Comparison of techniques to examine the diversity of fungi in adult patients with cystic fibrosis

This study compares conventional and molecular techniques for the detection of fungi in 77 adult cystic fibrosis (CF) patients. Three different methods were investigated, i.e., (1) conventional microbiological culture (including yeasts and filamentous fungi), (2) mycological culture with CF-derived fungal specific culture media, and (3) Non-culture and direct DNA extraction from patient sputa. Fungi isolated from environmental air samples of the CF unit were compared to fungi in sputa from CF patients. Fungi (n = 107) were detected in 14/77(18%) of patients by method 1, in 60/77 (78%) of patients by method 2 and with method 3, in 77/77(100%) of the patients. The majority of yeasts isolated were Candida albicans and C. dubliniensis. Exophiala (Wangiella) dermatitidis, Scedosporiumapiospermum, Penicillium spp., Aspergillus fumigatus, and Aspergillus versicolor were also identified by sequence analysis of the rDNA short internal transcribed spacer (ITS2) region. Conventional laboratory analysis failed to detect fungi in 63 patients mainly due to overgrowth by Gram-negative organisms. Mycological culture with antibiotics dramatically increased the number of fungi that could be detected. Molecular techniques detected fungi such as Saccharomyces cerevisiae, Malassezia spp., Fuscoporia ferrea, Fusarium culmorum, Acremonium strictum, Thanatephorus cucumeris and Cladosporium spp. which were not found with other methods. This study demonstrates that several potentially important fungi may not be detected if mycological culture methods alone are used. A polyphasic approach employing both enhanced mycological culture with molecular detection will help determine the presence of fungi in the sputa of patients with CF and their healthcare environment.

Implementation of European standards of care for cystic fibrosis - provision of care

Background: Several guidelines for cystic fibrosis (CF) caregivers exist, but information about their implementation is lacking.

Implementation of European standards of care for cystic fibrosis - Control and treatment of infection

Background: Several guidelines oil infection control and treatment of infection exist for cystic fibrosis (CF) caregivers, although the extent of implementation is variable.

Temocillin in cystic fibrosis: A retrospective pilot study

Background: Temocillin is currently used in the treatment of acute pulmonary exacerbations caused by Burkholderia cepacia complex and multiresistant Pseudomonas aeruginosa in cystic fibrosis (CF) patients despite little published clinical data. This study assessed if intravenous (IV) antibiotic therapy including temocillin was equivalent to standard combination therapy for an acute exacerbation.

Frequency of cytokine gene promoter polymorphisms in the Northern Ireland Cystic Fibrosis population

It has been postulated that cytokine allele frequencies are gender and perhaps geographically-specific. Cytokine release is crucial in the regulation of the type and magnitude of the immune response. This study observed no differences in the frequency of cytokine promoter polymorphisms associated with variant levels of expression in patients with CIF and a non-CF population of Northern Ireland. (c) 2007 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Clinical phenotype of cystic fibrosis patients with the G551D mutation

Background: Data on whether the phenotype of cystic fibrosis (CF) patients with compound heterozygocity for G551D (Gly551Asp) differs from patients with F508del (Phe508del) homozygous mutations is divergent.

The effect of feeding a high fibre diet on the welfare of sows housed in large dynamic groups

