31 research outputs found
Visualization of social support alters mood: clinical implications of a conceptual mapping tool.
Abstract 155
HiPERCAM: A high-speed quintuple-beam CCD camera for the study of rapid variability in the universe
HiPERCAM is a high-speed camera for the study of rapid variability in the Universe. The project is funded by a ϵ3.5M European Research Council Advanced Grant. HiPERCAM builds on the success of our previous instrument, ULTRACAM, with very significant improvements in performance thanks to the use of the latest technologies. HiPERCAM will use 4 dichroic beamsplitters to image simultaneously in 5 optical channels covering the u'g'r'I'z' bands. Frame rates of over 1000 per second will be achievable using an ESO CCD controller (NGC), with every frame GPS timestamped. The detectors are custom-made, frame-transfer CCDs from e2v, with 4 low noise (2.5e -) outputs, mounted in small thermoelectrically-cooled heads operated at 180 K, resulting in virtually no dark current. The two reddest CCDs will be deep-depletion devices with anti-etaloning, providing high quantum efficiencies across the red part of the spectrum with no fringing. The instrument will also incorporate scintillation noise correction via the conjugate-plane photometry technique. The opto-mechanical chassis will make use of additive manufacturing techniques in metal to make a light-weight, rigid and temperature-invariant structure. First light is expected on the 4.2m William Herschel Telescope on La Palma in 2017 (on which the field of view will be 10' with a 0.3"/pixel scale), with subsequent use planned on the 10.4m Gran Telescopio Canarias on La Palma (on which the field of view will be 4' with a 0.11"/pixel scale) and the 3.5m New Technology Telescope in Chile
Human Health Risk Assessment For Arsenic: A Critical Review
Millions of people are exposed to arsenic resulting in a range of health implications.This paper provides an up-to-date review of the different sources of arsenic (water, soil and food), indicators of human exposure (biomarker assessment of hair, nail, urine and blood), epidemiological and toxicological studies on carcinogenic and non-carcinogenic health outcomes, and risk assessment approaches. The review demonstrates a need for more work evaluating the risks of different arsenic species such as; arsenate, arsenite monomethylarsonic acid, monomethylarsonous acid, dimethylarsinic acid and dimethylarsinous acid as well as a need to better integrate the different exposure sources in risk assessments
Delayed mucosal antiviral responses despite robust peripheral inflammation in fatal COVID-19
Background
While inflammatory and immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in peripheral blood are extensively described, responses at the upper respiratory mucosal site of initial infection are relatively poorly defined. We sought to identify mucosal cytokine/chemokine signatures that distinguished coronavirus disease 2019 (COVID-19) severity categories, and relate these to disease progression and peripheral inflammation.
Methods
We measured 35 cytokines and chemokines in nasal samples from 274 patients hospitalized with COVID-19. Analysis considered the timing of sampling during disease, as either the early (0–5 days after symptom onset) or late (6–20 days after symptom onset) phase.
Results
Patients that survived severe COVID-19 showed interferon (IFN)-dominated mucosal immune responses (IFN-γ, CXCL10, and CXCL13) early in infection. These early mucosal responses were absent in patients who would progress to fatal disease despite equivalent SARS-CoV-2 viral load. Mucosal inflammation in later disease was dominated by interleukin 2 (IL-2), IL-10, IFN-γ, and IL-12p70, which scaled with severity but did not differentiate patients who would survive or succumb to disease. Cytokines and chemokines in the mucosa showed distinctions from responses evident in the peripheral blood, particularly during fatal disease.
Conclusions
Defective early mucosal antiviral responses anticipate fatal COVID-19 but are not associated with viral load. Early mucosal immune responses may define the trajectory of severe COVID-19
Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses
To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely
SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination
BACKGROUND: Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. METHODS: In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data. FINDINGS: Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination. INTERPRETATION: The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity. FUNDING: This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the National Institute for Health and Care Research and the Medical Research Council. Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research. The funders were not involved in the study design, interpretation of data or the writing of this manuscript
Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease
One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain–gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials
Assessing the impact of framing on the comparative favourability of nuclear power as an electricity generating option in the UK
In 2007 the UK government's public consultation on the future of nuclear power courted much criticism. Three studies were conducted to assess whether key arguments used by government within this consultation might have influenced public opinion about the technology. Participants first read a passage of text that made salient certain positive (climate change mitigation, increased energy security) or negative (nuclear waste) aspects of the nuclear debate. Participants then completed a task that required them to create an electricity mix for the UK by varying the contributions made by each of five energy sources (coal, gas, nuclear, renewables and electric import). Study 1 seemed to indicate that pitching the debate in terms of climate change mitigation was effective in increasing endorsement of nuclear power. The results of studies 2 and 3, however, contested this conclusion, suggesting that these arguments were having little direct impact upon participants' preferences for nuclear power. The results of these studies hold implications for UK energy policy and attitude assessment and can contribute to the understanding of how the arguments used by government in the 2007 consultation might have influenced public opinion. © 2011 Elsevier Ltd