ORCID Profile
0000-0002-5337-5944
Current Organisation
Karlsruher Institut für Technologie
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Publisher: Cold Spring Harbor Laboratory
Date: 26-05-2020
DOI: 10.1101/2020.05.18.20106187
Abstract: Background: Human infection challenge studies (HICS) with SARS-CoV-2 are under consideration as a way of accelerating vaccine development. We evaluate potential vaccine research strategies under a range of epidemic conditions determined, in part, by the intensity of public health interventions. Methods: We constructed a compartmental epidemiological model incorporating public health interventions, vaccine efficacy trials and a post-trial population vaccination c aign. The model was used to estimate the duration and benefits of large-scale field trials in comparison with HICS accompanied by an expanded safety trial, and to assess the marginal risk faced by HICS participants. Results: Field trials may demonstrate vaccine efficacy more rapidly than a HICS strategy under epidemic conditions consistent with moderate mitigation policies. A HICS strategy is the only feasible option for testing vaccine efficacy under epidemic suppression, and maximises the benefits of post-trial vaccination. Less successful or absent mitigation results in minimal or no benefit from post-trial vaccination, irrespective of trial design. Conclusions: SARS-CoV-2 HICS are the optimal method of vaccine testing for populations maintained under epidemic suppression, where vaccination offers the greatest benefits to the local population.
Publisher: European Respiratory Society (ERS)
Date: 31-05-2012
Publisher: Wiley
Date: 10-2020
DOI: 10.1111/IMJ.15038
Publisher: AMPCo
Date: 07-02-2021
DOI: 10.5694/MJA2.50930
Publisher: Copernicus GmbH
Date: 08-10-2021
DOI: 10.5194/ACP-2021-744
Abstract: Abstract. The formation of ice particles in Earth’s atmosphere strongly influences the dynamics and optical properties of clouds and their impacts on the climate system. Ice formation in clouds is often triggered heterogeneously by ice nucleating particles (INPs) that represent a very low number of particles in the atmosphere. To date, many sources of INPs, such as mineral and soil dust, have been investigated and identified in the lower latitudes. Although less is known about the sources of ice nucleation at higher latitudes, efforts have been made to identify the sources of INPs in the Arctic and boreal environments. In this study, we investigate the INP emission potential from high latitude boreal forests. We introduce the HyICE-2018 measurement c aign conducted in the boreal forest of Hyytiälä, Finland between February and June 2018. The c aign utilized the infrastructure of the SMEAR II research station with additional instrumentation for measuring INPs to quantify the concentrations and sources of INPs in the boreal environment. In this contribution, we describe the measurement infrastructure and operating procedures during HyICE-2018 and we report results from specific time periods where INP instruments were run in parallel for inter-comparison purposes. Our results show that the suite of instruments deployed during HyICE-2018 reports consistent results and therefore lays the foundation for forthcoming results to be considered holistically. In addition, we compare the INP concentration we measured to INP parameterizations, and we show a very good agreement with the Tobo et al. (2013) parameterization developed from measurements conducted in a ponderosa pine forest ecosystem in Colorado, USA.
Publisher: Wiley
Date: 23-06-2017
DOI: 10.1111/BJH.14814
Publisher: Springer Science and Business Media LLC
Date: 28-05-2019
DOI: 10.1007/S10096-019-03589-W
Abstract: To investigate the prognostic implications of findings on early transthoracic echocardiography (TTE) in patients with definite left-sided native valve infective endocarditis (LNVIE). We reviewed a 10-year retrospective cohort of consecutive patients with definite LNVIE treated at a tertiary cardiothoracic centre. TTE studies performed within the first seven days of the index blood culture (for culture-positive cases) or hospital admission (for culture-negative cases) were reviewed for the presence of valvular vegetations, perivalvular abscesses, aortic or mitral regurgitation of moderate or greater severity or a bicuspid aortic valve. Six-week outcomes included all-cause mortality, cardiac surgery for endocarditis or new embolic cerebral infarction. Early TTE was performed in 118 of 151 episodes of definite LNVIE at a median of two days after the index blood culture or hospital admission. Findings on these studies included valvular vegetations or abscesses in 74 patients, moderate or severe aortic or mitral regurgitation in 67 patients and a bicuspid aortic valve in 19 patients. The presence of any of these findings conferred a relative risk of any adverse six-week outcome of 4.80 (95% confidence interval 1.6-17, p = 0.001). The presence of a bicuspid aortic valve appeared particularly predictive of the need for cardiac surgery, including for clinically occult paravalvular abscesses. Early TTE can be used to stratify patients with LNVIE by the risk of major endocarditis-related adverse outcomes occurring within the first six weeks of treatment.
