A lab project on the design and implementation of programmable and configurable embedded systems

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Automated analysis of free-text comments and dashboard representations in patient experience surveys: a multimethod co-design study

BACKGROUND: Patient experience surveys (PESs) often include informative free-text comments, but with no way of systematically, efficiently and usefully analysing and reporting these. The National Cancer Patient Experience Survey (CPES), used to model the approach reported here, generates > 70,000 free-text comments annually. MAIN AIM: To improve the use and usefulness of PES free-text comments in driving health service changes that improve the patient experience. SECONDARY AIMS: (1) To structure CPES free-text comments using rule-based information retrieval (IR) (‘text engineering’), drawing on health-care domain-specific gazetteers of terms, with in-built transferability to other surveys and conditions; (2) to display the results usefully for health-care professionals, in a digital toolkit dashboard display that drills down to the original free text; (3) to explore the usefulness of interdisciplinary mixed stakeholder co-design and consensus-forming approaches in technology development, ensuring that outputs have meaning for all; and (4) to explore the usefulness of Normalisation Process Theory (NPT) in structuring outputs for implementation and sustainability. DESIGN: A scoping review, rapid review and surveys with stakeholders in health care (patients, carers, health-care providers, commissioners, policy-makers and charities) explored clinical dashboard design/patient experience themes. The findings informed the rules for the draft rule-based IR [developed using half of the 2013 Wales CPES (WCPES) data set] and prototype toolkit dashboards summarising PES data. These were refined following mixed stakeholder, concept-mapping workshops and interviews, which were structured to enable consensus-forming ‘co-design’ work. IR validation used the second half of the WCPES, with comparison against its manual analysis; transferability was tested using further health-care data sets. A discrete choice experiment (DCE) explored which toolkit features were preferred by health-care professionals, with a simple cost–benefit analysis. Structured walk-throughs with NHS managers in Wessex, London and Leeds explored usability and general implementation into practice. KEY OUTCOMES: A taxonomy of ranked PES themes, a checklist of key features recommended for digital clinical toolkits, rule-based IR validation and transferability scores, usability, and goal-oriented, cost–benefit and marketability results. The secondary outputs were a survey, scoping and rapid review findings, and concordance and discordance between stakeholders and methods. RESULTS: (1) The surveys, rapid review and workshops showed that stakeholders differed in their understandings of the patient experience and priorities for change, but that they reached consensus on a shortlist of 19 themes; six were considered to be core; (2) the scoping review and one survey explored the clinical toolkit design, emphasising that such toolkits should be quick and easy to use, and embedded in workflows; the workshop discussions, the DCE and the walk-throughs confirmed this and foregrounded other features to form the toolkit design checklist; and (3) the rule-based IR, developed using noun and verb phrases and lookup gazetteers, was 86% accurate on the WCPES, but needs modification to improve this and to be accurate with other data sets. The DCE and the walk-through suggest that the toolkit would be well accepted, with a favourable cost–benefit ratio, if implemented into practice with appropriate infrastructure support. LIMITATIONS: Small participant numbers and sampling bias across component studies. The scoping review studies mostly used top-down approaches and focused on professional dashboards. The rapid review of themes had limited scope, with no second reviewer. The IR needs further refinement, especially for transferability. New governance restrictions further limit immediate use. CONCLUSIONS: Using a multidisciplinary, mixed stakeholder, use of co-design, proof of concept was shown for an automated display of patient experience free-text comments in a way that could drive health-care improvements in real time. The approach is easily modified for transferable application. FUTURE WORK: Further exploration is needed of implementation into practice, transferable uses and technology development co-design approaches. FUNDING: The National Institute for Health Research Health Services and Delivery Research programme

Biopython: freely available Python tools for computational molecular biology and bioinformatics

Summary: The Biopython project is a mature open source international collaboration of volunteer developers, providing Python libraries for a wide range of bioinformatics problems. Biopython includes modules for reading and writing different sequence file formats and multiple sequence alignments, dealing with 3D macro molecular structures, interacting with common tools such as BLAST, ClustalW and EMBOSS, accessing key online databases, as well as providing numerical methods for statistical learning. Availability: Biopython is freely available, with documentation and source code at www.biopython.org under the Biopython license. Contact: All queries should be directed to the Biopython mailing lists, see www.biopython.org/wiki/[email protected]

Evidence for directional selection at a novel major histocompatibility class I marker in wild common frogs (Rana temporaria) exposed to a viral pathogen (Ranavirus).

