Showing papers by "University of Lausanne published in 2022"

Partisan dealignment and the personalisation of politics in West European parliamentary democracies, 1961–2018

Abstract: Partisan dealignment is recurrently presented in the literature as one of the main drivers of the ‘personalisation of politics’. Yet, on the one hand, the claim that leader effects on voting behavi...

Post‑COVID‑19 Syndrome in Outpatients: a Cohort Study

Abstract: After mild COVID-19, some outpatients experience persistent symptoms. However, data are scarce and prospective studies are urgently needed.To characterize the post-COVID-19 syndrome after mild COVID-19 and identify predictors.Outpatients with symptoms suggestive of COVID-19 with (1) PCR-confirmed COVID-19 (COVID-positive) or (2) SARS-CoV-2 negative PCR (COVID-negative).Monocentric cohort study with prospective phone interview between more than 3 months to 10 months after initial visit to the emergency department and outpatient clinics.Data of the initial visits were extracted from the electronic medical file. Predefined persistent symptoms were assessed through a structured phone interview. Associations between long-term symptoms and PCR results, as well as predictors of persistent symptoms among COVID-positive, were evaluated by multivariate logistic regression adjusted for age, gender, smoking, comorbidities, and timing of the survey.The study population consisted of 418 COVID-positive and 89 COVID-negative patients, mostly young adults (median age of 41 versus 36 years in COVID-positive and COVID-negative, respectively; p = 0.020) and healthcare workers (67% versus 82%; p = 0.006). Median time between the initial visit and the phone survey was 150 days in COVID-positive and 242 days in COVID-negative patients. Persistent symptoms were reported by 223 (53%) COVID-positive and 33 (37%) COVID-negative patients (p = 0.006) and proportions were stable among the periods of the phone interviews. Overall, 21% COVID-positive and 15% COVID-negative patients (p = 0.182) attended care for this purpose. Four surveyed symptoms were independently associated with COVID-19: fatigue (adjusted odds ratio 2.14, 95% CI 1.04-4.41), smell/taste disorder (26.5, 3.46-202), dyspnea (2.81, 1.10-7.16), and memory impairment (5.71, 1.53-21.3). Among COVID-positive, female gender (1.67, 1.09-2.56) and overweight/obesity (1.67, 1.10-2.56) were predictors of persistent symptoms.More than half of COVID-positive outpatients report persistent symptoms up to 10 months after a mild disease. Only 4 of 14 symptoms were associated with COVID-19 status. The symptoms and predictors of the post-COVID-19 syndrome need further characterization as this condition places a significant burden on society.

Convergent consequences of parthenogenesis on stick insect genomes

Abstract: The shift from sexual reproduction to parthenogenesis has occurred repeatedly in animals, but how the loss of sex affects genome evolution remains poorly understood. We generated reference genomes for five independently evolved parthenogenetic species in the stick insect genus Timema and their closest sexual relatives. Using these references and population genomic data, we show that parthenogenesis results in an extreme reduction of heterozygosity and often leads to genetically uniform populations. We also find evidence for less effective positive selection in parthenogenetic species, suggesting that sex is ubiquitous in natural populations because it facilitates fast rates of adaptation. Parthenogenetic species did not show increased transposable element (TE) accumulation, likely because there is little TE activity in the genus. By using replicated sexual-parthenogenetic comparisons, our study reveals how the absence of sex affects genome evolution in natural populations, providing empirical support for the negative consequences of parthenogenesis as predicted by theory.

Restoring statistical validity in group analyses of motion‐corrupted <scp>MRI</scp> data

Abstract: Motion during the acquisition of magnetic resonance imaging (MRI) data degrades image quality, hindering our capacity to characterise disease in patient populations. Quality control procedures allow the exclusion of the most affected images from analysis. However, the criterion for exclusion is difficult to determine objectively and exclusion can lead to a suboptimal compromise between image quality and sample size. We provide an alternative, data-driven solution that assigns weights to each image, computed from an index of image quality using restricted maximum likelihood. We illustrate this method through the analysis of quantitative MRI data. The proposed method restores the validity of statistical tests, and performs near optimally in all brain regions, despite local effects of head motion. This method is amenable to the analysis of a broad type of MRI data and can accommodate any measure of image quality.

Long-range prediction and the stratosphere

Abstract: Abstract. Over recent years there have been concomitant advances in the development of stratosphere-resolving numerical models, our understanding of stratosphere–troposphere interaction, and the extension of long-range forecasts to explicitly include the stratosphere. These advances are now allowing for new and improved capability in long-range prediction. We present an overview of this development and show how the inclusion of the stratosphere in forecast systems aids monthly, seasonal, and annual-to-decadal climate predictions and multidecadal projections. We end with an outlook towards the future and identify areas of improvement that could further benefit these rapidly evolving predictions.

