Disease-associated XMRV sequences are consistent with laboratory contamination.

BACKGROUND: Xenotropic murine leukaemia viruses (MLV-X) are endogenous gammaretroviruses that infect cells from many species, including humans. Xenotropic murine leukaemia virus-related virus (XMRV) is a retrovirus that has been the subject of intense debate since its detection in samples from humans with prostate cancer (PC) and chronic fatigue syndrome (CFS). Controversy has arisen from the failure of some studies to detect XMRV in PC or CFS patients and from inconsistent detection of XMRV in healthy controls. RESULTS: Here we demonstrate that Taqman PCR primers previously described as XMRV-specific can amplify common murine endogenous viral sequences from mouse suggesting that mouse DNA can contaminate patient samples and confound specific XMRV detection. To consider the provenance of XMRV we sequenced XMRV from the cell line 22Rv1, which is infected with an MLV-X that is indistinguishable from patient derived XMRV. Bayesian phylogenies clearly show that XMRV sequences reportedly derived from unlinked patients form a monophyletic clade with interspersed 22Rv1 clones (posterior probability >0.99). The cell line-derived sequences are ancestral to the patient-derived sequences (posterior probability >0.99). Furthermore, pol sequences apparently amplified from PC patient material (VP29 and VP184) are recombinants of XMRV and Moloney MLV (MoMLV) a virus with an envelope that lacks tropism for human cells. Considering the diversity of XMRV we show that the mean pairwise genetic distance among env and pol 22Rv1-derived sequences exceeds that of patient-associated sequences (Wilcoxon rank sum test: p = 0.005 and p < 0.001 for pol and env, respectively). Thus XMRV sequences acquire diversity in a cell line but not in patient samples. These observations are difficult to reconcile with the hypothesis that published XMRV sequences are related by a process of infectious transmission. CONCLUSIONS: We provide several independent lines of evidence that XMRV detected by sensitive PCR methods in patient samples is the likely result of PCR contamination with mouse DNA and that the described clones of XMRV arose from the tumour cell line 22Rv1, which was probably infected with XMRV during xenografting in mice. We propose that XMRV might not be a genuine human pathogen

What do changing weather and climate shocks and stresses mean for the UK food system?

In light of the publication of Henry Dimbleby’s National Food Strategy (www.nationalfoodstrategy. org/) and the COP26 climate meeting in Glasgow, it is timely to consider the impacts of weather and climate extremes on the UK food system. Climate change-driven changes in extreme weather events are one of the highest-risk future shocks to the UK food system [1], underlining the importance of preparedness across the food chain [2]. Here, we identify major knowledge gaps in the primary impacts of extreme weather and climate change across the UK’s food system, its functioning and their interactions to provide information to support adaptation and resilience planning. Research tends to focus on individual food system activities rather than taking a systematic approach [3, 4]. How- ever, strong evidence exists about the impacts of long- term climate trends and extremes [5] on primary food production [6]. The major knowledge gaps therefore concern post-primary production dimensions [4], notably food system activities between the ‘farm-gate’ and consumption—which are the core focus of this paper (supplementary material S1 available online at stacks.iop.org/ERL/17/051001/mmedia). These constitute major economic and social dimensions but are often the ‘missing middle’ in food system discus- sions. We use the UK food system as an illustrative case study, and consider both global and domestic risks and implications. We present methods, tools and frameworks for systemic analysis of climate impacts on food systems, consider the funding landscape, and highlight priorities for future research

Understanding the impact of a new pharmacy sore throat test and treat service on patient experience: a survey study

Background A pilot of the first NHS funded Sore Throat Test and Treat (STTT) service in the United Kingdom began in selected community pharmacies in Wales in November 2018. The aim of this research was to explore whether a pharmacist delivering consultation for sore throat that included clinical scoring and point-of-care testing was acceptable to patients and how this might influence future health-seeking behaviour. Methods A non-experimental design was employed using a survey research tool including a mix of closed and open questions. The patient experience survey was distributed to all patients who had completed a consultation between November 2018 and May 2019. Data from completed surveys were entered in Jisc Online Surveys® and exported to Excel® for descriptive statistics. Free-text comments were analysed using content and inductive thematic analysis. Results A total of 510 surveys were received (n = 2,839 total consultations, response rate 18%). Overall, 501 patients (98%) were satisfied with the service. Patients’ confidence in managing their condition and service satisfaction was not dependent on having been supplied antibiotics. After the service, 504 patients (99%) stated that they would return to the pharmacy for subsequent sore throat symptoms. Three themes were constructed after inductive analysis of free-text comments (n = 242) revealed 3 themes: convenience and accessibility; professionalism of pharmacy team; and perceived value of the service. Conclusions Results confirmed high levels of patient satisfaction with the new service, its delivery and the choice of options offered for sore throat symptom management. Whilst this research can only discuss patients’ reported future behaviour, the patient-reported stated intentions signify a potential shift in health-seeking behaviour towards a pharmacist-led service. This has important implications in supporting the long-term plan of the governments in Wales and England to redirect management of uncomplicated conditions from GPs to pharmacies

