An exploration of social and economic outcome and associated health-related quality of life after critical illness in general intensive care unit survivors: a 12-month follow-up study.

INTRODUCTION: The socio-economic impact of critical illnesses on patients and their families in Europe has yet to be determined. The aim of this exploratory study was to estimate changes in family circumstances, social and economic stability, care requirements and access to health services for patients during their first 12 months after ICU discharge. METHODS: Multi-center questionnaire-based study of survivors of critical illness at 6 and 12 months after ICU discharge. RESULTS: Data for 293 consenting patients who spent greater than 48 hours in one of 22 UK ICUs were obtained at 6 and 12 months post-ICU discharge. There was little evidence of a change in accommodation or relationship status between pre-admission and 12 months following discharge from an ICU. A negative impact on family income was reported by 33% of all patients at 6 months and 28% at 12 months. There was nearly a 50% reduction in the number of patients who reported employment as their sole source of income at 12 months (19% to 11%) compared with pre-admission. One quarter of patients reported themselves in need of care assistance at 6 months and 22% at 12 months. The majority of care was provided by family members (80% and 78%, respectively), for half of whom there was a negative impact on employment. Amongst all patients receiving care, 26% reported requiring greater than 50 hours a week. Following discharge, 79% of patients reported attending their primary care physician and 44% had seen a community nurse. Mobility problems nearly doubled between pre-admission and 6 months (32% to 64%). Furthermore, 73% reported moderate or severe pain at 12 months and 44% remained significantly anxious or depressed. CONCLUSIONS: Survivors of critical illness in the UK face a negative impact on employment and commonly have a care requirement after discharge from hospital. This has a corresponding negative impact on family income. The majority of the care required is provided by family members. This effect was apparent by 6 months and had not materially improved by 12 months. This exploratory study has identified the potential for a significant socio-economic burden following critical illness

On the stability of a heated rotating-disk boundary layer in a temperature-dependent viscosity fluid

The paper presents a linear stability analysis of the temperature-dependent boundary-layer flow over a rotating disk. Gas- and liquid-type responses of the viscosity to temperature are considered, and the disk rotates in both a quiescent and an incident axial flow. Temperature-dependent-viscosity flows are typically found to be less stable than the temperature independent cases, with temperature dependences that produce high wall viscosities yielding the least stable flows. Conversely, increasing the incident axial flow strength produces greater flow stability. Transitional Reynolds numbers for these flows are then approximated through an eN-type analysis and are found to vary in approximate concordance with the critical Reynolds number. Examination of the component energy contributions shows that flow stability is affected exclusively through changes to the mean flow. The results are discussed in the context of chemical vapor deposition reactors

Anthropogenic and ecological drivers of amphibian disease (ranavirosis)

This is the final version. Available on open access from Public Library of Science via the DOI in this recordData Availability: The data analysed in this manuscript has been deposited in Dryad (doi:http://dx.doi.org/10.5061/dryad.66k59). Third party data was obtained from Froglife and are therefore available through the charity Froglife (Registered Charity No. 1093372 in England and Wales). Please submit queries for data to [email protected] and asking for access to the data for research purposes. Further contact details can also be found on their website http://www.froglife.org/contact-us/.Ranaviruses are causing mass amphibian die-offs in North America, Europe and Asia, and have been implicated in the decline of common frog (Rana temporaria) populations in the UK. Despite this, we have very little understanding of the environmental drivers of disease occurrence and prevalence. Using a long term (1992-2000) dataset of public reports of amphibian mortalities, we assess a set of potential predictors of the occurrence and prevalence of Ranavirus-consistent common frog mortality events in Britain. We reveal the influence of biotic and abiotic drivers of this disease, with many of these abiotic characteristics being anthropogenic. Whilst controlling for the geographic distribution of mortality events, disease prevalence increases with increasing frog population density, presence of fish and wild newts, increasing pond depth and the use of garden chemicals. The presence of an alternative host reduces prevalence, potentially indicating a dilution effect. Ranavirosis occurrence is associated with the presence of toads, an urban setting and the use of fish care products, providing insight into the causes of emergence of disease. Links between occurrence, prevalence, pond characteristics and garden management practices provides useful management implications for reducing the impacts of Ranavirus in the wild

Differing HLA types influence inhibitory receptor signalling in CMV-specific CD8+ T cells.

