Effective contact investigations are paramount to the success of tuberculosis (TB) control in high-risk communities in low TB prevalence countries. National and international guidelines on TB contact ...investigations are available and vary widely on recommendations. Because of the limitations of traditional contact tracing, new approaches are under investigation, and in some cases in use, to ensure effective TB control in those persons and communities at greatest risk. These non-traditional approaches include the use of social network analysis, geographic information systems and genomics, in addition to the widespread use of genotyping, to better understand TB transmission. Detailed guidelines for the use of these methods during TB outbreaks and in routine follow-up of TB contact investigations do not currently exist despite evidence that they may improve TB control efforts. It remains unclear as to when it is most appropriate and effective to use a network-informed approach alone, or in combination with other methodologies as well as the extent of data collection required to inform practice. TB controllers should consider developing the capacity to facilitate the systematic collection, analysis, and interpretation of contact investigation data using such novel methodologies, particularly in high-risk communities. Further investigation should focus on questionnaire development and adaptation, electronic data management and infrastructure, development of local capability and consultant expertise, and the use of coordinated approaches, including deployment strategies and evaluation.
Summary
Reasons for performing the study: Endotoxaemia contributes to morbidity and mortality in horses with colic due to inflammatory cascade activation. Effective therapeutic interventions are ...limited for these horses. Ethyl pyruvate (EP), an anti‐inflammatory agent that alters the expression of proinflammatory cytokines, improved survival and organ function in sepsis and gastrointestinal injury in rodents and swine. Therapeutic efficacy of EP is unknown in endotoxaemic horses.
Objectives: Determine the effects of EP on signs of endotoxaemia and expression of proinflammatory cytokines following administration of lipopolysaccharide (LPS) in horses.
Methods: Horses received 30 ng/kg bwt LPS in saline to induce signs of endotoxaemia. Next, horses received lactated Ringer's solution (LRS), (n = 6), 150 mg/kg bwt EP in LRS, (n = 6), or 1.1 mg/kg bwt flunixin meglumine (FM), (n = 6). Controls received saline followed by LRS (n = 6). Physical examinations, behaviour pain scores and blood for clinical pathological testing and gene expression were obtained at predetermined intervals for 24 h.
Results: Lipopolysaccharide infusion produced clinical and clinicopathological signs of endotoxaemia and increased expression of tumour necrosis factor alpha (TNFα), interleukin 6 (IL‐6) and IL‐8 (P<0.001) compared with controls. Leucopenia and neutropenia occurred in all horses that received LPS. Horses treated with EP and FM had significantly (P<0.0001) reduced pain scores compared with horses receiving LPS followed by LRS. Flunixin meglumine was significantly more effective at ameliorating fever compared with EP. Both EP and FM significantly diminished TNFα expression. Ethyl pyruvate significantly decreased, but FM significantly increased, IL‐6 expression. Neither EP nor FM altered IL‐8 expression.
Conclusions and potential relevance: Ethyl pyruvate administered following LPS diminished the clinical effects of endotoxaemia and decreased proinflammatory gene expression in horses. Ethyl pyruvate suppressed expression of proinflammatory cytokines better than FM. However, FM was a superior anti‐pyretic compared with EP. Ethyl pyruvate may have therapeutic applications in endotoxaemic horses.
Health care and public health professionals rely on accurate, real-time monitoring of infectious diseases for outbreak preparedness and response. Early detection of outbreaks is improved by systems ...that are comprehensive and specific with respect to the pathogen but are rapid in reporting the data. It has proven difficult to implement these requirements on a large scale while maintaining patient privacy.
The aim of this study was to demonstrate the automated export, aggregation, and analysis of infectious disease diagnostic test results from clinical laboratories across the United States in a manner that protects patient confidentiality. We hypothesized that such a system could aid in monitoring the seasonal occurrence of respiratory pathogens and may have advantages with regard to scope and ease of reporting compared with existing surveillance systems.
We describe a system, BioFire Syndromic Trends, for rapid disease reporting that is syndrome-based but pathogen-specific. Deidentified patient test results from the BioFire FilmArray multiplex molecular diagnostic system are sent directly to a cloud database. Summaries of these data are displayed in near real time on the Syndromic Trends public website. We studied this dataset for the prevalence, seasonality, and coinfections of the 20 respiratory pathogens detected in over 362,000 patient samples acquired as a standard-of-care testing over the last 4 years from 20 clinical laboratories in the United States.
The majority of pathogens show influenza-like seasonality, rhinovirus has fall and spring peaks, and adenovirus and the bacterial pathogens show constant detection over the year. The dataset can also be considered in an ecological framework; the viruses and bacteria detected by this test are parasites of a host (the human patient). Interestingly, the rate of pathogen codetections, on average 7.94% (28,741/362,101), matches predictions based on the relative abundance of organisms present.
