Orbital characterization of superbolides observed from space: dynamical association with near-Earth objects, meteoroid streams and identification of hyperbolic meteoroids

There is an unceasing incoming flux of extraterrestrial materials reaching the Earth's atmosphere. Some of these objects produce luminous columns when they ablate during the hypersonic encounter with air molecules. A few fireballs occur each year bright enough to be detected from space. The source of these events is still a matter of debate, but it is generally accepted that they are of sporadic origin. We studied the NASA-JPL Center for NEOs Studies (CNEOS) fireball database to infer the dynamic origin of large bolides produced by meter-sized projectiles that impacted our planet. These likely meteorite-dropping events were recorded by the US Government satellite sensors. We estimated the false-positive rate and analyzed the time evolution of multiple orbit dissimilarity criteria concerning potential associations with near-Earth objects and meteoroid streams. We found that at least 16% of the large bolides could be associated with meteoroid streams, about 4% are likely associated with near-Earth asteroids, and 4% may be linked to near-Earth comets. This implies that a significant fraction of meter-sized impactors producing large bolides may have an asteroidal or cometary origin. In addition, we found at least three bolides having hyperbolic orbits with high tensile strength values. Meter-sized meteoroids of interstellar origin could be more common than previously thought, representing about 1% of the flux of large bolides. The inferred bulk physical properties suggest that the interstellar medium could bias these projectiles towards high strength rocks with the ability to survive prolonged exposure to the harsh interstellar space conditions.Comment: Accepted for publication in The Astronomical Journal (AAS38905R1

Causes of hOCT1-dependent cholangiocarcinoma resistance to sorafenib and sensitization by tumor-selective gene therapy

Although the multi-tyrosine kinase inhibitor sorafenib is useful in the treatment of several cancers, cholangiocarcinoma (CCA) is refractory to this drug. Among other mechanisms of chemoresistance, impaired uptake through human organic cation transporter type 1 (hOCT1) (gene SLC22A1) has been suggested. Here we have investigated the events accounting for this phenotypic characteristic and have evaluated the interest of selective gene therapy strategies to overcome this limitation. Gene expression and DNA methylation of SLC22A1 were analyzed using intrahepatic (iCCA) and extrahepatic (eCCA) biopsies (Copenhagen and Salamanca cohorts; n = 132) and The Cancer Genome Atlas (TCGA)-CHOL (n = 36). Decreased hOCT1 mRNA correlated with hypermethylation status of the SLC22A1 promoter. Treatment of CCA cells with decitabine (demethylating agent) or butyrate (histone deacetylase inhibitor) restored hOCT1 expression and increased sorafenib uptake. MicroRNAs able to induce hOCT1 mRNA decay were analyzed in paired samples of TCGA-CHOL (n = 9) and Copenhagen (n = 57) cohorts. Consistent up-regulation in tumor tissue was found for miR-141 and miR-330. High proportion of aberrant hOCT1 mRNA splicing in CCA was also seen. Lentiviral-mediated transduction of eCCA (EGI-1 and TFK-1) and iCCA (HuCCT1) cells with hOCT1 enhanced sorafenib uptake and cytotoxic effects. In chemically induced CCA in rats, reduced rOct1 expression was accompanied by impaired sorafenib uptake. In xenograft models of eCCA cells implanted in mouse liver, poor response to sorafenib was observed. However, tumor growth was markedly reduced by cotreatment with sorafenib and adenoviral vectors encoding hOCT1 under the control of the BIRC5 promoter, a gene highly up-regulated in CCA. Conclusion: The reason for impaired hOCT1-mediated sorafenib uptake by CCA is multifactorial. Gene therapy capable of selectively inducing hOCT1 in tumor cells can be considered a potentially useful chemosensitization strategy to improve the response of CCA to sorafenib

Dendritic cell deficiencies persist seven months after SARS-CoV-2 infection

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection induces an exacerbated inflammation driven by innate immunity components. Dendritic cells (DCs) play a key role in the defense against viral infections, for instance plasmacytoid DCs (pDCs), have the capacity to produce vast amounts of interferon-alpha (IFN-α). In COVID-19 there is a deficit in DC numbers and IFN-α production, which has been associated with disease severity. In this work, we described that in addition to the DC deficiency, several DC activation and homing markers were altered in acute COVID-19 patients, which were associated with multiple inflammatory markers. Remarkably, previously hospitalized and nonhospitalized patients remained with decreased numbers of CD1c+ myeloid DCs and pDCs seven months after SARS-CoV-2 infection. Moreover, the expression of DC markers such as CD86 and CD4 were only restored in previously nonhospitalized patients, while no restoration of integrin β7 and indoleamine 2,3-dyoxigenase (IDO) levels were observed. These findings contribute to a better understanding of the immunological sequelae of COVID-19

