2,599 results on '"Jan Albert"'
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2. Bootstrapping pions at large N. Part II. Background gauge fields and the chiral anomaly
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Jan Albert and Leonardo Rastelli
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1/N Expansion ,Anomalies in Field and String Theories ,Scattering Amplitudes ,Chiral Lagrangian ,Nuclear and particle physics. Atomic energy. Radioactivity ,QC770-798 - Abstract
Abstract We continue the program [1] of carving out the space of large N confining gauge theories by modern S-matrix bootstrap methods, with the ultimate goal of cornering large N QCD. In this paper, we focus on the effective field theory of massless pions coupled to background electromagnetic fields. We derive the full set of positivity constraints encoded in the system of 2 → 2 scattering amplitudes of pions and photons. This system probes a larger set of intermediate meson states, and is thus sensitive to intricate large N selection rules, especially when supplemented with expectations from Regge theory. It also has access to the coefficient of the chiral anomaly. We find novel numerical bounds on several ratios of Wilson coefficients, in units of the rho mass. By matching the chiral anomaly with the microscopic theory, we also derive bounds that contain an explicit N dependence.
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- 2024
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3. Delayed generation of functional virus-specific circulating T follicular helper cells correlates with severe COVID-19
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Meng Yu, Afandi Charles, Alberto Cagigi, Wanda Christ, Björn Österberg, Sara Falck-Jones, Lida Azizmohammadi, Eric Åhlberg, Ryan Falck-Jones, Julia Svensson, Mu Nie, Anna Warnqvist, Fredrika Hellgren, Klara Lenart, Rodrigo Arcoverde Cerveira, Sebastian Ols, Gustaf Lindgren, Ang Lin, Holden Maecker, Max Bell, Niclas Johansson, Jan Albert, Christopher Sundling, Paulo Czarnewski, Jonas Klingström, Anna Färnert, Karin Loré, and Anna Smed-Sörensen
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Science - Abstract
Abstract Effective humoral immune responses require well-orchestrated B and T follicular helper (Tfh) cell interactions. Whether these interactions are impaired and associated with COVID-19 disease severity is unclear. Here, longitudinal blood samples across COVID-19 disease severity are analysed. We find that during acute infection SARS-CoV-2-specific circulating Tfh (cTfh) cells expand with disease severity. SARS-CoV-2-specific cTfh cell frequencies correlate with plasmablast frequencies and SARS-CoV-2 antibody titers, avidity and neutralization. Furthermore, cTfh cells but not other memory CD4 T cells, from severe patients better induce plasmablast differentiation and antibody production compared to cTfh cells from mild patients. However, virus-specific cTfh cell development is delayed in patients that display or later develop severe disease compared to those with mild disease, which correlates with delayed induction of high-avidity neutralizing antibodies. Our study suggests that impaired generation of functional virus-specific cTfh cells delays high-quality antibody production at an early stage, potentially enabling progression to severe disease.
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- 2023
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4. Endovascular repair of a ruptured, extremely tortuous, descending thoracic aorta aneurysm with aortic coarctation
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Marieke Hoogewerf, MD, Martijn W.A. van Geldorp, MD, PhD, Joep G.F. Scholten, MD, Jan Albert Vos, MD, PhD, and Robin H. Heijmen, MD, PhD
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Aortic coarctation ,Descending thoracic aortic aneurysm ,Endovascular repair ,TEVAR ,Tortuosity ,Surgery ,RD1-811 ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
We have presented a case of a ruptured descending aortic aneurysm that was accompanied by extreme tortuosity and a pseudocoarctation at the level of the ligamentum arteriosum. We performed successful endovascular repair, covering the left subclavian artery, using a transapical-to-femoral artery (through-and-through) guidewire technique to overcome the tortuosity, with the option to perform balloon angioplasty in the case of an increased gradient over the coarctation. In the present case report, we have underlined the role of close collaborations with aortic expertise centers.
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- 2022
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5. Bootstrapping pions at large N
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Jan Albert and Leonardo Rastelli
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1/N Expansion ,Effective Field Theories ,Chiral Lagrangian ,Nuclear and particle physics. Atomic energy. Radioactivity ,QC770-798 - Abstract
Abstract We revisit from a modern bootstrap perspective the longstanding problem of solving QCD in the large N limit. We derive universal bounds on the effective field theory of massless pions by imposing the full set of positivity constraints that follow from 2 → 2 scattering. Some features of our exclusion plots have intriguing connections with hadronic phenomenology. The exclusion boundary exhibits a sharp kink, raising the tantalizing scenario that large N QCD may sit at this kink. We critically examine this possibility, developing in the process a partial analytic understanding of the geometry of the bounds.
