Conditions for use and implementation of globally-aligned versus local baseplate coordinate systems when computing migration using radiostereometric analysis

Radiostereometric analysis can be used for computing movement of a tibial baseplate relative to the tibia (termed migration) to determine stability of fixation. Quantifying migration in six degrees of freedom requires establishing a coordinate system in which to express the movement. Establishing consistent migration directions among patients and baseplate designs remains challenging. Deviations in imaging alignment (tibia/baseplate alignment during image acquisition) and surgical alignment (baseplate alignment on tibia) will affect computed migrations when using the conventional globally-aligned baseplate coordinate system (BCS) (defined by calibration box). Computing migration using a local BCS (defined by baseplate) may be preferrable. This paper (1) summarizes the migration equations when using a globally-aligned versus local BCS, (2) proposes a method for defining a local BCS, and (3) demonstrates differences in the two BCSs for an example patient whose baseplate has rotational deviations due to imaging or surgical alignments. Differences in migration for the two BCSs ranged from about +/- 0.5 mm in translations and -0.4 deg to 0.7 deg in rotations. Differences were largest for deviations in internal-external rotation and smallest for deviations in varus-valgus rotation. An example demonstrated that the globally-aligned BCS resulted in migration being quantified as subsidence instead of liftoff, thereby changing fundamental interpretations. Because migrations computed using a local BCS are independent of imaging and surgical alignments and instead characterize migration using baseplate features, a local BCS enhances consistency in migration directions among patients and baseplate designs relative to the interface in which fixation may be compromised.Orthopaedics, Trauma Surgery and Rehabilitatio

Size Doesn't Matter: Towards a More Inclusive Philosophy of Biology

notes: As the primary author, O’Malley drafted the paper, and gathered and analysed data (scientific papers and talks). Conceptual analysis was conducted by both authors.publication-status: Publishedtypes: ArticlePhilosophers of biology, along with everyone else, generally perceive life to fall into two broad categories, the microbes and macrobes, and then pay most of their attention to the latter. ‘Macrobe’ is the word we propose for larger life forms, and we use it as part of an argument for microbial equality. We suggest that taking more notice of microbes – the dominant life form on the planet, both now and throughout evolutionary history – will transform some of the philosophy of biology’s standard ideas on ontology, evolution, taxonomy and biodiversity. We set out a number of recent developments in microbiology – including biofilm formation, chemotaxis, quorum sensing and gene transfer – that highlight microbial capacities for cooperation and communication and break down conventional thinking that microbes are solely or primarily single-celled organisms. These insights also bring new perspectives to the levels of selection debate, as well as to discussions of the evolution and nature of multicellularity, and to neo-Darwinian understandings of evolutionary mechanisms. We show how these revisions lead to further complications for microbial classification and the philosophies of systematics and biodiversity. Incorporating microbial insights into the philosophy of biology will challenge many of its assumptions, but also give greater scope and depth to its investigations

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