[1] A global compilation of 170 time-averaged volumetric volcanic output rates (Q e ) is evaluated in terms of composition and petrotectonic setting to advance the understanding of long-term rates of magma generation and eruption on Earth. Repose periods between successive eruptions at a given site and intrusive:extrusive ratios were compiled for selected volcanic centers where long-term (>10 4 years) data were available. More silicic compositions, rhyolites and andesites, have a more limited range of eruption rates than basalts. Even when high Q e values contributed by flood basalts (9 ± 2 Â 10 À1 km 3 /yr) are removed, there is a trend in decreasing average Q e with lava composition from basaltic eruptions (2.6 ± 1.0 Â 10 À2 km 3 /yr) to andesites (2.3 ± 0.8 Â 10 À3 km 3 /yr) and rhyolites (4.0 ± 1.4 Â 10 À3 km 3 /yr). This trend is also seen in the difference between oceanic and continental settings, as eruptions on oceanic crust tend to be predominately basaltic. All of the volcanoes occurring in oceanic settings fail to have statistically different mean Q e and have an overall average of 2.8 ± 0.4 Â 10 À2 km 3 /yr, excluding flood basalts. Likewise, all of the volcanoes on continental crust also fail to have statistically different mean Q e and have an overall average of 4.4 ± 0.8 Â 10 À3 km 3 /yr. Flood basalts also form a distinctive class with an average Q e nearly two orders of magnitude higher than any other class. However, we have found no systematic evidence linking increased intrusive:extrusive ratios with lower volcanic rates. A simple heat balance analysis suggests that the preponderance of volcanic systems must be open magmatic systems with respect to heat and matter transport in order to maintain eruptible magma at shallow depth throughout the observed lifetime of the volcano. The empirical upper limit of $10 À2 km 3 /yr for magma eruption rate in systems with relatively high intrusive:extrusive ratios may be a consequence of the fundamental parameters governing rates of melt generation (e.g., subsolidus isentropic decompression, hydration due to slab dehydration and heat transfer between underplated magma and the overlying crust) in the Earth.

Background Middle East respiratory syndrome (MERS) coronavirus causes a highly fatal lower-respiratory tract infection. There are as yet no licensed MERS vaccines or therapeutics. This study (WRAIR-2274) assessed the safety, tolerability, and immunogenicity of the GLS-5300 MERS coronavirus DNA vaccine in healthy adults. Methods This study was a phase 1, open-label, single-arm, dose-escalation study of GLS-5300 done at the Walter ReedArmy Institute for Research Clinical Trials Center (Silver Spring, MD, USA). We enrolled healthy adults aged 18-50 years; exclusion criteria included previous infection or treatment of MERS. Eligible participants were enrolled sequentially using a dose-escalation protocol to receive 0·67 mg, 2 mg, or 6 mg GLS-5300 administered by trained clinical site staff via a single intramuscular 1 mL injection at each vaccination at baseline, week 4, and week 12 followed immediately by co-localised intramuscular electroporation. Enrolment into the higher dose groups occurred after a safety monitoring committee reviewed the data following vaccination of the first five participants at the previous lower dose in each group. The primary outcome of the study was safety, assessed in all participants who received at least one study treatment and for whom post-dose study data were available, during the vaccination period with follow-up through to 48 weeks after dose 3. Safety was measured by the incidence of adverse events; administration site reactions and pain; and changes in safety laboratory parameters. The secondary outcome was immunogenicity. This trial is registered at ClinicalTrials.gov (number NCT 02670187) and is completed.Findings Between Feb 17 and July 22, 2016, we enrolled 75 individuals and allocated 25 each to 0·67 mg, 2 mg, or 6 mg GLS-5300. No vaccine-associated serious adverse events were reported. The most common adverse events were injection-site reactions, reported in 70 participants (93%) of 75. Overall, 73 participants (97%) of 75 reported at least one solicited adverse event; the most common systemic symptoms were headache (five [20%] with 0·67 mg, 11 [44%] with 2 mg, and seven [28%] with 6 mg), and malaise or fatigue (five [20%] with 0·67 mg, seven [28%] with 2 mg, and two [8%] with 6 mg). The most common local solicited symptoms were administration site pain (23 [92%] with all three doses) and tenderness (21 [84%] with all three doses). Most solicited symptoms were reported as mild (19 [76%] with 0·67 mg, 20 [80%] with 2 mg, and 17 [68%] with 6 mg) and were self-limiting. Unsolicited symptoms were reported for 56 participants (75%) of 75 and were deemed treatment-related for 26 (35%). The most common unsolicited adverse events were infections, occurring in 27 participants (36%); six (8%) were deemed possibly related to study treatment. There were no laboratory abnormalities of grade 3 or higher that were related to study treatment; laboratory abnormalities were uncommon, except for 15 increases in creatine phosphokinase in 14 participants (three participants in the 0·67 mg grou...

