Consensus on pre-operative total knee replacement education and prehabilitation recommendations: a UK-based modified Delphi study

Background Over 90,000 total knee replacement (TKR) procedures are performed annually in the United Kingdom (UK). Patients awaiting TKR face long delays whilst enduring severe pain and functional limitations. Almost 20% of patients who undergo TKR are not satisfied post-operatively. Optimising pre-operative TKR education and prehabilitation could help improve patient outcomes pre- and post-operatively; however, current pre-operative TKR care varies widely. Definitive evidence on the optimal content and delivery of pre-operative TKR care is lacking. This study aimed to develop evidence- and consensus-based recommendations on pre-operative TKR education and prehabilitation. Methods A UK-based, three-round, online modified Delphi study was conducted with a 60-member expert panel. All panellists had experience of TKR services as patients (n = 30) or professionals (n = 30). Round 1 included initial recommendations developed from a mixed methods rapid review. Panellists rated the importance of each item on a five-point Likert scale. Panellists could also suggest additional items in Round 1. Rounds 2 and 3 included all items from Round 1, new items suggested in Round 1 and charts summarising panellists’ importance ratings from the preceding round. Free-text responses were analysed using content analysis. Quantitative data were analysed descriptively. All items rated as ‘Important’ or ‘Very important’ by at least 70% of all respondents in Round 3 were included in the final set of recommendations. Results Fifty-five panellists (92%) (patients n = 26; professionals n = 29) completed Round 3. Eighty-six recommendation items were included in Round 1. Fifteen new items were added in Round 2. Rounds 2 and 3 therefore included 101 items. Seventy-seven of these reached consensus in Round 3. Six items reached consensus amongst patient or professional panellists only in Round 3. The final set of recommendations comprises 34 education topics, 18 education delivery approaches, 10 exercise types, 13 exercise delivery approaches and two other treatments. Conclusions This modified Delphi study developed a comprehensive set of recommendations that represent a useful resource for guiding decision-making on the content and delivery of pre-operative TKR education and prehabilitation. The recommendations will need to be interpreted and reviewed periodically in light of emerging evidence

Refactoring bacteriophage T7

Natural biological systems are selected by evolution to continue to exist and evolve. Evolution likely gives rise to complicated systems that are difficult to understand and manipulate. Here, we redesign the genome of a natural biological system, bacteriophage T7, in order to specify an engineered surrogate that, if viable, would be easier to study and extend. Our initial design goals were to physically separate and enable unique manipulation of primary genetic elements. Implicit in our design are the hypotheses that overlapping genetic elements are, in aggregate, nonessential for T7 viability and that our models for the functions encoded by elements are sufficient. To test our initial design, we replaced the left 11 515 base pairs (bp) of the 39 937 bp wild-type genome with 12 179 bp of engineered DNA. The resulting chimeric genome encodes a viable bacteriophage that appears to maintain key features of the original while being simpler to model and easier to manipulate. The viability of our initial design suggests that the genomes encoding natural biological systems can be systematically redesigned and built anew in service of scientific understanding or human intention

Motion and position shifts induced by the double-drift stimulus are unaffected by attentional load.

The double-drift stimulus produces a strong shift in apparent motion direction that generates large errors of perceived position. In this study, we tested the effect of attentional load on the perceptual estimates of motion direction and position for double-drift stimuli. In each trial, four objects appeared, one in each quadrant of a large screen, and they moved upward or downward on an angled trajectory. The target object whose direction or position was to be judged was either cued with a small arrow prior to object motion (low attentional load condition) or cued after the objects stopped moving and disappeared (high attentional load condition). In Experiment 1, these objects appeared 10° from the central fixation, and participants reported the perceived direction of the target's trajectory after the stimulus disappeared by adjusting the direction of an arrow at the center of the response screen. In Experiment 2, the four double-drift objects could appear between 6 ° and 14° from the central fixation, and participants reported the location of the target object after its disappearance by moving the position of a small circle on the response screen. The errors in direction and position judgments showed little effect of the attentional manipulation-similar errors were seen in both experiments whether or not the participant knew which double-drift object would be tested. This suggests that orienting endogenous attention (i.e., by only attending to one object in the precued trials) does not interact with the strength of the motion or position shifts for the double-drift stimulus

A large-scale examination of the effectiveness of anonymous marking in reducing group performance differences in higher education assessment

The present research aims to more fully explore the issues of performance differences in higher education assessment, particularly in the context of a common measure taken to address them. The rationale for the study is that, while performance differences in written examinations are relatively well researched, few studies have examined the efficacy of anonymous marking in reducing these performance differences, particularly in modern student populations. By examining a large archive (N = 30674) of assessment data spanning a twelve-year period, the relationship between assessment marks and factors such as ethnic group, gender and socio-environmental background was investigated. In particular, analysis focused on the impact that the implementation of anonymous marking for assessment of written examinations and coursework has had on the magnitude of mean score differences between demographic groups of students. While group differences were found to be pervasive in higher education assessment, these differences were observed to be relatively small in practical terms. Further, it appears that the introduction of anonymous marking has had a negligible effect in reducing them. The implications of these results are discussed, focusing on two issues, firstly a defence of examinations as a fair and legitimate form of assessment in Higher Education, and, secondly, a call for the re-examination of the efficacy of anonymous marking in reducing group performance differences

