670 research outputs found

    PIN54 ADAPTATION & CALIBRATION OF A UK MODEL OF MENINGOCOCCAL DISEASE TO THE US SETTING

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    Guiding principles for evaluating the impacts of conservation interventions on human well-being

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    Measures of socio-economic impacts of conservation interventions have largely been restricted to externally defined indicators focused on income, which do not reflect people's priorities. Using a holistic, locally grounded conceptualization of human well-being instead provides a way to understand the multi-faceted impacts of conservation on aspects of people's lives that they value. Conservationists are engaging with well-being for both pragmatic and ethical reasons, yet current guidance on how to operationalize the concept is limited. We present nine guiding principles based around a well-being framework incorporating material, relational and subjective components, and focused on gaining knowledge needed for decision-making. The principles relate to four key components of an impact evaluation: (i) defining well-being indicators, giving primacy to the perceptions of those most impacted by interventions through qualitative research, and considering subjective well-being, which can affect engagement with conservation; (ii) attributing impacts to interventions through quasi-experimental designs, or alternative methods such as theory-based, case study and participatory approaches, depending on the setting and evidence required; (iii) understanding the processes of change including evidence of causal linkages, and consideration of trajectories of change and institutional processes; and (iv) data collection with methods selected and applied with sensitivity to research context, consideration of heterogeneity of impacts along relevant societal divisions, and conducted by evaluators with local expertise and independence from the intervention

    Improved hospital-level risk adjustment for surveillance of healthcare-associated bloodstream infections: a retrospective cohort study

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    Background: To allow direct comparison of bloodstream infection (BSI) rates between hospitals for performance measurement, observed rates need to be risk adjusted according to the types of patients cared for by the hospital. However, attribute data on all individual patients are often unavailable and hospital-level risk adjustment needs to be done using indirect indicator variables of patient case mix, such as hospital level. We aimed to identify medical services associated with high or low BSI rates, and to evaluate the services provided by the hospital as indicators that can be used for more objective hospital-level risk adjustment

    Mapping Helminth Co-Infection and Co-Intensity: Geostatistical Prediction in Ghana

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    Urinary schistosomiasis and hookworm infections cause considerable morbidity in school age children in West Africa. Severe morbidity is predominantly observed in individuals infected with both parasite types and, in particular, with heavy infections. We investigated for the first time the distribution of S. haematobium and hookworm co-infections and distribution of co-intensity of these parasites in Ghana. Bayesian geostatistical models were developed to generate a national co-infection map and national intensity maps for each parasite, using data on S. haematobium and hookworm prevalence and egg concentration (expressed as eggs per 10 mL of urine for S. haematobium and expressed as eggs per gram of faeces for hookworm), collected during a pre-intervention baseline survey in Ghana, 2008. In contrast with previous findings from the East Africa region, we found that both S. haematobium and hookworm infections are highly focal, resulting in small, localized clusters of co-infection and areas of high co-intensity. Overlaying on a single map the co-infection and the intensity of multiple parasite infections allows identification of areas where parasite environmental contamination and morbidity are at its highest, while providing an evidence base for the assessment of the progress of successive rounds of mass drug administration (MDA) in integrated parasitic disease control programs

    Burden of Illness in UK Subjects with Reported Respiratory Infections Vaccinated or Unvaccinated against Influenza: A Retrospective Observational Study

