Novel nucleotide-packaging vaccine delivers antigen and poly(I:C) to dendritic cells and generate a potent antibody response in vivo.

An issue with many current vaccines is the dependency on broadly inflammatory adjuvants, such as aluminum hydroxide or aluminum salts that affect many immune- and non-immune cells. These adjuvants are not necessarily activating all antigen-presenting cells (APCs) that take up the antigen and most likely they also activate APCs with no antigen uptake, as well as many non-immune cells. Conjugation of antigen and adjuvant would enable the use of smaller amounts of adjuvant and avoid unnecessary tissue damage and activation of bystander cells. It would ensure that all APCs that take up the antigen would also become activated and avoid that immature and non-activated APCs present the antigen to T cells without a co-stimulatory signal, leading to tolerogenesis. We have developed a novel vaccine that co-deliver antigen and a nucleotide adjuvant to the same APC and lead to a strong activation response in dendritic cells and macrophages. The vaccine is constructed as a fusion-protein with an antigen fused to the DNA/RNA-binding domain from the Hc2 protein from Chlamydia trachomatis. We have found that the fusion protein is able to package polyinosinic:polycytidylic acid (poly(I:C)) or dsDNA into small particles. These particles were taken up by macrophages and dendritic cells and led to strong activation and maturation of these cells. Immunization of mice with the fusion protein packaged poly(I:C) led to a stronger antibody response compared to immunization with a combination of poly(I:C) and antigen without the Hc2 DNA/RNA-binding domain.

Increasing use of computed tomography scans in the North Denmark Region raises patient safety concern.

PURPOSE: Use of computed tomography (CT) scans raises safety concern as lifetime cumulative ionising radiation exposure is associated with risk of developing malignancies. This study aimed to investigate use of abdominal CT scans in the Danish health care sector. METHODS: Data on abdominal CT scans performed annually in the North Denmark Region between 2005 and 2018 were extracted from the regional registry with emphasis on patients with a medical history of a repeated abdominal CT scan within 28 days. An audit of the medical files was subsequently conducted in 100 randomly selected patient cases to evaluate clinical information being provided, in addition to justification for a repeated abdominal CT scan, and finally if other radiology modalities could have been applied. RESULTS: Number of annually performed abdominal CT scans in this demographically stable regional population increased by a factor 4.3 from 15 in 2005 to 65 in 2018 per 1,000 inhabitants. The audit revealed that 31% of the secondabdominal CT scans within a 28 days period were categorized as either doubtful whether justified or not justified. Moreover, 20% of theCT scans were considered replaceable by ultrasonography. CONCLUSIONS: Annual performance of abdominal CT scans increased fourfold during the 14 years period. This tendency is probably attributable to changes in the Danish health care sector by which CT scan examination are used more frequently aiming at more accelerated patient investigation flow in conjunction with shorter length of hospitalization stay. Alertness is strongly warranted towards the associated risk of cancer due to life-time cumulative ionising radiation exposure by this strategy.

Centennial response of Greenland's three largest outlet glaciers.

The Greenland Ice Sheet is the largest land ice contributor to sea level rise. This will continue in the future but at an uncertain rate and observational estimates are limited to the last few decades. Understanding the long-term glacier response to external forcing is key to improving projections. Here we use historical photographs to calculate ice loss from 1880-2012 for Jakobshavn, Helheim, and Kangerlussuaq glacier. We estimate ice loss corresponding to a sea level rise of 8.1 ± 1.1 millimetres from these three glaciers. Projections of mass loss for these glaciers, using the worst-case scenario, Representative Concentration Pathways 8.5, suggest a sea level contribution of 9.1-14.9 mm by 2100. RCP8.5 implies an additional global temperature increase of 3.7 °C by 2100, approximately four times larger than that which has taken place since 1880. We infer that projections forced by RCP8.5 underestimate glacier mass loss which could exceed this worst-case scenario.

Complement mediated Klebsiella pneumoniae capsule changes.

