309 research outputs found
Exploring views on satisfaction with life in young children with chronic illness: an innovative approach to the collection of self-report data from children under 11
The objective of this study was to explore young childrenâs views on the impact of chronic illness on their life in order to inform future development of a patient-based self-report health outcome measure. We describe an approach to facilitating self-report views from young children with chronic illness. A board game was designed in order to obtain qualitative data from 39 children with a range of chronic illness conditions and 38 healthy controls ranging in age from 3 to 11 years. The format was effective in engaging young children in a self-report process of determining satisfaction with life and identified nine domains. The board game enabled children aged 5â11 years with chronic illness to describe the effects of living with illness on home, family, friends, school and life in general. It generated direct, non-interpreted material from children who, because of their age, may have been considered unable or limited their ability to discuss and describe how they feel. Obtaining this information for children aged 4 and under continues to be a challenge
Electrophysiologic actions of high plasma concentrations of propranolol in human subjects
The authors have previously shown that 40% of patients whose ventricular arrhythmias respond to propranolol require plasma concentrations in excess of those producing substantial beta-receptor blockade (> 150 ng/ml). However, the electrophysiologic actions of propranolol have only been examined in human beings after small intravenous doses achieving concentrations of less than 100 ng/ml. In this study, the electrophysiologic effects of a wider concentration range of propranolol was examined in nine patients. Using a series of loading and maintenance infusions, measurements were made at baseline, at low mean plasma propranolol concentrations (104 ± 17 ng/ml) and at high concentrations (472 ± 68 ng/ml). Significant (p < 0.05) increases in AH interval and sinus cycle length were seen at low concentrations of propranolol, with no further prolongation at the high concentrations; these effects are typical of those produced by beta-blockade. However, progressive shortening of the endocardial monophasic action potential duration and QTc interval were seen over the entire concentration range tested (p < 0.05). At high concentrations, there was significant (p < 0.05) further shortening of both the QTc and monophasic action potential duration beyond that seen at low propranolol concentrations, along with a progressive increase in the ratio of the ventricular effective refractory period to monophasic action potential duration. No significant changes were seen in HV interval, QRS duration or ventricular effective refractory period.In summary, the concentration-response relations for atrioventricular conductivity and sinus node automat-icity were flat above concentrations of 150 ng/ml. On the other hand, the durations of the monophasic action potential and the QTc interval shortened at high concentrations. It is concluded that propranolol, in addition to blocking beta-receptors, produces other beta-receptor independent electrophysiologic effects in human beings
Overview of Advanced LIGO Adaptive Optics
This is an overview of the adaptive optics used in Advanced LIGO (aLIGO), known as the thermal compensation system (TCS). The TCS was designed to minimize thermally induced spatial distortions in the interferometer optical modes and to provide some correction for static curvature errors in the core optics of aLIGO. The TCS is comprised of ring heater actuators, spatially tunable CO_2
laser projectors, and Hartmann wavefront sensors. The system meets the requirements of correcting for nominal distortion in aLIGO to a maximum residual error of 5.4 nm rms, weighted across the laser beam, for up to 125 W of laser input power into the interferometer
Overview of Advanced LIGO Adaptive Optics
This is an overview of the adaptive optics used in Advanced LIGO (aLIGO),
known as the thermal compensation system (TCS). The thermal compensation system
was designed to minimize thermally-induced spatial distortions in the
interferometer optical modes and to provide some correction for static
curvature errors in the core optics of aLIGO. The TCS is comprised of ring
heater actuators, spatially tunable CO laser projectors and Hartmann
wavefront sensors. The system meets the requirements of correcting for nominal
