770 research outputs found

    Study protocol for a multicentre longitudinal mixed methods study to explore the Outcomes of ChildrEn and fAmilies in the first year after paediatric Intensive Care: the OCEANIC study.

    Get PDF
    INTRODUCTION: Annually in the UK, 20 000 children become very ill or injured and need specialist care within a paediatric intensive care unit (PICU). Most children survive. However, some children and their families may experience problems after they have left the PICU including physical, functional and/or emotional problems. It is unknown which children and families experience such problems, when these occur or what causes them. The aim of this mixed-method longitudinal cohort study is to understand the physical, functional, emotional and social impact of children surviving PICU (aged: 1 month-17 years), their parents and siblings, during the first year after a PICU admission. METHODS AND ANALYSIS: A quantitative study involving 300 child survivors of PICU; 300 parents; and 150-300 siblings will collect data (using self-completion questionnaires) at baseline, PICU discharge, 1, 3, 6 and 12 months post-PICU discharge. Questionnaires will comprise validated and reliable instruments. Demographic data, PICU admission and treatment data, health-related quality of life, functional status, strengths and difficulties behaviour and post-traumatic stress symptoms will be collected from the child. Parent and sibling data will be collected on the impact of paediatric health conditions on the family's functioning capabilities, levels of anxiety and social impact of the child's PICU admission. Data will be analysed using descriptive and inferential statistics. Concurrently, an embedded qualitative study involving semistructured interviews with 24 enrolled families at 3 months and 9 months post-PICU discharge will be undertaken. Framework analysis will be used to analyse the qualitative data. ETHICS AND DISSEMINATION: The study has received ethical approval from the National Health Services Research Ethics Committee (Ref: 19/WM/0290) and full governance clearance. This will be the first UK study to comprehensively investigate physical, functional, emotional and social consequences of PICU survival in the first-year postdischarge.Clinical Trials Registration Number: ISRCTN28072812 [Pre-results]

    Estimating Health-State Utility Values in Kidney Transplant Recipients and Waiting-List Patients Using the EQ-5D-5L.

    Get PDF
    OBJECTIVES: To report health-state utility values measured using the five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) in a large sample of patients with end-stage renal disease and to explore how these values vary in relation to patient characteristics and treatment factors. METHODS: As part of the prospective observational study entitled "Access to Transplantation and Transplant Outcome Measures," we captured information on patient characteristics and treatment factors in a cohort of incident kidney transplant recipients and a cohort of prevalent patients on the transplant waiting list in the United Kingdom. We assessed patients' health status using the EQ-5D-5L and conducted multivariable regression analyses of index scores. RESULTS: EQ-5D-5L responses were available for 512 transplant recipients and 1704 waiting-list patients. Mean index scores were higher in transplant recipients at 6 months after transplant surgery (0.83) compared with patients on the waiting list (0.77). In combined regression analyses, a primary renal diagnosis of diabetes was associated with the largest decrement in utility scores. When separate regression models were fitted to each cohort, female gender and Asian ethnicity were associated with lower utility scores among waiting-list patients but not among transplant recipients. Among waiting-list patients, longer time spent on dialysis was also associated with poorer utility scores. When comorbidities were included, the presence of mental illness resulted in a utility decrement of 0.12 in both cohorts. CONCLUSIONS: This study provides new insights into variations in health-state utility values from a single source that can be used to inform cost-effectiveness evaluations in patients with end-stage renal disease

    Barriers to living donor kidney transplantation in the United Kingdom: a national observational study.

    Get PDF
    BACKGROUND: Living donor kidney transplantation (LDKT) provides more timely access to transplantation and better clinical outcomes than deceased donor kidney transplantation (DDKT). This study investigated disparities in the utilization of LDKT in the UK. METHODS: A total of 2055 adults undergoing kidney transplantation between November 2011 and March 2013 were prospectively recruited from all 23 UK transplant centres as part of the Access to Transplantation and Transplant Outcome Measures (ATTOM) study. Recipient variables independently associated with receipt of LDKT versus DDKT were identified. RESULTS: Of the 2055 patients, 807 (39.3%) received LDKT and 1248 (60.7%) received DDKT. Multivariable modelling demonstrated a significant reduction in the likelihood of LDKT for older age {odds ratio [OR] 0.11 [95% confidence interval (CI) 0.08-0.17], P < 0.0001 for 65-75 years versus 18-34 years}; Asian ethnicity [OR 0.55 (95% CI 0.39-0.77), P = 0.0006 versus White]; Black ethnicity [OR 0.64 (95% CI 0.42-0.99), P = 0.047 versus White]; divorced, separated or widowed [OR 0.63 (95% CI 0.46-0.88), P = 0.030 versus married]; no qualifications [OR 0.55 (95% CI 0.42-0.74), P < 0.0001 versus higher education qualifications]; no car ownership [OR 0.51 (95% CI 0.37-0.72), P = 0.0001] and no home ownership [OR 0.65 (95% CI 0.85-0.79), P = 0.002]. The odds of LDKT varied significantly between countries in the UK. CONCLUSIONS: Among patients undergoing kidney transplantation in the UK, there are significant age, ethnic, socio-economic and geographic disparities in the utilization of LDKT. Further work is needed to explore the potential for targeted interventions to improve equity in living donor transplantation

