Showing papers by "University of Milan published in 2020"

Planck 2018 results. VI. Cosmological parameters

Abstract: We present cosmological parameter results from the final full-mission Planck measurements of the cosmic microwave background (CMB) anisotropies, combining information from the temperature and polarization maps and the lensing reconstruction Compared to the 2015 results, improved measurements of large-scale polarization allow the reionization optical depth to be measured with higher precision, leading to significant gains in the precision of other correlated parameters Improved modelling of the small-scale polarization leads to more robust constraints on manyparameters,withresidualmodellinguncertaintiesestimatedtoaffectthemonlyatthe05σlevelWefindgoodconsistencywiththestandard spatially-flat6-parameter ΛCDMcosmologyhavingapower-lawspectrumofadiabaticscalarperturbations(denoted“base ΛCDM”inthispaper), from polarization, temperature, and lensing, separately and in combination A combined analysis gives dark matter density Ωch2 = 0120±0001, baryon density Ωbh2 = 00224±00001, scalar spectral index ns = 0965±0004, and optical depth τ = 0054±0007 (in this abstract we quote 68% confidence regions on measured parameters and 95% on upper limits) The angular acoustic scale is measured to 003% precision, with 100θ∗ = 10411±00003Theseresultsareonlyweaklydependentonthecosmologicalmodelandremainstable,withsomewhatincreasederrors, in many commonly considered extensions Assuming the base-ΛCDM cosmology, the inferred (model-dependent) late-Universe parameters are: HubbleconstantH0 = (674±05)kms−1Mpc−1;matterdensityparameterΩm = 0315±0007;andmatterfluctuationamplitudeσ8 = 0811±0006 We find no compelling evidence for extensions to the base-ΛCDM model Combining with baryon acoustic oscillation (BAO) measurements (and consideringsingle-parameterextensions)weconstraintheeffectiveextrarelativisticdegreesoffreedomtobe Neff = 299±017,inagreementwith the Standard Model prediction Neff = 3046, and find that the neutrino mass is tightly constrained toPmν < 012 eV The CMB spectra continue to prefer higher lensing amplitudesthan predicted in base ΛCDM at over 2σ, which pulls some parameters that affect thelensing amplitude away from the ΛCDM model; however, this is not supported by the lensing reconstruction or (in models that also change the background geometry) BAOdataThejointconstraintwithBAOmeasurementsonspatialcurvatureisconsistentwithaflatuniverse, ΩK = 0001±0002Alsocombining with Type Ia supernovae (SNe), the dark-energy equation of state parameter is measured to be w0 = −103±003, consistent with a cosmological constant We find no evidence for deviations from a purely power-law primordial spectrum, and combining with data from BAO, BICEP2, and Keck Array data, we place a limit on the tensor-to-scalar ratio r0002 < 006 Standard big-bang nucleosynthesis predictions for the helium and deuterium abundances for the base-ΛCDM cosmology are in excellent agreement with observations The Planck base-ΛCDM results are in good agreement with BAO, SNe, and some galaxy lensing observations, but in slight tension with the Dark Energy Survey’s combined-probe results including galaxy clustering (which prefers lower fluctuation amplitudes or matter density parameters), and in significant, 36σ, tension with local measurements of the Hubble constant (which prefer a higher value) Simple model extensions that can partially resolve these tensions are not favoured by the Planck data

Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy.

