When the reality of death strikes: Ways of dealing with existential fears in cancer patients.

In the present study existential fears and concerns in cancer patients were explored with respect to coping behavior and measures of subjective well-being. Thereby, cancer-related existential fears were assessed by means of a newly developed six-item scale. The study sample consisted of 126 patients undergoing ambulant treatment for different types of cancer. Data were collected at the University of Luxembourg, in cooperation with several medical centers and cancer foundations in Luxembourg, Germany and France. Results highlighted the importance of existential fears in cancer patients. Cluster analyses resulted in a two clustersolution, regrouping patients ‘‘high’’ and ‘‘low’’ levels of existential fears. Analyses of variance indicated that the cluster displaying high levels of existential fears showed significantly higher levels of ‘‘rumination’’ than the other cluster, associated with increased levels of ‘‘hopelessness’’ and lower ‘‘self-esteem’’. Results are discussed with respect to intervention programs focusing on the regulation of anxiety in cancer patients

Relating remotely sensed forest damage data to wind data: storms Lothar (1999) and Vivian (1990) in Switzerland

This study compares the surface wind speed and forest damage data of two exceptionally severe winter storms, Vivian 1990 and Lothar 1999. The study area comprises the region that suffered damage in Switzerland. The wind speed data were derived from simulations of MeteoSwiss (Federal Office of Meteorology and Climatology), measurements during the storm periods and expert analyses of the data. The remotely sensed forest damage data were provided by the Federal Office for the Environment and the forest cover data by Swiss Federal Statistical Office. We compared data on the peak gust and maximum average wind speed, with data on the spatially related forest area and forest damage area, and found some clear differences in the correlations between the different wind data and forest damage. Our results point generally to the damage-causing role of near-surface gusts at maximum wind speeds during the storm. These tended to be spatially distributed on a fine scale. In only a few cases were the results statistically significant. However, these results could probably be improved with better wind data. For example, gust measurements spatially closer to forests or simulations of gusts at maximum wind speed could be produced with a spatially higher resolutio

Social Isolation, Loneliness and Well-being in the Covid-19 Crisis: A Look at Nursing Home Residents in Luxembourg

During the COVID-19 crisis, older adults, in particular those with underlying health conditions, were at a special risk for severe illness and mortality, and efforts were made to shield them from exposure to the virus. While measures of physical distancing and reduction of in-person contacts were necessary to prevent contraction, they hit residents of care settings particularly hard since visits from family and friends were banned and the risk for loneliness and social isolation increased. In the present study, we therefore gave the voice to nursing home residents and focused on their perceived loneliness and subjective well-being during the crisis. We were both interested in difficulties but also in personal resources and resilience factors that might protect older adults from negative mental health outcomes and help to maintain subjective well-being. A sample of N = 76 residents in care homes in the Grand Duchy of Luxembourg were interviewed by use of a standardized questionnaire during July and August 2020. Participants reported on their loneliness and life satisfaction during the crisis, on their self-regulatory strategies as well as on personal and social resources (e.g. self-efficacy, generativity, social support). Data will be analyzed by use of regression analysis to predict loneliness and well-being by risk and protective factors. Results will be discussed applying a life-span developmental and systemic perspective to understand the mutual interplay of individual, social and institutional resources to mitigate negative side effects of protective measures on care home residents

Subjective age, worry and risk-related perceptions in older adults in times of a pandemic

During the Covid-19 pandemic, older people have been in the spotlight of the public debate. Given their higher risk of severe outcomes of the disease, they have been described as especially vulnerable and as a burden to others and society. We thus wanted to investigate how older people’s perception of their own age, that is their subjective age, as well as their Covid-19 related risks and worries were related during the pandemic and whether these relationships varied according to participants’ subjective health. We used data from the longitudinal CRISIS study which was conducted in the Grand-Duchy of Luxembourg in June and October 2020. Participants were aged 60–98 and responded on questionnaires regarding their subjective age, worry of falling ill with Covid-19, perceived risk of contracting the virus, perceived risk of falling seriously ill if they contracted Covid-19, as well as their subjective health and covariates. Three cross-lagged panel models were constructed to explore the longitudinal, bidirectional relationships between the variables. Cross-sectionally, a higher subjective age was related to more perceived risk of a serious course of disease. Longitudinally, subjective age and worry did not show any significant association over time, and neither did subjective age and perceived risk of contracting the virus. However, subjective health significantly moderated the relationship of worry and subjective age, showing different trajectories in the relationship depending on whether subjective health was good or bad. Higher perceived risk of falling seriously ill increased subjective age over time. Again, subjective health moderated this relationship: the perceived risk of falling seriously ill affected subjective age only for those with better subjective health. Our findings show the interactive relationship between subjective age and Covid-19 related cognitions and emotions and provide guidance for identifying older people that are most susceptible for negative age-related communication during the pandemic

