Integrated assessments that aim to support sustainable natural resources management require analysing how biophysical systems are impacted by human actions. These analyses are often performed by ...modelling the physical system, while human actions are prescribed as scenarios and introduced into the physical models by varying the model input. To achieve a more thorough analysis of the human system component in participatory integrated assessments, we developed a semi-quantitative approach for actor-based modelling which focuses on modelling actions of societal actors based on their problem perceptions but also computes the resulting changes of physical system variables. Our approach is intended to support transdisciplinary research and identification of sustainable development options in problem fields with high levels of uncertainty or ignorance, together with the actors that are being modelled. Actor-based modelling is done using an enhanced version of the DANA software. DANA allows modelling the actors in a specific problem field by representing the perception of each actor by directed graphs, and by computing optimal actions from the perspective of each actor. These perception graphs are semi-quantitative causal maps, which can easily be discussed among stakeholders in a participatory process. DANA was extended to support, in addition to actor modelling, the other two steps in actor-based modelling, modelling of actions and modelling of factors. Modelling of actions refers to determining the actions of each actor under certain scenario assumptions, taking into account the diverse problem perceptions of the individual actors in the problem field, the action of the other actors and exogenous changes. Modelling of factors refers to calculating, in a semi-quantitative way, the resulting changes of physical variables (e.g. pollutant emissions), which may serve as input to physical models. We applied actor-based modelling in an integrated assessment of mobile organic xenobiotics in rivers. Our study shows that actor-based modelling allows generating scientifically better founded and more transparent scenarios of the drivers of change in integrated assessments, in particular because they are based on a structured analysis of the actors' problem perceptions.
► We developed a semi-quantitative approach for actor-based modelling. ► Our approach focuses on modelling actions of actors based on their problem perceptions. ► We applied the method in an integrated assessment of mobile organic xenobiotics. ► The method allows generating scientifically better founded and more transparent scenarios.
To determine the willingness of women with extremely dense breasts to undergo breast cancer screening with magnetic resonance imaging (MRI) in a research setting, and to examine reasons for women to ...participate or not.
Between 2011 and 2015, 8,061 women (50–75 years) were invited for supplemental MRI as part of the Dense Tissue and Early Breast Neoplasm Screening (DENSE) trial (ClinicalTrials.gov Identifier: NCT01315015), after a negative screening mammography in the national population-based mammography screening programme. Demographics of participants and non-participants were compared. All invitees were asked to report reasons for (non)participation. Ethical approval was obtained. Participants provided written informed consent.
Of the 8,061 invitees, 66% answered that they were interested, and 59% eventually participated. Participants were on average 54-years old (interquartile range: 51–59 years), comparable to women with extremely dense breasts in the population-based screening programme (55 years). Women with higher socio-economic status (SES) were more often interested in participation than women with lower SES (68% versus 59%, p<0.001). The most frequently stated reasons for non-participation were “MRI-related inconveniences and/or self-reported contraindications to MRI” (27%) and “anxiety regarding the result of supplemental screening” (21%). “Expected personal health benefit” (68%) and “contribution to science” (43%) were the most frequent reasons for participation.
Of women invited for MRI because of extremely dense breasts, 59% participated. Common reasons for non-participation were “MRI-related inconveniences” and “anxiety regarding the result of supplemental screening”. In case of future implementation, availability of precise evidence on benefits and harms might reduce this anxiety.
•59% of women with extremely dense breasts participate in supplemental MRI screening.•Most common reasons for non-participation were ‘MRI-related inconveniences’.•Anxiety for the extra screening result was also a common non-participation reason.•Addressing this anxiety might improve participation in supplemental screening.
The worldwide burden of malaria remains a major public health problem due, in part, to the lack of an effective vaccine against the Plasmodium falciparum parasite. An effective vaccine will most ...likely require the induction of antigen specific CD8(+) and CD4(+) T-cells as well as long-lasting antibody responses all working in concert to eliminate the infection. We report here the effective modification of a self-assembling protein nanoparticle (SAPN) vaccine previously proven effective in control of a P. berghei infection in a rodent model to now present B- and T-cell epitopes of the human malaria parasite P. falciparum in a platform capable of being used in human subjects.
To establish the basis for a SAPN-based vaccine, B- and CD8(+) T-cell epitopes from the P. falciparum circumsporozoite protein (PfCSP) and the universal CD4 T-helper epitope PADRE were engineered into a versatile small protein (∼125 amino acids) that self-assembles into a spherical nanoparticle repetitively displaying the selected epitopes. P. falciparum epitope specific immune responses were evaluated in mice using a transgenic P. berghei malaria parasite of mice expressing the human malaria full-length P. falciparum circumsporozoite protein (Tg-Pb/PfCSP). We show that SAPN constructs, delivered in saline, can induce high-titer, long-lasting (1 year) protective antibody and poly-functional (IFNγ(+), IL-2(+)) long-lived central memory CD8(+) T-cells. Furthermore, we demonstrated that these Ab or CD8(+) T-cells can independently provide sterile protection against a lethal challenge of the transgenic parasites.
The SAPN construct induces long-lasting antibody and cellular immune responses to epitope specific sequences of the P. falciparum circumsporozoite protein (PfCSP) and prevents infection in mice by a transgenic P. berghei parasite displaying the full length PfCSP.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Within this work we demonstrate the fabrication of silicon nanopillar arrays for advanced cell/surface interaction studies and the results of the bacterial interaction of Escherichia coli with such ...highly ordered nanostructures. By combination of Electron Beam Lithography and Reactive Ion Etching a powerful and highly precise method for the fabrication of nanopillars with different diameters in the sub 100 nm region and high aspect ratios is available. The fabrication method allows building highly ordered nanotopographies which can help to increase the understanding of cell/substrate interaction. The biological results indicate that the adhesion of E. coli correlates to the available discrete adhesion bond points on top of the pillars and additionally that the cells align with the nanostructures to maximize their contact to the surface. The research of such structures will lead to the development of novel materials which might reduce biomaterial associated infections.
The nature of ultrahigh-energy cosmic rays (UHECRs) at energies >1020 eV remains a mystery. They are likely to be of extragalactic origin, but should be absorbed within ∼50 Mpc through interactions ...with the cosmic microwave background. As there are no sufficiently powerful accelerators within this distance from the Galaxy, explanations for UHECRs range from unusual astrophysical sources to exotic string physics. Also unclear is whether UHECRs consist of protons, heavy nuclei, neutrinos or γ-rays. To resolve these questions, larger detectors with higher duty cycles and which combine multiple detection techniques are needed. Radio emission from UHECRs, on the other hand, is unaffected by attenuation, has a high duty cycle, gives calorimetric measurements and provides high directional accuracy. Here we report the detection of radio flashes from cosmic-ray air showers using low-cost digital radio receivers. We show that the radiation can be understood in terms of the geosynchrotron effect. Our results show that it should be possible to determine the nature and composition of UHECRs with combined radio and particle detectors, and to detect the ultrahigh-energy neutrinos expected from flavour mixing.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We report the first direct measurement of the overall characteristics of microwave radio emission from extensive air showers. Using a trigger provided by the KASCADE-Grande air shower array, the ...signals of the microwave antennas of the Cosmic-Ray Observation via Microwave Emission experiment have been read out and searched for signatures of radio emission by high-energy air showers in the GHz frequency range. Microwave signals have been detected for more than 30 showers with energies above 3×10^{16} eV. The observations presented in this Letter are consistent with a mainly forward-directed and polarized emission process in the GHz frequency range. The measurements show that microwave radiation offers a new means of studying air showers at E≥10^{17} eV.
Global-scale assessments of freshwater fluxes and storages by hydrological models under historic climate conditions are subject to a variety of uncertainties. Using the global hydrological model ...WaterGAP (Water - Global Assessment and Prognosis) 2.2, we investigated the sensitivity of simulated freshwater fluxes and water storage variations to five major sources of uncertainty: climate forcing, land cover input, model structure/refinements, consideration of human water use and calibration (or no calibration) against observed mean river discharge. In a modeling experiment, five variants of the standard version of WaterGAP 2.2 were generated that differed from the standard version only regarding the investigated source of uncertainty. The basin-specific calibration approach for WaterGAP was found to have the largest effect on grid cell fluxes as well as on global AET (actual evapotranspiration) and discharge into oceans for the period 1971-2000. Regarding grid cell fluxes, climate forcing ranks second before land cover input. Global water storage trends are most sensitive to model refinements (mainly modeling of groundwater depletion) and consideration of human water use. The best fit to observed time series of monthly river discharge or discharge seasonality is obtained with the standard WaterGAP 2.2 model version which is calibrated and driven by daily reanalysis-based WFD/WFDEI (combination of Watch Forcing Data based on ERA40 and Watch Forcing Data based on ERA-Interim) climate data. Discharge computed by a calibrated model version using monthly CRU TS (Climate Research Unit time-series) 3.2 and GPCC (Global Precipitation Climatology Center) v6 climate input reduced the fit to observed discharge for most stations. Taking into account uncertainties of climate and land cover data, global 1971-2000 discharge into oceans and inland sinks ranges between 40 000 and 42 000 km super(3) yr super(-1). Global actual evapotranspiration, with 70 000 km super(3) yr super(-1), is rather unaffected by climate and land cover uncertainties. Human water use reduced river discharge by 1000 km super(3) yr super(-1), such that global renewable water resources are estimated to range between 41 000 and 43 000 km super(3) yr super(-1). The climate data sets WFD (available until 2001) and WFDEI (starting in 1979) were found to be inconsistent with respect to shortwave radiation data, resulting in strongly different actual evapotranspiration. Global assessments of freshwater fluxes and storages would therefore benefit from the development of a global data set of consistent daily climate forcing from 1900 to present.
A composition analysis of KASCADE air shower data is performed by means of unfolding the two-dimensional frequency spectrum of electron and muon numbers. Aim of the analysis is the determination of ...energy spectra for elemental groups representing the chemical composition of primary cosmic rays. Since such an analysis depends crucially on simulations of air showers the two different hadronic interaction models QGSJet and SIBYLL are used for their generation. The resulting primary energy spectra show that the knee in the all particle spectrum is due to a steepening of the spectra of light elements but, also, that neither of the two simulation sets is able to describe the measured data consistently over the whole energy range with discrepancies appearing in different energy regions.
Changing the neoadjuvant chemotherapy regimen in insufficiently responding breast cancer is not a standard policy. We analysed a series of patients with 'luminal'-type breast cancer in whom the ...second half of neoadjuvant chemotherapy was selected based on the response to the first half.
Patients with oestrogen receptor-positive (ER+) human epidermal growth factor receptor 2-negative (HER2-) breast cancer received three courses of neoadjuvant dose-dense doxorubicin and cyclophosphamide (ddAC). Three further courses of ddAC were administered in case of a 'favourable response' on the interim magnetic resonance imaging (MRI) and a switch to docetaxel and capecitabine (DC) was made in case of an 'unfavourable response', using previously published response criteria. The efficacy of this approach was evaluated by tumour size reductions on serial contrast-enhanced MRI, pathologic response and relapse-free survival.
Two hundred and forty-six patients received three courses of ddAC. One hundred and sixty-four patients (67%) had a favourable response at the interim MRI, with a mean tumour size reduction of 31% after the first three courses and 34% after the second three courses. Patients with unfavourable responsive tumours had a mean tumour size reduction of 12% after three courses and received three courses of DC rather than ddAC. This led to a mean shrinkage of 27%.
The tumour size reduction of initially less responsive tumours after treatment adaptation adds further evidence that a response-adapted strategy may enhance the efficacy of neoadjuvant chemotherapy.
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