Transcriptional response of Burkholderia cenocepacia J2315 sessile cells to treatments with high doses of hydrogen peroxide and sodium hypochlorite

Background: Burkholderia cepacia complex bacteria are opportunistic pathogens, which can cause severe respiratory tract infections in patients with cystic fibrosis (CF). As treatment of infected CF patients is problematic, multiple preventive measures are taken to reduce the infection risk. Besides a stringent segregation policy to prevent patient-to-patient transmission, clinicians also advise patients to clean and disinfect their respiratory equipment on a regular basis. However, problems regarding the efficacy of several disinfection procedures for the removal and/or killing of B. cepacia complex bacteria have been reported. In order to unravel the molecular mechanisms involved in the resistance of biofilm-grown Burkholderia cenocepacia cells against high concentrations of reactive oxygen species (ROS), the present study focussed on the transcriptional response in sessile B. cenocepacia J2315 cells following exposure to high levels of H2O2 or NaOCl. Results: The exposure to H2O2 and NaOCl resulted in an upregulation of the transcription of 315 (4.4%) and 386 (5.4%) genes, respectively. Transcription of 185 (2.6%) and 331 (4.6%) genes was decreased in response to the respective treatments. Many of the upregulated genes in the NaOCl- and H2O2-treated biofilms are involved in oxidative stress as well as general stress response, emphasizing the importance of the efficient neutralization and scavenging of ROS. In addition, multiple upregulated genes encode proteins that are necessary to repair ROS-induced cellular damage. Unexpectedly, a prolonged treatment with H2O2 also resulted in an increased transcription of multiple phage-related genes. A closer inspection of hybridisation signals obtained with probes targeting intergenic regions led to the identification of a putative 6S RNA. Conclusion: Our results reveal that the transcription of a large fraction of B. cenocepacia J2315 genes is altered upon exposure of sessile cells to ROS. These observations have highlighted that B. cenocepacia may alter several pathways in response to exposure to ROS and they have led to the identification of many genes not previously implicated in the stress response of this pathogen

Tourism Life Cycle Assessment (LCA): Proposal of a New Methodological Framework for Sustainable Consumption and Production

Tourism has become an important part of modern life styles, besides being one of the largest and fastest growing economic sectors worldwide, in spite of occasional shocks over the last decade (UNWTO 2010). Tourism’s contribution to the gross domestic product (GDP) is – when direct contribution and multipliers are included - estimated at up to 10% in some advanced, diversified economies. However, this strong growth also implies an increase of undesired environmental impacts. Tourism is globally responsible for 5% of all carbon dioxide emissions, the most important greenhouse gas causing climate change (UNWTO UNEP WMO 2008). However, in terms of radiative forcing, the direct measure for contribution to climate change, tourism even could have share of up to 12.5% (Scott et al., 2010). Also, the greenhouse gas emissions of tourism are estimated to grow at a rather large rate, while a globally emissions should be reduced with up to 80% by 2050 (e.g. Scott et al., 2010). Finally, it has been shown that the eco-efficiency – the economic contribution per ton emissions – of tourism is rather low (Gössling et al., 2005). Theses data totally clash with the view, actually slightly common to many re¬searchers in the past, according to which tourism is a low environmental impact industry (McCrory 2006). Now, it is a shared concept that tourist activities are strongly related to the environment, since, on the one hand, the natural environment itself may be consid¬ered as a major input resource to the processes of tourism industries, and, on the other hand, the development of tourism as a mass industry may severely increase its overall impact on the environment (Butler 2004; Raggi and Petti 2006; Romeril 1989). Given the predictions of an increased role of tourism industries in the world economy, the environmental aspects of, and impacts gen¬erated by tourist activities should be accurately considered according to a Life Cycle Thinking perspective. This concept has been extensively advocated as the proper way of addressing the challenges linked with sustainable development, and, in particular, with those measures for enhancing sustainable consumption and production. In the framework of sustainable development policies, the “Sustainable Consumption and Production and Sustainable Industrial Policy (SCP) Action Plan” (European Commission 2008) is a building block in the EU. In line with this policy, a wide range of environmental instruments have been developed so far for assessment and labelling/certification purposes of travel and tourist services. This ongoing proliferation of different initiatives shows a high degree of diversity in terms of scope, assessment methodologies and means and tools of communication. Although this proliferation reflects the vast variety of travel and tourist products and the complicated nature in assessing their environmental performance, these environmental instruments seem to suffer from a lack of integration and standardisation or quality control. This situation has the potential to confuse or even mislead travellers and the stakeholders within the industry. Research questions were: - What environmental instruments and initiatives are currently supporting the application of the European Sustainable Consumption and Production (SCP) Action Plan in the travel and tourism industry? - What are their key characteristics and how do they stand in relation to Life Cycle Assessment (LCA) principles? - How can these instruments be combined in a general framework capable to render this industry low carbon and more sustainable from an environmental point of view?JRC.H.8-Sustainability Assessmen

