66 research outputs found

    Non-Invasive Detection of Adeno-Associated Viral Gene Transfer Using a Genetically Encoded CEST-MRI Reporter Gene in the Murine Heart

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    Research into gene therapy for heart failure has gained renewed interest as a result of improved safety and availability of adeno-associated viral vectors (AAV). While magnetic resonance imaging (MRI) is standard for functional assessment of gene therapy outcomes, quantitation of gene transfer/expression relies upon tissue biopsy, fluorescence or nuclear imaging. Imaging of gene expression through the use of genetically encoded chemical exchange saturation transfer (CEST)-MRI reporter genes could be combined with clinical cardiac MRI methods to comprehensively probe therapeutic gene expression and subsequent outcomes. The CEST-MRI reporter gene Lysine Rich Protein (LRP) was cloned into an AAV9 vector and either administered systemically via tail vein injection or directly injected into the left ventricular free wall of mice. Longitudinal in vivo CEST-MRI performed at days 15 and 45 after direct injection or at 1, 60 and 90 days after systemic injection revealed robust CEST contrast in myocardium that was later confirmed to express LRP by immunostaining. Ventricular structure and function were not impacted by expression of LRP in either study arm. The ability to quantify and link therapeutic gene expression to functional outcomes can provide rich data for further development of gene therapy for heart failure

    Raman Spectroscopy: Toward a Portable Food Quality-Warning System

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    Food waste is one of the main problems contributing to climate change as its piling up in landfills produces the greenhouse gas methane. Food waste occurs at every stage of food production; however, the major source of food waste occurs at businesses that supply food to consumers. Industry 4.0 technologies have shown promises in helping reduce food waste in food supply chains. However, more innovative technologies such as Raman spectroscopy holds great promise in helping reduce food waste, but this has largely been ignored in the literature. In this context, we propose a portable Raman platform to monitor food quality during transportation. The developed system was tested in conditions mimicking those present in a refrigerated truck by analyzing chicken samples stored at temperatures of 4 °C. Raman spectra were acquired for non-packaged and packaged samples over the duration of 30 days resulting in 6000 spectra. The analysis of Raman spectra revealed that the system was able to detect noticeable changes in chicken quality starting day six. The main Raman bands contributing to this change were amide I and tyrosine. The proposed system will offer the potential to reduce food losses during transportation by consistently checking the food quality over time

    Global Disease Outbreaks Associated with the 2015–2016 El Niño Event

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    Interannual climate variability patterns associated with the El Niño-Southern Oscillation phenomenon result in climate and environmental anomaly conditions in specific regions worldwide that directly favor outbreaks and/or amplification of variety of diseases of public health concern including chikungunya, hantavirus, Rift Valley fever, cholera, plague, and Zika. We analyzed patterns of some disease outbreaks during the strong 2015–2016 El Niño event in relation to climate anomalies derived from satellite measurements. Disease outbreaks in multiple El Niño-connected regions worldwide (including Southeast Asia, Tanzania, western US, and Brazil) followed shifts in rainfall, temperature, and vegetation in which both drought and flooding occurred in excess (14–81% precipitation departures from normal). These shifts favored ecological conditions appropriate for pathogens and their vectors to emerge and propagate clusters of diseases activity in these regions. Our analysis indicates that intensity of disease activity in some ENSO-teleconnected regions were approximately 2.5–28% higher during years with El Niño events than those without. Plague in Colorado and New Mexico as well as cholera in Tanzania were significantly associated with above normal rainfall (p \u3c 0.05); while dengue in Brazil and southeast Asia were significantly associated with above normal land surface temperature (p \u3c 0.05). Routine and ongoing global satellite monitoring of key climate variable anomalies calibrated to specific regions could identify regions at risk for emergence and propagation of disease vectors. Such information can provide sufficient lead-time for outbreak prevention and potentially reduce the burden and spread of ecologically coupled diseases

    Assessing the assessments: evaluation of four impact assessment protocols for invasive alien species

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    Aim: Effective policy and management responses to the multiple threats posed by invasive alien species (IAS) rely on the ability to assess their impacts before conclusive empirical evidence is available. A plethora of different IAS risk and/or impact assessment protocols have been proposed, but it remains unclear whether, how and why the outcomes of such assessment protocols may differ. Location: Europe. Methods: Here, we present an in-depth evaluation and informed assessment of the consistency of four prominent protocols for assessing IAS impacts (EICAT, GISS, Harmonia and NNRA), using two non-native parrots in Europe: the widespread ring-necked parakeet (Psittacula krameri) and the rapidly spreading monk parakeet (Myiopsitta monachus). Results: Our findings show that the procedures used to assess impacts may influence assessment outcomes. We find that robust IAS prioritization can be obtained by assessing species based on their most severe documented impacts, as all protocols yield consistent outcomes across impact categories. Additive impact scoring offers complementary, more subtle information that may be especially relevant for guiding management decisions regarding already established invasive alien species. Such management decisions will also strongly benefit from consensus approaches that reduce disagreement between experts, fostering the uptake of scientific advice into policy-making decisions. Main conclusions: Invasive alien species assessments should take advantage of the capacity of consensus assessments to consolidate discussion and agreement between experts. Our results suggest that decision-makers could use the assessment protocol most fit for their purpose, on the condition they apply a precautionary approach by considering the most severe impacts only. We also recommend that screening for high-impact IAS should be performed on a more robust basis than current ad hoc practices, at least using the easiest assessment protocols and reporting confidence scores.This study is a joint effort from a workshop organized under COST European Cooperation in Science and Technology Actions Parrotnet (ES1304) and Alien Challenge (TD1209). We would also like to thank two anonymous referees for helpful comments on an earlier version of this manuscript. D.S is currently funded by a Marie SkƂodowska‐Curie Action under the Horizon 2020 call (H2020‐MSCA‐IF‐2015, grant number 706318) and acknowledges the Danish National Research Foundation for support to the Center for Macroecology, Evolution and Climate (grant number DNRF96). J.C.S. was supported by funds from the Ministry of Economy and Competitivity, Spanish Research Council (CGL‐2016‐79568‐C3‐3‐P)

