Resistance Development of Cystic Fibrosis Respiratory Pathogens When Exposed to Fosfomycin and Tobramycin Alone and in Combination under Aerobic and Anaerobic Conditions

Although antibiotics from different classes are frequently prescribed in combination to prevent the development of resistance amongst Cystic Fibrosis (CF) respiratory pathogens, there is a lack of data as to the efficacy of this approach. We have previously shown that a 4:1 (w/w) combination of fosfomycin and tobramycin (F:T) has excellent activity against CF pathogens with increased activity under physiologically relevant anaerobic conditions. Therefore, the aim of this study was to determine whether F:T could delay or prevent the onset of resistance compared to either fosfomycin or tobramycin alone under aerobic and anaerobic conditions. The frequency of spontaneous mutants arising following exposure to fosfomycin, tobramycin and F:T was determined for clinical Pseudomonas aeruginosa and MRSA isolates under aerobic and anaerobic conditions. The effect of sub-inhibitory concentrations of fosfomycin, tobramycin and F:T on the induction of resistance was also investigated, with the stability of resistance and fitness cost associated with resistance assessed if it developed. P. aeruginosa and MRSA isolates had a lower frequency of spontaneous mutants to F:T compared to fosfomycin and tobramycin under both aerobic and anaerobic conditions. There was a maximum two-fold increase in F:T MICs when P. aeruginosa and MRSA isolates were passaged in sub-inhibitory F:T for 12 days. In contrast, sequential resistance to fosfomycin and tobramycin developed quickly (n = 3 days for both) after passage in sub-inhibitory concentrations. Once developed, both fosfomycin and tobramycin resistance was stable and not associated with a biological fitness cost to either P. aeruginosa or MRSA isolates. The results of this study suggest that F:T may prevent the development of resistance compared to fosfomycin or tobramycin alone under aerobic and physiologically relevant anaerobic conditions. F:T may be a potential treatment option in CF patients chronically colonised by MRSA and/or P. aeruginosa.

Evaluation of Pt and Re oxidation state in a pressurized reactor: difference in reduction between gas and liquid phase

Determination of metal oxidation state under relevant working conditions is crucial to understand catalytic behaviour. The reduction behaviour of Pt and Re was evaluated simultaneously as a function of support and solvent in a pressurized reactor (autoclave). The bimetallic catalysts are used in selective hydrogenation of carboxylic acids and amides. Gas phase reduction reduced the metals more efficiently, in particular Pt.

Multimedia psycho-educational interventions to support patient self-care in degenerative conditions: a realist review

Objective: Multimedia interventions are increasingly used to deliver information in order to promote self-care among patients with degenerative conditions. We carried out a realist review of the literature to investigate how the characteristics of multimedia psychoeducational interventions combine with the contexts in which they are introduced to help or hinder their effectiveness in supporting self-care for patients with degenerative conditions.

Method: Electronic databases (Medline, Science Direct, PSYCHinfo, EBSCO, and Embase) were searched in order to identify papers containing information on multimedia psychoeducational interventions. Using a realist review approach, we reviewed all relevant studies to identify theories that explained how the interventions work.

Results: Ten papers were included in the review. All interventions sought to promote self-care behaviors among participants. We examined the development and content of the multimedia interventions and the impact of patient motivation and of the organizational context of implementation. We judged seven studies to be methodologically weak. All completed studies showed small effects in favor of the intervention.

Significance of Results: Multimedia interventions may provide high-quality information in an accessible format, with the potential to promote self-care among patients with degenerative conditions, if the patient perceives the information as important and develops confidence about self-care. The evidence base is weak, so that research is needed to investigate effective modes of delivery at different resource levels. We recommend that developers consider how an intervention will reduce uncertainty and increase confidence in self-care, as well as the impact of the context in which it will be employed.

A modified commercial DRIFTS cell for kinetically relevant operando studies of heterogeneous catalytic reactions

This paper discusses a number of checks that should be carried out to ensure that the kinetic and spectroscopic measurements made using a DRIFTS cell are meaningful. The observations reported here demonstrate how an appropriately modified commercial DRIFTS cell can provide pertinent kinetic information about both gaseous products and the related surface intermediates. The oxidation of CO with 02 was used as a test to assess the catalyst bed bypass by the reaction mixture. Full CO conversion was obtained after the light-off temperature in the case of the modified cell, contrary to the case of the original cell, for which 80% of the reaction mixture bypassed the catalyst bed. The water-gas shift reaction over a Pt/CeO2 catalyst was used as a model reaction to further characterize the behavior of the cell under reaction conditions. The catalyst bed was shown not to be a dead-zone and was purged in essentially the same time as that needed to purge the cell. The reaction chamber globally operated in a quasi plug-flow mode and the gas composition in the thin catalyst bed appears to be homogeneous when operated under differential conditions. The production of the gas-phase reaction product CO2 could be simultaneously followed both by mass spectrometry and DRIFTS, both techniques leading to identical results. Various IR bands integration methods were discussed to allow a precise and accurate determination of the surface concentration of adsorbates during isotopic exchange. (c) 2008 Elsevier B.V. All rights reserved.