Activation of lactate receptor HCAR1 down-modulates neuronal activity in rodent and human brain tissue

Abstract: Lactate can be used by neurons as an energy substrate to support their activity. Evidence suggests that lactate also acts on a metabotropic receptor called HCAR1, first described in the adipose tissue. Whether HCAR1 also modulates neuronal circuits remains unclear. In this study, using qRT-PCR, we show that HCAR1 is present in the human brain of epileptic patients who underwent resective surgery. In brain slices from these patients, pharmacological HCAR1 activation using a non-metabolized agonist decreased the frequency of both spontaneous neuronal Ca2+ spiking and excitatory post-synaptic currents (sEPSCs). In mouse brains, we found HCAR1 expression in different regions using a fluorescent reporter mouse line and in situ hybridization. In the dentate gyrus, HCAR1 is mainly present in mossy cells, key players in the hippocampal excitatory circuitry and known to be involved in temporal lobe epilepsy. By using whole-cell patch clamp recordings in mouse and rat slices, we found that HCAR1 activation causes a decrease in excitability, sEPSCs, and miniature EPSCs frequency of granule cells, the main output of mossy cells. Overall, we propose that lactate can be considered a neuromodulator decreasing synaptic activity in human and rodent brains, which makes HCAR1 an attractive target for the treatment of epilepsy.

Cost-Minimization Analysis for Cardiac Revascularization in 12 Health Care Systems Based on the EuroCMR/SPINS Registries

Abstract: The aim of this study was to compare the costs of a noninvasive cardiac magnetic resonance (CMR)-guided strategy versus 2 invasive strategies with and without fractional flow reserve (FFR).Coronary artery disease (CAD) is a major contributor to the public health burden. Stress perfusion CMR has excellent accuracy to detect CAD. International guidelines recommend as a first step noninvasive testing of patients in stable condition with known or suspected CAD. However, nonadherence in routine clinical practice is high.In the EuroCMR (European Cardiovascular Magnetic Resonance) registry (n = 3,647, 59 centers, 18 countries) and the U.S.-based SPINS (Stress-CMR Perfusion Imaging in the United States) registry (n = 2,349, 13 centers, 11 states), costs were calculated for 12 health care systems (8 in Europe, the United States, 2 in Latin America, and 1 in Asia). Costs included diagnostic examinations (CMR and x-ray coronary angiography [CXA] with and without FFR), revascularizations, and complications during 1-year follow-up. Seven subgroup analyses covered low- to high-risk cohorts. Patients with ischemia-positive CMR underwent CXA and revascularization at the treating physician's discretion (CMR+CXA strategy). In the hypothetical invasive CXA+FFR strategy, costs were calculated for initial CXA and FFR in vessels with ≥50% stenoses, assuming the same proportion of revascularizations and complications as with the CMR+CXA strategy and FFR-positive rates as given in the published research. In the CXA-only strategy, costs included CXA and revascularizations of ≥50% stenoses.Consistent cost savings were observed for the CMR+CXA strategy compared with the CXA+FFR strategy in all 12 health care systems, ranging from 42% ± 20% and 52% ± 15% in low-risk EuroCMR and SPINS patients with atypical chest pain, respectively, to 31% ± 16% in high-risk SPINS patients with known CAD (P < 0.0001 vs 0 in all groups). Cost savings were even higher compared with CXA only, at 63% ± 11%, 73% ± 6%, and 52% ± 9%, respectively (P < 0.0001 vs 0 in all groups).In 12 health care systems, a CMR+CXA strategy yielded consistent moderate to high cost savings compared with a hypothetical CXA+FFR strategy over the entire spectrum of risk. Cost savings were consistently high compared with CXA only for all risk groups.

Pilot tone navigation for respiratory and cardiac motion-resolved free-running 5D flow MRI.