Abstract: Importance In December 2019, a novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) emerged in China and has spread globally, creating a pandemic. Information about the clinical characteristics of infected patients who require intensive care is limited. Objective To characterize patients with coronavirus disease 2019 (COVID-19) requiring treatment in an intensive care unit (ICU) in the Lombardy region of Italy. Design, Setting, and Participants Retrospective case series of 1591 consecutive patients with laboratory-confirmed COVID-19 referred for ICU admission to the coordinator center (Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy) of the COVID-19 Lombardy ICU Network and treated at one of the ICUs of the 72 hospitals in this network between February 20 and March 18, 2020. Date of final follow-up was March 25, 2020. Exposures SARS-CoV-2 infection confirmed by real-time reverse transcriptase–polymerase chain reaction (RT-PCR) assay of nasal and pharyngeal swabs. Main Outcomes and Measures Demographic and clinical data were collected, including data on clinical management, respiratory failure, and patient mortality. Data were recorded by the coordinator center on an electronic worksheet during telephone calls by the staff of the COVID-19 Lombardy ICU Network. Results Of the 1591 patients included in the study, the median (IQR) age was 63 (56-70) years and 1304 (82%) were male. Of the 1043 patients with available data, 709 (68%) had at least 1 comorbidity and 509 (49%) had hypertension. Among 1300 patients with available respiratory support data, 1287 (99% [95% CI, 98%-99%]) needed respiratory support, including 1150 (88% [95% CI, 87%-90%]) who received mechanical ventilation and 137 (11% [95% CI, 9%-12%]) who received noninvasive ventilation. The median positive end-expiratory pressure (PEEP) was 14 (IQR, 12-16) cm H2O, and Fio2was greater than 50% in 89% of patients. The median Pao2/Fio2was 160 (IQR, 114-220). The median PEEP level was not different between younger patients (n = 503 aged ≤63 years) and older patients (n = 514 aged ≥64 years) (14 [IQR, 12-15] vs 14 [IQR, 12-16] cm H2O, respectively; median difference, 0 [95% CI, 0-0];P = .94). Median Fio2was lower in younger patients: 60% (IQR, 50%-80%) vs 70% (IQR, 50%-80%) (median difference, −10% [95% CI, −14% to 6%];P = .006), and median Pao2/Fio2was higher in younger patients: 163.5 (IQR, 120-230) vs 156 (IQR, 110-205) (median difference, 7 [95% CI, −8 to 22];P = .02). Patients with hypertension (n = 509) were older than those without hypertension (n = 526) (median [IQR] age, 66 years [60-72] vs 62 years [54-68];P Conclusions and Relevance In this case series of critically ill patients with laboratory-confirmed COVID-19 admitted to ICUs in Lombardy, Italy, the majority were older men, a large proportion required mechanical ventilation and high levels of PEEP, and ICU mortality was 26%.

The ATLAS Experiment at the CERN Large Hadron Collider

Abstract: The ATLAS detector as installed in its experimental cavern at point 1 at CERN is described in this paper. A brief overview of the expected performance of the detector when the Large Hadron Collider begins operation is also presented.

Critical Care Utilization for the COVID-19 Outbreak in Lombardy, Italy: Early Experience and Forecast During an Emergency Response.

Abstract: On February 20, 2020, a patient in his 30s admitted to the intensive care unit (ICU) in Codogno Hospital (Lodi, Lombardy, Italy) tested positive for a new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19). He had a history of atypical pneumonia that was not responding to treatment, but he was not considered at risk for COVID-19 infection.1 The positive result was immediately reported to the Lombardy health care system and governmental offices. During the next 24 hours, the number of reported positive cases increased to 36. This situation was considered a serious development for several reasons: the patient (“patient 1”) was healthy and young; in less than 24 hours, 36 additional cases were identified, without links to patient 1 or previously identified positive cases already in the country; it was not possible to identify with certainty the source of transmission to patient 1 at the time; and, because patient 1 was in the ICU and there were already 36 cases by day 2, chances were that a cluster of unknown magnitude was present and additional spread was likely. On February 21, an emergency task force was formed by the Government of Lombardy and local health authorities to lead the response to the outbreak. This Viewpoint provides a summary of the response of the COVID-19 Lombardy ICU network and a forecast of estimated ICU demand over the coming weeks (projected to March 20, 2020).

Planck 2018 results: XI. Polarized dust foregrounds

Abstract: The study of polarized dust emission has become entwined with the analysis of the cosmic microwave background (CMB) polarization. We use new Planck maps to characterize Galactic dust emission as a foreground to the CMB polarization. We present Planck EE, BB, and TE power spectra of dust polarization at 353 GHz for six nested sky regions covering from 24 to 71 % of the sky. We present power-law fits to the angular power spectra, yielding evidence for statistically significant variations of the exponents over sky regions and a difference between the values for the EE and BB spectra. The TE correlation and E/B power asymmetry extend to low multipoles that were not included in earlier Planck polarization papers. We also report evidence for a positive TB dust signal. Combining data from Planck and WMAP, we determine the amplitudes and spectral energy distributions (SEDs) of polarized foregrounds, including the correlation between dust and synchrotron polarized emission, for the six sky regions as a function of multipole. This quantifies the challenge of the component separation procedure required for detecting the reionization and recombination peaks of primordial CMB B modes. The SED of polarized dust emission is fit well by a single-temperature modified blackbody emission law from 353 GHz to below 70 GHz. For a dust temperature of 19.6 K, the mean spectral index for dust polarization is $\beta_{\rm d}^{P} = 1.53\pm0.02 $. By fitting multi-frequency cross-spectra, we examine the correlation of the dust polarization maps across frequency. We find no evidence for decorrelation. If the Planck limit for the largest sky region applies to the smaller sky regions observed by sub-orbital experiments, then decorrelation might not be a problem for CMB experiments aiming at a primordial B-mode detection limit on the tensor-to-scalar ratio $r\simeq0.01$ at the recombination peak.

