A computational model of cardiomyocyte metabolism predicts unique reperfusion protocols capable of reducing cell damage during ischemia/reperfusion.

If a coronary blood vessel is occluded and the neighboring cardiomyocytes deprived of oxygen, subsequent reperfusion of the ischemic tissue can lead to oxidative damage due to excessive generation of reactive oxygen species. Cardiomyocytes and their mitochondria are the main energy producers and consumers of the heart, and their metabolic changes during ischemia seem to be a key driver of reperfusion injury. Here, we hypothesized that tracking changes in cardiomyocyte metabolism, such as oxygen and ATP concentrations, would help in identifying points of metabolic failure during ischemia and reperfusion. To track some of these changes continuously from the onset of ischemia through reperfusion, we developed a system of differential equations representing the chemical reactions involved in the production and consumption of 67 molecular species. This model was validated and used to identify conditions present during periods of critical transition in ischemia and reperfusion that could lead to oxidative damage. These simulations identified a range of oxygen concentrations that lead to reverse mitochondrial electron transport at complex I of the respiratory chain and a spike in mitochondrial membrane potential, which are key suspects in the generation of reactive oxygen species at the onset of reperfusion. Our model predicts that a short initial reperfusion treatment with reduced oxygen content (5% of physiological levels) could reduce the cellular damage from both of these mechanisms. This model should serve as an open-source platform to test ideas for treatment of the ischemia reperfusion process by following the temporal evolution of molecular concentrations in the cardiomyocyte.

Medical infrared thermal imaging of syringomyelia in the Cavalier King Charles Spaniel.

BACKGROUND: Medical infrared thermal imaging (MITI) is a non-invasive imaging modality gaining popularity in the veterinary field. An infrared camera captures emission of heat and creates a color map in the form of a thermogram. Topical heat emission is influenced by localized disease processes as a result of autonomic nervous system imbalance. The purpose of this study was to determine the utility of using thermography to identify changes in thermographic patterns associated with syringomyelia (SM) presence or absence in Cavalier King Charles Spaniels (CKCS) with Chiari-like Malformation (CLM). RESULTS: In CKCS with CLM, MITI was most accurate at a texture distance of 6. Optimizing imaging feature sets produced a highest accuracy of 69.9% (95% CI: 59.5-79.0%), with 81.3% sensitivity and 57.8% specificity for identifying the presence of syringomyelia. CONCLUSION: Thermographic image analysis is a successful non-invasive, diagnostic test that can be used to screen for syringomyelia presence in a CKCS with CLM.

Medical infrared thermal imaging of canine appendicular bone neoplasia.

BACKGROUND: Medical infrared thermal imaging (MITI) is a noninvasive imaging modality used in veterinary medicine as a screening tool for musculoskeletal and neurological disease processes. An infrared camera measures the surface body heat and produces a color map that represents the heat distribution. Local trauma or disease can impair the autonomic nervous system, which leads to changes in the local dermal microcirculation and subsequent alteration of surface body heat. Disruption of autonomic flow to the cutaneous vasculature at deeper levels can also result in asymmetric thermographic results. The purpose of this study was to evaluate surface temperature differences between limbs affected by bone neoplasia and their normal contralateral limbs. RESULTS: A statistically significant difference in average temperature was noted between regions of interest of the two groups (paired difference: 0.53 C° ± 0.14; P = 0.0005). In addition, pattern recognition analysis yielded a 75-100% success rate in lesion identification. CONCLUSIONS: Significant alterations noted with average temperature and thermographic patterns indicate that MITI can document discernible changes associated with the presence of canine appendicular bone tumors. While MITI cannot be used as the sole diagnostic tool for bone cancer, it can be used as a screening modality and may be applicable in early detection of cancer.

Modeling oxygen requirements in ischemic cardiomyocytes.

