Due to early implementation of public health measures, Greece had low number of SARS-CoV-2 infections and COVID-19 severe incidents in hospitalized patients. The National and Kapodistrian University ...of Athens (ΝΚUA), especially its health-care/medical personnel, has been actively involved in the first line of state responses to COVID-19. To estimate the prevalence of antibodies (Igs) against SARS-CoV-2 among NKUA members, we designed a five consecutive monthly serosurvey among randomly selected NKUA consenting volunteers. Here, we present the results from the first 2500 plasma samples collected during June–July 2020. Twenty-five donors were tested positive for anti-SARS-CoV-2 Igs; thus, the overall seroprevalence was 1.00%. The weighted overall seroprevalence was 0.93% (95% CI: 0.27, 2.09) and varied between males 1.05% (95% CI: 0.18, 2.92) and females 0.84% (95% CI: 0.13, 2.49), age-groups and different categories (higher in participants from the School of Health Sciences and in scientific affiliates/faculty members/laboratory assistants), but no statistical differences were detected. Although focused on the specific population of NKUA members, our study shows that the prevalence of anti-SARS-CoV-2 Igs for the period June–July 2020 remained low and provides knowledge of public health importance for the NKUA members. Given that approximately one in three infections was asymptomatic, continuous monitoring of the progression of the pandemic by assessing Ig seroprevalence is needed.
Between June and November 2020, we assessed plasma antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein in 4996 participants (aged 18-82 years, 34.5% ...men) from the National and Kapodistrian University of Athens. The weighted overall prevalence was 1.6% and monthly prevalence correlated with viral RNA-confirmed SARS-CoV-2 infections in Greece, in the same period. Notably, 49% of seropositive cases reported no history of SARS-CoV-2 infection-related clinical symptoms and 33% were unsuspected of their previous infection. Additionally, levels of anti-SARS-CoV-2 antibodies against the spike-protein receptor-binding domain were similar between symptomatic and asymptomatic individuals, irrespective of age and gender. Using Food and Drug Administration Emergency Use Authorization-approved assays, these results support the need for such studies on pandemic evaluation and highlight the development of robust humoral immune responses even among asymptomatic individuals. The high percentage of unsuspected/asymptomatic active cases, which may contribute to community transmission for more days than that of cases who are aware and self-isolate, underscores the necessity of measures across the population for the efficient control of the pandemic.
Carfilzomib (CFZ) is a proteasome inhibitor associated with cardiovascular (CV) adverse events (AEs) mainly hypertension (HTN) and cardiac dysfunction. Endothelial dysfunction is a major mediating ...mechanism in cardiovascular diseases and endothelial function may be adversely affected by proteasome inhibition. However, CFZ effects on endothelial and vascular function and associations with inhibition of proteasome activity have not been explored in humans. We prospectively evaluated CFZ effects on endothelial function and underlying mechanisms as well as baseline vascular function and its response to treatment as potential predictors of CFZ-associated CV toxicity.
In this prospective study (NCT03543579), 48 relapsed/refractory myeloma patients (median 1 (1-3) lines of therapy, median age: 67.5, 67% men) received Kd CFZ 20/56 mg/m2 and dexamethasone in routine practice. A detailed medical history and evaluation of risk factors for cardiotoxicity age≥65 years, obesity, smoking, HTN, hypercholesterolemia, diabetes mellitus, previous anthracyclin use, chest or mediastinum radiotherapy and current myocardial disease were recorded. Before CFZ start and at prespecified timepoints cardiac echo, hemodynamic parameters and vascular function that reflect pivotal mechanisms involved in development of HTN and CV events were non-invasively assessed aortic blood pressure and arterial wave reflections, aortic stiffness and endothelial function using flow-mediated dilatation of the brachial artery (FMD) along with 24h ambulatory blood pressure monitoring. Proteasome activity (PrA) was measured in peripheral blood mononuclear cells (PBMC) before and 2 hours post CFZ infusion on days 1 (FMDbaseD1 and FMDpostCFZD1) and 2 (FMDbaseD2 and FMDpostCFZD2) of cycle 1 and at prespecified time points concurrently with vascular function assessment. CV AEs were recorded and rated according to CTCAE v4.03.
