Genomics reveals broad hybridization in deeply divergent Palearctic grass and water snakes (Natrix spp.).

Understanding speciation is one of the cornerstones of biological diversity research. Currently, speciation is often understood as a continuous process of divergence that continues until genetic or other incompatibilities minimize or prevent interbreeding. The Palearctic snake genus Natrix is an ideal group to study speciation, as it comprises taxa representing distinct stages of the speciation process, ranging from widely interbreeding parapatric taxa through parapatric species with very limited gene flow in narrow hybrid zones to widely sympatric species. To understand the evolution of reproductive isolation through time, we have sequenced the genomes of all five species within this genus and two additional subspecies. We used both long-read and short-read methods to sequence and de-novo-assemble two high-quality genomes (Natrix h. helvetica, Natrix n. natrix) to their 1.7 Gb length with a contig N50 of 4.6 Mbp and 1.5 Mbp, respectively, and used these as references to assemble the remaining short-read-based genomes. Our phylogenomic analyses yielded a well-supported dated phylogeny and evidence for a surprisingly complex history of interspecific gene flow, including between widely sympatric species. Furthermore, evidence for gene flow was also found for currently allopatric species pairs. Genetic exchange among these well-defined, distinct, and several million-year-old reptile species emphasizes that speciation and maintenance of species distinctness can occur despite continued genetic exchange.

Austerity and Professionalism: Being a Good Healthcare Professional in Bad Conditions.

In this paper we argue that austerity creates working conditions that can undermine professionalism in healthcare. We characterise austerity in terms of overlapping economic, social and ethical dimensions and explain how these can pose significant challenges for healthcare professionals. Amongst other things, austerity is detrimental to healthcare practice because it creates shortages of material and staff resources, negatively affects relationships and institutional cultures, and creates increased burdens and pressures for staff, not least as a result of deteriorating public health conditions. After discussing the multiple dimensions of austerity, we consider the challenges it creates for professional ethics in healthcare. We highlight three mechanisms-intensification of work, practitioner isolation, and organisational alienation-which pose acute problems for healthcare professionals working under conditions of austerity. These mechanisms can turn 'routine moral stress' into moral distress and, at the same time, make poor care much more likely. While professionalism clearly depends on individual capabilities and behaviours, it also depends upon a complex sets of social conditions being established and maintained. The problems caused by austerity reveal a need to broaden the scope of professional ethics so that it includes the responsibilities of 'role constructors' and not just 'role occupiers'. Austerity therefore presents opportunities for health professionals and associated 'role constructors' to contribute to a reimagining of future models of healthcare professionalism.

Why Health and Social Care Support for People with Long-Term Conditions Should be Oriented Towards Enabling Them to Live Well.

There are various reasons why efforts to promote "support for self-management" have rarely delivered the kinds of sustainable improvements in healthcare experiences, health and wellbeing that policy leaders internationally have hoped for. This paper explains how the basis of failure is in some respects built into the ideas that underpin many of these efforts. When (the promotion of) support for self-management is narrowly oriented towards educating and motivating patients to adopt the behaviours recommended for disease control, it implicitly reflects and perpetuates limited and somewhat instrumental views of patients. It tends to: restrict the pursuit of respectful and enabling 'partnership working'; run the risk of undermining patients' self-evaluative attitudes (and then of failing to notice that as harmful); limit recognition of the supportive value of clinician-patient relationships; and obscure the practical and ethical tensions that clinicians face in the delivery of support for self-management. We suggest that a focus on enabling people to live (and die) well with their long-term conditions is a promising starting point for a more adequate conception of support for self-management. We then outline the theoretical advantages that a capabilities approach to thinking about living well can bring to the development of an account of support for self-management, explaining, for example, how it can accommodate the range of what matters to people (both generally and more specifically) for living well, help keep the importance of disease control in perspective, recognize social influences on people's values, behaviours and wellbeing, and illuminate more of the rich potential and practical and ethical challenges of supporting self-management in practice.

We need to talk about purpose: a critical interpretive synthesis of health and social care professionals' approaches to self-management support for people with long-term conditions.

