Patients' unvoiced agendas in general practice consultations.

Objective: To investigate patients' agendas before consultation and to assess which aspects of agendas are voiced in the consultation and the effects of unvoiced agendas on outcomes. Design: Qualitative study. Setting: 20 general practices in south east England and the West Midlands. Participants: 35 patients consulting 20 general practitioners in appointment and emergency surgeries. Results: Patients' agendas are complex and multifarious. Only four of 35 patients voiced all their agendas in consultation. Agenda items most commonly voiced were symptoms and requests for diagnoses and prescriptions. The most common unvoiced agenda items were: worries about possible diagnosis and what the future holds; patients' ideas about what is wrong; side effects; not wanting a prescription; and information relating to social context. Agenda items that were not raised in the consultation often led to specific problem outcomes (for example, major misunderstandings), unwanted prescriptions, non-use of prescriptions, and non-adherence to treatment. In all of the 14 consultations with problem outcomes at least one of the problems was related to an unvoiced agenda item. Conclusion: Patients have many needs and when these are not voiced they can not be addressed. Some of the poor outcomes in the case studies were related to unvoiced agenda items. This suggests that when patients and their needs are more fully articulated in the consultation better health care may be effected. Steps should be taken in both daily clinical practice and research to encourage the voicing of patients' agenda

Misunderstandings in general practice prescribing decisions: a qualitative study

Objectives: To identify and describe misunderstandings between patients and doctors associated with prescribing decisions in general practice. Design: Qualitative study. Setting: 20 general practices in the West Midlands and south east England. Participants: 20 general practitioners and 35 consulting patients. Main outcome measures: Misunderstandings between patients and doctors that have potential or actual adverse consequences for taking medicine. Results: 14 categories of misunderstanding were identified relating to patient information unknown to the doctor, doctor information unknown to the patient, conflicting information, disagreement about attribution of side effects, failure of communication about doctor's decision, and relationship factors. All the misunderstandings were associated with lack of patients' participation in the consultation in terms of the voicing of expectations and preferences or the voicing of responses to doctors' decisions and actions. They were all associated with potential or actual adverse outcomes such as non-adherence to treatment. Many were based on inaccurate guesses and assumptions. In particular doctors seemed unaware of the relevance of patients' ideas about medicines for successful prescribing. Conclusions: Patients' participation in the consultation and the adverse consequences of lack of participation are important. The authors are developing an educational intervention that builds on these findings

X-ray Imaging of Transplanar Liquid Transport Mechanisms in Single Layer Textiles

Understanding the penetration of liquids within textile fibers is critical for the development of next-generation smart textiles. Despite substantial research on liquid penetration in the plane of the textile, little is known about how the liquid penetrates in the thickness direction. Here we report a time-resolved high-resolution X-ray measurement of the motion of the liquid–air interface within a single layer textile, as the liquid is transported across the textile thickness following the deposition of a droplet. The measurement of the time-dependent position of the liquid meniscus is made possible by the use of ultrahigh viscosity liquids (dynamic viscosity from 10⁵ to 2.5 × 10⁶ times larger than water). This approach enables imaging due to the slow penetration kinetics. Imaging results suggest a three-stage penetration process with each stage being associated with one of the three types of capillary channels existing in the textile geometry, providing insights into the effect of the textile structure on the path of the three-dimensional liquid meniscus. One dimensional kinetics studies show that our data for the transplanar penetration depth Δ<i>x</i>_L vs time do not conform to a power law, and that the measured rate of penetration for long times is smaller than that predicted by Lucas–Washburn kinetics, challenging commonly held assumptions regarding the validity of power laws when applied to relatively thin textiles

A low-cost method of skin swabbing for the collection of DNA samples from small laboratory fish

Fin clipping of live fish under anesthesia is widely used to collect samples for DNA extraction. An alternative, potentially less invasive, approach involves obtaining samples by swabbing the skin of nonanesthetized fish. However, this method has yet to be widely adopted for use in laboratory studies in the biological and biomedical sciences. Here, we compare DNA samples from zebrafish Danio rerio and three-spined sticklebacks Gasterosteus aculeatus collected via fin clipping and skin swabbing techniques, and test a range of DNA extraction methods, including commercially available kits and a lower-cost, in-house method. We verify the method for polymerase chain reaction analysis, and examine the potential risk of cross contamination between individual fish that are netted together. We show that swabbing, which may not require the use of anesthesia or analgesics, offers a reliable alternative to fin clipping. Further work is now required to determine the relative effects of fin clipping and swabbing on the stress responses and subsequent health of fish, and hence the potential of swabbing as a refinement to existing DNA sampling procedures

Phylogenomics resolves major relationships and reveals significant diversification rate shifts in the evolution of silk moths and relatives