(c) 2009 Teacher et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Whilst the Major Histocompatibility Complex (MHC) is well characterized in the anuran Xenopus, this region has not previously been studied in another popular model species, the common frog (Rana temporaria). Nor, to date, have there been any studies of MHC in wild amphibian host-pathogen systems. We characterise an MHC class I locus in the common frog, and present primers to amplify both the whole region, and specifically the antigen binding region. As no more than two expressed haplotypes were found in over 400 clones from 66 individuals, it is likely that there is a single class I locus in this species. This finding is consistent with the single class I locus in Xenopus, but contrasts with the multiple loci identified in axolotls, providing evidence that the diversification of MHC class I into multiple loci likely occurred after the Caudata/Anura divergence (approximately 350 million years ago) but before the Ranidae/Pipidae divergence (approximately 230 mya). We use this locus to compare wild populations of common frogs that have been infected with a viral pathogen (Ranavirus) with those that have no history of infection. We demonstrate that certain MHC supertypes are associated with infection status (even after accounting for shared ancestry), and that the diseased populations have more similar supertype frequencies (lower F(ST)) than the uninfected. These patterns were not seen in a suite of putatively neutral microsatellite loci. We interpret this pattern at the MHC locus to indicate that the disease has imposed selection for particular haplotypes, and hence that common frogs may be adapting to the presence of Ranavirus, which currently kills tens of thousands of amphibians in the UK each year

Helminth resistance is mediated by differential activation of recruited monocyte-derived alveolar macrophages and arginine depletion

Macrophages are known to mediate anti-helminth responses, but it remains uncertain which subsets are involved or how macrophages actually kill helminths. Here, we show rapid monocyte recruitment to the lung after infection with the nematode parasite Nippostrongylus brasiliensis. In this inflamed tissue microenvironment, these monocytes differentiate into an alveolar macrophage (AM)-like phenotype, expressing both SiglecF and CD11c, surround invading parasitic larvae, and preferentially kill parasites in vitro. Monocyte-derived AMs (Mo-AMs) express type 2-associated markers and show a distinct remodeling of the chromatin landscape relative to tissue-derived AMs (TD-AMs). In particular, they express high amounts of arginase-1 (Arg1), which we demonstrate mediates helminth killing through L-arginine depletion. These studies indicate that recruited monocytes are selectively programmed in the pulmonary environment to express AM markers and an anti-helminth phenotype

LOSITAN: A workbench to detect molecular adaptation based on a Fst-outlier method

<p>Abstract</p> <p>Background</p> <p>Testing for selection is becoming one of the most important steps in the analysis of multilocus population genetics data sets. Existing applications are difficult to use, leaving many non-trivial, error-prone tasks to the user.</p> <p>Results</p> <p>Here we present LOSITAN, a selection detection workbench based on a well evaluated <it>F</it>_<it>st</it>-outlier detection method. LOSITAN greatly facilitates correct approximation of model parameters (e.g., genome-wide average, neutral <it>F</it>_<it>st</it>), provides data import and export functions, iterative contour smoothing and generation of graphics in a easy to use graphical user interface. LOSITAN is able to use modern multi-core processor architectures by locally parallelizing fdist, reducing computation time by half in current dual core machines and with almost linear performance gains in machines with more cores.</p> <p>Conclusion</p> <p>LOSITAN makes selection detection feasible to a much wider range of users, even for large population genomic datasets, by both providing an easy to use interface and essential functionality to complete the whole selection detection process.</p

Massive introgression drives species radiation at the range limit of Anopheles gambiae

Impacts of introgressive hybridisation may range from genomic erosion and species collapse to rapid adaptation and speciation but opportunities to study these dynamics are rare. We investigated the extent, causes and consequences of a hybrid zone between Anopheles coluzzii and Anopheles gambiae in Guinea-Bissau, where high hybridisation rates appear to be stable at least since the 1990s. Anopheles gambiae was genetically partitioned into inland and coastal subpopulations, separated by a central region dominated by A. coluzzii. Surprisingly, whole genome sequencing revealed that the coastal region harbours a hybrid form characterised by an A. gambiae-like sex chromosome and massive introgression of A. coluzzii autosomal alleles. Local selection on chromosomal inversions may play a role in this process, suggesting potential for spatiotemporal stability of the coastal hybrid form and providing resilience against introgression of medically-important loci and traits, found to be more prevalent in inland A. gambiae

Environmental variables, habitat discontinuity and life history shaping the genetic structure of Pomatoschistus marmoratus

Coastal lagoons are semi-isolated ecosystems exposed to wide fluctuations of environmental conditions and showing habitat fragmentation. These features may play an important role in separating species into different populations, even at small spatial scales. In this study, we evaluate the concordance between mitochondrial (previous published data) and nuclear data analyzing the genetic variability of Pomatoschistus marmoratus in five localities, inside and outside the Mar Menor coastal lagoon (SE Spain) using eight microsatellites. High genetic diversity and similar levels of allele richness were observed across all loci and localities, although significant genic and genotypic differentiation was found between populations inside and outside the lagoon. In contrast to the FST values obtained from previous mitochondrial DNA analyses (control region), the microsatellite data exhibited significant differentiation among samples inside the Mar Menor and between lagoonal and marine samples. This pattern was corroborated using Cavalli-Sforza genetic distances. The habitat fragmentation inside the coastal lagoon and among lagoon and marine localities could be acting as a barrier to gene flow and contributing to the observed genetic structure. Our results from generalized additive models point a significant link between extreme lagoonal environmental conditions (mainly maximum salinity) and P. marmoratus genetic composition. Thereby, these environmental features could be also acting on genetic structure of coastal lagoon populations of P. marmoratus favoring their genetic divergence. The mating strategy of P. marmoratus could be also influencing our results obtained from mitochondrial and nuclear DNA. Therefore, a special consideration must be done in the selection of the DNA markers depending on the reproductive strategy of the species