An evidence based ranking system for multiple studies designs for informing public policy. An example using interventions associated with Salmonella in swine.

Using the association between feed characteristics and Salmonella prevalence we will present an approach to combining data with multiple outcomes from multiple studies designs. The approach may be a method of informing policy makers in the area of food safety when a large amount of heterogeneous literature is available about a topic. The procedure for a systematic review of the literature was followed until the synthesis component. However, to combine the evidence we modified of the FDA Interim Evidence Ranking System for Scientific Information. Each study was characterized as one of 5 study design types based on evidentiary value. After classification by evidentiary value, the studies were considered collectively to rate the strength of the body of evidence based on quantity and consistency. The quantity ranking considered the number of studies, the number of individuals studied and generalizability to the target population. The consistency ranking considered whether studies with different designs reported similar findings. After ranking the body of evidence, an overall ranking was assigned for the strength of the evidence. The final ranking system had four levels. For example, the highest rank of scientific evidence, reflects a high level of comfort among qualified scientists that the association/relationship is scientifically valid. This level ranked relationship would be considered to have a very low probability of significant new data overturning the conclusion that the relationship is valid or significantly changing the nature of the relationship

Interventions associated with feeding management practices and feed characteristics, and measures of Salmonella prevalence in live and slaughtered swine: A systematic review and summation of evidence

The aim of this review is to evaluate and summarize the evidence for associations between feeding management practices and feed characteristics, and Salmonella prevalence in swine, which may represent opportunities for interventions. Salmonella prevalence in the reviewed literature was measured either by culture or by the presence of antibodies. A systematic review of the area was conducted, the goal being to minimize the impact of bias. Systematic reviews include an assessment of the quality of studies and exclusion of studies that fail to meet standards for published material. The review evaluated evidence for an association between feed withdrawal from swine prior to slaughter, acidification of feed, heat treatment of feed, pellet vs. mash, course vs fine grind, and wet vs. dry. A large number of intervention studies were excluded from the review because they failed to report design features designed to limit the introduction of bias such as randomization and blinding. The majority of studies included were cross sectional studies, however these failed to provide strong evidence of an association because of the potential for confounding and the failure to document a temporal association between exposure to the risk factor and the outcome. The review concluded that title strongest body of work was available for pelleted feed and dry feed, however there was still uncertainty about the situations were this association may be effective. The conclusion was that there should be a low level of comfort among qualified scientists that the claimed association/relationship is scientifically valid. This ranking is primarily based on moderate to low quality studies, or insufficient numbers of tested individuals or herds, resulting in a low degree of confidence that results could be extrapolated to the target population

Vaccination against Salmonella and the association with measures of Salmonella prevalence in live and slaughtered swine - A systematic review

A systematic review was conducted to evaluate the effectiveness of vaccination to reduce Salmonella prevalence in market weight finisher swine. To identify relevant studies, online databases and selected conference proceedings were searched. Two reviewers independently assessed the relevance screening and methodological quality of studies. Data of characteristics of study population, intervention, outcome, statistical analysis, and results were extracted. Four clinical trials and 21 challenge studies were identified for the final review as they described vaccination to reduce Salmonella in swine Present evidence suggests that vaccination is associated with reduced Salmonella prevalence in swine

Atmospheric composition and climate impacts of a future hydrogen economy

Hydrogen is expected to play a key role in the global energy transition to net zero emissions in many scenarios. However, fugitive emissions of hydrogen into the atmosphere during its production, storage, distribution and use could reduce the climate benefit and also have implications for air quality. Here we explore the atmospheric composition and climate impacts of increases in atmospheric hydrogen abundance using the UKESM1 chemistry-climate model. We find that increases in hydrogen result in increases in methane, tropospheric ozone and stratospheric water vapour, resulting in a positive radiative forcing. However, some of the impacts of hydrogen leakage are partially offset by potential reductions in emissions of methane, carbon monoxide, nitrogen oxides and volatile organic compounds from the consumption of fossil fuels. We derive a new methodology for determining indirect Global Warming Potentials from steady-state simulations which is applicable to both shorter-lived species and those with intermediate and longer lifetimes, such as hydrogen. Using this methodology, we determine a 100-year Global Warming Potential for hydrogen of 12 &plusmn; 6. To maximise the benefit of hydrogen as an energy source, emissions associated with hydrogen leakage and emissions of the ozone precursor gases need to be minimised.</p

Quantifying Drug-Induced Bone Marrow Toxicity Using a Novel Haematopoiesis Systems Pharmacology Model.

