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1.
Eur J Immunol ; 2022 Jun 10.
Article in English | MEDLINE | ID: covidwho-1885394

ABSTRACT

We used unsupervised immunophenotyping of blood leukocytes and measured cytokine production by innate immune cell exposed to LPS and R848. We show that COVID-19 induces a rapid, transient upregulation of myeloid-derived suppressor cells (MDSCs) accompanied by a rapid, sustained (up to 3 months) hyporesponsiveness of dendritic cells and monocytes. Blood MDSCs may represent biomarkers and targets for intervention strategies in COVID-19 patients.

2.
Biomedicines ; 10(6)2022 Jun 02.
Article in English | MEDLINE | ID: covidwho-1883993

ABSTRACT

BACKGROUND: Vascular abnormalities, including venous congestion (VC) and pulmonary embolism (PE), have been recognized as frequent COVID-19 imaging patterns and proposed as severity markers. However, the underlying pathophysiological mechanisms remain unclear. In this study, we aimed to characterize the relationship between VC, PE distribution, and alveolar opacities (AO). METHODS: This multicenter observational registry (clinicaltrials.gov identifier NCT04824313) included 268 patients diagnosed with SARS-CoV-2 infection and subjected to contrast-enhanced CT between March and June 2020. Acute PE was diagnosed in 61 (22.8%) patients, including 17 females (27.9%), at a mean age of 61.7 ± 14.2 years. Demographic, laboratory, and outcome data were retrieved. We analyzed CT images at the segmental level regarding VC (qualitatively and quantitatively [diameter]), AO (semi-quantitatively as absent, <50%, or >50% involvement), clot location, and distribution related to VC and AO. Segments with vs. without PE were compared. RESULTS: Out of 411 emboli, 82 (20%) were lobar or more proximal and 329 (80%) were segmental or subsegmental. Venous diameters were significantly higher in segments with AO (p = 0.031), unlike arteries (p = 0.138). At the segmental level, 77% of emboli were associated with VC. Overall, PE occurred in 28.2% of segments with AO vs. 21.8% without (p = 0.047). In the absence of VC, however, AO did not affect PE rates (p = 0.94). CONCLUSIONS: Vascular changes predominantly affected veins, and most PEs were located in segments with VC. In the absence of VC, AOs were not associated with the PE rate. VC might result from increased flow supported by the hypothesis of pulmonary arteriovenous anastomosis dysregulation as a relevant contributing factor.

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-323348

ABSTRACT

Background: Need for catecholamines is frequent in COVID-19 patients, but the main echocardiographic patterns are unknown. The objective was to report the main echo patterns in critically-ill COVID-19 patients. Methods: Observational and descriptive study in consecutive COVID-19 patients admitted to the ICU between March 12 and May 8, 2020. Systematic critical care echocardiography (CCE) was performed and retrospectively analyzed off-line. Echo values are reported in the overall population and in patients who required catecholamine infusion during the first 2 days following admission (D 1-2 ) or afterwards until day 7 (D 3-7 ). Results: Of the 79 patients (78% male;median age 63 [56-71];body mass index 29 [26-30]) included, 90% had at least 1 comorbidity. PaO 2 /FiO 2 at admission was 85 [67-162] mmHg. 53% of patients were mechanically ventilated. ICU length of stay was 9 [5-16] days and mortality 34%. 134 echocardiographic studies were performed during the first week in 65 patients. Pulmonary artery acceleration time was decreased (77 [65-97] ms), suggesting pulmonary hypertension. All 39 patients (49%) who required catecholamine infusion underwent CCE and 25.6% had left ventricular (LV) systolic dysfunction, 28.2% acute cor pulmonale (ACP), 7.7% hypovolemia, and 38.5% vasoplegia. Modification of echo patterns was observed at D 3-7 , with less LV systolic dysfunction and more ACP, which was the most frequent pattern. Computed tomography pulmonary angiography in 6 patients with ACP indicated intrapulmonary thrombus in 4. Conclusion: Different echocardiographic patterns were observed during the first week following ICU admission in COVID-19 patients. ACP was frequent and often related to thrombus in the pulmonary circulation.