BACKGROUND: Health policies internationally advocate 'support for self-management', but it is not clear how the promise of the concept can be fulfilled. OBJECTIVE: To synthesize research into professional practitioners' perspectives, practices and experiences to help inform a reconceptualization of support for self-management. DESIGN: Critical interpretive synthesis using systematic searches of literature published 2000-2014. FINDINGS: We summarized key insights from 164 relevant papers in an annotated bibliography. The literature illustrates striking variations in approaches to support for self-management and interpretations of associated concepts. We focused particularly on the somewhat neglected question of the purpose of support. We suggest that this can illuminate and explain important differences between narrower and broader approaches. Narrower approaches support people to manage their condition(s) well in terms of disease control. This purpose can underpin more hierarchical practitioner-patient communication and more limited views of patient empowerment. It is often associated with experiences of failure and frustration. Broader approaches support people to manage well with their condition(s). They can keep work on disease control in perspective as attention focuses on what matters to people and how they can be supported to shape their own lives. Broader approaches are currently less evident in practice. DISCUSSION AND CONCLUSION: Broader approaches seem necessary to fulfil the promise of support for self-management, especially for patient empowerment. A commitment to enable people to live well with long-term conditions could provide a coherent basis for the forms and outcomes of support that policies aspire to. The implications of such a commitment need further attention.

"Was that a success or not a success?": a qualitative study of health professionals' perspectives on support for people with long-term conditions.

BACKGROUND: Support for self-management (SSM) is a prominent strand of health policy internationally, particularly for primary care. It is often discussed and evaluated in terms of patients' knowledge, skills and confidence, health-related behaviours, disease control or risk reduction, and service use and costs. However, these goals are limited, both as guides to professional practice and as indicators of its quality. In order to better understand what it means to support self-management well, we examined health professionals' views of success in their work with people with long-term conditions. This study formed part of a broader project to develop a conceptual account of SSM that can reflect and promote good practice. METHODS: Semi-structured individual interviews (n = 26) and subsequent group discussions (n = 5 groups, 30 participants) with diverse health professionals working with people with diabetes and/or Parkinson's disease in NHS services in London, northern England or Scotland. The interviews explored examples of more and less successful work, ways of defining success, and ideas about what facilitates success in practice. Subsequent group discussions considered the practical implications of different accounts of SSM. Interviews and group discussions were audio-recorded, transcribed and analysed thematically. RESULTS: Participants identified a wide range of interlinked aspects or elements of success relating to: health, wellbeing and quality of life; how well people (can) manage; and professional-patient relationships. They also mentioned a number of considerations that have important implications for assessing the quality of their own performance. These considerations in part reflect variations in what matters and what is realistically achievable for particular people, in particular situations and at particular times, as well as the complexity of questions of attribution. CONCLUSIONS: A nuanced assessment of the quality of support for self-management requires attention to the responsiveness of professional practice to a wide, complex range of personal and situational states, as well as actions and interactions over time. A narrow focus on particular indicators can lead to insensitive or even perverse judgements and perhaps counterproductive effects. More open, critical discussions about both success and the assessment of quality are needed to facilitate good professional practice and service improvement initiatives.

Creating an impersonal NHS? Personalization, choice and the erosion of intimacy.

BACKGROUND: Personalization - most often understood in terms of granting patients greater opportunity to participate in, and make choices about, the services they receive - has become a key principle guiding reform of the English NHS. OBJECTIVE: This study sets out to explore the relationship between two senses of the term 'personal' within the context of personalization. Firstly, much of the policy literature equates a 'personal' service with one that is responsive to the choices of individual patients. Secondly, the term 'personal' can be thought to refer to the intimate relationships between patients and medical professionals that have typified traditional models of good practice. METHODOLOGY AND DISCUSSION: I combine a review of the relevant academic and policy literature on personalization with a process of conceptual analysis to uncover three arguments, which suggest that personalization based on choice may adversely affect standards of care by eroding the qualities of intimacy at the heart of the care process. Thus, an unintended consequence of the drive for personalization may be the creation of an NHS that is, in an important sense, less personal than it once was. CONCLUSION: Whilst personalization may deliver many potential benefits, the tension between promoting patient choice and retaining intimate professional-patient relationships ought to be taken seriously. Thus, the task of promoting choice whilst retaining intimacy represents a key policy challenge for advocates of personalization.

The influence of Hurricanes Katrina and Rita on the inflammatory cytokine response and protein expression in A549 cells exposed to PM2.5 collected in the Baton Rouge-Port Allen industrial corridor of Southeastern Louisiana in 2005.

Hurricanes Katrina and Rita hit the coast of Louisiana in 2005 and killed more than 2000 people. The two storms resulted in a significant spike in particulate matter (PM2.5) levels across the state of Louisiana. This report focuses on PM2.5 samples collected in 2005 from two monitoring sites in the neighboring cities of Baton Rouge and Port Allen, Louisiana. Inductively coupled plasma (ICP) revealed the presence of PM2.5-adsorbed representative and Fenton-active transition metals. Gas chromatography/mass spectrometry (GC-MS) analyses revealed the presence of 23 PAH compounds. Endotoxins were also detected. Metals and endotoxins were extracted with water. PAH were extracted with dichloromethane. In order to assess cytotoxicity, aqueous PM2.5 extracts were introduced to A549 Human Epithelial Lung Carcinoma Cells. Results indicated decreased cell viability in a dose-dependent manner, with an LC50 of 235 µg/ml and 250 µg/ml, respectively, for the two sites featured here. Endotoxins alone were not cytotoxic. The concentration of reactive oxygen species (ROS) and released LDH activity increased following exposure of A549 cells to aqueous PM2.5 extracts. Fluorescence microscopy revealed apoptotic and necrotic cell death mechanisms. ELISA revealed increased secretion of primary pro-inflammatory cytokines, IL-6, IL-8, and TNF-α. Global PCR gene expression revealed up-regulation of proteins associated with the cytokine storm; e.g. interleukins, chemokines, and TNF-α. Global antibody microarray was consistent with an inflammatory response, with up-regulation of cytokines involved in the down-field activation of the caspase cascade and kinase pathways. The up-regulation of metal-redox sensitive transcription factors, NF-κß and AP-1, is consistent with a cell death mechanism initiated by Fenton-active transition metal redox catalysis.

Enhanced cryoprecipitate for skin graft and donor site wound healing in pigs.

Due to similarities in skin characteristics, the authors hypothesise that a pig model would most accurately show the ability of autologous, enhanced cryoprecipitate (eCryo) to improve the wound healing of split-thickness skin grafts (STSGs) and corresponding donor sites. Fifty-two STSGs (5 × 5 cm) were fashioned and treated according to a randomised protocol with an autologous eCryo-treated and a control group. Macroscopic assessment, histological evaluation and cellular composition were completed at days 7, 14, 21 and 28. Thirty-two donor sites were also created and assessed in a similar manner. Histologic analysis showed enhancement of healing over all time points for eCryo-treated donor sites. All other results showed no statistically significant improvement with the use of eCryo. Autologous cryoprecipitate appears to be a safe, inexpensive and easy-to-use alternative to fibrin glue, which carries risks and is, in many cases, prohibitively expensive. Further studies are necessary to evaluate the full potential of eCryo. Interestingly, eCryo application may improve donor site aesthetic appearance. We believe that a pig model most reliably simulates eCryo's behaviour in humans to accurately reflect its future clinical applicability.

Multilevel Comparison of Indian Naja Venoms and Their Cross-Reactivity with Indian Polyvalent Antivenoms.

Snake envenoming is caused by many biological species, rather than a single infectious agent, each with a multiplicity of toxins in their venom. Hence, developing effective treatments is challenging, especially in biodiverse and biogeographically complex countries such as India. The present study represents the first genus-wide proteomics analysis of venom composition across Naja species (N. naja, N. oxiana, and N. kaouthia) found in mainland India. Venom proteomes were consistent between individuals from the same localities in terms of the toxin families present, but not in the relative abundance of those in the venom. There appears to be more compositional variation among N. naja from different locations than among N. kaouthia. Immunoblotting and in vitro neutralization assays indicated cross-reactivity with Indian polyvalent antivenom, in which antibodies raised against N. naja are present. However, we observed ineffective neutralization of PLA2 activities of N. naja venoms from locations distant from the source of immunizing venoms. Antivenom immunoprofiling by antivenomics revealed differential antigenicity of venoms from N. kaouthia and N. oxiana, and poor reactivity towards 3FTxs and PLA2s. Moreover, there was considerable variation between antivenoms from different manufacturers. These data indicate that improvements to antivenom manufacturing in India are highly desirable.

