The Population-Level Impacts of Excluding Norovirus-Infected Food Workers From the Workplace: A Mathematical Modeling Study.
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ABSTRACT:
SUBMITTER: Yang W
PROVIDER: S-EPMC6676972 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Trypanosome RNA polymerase II transcription is polycistronic, individual mRNAs being excised by trans splicing and polyadenylation. In this study, we refined the previously published mathematical model for bloodstream form parasites and extended it to the procyclic form. We used the model, together with known mRNA half-lives, to predict the abundances of individual mRNAs, assuming rapid, unregulated mRNA processing; then we compared the results with measured mRNA abundances. Remarkably, the abundances of most mRNAs in procyclic forms are predicted quite well by the model, being largely explained by variations in mRNA decay rates and length. In bloodstream forms substantially more mRNAs are less abundant than predicted. We list mRNAs that are likely to show particularly slow or inefficient processing, either in both forms or with developmental regulation. We also measured ribosome occupancies of all mRNAs in trypanosomes grown in the same conditions as were used to measure mRNA turnover. In procyclic forms there was a weak positive correlation between ribosome density and mRNA half-life, suggesting cross-talk between translation and mRNA decay; ribosome density was related to the proportion of the mRNA on polysomes, indicating control of translation initiation. Ribosomal protein mRNAs in procyclics appeared to be exceptionally rapidly processed but poorly translated. Through this study, we conclude that lLevels of mRNAs in procyclic form trypanosomes are determined mainly by length and mRNA decay, with some control of precursor processing. In bloodstream forms variations in nuclear events play a larger role in transcriptome regulation, suggesting acquisition of new control mechanisms during adaptation to mammalian parasitism. Ribosome profiling and mRNA libraries were constructed in triplicate from in vitro PCF and in duplicate from in vitro T. brucei Lister427, to understand global differntial gene transcription.
2016-03-16 | E-GEOD-79208 | biostudies-arrayexpress
Project description:Trypanosome RNA polymerase II transcription is polycistronic, individual mRNAs being excised by trans splicing and polyadenylation. In this study, we refined the previously published mathematical model for bloodstream form parasites and extended it to the procyclic form. We used the model, together with known mRNA half-lives, to predict the abundances of individual mRNAs, assuming rapid, unregulated mRNA processing; then we compared the results with measured mRNA abundances. Remarkably, the abundances of most mRNAs in procyclic forms are predicted quite well by the model, being largely explained by variations in mRNA decay rates and length. In bloodstream forms substantially more mRNAs are less abundant than predicted. We list mRNAs that are likely to show particularly slow or inefficient processing, either in both forms or with developmental regulation. We also measured ribosome occupancies of all mRNAs in trypanosomes grown in the same conditions as were used to measure mRNA turnover. In procyclic forms there was a weak positive correlation between ribosome density and mRNA half-life, suggesting cross-talk between translation and mRNA decay; ribosome density was related to the proportion of the mRNA on polysomes, indicating control of translation initiation. Ribosomal protein mRNAs in procyclics appeared to be exceptionally rapidly processed but poorly translated. Through this study, we conclude that lLevels of mRNAs in procyclic form trypanosomes are determined mainly by length and mRNA decay, with some control of precursor processing. In bloodstream forms variations in nuclear events play a larger role in transcriptome regulation, suggesting acquisition of new control mechanisms during adaptation to mammalian parasitism.
2016-03-16 | GSE79208 | GEO
Project description:BackgroundMathematical transmission models are increasingly used to guide public health interventions for infectious diseases, particularly in the context of emerging pathogens; however, the contribution of modeling to the growing issue of antimicrobial resistance (AMR) remains unclear. Here, we systematically evaluate publications on population-level transmission models of AMR over a recent period (2006-2016) to gauge the state of research and identify gaps warranting further work.MethodsWe performed a systematic literature search of relevant databases to identify transmission studies of AMR in viral, bacterial, and parasitic disease systems. We analyzed the temporal, geographic, and subject matter trends, described the predominant medical and behavioral interventions studied, and identified central findings relating to key pathogens.ResultsWe identified 273 modeling studies; the majority of which (> 70%) focused on 5 infectious diseases (human immunodeficiency virus (HIV), influenza virus, Plasmodium falciparum (malaria), Mycobacterium tuberculosis (TB), and methicillin-resistant Staphylococcus aureus (MRSA)). AMR studies of influenza and nosocomial pathogens were mainly set in industrialized nations, while HIV, TB, and malaria studies were heavily skewed towards developing countries. The majority of articles focused on AMR exclusively in humans (89%), either in community (58%) or healthcare (27%) settings. Model systems were largely compartmental (76%) and deterministic (66%). Only 43% of models were calibrated against epidemiological data, and few were validated against out-of-sample datasets (14%). The interventions considered were primarily the impact of different drug regimens, hygiene and infection control measures, screening, and diagnostics, while few studies addressed de novo resistance, vaccination strategies, economic, or behavioral changes to reduce antibiotic use in humans and animals.ConclusionsThe AMR modeling literature concentrates on disease systems where resistance has been long-established, while few studies pro-actively address recent rise in resistance in new pathogens or explore upstream strategies to reduce overall antibiotic consumption. Notable gaps include research on emerging resistance in Enterobacteriaceae and Neisseria gonorrhoeae; AMR transmission at the animal-human interface, particularly in agricultural and veterinary settings; transmission between hospitals and the community; the role of environmental factors in AMR transmission; and the potential of vaccines to combat AMR.