Background: Silkmoths and their relatives constitute the ecologically and taxonomically diverse superfamily Bombycoidea, which includes some of the most charismatic species of Lepidoptera. Despite displaying spectacular forms and diverse ecological traits, relatively little attention has been given to understanding their evolution and drivers of their diversity. To begin to address this problem, we created a new Bombycoidea-specific Anchored Hybrid Enrichment (AHE) probe set and sampled up to 571 loci for 117 taxa across all major lineages of the Bombycoidea, with a newly developed DNA extraction protocol that allows Lepidoptera specimens to be readily sequenced from pinned natural history collections. Results: The well-supported tree was overall consistent with prior morphological and molecular studies, although some taxa were misplaced. The bombycid Arotros Schaus was formally transferred to Apatelodidae. We identified important evolutionary patterns (e.g., morphology, biogeography, and differences in speciation and extinction), and our analysis of diversification rates highlights the stark increases that exist within the Sphingidae (hawkmoths) and Saturniidae (wild silkmoths). Conclusions: Our study establishes a backbone for future evolutionary, comparative, and taxonomic studies of Bombycoidea. We postulate that the rate shifts identified are due to the well-documented bat-moth “arms race”. Our research highlights the flexibility of AHE to generate genomic data from a wide range of museum specimens, both age and preservation method, and will allow researchers to tap into the wealth of biological data residing in natural history collections around the globe.Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.NHM Repositor

Structural and functional conservation of non-lumenized lymphatic endothelial cells in the mammalian leptomeninges

The vertebrate CNS is surrounded by the meninges, a protective barrier comprised of the outer dura mater and the inner leptomeninges, which includes the arachnoid and pial layers. While the dura mater contains lymphatic vessels, no conventional lymphatics have been found within the brain or leptomeninges. However, non-lumenized cells called Brain/Mural Lymphatic Endothelial Cells or Fluorescent Granule Perithelial cells (muLECs/BLECs/FGPs) that share a developmental program and gene expression with peripheral lymphatic vessels have been described in the meninges of zebrafish. Here we identify a structurally and functionally similar cell type in the mammalian leptomeninges that we name Leptomeningeal Lymphatic Endothelial Cells (LLEC). As in zebrafish, LLECs express multiple lymphatic markers, containing very large, spherical inclusions, and develop independently from the meningeal macrophage lineage. Mouse LLECs also internalize macromolecules from the cerebrospinal fluid, including Amyloid-β, the toxic driver of Alzheimer's disease progression. Finally, we identify morphologically similar cells co-expressing LLEC markers in human post-mortem leptomeninges. Given that LLECs share molecular, morphological, and functional characteristics with both lymphatics and macrophages, we propose they represent a novel, evolutionary conserved cell type with potential roles in homeostasis and immune organization of the meninges

Skin swabbing is a refined technique to collect DNA from model fish species

Model fish species such as sticklebacks and zebrafish are frequently used in studies that require DNA to be collected from live animals. This is typically achieved by fin clipping, a procedure that is simple and reliable to perform but that can harm fish. An alternative procedure to sample DNA involves swabbing the skin to collect mucus and epithelial cells. Although swabbing appears to be less invasive than fin clipping, it still requires fish to be netted, held in air and handled—procedures that can cause stress. In this study we combine behavioural and physiological analyses to investigate changes in gene expression, behaviour and welfare after fin clipping and swabbing. Swabbing led to a smaller change in cortisol release and behaviour on the first day of analysis compared to fin clipping. It also led to less variability in data suggesting that fewer animals need to be measured after using this technique. However, swabbing triggered some longer term changes in zebrafish behaviour suggesting a delayed response to sample collection. Skin swabbing does not require the use of anaesthetics and triggers fewer changes in behaviour and physiology than fin clipping. It is therefore a more refined technique for DNA collection with the potential to improve fish health and welfare

Spatial heterogeneity and peptide availability determine CTL killing efficiency in vivo

The rate at which a cytotoxic T lymphocyte (CTL) can survey for infected cells is a key ingredient of models of vertebrate immune responses to intracellular pathogens. Estimates have been obtained using in vivo cytotoxicity assays in which peptide-pulsed splenocytes are killed by CTL in the spleens of immunised mice. However the spleen is a heterogeneous environment and splenocytes comprise multiple cell types. Are some cell types intrinsically more susceptible to lysis than others? Quantitatively, what impacts are made by the spatial distribution of targets and effectors, and the level of peptide-MHC on the target cell surface? To address these questions we revisited the splenocyte killing assay, using CTL specific for an epitope of influenza virus. We found that at the cell population level T cell targets were killed more rapidly than B cells. Using modeling, quantitative imaging and in vitro killing assays we conclude that this difference in vivo likely reflects different migratory patterns of targets within the spleen and a heterogeneous distribution of CTL, with no detectable difference in the intrinsic susceptibilities of the two populations to lysis. Modeling of the stages involved in the detection and killing of peptide-pulsed targets in vitro revealed that peptide dose influenced the ability of CTL to form conjugates with targets but had no detectable effect on the probability that conjugation resulted in lysis, and that T cell targets took longer to lyse than B cells. We also infer that incomplete killing in vivo of cells pulsed with low doses of peptide may be due to a combination of heterogeneity in peptide uptake and the dissociation, but not internalisation, of peptide-MHC complexes. Our analyses demonstrate how population-averaged parameters in models of immune responses can be dissected to account for both spatial and cellular heterogeneity