Advanced fluorescence microscopy reveals disruption of dynamic CXCR4 dimerization by subpocket-specific inverse agonists

Funding: This research was funded by European Union’s Horizon2020 Marie Skłodowska-Curie Actions (MSCA) Program under Grant Agreement 641833 (ONCORNET) and European Cooperation in Science and Technology (COST) Action CA18133 European Research Network on Signal Transduction (ERNEST). A. Inoue was funded by the Leading Advanced Projects for Medical Innovation (LEAP) JP19gm0010004 from the Japan Agency for Medical Research and Development.Although class A G protein−coupled receptors (GPCRs) can function as monomers, many of them form dimers and oligomers, but the mechanisms and functional relevance of such oligomerization is ill understood. Here, we investigate this problem for the CXC chemokine receptor 4 (CXCR4), a GPCR that regulates immune and hematopoietic cell trafficking, and a major drug target in cancer therapy. We combine single-molecule microscopy and fluorescence fluctuation spectroscopy to investigate CXCR4 membrane organization in living cells at densities ranging from a few molecules to hundreds of molecules per square micrometer of the plasma membrane. We observe that CXCR4 forms dynamic, transient homodimers, and that the monomer−dimer equilibrium is governed by receptor density. CXCR4 inverse agonists that bind to the receptor minor pocket inhibit CXCR4 constitutive activity and abolish receptor dimerization. A mutation in the minor binding pocket reduced the dimer-disrupting ability of these ligands. In addition, mutating critical residues in the sixth transmembrane helix of CXCR4 markedly diminished both basal activity and dimerization, supporting the notion that CXCR4 basal activity is required for dimer formation. Together, these results link CXCR4 dimerization to its density and to its activity. They further suggest that inverse agonists binding to the minor pocket suppress both dimerization and constitutive activity and may represent a specific strategy to target CXCR4.Publisher PDFPeer reviewe

Negative Effect of Smoking on the Performance of the QuantiFERON TB Gold in Tube Test.

False negative and indeterminate Interferon Gamma Release Assay (IGRA) results are a well documented problem. Cigarette smoking is known to increase the risk of tuberculosis (TB) and to impair Interferon-gamma (IFN-γ) responses to antigenic challenge, but the impact of smoking on IGRA performance is not known. The aim of this study was to evaluate the effect of smoking on IGRA performance in TB patients in a low and high TB prevalence setting respectively. Patients with confirmed TB from Denmark (DK, n = 34; 20 smokers) and Tanzania (TZ, n = 172; 23 smokers) were tested with the QuantiFERON-TB Gold In tube (QFT). Median IFN-γ level in smokers and non smokers were compared and smoking was analysed as a risk factor for false negative and indeterminate QFT results. Smokers from both DK and TZ had lower IFN-γ antigen responses (median 0.9 vs. 4.2 IU/ml, p = 0.04 and 0.4 vs. 1.6, p < 0.01), less positive (50 vs. 86%, p = 0.03 and 48 vs. 75%, p < 0.01) and more false negative (45 vs. 0%, p < 0.01 and 26 vs. 11%, p = 0.04) QFT results. In Tanzanian patients, logistic regression analysis adjusted for sex, age, HIV and alcohol consumption showed an association of smoking with false negative (OR 17.1, CI: 3.0-99.1, p < 0.01) and indeterminate QFT results (OR 5.1, CI: 1.2-21.3, p = 0.02). Cigarette smoking was associated with false negative and indeterminate IGRA results in both a high and a low TB endemic setting independent of HIV status

Intercomparison of low- and high-resolution infrared spectrometers for ground-based solar remote sensing measurements of total column concentrations of CO2, CH4, and CO

