A system for investigating oesophageal photoplethysmographic signals in anaesthetised patients

The monitoring of arterial blood oxygen saturation in patients with compromised peripheral perfusion is often difficult, because conventional non-invasive techniques such as pulse oximetry (SpO2) can fail. Poor peripheral circulation commonly occurs after major surgery including cardiopulmonary bypass. The difficulties in these clinical situations might be overcome if the sensor were to monitor a better perfused central part of the body such as the oesophagus. A new oesophageal photoplethysmographic (PPG) probe and an isolated processing system have been developed to investigate the pulsatile signals of anaesthetised adult patients undergoing routine surgery. Measurements were made in the middle third of the oesophagus, 25 cm to 30 cm from the upper incisors. The AC PPG signals are sampled by a data acquisition system connected to a laptop computer. The signals recorded correspond to infrared and red AC PPGs from the middle third oesophagus and the finger. Preliminary results from 20 patients show that good quality AC PPG signals can be measured in the human oesophagus. The ratio of the oesophageal to finger AC PPG amplitudes was calculated for the infrared and red wavelengths for each patient. The mean (+/- standard deviation) of this ratio was 2.9 +/- 2.1 (n = 19) for the infrared wavelength and 3.1 +/- 2.4 (n = 16) for the red wavelength. The red and infrared wavelengths used are appropriate for pulse oximetry and this investigation indicates that the mid-oesophagus may be a suitable site for the reliable monitoring of SpO2 in patients with poor peripheral perfusion

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

Seasonal nutrient dynamics in a chalk stream: the River Frome, Dorset, UK

Chalk streams provide unique, environmentally important habitats, but are particularly susceptible to human activities, such as water abstraction, fish farming and intensive agricultural activity on their fertile flood-meadows, resulting in increased nutrient concentrations. Weekly phosphorus, nitrate, dissolved silicon, chloride and flow measurements were made at nine sites along a 32 km stretch of the River Frome and its tributaries, over a 15 month period. The stretch was divided into two sections (termed the middle and lower reach) and mass balances were calculated for each determinand by totalling the inputs from upstream, tributaries, sewage treatment works and an estimate of groundwater input, and subtracting this from the load exported from each reach. Phosphorus and nitrate were retained within the river channel during the summer months, due to bioaccumulation into river biota and adsorption of phosphorus to bed sediments. During the autumn to spring periods, there was a net export, attributed to increased diffuse inputs from the catchment during storms, decomposition of channel biomass and remobilisation of phosphorus from the bed sediment. This seasonality of retention and remobilisation was higher in the lower reach than the middle reach, which was attributed to downstream changes in land use and fine sediment availability. Silicon showed much less seasonality, but did have periods of rapid retention in spring, due to diatom uptake within the river channel, and a subsequent release from the bed sediments during storm events. Chloride did not produce a seasonal pattern, indicating that the observed phosphor-us and nitrate seasonality was a product of annual variation in diffuse inputs and internal riverine processes, rather than an artefact of sampling, flow gauging and analytical errors