Radiomics-Based Texture Analysis of Ga-68-DOTATATE Positron Emission Tomography and Computed Tomography Images as a Prognostic Biomarker in Adults With Neuroendocrine Cancers Treated With Lu-177-DOTATATE

Purpose: Neuroendocrine tumors (NET) are rare cancers with variable behavior. A better understanding of prognosis would aid individualized management. The aim of this hypothesis-generating pilot study was to investigate the prognostic potential of tumor heterogeneity and tracer avidity in NET using texture analysis (TA) of 68Ga-DOTATATE positron emission tomography (PET) and non-enhanced computed tomography (CT) performed at baseline in patients treated with 177Lu-DOTATATE. It aims to justify a larger-scale study to evaluate its clinical value. Methods: The pretherapy 68Ga-DOTATATE PET-CT scans of 44 patients with metastatic NET (carcinoid, pancreatic, thyroid, head and neck, catecholamine-secreting, and unknown primary NET) treated with 177Lu-DOTATATE were analyzed retrospectively using commercially available texture analysis research software. Image filtration extracted and enhanced objects of different sizes (fine, medium, coarse), then quantified heterogeneity by statistical and histogram-based parameters (mean intensity, standard deviation, entropy, mean of positive pixels, skewness, and kurtosis). Regions of interest were manually drawn around up to five of the most 68Ga-DOTATATE avid lesions for each patient. 68Gallium uptake on PET was quantified as SUVmax and SUVmean. Associations between imaging and clinical markers with progression-free (PFS) and overall survival (OS) were assessed using univariate Kaplan-Meier analysis. Independence of the significant univariate markers of survival was tested using multivariate Cox regression analysis. Results: Measures of heterogeneity (higher kurtosis, higher entropy, and lower skewness) on coarse-texture scale CT and unfiltered PET images predicted shorter PFS (CT coarse kurtosis: p=0.05, PET entropy: p=0.01, PET skewness: p=0.03) and shorter OS (CT coarse kurtosis: p=0.05, PET entropy: p=0.01, PET skewness p=0.02). Conventional PET parameters such as SUVmax and SUVmean showed trends towards predicting outcome but were not statistically significant. Multivariate analysis identified that CT-TA (coarse kurtosis: HR=2.57, 95% CI=1.22–5.38, p=0.013) independently predicted PFS, and PET-TA (unfiltered skewness: HR=9.05, 95% CI=1.19–68.91, p=0.033) independently predicted OS. Conclusion: These preliminary data generate a hypothesis that radiomic analysis of neuroendocrine cancer on 68Ga-DOTATATE PET-CT may be of prognostic value and a valuable addition to the assessment of patients

Co-selection for antibiotic resistance by environmental contaminants

This is the final version. Available from Springer Nature via the DOI in this record. The environment is increasingly recognised as a hotspot for the selection and dissemination of antibiotic resistant bacteria and antibiotic resistance genes. These can be selected for by antibiotics and non-antibiotic agents (such as metals and biocides), with the evidence to support this well established by observational and experimental studies. However, there is emerging evidence to suggest that plant protection products (such as herbicides), and non-antibiotic drugs (such as chemotherapeutic agents), can also co-select for antibiotic resistance. This review aims to provide an overview of four classes of non-antibiotic agents (metals, biocides, plant protection products, and non-antibiotic drugs) and how they may co-select for antibiotic resistance, with a particular focus on the environment. It also aims to identify key knowledge gaps that should be addressed in future work, to better understand these potential co-selective agents.BBSRC/AstraZenecaCDT/AstraZenecaNatural Environment Research Council (NERC)Natural Environment Research Council (NERC

Coastal clustering of HEV; Cornwall, UK.