6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-317956

ABSTRACT

Testing is a crucial control mechanism in the beginning phase of an epidemic when the vaccines are not yet available. It enables the public health authority to detect and isolate the infected cases from the population, thereby limiting the disease transmission to susceptible people. However, despite the significance of testing in epidemic control, the recent literature on the subject lacks a control-theoretic perspective. In this paper, an epidemic model is proposed that incorporates the testing rate as a control input and differentiates the undetected infected from the detected infected cases, who are assumed to be removed from the disease spreading process in the population. After estimating the model on the data corresponding to the beginning phase of COVID-19 in France, two testing policies are proposed: the so-called best-effort strategy for testing (BEST) and constant optimal strategy for testing (COST). The BEST policy is a suppression strategy that provides a minimum testing rate that stops the growth of the epidemic when implemented. The COST policy, on the other hand, is a mitigation strategy that provides an optimal value of testing rate minimizing the peak value of the infected population when the total stockpile of tests is limited. Both testing policies are evaluated by their impact on the number of active intensive care unit (ICU) cases and the cumulative number of deaths for the COVID-19 case of France.

7.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-307032

ABSTRACT

Until a vaccine or therapy is found against the SARS-CoV-2 coronavirus, reaching herd immunity appears to be the only mid-term option. However, if the number of infected individuals decreases and eventually fades only beyond this threshold, a significant proportion of susceptible may still be infected until the epidemic is over. A containment strategy is likely the best policy in the worst case where no vaccine or therapy is found. In order to keep the number of newly infected persons to a minimum, a possible strategy is to apply strict containment measures, so that the number of susceptible individuals remains close to herd immunity. Such an action is unrealistic since containment can only last for a finite amount of time and is never total. In this article, using a classical SIR model, we determine the (partial or total) containment strategy on a given finite time interval that maximizes the number of susceptible individuals over an infinite horizon, or equivalently that minimizes the total infection burden during the curse of the epidemic. The existence and uniqueness of the optimal strategy is proved and the latter is fully characterized. If applicable in practice, such a strategy would lead theoretically to an increase by 30% of the proportion of susceptible on an infinite horizon, for a containment level corresponding to the sanitary measures put in place in France from March to May 2020. We also analyze the minimum intervention time to reach a fixed distance from herd immunity, and show the relationship with the previous problem. Simulations are provided that illustrate and validate the theoretical results.

9.
Crit Care ; 26(1): 11, 2022 01 04.
Article in English | MEDLINE | ID: covidwho-1607559

ABSTRACT

BACKGROUND: Recent multicenter studies identified COVID-19 as a risk factor for invasive pulmonary aspergillosis (IPA). However, no large multicenter study has compared the incidence of IPA between COVID-19 and influenza patients. OBJECTIVES: To determine the incidence of putative IPA in critically ill SARS-CoV-2 patients, compared with influenza patients. METHODS: This study was a planned ancillary analysis of the coVAPid multicenter retrospective European cohort. Consecutive adult patients requiring invasive mechanical ventilation for > 48 h for SARS-CoV-2 pneumonia or influenza pneumonia were included. The 28-day cumulative incidence of putative IPA, based on Blot definition, was the primary outcome. IPA incidence was estimated using the Kalbfleisch and Prentice method, considering extubation (dead or alive) within 28 days as competing event. RESULTS: A total of 1047 patients were included (566 in the SARS-CoV-2 group and 481 in the influenza group). The incidence of putative IPA was lower in SARS-CoV-2 pneumonia group (14, 2.5%) than in influenza pneumonia group (29, 6%), adjusted cause-specific hazard ratio (cHR) 3.29 (95% CI 1.53-7.02, p = 0.0006). When putative IPA and Aspergillus respiratory tract colonization were combined, the incidence was also significantly lower in the SARS-CoV-2 group, as compared to influenza group (4.1% vs. 10.2%), adjusted cHR 3.21 (95% CI 1.88-5.46, p < 0.0001). In the whole study population, putative IPA was associated with significant increase in 28-day mortality rate, and length of ICU stay, compared with colonized patients, or those with no IPA or Aspergillus colonization. CONCLUSIONS: Overall, the incidence of putative IPA was low. Its incidence was significantly lower in patients with SARS-CoV-2 pneumonia than in those with influenza pneumonia. Clinical trial registration The study was registered at ClinicalTrials.gov, number NCT04359693 .