Abstract: PURPOSE: In this work, we integrated the pilot tone (PT) navigation system into a reconstruction framework for respiratory and cardiac motion-resolved 5D flow. We tested the hypotheses that PT would provide equivalent respiratory curves, cardiac triggers, and corresponding flow measurements to a previously established self-gating (SG) technique while being independent from changes to the acquisition parameters. METHODS: Fifteen volunteers and 9 patients were scanned with a free-running 5D flow sequence, with PT integrated. Respiratory curves and cardiac triggers from PT and SG were compared across all subjects. Flow measurements from 5D flow reconstructions using both PT and SG were compared to each other and to a reference electrocardiogram-gated and respiratory triggered 4D flow acquisition. Radial trajectories with variable readouts per interleave were also tested in 1 subject to compare cardiac trigger quality between PT and SG. RESULTS: The correlation between PT and SG respiratory curves were 0.95 ± 0.06 for volunteers and 0.95 ± 0.04 for patients. Heartbeat duration measurements in volunteers and patients showed a bias to electrocardiogram measurements of, respectively, 0.16 ± 64.94 ms and 0.01 ± 39.29 ms for PT versus electrocardiogram and of 0.24 ± 63.68 ms and 0.09 ± 32.79 ms for SG versus electrocardiogram. No significant differences were reported for the flow measurements between 5D flow PT and from 5D flow SG. A decrease in the cardiac triggering quality of SG was observed for increasing readouts per interleave, whereas PT quality remained constant. CONCLUSION: PT has been successfully integrated in 5D flow MRI and has shown equivalent results to the previously described 5D flow SG technique, while being completely acquisition-independent.

Navigating Critical Challenges Associated with Immunopeptidomics-Based Detection of Proteasomal Spliced Peptide Candidates

Abstract: Within the tumor immunology community, the topic of proteasomal spliced peptides (PSP) has generated a great deal of controversy. In the earliest reports, careful biological validation led to the conclusion that proteasome-catalyzed peptide splicing was a rare event. To date, six PSPs have been validated biologically. However, the advent of algorithms to identify candidate PSPs in mass spectrometry data challenged this notion, with several studies concluding that the frequency of spliced peptides binding to MHC class I was quite high. Since this time, much debate has centered around the methodologies used in these studies. Several reanalyses of data from these studies have led to questions about the validity of the conclusions. Furthermore, the biological and technical validation that should be necessary for verifying PSP assignments was often lacking. It has been suggested therefore that the research community should unite around a common set of standards for validating candidate PSPs. In this review, we propose and highlight the necessary steps for validation of proteasomal splicing at both the mass spectrometry and biological levels. We hope that these guidelines will serve as a foundation for critical assessment of results from proteasomal splicing studies.

Bedside formulation of a personalized multi-neoantigen vaccine against mammary carcinoma

Abstract: Harnessing the immune system to purposely recognize and destroy tumors represents a significant breakthrough in clinical oncology. Non-synonymous mutations (neoantigenic peptides) were identified as powerful cancer targets. This knowledge can be exploited for further improvements of active immunotherapies, including cancer vaccines, as T cells specific for neoantigens are not attenuated by immune tolerance mechanism and do not harm healthy tissues. The current study aimed at developing an optimized multitarget vaccine using short or long neoantigenic peptides utilizing virus-like particles (VLPs) as an efficient vaccine platform.Mutations of murine mammary carcinoma cells were identified by integrating mass spectrometry-based immunopeptidomics and whole exome sequencing. Neoantigenic peptides were synthesized and covalently linked to virus-like nanoparticles using a Cu-free click chemistry method for easy preparation of vaccines against mouse mammary carcinoma.As compared with short peptides, vaccination with long peptides was superior in the generation of neoantigen-specific CD4+ and CD8+ T cells, which readily produced interferon gamma (IFN-γ) and tumor-necrosis factor α (TNF-α). The resulting anti-tumor effect was associated with favorable immune re-polarization in the tumor microenvironment through reduction of myeloid-derived suppressor cells. Vaccination with long neoantigenic peptides also decreased post-surgical tumor recurrence and metastases, and prolonged mouse survival, despite the tumor's low mutational burden.Integrating mass spectrometry-based immunopeptidomics and whole exome sequencing is an efficient approach for identifying neoantigenic peptides. Our multitarget VLP-based vaccine shows a promising anti-tumor effect in an aggressive murine mammary carcinoma model. Future clinical application using this strategy is readily feasible and practical, as click chemistry coupling of personalized synthetic peptides to the nanoparticles can be done at the bedside directly before injection.