Haematological toxicity associated with cancer therapeutics is monitored by changes in blood cell count, and their primary effect is on proliferative progenitors in the bone marrow. Using observations in rat bone marrow and blood, we characterize a mathematical model that comprises cell proliferation and differentiation of the full haematopoietic phylogeny, with interacting feedback loops between lineages in homeostasis as well as following carboplatin exposure. We accurately predicted the temporal dynamics of several mature cell types related to carboplatin-induced bone marrow toxicity and identified novel insights into haematopoiesis. Our model confirms a significant degree of plasticity within bone marrow cells, with the number and type of both early progenitors and circulating cells affecting cell balance, via feedback mechanisms, through fate decisions of the multipotent progenitors. We also demonstrated cross-species translation of our predictions to patients, applying the same core model structure and considering differences in drug-dependent and physiology-dependent parameters

A role for Dicer in immune regulation

Micro RNAs (miRNAs) regulate gene expression at the posttranscriptional level. Here we show that regulatory T (T reg) cells have a miRNA profile distinct from conventional CD4 T cells. A partial T reg cell–like miRNA profile is conferred by the enforced expression of Foxp3 and, surprisingly, by the activation of conventional CD4 T cells. Depleting miRNAs by eliminating Dicer, the RNAse III enzyme that generates functional miRNAs, reduces T reg cell numbers and results in immune pathology. Dicer facilitates, in a cell-autonomous fashion, the development of T reg cells in the thymus and the efficient induction of Foxp3 by transforming growth factor β. These results suggest that T reg cell development involves Dicer-generated RNAs

Phytoplankton Cell Size Reduction in Response to Warming Mediated by Nutrient Limitation

Shrinking of body size has been proposed as one of the universal responses of organisms to global climate warming. Using phytoplankton as an experimental model system has supported the negative effect of warming on body-size, but it remains controversial whether the size reduction under increasing temperatures is a direct temperature effect or an indirect effect mediated over changes in size selective grazing or enhanced nutrient limitation which should favor smaller cell-sizes. Here we present an experiment with a factorial combination of temperature and nutrient stress which shows that most of the temperature effects on phytoplankton cell size are mediated via nutrient stress. This was found both for community mean cell size and for the cell sizes of most species analyzed. At the highest level of nutrient stress, community mean cell size decreased by 46% per degrees C, while it decreased only by 4.7% at the lowest level of nutrient stress. Individual species showed qualitatively the same trend, but shrinkage per degrees C was smaller. Overall, our results support the hypothesis that temperature effects on cell size are to a great extent mediated by nutrient limitation. This effect is expected to be exacerbated under field conditions, where higher temperatures of the surface waters reduce the vertical nutrient transport

The REFLECT Statement: Methods and Processes of Creating Reporting Guidelines for Randomized Controlled Trials for Livestock and Food Safety by Modifying the CONSORT Statement

The conduct of randomized controlled trials in livestock with production, health and food-safety outcomes presents unique challenges that may not be adequately reported in trial reports. The objective of this project was to modify the CONSORT (Consolidated Standards of Reporting Trials) statement to reflect the unique aspects of reporting these livestock trials. A 2-day consensus meeting was held on 18–19 November 2008 in Chicago, IL, USA, to achieve the objective. Prior to the meeting, a Web-based survey was conducted to identify issues for discussion. The 24 attendees were biostatisticians, epidemiologists, food-safety researchers, livestock-production specialists, journal editors, assistant editors and associate editors. Prior to the meeting, the attendees completed a Web-based survey indicating which CONSORT statement items may need to be modified to address unique issues for livestock trials. The consensus meeting resulted in the production of the REFLECT (Reporting Guidelines for Randomized Control Trials) statement for livestock and food safety and 22-item checklist. Fourteen items were modified from the CONSORT checklist and an additional sub-item was proposed to address challenge trials. The REFLECT statement proposes new terminology, more consistent with common usage in livestock production, to describe study subjects. Evidence was not always available to support modification to or inclusion of an item. The use of the REFLECT statement, which addresses issues unique to livestock trials, should improve the quality of reporting and design for trials reporting production, health and food-safety outcomes