distortion in Advanced LIGO to a maximum residual error of 5.4nm, weighted
across the laser beam, for up to 125W of laser input power into the
interferometer
Switching the stereochemical outcome of 6-endo-trig cyclizations; Synthesis of 2,6-Cis-6-substituted 4-oxopipecolic acids
A base-mediated 6-endo-trig cyclization of
readily accessible enone-derived α-amino acids has been
developed for the direct synthesis of novel 2,6-cis-6-
substituted-4-oxo-L-pipecolic acids. A range of aliphatic and
aryl side chains were tolerated by this mild procedure to give
the target compounds in good overall yields. Molecular
modeling of the 6-endo-trig cyclization allowed some insight as
to how these compounds were formed, with the enolate
intermediate generated via an equilibrium process, followed by irreversible tautomerization/neutralization providing the driving force for product formation. Stereoselective reduction and deprotection of the resulting 2,6-cis-6-substituted 4-oxo-L-pipecolic acids to the corresponding 4-hydroxy-L-pipecolic acids was also performed
Uptake and transport of novel amphiphilic polyelectrolyte-insulin nanocomplexes by caco-2 cells - towards oral insulin
âThe original publication is available at www.springerlink.comâ. Copyright SpringerPurpose: The influence of polymer architecture on cellular uptake and transport across Caco-2 cells of novel amphiphilic polyelectrolyte-insulin nanocomplexes was investigated. Method: Polyallylamine (PAA) (15 kDa) was grafted with palmitoyl chains (Pa) and subsequently modified with quaternary ammonium moieties (QPa). These two amphiphilic polyelectrolytes (APs) were tagged with rhodamine and their uptake by Caco-2 cells or their polyelectrolyte complexes (PECs) with fluorescein isothiocyanate-insulin (FITC-insulin) uptake were investigated using fluorescence microscopy. The integrity of the monolayer was determined by measurement of transepithelial electrical resistance (TEER). Insulin transport through Caco-2 monolayers was determined during TEER experiments. Result: Pa and insulin were co-localised in the cell membranes while QPa complexes were found within the cytoplasm. QPa complex uptake was not affected by calcium, cytochalasin D or nocodazole. Uptake was reduced by co-incubation with sodium azide, an active transport inhibitor. Both polymers opened tight junctions reversibly where the TEER values fell by up to 35 % within 30 minutes incubation with Caco-2 cells. Insulin transport through monolayers increased when QPa was used (0.27 ngmL-1 of insulin in basal compartment) compared to Pa (0.14 ngmL-1 of insulin in basal compartment) after 2 hours. Conclusion: These APs have been shown to be taken up by Caco-2 cells and reversibly open tight cell junctions. Further work is required to optimise these formulations with a view to maximising their potential to facilitate oral delivery of insulin.Peer reviewe
Self-organized Vortex State in Two-dimensional Dictyostelium Dynamics
We present results of experiments on the dynamics of Dictyostelium discoideum
in a novel set-up which constraints cell motion to a plane. After aggregation,
the amoebae collect into round ''pancake" structures in which the cells rotate
around the center of the pancake. This vortex state persists for many hours and
we have explicitly verified that the motion is not due to rotating waves of
cAMP. To provide an alternative mechanism for the self-organization of the
Dictyostelium cells, we have developed a new model of the dynamics of
self-propelled deformable objects. In this model, we show that cohesive energy
between the cells, together with a coupling between the self-generated
propulsive force and the cell's configuration produces a self-organized vortex
state. The angular velocity profiles of the experiment and of the model are
qualitatively similar. The mechanism for self-organization reported here can
possibly explain similar vortex states in other biological systems.Comment: submitted to PRL; revised version dated 3/8/9
Resuscitation with pre-hospital blood products in adults with trauma-related haemorrhagic shock:the RePHILL RCT