| S-EPMC6480522 | biostudies-literature
Project description:Immunomodulatory drugs could contribute to a functional cure for Human Immunodeficiency Virus (HIV). Interleukin-15 (IL-15) promotes expansion and activation of CD8+ T cell and natural killer (NK) cell populations. In one study, an IL-15 superagonist, N-803, suppressed Simian Immunodeficiency Virus (SIV) in non-human primates (NHPs) who had received prior SIV vaccination. However, viral suppression attenuated with continued N-803 treatment, partially returning after long treatment interruption. While there is evidence of concurrent drug tolerance, immune regulation, and viral escape, the relative contributions of these mechanisms to the observed viral dynamics have not been quantified. Here, we utilize mathematical models of N-803 treatment in SIV-infected macaques to estimate contributions of these three key mechanisms to treatment outcomes: 1) drug tolerance, 2) immune regulation, and 3) viral escape. We calibrated our model to viral and lymphocyte responses from the above-mentioned NHP study. Our models track CD8+ T cell and NK cell populations with N-803-dependent proliferation and activation, as well as viral dynamics in response to these immune cell populations. We compared mathematical models with different combinations of the three key mechanisms based on Akaike Information Criterion and important qualitative features of the NHP data. Two minimal models were capable of reproducing the observed SIV response to N-803. In both models, immune regulation strongly reduced cytotoxic cell activation to enable viral rebound. Either long-term drug tolerance or viral escape (or some combination thereof) could account for changes to viral dynamics across long breaks in N-803 treatment. Theoretical explorations with the models showed that less-frequent N-803 dosing and concurrent immune regulation blockade (e.g. PD-L1 inhibition) may improve N-803 efficacy. However, N-803 may need to be combined with other immune therapies to countermand viral escape from the CD8+ T cell response. Our mechanistic model will inform such therapy design and guide future studies.
| S-EPMC8351941 | biostudies-literature
Project description:Multiple norovirus outbreaks following catered events in Auckland, New Zealand, in September 2010 were linked to the same catering company and investigated. Retrospective cohort studies were undertaken with attendees of two events: 38 (24·1%) of 158 surveyed attendees developed norovirus-compatible illness. Attendees were at increased risk of illness if they had consumed food that had received manual preparation following cooking or that had been prepared within 45 h following end of symptoms in a food handler with prior gastroenteritis. All food handlers were tested for norovirus. A recombinant norovirus GII.e/GII.4 was detected in specimens from event attendees and the convalescent food handler. All catering company staff were tested; no asymptomatic norovirus carriers were detected. This investigation improved the characterization of norovirus risk from post-symptomatic food handlers by narrowing the potential source of transmission to one individual. Food handlers with gastroenteritis should be excluded from the workplace for 45 h following resolution of symptoms.
| S-EPMC9151622 | biostudies-literature
Project description:BackgroundInternationally, key workers such as healthcare staff are advised to stay at home if they or household members experience coronavirus disease 2019 (COVID-19)-like symptoms. This potentially isolates/quarantines many staff without SARS-CoV-2, while not preventing transmission from staff with asymptomatic infection. We explored the impact of testing staff on absence durations from work and transmission risks to others.MethodsWe used a decision-analytic model for 1000 key workers to compare the baseline strategy of (S0) no RT-PCR testing of workers to testing workers (S1) with COVID-19-like symptoms in isolation, (S2) without COVID-19-like symptoms but in household quarantine, and (S3) all staff. We explored confirmatory re-testing scenarios of repeating all initial tests, initially positive tests, initially negative tests, or no re-testing. We varied all parameters, including the infection rate (0.1-20%), proportion asymptomatic (10-80%), sensitivity (60-95%), and specificity (90-100%).ResultsTesting all staff (S3) changes the risk of workplace transmission by -56.9 to +1.0 workers/1000 tests (with reductions throughout at RT-PCR sensitivity ≥65%), and absences by -0.5 to +3.6 days/test but at heightened testing needs of 989.6-1995.9 tests/1000 workers. Testing workers in household quarantine (S2) reduces absences the most by 3.0-6.9 days/test (at 47.0-210.4 tests/1000 workers), while increasing risk of workplace transmission by 0.02-49.5 infected workers/1000 tests (which can be minimized when re-testing initially negative tests).ConclusionsBased on optimizing absence durations or transmission risk, our modeling suggests testing staff in household quarantine or all staff, depending on infection levels and testing capacities.