Heart disease remains the leading cause of death globally. Although reperfusion following myocardial ischemia can prevent death by restoring nutrient flow, ischemia/reperfusion injury can cause significant heart damage. The mechanisms that drive ischemia/reperfusion injury are not well understood; currently, few methods can predict the state of the cardiac muscle cell and its metabolic conditions during ischemia. Here, we explored the energetic sustainability of cardiomyocytes, using a model for cellular metabolism to predict the levels of ATP following hypoxia. We modeled glycolytic metabolism with a system of coupled ordinary differential equations describing the individual metabolic reactions within the cardiomyocyte over time. Reduced oxygen levels and ATP consumption rates were simulated to characterize metabolite responses to ischemia. By tracking biochemical species within the cell, our model enables prediction of the cell's condition up to the moment of reperfusion. The simulations revealed a distinct transition between energetically sustainable and unsustainable ATP concentrations for various energetic demands. Our model illustrates how even low oxygen concentrations allow the cell to perform essential functions. We found that the oxygen level required for a sustainable level of ATP increases roughly linearly with the ATP consumption rate. An extracellular O2 concentration of ∼0.007 mm could supply basic energy needs in non-beating cardiomyocytes, suggesting that increased collateral circulation may provide an important source of oxygen to sustain the cardiomyocyte during extended ischemia. Our model provides a time-dependent framework for studying various intervention strategies to change the outcome of reperfusion.

TENET: topological feature-based target characterization in signalling networks.

MOTIVATION: Target characterization for a biochemical network is a heuristic evaluation process that produces a characterization model that may aid in predicting the suitability of each molecule for drug targeting. These approaches are typically used in drug research to identify novel potential targets using insights from known targets. Traditional approaches that characterize targets based on their molecular characteristics and biological function require extensive experimental study of each protein and are infeasible for evaluating larger networks with poorly understood proteins. Moreover, they fail to exploit network connectivity information which is now available from systems biology methods. Adopting a network-based approach by characterizing targets using network features provides greater insights that complement these traditional techniques. To this end, we present Tenet (Target charactErization using NEtwork Topology), a network-based approach that characterizes known targets in signalling networks using topological features. RESULTS: Tenet first computes a set of topological features and then leverages a support vector machine-based approach to identify predictive topological features that characterizes known targets. A characterization model is generated and it specifies which topological features are important for discriminating the targets and how these features should be combined to quantify the likelihood of a node being a target. We empirically study the performance of Tenet from a wide variety of aspects, using several signalling networks from BioModels with real-world curated outcomes. Results demonstrate its effectiveness and superiority in comparison to state-of-the-art approaches. AVAILABILITY AND IMPLEMENTATION: Our software is available freely for non-commercial purposes from: https://sites.google.com/site/cosbyntu/softwares/tenet CONTACT: hechua@ntu.edu.sg or assourav@ntu.edu.sg SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

DualAligner: a dual alignment-based strategy to align protein interaction networks.

MOTIVATION: Given the growth of large-scale protein-protein interaction (PPI) networks obtained across multiple species and conditions, network alignment is now an important research problem. Network alignment performs comparative analysis across multiple PPI networks to understand their connections and relationships. However, PPI data in high-throughput experiments still suffer from significant false-positive and false-negatives rates. Consequently, high-confidence network alignment across entire PPI networks is not possible. At best, local network alignment attempts to alleviate this problem by completely ignoring low-confidence mappings; global network alignment, on the other hand, pairs all proteins regardless. To this end, we propose an alternative strategy: instead of full alignment across the entire network or completely ignoring low-confidence regions, we aim to perform highly specific protein-to-protein alignments where data confidence is high, and fall back on broader functional region-to-region alignment where detailed protein-protein alignment cannot be ascertained. The basic idea is to provide an alignment of multiple granularities to allow biological predictions at varying specificity. RESULTS: DualAligner performs dual network alignment, in which both region-to-region alignment, where whole subgraph of one network is aligned to subgraph of another, and protein-to-protein alignment, where individual proteins in networks are aligned to one another, are performed to achieve higher accuracy network alignments. Dual network alignment is achieved in DualAligner via background information provided by a combination of Gene Ontology annotation information and protein interaction network data. We tested DualAligner on the global networks from IntAct and demonstrated the superiority of our approach compared with state-of-the-art network alignment methods. We studied the effects of parameters in DualAligner in controlling the quality of the alignment. We also performed a case study that illustrates the utility of our approach. AVAILABILITY AND IMPLEMENTATION: http://www.cais.ntu.edu.sg/∼assourav/DualAligner/.

Habitual condom use across partner type and sexual position among younger gay and bisexual men: findings from New Zealand HIV behavioural surveillance 2006-2011.

