New Technologies for Space Avionics, 1993

The report reviews a 1993 effort that investigated issues associated with the development of requirements, with the practice of concurrent engineering and with rapid prototyping, in the development of a next-generation Reaction Jet Drive Controller. This report details lessons learned, the current status of the prototype, and suggestions for future work. The report concludes with a discussion of the vision of future avionics architectures based on the principles associated with open architectures and integrated vehicle health management

Intra-individual movement variability during skill transitions: A useful marker?

Applied research suggests athletes and coaches need to be challenged in knowing when and how much a movement should be consciously attended to. This is exacerbated when the skill is in transition between two more stable states, such as when an already well learnt skill is being refined. Using existing theory and research, this paper highlights the potential application of movement variability as a tool to inform a coach’s decision-making process when implementing a systematic approach to technical refinement. Of particular interest is the structure of co-variability between mechanical degrees-of-freedom (e.g., joints) within the movement system’s entirety when undergoing a skill transition. Exemplar data from golf are presented, demonstrating the link between movement variability and mental effort as an important feature of automaticity, and thus intervention design throughout the different stages of refinement. Movement variability was shown to reduce when mental effort directed towards an individual aspect of the skill was high (target variable). The opposite pattern was apparent for variables unrelated to the technical refinement. Therefore, two related indicators, movement variability and mental effort, are offered as a basis through which the evaluation of automaticity during technical refinements may be made

Prevalence of Disorders Recorded in Dogs Attending Primary-Care Veterinary Practices in England

Purebred dog health is thought to be compromised by an increasing occurence of inherited diseases but inadequate prevalence data on common disorders have hampered efforts to prioritise health reforms. Analysis of primary veterinary practice clinical data has been proposed for reliable estimation of disorder prevalence in dogs. Electronic patient record (EPR) data were collected on 148,741 dogs attending 93 clinics across central and south-eastern England. Analysis in detail of a random sample of EPRs relating to 3,884 dogs from 89 clinics identified the most frequently recorded disorders as otitis externa (prevalence 10.2%, 95% CI: 9.1-11.3), periodontal disease (9.3%, 95% CI: 8.3-10.3) and anal sac impaction (7.1%, 95% CI: 6.1-8.1). Using syndromic classification, the most prevalent body location affected was the head-and-neck (32.8%, 95% CI: 30.7-34.9), the most prevalent organ system affected was the integument (36.3%, 95% CI: 33.9-38.6) and the most prevalent pathophysiologic process diagnosed was inflammation (32.1%, 95% CI: 29.8-34.3). Among the twenty most-frequently recorded disorders, purebred dogs had a significantly higher prevalence compared with crossbreds for three: otitis externa (P = 0.001), obesity (P = 0.006) and skin mass lesion (P = 0.033), and popular breeds differed significantly from each other in their prevalence for five: periodontal disease (P = 0.002), overgrown nails (P = 0.004), degenerative joint disease (P = 0.005), obesity (P = 0.001) and lipoma (P = 0.003). These results fill a crucial data gap in disorder prevalence information and assist with disorder prioritisation. The results suggest that, for maximal impact, breeding reforms should target commonly-diagnosed complex disorders that are amenable to genetic improvement and should place special focus on at-risk breeds. Future studies evaluating disorder severity and duration will augment the usefulness of the disorder prevalence information reported herein

The environmental costs and benefits of high-yield farming

How we manage farming and food systems to meet rising demand is pivotal to the future of biodiversity. Extensive field data suggest impacts on wild populations would be greatly reduced through boosting yields on existing farmland so as to spare remaining natural habitats. High-yield farming raises other concerns because expressed per unit area it can generate high levels of externalities such as greenhouse gas (GHG) emissions and nutrient losses. However, such metrics underestimate the overall impacts of lower-yield systems, so here we develop a framework that instead compares externality and land costs per unit production. Applying this to diverse datasets describing the externalities of four major farm sectors reveals that, rather than involving trade-offs, the externality and land costs of alternative production systems can co-vary positively: per unit production, land-efficient systems often produce lower externalities. For GHG emissions these associations become more strongly positive once forgone sequestration is included. Our conclusions are limited: remarkably few studies report externalities alongside yields; many important externalities and farming systems are inadequately measured; and realising the environmental benefits of high-yield systems typically requires additional measures to limit farmland expansion. Yet our results nevertheless suggest that trade-offs among key cost metrics are not as ubiquitous as sometimes perceived. There is an author correction to this article. See: https://doi.org/10.1038/s41893-018-0138-5We are grateful for funding from the Cambridge Conservation Initiative Collaborative Fund and Arcadia, the Grantham Foundation for the Protection of the Environment, the Kenneth Miller Trust the UK-China Virtual Joint Centre for Agricultural Nitrogen (CINAg, 780 BB/N013468/1, financed by the Newton Fund via BBSRC and NERC), BBSRC (BBS/E/C/000I0330), DEVIL (NE/M021327/1), U-GRASS (NE/M016900/1), Soils-R-GRREAT (NE/P019455/1), N-Circle (BB/N013484/1), BBSRC Soil to Nutrition (S2N) strategic programme (BBS/E/C/000I0330), UNAM-PAPIIT (IV200715), the Belmont Forum/FACEE-JPI (NE/M021327/1 ‘DEVIL’), and the Cambridge Earth System Science NERC DTP (NE/L002507/1); AB is supported by a Royal Society Wolfson Research Merit award

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin