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Tuberculosis (TB) screening programmes among asylum seekers tend to focus on chest radiography (CXR) for early diagnosis, whereas knowledge on sputum examination is limited. We evaluated active TB screening using CXR and sputum culture among asylum seekers arriving in Denmark. In addition, we assessed the coverage of a voluntary health assessment.Between 1 February 2017 and 31 March 2019, all newly arrived asylum seekers in Denmark ≥ 18 years from TB high-incidence countries or risk groups, who attended a voluntary general health assessment, were offered active TB screening with CXR and spot sputum examination. Sputum samples were examined by culture and smear microscopy.Coverage of the general health assessment was 65.1%. Among 1,154 referred for active TB screening, 923 (80.0%) attended. Of these, 854 were screened by CXR and one case of active TB was identified equivalent to a yield of 0.12%. Sputum samples were collected from 758 and oneWe suggest that TB screening should focus on asylum seekers from TB high-incidence countries. Furthermore, early health assessments should be of high priority to ensure migrant health.

The design of ion sensors has gained importance for the study of ion dynamics in cells, with fluorescent proton nanosensors attracting particular interest because of their applicability in monitoring pH gradients in biological microcompartments and reconstituted membrane systems. In this work, we describe the improved synthesis, photophysical properties and applications of pH sensors based on amine-reactive pHrodo esters and short-chain lipid derivatives of phosphoethanolamine. The major features of these novel probes include strong fluorescence under acidic conditions, efficient partitioning into membranes, and extractability by back exchange to albumin. These features allow for the selective labeling of the inner liposomal leaflet in reconstituted membrane systems for studying proton pumping activities in a quantitative fashion, as demonstrated by assaying the activity of a plant plasma membrane H+-ATPase. Furthermore, the short-chain lipid-conjugated pH sensors enable the monitoring of pH changes from neutral to acidic conditions in the endocytic pathway of living cells. Collectively, our results demonstrate the applicability of short-chain lipid-conjugated sensors for in vivo and in vitro studies and thus pave the way for the design of lipid-conjugated sensors selective to other biologically relevant ions, e.g. calcium and sodium.

In eukaryotes, P-type adenosine triphosphatases (ATPases) generate the plasma membrane potential and drive secondary transport systems; however, despite their importance, their regulation remains poorly understood. We monitored at the single-molecule level the activity of the prototypic proton-pumping P-type ATPase Arabidopsis thaliana isoform 2 (AHA2). Our measurements, combined with a physical nonequilibrium model of vesicle acidification, revealed that pumping is stochastically interrupted by long-lived (~100 seconds) inactive or leaky states. Allosteric regulation by pH gradients modulated the switch between these states but not the pumping or leakage rates. The autoinhibitory regulatory domain of AHA2 reduced the intrinsic pumping rates but increased the dwell time in the active pumping state. We anticipate that similar functional dynamics underlie the operation and regulation of many other active transporters.

Denne oppgaven handler om kvinner som har blitt voldtatt, men som ikke har anmeldt voldtekten. Voldtekt forstås i denne oppgaven som en handling der offerets vilje overvinnes på en særlig seksuell måte. I denne handlingen frarøves hennes mulighet til å handle. Hun nektes å være aktiv og anerkjent som en fullverdig deltaker i den seksuelle interaksjonen. Hun har ingen kontroll og hun har ingen reelle valg. Begrepet voldtekt er nærmest uløselig knyttet til forventningen om å anmelde. De siste tiårene har det blitt satt inn ressurser og for å bekjempe seksuell vold mot kvinner. Derfor kan en kan trolig hevde at holdninger til voldtekt har blitt bedre, og at støtte- og rettsapparatet er bedre egnet til å hjelpe og å behandle voldtekt. Likevel er det mye som tyder på at de fleste voldtektsutsatte forblir tause. Få ber om hjelp, få forteller om voldtekten til andre, og enda færre anmelder den. En vanlig forklaring på dette er at personer som har blitt voldtatt ikke kjenner seg, og sin erfaring, igjen i de eksisterende fortellingene om voldtekt og voldtektsutsatte. Dette hindrer dem i å anmelde eller fortelle om sine opplevelser. Til denne oppgaven har jeg intervjuet elleve kvinner som har blitt voldtatt. Selv om de, mer eller mindre, begrepsfester sin erfaring som voldtekt, har de ikke anmeldt denne. Jeg bruker derfor deres fortellinger til å forsøke å belyse følgende spørsmål: Hva handler fortellingene bak ikke-anmeldte voldtekter om, og hvordan kan slike fortellinger forklare hvorfor noen kvinner ikke anmelder, eller forteller om, voldtekt?

With “Horizon Europe”, the European Commission sets out the framework for research and innovation in Europe over the next seven years. The proposal outlines the contours of an innovative science policy that is open and responsive to societal needs, and where societal actors jointly undertake missions to discover sustainable solutions to present-day and future challenges. In our commentary we point to a number of modifications needed to strengthen the cross-cutting implementation of activities for societal engagement and responsible research and innovation.

Studying membrane proteins at the molecular level represents a major challenge in biochemistry due to the complexity of the membrane in which they are embedded. As an important step towards a detailed understanding of their action and molecular functioning, current studies focus on membrane proteins reconstituted into artificial lipid environments. Such reconstituted systems allow for a more flexible choice of biochemical, biophysical, and microscopy techniques for characterizing the proteins. This review gives an overview of the methods currently available for reconstituting membrane proteins in a functional state into giant unilamellar vesicles, and discusses some key methods to verify successful reconstitution.

A common statement from the organizations involved in the PACITA project, the PACITA manifesto argues for the necessity of European political support of future efforts to expand technology assessment (TA) capacities in the European member states. The authors posit the tradition of technology assessment in European as a democratic project to inform policy makers on societal and environmental topics related to science, technology and innovation. And they call attention to the necessity of countering the increasing influence of science and technology on societal development and policy making with increasing capacities for technology assessment. Developing a more comprehensive ‘policy-oriented’ approach to TA is called for by the authors along with an increase in cross-European collaboration in TA.

Jorgensen, Kozarev and Lindegaard Juul lay out the rationale and methodology for a multi-site citizen participation exercise carried out within the larger framework of the PACITA project. The exercise gathered more than 1,000 citizens at parallel citizens’ summits in eleven European countries, exemplifying the practicability of orchestrating public engagement in connected national arenas across Europe. The authors argue that not only did the events themselves provide comparable samples of informed and deliberated opinions, but also the cross-national collaboration to prepare the events, which involved both central stakeholders and policymakers, served as a vehicle for consensus building among these actors. Based on the response of participants and political recipients, a call is made for further capacity building for cross-European citizen participation.

Regulated and selective transport of biomolecules across biological membranes is mediated by transporter proteins. These are essential in physiological processes ranging from electrical signaling in the nervous system to secretion of hormones and maintenance of electrochemical gradients. Though transporters are extensively studied, there are currently no techniques available to investigate their function at the single molecule level. We have developed a fluorescence-based assay to monitor thousands of individual nanoscale proteoliposomes in parallel by immobilizing them on functionalized glass surfaces (1-5).We recently extended this assay to allow real-time observation of substrate translocation mediated by single transporters reconstituted into liposomes. Here we present the development of the assay including characterization and optimization of the most critical system components including: minimization of leakage, in situ real-time calibration of absolute transport rates and increase of photostability for long term recordings (∼40min). We also present high-resolution single molecule activity recordings of the transporter protein, Arabidopsis thaliana H+-ATPase (AHA2).References:1. Mathiasen et al., Nature Methods. (2014) 11:931-342. Christensen. et al. Nat Nanotechnol. (2012) 7:51-53. Hatzakis. et al. Nat. Chem. Biol. (2009) 5:835-414. Bendix. et al. PNAS. (2009) 106:12341-65. Kunding. et al. Biophys J. (2008) 95:1176-88

A 28-year-old woman presented with abdominal pain. Prior to admission she had injected human chorionic gonadotropin (hCG) intramuscularly as part of a weight loss programme. A computed tomography detected a thrombosis of the superior mesenteric vein and with a gynaecologic scan she was found to be six weeks pregnant despite using oral contraception. Treatment with anticoagulant therapy was started, and a surgical abortion was performed. hCG bought illegal is used as a part of a weight loss program. Whether HCG injected in small amounts is a risk factor of venous thrombosis and whether it is able to reduce the effect of oral contraception is unknown.

Electrochemical gradients across cellular membranes control a plethora of vital biological processes. These gradients are generated by primary active transporters and are subsequently used to drive the exchange of other solutes through secondary active transporters and to facilitate signaling via ion channels. The macroscopic biological phenomena that channels and transporters give rise to are intimately connected to how they function at the single molecule level. For decades, patch clamp recording has been used to observe the functional dynamics of single ion channels revealing discrete on and off states, subconductance states, and other mechanistically important features that macroscopic experiments cannot probe(1). Currently, there aren’t any techniques available to investigate transporter function at the single molecule level, thus they are only studied using ensemble biochemical methods.For a decade we have been developing quantitative fluorescence microscopy based assays of arrayed proteoliposomes for investigating membrane proteins(2-6). Here we extended the platform to monitor the single-molecule activity and the regulation of a prototypic P-type ATPase, Arabidopsis thaliana H+-ATPase (AHA2). For the first time we have shown that individual proton pumps are not active continuously but rather transitioning between active and inactive states separated by a large activation barrier (kJMole−1). We found that the dynamics of these states form the basis of the regulation of the macroscopic activity either by regulatory R-domain, pH gradients, or ATP. Like for ion channels we often found that regulatory inputs do not affect the intrinsic pumping rates but rather active probabilities.References:1. Neher & Sajmann, Nature, (1976)2. Mathiasen et al., Nature Methods, (2014)3. Larsen et al., Nature Chemical Biology, (2015)4. Christensen et al., Nature Nanotechnology, (2012)5. Hatzakis et al., Nature Chemical Biology, (2009)6. Bendix et al., PNAS, (2009)

Membrane transporters regulate multiple physiological processes including the pumping of ions, peptides and other metabolites such as neurotransmitters. Despite plethora of information available on transmembrane transporters, the possibility that transporters like all other enzymes studied to date display static and dynamic fluctuations in activity remains open. Importantly we currently ignore the impact such fluctuation have on the critical issue of pumping stoichiometry and therefore pumping efficiency. For example, several studies on P-type ATPases suggest substantially less amount of cations being transported to ATP hydrolyzed, possibly due to uncoupling of ATP-hydrolysis from cation transport during resting state.(1,2)Here, we present results from our ongoing investigation on time-resolved recording of single transporter events, using surface-based arrays of proteoliposomes.(3-5) Our single molecule studies have revealed fluctuations (on/off states) in the activity the P-type H+-ATPases-2 from Arabidopsis thaliana (AHA2). Insights from these on and off activity states for proton transporter will be used to estimate the true proton to ATP stoichiometry. Preliminary experiments were also performed to understand the role of the regulatory domain that is thought to be critical in coupling hydrolysis to proton coupling.(6)References:(1)Berman, M. C. Biochim. Biophys. Acta 2001, 1513, 95.(2)Venema, K. et al. J. Biol. Chem. 1995, 270, 19659.(3)Christensen, S. M. et al. Nat. Nanotechnol. 2012, 7, 51.(4)Hatzakis, N. S. et al. Nat. Chem. Biol. 2009, 5, 835.(5)Mathiasen, S. et. al. Nat. Methods 2014, 11, 931.(6)Pedersen, B. P. et al. Nature 2007, 450, 1111.