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- 2022
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6. Human influenza virus infection elicits distinct patterns of monocyte and dendritic cell mobilization in blood and the nasopharynx
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Sindhu Vangeti, Sara Falck-Jones, Meng Yu, Björn Österberg, Sang Liu, Muhammad Asghar, Klara Sondén, Clare Paterson, Penn Whitley, Jan Albert, Niclas Johansson, Anna Färnert, and Anna Smed-Sörensen
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influenza A virus ,nasopharynx ,dendritic cells ,intermediate monocytes ,TNF ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
During respiratory viral infections, the precise roles of monocytes and dendritic cells (DCs) in the nasopharynx in limiting infection and influencing disease severity are incompletely described. We studied circulating and nasopharyngeal monocytes and DCs in healthy controls (HCs) and in patients with mild to moderate infections (primarily influenza A virus [IAV]). As compared to HCs, patients with acute IAV infection displayed reduced DC but increased intermediate monocytes frequencies in blood, and an accumulation of most monocyte and DC subsets in the nasopharynx. IAV patients had more mature monocytes and DCs in the nasopharynx, and higher levels of TNFα, IL-6, and IFNα in plasma and the nasopharynx than HCs. In blood, monocytes were the most frequent cellular source of TNFα during IAV infection and remained responsive to additional stimulation with TLR7/8L. Immune responses in older patients skewed towards increased monocyte frequencies rather than DCs, suggesting a contributory role for monocytes in disease severity. In patients with other respiratory virus infections, we observed changes in monocyte and DC frequencies in the nasopharynx distinct from IAV patients, while differences in blood were more similar across infection groups. Using SomaScan, a high-throughput aptamer-based assay to study proteomic changes between patients and HCs, we found differential expression of innate immunity-related proteins in plasma and nasopharyngeal secretions of IAV and SARS-CoV-2 patients. Together, our findings demonstrate tissue-specific and pathogen-specific patterns of monocyte and DC function during human respiratory viral infections and highlight the importance of comparative investigations in blood and the nasopharynx.
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- 2023
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7. The Abrikosov vortex in curved space
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Jan Albert
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Solitons Monopoles and Instantons ,Black Holes ,AdS-CFT Correspondence ,Nuclear and particle physics. Atomic energy. Radioactivity ,QC770-798 - Abstract
Abstract We study the self-gravitating Abrikosov vortex in curved space with and with-out a (negative) cosmological constant, considering both singular and non-singular solutions with an eye to hairy black holes. In the asymptotically flat case, we find that non-singular vortices round off the singularity of the point particle’s metric in 3 dimensions, whereas singular solutions consist of vortices holding a conical singularity at their core. There are no black hole vortex solutions. In the asymptotically AdS case, in addition to these solutions there exist singular solutions containing a BTZ black hole, but they are always hairless. So we find that in contrast with 4-dimensional ’t Hooft-Polyakov monopoles, which can be regarded as their higher-dimensional analogues, Abrikosov vortices cannot hold a black hole at their core. We also describe the implications of these results in the context of AdS/CFT and propose an interpretation for their CFT dual along the lines of the holographic superconductor.
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- 2021
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8. Combining biomarker and virus phylogenetic models improves HIV-1 epidemiological source identification.
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Erik Lundgren, Ethan Romero-Severson, Jan Albert, and Thomas Leitner
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Biology (General) ,QH301-705.5 - Abstract
To identify and stop active HIV transmission chains new epidemiological techniques are needed. Here, we describe the development of a multi-biomarker augmentation to phylogenetic inference of the underlying transmission history in a local population. HIV biomarkers are measurable biological quantities that have some relationship to the amount of time someone has been infected with HIV. To train our model, we used five biomarkers based on real data from serological assays, HIV sequence data, and target cell counts in longitudinally followed, untreated patients with known infection times. The biomarkers were modeled with a mixed effects framework to allow for patient specific variation and general trends, and fit to patient data using Markov Chain Monte Carlo (MCMC) methods. Subsequently, the density of the unobserved infection time conditional on observed biomarkers were obtained by integrating out the random effects from the model fit. This probabilistic information about infection times was incorporated into the likelihood function for the transmission history and phylogenetic tree reconstruction, informed by the HIV sequence data. To critically test our methodology, we developed a coalescent-based simulation framework that generates phylogenies and biomarkers given a specific or general transmission history. Testing on many epidemiological scenarios showed that biomarker augmented phylogenetics can reach 90% accuracy under idealized situations. Under realistic within-host HIV-1 evolution, involving substantial within-host diversification and frequent transmission of multiple lineages, the average accuracy was at about 50% in transmission clusters involving 5-50 hosts. Realistic biomarker data added on average 16 percentage points over using the phylogeny alone. Using more biomarkers improved the performance. Shorter temporal spacing between transmission events and increased transmission heterogeneity reduced reconstruction accuracy, but larger clusters were not harder to get right. More sequence data per infected host also improved accuracy. We show that the method is robust to incomplete sampling and that adding biomarkers improves reconstructions of real HIV-1 transmission histories. The technology presented here could allow for better prevention programs by providing data for locally informed and tailored strategies.
