A Biological Model for Influenza Transmission: Pandemic Planning Implications of Asymptomatic Infection and Immunity

Background: The clinical attack rate of influenza is influenced by prior immunity and mixing patterns in the host population, and also by the proportion of infections that are asymptomatic. This complexity makes it difficult to directly estimate R0 from the attack rate, contributing to uncertainty in epidemiological models to guide pandemic planning. We have modelled multiple wave outbreaks of influenza from different populations to allow for changing immunity and asymptomatic infection and to make inferences about R0. \ud \ud Data and Methods. On the island of Tristan da Cunha (TdC), 96% of residents reported illness during an H3N2 outbreak in 1971, compared with only 25% of RAF personnel in military camps during the 1918 H1N1 pandemic. Monte Carlo Markov Chain (MCMC) methods were used to estimate model parameter distributions. \ud \ud Findings. We estimated that most islanders on TdC were non-immune (susceptible) before the first wave, and that almost all exposures of susceptible persons caused symptoms. The median R0 of 6.4 (95% credibility interval 3.7–10.7) implied that most islanders were exposed twice, although only a minority became ill in the second wave because of temporary protection following the first wave. In contrast, only 51% of RAF personnel were susceptible before the first wave, and only 38% of exposed susceptibles reported symptoms. R0 in this population was also lower [2.9 (2.3–4.3)], suggesting reduced viral transmission in a partially immune population. \ud \ud Interpretation: Our model implies that the RAF population was partially protected before the summer pandemic wave of 1918, arguably because of prior exposure to interpandemic influenza. Without such protection, each symptomatic case of influenza would transmit to between 2 and 10 new cases, with incidence initially doubling every 1–2 days. Containment of a novel virus could be more difficult than hitherto supposed

Changing practice in dementia care in the community: developing and testing evidence-based interventions, from timely diagnosis to end of life (EVIDEM)

Background Dementia has an enormous impact on the lives of individuals and families, and on health and social services, and this will increase as the population ages. The needs of people with dementia and their carers for information and support are inadequately addressed at all key points in the illness trajectory. Methods The Unit is working specifically on an evaluation of the impact of the Mental Capacity Act 2005, and will develop practice guidance to enhance concordance with the Act. Phase One of the study has involved baseline interviews with practitioners across a wide range of services to establish knowledge and expectations of the Act, and to consider change processes when new policy and legislation are implemented. Findings Phase 1, involving baseline interviews with 115 practitioners, identified variable knowledge and understanding about the principles of the Act. Phase 2 is exploring everyday decision-making by people with memory problems and their carers

Quantitative metabolomics based on gas chromatography mass spectrometry: status and perspectives

Metabolomics involves the unbiased quantitative and qualitative analysis of the complete set of metabolites present in cells, body fluids and tissues (the metabolome). By analyzing differences between metabolomes using biostatistics (multivariate data analysis; pattern recognition), metabolites relevant to a specific phenotypic characteristic can be identified. However, the reliability of the analytical data is a prerequisite for correct biological interpretation in metabolomics analysis. In this review the challenges in quantitative metabolomics analysis with regards to analytical as well as data preprocessing steps are discussed. Recommendations are given on how to optimize and validate comprehensive silylation-based methods from sample extraction and derivatization up to data preprocessing and how to perform quality control during metabolomics studies. The current state of method validation and data preprocessing methods used in published literature are discussed and a perspective on the future research necessary to obtain accurate quantitative data from comprehensive GC-MS data is provided

‘‘The Soldiers Came to the House’’: Young Children’s Responses to The Colour of Home

This article begins by reflecting on the present refugee crisis and its relevance to children in the UK. It identifies the need for teaching about the refugee experience to young children and argues that literature can provide a conduit for this. Sincethemillenniumtherehasbeenarapidincreaseinthenumberofbookspublished forchildren whichtake thisastheir theme, aimed atever-youngerreaders.Takingasa case study The Colour of Home by Mary Hoffman, a picturebook commonly used in lower primary classrooms, the article considers how this text promotes understanding and validates the circumstances of refugees. It closely examines the motivations and aims of the writer, how the book was mediated by teachers in the primary classroom, and how refugee and non-refugee children read and responded to it. Findings are presented from an interview with Mary Hoffman herself, juxtaposed with data from threeclassroomssuggestingthatpupilsgainedvaluableinsightintoacomplicatedand controversial issue. However the research concludes that viewing children through a refugee/non-refugee binary was reductive in not recognising the multi-layered nuances of meaning which were constructed by young readers who brought to bear a wide variety of individual life and family experiences. Furthermore, teachers in the study played a powerful role in mediating the texts when sharing them in the classroom, and devised a selection of stimulating resources to provoke reader response in terms of empathy, ‘‘social action’’, and some critical literacy