PublishedBACKGROUND AND AIMS: Autochthonous hepatitis E virus (HEV) infection is a porcine zoonosis and increasingly recognized in developed countries. In most cases the route of infection is uncertain. A previous study showed that HEV was associated geographically with pig farms and coastal areas. AIM: The aim of the present research was to study the geographical, environmental and social factors in autochthonous HEV infection. METHODS: Cases of HEV genotype 3 infection and controls were identified from 2047 consecutive patients attending a rapid-access hepatology clinic. For each case/control the following were recorded: distance from home to nearest pig farm, distance from home to coast, rainfall levels during the 8 weeks before presentation, and socioeconomic status. RESULTS: A total of 36 acute hepatitis E cases, 170 age/sex-matched controls and 53 hepatitis controls were identified. The geographical spread of hepatitis E cases was not even when compared with both control groups. Cases were more likely to live within 2000 m of the coast (odds ratio=2.32, 95% confidence interval=1.08-5.19, P=0.03). There was no regional difference in the incidence of cases and controls between west and central Cornwall. There was no difference between cases and controls in terms of distance from the nearest pig farm, socioeconomic status or rainfall during the 8 weeks before disease presentation. CONCLUSION: Cases of HEV infection in Cornwall are associated with coastal residence. The reason for this observation is uncertain, but might be related to recreational exposure to beach areas exposed to HEV-contaminated 'run-off' from pig farms. This hypothesis merits further study.The European Centre for the Environment and Human Health (part of the Peninsula College of Medicine and Dentistry which is a joint entity of the University of Exeter, the University of Plymouth and the NHS in the South West) is supported by investment from the European Regional Development Fund and the European Social Fund Convergence Programme for Cornwall and the Isles of Scilly

Stereoselective metabolism of chloramphenicol by bacteria isolated from wastewater, and the importance of stereochemistry in environmental risk assessments for antibiotics

This is the final version. Available on open access from Elsevier via the DOI in this recordWastewater treatment plants have been highlighted as a potential hotspot for the development and spread of antibiotic resistance. Although antibiotic resistant bacteria in wastewater present a public health threat, it is also possible that these bacteria play an important role in the bioremediation through the metabolism of antibiotics before they reach the wider environment. Here we address this possibility with a particular emphasis on stereochemistry using a combination of microbiology and analytical chemistry tools including the use of supercritical-fluid chromatography coupled with mass spectrometry for chiral analysis and high-resolution mass spectrometry to investigate metabolites. Due to the complexities around chiral analysis the antibiotic chloramphenicol was used as a proof of concept to demonstrate stereoselective metabolism due to its relatively simple chemical structure and availability over the counter in the U.K. The results presented here demonstrate the chloramphenicol can be stereoselectively transformed by the chloramphenicol acetyltransferase enzyme with the orientation around the first stereocentre being key for this process, meaning that accumulation of two isomers may occur within the environment with potential impacts on ecotoxicity and emergence of bacterial antibiotic resistance within the environment.Engineering and Physical Sciences Research Council (EPSRC)Natural Environment Research Council (NERC)AstraZeneca Global Safety, Health and Environmen

Star formation in young star cluster NGC 1893

We present a comprehensive multi-wavelength study of the star-forming region NGC 1893 to explore the effects of massive stars on low-mass star formation. Using near-infrared colours, slitless spectroscopy and narrow-band $H\alpha$ photometry in the cluster region we have identified candidate young stellar objects (YSOs) distributed in a pattern from the cluster to one of the nearby nebulae Sim 129. The $V, (V-I)$ colour-magnitude diagram of the YSOs indicates that majority of these objects have ages between 1 to 5 Myr. The spread in the ages of the YSOs may indicate a non-coeval star formation in the cluster. The slope of the KLF for the cluster is estimated to be $0.34\pm0.07$, which agrees well with the average value ($\sim 0.4$) reported for young clusters. For the entire observed mass range $0.6 < M/M_\odot \le 17.7$ the value of the slope of the initial mass function, $`\Gamma$', comes out to be $-1.27\pm0.08$, which is in agreement with the Salpeter value of -1.35 in the solar neighborhood. However, the value of $`\Gamma$' for PMS phase stars (mass range $0.6 < M/M_\odot \le 2.0$) is found to be $-0.88\pm0.09$ which is shallower than the value ($-1.71\pm0.20$) obtained for MS stars having mass range $2.5 < M/M_\odot \le 17.7$ indicating a break in the slope of the mass function at $\sim 2 M_\odot$. Estimated $`\Gamma$' values indicate an effect of mass segregation for main-sequence stars, in the sense that massive stars are preferentially located towards the cluster center. The estimated dynamical evolution time is found to be greater than the age of the cluster, therefore the observed mass segregation in the cluster may be the imprint of the star formation process. There is evidence for triggered star formation in the region, which seems to govern initial morphology of the cluster.Comment: Accepted for the publication in MNRAS, 21 pages, 26 figures, 10 table

Shedding of SARS-CoV-2 in feces and urine and its potential role in person-to-person transmission and the environment-based spread of COVID-19

