The development and sea trials of a subsea holographic camera for large volume in-situ recording of marine organisms

We describe the development, construction and sea testing of an underwater holographic camera (HoloCam) for in situ recording of marine organisms and particles in large volumes of sea water. HoloCam comprises a laser, power supply, holographic recording optics and plate holders, a water-tight housing and a support frame. Added to this are control electronics such that the entire camera is remotely operable and controllable from ship or dock-side. Uniquely the camera can simultaneously record both in-line and off-axis holograms using a pulsed frequency doubled Nd-YAG laser. In-line holography is capable of producing images of organisms with a resolution of better than 10 Pm (at concentrations up to a few thousand per cubic centimetre at the smallest sizes). Off-axis holograms of aquatic systems of up to 50,000 cm3 volume, have been recorded. Following initial laboratory testing, the holo-camera was evaluated in an observation tank and ultimately was tested in Loch Etive, Scotland. In-line and off-axis holograms were recorded to a depth of 100 m. We will present results on the test dives and evaluation of the camera performance

HoloCam: A subsea holographic camera for recording marine organisms and particles

The HoloCam system is a major component of a multi-national multi-discipline project known as HoloMar (funded by the European Commission under the MAST III initiative). The project is concerned with the development of pulsed laser holography to analyse and monitor the populations of living organisms and inanimate particles within the world's oceans. We describe here the development, construction and evaluation of a prototype underwater camera, the purpose of which is to record marine organisms and particles, in-situ. Recording using holography provides several advantages over conventional sampling methods in that it allows non-intrusive, non-destructive, high-resolution imaging of large volumes (up to 10^5 cm^3) in three dimensions. The camera incorporates both in-line and off-axis holographic techniques, which allows particles from a few micrometres to tens of centimetres to be captured. In tandem with development of the HoloCam, a dedicated holographic replay system and an automated data extraction and image processing facility are being developed. These will allow, optimisation of the images recorded by the camera, identification of species and particle concentration plotting

A holographic system for subsea recording and analysis of plankton and other marine particles

We report here details of the design, development, initial testing and field-deployment of the HOLOMAR system for in-situ subsea holography and analysis of marine plankton and nonliving particles. HOLOMAR comprises a submersible holographic camera ("HoloCam") able to record in-line and off-axis holograms at depths down to 100 m, together with specialised reconstruction hardware ("HoloScan") linked to custom image processing and classification software. The HoloCam consists of a laser and power supply, holographic recording optics and holographic plate holders, a water-tight housing and a support frame. It utilises two basic holographic geometries, in-line and off-axis such that a wide range of species, sizes and concentrations can be recorded. After holograms have been recorded and processed they are reconstructed in full three-dimensional detail in air in a dedicated replay facility. A computer-controlled microscope, using video cameras to record the image at a given depth, is used to digitise the scene. Specially written software extracts a binarised image of an object in its true focal plane and is classified using a neural network. The HoloCam was deployed on two separate cruises in a Scottish sea loch (Loch Etive) to a depth of 100 m and over 300 holograms were recorded

Emerging concepts in biomarker discovery; The US-Japan workshop on immunological molecular markers in oncology

Supported by the Office of International Affairs, National Cancer Institute (NCI), the "US-Japan Workshop on Immunological Biomarkers in Oncology" was held in March 2009. The workshop was related to a task force launched by the International Society for the Biological Therapy of Cancer (iSBTc) and the United States Food and Drug Administration (FDA) to identify strategies for biomarker discovery and validation in the field of biotherapy. The effort will culminate on October 28th 2009 in the "iSBTc-FDA-NCI Workshop on Prognostic and Predictive Immunologic Biomarkers in Cancer", which will be held in Washington DC in association with the Annual Meeting. The purposes of the US-Japan workshop were a) to discuss novel approaches to enhance the discovery of predictive and/or prognostic markers in cancer immunotherapy; b) to define the state of the science in biomarker discovery and validation. The participation of Japanese and US scientists provided the opportunity to identify shared or discordant themes across the distinct immune genetic background and the diverse prevalence of disease between the two Nations

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, 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 hospitalization2–4 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

Genetic mechanisms of critical illness in Covid-19.

Host-mediated lung inflammation is present,1 and drives mortality,2 in critical illness caused by Covid-19. Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development.3 Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study(GWAS) in 2244 critically ill Covid-19 patients from 208 UK intensive care units (ICUs). We identify and replicate novel genome-wide significant associations, on chr12q24.13 (rs10735079, p=1.65 [Formula: see text] 10-8) in a gene cluster encoding antiviral restriction enzyme activators (OAS1, OAS2, OAS3), on chr19p13.2 (rs2109069, p=2.3 [Formula: see text] 10-12) near the gene encoding tyrosine kinase 2 (TYK2), on chr19p13.3 (rs2109069, p=3.98 [Formula: see text] 10-12) within the gene encoding dipeptidyl peptidase 9 (DPP9), and on chr21q22.1 (rs2236757, p=4.99 [Formula: see text] 10-8) in the interferon receptor gene IFNAR2. We identify potential targets for repurposing of licensed medications: using Mendelian randomisation we found evidence in support of a causal link from low expression of IFNAR2, and high expression of TYK2, to life-threatening disease; transcriptome-wide association in lung tissue revealed that high expression of the monocyte/macrophage chemotactic receptor CCR2 is associated with severe Covid-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms, and mediators of inflammatory organ damage in Covid-19. Both mechanisms may be amenable to targeted treatment with existing drugs. Large-scale randomised clinical trials will be essential before any change to clinical practice