OBJECTIVES: Our objectives were to investigate demographic and behavioural factors associated with condom use and to examine how habitual condom use was across partner types and sexual positions among younger men who have sex with men (YMSM), aged 16-29, surveyed in New Zealand. METHODS: We analysed the 2006-2011 national HIV behavioural surveillance data from YMSM who reported anal intercourse in four scenarios of partner type and sexual position: casual insertive, casual receptive, regular insertive and regular receptive. For each, respondents' condom use was classified as frequent (always/almost always) or otherwise, with associated factors identified with multivariate mixed-effect logistic regression. Habitual condom use across scenarios was examined using a latent variable technique that estimated the intraclass correlation coefficient (ICC). RESULTS: Frequent condom use was reported for 63.6% of 5153 scenarios reported from 2412 YMSM. Frequent use increased from boyfriend to fuckbuddy to casual partners. Infrequent use was associated with online recruitment, Pacific ethnicity, less education, HIV positivity, sex with women, having ≥20 sexual partners versus 1 and reporting insertive and receptive sexual positions. Frequent condom use was associated with having two to five sexual partners versus one and shorter regular partnerships. The ICC=0.865 indicated highly habitual patterns of use; habitual infrequent condom use was most prevalent with regular partners (53.3%) and habitual frequent condom use was most prevalent with casual partners (70.2%) and for either sexual position (50.5% and 49.1%). CONCLUSIONS: Habitual condom use among YMSM highlights the value of early, engaging and sustained condom promotion. Public health should provide better and more compelling condom education, training and promotion for YMSM.

DiffNet: automatic differential functional summarization of dE-MAP networks.

The study of genetic interaction networks that respond to changing conditions is an emerging research problem. Recently, Bandyopadhyay et al. (2010) proposed a technique to construct a differential network (dE-MAPnetwork) from two static gene interaction networks in order to map the interaction differences between them under environment or condition change (e.g., DNA-damaging agent). This differential network is then manually analyzed to conclude that DNA repair is differentially effected by the condition change. Unfortunately, manual construction of differential functional summary from a dE-MAP network that summarizes all pertinent functional responses is time-consuming, laborious and error-prone, impeding large-scale analysis on it. To this end, we propose DiffNet, a novel data-driven algorithm that leverages Gene Ontology (go) annotations to automatically summarize a dE-MAP network to obtain a high-level map of functional responses due to condition change. We tested DiffNet on the dynamic interaction networks following MMS treatment and demonstrated the superiority of our approach in generating differential functional summaries compared to state-of-the-art graph clustering methods. We studied the effects of parameters in DiffNet in controlling the quality of the summary. We also performed a case study that illustrates its utility.

In silico modeling of shear-stress-induced nitric oxide production in endothelial cells through systems biology.

Nitric oxide (NO) produced by vascular endothelial cells is a potent vasodilator and an antiinflammatory mediator. Regulating production of endothelial-derived NO is a complex undertaking, involving multiple signaling and genetic pathways that are activated by diverse humoral and biomechanical stimuli. To gain a thorough understanding of the rich diversity of responses observed experimentally, it is necessary to account for an ensemble of these pathways acting simultaneously. In this article, we have assembled four quantitative molecular pathways previously proposed for shear-stress-induced NO production. In these pathways, endothelial NO synthase is activated 1), via calcium release, 2), via phosphorylation reactions, and 3), via enhanced protein expression. To these activation pathways, we have added a fourth, a pathway describing actual NO production from endothelial NO synthase and its various protein partners. These pathways were combined and simulated using CytoSolve, a computational environment for combining independent pathway calculations. The integrated model is able to describe the experimentally observed change in NO production with time after the application of fluid shear stress. This model can also be used to predict the specific effects on the system after interventional pharmacological or genetic changes. Importantly, this model reflects the up-to-date understanding of the NO system, providing a platform upon which information can be aggregated in an additive way.

Hemodynamic shear stress characteristic of atherosclerosis-resistant regions promotes glycocalyx formation in cultured endothelial cells.