Benchmarking information aggregation in experimental markets

Theoretical and experimental literature have provided mixed insights on the ability of financial markets to perfectly aggregate private information into asset prices. We conduct an experiment designed to benchmark information aggregation in markets. In our lab experiment, we randomly assign subjects to different institutional environments, either a market or a Becker–DeGroot–Marschak mechanism. We find evidence that market interaction is worse for information aggregation. The difference between the two environments is driven by price-insensitive traders who seem unable to learn from market prices. Price-sensitive traders, by contrast, learn equally well in both environments

The case for action on socioeconomic differences in overweight and obesity among Australian adults: modelling the disease burden and healthcare co

Objective: We aimed to quantify the extent to which socioeconomic differences in body mass index (BMI) drive avoidable deaths, incident disease cases and healthcare costs. Methods: We used population attributable fractions to quantify the annual burden of disease attributable to socioeconomic differences in BMI for Australian adults aged 20 to <85 years in 2016, stratified by quintiles of an area-level indicator of socioeconomic disadvantage (SocioEconomic Index For Areas Indicator of Relative Socioeconomic Disadvantage; SEIFA) and BMI (normal weight, overweight, obese). We estimated direct healthcare costs using annual estimates per person per BMI category. Results: We attributed $AU1.06 billion in direct healthcare costs to socioeconomic differences in BMI in 2016. The greatest number (proportion) of cases and deaths attributable to socioeconomic differences in BMI was observed for type 2 diabetes among women (8,602 total cases [16%], with 3,471 cases [22%] in the most disadvantaged quintile [SEIFA 1]) and all-cause mortality among men (2027 total deaths [4%], with 815 deaths [6%] in SEIFA 1). Conclusions: Socioeconomic differences in BMI substantially contribute to avoidable deaths, disease cases and direct healthcare costs in Australia. Implications for public health: Population-level policies to reduce socioeconomic differences in overweight and obesity must be identified and implemented

Chester supersolid of spatially indirect excitons in double-layer semiconductor heterostructures

A supersolid, a counter-intuitive quantum state in which a rigid lattice of particles flows without resistance, has to date not been unambiguously realised. Here we reveal a supersolid ground state of excitons in a double-layer semiconductor heterostructure over a wide range of layer separations outside the focus of recent experiments. This supersolid conforms to the original Chester supersolid with one exciton per supersolid site, as distinct from the alternative version reported in cold-atom systems of a periodic modulation of the superfluid density. We provide the phase diagram augmented by the supersolid. This new phase appears at layer separations much smaller than the predicted exciton normal solid, and it persists up to a solid--solid transition where the quantum phase coherence collapses. The ranges of layer separations and exciton densities in our phase diagram are well within reach of the current experimental capabilities

Experimental conditions for observation of electron-hole superfluidity in GaAs heterostructures

The experimental parameter ranges needed to generate superfluidity in optical and drag experiments in GaAs double quantum wells are determined, using a formalism that includes self-consistent screening of the Coulomb pairing interaction in the presence of the superfluid. The very different electron and hole masses in GaAs make this a particularly interesting system for superfluidity, with exotic superfluid phases predicted in the BCS-BEC crossover regime. We find that the density and temperature ranges for superfluidity cover the range for which optical experiments have observed indications of superfluidity, but that existing drag experiments lie outside the superfluid range. However we also show that for samples with low mobility with no macroscopically connected superfluidity, if the superfluidity survived in randomly distributed localized pockets, standard quantum capacitance measurements could detect these pockets.Comment: 7 pages, 4 figure

