The unrooted set covering connected subgraph problem differentiating between HIV envelope sequences

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this recordThis paper presents a novel application of operations research techniques to the analysis of HIV Env gene sequences, aiming to identify key features that are possible vaccine targets. These targets are identified as being critical to the transmission of HIV by being present in early transmitted (founder) sequences and absent in later chronic sequences. Identifying the key features of Env involves two steps: first, calculating the covariance of amino acid combinations and positions to form a network of related and compensatory mutations; and second, developing an integer program to identify the smallest connected subgraph of the constructed covariance network that exhibits a set covering property. The integer program developed for this analysis, labelled the unrooted set covering connected subgraph problem (USCCSP), integrates a set covering problem and connectivity evaluation, the latter formulated as a network flow problem. The resulting integer program is very large and complex, requiring the use of Benders’ decomposition to develop an efficient solution approach. The results will demonstrate the necessity of applying acceleration techniques to the Benders’ decomposition solution approach and the effectiveness of these techniques and heuristic approaches for solving the USCCSP

Interoperability of Remote Laboratories Systems

There has been growing interest in, and development of, remotely accessible laboratories as a mechanism for improving access and flexibility, and enabling sharing of facilities. Differences in focus, philosophy, approach or domain have led to quite different technical solutions in supporting remote laboratories. Whilst this diversity represents a significant strength in terms of the ability to explore different issues and support diverse applications, it does however potentially hamper the sharing of labs between different institutions. Investigation into interoperability between two remote lab platforms has realized a need for a common application protocol to achieve the goals remote labs aims to provide. We describe our approach to providing a bridge between two current remote laboratory architectures Labshares Sahara and MITs iLabs and report on the issues that arise with regard to the protocol translations

Perceptions of risk and safety in the ICU: a qualitative study of cognitive processes relating to staffing

Objectives: The aims of this study were to 1) examine individual professionals’ perceptions of staffing risks and safe staffing in intensive care and 2) identify and examine the cognitive processes that underlie these perceptions. Design: Qualitative case study methodology with nurses, doctors, and physiotherapists. Setting: Three mixed medical and surgical adult ICUs, each on a separate hospital site within a 1,200-bed academic, tertiary London hospital group. Subjects: Forty-four ICU team members of diverse professional backgrounds and seniority. Interventions: None. Main Results: Four themes (individual, team, unit, and organizational) were identified. Individual care provision was influenced by the pragmatist versus perfectionist stance of individuals and team dynamics by the concept of an “A” team and interdisciplinary tensions. Perceptions of safety hinged around the importance of achieving a “dynamic balance” influenced by the burden of prevailing circumstances and the clinical status of patients. Organizationally, professionals’ risk perceptions affected their willingness to take personal responsibility for interactions beyond the unit. Conclusions: This study drew on cognitive research, specifically theories of cognitive dissonance, psychological safety, and situational awareness to explain how professionals’ cognitive processes impacted on ICU behaviors. Our results may have implications for relationships, management, and leadership in ICU. First, patient care delivery may be affected by professionals’ perfectionist or pragmatic approach. Perfectionists’ team role may be compromised and they may experience cognitive dissonance and subsequent isolation/stress. Second, psychological safety in a team may be improved within the confines of a perceived “A” team but diminished by interdisciplinary tensions. Third, counter intuitively, higher “situational” awareness for some individuals increased their stress and anxiety. Finally, our results suggest that professionals have varying concepts of where their personal responsibility to minimize risk begins and ends, which we have termed “risk horizons” and that these horizons may affect their behavior both within and beyond the unit

Tissue resolved, gene structure refined equine transcriptome.

BackgroundTranscriptome interpretation relies on a good-quality reference transcriptome for accurate quantification of gene expression as well as functional analysis of genetic variants. The current annotation of the horse genome lacks the specificity and sensitivity necessary to assess gene expression especially at the isoform level, and suffers from insufficient annotation of untranslated regions (UTR) usage. We built an annotation pipeline for horse and used it to integrate 1.9 billion reads from multiple RNA-seq data sets into a new refined transcriptome.ResultsThis equine transcriptome integrates eight different tissues from 59 individuals and improves gene structure and isoform resolution, while providing considerable tissue-specific information. We utilized four levels of transcript filtration in our pipeline, aimed at producing several transcriptome versions that are suitable for different downstream analyses. Our most refined transcriptome includes 36,876 genes and 76,125 isoforms, with 6474 candidate transcriptional loci novel to the equine transcriptome.ConclusionsWe have employed a variety of descriptive statistics and figures that demonstrate the quality and content of the transcriptome. The equine transcriptomes that are provided by this pipeline show the best tissue-specific resolution of any equine transcriptome to date and are flexible for several downstream analyses. We encourage the integration of further equine transcriptomes with our annotation pipeline to continue and improve the equine transcriptome

Derivation of Suitability Metrics for Remote Access Mode Experiments

When considering the possible use of an online mode of experimentation it is important to evaluate the suitability of the remote access mode to a particular learning exercise. Within a large and diverse set of possible experiment-oriented learning exercises, it follows that not all laboratory experiments are well-suited for conversion to the remote access mode. In this paper we consider a range of factors that should be considered before the decision is taken to implement a remote laboratory. These factors fit broadly into four categories: learning factors, equipment factors, cohort factors and accreditation factors. Some of the factors may demonstrate a tendency to belong to more than one category, and some may present with a more significant weighting than others, but the categorical organization of the factors adds an ability to apply an objective assessment to remote access mode suitability

