Mathematical modeling to inform the development of national guidelines on infant feeding in Thailand.
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ABSTRACT:
SUBMITTER: Chittchang U
PROVIDER: S-EPMC9303245 | 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:BackgroundMore than ever, it is crucial to make the best use of existing country data, and analytical tools for developing malaria control strategies as the heterogeneity in malaria risk within countries is increasing, and the available malaria control tools are expanding while large funding gaps exist. Global and local policymakers, as well as funders, increasingly recognize the value of mathematical modelling as a strategic tool to support decision making. This case study article describes the long-term use of modelling in close collaboration with the National Malaria Control Programme (NMCP) in Tanzania, the challenges encountered and lessons learned.Case descriptionIn Tanzania, a recent rebound in prevalence led to the revision of the national malaria strategic plan with interventions targeted to the malaria risk at the sub-regional level. As part of the revision, a mathematical malaria modelling framework for setting specific predictions was developed and used between 2016 and 2019 to (1) reproduce setting specific historical malaria trends, and (2) to simulate in silico the impact of future interventions. Throughout the project, multiple stakeholder workshops were attended and the use of mathematical modelling interactively discussed.EvaluationIn Tanzania, the model application created an interdisciplinary and multisectoral dialogue platform between modellers, NMCP and partners and contributed to the revision of the national malaria strategic plan by simulating strategies suggested by the NMCP. The uptake of the modelling outputs and sustained interest by the NMCP were critically associated with following factors: (1) effective sensitization to the NMCP, (2) regular and intense communication, (3) invitation for the modellers to participate in the strategic plan process, and (4) model application tailored to the local context.ConclusionEmpirical data analysis and its use for strategic thinking remain the cornerstone for evidence-based decision-making. Mathematical impact modelling can support the process both by unifying all stakeholders in one strategic process and by adding new key evidence required for optimized decision-making. However, without a long-standing partnership, it will be much more challenging to sensibilize programmes to the usefulness and sustained use of modelling and local resources within the programme or collaborating research institutions need to be mobilized.
| S-EPMC7053121 | biostudies-literature
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:To determine how infant feeding recommendations can maximize HIV-free survival (HFS) among HIV-exposed, uninfected African infants, balancing risks of breast milk-associated HIV infection with setting-specific risks of illness and death associated with replacement feeding.Validated mathematical model of HIV-exposed, uninfected infants, with published data from Africa.We projected 24-month HFS using combinations of: maternal CD4, antiretroviral drug availability, and relative risk of mortality among replacement-fed compared to breastfed infants ('RR-RF', range 1.0-6.0). For each combination, we identified the 'optimal' breastfeeding duration (0-24 months) maximizing HFS. We compared HFS under an 'individualized' approach, based on the above parameters, to the WHO 'public health approach' (12 months breastfeeding for all HIV-infected women).Projected HFS was 65-93%. When the value of RR-RF is 1.0, replacement feeding from birth maximized HFS. At a commonly reported RR-RF value (2.0), optimal breastfeeding duration was 3-12 months, depending on maternal CD4 and antiretroviral drug availability. As the value of RR-RF increased, optimal breastfeeding duration increased. Compared to the public health approach, an individualized approach improved absolute HFS by less than 1% if RR-RF value was 2.0-4.0, by 3% if RR-RF value was 1.0 or 6.0, and by greater amounts if access to antiretroviral drugs was limited.Tailoring breastfeeding duration to maternal CD4, antiretroviral drug availability, and local replacement feeding safety can optimize HFS among HIV-exposed infants. An individualized approach leads to moderate gains in HFS, but only when mortality risks from replacement feeding are very low or very high, or antiretroviral drug availability is limited. The WHO public health approach is beneficial in most resource-limited settings.