The recent detection of SARS-CoV-2 RNA in feces has led to speculation that it can be transmitted via the fecal-oral/ocular route. This review aims to critically evaluate the incidence of gastrointestinal (GI) symptoms, the quantity and infectivity of SARS-CoV-2 in feces and urine, and whether these pose an infection risk in sanitary settings, sewage networks, wastewater treatment plants, and the wider environment (e.g. rivers, lakes and marine waters). A review of 48 independent studies revealed that severe GI dysfunction is only evident in a small number of COVID-19 cases, with 11 ± 2% exhibiting diarrhea and 12 ± 3% exhibiting vomiting and nausea. In addition to these cases, SARS-CoV-2 RNA can be detected in feces from some asymptomatic, mildly- and pre-symptomatic individuals. Fecal shedding of the virus peaks in the symptomatic period and can persist for several weeks, but with declining abundances in the post-symptomatic phase. SARS-CoV-2 RNA is occasionally detected in urine, but reports in fecal samples are more frequent. The abundance of the virus genetic material in both urine (ca. 102–105 gc/ml) and feces (ca. 102–107 gc/ml) is much lower than in nasopharyngeal fluids (ca. 105–1011 gc/ml). There is strong evidence of multiplication of SARS-CoV-2 in the gut and infectious virus has occasionally been recovered from both urine and stool samples. The level and infectious capability of SARS-CoV-2 in vomit remain unknown. In comparison to enteric viruses transmitted via the fecal-oral route (e.g. norovirus, adenovirus), the likelihood of SARS-CoV-2 being transmitted via feces or urine appears much lower due to the lower relative amounts of virus present in feces/urine. The biggest risk of transmission will occur in clinical and care home settings where secondary handling of people and urine/fecal matter occurs. In addition, while SARS-CoV-2 RNA genetic material can be detected by in wastewater, this signal is greatly reduced by conventional treatment. Our analysis also suggests the likelihood of infection due to contact with sewage-contaminated water (e.g. swimming, surfing, angling) or food (e.g. salads, shellfish) is extremely low or negligible based on very low predicted abundances and limited environmental survival of SARS-CoV-2. These conclusions are corroborated by the fact that tens of million cases of COVID-19 have occurred globally, but exposure to feces or wastewater has never been implicated as a transmission vector

Open-access mega-journals: A bibliometric profile

In this paper we present the first comprehensive bibliometric analysis of eleven open-access mega-journals (OAMJs). OAMJs are a relatively recent phenomenon, and have been characterised as having four key characteristics: large size; broad disciplinary scope; a GoldOA business model; and a peer-review policy that seeks to determine only the scientific soundness of the research rather than evaluate the novelty or significance of the work. Our investigation focuses on four key modes of analysis: journal outputs (the number of articles published and changes in output over time); OAMJ author characteristics (nationalities and institutional affiliations); subject areas (the disciplinary scope of OAMJs, and variations in sub-disciplinary output); and citation profiles (the citation distributions of each OAMJ, and the impact of citing journals). We found that while the total output of the eleven megajournals grew by 14.9% between 2014 and 2015, this growth is largely attributable to the increased output of Scientific Reports and Medicine. We also found substantial variation in the geographical distribution of authors. Several journals have a relatively high proportion of Chinese authors, and we suggest this may be linked to these journals’ high Journal Impact Factors (JIFs). The mega-journals were also found to vary in subject scope, with several journals publishing disproportionately high numbers of articles in certain sub-disciplines. Our citation analsysis offers support for Björk & Catani’s suggestion that OAMJs’s citation distributions can be similar to those of traditional journals, while noting considerable variation in citation rates across the eleven titles. We conclude that while the OAMJ term is useful as a means of grouping journals which share a set of key characteristics, there is no such thing as a “typical” mega-journal, and we suggest several areas for additional research that might help us better understand the current and future role of OAMJs in scholarly communication

Radiation Reveal: Moving from research engagement to involvement.

Here, we report on the process of a highly impactful and successful creative, collaborative, and multi-partner public engagement project, Radiation Reveal. It brought together ten young adults aged 17-25-year-olds with experience of radiotherapy with researchers at Cancer Research UK RadNet City of London across three 2-hour online workshops. Our aims were to 1) initiate discussions between young adults and radiation researchers, and 2) identify what people wish they had known about radiotherapy before or during treatment. These aims were surpassed; other benefits included peer support, participants' continued involvement in subsequent engagement projects, lasting friendships, creation of support groups for others, and creation and national dissemination of top ten tips for medical professionals and social media resources. A key learning was that this project required a dedicated and (com)passionate person with connections to national cancer charities. When designing the project, constant feedback is also needed from charities and young adults with and without radiotherapy experience. Finally, visually capturing discussions and keeping the door open beyond workshops further enhanced impact. Here, we hope to inform and inspire people to help project the patient voice in all we do