Sediment-rich meltwater plumes and ice-proximal fans at the margins of modern and ancient tidewater glaciers: Observations and modeling

Turbid meltwater plumes and ice-proximal fans occur where subglacial streams reach the grounded marine margins of modern and ancient tidewater glaciers. However, the spacing and temporal stability of these subglacial channels is poorly understood. This has significant implications for understanding the geometry and distribution of Quaternary and ancient ice-proximal fans that can form important aquifers and hydrocarbon reservoirs. Remote-sensing and numerical-modelling techniques are applied to the 200 km-long marine margin of a Svalbard ice cap, Austfonna, to quantify turbid meltwaterplume distribution and predict its temporal stability. Results are combined with observations from geophysical data close to the modern ice front to refine existing depositional models for ice-proximal fans. Plumes are spaced about 3 km apart and their distribution along the ice front is stable over decades. Numerical modelling also predicts the drainage pattern and meltwater discharge beneath the ice cap; modelled water-routing patterns are in reasonable agreement with satellite-mapped plume locations. However, glacial retreat of several kilometres over the past 40 years has limited build-up of significant ice-proximal fans. A single fan and moraine ridge is noted from marine-geophysical surveys. Closer to the ice front there are smaller recessional moraines and polygonal sediment lobes but no identifiable fans. Schematic models of ice-proximal deposits represent varying glacierterminus stability: (i) stable terminus where meltwater sedimentation produces an ice-proximal fan; (ii) quasi-stable terminus, where glacier readvance pushes or thrusts up ice-proximal deposits into a morainal bank; (iii) retreating terminus, with short still-stands, allowing only small sediment lobes to build up at melt-stream portals. These modern investigations are complemented with outcrop and subsurface observations and numerical modelling of an ancient, Ordovician glacial system. Thick turbidite successions and large fans in the Late Ordovician suggest either high-magnitude events or sustained high discharge, consistent with a relatively mild palaeo-glacial setting.We thank BP Algeria for sponsorship, Ed Jones and Liz Jolley of BP for supporting the project.This is the accepted manuscript. The final published version is available from Wiley at http://dx.doi.org/10.1111/sed.1219

Past water flow beneath Pine Island and Thwaites glaciers, West Antarctica

Abstract. Outburst floods from subglacial lakes beneath the Antarctic Ice Sheet modulate ice-flow velocities over periods of months to years. Although subglacial lake drainage events have been observed from satellite-altimetric data, little is known about their role in the long-term evolution of ice-sheet basal hydrology. Here, we systematically map and model past water flow through an extensive area containing over 1000 subglacial channels and 19 former lake basins exposed on over 19 000 km2 of seafloor by the retreat of Pine Island and Thwaites glaciers, West Antarctica. At 507 m wide and 43 m deep on average, the channels offshore of present-day Pine Island and Thwaites glaciers are approximately twice as deep, 3 times as wide, and cover an area over 400 times larger than the terrestrial meltwater channels comprising the Labyrinth in the Antarctic Dry Valleys. The channels incised into bedrock offshore of contemporary Pine Island and Thwaites glaciers would have been capable of accommodating discharges of up to 8.8×106 m3 s−1. We suggest that the channels were formed by episodic discharges from subglacial lakes trapped during ice-sheet advance and retreat over multiple glacial periods. Our results document the widespread influence of episodic subglacial drainage events during past glacial periods, in particular beneath large ice streams similar to those that continue to dominate contemporary ice-sheet discharge. UK Natural Environment Research Council’s iSTAR programme (grant nos. NE/J005703/1, NE/J005746/1, and NE/J005770/1). James D. Kirkham: Debenham Scholarship from the Scott Polar Research Institute, University of Cambridge, and a UK Natural Environment Research Council Ph.D. studentship awarded through the Cambridge Earth System Science Doctoral Training Partnership (grant no. NE/L002507/1

A novel potent Fas agonist for selective depletion of tumor cells in hematopoietic transplants

There remains a clear need for effective tumor cell purging in autologous stem cell transplantation (ASCT) where residual malignant cells within the autograft contribute to disease relapse. Here we propose the use of a novel Fas agonist with potent pro-apoptotic activity, termed MegaFasL, as an effective ex-vivo purging agent. MegaFasL selectively kills hematological cancer cells from lymphomas and leukemias and prevents tumor development at concentrations that do not reduce the functional capacity of human hematopoietic stem/progenitor cells both in in vitro and in in vivo transplantation models. These findings highlight the potential use of MegaFasL as an ex-vivo purging agent in ASCT

Low Self-Esteem and Impairments in Emotion Recognition Predict Behavioural Problems in Children