Subject(s)
COVID-19 , Influenza, Human , Intubation , Invasive Pulmonary Aspergillosis , Adult , COVID-19/epidemiology , COVID-19/therapy , Europe/epidemiology , Humans , Incidence , Influenza, Human/epidemiology , Influenza, Human/therapy , Invasive Pulmonary Aspergillosis/epidemiology , Retrospective Studies , SARS-CoV-2
10.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-295609

ABSTRACT

Testing is a crucial control mechanism for an epidemic outbreak because it enables the health authority to detect and isolate the infected cases, thereby limiting the disease transmission to susceptible people, when no effective treatment or vaccine is available. In this paper, an epidemic model that incorporates the testing rate as a control input is presented. The proposed model distinguishes between the undetected infected and the detected infected cases with the latter assumed to be isolated from the disease spreading process in the population. Two testing policies, effective during the onset of an epidemic when no treatment or vaccine is available, are devised: (i) best-effort strategy for testing (BEST) and (ii) constant optimal strategy for testing (COST). The BEST is a suppression policy that provides a lower bound on the testing rate to stop the growth of the epidemic. The COST is a mitigation policy that minimizes the peak of the epidemic by providing a constant, optimal allocation of tests in a certain time interval when the total stockpile of tests is limited. Both testing policies are evaluated by their impact on the number of active intensive care unit (ICU) cases and the cumulative number of deaths due to COVID-19 in France.

12.
Annu Rev Control ; 52: 554-572, 2021.
Article in English | MEDLINE | ID: covidwho-1525687

ABSTRACT

Testing is a crucial control mechanism in the beginning phase of an epidemic when the vaccines are not yet available. It enables the public health authority to detect and isolate the infected cases from the population, thereby limiting the disease transmission to susceptible people. However, despite the significance of testing in epidemic control, the recent literature on the subject lacks a control-theoretic perspective. In this paper, an epidemic model is proposed that incorporates the testing rate as a control input and differentiates the undetected infected from the detected infected cases, who are assumed to be removed from the disease spreading process in the population. After estimating the model on the data corresponding to the beginning phase of COVID-19 in France, two testing policies are proposed: the so-called best-effort strategy for testing (BEST) and constant optimal strategy for testing (COST). The BEST policy is a suppression strategy that provides a minimum testing rate that stops the growth of the epidemic when implemented. The COST policy, on the other hand, is a mitigation strategy that provides an optimal value of testing rate minimizing the peak value of the infected population when the total stockpile of tests is limited. Both testing policies are evaluated by their impact on the number of active intensive care unit (ICU) cases and the cumulative number of deaths for the COVID-19 case of France.

13.
Respir Care ; 67(2): 157-166, 2022 02.
Article in English | MEDLINE | ID: covidwho-1478295

ABSTRACT

BACKGROUND: Humidification of inspiratory gases is mandatory in all mechanically ventilated patients in ICUs, either with heated humidifiers (HHs) or with heat and moisture exchangers (HMEs). In patients with COVID-19, the choice of the humidification device may have relevant impact on patients' management as demonstrated in recent studies. We reported data from 2 ICUs using either HME or HH. METHODS: Data from patients with COVID-19 requiring invasive mechanical ventilation during the first wave in 2 ICUs in Québec City were reviewed. In one ICU, HMEs were used, whereas heated-wire HHs were used in the other ICU. We compared ventilator settings and arterial blood gases at day one after adjustment of ventilator settings. Episodes of endotracheal tube occlusions (ETOs) or subocclusions and a strategy to limit the risk of under-humidification were reported. On a bench test, we measured humidity with psychrometry with HH at different ambient temperature and evaluated the relation with heater plate temperature. RESULTS: We reported data from 20 subjects positive for SARS-Cov-2, including 6 in the ICU using HME and 14 in the ICU using HH. In the HME group, PaCO2 was higher (48 vs 42 mm Hg) despite higher minute ventilation (171 vs 145 mL/kg/min predicted body weight [PBW]). We also reported 3 ETOs occurring in the ICU using HH. The hygrometric bench study reported a strong correlation between heater plate temperatures of the HH and humidity delivered. After implementation of measures to avoid under-humidification, including heater plate temperature monitoring, no more ETOs occurred. CONCLUSIONS: The choice of the humidification device used in subjects with COVID-19 had a relevant impact on ventilation efficiency (increased CO2 removal with lower dead space) and on complications related to low humidity, including ETOs that may be present with heated-wire HHs when used with high ambient temperatures.


