Integrated RNA and DNA sequencing reveals early drivers of metastatic breast cancer

Breast cancer metastasis remains a clinical challenge, even within a single patient across multiple sites of the disease. Genome-wide comparisons of both the DNA and gene expression of primary tumors and metastases in multiple patients could help elucidate the underlying mechanisms that cause breast cancer metastasis. To address this issue, we performed DNA exome and RNA sequencing of matched primary tumors and multiple metastases from 16 patients, totaling 83 distinct specimens. We identified tumor-specific drivers by integrating known protein-protein network information with RNA expression and somatic DNA alterations and found that genetic drivers were predominantly established in the primary tumor and maintained through metastatic spreading. In addition, our analyses revealed that most genetic drivers were DNA copy number changes, the TP53 mutation was a recurrent founding mutation regardless of subtype, and that multiclonal seeding of metastases was frequent and occurred in multiple subtypes. Genetic drivers unique to metastasis were identified as somatic mutations in the estrogen and androgen receptor genes. These results highlight the complexity of metastatic spreading, be it monoclonal or multiclonal, and suggest that most metastatic drivers are established in the primary tumor, despite the substantial heterogeneity seen in the metastases

Open data from the third observing run of LIGO, Virgo, KAGRA, and GEO

The global network of gravitational-wave observatories now includes five detectors, namely LIGO Hanford, LIGO Livingston, Virgo, KAGRA, and GEO 600. These detectors collected data during their third observing run, O3, composed of three phases: O3a starting in 2019 April and lasting six months, O3b starting in 2019 November and lasting five months, and O3GK starting in 2020 April and lasting two weeks. In this paper we describe these data and various other science products that can be freely accessed through the Gravitational Wave Open Science Center at https://gwosc.org. The main data set, consisting of the gravitational-wave strain time series that contains the astrophysical signals, is released together with supporting data useful for their analysis and documentation, tutorials, as well as analysis software packages

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of binary black hole coalescences confidently observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include the effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that have already been identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total source-frame mass M > 70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz emitted gravitational-wave frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place a conservative upper limit for the merger rate density of high-mass binaries with eccentricities 0 < e ≤ 0.3 at 16.9 Gpc−3 yr−1 at the 90% confidence level

Rational suicide: uncertain moral ground

Background. The ambiguities involving end-of-life issues, such as physician-assisted suicide and voluntary stopping of eating and drinking, have caused a blurring of the definition of rational suicide and have prompted rich dialogue with moral deliberations that seem to be on disparate paths among bioethicists and other health care professionals. With the evolution of advanced medical technology extending life expectancy in older, disabled, and terminally ill people, rational suicide has become a critical issue of debate. Aim. The purpose of this article is to address the ethical positions supporting and opposing rational suicide and to consider whether coherence can be achieved through an ethic of care. Findings. Attitudes towards suicide have been controversial, varying from acceptance to non-acceptance depending on social, political and religious influences. Nursing attitudes are no different from general societal attitudes and, consequently, nurses are treading on uncertain moral ground. Conclusion. Nurses who have not reflected on the moral issues involved with rational suicide may be unprepared psychologically and professionally when working with patients who may be contemplating such actions

Correctness of Service Components and Service Component Ensembles

Nowadays, cyber-physical systems consist of a large and possibly unbounded number of nodes operating in a partially unknown environment to which they need to adapt. They also have strong requirements in terms of performances, resource usage, reliability, or security. To face this inherent complexity it is crucial to develop adequate tools and underlying models to analyze these properties at design time. Proposed models must be able to capture essential aspects of the behavior (e.g. interactions between the components, adaptive behavior, uncertain or changing environments), and the corresponding analysis techniques can only succeed if they exploit as much as possible the specific structure of the considered systems (e.g. large replication of the same component, hierarchical compositions). We consider qualitative analyses targeting boolean properties stating that the system behaves without any flaw, as well as quantitative analyses that evaluate expected performances according to predefined metrics (energy/memory consumption, average/maximum time to accomplish a task, probability to fulfil a goal, etc.). We also address security specific issues such as control policies and information flow