Social Learning and Course Choice

We use a broad sample of students to examine the course selection process and find evidence of social learning from peers. We also find that as the number of times students solve the course selection problem increases, they rely less on social learning and more on their own experience, limiting the potential for herd behaviour. Our results give insight to instructors about the reasons why students may be in their classes and suggest that information about courses and help in evaluating this information is especially important for students early in their college careers.

Development and validation of a bovine macrophage specific cDNA microarray

BACKGROUND: The response of macrophages to danger signals is an important early stage in the immune response. Our understanding of this complex event has been furthered by microarray analysis, which allows the simultaneous investigation of the expression of large numbers of genes. However, the microarray resources available to study these events in livestock animals are limited. RESULTS: Here we report the development of a bovine macrophage specific (BoMP) cDNA microarray. The BoMP microarray contains 5026 sequence elements (printed in duplicate) and numerous controls. The majority of the clones incorporated on the microarray were derived from the BoMP cDNA library generated from bovine myeloid cells subjected to various stimuli, including over 900 sequences unique to the library. Additional clones representing immunologically important genes have been included on the BoMP microarray. The microarray was validated by investigating the response of bovine monocytes to stimulation with interferon-γ and lipopolysaccharide using amplified RNA. At 2 and 16 hours post stimulation 695 genes exhibited statistically significant differential expression, including; 26 sequences unique to the BoMP library, interleukin 6, prion protein and toll-like receptor 4. CONCLUSION: A 5 K cDNA microarray has been successfully developed to investigate gene expression in bovine myeloid cells. The BoMP microarray is available from the ARK-Genomics Centre for Functional Genomics in Farm Animals, UK

Variation in the Early Host-Pathogen Interaction of Bovine Macrophages with Divergent Mycobacterium bovis Strains in the United Kingdom

Publication history: Accepted - 8 December 2017; Published online - 20 December 2017.Bovine tuberculosis has been an escalating animal health issue in the United Kingdom since the 1980s, even though control policies have been in place for over 60 years. The importance of the genetics of the etiological agent, Mycobacterium bovis, in the reemergence of the disease has been largely overlooked. We compared the interaction between bovine monocyte-derived macrophages (bMDM) and two M. bovis strains, AF2122/97 and G18, representing distinct genotypes currently circulating in the United Kingdom. These M. bovis strains exhibited differences in survival and growth in bMDM. Although uptake was similar, the number of viable intracellular AF2122/97 organisms increased rapidly, while G18 growth was constrained for the first 24 h. AF2122/97 infection induced a greater transcriptional response by bMDM than G18 infection with respect to the number of differentially expressed genes and the fold changes measured. AF2122/97 infection induced more bMDM cell death, with characteristics of necrosis and apoptosis, more inflammasome activation, and a greater type I interferon response than G18. In conclusion, the two investigated M. bovis strains interact in significantly different ways with the host macrophage. In contrast to the relatively silent infection by G18, AF2122/97 induces greater signaling to attract other immune cells and induces host cell death, which may promote secondary infections of naive macrophages. These differences may affect early events in the host-pathogen interaction, including granuloma development, which could in turn alter the progression of the disease. Therefore, the potential involvement of M. bovis genotypes in the reemergence of bovine tuberculosis in the United Kingdom warrants further investigation.Recombinant TNF and IL-10 were provided under the auspices of the Biotechnology and Biological Sciences Research Council (BBSRC) grants (BB/I019863/1 and BB/I020519/1) with the support of the Scottish Government as an Industrial Partnership Award with AbD Serotec (a Bio-Rad Company). This work was supported by the European Framework 7 small collaborative project MACROSYS (FP7-KBBE-2007-1-1-2). E.J.G. was also supported by a BBSRC Strategic Programme grant (Control of Infectious Diseases [BB/P013740/1]

An Overview of Antithrombotics in Ischemic Stroke

The use of antithrombotic medications is an important component of ischemic stroke treatment and prevention. This article reviews the evidence for best practices for antithrombotic use in stroke with focused discussion on the specific agents used to treat and prevent stroke

Susceptibility to disease (tropical theileriosis) is associated with differential expression of host genes that possess motifs recognised by a pathogen DNA binding protein

BACKGROUND: Knowledge of factors that influence the outcome of infection are crucial for determining the risk of severe disease and requires the characterisation of pathogen-host interactions that have evolved to confer variable susceptibility to infection. Cattle infected by Theileria annulata show a wide range in disease severity. Native (Bos indicus) Sahiwal cattle are tolerant to infection, whereas exotic (Bos taurus) Holstein cattle are susceptible to acute disease. METHODOLOGY/PRINCIPAL FINDINGS: We used RNA-seq to assess whether Theileria infected cell lines from Sahiwal cattle display a different transcriptome profile compared to Holstein and screened for altered expression of parasite factors that could generate differences in host cell gene expression. Significant differences (<0.1 FDR) in the expression level of a large number (2211) of bovine genes were identified, with enrichment of genes associated with Type I IFN, cholesterol biosynthesis, oncogenesis and parasite infection. A screen for parasite factors found limited evidence for differential expression. However, the number and location of DNA motifs bound by the TashAT2 factor (TA20095) were found to differ between the genomes of B. indicus vs. B. taurus, and divergent motif patterns were identified in infection-associated genes differentially expressed between Sahiwal and Holstein infected cells. CONCLUSIONS/SIGNIFICANCE: We conclude that divergent pathogen-host molecular interactions that influence chromatin architecture of the infected cell are a major determinant in the generation of gene expression differences linked to disease susceptibility

Differential response of bovine mammary epithelial cells to Staphylococcus aureus or Escherichia coli agonists of the innate immune system