The endothelial glycocalyx, a glycosaminoglycan layer located on the apical surface of vascular endothelial cells, has been shown to be important for several endothelial functions. Previous studies have documented that the glycocalyx is highly abundant in the mouse common carotid region, where the endothelium is exposed to laminar shear stress, and it is resistant to atherosclerosis. In contrast, the glycocalyx is scarce or absent in the mouse internal carotid sinus region, an area exposed to nonlaminar shear stress and highly susceptible to atherosclerosis. On the basis of these observations, we hypothesized that the expression of components of the endothelial glycocalyx is differentially regulated by distinct hemodynamic environments. To test this hypothesis, human endothelial cells were exposed to shear stress waveforms characteristic of atherosclerosis-resistant or atherosclerosis-susceptible regions of the human carotid, and the expression of several components of the glycocalyx was assessed. These experiments revealed that expression of several components of the endothelial glycocalyx is differentially regulated by distinct shear stress waveforms. Interestingly, we found that heparan sulfate expression is increased and evenly distributed on the apical surface of endothelial cells exposed to the atheroprotective waveform and is irregularly present in cells exposed to the atheroprone waveform. Furthermore, expression of a heparan sulfate proteoglycan, syndecan-1, is also differentially regulated by the two waveforms, and its suppression mutes the atheroprotective flow-induced cell surface expression of heparan sulfate. Collectively, these data link distinct hemodynamic environments to the differential expression of critical components of the endothelial glycocalyx.

FACETS: multi-faceted functional decomposition of protein interaction networks.

MOTIVATION: The availability of large-scale curated protein interaction datasets has given rise to the opportunity to investigate higher level organization and modularity within the protein-protein interaction (PPI) network using graph theoretic analysis. Despite the recent progress, systems level analysis of high-throughput PPIs remains a daunting task because of the amount of data they present. In this article, we propose a novel PPI network decomposition algorithm called FACETS in order to make sense of the deluge of interaction data using Gene Ontology (GO) annotations. FACETS finds not just a single functional decomposition of the PPI network, but a multi-faceted atlas of functional decompositions that portray alternative perspectives of the functional landscape of the underlying PPI network. Each facet in the atlas represents a distinct interpretation of how the network can be functionally decomposed and organized. Our algorithm maximizes interpretative value of the atlas by optimizing inter-facet orthogonality and intra-facet cluster modularity. RESULTS: We tested our algorithm on the global networks from IntAct, and compared it with gold standard datasets from MIPS and KEGG. We demonstrated the performance of FACETS. We also performed a case study that illustrates the utility of our approach. SUPPLEMENTARY INFORMATION: Supplementary data are available at the Bioinformatics online. AVAILABILITY: Our software is available freely for non-commercial purposes from: http://www.cais.ntu.edu.sg/~assourav/Facets/

Burden of illness and factors associated with duration of illness in clinical campylobacteriosis.

A population-based study investigated the burden of illness, including the duration of illness associated with laboratory-confirmed cases of campylobacteriosis in two health unit areas. Questionnaire data were collected for 250 cases. The median duration of illness was 8 days and 66% of cases reported symptoms of moderate severity or greater. A Cox proportional hazards model identified antimicrobial use factors associated with a significantly increased rate of symptom resolution (shorter duration of illness): macrolides for less than the recommended number of days, ciprofloxacin for at least 3 days, and antimicrobials not recommended for campylobacteriosis. The impact of antimicrobial use was consistent regardless of when, during the course of illness, the antimicrobial use began. The effectiveness of ciprofloxacin in these results may be due to the low prevalence of resistance to ciprofloxacin in isolates from this study. The effect of antimicrobials not recommended for campylobacteriosis should be further investigated.

Plasmin triggers a switch-like decrease in thrombospondin-dependent activation of TGF-ß1.

