Geographical differences in first acquisition of Pseudomonas aeruginosa in cystic fibrosis

RATIONALE: Risk of infection with Pseudomonas aeruginosa in cystic fibrosis (CF) may be associated with environmental factors.

OBJECTIVES: To determine whether residential location is associated with risk of first acquisition of P. aeruginosa.

METHODS: We performed bronchoalveolar lavage and upper airway cultures in children newly diagnosed with CF to identify infection with P. aeruginosa during infancy and early childhood. Children were assessed according to their residence in a regional or metropolitan area. Multilocus sequence typing was used to determine P. aeruginosa genotype. An environmental questionnaire was also administered.

MEASUREMENTS AND MAIN RESULTS: A total of 105 of 120 (87.5%) infants diagnosed with CF were included in this study. Diagnosis in 65 infants (61.9%) followed newborn screening at mean age of 4.6 weeks. Sixty subjects (57.1%) were homozygous ΔF508, and 47 (44.8%) were female. Fifty-five (52.3%) infants were regional, of whom 26 (47.3%), compared with 9 of 50 (18.0%) metropolitan children, acquired infection with P. aeruginosa (odds ratio, 4.084; 95% confidence interval, 1.55-11.30). Age at acquisition was similar (regional: median, 2.31 yr; range, 0.27-5.96 yr; metropolitan: median, 3.10 yr, range, 0.89-3.70 yr). Strain typing identified P. aeruginosa genotypes often encountered in different ecological settings and little evidence of cross-infection. Ninety questionnaires (85.7%) were completed. Those who acquired P. aeruginosa were more likely to be living in a household that used water sprinkler systems (P = 0.032), but no differences were identified to explain increased risk of acquisition of P. aeruginosa in regional children.

CONCLUSIONS: Geographical difference in residence of children with CF was associated with increased risk of first acquisition of P. aeruginosa, usually with strains associated with the environment rather than with cross-infection.

RAS testing of colorectal carcinoma—a guidance document from the Association of Clinical Pathologists Molecular Pathology and Diagnostics Group

Analysis of colorectal carcinoma (CRC) tissue for KRAS codon 12 or 13 mutations to guide use of anti-epidermal growth factor receptor (EGFR) therapy is now considered mandatory in the UK. The scope of this practice has been recently extended because of data indicating that NRAS mutations and additional KRAS mutations also predict for poor response to anti-EGFR therapy. The following document provides guidance on RAS (i.e., KRAS and NRAS) testing of CRC tissue in the setting of personalised medicine within the UK and particularly within the NHS. This guidance covers issues related to case selection, preanalytical aspects, analysis and interpretation of such RAS testing.

The Prenatal Distress Questionnaire:An investigation of factor structure in a high risk population

Background: The Prenatal Distress Questionnaire (PDQ) is a short measure designed to assess specific worries and concerns related to pregnancy. The aim of this study was to confirm the factor structure of the PDQ in a group of pregnant women with a small for gestational age infant (< 10th centile). Methods: The first PDQ assessment for each of 337 pregnant women participating in the Prospective Observational Trial to Optimise paediatric health (PORTO) study was analysed. All women enrolled in the study were identified as having a small for gestational age foetus (< 10th centile), thus representing an 'elevated risk' group. Data were analysed using confirmatory factor analysis (CFA). Three models of the PDQ were evaluated and compared in the current study: a theoretical uni-dimensional measurement model, a bi-dimensional model, and a three-factor model solution. Results: The three-factor model offered the best fit to the data while maintaining sound theoretical grounds(χ² (51df) = 128.52; CFI = 0.97; TLI = 0.96; RMSEA = 0.07). Factor 1 contained items reflecting concerns about birth and the baby, factor 2 concerns about physical symptoms and body image and factor 3 concerns about emotions and relationships. Conclusions: CFA confirmed that the three-factor model provided the best fit, with the items in each factor reflecting the findings of an earlier exploratory data analysis. © 2013 Society for Reproductive and Infant Psychology.