Cross-reactive HIV-1-neutralizing human monoclonal antibodies identified from a patient with 2F5-like antibodies.

The genes encoding broadly HIV-1-neutralizing human monoclonal antibodies (MAbs) are highly divergent from their germ line counterparts. We have hypothesized that such high levels of somatic hypermutation could pose a challenge for elicitation of the broadly neutralizing (bn) Abs and that identification of less somatically mutated bn Abs may help in the design of effective vaccine immunogens. In a quest for such bn Abs, phage- and yeast-displayed antibody libraries, constructed using peripheral blood mononuclear cells (PBMCs) from a patient with bn serum containing Abs targeting the epitope of the bn MAb 2F5, were panned against peptides containing the 2F5 epitope and against the HIV-1 gp140(JR-FL). Two MAbs (m66 and m66.6) were identified; the more mutated variant (m66.6) exhibited higher HIV-1-neutralizing activity than m66, although it was weaker than 2F5 in a TZM-bl cell assay. Binding of both MAbs to gp41 alanine substitution mutant peptides required the DKW(664-666) core of the 2F5 epitope and two additional upstream residues (L(660,663)). The MAbs have long (21-residue) heavy-chain third complementarity-determining regions (CDR-H3s), and m66.6 (but not m66) exhibited polyspecific reactivity to self- and non-self-antigens. Both m66 and m66.6 are significantly less divergent from their germ line Ab counterparts than 2F5--they have a total of 11 and 18 amino acid changes, respectively, from the closest VH and Vκ germ line gene products compared to 25 for 2F5. These new MAbs could help explore the complex maturation pathways involved in broad neutralization and its relationship with auto- and polyreactivity and may aid design of vaccine immunogens and development of therapeutics against HIV-1 infection.

Conflict in medical co-production: can a stratified conception of health help?

This paper considers proposals for developing 'co-productive' medical partnerships, within the UK National Health Service (NHS), concentrating in particular on the potential problem involved in combining professional and lay conceptions of health. Much of the literature that advocates the introduction of co-productive healthcare partnerships assumes that medical professionals and patients share, or can easily come to share, a common set of beliefs about what is valuable with regard to health interventions and outcomes. However, a substantial literature documents the contestability of the concept of health, particular across professional and lay divides. We suggest that this potential disagreement ought to be taken seriously, and suggest that the prospect of a co-productive NHS in which patients and professionals act in partnership is threatened by the existence of unresolved epistemic differences. We suggest that part of the solution may lie in re-framing this potential disagreement in the terms provided by Engel's bio-psycho-social account of health, and demonstrate how support for this account can be grounded upon a critical realist foundation. What we call a 'stratified conception of health' reveals the potential complementarity between health beliefs which may have at first seemed to be essentially contradictory. We consider some of the practical implications this idea has for conceiving and creating co-productive medical partnerships.

Modeled comparisons of health risks posed by fluorinated solvents in a workplace spill scenario.

The purpose of this study was to illustrate how available physical-chemical exposure models can be used to compare potential risks and define risk management measures for non-routine exposure events, such as spills, leaks, or process upset conditions. A two-zone physical-chemical model was used to quantify and compare the potential exposure risks from five fluorinated solvents used in the manufacturing of electronic materials during an anticipated spill scenario. A 1-l spill scenario in a room measuring 2.74 m (9 ft) high by 3.66 m (12 ft) wide by 9.14 m (30 ft) long was constructed for modeling exposures using 'The Two-zone Model with An Exponentially Decreasing Contaminant' in available freeware 'IH MOD' (a PC based program available from the American Industrial Hygiene Association). This treatment was followed by using the results from an experimental chamber study in which the evaporation rates and vapor concentrations of the five fluorinated solvents were measured under realistic conditions and then compared to exposure model outputs. The breathing zone concentration/time profiles predicted for the five solvents were compared to their exposure limits to estimate the relative risk. This information was used to help define operationally sufficient risk management options for the safe handling of spills in laboratories, warehouses, or manufacturing facilities. The model indicated that each solvent presented very different risk profiles for the same 1-l liquid spill scenario. Potential exposure concentrations relative to short-term exposure limit (15 min) and Ceiling (C) exposure limit available for some of the solvents are predicted to be exceeded within a few minutes in the area near the spill and in the far field. In addition, the model showed that near-field concentrations for one solvent exceeded the published LC-50 (the concentration predicted to cause 50% mortality in the test animals), which indicates a very high degree of risk for this material in similar scenarios. Given the speed of evaporation during these spills for the materials tested in this study, donning personal protective equipment in the area may not be a viable option and short-term evacuation of the area immediately surrounding the spill would appear to be a practical risk management response.

