Degeneracy in the characterization of non-transiting planets from transit timing variations

The transit timing variation (TTV) method allows the detection of non-transiting planets through their gravitational perturbations. Since TTVs are strongly enhanced in systems close to mean-motion resonances (MMR), even a low mass planet can produce an observable signal. This technique has thus been proposed to detect terrestrial planets. In this letter, we analyse TTV signals for systems in or close to MMR in order to illustrate the difficulties arising in the determination of planetary parameters. TTVs are computed numerically with an n-body integrator for a variety of systems close to MMR. The main features of these TTVs are also derived analytically. Systems deeply inside MMR do not produce particularly strong TTVs, while those close to MMR generate quasiperiodic TTVs characterised by a dominant long period term and a low amplitude remainder. If the remainder is too weak to be detected, then the signal is strongly degenerate and this prevents the determination of the planetary parameters. Even though an Earth mass planet can be detected by the TTV method if it is close to a MMR, it may not be possible to assert that this planet is actually an Earth mass planet. On the other hand, if the system is right in the center of a MMR, the high amplitude oscillation of the TTV signal vanishes and the detection of the perturber becomes as difficult as it is far from MMR.Comment: 5 pages, 3 figures, submitted to MNRA

Awaiting a cure for COVID-19: therapeutic approach in patients with different severity levels of COVID-19

COVID-19 is an unpredictable infectious disease caused by SARS-CoV-2. The development of effective anti-COVID-19 vaccines has enormously minimized the risk of severe illness in most immunocompetent patients. However, unvaccinated patients and non-re-sponders to the COVID-19 vaccine are at risk of short-and long-term consequences. In these patients, the outcome of COVID-19 relies on an interplay of multiple factors including age, immunocompetence, comorbid-ities, inflammatory response triggered by the virus as well as the virulence of SARS-CoV-2 variants. General-ly, COVID-19 is asymptomatic or mildly symptomatic in young people, but it may manifest with respiratory insufficiency requiring mechanical ventilation in cer-tain susceptible groups of patients. Furthermore, severe SARS-CoV-2 infection induces multiorgan failure syndrome by affecting liver, kidney heart and nervous system. Since December 2019, multiple drugs have been test-ed to treat COVID-19, but only a few have been prov-en effective to mitigate the course of the disease that continues to cause death and comorbidity worldwide. Current treatment of COVID-19 patients is essential-ly based on the administration of supportive oxygen therapy and the use of specific drugs such as steroids, anticoagulants, antivirals, anti-SARS-CoV-2 antibodies and immunomodulators. However, the rapid spread of new variants and the release of new data coming from the numerous ongoing clinical trials have cre-ated the conditions for maintaining a continuous up-dating of the therapeutic management of COVID-19 patients. Furthermore, we believe that a well-estab-lished therapeutic strategy along with the continu-um of medical care for all patients with COVID-19 is pivotal to improving disease outcomes and restoring healthcare care fragmentation caused by the pandem-ic. This narrative review, focusing on the therapeutic management of COVID-19 patients, aimed to provide an overview of current therapies for (i) asymptomatic or mildly/moderate symptomatic patients, (ii) hospitalized patients requiring low-flow oxygen, (iii) high-flow oxygen and (iv) mechanical ventilation

Surfactant replacement might help recovery of low-compliance lung in severe COVID-19 pneumonia.

It has been hypothesized that there is a reduced AT2 cells number with low ability to synthesize and secrete endogenous surfactant in COVID-19 patients. To our knowledge, exogenous surfactant replacement has not been described so far in COVID-19 patients. We here report five cases of critically ill COVID-19 undergoing exogenous surfactant instillation through the airways

Modelling circumbinary protoplanetary disks II. Gas disk feedback on planetesimal dynamical and collisional evolution in the circumbinary systems Kepler-16 and 34

Aims. We investigate the feasibility of planetesimal growth in circumbinary protoplanetary disks around the observed systems Kepler- 16 and Kepler-34 under the gravitational influence of a precessing eccentric gas disk. Methods. We embed the results of our previous hydrodynamical simulations of protoplanetary disks around binaries into an N-body code to perform 3D, high-resolution, inter-particle gravity-enabled simulations of planetesimal growth and dynamics that include the gravitational force imparted by the gas. Results. Including the full, precessing asymmetric gas disk generates high eccentricity orbits for planetesimals orbiting at the edge of the circumbinary cavity, where the gas surface density and eccentricity have their largest values. The gas disk is able to efficiently align planetesimal pericenters in some regions leading to phased, non-interacting orbits. Outside of these areas eccentric planetesimal orbits become misaligned and overlap leading to crossing orbits and high relative velocities during planetesimal collisions. This can lead to an increase in the number of erosive collisions that far outweighs the number of collisions that result in growth. Gravitational focusing from the static axisymmetric gas disk is weak and does not significantly alter collision outcomes from the gas free case. Conclusions. Due to asymmetries in the gas disk, planetesimals are strongly perturbed onto highly eccentric orbits. Where planetesimals orbits are not well aligned, orbit crossings lead to an increase in the number of erosive collisions. This makes it difficult for sustained planetesimal accretion to occur at the location of Kepler-16b and Kepler-34b and we therefore rule out in-situ growth. This adds further support to our initial suggestions that most circumbinary planets should form further out in the disk and migrate inwards.Comment: 12 pages and 12 figure