The Total Carbon Column Observing Network (TCCON) is the baseline ground-based network of instruments that record solar absorption spectra from which accurate and precise column-averaged dry-air mole fractions of CO$_{2}$ (XCO$_{2}$), CH$_{4}$ (XCH$_{4}$), CO (XCO), and other gases are retrieved. The TCCON data have been widely used for carbon cycle science and validation of satellites measuring greenhouse gas concentrations globally. The number of stations in the network (currently about 25) is limited and has a very uneven geographical coverage: the stations in the Northern Hemisphere are distributed mostly in North America, Europe, and Japan, and only 20 % of the stations are located in the Southern Hemisphere, leaving gaps in the global coverage. A denser distribution of ground-based solar absorption measurements is needed to improve the representativeness of the measurement data for various atmospheric conditions (humid, dry, polluted, presence of aerosol), various surface conditions such as high albedo (>0.4) and very low albedo, and a larger latitudinal distribution. More stations in the Southern Hemisphere are also needed, but a further expansion of the network is limited by its costs and logistical requirements. For this reason, several groups are investigating supplemental portable low-cost instruments. The European Space Agency (ESA) funded campaign Fiducial Reference Measurements for Ground-Based Infrared Greenhouse Gas Observations (FRM4GHG) at the Sodankylä TCCON site in northern Finland aims to characterise the assessment of several low-cost portable instruments for precise solar absorption measurements of XCO$_{2}$, XCH$_{4}$, and XCO. The test instruments under investigation are three Fourier transform spectrometers (FTSs): a Bruker EM27/SUN, a Bruker IRcube, and a Bruker Vertex70, as well as a laser heterodyne spectroradiometer (LHR) developed by the UK Rutherford Appleton Laboratory. All four remote sensing instruments performed measurements simultaneously next to the reference TCCON instrument, a Bruker IFS 125HR, for a full year in 2017. The TCCON FTS was operated in its normal high-resolution mode (TCCON data set) and in a special low-resolution mode (HR125LR data set), similar to the portable spectrometers. The remote sensing measurements are complemented by regular AirCore launches performed from the same site. They provide in situ vertical profiles of the target gas concentrations as auxiliary reference data for the column retrievals, which are traceable to the WMO SI standards. The reference measurements performed with the Bruker IFS 125HR were found to be affected by non-linearity of the indium gallium arsenide (InGaAs) detector. Therefore, a non-linearity correction of the 125HR data was performed for the whole campaign period and compared with the test instruments and AirCore. The non-linearity-corrected data (TCCONmod data set) show a better match with the test instruments and AirCore data compared to the non-corrected reference data. The time series, the bias relative to the reference instrument and its scatter, and the seasonal and the day-to-day variations of the target gases are shown and discussed. The comparisons with the HR125LR data set gave a useful analysis of the resolution-dependent effects on the target gas retrieval. The solar zenith angle dependence of the retrievals is shown and discussed. The intercomparison results show that the LHR data have a large scatter and biases with a strong diurnal variation relative to the TCCON and other FTS instruments. The LHR is a new instrument under development, and these biases are currently being investigated and addressed. The campaign helped to characterise and identify instrumental biases and possibly retrieval biases, which are currently under investigation. Further improvements of the instrument are ongoing. The EM27/SUN, the IRcube, the modified Vertex70, and the HR125LR provided stable and precise measurements of the target gases during the campaign with quantified small biases. The bias dependence on the humidity along the measurement line of sight has been investigated and no dependence was found. These three portable low-resolution FTS instruments are suitable to be used for campaign deployment or long-term measurements from any site and offer the ability to complement the TCCON and expand the global coverage of ground-based reference measurements of the target gases

Intercomparison of low- and high-resolution infrared spectrometers for ground-based solar remote sensing measurements of total column concentrations of CO2, CH4, and CO