COVID-19 pneumonia: different respiratory treatments for different phenotypes?

Abstract: The Surviving Sepsis Campaign panel recently recommended that “mechanically ventilated patients with COVID-19 should be managed similarly to other patients with acute respiratory failure in the ICU [1].” Yet, COVID-19 pneumonia [2], despite falling in most of the circumstances under the Berlin definition of ARDS [3], is a specific disease, whose distinctive features are severe hypoxemia often associated with near normal respiratory system compliance (more than 50% of the 150 patients measured by the authors and further confirmed by several colleagues in Northern Italy). This remarkable combination is almost never seen in severe ARDS. These severely hypoxemic patients despite sharing a single etiology (SARS-CoV-2) may present quite differently from one another: normally breathing (“silent” hypoxemia) or remarkably dyspneic; quite responsive to nitric oxide or not; deeply hypocapnic or normo/hypercapnic; and either responsive to prone position or not. Therefore, the same disease actually presents itself with impressive non-uniformity. Based on detailed observation of several cases and discussions with colleagues treating these patients, we hypothesize that the different COVID-19 patterns found at presentation in the emergency department depend on the interaction between three factors: (1) the severity of the infection, the host response, physiological reserve and comorbidities; (2) the ventilatory responsiveness of the patient to hypoxemia; (3) the time elapsed between the onset of the disease and the observation in the hospital. The interaction between these factors leads to the development of a time-related disease spectrum within two primary “phenotypes”: Type L, characterized by Low elastance (i.e., high compliance), Low ventilation-to-perfusion ratio, Low lung weight and Low recruitability and Type H, characterized by High elastance, High right-toleft shunt, High lung weight and High recruitability.

Eating habits and lifestyle changes during COVID-19 lockdown: an Italian survey.

Abstract: On December 12th 2019, a new coronavirus (SARS-Cov2) emerged in Wuhan, China, sparking a pandemic of acute respiratory syndrome in humans (COVID-19). On the 24th of April 2020, the number of COVID-19 deaths in the world, according to the COVID-Case Tracker by Johns Hopkins University, was 195,313, and the number of COVID-19 confirmed cases was 2,783,512. The COVID-19 pandemic represents a massive impact on human health, causing sudden lifestyle changes, through social distancing and isolation at home, with social and economic consequences. Optimizing public health during this pandemic requires not only knowledge from the medical and biological sciences, but also of all human sciences related to lifestyle, social and behavioural studies, including dietary habits and lifestyle. Our study aimed to investigate the immediate impact of the COVID-19 pandemic on eating habits and lifestyle changes among the Italian population aged ≥ 12 years. The study comprised a structured questionnaire packet that inquired demographic information (age, gender, place of residence, current employment); anthropometric data (reported weight and height); dietary habits information (adherence to the Mediterranean diet, daily intake of certain foods, food frequency, and number of meals/day); lifestyle habits information (grocery shopping, habit of smoking, sleep quality and physical activity). The survey was conducted from the 5th to the 24th of April 2020. A total of 3533 respondents have been included in the study, aged between 12 and 86 years (76.1% females). The perception of weight gain was observed in 48.6% of the population; 3.3% of smokers decided to quit smoking; a slight increased physical activity has been reported, especially for bodyweight training, in 38.3% of respondents; the population group aged 18–30 years resulted in having a higher adherence to the Mediterranean diet when compared to the younger and the elderly population (p < 0.001; p < 0.001, respectively); 15% of respondents turned to farmers or organic, purchasing fruits and vegetables, especially in the North and Center of Italy, where BMI values were lower. In this study, we have provided for the first time data on the Italian population lifestyle, eating habits and adherence to the Mediterranean Diet pattern during the COVID-19 lockdown. However, as the COVID-19 pandemic is ongoing, our data need to be confirmed and investigated in future more extensive population studies.