Previous studies have demonstrated an inverse relationship between plasma high density lipoproteins (HDL) cholesterol and coronary heart disease risk. In the present study we investigated prospectively the effect of a moderate physical conditioning programme on plasma lipids and lipoproteins, especially HDL-cholesterol and apolipoprotein A-I (apo A-I), the major apoprotein of HDL. Healthy, sedentary, middle-aged men were randomly selected and assigned either to a training group (n = 24, age 40 +/- 3.4, mean +/- SD) or to a control group (n = 13, age 39 +/- 5.0). Training consisted of various indoor and outdoor sports activities 45 min/day, 3 times/week for 12 weeks at an intensity of approximately 80% of measured maximal oxygen uptake (VO2 max). The trained subjects were studied at 4, 8 and 12 weeks. The training increased VO2 max by 12% (P less than 0.01). Increases were observed in both apo A-I (10%, P less than 0.02) and HDL-cholesterol (8%, P less than 0.02) after training, with significant increases already after 4 and 8 weeks, respectively. Furthermore, decreases in total plasma cholesterol (5%, P less than 0.004) and plasma triglycerides (26%, P less than 0.003) were found without changes in body weight, body composition, cigarette smoking, alcohol consumption or the percentage composition of dietary intake. Fasting serum-insulin concentrations decreased significantly during training. No changes were noted in the control group. The present study demonstrates prospectively that moderate physical training can increase HDL.

The aim of the “Engage2020 Project” 1 is to promote the use of engagement methods and policies that support societal engagement in research and innovation by mapping what is practiced and spreading awareness of the opportunities amongst researchers, policy makers, and other interested parties. The project is tasked with scanning existing policies and activities, structures, methods, approaches, tools and instruments, as well as highlighting promising new or adapted approaches for the future. This report includes results of the scanning process on current praxis of policies and activities that support societal engagement in research and innovation in Europe and beyond. Desktop research and interviews, done by all partners of the Engage2020 consortium, were the main methods used to collect data. Overall, information and data on around 200 policies and activities that support societal engagement in research and innovation activities was collected and documented in the form of factsheets. After further analysis and verification, 124 factsheets that form the basis for analysis in this report were selected. The report focuses on policies and activities that support the engagement of societal actors in research and innovation. Specifically, the following actors were considered: Civil Society Organizations (CSOs), citizens, affected populations, consumers, employees, users, and others. These can be engaged at one or more of the different levels of research and innovation process: policy formation, programme development, project definition and research and innovation activity. Furthermore, this engagement could take place in relation to one or more of the seven Grand Challenges identified by the European Commission: health and demographic change, food security and sustainable agriculture, clean and efficient energy, green transport, climate change and resource efficiency, inclusive and innovative societies, and security. Results show that there is developing support for societal engagement in research and innovation activities at all four levels of the research and innovation process. Moreover, we found that there is growing interest at the European Union level to engage citizens in research and innovation activities. A total of 46 cases at this level were reviewed. At the national level, our results show that societal engagement was more prevalent in the Western European countries than in the Central and Eastern European countries. At the international level, we found strong policy support for societal engagement in North America and Canada. Only a few such cases were found in Africa and Asia. We cannot claim to have exhausted all the available policies and activities that support the engagement of societal actors in research and innovation activities in Europe and beyond. However, the results showed that there are many good examples of policies and activities that support societal engagement. These could be used as building blocks to further support societal engagement throughout Europe. The results also showed that there are several gaps and barriers that need to be filled and addressed for societal engagement to achieve its intended outcomes. Several barriers to societal engagement such as lack of time and resources, training and skills, poor infrastructure, as well as lack of evaluation and an underdeveloped culture of engagement are also highlighted. These and other gaps in the research and innovation process have the potentials to interfere with the quality and quantity of engagement processes. Overall, we found that most of the examples given in this report could be used as a source of inspiration for those interested in developing or using supportive policies for societal engagement in research and innovation. Many policies and activities could support engagement at one or more levels of the research and innovation process and most could be used in stimulating engagement for any Grand Challenge related research or innovative activity. 1 http://engage2020.eu