Emerging drugs for respiratory syncytial virus infection

Although respiratory syncytial virus (RSV) was discovered > 40 years ago, treatment remains largely supportive. There are no safe and effective vaccines or specific treatments other than prophylaxis with passive antibody therapy (palivizumab). However, there are good reasons to think that the scene may soon change. As the pace of development of anti-viral drugs accelerates and optimism over vaccines increases, novel therapies are set to make a major impact in the management of this very common infection. The use and effect of such interventions are not easy to anticipate, but could ultimately include the interruption of RSV's transmission resulting in profound changes to the impact of RSV on human health

Precision planar drift chambers and cradle for the TWIST muon decay spectrometer

To measure the muon decay parameters with high accuracy, we require an array of precision drift detector layers whose relative position is known with very high accuracy. This article describes the design, construction and performance of these detectors in the TWIST (TRIUMF Weak Interaction Symmetry Test) spectrometer.Comment: 44 pages, 16 Postscript figures, LaTeX2e, uses Elsevier class elsart.cls, package graphicx, submitted to Nuclear Instruments & Methods in Physics Researc

Visualisation of Origins, Destinations and Flows with OD Maps

We present a new technique for the visual exploration of origins (O) and destinations (D) arranged in geographic space. Previous attempts to map the flows between origins and destinations have suffered from problems of occlusion usually requiring some form of generalisation, such as aggregation or flow density estimation before they can be visualized. This can lead to loss of detail or the introduction of arbitrary artefacts in the visual representation. Here, we propose mapping OD vectors as cells rather than lines, comparable with the process of constructing OD matrices, but unlike the OD matrix, we preserve the spatial layout of all origin and destination locations by constructing a gridded two‐level spatial treemap. The result is a set of spatially ordered small multiples upon which any arbitrary geographic data may be projected. Using a hash grid spatial data structure, we explore the characteristics of the technique through a software prototype that allows interactive query and visualisation of 105‐106 simulated and recorded OD vectors. The technique is illustrated using US county to county migration and commuting statistics

The HERMES Back Drift Chambers

The tracking system of the HERMES spectrometer behind the bending magnet consists of two pairs of large planar 6-plane drift chambers. The design and performance of these chambers is described. This description comprises details on the mechanical and electronical design, information about the gas mixture used and its properties, results on alignment, calibration, resolution, and efficiencies, and a discussion of the experience gained through the first three years of operation.Comment: 21 pages, LaTex, 16 figures include

Spatial segregation measures: a methodological review

Quantitative indices of segregation are powerful tools for summarising the spatial relationships between population groups and thereby providing the basis for analysis and public policy intervention. While the broad concept of segregation may be intuitive, measurement is challenging because of the complexity of varied dimensions and spatial arrangements. Many traditional measures can be criticised for over-simplification or over-reduction, not least in their treatment of geographical space. Over the last several decades, however, a series of measures has been developed to explicitly incorporate the spatial arrangement of population groups as well as their interactions. This paper reviews the development of spatial segregation measures, particularly focusing on the mathematical formulation of spatial arrangement/relations. In addition, several related issues are discussed, including representation of spatial interaction, spatial scale and statistical inferences. Also, this paper presents an overview of existing software tools that are readily available for calculating some of the reviewed measures. Finally, discussions on challenges and future research are provided

Hospital-based zoonotic disease surveillance in Bangladesh: design, field data and difficulties.

Early detection of zoonotic diseases allows for the implementation of early response measures, reducing loss of human life and economic disruption. We implemented a surveillance system in hospitals in Bangladesh to screen acutely ill hospitalized patients with severe respiratory infection and meningoencephalitis for zoonotic exposures. Patients were screened for the risk of zoonotic exposures with five questions covering vocational exposures, sick domestic animal and wild animal contact, and date palm sap consumption in the three weeks preceding illness onset. Patients giving at least one positive response were considered a potential zoonotic exposure. From September 2013 to March 2017, a total of 11 429 hospitalized patients across 14 participating hospitals were screened for exposures. Overall, 2% of patients reported a potential zoonotic exposure in the three-week period prior to becoming ill. Sixteen per cent of hospitalized patients with reported exposures died. After routine surveillance diagnostic testing, 88% of patients admitted to the hospital after a potential zoonotic exposure did not have a laboratory diagnosed aetiology for their illness. Hospital-based surveillance systems such as the Bangladeshi example presented here could play an important future role in the early detection of zoonotic spillover diseases. This article is part of the theme issue Dynamic and integrative approaches to understanding pathogen spillover