This study assessed the effect of increasing fibre levels in the concentrate ration on the welfare of sows housed in a large dynamic group. One hundred and twelve Large White x Landrace sows were allocated to one of two treatments over six replicates. Treatments were as follows: (i) High Fibre diet (similar to 15% CF [Crude Fibre]), and (ii) Control diet (similar to 5% CF). Treatments were applied to two separate dynamic groups each containing 33 (+/- 3) sows in a cross-over design, after three replicates the treatments were switched between the groups. Approximately nine sows were replaced in each of these groups at 3-week intervals (each replacement constituting a replicate of the study). Sows on the high fibre diet spent a greater percentage of time lying (High Fibre: 43.8, Control. 28.0, SEM 3.25%), while sows on the control diet spent more time sham chewing (High Fibre: 7.2, Control: 28.8, SEM 1.55%). Sows newly introduced to the group on the high fibre treatment spent proportionally more time in the kennel areas compared to newly introduced sows in the control treatment (High Fibre. 0.893, Control. 0 788, SEM 5 10) In general, aggression occurred at a very low frequency and overall levels did not differ between treatments (High Fibre: 0.005, Control: 0.003, SEM 0.0007 [occurrences per min)). However, sows in the control treatment performed head thrusting (High Fibre: 0.02, Control: 0.00, SEM 0.001 [occurrences per mini), and biting behaviour (High Fibre. 002, Control. 0.01, SEM 0.002 [occurrences per min]) more frequently than sows on the high fibre diet. There was no effect of treatment on physiological parameters such as plasma cortisol (High Fibre: 1.34, Control: 1.44, SEM 0.114 ng ml(-1)) or haptoglobin levels (High Fibre. 0.73, Control. 0.64, SEM 0.080 mg ml(-1)). In summary, provision of a high fibre diet had a positive effect on the welfare of group-housed dry sows Sows on the high fibre treatment spent more time resting in the kennel areas, less time performing stereotypic behaviours and showed a reduction in some aggressive behaviours relative to sows fed the control diet.

Association of airway cathepsin B and S with inflammation in cystic fibrosis.

Irreversible tissue damage within the cystic fibrosis (CF) lung is mediated by proteolytic enzymes during an inflammatory response. Serine proteinases, in particular neutrophil elastase (NE), have been implicated however, members of the cysteine proteinase family may also be involved. The aim of this study was to determine cathepsin B and S levels in cystic fibrosis (CF) sputum and to assess any relationship to recognized markers of inflammation such as sputum NE, interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-a), urine TNF receptor 1 (TNFr1), plasma IL-6, and serum C-reactive protein (CRP). Proteinase activities were measured in the sputum of 36 clinically stable CF patients using spectrophotometric and fluorogenic assays. Immunoblots were also used to confirm enzyme activity data. All other parameters were measured by ELISA. Patients had a mean age of 27.2 (8.2) years, FEV. of 1.6 (0.79) L and BMI of 20.7 (2.8). Both cathepsin B and S activities were detected in all samples, with mean concentrations of 18.0 (13.5)?µg/ml and 1.6 (0.88)?µg/ml, respectively and were found to correlate not only with each other but with NE, TNF-a and IL-8 (in all cases .?<?0.05). Airway cathepsin B further correlated with circulatory IL-6 and CRP however, no relationship for either cathepsin was observed with urine TNFr1. This data indicates that cathepsin B and S may have important roles in the pathophysiology of CF lung disease and could have potential as markers of inflammation in future studies. Pediatr. Pulmonol. 2010; 45:860–868.

Kinematics of the ring-like nebula SuWt 2

We present the first detailed spatio-kinematical analysis and modelling of the southern planetary nebula SuWt 2. This object presents a problem for current theories of planetary nebula formation and evolution, as it is not known to contain a central post-main-sequence star. Deep narrow-band [NII]6584Å images reveal the presence of faint bipolar lobes emanating from the edges of the nebular ring. Long-slit observations of the Ha and [NII]6584Å emission lines were obtained using the ESO (European Southern Observatory) Multi-Mode Instrument on the 3.6-m ESO New Technology Telescope. The spectra reveal the nebular morphology as a bright torus encircling the waist of an extended bipolar structure. By deprojection, the inclination of the ring is found to be 68° +/- 2° (cf. ~90° for the double A-type binary believed to lie at the centre of the nebula), and the ring expansion velocity is found to be 28 kms-1. Our findings are discussed with relation to possible formation scenarios for SuWt 2. Through comparison of the nebular heliocentric systemic velocity, found here to be -25 +/- 5km s-1, and the heliocentric systemic velocity of the double A-type binary, we conclude that neither component of the binary could have been the nebular progenitor. However, we are unable to rule out the presence of a third component to the system, which would have been the nebula progenitor.

