Molecular signatures of a TLR4 agonist-adjuvanted HIV-1 vaccine candidate in humans

Systems biology approaches have recently provided new insights into the mechanisms of action of human vaccines and adjuvants. Here, we investigated early transcriptional signatures induced in whole blood of healthy subjects following vaccination with a recombinant HIV-1 envelope glycoprotein subunit CN54gp140 adjuvanted with the TLR4 agonist glucopyranosyl lipid adjuvant-aqueous formulation (GLA-AF) and correlated signatures to CN54gp140-specific serum antibody responses. Fourteen healthy volunteers aged 18-45 years were immunized intramuscularly three times at 1-month intervals and whole blood samples were collected at baseline, 6 h, and 1, 3, and 7 days post first immunization. Subtle changes in the transcriptomic profiles were observed following immunization, ranging from over 300 differentially expressed genes (DEGs) at day 1 to nearly 100 DEGs at day 7 following immunization. Functional pathway analysis revealed blood transcription modules (BTMs) related to general cell cycle activation, and innate immune cell activation at early time points, as well as BTMs related to T cells and B cell activation at the later time points post-immunization. Diverse CN54gp140-specific serum antibody responses of the subjects enabled their categorization into high or low responders, at early ( < 1 month) and late (up to 6 months) time points post vaccination. BTM analyses revealed repression of modules enriched in NK cells, and the mitochondrial electron chain, in individuals with high or sustained antigen-specific antibody responses. However, low responders showed an enhancement of BTMs associated with enrichment in myeloid cells and monocytes as well as integrin cell surface interactions. Flow cytometry analysis of peripheral blood mononuclear cells obtained from the subjects revealed an enhanced frequency of CD56 dim NK cells in the majority of vaccines 14 days after vaccination as compared with the baseline. These results emphasize the utility of a systems biology approach to enhance our understanding on the mechanisms of action of TLR4 adjuvanted human vaccines

Radiocarbon Date List XI: Radiocarbon Dates from Marine Sediment Cores of the Iceland, Greenland, and Northeast Canadian Arctic Shelves and Nares Strait

Radiocarbon Date List XI contains an annotated listing of 178 AMS radiocarbon dates on samples from marine (169 samples) and lake (9 samples) sediment cores. Marine sediment cores, from which the samples for dating were taken, were collected on the Greenland Shelf, Baffin Bay, and the Eastern Canadian Arctic shelf. About 80% of the marine samples for dating were collected on the SW to N Icelandic shelf. The lake sediment cores were collected in northwestern Iceland. For dating of the marine samples, we submitted molluscs (117 samples), benthic and planktic foraminifera (45 samples), plant macrofauna (3 samples), and one serpulid worm. For dating of the lake cores, we submitted wood (8 samples) and one peat sample. The Conventional Radiocarbon Ages range from 294±9114C yr BP to 34,600±640 14C yr BP. The dates have been used to address a variety of research questions. The dates constrain the timing of high northern latitude late Quaternary environmental fluctuations, which include glacier extent, sea level history, isostatic rebound, sediment input, and ocean circulation. The dates also allowed assessment of the accuracy of commonly used reservoir correction. The samples were submitted by INSTAAR and affiliated researchers

SciKit-SurgeryGlenoid, an Open Source Toolkit for Glenoid Version Measurement

Correct understanding of the geometry of the glenoid (the socket of the shoulder joint) is key to successful planning of shoulder replacement surgery. This surgery typically involves placing an implant in the shoulder joint to restore joint function. The most relevant geometry is the glenoid version, which is the angular orientation of the glenoid surface relative to the long axis of the scapula in the axial plane. However, measuring the glenoid version is not straightforward and there are multiple measurement methods in the literature and used in commercial planning software. In this paper we introduce SciKit-SurgeryGlenoid, an open source toolkit for the measurement of glenoid version. SciKit-SurgeryGlenoid contains implementations of the 4 most frequently used glenoid version measurement algorithms enabling easy and unbiased comparison of the different techniques. We present the results of using the software on 10 sets of pre-operative CT scans taken from patients who have subsequently undergone shoulder replacement surgery. We further compare these results with those obtained from a commercial implant planning software. SciKit-SurgeryGlenoid currently requires manual segmentation of the relevant anatomical features for each method. Future work will look at automating the segmentation process to build an automatic and repeatable pipeline from CT or radiograph to quantitative glenoid version measurement

Invasive infections due to Streptococcus pyogenes: seasonal variation of severity and clinical characteristics, Iceland, 1975 to 2012.