The prevalence of risk factors for cardiotoxicity was high (median 3 factors, IQR 2-4). After first CFZ dose, FMD decreased acutely at 2 hours (FMDbaseD1: 5.2%, IQR: 3.2-7.4 vs FMDpostCFZD1: 3.6%, IQR: 1.5-4.7, p=0.008), which partially recovered before and after second CFZ infusion (FMDbaseD2: 4.1% and FMDpostCFZD2: 4%, as compared to FMDbaseD1) (Figure1A). However, FMD decrease was more pronounced among patients who subsequently had lower recovery rate of PBMC PrA 24 hours after first CFZ administration (FMDbaseD1: 5.1%, vs FMDpostCFZD1: 3%, p=0.002) while FMD was not decreased significantly in those who had higher recovery rates of PrA (FMDbaseD1: 5.3%, vs FMDpost CFZD1: 4.5%, p=0.197, Figure 1B), suggesting that the ability to recover PrA is implicated in CFZ induced endothelial dysfunction.
At the time of analysis, enrolment has completed; 35 patients are still receiving therapy, 13 have discontinued Kd and median follow up is 4.73 months. CV AEs were recorded in 17 (35.4%) patients HTN(Gr3): 20.8%, Gr3 Left Ventricular dysfunction : 8.3%, Gr3 acute coronary syndrome: 4.2%, Gr3 pulmonary embolism: 2.1% and generally occurred early (median time to CV event 2.9 months). Kd was discontinued in 2 patients (4.2%) due to cardiotoxicity and in 2 patients (4.2%) CFZ dose was reduced due to cardiotoxicity; no CFZ dose reduction or discontinuation was needed for HTN.
Among clinical and hemodynamic parameters assessed at baseline, patients with higher aortic SBP (i.e at higher quartile) had a higher risk of HTN even after adjustment for age, gender and baseline HTN (HR=8, 95%CI 2.4-26, p=0.001 and HR=4.9, 95%CI 1.5-15, p=0.007 respectively). Lower PrA recovery rate was associated with increased risk of developing Gr3 HTN (log-rank test p=0.01). Higher post-CFZ reduction of FMD was associated with HTN in patients not receiving statins but not in those receiving statins (a drug class strongly affecting FMD), indicating that statin treatment may exert protective effects against CFZ-related CV toxicity.
In conclusion, CFZ causes acute endothelial dysfunction; however, higher recovery of proteasome activity is associated with ameliorated depression of endothelial function. Given that poor proteasome recovery rate and acute deterioration of endothelial function are both associated with development of HTN, these findings may improve our understanding of CFZ-related CV toxicity and its prevention. The study is ongoing and more data will be presented at the meeting.
Kastritis:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Prothena: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Terpos:Amgen Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grant, steering committee member, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: member of DMC, Research Funding; Genesis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grant, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: member of steering committee, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grant, Research Funding; BMS: Consultancy; Novartis: Consultancy. Dimopoulos:Bristol-Myers Squibb: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Janssen: Honoraria.
Acoustics has received a great research interest for human activity detection in indoor and outdoor environments. Compared to vision-based approaches, microphones can achieve a high percentage of ...recognition accuracy in a variety of activities, while not being affected by lighting conditions. Furthermore, audio-based activity detection can be considered an unobtrusive method, as long as the data is not related to speech or other sensitive information and no data is sent on cloud. Selecting the appropriate audio features that can achieve a high recognition accuracy and generalize in multiple domestic environments is a challenging task. In this work, three of the most commonly used spectrogram representations are evaluated, based on their spectral magnitude and the spectral energies. Specifically, using multi-channel audio data, the Short-time Fourier Transform (STFT), the Mel and the Gammatone spectrograms are extracted and trained on a 2D Convolutional Neural Network (CNN). The F1-Scores of each feature representation are computed, while the McNemar tests and the Receiver Operating Characteristic (ROC) curves ensure the statistical independence between the magnitude and the energy representations. Extensive experimental results on a public database for detection of daily activities in a home environment, show that the overall highest recognition accuracy is achieved by the STFT magnitude representations.
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