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    <div><p>Objective</p><p>Detailed data are lacking on influenza burden in the United Kingdom (UK). The objective of this study was to estimate the disease burden associated with influenza-like illness (ILI) in the United Kingdom stratified by age, risk and influenza vaccination status.</p><p>Methods</p><p>This retrospective, cross-sectional, exploratory, observational study used linked data from the General Practice Research Database and the Hospital Episode Statistics databases to estimate resource use and cost associated with ILI in the UK.</p><p>Results</p><p>Data were included from 156,193 patients with ≥1 general practitioner visit with ILI. There were 21,518 high-risk patients, of whom 12,514 (58.2%) were vaccinated and 9,004 (41.8%) were not vaccinated, and 134,675 low-risk patients, of whom 17,482 (13.0%) were vaccinated and 117,193 (87.0%) were not vaccinated. High-risk vaccinated patients were older (p<0.001) and had more risk conditions (p<0.001). High-risk (odds ratio [OR] 2.16) or vaccinated (OR 1.19) patients had a higher probability of >1 general practitioner visit compared with low-risk and unvaccinated patients. Patients who were high-risk and vaccinated had a reduced risk of >1 general practitioner visit (OR 0.82; p<0.001). High-risk individuals who were also vaccinated had a lower probability of ILI-related hospitalisation than individuals who were high-risk or vaccinated alone (OR 0.59). In people aged ≥65 years, the mortality rate was lower in vaccinated than unvaccinated individuals (OR 0.75). The cost of ILI-related GP visits and hospital admissions in the UK over the study period in low-risk vaccinated patients was £27,391,142 and £141,932,471, respectively. In low-risk unvaccinated patients the corresponding values were £168,318,709 and £112,534,130, respectively.</p><p>Conclusions</p><p>Although vaccination rates in target groups have increased, many people are still not receiving influenza vaccination, and the burden of ILI in the United Kingdom remains substantial. Improving influenza vaccination uptake may have the potential to reduce this burden.</p></div

    Deletion of Porcn in Mice Leads to Multiple Developmental Defects and Models Human Focal Dermal Hypoplasia (Goltz Syndrome)

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    Focal Dermal Hypoplasia (FDH) is a genetic disorder characterized by developmental defects in skin, skeleton and ectodermal appendages. FDH is caused by dominant loss-of-function mutations in X-linked PORCN. PORCN orthologues in Drosophila and mice encode endoplasmic reticulum proteins required for secretion and function of Wnt proteins. Wnt proteins play important roles in embryo development, tissue homeostasis and stem cell maintenance. Since features of FDH overlap with those seen in mouse Wnt pathway mutants, FDH likely results from defective Wnt signaling but molecular mechanisms by which inactivation of PORCN affects Wnt signaling and manifestations of FDH remain to be elucidated.We introduced intronic loxP sites and a neomycin gene in the mouse Porcn locus for conditional inactivation. Porcn-ex3-7flox mice have no apparent developmental defects, but chimeric mice retaining the neomycin gene (Porcn-ex3-7Neo-flox) have limb, skin, and urogenital abnormalities. Conditional Porcn inactivation by EIIa-driven or Hprt-driven Cre recombinase results in increased early embryonic lethality. Mesenchyme-specific Prx-Cre-driven inactivation of Porcn produces FDH-like limb defects, while ectodermal Krt14-Cre-driven inactivation produces thin skin, alopecia, and abnormal dentition. Furthermore, cell-based assays confirm that human PORCN mutations reduce WNT3A secretion.These data indicate that Porcn inactivation in the mouse produces a model for human FDH and that phenotypic features result from defective WNT signaling in ectodermal- and mesenchymal-derived structures

    Safety and immunogenicity of three doses of an eleven-valent diphtheria toxoid and tetanus protein – conjugated pneumococcal vaccine in Filipino infants

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    BACKGROUND: An 11-valent pneumococcal conjugate vaccine could provide significantly larger reduction in pneumococcal disease burden than the currently available 7-valent vaccine formulation in many countries. METHODS: In total, 50 infants were enrolled to this open, uncontrolled study, which evaluated the safety and immunogenicity of an aluminium adjuvanted 11-valent mixed-carrier diphtheria toxoid or tetanus protein-conjugated vaccine (11-PncTD) when administered in three doses at 6, 10 and 14 weeks of age simultaneously with DTwP//PRP-T and OPV vaccines in Filipino infants. RESULTS: The rates of local reactions between the two injection sites, those associated with the 11-PncTD vaccine and those with the DTwP//PRP-T were almost of equal frequency for all three vaccine doses except for induration, which was significantly more common in the DTP//PRP-T injection site. Fever was present in 39%, 22% and 21% of infants following each of the three doses. Antibody responses were determined by an enzyme immunoassay method before the first vaccination and after the three doses. The vaccine elicited a significant anti-pneumococcal polysaccharide antibody response against all serotypes included in the vaccine, except for type 14, for which the pre-vaccination geometric mean antibody concentration (GMC) was high (1.61 μg/ml). The GMCs one month after the vaccination series ranged from 1.1 micrograms/ml for type 6B to 23.4 μg/ml for type 4. CONCLUSION: The 11-PncTD vaccine is safe, well-tolerated and immunogenic. The effectiveness of the non-adjuvanted formulation of the vaccine in preventing pneumonia is currently being evaluated in the Philippines

