A computational design of experiments based method for evaluation of off-the-shelf total knee replacement implants

A methodology to explore the design space of off-the-shelf total knee replacement implant designs is outlined. Generic femur component and tibia plate designs were scaled to thousands of sizes and virtually fitted to 244 test subjects. Various implant designs and sizing requirements between genders and ethnicities were evaluated. 5 sizes optimised via the methodology produced a good global fit for most subjects. However, clinically significant over/underhang was present in 19% of subjects for tibia plates and 25% for femur components, reducing to 11/20% with 8 sizes. The analysis highlighted subtly better fit performance was obtained using sizes with unequal spacing

Applying machine learning methods to enable automatic customisation of knee replacement implants from CT data

The aim of this study was to develop an automated pipeline capable of designing custom total knee replacement implants from CT scans. The developed pipeline firstly utilised a series of machine learning methods including classification, object detection, and image segmentation models, to extract geometrical information from inputted DICOM files. Statistical shape models then used the information to create femur and tibia 3D surface model predictions which were ultimately used by computer aided design scripts to generate customised implant designs. The developed pipeline was trained and tested using CT scan images, along with segmented 3D models, obtained for 98 Korean Asian subjects. The performance of the pipeline was tested computationally by virtually fitting outputted implant designs with ‘ground truth’ 3D models for each test subject’s bones. This demonstrated the pipeline was capable of repeatably producing highly accurate designs, and its performance was not impacted by subject sex, height, age, or knee side. In conclusion, a robust, accurate and automatic, CT-based total knee replacement customisation pipeline was shown to be feasible and could afford significant time and cost advantages over conventional methods. The pipeline framework could also be adapted to enable customisation of other medical implants

A comparison of the palatability of racemic praziquantel and its two enantioseparated isomers in yellowtail kingfish Seriola lalandi (Valenciennes, 1833)

The bitterness of racemic praziquantel (Rac-PZQ) constrains its use as an in-feed treatment against monogenean flukes in finfish aquaculture. Evidence exists in mammals that the R-(-) enantiomer of PZQ is less bitter than the S-(+) enantiomer. If fish exhibit this same response, then the recently described techniques for the large-scale resolution of R-(-)-PZQ from Rac-PZQ could facilitate the wide-spread application of this effective anthelmintic compound via feed. The hypothesis that yellowtail kingfish Seriola lalandi would find R-(-)-PZQ more palatable than Rac-PZQ and S-(+)-PZQ was tested in four trials. During the first three trials, the palatability of diets top-coated with 10 g kg-1 of Rac-PZQ or its two enantioseparated isomers were compared in small (85-160 g) and large (1.2 kg) yellowtail kingfish. A fourth trial compared the palatability of R-(-)-PZQ and Rac-PZQ at dietary inclusion levels of 2.5, 5.0 and 10.0 g kg-1 in small yellowtail kingfish (170 g). Ingestion data showed that R-(-)-PZQ to be no more palatable than either Rac-PZQ or S-(+)-PZQ to yellowtail kingfish, regardless of size. Indeed, evidence suggested that the S-(+)-PZQ to be slightly more palatable than both R-(-)-PZQ and Rac-PZQ. From these data, we hypothesize that the strong smell of R-(-)-PZQ (which was not present in S-(+)-PZQ) is an equally important determinant to palatability as taste in yellowtail kingfish. Results demonstrate that dietary inclusion level is a more important determinant to palatability than PZQ chirality; however, administration of R-(-)-PZQ may still be advantageous if it is demonstrated to be the only enantiomer efficacious against monogeneans

Wittgensteinian content‐externalism

Content-externalism is the view that a subject’s relations to a context can play a role in individuating the content of her mental states. According to social content-externalists, relations to a socio-linguistic context can play a fundamental individuating role. Åsa Wikforss has suggested that ‘social externalism depends on the assumption that individuals have an incomplete grasp of their own concepts’ (Wikforss 2004, p. 287). In this paper, I show that this isn’t so. I develop and defend an argument for social content-externalism which does not depend on this assumption. The argument is animated by strands of thought in the later work of Wittgenstein. In addition to demonstrating that social externalists are not necessarily committed to thinking that a subject can have thoughts involving concepts which she incompletely understands, this argument is important insofar as it: (1) supports a form of content-externalism with extended scope; (2) avoids the controversy surrounding the claim that subjects can think with concepts which they incompletely understand; and (3) situates Wittgenstein’s later work with respect to contemporary debates about content-externalism