Background:âThe treatment of traumatic haemorrhagic shock has been transformed through better haemorrhage control, use of tranexamic acid and use of blood products. The improved survival seen from these strategies has stimulated an interest in pre-hospital transfusion.Objectives:âTo determine if the clinical effectiveness of resuscitation with red blood cells and lyophilised plasma was superior to 0.9% saline for improving tissue perfusion and reducing mortality in adults with haemorrhagic shock following major trauma.Design:âA multi-centre, allocation concealed, open-label, parallel group, randomised controlled trial (with internal pilot).Setting:âThe trial was conducted in four civilian pre-hospital critical care services who operated within the National Health Service (NHS) England Major Trauma Networks.Participants:âAdults (aged â„16 years) who had sustained traumatic injuries, were attended by a pre-hospital emergency medical team and were hypotensive (systolic blood pressure <90 mmHg or absence of radial pulse) as a consequence of traumatic haemorrhage were eligible for inclusion. The exclusion criteria were known or apparently <16 years, blood administered on scene prior to the arrival of the RePHILL team, traumatic cardiac arrest where (1) the arrest occurred prior to arrival of the team and/or (2) the primary cause is not hypovolaemia, refusal of blood product administration, known Jehovahâs Witness, pregnancy, isolated head injury without evidence of external haemorrhage, prisoners in the custody of HM Prison and Probation Service.Interventions:âParticipants were randomised to receive up to either two units each of red blood cells and lyophilised plasma or up to 1âL 0.9% saline. Treatment was administered through the intravenous or intraosseous route.Main outcome measures:âThe primary outcome was a composite of episode mortality and/or impaired lactate clearance. The secondary outcomes included the individual components of the primary outcome.Results:âFrom 6 December 2016 to 2 January 2021, pre-hospital medical teams randomised 432 participants to red blood cell/lyophilised plasma (n = 209) or 0.9% saline (n = 223) out of a target sample size of 490. Most participants were white (62%), males (82%), median age 38 (interquartile range 26 to 58), involved in a road traffic collision (62%) with severe injuries (median injury severity score 36, interquartile range 25 to 50). Prior to randomisation participants had received on average 430 ml crystalloid fluids and tranexamic acid (90%). The primary outcome occurred in 128/199 (64.3%) of participants randomised to red blood cell/lyophilised plasma and 136/210 (64.8%) randomised to 0.9% saline [adjusted risk difference â0.025% (95% confidence interval â9.0% to 9.0%), p = 0.996]. The event rates for the individual components of the primary outcome, episode mortality and lactate clearance were not statistically different between groups [adjusted average differences â3% (â12% to 7%); p = 0.57 and â5% (â14% to 5%), p = 0.33, respectively].Limitations:âRecruitment stopped prematurely due to disruption caused by the COVID-19 pandemic.Future work:âIdentify the characteristics of patients who may benefit from pre-hospital blood products and whether alternative transfusion regimens are superior to standard care.Conclusions:âThe trial did not demonstrate that pre-hospital red blood cell/lyophilised plasma resuscitation was superior to 0.9% saline for trauma-related haemorrhagic shock.Trial registration:âThis trial is registered as ISRCTN62326938.Funding:âThis award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation Programme (NIHR award ref: 14/152/14) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 2. See the NIHR Funding and Awards website for further award information.<br/
PuLSE:Quality control and quantification of peptide sequences explored by phage display libraries
The design of highly diverse phage display libraries is based on assumption that DNA bases are incorporated at similar rates within the randomized sequence. As library complexity increases and expected copy numbers of unique sequences decrease, the exploration of library space becomes sparser and the presence of truly random sequences becomes critical. We present the program PuLSE (Phage Library Sequence Evaluation) as a tool for assessing randomness and therefore diversity of phage display libraries. PuLSE runs on a collection of sequence reads in the fastq file format and generates tables profiling the library in terms of unique DNA sequence counts and positions, translated peptide sequences, and normalized 'expected' occurrences from base to residue codon frequencies. The output allows at-a-glance quantitative quality control of a phage library in terms of sequence coverage both at the DNA base and translated protein residue level, which has been missing from toolsets and literature. The open source program PuLSE is available in two formats, a C++ source code package for compilation and integration into existing bioinformatics pipelines and precompiled binaries for ease of use
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