Comparison of limb kinematics between collected and lengthened (medium/extended) trot in two groups of dressage horses on two different surfaces

Background: Dressage horses are often asked to work in lengthened paces during training and competition, but to date there is limited information about the biomechanics of dressage-specific paces. Preliminary work has shown increased fetlock extension in extended compared with collected paces, but further investigation of the kinematic differences between collected, medium and extended trot in dressage horses is warranted. Objectives: Investigation of the effect of collected versus medium/extended trot on limb kinematics of dressage horses. Study design: Prospective kinematic evaluation. Methods: Twenty clinically sound horses in active dressage training were used: Group 1) ten young horses (≤ 6 years) were assessed at collected and medium trot; Group 2) ten mature horses (≥9 years) were assessed at collected and extended trot. All horses were evaluated on two different surfaces. High-speed motion-capture (240Hz) was used to determine kinematic variables. Forelimb and hindlimb angles were measured at midstance. Descriptive statistics and mixed-effect multilevel-regression analyses were performed. Results: Speed and stride length were reduced and stride duration increased at collected compared with medium/extended trot. Lengthened trot (medium/extended trot) was associated with increased fetlock extension in both the forelimbs and hindlimbs in both groups of horses. Changes were greater in Group 2 compared with Group 1. Shoulder and carpus angles were associated with forelimb fetlock angle. Hock angle was not significantly influenced by pace. Surface had no effect on fetlock or hock angles. Main limitations: Only 2D motion analysis was carried out. Results may have been different in horses with more extreme gait characteristics. Conclusions: Medium/extended trot increases extension of the forelimb and the hindlimb fetlock joints compared with collected trot in both young and mature dressage horses, respectively

A qualitative study of patients’ feedback about Outpatient Parenteral Antimicrobial Therapy (OPAT) services in Northern England: implications for service improvement

Objective Outpatient parenteral antimicrobial therapy (OPAT) provides opportunities for improved cost savings, but in the UK, implementation is patchy and a variety of service models are in use. The slow uptake in the UK and Europe is due to a number of clinical, financial and logistical issues, including concern about patient safety. The measurement of patient experience data is commonly used to inform commissioning decisions, but these focus on functional aspects of services and fail to examine the relational aspects of care. This qualitative study examines patients’ experiences of OPAT. Design In-depth, semistructured interviews. Setting Purposive sample of OPAT patients recruited from four acute National Health Service (NHS) Trusts in Northern England. These NHS Trusts between them represented both well-established and recently set-up services running nurse at home, hospital outpatient and/or selfadministration models. Participants We undertook 28 semistructured interviews and one focus group (n=4). Results Despite good patient outcomes, experiences were coloured by patients' personal situation and material circumstances. Many found looking after themselves at home more difficult than they expected, while others continued to work despite their infection. Expensive car parking, late running services and the inconvenience of waiting in for the nurse to arrive frustrated patients, while efficient services, staffed by nurses with the specialist skills needed to manage intravenous treatment had the opposite effect. Many patients felt a local, general practitioner or community health centre based service would resolve many of the practical difficulties that made OPAT inconvenient. Patients could find OPAT anxiety provoking but this could be ameliorated by staff taking the time to reassure patients and provide tailored information. Conclusion Services configurations must accommodate the diversity of the local population. Poor communication can leave patients lacking the confidence needed to be a competent collaborator in their own care and affect their perceptions of the service

Mutational networks of escape from transmitted HIV-1 infection

This is the final version. Available on open access from the Public Library of Science via the DOI in this recordData availability: The sequence data are available in the Dryad Data Depository, DOI: doi:10.5061/dryad.r19c2 Data files: HIV envelope sequences Seroconverter HIV subtype B envelope sequences.Human immunodeficiency virus (HIV) is subject to immune selective pressure soon after it establishes infection at the founder stage. As an individual progresses from the founder to chronic stage of infection, immune pressure forces a history of mutations that are embedded in envelope sequences. Determining this pathway of coevolving mutations can assist in understanding what is different with the founder virus and the essential pathways it takes to maintain infection. We have combined operations research and bioinformatics methods to extract key networks of mutations that differentiate founder and chronic stages for 156 subtype B and 107 subtype C envelope (gp160) sequences. The chronic networks for both subtypes revealed strikingly different hub-and-spoke topologies compared to the less structured transmission networks. This suggests that the hub nodes are impacted by the immune response and the resulting loss of fitness is compensated by mutations at the spoke positions. The major hubs in the chronic C network occur at positions 12, 137 (within the N136 glycan), and 822, and at position 306 for subtype B. While both founder networks had a more heterogeneous connected network structure, interestingly founder B subnetworks around positions 640 and 837 preferentially contained CD4 and coreceptor binding domains. Finally, we observed a differential effect of glycosylation between founder and chronic subtype B where the latter had mutational pathways significantly driven by N-glycosylation. Our study provides insights into the mutational pathways HIV takes to evade the immune response, and presents features more likely to establish founder infection, valuable for effective vaccine design.Australian Research Council (ARC