GW190425: Observation of a Compact Binary Coalescence with Total Mass ∼ 3.4 M O

Abstract: On 2019 April 25, the LIGO Livingston detector observed a compact binary coalescence with signal-to-noise ratio 12.9. The Virgo detector was also taking data that did not contribute to detection due to a low signal-to-noise ratio, but were used for subsequent parameter estimation. The 90% credible intervals for the component masses range from to if we restrict the dimensionless component spin magnitudes to be smaller than 0.05). These mass parameters are consistent with the individual binary components being neutron stars. However, both the source-frame chirp mass and the total mass of this system are significantly larger than those of any other known binary neutron star (BNS) system. The possibility that one or both binary components of the system are black holes cannot be ruled out from gravitational-wave data. We discuss possible origins of the system based on its inconsistency with the known Galactic BNS population. Under the assumption that the signal was produced by a BNS coalescence, the local rate of neutron star mergers is updated to 250-2810.

COVID-19 Does Not Lead to a "Typical" Acute Respiratory Distress Syndrome.

Abstract: ventilation strategy was applied to the first four patients to increase pulmonary efficiency to eliminate CO2, and this was used in the next four patients. Gas exchange consists of oxygenation and ventilation. Oxygenation is quantified by the PaO2/FIO2 ratio, and this method has gained wide acceptance, particularly since publication of the Berlin definition of ARDS (7). However, the Berlin definition does not include additional pathophysiological information about ARDS, such as alveolar ventilation, as measured by pulmonary dead space, which is an important predictor of outcome (8). Increased pulmonary dead space reflects the inefficiency of the lungs to eliminate CO2, which may lead to hypercapnia. In our patients with ARDS with COVID-19, hypercapnia was common at ICU admission with low VT ventilation. Assuming the anatomic portion of dead space is constant, increasing VT with constant respiratory rate would effectively increase alveolar ventilation. Any such increase in VT would decrease PaCO2, which would be captured by VR (6). VR, a novel method to monitor ventilatory adequacy at the bedside (4–6), was very high in our patients, reflecting increased pulmonary dead space and inadequacy of ventilation. With an acceptable plateau pressure and driving pressure, titration of VT was performed. PaCO2 and VR were significantly decreased when an intermediate VT (7–8 ml/kg PBW) was applied. We suggest that intermediate VT (7–8 ml/kg PBW) is recommended for such patients. Therefore, low VT may not be the best approach for all patients with ARDS, particularly those with a less severe decrease in respiratory system compliance and inadequacy of ventilation. In summary, we found that hypercapnia was common in patients with COVID-19–associated ARDS while using low VT ventilation. VR was increased in these patients, which reflected increased pulmonary dead space and inadequacy of ventilation. An intermediate VT was used to correct hypercapnia efficiently, while not excessively increasing driving pressure. Clinicians must have a high index of suspicion for increased pulmonary dead space when patients with COVID19–related ARDS present with hypercapnia. n

Remdesivir for 5 or 10 Days in Patients with Severe Covid-19.

Abstract: Background Remdesivir is an RNA polymerase inhibitor with potent antiviral activity in vitro and efficacy in animal models of coronavirus disease 2019 (Covid-19). Methods We conducted a ra...

Risk factors associated with mortality among patients with COVID-19 in intensive care units in Lombardy, Italy

Abstract: Importance Many patients with coronavirus disease 2019 (COVID-19) are critically ill and require care in the intensive care unit (ICU). Objective To evaluate the independent risk factors associated with mortality of patients with COVID-19 requiring treatment in ICUs in the Lombardy region of Italy. Design, Setting, and Participants This retrospective, observational cohort study included 3988 consecutive critically ill patients with laboratory-confirmed COVID-19 referred for ICU admission to the coordinating center (Fondazione IRCCS [Istituto di Ricovero e Cura a Carattere Scientifico] Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy) of the COVID-19 Lombardy ICU Network from February 20 to April 22, 2020. Infection with severe acute respiratory syndrome coronavirus 2 was confirmed by real-time reverse transcriptase–polymerase chain reaction assay of nasopharyngeal swabs. Follow-up was completed on May 30, 2020. Exposures Baseline characteristics, comorbidities, long-term medications, and ventilatory support at ICU admission. Main Outcomes and Measures Time to death in days from ICU admission to hospital discharge. The independent risk factors associated with mortality were evaluated with a multivariable Cox proportional hazards regression. Results Of the 3988 patients included in this cohort study, the median age was 63 (interquartile range [IQR] 56-69) years; 3188 (79.9%; 95% CI, 78.7%-81.1%) were men, and 1998 of 3300 (60.5%; 95% CI, 58.9%-62.2%) had at least 1 comorbidity. At ICU admission, 2929 patients (87.3%; 95% CI, 86.1%-88.4%) required invasive mechanical ventilation (IMV). The median follow-up was 44 (95% CI, 40-47; IQR, 11-69; range, 0-100) days; median time from symptoms onset to ICU admission was 10 (95% CI, 9-10; IQR, 6-14) days; median length of ICU stay was 12 (95% CI, 12-13; IQR, 6-21) days; and median length of IMV was 10 (95% CI, 10-11; IQR, 6-17) days. Cumulative observation time was 164 305 patient-days. Hospital and ICU mortality rates were 12 (95% CI, 11-12) and 27 (95% CI, 26-29) per 1000 patients-days, respectively. In the subgroup of the first 1715 patients, as of May 30, 2020, 865 (50.4%) had been discharged from the ICU, 836 (48.7%) had died in the ICU, and 14 (0.8%) were still in the ICU; overall, 915 patients (53.4%) died in the hospital. Independent risk factors associated with mortality included older age (hazard ratio [HR], 1.75; 95% CI, 1.60-1.92), male sex (HR, 1.57; 95% CI, 1.31-1.88), high fraction of inspired oxygen (Fio2) (HR, 1.14; 95% CI, 1.10-1.19), high positive end-expiratory pressure (HR, 1.04; 95% CI, 1.01-1.06) or low Pao2:Fio2ratio (HR, 0.80; 95% CI, 0.74-0.87) on ICU admission, and history of chronic obstructive pulmonary disease (HR, 1.68; 95% CI, 1.28-2.19), hypercholesterolemia (HR, 1.25; 95% CI, 1.02-1.52), and type 2 diabetes (HR, 1.18; 95% CI, 1.01-1.39). No medication was independently associated with mortality (angiotensin-converting enzyme inhibitors HR, 1.17; 95% CI, 0.97-1.42; angiotensin receptor blockers HR, 1.05; 95% CI, 0.85-1.29). Conclusions and Relevance In this retrospective cohort study of critically ill patients admitted to ICUs in Lombardy, Italy, with laboratory-confirmed COVID-19, most patients required IMV. The mortality rate and absolute mortality were high.

Pulmonary post-mortem findings in a series of COVID-19 cases from northern Italy: a two-centre descriptive study.

Abstract: Summary Background COVID-19 is characterised by respiratory symptoms, which deteriorate into respiratory failure in a substantial proportion of cases, requiring intensive care in up to a third of patients admitted to hospital. Analysis of the pathological features in the lung tissues of patients who have died with COVID-19 could help us to understand the disease pathogenesis and clinical outcomes. Methods We systematically analysed lung tissue samples from 38 patients who died from COVID-19 in two hospitals in northern Italy between Feb 29 and March 24, 2020. The most representative areas identified at macroscopic examination were selected, and tissue blocks (median seven, range five to nine) were taken from each lung and fixed in 10% buffered formalin for at least 48 h. Tissues were assessed with use of haematoxylin and eosin staining, immunohistochemical staining for inflammatory infiltrate and cellular components (including staining with antibodies against CD68, CD3, CD45, CD61, TTF1, p40, and Ki-67), and electron microscopy to identify virion localisation. Findings All cases showed features of the exudative and proliferative phases of diffuse alveolar damage, which included capillary congestion (in all cases), necrosis of pneumocytes (in all cases), hyaline membranes (in 33 cases), interstitial and intra-alveolar oedema (in 37 cases), type 2 pneumocyte hyperplasia (in all cases), squamous metaplasia with atypia (in 21 cases), and platelet–fibrin thrombi (in 33 cases). The inflammatory infiltrate, observed in all cases, was largely composed of macrophages in the alveolar lumina (in 24 cases) and lymphocytes in the interstitium (in 31 cases). Electron microscopy revealed that viral particles were predominantly located in the pneumocytes. Interpretation The predominant pattern of lung lesions in patients with COVID-19 patients is diffuse alveolar damage, as described in patients infected with severe acute respiratory syndrome and Middle East respiratory syndrome coronaviruses. Hyaline membrane formation and pneumocyte atypical hyperplasia are frequent. Importantly, the presence of platelet–fibrin thrombi in small arterial vessels is consistent with coagulopathy, which appears to be common in patients with COVID-19 and should be one of the main targets of therapy. Funding None.