| S-EPMC4098721 | biostudies-literature
Project description:Food allergy is a significant issue worldwide, particularly in Westernised countries. There is no clear explanation why food allergy appears to have increased so rapidly in recent years, particularly in young children, hence ongoing research to identify effective primary prevention strategies. Food allergy prevention guidelines for health professionals have been developed based on existing clinical trial evidence for effective translation and implementation. As these guidelines underpin clinical practice, it is important to ensure robust processes of development. We conducted a systematic review to identify food allergy prevention guidelines for health professional use; to compare the recommendations made by the identified guideline documents; and to assess the quality of the identified guideline documents. We searched Medline, EMBASE, CINAHL, Scopus, Global Health and Guidelines International Network for the period 1990 to 13 August 2019, to identify articles referring to English-language food allergy prevention guidelines or the guidelines themselves. A grey literature search of Google Scholar and reference checking was also undertaken. The guidelines were compared for recommendation similarities and differences. An Appraisal Guidelines for Research and Evaluation (AGREE II) appraisal was undertaken to assess guideline quality. The electronic database search yielded 1121 publications and reference checking identified an additional 16 publications. After title, abstract and full text screening, data extraction was undertaken on 156 publications and with additional reference checking, 28 food allergy prevention guidelines and advice documents were identified. Comparison of the recommendations within the guidelines and advice documents indicated the greatest variation in recommendations related to exclusive breastfeeding and timing of solid food introduction. Eight of the 10 guidelines and none of the 18 advice documents met the quality threshold set by the reviewers. Overall, documents specifically termed "guidelines" scored better than advice documents when assessed using the AGREE II tool. Variation in recommendations may create confusion for health professionals and result in inconsistent advice being provided to parents, and less translation of the evidence into actual food allergy reduction in the population. Appraisal using the AGREE II tool identified that there is considerable room for improvement in the development of guidelines and advice documents for food allergy prevention. The AGREE II appraisal identified common areas of poorer quality development and/or documentation of processes to inform future guideline development. Based on this study, we recommend the use of validated guideline development tools, to direct food allergy prevention guideline review or development. Use of the AGREE II tool, to direct the review and development of guidelines, is very likely to improve guideline quality.
| S-EPMC8173304 | biostudies-literature
Project description:BackgroundNursing home residents and staff were included in the first phase of COVID-19 vaccination in the United States. Because the primary trial endpoint was vaccine efficacy (VE) against symptomatic disease, there are limited data on the extent to which vaccines protect against SARS-CoV-2 infection and the ability to infect others (infectiousness). Assumptions about VE against infection and infectiousness have implications for changes to infection prevention guidance for vaccinated populations, including testing strategies.MethodsWe use a stochastic agent-based SEIR model of a nursing home to simulate SARS-CoV-2 transmission. We model three scenarios, varying VE against infection, infectiousness, and symptoms, to understand the expected impact of vaccination in nursing homes, increasing staff vaccination coverage, and different screening testing strategies under each scenario.ResultsIncreasing vaccination coverage in staff decreases total symptomatic cases in the nursing home (among staff and residents combined) in each VE scenario. In scenarios with 50% and 90% VE against infection and infectiousness, increasing staff coverage reduces symptomatic cases among residents. If vaccination only protects against symptoms, and asymptomatic cases remain infectious, increased staff coverage increases symptomatic cases among residents. However, this is outweighed by the reduction in symptomatic cases among staff. Higher frequency testing-more than once weekly-is needed to reduce total symptomatic cases if the vaccine has lower efficacy against infection and infectiousness, or only protects against symptoms.ConclusionsEncouraging staff vaccination is not only important for protecting staff, but might also reduce symptomatic cases in residents if a vaccine confers at least some protection against infection or infectiousness.
| S-EPMC8244782 | biostudies-literature
Project description:Nursing home residents and staff were included in the first phase of COVID-19 vaccination in the United States. Because the primary trial endpoint was vaccine efficacy (VE) against symptomatic disease, there are limited data on the extent to which vaccines protect against SARS-CoV-2 infection and the ability to infect others (infectiousness). Assumptions about VE against infection and infectiousness have implications for possible changes to infection prevention guidance for vaccinated populations, including testing strategies. We use a stochastic agent-based SEIR model of a nursing home to simulate SARS-CoV-2 transmission. We model three scenarios, varying VE against infection, infectiousness, and symptoms, to understand the expected impact of vaccination in nursing homes, increasing staff vaccination coverage, and different screening testing strategies under each scenario. Increasing vaccination coverage in staff decreases total symptomatic cases in each scenario. When there is low VE against infection and infectiousness, increasing staff coverage reduces symptomatic cases among residents. If vaccination only protects against symptoms, but asymptomatic cases remain infectious, increased staff coverage increases symptomatic cases among residents through exposure to asymptomatic but infected staff. High frequency testing is needed to reduce total symptomatic cases if the vaccine has low efficacy against infection and infectiousness, or only protects against symptoms. Encouraging staff vaccination is not only important for protecting staff, but might also reduce symptomatic cases in residents if a vaccine confers at least some protection against infection or infectiousness. The extent of efficacy of SARS-CoV-2 vaccines against infection, infectiousness, or disease, impacts strategies for vaccination and testing in nursing homes. If vaccines confer some protection against infection or infectiousness, encouraging vaccination in staff may reduce symptomatic cases in residents.
