Reduced Bacterial Colony Count of Anaerobic Bacteria Is Associated with a Worsening in Lung Clearance Index and Inflammation in Cystic Fibrosis

Anaerobic bacteria have been identified in abundance in the airways of cystic fibrosis (CF) subjects. The impact their presence and abundance has on lung function and inflammation is unclear. The aim of this study was to investigate the relationship between the colony count of aerobic and anaerobic bacteria, lung clearance index (LCI), spirometry and C-Reactive Protein (CRP) in patients with CF. Sputum and blood were collected from CF patients at a single cross-sectional visit when clinically stable. Community composition and bacterial colony counts were analysed using extended aerobic and anaerobic culture. Patients completed spirometry and a multiple breath washout (MBW) test to obtain LCI. An inverse correlation between colony count of aerobic bacteria (n = 41, r = -0.35; p = 0.02), anaerobic bacteria (n = 41, r = -0.44, p = 0.004) and LCI was observed. There was an inverse correlation between colony count of anaerobic bacteria and CRP (n = 25, r = -0.44, p = 0.03) only. The results of this study demonstrate that a lower colony count of aerobic and anaerobic bacteria correlated with a worse LCI. A lower colony count of anaerobic bacteria also correlated with higher CRP levels. These results indicate that lower abundance of aerobic and anaerobic bacteria may reflect microbiota disruption and disease progression in the CF lung.

The first major step in the peace process’? Exploring the impact of the Anglo-Irish Agreement on Irish Republican thinking

This article supports interpretations of the Anglo-Irish Agreement of 1985 as a significant factor contributing to the development of the Northern Ireland peace process. However, it also emphasises a certain serendipity in the Agreement's effect on northern nationalist, and more specifically republican, politics in the region. In particular, it stresses that a specific interpretation of the Agreement promoted by the Social Democratic and Labour Party inspired a dialogue with republicanism, encouraging an ongoing reappraisal within the latter about the nature of Britain's role in Northern Ireland. This, the article argues, reinforced the movement towards a more political approach that republicans had begun in the 1980s, and encouraged their eventual embrace of a constitutional strategy in the 1990s. However, in advancing this argument, the article notes that such an outcome was far from the minds of the British and Irish officials who negotiated the Anglo-Irish Agreement. The Agreement was intended to marginalise rather than accommodate republicans. Despite this, it provided an inadvertent incentive to draw militant republicanism into the democratic process in Northern Ireland.

The first major step in the peace process’? Exploring the impact of the Anglo-Irish Agreement on Irish republican thinking

This article supports interpretations of the Anglo-Irish Agreement of 1985 as a significant factor contributing towards the development of the Northern Ireland peace process. However, it also emphasises a certain serendipity in the Agreement’s effect on northern nationalist, and more specifically republican, politics in the region. In particular, it stresses that a specific interpretation of the Agreement promoted by the SDLP inspired a dialogue with republicanism, encouraging an ongoing re-appraisal within the latter about the nature of Britain’s role in Northern Ireland. This, the article argues, reinforced the movement towards a more political approach that republicans had begun in the 1980s, and encouraged their eventual embrace of a constitutional strategy in the 1990s. However, in advancing this argument, the article notes that such an outcome was far from the minds of the British and Irish officials who negotiated the Anglo-Irish Agreement. The Agreement was intended to marginalise rather than accommodate republicans. Despite this, it provided an inadvertent incentive to draw militant republicanism into the democratic process in Northern Ireland.

Can I Count on Getting Better? Association between Math Anxiety and Poorer Understanding of Medical Risk Reductions

BACKGROUND: Lower numerical ability is associated with poorer understanding of health statistics, such as risk reductions of medical treatment. For many people, despite good numeracy skills, math provokes anxiety that impedes an ability to evaluate numerical information. Math-anxious individuals also report less confidence in their ability to perform math tasks. We hypothesized that, independent of objective numeracy, math anxiety would be associated with poorer responding and lower confidence when calculating risk reductions of medical treatments.

METHODS: Objective numeracy was assessed using an 11-item objective numeracy scale. A 13-item self-report scale was used to assess math anxiety. In experiment 1, participants were asked to interpret the baseline risk of disease and risk reductions associated with treatment options. Participants in experiment 2 were additionally provided a graphical display designed to facilitate the processing of math information and alleviate effects of math anxiety. Confidence ratings were provided on a 7-point scale.