Molecular phylogenetic analysis of the genus Gloydius (Squamata, Viperidae, Crotalinae), with description of two new alpine species from Qinghai-Tibet Plateau, China.

We provide a molecular phylogeny of Asian pit vipers (the genus Gloydius) based on four mitochondrial genes (12S, 16S, ND4, and cytb). Sequences of Gloydiushimalayanus, the only member of the genus that occurs south of the Himalayan range, are included for the first time. In addition, two new species of the genus Gloydius are described based on specimens collected from Zayu, Tibet, west of the Nujiang River and Heishui, Sichuan, east of the Qinghai-Tibet Plateau. The new species, Gloydiuslipipengi sp. nov., can be differentiated from its congeners by the combination of the following characters: the third supralabial not reaching the orbit (separated from it by a suborbital scale); wide, black-bordered greyish postorbital stripe extending from the posterior margin of the orbit (not separated by the postoculars, covering most of the anterior temporal scale) to the ventral surface of the neck; irregular black annular crossbands on the mid-body; 23-21-15 dorsal scales; 165 ventral scales, and 46 subcaudal scales. Gloydiusswild sp. nov. can be differentiated from its congeners by the narrower postorbital stripe (only half the width of the anterior temporal scale, the lower edge is approximately straight and bordered with white); a pair of arched stripes on the occiput; lateral body lakes black spots; a pair of round spots on the parietal scales; 21 rows of mid-body dorsal scales; zigzag dark brown stripes on the dorsum; 168-170 ventral scales, and 43-46 subcaudal scales. The molecular phylogeny in this study supports the sister relationship between G.lipipengi sp. nov. and G.rubromaculatus, another recently described species from the Qinghai-Tibet Plateau, more than 500 km away, and indicate the basal position of G.himalayanus within the genus and relatively distant relationship to its congeners.

Promoting co-existence between humans and venomous snakes through increasing the herpetological knowledge base.

Snakebite incidence at least partly depends on the biology of the snakes involved. However, studies of snake biology have been largely neglected in favour of anthropic factors, with the exception of taxonomy, which has been recognised for some decades to affect the design of antivenoms. Despite this, within-species venom variation and the unpredictability of the correlation with antivenom cross-reactivity has continued to be problematic. Meanwhile, other aspects of snake biology, including behaviour, spatial ecology and activity patterns, distribution, and population demography, which can contribute to snakebite mitigation and prevention, remain underfunded and understudied. Here, we review the literature relevant to these aspects of snakebite and illustrate how demographic, spatial, and behavioural studies can improve our understanding of why snakebites occur and provide evidence for prevention strategies. We identify the large gaps that remain to be filled and urge that, in the future, data and relevant metadata be shared openly via public data repositories so that studies can be properly replicated and data used in future meta-analyses.

Anti-microbial Activity of Urine after Ingestion of Cranberry: A Pilot Study.

We explore the anti-microbial activity of urine specimens after the ingestion of a commercial cranberry preparation. Twenty subjects without urinary infection, off antibiotics and all supplements or vitamins were recruited. The study was conducted in two phases: in phase 1, subjects collected the first morning urine prior to ingesting 900 mg of cranberry and then at 2, 4 and 6 h. In phase 2, subjects collected urine on 2 consecutive days: on Day 1 no cranberry was ingested (control specimens), on Day 2, cranberry was ingested. The pH of all urine specimens were adjusted to the same pH as that of the first morning urine specimen. Aliquots of each specimen were independently inoculated with Escherichia coli, Klebsiella pneumoniae or Candida albicans. After incubation, colony forming units/ml (CFU ml(-1)) in the control specimen was compared with CFU ml(-1) in specimens collected 2, 4 and 6 h later. Specimens showing ≥50% reduction in CFU ml(-1) were considered as having 'activity' against the strains tested. In phase 1, 7/20 (35%) subjects had anti-microbial activity against E. coli, 13/20 (65%) against K. pneumoniae and 9/20 (45%) against C. albicans in specimens collected 2-6 h after ingestion of cranberry. In phase 2, 6/9 (67%) of the subjects had activity against K. pneumoniae. This pilot study demonstrates weak anti-microbial activity in urine specimens after ingestion of a single dose of commercial cranberry. Anti-microbial activity was noted only against K. pneumoniae 2-6 h after ingestion of the cranberry preparation.

