4,794 research outputs found
The implausibility of ‘usual care’ in an open system: sedation and weaning practices in Paediatric Intensive Care Units (PICUs) in the United Kingdom (UK)
Background: The power of the randomised controlled trial depends upon its capacity to operate in a closed
system whereby the intervention is the only causal force acting upon the experimental group and absent in the
control group, permitting a valid assessment of intervention efficacy. Conversely, clinical arenas are open systems
where factors relating to context, resources, interpretation and actions of individuals will affect implementation and
effectiveness of interventions. Consequently, the comparator (usual care) can be difficult to define and variable in
multi-centre trials. Hence outcomes cannot be understood without considering usual care and factors that may
affect implementation and impact on the intervention.
Methods: Using a fieldwork approach, we describe PICU context, ‘usual’ practice in sedation and weaning from
mechanical ventilation, and factors affecting implementation prior to designing a trial involving a sedation and
ventilation weaning intervention. We collected data from 23 UK PICUs between June and November 2014 using
observation, individual and multi-disciplinary group interviews with staff.
Results: Pain and sedation practices were broadly similar in terms of drug usage and assessment tools. Sedation
protocols linking assessment to appropriate titration of sedatives and sedation holds were rarely used (9 % and 4 %
of PICUs respectively). Ventilator weaning was primarily a medical-led process with 39 % of PICUs engaging senior
nurses in the process: weaning protocols were rarely used (9 % of PICUs). Weaning methods were variably based
on clinician preference. No formal criteria or use of spontaneous breathing trials were used to test weaning
readiness. Seventeen PICUs (74 %) had prior engagement in multi-centre trials, but limited research nurse
availability. Barriers to previous trial implementation were intervention complexity, lack of belief in the evidence and
inadequate training. Facilitating factors were senior staff buy-in and dedicated research nurse provision.
Conclusions: We examined and identified contextual and organisational factors that may impact on the
implementation of our intervention. We found usual practice relating to sedation, analgesia and ventilator weaning
broadly similar, yet distinctively different from our proposed intervention, providing assurance in our ability to
evaluate intervention effects. The data will enable us to develop an implementation plan; considering these factors
we can more fully understand their impact on study outcomes
Testing A (Stringy) Model of Quantum Gravity
I discuss a specific model of space-time foam, inspired by the modern
non-perturbative approach to string theory (D-branes). The model views our
world as a three brane, intersecting with D-particles that represent stringy
quantum gravity effects, which can be real or virtual. In this picture, matter
is represented generically by (closed or open) strings on the D3 brane
propagating in such a background. Scattering of the (matter) strings off the
D-particles causes recoil of the latter, which in turn results in a distortion
of the surrounding space-time fluid and the formation of (microscopic, i.e.
Planckian size) horizons around the defects. As a mean-field result, the
dispersion relation of the various particle excitations is modified, leading to
non-trivial optical properties of the space time, for instance a non-trivial
refractive index for the case of photons or other massless probes. Such models
make falsifiable predictions, that may be tested experimentally in the
foreseeable future. I describe a few such tests, ranging from observations of
light from distant gamma-ray-bursters and ultra high energy cosmic rays, to
tests using gravity-wave interferometric devices and terrestrial particle
physics experients involving, for instance, neutral kaons.Comment: 25 pages LATEX, four figures incorporated, uses special proceedings
style. Invited talk at the third international conference on Dark Matter in
Astro and Particle Physics, DARK2000, Heidelberg, Germany, July 10-15 200
How victim age affects the context and timing of child sexual abuse: applying the routine activities approach to the first sexual abuse incident