Sashimi plots: Quantitative visualization of RNA sequencing read alignments

We introduce Sashimi plots, a quantitative multi-sample visualization of mRNA sequencing reads aligned to gene annotations. Sashimi plots are made using alignments (stored in the SAM/BAM format) and gene model annotations (in GFF format), which can be custom-made by the user or obtained from databases such as Ensembl or UCSC. We describe two implementations of Sashimi plots: (1) a stand-alone command line implementation aimed at making customizable publication quality figures, and (2) an implementation built into the Integrated Genome Viewer (IGV) browser, which enables rapid and dynamic creation of Sashimi plots for any genomic region of interest, suitable for exploratory analysis of alternatively spliced regions of the transcriptome. Isoform expression estimates outputted by the MISO program can be optionally plotted along with Sashimi plots. Sashimi plots can be used to quickly screen differentially spliced exons along genomic regions of interest and can be used in publication quality figures. The Sashimi plot software and documentation is available from: http://genes.mit.edu/burgelab/miso/docs/sashimi.htmlComment: 2 figure

Counting approximately-shortest paths in directed acyclic graphs

Given a directed acyclic graph with positive edge-weights, two vertices s and t, and a threshold-weight L, we present a fully-polynomial time approximation-scheme for the problem of counting the s-t paths of length at most L. We extend the algorithm for the case of two (or more) instances of the same problem. That is, given two graphs that have the same vertices and edges and differ only in edge-weights, and given two threshold-weights L_1 and L_2, we show how to approximately count the s-t paths that have length at most L_1 in the first graph and length at most L_2 in the second graph. We believe that our algorithms should find application in counting approximate solutions of related optimization problems, where finding an (optimum) solution can be reduced to the computation of a shortest path in a purpose-built auxiliary graph

Impact micro-positioning actuator

An impact micro-positioning actuator. In one aspect of the invention, a threaded shaft is threadably received in a nut and the nut is impacted by an impacting device, causing the nut first to rotate relative to the shaft by slipping as a result of shaft inertia and subsequently to stick to the shaft as a result of the frictional force therebetween. The nut is returned to its initial position by a return force provided by a return mechanism after impact. The micro-positioning actuator is further improved by controlling at least one and preferably all of the following: the friction, the impact provided by the impacting device, the return force provided by the return mechanism, and the inertia of the shaft. In another aspect of the invention, a threaded shaft is threadably received in a nut and the shaft is impacted by an impacting device, causing the shaft to rotate relative to the nut

Splice site strength–dependent activity and genetic buffering by poly-G runs

Pre-mRNA splicing is regulated through the combinatorial activity of RNA motifs, including splice sites and splicing regulatory elements. Here we show that the activity of the G-run (polyguanine sequence) class of splicing enhancer elements is approx4-fold higher when adjacent to intermediate strength 5' splice sites (ss) than when adjacent to weak 5' ss, and approx1.3-fold higher relative to strong 5' ss. We observed this dependence on 5' ss strength in both splicing reporters and in global microarray and mRNA-Seq analyses of splicing changes following RNA interference against heterogeneous nuclear ribonucleoprotein (hnRNP) H, which cross-linked to G-runs adjacent to many regulated exons. An exon's responsiveness to changes in hnRNP H levels therefore depends in a complex way on G-run abundance and 5' ss strength. This pattern of activity enables G-runs and hnRNP H to buffer the effects of 5' ss mutations, augmenting both the frequency of 5' ss polymorphism and the evolution of new splicing patterns. Certain other splicing factors may function similarly.American Heart AssociationHuman Frontier Science Program (Strasbourg, France)National Institutes of Health (U.S.)National Science Foundation (U.S.) (equipment grant DBI-0821391

Single shot measurement of a silicon single electron transistor

We have fabricated a custom cryogenic Complementary Metal-Oxide-Semiconductor (CMOS) integrated circuit that has a higher measurement bandwidth compared with conventional room temperature electronics. This allowed implementing single shot operations and observe the real-time evolution of the current of a phosphorous-doped silicon single electron transistor that was irradiated with a microwave pulse. Relaxation times up to 90 us are observed, suggesting the presence of well isolated electron excitations within the device. It is expected that these are associated with long decoherence time and the device may be suitable for quantum information processing

Epistemic Two-Dimensionalism and Arguments From Epistemic Misclassification

According to Epistemic Two-Dimensional Semantics (E2D), expressions have a counterfactual intension and an epistemic intension. Epistemic intensions reflect cognitive significance such that sentences with necessary epistemic intensions are a priori. We defend E2D against an influential line of criticism: arguments from epistemic misclassification. We focus in particular on the arguments of Speaks [2010] and Schroeter [2005]. Such arguments conclude that E2D is mistaken from (i) the claim that E2D is committed to classifying certain sentences as a priori, and (ii) the claim that such sentences are a posteriori. We aim to show that these arguments are unsuccessful as (i) and (ii) undercut each other. One must distinguish the general framework of E2D from a specific implementation of it. The framework is flexible enough to avoid commitment to the apriority of any particular sentence; only specific implementations are so committed. Arguments from epistemic misclassification are therefore better understood as arguments for favouring one implementation of E2D over another, rather than as refutations of E2D