Rapid sympatric ecological differentiation of crater lake cichlid fishes within historic times

Background: After a volcano erupts, a lake may form in the cooled crater and become an isolated aquatic ecosystem. This makes fishes in crater lakes informative for understanding sympatric evolution and ecological diversification in barren environments. From a geological and limnological perspective, such research offers insight about the process of crater lake ecosystem establishment and speciation. In the present study we use genetic and coalescence approaches to infer the colonization history of Midas cichlid fishes (Amphilophus cf. citrinellus) that inhabit a very young crater lake in Nicaragua-the ca. 1800 year-old Lake Apoyeque. This lake holds two sympatric, endemic morphs of Midas cichlid: one with large, hypertrophied lips (~20% of the total population) and another with thin lips. Here we test the associated ecological, morphological and genetic diversification of these two morphs and their potential to represent incipient speciation.
Results: Gene coalescence analyses [11 microsatellite loci and mitochondrial DNA (mtDNA) sequences] suggest that crater lake Apoyeque was colonized in a single event from the large neighbouring great lake Managua only about 100 years ago. This founding in historic times is also reflected in the extremely low nuclear and mitochondrial genetic diversity in Apoyeque. We found that sympatric adult thin- and thick-lipped fishes occupy distinct ecological trophic niches. Diet, body shape, head width, pharyngeal jaw size and shape and stable isotope values all differ significantly between the two lip-morphs. The eco-morphological features pharyngeal jaw shape, body shape, stomach contents and stable isotopes (d15N) all show a bimodal distribution of traits, which is compatible with the expectations of an initial stage of ecological speciation under disruptive selection. Genetic differentiation between the thin- and thick-lipped population is weak at mtDNA sequence (FST = 0.018) and absent at nuclear microsatellite loci (FST < 0.001).
Conclusions: This study provides empirical evidence of eco-morphological differentiation occurring very quickly after the colonization of a new and vacant habitat. Exceptionally low levels of neutral genetic diversity and inference from coalescence indicates that the Midas cichlid population in Apoyeque is much younger (ca. 100 years or generations old) than the crater itself (ca. 1 800 years old). This suggests either that the crater remained empty for many hundreds of years after its formation or that remnant volcanic activity prevented the establishment of a stable fish population during the early life of the crater lake. Based on our findings of eco-morphological variation in the Apoyeque Midas cichlids, and known patterns of adaptation in Midas cichlids in general, we suggest that this population may be in a very early stage of speciation (incipient species), promoted by disruptive selection and ecological diversification.

Antiproteases as therapeutics to target inflammation in cystic fibrosis.

Cystic Fibrosis (CF) is the most common fatal inherited disease of Caucasians, affecting about 1 in 3000 births. Patients with CF have a recessive mutation in the gene encoding the CF transmembrane conductance regulator (CFTR). CFTR is expressed in the epithelium of many organs throughout the exocrine system, however, inflammation and damage of the airways as a result of persistent progressive endobronchial infection is a central feature of CF. The inflammatory response to infection brings about a sustained recruitment of neutrophils to the site of infection. These neutrophils release various pro-inflammatory compounds including proteases, which when expressed at aberrant levels can overcome the endogenous antiprotease defence mechanisms of the lung. Unregulated, these proteases can exacerbate inflammation and result in the degradation of structural proteins and tissue damage leading to bronchiectasis and loss of respiratory function. Other host-derived and bacterial proteases may also contribute to the inflammation and lung destruction observed in the CF lung. Antiprotease strategies to dampen the excessive inflammatory response and concomitant damage to the airways remains an attractive therapeutic option for CF patients.

On the dissolution of non-metallic solid elements (sulfur, selenium, tellurium and phosphorus) in ionic liquids

Ionic liquids are shown to be good solvents for elemental sulfur, selenium, phosphorus and tellurium, and can be designed to maximise the solubility of these elements. The presence of the [S-3](center dot-) radical anion in diluted solutions of sulfur in some ionic liquids has been confirmed, and is the origin of their intense blue colour (cf. lapis lazuli).