    Global Disease Outbreaks Associated with the 2015-2016 El Nio Event

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    Interannual climate variability patterns associated with the El Nio-Southern Oscillation phenomenon result in climate and environmental anomaly conditions in specific regions worldwide that directly favor outbreaks and/or amplification of variety of diseases of public health concern including chikungunya, hantavirus, Rift Valley fever, cholera, plague, and Zika. We analyzed patterns of some disease outbreaks during the strong 20152016 El Nio event in relation to climate anomalies derived from satellite measurements. Disease outbreaks in multiple El Nio-connected regions worldwide (including Southeast Asia, Tanzania, western US, and Brazil) followed shifts in rainfall, temperature, and vegetation in which both drought and flooding occurred in excess (1481% precipitation departures from normal). These shifts favored ecological conditions appropriate for pathogens and their vectors to emerge and propagate clusters of diseases activity in these regions. Our analysis indicates that intensity of disease activity in some ENSO-teleconnected regions were approximately 2.528% higher during years with El Nio events than those without. Plague in Colorado and New Mexico as well as cholera in Tanzania were significantly associated with above normal rainfall (p < 0.05); while dengue in Brazil and southeast Asia were significantly associated with above normal land surface temperature (p < 0.05). Routine and ongoing global satellite monitoring of key climate variable anomalies calibrated to specific regions could identify regions at risk for emergence and propagation of disease vectors. Such information can provide sufficient lead-time for outbreak prevention and potentially reduce the burden and spread of ecologically coupled diseases

    Trends in invasive bacterial diseases during the first 2 years of the COVID-19 pandemic: analyses of prospective surveillance data from 30 countries and territories in the IRIS Consortium.

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    BACKGROUND The Invasive Respiratory Infection Surveillance (IRIS) Consortium was established to assess the impact of the COVID-19 pandemic on invasive diseases caused by Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, and Streptococcus agalactiae. We aimed to analyse the incidence and distribution of these diseases during the first 2 years of the COVID-19 pandemic compared to the 2 years preceding the pandemic. METHODS For this prospective analysis, laboratories in 30 countries and territories representing five continents submitted surveillance data from Jan 1, 2018, to Jan 2, 2022, to private projects within databases in PubMLST. The impact of COVID-19 containment measures on the overall number of cases was analysed, and changes in disease distributions by patient age and serotype or group were examined. Interrupted time-series analyses were done to quantify the impact of pandemic response measures and their relaxation on disease rates, and autoregressive integrated moving average models were used to estimate effect sizes and forecast counterfactual trends by hemisphere. FINDINGS Overall, 116 841 cases were analysed: 76 481 in 2018-19, before the pandemic, and 40 360 in 2020-21, during the pandemic. During the pandemic there was a significant reduction in the risk of disease caused by S pneumoniae (risk ratio 0·47; 95% CI 0·40-0·55), H influenzae (0·51; 0·40-0·66) and N meningitidis (0·26; 0·21-0·31), while no significant changes were observed for S agalactiae (1·02; 0·75-1·40), which is not transmitted via the respiratory route. No major changes in the distribution of cases were observed when stratified by patient age or serotype or group. An estimated 36 289 (95% prediction interval 17 145-55 434) cases of invasive bacterial disease were averted during the first 2 years of the pandemic among IRIS-participating countries and territories. INTERPRETATION COVID-19 containment measures were associated with a sustained decrease in the incidence of invasive disease caused by S pneumoniae, H influenzae, and N meningitidis during the first 2 years of the pandemic, but cases began to increase in some countries towards the end of 2021 as pandemic restrictions were lifted. These IRIS data provide a better understanding of microbial transmission, will inform vaccine development and implementation, and can contribute to health-care service planning and provision of policies. FUNDING Wellcome Trust, NIHR Oxford Biomedical Research Centre, Spanish Ministry of Science and Innovation, Korea Disease Control and Prevention Agency, Torsten Söderberg Foundation, Stockholm County Council, Swedish Research Council, German Federal Ministry of Health, Robert Koch Institute, Pfizer, Merck, and the Greek National Public Health Organization

    Global wealth disparities drive adherence to COVID-safe pathways in head and neck cancer surgery

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    Black holes, gravitational waves and fundamental physics: a roadmap

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    The grand challenges of contemporary fundamental physics—dark matter, dark energy, vacuum energy, inflation and early universe cosmology, singularities and the hierarchy problem—all involve gravity as a key component. And of all gravitational phenomena, black holes stand out in their elegant simplicity, while harbouring some of the most remarkable predictions of General Relativity: event horizons, singularities and ergoregions. The hitherto invisible landscape of the gravitational Universe is being unveiled before our eyes: the historical direct detection of gravitational waves by the LIGO-Virgo collaboration marks the dawn of a new era of scientific exploration. Gravitational-wave astronomy will allow us to test models of black hole formation, growth and evolution, as well as models of gravitational-wave generation and propagation. It will provide evidence for event horizons and ergoregions, test the theory of General Relativity itself, and may reveal the existence of new fundamental fields. The synthesis of these results has the potential to radically reshape our understanding of the cosmos and of the laws of Nature. The purpose of this work is to present a concise, yet comprehensive overview of the state of the art in the relevant fields of research, summarize important open problems, and lay out a roadmap for future progress. This write-up is an initiative taken within the framework of the European Action on 'Black holes, Gravitational waves and Fundamental Physics'
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