The dysregulated immune response to CMV constitutes a major force driving T cell immunosenescence and growing evidence suggests that it is not a benign virus in old age. We show here that the PD-1/L pathway defines a reversible defect in CMV specific CD8(+) T cell proliferative responses in both young and old individuals. More specifically, highly differentiated CD45RA(+)CD27(-) CMV-specific CD8(+) T cells exhibit a proliferative deficit compared their central and effector memory counterparts, which is reversed following PD-L blockade. However, we also report that HLA-B(∗)07/TPR specific CD8(+) T cells express higher levels of PD-1 than HLA-A(∗)02/NLV specific cells and HLA-A(∗)02 individuals show a higher proliferative response to PD-L blockade, than HLA-B(∗)07 individuals, which we postulate may be due to the differing functional avidities for these two CMV-specific CD8(+) T cells populations. Nevertheless data presented here demonstrate that CMV-specific CD8(+) T cells can be functionally enhanced by perturbation of the PD-1/L signalling pathway, whose manipulation may provide a therapeutic modality to combat age-associated immune decline

A biopsychosocial interpretation of the Neuropsychiatric Inventory – Nursing Home assessment: reconceptualising psychiatric symptom attributions

Background: The Neuropsychiatric Inventory is predicated on the assumption that psychiatric symptoms are manifestations of disease. Biopsychosocial theories suggest behavioural changes viewed as psychiatric may also arise as a result of external behavioural triggers. Knowing the causes of psychiatric is important since the treatment and management of psychiatric symptoms relies on this understanding. Aims: This study sought to understand the causes of psychiatric symptoms recorded in care home settings by investigating qualitatively described symptoms in NPI-NH interviews. Method: The current study examined the NPI-NH interviews of 725 participants across 50 care homes. The qualitatively described symptoms from each of the 12 subscales of the NPI were extracted: 347 interviews included at least one qualitatively described symptom (n=651 descriptions). A biopsychosocial algorithm developed following a process of independent researcher coding (n=3) was applied to the symptom descriptions. This determined whether the description had predominantly psychiatric features, or features that were cognitive or attributable to other causes (i.e. issues with Orientation & Memory, Expressions of Need, Poor Care and Communication or Understandable Reactions) Results: Our findings suggest that the majority (over 80%) of descriptions described symptoms with features that could be attributable to cognitive changes and external triggers (e.g. poor care and communication). Conclusions: The finding suggest that in its current form the NPI-NH may over attribute the incidence of psychiatric symptoms in care homes by overlooking triggers for behavioural changes. Measures of psychiatric symptoms should determine the causes of behavioural changes in order to guide treatments more effectively

A de novo assembly of the common frog (Rana temporaria) transcriptome and comparison of transcription following exposure to Ranavirus and Batrachochytrium dendrobatidis

This is the final version. Available on open access from Public Library of Science via the DOI in this recordata Availability: All raw data is available through EMBL-EBI Array Express, accession number E-MTAB-3632Amphibians are experiencing global declines and extinctions, with infectious diseases representing a major factor. In this study we examined the transcriptional response of metamorphic hosts (common frog, Rana temporaria) to the two most important amphibian pathogens: Batrachochytrium dendrobatidis (Bd) and Ranavirus. We found strong up-regulation of a gene involved in the adaptive immune response (AP4S1) at four days post-exposure to both pathogens. We detected a significant transcriptional response to Bd, covering the immune response (innate and adaptive immunity, complement activation, and general inflammatory responses), but relatively little transcriptional response to Ranavirus. This may reflect the higher mortality rates found in wild common frogs infected with Ranavirusas opposed to Bd. These data provide a valuable genomic resource for the amphibians, contribute insight into gene expression changes after pathogen exposure, and suggest potential candidate genes for future host-pathogen research.European UnionRoyal SocietyZoological Society of LondonEuropean Research Counci

Complete analysis of the B-cell response to a protein antigen, from in vivo germinal centre formation to 3-D modelling of affinity maturation

