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Supplementary Figure Legends 1-2 from Cancer-Specific Transgene Expression Mediated by Systemic Injection of Nanoparticles

Supplementary Figure 1 from Cancer-Specific Transgene Expression Mediated by Systemic Injection of Nanoparticles

The lack of safe and efficient systemic gene delivery vectors has largely reduced the potential of gene therapy in the clinic. Previously, we have reported that polypropylenimine dendrimer PPIG3/DNA nanoparticles are capable of tumor transfection upon systemic administration in tumor-bearing mice. To be safely applicable in the clinic, it is crucial to investigate the colloidal stability of nanoparticles and to monitor the exact biodistribution of gene transfer in the whole body of the live subject. Our biophysical characterization shows that dendrimers, when complexed with DNA, are capable of forming spontaneously in solution a supramolecular assembly that possesses all the features required to diffuse in experimental tumors through the enhanced permeability and retention effect. We show that these nanoparticles are of sizes ranging from 33 to 286 nm depending on the DNA concentration, with a colloidal stable and well-organized fingerprint-like structure in which DNA molecules are condensed with an even periodicity of 2.8 nm. Whole-body nuclear imaging using small-animal nano-single-photon emission computed tomography/computer tomography scanner and the human Na/I symporter (NIS) as reporter gene shows unique and highly specific tumor targeting with no detection of gene transfer in any of the other tissues of tumor-bearing mice. Tumor-selective transgene expression was confirmed by quantitative reverse transcription-PCR at autopsy of scanned animals, whereas genomic PCR showed that the tumor sites are the predominant sites of nanoparticle accumulation. Considering that NIS imaging of transgene expression has been recently validated in humans, our data highlight the potential of these nanoparticles as a new formulation for cancer gene therapy. [Cancer Res 2009;69(6):2655–62]

Supplementary Figure 2 from Cancer-Specific Transgene Expression Mediated by Systemic Injection of Nanoparticles

In this paper we define RAL2 – the second Regional Atmosphere and Land (RAL) science configuration for regional modelling. RAL2 uses the Unified Model (UM) as the basis for the atmosphere and the Joint UK Land Environment Simulator (JULES) for the land. RAL2 defines the science configuration of the dynamics and physics schemes of the atmosphere and land and builds on the baseline of RAL1. There are two RAL2 sub-releases, one for mid-latitudes (RAL2-M) and one for tropical regions (RAL2-T). We document the differences between them and where appropriate discuss how RAL2 relates to RAL1 and the corresponding configuration of the global forecasting model. Our results show an increase in medium and low cloud amounts in the mid-latitudes leading to improved cloud forecasts. The increase in cloud amount leads to a reduced diurnal cycle of screen temperature. There is also a reduction in the frequency of heavier precipitation rates. RAL2 is expected to be the last RAL science configuration with two sub-releases as research effort is focused on producing a single defined configuration of the model that performs effectively in all regions of the world.

Purpose The purpose of this opinion piece is to present a case for the potential of positive autoethnography (PosAE) as a new autoethnographic approach. Design/methodology/approach This work resulted from on-going discussions between the authors as to the practicalities and benefits of associating the qualitative approach of autoethnography with the field of positive psychology. Findings PosAE is proposed to encourage writers to actively reflect on the importance for themselves, and their readers, of including positive narrative elements, prospective visions and exploratory trajectories in their work. Research limitations/implications This research builds on existing research that has included positive psychology in autoethnography. As positive psychology is grounded in empirical research, the authors are suggesting that PosAE is allied to pragmatic autoethnography. Practical implications PosAE offers to facilitate positive thought, affect and strategies that could improve well-being. For example, some people struggling with serious health issues, and those helping them, may find it useful for articulating conditions and envisioning, even experiencing, positive change. Social implications With so many lives impacted by mental health issues globally, and with rapidly changing societies struggling to provide stability and purpose, an autoethnography that provides tools such as PERMA (Positive emotions, Engagement, Positive Relationships, Meaning, Accomplishments/Achievements) to communicate the positive seems timely. Originality/value To the best of the authors’ knowledge, this is the first time the creation of an autoethnographic approach explicitly linked to positive psychology has been proposed.

