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Shared decision making (SDM) contributes to personalized decisions that fit patients’ preferences when choosing treatment for a condition. However, older adults often experience multiple chronic conditions (MCCs). Therefore, the implementation of SDM requires special characteristics. The aim of this thesis was to describe the development and evaluation of an intervention to improve SDM in older adults with MCC. Following the Medical Research Council framework for developing complex interventions, the SDMMCC intervention was developed step-wise. First, a literature review on barriers and facilitators for SDM and empirical research about older adults’ views and preferences on important health topics were conducted. Secondly, we developed the measuring instrument Observer OPTIONMCC for SDM with older adults with MCCs. Subsequently, in a co-creation process with end-users, we developed a training for geriatricians and a preparatory tool for older adults with MCCs and informal caregivers. After assessing feasibility, the intervention was implemented and evaluated in a pragmatic trial (N=216) in geriatric outpatient clinics of two Dutch hospitals. Finally, we studied the influence of personal characteristics of older adults, such as health literacy, anxiety and education in participation and outcomes of SDM. The SDMMCC intervention resulted in improvement in the discussion of a number of essential SDM topics, while other topics declined. The process evaluation showed clear indicators for how the intervention could be further improved to also result in effects on the reported outcomes of patients and caregivers. Tailoring SDM communication to health literacy levels is important for high-quality SDM communication and thus for better outcomes.

The International Geodynamics and Earth Tide Service (IGETS) was established in 2015 by the International Association of Geodesy. IGETS continues the activities of the Global Geodynamics Project (GGP) between 1997 and 2015 to provide support to geodetic and geophysical research activities using superconducting gravimeter (SG) data within the context of an international network. As part of this network, the Rustrel station (code RU) was established in 2015 thanks to the financial support of the EQUIPEX MIGA (Matter wave-laser based Interferometer Gravitation Antenna) ANR-11-EQPX-0028 and by the European FEDER 2006-2013 “PFM LSBB - Développement des qualités environnementales du LSBB”. Continuous time-varying gravity and atmospheric pressure data from RU are integrated in the IGETS data base hosted by ISDC (Information System and Data Centre) at GFZ. The operation and maintenance of the RU instrumentation is done by staff at EOST/IPG Strasbourg. The RU station is located about 500 m beneath the surface in the underground research laboratory of the LSBB (« Laboratoire Souterrain à Bas Bruit ») built in 1997. The LSBB is located within the Regional Natural Park of Luberon (longitude: 5.4837 E, latitude: 43.9411 N, height above MSL: 499.3 m). The LSBB gallery is located in the unsaturated zone of the Fontaine de Vaucluse karst hydrosystem. There is no industry around the site so the anthropogenic noise is very low. The time series of gravity and barometric pressure from iOSG-24 starts in October 2015 and is going on. The time sampling of the raw gravity and barometric pressure data of IGETS Level 1 is 1 minute. For a detailed description of the IGETS data base and the provided files see Voigt et al. (2016, https://doi.org/10.2312/GFZ.b103-16087).

Additional file 1. Flowchart of the inclusion.

Respiratory syncytial virus (RSV) causes acute respiratory tract infections in infants, the elderly and immunocompromised individuals. No licensed vaccine is available against RSV. We previously reported that intranasal immunization of rodents and lambs with a RSV vaccine candidate (ΔF/TriAdj) induces protective immunity with a good safety profile. ΔF/TriAdj promoted innate immune responses in respiratory mucosal tissues in vivo, by local chemokine and cytokine production, as well as infiltration and activation of immune cells including macrophages. The macrophage is an important cell type in context of both innate and adaptive immune responses against RSV. Therefore, we characterized the effects of ΔF/TriAdj on a murine macrophage cell line, RAW264.7, and bone marrow-derived macrophages (BMMs). A gene expression study of pattern recognition receptors (PRRs) revealed induction of endosomal and cytosolic receptors in RAW264.7 cells and BMMs by ΔF/TriAdj, but no up-regulation by ΔF in PBS. As a secondary response to the PRR gene expression, induction of several chemokines and pro-inflammatory cytokines, as well as up-regulation of MHC-II and co-stimulatory immune markers, was observed. To further investigate the mechanisms involved in ΔF/TriAdj-mediated secondary responses, we used relevant signal transduction pathway inhibitors. Based on inhibition studies at both transcript and protein levels, JNK, ERK1/2, CaMKII, PI3K and JAK pathways were clearly responsible for ΔF/TriAdj-mediated chemokine and pro-inflammatory cytokine responses, while the p38 and NF-κB pathways appeared to be not or minimally involved. ΔF/TriAdj induced IFN-β, which may participate in the JAK-STAT pathway to further amplify CXCL-10 production, which was strongly up-regulated. Blocking this pathway by a JAK inhibitor almost completely abrogated CXCL-10 production and caused a significant reduction in the cell surface expression of MHC-II and co-stimulatory immune markers. These data demonstrate that ΔF/TriAdj induces multiple signaling pathways in macrophages.