RESULTS: Individuals of higher objective numeracy were more likely to respond correctly to baseline risks and risk reductions associated with treatment options and were more confident in their interpretations. Individuals who scored high in math anxiety were instead less likely to correctly interpret the baseline risks and risk reductions and were less confident in their risk calculations as well as in their assessments of the effectiveness of treatment options. Math anxiety predicted confidence levels but not correct responding when controlling for objective numeracy. The graphical display was most effective in increasing confidence among math-anxious individuals.

CONCLUSIONS: The findings suggest that math anxiety is associated with poorer medical risk interpretation but is more strongly related to confidence in interpretations.

Utilisation of a novel ProteaseTag™ activity immunoassay for the specific measurement of neutrophil elastase in BAL from children with cystic fibrosis

Introduction: Neutrophil elastase (NE) is a serine protease implicated in the pathogenesis of several respiratory diseases including cystic fibrosis (CF). The presence of free NE in BAL is a predictor of subsequent bronchiectasis in children with CF (Sly et al, 2013, NEJM 368: 1963-1970). Furthermore, children with higher levels of sputum NE activity (NEa) tend to experience a more rapid decline in FEV1 over time even after adjusting for age, gender and baseline FEV1 (Sagel et al, 2012, AJRCCM 186: 857-865). Its detection and quantification in biological samples is however confounded by a lack of robust methodologies. Standard assays using chromogenic or fluorogenic substrates are not specific when added to complex samples containing multiple proteolytic and hydrolytic enzymes. ELISA systems measure total protein levels which can be a mixture of latent, active and protease-inhibitor complexes. We have therefore developed a novel assay (ProteaseTag™ Active NE Immunoassay), which couples an activity dependent NE-Tag with a specific antibody step, resulting in an assay which is both selective and specific for NEa. Aims: To clinically validate ProteaseTag™ Active NE for the detection of free NEa in BAL from children with CF. Methods: A total of 95 paediatric BAL samples [CF (n=76; 44M, 32F) non-CF (n=19; 12M, 7F)] collected through the Study of Host Immunity and Early Lung Disease in CF (SHIELD CF) were analysed for NEa using ProteaseTag™ Active NE (ProAxsis Ltd) and a fluorogenic substrate-based assay utilising Suc-AAPV-AMC (Sigma). IL-8 was measured by ELISA (R&D Systems). Results were analysed to show comparisons in free NEa between CF and non-CF samples alongside correlations with a range of clinical parameters. Results: NEa measured by ProteaseTag™ Active NE correlated significantly with age (r=0.3, p=0.01) and highly significantly with both IL-8 (r=0.4, p=<0.0001) and the absolute neutrophil count (ANC) (r=0.4, p=<0.0001). These correlations were not observed when NEa was measured by the substrate assay even though a significant correlation was found between the two assays (r=0.8, p<0.0001). A trend towards significance was found between NEa in the CF and non-CF groups when measured by ProteaseTag™ Active NE (p=0.07). Highly significant differences were found with the other inflammatory parameters between the 2 groups (IL-8: p=0.0002 and ANC: p=0.006). Conclusion: NEa as a primary efficacy endpoint in clinical trials or as a marker of inflammation within the clinic has been hampered by the lack of a robust and simple to use assay. ProteaseTag™ Active NE has been shown to be a specific and superior tool in the measurement of NEa in paediatric CF BAL samples (supporting data from previous studies using adult CF expectorated samples). The technology is currently being transferred to a lateral flow device for use at Point of Care. Acknowledgements: This work was supported by the National Children’s Research Centre, Dublin (SHIELD CF) and grants from the Medical Research Council and Cystic Fibrosis Foundation Therapeutics.

Smartphone and GPS technology for freeroaming dog population surveillance -a methodological study (Studio metodologico sull’applicazione di smartphone e tecnologia GPS alla sorveglianza delle popolazioni di cani vaganti)

Free-roaming dogs (FRD) represent a potential threat to the quality of life in cities from an ecological, social and public health point of view. One of the most urgent concerns is the role of uncontrolled dogs as reservoirs of infectious diseases transmittable to humans and, above all, rabies. An estimate of the FRD population size and characteristics in a given area is the first step for any relevant intervention programme. Direct count methods are still prominent because of their non-invasive approach, information technologies can support such methods facilitating data collection and allowing for a more efficient data handling. This paper presents a new framework for data collection using a topological algorithm implemented as ArcScript in ESRI® ArcGIS software, which allows for a random selection of the sampling areas. It also supplies a mobile phone application for Android® operating system devices which integrates Global Positioning System (GPS) and Google Maps™. The potential of such a framework was tested in 2 Italian regions. Coupling technological and innovative solutions associated with common counting methods facilitate data collection and transcription. It also paves the way to future applications, which could support dog population management systems.