Syndromic Trends preserves patient privacy by removing or obfuscating patient identifiers while still collecting much useful information about the bacterial and viral pathogens that they harbor. Test results are uploaded to the database within a few hours of completion compared with delays of up to 10 days for other diagnostic-based reporting systems. This work shows that the barriers to establishing epidemiology systems are no longer scientific and technical but rather administrative, involving questions of patient privacy and data ownership. We have demonstrated here that these barriers can be overcome. This first look at the resulting data stream suggests that Syndromic Trends will be able to provide high-resolution analysis of circulating respiratory pathogens and may aid in the detection of new outbreaks.
The objectives of this study were to determine rates of prenatal care utilization in Winnipeg, Manitoba, Canada from 1991 to 2000; to compare two indices of prenatal care utilization in identifying ...the proportion of the population receiving inadequate prenatal care; to determine the association between inadequate prenatal care and adverse pregnancy outcomes (preterm birth, low birth weight LBW, and small-for-gestational age SGA), using each of the indices; and, to assess whether or not, and to what extent, gestational age modifies this association.
We conducted a population-based study of women having a hospital-based singleton live birth from 1991 to 2000 (N = 80,989). Data sources consisted of a linked mother-baby database and a physician claims file maintained by Manitoba Health. Rates of inadequate prenatal care were calculated using two indices, the R-GINDEX and the APNCU. Logistic regression analysis was used to determine the association between inadequate prenatal care and adverse pregnancy outcomes. Stratified analysis was then used to determine whether the association between inadequate prenatal care and LBW or SGA differed by gestational age.
Rates of inadequate/no prenatal care ranged from 8.3% using APNCU to 8.9% using R-GINDEX. The association between inadequate prenatal care and preterm birth and LBW varied depending on the index used, with adjusted odds ratios (AOR) ranging from 1.0 to 1.3. In contrast, both indices revealed the same strength of association of inadequate prenatal care with SGA (AOR 1.4). Both indices demonstrated heterogeneity (non-uniformity) across gestational age strata, indicating the presence of effect modification by gestational age.
Selection of a prenatal care utilization index requires careful consideration of its methodological underpinnings and limitations. The two indices compared in this study revealed different patterns of utilization of prenatal care, and should not be used interchangeably. Use of these indices to study the association between utilization of prenatal care and pregnancy outcomes affected by the duration of pregnancy should be approached cautiously.
Heat-resistant spores of Clostridium perfringens may germinate and multiply in cooked meat and poultry products when the rate and extent of cooling does not occur in a timely manner. Therefore, six ...cooling models (PMP 7.0 broth model; PMIP uncured beef, chicken, and pork models; Smith-Schaffner version 3; and UK IFR ComBase Perfringens Predictor) were evaluated for relative performance in predicting growth of C. perfringens under dynamic temperature conditions encountered during cooling of cooked, uncured meat and poultry products. The predicted growth responses from the models were extensively compared with those observed in food. Data from 188 time-temperature cooling profiles (176 for single-rate exponential cooling and 12 for dual-rate exponential cooling) were collected from 17 independent sources (16 peer-reviewed publications and one report) for model evaluation. Data were obtained for a variety of cooked products, including meat and poultry slurries, ground meat and poultry products with and without added ingredients (e.g., potato starch, sodium triphosphate, and potassium tetrapyrophosphate), and processed products such as ham and roast beef. Performance of the models was evaluated using three sets of criteria, and accuracy was defined within a 1- to 2-log range. The percentages of accurate, fail-safe, or fail-dangerous predictions for each cooling model differed depending on which criterion was used to evaluate the data set. Nevertheless, the combined percentages of accurate and fail-safe predictions based on the three performance criteria were 34.66 to 42.61% for the PMP 7.0 beef broth model, 100% for the PMIP cooling models for uncured beef, uncured pork and uncured chicken, 80.11 to 93.18% for the Smith-Schaffner cooling model, and 74.43 to 85.23% for the UK IFR ComBase Perfringens Predictor model during single-rate exponential chilling. Except for the PMP 7.0 broth model, the other five cooling models (PMIP, Smith-Schaffner, and UK IFR ComBase) are useful and reliable tools that food processors and regulatory agencies can use to evaluate the safety of cooked or heat-treated uncured meat and poultry products exposed to cooling deviations or to develop customized cooling schedules.
Recent advances in single-cell RNA-sequencing (scRNA-seq) in combination with CRISPR/Cas9 technologies have enabled the development of methods for large-scale perturbation studies with ...transcriptional readouts. These methods are highly scalable and have the potential to provide a wealth of information on the biological networks that underlie cellular response.
Here we discuss how to overcome several key challenges to generate and analyse data for the confident reconstruction of models of the underlying cellular network. Some challenges are generic, and apply to analysing any single-cell transcriptomic data, while others are specific to combined single-cell CRISPR/Cas9 data, in particular barcode swapping, knockdown efficiency, multiplicity of infection and potential confounding factors. We also provide a curated collection of published data sets to aid the development of analysis strategies.
Finally, we discuss several network reconstruction approaches, including co-expression networks and Bayesian networks, as well as their limitations, and highlight the potential of Nested Effects Models for network reconstruction from scRNA-seq data.
This article is part of a Special Issue entitled: Transcriptional Profiles and Regulatory Gene Networks edited by Dr. Dr. Federico Manuel Giorgi and Dr. Shaun Mahony.
