Quest for certainty regarding early discharge in paediatric low-risk febrile neutropenia : a multicentre qualitative focus group discussion study involving patients, parents and healthcare professionals in the UK

OBJECTIVES: A systematic review of paediatric low-risk febrile neutropenia found that outpatient care is safe, with low rates of treatment failure. However, this review, and a subsequent meta-ethnography, suggested that early discharge of these patients may not be acceptable to key stakeholders. This study aimed to explore experiences and perceptions of patients, parents and healthcare professionals involved in paediatric febrile neutropenia care in the UK. SETTING: Three different centres within the UK, purposively selected from a national survey on the basis of differences in their service structure and febrile neutropenia management. PARTICIPANTS: Thirty-two participants were included in eight focus group discussions. PRIMARY OUTCOMES: Experiences and perceptions of paediatric febrile neutropenia care, including possible future reductions in therapy. RESULTS: Participants described a quest for certainty, in which they attempted to balance the uncertainty involved in understanding, expressing and negotiating risk with the illusion of certainty provided by strict protocols. Participants assessed risk using both formal and informal stratification tools, overlaid with emotional reactions to risk and experiences of risk within other situations. The benefits of certainty provided by protocols were counterbalanced by frustration at their strict constraints. The perceived benefits and harms of previous inpatient care informed participants' appraisals of future treatment strategies. CONCLUSIONS: This study highlighted the previously underestimated harms of admission for febrile neutropenia and the paternalistic nature of decision making, along with the frustrations and challenges for all parties involved in febrile neutropenia care. It demonstrates how the same statistics, generated by systematic reviews, can be used by key stakeholders to interpret risk differently, and how families in particular can view the harms of therapeutic options as different from the outcomes used within the literature. It justifies a reassessment of current treatment strategies for these children and further exploration of the potential to introduce shared decision making

Community transcriptomics reveals universal patterns of protein sequence conservation in natural microbial communities

Background Combined metagenomic and metatranscriptomic datasets make it possible to study the molecular evolution of diverse microbial species recovered from their native habitats. The link between gene expression level and sequence conservation was examined using shotgun pyrosequencing of microbial community DNA and RNA from diverse marine environments, and from forest soil. Results Across all samples, expressed genes with transcripts in the RNA sample were significantly more conserved than non-expressed gene sets relative to best matches in reference databases. This discrepancy, observed for many diverse individual genomes and across entire communities, coincided with a shift in amino acid usage between these gene fractions. Expressed genes trended toward GC-enriched amino acids, consistent with a hypothesis of higher levels of functional constraint in this gene pool. Highly expressed genes were significantly more likely to fall within an orthologous gene set shared between closely related taxa (core genes). However, non-core genes, when expressed above the level of detection, were, on average, significantly more highly expressed than core genes based on transcript abundance normalized to gene abundance. Finally, expressed genes showed broad similarities in function across samples, being relatively enriched in genes of energy metabolism and underrepresented by genes of cell growth. Conclusions These patterns support the hypothesis, predicated on studies of model organisms, that gene expression level is a primary correlate of evolutionary rate across diverse microbial taxa from natural environments. Despite their complexity, meta-omic datasets can reveal broad evolutionary patterns across taxonomically, functionally, and environmentally diverse communities.Gordon and Betty Moore FoundationAgouron InstituteNational Science Foundation (U.S.)Center for Microbial Oceanography: Research and Educatio

Inorganic–organic nanocomposites of CdSe nanocrystals surface-modified with oligo- and poly(fluorene) moieties

We report a facile grafting-from strategy towards the synthesis of inorganic–organic composites of semiconductor nanocrystals and wide-bandgap polymers. Amino-functional fluorenes have been used as co-ligands for CdSe nanocrystals, thus enabling us to design their surface directly during the synthesis. Highly monodisperse, strongly emitting CdSe nanocrystals have been obtained. Subsequently, a straightforward Yamamoto C–C coupling protocol was used to carry out surface polymerisation, hence modifying CdSe nanocrystals with oligo- and poly(fluorene) moieties. Both amino-fluorene capped CdSe nanocrystals and the resulting nanocrystal–polymer composites were characterized in detail by optical and FT-IR spectroscopy, TEM, AFM, and gel permeation chromatography, showing their potential as novel functional inorganic–organic hybrid materials

