Design and rationale of the B-lines lung ultrasound guided emergency department management of acute heart failure (BLUSHED-AHF) pilot trial

Background Medical treatment for acute heart failure (AHF) has not changed substantially over the last four decades. Emergency department (ED)-based evidence for treatment is limited. Outcomes remain poor, with a 25% mortality or re-admission rate within 30 days post discharge. Targeting pulmonary congestion, which can be objectively assessed using lung ultrasound (LUS), may be associated with improved outcomes. Methods BLUSHED-AHF is a multicenter, randomized, pilot trial designed to test whether a strategy of care that utilizes a LUS-driven treatment protocol outperforms usual care for reducing pulmonary congestion in the ED. We will randomize 130 ED patients with AHF across five sites to, a) a structured treatment strategy guided by LUS vs. b) a structured treatment strategy guided by usual care. LUS-guided care will continue until there are ≤15 B-lines on LUS or 6h post enrollment. The primary outcome is the proportion of patients with B-lines ≤ 15 at the conclusion of 6 h of management. Patients will continue to undergo serial LUS exams during hospitalization, to better understand the time course of pulmonary congestion. Follow up will occur through 90 days, exploring days-alive-and-out-of-hospital between the two arms. The study is registered on ClinicalTrials.gov (NCT03136198). Conclusion If successful, this pilot study will inform future, larger trial design on LUS driven therapy aimed at guiding treatment and improving outcomes in patients with AHF

Melting, bubble-like expansion and explosion of superheated plasmonic nanoparticles

We report on time-resolved coherent diffraction imaging of gas-phase silver nanoparticles, strongly heated via their plasmon resonance. The x-ray diffraction images reveal a broad range of phenomena for different excitation strengths, from simple melting over strong cavitation to explosive disintegration. Molecular dynamics simulations fully reproduce this behavior and show that the heating induces rather similar trajectories through the phase diagram in all cases, with the very different outcomes being due only to whether and where the stability limit of the metastable superheated liquid is crossed.Comment: 17 pages, 8 figures (including supplemental material

Matrix Metalloproteinase-Induced Epithelial-Mesenchymal Transition in Breast Cancer

Matrix metalloproteinases (MMPs) degrade and modify the extracellular matrix (ECM) as well as cell-ECM and cell-cell contacts, facilitating detachment of epithelial cells from the surrounding tissue. MMPs play key functions in embryonic development and mammary gland branching morphogenesis, but they are also upregulated in breast cancer, where they stimulate tumorigenesis, cancer cell invasion and metastasis. MMPs have been investigated as potential targets for cancer therapy, but clinical trials using broad-spectrum MMP inhibitors yielded disappointing results, due in part to lack of specificity toward individual MMPs and specific stages of tumor development. Epithelial-mesenchymal transition (EMT) is a developmental process in which epithelial cells take on the characteristics of invasive mesenchymal cells, and activation of EMT has been implicated in tumor progression. Recent findings have implicated MMPs as promoters and mediators of developmental and pathogenic EMT processes in the breast. In this review, we will summarize recent studies showing how MMPs activate EMT in mammary gland development and in breast cancer, and how MMPs mediate breast cancer cell motility, invasion, and EMT-driven breast cancer progression. We also suggest approaches to inhibit these MMP-mediated malignant processes for therapeutic benefit

DNA methylation and methyl-CpG binding proteins: developmental requirements and function

DNA methylation is a major epigenetic modification in the genomes of higher eukaryotes. In vertebrates, DNA methylation occurs predominantly on the CpG dinucleotide, and approximately 60% to 90% of these dinucleotides are modified. Distinct DNA methylation patterns, which can vary between different tissues and developmental stages, exist on specific loci. Sites of DNA methylation are occupied by various proteins, including methyl-CpG binding domain (MBD) proteins which recruit the enzymatic machinery to establish silent chromatin. Mutations in the MBD family member MeCP2 are the cause of Rett syndrome, a severe neurodevelopmental disorder, whereas other MBDs are known to bind sites of hypermethylation in human cancer cell lines. Here, we review the advances in our understanding of the function of DNA methylation, DNA methyltransferases, and methyl-CpG binding proteins in vertebrate embryonic development. MBDs function in transcriptional repression and long-range interactions in chromatin and also appear to play a role in genomic stability, neural signaling, and transcriptional activation. DNA methylation makes an essential and versatile epigenetic contribution to genome integrity and function

