Analysis of immune responses to attenuated alcelaphine herpesvirus 1 formulated with and without adjuvant

The experimental vaccine for bovine malignant catarrhal fever consists of viable attenuated alcelaphine herpesvirus 1 (AlHV-1) derived by extensive culture passage, combined with an oil-in-water adjuvant, delivered intramuscularly. This immunisation strategy was over 80% effective in previous experimental and field trials and protection appeared to be associated with induction of virus-neutralising antibodies. Whether the vaccine virus is required to be viable at the point of immunisation and whether adjuvant is required to induce the appropriate immune responses remains unclear. To address these issues two studies were performed, firstly to analyse immune responses in the presence and absence of adjuvant and secondly, to investigate immune responses to vaccines containing adjuvant plus viable or inactivated AlHV-1.The first study showed that viable attenuated AlHV-1 in the absence of adjuvant induced virus-specific antibodies but the titres of virus-neutralising antibodies were significantly lower than those induced by vaccine containing viable virus and adjuvant, suggesting adjuvant was required for optimal responses. In contrast, the second study found that the vaccine containing inactivated (>99.9%) AlHV-1 induced similar levels of virus-neutralising antibody to the equivalent formulation containing viable AlHV-1.Together these studies suggest that the MCF vaccine acts as an antigen depot for induction of immune responses, requiring adjuvant and a suitable antigen source, which need not be viable virus. These observations may help in directing the development of alternative MCF vaccine formulations for distribution in the absence of an extensive cold chain

Improving the Reporting of Primary Care Research: An International Survey of Researchers

PURPOSE: To assess opportunities to improve reporting of primary care (PC) research to better meet the needs of its varied users. METHODS: International, interprofessional online survey of PC researchers and users, 2018 to 2019. Respondents used Likert scales to rate frequency of difficulties in interpreting, synthesizing, and applying PC research reports. Free-text short answers were categorized by template analysis to record experiences, concerns, and suggestions. Areas of need were checked across existing reporting guidelines. RESULTS: Survey yielded 255 respondents across 24 nations, including 138 women (54.1%), 169 physicians (60%), 32 scientists (11%), 20 educators (7%), and 18 public health professionals (6%). Overall, 37.4% indicated difficulties using PC research reports "50% or more of the time." The most common problems were synthesizing findings (58%) and assessing generalizability (42%). Difficulty was reported by 49% for qualitative, 46% for mixed methods, and 38% for observational research. Most users wanted richer reporting of theoretical foundation (53.7%); teams, roles, and organization of care (53.4%); and patient involvement in the research process (52.7%). Few reported difficulties with ethics or disclosure of funding or conflicts. Free-text answers described special challenges in reporting PC research: context of clinical care and setting; practical details of interventions; patient-clinician and team relationships; and generalizability, applicability and impact in the great variety of PC settings. Cross-check showed that few current reporting guidelines focus on these needs. CONCLUSIONS: Opportunities exist to improve the reporting of PC research to make it more useful for its many users, suggesting a role for a PC research reporting guideline

The association of plasma biomarkers with computed tomography-assessed emphysema phenotypes

Rationale: Chronic obstructive pulmonary disease (COPD) is a phenotypically heterogeneous disease. In COPD, the presence of emphysema is associated with increased mortality and risk of lung cancer. High resolution computed tomography (HRCT) scans are useful in quantifying emphysema but are associated with radiation exposure and high incidence of false positive findings (i.e., nodules). Using a comprehensive biomarker panel, we sought to determine if there was a peripheral blood biomarker signature of emphysema. Methods: 114 plasma biomarkers were measured using a custom assay in 588 individuals enrolled in the COPDGene study. Quantitative emphysema measurements included percent low lung attenuation (%LAA) ≤ −950 HU, ≤ − 910 HU and mean lung attenuation at the 15th percentile on lung attenuation curve (LP15A). Multiple regression analysis was performed to determine plasma biomarkers associated with emphysema independent of covariates age, gender, smoking status, body mass index and FEV1. The findings were subsequently validated using baseline blood samples from a separate cohort of 388 subjects enrolled in the Treatment of Emphysema with a Selective Retinoid Agonist (TESRA) study. Results: Regression analysis identified multiple biomarkers associated with CT-assessed emphysema in COPDGene, including advanced glycosylation end-products receptor (AGER or RAGE, p < 0.001), intercellular adhesion molecule 1 (ICAM, p < 0.001), and chemokine ligand 20 (CCL20, p < 0.001). Validation in the TESRA cohort revealed significant associations with RAGE, ICAM1, and CCL20 with radiologic emphysema (p < 0.001 after meta-analysis). Other biomarkers that were associated with emphysema include CDH1, CDH 13 and SERPINA7, but were not available for validation in the TESRA study. Receiver operating characteristics analysis demonstrated a benefit of adding a biomarker panel to clinical covariates for detecting emphysema, especially in those without severe airflow limitation (AUC 0.85). Conclusions: Our findings, suggest that a panel of blood biomarkers including sRAGE, ICAM1 and CCL20 may serve as a useful surrogate measure of emphysema, and when combined with clinical covariates, may be useful clinically in predicting the presence of emphysema compared to just using covariates alone, especially in those with less severe COPD. Ultimately biomarkers may shed light on disease pathogenesis, providing targets for new treatments. Electronic supplementary material The online version of this article (doi:10.1186/s12931-014-0127-9) contains supplementary material, which is available to authorized users