Subject(s)
COVID-19 , Respiration, Artificial , Hot Temperature , Humans , Humidifiers , Humidity , SARS-CoV-2
14.
Am J Respir Crit Care Med ; 2021 May 26.
Article in English | MEDLINE | ID: covidwho-1416749

ABSTRACT

RATIONALE: Early empirical antimicrobial treatment is frequently prescribed to critically ill patients with COVID-19, based on Surviving Sepsis Campaign guidelines. OBJECTIVE: We aimed to determine the prevalence of early bacterial identification in intubated patients with SARS-CoV-2 pneumonia, as compared to influenza pneumonia, and to characterize its microbiology and impact on outcomes. METHODS: Multicenter retrospective European cohort performed in 36 ICUs. All adult patients receiving invasive mechanical ventilation >48h were eligible if they had SARS-CoV-2 or influenza pneumonia at ICU admission. Bacterial identification was defined by a positive bacterial culture, within 48h after intubation, in endotracheal aspirates, bronchoalveolar lavage, blood cultures, or a positive pneumococcal or legionella urinary antigen test. MEASUREMENTS AND MAIN RESULTS: 1,050 patients were included (568 in SARS-CoV-2 and 482 in influenza groups). The prevalence of bacterial identification was significantly lower in patients with SARS-CoV-2 pneumonia as compared to patients with influenza pneumonia (9.7 vs 33.6%, unadjusted odds ratio (OR) 0.21 (95% confidence interval (CI) 0.15 to 0.30), adjusted OR 0.23 (95% CI 0.16 to 0.33), p<0.0001). Gram-positive cocci were responsible for 58% and 72% of co-infection in patients with SARS-CoV-2 and influenza pneumonia, respectively. Bacterial identification was associated with increased adjusted hazard ratio for 28-day mortality in patients with SARS-CoV-2 pneumonia (1.57 (95% CI 1.01 to 2.44), p=0.043). However, no significant difference was found in heterogeneity of outcomes related to bacterial identification between the two study groups, suggesting that the impact of co-infection on mortality was not different between SARS-CoV-2 and influenza patients. CONCLUSIONS: Bacterial identification within 48h after intubation is significantly less frequent in patients with SARS-CoV-2 pneumonia as compared to patients with influenza pneumonia. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

15.
Microorganisms ; 9(9)2021 Sep 09.
Article in English | MEDLINE | ID: covidwho-1410331

ABSTRACT

Saliva sampling could serve as an alternative non-invasive sample for SARS-CoV-2 diagnosis while rapid antigen tests (RATs) might help to mitigate the shortage of reagents sporadically encountered with RT-PCR. Thus, in the RESTART study we compared antigen and RT-PCR testing methods on nasopharyngeal (NP) swabs and salivary samples. We conducted a prospective observational study among COVID-19 hospitalized patients between 10 December 2020 and 1 February 2021. Paired saliva and NP samples were investigated by RT-PCR (Cobas 6800, Roche-Switzerland, Basel, Switzerland) and by two rapid antigen tests: One Step Immunoassay Exdia® COVID-19 Ag (Precision Biosensor, Daejeon, Korea) and Standard Q® COVID-19 Rapid Antigen Test (Roche-Switzerland). A total of 58 paired NP-saliva specimens were collected. A total of 32 of 58 (55%) patients were hospitalized in the intensive care unit, and the median duration of symptoms was 11 days (IQR 5-19). NP and salivary RT-PCR exhibited sensitivity of 98% and 69% respectively, whereas the specificity of these RT-PCRs assays was 100%. The NP RATs exhibited much lower diagnostic performance, with sensitivities of 35% and 41% for the Standard Q® and Exdia® assays, respectively, when a wet-swab approach was used (i.e., when the swab was diluted in the viral transport medium (VTM) before testing). The sensitivity of the dry-swab approach was slightly better (47%). These antigen tests exhibited very low sensitivity (4% and 8%) when applied to salivary swabs. Nasopharyngeal RT-PCR is the most accurate test for COVID-19 diagnosis in hospitalized patients. RT-PCR on salivary samples may be used when nasopharyngeal swabs are contraindicated. RATs are not appropriate for hospitalized patients.

