Magma mixing and high fountaining during the 1959 K īlauea Iki eruption, Hawai'i

The 1959 Kīlauea Iki eruption provides a unique opportunity to investigate the process of shallow magma mixing, its impact on the magmatic volatile budget and its role in triggering and driving episodes of Hawaiian fountaining. Melt inclusions hosted by olivine record a continuous decrease in H2O concentration through the 17 episodes of the eruption, while CO2 concentrations correlate with the degree of post-entrapment crystallization of olivine on the inclusion walls. Geochemical data, when combined with the magma budget and with contemporaneous eruption observations, show complex mixing between episodes involving hot, geochemically heterogeneous melts from depth, likely carrying exsolved vapour, and melts which had erupted at the surface, degassed and drained-back into the vent. The drained-back melts acted as a coolant, inducing rapid cooling of the more primitive melts and their olivines at shallow depths and inducing crystallization and vesiculation and triggering renewed fountaining. A consequence of the mixing is that the melts became vapor-undersaturated, so equilibration pressures cannot be inferred from them using saturation models. After the melt inclusions were trapped, continued growth of vapor bubbles, caused by enhanced post-entrapment crystallization, sequestered a large fraction of CO2 from the melt within the inclusions. This study, while cautioning against accepting melt inclusion CO2 concentrations “as measured” in mixed magmas, also illustrates that careful analysis and interpretation of post-entrapment modifications can turn this apparent challenge into a way to yield novel useful insights into the geochemical controls on eruption intensity.IS was supported by a NERC-funded studentship and a USGS Jack Kleinman Grant for Volcano Research. ME acknowledges NERC ion probe grant IMF376/0509. BH’s participation was funded by NSF EAR-1145159. We acknowledge the NERC Edinburgh Ion Microprobe facility, where we undertook the SIMS analyses.This version is the author accepted manuscript and will be under embargo until the 6th of June 2015. The final version has been published by Elsevier in Earth and Planetary Science Letters here: http://www.sciencedirect.com/science/article/pii/S0012821X14003264

Exploiting inflammation for therapeutic gain in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy associated with <5% 5-year survival, in which standard chemotherapeutics have limited benefit. The disease is associated with significant intra- and peritumoral inflammation and failure of protective immunosurveillance. Indeed, inflammatory signals are implicated in both tumour initiation and tumour progression. The major pathways regulating PDAC-associated inflammation are now being explored. Activation of leukocytes, and upregulation of cytokine and chemokine signalling pathways, both have been shown to modulate PDAC progression. Therefore, targeting inflammatory pathways may be of benefit as part of a multi-target approach to PDAC therapy. This review explores the pathways known to modulate inflammation at different stages of tumour development, drawing conclusions on their potential as therapeutic targets in PDAC

Food Anticipatory Activity Behavior of Mice across a Wide Range of Circadian and Non-Circadian Intervals

When rodents are fed in a limited amount during the daytime, they rapidly redistribute some of their nocturnal activity to the time preceding the delivery of food. In rats, anticipation of a daily meal has been interpreted as a circadian rhythm controlled by a food-entrained oscillator (FEO) with circadian limits to entrainment. Lesion experiments place this FEO outside of the light-entrainable circadian pacemaker in the suprachiasmatic nucleus. Mice also anticipate a fixed daily meal, but circadian limits to entrainment and anticipation of more than 2 daily meals, have not been assessed. We used a video-based behavior recognition system to quantify food anticipatory activity in mice receiving 2, 3, or 6 daily meals at intervals of 12, 8, or 4-hours (h). Individual mice were able to anticipate as many as 4 of 6 daily meals, and anticipation persisted during meal omission tests. On the 6 meal schedule, pre-prandial activity and body temperature were poorly correlated, suggesting independent regulation. Mice showed a limited ability to anticipate an 18 h feeding schedule. Finally, mice showed concurrent circadian and sub-hourly anticipation when provided with 6 small meals, at 30 minute intervals, at a fixed time of day. These results indicate that mice can anticipate feeding opportunities at a fixed time of day across a wide range of intervals not previously associated with anticipatory behavior in studies of rats. The methods described here can be exploited to determine the extent to which timing of different intervals in mice relies on common or distinct neural and molecular mechanisms

The Study of Rule-Governed Behavior and Derived Stimulus Relations: Bridging the Gap

The concept of rule-governed behavior or instructional control has been widely recognized for many decades within the behavior-analytic literature. It has also been argued that the human capacity to formulate and follow increasingly complex rules may undermine sensitivity to direct contingencies of reinforcement, and that excessive reliance upon rules may be an important variable in human psychological suffering. Although the concept of rules would appear to have been relatively useful within behavior analysis, it seems wise from time to time to reflect upon the utility of even well-established concepts within a scientific discipline. Doing so may be particularly important if it begins to emerge that the existing concept does not readily orient researchers toward potentially important variables associated with that very concept. The primary purpose of this article is to engage in this reflection. In particular, we will focus on the link that has been made between rule-governed behavior and derived relational responding, and consider the extent to which it might be useful to supplement talk of rules or instructions with terms that refer to the dynamics of derived relational responding

Comprehensive Mapping of Common Immunodominant Epitopes in the West Nile Virus Nonstructural Protein 1 Recognized by Avian Antibody Responses

