A hybrid 3d reconstruction/registration algorithm for correction of head motion in emission tomography

Even with head restraint, small head movements can occur during data acquisition for emission tomography, sufficiently large to result in detectable artifacts in the final reconstruction. Direct measurement of motion can be cumbersome and difficult to implement, whereas previous attempts to correct for motion based on measured projections have been limited to simple translation orthogonal to the projection. A fully 3D algorithm is proposed that estimates the patient orientation at any time based on the projection of motion-corrupted data, with incorporation of the measured motion within subsequent OSEM sub-iterations. Preliminary studies have been performed using a digital version of the Hoffman brain phantom. Movement was simulated by constructing a mixed set of projections in two discrete positions of the phantom. The algorithm determined the phantom orientation that best aligned each constructed projection with its corresponding, measured projection. In the case of simulated movement of 24 of 64 projections, all mis-positioned projections were correctly identified. The algorithm resulted in a reduction of mean square difference (MSD) between motion corrected and motion-free reconstructions compared to the MSD between uncorrected and motion-free reconstructions by a factor of 2.7

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

Photochemistry of the pyruvate anion produces CO2, CO, CH3–, CH3, and a low energy electron

The photochemistry of pyruvic acid has attracted much scientific interest because it is believed to play critical roles in atmospheric chemistry. However, under most atmospherically relevant conditions, pyruvic acid deprotonates to form its conjugate base, the photochemistry of which is essentially unknown. Here, we present a detailed study of the photochemistry of the isolated pyruvate anion and uncover that it is extremely rich. Using photoelectron imaging and computational chemistry, we show that photoexcitation by UVA light leads to the formation of CO2, CO, and CH3−. The observation of the unusual methide anion formation and its subsequent decomposition into methyl radical and a free electron may hold important consequences for atmospheric chemistry. From a mechanistic perspective, the initial decarboxylation of pyruvate necessarily differs from that in pyruvic acid, due to the missing proton in the anion