The association of plasma biomarkers with computed tomography-assessed emphysema phenotypes

Abstract Rationale Chronic obstructive pulmonary disease (COPD) is a phenotypically heterogeneous disease. In COPD, the presence of emphysema is associated with increased mortality and risk of lung cancer. High resolution computed tomography (HRCT) scans are useful in quantifying emphysema but are associated with radiation exposure and high incidence of false positive findings (i.e., nodules). Using a comprehensive biomarker panel, we sought to determine if there was a peripheral blood biomarker signature of emphysema. Methods 114 plasma biomarkers were measured using a custom assay in 588 individuals enrolled in the COPDGene study. Quantitative emphysema measurements included percent low lung attenuation (%LAA)≤ - 950 HU, ≤ -910 HU and mean lung attenuation at the 15th percentile on lung attenuation curve (LP15A). Multiple regression analysis was performed to determine plasma biomarkers associated with emphysema independent of covariates age, gender, smoking status, body mass index and FEV1. The findings were subsequently validated using baseline blood samples from a separate cohort of 388 subjects enrolled in the Treatment of Emphysema with a Selective Retinoid Agonist (TESRA) study. Results Regression analysis identified multiple biomarkers associated with CT-assessed emphysema in COPDGene, including advanced glycosylation end-products receptor (AGER or RAGE, p < 0.001), intercellular adhesion molecule 1 (ICAM, p < 0.001), and chemokine ligand 20 (CCL20, p < 0.001). Validation in the TESRA cohort revealed significant associations with RAGE, ICAM1, and CCL20 with radiologic emphysema (p < 0.001 after meta-analysis). Other biomarkers that were associated with emphysema include CDH1, CDH 13 and SERPINA7, but were not available for validation in the TESRA study. Receiver operating characteristics analysis demonstrated a benefit of adding a biomarker panel to clinical covariates for detecting emphysema, especially in those without severe airflow limitation (AUC 0.85). Conclusions Our findings, suggest that a panel of blood biomarkers including sRAGE, ICAM1 and CCL20 may serve as a useful surrogate measure of emphysema, and when combined with clinical covariates, may be useful clinically in predicting the presence of emphysema compared to just using covariates alone, especially in those with less severe COPD. Ultimately biomarkers may shed light on disease pathogenesis, providing targets for new treatments.http://deepblue.lib.umich.edu/bitstream/2027.42/134591/1/12931_2014_Article_127.pd

Leveraging Motivations, Personality, and Sensory Cues for Vertebrate Pest Management

Acknowledgments: We wish to thank Manaaki Whenua – Landcare Research staff, particularly Peter Millard and Bruce Warburton, for facilitating and supporting this research. Thanks to Jenna Bytheway for infographic design. This research was supported by Strategic Science Investment funding from the New Zealand Ministry of Business, Innovation and Employment’s Science and Innovation Group, awarded to Manaaki Whenua – Landcare Research. T.W.B. was supported by Marie Skłodowska-Curie grant number 747120, and A.S. was supported by National Science Foundation grant IOS 1456724.Peer reviewedPublisher PD

Cluster M Mycobacteriophages Bongo, PegLeg, and Rey with Unusually Large Repertoires of tRNA Isotopes