Genomic instability after targeted irradiation of human lymphocytes: Evidence for inter-individual differences under bystander conditions

Environmental (222)radon exposure is a human health concern, and many studies demonstrate that very low doses of high LET alpha-particle irradiation initiate deleterious genetic consequences in both radiated and non-irradiated bystander cells. One consequence, radiation-induced genomic instability (RIGI), is a hallmark of tumorigenesis and is often assessed by measuring delayed chromosomal aberrations We utilised a technique that facilitates transient immobilization of primary lymphocytes for targeted microbeam irradiation and have reported that environmentally relevant doses, e.g. a single He-3(2+) particle traversal to a single cell, are sufficient to Induce RIGI Herein we sought to determine differences in radiation response in lymphocytes isolated from five healthy male donors Primary lymphocytes were irradiated with a single particle per cell nucleus. We found evidence for inter-individual variation in radiation response (Rid, measured as delayed chromosome aberrations) Although this was not highly significant, it was possibly masked by high levels of intra-individual variation While there are many studies showing a link between genetic predisposition and RIGI, there are few studies linking genetic background with bystander effects in normal human lymphocytes In an attempt to investigate inter-individual variation in the induction of bystander effects, primary lymphocytes were irradiated with a single particle under conditions where fractions of the population were traversed We showed a marked genotype-dependent bystander response in one donor after exposure to 15% of the population The findings may also be regarded as a radiation-induced genotype-dependent bystander effect triggering an instability phenotype (C) 2010 Elsevier B.V. All rights reserved.

A Diagnostic System Using Broad Categories With Clinicaly Relevant Specifiers: Lessons for ICD-10

A diagnostic system for ICD-11 is proposed which commences with broad reorganization and simplification of the current categories and the use of clinically relevant specifiers. Such changes have implications for the positioning of diagnostic groups and lead to a range of possibilities for improving terminology and the juxtaposition of individual conditions. The development of ICD-11 provides the first opportunity in almost two decades to improve the validity and reliability of the international classification system. Widespread change in broad categories and criteria cannot be justified by research that has emerged since the last revision. It would also be disruptive to clinical practice and might devalue past research work. However, the case for reorganization of the categories is stronger and has recently been made by an eminent international group of researchers (Andrews et al., 2009). A simpler, interlinked diagnostic system is proposed here which is likely to have fewer categories than its predecessor. There are major advantages of such a system for clinical practice and research and it could also produce much needed simplification for primary care (Gask et al., 2008) and the developing world (Wig, 1990; Kohn et al., 2004).

Progress in proton radiography for diagnosis of ICF-relevant plasmas

Proton radiography using laser-driven sources has been developed as a diagnostic since the beginning of the decade, and applied successfully to a range of experimental situations. Multi-MeV protons driven from thin foils via the Target Normal Sheath Acceleration mechanism, offer, under optimal conditions, the possibility of probing laser-plasma interactions, and detecting electric and magnetic fields as well as plasma density gradients with similar to ps temporal resolution and similar to 5-10 mu m spatial resolution. In view of these advantages, the use of proton radiography as a diagnostic in experiments of relevance to Inertial Confinement Fusion is currently considered in the main fusion laboratories. This paper will discuss recent advances in the application of laser-driven radiography to experiments of relevance to Inertial Confinement Fusion. In particular we will discuss radiography of hohlraum and gasbag targets following the interaction of intense ns pulses. These experiments were carried out at the HELEN laser facility at AWE (UK), and proved the suitability of this diagnostic for studying, with unprecedented detail, laser-plasma interaction mechanisms of high relevance to Inertial Confinement Fusion. Non-linear solitary structures of relevance to space physics, namely phase space electron holes, have also been highlighted by the measurements. These measurements are discussed and compared to existing models.

The triazatruxene derivative azatrux binds to the parallel form of the human telomeric G-quadruplex under molecular crowding conditions: Biophysical and molecular modeling studies

The present study has employed a combination of spectroscopic, calorimetric and computational methods to explore the binding of the three side-chained triazatruxene derivative, termed azatrux, to a human telomeric G-quadruplex sequence, under conditions of molecular crowding. The binding of azatrux to the tetramolecular parallel [d(TGGGGT)](4) quadruplex in the presence and absence of crowding conditions, was also characterized. The data indicate that azatrux binds in an end-stacking mode to the parallel G-quadruplex scaffold and highlights the key structural elements involved in the binding. The selectivity of azatrux for the human telomeric G-quadruplex relative to another biologically relevant G-quadruplex (c-Kit87up) and to duplex DNA was also investigated under molecular crowding conditions, showing that azatrux has good selectivity for the human telomeric G-quadruplex over the other investigated DNA structures. (C) 2011 Elsevier Masson SAS. All rights reserved.

