Colorectal cancer screening programmes worldwide have been disrupted during the COVID-19 pandemic. We aimed to estimate the impact of hypothetical disruptions to organised faecal immunochemical ...test-based colorectal cancer screening programmes on short-term and long-term colorectal cancer incidence and mortality in three countries using microsimulation modelling.
In this modelling study, we used four country-specific colorectal cancer microsimulation models-Policy1-Bowel (Australia), OncoSim (Canada), and ASCCA and MISCAN-Colon (the Netherlands)-to estimate the potential impact of COVID-19-related disruptions to screening on colorectal cancer incidence and mortality in Australia, Canada, and the Netherlands annually for the period 2020-24 and cumulatively for the period 2020-50. Modelled scenarios varied by duration of disruption (3, 6, and 12 months), decreases in screening participation after the period of disruption (0%, 25%, or 50% reduction), and catch-up screening strategies (within 6 months after the disruption period or all screening delayed by 6 months).
Without catch-up screening, our analysis predicted that colorectal cancer deaths among individuals aged 50 years and older, a 3-month disruption would result in 414-902 additional new colorectal cancer diagnoses (relative increase 0·1-0·2%) and 324-440 additional deaths (relative increase 0·2-0·3%) in the Netherlands, 1672 additional diagnoses (relative increase 0·3%) and 979 additional deaths (relative increase 0·5%) in Australia, and 1671 additional diagnoses (relative increase 0·2%) and 799 additional deaths (relative increase 0·3%) in Canada between 2020 and 2050, compared with undisrupted screening. A 6-month disruption would result in 803-1803 additional diagnoses (relative increase 0·2-0·4%) and 678-881 additional deaths (relative increase 0·4-0·6%) in the Netherlands, 3552 additional diagnoses (relative increase 0·6%) and 1961 additional deaths (relative increase 1·0%) in Australia, and 2844 additional diagnoses (relative increase 0·3%) and 1319 additional deaths (relative increase 0·4%) in Canada between 2020 and 2050, compared with undisrupted screening. A 12-month disruption would result in 1619-3615 additional diagnoses (relative increase 0·4-0·9%) and 1360-1762 additional deaths (relative increase 0·8-1·2%) in the Netherlands, 7140 additional diagnoses (relative increase 1·2%) and 3968 additional deaths (relative increase 2·0%) in Australia, and 5212 additional diagnoses (relative increase 0·6%) and 2366 additional deaths (relative increase 0·8%) in Canada between 2020 and 2050, compared with undisrupted screening. Providing immediate catch-up screening could minimise the impact of the disruption, restricting the relative increase in colorectal cancer incidence and deaths between 2020 and 2050 to less than 0·1% in all countries. A post-disruption decrease in participation could increase colorectal cancer incidence by 0·2-0·9% and deaths by 0·6-1·6% between 2020 and 2050, compared with undisrupted screening.
Although the projected effect of short-term disruption to colorectal cancer screening is modest, such disruption will have a marked impact on colorectal cancer incidence and deaths between 2020 and 2050 attributable to missed screening. Thus, it is crucial that, if disrupted, screening programmes ensure participation rates return to previously observed rates and provide catch-up screening wherever possible, since this could mitigate the impact on colorectal cancer deaths.
Cancer Council New South Wales, Health Canada, and Dutch National Institute for Public Health and Environment.
The BioKnowledge Library is a relational database and web site (http://www.proteome.com) composed of protein-specific information collected from the scientific literature. Each Protein Report on the ...web site summarizes and displays published information about a single protein, including its biochemical function, role in the cell and in the whole organism, localization, mutant phenotype and genetic interactions, regulation, domains and motifs, interactions with other proteins and other relevant data. This report describes four species-specific volumes of the BioKnowledge Library, concerned with the model organisms Saccharomyces cerevisiae (YPD), Schizosaccharomyces pombe (PombePD) and Caenorhabditis elegans (WormPD), and with the fungal pathogen Candida albicans (CalPD). Protein Reports of each species are unified in format, easily searchable and extensively cross-referenced between species. The relevance of these comprehensively curated resources to analysis of proteins in other species is discussed, and is illustrated by a survey of model organism proteins that have similarity to human proteins involved in disease.