Emergent global patterns of ecosystem structure and function from a mechanistic general ecosystem model

Anthropogenic activities are causing widespread degradation of ecosystems worldwide, threatening the ecosystem services upon which all human life depends. Improved understanding of this degradation is urgently needed to improve avoidance and mitigation measures. One tool to assist these efforts is predictive models of ecosystem structure and function that are mechanistic: based on fundamental ecological principles. Here we present the first mechanistic General Ecosystem Model (GEM) of ecosystem structure and function that is both global and applies in all terrestrial and marine environments. Functional forms and parameter values were derived from the theoretical and empirical literature where possible. Simulations of the fate of all organisms with body masses between 10 µg and 150,000 kg (a range of 14 orders of magnitude) across the globe led to emergent properties at individual (e.g., growth rate), community (e.g., biomass turnover rates), ecosystem (e.g., trophic pyramids), and macroecological scales (e.g., global patterns of trophic structure) that are in general agreement with current data and theory. These properties emerged from our encoding of the biology of, and interactions among, individual organisms without any direct constraints on the properties themselves. Our results indicate that ecologists have gathered sufficient information to begin to build realistic, global, and mechanistic models of ecosystems, capable of predicting a diverse range of ecosystem properties and their response to human pressures

5-Formylcytosine alters the structure of the DNA double helix.

The modified base 5-formylcytosine (5fC) was recently identified in mammalian DNA and might be considered to be the 'seventh' base of the genome. This nucleotide has been implicated in active demethylation mediated by the base excision repair enzyme thymine DNA glycosylase. Genomics and proteomics studies have suggested an additional role for 5fC in transcription regulation through chromatin remodeling. Here we propose that 5fC might affect these processes through its effect on DNA conformation. Biophysical and structural analysis revealed that 5fC alters the structure of the DNA double helix and leads to a conformation unique among known DNA structures including those comprising other cytosine modifications. The 1.4-Å-resolution X-ray crystal structure of a DNA dodecamer comprising three 5fCpG sites shows how 5fC changes the geometry of the grooves and base pairs associated with the modified base, leading to helical underwinding.E.-A.R. is supported as a Herchel Smith Fellow. The Balasubramanian laboratory is supported by a Senior Investigator Award from the Wellcome Trust (099232/Z/12/Z to S.B.), and it also receives core funding from Cancer Research UK (C9681/A11961 to S.B.). D.Y.C. is supported by the Crystallographic X-ray Facility (CXF) at the Department of Biochemistry, University of Cambridge, and B.F.L. is supported by the Wellcome Trust (076846/Z/05/A to B.F.L.). We thank the staff of Soleil and Diamond Light Source for use of facilities. We thank C. Calladine for stimulating discussions.This is the accepted manuscript for a paper published in Nature Structural & Molecular Biology 22, 44–49 (2015) doi: 10.1038/nsmb.293

EEG Correlates of Attentional Load during Multiple Object Tracking

While human subjects tracked a subset of ten identical, randomly-moving objects, event-related potentials (ERPs) were evoked at parieto-occipital sites by task-irrelevant flashes that were superimposed on either tracked (Target) or non-tracked (Distractor) objects. With ERPs as markers of attention, we investigated how allocation of attention varied with tracking load, that is, with the number of objects that were tracked. Flashes on Target discs elicited stronger ERPs than did flashes on Distractor discs; ERP amplitude (0–250 ms) decreased monotonically as load increased from two to three to four (of ten) discs. Amplitude decreased more rapidly for Target discs than Distractor discs. As a result, with increasing tracking loads, the difference between ERPs to Targets and Distractors diminished. This change in ERP amplitudes with load accords well with behavioral performance, suggesting that successful tracking depends upon the relationship between the neural signals associated with attended and non-attended objects

The dynamics and neural correlates of audio-visual integration capacity as determined by temporal unpredictability, proactive interference, and SOA

Over 5 experiments, we challenge the idea that the capacity of audio-visual integration need be fixed at 1 item. We observe that the conditions under which audio-visual integration is most likely to exceed 1 occur when stimulus change operates at a slow rather than fast rate of presentation and when the task is of intermediate difficulty such as when low levels of proactive interference (3 rather than 8 interfering visual presentations) are combined with the temporal unpredictability of the critical frame (Experiment 2), or, high levels of proactive interference are combined with the temporal predictability of the critical frame (Experiment 4). Neural data suggest that capacity might also be determined by the quality of perceptual information entering working memory. Experiment 5 supported the proposition that audio-visual integration was at play during the previous experiments. The data are consistent with the dynamic nature usually associated with cross-modal binding, and while audio-visual integration capacity likely cannot exceed uni-modal capacity estimates, performance may be better than being able to associate only one visual stimulus with one auditory stimulus