16.
J Optim Theory Appl ; 189(2): 408-436, 2021.
Article in English | MEDLINE | ID: covidwho-1396392

ABSTRACT

The aim of this article is to understand how to apply partial or total containment to SIR epidemic model during a given finite time interval in order to minimize the epidemic final size, that is the cumulative number of cases infected during the complete course of an epidemic. The existence and uniqueness of an optimal strategy are proved for this infinite-horizon problem, and a full characterization of the solution is provided. The best policy consists in applying the maximal allowed social distancing effort until the end of the interval, starting at a date that is not always the closest date and may be found by a simple algorithm. Both theoretical results and numerical simulations demonstrate that it leads to a significant decrease in the epidemic final size. We show that in any case the optimal intervention has to begin before the number of susceptible cases has crossed the herd immunity level, and that its limit is always smaller than this threshold. This problem is also shown to be equivalent to the minimum containment time necessary to stop at a given distance after this threshold value.

17.
Intensive Care Med ; 47(2): 188-198, 2021 02.
Article in English | MEDLINE | ID: covidwho-1384370

ABSTRACT

PURPOSE: Although patients with SARS-CoV-2 infection have several risk factors for ventilator-associated lower respiratory tract infections (VA-LRTI), the reported incidence of hospital-acquired infections is low. We aimed to determine the relationship between SARS-CoV-2 pneumonia, as compared to influenza pneumonia or no viral infection, and the incidence of VA-LRTI. METHODS: Multicenter retrospective European cohort performed in 36 ICUs. All adult patients receiving invasive mechanical ventilation > 48 h were eligible if they had: SARS-CoV-2 pneumonia, influenza pneumonia, or no viral infection at ICU admission. VA-LRTI, including ventilator-associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP), were diagnosed using clinical, radiological and quantitative microbiological criteria. All VA-LRTI were prospectively identified, and chest-X rays were analyzed by at least two physicians. Cumulative incidence of first episodes of VA-LRTI was estimated using the Kalbfleisch and Prentice method, and compared using Fine-and Gray models. RESULTS: 1576 patients were included (568 in SARS-CoV-2, 482 in influenza, and 526 in no viral infection groups). VA-LRTI incidence was significantly higher in SARS-CoV-2 patients (287, 50.5%), as compared to influenza patients (146, 30.3%, adjusted sub hazard ratio (sHR) 1.60 (95% confidence interval (CI) 1.26 to 2.04)) or patients with no viral infection (133, 25.3%, adjusted sHR 1.7 (95% CI 1.2 to 2.39)). Gram-negative bacilli were responsible for a large proportion (82% to 89.7%) of VA-LRTI, mainly Pseudomonas aeruginosa, Enterobacter spp., and Klebsiella spp. CONCLUSIONS: The incidence of VA-LRTI is significantly higher in patients with SARS-CoV-2 infection, as compared to patients with influenza pneumonia, or no viral infection after statistical adjustment, but residual confounding may still play a role in the effect estimates.


Subject(s)
COVID-19 , Pneumonia, Ventilator-Associated , Respiratory Tract Infections , Aged , COVID-19/epidemiology , Europe , Female , Humans , Incidence , Influenza, Human/epidemiology , Male , Middle Aged , Pneumonia, Ventilator-Associated/epidemiology , Respiratory Tract Infections/epidemiology , Retrospective Studies , Ventilators, Mechanical
19.
Front Public Health ; 9: 695139, 2021.
Article in English | MEDLINE | ID: covidwho-1359259