| S-EPMC7454477 | biostudies-literature
Project description:BACKGROUND: Mycobacterium tuberculosis is a particularly aggressive microorganism and the host's defense is based on the induction of cellular immunity, in which the creation of a granulomatous structure has an important role. METHODOLOGY: We present here a new 2D cellular automata model based on the concept of a multifunctional process that includes key factors such as the chemokine attraction of the cells; the role of innate immunity triggered by natural killers; the presence of neutrophils; apoptosis and necrosis of infected macrophages; the removal of dead cells by macrophages, which induces the production of foamy macrophages (FMs); the life cycle of the bacilli as a determinant for the evolution of infected macrophages; and the immune response. RESULTS: The results obtained after the inclusion of two degrees of tolerance to the inflammatory response triggered by the infection shows that the model can cover a wide spectrum, ranging from highly-tolerant (i.e. mice) to poorly-tolerant hosts (i.e. mini-pigs or humans). CONCLUSIONS: This model suggest that stopping bacillary growth at the onset of the infection might be difficult and the important role played by FMs in bacillary drainage in poorly-tolerant hosts together with apoptosis and innate lymphocytes. It also shows the poor ability of the cellular immunity to control the infection, provides a clear protective character to the granuloma, due its ability to attract a sufficient number of cells, and explains why an already infected host can be constantly reinfected.
| S-EPMC2944881 | biostudies-literature
Project description:Affymetrix GeneChip PM-MM probe pair is designed with the intension of measuring non-specific binding. Though the rationale behind the design id that a PM probe is expected to have a larger value than that of the MM probe, there are many exceptions in actual data. We gave an explanation for this inconsistency based on the assumption of functional states of a gene ‘ON/OFF’. Our hypothesis on PM-MM probe pairs is that the logarithmic of PM and MM values have the same distribution when gene is in OFF state. It means that the probability of MM > PM is expected to be equal to that of MM < PM for OFF genes. The validity of the hypothesis was given by inter-platform comparisons using common targets among three different types of platforms. Keywords: Affymetrix Gene Chip; Binomial distribution; Mathematical modeling; Oligonucleotide microarray; ON/OFF genes
2007-12-31 | GSE8353 | GEO
Project description:Benign paroxysmal positional vertigo has typically been reported to be the most common cause of post-traumatic dizziness. There is however paucity in the literature about other peripheral vestibular disorders post-head injury. This article provides an overview of other causes of non-positional dizziness post-head trauma from our large institutional experience. The UHN WSIB Neurotology database (n = 4291) between 1998 and 2018 was retrospectively studied for those head-injured workers presenting with non-positional peripheral vestibular disorders. All subjects had a detailed neurotological history and examination and vestibular testing including video nystagmography, video head impulse testing (or a magnetic scleral search coil study), vestibular-evoked myogenic potentials, and audiometry. Imaging studies included routine brain and high-resolution temporal bone CT scans and/or brain MRI. Based on a database of 4291 head-injured workers with dizziness, 244 were diagnosed with non-positional peripheral vertigo. Recurrent vestibulopathy (RV) was the most common cause of non-positional post-traumatic vertigo. The incidence of Meniere's disease in the post-traumatic setting did not appear greater than found in the general population. The clinical spectrum pertaining to recurrent vestibulopathy, Meniere's disease, delayed endolymphatic hydrops, drop attacks, superior semicircular canal dehiscence syndrome, and uncompensated peripheral vestibular loss are discussed.
| S-EPMC8648866 | biostudies-literature
Project description:Workplace bullying has been identified as a global problem because of its growing magnitude and the harmful effects in victims and organizations. Workplace vulnerability is a component of job precarious1ness that reflects insecurity, fear, and labor uncertainty. This paper aims to analyze the associations between the exposure to workplace vulnerability and psychological distress, and to explore the associations between exposure to workplace bullying and psychological distress, by sex. A cross-sectional and probabilistic survey was applied to a randomly-selected valid sample of 1995 salaried workers in three main metropolitan areas of Chile. Chi-square test and logistic regression models controlling for confounders were tested. Female workers were more exposed to workplace vulnerability and presented a higher prevalence of psychological distress. Among women who were vulnerable, one of three reported psychological distress (30.8%), which is higher than men (16.5%). Workers exposed to workplace vulnerability had a greater chance of workplace bullying, workers who perceived high workplace vulnerability had a greater chance of psychological distress, and workers exposed to workplace violence had a greater likelihood of psychological distress in comparison to those who were not exposed. Increasing employment security can reduce the perception of job vulnerability and help prevent the existence of workplace bullying. Additionally, occupational health protection policies should prevent, protect from, and intervene in workplace bullying as a precursor to mental health problems in Chile.
| S-EPMC6843971 | biostudies-literature