Sex‐ and age‐specific associations between cardiometabolic risk and white matter brain age in the <scp>UK</scp> Biobank cohort

Abstract: Cardiometabolic risk (CMR) factors are associated with accelerated brain aging and increased risk for sex-dimorphic illnesses such as Alzheimer's disease (AD). Yet, it is unknown how CMRs interact with sex and apolipoprotein E-ϵ4 (APOE4), a known genetic risk factor for AD, to influence brain age across different life stages. Using age prediction based on multi-shell diffusion-weighted imaging data in 21,308 UK Biobank participants, we investigated whether associations between white matter Brain Age Gap (BAG) and body mass index (BMI), waist-to-hip ratio (WHR), body fat percentage (BF%), and APOE4 status varied (i) between males and females, (ii) according to age at menopause in females, and (iii) across different age groups in males and females. We report sex differences in associations between BAG and all three CMRs, with stronger positive associations among males compared to females. Independent of APOE4 status, higher BAG (older brain age relative to chronological age) was associated with greater BMI, WHR, and BF% in males, whereas in females, higher BAG was associated with greater WHR, but not BMI and BF%. These divergent associations were most prominent within the oldest group of females (66–81 years), where greater BF% was linked to lower BAG. Earlier menopause transition was associated with higher BAG, but no interactions were found with CMRs. In conclusion, the findings point to sex- and age-specific associations between CMRs and brain age. Incorporating sex as a factor of interest in studies addressing CMR may promote sex-specific precision medicine, consequently improving health care for both males and females.

Empirical Evidence of Frequency‐Dependent Directivity Effects From Small‐To‐Moderate Normal Fault Earthquakes in Central Italy

Abstract: Rupture directivity and its potential frequency dependence is an open issue within the seismological community, especially for small-to-moderate events. Here, we provide a statistical overview based on empirical evidence of seismological observations, thanks to the large amount of high-quality seismic recordings (more than 30,000 waveforms) from Central Italy, which represents an excellent and almost unique natural laboratory of normal faulting earthquakes in the magnitude range between 3.4 and 6.5 within the time frame 2008–2018. In order to detect an anisotropic distribution of ground motion amplitudes due to the rupture directivity, we fit the smoothed Fourier Amplitude Spectra (FAS) cleared of source-, site- and path-effects. According to our criteria, about 36% of the analyzed events (162 out of 456) are directive and the distribution of rupture direction is aligned with the strikes of the major faults of the Central Apennines. We find that the directivity is a band-limited phenomenon whose width may extend up to five times the corner frequency. The results of this research provide useful insights to parameterize directivity, to be explicitly implemented in future ground motion modeling and scenario predictions.

High-resolution velocity estimation from surface-based common-offset GPR reflection data

Abstract: SUMMARY Surface-based common-offset ground-penetrating radar (GPR) reflection profiling is a popular geophysical exploration technique for obtaining high-resolution images of the shallow subsurface in a cost-effective manner. One drawback of this technique is that, without complementary borehole information in form of dielectric permittivity and/or porosity logs along the profile, it is currently not possible to obtain reliable estimates of the high-frequency electromagnetic velocity distribution of the probed subsurface region. This is problematic because adequate knowledge of the velocity is needed for accurate imaging and depth conversion of the data, as well as for quantifying the distribution of soil water content. To overcome this issue, we have developed a novel methodology for estimating the detailed subsurface velocity structure from common-offset GPR reflection measurements, which does not require additional conditioning information. The proposed approach combines two key components: diffraction analysis is used to infer the smooth, large-scale component of the velocity distribution, whereas the superimposed small-scale fluctuations are inferred via inversion of the reflected wavefield. We test and validate our method on two synthetic data sets having increasing degrees of complexity and realism before applying it to a field example from the Boise Hydrogeophysical Research Site, where independent control data in the form of neutron–neutron porosity logs are available for validation. The results obtained demonstrate the viability and robustness of the proposed approach. Further, due to its efficiency, both in terms of field effort and computational cost, the method can be readily extended to 3-D, which further enhances its attractiveness compared to multi-offset-based GPR velocity estimation techniques.

