Variation in dengue virus plaque reduction neutralization testing: systematic review and pooled analysis.

BackgroundThe plaque reduction neutralization test (PRNT) remains the gold standard for the detection of serologic immune responses to dengue virus (DENV). While the basic concept of the PRNT remains constant, this test has evolved in multiple laboratories, introducing variation in materials and methods. Despite the importance of laboratory-to-laboratory comparability in DENV vaccine development, the effects of differing PRNT techniques on assay results, particularly the use of different dengue strains within a serotype, have not been fully characterized.MethodsWe conducted a systematic review and pooled analysis of published literature reporting individual-level PRNT titers to identify factors associated with heterogeneity in PRNT results and compared variation between strains within DENV serotypes and between articles using hierarchical models.ResultsThe literature search and selection criteria identified 8 vaccine trials and 25 natural exposure studies reporting 4,411 titers from 605 individuals using 4 different neutralization percentages, 3 cell lines, 12 virus concentrations and 51 strains. Of 1,057 titers from primary DENV exposure, titers to the exposure serotype were consistently higher than titers to non-exposure serotypes. In contrast, titers from secondary DENV exposures (n = 628) demonstrated high titers to exposure and non-exposure serotypes. Additionally, PRNT titers from different strains within a serotype varied substantially. A pooled analysis of 1,689 titers demonstrated strain choice accounted for 8.04% (90% credible interval [CrI]: 3.05%, 15.7%) of between-titer variation after adjusting for secondary exposure, time since DENV exposure, vaccination and neutralization percentage. Differences between articles (a proxy for inter-laboratory differences) accounted for 50.7% (90% CrI: 30.8%, 71.6%) of between-titer variance.ConclusionsAs promising vaccine candidates arise, the lack of standardized assays among diagnostic and research laboratories make unbiased inferences about vaccine-induced protection difficult. Clearly defined, widely accessible reference reagents, proficiency testing or algorithms to adjust for protocol differences would be a useful first step in improving dengue PRNT comparability and quality assurance

Promoting inclusion oral-health:social interventions to reduce oral health inequities

The aim of this collection of papers is to provide the reader with a cogent understanding of the role of evidence in the development of social or community-based interventions to promote inclusion oral-health and reduce oral health, health, and psychosocial inequities. In addition, this material will include various methods used for their implementation and evaluation. At the outset, the reader will be offered a working definition of inclusion oral-health, which will be modelled on the work of Luchenski et al. [1]. The interventions described are theoretically underpinned by a pluralistic definition of evidence-based practice [2] and the radical discourse of health promotion as postulated by Laverack and Labonte [3] and others [4,5]. This Special Issue will consist of eight papers, including an introduction. The first three papers will examine the various sources of evidence used to transform top-down into bottom-up community-based interventions for people experiencing homelessness; people in custody and for families residing in areas of high social deprivation. The final four papers will report on the implementation and evaluation of social or community-based interventions. This collection of research papers will highlight the importance of focusing on prevention and the adoption of a common risk factor agenda to tackle oral health, health and psychosocial inequities felt by those most excluded in our societies

Accuracy and consistency of grass pollen identification by human analysts using electron micrographs of surface ornamentation

• Premise of the study: Humans frequently identify pollen grains at a taxonomic rank above species. Grass pollen is a classic case of this situation, which has led to the development of computational methods for identifying grass pollen species. This paper aims to provide context for these computational methods by quantifying the accuracy and consistency of human identification. • Methods: We measured the ability of nine human analysts to identify 12 species of grass pollen using scanning electron microscopy images. These are the same images that were used in computational identifications. We have measured the coverage, accuracy, and consistency of each analyst, and investigated their ability to recognize duplicate images. • Results: Coverage ranged from 87.5% to 100%. Mean identification accuracy ranged from 46.67% to 87.5%. The identification consistency of each analyst ranged from 32.5% to 87.5%, and each of the nine analysts produced considerably different identification schemes. The proportion of duplicate image pairs that were missed ranged from 6.25% to 58.33%. • Discussion: The identification errors made by each analyst, which result in a decline in accuracy and consistency, are likely related to psychological factors such as the limited capacity of human memory, fatigue and boredom, recency effects, and positivity bias

Could the GRB-Supernovae GRB 031203 and XRF 060218 be Cosmic Twins?