The comparative clinical course of pregnant and non-pregnant women hospitalised with influenza A(H1N1)pdm09 infection

Introduction: The Influenza Clinical Information Network (FLU-CIN) was established to gather detailed clinical and epidemiological information about patients with laboratory confirmed A(H1N1)pdm09 infection in UK hospitals. This report focuses on the clinical course and outcomes of infection in pregnancy.Methods: A standardised data extraction form was used to obtain detailed clinical information from hospital case notes and electronic records, for patients with PCR-confirmed A(H1N1)pdm09 infection admitted to 13 sentinel hospitals in five clinical 'hubs' and a further 62 non-sentinel hospitals, between 11th May 2009 and 31st January 2010.Outcomes were compared for pregnant and non-pregnant women aged 15-44 years, using univariate and multivariable techniques.Results: Of the 395 women aged 15-44 years, 82 (21%) were pregnant; 73 (89%) in the second or third trimester. Pregnant women were significantly less likely to exhibit severe respiratory distress at initial assessment (OR?=?0.49 (95% CI: 0.30-0.82)), require supplemental oxygen on admission (OR?=?0.40 (95% CI: 0.20-0.80)), or have underlying co-morbidities (p-trend <0.001). However, they were equally likely to be admitted to high dependency (Level 2) or intensive care (Level 3) and/or to die, after adjustment for potential confounders (adj. OR?=?0.93 (95% CI: 0.46-1.92). Of 11 pregnant women needing Level 2/3 care, 10 required mechanical ventilation and three died.Conclusions: Since the expected prevalence of pregnancy in the source population was 6%, our data suggest that pregnancy greatly increased the likelihood of hospital admission with A(H1N1)pdm09. Pregnant women were less likely than non-pregnant women to have respiratory distress on admission, but severe outcomes were equally likely in both groups

Measurement of two-halo neutron transfer reaction p(11^{11}Li,9^{9}Li)t at 3AA MeV

The p(\nuc{11}{Li},\nuc{9}{Li})t reaction has been studied for the first time at an incident energy of 3$A$ MeV delivered by the new ISAC-2 facility at TRIUMF. An active target detector MAYA, build at GANIL, was used for the measurement. The differential cross sectionshave been determined for transitions to the \nuc{9}{Li} ground andthe first excited states in a wide range of scattering angles. Multistep transfer calculations using different \nuc{11}{Li} model wave functions, shows that wave functions with strong correlations between the halo neutrons are the most successful in reproducing the observation.Comment: 6 pages, 3 figures, submitted to Physical Review Letter

Potential therapeutic implications of new insights into respiratory syncytial virus disease

Viral bronchiolitis is the most common cause of hospitalization in infants under 6 months of age, and 70% of all cases of bronchiolitis are caused by respiratory syncytial virus (RSV). Early RSV infection is associated with respiratory problems such as asthma and wheezing later in life. RSV infection is usually spread by contaminated secretions and infects the upper then lower respiratory tracts. Infected cells release proinflammatory cytokines and chemokines, including IL-1, tumor necrosis factor-α, IL-6, and IL-8. These activate other cells and recruit inflammatory cells, including macrophages, neutrophils, eosinophils, and T lymphocytes, into the airway wall and surrounding tissues. The pattern of cytokine production by T lymphocytes can be biased toward 'T-helper-1' or 'T-helper-2' cytokines, depending on the local immunologic environment, infection history, and host genetics. T-helper-1 responses are generally efficient in antiviral defense, but young infants have an inherent bias toward T-helper-2 responses. The ideal intervention for RSV infection would be preventive, but the options are currently limited. Vaccines based on protein subunits, live attenuated strains of RSV, DNA vaccines, and synthetic peptides are being developed; passive antibody therapy is at present impractical in otherwise healthy children. Effective vaccines for use in neonates continue to be elusive but simply delaying infection beyond the first 6 months of life might reduce the delayed morbidity associated with infantile disease