Photon-Counting Detector CT With Quantum Iterative Reconstruction

Abstract: Objectives To assess image noise, diagnostic performance, and potential for radiation dose reduction of photon-counting detector (PCD) computed tomography (CT) with quantum iterative reconstruction (QIR) in the detection of hypoattenuating and hyperattenuating focal liver lesions compared with energy-integrating detector (EID) CT. Materials and Methods A medium-sized anthropomorphic abdominal phantom with liver parenchyma and lesions (diameter, 5–10 mm; hypoattenuating and hyperattenuating from −30 HU to +90 HU at 120 kVp) was used. The phantom was imaged on (a) a third-generation dual-source EID-CT (SOMATOM Force, Siemens Healthineers) in the dual-energy mode at 100 and 150 kVp with tin filtration and (b) a clinical dual-source PCD-CT at 120 kVp (NAEOTOM Alpha, Siemens). Scans were repeated 10 times for each of 3 different radiation doses of 5, 2.5, and 1.25 mGy. Datasets were reconstructed as virtual monoenergetic images (VMIs) at 60 keV for both scanners and as linear-blended images (LBIs) for EID-CT. For PCD-CT, VMIs were reconstructed with different strength levels of QIR (QIR 1–4) and without QIR (QIR-off). For EID-CT, VMIs and LBIs were reconstructed using advanced modeled iterative reconstruction at a strength level of 3. Noise power spectrum was measured to compare image noise magnitude and texture. A channelized Hotelling model observer was used to assess diagnostic accuracy for lesion detection. The potential for radiation dose reduction using PCD-CT was estimated for the QIR strength level with the highest area under the curve compared with EID-CT for each radiation dose. Results Image noise decreased with increasing QIR level at all radiation doses. Using QIR-4, noise reduction was 41%, 45%, and 59% compared with EID-CT VMIs and 12%, 18%, and 33% compared with EID-CT LBIs at 5, 2.5, and 1.25 mGy, respectively. The peak spatial frequency shifted slightly to lower frequencies at higher QIR levels. Lesion detection accuracy increased at higher QIR levels and was higher for PCD-CT compared with EID-CT VMIs. The improvement in detection with PCD-CT was strongest at the lowest radiation dose, with an area under the receiver operating curve of 0.917 for QIR-4 versus 0.677 for EID-CT VMIs for hyperattenuating lesions, and 0.900 for QIR-4 versus 0.726 for EID-CT VMIs for hypoattenuating lesions. Compared with EID-CT LBIs, detection was higher for QIR 1–4 at 2.5 mGy and for QIR 2–4 at 1.25 mGy (eg, 0.900 for QIR-4 compared with 0.854 for EID-CT LBIs at 1.25 mGy). Radiation dose reduction potential of PCD-CT with QIR-4 was 54% at 5 mGy compared with VMIs and 39% at 2.5 mGy compared with LBIs. Conclusions Compared with EID-CT, PCD-CT with QIR substantially improved focal liver lesion detection, especially at low radiation dose. This enables substantial radiation dose reduction while maintaining diagnostic accuracy.

Pivotal role of O-antigenic polysaccharide display in the sensitivity against phage tail-like particles in environmental Pseudomonas kin competition

Abstract: Environmental pseudomonads colonize various niches including insect and plant environments. When invading these environments, bacteria are confronted with the resident microbiota. To oppose with closely related strains, they rely on narrow-spectrum weaponry such as tailocins, i.e., phage tail-like particles. Little is known about the receptors for these tailocins especially among phylogenetically closely related species. Here, we studied the interaction between an R-tailocin from Pseudomonas protegens CHA0 and a targeted kin, Pseudomonas protegens Pf-5. Using genome-wide transposon insertion sequencing, we identified that lipopolysaccharides are involved in the sensitivity of Pf-5 towards the tailocin of CHA0. By generating Pf-5 lipopolysaccharide mutants and exposing them to extracted tailocin, we specified the two O-antigenic polysaccharides (O-PS) targeted by the tailocin. We affirmed the role of these O-PS through competition assays in vitro as well as in insects. Further, we demonstrate that O-PS are double-edge swords that are responsible for the sensitivity of P. protegens towards tailocins and phages produced by their kin, but shield bacteria from the immune system of the insect. Our results shed light on the trade-off that bacteria are confronted with, where specific O-PS decorations can both be of benefit or disadvantage depending on the host environment and its bacterial inhabitants.

Assessing species coverage and assembly quality of rapidly accumulating sequenced genomes

Abstract: Ambitious initiatives to coordinate genome sequencing of Earth's biodiversity mean that the accumulation of genomic data is growing rapidly. In addition to cataloguing biodiversity, these data provide the basis for understanding biological function and evolution. Accurate and complete genome assemblies offer a comprehensive and reliable foundation upon which to advance our understanding of organismal biology at genetic, species, and ecosystem levels. However, ever-changing sequencing technologies and analysis methods mean that available data are often heterogeneous in quality. To guide forthcoming genome generation efforts and promote efficient prioritization of resources, it is thus essential to define and monitor taxonomic coverage and quality of the data.Here we present an automated analysis workflow that surveys genome assemblies from the United States NCBI, assesses their completeness using the relevant BUSCO datasets, and collates the results into an interactively browsable resource. We apply our workflow to produce a community resource of available assemblies from the phylum Arthropoda, the Arthropoda Assembly Assessment Catalogue. Using this resource, we survey current taxonomic coverage and assembly quality at the NCBI, examine how key assembly metrics relate to gene content completeness, and compare results from using different BUSCO lineage datasets.These results demonstrate how the workflow can be used to build a community resource that enables large-scale assessments to survey species coverage and data quality of available genome assemblies, and to guide prioritizations for ongoing and future sampling, sequencing, and genome generation initiatives.