SARS-CoV-2 viral load in nasopharyngeal swabs is not an independent predictor of unfavorable outcome

The aim was to assess the ability of nasopharyngeal SARS-CoV-2 viral load at first patient’s hospital evaluation to predict unfavorable outcomes. We conducted a prospective cohort study including 321 adult patients with confirmed COVID-19 through RT-PCR in nasopharyngeal swabs. Quantitative Synthetic SARS-CoV-2 RNA cycle threshold values were used to calculate the viral load in log10 copies/mL. Disease severity at the end of follow up was categorized into mild, moderate, and severe. Primary endpoint was a composite of intensive care unit (ICU) admission and/or death (n = 85, 26.4%). Univariable and multivariable logistic regression analyses were performed. Nasopharyngeal SARS-CoV-2 viral load over the second quartile (≥ 7.35 log10 copies/mL, p = 0.003) and second tertile (≥ 8.27 log10 copies/mL, p = 0.01) were associated to unfavorable outcome in the unadjusted logistic regression analysis. However, in the final multivariable analysis, viral load was not independently associated with an unfavorable outcome. Five predictors were independently associated with increased odds of ICU admission and/or death: age ≥ 70 years, SpO2, neutrophils > 7.5 × 103/µL, lactate dehydrogenase ≥ 300 U/L, and C-reactive protein ≥ 100 mg/L. In summary, nasopharyngeal SARS-CoV-2 viral load on admission is generally high in patients with COVID-19, regardless of illness severity, but it cannot be used as an independent predictor of unfavorable clinical outcome

Luminous efficiency based on FRIPON meteors and limitations of ablation models

Context. In meteor physics, the luminous efficiency τ is used to convert the meteor's magnitude to the corresponding meteoroid's mass. However, a lack of sufficiently accurate verification methods or adequate laboratory tests mean that discussions around this parameter are a subject of controversy. Aims: In this work, we aim to use meteor data obtained by the Fireball Recovery and InterPlanetary Observation to calculate the luminous efficiencies of the recorded meteors. We also show the limitations of the methods presented herein. Methods: Deceleration-based formulas were used to calculate the masses of the pre-atmospheric meteoroids. These can in turn be compared to the meteor brightnesses to assess the luminous efficiencies of the recorded objects. Fragmentation of the meteoroids is not considered within this model. Good measurements of the meteor deceleration are required. Results: We find τ-values, as well as the shape change coefficients, of 294 meteors and fireballs with determined masses in the range of 10^−6 / -100 kg. The derived τ-values have a median of τ_median = 2.17%. Most of them are of the order of 0.1-10%. We present how our values are obtained, compare them with data reported in the literature, and discuss several methods. A dependence of τ on the pre-atmospheric velocity of the meteor, ve, is noticeable with a relation of τ = 0.0023⋅ve^2.3. Furthermore, a dependence of τ on the initial meteoroid mass, Me, is found with negative linear behaviour in log-log space: τ = 0.48⋅Me/−0.47. Conclusions: The higher luminous efficiency of fast meteors could be explained by the higher amount of energy released. Fast meteoroids produce additional emission lines that radiate more efficiently in specific wavelengths due to the appearance of the so-called second component of higher temperature. Furthermore, the negative dependence of τ on Me implies that the radiation of smaller meteoroids is more efficient. The results of this study also show the limitations of the ablation-based model for the determination of the luminous efficiency

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

From impact refugees to deterritorialized states: Foresighting extreme legal-policy cases in asteroid impact scenarios

