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

FIRST-line support for Assistance in Breathing in Children (FIRST-ABC): protocol for a multicentre randomised feasibility trial of non-invasive respiratory support in critically ill children.

INTRODUCTION: Over 18 000 children are admitted annually to UK paediatric intensive care units (PICUs), of whom nearly 75% receive respiratory support (invasive and/or non-invasive). Continuous positive airway pressure (CPAP) has traditionally been used to provide first-line non-invasive respiratory support (NRS) in PICUs; however, high-flow nasal cannula therapy (HFNC), a novel mode of NRS, has recently gained popularity despite the lack of high-quality trial evidence to support its effectiveness. This feasibility study aims to inform the design and conduct of a future definitive randomised clinical trial (RCT) comparing the two modes of respiratory support. METHODS AND ANALYSIS: We will conduct a three-centre randomised feasibility study over 12 months. Patients admitted to participating PICUs who satisfy eligibility criteria will be recruited to either group A (primary respiratory failure) or group B (postextubation). Consent will be obtained from parents/guardians prior to randomisation in 'planned' group B, and deferred in emergency situations (group A and 'rescue' group B). Participants will be randomised (1:1) to either CPAP or HFNC using sealed, opaque envelopes, from a computer-generated randomisation sequence with variable block sizes. The study protocol specifies algorithms for the initiation, maintenance and weaning of HFNC and CPAP. The primary outcomes are related to feasibility, including the number of eligible patients in each group, feasibility of randomising >50% of eligible patients and measures of adherence to the treatment protocols. Data will also be collected on patient outcomes (eg, mortality and length of PICU stay) to inform the selection of an appropriate outcome measure in a future RCT. We aim to recruit 120 patients to the study. ETHICS AND DISSEMINATION: Ethical approval was granted by the National Research Ethics Service Committee North East-Tyne&Wear South (15/NE/0296). Study findings will be disseminated through peer-reviewed journals, national and international conferences. TRIALS REGISTRATION NUMBER: NCT02612415; pre-results

Pharmacological levels of withaferin A (Withania somnifera) trigger clinically relevant anticancer effects specific to triple negative breast cancer cells

Withaferin A (WA) isolated from Withania somnifera (Ashwagandha) has recently become an attractive phytochemical under investigation in various preclinical studies for treatment of different cancer types. In the present study, a comparative pathway-based transcriptome analysis was applied in epithelial-like MCF-7 and triple negative mesenchymal MDA-MB-231 breast cancer cells exposed to different concentrations of WA which can be detected systemically in in vivo experiments. Whereas WA treatment demonstrated attenuation of multiple cancer hallmarks, the withanolide analogue Withanone (WN) did not exert any of the described effects at comparable concentrations. Pathway enrichment analysis revealed that WA targets specific cancer processes related to cell death, cell cycle and proliferation, which could be functionally validated by flow cytometry and real-time cell proliferation assays. WA also strongly decreased MDA-MB-231 invasion as determined by single-cell collagen invasion assay. This was further supported by decreased gene expression of extracellular matrix-degrading proteases (uPA, PLAT, ADAM8), cell adhesion molecules (integrins, laminins), pro-inflammatory mediators of the metastasis-promoting tumor microenvironment (TNFSF12, IL6, ANGPTL2, CSF1R) and concomitant increased expression of the validated breast cancer metastasis suppressor gene (BRMS1). In line with the transcriptional changes, nanomolar concentrations of WA significantly decreased protein levels and corresponding activity of uPA in MDA-MB-231 cell supernatant, further supporting its anti-metastatic properties. Finally, hierarchical clustering analysis of 84 chromatin writer-reader-eraser enzymes revealed that WA treatment of invasive mesenchymal MDA-MB-231 cells reprogrammed their transcription levels more similarly towards the pattern observed in non-invasive MCF-7 cells. In conclusion, taking into account that sub-cytotoxic concentrations of WA target multiple metastatic effectors in therapy-resistant triple negative breast cancer, WA-based therapeutic strategies targeting the uPA pathway hold promise for further (pre)clinical development to defeat aggressive metastatic breast cancer