Somatic hypermutation of immunoglobulin variable region genes occurs within germinal centres (GCs) and is the process responsible for affinity maturation of antibodies during an immune response. Previous studies have focused almost exclusively on the immune response to haptens, which may be unrepresentative of epitopes on protein antigens. In this study, we have exploited a model system that uses transgenic B and CD4<sup>+</sup> T cells specific for hen egg lysozyme (HEL) and a chicken ovalbumin peptide, respectively, to investigate a tightly synchronized immune response to protein antigens of widely differing affinities, thus allowing us to track many facets of the development of an antibody response at the antigen-specific B cell level in an integrated system <i>in</i> <i>vivo</i>. Somatic hypermutation of immunoglobulin variable genes was analysed in clones of transgenic B cells proliferating in individual GCs in response to HEL or the cross-reactive low-affinity antigen, duck egg lysozyme (DEL). Molecular modelling of the antibody–antigen interface demonstrates that recurring mutations in the antigen-binding site, selected in GCs, enhance interactions of the antibody with DEL. The effects of these mutations on affinity maturation are demonstrated by a shift of transgenic serum antibodies towards higher affinity for DEL in DEL-cOVA immunized mice. The results show that B cells with high affinity antigen receptors can revise their specificity by somatic hypermutation and antigen selection in response to a low-affinity, cross-reactive antigen. These observations shed further light on the nature of the immune response to pathogens and autoimmunity and demonstrate the utility of this novel model for studies of the mechanisms of somatic hypermutation

Dependence on Dectin-1 Varies With Multiple Candida Species

This is the final version. Available from Frontiers Media via the DOI in this recordFour Candida spp. (albicans, glabrata, tropicalis, parapsilosis) cause >95% of invasive Candida infections. C. albicans elicits immune responses via pathogen recognition receptors including C-type lectin-like receptors (CLRs). The CLR, Dectin-1 is important for host immunity to C. albicans and C. glabrata, however, whether Dectin-1 is important for host defense against C. tropicalis or C. parapsilosis is unknown. Therefore, we compared the involvement of Dectin-1 in response to these four diverse Candida spp. We found that Dectin-1 mediates innate cytokine responses to these Candida spp. in a species- and cell-dependent manner. Dectin-1 KO mice succumbed to infection with highly virulent C. albicans while they mostly survived infection with less virulent Candida spp. However, Dectin-1 KO mice displayed increased fungal burden following infection with each Candida spp. Additionally, T cells from Dectin-1 KO mice displayed enhanced effector functions likely due to the inability of Dectin-1 KO mice to clear the infections. Together, these data indicate that Dectin-1 is important for host defense to multiple Candida spp., although the specific roles for Dectin-1 varies with different Candida spp.Wellcome TrustRoyal SocietyUK Dementia Research InstituteMRC Centre for Medical Mycolog

Automatic mental processes, automatic actions and behaviours in game transfer phenomena: an empirical self-report study using online forum data

Previous studies have demonstrated that the playing of videogames can have both intended and unintended effects. The purpose of this study was to investigate the influence of videogames on players’ mental processes and behaviours in day-to-day settings. A total of 1,023 self-reports from 762 gamers collected from online videogame forums were classified, quantified, described and explained. The data include automatic thoughts, sensations and impulses, automatic mental replays of the game in real life, and voluntary/involuntary behaviours with videogame content. Many gamers reported that they had responded – at least sometimes – to real life stimuli as if they were still playing videogames. This included overreactions, avoidances, and involuntary movements of limbs. These experiences lasted relatively short periods of time but in a minority of players were recurrent. The gamers' experiences appeared to be enhanced by virtual embodiment, repetitive manipulation of game controls, and their gaming habits. However, similar phenomena may also occur when doing other non-gaming activities. The implications of these game transfer experiences are discussed

Quantifying non-Newtonian effects in rotating boundary-layer flows

© 2016 Elsevier Masson SAS The stability of the boundary-layer on a rotating disk is considered for fluids that adhere to a non-Newtonian governing viscosity relationship. For fluids with shear-rate dependent viscosity the base flow is no longer an exact solution of the Navier–Stokes equations, however, in the limit of large Reynolds number the flow inside the three-dimensional boundary-layer can be determined via a similarity solution. The convective instabilities associated with flows of this nature are described both asymptotically and numerically via separate linear stability analyses. Akin to previous Newtonian studies it is found that there exists two primary modes of instability; the upper-branch type I modes, and the lower-branch type II modes. Results show that both these modes can be stabilised or destabilised depending on the choice of non-Newtonian viscosity model. A number of comments are made regarding the suitability of some of the more well-known non-Newtonian constitutive relationships within the context of the rotating disk model. Such a study is presented with a view to suggesting potential control mechanisms for flows that are practically relevant to the turbo-machinery industry