Direct and indirect effects of rotavirus vaccination: Comparing predictions from transmission dynamic models

Early observations from countries that have introduced rotavirus vaccination suggest that there may be indirect protection for unvaccinated individuals, but it is unclear whether these benefits will extend to the long term. Transmission dynamic models have attempted to quantify the indirect protection that might be expected from rotavirus vaccination in developed countries, but results have varied. To better understand the magnitude and sources of variability in model projections, we undertook a comparative analysis of transmission dynamic models for rotavirus. We fit five models to reported rotavirus gastroenteritis (RVGE) data from England and Wales, and evaluated outcomes for short- and long-term vaccination effects. All of our models reproduced the important features of rotavirus epidemics in England and Wales. Models predicted that during the initial year after vaccine introduction, incidence of severe RVGE would be reduced 1.8-2.9 times more than expected from the direct effects of the vaccine alone (28-50% at 90% coverage), but over a 5-year period following vaccine introduction severe RVGE would be reduced only by 1.1-1.7 times more than expected from the direct effects (54-90% at 90% coverage). Projections for the long-term reduction of severe RVGE ranged from a 55% reduction at full coverage to elimination with at least 80% coverage. Our models predicted short-term reductions in the incidence of RVGE that exceeded estimates of the direct effects, consistent with observations from the United States and other countries. Some of the models predicted that the short-term indirect benefits may be offset by a partial shifting of the burden of RVGE to older unvaccinated individuals. Nonetheless, even when such a shift occurs, the overall reduction in severe RVGE is considerable. Discrepancies among model predictions reflect uncertainties about age variation in the risk and reporting of RVGE, and the duration of natural and vaccine-induced immunity, highlighting important questions for future research

Citrullinated proteins in arthritis: presence in joints and effects on immunogenicity

Contains fulltext : 60098.pdf (publisher's version ) (Open Access

Generalisation in environmental sound classification : the ‘making sense of sounds’ data set and challenge

Humans are able to identify a large number of environmental sounds and categorise them according to high-level semantic categories, e.g. urban sounds or music. They are also capable of generalising from past experience to new sounds when applying these categories. In this paper we report on the creation of a data set that is structured according to the top-level of a taxonomy derived from human judgements and the design of an associated machine learning challenge, in which strong generalisation abilities are required to be successful. We introduce a baseline classification system, a deep convolutional network, which showed strong performance with an average accuracy on the evaluation data of 80.8%. The result is discussed in the light of two alternative explanations: An unlikely accidental category bias in the sound recordings or a more plausible true acoustic grounding of the high-level categories

Environmental noise levels in hospital settings : a rapid review of measurement techniques and implementation in hospital settings

Background: Hospitals provide treatment to improve patient health and well-being but the characteristics of the care environment receive little attention. Excessive noise at night has a negative impact on in-patient health through disturbed sleep. To address this hospital staff must measure night-time environmental noise levels. Therefore, an understanding of environmental noise measurement techniques is required. In this review, we aim to 1) provide a technical overview of factors to consider when measuring environmental noise in hospital settings; 2) conduct a rapid review on the equipment and approaches used to objectively measured noise in hospitals and identify methodological limitations. Design: A rapid review of original research articles, from 3 databases, published since 2008. Studies were included if noise levels were objectively measured in a hospital setting where patients were receiving treatment. Results: 1429 articles were identified with 76 included in the review. There was significant variability in the approaches used to measure environmental noise in hospitals. Only 14.5% of studies contained sufficient information to support replication of the measurement process. Most studies measured noise levels using a sound level meter positioned closed to a patient’s bed area in an intensive care unit. Conclusion: Unwanted environmental noise in hospital setting impacts negatively on patient and staff health and well-being. However, this literature review found that the approaches used to objectively measure noise level in hospital settings have been inconsistent and poorly reported. Recommendations on best-practice methods to measure noise levels in hospital environments are provided

Use of the ODD-Luciferase Transgene for the Non-Invasive Imaging of Spontaneous Tumors in Mice

In humans, imaging of tumors provides rapid, accurate assessment of tumor growth and location. In laboratory animals, however, the imaging of spontaneously occurring tumors continues to pose many technical and logistical problems. Recently a mouse model was generated in which a chimeric protein consisting of HIF-1α oxygen-dependent degradation domain (ODD) fused to luciferase was ubiquitously expressed in all tissues. Hypoxic stress leads to the accumulation of ODD-luciferase in the tissues of this mouse model which can be identified by non-invasive bioluminescence measurement. Since solid tumors often contain hypoxic regions, we performed proof-of-principle experiments testing whether this transgenic mouse model may be used as a universal platform for non-invasive imaging analysis of spontaneous solid tumors.ODD-luciferase transgenic mice were bred with MMTV-neu/beclin1+/- mice. Upon injection of luciferin, bioluminescent background of normal tissues in the transgenic mice and bioluminescent signals from spontaneously mammary carcinomas were measured non-invasively with an IVIS Spectrum imaging station. Tumor volumes were measured manually and the histology of tumor tissues was analyzed.Our results show that spontaneous mammary tumors in ODD-luciferase transgenic mice generate substantial bioluminescent signals, which are clearly discernable from background tissue luminescence. Moreover, we demonstrate a strong quantitative correlation between the bioluminescent tumor contour and the volume of palpable tumors. We further demonstrate that shrinkage of the volume of spontaneous tumors in response to chemotherapeutic treatment can be determined quantitatively using this system. Finally, we show that the growth and development of spontaneous tumors can be monitored longitudinally over several weeks. Thus, our results suggest that this model could potentially provide a practical, reliable, and cost-effective non-invasive quantitative method for imaging spontaneous solid tumors in mice

Annotations for Rule-Based Models

The chapter reviews the syntax to store machine-readable annotations and describes the mapping between rule-based modelling entities (e.g., agents and rules) and these annotations. In particular, we review an annotation framework and the associated guidelines for annotating rule-based models of molecular interactions, encoded in the commonly used Kappa and BioNetGen languages, and present prototypes that can be used to extract and query the annotations. An ontology is used to annotate models and facilitate their description