The gamma-ray burst (GRB) / X-ray flash (XRF) events GRB 031203, discovered by INTEGRAL, and XRF 060218, discovered by Swift, represent two of only five GRB-SNe with optical spectroscopic confirmation of their SN components. Yet their observed high-energy properties offer a sharp contrast: While GRB 031203 was detected as a short 40-s burst with a spectrum peaking at E_peak > 190 keV, XRF 060218 was a T_90 ~ 2100-s long, smoothly-evolving burst with peak energy E_peak = 4.9 keV. At the same time, the properties of the two expanding dust-scattered X-ray halos observed in a fast-response XMM-Newton observation of GRB 031203 reveal that this event was accompanied by an "X-ray blast" with fluence comparable to or greater than that of the prompt gamma-ray event. Taking this observation as our starting point, we investigate the likely properties of the X-ray blast from GRB 031203 via detailed modeling of the XMM data, discovering a third halo due to scattering off a more distant dust sheet at d_3 = 9.94 +/- 0.39 kpc, and constraining the timing of the X-ray blast relative to the GRB trigger time to be t_0 = 11 +/- 417 s. Using our constraints, we compare the properties of GRB 031203 to those of other GRB-SNe in order to understand the likely nature of its X-ray blast, concluding that a bright X-ray flare, as in GRB 050502B, or shock breakout event, as in XRF 060218, provide the most likely explanations. In the latter case, we consider the added possibility that XRF 060218 may have manifested an episode of bright gamma-ray emission prior to the burst observed by Swift, in which case GRB 031203 and XRF 060218 would be "cosmic twin" explosions with nearly identical high-energy properties.Comment: MNRAS in press; 12 pages, 6 figures. v2: Expanded discussion of related papers and minor changes in response to referee repor

Combined In Silico, In Vivo, and In Vitro Studies Shed Insights into the Acute Inflammatory Response in Middle-Aged Mice

We combined in silico, in vivo, and in vitro studies to gain insights into age-dependent changes in acute inflammation in response to bacterial endotoxin (LPS). Time-course cytokine, chemokine, and NO2-/NO3- data from "middle-aged" (6-8 months old) C57BL/6 mice were used to re-parameterize a mechanistic mathematical model of acute inflammation originally calibrated for "young" (2-3 months old) mice. These studies suggested that macrophages from middle-aged mice are more susceptible to cell death, as well as producing higher levels of pro-inflammatory cytokines, vs. macrophages from young mice. In support of the in silico-derived hypotheses, resident peritoneal cells from endotoxemic middle-aged mice exhibited reduced viability and produced elevated levels of TNF-α, IL-6, IL-10, and KC/CXCL1 as compared to cells from young mice. Our studies demonstrate the utility of a combined in silico, in vivo, and in vitro approach to the study of acute inflammation in shock states, and suggest hypotheses with regard to the changes in the cytokine milieu that accompany aging. © 2013 Namas et al

The effect of age on outcomes of coronary artery bypass surgery compared with balloon angioplasty or bare-metal stent implantation among patients with multivessel coronary disease. A collaborative analysis of individual patient data from 10 randomized trials.

OBJECTIVES: This study sought to assess whether patient age modifies the comparative effectiveness of coronary artery bypass graft (CABG) surgery and percutaneous coronary intervention (PCI). BACKGROUND: Increasingly, CABG and PCI are performed in older patients to treat multivessel disease, but their comparative effectiveness is uncertain. METHODS: Individual data from 7,812 patients randomized in 1 of 10 clinical trials of CABG or PCI were pooled. Age was analyzed as a continuous variable in the primary analysis and was divided into tertiles for descriptive purposes (≤56.2 years, 56.3 to 65.1 years, ≥65.2 years). The outcomes assessed were death, myocardial infarction and repeat revascularization over complete follow-up, and angina at 1 year. RESULTS: Older patients were more likely to have hypertension, diabetes, and 3-vessel disease compared with younger patients (p < 0.001 for trend). Over a median follow-up of 5.9 years, the effect of CABG versus PCI on mortality varied according to age (interaction p < 0.01), with adjusted CABG-to-PCI hazard ratios and 95% confidence intervals (CI) of 1.23 (95% CI: 0.95 to 1.59) in the youngest tertile; 0.89 (95% CI: 0.73 to 1.10) in the middle tertile; and 0.79 (95% CI: 0.67 to 0.94) in the oldest tertile. The CABG-to-PCI hazard ratio of less than 1 for patients 59 years of age and older. A similar interaction of age with treatment was present for the composite outcome of death or myocardial infarction. In contrast, patient age did not alter the comparative effectiveness of CABG and PCI on the outcomes of repeat revascularization or angina. CONCLUSIONS: Patient age modifies the comparative effectiveness of CABG and PCI on hard cardiac events, with CABG favored at older ages and PCI favored at younger ages

