Influenza virus remains a threat because of its ability to evade vaccine-induced immune responses due to antigenic drift. Here, we describe the isolation, evolution, and structure of a broad-spectrum ...human monoclonal antibody (mAb), MEDI8852, effectively reacting with all influenza A hemagglutinin (HA) subtypes. MEDI8852 uses the heavy-chain VH6-1 gene and has higher potency and breadth when compared to other anti-stem antibodies. MEDI8852 is effective in mice and ferrets with a therapeutic window superior to that of oseltamivir. Crystallographic analysis of Fab alone or in complex with H5 or H7 HA proteins reveals that MEDI8852 binds through a coordinated movement of CDRs to a highly conserved epitope encompassing a hydrophobic groove in the fusion domain and a large portion of the fusion peptide, distinguishing it from other structurally characterized cross-reactive antibodies. The unprecedented breadth and potency of neutralization by MEDI8852 support its development as immunotherapy for influenza virus-infected humans.
Display omitted
•Binding to all influenza A subtypes neutralizing seasonal and pandemic strains•Utilizes a rare VH (VH6-1) and carries a low level of somatic mutations•Highly conserved epitope encompassing fusion peptide and hydrophobic groove•Superior therapeutic window compared to oseltamivir in animals
Identification of a human monoclonal antibody that reacts effectively with all influenza A hemagglutinin subtypes paves the way for developing immunotherapy for people infected with the flu virus.
This book presents a state-of-the-art, robust, and adaptable process, the Theory of Being, that offers strategies for working across Difference, and for embarking on constructive dialogue around the ...issues that drive us apart, both individually and collectively. Whether around racial, gender, and/or social class inequity, core beliefs, uses of power or other points of cultural conflict, this book offers a research-validated approach, developed and refined over twenty years, to engage in difficult dialogues. "The Theory of Being" includes personal, relational, and community practices that support individuals and communities to better work through the difficult dialogues necessary to transform systems of structural inequity. It describes and offers applications of Being to help the reader understand and apply principles and practices that invite openness to controversy through facilitating deep reflection and shifting the focus of conflict from individuals to centering the issue of contention as a Third Thing about which participants can more safely express experiences and emotions. Via cases and narratives, the editors and contributors demonstrate how, through productively situating feelings of vulnerability and anger, individuals, organizations, and communities can work together to continuously evolve responsive, inclusive, and equitable practices that value social and cultural differences. This book focuses on strategies for the "how" we interact, demonstrating an orientation to process rather than prioritizing outcomes. A process-orientation can increase the quality of interaction between individuals, and the likelihood of traversing problems associated with controversial social difference in ways that result in sustainable strategies to disrupt systems of oppression. A range of applications exemplify this approach throughout the text. The primary audience is higher education leaders and leaders-in-training including student affairs professional staff, campus administrators, higher education and student affairs faculty, and undergraduate and graduate students. However, the approach has broad implications for any persons who want to productively engage across Difference in their personal and/or professional lives. Foreword written by Parker J. Palmer.
The Twyfelskupje carbonatite complex, Southern Namibia, exhibits the typical igneous emplacement structures of carbonatites, including plugs, cone sheets and dyke stockworks. The excellent exposure ...allows for detailed studies of the high-level geochemical and structural evolution of the carbonatite, and the nature of the concomitant rare earth element mineralization. Radiogenic isotope analyses (Sr, Nd, Pb) reveal that, in common with many other carbonatites, the Twyfelskupje carbonatite complex appears to be predominantly derived from mixing between HIMU and EM1 mantle end-members. Following partial melting of these mantle sources, the geochemical and structural evolution of the Twyfelskupje carbonatite complex proceeded by a staged process involving separate magma pulses, a series of emplacement structures, sub-solidus crystallization, fractionation and low-temperature hydrothermal alteration. The dominant rare earth element minerals in the Twyfelskupje carbonatite complex are fluorcarbonates and monazite, and are characterized by variable Ca, high F and light rare earth elements in the order Ce>La>Nd. Comparison between the rare earth element concentrations of the whole rocks, dominant rare earth element minerals and carbonates suggests that ∼95 % of the total rare earth element abundance of the Twyfelskupje carbonatite complex is contained within fluorcarbonates and monazite. Overall, the early calcio-carbonatite plugs are rare earth element enriched (mean 4.47 wt % rare earth oxides) relative to the magnesio-carbonatite cone sheets (mean 2.51 wt % rare earth oxides).