Genomic analysis of a large set of phages infecting the common hostMycobacterium smegmatis mc2155 shows that they span considerable genetic diversity. There are more than 20 distinct types that lack nucleotide similarity with each other, and there is considerable diversity within most of the groups. Three newly isolated temperate mycobacteriophages, Bongo, PegLeg, and Rey, constitute a new group (cluster M), with the closely related phages Bongo and PegLeg forming subcluster M1 and the more distantly related Rey forming subcluster M2. The cluster M mycobacteriophages have siphoviral morphologies with unusually long tails, are homoimmune, and have larger than average genomes (80.2 to 83.7 kbp). They exhibit a variety of features not previously described in other mycobacteriophages, including noncanonical genome architectures and several unusual sets of conserved repeated sequences suggesting novel regulatory systems for both transcription and translation. In addition to containing transfer-messenger RNA and RtcB-like RNA ligase genes, their genomes encode 21 to 24 tRNA genes encompassing complete or nearly complete sets of isotypes. We predict that these tRNAs are used in late lytic growth, likely compensating for the degradation or inadequacy of host tRNAs. They may represent a complete set of tRNAs necessary for late lytic growth, especially when taken together with the apparent lack of codons in the same late genes that correspond to tRNAs that the genomes of the phages do not obviously encode

Radiation-free CMR diagnostic heart catheterization in children.

BACKGROUND: Children with heart disease may require repeated X-Ray cardiac catheterization procedures, are more radiosensitive, and more likely to survive to experience oncologic risks of medical radiation. Cardiovascular magnetic resonance (CMR) is radiation-free and offers information about structure, function, and perfusion but not hemodynamics. We intend to perform complete radiation-free diagnostic right heart catheterization entirely using CMR fluoroscopy guidance in an unselected cohort of pediatric patients; we report the feasibility and safety. METHODS: We performed 50 CMR fluoroscopy guided comprehensive transfemoral right heart catheterizations in 39 pediatric (12.7 ± 4.7 years) subjects referred for clinically indicated cardiac catheterization. CMR guided catheterizations were assessed by completion (success/failure), procedure time, and safety events (catheterization, anesthesia). Pre and post CMR body temperature was recorded. Concurrent invasive hemodynamic and diagnostic CMR data were collected. RESULTS: During a twenty-two month period (3/2015 - 12/2016), enrolled subjects had the following clinical indications: post-heart transplant 33%, shunt 28%, pulmonary hypertension 18%, cardiomyopathy 15%, valvular heart disease 3%, and other 3%. Radiation-free CMR guided right heart catheterization attempts were all successful using passive catheters. In two subjects with septal defects, right and left heart catheterization were performed. There were no complications. One subject had six such procedures. Most subjects (51%) had undergone multiple (5.5 ± 5) previous X-Ray cardiac catheterizations. Retained thoracic surgical or transcatheter implants (36%) did not preclude successful CMR fluoroscopy heart catheterization. During the procedure, two subjects were receiving vasopressor infusions at baseline because of poor cardiac function, and in ten procedures, multiple hemodynamic conditions were tested. CONCLUSIONS: Comprehensive CMR fluoroscopy guided right heart catheterization was feasible and safe in this small cohort of pediatric subjects. This includes subjects with previous metallic implants, those requiring continuous vasopressor medication infusions, and those requiring pharmacologic provocation. Children requiring multiple, serial X-Ray cardiac catheterizations may benefit most from radiation sparing. This is a step toward wholly CMR guided diagnostic (right and left heart) cardiac catheterization and future CMR guided cardiac intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT02739087 registered February 17, 2016

Helpers and egg investment in the cooperatively breeding acorn woodpecker: testing the concealed helper effects hypothesis

In cooperatively breeding acorn woodpeckers (Melanerpes formicivorus), helper males have a large positive effect on fledging success in good acorn crop years but only a small positive effect in poor acorn crop years, while helper females exhibit the opposite pattern. Based on these findings, we tested the “concealed helper effects” hypothesis, which proposes that laying females reduce investment in eggs (with respect to their size, number, or quality) in a way that confounds helper effects and results in an absence of a relationship between helpers and breeding success. Results generally failed to support the hypothesis. Mean egg size was positively related to temperatures during the 10 days prior to egg-laying and negatively related to the food supply as indexed by the prior fall’s acorn crop, but there were no significant differences vis-à-vis helpers except for interactions with the acorn crop that only partly corresponded to those predicted. With respect to clutch size, females laid larger clutches when assisted by female helpers, opposite the pattern predicted. Although our results suggest that egg size is adjusted to particular ecological circumstances, we conclude that neither egg nor clutch size is adjusted in a way that confounds the apparent effects of helpers, as proposed by the concealed helper effects hypothesis