Publisher: Oxford University Press (OUP)
Date: 12-2018
DOI: 10.1093/OFID/OFY303
Abstract: The risk of endocarditis among patients with Staphylococcus aureus bacteremia is not uniform, and a number of different scores have been developed to identify patients whose risk is less than 5%. The optimal echocardiography strategy for these patients is uncertain. We used decision analysis and Monte Carlo simulation using input parameters taken from the existing literature. The model examined patients with S aureus bacteremia whose risk of endocarditis is less than 5%, generally those with nosocomial or healthcare-acquired bacteremia, no intracardiac prosthetic devices, and a brief duration of bacteremia. We examined 6 echocardiography strategies, including the use of transesophageal echocardiography, transthoracic echocardiography, both modalities, and neither. The outcome of the model was 90-day survival. The optimal echocardiography strategy varied with the risk of endocarditis and the procedural mortality associated with transesophageal echocardiography. No echocardiography strategy offered an absolute benefit in 90-day survival of more than 0.5% compared with the strategy of not performing echocardiography and treating with short-course therapy. Strategies using transesophageal echocardiography were never preferred if the mortality of this procedure was greater than 0.5%. In patients identified to be at low risk of endocarditis, the choice of echocardiography strategy appears to exert a very small influence on 90-day survival. This finding may render test-treatment trials unfeasible and should prompt clinicians to focus on other, more important, management considerations in these patients.
Publisher: Springer Science and Business Media LLC
Date: 06-2021
Publisher: Elsevier BV
Date: 03-2018
Publisher: American Association for the Advancement of Science (AAAS)
Date: 05-05-2023
Abstract: Infectious disease control measures often require collective compliance of large numbers of in iduals to benefit public health. This raises ethical questions regarding the value of the public health benefit created by in idual and collective compliance. Answering these requires estimating the extent to which in idual actions prevent infection of others. We develop mathematical techniques enabling quantification of the impacts of in iduals or groups complying with three public health measures: border quarantine, isolation of infected in iduals, and prevention via vaccination rophylaxis. The results suggest that (i) these interventions exhibit synergy: They become more effective on a per-in idual basis as compliance increases, and (ii) there is often substantial “overdetermination” of transmission. If a susceptible person contacts multiple infectious in iduals, an intervention preventing one transmission may not change the ultimate outcome (thus, risk imposed by some in iduals may erode the benefits of others’ compliance). These results have implications for public health policy during epidemics.
Publisher: Cold Spring Harbor Laboratory
Date: 05-12-2021
DOI: 10.1101/2021.12.02.21267207
Abstract: Infectious disease control measures often require collective compliance of large numbers of in iduals to benefit public health. This raises ethical questions regarding the value of the public health benefit created by in idual and collective compliance. Answering these requires estimating the extent to which in idual actions prevent infection of others. We develop mathematical techniques enabling quantification of the impacts of in iduals or groups complying with three public health measures: border quarantine, isolation of infected in iduals, and prevention via vaccination rophylaxis. The results suggest that (i) these interventions exhibit synergy: they become more effective on a per-in idual basis as compliance increases and (ii) There is often significant “overdetermination” of transmission: if a susceptible person contacts multiple infectious in iduals, an intervention preventing one transmission may not change the ultimate outcome (thus risk imposed by some in iduals may erode the benefits of others’ compliance). These results have implications for public health policy during epidemics.