Background Although Zika virus (ZIKV) infection is typically self-limiting, other associated complications such as congenital birth defects and the Guillain-Barré syndrome are well described. There are no approved vaccines against ZIKV infection. Methods In this phase 1, open-label clinical trial, we evaluated the safety and immunogenicity of a synthetic, consensus DNA vaccine (GLS-5700) encoding the ZIKV premembrane and envelope proteins in two groups of 20 participants each. The participants received either 1 mg or 2 mg of vaccine intradermally, with each injection followed by electroporation (the use of a pulsed electric field to introduce the DNA sequence into cells) at baseline, 4 weeks, and 12 weeks. Results The median age of the participants was 38 years, and 60% were women; 78% were white, and 22% black; in addition, 30% were Hispanic. At the interim analysis at 14 weeks (i.e., after the third dose of vaccine), no serious adverse events were reported. Local reactions at the vaccination site (e.g., injection-site pain, redness, swelling, and itching) occurred in approximately 50% of the participants. After the third dose of vaccine, binding antibodies (as measured on enzyme-linked immunosorbent assay) were detected in all the participants, with geometric mean titers of 1642 and 2871 in recipients of 1 mg and 2 mg of vaccine, respectively. Neutralizing antibodies developed in 62% of the samples on Vero-cell assay. On neuronal-cell assay, there was 90% inhibition of ZIKV infection in 70% of the serum samples and 50% inhibition in 95% of the samples. The intraperitoneal injection of postvaccination serum protected 103 of 112 IFNAR knockout mice (bred with deletion of genes encoding interferon-α and interferon-β receptors) (92%) that were challenged with a lethal dose of ZIKV-PR209 strain; none of the mice receiving baseline serum survived the challenge. Survival was independent of the neutralization titer. Conclusions In this phase 1, open-label clinical trial, a DNA vaccine elicited anti-ZIKV immune responses. Further studies are needed to better evaluate the safety and efficacy of the vaccine. (Funded by GeneOne Life Science and others; ZIKA-001 ClinicalTrials.gov number, NCT02809443 .).

Large and complex graphs representing relationships among sets of entities are an increasingly common focus of interest in data analysis-examples include social networks, Web graphs, telecommunication networks, and biological networks. In interactive analysis of such data a natural query is "which entities are most important in the network relative to a particular individual or set of individuals?" We investigate the problem of answering such queries in this paper, focusing in particular on defining and computing the importance of nodes in a graph relative to one or more root nodes. We define a general framework and a number of different algorithms, building on ideas from social networks, graph theory, Markov models, and Web graph analysis. We experimentally evaluate the different properties of these algorithms on toy graphs and demonstrate how our approach can be used to study relative importance in real-world networks including a network of interactions among September 11th terrorists, a network of collaborative research in biotechnology among companies and universities, and a network of co-authorship relationships among computer science researchers.

[1] Side-scan sonar, submersible observations and sampling of lava flows from the East Pacific Rise, 17°-19°S constrain the character and variability of submarine volcanic eruptions along mid-ocean ridges. Nine separate lava sequences were mapped using relative age and lithological contrasts among recovered samples. Axial lengths activated during eruptive episodes range from $1 to >18 km; individual flow field areas vary from <1 to >19 km 2 . Estimated erupted volumes range from <1 to >200 Â 10 6 m 3 . The largest unit is the chemically uniform Animal Farm lava near 18°37 0 S. The youngest lava is the Aldo-Kihi flow field, 17°24 0 -34 0 S, probably erupted in the early 1990s from a fissure system extending >18 km along axis. Near 18°33 0 S two distinct lava compositions with uniform sediment cover were recovered from lava that buries older faulted terrain. The boundary in lava composition coincides with a change in depth to the top of an axial magma lens seismic reflector, consistent with magmas from two separate reservoirs being erupted in the same event. Chemical compositions from throughout the area indicate that lavas with identical compositions can be emplaced in separate volcanic eruptions within individual segments. A comparison of our results to global data on submarine mid-ocean ridge eruptions suggests consistent dependencies of erupted volume, activated fissure lengths, and chemical heterogeneity with spreading rate, consistent with expected eruptive characteristics from ridges with contrasting thermal properties and magma reservoir depths.