Ferromagnetic Semiconductors: Moving Beyond (Ga,Mn)As

The recent development of MBE techniques for growth of III-V ferromagnetic semiconductors has created materials with exceptional promise in spintronics, i.e. electronics that exploit carrier spin polarization. Among the most carefully studied of these materials is (Ga,Mn)As, in which meticulous optimization of growth techniques has led to reproducible materials properties and ferromagnetic transition temperatures well above 150 K. We review progress in the understanding of this particular material and efforts to address ferromagnetic semiconductors as a class. We then discuss proposals for how these materials might find applications in spintronics. Finally, we propose criteria that can be used to judge the potential utility of newly discovered ferromagnetic semiconductors, and we suggest guidelines that may be helpful in shaping the search for the ideal material.Comment: 37 pages, 4 figure

Cohort profile of the Biomarkers of Acute Serious Illness in Children (BASIC) study: a prospective multicentre cohort study in critically ill children

PURPOSE: Despite significant progress, challenges remain in the management of critically ill children, including early identification of infection and organ failure and robust early risk stratification to predict poor outcome. The Biomarkers of Acute Serious Illness in Children study aims to identify genetic and biological pathways underlying the development of critical illness in infections and organ failure and those leading to poor outcome (death or severe disability) in children requiring emergency intensive care. PARTICIPANTS: We recruited a prospective cohort of critically ill children undergoing emergency transport to four paediatric intensive care units (PICUs) in Southeast England between April 2014 and December 2016. FINDINGS TO DATE: During the study period, 1017 patients were recruited by the regional PICU transport team, and blood and urine samples were obtained at/around first contact with the patient by the transport team. Consent for participation in the study was deferred until after PICU admission and 674 parents/carers were consented. Further samples (blood, urine, stool and throat swabs) were collected after consent. Samples were processed and stored for genomic, transcriptomic, proteomic and metabolomic analyses. Demographic, clinical and laboratory data at first contact, during PICU stay and at discharge, were collected, as were detailed data regarding infectious or non-infectious aetiology. In addition, 115 families have completed 12-month validated follow-up questionnaires to assess quality of life and child behaviour.The first phase of sample analyses (transcriptomic profiling) is currently in progress. FUTURE PLANS: Stored samples will be analysed using genomic, proteomic and metabolic profiling. Advanced bioinformatics techniques will be used to identify biomarkers for early diagnosis of infection, identification of organ failure and risk stratification to predict poor outcome (death/severe disability). TRIAL REGISTRATION NUMBER: NCT03238040

Comparative Proteomics Analyses Reveal the virB of B. melitensis Affects Expression of Intracellular Survival Related Proteins

BACKGROUND: Brucella melitensis is a facultative, intracellular, pathogenic bacterium that replicates within macrophages. The type IV secretion system encoded by the virB operon (virB) is involved in Brucella intracellular survival. However, the underlying molecular mechanisms, especially the target proteins affected by the virB, remain largely unclear. METHODOLOGY/PRINCIPAL FINDINGS: In order to define the proteins affected by virB, the proteomes of wild-type and the virB mutant were compared under in vitro conditions where virB was highly activated. The differentially expressed proteins were identified by MALDI-TOF-MS. Forty-four down-regulated and eighteen up-regulated proteins which exhibited a 2-fold or greater change were identified. These proteins included those involved in amino acid transport and metabolism, lipid metabolism, energy production, cell membrane biogenesis, translation, post-translational modifications and protein turnover, as well as unknown proteins. Interestingly, several important virulence related proteins involved in intracellular survival, including VjbR, DnaK, HtrA, Omp25, and GntR, were down-regulated in the virB mutant. Transcription analysis of virB and vjbR at different growth phase showed that virB positively affect transcription of vjbR in a growth phase dependent manner. Quantitative RT-PCR showed that transcription of these genes was also affected by virB during macrophage cell infection, consistent with the observed decreased survival of the virB mutant in macrophage. CONCLUSIONS/SIGNIFICANCE: These data indicated that the virB operon may control the intracellular survival of Brucella by affecting the expression of relevant proteins