A material model for multiaxial stretching and stress relaxation of polypropylene under process conditions

Polypropylene sheets have been stretched at 160 °C to a state of large biaxial strain of extension ratio 3, and the stresses then allowed to relax at constant strain. The state of strain is reached via a path consisting of two sequential planar extensions, the second perpendicular to the first, under plane stress conditions with zero stress acting normal to the sheet. This strain path is highly relevant to solid phase deformation processes such as stretch blow moulding and thermoforming, and also reveals fundamental aspects of the flow rule required in the constitutive behaviour of the material. The rate of decay of stress is rapid, and such as to be highly significant in the modelling of processes that include stages of constant strain. A constitutive equation is developed that includes Eyring processes to model both the stress relaxation and strain rate dependence of the stress. The axial and transverse stresses observed during loading show that the use of a conventional Levy-Mises flow rule is ineffective, and instead a flow rule is used that takes account of the anisotropic state of the material via a power law function of the principal extension ratios. Finally the constitutive model is demonstrated to give quantitatively useful representation of the stresses both in loading and in stress relaxation.

The effect of choice on motivation for young children on the autism spectrum during discrete trial teaching

Self-determination and decision-making are acknowledged internationally as key rights of persons with disabilities and should play an important role in the development of educational plans and procedures. Not only is the chance for individuals with developmental disabilities to select their own tasks, leisure activities or reinforcers a valuable way of enhancing rights-based education and personal dignity, but choice-making opportunities may also function as a useful clinical or educational tool if they actually improve the efficacy of programmes aimed at the acquisition of socially relevant behaviours and life skills or the reduction of challenging behaviours.

The study reported here assessed whether or not choice affected effectiveness of an educational procedure for three children on the autism spectrum. Following a preference assessment, a number of discrete teaching trials were conducted with each child and, contingent upon targeted responses, either the child or the therapist selected one of three preferred reinforcer items. Reinforcer choice did not affect intervention effectiveness for two of the children; however, performance and motivation improved for the third child. Results re-affirmed the importance of thorough preference assessments prior to intervention and showed that additional stimulus choice contingent on the target response may improve motivation and outcomes for some children.

A realist literature review of transition to adult services by young people with life-limiting conditions in ireland.

Background As a result of improvements in care and treatment more young people with life-limiting conditions are now living beyond childhood, meaning they must make the transition from children's to adult services. The loss of long-standing relationships with providers of children's services combines with poor co-ordination of services to make this a daunting prospect for young people and their families. However, there is little evidence on transition services for young people with life limiting conditions, with few models of good practice in the literature.


Aims The purpose of this review was to determine the factors that promote or hinder the transition to adult services for young adults with life limiting conditions, and identify gaps to be addressed.


Methods A comprehensive search of the literature was undertaken using key terms, of the following databases; MEDLINE and the Cochrane Database of Systematic Reviews. 314 articles were sourced and inclusion and exclusion criteria were applied to highlight the most relevant literature.


Results Studies were reviewed using a realist review approach and three themes emerged from the literature. Barriers and facilitators to the transition process were identified associated with: 1. The patient 2. Parents/carers 3. The organisation.


Conclusion It is unclear from the literature what the specific factors are that promote or hinder the transition process for young adults with life limiting conditions who go through the transition from children's to adult services, therefore, research is required to identify the factors that promote and hinder the transition process in Ireland. This research is currently being carried out by the author as part of Doctoral studies. The three year full time Doctoral study commenced in January 2013 and is funded by the All Ireland Institute of Hospice and Palliative Care.

Progress at JET in integrating ITER-relevant core and edge plasmas within the constraints of an ITER-like wall

This paper reports the progress made at JET-ILW on integrating the requirements of the reference ITER baseline scenario with normalized confinement factor of 1, at a normalized pressure of 1.8 together with partially detached divertor whilst maintaining these conditions over many energy confinement times. The 2.5 MA high triangularity ELMy H-modes are studied with two different divertor configurations with D-gas injection and nitrogen seeding. The power load reduction with N seeding is reported. The relationship between an increase in energy confinement and pedestal pressure with triangularity is investigated. The operational space of both plasma configurations is studied together with the ELM energy losses and stability of the pedestal of unseeded and seeded plasmas. The achievement of stationary plasma conditions over many energy confinement times is also reported.