Multiple-Strain Infections of Human Cytomegalovirus with High Genomic Diversity are Common In Breast Milk from HIV-Positive Women in Zambia

Background In developed countries, human cytomegalovirus (HCMV) is a major pathogen in congenitally infected and immunocompromised individuals, where multiple-strain infection appears linked to disease severity. The situation is less documented in developing countries. In Zambia, breast milk is a key route for transmitting HCMV and carries higher viral loads in human immunodeficiency virus (HIV)–infected women. We investigated HCMV strain diversity. Methods High-throughput sequence datasets were generated from 28 HCMV-positive breast milk samples donated by 22 mothers (15 HIV-infected and 7 HIV-negative) at 4–16 weeks postpartum, then analyzed by genome assembly and novel motif-based genotyping in 12 hypervariable HCMV genes. Results Among the 20 samples from 14 donors (13 HIV-infected and one HIV-negative) who yielded data meeting quality thresholds, 89 of the possible 109 genotypes were detected, and multiple-strain infections involving up to 5 strains per person were apparent in 9 HIV-infected women. Strain diversity was extensive among individuals but conserved compartmentally and longitudinally within them. Genotypic linkage was maintained within hypervariable UL73/UL74 and RL12/RL13/UL1 loci for virus entry and immunomodulation, but not between genes more distant from each other. Conclusions Breast milk from HIV-infected women contains multiple HCMV strains of high genotypic complexity and thus constitutes a major source for transmitting viral diversity

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Genomic epidemiology of COVID-19 in care homes in the east of England

Funder: National Institute for Health Research; FundRef: http://dx.doi.org/10.13039/501100000272COVID-19 poses a major challenge to care homes, as SARS-CoV-2 is readily transmitted and causes disproportionately severe disease in older people. Here, 1167 residents from 337 care homes were identified from a dataset of 6600 COVID-19 cases from the East of England. Older age and being a care home resident were associated with increased mortality. SARS-CoV-2 genomes were available for 700 residents from 292 care homes. By integrating genomic and temporal data, 409 viral clusters within the 292 homes were identified, indicating two different patterns – outbreaks among care home residents and independent introductions with limited onward transmission. Approximately 70% of residents in the genomic analysis were admitted to hospital during the study, providing extensive opportunities for transmission between care homes and hospitals. Limiting viral transmission within care homes should be a key target for infection control to reduce COVID-19 mortality in this population

Screening of healthcare workers for SARS-CoV-2 highlights the role of asymptomatic carriage in COVID-19 transmission

Funder: Addenbrooke's Charitable Trust, Cambridge University Hospitals; FundRef: http://dx.doi.org/10.13039/501100002927Significant differences exist in the availability of healthcare worker (HCW) SARS-CoV-2 testing between countries, and existing programmes focus on screening symptomatic rather than asymptomatic staff. Over a 3 week period (April 2020), 1032 asymptomatic HCWs were screened for SARS-CoV-2 in a large UK teaching hospital. Symptomatic staff and symptomatic household contacts were additionally tested. Real-time RT-PCR was used to detect viral RNA from a throat+nose self-swab. 3% of HCWs in the asymptomatic screening group tested positive for SARS-CoV-2. 17/30 (57%) were truly asymptomatic/pauci-symptomatic. 12/30 (40%) had experienced symptoms compatible with coronavirus disease 2019 (COVID-19)>7 days prior to testing, most self-isolating, returning well. Clusters of HCW infection were discovered on two independent wards. Viral genome sequencing showed that the majority of HCWs had the dominant lineage B∙1. Our data demonstrates the utility of comprehensive screening of HCWs with minimal or no symptoms. This approach will be critical for protecting patients and hospital staff

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant