Improving Colorectal Cancer Screening Decision Making Processes

Introduction: Although shared decision making is recommended for cancer screening, it is not routinely completed in practice because of time constraints. We evaluated a process for improving decision making about colorectal cancer (CRC) screening using mailed decision aids (DA) with follow-up telephone support in primary care practices. Methods: We identified patients aged 50-75 who were not up to date with CRC screening in three primary care practices. DA were distributed via mail with telephone follow-up to eligible patients, and charts were reviewed six months later for CRC screening completion. Results: Among 1,064 eligible patients who received the mailed DA, 513 (48.2%) were reached by phone. During the six months after the intervention, 148/1064 (13.9%) patients were screened for CRC (4.8% underwent FIT, 9.1% underwent colonoscopy). Younger patients (aged 50-54) had higher rates of any screening (32.4%) compared with all other age groups (range 12.8%-19.6%), p=0.026, while Medicaid patients had the lowest rates of screening (4.0%), and insured patients had the highest rates (45.3%), p=0.003. Overall, 113/513 (22.0%) who were reached by phone went on to complete screening within 6 months, compared with 35/551 (6.4%) of patients who were not reached by phone (p Conclusion: A standard process for identifying patients unscreened for CRC and DA distribution via mail with telephone decision support modestly increased CRC screening and is consistent with the goal of providing preference-sensitive care and informed decision making. Improving care processes to include decision support outside of office visits is possible in primary care practices

Domestic Water Demand During Droughts in Temperate Climates: Synthesising Evidence for an Integrated Framework

In the upcoming years, as the population is growing and ageing, as lifestyle changes create the need for more water and as fewer people live in each household, the UK water sector will have to deal with challenges in the provision of adequate water services. Unless critical action is taken, every area in the UK may face a supply-demand gap by the 2080s. Extreme weather events and variations that alter drought and flood frequency add to these pressures. However, little evidence is available about householders’ response to drought and there are few if any studies incorporating this evidence into models of demand forecasting. The present work lays the groundwork for modelling domestic water demand response under drought conditions in temperate climates. After discussing the current literature on estimating and forecasting domestic water consumption under both ‘normal’ and drought conditions, this paper identifies the limited ability of current domestic demand forecasting techniques to include the many different and evolving factors affecting domestic consumption and it stresses the need for the inclusion of inter and intra household factors as well as water use practices in future demand forecasting models

Isolation of a natural DNA virus of <i>Drosophila melanogaster</i>, and characterisation of host resistance and immune responses

<div><p><i>Drosophila melanogaster</i> has played a key role in our understanding of invertebrate immunity. However, both functional and evolutionary studies of host-virus interaction in <i>Drosophila</i> have been limited by a dearth of native virus isolates. In particular, despite a long history of virus research, DNA viruses of <i>D</i>. <i>melanogaster</i> have only recently been described, and none have been available for experimental study. Here we report the isolation and comprehensive characterisation of Kallithea virus, a large double-stranded DNA virus, and the first DNA virus to have been reported from wild populations of <i>D</i>. <i>melanogaster</i>. We find that Kallithea virus infection is costly for adult flies, reaching high titres in both sexes and disproportionately reducing survival in males, and movement and late fecundity in females. Using the <i>Drosophila</i> Genetic Reference Panel, we quantify host genetic variance for virus-induced mortality and viral titre and identify candidate host genes that may underlie this variation, including <i>Cdc42-interacting protein 4</i>. Using full transcriptome sequencing of infected males and females, we examine the transcriptional response of flies to Kallithea virus infection and describe differential regulation of virus-responsive genes. This work establishes Kallithea virus as a new tractable model to study the natural interaction between <i>D</i>. <i>melanogaster</i> and DNA viruses, and we hope it will serve as a basis for future studies of immune responses to DNA viruses in insects.</p></div

The impact of viral mutations on recognition by SARS-CoV-2 specific T cells.

We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.This work is supported by the UK Medical Research Council (MRC); Chinese Academy of Medical Sciences(CAMS) Innovation Fund for Medical Sciences (CIFMS), China; National Institute for Health Research (NIHR)Oxford Biomedical Research Centre, and UK Researchand Innovation (UKRI)/NIHR through the UK Coro-navirus Immunology Consortium (UK-CIC). Sequencing of SARS-CoV-2 samples and collation of data wasundertaken by the COG-UK CONSORTIUM. COG-UK is supported by funding from the Medical ResearchCouncil (MRC) part of UK Research & Innovation (UKRI),the National Institute of Health Research (NIHR),and Genome Research Limited, operating as the Wellcome Sanger Institute. T.I.d.S. is supported by a Well-come Trust Intermediate Clinical Fellowship (110058/Z/15/Z). L.T. is supported by the Wellcome Trust(grant number 205228/Z/16/Z) and by theUniversity of Liverpool Centre for Excellence in Infectious DiseaseResearch (CEIDR). S.D. is funded by an NIHR GlobalResearch Professorship (NIHR300791). L.T. and S.C.M.are also supported by the U.S. Food and Drug Administration Medical Countermeasures Initiative contract75F40120C00085 and the National Institute for Health Research Health Protection Research Unit (HPRU) inEmerging and Zoonotic Infections (NIHR200907) at University of Liverpool inpartnership with Public HealthEngland (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford.L.T. is based at the University of Liverpool. M.D.P. is funded by the NIHR Sheffield Biomedical ResearchCentre (BRC – IS-BRC-1215-20017). ISARIC4C is supported by the MRC (grant no MC_PC_19059). J.C.K.is a Wellcome Investigator (WT204969/Z/16/Z) and supported by NIHR Oxford Biomedical Research Centreand CIFMS. The views expressed are those of the authors and not necessarily those of the NIHR or MRC