West Nile virus (WNV) is a mosquito-borne flavivirus that primarily infects birds but occasionally infects humans and horses. Certain species of birds, including crows, house sparrows, geese, blue jays and ravens, are considered highly susceptible hosts to WNV. The nonstructural protein 1 (NS1) of WNV can elicit protective immune responses, including NS1-reactive antibodies, during infection of animals. The antigenicity of NS1 suggests that NS1-reactive antibodies could provide a basis for serological diagnostic reagents. To further define serological reagents for diagnostic use, the antigenic sites in NS1 that are targeted by host immune responses need to be identified and the potential diagnostic value of individual antigenic sites also needs to be defined. The present study describes comprehensive mapping of common immunodominant linear B-cell epitopes in the WNV NS1 using avian WNV NS1 antisera. We screened antisera from chickens, ducks and geese immunized with purified NS1 for reactivity against 35 partially overlapping peptides covering the entire WNV NS1. This study identified twelve, nine and six peptide epitopes recognized by chicken, duck and goose antibody responses, respectively. Three epitopes (NS1-3, 14 and 24) were recognized by antibodies elicited by immunization in all three avian species tested. We also found that NS1-3 and 24 were WNV-specific epitopes, whereas the NS1-14 epitope was conserved among the Japanese encephalitis virus (JEV) serocomplex viruses based on the reactivity of avian WNV NS1 antisera against polypeptides derived from the NS1 sequences of viruses of the JEV serocomplex. Further analysis showed that the three common polypeptide epitopes were not recognized by antibodies in Avian Influenza Virus (AIV), Newcastle Disease Virus (NDV), Duck Plague Virus (DPV) and Goose Parvovirus (GPV) antisera. The knowledge and reagents generated in this study have potential applications in differential diagnostic approaches and subunit vaccines development for WNV and other viruses of the JEV serocomplex

Changing behaviour 'more or less'-do theories of behaviour inform strategies for implementation and de-implementation? A critical interpretive synthesis

BACKGROUND: Implementing evidence-based care requires healthcare practitioners to do less of some things (de-implementation) and more of others (implementation). Variations in effectiveness of behaviour change interventions may result from failure to consider a distinction between approaches by which behaviour increases and decreases in frequency. The distinction is not well represented in methods for designing interventions. This review aimed to identify whether there is a theoretical rationale to support this distinction. METHODS: Using Critical Interpretative Synthesis, this conceptual review included papers from a broad range of fields (biology, psychology, education, business) likely to report approaches for increasing or decreasing behaviour. Articles were identified from databases using search terms related to theory and behaviour change. Articles reporting changes in frequency of behaviour and explicit use of theory were included. Data extracted were direction of behaviour change, how theory was operationalised, and theory-based recommendations for behaviour change. Analyses of extracted data were conducted iteratively and involved inductive coding and critical exploration of ideas and purposive sampling of additional papers to explore theoretical concepts in greater detail. RESULTS: Critical analysis of 66 papers and their theoretical sources identified three key findings: (1) 9 of the 15 behavioural theories identified do not distinguish between implementation and de-implementation (5 theories were applied to only implementation or de-implementation, not both); (2) a common strategy for decreasing frequency was substituting one behaviour with another. No theoretical basis for this strategy was articulated, nor were methods proposed for selecting appropriate substitute behaviours; (3) Operant Learning Theory makes an explicit distinction between techniques for increasing and decreasing frequency. DISCUSSION: Behavioural theories provide little insight into the distinction between implementation and de-implementation. Operant Learning Theory identified different strategies for implementation and de-implementation, but these strategies may not be acceptable in health systems. Additionally, if behaviour substitution is an approach for de-implementation, further investigation may inform methods or rationale for selecting the substitute behaviour

Exome Sequencing and Genetic Testing for MODY

Context: Genetic testing for monogenic diabetes is important for patient care. Given the extensive genetic and clinical heterogeneity of diabetes, exome sequencing might provide additional diagnostic potential when standard Sanger sequencing-based diagnostics is inconclusive. Objective: The aim of the study was to examine the performance of exome sequencing for a molecular diagnosis of MODY in patients who have undergone conventional diagnostic sequencing of candidate genes with negative results. Research Design and Methods: We performed exome enrichment followed by high-throughput sequencing in nine patients with suspected MODY. They were Sanger sequencing-negative for mutations in the HNF1A, HNF4A, GCK, HNF1B and INS genes. We excluded common, non-coding and synonymous gene variants, and performed in-depth analysis on filtered sequence variants in a pre-defined set of 111 genes implicated in glucose metabolism. Results: On average, we obtained 45 X median coverage of the entire targeted exome and found 199 rare coding variants per individual. We identified 0–4 rare non-synonymous and nonsense variants per individual in our a priori list of 111 candidate genes. Three of the variants were considered pathogenic (in ABCC8, HNF4A and PPARG, respectively), thus exome sequencing led to a genetic diagnosis in at least three of the nine patients. Approximately 91% of known heterozygous SNPs in the target exomes were detected, but we also found low coverage in some key diabetes genes using our current exome sequencing approach. Novel variants in the genes ARAP1, GLIS3, MADD, NOTCH2 and WFS1 need further investigation to reveal their possible role in diabetes. Conclusion: Our results demonstrate that exome sequencing can improve molecular diagnostics of MODY when used as a complement to Sanger sequencing. However, improvements will be needed, especially concerning coverage, before the full potential of exome sequencing can be realized

Food additives : Assessing the impact of exposure to permitted emulsifiers on bowel and metabolic health – introducing the FADiets study

Acknowledgements Additional members of the academic team including Dr Carrie Duckworth, Professor John Wilding, Professor Mark Pritchard and Professor Chris Probert (University of Liverpool, UK), Professor Harry Flint (Rowett Institute, UK), Dr Graham Horgan (Biomathematics and Statistics Scotland), Professor Johan Söderholm and Dr Åsa Keita (University Hospital Linköping, Sweden). Funding This study is funded by the Medical Research Council (MR/P023606/1).Peer reviewedPublisher PD