    Determining the neurotransmitter concentration profile at active synapses

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    Establishing the temporal and concentration profiles of neurotransmitters during synaptic release is an essential step towards understanding the basic properties of inter-neuronal communication in the central nervous system. A variety of ingenious attempts has been made to gain insights into this process, but the general inaccessibility of central synapses, intrinsic limitations of the techniques used, and natural variety of different synaptic environments have hindered a comprehensive description of this fundamental phenomenon. Here, we describe a number of experimental and theoretical findings that has been instrumental for advancing our knowledge of various features of neurotransmitter release, as well as newly developed tools that could overcome some limits of traditional pharmacological approaches and bring new impetus to the description of the complex mechanisms of synaptic transmission

    Do herbivorous minnows have “plug-flow reactor” guts? Evidence from digestive enzyme activities, gastrointestinal fermentation, and luminal nutrient concentrations

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    Few investigations have empirically analyzed fish gut function in the context of chemical reactor models. In this study, digestive enzyme activities, levels of gastrointestinal fermentation products [short chain fatty acids (SCFA)], luminal nutrient concentrations, and the mass of gut contents were measured along the digestive tract in herbivorous and carnivorous minnows to ascertain whether their guts function as “plug-flow reactors” (PFRs). Four of the species, Campostoma anomalum, C. ornatum, C. oligolepis, and C. pauciradii, are members of a monophyletic herbivorous clade, whereas the fifth species, Nocomis micropogon, is a carnivore from an adjacent carnivorous clade. In the context of a PFR model, the activities of amylase, trypsin and lipase, and the concentrations of glucose, protein, and lipid were predicted to decrease moving from the proximal to the distal intestine. I found support for this as these enzyme activities and nutrient concentrations generally decreased moving distally along the intestine of the four Campostoma species. Furthermore, gut content mass and the low SCFA concentrations did not change (increase or decrease) along the gut of any species. Combined with a previous investigation suggesting that species of Campostoma have rapid gut throughput rates, the data presented here generally support Campostoma as having guts that function as PFRs. The carnivorous N. micropogon showed some differences in the measured parameters, which were interpreted in the contexts of intake and retention time to suggest that PFR function breaks down in this carnivorous species

    Planck intermediate results. XLI. A map of lensing-induced B-modes

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    The secondary cosmic microwave background (CMB) BB-modes stem from the post-decoupling distortion of the polarization EE-modes due to the gravitational lensing effect of large-scale structures. These lensing-induced BB-modes constitute both a valuable probe of the dark matter distribution and an important contaminant for the extraction of the primary CMB BB-modes from inflation. Planck provides accurate nearly all-sky measurements of both the polarization EE-modes and the integrated mass distribution via the reconstruction of the CMB lensing potential. By combining these two data products, we have produced an all-sky template map of the lensing-induced BB-modes using a real-space algorithm that minimizes the impact of sky masks. The cross-correlation of this template with an observed (primordial and secondary) BB-mode map can be used to measure the lensing BB-mode power spectrum at multipoles up to 20002000. In particular, when cross-correlating with the BB-mode contribution directly derived from the Planck polarization maps, we obtain lensing-induced BB-mode power spectrum measurement at a significance level of 12σ12\,\sigma, which agrees with the theoretical expectation derived from the Planck best-fit Λ\LambdaCDM model. This unique nearly all-sky secondary BB-mode template, which includes the lensing-induced information from intermediate to small (10100010\lesssim \ell\lesssim 1000) angular scales, is delivered as part of the Planck 2015 public data release. It will be particularly useful for experiments searching for primordial BB-modes, such as BICEP2/Keck Array or LiteBIRD, since it will enable an estimate to be made of the lensing-induced contribution to the measured total CMB BB-modes.Comment: 20 pages, 12 figures; Accepted for publication in A&A; The B-mode map is part of the PR2-2015 Cosmology Products; available as Lensing Products in the Planck Legacy Archive http://pla.esac.esa.int/pla/#cosmology; and described in the 'Explanatory Supplement' https://wiki.cosmos.esa.int/planckpla2015/index.php/Specially_processed_maps#2015_Lensing-induced_B-mode_ma
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