The aim of this study was to examine from the routine activities approach how victim age might help to explain the timing, context and nature of offenders’ first known contact sexual abuse incident. One-hundred adult male child sexual abusers (M = 45.8 years, SD = 12.2; range = 20–84) were surveyed about the first time they had sexual contact with a child. Afternoon and early evening (between 3 pm and 9 pm) was the most common time in which sexual contact first occurred. Most incidents occurred in a home. Two-thirds of incidents occurred when another person was in close proximity, usually elsewhere in the home. Older victims were more likely to be sexually abused by someone outside their families and in the later hours of the day compared to younger victims. Proximity of another person (adult and/or child) appeared to have little effect on offenders’ decisions to abuse, although it had some impact on the level of intrusion and duration of these incidents. Overall, the findings lend support to the application of the routine activities approach for considering how contextual risk factors (i.e., the timing and relationship context) change as children age, and raise questions about how to best conceptualize guardianship in the context of child sexual abuse. These factors should be key considerations when devising and implementing sexual abuse prevention strategies and for informing theory development
Cysteine oxidation targets peroxiredoxins 1 and 2 for exosomal release through a novel mechanism of redox-dependent secretion
Non-classical protein secretion is of major importance as a number of cytokines and inflammatory mediators are secreted via this route. Current evidence indicates that there are several mechanistically distinct methods of non-classical secretion. We have recently shown that peroxiredoxin (Prdx) 1 and Prdx2 are released by various cells upon exposure to inflammatory stimuli such as LPS or TNF-α. The released Prdx then acts to induce production of inflammatory cytokines. However, Prdx1 and 2 do not have signal peptides and therefore must be secreted by alternative mechanisms as has been postulated for the inflammatory mediators IL-1β and HMGB1. We show here that circulating Prdx1 and 2 are present exclusively as disulphide-linked homodimers. Inflammatory stimuli also induce in vitro release of Prdx1 and 2 as disulfide-linked homodimers. Mutation of cysteines Cys51 or Cys172 (but not Cys70) in Prdx2, and Cys52 or Cys173 (but not Cys71 or Cys83) in Prdx1 prevented dimer formation and this was associated with inhibition of their TNF-α-induced release. Thus, the presence and oxidation of key cysteine residues in these proteins are a prerequisite for their secretion in response to TNF-α and this release can be induced with an oxidant. In contrast, the secretion of the nuclear-associated danger signal HMGB1 is independent of cysteine oxidation, as shown by experiments with a cysteine-free HMGB1 mutant. Release of Prdx1 and 2 is not prevented by inhibitors of the classical secretory pathway; instead, both Prdx1 and 2 are released in exosomes from both HEK cells and monocytic cells. Serum Prdx1 and 2 are also associated with the exosomes. These results describe a novel pathway of protein secretion mediated by cysteine oxidation that underlines the importance of redox-dependent signalling mechanisms in inflammation
Assessing the psychometric and ecometric properties of neighborhood scales using adolescent survey data from urban and rural Scotland
This work was supported by NHS Health Scotland and the University of St Andrews.Background: Despite the well-established need for specific measurement instruments to examine the relationship between neighborhood conditions and adolescent well-being outcomes, few studies have developed scales to measure features of the neighborhoods in which adolescents reside. Moreover, measures of neighborhood features may be operationalised differently by adolescents living in different levels of urban/rurality. This has not been addressed in previous studies. The objectives of this study were to: 1) establish instruments to measure adolescent neighborhood features at both the individual and neighborhood level, 2) assess their psychometric and ecometric properties, 3) test for invariance by urban/rurality, and 4) generate neighborhood level scores for use in further analysis. Methods: Data were from the Scottish 2010 Health Behaviour in School-aged Children Survey, which included an over-sample of rural adolescents. The survey responses of interest came from questions designed to capture different facets of the local area in which each respondent resided. Intermediate data zones were used as proxies for neighborhoods. Internal consistency was evaluated by Cronbach’s alpha. Invariance was examined using confirmatory factor analysis. Multilevel models were used to estimate ecometric properties and generate neighborhood scores. Results: Two constructs labeled neighborhood social cohesion and neighborhood disorder were identified. Adjustment was made to the originally specified model to improve model fit and measures of invariance. At the individual level, reliability was .760 for social cohesion and .765 for disorder, and between .524 and .571 for both constructs at the neighborhood level. Individuals in rural areas experienced greater neighborhood social cohesion and lower levels of neighborhood disorder compared with those in urban areas. Conclusions: The scales are appropriate for measuring neighborhood characteristics experienced by adolescents across urban and rural Scotland, and can be used in future studies of neighborhoods and health. However, trade-offs between neighborhood sample size and reliability must be considered.Publisher PDFPeer reviewe