The Total Carbon Column Observing Network (TCCON) is the baseline ground-based network of instruments that record solar absorption spectra from which accurate and precise column-averaged dry-air mole fractions of CO$_{2}$ (XCO$_{2}$), CH$_{4}$ (XCH$_{4}$), CO (XCO), and other gases are retrieved. The TCCON data have been widely used for carbon cycle science and validation of satellites measuring greenhouse gas concentrations globally. The number of stations in the network (currently about 25) is limited and has a very uneven geographical coverage: the stations in the Northern Hemisphere are distributed mostly in North America, Europe, and Japan, and only 20 % of the stations are located in the Southern Hemisphere, leaving gaps in the global coverage. A denser distribution of ground-based solar absorption measurements is needed to improve the representativeness of the measurement data for various atmospheric conditions (humid, dry, polluted, presence of aerosol), various surface conditions such as high albedo (>0.4) and very low albedo, and a larger latitudinal distribution. More stations in the Southern Hemisphere are also needed, but a further expansion of the network is limited by its costs and logistical requirements. For this reason, several groups are investigating supplemental portable low-cost instruments. The European Space Agency (ESA) funded campaign Fiducial Reference Measurements for Ground-Based Infrared Greenhouse Gas Observations (FRM4GHG) at the Sodankylä TCCON site in northern Finland aims to characterise the assessment of several low-cost portable instruments for precise solar absorption measurements of XCO$_{2}$, XCH$_{4}$, and XCO. The test instruments under investigation are three Fourier transform spectrometers (FTSs): a Bruker EM27/SUN, a Bruker IRcube, and a Bruker Vertex70, as well as a laser heterodyne spectroradiometer (LHR) developed by the UK Rutherford Appleton Laboratory. All four remote sensing instruments performed measurements simultaneously next to the reference TCCON instrument, a Bruker IFS 125HR, for a full year in 2017. The TCCON FTS was operated in its normal high-resolution mode (TCCON data set) and in a special low-resolution mode (HR125LR data set), similar to the portable spectrometers. The remote sensing measurements are complemented by regular AirCore launches performed from the same site. They provide in situ vertical profiles of the target gas concentrations as auxiliary reference data for the column retrievals, which are traceable to the WMO SI standards. The reference measurements performed with the Bruker IFS 125HR were found to be affected by non-linearity of the indium gallium arsenide (InGaAs) detector. Therefore, a non-linearity correction of the 125HR data was performed for the whole campaign period and compared with the test instruments and AirCore. The non-linearity-corrected data (TCCONmod data set) show a better match with the test instruments and AirCore data compared to the non-corrected reference data. The time series, the bias relative to the reference instrument and its scatter, and the seasonal and the day-to-day variations of the target gases are shown and discussed. The comparisons with the HR125LR data set gave a useful analysis of the resolution-dependent effects on the target gas retrieval. The solar zenith angle dependence of the retrievals is shown and discussed. The intercomparison results show that the LHR data have a large scatter and biases with a strong diurnal variation relative to the TCCON and other FTS instruments. The LHR is a new instrument under development, and these biases are currently being investigated and addressed. The campaign helped to characterise and identify instrumental biases and possibly retrieval biases, which are currently under investigation. Further improvements of the instrument are ongoing. The EM27/SUN, the IRcube, the modified Vertex70, and the HR125LR provided stable and precise measurements of the target gases during the campaign with quantified small biases. The bias dependence on the humidity along the measurement line of sight has been investigated and no dependence was found. These three portable low-resolution FTS instruments are suitable to be used for campaign deployment or long-term measurements from any site and offer the ability to complement the TCCON and expand the global coverage of ground-based reference measurements of the target gases

Mechanisms Involved in Alleviation of Intestinal Inflammation by Bifidobacterium Breve Soluble Factors

Objectives: Soluble factors released by Bifidobacterium breve C50 (Bb) alleviate the secretion of pro-inflammatory cytokines by immune cells, but their effect on intestinal epithelium remains elusive. To decipher the mechanisms accounting for the cross-talk between bacteria/soluble factors and intestinal epithelium, we measured the capacity of the bacteria, its conditioned medium (Bb-CM) and other Gram(+) commensal bacteria to dampen inflammatory chemokine secretion. Methods: TNFa-induced chemokine (CXCL8) secretion and alteration of NF-kB and AP-1 signalling pathways by Bb were studied by EMSA, confocal microscopy and western blotting. Anti-inflammatory capacity was also tested in vivo in a model of TNBS-induced colitis in mice. Results: Bb and Bb-CM, but not other commensal bacteria, induced a time and dose-dependent inhibition of CXCL8 secretion by epithelial cells driven by both AP-1 and NF-kB transcription pathways and implying decreased phosphorylation of p38-MAPK and IkB-a molecules. In TNBS-induced colitis in mice, Bb-CM decreased the colitis score and inflammatory cytokine expression, an effect reproduced by dendritic cell conditioning with Bb-CM. Conclusions: Bb and secreted soluble factors contribute positively to intestinal homeostasis by attenuating chemokine production. The results indicate that Bb down regulate inflammation at the epithelial level by inhibiting phosphorylation