Real-time error detection but not error correction drives automatic visuomotor adaptation

We investigated the role of visual feedback of task performance in visuomotor adaptation. Participants produced novel two degrees of freedom movements (elbow flexion-extension, forearm pronation-supination) to move a cursor towards visual targets. Following trials with no rotation, participants were exposed to a 60A degrees visuomotor rotation, before returning to the non-rotated condition. A colour cue on each trial permitted identification of the rotated/non-rotated contexts. Participants could not see their arm but received continuous and concurrent visual feedback (CF) of a cursor representing limb position or post-trial visual feedback (PF) representing the movement trajectory. Separate groups of participants who received CF were instructed that online modifications of their movements either were, or were not, permissible as a means of improving performance. Feedforward-mediated performance improvements occurred for both CF and PF groups in the rotated environment. Furthermore, for CF participants this adaptation occurred regardless of whether feedback modifications of motor commands were permissible. Upon re-exposure to the non-rotated environment participants in the CF, but not PF, groups exhibited post-training aftereffects, manifested as greater angular deviations from a straight initial trajectory, with respect to the pre-rotation trials. Accordingly, the nature of the performance improvements that occurred was dependent upon the timing of the visual feedback of task performance. Continuous visual feedback of task performance during task execution appears critical in realising automatic visuomotor adaptation through a recalibration of the visuomotor mapping that transforms visual inputs into appropriate motor commands.

High concentrations of pepsin in bronchoalveolar lavage from children with cystic fibrosis are associated with high interleukin-8

Background Gastro-oesophageal reflux is common in children with cystic fibrosis (CF) and is thought to be associated with pulmonary aspiration of gastric contents. The measurement of pepsin in bronchoalveolar lavage (BAL) fluid has recently been suggested to be a reliable indicator of aspiration. The prevalence of pulmonary aspiration in a group of children with CF was assessed and its association with lung inflammation investigated. Methods This was a cross-sectional case–control study. BAL fluid was collected from individuals with CF (n=31) and healthy controls (n=7). Interleukin-8 (IL-8), pepsin, neutrophil numbers and neutrophil elastase activity levels were measured in all samples. Clinical, microbiological and lung function data were collected from medical notes. Results The pepsin concentration in BAL fluid was higher in the CF group than in controls (mean (SD) 24.4 (27.4) ng/ml vs 4.3 (4.0) ng/ml, p=0.03). Those with CF who had raised pepsin concentrations had higher levels of IL-8 in the BAL fluid than those with a concentration comparable to controls (3.7 (2.7) ng/ml vs 1.4 (0.9) ng/ml, p=0.004). Within the CF group there was a moderate positive correlation between pepsin concentration and IL-8 in BAL fluid (r=0.48, p=0.04). There was no association between BAL fluid pepsin concentrations and age, sex, body mass index z score, forced expiratory volume in 1 s or Pseudomonas aeruginosa colonisation status. Conclusions Many children with CF have increased levels of pepsin in the BAL fluid compared with normal controls. Increased pepsin levels were associated with higher IL-8 concentrations in BAL fluid. These data suggest that aspiration of gastric contents occurs in a subset of patients with CF and is associated with more pronounced lung inflammation.

TESTING FOR STATIONARITY IN HETEROGENEOUS PANEL DATA IN THE CASE OF MODEL MISSPECIFICATION

This paper investigates the performance of the tests proposed by Hadri and by Hadri and Larsson for testing for stationarity in heterogeneous panel data under model misspecification. The panel tests are based on the well known KPSS test (cf. Kwiatkowski et al.) which considers two models: stationarity around a deterministic level and stationarity around a deterministic trend. There is no study, as far as we know, on the statistical properties of the test when the wrong model is used. We also consider the case of the simultaneous presence of the two types of models in a panel. We employ two asymptotics: joint asymptotic, T, N -> infinity simultaneously, and T fixed and N allowed to grow indefinitely. We use Monte Carlo experiments to investigate the effects of misspecification in sample sizes usually used in practice. The results indicate that the assumption that T is fixed rather than asymptotic leads to tests that have less size distortions, particularly for relatively small T with large N panels (micro-panels) than the tests derived under the joint asymptotics. We also find that choosing a deterministic trend when a deterministic level is true does not significantly affect the properties of the test. But, choosing a deterministic level when a deterministic trend is true leads to extreme over-rejections. Therefore, when unsure about which model has generated the data, it is suggested to use the model with a trend. We also propose a new statistic for testing for stationarity in mixed panel data where the mixture is known. The performance of this new test is very good for both cases of T asymptotic and T fixed. The statistic for T asymptotic is slightly undersized when T is very small (