ABSTRACT

SARS-CoV-2 started spreading toward the end of 2019 causing COVID-19, a disease that reached pandemic proportions among the human population within months. The reasons for the spectrum of differences in the severity of the disease across the population, and in particular why the disease affects more severely the aging population and those with specific preconditions are unclear. We developed machine learning models to mine 240,000 scientific articles openly accessible in the CORD-19 database, and constructed knowledge graphs to synthesize the extracted information and navigate the collective knowledge in an attempt to search for a potential common underlying reason for disease severity. The machine-driven framework we developed repeatedly pointed to elevated blood glucose as a key facilitator in the progression of COVID-19. Indeed, when we systematically retraced the steps of the SARS-CoV-2 infection, we found evidence linking elevated glucose to each major step of the life-cycle of the virus, progression of the disease, and presentation of symptoms. Specifically, elevations of glucose provide ideal conditions for the virus to evade and weaken the first level of the immune defense system in the lungs, gain access to deep alveolar cells, bind to the ACE2 receptor and enter the pulmonary cells, accelerate replication of the virus within cells increasing cell death and inducing an pulmonary inflammatory response, which overwhelms an already weakened innate immune system to trigger an avalanche of systemic infections, inflammation and cell damage, a cytokine storm and thrombotic events. We tested the feasibility of the hypothesis by manually reviewing the literature referenced by the machine-generated synthesis, reconstructing atomistically the virus at the surface of the pulmonary airways, and performing quantitative computational modeling of the effects of glucose levels on the infection process. We conclude that elevation in glucose levels can facilitate the progression of the disease through multiple mechanisms and can explain much of the differences in disease severity seen across the population. The study provides diagnostic considerations, new areas of research and potential treatments, and cautions on treatment strategies and critical care conditions that induce elevations in blood glucose levels.


Subject(s)
COVID-19 , Aged , Blood Glucose , Cytokine Release Syndrome , Humans , Inflammation , SARS-CoV-2
20.
Crit Care ; 25(1): 177, 2021 05 25.
Article in English | MEDLINE | ID: covidwho-1352667

ABSTRACT

BACKGROUND: Patients with SARS-CoV-2 infection are at higher risk for ventilator-associated pneumonia (VAP). No study has evaluated the relationship between VAP and mortality in this population, or compared this relationship between SARS-CoV-2 patients and other populations. The main objective of our study was to determine the relationship between VAP and mortality in SARS-CoV-2 patients. METHODS: Planned ancillary analysis of a multicenter retrospective European cohort. VAP was diagnosed using clinical, radiological and quantitative microbiological criteria. Univariable and multivariable marginal Cox's regression models, with cause-specific hazard for duration of mechanical ventilation and ICU stay, were used to compare outcomes between study groups. Extubation, and ICU discharge alive were considered as events of interest, and mortality as competing event. FINDINGS: Of 1576 included patients, 568 were SARS-CoV-2 pneumonia, 482 influenza pneumonia, and 526 no evidence of viral infection at ICU admission. VAP was associated with significantly higher risk for 28-day mortality in SARS-CoV-2 (adjusted HR 1.70 (95% CI 1.16-2.47), p = 0.006), and influenza groups (1.75 (1.03-3.02), p = 0.045), but not in the no viral infection group (1.07 (0.64-1.78), p = 0.79). VAP was associated with significantly longer duration of mechanical ventilation in the SARS-CoV-2 group, but not in the influenza or no viral infection groups. VAP was associated with significantly longer duration of ICU stay in the 3 study groups. No significant difference was found in heterogeneity of outcomes related to VAP between the 3 groups, suggesting that the impact of VAP on mortality was not different between study groups. INTERPRETATION: VAP was associated with significantly increased 28-day mortality rate in SARS-CoV-2 patients. However, SARS-CoV-2 pneumonia, as compared to influenza pneumonia or no viral infection, did not significantly modify the relationship between VAP and 28-day mortality. CLINICAL TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov, number NCT04359693.


Subject(s)
COVID-19/mortality , COVID-19/therapy , Pneumonia, Ventilator-Associated/epidemiology , Aged , Europe/epidemiology , Female , Hospital Mortality , Humans , Intensive Care Units , Length of Stay/statistics & numerical data , Male , Middle Aged , Respiration, Artificial/statistics & numerical data , Retrospective Studies
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