Sensitivity of a national coronial database for monitoring unnatural deaths among ex-prisoners in Australia

<p>Abstract</p> <p>Background</p> <p>The period immediately after release from custody is a time of marked vulnerability and increased risk of death for ex-prisoners. Despite this, there is currently no routine, national system for monitoring ex-prisoner mortality in Australia. This study subsequently aimed to evaluate the sensitivity of Australia's National Coroners Information System (NCIS) for identifying reportable deaths among prisoners and ex-prisoners.</p> <p>Findings</p> <p>Prisoner and ex-prisoner deaths identified through an independent search of the NCIS were compared with 'gold standard' records of prisoner and ex-prisoner deaths, generated from a national monitoring system and a state-based record linkage study, respectively. Of 294 known deaths in custody from 2001-2007, an independent search of the NCIS identified 229, giving a sensitivity of 77.9% (72.8%-82.3%). Of 677 known deaths among ex-prisoners from 2001-2007, an independent search of the NCIS identified 37, giving a sensitivity of 5.5% (4.0-7.4%). Ex-prisoner deaths that were detected were disproportionately drug-related, occurring within the first four weeks post-release, among younger prisoners and among those with more than two prior prison admissions.</p> <p>Conclusions</p> <p>Although a search of the NCIS detected the majority of reportable deaths among prisoners, it was only able to detect a small minority of reportable deaths among ex-prisoners. This suggests that the NCIS is not effective for monitoring mortality among ex-prisoners in Australia. Given the elevated rates of mortality among ex-prisoners in Australia and elsewhere, there remains an urgent need to establish a process for routine monitoring of ex-prisoner mortality, preferably through record linkage.</p

PPE51 mediates uptake of trehalose across the mycomembrane of Mycobacterium tuberculosis

The disaccharide trehalose is essential for viability of Mycobacterium tuberculosis, which synthesizes trehalose de novo but can also utilize exogenous trehalose. The mycobacterial cell wall encompasses two permeability barriers, the cytoplasmic membrane and the outer mycolic acid-containing mycomembrane. The ABC transporter LpqY-SugA-SugB-SugC has previously been demonstrated to mediate the specific uptake of trehalose across the cytoplasmic membrane. However, it is still unclear how the transport of trehalose molecules across the mycomembrane is mediated. In this study, we harnessed the antimycobacterial activity of the analogue 6-azido trehalose to select for spontaneous resistant M. tuberculosis mutants in a merodiploid strain harbouring two LpqY-SugA-SugB-SugC copies. Mutations mediating resistance to 6-azido trehalose mapped to the proline-proline-glutamate (PPE) family member PPE51 (Rv3136), which has recently been shown to be an integral mycomembrane protein involved in uptake of low-molecular weight compounds. A site-specific ppe51 gene deletion mutant of M. tuberculosis was unable to grow on trehalose as the sole carbon source. Furthermore, bioorthogonal labelling of the M. tuberculosis Δppe51 mutant incubated with 6-azido trehalose corroborated the impaired internalization. Taken together, the results indicate that the transport of trehalose and trehalose analogues across the mycomembrane of M. tuberculosis is exclusively mediated by PPE51

Can't play, won't play : longitudinal changes in perceived barriers to participation in sports clubs across the child-adolescent transition

Participation in sports is associated with numerous physical and psychosocial health benefits, however, participation declines with age, and knowledge of perceived barriers to participation in children is lacking. This longitudinal study of children and adolescents aimed to use the ecological model of physical activity to assess changes in barriers to participation in sports clubs to identify age- and weight-specific targets for intervention