Throughout recorded history, humans have crossed national borders to seek safety in nearby countries. The reasons for displacement have been generated by phenomena of terrestrial origin, but exposure to unexpected extra-terrestrial threats poses a different scenario. An asteroid impact warning implies a change of paradigm which would represent a historic precedent. In this regard, the analogies with natural disasters must be considered, along with multiple possible scenarios, and legal aspects related to (a) the legal framework to regulate this situation; (b) the action and responsibility of the states; and (c) the definition of impact refugee and the reconfiguration of traditional concepts such as deterritorialized states. In addition, the decision-making process and the actors involved must be led by a cooperative effort to improve international law. These new circumstances should be established with a consideration of inequalities between the states, and an aim of protecting humanity through democratic solutions using the safest, most effective techniques.ESS acknowledges financial support from the Spanish Ministry of Science, Innovation and Universities (FPU 17/04436). EPA acknowledges support from the FEDER/Ministerio de Ciencia e Innovación – Agencia Estatal de Investigación (PGC2018-097374-B-I00, PI: JMT-R). This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 865657) for the project “Quantum Chemistry on Interstellar Grains” (QUANTUMGRAIN)

Luminous efficiency of meteors derived from ablation model after assessment of its range of validity

Drolshagen, E., et al.[Context] The luminous efficiency, τ, can be used to compute the pre-Atmospheric masses of meteoroids from corresponding recorded meteor brightnesses. The derivation of the luminous efficiency is non-Trivial and is subject to biases and model assumptions. This has led to greatly varying results in the last decades of studies. [Aims] The present paper aims to investigate how a reduction in various observational biases can be achieved to derive (more) reliable values for the luminous efficiency. [Methods] A total of 281 meteors observed by the Fireball Recovery and InterPlanetary Observation Network (FRIPON) are studied. The luminous efficiencies of the events are computed using an ablation-based model. The relations of τ as a function of the pre-Atmospheric meteoroid velocity, ve, and mass, Me, are studied. Various aspects that could render the method less valid, cause inaccuracies, or bias the results are investigated. On this basis, the best suitable meteors were selected for luminous efficiency computations. [Results] The presented analysis shows the limits of the used method. The most influential characteristics that are necessary for reliable results for the τ computation were identified. We study the dependence of τ on the assumed meteoroid's density, ρ, and include improved ρ-values for objects with identified meteoroid stream association. Based on the discovered individual biases and constraints we create a pre-debiased subset of 54 well-recorded events with a relative velocity change >80%, a final height <70 km, and a Knudsen number Kn < 0.01; this last value indicates that the events were observed in the continuum-flow regime. We find τ-values in the range between 0.012% and 1.1% for this pre-debiased subset and relations of τ to ve and Me of: τ=7.33â ve-1.10 and τ=0.28â Me-0.33. [Conclusions] The derived luminous efficiency of meteoroids depends on the assumed material density. Our results indicate that the applied debiasing method improves the analysis of τ from decelerated meteoroids. The underlying method is only valid for meteors in the continuum-flow regime. These events tend to have low end heights, large masses, and high deceleration

Luminous efficiency based on FRIPON meteors and limitations of ablation models

Drolshagen, E., et al.[Context] In meteor physics, the luminous efficiency τ is used to convert the meteor's magnitude to the corresponding meteoroid's mass. However, a lack of sufficiently accurate verification methods or adequate laboratory tests mean that discussions around this parameter are a subject of controversy. [Aims] In this work, we aim to use meteor data obtained by the Fireball Recovery and InterPlanetary Observation to calculate the luminous efficiencies of the recorded meteors. We also show the limitations of the methods presented herein. [Methods] Deceleration-based formulas were used to calculate the masses of the pre-atmospheric meteoroids. These can in turn be compared to the meteor brightnesses to assess the luminous efficiencies of the recorded objects. Fragmentation of the meteoroids is not considered within this model. Good measurements of the meteor deceleration are required. [Results] We find τ-values, as well as the shape change coefficients, of 294 meteors and fireballs with determined masses in the range of 10-6-100 kg. The derived τ-values have a median of τmedian = 2.17%. Most of them are of the order of 0.1-10%. We present how our values are obtained, compare them with data reported in the literature, and discuss several methods. A dependence of τ on the pre-atmospheric velocity of the meteor, ve, is noticeable with a relation of τ = 0.0023 ve2.3. Furthermore, a dependence of τ on the initial meteoroid mass, Me, is found with negative linear behaviour in log-log space: τ = 0.48 Me-0.47. [Conclusions] The higher luminous efficiency of fast meteors could be explained by the higher amount of energy released. Fast meteoroids produce additional emission lines that radiate more efficiently in specific wavelengths due to the appearance of the so-called second component of higher temperature. Furthermore, the negative dependence of τ on Me implies that the radiation of smaller meteoroids is more efficient. The results of this study also show the limitations of the ablation-based model for the determination of the luminous efficiency