To access publisher's full text version of this article click on the hyperlink at the bottom of the pageEpidemiology and clinical characteristics of invasive Group A streptococcal infections (IGASI) are highly variable. Long-term studies are needed to understand the interplay between epidemiology and virulence. In a population-based study of IGASI in Iceland from 1975 to 2012, 288 cases were identified by positive cultures from normally sterile body sites. Charts were reviewed retrospectively and emm-types of viable Streptococcus pyogenes isolates (n=226) determined. Comparing the first and last decade of the study period, IGASI incidence increased from 1.09 to 3.96 cases per 100,000 inhabitants per year. The most common were emm types 1 (25%), 28 (11%) and 89 (11%); emm1 strains were most likely to cause severe infections. Infections in adults were significantly more likely to be severe during the seasonal peak from January to April (risk ratio: 2.36, 95% confidence interval: 1.34–4.15). Significant seasonal variability in severity was noted among patients with diagnosis of sepsis, respiratory infection and cellulitis, with 38% of severe infections in January to April compared with 16% in other months (p<0.01). A seasonal increase in severity of IGASI suggested that generalised seasonal increase in host susceptibility, rather than introduction of more virulent strains may play a role in the pathogenesis of these potentially fatal infections.Icelandic Center for Research, Rannis/100436021 Landspitali University Hospital Science Fun

Molecular signatures of vaccine adjuvants

AbstractMass vaccination has saved millions of human lives and improved the quality of life in both developing and developed countries. The emergence of new pathogens and inadequate protection conferred by some of the existing vaccines such as vaccines for tuberculosis, influenza and pertussis especially in certain age groups have resulted in a move from empirically developed vaccines toward more pathogen tailored and rationally engineered vaccines. A deeper understanding of the interaction of innate and adaptive immunity at molecular level enables the development of vaccines that selectively target certain type of immune responses without excessive reactogenicity. Adjuvants constitute an imperative element of modern vaccines. Although a variety of candidate adjuvants have been evaluated in the past few decades, only a limited number of vaccine adjuvants are currently available for human use. A better understanding of the mode of action of adjuvants is pivotal to harness the potential of existing and new adjuvants in shaping a desired immune response. Recent advancement in systems biology powered by the emerging cutting edge omics technology has led to the identification of molecular signatures rapidly induced after vaccination in the blood that correlate and predict a later protective immune response or vaccine safety. This can pave ways to prospectively determine the potency and safety of vaccines and adjuvants. This review is intended to highlight the importance of big data analysis in advancing our understanding of the mechanisms of actions of adjuvants to inform rational development of future human vaccines

Producing valid statistics when legislation, culture, and medical practices differ for births at or before the threshold of survival: Report of a European workshop

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Stakeholder perceptions of policy tools in support of sustainable food consumption in Europe: Policy implications

Transitioning agri-food systems towards increased sustainability and resilience requires that attention be paid to sustainable food consumption policies. Policy-making processes often require the engagement and acceptance of key stakeholders. This study analyses stakeholders' solutions for creating sustainable agri-food systems, through interviews with a broad range of stakeholders including food value chain actors, non-governmental organizations, governmental institutions, research institutions and academic experts. The study draws on 38 in-depth, semi-structured interviews conducted in four European countries: France, Iceland, Italy and the UK, as well as three interviews with high-level EU experts. The interviewees' solutions were analysed according to a five-category typology of policy tools, encompassing direct activity regulations, and market-based, knowledge-based, governance and strategic policy tools. Most of the identified solutions were located in the strategic tools category, reflecting shared recognition of the need to integrate food policy to achieve long-term goals. Emerging solutions-those which were most commonly identified among the different national contexts-were then used to derive empirically-grounded and more universally applicable recommendations for the advancement of sustainable food consumption policies