Step by step: reconstruction of terrestrial animal movement paths by dead-reckoning

BACKGROUND: Research on wild animal ecology is increasingly employing GPS telemetry in order to determine animal movement. However, GPS systems record position intermittently, providing no information on latent position or track tortuosity. High frequency GPS have high power requirements, which necessitates large batteries (often effectively precluding their use on small animals) or reduced deployment duration. Dead-reckoning is an alternative approach which has the potential to 'fill in the gaps' between less resolute forms of telemetry without incurring the power costs. However, although this method has been used in aquatic environments, no explicit demonstration of terrestrial dead-reckoning has been presented.

RESULTS: We perform a simple validation experiment to assess the rate of error accumulation in terrestrial dead-reckoning. In addition, examples of successful implementation of dead-reckoning are given using data from the domestic dog Canus lupus, horse Equus ferus, cow Bos taurus and wild badger Meles meles.

CONCLUSIONS: This study documents how terrestrial dead-reckoning can be undertaken, describing derivation of heading from tri-axial accelerometer and tri-axial magnetometer data, correction for hard and soft iron distortions on the magnetometer output, and presenting a novel correction procedure to marry dead-reckoned paths to ground-truthed positions. This study is the first explicit demonstration of terrestrial dead-reckoning, which provides a workable method of deriving the paths of animals on a step-by-step scale. The wider implications of this method for the understanding of animal movement ecology are discussed.

The Effect of Changes to the Method of Estimating the Pollen Count from Aerobiological Samples

Pollen data have been recorded at Novi Sad in Serbia since 2000. The adopted method of producing pollen counts has been the use of five longitudinal transects that examine 19.64% of total sample surface. However, counting five transects is time consuming and so the main objective of this study is to investigate whether reducing the number to three or even two transects would have a significant effect on daily average and bi-hourly pollen concentrations, as well as the main characteristics of the pollen season and long-term trends. This study has shown that there is a loss of accuracy in daily average and bi-hourly pollen concentrations (an increase in % ERROR) as the sub-sampling area is reduced from five to three or two longitudinal transects. However, this loss of accuracy does not impact on the main characteristics of the season or long-term trends. As a result, this study can be used to justify changing the sub-sampling method used at Novi Sad from five to three longitudinal transects. The use of two longitudinal transects has been ruled out because, although quicker, the counts produced: (a) had the greatest amount of % ERROR, (b) altered the amount of influence of the independent variable on the dependent variable (the slope in regression analysis) and (c) the total sampled surface (7.86%) was less than the minimum requirement recommended by the European Aerobiology Society working group on Quality Control (at least 10% of total slide area).

A novel method to count the red blood cells in thin blood films

This paper describes a novel idea to identify the total number of red blood cells (RBCs) as well as their location in a Giemsa stained thin blood film image. This work is being undertaken as a part of developing an automated malaria parasite detection system by scanning a photograph of thin blood film in order to evaluate the parasitemia of the blood. Not only will this method eliminates the segmentation procedures that are normally used to segment the cells in the microscopic image, but also avoids any image pre-processing to deal with non uniform illumination prior to cell detection. The method utilizes basic knowledge on cell structure and brightness of the components due to Giemsa staining of the sample and detects and locates the RBCs in the image.

The effect of a selective CXCR2 antagonist (AZD5069) on human blood neutrophil count and innate immune functions.