The effect of early pregnancy following chemotherapy on disease relapse and foetal outcome in women treated for gestational trophoblastic tumours

Little literature exists on the safety of early pregnancy following chemotherapy. Here we assess the rate of relapse and foetal outcome in women who have completed single and multi-agent chemotherapy for gestational trophoblastic tumours. The records of 1532 patients treated for persistent gestational trophoblastic tumours at Charing Cross Hospital between 1969 and 1998 were reviewed. Patients were defined as receiving single agent or multi-agent treatment. Relapse rates and foetal outcome were reviewed in the 230 patients who became pregnant within 12 months of completing chemotherapy. In the single agent group 153 (22%) of 691 patients conceived early. Three subsequently relapsed. In the multi-agent group, 77 (10%) of 779 patients conceived early, two then relapsed. Relapse rates were 2% (3 out of 153) and 2.5% (2 out of 77) for each group compared to 5% and 5.6% in the comparative non-pregnant groups. Outcomes of 230 early pregnancies: 164 (71%) delivered at full term, 35 (15%) terminations, 26 (11%) spontaneous abortions, three (1.3%) new hydatidiform moles and two (1%) stillbirths. Early pregnancies were more common in the single agent group (P<0.001), but spontaneous miscarriages and terminations were more likely to occur in the multi-agent group (P=0.04 and 0.03, respectively). Of the full-term pregnancies, three (1.8%) babies were born with congenital abnormalities. Patients in either group who conceive within 12 months of completing chemotherapy are not at increased risk of relapse. Though, we still advise avoiding pregnancy within 12 months of completing chemotherapy, those that do conceive can be reassured of a likely favourable outcome

Meeting the support and information needs of women with advanced breast cancer: a randomised controlled trial

Addressing psychosocial and quality of life needs is central to provision of excellent care for people with advanced cancer. This study tested a brief nurse-delivered intervention to address the needs of urban women with advanced breast cancer. This study was conducted at four large urban hospitals in Australia. One hundred and five women with advanced breast cancer were recruited and randomised to receive the intervention or usual care, then asked to complete the European Organisation of Research and Treatment of Quality of life Q-C30 version (2.0) (EORTC Q-C30) (version 2) and Supportive Care Needs Survey (SCNS) at 1 month and 3 months postrecruitment. No significant differences were detected between intervention and usual care groups in the SCNS or the EORTC Q-C30 subscale scores. However, when the groups were divided into high needs (score of above 50) and low baseline needs (score of 50 or below) for each SCNS subscale, a significant difference between intervention and usual care groups was found in the psychological/emotional subscale among women with high baseline needs. In conclusions, this study demonstrated that a face-to-face session and follow-up phone call with a breast care nurse significantly reduced the psychological and emotional needs of those with high initial needs. There was no evidence of the intervention influencing the quality of life; or perceived needs of women with low initial psychological/emotional needs or perceived needs in other domains. Possibly, the intervention was not sufficiently intense to achieve an effect

Hydrothermal alteration of andesitic lava domes can lead to explosive volcanic behaviour

Dome-forming volcanoes are among the most hazardous volcanoes on Earth. Magmatic outgassing can be hindered if the permeability of a lava dome is reduced, promoting pore pressure augmentation and explosive behaviour. Laboratory data show that acid-sulphate alteration, common to volcanoes worldwide, can reduce the permeability on the sample lengthscale by up to four orders of magnitude and is the result of pore- and microfracture-filling mineral precipitation. Calculations using these data demonstrate that intense alteration can reduce the equivalent permeability of a dome by two orders of magnitude, which we show using numerical modelling to be sufficient to increase pore pressure. The fragmentation criterion shows that the predicted pore pressure increase is capable of fragmenting the majority of dome-forming materials, thus promoting explosive volcanism. It is crucial that hydrothermal alteration, which develops over months to years, is monitored at dome-forming volcanoes and is incorporated into real-time hazard assessments