Acute cholecystitis preceding mycotic aortic pseudoaneurysm in a heart transplant recipient.

Mycotic pseudoaneurysm is a rare complication after orthotopic heart transplantation (OHT). This case describes a middle-aged OHT recipient who developed a mycotic pseudoaneurysm after an episode of acute cholecystitis. The region of involved aorta was effectively repaired using a patch of bovine pericardium and a brief period of hypothermic circulatory arrest.

Can student-peers teach using simulated-based learning as well as faculty: A non-equivalent posttest-only study.

BACKGROUND: Peer-assisted learning has an important place in the delivery of health care education with benefits for both the learners and the peer teachers. Simulation-based learning (SBL) is evolving in healthcare professions training and academic programs as a modality that conveys realism and fidelity through immersion. OBJECTIVES: The primary aim was to compare physiotherapy student's motivation to learn between a conventional faculty-led SBL activity and the same SBL activity delivered by trained final year physiotherapy peer tutors. METHODS: Physiotherapy students from two Universities (n = 226) undertook a SBL learning activity (either faculty led or peer led) and completed the Instructional Materials Motivation Scale questionnaire to assess motivation to learn. RESULTS: There was a high level of learner motivation in all learning groups, with significantly higher learner satisfaction (p < 0.001) and lower attention (p < 0.001) in student-led SBL than faculty-led SBL. CONCLUSIONS: This study has highlighted the potential to incorporate peer-assisted and simulation-based learning together in the development of future educational activities in health care training.

VoroCrust: Voronoi Meshing Without Clipping.

Polyhedral meshes are increasingly becoming an attractive option with particular advantages over traditional meshes for certain applications. What has been missing is a robust polyhedral meshing algorithm that can handle broad classes of domains exhibiting arbitrary curved boundaries and sharp features. In addition, the power of primal-dual mesh pairs, exemplified by Voronoi-Delaunay meshes, has been recognized as an important ingredient in numerous formulations. The VoroCrust algorithm is the first provably correct algorithm for conforming Voronoi meshing for non-convex and possibly non-manifold domains with guarantees on the quality of both surface and volume elements. A robust refinement process estimates a suitable sizing field that enables the careful placement of Voronoi seeds across the surface circumventing the need for clipping and avoiding its many drawbacks. The algorithm has the flexibility of filling the interior by either structured or random samples, while all sharp features are preserved in the output mesh. We demonstrate the capabilities of the algorithm on a variety of models and compare against state-of-the-art polyhedral meshing methods based on clipped Voronoi cells establishing the clear advantage of VoroCrust output.

Organizing, exploring, and analyzing antibody sequence data: the case for relational-database managers.

Technological advances in the acquisition of DNA and protein sequence information and the resulting onrush of data can quickly overwhelm the scientist unprepared for the volume of information that must be evaluated and carefully dissected to discover its significance. Few laboratories have the luxury of dedicated personnel to organize, analyze, or consistently record a mix of arriving sequence data. A methodology based on a modern relational-database manager is presented that is both a natural storage vessel for antibody sequence information and a conduit for organizing and exploring sequence data and accompanying annotation text. The expertise necessary to implement such a plan is equal to that required by electronic word processors or spreadsheet applications. Antibody sequence projects maintained as independent databases are selectively unified by the relational-database manager into larger database families that contribute to local analyses, reports, interactive HTML pages, or exported to facilities dedicated to sophisticated sequence analysis techniques. Database files are transposable among current versions of Microsoft, Macintosh, and UNIX operating systems.