Transforming growth factor-ß1 (TGF-ß1) is a potent regulator of extracellular matrix production, wound healing, differentiation, and immune response, and is implicated in the progression of fibrotic diseases and cancer. Extracellular activation of TGF-ß1 from its latent form provides spatiotemporal control over TGF-ß1 signaling, but the current understanding of TGF-ß1 activation does not emphasize cross talk between activators. Plasmin (PLS) and thrombospondin-1 (TSP1) have been studied individually as activators of TGF-ß1, and in this work we used a systems-level approach with mathematical modeling and in vitro experiments to study the interplay between PLS and TSP1 in TGF-ß1 activation. Simulations and steady-state analysis predicted a switch-like bistable transition between two levels of active TGF-ß1, with an inverse correlation between PLS and TSP1. In particular, the model predicted that increasing PLS breaks a TSP1-TGF-ß1 positive feedback loop and causes an unexpected net decrease in TGF-ß1 activation. To test these predictions in vitro, we treated rat hepatocytes and hepatic stellate cells with PLS, which caused proteolytic cleavage of TSP1 and decreased activation of TGF-ß1. The TGF-ß1 activation levels showed a cooperative dose response, and a test of hysteresis in the cocultured cells validated that TGF-ß1 activation is bistable. We conclude that switch-like behavior arises from natural competition between two distinct modes of TGF-ß1 activation: a TSP1-mediated mode of high activation and a PLS-mediated mode of low activation. This switch suggests an explanation for the unexpected effects of the plasminogen activation system on TGF-ß1 in fibrotic diseases in vivo, as well as novel prognostic and therapeutic approaches for diseases with TGF-ß dysregulation.

OREMPdb: a semantic dictionary of computational pathway models.

BACKGROUND: The information coming from biomedical ontologies and computational pathway models is expanding continuously: research communities keep this process up and their advances are generally shared by means of dedicated resources published on the web. In fact, such models are shared to provide the characterization of molecular processes, while biomedical ontologies detail a semantic context to the majority of those pathways. Recent advances in both fields pave the way for a scalable information integration based on aggregate knowledge repositories, but the lack of overall standard formats impedes this progress. Indeed, having different objectives and different abstraction levels, most of these resources "speak" different languages. Semantic web technologies are here explored as a means to address some of these problems. METHODS: Employing an extensible collection of interpreters, we developed OREMP (Ontology Reasoning Engine for Molecular Pathways), a system that abstracts the information from different resources and combines them together into a coherent ontology. Continuing this effort we present OREMPdb; once different pathways are fed into OREMP, species are linked to the external ontologies referred and to reactions in which they participate. Exploiting these links, the system builds species-sets, which encapsulate species that operate together. Composing all of the reactions together, the system computes all of the reaction paths from-and-to all of the species-sets. RESULTS: OREMP has been applied to the curated branch of BioModels (2011/04/15 release) which overall contains 326 models, 9244 reactions, and 5636 species. OREMPdb is the semantic dictionary created as a result, which is made of 7360 species-sets. For each one of these sets, OREMPdb links the original pathway and the link to the original paper where this information first appeared.

FUSE: a profit maximization approach for functional summarization of biological networks.

BACKGROUND: The availability of large-scale curated protein interaction datasets has given rise to the opportunity to investigate higher level organization and modularity within the protein interaction network (PPI) using graph theoretic analysis. Despite the recent progress, systems level analysis of PPIS remains a daunting task as it is challenging to make sense out of the deluge of high-dimensional interaction data. Specifically, techniques that automatically abstract and summarize PPIS at multiple resolutions to provide high level views of its functional landscape are still lacking. We present a novel data-driven and generic algorithm called FUSE (Functional Summary Generator) that generates functional maps of a PPI at different levels of organization, from broad process-process level interactions to in-depth complex-complex level interactions, through a pro t maximization approach that exploits Minimum Description Length (MDL) principle to maximize information gain of the summary graph while satisfying the level of detail constraint. RESULTS: We evaluate the performance of FUSE on several real-world PPIS. We also compare FUSE to state-of-the-art graph clustering methods with GO term enrichment by constructing the biological process landscape of the PPIS. Using AD network as our case study, we further demonstrate the ability of FUSE to quickly summarize the network and identify many different processes and complexes that regulate it. Finally, we study the higher-order connectivity of the human PPI. CONCLUSION: By simultaneously evaluating interaction and annotation data, FUSE abstracts higher-order interaction maps by reducing the details of the underlying PPI to form a functional summary graph of interconnected functional clusters. Our results demonstrate its effectiveness and superiority over state-of-the-art graph clustering methods with GO term enrichment.

Vertebral stabilisation for thoracolumbar vertebral instability associated with cranial and caudal articular process anomalies in pugs: Seven cases (2010-2019).