Developing the 'Understanding Library Impacts' Protocol: A Method for Detecting and Communicating Academic Library Impact on Student Learning

The Understanding Library Impacts (ULI) protocol is a suite of instruments designed to demonstrate connections between undergraduate student use of the academic library and faculty-defined expectations for student learning. The ULI protocol features a Critical Incident Technique (CIT) survey for exploring student use of the library during `high-impact' academic experiences such as capstone courses. A `Learning Activities Crosswalk' links student use of the library to faculty-defined, discipline-specific and general education expectations for student learning. This methodological study evaluated the protocol with a population of undergraduate students enrolled in upper-level and capstone history courses at six colleges and universities. The protocol focuses on students' use of traditional and electronic information resources, library services, and library facilities during learning activities associated with `high-impact' experiences in the academic major. Learning activities are stages in `high-impact' coursework during which students develop and demonstrate desired learning outcomes. The Learning Activities Crosswalk creates credible connections between information use behaviors during these learning activities and faculty-defined expectations for student learning. A web-based survey using the Critical Incident Technique gathers quantitative and qualitative data about students' information uses when completing `high-impact' coursework. Created and refined in two interview-based pilot studies, respondents identify the information resources, services, and facilities used when completing coursework and the learning activities each use supported. Partially-open questions identify the factors of library use that were helpful or problematic to students during their coursework. Open-ended questions gather qualitative data and user stories that reinforce other findings. Undergraduates enrolled in history courses at the six study sites reported 127 critical incidents. Responses from the survey and results from the Learning Activities Crosswalk were entered into a database for analysis and presentation to study sites. Statistical and qualitative techniques were used to assess the validity and reliability of findings. The study demonstrated a method for exploring library use as a component of student effort within the context of academic `work tasks' and illustrated the power of the CIT for exploring library impact. The project also generated an extensible and scalable framework for detecting and communicating library contributions to student learning.Doctor of Philosoph

Estimating potential incidence of MERS-CoV associated with Hajj pilgrims to Saudi Arabia, 2014

Between March and June 2014 the Kingdom of Saudi Arabia (KSA) had a large outbreak of MERS-CoV, renewing fears of a major outbreak during the Hajj this October. Using KSA Ministry of Health data, the MERS-CoV Scenario and Modeling Working Group forecast incidence under three scenarios. In the expected incidence scenario, we estimate 6.2 (95% Prediction Interval [PI]: 1-17) pilgrims will develop MERS-CoV symptoms during the Hajj, and 4.0 (95% PI: 0-12) foreign pilgrims will be infected but return home before developing symptoms. In the most pessimistic scenario, 47.6 (95% PI: 32-66) cases will develop symptoms during the Hajj, and 29.0 (95% PI: 17-43) will be infected but return home asymptomatic. Large numbers of MERS-CoV cases are unlikely to occur during the 2014 Hajj even under pessimistic assumptions, but careful monitoring is still needed to detect possible mass infection events and minimize introductions into other countries

Opportunities for improved surveillance and control of dengue from age-specific case data.

One of the challenges faced by global disease surveillance efforts is the lack of comparability across systems. Reporting commonly focuses on overall incidence, despite differences in surveillance quality between and within countries. For most immunizing infections, the age distribution of incident cases provides a more robust picture of trends in transmission. We present a framework to estimate transmission intensity for dengue virus from age-specific incidence data, and apply it to 359 administrative units in Thailand, Colombia, Brazil and Mexico. Our estimates correlate well with those derived from seroprevalence data (the gold standard), capture the expected spatial heterogeneity in risk, and correlate with known environmental drivers of transmission. We show how this approach could be used to guide the implementation of control strategies such as vaccination. Since age-specific counts are routinely collected by masany surveillance systems, they represent a unique opportunity to further our understanding of disease burden and risk for many diseases