A pilot search for mm-wavelength recombination lines from emerging ionized winds in pre-planetary nebulae candidates

We report the results from a pilot search for radio recombination line (RRL) emission at millimeter wavelengths in a small sample of pre-planetary nebulae (pPNe) and young PNe (yPNe) with emerging central ionized regions. Observations of the H30\alpha, H31a, H39a, H41a, H48b, H49b, H51b, and H55g lines at 1 and 3mm have been performed with the IRAM 30 m radio telescope. These lines are excellent probes of the dense inner (<~150 au) and heavily obscured regions of these objects, where the yet unknown agents for PN-shaping originate. We detected mm-RRLs in three objects: CRL 618, MWC 922, and M 2-9. For CRL 618, the only pPN with previous published detections of H41a, H35a, and H30a emission, we find significant changes in the line profiles indicating that current observations are probing regions of the ionized wind with larger expansion velocities and mass-loss rate than ~29 years ago. In the case of MWC 922, we observe a drastic transition from single-peaked profiles at 3mm to double-peaked profiles at 1mm, which is consistent with maser amplification of the highest frequency lines; the observed line profiles are compatible with rotation and expansion of the ionized gas, probably arranged in a disk+wind system around a ~5-10 Msun central mass. In M 2-9, the mm-RRL emission appears to be tracing a recent mass outburst by one of the stars of the central binary system. We present the results from non-LTE line and continuum radiative transfer models, which enables us to constrain the structure, kinematics, and physical conditions (electron temperature and density) of the ionized cores of our sample. (abridged). We deduce mass-loss rates of ~1e-6-1e-7 Msun/yr, which are significantly higher than the values adopted by stellar evolution models currently in use and would result in a transition from the asymptotic giant branch to the PN phase faster than hitherto assumed.Comment: Accepted by Astronomy and Astrophysics. 28 pages, including figure

Direct estimation of electron density in the Orion Bar PDR from mm-wave carbon recombination lines

A significant fraction of the molecular gas in star-forming regions is irradiated by stellar UV photons. In these environments, the electron density (n_e) plays a critical role in the gas dynamics, chemistry, and collisional excitation of certain molecules. We determine n_e in the prototypical strongly irradiated photodissociation region (PDR), the Orion Bar, from the detection of new millimeter-wave carbon recombination lines (mmCRLs) and existing far-IR [13CII] hyperfine line observations. We detect 12 mmCRLs (including alpha, beta, and gamma transitions) observed with the IRAM 30m telescope, at ~25'' angular resolution, toward the H/H2 dissociation front (DF) of the Bar. We also present a mmCRL emission cut across the PDR. These lines trace the C+/C/CO gas transition layer. As the much lower frequency carbon radio recombination lines, mmCRLs arise from neutral PDR gas and not from ionized gas in the adjacent HII region. This is readily seen from their narrow line profiles (dv=2.6+/-0.4 km/s) and line peak LSR velocities (v_LSR=+10.7+/-0.2 km/s). Optically thin [13CII] hyperfine lines and molecular lines - emitted close to the DF by trace species such as reactive ions CO+ and HOC+ - show the same line profiles. We use non-LTE excitation models of [13CII] and mmCRLs and derive n_e = 60-100 cm^-3 and T_e = 500-600 K toward the DF. The inferred electron densities are high, up to an order of magnitude higher than previously thought. They provide a lower limit to the gas thermal pressure at the PDR edge without using molecular tracers. We obtain P_th > (2-4)x10^8 cm^-3 K assuming that the electron abundance is equal or lower than the gas-phase elemental abundance of carbon. Such elevated thermal pressures leave little room for magnetic pressure support and agree with a scenario in which the PDR photoevaporates.Comment: Accepted for publication in A&A Letters (includes language editor corrections

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access

Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing

Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we analyze patterns of chromothripsis across 2,658 tumors from 38 cancer types using whole-genome sequencing data. We find that chromothripsis events are pervasive across cancers, with a frequency of more than 50% in several cancer types. Whereas canonical chromothripsis profiles display oscillations between two copy-number states, a considerable fraction of events involve multiple chromosomes and additional structural alterations. In addition to non-homologous end joining, we detect signatures of replication-associated processes and templated insertions. Chromothripsis contributes to oncogene amplification and to inactivation of genes such as mismatch-repair-related genes. These findings show that chromothripsis is a major process that drives genome evolution in human cancer

Analyses of non-coding somatic drivers in 2,658 cancer whole genomes.

The discovery of drivers of cancer has traditionally focused on protein-coding genes1-4. Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium5 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For point mutations, we developed a statistically rigorous strategy for combining significance levels from multiple methods of driver discovery that overcomes the limitations of individual methods. For structural variants, we present two methods of driver discovery, and identify regions that are significantly affected by recurrent breakpoints and recurrent somatic juxtapositions. Our analyses confirm previously reported drivers6,7, raise doubts about others and identify novel candidates, including point mutations in the 5' region of TP53, in the 3' untranslated regions of NFKBIZ and TOB1, focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available

Early mobilisation in critically ill COVID-19 patients: a subanalysis of the ESICM-initiated UNITE-COVID observational study

Background Early mobilisation (EM) is an intervention that may improve the outcome of critically ill patients. There is limited data on EM in COVID-19 patients and its use during the first pandemic wave. Methods This is a pre-planned subanalysis of the ESICM UNITE-COVID, an international multicenter observational study involving critically ill COVID-19 patients in the ICU between February 15th and May 15th, 2020. We analysed variables associated with the initiation of EM (within 72 h of ICU admission) and explored the impact of EM on mortality, ICU and hospital length of stay, as well as discharge location. Statistical analyses were done using (generalised) linear mixed-effect models and ANOVAs. Results Mobilisation data from 4190 patients from 280 ICUs in 45 countries were analysed. 1114 (26.6%) of these patients received mobilisation within 72 h after ICU admission; 3076 (73.4%) did not. In our analysis of factors associated with EM, mechanical ventilation at admission (OR 0.29; 95% CI 0.25, 0.35; p = 0.001), higher age (OR 0.99; 95% CI 0.98, 1.00; p ≤ 0.001), pre-existing asthma (OR 0.84; 95% CI 0.73, 0.98; p = 0.028), and pre-existing kidney disease (OR 0.84; 95% CI 0.71, 0.99; p = 0.036) were negatively associated with the initiation of EM. EM was associated with a higher chance of being discharged home (OR 1.31; 95% CI 1.08, 1.58; p = 0.007) but was not associated with length of stay in ICU (adj. difference 0.91 days; 95% CI − 0.47, 1.37, p = 0.34) and hospital (adj. difference 1.4 days; 95% CI − 0.62, 2.35, p = 0.24) or mortality (OR 0.88; 95% CI 0.7, 1.09, p = 0.24) when adjusted for covariates. Conclusions Our findings demonstrate that a quarter of COVID-19 patients received EM. There was no association found between EM in COVID-19 patients' ICU and hospital length of stay or mortality. However, EM in COVID-19 patients was associated with increased odds of being discharged home rather than to a care facility. Trial registration ClinicalTrials.gov: NCT04836065 (retrospectively registered April 8th 2021)