Targeting Siglecs with a sialic acid-decorated nanoparticle abrogates inflammation

Sepsis is the most frequent cause of death in hospitalized patients, and severe sepsis is a leading contributory factor to acute respiratory distress syndrome (ARDS). At present, there is no effective treatment for these conditions, and care is primarily supportive. Murine sialic acid-binding immunoglobulin-like lectin-E (Siglec-E) and its human orthologs Siglec-7 and Siglec-9 are immunomodulatory receptors found predominantly on hematopoietic cells. These receptors are important negative regulators of acute inflammatory responses and are potential targets for the treatment of sepsis and ARDS. We describe a Siglec-targeting platform consisting of poly(lactic-co-glycolic acid) nanoparticles decorated with a natural Siglec ligand, di(α2→8) N-acetylneuraminic acid (α2,8 NANA-NP). This nanoparticle induced enhanced oligomerization of the murine Siglec-E receptor on the surface of macrophages, unlike the free α2,8 NANA ligand. Furthermore, treatment of murine macrophages with these nanoparticles blocked the production of lipopolysaccharide-induced inflammatory cytokines in a Siglec-E-dependent manner. The nanoparticles were also therapeutically beneficial in vivo in both systemic and pulmonary murine models replicating inflammatory features of sepsis and ARDS. Moreover, we confirmed the anti-inflammatory effect of these nanoparticles on human monocytes and macrophages in vitro and in a human ex vivo lung perfusion (EVLP) model of lung injury. We also established that interleukin-10 (IL-10) induced Siglec-E expression and α2,8 NANA-NP further augmented the expression of IL-10. Indeed, the effectiveness of the nanoparticle depended on IL-10. Collectively, these results demonstrated a therapeutic effect of targeting Siglec receptors with a nanoparticle-based platform under inflammatory conditions.

Prying into the intimate secrets of animal lives; software beyond hardware for comprehensive annotation in 'Daily Diary' tags

BACKGROUND: Smart tags attached to freely-roaming animals recording multiple parameters at infra-second rates are becoming commonplace, and are transforming our understanding of the way wild animals behave. Interpretation of such data is complex and currently limits the ability of biologists to realise the value of their recorded information.

DESCRIPTION: This work presents Framework4, an all-encompassing software suite which operates on smart sensor data to determine the 4 key elements considered pivotal for movement analysis from such tags (Endangered Species Res 4: 123-37, 2008). These are; animal trajectory, behaviour, energy expenditure and quantification of the environment in which the animal moves. The program transforms smart sensor data into dead-reckoned movements, template-matched behaviours, dynamic body acceleration-derived energetics and position-linked environmental data before outputting it all into a single file. Biologists are thus left with a single data set where animal actions and environmental conditions can be linked across time and space.

CONCLUSIONS: Framework4 is a user-friendly software that assists biologists in elucidating 4 key aspects of wild animal ecology using data derived from tags with multiple sensors recording at high rates. Its use should enhance the ability of biologists to derive meaningful data rapidly from complex data.

Species composition of coastal dune vegetation in Scotland has proved resistant to climate change over a third of a century

Climate change is expected to have an impact on plant communities as increased temperatures are expected to drive individual species' distributions polewards. The results of a revisitation study after c. 34years of 89 coastal sites in Scotland, UK, were examined to assess the degree of shifts in species composition that could be accounted for by climate change. There was little evidence for either species retreat northwards or for plots to become more dominated by species with a more southern distribution. At a few sites where significant change occurred, the changes were accounted for by the invasion, or in one instance the removal, of woody species. Also, the vegetation types that showed the most sensitivity to change were all early successional types and changes were primarily the result of succession rather than climate-driven changes. Dune vegetation appears resistant to climate change impacts on the vegetation, either as the vegetation is inherently resistant to change, management prevents increased dominance of more southerly species or because of dispersal limitation to geographically isolated sites.

Battles, Boats & Bones:Archaeological Discoveries in Northern Ireland 1987-2008

How did our ancestors build their homes? What weapons did they use? What religious rituals did they follow? What did they eat? How did technology develop over the centuries? These are just some of the questions answered in Battles, Boats & Bones, which offers a fascinating insight into the daily lives of our ancestors stretching back as far as the Early Neolithic period. Bringing together details and interpretations of discoveries made as a result of 25 archaeological excavations across Northern Ireland over the last 20 years, the book is a window into our collective past. https://www.tsoshop.co.uk/gempdf/Timeline_Circles.swf