•Recent single-cell RNA technologies combined with CRISPR/Cas9 enable large scale perturbation studies linked to transcriptional readouts.•Discussion of the key challenges of network reconstruction on these data and how to overcome them•Overview of current network reconstruction approaches, including their advantages and limitations•Curated collection of key data for the development of analysis strategies
Background: While smear positive patients with tuberculosis (TB) are considered more infectious than smear negative patients, the latter can also transmit TB. Methods: In a molecular epidemiology ...study of 791 patients in the Greater Vancouver regional district, the number of episodes of TB transmission from two groups of smear negative clustered patients by RFLP (assumed to be involved in recent transmission) was estimated after assessing for potential bias. Group 1 (n = 79) included patients with pulmonary TB or pulmonary + extrapulmonary disease (PTB or PTB+EPTB); group 2 (n = 129) included all patients in group 1 + extrapulmonary cases alone. Results: In the total sample the mean (SD) age was 51 (21) years, 54.3% were male, and 17.0% of patients were clustered. Compared with smear negative patients, smear positive patients were more likely to be in a cluster (OR = 2.0, 95% CI 1.1 to 3.6) and to have had a history of ethanol abuse (OR = 2.7, 95% CI 1.0 to 6.7), diabetes mellitus (OR = 2.8, 95% CI 1.1 to 7.0), injection drug use (OR = 3.1, 95% CI 1.1 to 8.3), and to have had a previous hospital admission (OR = 8.5, 95% CI 5.1 to 14.0). The proportion of episodes of transmission from smear negative clustered patients ranged from 17.3% to 22.2% in group 1 and from 25% to 41% in group 2. Conclusion: In Greater Vancouver, smear negative cases appear responsible for at least one sixth of culture positive episodes of TB transmission.
Exposing fish to air following capture influences postrelease survival and behavior. Air exposure causes acute hypoxia and physical damage to the gill lamellae, resulting in physiological stress and ...physical damage that increases with air exposure duration. Air exposure duration is a relevant and easily quantified metric for both fishers and managers and can therefore provide a definitive benchmark for improving postrelease survival. Yet, fishers are rarely provided with specific recommendations other than simply to “minimize” air exposure. This is a subjective recommendation, potentially causing confusion and noncompliance. Here we discuss and summarize the literature regarding air exposure thresholds in both commercial and recreational fisheries, the factors influencing these thresholds, and identify knowledge gaps limiting our understanding of tolerance to air exposure in captured fish.
Exponer a los peces al aire tras ser capturados influencia su supervivencia y comportamiento a la hora de liberarlos. La exposición al aire causa hipoxia aguda y maltrata las lamelas de las branquias, lo que resulta en estrés fisiológico y daño físico, el cual se incrementa a medida que se expone el pez al aire por más tiempo. La duración de la exposición al aire es una medida relevante y fácil de cuantificar tanto para los pescadores como para los manejadores y, por lo tanto, brinda un punto de referencia para mejorar la supervivencia tras la liberación. Aun así, a los pescadores rara vez se les dan recomendaciones específicas que van más allá de “minimizar” la exposición de los peces. Esta es una recomendación subjetiva que potencialmente causa confusión y no se acata. Aquí se discute y resume la literatura referente a los límites de exposición al aire tanto en pesquerías comerciales como recreativas, los factores que afectan esos límites y se identifican huecos del conocimiento que limitan el entendimiento de la tolerancia de los peces capturados cuando se les expone al aire.
Exposer les poissons à l'air après leur capture influe sur la survie et le comportement après remise à l'eau. L'exposition à l'air provoque une hypoxie aiguë et des dommages physiques aux lamelles des branchies, ce qui entraîne un stress physiologique et des dommages physiques qui augmentent avec la durée d'exposition à l'air. La durée d'exposition à l'air est une mesure pertinente et facilement quantifiée pour les pêcheurs et les gestionnaires et peut donc constituer une référence définitive pour l'amélioration de la survie après remise à l'eau. Pourtant, les pêcheurs reçoivent rarement des recommandations spécifiques autres que de simplement « minimiser » l'exposition à l'air. Cette recommandation est subjective, et peut semer la confusion et conduire à la non‐conformité. Ici, nous discutons et faisons le point sur la documentation concernant les seuils d'exposition à l'air à la fois pour la pêche commerciale et la pêche récréative, les facteurs influençant ces seuils, et identifions les lacunes dans les connaissances qui limitent notre compréhension de la tolérance à l'exposition de l'air chez les poissons capturés.
Derogation of the victim refers to the tendency of an observer to negatively evaluate someone hurt by the action of another. Victim derogation has been a core feature of social psychology for ...decades, but evidence suggests this phenomenon is weakening. It may even be reversing into a valorization of victims. Is this empirical pattern due to methodological changes and shifts in theoretical framing of victim studies, or have there been large-scale cultural changes in how we view victims? This review outlines the theoretical and methodological origins of the derogation effect. It then discusses contemporary research streams that show the malleability of victim perception in research that considers the entire harmful social interaction. These studies suggest that shifts in broader social, political, and cultural environments may have impacted the social psychological foundations of derogation.
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