or at 7-days. No-reflow phenomenon (NRP) is a possible cause of FR and fENI, described in animal models and myocardial infarction as deficient microvascular reperfusion. Evidence of NRP in AIS patients is scarce. Proposed determinants of NRP include vasoactive agents such as Endothelin-1 (ET-1) and Nitric oxide (NO), possibly involved in microvascular disfunction of NRP. Aim of our research was to define NRP in AIS from LVO of the anterior circulation treated with MT with successful recanalization. STUDY 1. Methods. We retrospectively analyzed 185 post-interventional digital subtraction angiographies (DSA) of anterior circulation LVO AIS patients treated with MT. We created a score, called modified capillary index score (mCIS), dividing middle cerebral artery territory in three segments. For each segment we gave 2 points if the capillary blush was present without any delay, 1 if delayed and 0 if absent. We used ROC curve to define mCIS≤3 as cut-off and marker of NRP. The primary endpoint was to identify a marker of NRP on post interventional DSA and to test whether this marker may predict FR and fENI. Secondary endpoint was to search a correlation between NRP, lesion volume and hemorrhagic transformation. Results. NRP was present in 35.1% of patients. NRP predicted fENI at 24h (aOR2.617, 95%CI1.192–5.745, p=0.016) and at 7 days (aOR4.601, 95%CI1.636–12.936, p=0.004), but not FR. Moreover, NRP predicted hemorrhagic transformation (aOR2.444, 95%CI 1.266–4.717, p=0.008). Discussion. NRP is poorly investigated in AIS. We identified an angiographic score able to identify NRP in AIS patients. Our angiographic marker was able to predict early outcome and hemorrhagic transformation of the ischemic lesion. STUDY 2. Methods. We prospectively enrolled 61 patients with AIS from LVO of the anterior circulation, successfully treated with MT. Patients were divided in groups according to the presence of NRP, as defined in study1. Peripheral venous blood samples were taken to dose ET-1 and NO at admission, after 24 and 48 hours. When technically possible, intracranial arterial blood samples, before and after recanalization, were taken. Primary endpoint was to test the association between ET-1 and NO levels and NRP. Secondary endpoint was to explore the association between ET-1 and NO levels and clinical outcome. Results. NRP Patients showed lower pre-MT intracranial levels of NO (9.60 µM ±2.80 vs 18.58 µM ±5.92, p=0.004) but the association was not confirmed at logistic regression (aOR0.561, 95%CI 0.297–1.061, p=0.075). Mean peripheral NO levels at 48 hours were 20.46 µM ±7.08 in the NRP group and 14.00 µM ± 8.06 in the no-NRP group (p=0.084). fENI at 24h was associated to lower serum NO levels at 24h (aOR1.19, 95%CI 1.014–1.213, p=0.023). Discussion. Our study tried to explore the role of ET-1 and NO in NRP. The trend to lower pre-MT levels of NO, might be the consequence of a reduced activity of the endothelial isoform of nitric oxide synthase (NOS). The increased values of NO at 24h in NRP patients might be due to the activation of the neuronal NOS. NO rather than ET-1 seems to have a major role in NRP. Conclusion. Reperfusion of main arteries in AIS from LVO is not always sufficient to ensure clinical improvement, a possible cause might be deficient microvascular reperfusion. We identified a marker of NRP in AIS patients, which could represent a useful tool to study this poorly recognized condition. Furthermore, we outlined a possible role of NO in NRP. Our data may contribute to future research studying NRP pathophysiology and possibly treatment

Emergenze e urgenze medico-chirurgiche. Sintomo diagnosi terapia

Chi esercita la propria attività in area di emergenza, sia ospedaliera sia territoriale, necessita di un continuo aggiornamento e di un supporto nelle scelte cliniche e organizzative. Oggi è sempre maggiore la richiesta di interventi non solo efficaci, ma anche appropriati ed efficienti; il tema dell'organizzazione, dei tempi, delle modalità e della sicurezza di erogazione delle cure, è quindi cruciale anche per i risvolti medico-legali e alla luce delle più recenti disposizioni normative. Il volume concilia l'autorevolezza della letteratura internazionale più recente - le ultime linee guida, le buone pratiche clinico-assistenziali e le raccomandazioni basate sulle evidenze scientifiche - con la praticità dei manuali professionali. Numerose procedure vengono infatti spiegante nel dettaglio tra cui i blocchi nervosi regionali, le tecniche di sutura e gli accessi venosi centrale e periferici. Grande spazio è dedicato alla gestione avanzata delle vie aeree, con la toracentesi, la rachicentesi e la pericardiocentesi. Tutti i medici che lavorano nell'area dell'emergenza e urgenza avranno in questo testo un riferimento per l'approccio diagnostico-terapeutico e la gestione clinica del paziente acuto