Hypersurface-Invariant Approach to Cosmological Perturbations

Using Hamilton-Jacobi theory, we develop a formalism for solving semi-classical cosmological perturbations which does not require an explicit choice of time-hypersurface. The Hamilton-Jacobi equation for gravity interacting with matter (either a scalar or dust field) is solved by making an Ansatz which includes all terms quadratic in the spatial curvature. Gravitational radiation and scalar perturbations are treated on an equal footing. Our technique encompasses linear perturbation theory and it also describes some mild nonlinear effects. As a concrete example of the method, we compute the galaxy-galaxy correlation function as well as large-angle microwave background fluctuations for power-law inflation, and we compare with recent observations.Comment: 51 pages, Latex 2.09 ALBERTA THY/20-94, DAMTP R94/25 To appear in Phys. Rev.

Astronomical Distance Determination in the Space Age: Secondary Distance Indicators

The formal division of the distance indicators into primary and secondary leads to difficulties in description of methods which can actually be used in two ways: with, and without the support of the other methods for scaling. Thus instead of concentrating on the scaling requirement we concentrate on all methods of distance determination to extragalactic sources which are designated, at least formally, to use for individual sources. Among those, the Supernovae Ia is clearly the leader due to its enormous success in determination of the expansion rate of the Universe. However, new methods are rapidly developing, and there is also a progress in more traditional methods. We give a general overview of the methods but we mostly concentrate on the most recent developments in each field, and future expectations. © 2018, The Author(s)

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

Model-based estimation of land subsidence in Kathmandu Valley, Nepal

This study is the first to assess land subsidence in the Kathmandu Valley, Nepal. Land subsidence simulations were based on a fully calibrated groundwater (GW) flow model developed using a coupled surface–subsurface modelling system. Subsidence is predicted to occur as a result of deep aquifer compaction due to excessive GW abstraction. The north and north-east areas at the periphery of the GW basin are hotspots for this subsidence. The estimated subsidence is most sensitive to changes in land cover within the recharge areas. The model shows the Melamchi water supply project assists in the control of subsidence to some extent. In the absence of land subsidence measurements, this paper highlights the location and the potential levels of the subsidence hazard which will be useful for hazard prevention management. Additionally, this work provides a basis to design field investigations, monitoring networks for land subsidence and upgrading the present GW monitoring network. Although the study has presented a preliminary analysis, a more comprehensive model inclusive of clay subsidence is required to address the subsidence vulnerability of the central densely populated core of the valley, which reflects the need for a comprehensive database of the hydrogeology in the valley

Negotiating Transparency: The Role of Institutions

On 30 May 2001, a new regulation on public access to EU documents was presented and was heralded in the European press as a breakthrough for transparency. We argue that a focus on institutions can cast light on the negotiation processes that led to this decision, and explain the final-for realist negotiation theory puzzling-outcome. We demonstrate the importance of institutions in EU negotiations by detailing actor interests and strategies in the transparency case, and by tracing and analysing the negotiation process that resulted in the regulation. The institutions that receive particular attention are: agenda-shaping rules, decision-making procedures and voting rules, informal norms, time tables and deadlines, and intervention by institutional actors. Copyright Blackwell Publishing Ltd 2004.