Objectives: For older persons with two or more chronic diseases (multiple chronic conditions) insight into what they perceive as important in their lives is essential when discussing preferences in the shared decision making process. The aims of this study were to 1) investigate the personal views on the ageing process communicated by older persons and 2) compare the personal views of older persons with and without multiple chronic conditions. Design: Using structured interviews participants were asked five questions about what they perceived as important in terms of ageing, worries, their future, healthy ageing and quality of life. Two independent researchers coded the data and performed content analyses. A stratified content analysis was performed to explore whether persons with and without multiple chronic conditions expressed different personal views with regard to the ageing process. Participants & setting: 547 community dwelling older persons aged 70 years and above. Results: The mean (SD) age was 78.9 (5.9) years, and 60.3% were female. Multiple chronic conditions were present in 72% of the study sample. There were no significant differences in demographic characteristics between persons with and without multiple chronic conditions . However persons with multiple chronic conditions more often had polypharmacy (43% vs 24%; p

CpG oligodeoxynucleotides (CpG ODNs) which can induce innate immune responses and promote adaptive immune responses, are powerful tools in defeating diseases. Here, a novel chitosan nanoparticle (CS-NPs) based on host-guest interaction has been designed for encapsulation and delivery of CpG ODNs for the first time. The CS-NPs exhibited high encapsulation efficiency (98.3%) of CpG ODNs and remained stable in storage under room temperature for at least 7 days. CS-NPs can also prevent CpG ODN diffusion at pH 7. The results of confocal laser scanning microscope images and flow cytometry show that CS-NPs can also be efficiently delivered into living cells. Furthermore, CpG@CS-NPs can increase the immunostimulatory activity of CpG ODNs. Raw 264.7 cells treated with CpG@CS-NPs demonstrated upregulation of both TNF-α and IL-6 cytokines by 13% and 40%, respectively. The newly developed CpG@CS-NPs were thus identified as an efficient system to deliver CpG-ODNs to treat various diseases.

Human parainfluenza virus type 3 (PIV3) is a major cause of lower respiratory disease i.e. bronchitis, bronchiolitis or pneumonia, in infants and young children. Presently there is no licensed vaccine against PIV3. To produce an effective subunit vaccine, a chimeric FHN glycoprotein consisting of the N-terminal ectodomain of the fusion (F) protein linked to the haemagglutinin-neuraminidase (HN) protein without transmembrane domain, and secreted forms of the individual F and HN glycoproteins, were expressed in mammalian cells and purified. Mice and cotton rats were immunized intramuscularly (IM) with FHN or both F and HN proteins (F + HN), formulated with poly(I:C) and an innate defense regulator peptide in polyphosphazene (TriAdj). Significantly higher levels of systemic virus-neutralizing antibodies were observed in mice and cotton rats immunized with FHN/TriAdj when compared to animals immunized with the combination of F and HN proteins (F + HN/TriAdj). As PIV3 is a pneumotropic virus, another goal is to produce an effective mucosal subunit vaccine. Intranasal (IN) administration with FHN/TriAdj resulted in mucosal IgA production in the lung and virus neutralizing antibodies in the sera. After PIV3 challenge no virus was detected in cotton rats immunized with FHN/TriAdj regardless of the route of delivery. Protective immunity against PIV3 was also induced by FHN/TriAdj in hamsters. In conclusion, the FHN protein formulated with TriAdj has potential for development of a safe and effective vaccine against PIV3.