Self-reported Olfactory and Taste Disorders in Patients With Severe Acute Respiratory Coronavirus 2 Infection: A Cross-sectional Study.

Abstract: To the Editor—We read with interest the article by Wang et al [1] describing the clinical features of 69 patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Wuhan, China. The authors provide a detailed description of major signs and symptoms of overt disease [2, 3], but fail to give an account of minor symptoms that may be present at earlier stages of the infection. After some patients admitted for coronavirus disease 2019 (COVID-19) at the Infectious Disease Department of L. Sacco Hospital in Milan, Italy, complained of olfactory and taste disorders (OTDs), we performed a cross-sectional survey of the prevalence of these alterations in the context of SARS-CoV-2 infection. On 19 March 2020, a simple questionnaire including questions about the presence or absence of OTDs, their type and time of onset respective to hospitalization were submitted through verbal interview to all SARS-CoV-2– positive hospitalized patients who were able to give informed consent. Of 88 hospitalized patients, 59 were able to be interviewed (29 were nonrespondents, of whom 4 had dementia, 2 had a linguistic barrier, and 23 were on noninvasive ventilation) (Table 1). Of these, 20 (33.9%) reported at least 1 taste or olfactory disorder and 11 (18.6%) both. Twelve patients (20.3%) presented the symptoms before the hospital admission, whereas 8 (13.5%) experienced the symptoms during the hospital stay. Taste alterations were more frequently (91%) before hospitalization, whereas after hospitalization taste and olfactory alteration appeared with equal frequency. Females reported OTDs more frequently than males (10/19 [52.6%] vs 10/40 [25%]; P = .036). Moreover, patients with at least 1 OTD were younger than those without (median, 56 years [interquartile range {IQR}, 47–60] vs 66 [IQR, 52–77]; P = .035). All patients reported the persistence of OTDs at the time of the interview. Olfactory and taste disorders are well known to be related with a wide range of viral infections [4, 5]. SARS-CoV has demonstrated in a mice model a transneural penetration through the olfactory bulb [6]. Moreover, angiotensinconverting enzyme 2 receptor, which is used by SARS-CoV-2 to bind and penetrate into the cell, is widely expressed on the epithelial cells of the mucosa of the oral cavity [7]. These findings could explain the underlying pathogenetic mechanism of taste and olfactory disorders in SARS-CoV-2 infection. Due to limitations related to the diffusivity of the disease and emergency contingencies, it was impossible to perform a more structured questionnaire associated with validated tests (ie, Pennsylvania smell identification test) [8]. However, our survey shows that OTDs are fairly frequent in patients with SARS-CoV-2 infection and may precede the onset of full-blown clinical disease. In a pandemic context, further investigations on nonhospitalized infected patients are required to ascertain if these symptoms, albeit unspecific, may represent a clinical screening tool to orientate testing of pauci-symptomatic individuals.

GW190814: Gravitational Waves from the Coalescence of a 23 Solar Mass Black Hole with a 2.6 Solar Mass Compact Object

Abstract: We report the observation of a compact binary coalescence involving a 222–243 M ⊙ black hole and a compact object with a mass of 250–267 M ⊙ (all measurements quoted at the 90% credible level) The gravitational-wave signal, GW190814, was observed during LIGO's and Virgo's third observing run on 2019 August 14 at 21:10:39 UTC and has a signal-to-noise ratio of 25 in the three-detector network The source was localized to 185 deg2 at a distance of ${241}_{-45}^{+41}$ Mpc; no electromagnetic counterpart has been confirmed to date The source has the most unequal mass ratio yet measured with gravitational waves, ${0112}_{-0009}^{+0008}$, and its secondary component is either the lightest black hole or the heaviest neutron star ever discovered in a double compact-object system The dimensionless spin of the primary black hole is tightly constrained to ≤007 Tests of general relativity reveal no measurable deviations from the theory, and its prediction of higher-multipole emission is confirmed at high confidence We estimate a merger rate density of 1–23 Gpc−3 yr−1 for the new class of binary coalescence sources that GW190814 represents Astrophysical models predict that binaries with mass ratios similar to this event can form through several channels, but are unlikely to have formed in globular clusters However, the combination of mass ratio, component masses, and the inferred merger rate for this event challenges all current models of the formation and mass distribution of compact-object binaries

Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: ASCO Clinical Practice Guideline Update

Abstract: PURPOSETo provide updated recommendations about prophylaxis and treatment of venous thromboembolism (VTE) in patients with cancer.METHODSPubMed and the Cochrane Library were searched for randomized...