Acoustic Processing of Fluidic Samples for Planetary Exploration

The search for life on other planetary bodies is driven by our quest to determine if Earth is unique with respect to harboring life. In order to answer this question, instrumentation with suitable sensitivity is required to measure biosignatures. In addition to accurate measurements by in-situ instruments, specialized sample acquisition and sample handling hardware is required to maximize the scientific information obtained from an acquired sample. This paper discusses a class of compact sample processing instrumentation using solid-state mechanisms that use acoustic waves to process samples prior to delivery to the instrument. Some of the acoustic sample processes that can be used to aid in preparation of liquid and liquid/solid mixtures include: mixing, milling, cavitating, lysing, heating, streaming, stirring, lofting, concentrating, segregating, and filtering. We will review these acoustic processes and show how they are generated using electromechanical systems. In addition to processing, these transduction systems could also use acoustics to interrogate physical properties such as the state of the sample, the acoustic velocity, and its attenuation. In order to generate these processes and sensing capabilities at these frequencies, a transduction mechanism is required to produce stress waves from electrical signals and vice versa. One commonly used technique is to use piezoelectric transducers that generate a stress that is linearly proportional to the voltage across the transducer and a voltage that is proportional to the stress on a transducer’s face. A variety of transducer modes are available to excite the sample, including thickness, transverse, radial, and shear extensional, and these can be used to build composite resonance structures including ultrasonic horns, tuning forks, bimorph, and unimorph benders to increase stress generated in the sample. We discuss how to model the acoustic interactions with the sample and the sample chamber in order to produce the required stress waves and illustrate the use of network models of piezoelectric transducers to accomplish this modeling. We demonstrate how to build up these models using Mason’s equivalent circuit for a piezoelectric and network models for acoustic layers in a design. Finally, to illustrate this acoustic processing ability, we will discuss a few systems that we have developed for sample handling systems for other planetary bodies like Mars and ocean worlds Enceladus and Europa

Design and Implementation of a Studio-Based General Chemistry Course

Most students taking general chemistry courses do not intend to pursue careers in chemistry; in fact, they are more likely to end up in positions where they fund, write, or vote for chemical research and policies. Our profession continues to ask how we can teach students scientific reasoning skills and chemical understanding in general chemistry that they are able to take beyond the classroom into their everyday lives. The emerging answer at this university is the studio teaching method, which incorporates the “best teaching and learning practices†recommended by chemical education research within an integrated lecture–lab technology-intensive environment. The design, implementation, and pedagogical rationale of studio general chemistry are described

Sequence analysis and characterization of active human alu subfamilies based on the 1000 genomes pilot project

© The Author(s) 2015. The goal of the 1000 Genomes Consortium is to characterize human genome structural variation (SV), including forms of copy number variations such as deletions, duplications, and insertions. Mobile element insertions, particularly Alu elements, are major contributors to genomic SV among humans. During the pilot phase of the project we experimentally validated 645 (611 intergenic and 34 exon targeted) polymorphic young Alu insertion events, absent fromthe human reference genome. Here, we report high resolution sequencing of 343 (322 unique) recent Alu insertion events, along with their respective target site duplications, precise genomic breakpoint coordinates, subfamily assignment, percent divergence, and estimated A-rich tail lengths.All the sequenced Alu lociwerederived from the Alu Y lineagewith no evidence of retrotransposition activity involving older Alu families (e.g., AluJandAluS). AluYa5 is currently themost active Alu subfamily in the human lineage, followed by AluYb8, andmany others including three newly identified subfamilieswe have termed AluYb7a3, AluYb8b1, and AluYa4a1. This report provides the structural details of 322 unique Alu variants from individual human genomes collectively adding about 100 kb of genomic variation. Many Alu subfamilies are currently active in human populations, including a surprising level of AluY retrotransposition. Human Alu subfamilies exhibit continuous evolution with potential drivers sprouting new Alu lineages