The Yeast Proteome Database (YPDtrade mark) has been for several years a resource for organized and accessible information about the proteins of Saccharomyces cerevisiae. We have now extended the YPD ...format to create a database containing complete proteome information about the model organism Caenorhabditis elegans (WormPDtrade mark). YPD and WormPD are designed for use not only by their respective research communities but also by the broader scientific community. In both databases, information gleaned from the literature is presented in a consistent, user-friendly Protein Report format: a single Web page presenting all available knowledge about a particular protein. Each Protein Report begins with a Title Line, a concise description of the function of that protein that is continually updated as curators review new literature. Properties and functions of the protein are presented in tabular form in the upper part of the Report, and free-text annotations organized by topic are presented in the lower part. Each Protein Report ends with a comprehensive reference list whose entries are linked to their MEDLINE s. YPD and WormPD are seamlessly integrated, with extensive links between the species. They are freely accessible to academic users on the WWW at http://www. proteome.com/databases/index.html, and are available by subscription to corporate users.
The gut microbiota influences development
and homeostasis
of the mammalian immune system, and is associated with human inflammatory
and immune diseases
as well as responses to immunotherapy
. ...Nevertheless, our understanding of how gut bacteria modulate the immune system remains limited, particularly in humans, where the difficulty of direct experimentation makes inference challenging. Here we study hundreds of hospitalized-and closely monitored-patients with cancer receiving haematopoietic cell transplantation as they recover from chemotherapy and stem-cell engraftment. This aggressive treatment causes large shifts in both circulatory immune cell and microbiota populations, enabling the relationships between the two to be studied simultaneously. Analysis of observed daily changes in circulating neutrophil, lymphocyte and monocyte counts and more than 10,000 longitudinal microbiota samples revealed consistent associations between gut bacteria and immune cell dynamics. High-resolution clinical metadata and Bayesian inference allowed us to compare the effects of bacterial genera in relation to those of immunomodulatory medications, revealing a considerable influence of the gut microbiota-together and over time-on systemic immune cell dynamics. Our analysis establishes and quantifies the link between the gut microbiota and the human immune system, with implications for microbiota-driven modulation of immunity.
Greater penetrations of variable renewable generation on some electric grids have resulted in increased levels of curtailment in recent years. Studies of renewable energy grid integration have found ...that curtailment levels may grow as the penetration of wind and solar energy generation increases. This paper reviews international experience with curtailment of wind and solar energy on bulk power systems in recent years, with a focus on eleven countries in Europe, North America, and Asia. It examines levels of curtailment, the causes of curtailment, curtailment methods and use of market-based dispatch, as well as operational, institutional, and other changes that are being made to reduce renewable energy curtailment.
Background: Angiotensin converting enzyme (ACE) 2 is a recently identified homologue of ACE that may counterregulate the actions of angiotensin (Ang) II by facilitating its breakdown to Ang 1–7. The ...renin-angiotensin system (RAS) has been implicated in the pathogenesis of cirrhosis but the role of ACE2 in liver disease is not known. Aims: This study examined the effects of liver injury on ACE2 expression and activity in experimental hepatic fibrosis and human cirrhosis, and the effects of Ang 1–7 on vascular tone in cirrhotic rat aorta. Methods: In sham operated and bile duct ligated (BDL) rats, quantitative reverse transcriptase-polymerase chain reaction was used to assess hepatic ACE2 mRNA, and western blotting and immunohistochemistry to quantify and localise ACE2 protein. ACE2 activity was quantified by quenched fluorescent substrate assay. Similar studies were performed in normal human liver and in hepatitis C cirrhosis. Results: ACE2 mRNA was detectable at low levels in rat liver and increased following BDL (363-fold; p<0.01). ACE2 protein increased after BDL (23.5-fold; p<0.05) as did ACE2 activity (fourfold; p<0.05). In human cirrhotic liver, gene (>30-fold), protein expression (97-fold), and activity of ACE2 (2.4 fold) were increased compared with controls (all p<0.01). In healthy livers, ACE2 was confined to endothelial cells, occasional bile ducts, and perivenular hepatocytes but in both BDL and human cirrhosis there was widespread parenchymal expression of ACE2 protein. Exposure of cultured human hepatocytes to hypoxia led to increased ACE2 expression. In preconstricted rat aorta, Ang 1–7 alone did not affect vascular tone but it significantly enhanced acetylcholine mediated vasodilatation in cirrhotic vessels. Conclusions: ACE2 expression is significantly increased in liver injury in both humans and rat, possibly in response to increasing hepatocellular hypoxia, and may modulate RAS activity in cirrhosis.
