Detection of antibody-dependent complement mediated inactivation of both autologous and heterologous virus in primary HIV-1 infection

Specific CD8 T-cell responses to human immunodeficiency virus type 1 (HIV-1) are induced in primary infection and make an important contribution to the control of early viral replication. The importance of neutralizing antibodies in containing primary viremia is questioned because they usually arise much later. Nevertheless antienvelope antibodies develop simultaneously with, or even before, peak viremia. We determined whether such antibodies might control viremia by complement-mediated inactivation (CMI). In each of seven patients studied, antibodies capable of CMI appeared at or shortly after the peak in viremia, concomitantly with detection of virus-specific T-cell responses. The CMI was effective on both autologous and heterologous HIV-1 isolates. Activation of the classical pathway and direct viral lysis were at least partly responsible. Since immunoglobulin G (IgG)-antibodies triggered the CMI, specific memory B cells could also be induced by vaccination. Thus, consideration should be given to vaccination strategies that induce IgG antibodies capable of CMI

End stage renal disease and survival in people with diabetes:a national database linkage study

© The Author 2014. Published by Oxford University Press on behalf of the Association of Physicians. Funding This work was supported by the Wellcome Trust through the Scottish Health Informatics Programme (SHIP). The SHIP is collaboration between the Universities of Aberdeen, Dundee, Edinburgh, Glasgow and St Andrews and the Information Services Division of National Health Service National Service Scotland. Funding for diabetes register linkage and data extraction was provided by the Chief Scientist’s Office of the Scottish Government. The Scottish Diabetes Research Network receives financial support from National Health Services Research Scotland. The Scottish Renal Registry is funded by the Information Services Division of National Health Service National Services Scotland but relies heavily on the goodwill of the contributing renal units who spent a large amount time working with Scottish Renal Registry staff to ensure that the data held within the register are accurate and complete.Peer reviewedPublisher PD

E-government adoption: A cultural comparison

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ Springer Science + Business Media, LLC 2008.E-government diffusion is an international phenomenon. This study compares e-government adoption in the U.K. to adoption in the U.S. In particular, this study seeks to determine if the same factors are salient in both countries. Several studies have explored citizen acceptance of e-government services in the U.S. However, few studies have explored this phenomenon in the U.K. To identify the similarities and differences between the U.K. and the U.S. a survey is conducted in the U.K. and the findings are compared to the literature that investigates diffusion in the U.S. This study proposes a model of e-government adoption in the U.K. based on salient factors in the U.S. A survey is administered to 260 citizens in London to assess the importance of relative advantage, trust and the digital divide on intention to use e-government. The results of binary logistic regression indicate that there are cultural differences in e-government adoption in the U.K. and the U.S. The results indicate that of the prevailing adoption constructs, relative advantage and trust are pertinent in both the U.S. and the U.K., while ICT adoption barriers such as access and skill may vary by culture. Implications for research and practice are discussed

Visualisation of trust and quality information for geospatial dataset selection and use:Drawing trust presentation comparisons with B2C e-Commerce

The evaluation of geospatial data quality and trustworthiness presents a major challenge to geospatial data users when making a dataset selection decision. Part of the problem arises from the inconsistent and patchy nature of data quality information, which makes intercomparison very difficult. Over recent years, the production and availability of geospatial data has significantly increased, facilitated by the recent explosion of Web-based catalogues, portals, standards and services, and by initiatives such as INSPIRE and GEOSS. Despite this significant growth in availability of geospatial data and the fact that geospatial datasets can, in many respects, be considered commercial products that are available for purchase online, consumer trust has to date received relatively little attention in the GIS domain. In this paper, we discuss how concepts of trust, trust models, and trust indicators (largely derived from B2C e-Commerce) apply to the GIS domain and to geospatial data selection and use. Our research aim is to support data users in more efficient and effective geospatial dataset selection on the basis of quality, trustworthiness and fitness for purpose. To achieve this, we propose a GEO label – a decision support mechanism that visually summarises availability of key geospatial data informational aspects. We also present a Web service that was developed to support generation of dynamic GEO label representations for datasets by combining producer metadata (from standard catalogues or other published locations) with structured user feedback

Trust Building in Electronic Markets: Relative Importance and Interaction Effects of Trust Building Mechanisms

We examine the relative and complementary effectiveness of trust-building strategies in online environments. While prior research has examined various antecedents to trust, we investigated two trust-building mechanisms more in depth: Web site trust and vendor reputation. We tried to understand the relative effectiveness of these two important mechanisms to provide online businesses with a clear recommendation of how to establish trust in an effective and efficient manner. Drawing from the literature on trust, we proposed vendor reputation to be more effective than Web site trust. Moreover, we examined a potential complementary effect of these mechanisms so as to provide online businesses with a deeper understanding of how to derive superior trust. We hypothesize a small such effect. The study proposes a laboratory experiment to test the model