Abstract AIMS: The aim of the present study was to investigate whether selective antagonism of the cysteine-X-cysteine chemokine receptor-2 (CXCR2) receptor has any adverse effects on the key innate effector functions of human neutrophils for defence against microbial pathogens. METHODS: In a double-blind, crossover study, 30 healthy volunteers were randomized to treatment with the CXCR2 antagonist AZD5069 (100 mg) or placebo, twice daily orally for 6 days. The peripheral blood neutrophil count was assessed at baseline, daily during treatment and in response to exercise challenge and subcutaneous injection of granulocyte-colony stimulating factor (G-CSF). Neutrophil function was evaluated by phagocytosis of Escherichia coli and by the oxidative burst response to E. coli. RESULTS: AZD5069 treatment reversibly reduced circulating neutrophil count from baseline by a mean [standard deviation (SD)] of -1.67 (0.67) ×10(9) l(-1) vs. 0.19 (0.78) ×10(9) l(-1) for placebo on day 2, returning to baseline by day 7 after the last dose. Despite low counts on day 4, a 10-min exercise challenge increased absolute blood neutrophil count, but the effect with AZD5069 was smaller and not sustained, compared with placebo treatment. Subcutaneous G-CSF on day 5 caused a substantial increase in blood neutrophil count in both placebo- and AZD5069-treated subjects. Superoxide anion production in E. coli-stimulated neutrophils and phagocytosis of E. coli were unaffected by AZD5069 (P = 0.375, P = 0.721, respectively vs. baseline, Day 4). AZD5069 was well tolerated. CONCLUSIONS: CXCR2 antagonism did not appear adversely to affect the mobilization of neutrophils from bone marrow into the peripheral circulation, phagocytosis or the oxidative burst response to bacterial pathogens. This supports the potential of CXCR2 antagonists as a treatment option for diseases in which neutrophils play a pathological role.

Delamination analysis of carbon fibre reinforced laminates: evaluation of a special step drill

Drilling of carbon fibre/epoxy laminates is usually carried out using standard drills. However, it is necessary to adapt the processes and/or tooling as the risk of delamination, or other damages, is high. These problems can affect mechanical properties of produced parts, therefore, lower reliability. In this paper, four different drills – three commercial and a special step (prototype) – are compared in terms of thrust force during drilling and delamination. In order to evaluate damage, enhanced radiography is applied. The resulting images were then computational processed using a previously developed image processing and analysis platform. Results show that the prototype drill had encouraging results in terms of maximum thrust force and delamination reduction. Furthermore, it is possible to state that a correct choice of drill geometry, particularly the use of a pilot hole, a conservative cutting speed – 53 m/min – and a low feed rate – 0.025 mm/rev – can help to prevent delamination.

A 3-step therapeutic strategy for severe alveolar proteinosis.

Pulmonary alveolar proteinosis (PAP) is characterized by accumulation of lipoproteinaceous material in the terminal airways. Whole lung lavage (WLL) remains the gold standard treatment but may be particularly challenging in cases of severe hypoxemia. We present a 3-step strategy that was used in a patient with PAP-associated refractory hypoxemia and that combined venovenous extracorporeal membrane oxygenation (vvECMO), double-lumen orotracheal intubation, and bilateral multisegmental sequential lavage (MSL). The procedure was well tolerated and permitted weaning from the ventilator.

Cost-effectivness in a DRG system for two-step exchange of infected total joint arthroplasty

The costs related to the treatment of infected total joint arthroplasties represent an ever groving burden to the society. Different patient-adapted therapeutic options like débridement and retention, 1- or 2-step exchange can be used. If a 2-step exchange is used we have to consider short (2-4 weeks) or long (>4-6 weeks) interval treatment. The Swiss DRG (Diagnose related Groups) determines the reimboursement the hopsital receives for the treatment of an infected total arthroplasty. The review assesses the cost-effectiveness of hospitalisation practices linked to surgical treatment in the two-stage exchange of a prosthetic-joint infection. The aim of this retrospectiv study is to compare the economical impact between a short (2 to 4 weeks) versus a long (6 weeks and above) interval during a two-satge procedure to determine the financial impact. Retrospectiv study of the patients with a two-stage procedure for a hip or knee prosthetic joint infection at CHUV hospital Lausanne (Switzerland) between 2012 and 2013. The review analyses the correlation between the interval length and the length of the hospital stay as well as with the costs and revenues per hospital stay. In average there is a loss of 40′000 Euro per hospitalisation for the treatment of prosthetic joint infection. Revenues never cover all the costs, even with a short interval procedure. This economical loss increases with the length of the hospital stay if a long-term intervall is choosen. The review explores potential for improvement in reimbourement practices and hospitalisation practices in the current Swiss healthcare setting. There should be alternative setups to decrease the burden of medical costs by a) increase the reimboursment for the treatment of infected total joints or by b) splitting the hospital stay with partners (rapid transfer after first operation from center hospital to level 2 hospital and retransfer for second operation to center) in order to increase revenues.