GLAST: Understanding the High Energy Gamma-Ray Sky
We discuss the ability of the GLAST Large Area Telescope (LAT) to identify,
resolve, and study the high energy gamma-ray sky. Compared to previous
instruments the telescope will have greatly improved sensitivity and ability to
localize gamma-ray point sources. The ability to resolve the location and
identity of EGRET unidentified sources is described. We summarize the current
knowledge of the high energy gamma-ray sky and discuss the astrophysics of
known and some prospective classes of gamma-ray emitters. In addition, we also
describe the potential of GLAST to resolve old puzzles and to discover new
classes of sources.Comment: To appear in Cosmic Gamma Ray Sources, Kluwer ASSL Series, Edited by
K.S. Cheng and G.E. Romer
SRA-Domain Proteins Required for DRM2-Mediated De Novo DNA Methylation
De novo DNA methylation and the maintenance of DNA methylation in asymmetrical sequence contexts is catalyzed by homologous proteins in plants (DRM2) and animals (DNMT3a/b). In plants, targeting of DRM2 depends on small interfering RNAs (siRNAs), although the molecular details are still unclear. Here, we show that two SRA-domain proteins (SUVH9 and SUVH2) are also essential for DRM2-mediated de novo and maintenance DNA methylation in Arabidopsis thaliana. At some loci, SUVH9 and SUVH2 act redundantly, while at other loci only SUVH2 is required, and this locus specificity correlates with the differing DNA-binding affinity of the SRA domains within SUVH9 and SUVH2. Specifically, SUVH9 preferentially binds methylated asymmetric sites, while SUVH2 preferentially binds methylated CG sites. The suvh9 and suvh2 mutations do not eliminate siRNAs, suggesting a role for SUVH9 and SUVH2 late in the RNA-directed DNA methylation pathway. With these new results, it is clear that SRA-domain proteins are involved in each of the three pathways leading to DNA methylation in Arabidopsis
Upper- and mid-mantle interaction between the Samoan plume and the Tonga-Kermadec slabs
Mantle plumes are thought to play a key role in transferring heat from the core\u2013mantle
boundary to the lithosphere, where it can significantly influence plate tectonics. On impinging
on the lithosphere at spreading ridges or in intra-plate settings, mantle plumes may generate
hotspots, large igneous provinces and hence considerable dynamic topography. However, the
active role of mantle plumes on subducting slabs remains poorly understood. Here we show
that the stagnation at 660 km and fastest trench retreat of the Tonga slab in Southwestern
Pacific are consistent with an interaction with the Samoan plume and the Hikurangi plateau.
Our findings are based on comparisons between 3D anisotropic tomography images and 3D
petrological-thermo-mechanical models, which self-consistently explain several unique
features of the Fiji\u2013Tonga region. We identify four possible slip systems of bridgmanite in the
lower mantle that reconcile the observed seismic anisotropy beneath the Tonga slab
(VSH4VSV) with thermo-mechanical calculations
Differential postural effects of plantar-flexor muscles fatigue under normal, altered and improved vestibular and neck somatosensory conditions
The aim of the present study was to assess the effects of plantar-flexor
muscles fatigue on postural control during quiet standing under normal, altered
and improved vestibular and neck somatosensory conditions. To address this
objective, young male university students were asked to stand upright as still
as possible with their eyes closed in two conditions of No Fatigue and Fatigue
of the plantar-flexor muscles. In Experiment 1 (n=15), the postural task was
executed in two Neutral head and Head tilted backward postures, recognized to
degrade vestibular and neck somatosensory information. In Experiment 2 (n=15),
the postural task was executed in two conditions of No tactile and Tactile
stimulation of the neck provided by the application of strips of adhesive
bandage to the skin over and around the neck. Centre of foot pressure
displacements were recorded using a force platform. Results showed that (1) the
Fatigue condition yielded increased CoP displacements relative to the No
Fatigue condition (Experiment 1 and Experiment 2), (2) this destabilizing
effect was more accentuated in the Head tilted backward posture than Neutral
head posture (Experiment 1) and (3) this destabilizing effect was less
accentuated in the condition of Tactile stimulation than that of No tactile
stimulation of the neck (Experiment 2). In the context of the multisensory
control of balance, these results suggest an increased reliance on vestibular
and neck somatosensory information for controlling posture during quiet
standing in condition of altered ankle neuromuscular function
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