Small RNA analysis in Sindbis virus infected human HEK293 cells

In contrast to the defence mechanism of RNA interference (RNAi) in plants and invertebrates, its role in the innate response to virus infection of mammals is a matter of debate. Since RNAi has a well-established role in controlling infection of the alphavirus Sindbis virus (SINV) in insects, we have used this virus to investigate the role of RNAi in SINV infection of human cells

Plasma proteomic signature predicts who will get persistent symptoms following SARS-CoV-2 infection

BACKGROUND: The majority of those infected by ancestral Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) during the UK first wave (starting March 2020) did not require hospitalisation. Most had a short-lived mild or asymptomatic infection, while others had symptoms that persisted for weeks or months. We hypothesized that the plasma proteome at the time of first infection would reflect differences in the inflammatory response that linked to symptom severity and duration. METHODS: We performed a nested longitudinal case-control study and targeted analysis of the plasma proteome of 156 healthcare workers (HCW) with and without lab confirmed SARS-CoV-2 infection. Targeted proteomic multiple-reaction monitoring analysis of 91 pre-selected proteins was undertaken in uninfected healthcare workers at baseline, and in infected healthcare workers serially, from 1 week prior to 6 weeks after their first confirmed SARS-CoV-2 infection. Symptom severity and antibody responses were also tracked. Questionnaires at 6 and 12 months collected data on persistent symptoms. FINDINGS: Within this cohort (median age 39 years, interquartile range 30-47 years), 54 healthcare workers (44% male) had PCR or antibody confirmed infection, with the remaining 102 (38% male) serving as uninfected controls. Following the first confirmed SARS-CoV-2 infection, perturbation of the plasma proteome persisted for up to 6 weeks, tracking symptom severity and antibody responses. Differentially abundant proteins were mostly coordinated around lipid, atherosclerosis and cholesterol metabolism pathways, complement and coagulation cascades, autophagy, and lysosomal function. The proteomic profile at the time of seroconversion associated with persistent symptoms out to 12 months. Data are available via ProteomeXchange with identifier PXD036590. INTERPRETATION: Our findings show that non-severe SARS-CoV-2 infection perturbs the plasma proteome for at least 6 weeks. The plasma proteomic signature at the time of seroconversion has the potential to identify which individuals are more likely to suffer from persistent symptoms related to SARS-CoV-2 infection. FUNDING INFORMATION: The COVIDsortium is supported by funding donated by individuals, charitable Trusts, and corporations including Goldman Sachs, Citadel and Citadel Securities, The Guy Foundation, GW Pharmaceuticals, Kusuma Trust, and Jagclif Charitable Trust, and enabled by Barts Charity with support from University College London Hospitals (UCLH) Charity. This work was additionally supported by the Translational Mass Spectrometry Research Group and the Biomedical Research Center (BRC) at Great Ormond Street Hospital

EPidemiology Of Cardiogenic sHock in Scotland (EPOCHS):a multicentre, prospective observational study of the prevalence, management and outcomes of cardiogenic shock in Scotland

BackgroundDespite high rates of cardiovascular disease in Scotland, the prevalence and outcomes of patients with cardiogenic shock are unknown.MethodsWe undertook a prospective observational cohort study of consecutive patients with cardiogenic shock admitted to the intensive care unit (ICU) or coronary care unit at 13 hospitals in Scotland for a six-month period. Denominator data from the Scottish Intensive Care Society Audit Group were used to estimate ICU prevalence; data for coronary care units were unavailable. We undertook multivariable logistic regression to identify factors associated with in-hospital mortality.ResultsIn total, 247 patients with cardiogenic shock were included. After exclusion of coronary care unit admissions, this comprised 3.0% of all ICU admissions during the study period (95% confidence interval [CI] 2.6 to 3.5%). Aetiology was acute myocardial infarction (AMI) in 48%. The commonest vasoactive treatment was noradrenaline (56%) followed by adrenaline (46%) and dobutamine (40%). Mechanical circulatory support was used in 30%. Overall in-hospital mortality was 55%. After multivariable logistic regression, age (odds ratio [OR] 1.04, 95% CI 1.02 to 1.06), admission lactate (OR 1.10, 95% CI 1.05 to 1.19), Society for Cardiovascular Angiographic Intervention stage D or E at presentation (OR 2.16, 95% CI 1.10 to 4.29), and use of adrenaline (OR 2.73, 95% CI 1.40 to 5.40) were associated with mortality.ConclusionsIn Scotland the prevalence of cardiogenic shock was 3% of all ICU admissions; more than half died prior to discharge. There was significant variation in treatment approaches, particularly with respect to vasoactive support strategy. <br/