Federal health agency leaders describe plans to develop infrastructure for generating high-quality evidence to improve care. They argue that it will be necessary to embed research in clinical care, ...create interoperable research data networks, and apply new research methods.
Making better choices about health and health care requires the best possible evidence. Unfortunately, many of the decisions made today in our health care system are not supported by high-quality evidence
1
–
4
derived from randomized, controlled trials or well-designed observational studies. But as rich, diverse sources of digital data become widely available for research and as analytical tools continue to grow in power and sophistication, the research and health care communities now have the opportunity to quickly and efficiently generate the scientific evidence needed to support improved decision making about health and health care.
The pursuit of high-quality, data-driven evidence . . .
Aims Angiotensin converting enzyme (ACE) 2 catalyses the cleavage of angiotensin (Ang) I to Ang 1‐9 and of Ang II to Ang 1‐7. ACE2 deficiency impairs cardiac contractility and upregulates ...hypoxia-induced genes, suggesting a link with myocardial ischaemia. We studied the expression of ACE2 after myocardial infarction (MI) in the rat as well as in human failing hearts. Methods and results Rats were killed at days 1, 3, and 28 after MI, or treated for 4 weeks with the ACE inhibitor ramipril (1 mg/kg). Cardiac gene and protein expression of ACE and ACE2 were assessed by quantitative real-time reverse transcriptase–polymerase chain reaction and immunohistochemistry/activity assays/in vitro autoradiography, respectively. Both ACE (P=0.022) and ACE2 (P=0.015) mRNA increased in the border/infarct area compared with the viable area at day 3 after MI. By day 28, increases in ACE (P=0.005) and ACE2 (P=0.006) mRNA were also seen in the viable myocardium of MI rats compared with myocardium of control rats. ACE2 protein localized to macrophages, vascular endothelium, smooth muscle, and myocytes. Ramipril attenuated cardiac hypertrophy and inhibited cardiac ACE. In contrast, ramipril had no effect on cardiac ACE2 mRNA, which remained elevated in all areas of the MI rat heart. Immunoreactivity of both ACE and ACE2 increased in failing human hearts. Conclusion The increase in ACE2 after MI suggests that it plays an important role in the negative modulation of the renin angiotensin system in the generation and degradation of angiotensin peptides after cardiac injury.
We performed a preimplementation assessment of workflows, resources, needs, and antibiotic prescribing practices of trainees and practicing dentists to inform the development of an ...antibiotic-stewardship clinical decision-support tool (CDST) for dentists.
We used a technology implementation framework to conduct the preimplementation assessment via surveys and focus groups of students, residents, and faculty members. Using Likert scales, the survey assessed baseline knowledge and confidence in dental providers' antibiotic prescribing. The focus groups gathered information on existing workflows, resources, and needs for end users for our CDST.
Of 355 dental providers recruited to take the survey, 213 (60%) responded: 151 students, 27 residents, and 35 faculty. The average confidence in antibiotic prescribing decisions was 3.2 ± 1.0 on a scale of 1 to 5 (ie, moderate). Dental students were less confident about prescribing antibiotics than residents and faculty (
< .01). However, antibiotic prescribing knowledge was no different between dental students, residents, and faculty. The mean likelihood of prescribing an antibiotic when it was not needed was 2.7 ± 0.6 on a scale of 1 to 5 (unlikely to maybe) and was not meaningfully different across subgroups (
= .10). We had 10 participants across 3 focus groups: 7 students, 2 residents, and 1 faculty member. Four major themes emerged, which indicated that dentists: (1) make antibiotic prescribing decisions based on anecdotal experiences; (2) defer to physicians' recommendations; (3) have limited access to evidence-based resources; and (4) want CDST for antibiotic prescribing.
Dentists' confidence in antibiotic prescribing increased by training level, but knowledge did not. Trainees and practicing dentists would benefit from a CDST to improve appropriateness of antibiotic prescribing.
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