A retrospective whole-genome sequencing analysis of carbapenem and colistin-resistant klebsiella pneumoniae nosocomial strains isolated during an MDR surveillance program

Multidrug-resistant Klebsiella pneumoniae (MDR Kp), in particular carbapenem-resistant Kp (CR-Kp), has become endemic in Italy, where alarming data have been reported on the spread of colistin-resistant CR-Kp (CRCR-Kp). During the period 2013–2014, 27 CRCR-Kp nosocomial strains were isolated within the Modena University Hospital Policlinico (MUHP) multidrug resistance surveillance program. We retrospectively investigated these isolates by whole-genome sequencing (WGS) analysis of the resistome, virulome, plasmid content, and core single nucleotide polymorphisms (cSNPs) in order to gain insights into their molecular epidemiology. The in silico WGS analysis of the resistome revealed the presence of genes, such as blaKPC, related to the phenotypically detected resistances to carbapenems. Concerning colistin resistance, the plasmidic genes mcr 1–9 were not detected, while known and new genetic variations in mgrB, phoQ, and pmrB were found. The virulome profile revealed the presence of type-3 fimbriae, capsular polysaccharide, and iron acquisition system genes. The detected plasmid replicons were classified as IncFIB(pQil), IncFIB(K), ColRNAI, IncX3, and IncFII(K) types. The cSNPs genotyping was consistent with the multi locus sequence typing (MLST) and with the distribution of mutations related to colistin resistance genes. In a nosocomial drug resistance surveillance program, WGS proved to be a useful tool for elucidating the spread dynamics of CRCR-Kp nosocomial strains and could help to limit their diffusion

Multidrug-resistant tuberculosis outbreak in an Italian prison: Tolerance of pyrazinamide plus levofloxacin prophylaxis and serial interferon gamma release assays

The optimal treatment for latent tuberculosis infection (LTBI) in subjects exposed to multidrug-resistant (MDR) tuberculosis (TB) remains unclear, and the change in response of the QuantiFERON-TB Gold In-Tube (QTB-IT) test during and after treatment is unknown. Between May 2010 and August 2010, 39 prisoners at the 'Casa Circondariale' of Modena, Italy, were exposed to a patient with active pulmonary MDR TB. All contacts were tested with the tuberculin skin test and QTB-IT. Upon exclusion of active TB, subjects positive to both tests were offered 6 months' treatment with pyrazinamide (PZA) and levofloxacin (LVX). QTB-IT testing was repeated at 3 and 6 months after initial testing in all subjects who were offered LTBI treatment. Seventeen (43.5%) of 39 subjects tested positive to both tuberculin skin test and QTB-IT test, and 12 (70.5%) agreed to receive therapy with PZA and LVX at standard doses. Only five (41.6%) of 12 subjects completed 6 months' treatment. Reasons for discontinuation were asymptomatic hepatitis, gastritis and diarrhoea. The QTB-IT values decreased in all subjects who completed the treatment, in two (33%) of six of those who received treatment for less than 3 months and in one (50%) of two patients who discontinued therapy after 3 months. The QTB-IT test results never turned negative. Despite the small number of subjects, the study confirmed that PZA plus LVX is a poorly tolerated option for MDR LTBI treatment. We observed a large degree of variation in the results of the QTB-IT test results among participants. The study confirmed that the interferon gamma release assay is not a reliable tool for monitoring the treatment of MDR LTBI in clinical practice

Modelling circumbinary protoplanetary disks I. Fluid simulations of the Kepler-16 and 34 systems

S.L and Z.M.L are supported by the STFC. P.J.C is grateful to NERC Grant NE/K004778/1. S.J.P. is supported by a Royal Society University Research Fellowship

Epidemiology and Outcomes of Bloodstream Infections in HIV-Patients during a 13-Year Period

No data on antibiotic resistance in bloodstream infection (BSI) in people living with HIV (PLWH) exist. The objective of this study was to describe BSI epidemiology in PLWH focusing on multidrug resistant (MDR) organisms. A retrospective, single-center, observational study was conducted including all positive blood isolates in PLWH from 2004 to 2017. Univariable and multivariable GEE models using binomial distribution family were created to evaluate the association between MDR and mortality risk. In total, 263 episodes (299 isolates) from 164 patients were analyzed; 126 (48%) BSI were community-acquired, 137 (52%) hospital-acquired. At diagnosis, 34.7% of the patients had virological failure, median CD4 count was 207/μL. Thirty- and 90-day mortality rates were 24.2% and 32.4%, respectively. Thirty- and 90-day mortality rates for MDR isolates were 33.3% and 46.9%, respectively (p < 0.05). Enterobacteriaceae were the most prevalent microorganisms (29.8%), followed by Coagulase-negative staphylococci (21.4%), and S. aureus (12.7%). In BSI due to MDR organisms, carbapenem-resistant K. pneumoniae and methicillin-resistant S. aureus were associated with mortality after adjustment for age, although this correlation was not confirmed after further adjustment for CD4 < 200/μL. In conclusion, BSI in PLWH is still a major problem in the combination antiretroviral treatment era and it is related to a poor viro-immunological status, posing the question of whether it should be considered as an AIDS-defining event