Mastitis caused by Escherichia coli and Staphylococcus aureus is a major pathology of dairy cows. To better understand the differential response of the mammary gland to these two pathogens, we stimulated bovine mammary epithelial cells (bMEC) with either E. coli crude lipopolysaccharide (LPS) or with S. aureus culture supernatant (SaS) to compare the transcriptomic profiles of the initial bMEC response. By using HEK 293 reporter cells for pattern recognition receptors, the LPS preparation was found to stimulate TLR2 and TLR4 but not TLR5, Nod1 or Nod2, whereas SaS stimulated TLR2. Biochemical analysis revealed that lipoteichoic acid, protein A and alpha-hemolysin were all present in SaS, and bMEC were found to be responsive to each of these molecules. Transcriptome profiling revealed a core innate immune response partly shared by LPS and SaS. However, LPS induced expression of a significant higher number of genes and the fold changes were of greater magnitude than those induced by SaS. Microarray data analysis suggests that the activation pathways and the early chemokine and cytokine production preceded the defense and stress responses. A major differential response was the activation of the type I IFN pathway by LPS but not by SaS. The higher upregulation of chemokines (Cxcl10, Ccl2, Ccl5 and Ccl20) that target mononuclear leucocytes by LPS than by SaS is likely to be related to the differential activation of the type I IFN pathway, and could induce a different profile of the initial recruitment of leucocytes. The MEC responses to the two stimuli were different, as LPS was associated with NF-kappaB and Fas signaling pathways, whereas SaS was associated with AP-1 and IL-17A signaling pathways. It is noteworthy that at the protein level secretion of TNF-alpha and IL-1beta was not induced by either stimulus. These results suggest that the response of MEC to diffusible stimuli from E. coli and S. aureus contributes to the onset of the response with differential leucocyte recruitment and distinct inflammatory and innate immune reactions of the mammary gland to infection

Patient-reported outcomes in performance measurement

Patient-reported outcomes (PROs) are measures of how patients feel or what they are able to do in the context of their health status; PROs are reports, usually on questionnaires, about a patient's health conditions, health behaviors, or experiences with health care that individuals report directly, without modification of responses by clinicians or others; thus, they directly reflect the voice of the patient. PROs cover domains such as physical health, mental and emotional health, functioning, symptoms and symptom burden, and health behaviors. They are relevant for many activities: helping patients and their clinicians make informed decisions about health care, monitoring the progress of care, setting policies for coverage and reimbursement of health services, improving the quality of health care services, and tracking or reporting on the performance of health care delivery organizations. We address the major methodological issues related to choosing, administering, and using PROs for these purposes, particularly in clinical practice settings. We include a framework for best practices in selecting PROs, focusing on choosing appropriate methods and modes for administering PRO measures to accommodate patients with diverse linguistic, cultural, educational, and functional skills, understanding measures developed through both classic and modern test theory, and addressing complex issues relating to scoring and analyzing PRO data.Publishe

Direct Effects, Compensation, and Recovery in Female Fathead Minnows Exposed to a Model Aromatase Inhibitor

BackgroundSeveral chemicals in the environment have the potential to inhibit aromatase, an enzyme critical to estrogen synthesis.ObjectivesThe objective of this study was to provide a detailed characterization of molecular and biochemical responses of female fathead minnows to a model aromatase inhibitor, fadrozole (FAD).MethodsFish were exposed via water to 0, 3, or 30 microg FAD/L for 8 days and then held in clean water for 8 days, with samples collected at four time points during each 8-day period. We quantified ex vivo steroid production, plasma steroids, and plasma vitellogenin (Vtg) concentrations and analyzed relative transcript abundance of 10 key regulatory genes in ovaries and 3 in pituitary tissue by real-time polymerase chain reaction.ResultsEx vivo 17beta-estradiol (E2) production and plasma E2 and Vtg concentrations were significantly reduced after a single day of exposure to 3 microg or 30 microg FAD/L. However, plasma E2 concentrations recovered by the eighth day of exposure in the 3-microg/L group and within 1 day of cessation of exposure in the 30-microg/L group, indicating concentration- and time-dependent physiologic compensation and recovery. Concentration-dependent increases in transcripts coding for aromatase (A isoform), cytochrome P450 side-chain cleavage, steroidogenic acute regulatory protein, and follicle-stimulating hormone receptor all coincided with increased E2 production and recovery of plasma E2 concentrations.ConclusionsResults of this research highlight the need to consider compensation/adaptation and recovery when developing and interpreting short-term bioassays or biomarkers or when trying to predict the effects of chemical exposures based on mode of action

Intentional research design in implementation science: implications for the use of nomothetic and idiographic assessment

The advancement of implementation science is dependent on identifying assessment strategies that can address implementation and clinical outcome variables in ways that are valid, relevant to stakeholders, and scalable. This paper presents a measurement agenda for implementation science that integrates the previously disparate assessment traditions of idiographic and nomothetic approaches. Although idiographic and nomothetic approaches are both used in implementation science, a review of the literature on this topic suggests that their selection can be indiscriminate, driven by convenience, and not explicitly tied to research study design. As a result, they are not typically combined deliberately or effectively. Thoughtful integration may simultaneously enhance both the rigor and relevance of assessments across multiple levels within health service systems. Background on nomothetic and idiographic assessment is provided as well as their potential to support research in implementation science. Drawing from an existing framework, seven structures (of various sequencing and weighting options) and five functions (Convergence, Complementarity, Expansion, Development, Sampling) for integrating conceptually distinct research methods are articulated as they apply to the deliberate, design-driven integration of nomothetic and idiographic assessment approaches. Specific examples and practical guidance are provided to inform research consistent with this framework. Selection and integration of idiographic and nomothetic assessments for implementation science research designs can be improved. The current paper argues for the deliberate application of a clear framework to improve the rigor and relevance of contemporary assessment strategies