Imaging Biomarkers in Prostate Stereotactic Body Radiotherapy: A Review and Clinical Trial Protocol

Advances in imaging have changed prostate radiotherapy through improved biochemical control from focal boost and improved detection of recurrence. These advances are reviewed in the context of prostate stereotactic body radiation therapy (SBRT) and the ARGOS/CLIMBER trial protocol. ARGOS/CLIMBER will evaluate 1) the safety and feasibility of SBRT with focal boost guided by multiparametric MRI (mpMRI) and 18F-PSMA-1007 PET and 2) imaging and laboratory biomarkers for response to SBRT. To date, response to prostate SBRT is most commonly evaluated using the Phoenix Criteria for biochemical failure. The drawbacks of this approach include lack of lesion identification, a high false-positive rate, and delay in identifying treatment failure. Patients in ARGOS/CLIMBER will receive dynamic 18F-PSMA-1007 PET and mpMRI prior to SBRT for treatment planning and at 6 and 24 months after SBRT to assess response. Imaging findings will be correlated with prostate-specific antigen (PSA) and biopsy results, with the goal of early, non-invasive, and accurate identification of treatment failure

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

The factors influencing entry level airline pilot retention: An empirical study of Ryanair

Pilot retention has been a significant concern for airlines that find it difficult to recruit and maintain pilots who are classified as high skilled employees. The aim of this research is to determine the factors that influence pilot retention and investigate if these factors differ based on gender, age and level of commercial flying experience of pilots. A mixed methods approach was used. Quantitative information was collected via an online survey sent to 394 Ryanair pilots. Nine in-depth expert interviews were conducted. The pilots ranked, in order of importance, a number of retention-influencing factors spanning seven areas, identified with the help of interviewees and secondary research. The results of the survey indicate that the most important retention influencing factors are being based at home, working a fixed roster pattern for a financially stable airline, being paid a competitive salary and having job security. This research provides qualitative evidence that airlines can use to develop or update their financial and non-financial benefits packages and where necessary, amend work practices and maximise pilot motivation to stay

Supplement 1. Code to compute the habitat connectivity index for upstream passage (HCIU) for the analyses presented.

<h2>File List</h2><div> <p><a href="PassageNetwork_Code_2013-01-23.txt">PassageNetwork_Code_2013-01-23.txt</a> (MD5: e871e22831e144932522c05fd7efab08) </p> </div><h2>Description</h2><div> <p>Computational code used in analyses to compute fish passage connectivity via the metric described in the paper (i.e., the habitat connectivity index for upstream passage, HCIU). All code is provided in the R computational language. Comment lines specify the inputs and outputs of the model. The code may be called from an R program.</p> </div

Rites of Passage: The Coffin Ship as Site of Immigrants’ Identity Formation in Irish and Irish-American Fiction, 1855-1885

Item does not contain fulltextThe statue of Annie Moore and her brothers in Cobh, Ireland, is one of the many lieux de mémoire which seek to crystallise the recollections of the Irish exodus to North America between 1845 and 1900. Scholars have examined the monuments erected to commemorate the massive exodus of 1.8 million Irish to Canada and the United States. Hitherto, however, very little attention has been paid to a transatlantic corpus of fiction, mainly written by the so-called “Famine generation,” which recollects the conditions of Irish immigrants to the New World. These novels and stories, by Irish writers at home who witnessed the outflux of population as well as authors who had migrated themselves to escape starvation and poverty, not only describe their migrant characters’ conditions of departure from the homeland and settlement in North American communities. An equally central role is reserved for the transition from home to diaspora, on-board the so-called “coffin ships.” While the texts remember the fearful realities of poor hygiene and high mortality rates on-board, the voyage also has a symbolic function, featuring as a rite of passage for the characters and their sense of ethnic identity. This article discusses several examples of the iconic image of the coffin ship in Irish and Irish American fiction on immigration, written between 1855 and 1885. In these texts, the storms that the immigrant characters have to endure during their passage at sea prefigure the trials the characters will face in the urban New World. Moreover, the coffin ships represent microcosmic Irish “imagined communities” that function as utopian heterotopia where the cultural clashes experienced in the homeland and the pending assimilation in the New World have to be negotiated.9 augustus 201117 p

Mapping out the Great Irish Famine in fiction, 1847–1870: imperial counternarratives

Item does not contain fulltext5 p