    Middleborns disadvantaged? testing birth-order effects on fitness in pre-industrial finns

    Get PDF
    Parental investment is a limited resource for which offspring compete in order to increase their own survival and reproductive success. However, parents might be selected to influence the outcome of sibling competition through differential investment. While evidence for this is widespread in egg-laying species, whether or not this may also be the case in viviparous species is more difficult to determine. We use pre-industrial Finns as our model system and an equal investment model as our null hypothesis, which predicts that (all else being equal) middleborns should be disadvantaged through competition. We found no overall evidence to suggest that middleborns in a family are disadvantaged in terms of their survival, age at first reproduction or lifetime reproductive success. However, when considering birth-order only among same-sexed siblings, first-, middle-and lastborn sons significantly differed in the number of offspring they were able to rear to adulthood, although there was no similar effect among females. Middleborn sons appeared to produce significantly less offspring than first-or lastborn sons, but they did not significantly differ from lastborn sons in the number of offspring reared to adulthood. Our results thus show that taking sex differences into account is important when modelling birth-order effects. We found clear evidence of firstborn sons being advantaged over other sons in the family, and over firstborn daughters. Therefore, our results suggest that parents invest differentially in their offspring in order to both preferentially favour particular offspring or reduce offspring inequalities arising from sibling competition

    Singlet-doublet Higgs mixing and its implications on the Higgs mass in the PQ-NMSSM

    Full text link
    We examine the implications of singlet-doublet Higgs mixing on the properties of a Standard Model (SM)-like Higgs boson within the Peccei-Quinn invariant extension of the NMSSM (PQ-NMSSM). The SM singlet added to the Higgs sector connects the PQ and visible sectors through a PQ-invariant non-renormalizable K\"ahler potential term, making the model free from the tadpole and domain-wall problems. For the case that the lightest Higgs boson is dominated by the singlet scalar, the Higgs mixing increases the mass of a SM-like Higgs boson while reducing its signal rate at collider experiments compared to the SM case. The Higgs mixing is important also in the region of parameter space where the NMSSM contribution to the Higgs mass is small, but its size is limited by the experimental constraints on the singlet-like Higgs boson and on the lightest neutralino constituted mainly by the singlino whose Majorana mass term is forbidden by the PQ symmetry. Nonetheless the Higgs mixing can increase the SM-like Higgs boson mass by a few GeV or more even when the Higgs signal rate is close to the SM prediction, and thus may be crucial for achieving a 125 GeV Higgs mass, as hinted by the recent ATLAS and CMS data. Such an effect can reduce the role of stop mixing.Comment: 26 pages, 3 figures; published in JHE

    Rpgrip1 is required for rod outer segment development and ciliary protein trafficking in zebrafish

    Get PDF
    The authors would like to thank the Royal Society of London, the National Eye Research Centre, the Visual Research Trust, Fight for Sight, the W.H. Ross Foundation, the Rosetrees Trust, and the Glasgow Children’s Hospital Charity for supporting this work. This work was also supported by the Deanship of Scientific Research at King Saud University for funding this research (Research Project) grant number ‘RGP – VPP – 219’.Mutations in the RPGR-interacting protein 1 (RPGRIP1) gene cause recessive Leber congenital amaurosis (LCA), juvenile retinitis pigmentosa (RP) and cone-rod dystrophy. RPGRIP1 interacts with other retinal disease-causing proteins and has been proposed to have a role in ciliary protein transport; however, its function remains elusive. Here, we describe a new zebrafish model carrying a nonsense mutation in the rpgrip1 gene. Rpgrip1homozygous mutants do not form rod outer segments and display mislocalization of rhodopsin, suggesting a role for RPGRIP1 in rhodopsin-bearing vesicle trafficking. Furthermore, Rab8, the key regulator of rhodopsin ciliary trafficking, was mislocalized in photoreceptor cells of rpgrip1 mutants. The degeneration of rod cells is early onset, followed by the death of cone cells. These phenotypes are similar to that observed in LCA and juvenile RP patients. Our data indicate RPGRIP1 is necessary for rod outer segment development through regulating ciliary protein trafficking. The rpgrip1 mutant zebrafish may provide a platform for developing therapeutic treatments for RP patients.Publisher PDFPeer reviewe

    An empirical approach towards the efficient and optimal production of influenza-neutralizing ovine polyclonal antibodies demonstrates that the novel adjuvant CoVaccine HT(TM) is functionally superior to Freund's adjuvant

