A robust semantics hides fewer errors

In this paper we explore how formal models are interpreted and to what degree meaning is captured in the formal semantics and to what degree it remains in the informal interpretation of the semantics. By applying a robust approach to the definition of refinement and semantics, favoured by the event-based community, to state-based theory we are able to move some aspects from the informal interpretation into the formal semantics

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

An implantable instrument for studying the long-term flight biology of migratory birds

The design of an instrument deployed in a project studying the high altitude Himalayan migrations of bar-headed geese (Anser indicus) is described. The electronics of this archival datalogger measured 22 � 14 � 6.5 mm, weighed 3 g, was powered by a ½AA-sized battery weighing 10 g and housed in a transparent biocompatible tube sealed with titanium electrodes for electrocardiography (ECG). The combined weight of 32 g represented less than 2% of the typical bodyweight of the geese. The primary tasks of the instrument were to continuously record a digitised ECG signal for heart-rate determination and store 12-bit triaxial accelerations sampled at 100 Hz with 15% coverage over each 2 min period. Measurement of atmospheric pressure provided an indication of altitude and rate of ascent or descent during flight. Geomagnetic field readings allowed for latitude estimation. These parameters were logged twice per minute along with body temperature. Data were stored to a memory card of 8 GB capacity. Instruments were implanted in geese captured on Mongolian lakes during the breeding season when the birds are temporarily flightless due to moulting. The goal was to collect data over a ten month period, covering both southward and northward migrations. This imposed extreme constraints on the design's power consumption. Raw ECG can be post-processed to obtain heart-rate, allowing improved rejection of signal interference due to strenuous activity of locomotory muscles during flight. Accelerometry can be used to monitor wing-beat frequency and body kinematics, and since the geese continued to flap their wings continuously even during rather steep descents, act as a proxy for biomechanical power. The instrument enables detailed investigation of the challenges faced by the geese during these arduous migrations which typically involve flying at extreme altitudes through cold, low density air where oxygen availability is significantly reduced compared to sea level

Analysing the intermittent flapping flight of a Manx Shearwater, Puffinus puffinus, and its sporadic use of a wave-meandering wing-sailing flight strategy

Flights of Manx Shearwaters over the Irish Sea were investigated using GPS (n = 6) and simultaneous high sample rate triaxial accelerometry (n = 1). This pelagic species executes flight through intermittent bursts of flapping flight interspersed with gliding phases while meandering low over the waves. To facilitate the analysis and interpretation of body-mounted accelerometry in these challenging circumstances we introduce a combined time and frequency domain technique allowing accurate separation of flapping from gliding, measurement of wing-beat frequency and determination of flapping duty cycle. Considerable fluctuations in cycle period and time-averaged flapping duty cycle were found. Our approach offered high temporal precision, which was crucial as half the flapping bursts were briefer than 0.8 s and half the cycle times shorter than 2.55 s. Flapping duty cycles exceeding 38% were likeliest for short range flights and ascending flights. At higher duty cycles, cycle time decreased and wing-beat frequency and amplitude was only moderately elevated. Near-continuous flapping was only observed during steep ascents and strong headwinds. During a long-range foraging flight with good GPS coverage duty cycles between 7% and 63% were observed. We posit that flapping was modulated in order to maintain a steady airspeed in somewhat variable wind and wave conditions as part of a complex wave-meandering wing-sailing flight strategy that was often effective in reducing locomotion costs. Periods of very low duty cycle flight appear to have benefited from instantaneous crosswinds exceeding 10 m s�1 with an estimated three-fold reduction in biomechanical power. Accelerometry offers a very practical tool for studying flight performance and the methods herein described can be readily adapted to other species that intermittently beat their wings