| S-EPMC7941643 | biostudies-literature
Project description:Genome sequencing studies have uncovered the most frequent mutations in cancer and novel targets for therapy. While successful in many tumors, this approach has failed in others. Lethal infant ependymomas (Group A) lies at the far end of this spectrum with no recurrent focal genomic alterations, no recurrent somatic mutations, and no clear driver for targeted therapy. Despite a paucity of genetic aberrations, Group A ependymomas demonstrate widespread epigenetic alterations. We therefore sought to interrogate the oncogenic drivers of ependymoma by characterizing the enhancer landscapes of 30 primary tumors. Super enhancer (SE) mapping revealed novel ependymoma oncogenes such as PAX6, SKI, and FGFRL1 and uncovered subgroup specific SE lesions across ependymoma, specifically, in Group A such as PAX3, MEIS1, and IGF2BP1. Finally, we identified SE associated gene dependencies that maintain FGFR1 and WEE1 expression in ependymoma, demonstrating the utility of SE lesions to predict novel targets for cancer therapy.
2018-11-15 | GSE75017 | GEO
Project description:South Africa has the highest tuberculosis (TB) disease incidence rate in the world, and TB is the leading infectious cause of death. Decisions on, and funding for, TB prevention and care policies are decentralised to the provincial governments and therefore, tools to inform policy need to operate at this level. We describe the use of a mathematical model planning tool at provincial level in a high HIV and TB burden country, to estimate the impact on TB burden of achieving the 90-(90)-90 targets of the Stop TB Partnership Global Plan to End TB. "TIME Impact" is a freely available, user-friendly TB modelling tool. In collaboration with provincial TB programme staff, and the South African National TB Programme, models for three (of nine) provinces were calibrated to TB notifications, incidence, and screening data. Reported levels of TB programme activities were used as baseline inputs into the models, which were used to estimate the impact of scale-up of interventions focusing on screening, linkage to care and treatment success. All baseline models predicted a trend of decreasing TB incidence and mortality, consistent with recent data from South Africa. The projected impacts of the interventions differed by province and were greatly influenced by assumed current coverage levels. The absence of provincial TB burden estimates and uncertainty in current activity coverage levels were key data gaps. A user-friendly modelling tool allows TB burden and intervention impact projection at the sub-national level. Key sub-national data gaps should be addressed to improve the quality of sub-national model predictions.
| S-EPMC6347133 | biostudies-literature
Project description:OBJECTIVE:The Manitoba Infant Feeding Database (MIFD) is being piloted as a surveillance system leveraging infant vaccination visits as a point of contact to collect infant feeding data during the first year of life. The objective of this study was to assess data quality and acceptability of the MIFD as a sustainable population-based surveillance system. METHODS:Internal completeness and internal validity were measured to assess data quality. Internal completeness was defined as the number of completed data fields out of the total number of data fields. Internal validity was defined as the proportion of translation errors from one level of the system, the paper questionnaire, to the next, the electronic database. A survey assessed staff's acceptance of data collection and submission processes. RESULTS:A total of 947 records were reviewed. Data were 98.5% complete. Discrepancies were noted in 13.5% of data. The survey response rate was 78.4%. Nearly all respondents reported that the MIFD data collection tool was easy to use (96.6% agreed or strongly agreed). Whereas some challenges were identified, the majority were willing to continue with the MIFD data collection tool and process (93.1%). CONCLUSION:Results from this evaluation suggest that the MIFD data collection process worked well; however, data validation will require human resources. The MIFD approach provides a sustainable mechanism for collecting data on infant feeding for surveillance and research purposes.
| S-EPMC6964465 | biostudies-literature