Research indicates that low self-esteem and impaired emotion recognition are risk factors for antisocial behaviour (ASB). Self-esteem and emotion recognition are essential for successful social interaction and previous research suggests that self-esteem and emotional intelligence are positively related. However, to our knowledge the relationship between these two risk factors for ASB has not been explored in children with behavioural problems. Thus, this study investigated self-esteem and emotion recognition, their relationship with one another and with behavioural problem severity. Participants were 8–11 year olds with behavioural problems (BP; n = 78) who were taking part in an early intervention program, and typically developing controls (TD; n = 54). Participants completed a self-esteem questionnaire and a computerised emotion recognition task. Teachers and parents rated children’s emotional and behavioural problems. BP participants had significantly lower self-esteem and exhibited an impairment in emotion recognition. Self-esteem and emotion recognition were positively related and inversely associated with behavioural problem severity and they predicted behaviour problems independently of one another. This is the first study to show that self-esteem and emotion recognition are related processes in children with behavioural problems and that both predict behavioural problems. This has important implications for the development of intervention strategies

An in vitro co-culture model of esophageal cells identifies ascorbic acid as a modulator of cell competition

<p>Abstract</p> <p>Background</p> <p>The evolutionary dynamics between interacting heterogeneous cell types are fundamental properties of neoplastic progression but can be difficult to measure and quantify. Cancers are heterogeneous mixtures of mutant clones but the direct effect of interactions between these clones is rarely documented. The implicit goal of most preventive interventions is to bias competition in favor of normal cells over neoplastic cells. However, this is rarely explicitly tested. Here we have developed a cell culture competition model to allow for direct observation of the effect of chemopreventive or therapeutic agents on two interacting cell types. We have examined competition between normal and Barrett's esophagus cell lines, in the hopes of identifying a system that could screen for potential chemopreventive agents.</p> <p>Methods</p> <p>One fluorescently-labeled normal squamous esophageal cell line (EPC2-hTERT) was grown in competition with one of four Barrett's esophagus cell lines (CP-A, CP-B, CP-C, CP-D) under varying conditions and the outcome of competition measured over 14 days by flow cytometry.</p> <p>Results</p> <p>We demonstrate that ascorbic acid (vitamin C) can help squamous cells outcompete Barrett's cells in this system. We are also able to show that ascorbic acid's boost to the relative fitness of squamous cells was increased in most cases by mimicking the pH conditions of gastrointestinal reflux in the lower esophagus.</p> <p>Conclusions</p> <p>This model is able to integrate differential fitness effects on various cell types, allowing us to simultaneously capture effects on interacting cell types without having to perform separate experiments. This model system may be used to screen for new classes of cancer prevention agents designed to modulate the competition between normal and neoplastic cells.</p

Expansion of Cord Blood CD34+ Cells in Presence of zVADfmk and zLLYfmk Improved Their In Vitro Functionality and In Vivo Engraftment in NOD/SCID Mouse

BACKGROUND: Cord blood (CB) is a promising source for hematopoietic stem cell transplantations. The limitation of cell dose associated with this source has prompted the ex vivo expansion of hematopoietic stem and progenitor cells (HSPCs). However, the expansion procedure is known to exhaust the stem cell pool causing cellular defects that promote apoptosis and disrupt homing to the bone marrow. The role of apoptotic machinery in the regulation of stem cell compartment has been speculated in mouse hematopoietic and embryonic systems. We have consistently observed an increase in apoptosis in the cord blood derived CD34(+) cells cultured with cytokines compared to their freshly isolated counterpart. The present study was undertaken to assess whether pharmacological inhibition of apoptosis could improve the outcome of expansion. METHODOLOGY/PRINCIPAL FINDINGS: CB CD34(+) cells were expanded with cytokines in the presence or absence of cell permeable inhibitors of caspases and calpains; zVADfmk and zLLYfmk respectively. A novel role of apoptotic protease inhibitors was observed in increasing the CD34(+) cell content of the graft during ex vivo expansion. This was further reflected in improved in vitro functional aspects of the HSPCs; a higher clonogenicity and long term culture initiating potential. These cells sustained superior long term engraftment and an efficient regeneration of major lympho-myeloid lineages in the bone marrow of NOD/SCID mouse compared to the cells expanded with growth factors alone. CONCLUSION/SIGNIFICANCE: Our data show that, use of either zVADfmk or zLLYfmk in the culture medium improves expansion of CD34(+) cells. The strategy protects stem cell pool and committed progenitors, and improves their in vitro functionality and in vivo engraftment. This observation may complement the existing protocols used in the manipulation of hematopoietic cells for therapeutic purposes. These findings may have an impact in the CB transplant procedures involving a combined infusion of unmanipulated and expanded grafts

The effect of participatory women's groups on birth outcomes in Bangladesh: does coverage matter? Study protocol for a randomized controlled trial