RATIONALE: Shared symptoms and genetic architecture between COVID-19 and lung fibrosis suggests SARS-CoV-2 infection may lead to progressive lung damage.OBJECTIVES: The UKILD Post-COVID study interim analysis was planned to estimate the prevalence of residual lung abnormalities in people hospitalized with COVID-19 based on risk strata.METHODS: The Post-HOSPitalisation COVID Study (PHOSP-COVID) was used for capture of routine and research follow-up within 240 days from discharge. Thoracic CTs linked by PHOSP-COVID identifiers were scored for percentage of residual lung abnormalities (ground glass opacities and reticulations). Risk factors in linked CT were estimated with Bayesian binomial regression and risk strata were generated. Numbers within strata were used to estimate post-hospitalization prevalence using Bayesian binomial distributions. Sensitivity analysis was restricted to participants with protocol driven research follow-up.MEASUREMENTS AND MAIN RESULTS: The interim cohort comprised 3700 people. Of 209 subjects with linked CTs (median 119 days, interquartile range 83-155), 166 people (79.4%) had >10% involvement of residual lung abnormalities. Risk factors included abnormal chest X-ray (RR 1·21 95%CrI 1·05; 1·40), percent predicted DLcoCONCLUSIONS: Residual lung abnormalities were estimated in up to 11% of people discharged following COVID-19 related hospitalization. Health services should monitor at-risk individuals to elucidate long-term functional implications. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

In this paper we define RAL2 - the second "Regional Atmosphere and Land" (RAL) science configuration for regional modelling. RAL2 uses the Unified Model (UM) as the basis for the atmosphere and the Joint UK Land Environment Simulator (JULES) for the land. RAL2 defines the science configuration of the dynamics and physics schemes of the atmosphere and land and builds on the baseline of RAL1. There are two RAL2 sub-releases, one for mid-latitudes (RAL2-M) and one for tropical regions (RAL2-T). We document the differences between them and where appropriate discuss how RAL2 relates to RAL1 and the corresponding configuration of the global forecasting model. Our results show an increase in medium and low cloud amounts in the mid-latitudes leading to improved cloud forecasts. The increase in cloud amount leads to a reduced diurnal cycle of screen temperature. There is also a reduction in the frequency of heavier precipitation rates. RAL2 is expected to be the last RAL science configuration with two sub-releases as research effort is focused on producing a single defined configuration of the model that performs effectively in all regions of the world.

ObjectivesTo describe the rates for consulting a general practitioner (GP) for sequelae after acute covid-19 in patients admitted to hospital with covid-19 and those managed in the community, and to determine how the rates change over time for patients in the community and after vaccination for covid-19.DesignPopulation based study.Setting1392 general practices in England contributing to the Clinical Practice Research Datalink Aurum database.Participants456 002 patients with a diagnosis of covid-19 between 1 August 2020 and 14 February 2021 (44.7% men; median age 61 years), admitted to hospital within two weeks of diagnosis or managed in the community, and followed-up for a maximum of 9.2 months. A negative control group included individuals without covid-19 (n=38 511) and patients with influenza before the pandemic (n=21 803).Main outcome measuresComparison of rates for consulting a GP for new symptoms, diseases, prescriptions, and healthcare use in individuals admitted to hospital and those managed in the community, separately, before and after covid-19 infection, using Cox regression and negative binomial regression for healthcare use. The analysis was repeated for the negative control and influenza cohorts. In individuals in the community, outcomes were also described over time after a diagnosis of covid-19, and compared before and after vaccination for individuals who were symptomatic after covid-19 infection, using negative binomial regression.ResultsRelative to the negative control and influenza cohorts, patients in the community (n=437 943) had significantly higher GP consultation rates for multiple sequelae, and the most common were loss of smell or taste, or both (adjusted hazard ratio 5.28, 95% confidence interval 3.89 to 7.17, PConclusionsGP consultation rates for sequelae after acute covid-19 infection differed between patients with covid-19 who were admitted to hospital and those managed in the community. For individuals in the community, rates of some sequelae decreased over time but those for others, such as anxiety and depression, persisted. Rates of some outcomes decreased after vaccination in this group.