In eastern Anatolia, the Divriği-Hekimhan Magmatic Province (DHMP) includes ~77-69 Ma alkaline rock units which are located to the NW of the Baskil Arc of ~85-74 Ma. The magmatic rocks are composed ...of nepheline (Ne)-to quartz (Q)-normative alkaline basaltic to trachytic/syenitic units. Among them, the basaltic rocks are composed of plagioclase (Or
2-11
Ab
32-51
An
39-64
) + clinopyroxene (Wo
47-51
En
35-42
Fs
9-16
) + Fe-Ti oxide ± alkali feldspar (Or
57-98
Ab
2-42
An
1
) ± biotite ± olivine. Their
87
Sr/
86
Sr
(I)
ratios and ɛNd
(I)
values vary in the ranges of 0.70591-0.70871 and−3.2-1.6, respectively. The subvolcanic trachytic rocks are composed of perthitic alkali feldspar phenocryst in a matrix of feldspar (Or
45-61
Ab
38-54
An
0-2
), biotite, and Fe-Ti oxides. The trachytic volcanic rocks are made up of feldspar (Or
38-63
Ab
34-59
An
1-4
) in a fine-grained matrix. Their
87
Sr/
86
Sr
(I)
ratios and ɛNd
(I)
values vary in the ranges of 0.70532-0.70952 and−3.2-0.7, respectively. The syenitic rocks in the region contain both quartz- and nepheline-sodalite-bearing syenites. Geochemical features reveal that the Ne-normative basaltic magmas have undergone mafic mineral fractionation coupled with crustal contamination to produce the Q-normative derivatives. Enhanced differentiation of the Ne- and Q-normative fractionated magmas via feldspar-dominated fractionation created the silica-undersaturated and -oversaturated trachytic magmas, respectively. During the feldspar-dominated differentiation, the re-melting of accumulated alkali feldspars in the magma chamber likely gave rise to the formation of trachytic rocks with alkali feldspar-like whole rock compositions. The final products of the Ne-normative magmas are represented by the phonolites and foid-syenites with silica-undersaturated eutectic compositions. A geochemical evaluation of the basaltic rocks revealed that the alkaline magmatism mainly originated from a shallow asthenospheric mantle source which had previously been metasomatized by oceanic to continental subduction. We suggest that the DHMP was formed in response to STEP fault-controlled rolling back of the northward subducting slab of the Baskil Arc, which created a localized gap for asthenospheric upwelling.
Preservation of organic carbon (OC) in marine sediments exerts a major control on the cycling of carbon in the Earth system. In these marine environments, OC preservation may be enhanced by ...diagenetic reactions in locations where deposition of fragmental volcanic material called tephra occurs. While the mechanisms by which this process occurs are well understood, site‐specific studies of this process are limited. Here, we report a study of sediments from the Bering Sea (IODP Site U1339D) to investigate the effects of marine tephra deposition on carbon cycling during the Pleistocene and Holocene. Our results suggest that tephra layers are loci of OC burial with distinct δ13C values, and that this process is primarily linked to bonding of OC with reactive metals, accounting for ∼80% of all OC within tephra layers. In addition, distribution of reactive metals from the tephra into non‐volcanic sediments above and below the tephra layers enhances OC preservation in these sediments, with ∼33% of OC bound to reactive phases. Importantly, OC‐Fe coupling is evident in sediments >700,000 years old. Thus, these interactions may help explain the observed preservation of OC in ancient marine sediments.