Background: Progress on neonatal survival has been slow in most countries. While there is evidence on what works to reduce newborn mortality, there is limited knowledge on how to deliver interventions effectively when health systems are weak. Cluster randomized trials have shown strong reductions in neonatal mortality using community mobilisation with women's groups in rural Nepal and India. A similar trial in Bangladesh showed no impact. A main hypothesis is that this negative finding is due to the much lower coverage of women's groups in the intervention population in Bangladesh compared to India and Nepal. For evidence-based policy making it is important to examine if women's group coverage is a main determinant of their impact. The study aims to test the effect on newborn and maternal health outcomes of a participatory women's group intervention with a high population coverage of women's groups.Methods: A cluster randomised trial of a participatory women's group intervention will be conducted in 3 districts of rural Bangladesh. As we aim to study a women's group intervention with high population coverage, the same 9 intervention and 9 control unions will be used as in the 2005-2007 trial. These had been randomly allocated using the districts as strata. To increase coverage, 648 new groups were formed in addition to the 162 existing groups that were part of the previous trial. An open cohort of women who are permanent residents in the union in which their delivery or death was identified, is enrolled. Women and their newborns are included after birth, or, if a woman dies during pregnancy, after her death. Excluded are women who are temporary residents in the union in which their birth or death was identified. The primary outcome is neonatal mortality in the last 24 months of the study. A low cost surveillance system will be used to record all birth outcomes and deaths to women of reproductive age in the study population. Data on home care practices and health care use are collected through interviews

Improving eye care for veterans with diabetes: An example of using the QUERI steps to move from evidence to implementation: QUERI Series

<p>Abstract</p> <p>Background</p> <p>Despite being a critical part of improving healthcare quality, little is known about how best to move important research findings into clinical practice. To address this issue, the Department of Veterans Affairs (VA) developed the Quality Enhancement Research Initiative (QUERI), which provides a framework, a supportive structure, and resources to promote the more rapid implementation of evidence into practice.</p> <p>Methods</p> <p>This paper uses a practical example to demonstrate the use of the six-step QUERI process, which was developed as part of QUERI and provides a systematic approach for moving along the research to practice pipeline. Specifically, we describe a series of projects using the six-step framework to illustrate how this process guided work by the Diabetes Mellitus QUERI (DM-QUERI) Center to assess and improve eye care for veterans with diabetes.</p> <p>Results</p> <p>Within a relatively short time, DM-QUERI identified a high-priority issue, developed evidence to support a change in the diabetes eye screening performance measure, and identified a gap in quality of care. A prototype scheduling system to address gaps in screening and follow-up also was tested as part of an implementation project. We did not succeed in developing a fully functional pro-active scheduling system. This work did, however, provide important information to help us further understand patients' risk status, gaps in follow-up at participating eye clinics, specific considerations for additional implementation work in the area of proactive scheduling, and contributed to a change in the prevailing diabetes eye care performance measure.</p> <p>Conclusion</p> <p>Work by DM-QUERI to promote changes in the delivery of eye care services for veterans with diabetes demonstrates the value of the QUERI process in facilitating the more rapid implementation of evidence into practice. However, our experience with using the QUERI process also highlights certain challenges, including those related to the hybrid nature of the research-operations partnership as a mechanism for promoting rapid, system-wide implementation of important research findings. In addition, this paper suggests a number of important considerations for future implementation work, both in the area of pro-active scheduling interventions, as well as for implementation science in general.</p

The Pathogenic Properties of a Novel and Conserved Gene Product, KerV, in Proteobacteria

Identification of novel virulence factors is essential for understanding bacterial pathogenesis and designing antibacterial strategies. In this study, we uncover such a factor, termed KerV, in Proteobacteria. Experiments carried out in a variety of eukaryotic host infection models revealed that the virulence of a Pseudomonas aeruginosa kerV null mutant was compromised when it interacted with amoebae, plants, flies, and mice. Bioinformatics analyses indicated that KerV is a hypothetical methyltransferase and is well-conserved across numerous Proteobacteria, including both well-known and emerging pathogens (e.g., virulent Burkholderia, Escherichia, Shigella, Vibrio, Salmonella, Yersinia and Brucella species). Furthermore, among the 197 kerV orthologs analyzed in this study, about 89% reside in a defined genomic neighborhood, which also possesses essential DNA replication and repair genes and detoxification gene. Finally, infection of Drosophila melanogaster with null mutants demonstrated that KerV orthologs are also crucial in Vibrio cholerae and Yersinia pseudotuberculosis pathogenesis. Our findings suggested that KerV has a novel and broad significance as a virulence factor in pathogenic Proteobacteria and it might serve as a new target for antibiotic drug design