Detecting functional decline from normal aging to dementia: Development and validation of a short version of the Amsterdam IADL Questionnaire

Introduction Detecting functional decline from normal aging to dementia is relevant for diagnostic and prognostic purposes. Therefore, the Amsterdam IADL Questionnaire (A-IADL-Q) was developed: a 70-item proxy-based tool with good psychometric properties. We aimed to design a short version while preserving its psychometric quality. Methods Study partners of subjects (n = 1355), ranging from cognitively normal to dementia subjects, completed the original A-IADL-Q. We selected the short version items using a stepwise procedure combining missing data, Item Response Theory, and input from respondents and experts. We investigated internal consistency of the short version and concordance with the original version. To assess its construct validity, we additionally investigated concordance between the short version and the Mini–Mental State Examination (MMSE) and Disability Assessment for Dementia (DAD). Finally, we investigated differences in instrumental activities of daily living (IADL) scores between diagnostic groups across the dementia spectrum. Results We selected 30 items covering the entire spectrum of IADL functioning. Internal consistency (0.98) and concordance with the original version (0.97) were very high. Concordance with the MMSE (0.72) and DAD (0.87) scores was high. IADL impairment scores increased across the spectrum from normal cognition to dementia. Discussion The A-IADL-Q short version (A-IADL-Q-SV) consists of 30 items and has maintained the psychometric quality of the original A-IADL-Q. As such, the A-IADL-Q-SV is a concise measure of functional decline

Filgotinib for Treating Moderately to Severely Active Ulcerative Colitis:An Evidence Review Group Perspective of a NICE Single Technology Appraisal

The National Institute for Health and Care Excellence invited the manufacturer (Galapagos) of filgotinib (Jyseleca®), as part of the Single Technology Appraisal process, to submit evidence for the clinical effectiveness and cost effectiveness of filgotinib for treating moderately to severely active ulcerative colitis in adults who have had an inadequate response, loss of response or were intolerant to a previous biologic agent or conventional therapy. Kleijnen Systematic Reviews Ltd, in collaboration with Maastricht University Medical Centre+, was commissioned to act as the independent Evidence Review Group. This paper summarises the company submission, presents the Evidence Review Group’s critical review on the clinical and cost-effectiveness evidence in the company submission, highlights the key methodological considerations and describes the development of the National Institute for Health and Care Excellence guidance by the Appraisal Committee. The company submission included one relevant study for the comparison of filgotinib versus placebo: the SELECTION trial. As there was no head-to-head evidence with any of the comparators, the company performed two separate network meta-analyses, one for the biologic-naïve population and one for the biologic-experienced population, and for both the induction and maintenance phases. The Evidence Review Group questioned the validity of the maintenance network meta-analysis because it assumed all active treatments to be comparators in this phase, which is not in line with clinical practice. The economic analysis used a number of assumptions that introduced substantial uncertainty, which could not be fully explored, for instance, the assumption that a risk of loss of response would be independent of health state and constant over time. Company and Evidence Review Group results indicate that at its current price, and disregarding confidential discounts for comparators and subsequent treatments, filgotinib dominates some comparators (golimumab and adalimumab in the company base case, all but intravenous and subcutaneous vedolizumab in the Evidence Review Group’s base case) in the biologic-naïve population. In the biologic-experienced population, filgotinib dominates all comparators in both the company and the Evidence Review Group’s base case. Results should be interpreted with caution as some important uncertainties were not included in the modelling. These uncertainties were mostly centred around the maintenance network meta-analysis, loss of response, health-related quality-of-life estimates and modelling of dose escalation. The National Institute for Health and Care Excellence recommended filgotinib within its marketing authorisation, as an option for treating moderately to severely active ulcerative colitis in adults when conventional or biological treatment cannot be tolerated, or if the disease has not responded well enough or has stopped responding to these treatments, and if the company provides filgotinib according to the commercial arrangement.</p