Plain Language Summary
The burial of organic carbon (OC) in marine sediments is one of the major carbon sinks on Earth, meaning that it removes carbon dioxide from the ocean‐atmosphere system. However, the speed at which burial occurs varies across the globe, and is dependent on a range of factors, from the amount of nutrients in the water column, to the type of sediment. Despite evidence suggesting that when tephra is deposited to the seafloor carbon burial is enhanced, very little work has been done to investigate this process. We have therefore analyzed sediments from the Bering Sea, where volcanoes from the Aleutian Islands and Kamchatka regularly deposit tephra in the ocean. We found that OC burial is indeed associated with ash deposition, and importantly, that OC is preserved in the ash layers themselves. We show here that this carbon is preserved effectively because of chemical reactions between the OC and reactive iron, which is released by the ash, creating conditions which preserve carbon for hundreds of thousands of years.
Key Points
Tephra layers are loci of marine organic carbon (OC) burial with distinct carbon isotopic compositions
Preservation primarily linked to association of OC with reactive iron phases, accounting for ∼80% of all OC in tephra layers
OC‐reactive Fe coupling is observed in sediments >700,000 years old, indicating long‐term persistence of these complexes
Kimberlites are volatile-rich, occasionally diamond-bearing magmas that have erupted explosively at Earth's surface in the geologic past
. These enigmatic magmas, originating from depths exceeding ...150 km in Earth's mantle
, occur in stable cratons and in pulses broadly synchronous with supercontinent cyclicity
. Whether their mobilization is driven by mantle plumes
or by mechanical weakening of cratonic lithosphere
remains unclear. Here we show that most kimberlites spanning the past billion years erupted about 30 million years (Myr) after continental breakup, suggesting an association with rifting processes. Our dynamical and analytical models show that physically steep lithosphere-asthenosphere boundaries (LABs) formed during rifting generate convective instabilities in the asthenosphere that slowly migrate many hundreds to thousands of kilometres inboard of rift zones. These instabilities endure many tens of millions of years after continental breakup and destabilize the basal tens of kilometres of the cratonic lithosphere, or keel. Displaced keel is replaced by a hot, upwelling mixture of asthenosphere and recycled volatile-rich keel in the return flow, causing decompressional partial melting. Our calculations show that this process can generate small-volume, low-degree, volatile-rich melts, closely matching the characteristics expected of kimberlites
. Together, these results provide a quantitative and mechanistic link between kimberlite episodicity and supercontinent cycles through progressive disruption of cratonic keels.
ObjectivesPatient-reported outcomes (PROs) provide important information about the impact of treatment from the patients' perspective. However, missing PRO data may compromise the interpretability ...and value of the findings. We aimed to report: (1) a non-technical summary of problems caused by missing PRO data; and (2) a systematic review by collating strategies to: (A) minimise rates of missing PRO data, and (B) facilitate transparent interpretation and reporting of missing PRO data in clinical research. Our systematic review does not address statistical handling of missing PRO data.Data sourcesMEDLINE and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases (inception to 31 March 2015), and citing articles and reference lists from relevant sources.Eligibility criteriaEnglish articles providing recommendations for reducing missing PRO data rates, or strategies to facilitate transparent interpretation and reporting of missing PRO data were included.Methods2 reviewers independently screened articles against eligibility criteria. Discrepancies were resolved with the research team. Recommendations were extracted and coded according to framework synthesis.Results117 sources (55% discussion papers, 26% original research) met the eligibility criteria. Design and methodological strategies for reducing rates of missing PRO data included: incorporating PRO-specific information into the protocol; carefully designing PRO assessment schedules and defining termination rules; minimising patient burden; appointing a PRO coordinator; PRO-specific training for staff; ensuring PRO studies are adequately resourced; and continuous quality assurance. Strategies for transparent interpretation and reporting of missing PRO data include utilising auxiliary data to inform analysis; transparently reporting baseline PRO scores, rates and reasons for missing data; and methods for handling missing PRO data.ConclusionsThe instance of missing PRO data and its potential to bias clinical research can be minimised by implementing thoughtful design, rigorous methodology and transparent reporting strategies. All members of the research team have a responsibility in implementing such strategies.
PDF