Forging connections: anthologies, arts collectives, and the politics of inclusion

The changing social and political landscape of twentieth-century Britain catalysed a remarkable rise in collaborative activity by artists and activists of black and Asian heritage. Creative communities began to gather in both local and regional contexts, with the aim of sharing resources and securing an audience. This chapter records some of these many activities, tracing the groups’ genesis, manifest objectives, and key contributions. It argues that anthologising should be understood as a specifically motivated activity. Literary anthologies of poetry and fiction served to showcase the diversity of contemporary writing, while also suggesting its coherence. Drawing on the concept of “strategic essentialism” elucidated by Gayatri Chakravorty Spivak, I show that the anthology acts to ensure the visibility of a group, bannered as a unified and singly-titled selection of texts, while also insisting on the differences within: the heterogeneous multiplicity of black and Asian British experiences and creative practices

'Vernacular Voices: Black British Poetry'

ABSTRACT Black British poetry is the province of experimenting with voice and recording rhythms beyond the iambic pentameter. Not only in performance poetry and through the spoken word, but also on the page, black British poetry constitutes and preserves a sound archive of distinct linguistic varieties. In Slave Song (1984) and Coolie Odyssey (1988), David Dabydeen employs a form of Guyanese Creole in order to linguistically render and thus commemorate the experience of slaves and indentured labourers, respectively, with the earlier collection providing annotated translations into Standard English. James Berry, Louise Bennett, and Valerie Bloom adapt Jamaican Patois to celebrate Jamaican folk culture and at times to represent and record experiences and linguistic interactions in the postcolonial metropolis. Grace Nichols and John Agard use modified forms of Guyanese Creole, with Nichols frequently constructing gendered voices whilst Agard often celebrates linguistic playfulness. The borders between linguistic varieties are by no means absolute or static, as the emergence and marked growth of ‘London Jamaican’ (Mark Sebba) indicates. Asian British writer Daljit Nagra takes liberties with English for different reasons. Rather than having recourse to established Creole languages, and blending them with Standard English, his heteroglot poems frequently emulate ‘Punglish’, the English of migrants whose first language is Punjabi. Whilst it is the language prestige of London Jamaican that has been significantly enhanced since the 1990s, a fact not only confirmed by linguistic research but also by its transethnic uses both in the streets and on the page, Nagra’s substantial success and the mainstream attention he receives also indicate the clout of vernacular voices in poetry. They have the potential to connect with oral traditions and cultural memories, to record linguistic varieties, and to endow ‘street cred’ to authors and texts. In this chapter, these double-voiced poetic languages are also read as signs of resistance against residual monologic ideologies of Englishness. © Book proposal (02/2016): The Cambridge History of Black and Asian British Writing p. 27 of 4

25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong

Evaluation of an emergency medicine point-of-care ultrasound curriculum adapted for a resource-limited setting in Guyana

Abstract Background This is a cohort pilot study of senior emergency medicine residents and residency-trained emergency medicine registrars practicing in an urban tertiary academic hospital in Guyana in South America. The primary aim was to assess the effectiveness of the current adapted residency ultrasound training curriculum and guide future ultrasound-specific continuing medical education. Ultrasound image acquisition, interpretation, and integration of ultrasound findings into clinical medical decision-making competency were assessed in a multimodal fashion: a written assessment and a practical assessment. Methods This was a cross-sectional cohort pilot study of senior emergency medicine residents and registrars (residency graduates) practicing in Guyana, a low-middle-income country. Ultrasound image acquisition and interpretation competency were assessed in a multimodal fashion: a written assessment and a practical assessment. The results will be reported as simple percentages. Participants will be deemed competent if the combined score is greater than 80% on the assessment. Results All senior residents and graduates of the residency program were competent in the core point-of-care ultrasound applications. The senior residents averaged 89% proficiency, and the residency graduates subdivided based on years since graduation averaged 87–100% proficiency. The more experienced providers performed better on the practical portion of the evaluation. Evaluating the composite analysis of all the participants revealed the Extended Focused Assessment with Sonography in Trauma (EFAST) exam (96%) and cardiac exam (93%) were done with the most proficiency. Conclusion The assessment results of this pilot study suggest that the current residency ultrasound training curriculum adapted to the resources available is associated with sustained competency after graduation. There was minor attrition of knowledge amongst the senior physicians, but all senior residents and all participating residency graduates were competent in the core ultrasound applications