OBJECTIVES: To describe the diagnostic findings, surgical technique and outcomes in seven pugs with thoracolumbar vertebral instability due to articular process anomalies. MATERIALS AND METHODS: Records (2010 to 2019) of pugs with thoracolumbar vertebral instability associated with articular process anomalies that underwent decompressive laminectomy and vertebral stabilisation were reviewed. Data on preoperative and postoperative neurologic status, diagnostic findings, surgical techniques and outcomes were retrieved. RESULTS: Seven dogs were presented with ambulatory or non-ambulatory paraparesis. Caudal articular process anomalies (three dogs) and concomitant cranial and caudal articular process anomalies (four dogs) were noted. Myelography (six dogs) or magnetic resonance imaging (one dog) showed none to severe spinal cord compression. Dynamic myelography in six dogs demonstrated nine distinct sites of spinal cord dimension reduction positioned in extension and/or flexion (mean reduction: 16.0%, range: 8.5 to 24.0%). These dynamic compressions were located at sites with articular process anomalies (seven sites) and sites with no articular process anomalies (two sites). Vertebral instability was confirmed by intraoperative spinal manipulation in all dogs. All dogs remained ambulatory with improved (five dogs) or static (two dogs) neurological deficits at the last follow-up (median: 16 months; range: 1.5 to 66 months). CLINICAL SIGNIFICANCE: Dynamic myelography and/or intraoperative spinal manipulation demonstrated vertebral instabilities at sites with or without articular process anomalies on imaging. Decompressive laminectomy with vertebral stabilisation resulted in long-term neurological improvement in most dogs.

Steady states and dynamics of urokinase-mediated plasmin activation in silico and in vitro.

Plasmin (PLS) and urokinase-type plasminogen activator (UPA) are ubiquitous proteases that regulate the extracellular environment. Although they are secreted in inactive forms, they can activate each other through proteolytic cleavage. This mutual interplay creates the potential for complex dynamics, which we investigated using mathematical modeling and in vitro experiments. We constructed ordinary differential equations to model the conversion of precursor plasminogen into active PLS, and precursor urokinase (scUPA) into active urokinase (tcUPA). Although neither PLS nor UPA exhibits allosteric cooperativity, modeling showed that cooperativity occurred at the system level because of substrate competition. Computational simulations and bifurcation analysis predicted that the system would be bistable over a range of parameters for cooperativity and positive feedback. Cell-free experiments with recombinant proteins tested key predictions of the model. PLS activation in response to scUPA stimulus was found to be cooperative in vitro. Finally, bistability was demonstrated in vitro by the presence of two significantly different steady-state levels of PLS activation for the same levels of stimulus. We conclude that ultrasensitive, bistable activation of UPA-PLS is possible in the presence of substrate competition. An ultrasensitive threshold for activation of PLS and UPA would have ramifications for normal and disease processes, including angiogenesis, metastasis, wound healing, and fibrosis.

A computational model of mutual antagonism in the mechano-signaling network of RhoA and nitric oxide.

BACKGROUND: RhoA is a master regulator of cytoskeletal contractility, while nitric oxide (NO) is a master regulator of relaxation, e.g., vasodilation. There are multiple forms of cross-talk between the RhoA/ROCK pathway and the eNOS/NO/cGMP pathway, but previous work has not studied their interplay at a systems level. Literature review suggests that the majority of their cross-talk interactions are antagonistic, which motivates us to ask whether the RhoA and NO pathways exhibit mutual antagonism in vitro, and if so, to seek the theoretical implications of their mutual antagonism. RESULTS: Experiments found mutual antagonism between RhoA and NO in epithelial cells. Since mutual antagonism is a common motif for bistability, we sought to explore through theoretical simulations whether the RhoA-NO network is capable of bistability. Qualitative modeling showed that there are parameters that can cause bistable switching in the RhoA-NO network, and that the robustness of the bistability would be increased by positive feedback between RhoA and mechanical tension. CONCLUSIONS: We conclude that the RhoA-NO bistability is robust enough in silico to warrant the investment of further experimental testing. Tension-dependent bistability has the potential to create sharp concentration gradients, which could contribute to the localization and self-organization of signaling domains during cytoskeletal remodeling and cell migration.

The REFLECT statement: methods and processes of creating reporting guidelines for randomized controlled trials for livestock and food safety.

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 two-day consensus meeting was held on November 18-19, 2008 in Chicago, Ill, United States of America, 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 (LFS) 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.