    Get PDF
    Passive immunotherapies utilising polyclonal antibodies could have a valuable role in preventing and treating infectious diseases such as influenza, particularly in pandemic situations but also in immunocompromised populations such as the elderly, the chronically immunosuppressed, pregnant women, infants and those with chronic diseases. The aim of this study was to optimise current methods used to generate ovine polyclonal antibodies. Polyclonal antibodies to baculovirus-expressed recombinant influenza haemagglutinin from A/Puerto Rico/8/1934 H1N1 (PR8) were elicited in sheep using various immunisation regimens designed to investigate the priming immunisation route, adjuvant formulation, sheep age, and antigen dose, and to empirically ascertain which combination maximised antibody output. The novel adjuvant CoVaccine HT™ was compared to Freund’s adjuvant which is currently the adjuvant of choice for commercial production of ovine polyclonal Fab therapies. CoVaccine HT™ induced significantly higher titres of functional ovine anti-haemagglutinin IgG than Freund’s adjuvant but with fewer side effects, including reduced site reactions. Polyclonal hyperimmune sheep sera effectively neutralised influenza virus in vitro and, when given before or after influenza virus challenge, prevented the death of infected mice. Neither the age of the sheep nor the route of antigen administration appeared to influence antibody titre. Moreover, reducing the administrated dose of haemagglutinin antigen minimally affected antibody titre. Together, these results suggest a cost effective way of producing high and sustained yields of functional ovine polyclonal antibodies specifically for the prevention and treatment of globally significant diseases.Natalie E. Stevens, Cara K. Fraser, Mohammed Alsharifi, Michael P. Brown, Kerrilyn R. Diener, John D. Haybal

    Distribution and symmetrical patellofemoral pain patterns as revealed by high-resolution 3D body mapping:a cross-sectional study

    Get PDF
    Abstract Background Detailed pain mapping of extent and distribution in individuals with patellofemoral pain (PFP) within and around a complex structure such as the knee has yet to be explored. Methods Perceptions of on-going pain from adolescents and young adults (N = 35) with long-standing (>10 months) PFP were collected on high-resolution 3D digital body-schema of the knees. Location, area of pain, pain intensity, laterality, worse side of knee pain, symptom duration, and symmetry in bilateral knee pain were recorded. A threshold for naturally occurring variations in symmetrical knee pain drawings were collected from 18 healthy controls and used in combination with the development a symmetry index (0–1) to create a fuzzy rule for classifying symmetrical and non-symmetrical PFP patterns as compared to a PFP expert. The symmetry index was computed and tested using a correlation coefficient alone or in combination with the Jaccard index and the true and false positive rates (TPR and FPR, respectively) determined. Results The peripatellar region was the common report of pain location however, novel and nonconforming PFP patterns were identified and the majority of individuals (22 of 27) with bilateral PFP expressed highly-symmetric mirror-image pain. Individuals with symptom duration of 5 years or more had a greater area of pain, compared to those with symptoms for less than 5 years. The total area of pain was correlated to symptom duration for those with extended symptoms durations and a progression towards an “O” shaped pattern emerged. A TPR of 100% for identifying symmetrical knee pain patterns was found however the expert PFP tended to be stricter, as reflected in FPR of 20%. Conclusions A high proportion of PFP patterns or symptoms occur in mirrored locations and are exceptionally symmetrical, and long duration of symptoms appear to converge to an ‘O’ shape. Classifying symmetrical pain patterns is subjective however simple fuzzy rules and correlations can be used to increase objectivity. This study highlights a gap in knowledge of PFP symptom presentation, reveals what may be a natural progression of symptoms, and provides valuable clinical insight for both pain management and treatment

    MIMOX: a web tool for phage display based epitope mapping

    Get PDF
    BACKGROUND: Phage display is widely used in basic research such as the exploration of protein-protein interaction sites and networks, and applied research such as the development of new drugs, vaccines, and diagnostics. It has also become a promising method for epitope mapping. Research on new algorithms that assist and automate phage display based epitope mapping has attracted many groups. Most of the existing tools have not been implemented as an online service until now however, making it less convenient for the community to access, utilize, and evaluate them. RESULTS: We present MIMOX, a free web tool that helps to map the native epitope of an antibody based on one or more user supplied mimotopes and the antigen structure. MIMOX was coded in Perl using modules from the Bioperl project. It has two sections. In the first section, MIMOX provides a simple interface for ClustalW to align a set of mimotopes. It also provides a simple statistical method to derive the consensus sequence and embeds JalView as a Java applet to view and manage the alignment. In the second section, MIMOX can map a single mimotope or a consensus sequence of a set of mimotopes, on to the corresponding antigen structure and search for all of the clusters of residues that could represent the native epitope. NACCESS is used to evaluate the surface accessibility of the candidate clusters; and Jmol is embedded to view them interactively in their 3D context. Initial case studies show that MIMOX can reproduce mappings from existing tools such as FINDMAP and 3DEX, as well as providing novel, rational results. CONCLUSION: A web-based tool called MIMOX has been developed for phage display based epitope mapping. As a publicly available online service in this area, it is convenient for the community to access, utilize, and evaluate, complementing other existing programs. MIMOX is freely available at
    corecore