Publisher: Copernicus GmbH
Date: 19-04-2022
Abstract: Abstract. The formation of ice particles in Earth's atmosphere strongly influences the dynamics and optical properties of clouds and their impacts on the climate system. Ice formation in clouds is often triggered heterogeneously by ice-nucleating particles (INPs) that represent a very low number of particles in the atmosphere. To date, many sources of INPs, such as mineral and soil dust, have been investigated and identified in the low and mid latitudes. Although less is known about the sources of ice nucleation at high latitudes, efforts have been made to identify the sources of INPs in the Arctic and boreal environments. In this study, we investigate the INP emission potential from high-latitude boreal forests in the mixed-phase cloud regime. We introduce the HyICE-2018 measurement c aign conducted in the boreal forest of Hyytiälä, Finland, between February and June 2018. The c aign utilized the infrastructure of the Station for Measuring Ecosystem-Atmosphere Relations (SMEAR) II, with additional INP instruments, including the Portable Ice Nucleation Chamber I and II (PINC and PINCii), the SPectrometer for Ice Nuclei (SPIN), the Portable Ice Nucleation Experiment (PINE), the Ice Nucleation SpEctrometer of the Karlsruhe Institute of Technology (INSEKT) and the Microlitre Nucleation by Immersed Particle Instrument (µL-NIPI), used to quantify the INP concentrations and sources in the boreal environment. In this contribution, we describe the measurement infrastructure and operating procedures during HyICE-2018, and we report results from specific time periods where INP instruments were run in parallel for inter-comparison purposes. Our results show that the suite of instruments deployed during HyICE-2018 reports consistent results and therefore lays the foundation for forthcoming results to be considered holistically. In addition, we compare measured INP concentrations to INP parameterizations, and we observe good agreement with the Tobo et al. (2013) parameterization developed from measurements conducted in a ponderosa pine forest ecosystem in Colorado, USA.
Publisher: Oxford University Press (OUP)
Date: 2017
DOI: 10.1093/OFID/OFX261
Abstract: This systematic review examines the methods and results of recent studies reporting clinical criteria able to identify patients with Staphylococcus aureus bacteremia who are at very low risk of endocarditis. We searched PubMed, EMBASE, and the Cochrane Collaboration CENTRAL database for articles published after March 1994 using a combination of MeSH and free text search terms for S. aureus AND bacteremia AND endocarditis. Studies were included if they presented a combination of clinical and microbiological criteria with a negative likelihood ratio of ≤0.20 for endocarditis. We found 8 studies employing various criteria and reference standards whose criteria were associated with negative likelihood ratios between 0.00 and 0.19 (corresponding to 0%–5% risk of endocarditis at 20% background prevalence). The benefit of echocardiography for patients fulfilling these criteria is uncertain.
Publisher: Elsevier BV
Date: 12-2018
DOI: 10.1016/J.CMI.2018.03.027
Abstract: Recent criteria which can identify patients with Staphylococcus aureus bacteraemia (SAB) who are at very low risk of endocarditis raise the question of whether transoesophageal echocardiography (TOE) is appropriate for these patients. To estimate the probability of occult endocarditis complicating SAB below which a TOE-guided treatment strategy no longer offers the best 180-day survival, and to examine the key uncertainties affecting this result. Estimates of the parameters required to calculate the Pauker-Kassirer testing threshold were identified from studies published prior to 1 June 2017 using a composite search strategy that involved a systematic search for relevant controlled trials and guidelines, followed by a non-systematic iterative search of the observational literature. Estimates of the necessary parameters were generally consistent across the literature with the exception of the procedural mortality of TOE. In our base-case scenario (TOE mortality 0.1%), the testing threshold for TOE in apparently uncomplicated SAB was a 1.1% probability of occult endocarditis. Sensitivity analyses revealed that the procedural mortality of TOE was a key uncertainty affecting estimates of the testing threshold. None of the available clinical tools can place patients with SAB below this probability of endocarditis with 95% confidence. Future work in this area should concentrate on improving the precision of these tools and on exploring the value of alternative echocardiography strategies. In addition, a better understanding of the harms of TOE is required to ensure that recommendations regarding the role of this investigation in the management of patients with SAB are appropriate.
No related grants have been discovered for George Heriot.