What Should We Learn From Early Hemodialysis Allocation About How We Should Be Using ECMO?

Early hemodialysis allocation deliberations should inform our current considerations of what constitutes reasonable uses of extracorporeal membrane oxygenation. Deliberative democracy can be used as a strategy to gather a plurality of views, consider criteria, and guide policy making

Applications, Potential Problems and a Suggested Policy for Institutional E-Print Archives

EPrints archives and similar archives promise many benefits for academics and their institutions, but there are complications in trying to solve too many problems at once. We describe the potential uses for an institutional archive running either the GNU EPrints software or software intended to provide similar functionality and how those applications may complement or interfere with each other. We then discusses policy decisions which should be made when implementing an archive and suggest a possible policy based on our own experience at Southampton University where the Electronics and Computer Science Department has been running an archive and database of our publications since 1998 and has provided software and assistance to many other institutions setting up a variety of electronic archives

Benchmarking network propagation methods for disease gene identification

In-silico identification of potential target genes for disease is an essential aspect of drug target discovery. Recent studies suggest that successful targets can be found through by leveraging genetic, genomic and protein interaction information. Here, we systematically tested the ability of 12 varied algorithms, based on network propagation, to identify genes that have been targeted by any drug, on gene-disease data from 22 common non-cancerous diseases in OpenTargets. We considered two biological networks, six performance metrics and compared two types of input gene-disease association scores. The impact of the design factors in performance was quantified through additive explanatory models. Standard cross-validation led to over-optimistic performance estimates due to the presence of protein complexes. In order to obtain realistic estimates, we introduced two novel protein complex-aware cross-validation schemes. When seeding biological networks with known drug targets, machine learning and diffusion-based methods found around 2-4 true targets within the top 20 suggestions. Seeding the networks with genes associated to disease by genetics decreased performance below 1 true hit on average. The use of a larger network, although noisier, improved overall performance. We conclude that diffusion-based prioritisers and machine learning applied to diffusion-based features are suited for drug discovery in practice and improve over simpler neighbour-voting methods. We also demonstrate the large impact of choosing an adequate validation strategy and the definition of seed disease genesPeer ReviewedPostprint (published version

Early experiences of computer‐aided assessment and administration when teaching computer programming

This paper describes early experiences with the Ceilidh system currently being piloted at over 30 institutions of higher education. Ceilidh is a course‐management system for teaching computer programming whose core is an auto‐assessment facility. This facility automatically marks students programs from a range of perspectives, and may be used in an iterative manner, enabling students to work towards a target level of attainment. Ceilidh also includes extensive course‐administration and progress‐monitoring facilities, as well as support for other forms of assessment including short‐answer marking and the collation of essays for later hand‐marking. The paper discusses the motivation for developing Ceilidh, outlines its major facilities, then summarizes experiences of developing and actually using it at the coal‐face over three years of teaching

Cross-species analysis traces adaptation of Rubisco towards optimality in a low dimensional landscape

Rubisco, probably the most abundant protein in the biosphere, performs an essential part in the process of carbon fixation through photosynthesis thus facilitating life on earth. Despite the significant effect that Rubisco has on the fitness of plants and other photosynthetic organisms, this enzyme is known to have a remarkably low catalytic rate and a tendency to confuse its substrate, carbon dioxide, with oxygen. This apparent inefficiency is puzzling and raises questions regarding the roles of evolution versus biochemical constraints in shaping Rubisco. Here we examine these questions by analyzing the measured kinetic parameters of Rubisco from various organisms in various environments. The analysis presented here suggests that the evolution of Rubisco is confined to an effectively one-dimensional landscape, which is manifested in simple power law correlations between its kinetic parameters. Within this one dimensional landscape, which may represent biochemical and structural constraints, Rubisco appears to be tuned to the intracellular environment in which it resides such that the net photosynthesis rate is nearly optimal. Our analysis indicates that the specificity of Rubisco is not the main determinant of its efficiency but rather the tradeoff between the carboxylation velocity and CO2 affinity. As a result, the presence of oxygen has only moderate effect on the optimal performance of Rubisco, which is determined mostly by the local CO2 concentration. Rubisco appears as an experimentally testable example for the evolution of proteins subject both to strong selection pressure and to biochemical constraints which strongly confine the evolutionary plasticity to a low dimensional landscape.Comment: http://www.pnas.org/content/107/8/3475.short http://www.ncbi.nlm.nih.gov/pubmed/20142476 http://www.weizmann.ac.il/complex/tlusty/papers/PNAS2010.pd

3D-printed individual labware in biosciences by rapid prototyping: In vitro biocompatibility and applications for eukaryotic cell cultures

Three-dimensional (3D) printing techniques are continuously evolving, thus their application fields are also growing very fast. The applications discussed here highlight the use of rapid prototyping in a dedicated biotechnology laboratory environment. The combination of improving prototypes using fused deposition modeling printers and producing useable parts with selective laser sintering printers enables a cost- and time-efficient use of such techniques. Biocompatible materials for 3D printing are already available and the printed parts can directly be used in the laboratory. To demonstrate this, we tested 3D printing materials for their in vitro biocompatibility. To exemplify the versatility of the 3D printing process applied to a biotechnology laboratory, a normal well plate design was modified in silico to include different baffle geometries. This plate was subsequently 3D printed and used for cultivation. In the near future, this design and print possibility will revolutionize the industry. Advanced printers will be available for laboratories and can be used for creating individual labware or standard disposables on demand. These applications have the potential to change the way research is done and change the management of stock-keeping, leading to more flexibility and promoting creativity of the scientists

Dogs perceive and spontaneously normalise formant-related speaker and vowel differences in human speech sounds

Domesticated animals have been shown to recognise basic phonemic information from human speech sounds and to recognise familiar speakers from their voices. However, whether animals can spontaneously identify words across unfamiliar speakers (speaker normalisation) or spontaneously discriminate between unfamiliar speakers across words remains to be investigated. Here, we assessed these abilities in domestic dogs using the habituation-dishabituation paradigm. We found that while dogs habituated to the presentation of a series of different short words from the same unfamiliar speaker, they significantly dishabituated to the presentation of a novel word from a new speaker of the same gender. This suggests that dogs spontaneously categorised the initial speaker across different words. Conversely, dogs who habituated to the same short word produced by different speakers of the same gender significantly dishabituated to a novel word, suggesting that they had spontaneously categorised the word across different speakers. Our results indicate that the ability to spontaneously recognise both the same phonemes across different speakers, and cues to identity across speech utterances from unfamiliar speakers, is present in domestic dogs and thus not a uniquely human trait

Finding the elusive balance between reducing fatigue and enhancing education: perspectives from American residents

Duty hour restrictions for residency training were implemented in the United States to improve residents' educational experience and quality of life, as well as to improve patient care and safety; however, these restrictions are by no means problem-free. In this paper, we discuss the positive and negative aspects of duty hour restrictions, briefly highlighting research on the impact of reduced duty hours and the experiences of American residents. We also consider whether certain specialties (e.g., Emergency Medicine, Radiology) may be more amenable than others (e.g., Surgery) to duty hour restrictions. We conclude that feedback from residents is a crucial element that must be considered in any future attempts to strike a balance between reducing fatigue and enhancing education