Historical influences on the current provision of multiple ecosystem services: is there a legacy of past landcover?

Ecosystem service provision varies temporally in response to natural and human-induced factors, yet research in this field is dominated by analyses that ignore the time-lags and feedbacks that occur within socio-ecological systems. The implications of this have been unstudied, but are central to understanding how service delivery will alter due to future land-use/cover change. Urban areas are expanding faster than any other land-use, making cities ideal study systems for examining such legacy effects. We assess the extent to which present-day provision of a suite of eight ecosystem services, quantified using field-gathered data, is explained by current and historical (stretching back 150 years) landcover. Five services (above-ground carbon density, recreational use, bird species richness, bird density, and a metric of recreation experience quality (continuity with the past) were more strongly determined by past landcover. Time-lags ranged from 20 (bird species richness and density) to over 100 years (above-ground carbon density). Historical landcover, therefore, can have a strong influence on current service provision. By ignoring such time-lags, we risk drawing incorrect conclusions regarding how the distribution and quality of some ecosystem services may alter in response to land-use/cover change. Although such a finding adds to the complexity of predicting future scenarios, ecologists may find that they can link the biodiversity conservation agenda to the preservation of cultural heritage, and that certain courses of action provide win-win outcomes across multiple environmental and cultural goods

Release of Intracellular Calcium Stores Facilitates Coxsackievirus Entry into Polarized Endothelial Cells

Group B coxsackieviruses (CVB) are associated with viral-induced heart disease and are among the leading causes of aseptic meningitis worldwide. Here we show that CVB entry into polarized brain microvasculature and aortic endothelial cells triggers a depletion of intracellular calcium stores initiated through viral attachment to the apical attachment factor decay-accelerating factor. Calcium release was dependent upon a signaling cascade that required the activity of the Src family of tyrosine kinases, phospholipase C, and the inositol 1,4,5-trisphosphate receptor isoform 3. CVB-mediated calcium release was required for the activation of calpain-2, a calcium-dependent cysteine protease, which controlled the vesicular trafficking of internalized CVB particles. These data point to a specific role for calcium signaling in CVB entry into polarized endothelial monolayers and highlight the unique signaling mechanisms used by these viruses to cross endothelial barriers

Radiation damage in macromolecular crystallography: what is it and why should we care?

The basic causes of the radiation damage inflicted on macromolecular crystals during diffraction experiments are summarized, as well as the current state of research which attempts to understand and to mitigate it

Cell-Cell Transmission Enables HIV-1 to Evade Inhibition by Potent CD4bs Directed Antibodies

HIV is known to spread efficiently both in a cell-free state and from cell to cell, however the relative importance of the cell-cell transmission mode in natural infection has not yet been resolved. Likewise to what extent cell-cell transmission is vulnerable to inhibition by neutralizing antibodies and entry inhibitors remains to be determined. Here we report on neutralizing antibody activity during cell-cell transmission using specifically tailored experimental strategies which enable unambiguous discrimination between the two transmission routes. We demonstrate that the activity of neutralizing monoclonal antibodies (mAbs) and entry inhibitors during cell-cell transmission varies depending on their mode of action. While gp41 directed agents remain active, CD4 binding site (CD4bs) directed inhibitors, including the potent neutralizing mAb VRC01, dramatically lose potency during cell-cell transmission. This implies that CD4bs mAbs act preferentially through blocking free virus transmission, while still allowing HIV to spread through cell-cell contacts. Thus providing a plausible explanation for how HIV maintains infectivity and rapidly escapes potent and broadly active CD4bs directed antibody responses in vivo