TRY plant trait database : Enhanced coverage and open access

Abstract: Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.

Planck 2018 results. I. Overview and the cosmological legacy of Planck

Abstract: The European Space Agency’s Planck satellite, which was dedicated to studying the early Universe and its subsequent evolution, was launched on 14 May 2009. It scanned the microwave and submillimetre sky continuously between 12 August 2009 and 23 October 2013, producing deep, high-resolution, all-sky maps in nine frequency bands from 30 to 857 GHz. This paper presents the cosmological legacy of Planck, which currently provides our strongest constraints on the parameters of the standard cosmological model and some of the tightest limits available on deviations from that model. The 6-parameter ΛCDM model continues to provide an excellent fit to the cosmic microwave background data at high and low redshift, describing the cosmological information in over a billion map pixels with just six parameters. With 18 peaks in the temperature and polarization angular power spectra constrained well, Planck measures five of the six parameters to better than 1% (simultaneously), with the best-determined parameter (θ*) now known to 0.03%. We describe the multi-component sky as seen by Planck, the success of the ΛCDM model, and the connection to lower-redshift probes of structure formation. We also give a comprehensive summary of the major changes introduced in this 2018 release. The Planck data, alone and in combination with other probes, provide stringent constraints on our models of the early Universe and the large-scale structure within which all astrophysical objects form and evolve. We discuss some lessons learned from the Planck mission, and highlight areas ripe for further experimental advances.

GW190521: A Binary Black Hole Merger with a Total Mass of 150 M

Abstract: On May 21, 2019 at 03:02:29 UTC Advanced LIGO and Advanced Virgo observed a short duration gravitational-wave signal, GW190521, with a three-detector network signal-to-noise ratio of 14.7, and an estimated false-alarm rate of 1 in 4900 yr using a search sensitive to generic transients. If GW190521 is from a quasicircular binary inspiral, then the detected signal is consistent with the merger of two black holes with masses of 85_{-14}^{+21} M_{⊙} and 66_{-18}^{+17} M_{⊙} (90% credible intervals). We infer that the primary black hole mass lies within the gap produced by (pulsational) pair-instability supernova processes, with only a 0.32% probability of being below 65 M_{⊙}. We calculate the mass of the remnant to be 142_{-16}^{+28} M_{⊙}, which can be considered an intermediate mass black hole (IMBH). The luminosity distance of the source is 5.3_{-2.6}^{+2.4} Gpc, corresponding to a redshift of 0.82_{-0.34}^{+0.28}. The inferred rate of mergers similar to GW190521 is 0.13_{-0.11}^{+0.30} Gpc^{-3} yr^{-1}.

Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1–2 trials

Abstract: Summary Background Entrectinib is a potent inhibitor of tropomyosin receptor kinase (TRK) A, B, and C, which has been shown to have anti-tumour activity against NTRK gene fusion-positive solid tumours, including CNS activity due to its ability to penetrate the blood–brain barrier. We present an integrated efficacy and safety analysis of patients with metastatic or locally advanced solid tumours harbouring oncogenic NTRK1, NTRK2, and NTRK3 gene fusions treated in three ongoing, early-phase trials. Methods An integrated database comprised the pivotal datasets of three, ongoing phase 1 or 2 clinical trials (ALKA-372-001, STARTRK-1, and STARTRK-2), which enrolled patients aged 18 years or older with metastatic or locally advanced NTRK fusion-positive solid tumours who received entrectinib orally at a dose of at least 600 mg once per day in a capsule. All patients had an Eastern Cooperative Oncology Group performance status of 0–2 and could have received previous anti-cancer therapy (except previous TRK inhibitors). The primary endpoints, the proportion of patients with an objective response and median duration of response, were evaluated by blinded independent central review in the efficacy-evaluable population (ie, patients with NTRK fusion-positive solid tumours who were TRK inhibitor-naive and had received at least one dose of entrectinib). Overall safety evaluable population included patients from STARTRK-1, STARTRK-2, ALKA-372-001, and STARTRK-NG ( NCT02650401 ; treating young adult and paediatric patients [aged ≤21 years]), who received at least one dose of entrectinib, regardless of tumour type or gene rearrangement. NTRK fusion-positive safety evaluable population comprised all patients who have received at least one dose of entrectinib regardless of dose or follow-up. These ongoing studies are registered with ClinicalTrials.gov , NCT02097810 (STARTRK-1) and NCT02568267 (STARTRK-2), and EudraCT, 2012–000148–88 (ALKA-372-001). Findings Patients were enrolled in ALKA-372–001 from Oct 26, 2012, to March 27, 2018; in STARTRK-1 from Aug 7, 2014, to May 10, 2018; and in STARTRK-2 from Nov 19, 2015 (enrolment is ongoing). At the data cutoff date for this analysis (May 31, 2018) the efficacy-evaluable population comprised 54 adults with advanced or metastatic NTRK fusion-positive solid tumours comprising ten different tumour types and 19 different histologies. Median follow-up was 12.9 months (IQR 8·77–18·76). 31 (57%; 95% CI 43·2–70·8) of 54 patients had an objective response, of which four (7%) were complete responses and 27 (50%) partial reponses. Median duration of response was 10 months (95% CI 7·1 to not estimable). The most common grade 3 or 4 treatment-related adverse events in both safety populations were increased weight (seven [10%] of 68 patients in the NTRK fusion-positive safety population and in 18 [5%] of 355 patients in the overall safety-evaluable population) and anaemia (8 [12%] and 16 [5%]). The most common serious treatment-related adverse events were nervous system disorders (three [4%] of 68 patients and ten [3%] of 355 patients). No treatment-related deaths occurred. Interpretation Entrectinib induced durable and clinically meaningful responses in patients with NTRK fusion-positive solid tumours, and was well tolerated with a manageable safety profile. These results show that entrectinib is a safe and active treatment option for patients with NTRK fusion-positive solid tumours. These data highlight the need to routinely test for NTRK fusions to broaden the therapeutic options available for patients with NTRK fusion-positive solid tumours. Funding Ignyta/F Hoffmann-La Roche.

Diversity, Mechanisms, and Significance of Macrophage Plasticity

Abstract: Macrophages are a diverse set of cells present in all body compartments. This diversity is imprinted by their ontogenetic origin (embryonal versus adult bone marrow-derived cells); the organ context; by their activation or deactivation by various signals in the contexts of microbial invasion, tissue damage, and metabolic derangement; and by polarization of adaptive T cell responses. Classic adaptive responses of macrophages include tolerance, priming, and a wide spectrum of activation states, including M1, M2, or M2-like. Moreover, macrophages can retain long-term imprinting of microbial encounters (trained innate immunity). Single-cell analysis of mononuclear phagocytes in health and disease has added a new dimension to our understanding of the diversity of macrophage differentiation and activation. Epigenetic landscapes, transcription factors, and microRNA networks underlie the adaptability of macrophages to different environmental cues. Macrophage plasticity, an essential component of chronic inflammation, and its involvement in diverse human diseases, most notably cancer, is discussed here as a paradigm.

Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the European Atherosclerosis Society Consensus Panel

Abstract: Abstract

Waist circumference as a vital sign in clinical practice: a Consensus Statement from the IAS and ICCR Working Group on Visceral Obesity

Abstract: Despite decades of unequivocal evidence that waist circumference provides both independent and additive information to BMI for predicting morbidity and risk of death, this measurement is not routinely obtained in clinical practice. This Consensus Statement proposes that measurements of waist circumference afford practitioners with an important opportunity to improve the management and health of patients. We argue that BMI alone is not sufficient to properly assess or manage the cardiometabolic risk associated with increased adiposity in adults and provide a thorough review of the evidence that will empower health practitioners and professional societies to routinely include waist circumference in the evaluation and management of patients with overweight or obesity. We recommend that decreases in waist circumference are a critically important treatment target for reducing adverse health risks for both men and women. Moreover, we describe evidence that clinically relevant reductions in waist circumference can be achieved by routine, moderate-intensity exercise and/or dietary interventions. We identify gaps in the knowledge, including the refinement of waist circumference threshold values for a given BMI category, to optimize obesity risk stratification across age, sex and ethnicity. We recommend that health professionals are trained to properly perform this simple measurement and consider it as an important 'vital sign' in clinical practice.