The Gram-negative bacterium Klebsiella pneumoniae is an opportunistic pathogen, which can cause life-threatening infections such as sepsis. Worldwide, emerging multidrug resistant K. pneumoniae infections are challenging to treat, hence leading to increased mortality. Therefore, understanding the interactions between K. pneumoniae and the immune system is important to develop new treatment options. We characterized ten clinical K. pneumoniae isolates obtained from blood of bacteremia patients. The interaction of the isolates with human serum was investigated to elucidate how K. pneumoniae escapes the host immune system, and how complement activation by K. pneumoniae changed the capsule structure. All K. pneumoniae isolates activated the alternative complement pathway despite serum resistance of seven isolates. One serum sensitive isolate activated two or all three pathways, and this isolate was lysed and had numerous membrane attack complexes in the outer membrane. However, we also found deposition of complement components in the capsule of serum resistant isolates resulting in morphological capsule changes and capsule shedding. These bacteria did not lyse, and no membrane attack complex was observed despite deposition of C5b-9 within the capsule, indicating that the capsule of serum resistant K. pneumoniae isolates is a defense mechanism against complement-mediated lysis.

Development and implementation of a near-real-time web reporting system on ground-level ozone in Europe.

This article presents the development and results of Ozone Web--near-real-time approach to communicate environmental information to policy makers, researchers, and the general public. In Ozone Web, ground-level ozone information from 750 air quality measurement stations across Europe is collected on an hourly basis, filtered, interpolated, and presented on zoomable maps and graphs. Compared with other environmental information initiatives, the main aspects of this Website is the allowance for user interactivity, free access to data, and high timeliness. Data are published 2 to 3 h after actual monitoring. In a response to the acute characteristics of air pollution, the basic principle is that up-to-date and accurate information about air pollution levels will help (1) citizens to protect their health, (2) policy makers in assessing the state of the environment, and (3) researchers in exchanging data and knowledge. Near-real-time information systems on the Web seem to be a valuable complement to future environmental reporting, and the European Environment Agency is currently investigating the requirements needed to extend the use of near-real-time data, including reporting on air pollutants other than ozone.

Environmental sub models for a macroeconomic model: agricultural contribution to climate change and acidification in Denmark.

Integrated modelling of the interaction between environmental pressure and economic development is a useful tool to evaluate environmental consequences of policy initiatives. However, the usefulness of such models is often restricted by the fact that these models only include a limited set of environmental impacts, which are often energy-related emissions. In order to evaluate the development in the overall environmental pressure correctly, these model systems must be extended. In this article an integrated macroeconomic model system of the Danish economy with environmental modules of energy related emissions is extended to include the agricultural contribution to climate change and acidification. Next to the energy sector, the agricultural sector is the most important contributor to these environmental themes and subsequently the extended model complex calculates more than 99% of the contribution to both climate change and acidification. Environmental sub-models are developed for agriculture-related emissions of CH(4), N(2)O and NH(3). Agricultural emission sources related to the production specific activity variables are mapped and emission dependent parameters are identified in order to calculate emission coefficients. The emission coefficients are linked to the economic activity variables of the Danish agricultural production. The model system is demonstrated by projections of agriculture-related emissions in Denmark under two alternative sets of assumptions: a baseline projection of the general economic development and a policy scenario for changes in the husbandry sector within the agricultural sector.

Ranking contaminated sites using a partial ordering method.

In this project, we apply the method of partial ordering on the ranking of 74 contaminated sites located in the county of West Zealand (Denmark). The method is based on the concept that the parameters are kept separated through the ranking analysis, and thus no weighing of the different parameter values is necessary. The ranking is displayed in a graphical form by the Hasse diagram technique to ease the interpretation. A critical comparison is made of the ranking of contaminated sites by the partial ordering method and an index function used by the county of West Zealand. Comparing the ranking by the partial ordering method to the index function shows that the choice of score points and index function highly influences the ranking result, as only four sites are equally ranked. The importance of the parameters used to identify the environmental hazard of the contaminated sites is analyzed in order to evaluate the influence of each parameter on the ranking. From among a total of six different parameters, two have high influence, two medium, and two low because of both the construction of the scoring system and the characteristics of the data.