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- 2022
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9. Molecular Epidemiology and Evolutionary Trajectory of Emerging Echovirus 30, Europe
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Kimberley S.M. Benschop, Eeva K. Broberg, Emma Hodcroft, Dennis Schmitz, Jan Albert, Anda Baicus, Jean-Luc Bailly, Gudrun Baldvinsdottir, Natasa Berginc, Soile Blomqvist, Sindy Böttcher, Mia Brytting, Erika Bujaki, Maria Cabrerizo, Cristina Celma, Ondrej Cinek, Eric C.J. Claas, Jeroen Cremer, Jonathan Dean, Jennifer L. Dembinski, Iryna Demchyshyna, Sabine Diedrich, Susanne Dudman, Jake Dunning, Robert Dyrdak, Mary Emmanouil, Agnes Farkas, Cillian De Gascun, Guillaume Fournier, Irina Georgieva, Ruben Gonzalez-Sanz, Jolanda van Hooydonk-Elving, Anne J. Jääskeläinen, Ruta Jancauskaite, Kathrin Keeren, Thea K. Fischer, Sidsel Krokstad, Lubomira Nikolaeva–Glomb, Ludmila Novakova, Sofie E. Midgley, Audrey Mirand, Richard Molenkamp, Ursula Morley, Joël Mossong, Svajune Muralyte, Jean-Luc Murk, Trung Nguyen, Svein A. Nordbø, Riikka Österback, Suzan Pas, Laura Pellegrinelli, Vassiliki Pogka, Birgit Prochazka, Petra Rainetova, Marc Van Ranst, Lieuwe Roorda, Isabelle Schuffenecker, Rob Schuurman, Asya Stoyanova, Kate Templeton, Jaco J. Verweij, Androniki Voulgari-Kokota, Tytti Vuorinen, Elke Wollants, Katja C. Wolthers, Katherina Zakikhany, Richard Neher, Heli Harvala, and Peter Simmonds
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Molecular epidemiology ,evolutionary trajectory ,epidemiological monitoring ,whole-genome sequencing ,genetic recombination ,neurological manifestations ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
In 2018, an upsurge in echovirus 30 (E30) infections was reported in Europe. We conducted a large-scale epidemiologic and evolutionary study of 1,329 E30 strains collected in 22 countries in Europe during 2016–2018. Most E30 cases affected persons 0–4 years of age (29%) and 25–34 years of age (27%). Sequences were divided into 6 genetic clades (G1–G6). Most (53%) sequences belonged to G1, followed by G6 (23%), G2 (17%), G4 (4%), G3 (0.3%), and G5 (0.2%). Each clade encompassed unique individual recombinant forms; G1 and G4 displayed >2 unique recombinant forms. Rapid turnover of new clades and recombinant forms occurred over time. Clades G1 and G6 dominated in 2018, suggesting the E30 upsurge was caused by emergence of 2 distinct clades circulating in Europe. Investigation into the mechanisms behind the rapid turnover of E30 is crucial for clarifying the epidemiology and evolution of these enterovirus infections.
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- 2021
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10. The Effect of a Future-Self Avatar Mobile Health Intervention (FutureMe) on Physical Activity and Food Purchases: Randomized Controlled Trial
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Annette Mönninghoff, Klaus Fuchs, Jing Wu, Jan Albert, and Simon Mayer
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Computer applications to medicine. Medical informatics ,R858-859.7 ,Public aspects of medicine ,RA1-1270 - Abstract
BackgroundInsufficient physical activity and unhealthy diets are contributing to the rise in noncommunicable diseases. Preventative mobile health (mHealth) interventions may help reverse this trend, but present bias might reduce their effectiveness. Future-self avatar interventions have resulted in behavior change in related fields, yet evidence of whether such interventions can change health behavior is lacking. ObjectiveWe aimed to investigate the impact of a future-self avatar mHealth intervention on physical activity and food purchasing behavior and examine the feasibility of a novel automated nutrition tracking system. We also aimed to understand how this intervention impacts related attitudinal and motivational constructs. MethodsWe conducted a 12-week parallel randomized controlled trial (RCT), followed by semistructured interviews. German-speaking smartphone users aged ≥18 years living in Switzerland and using at least one of the two leading Swiss grocery loyalty cards, were recruited for the trial. Data were collected from November 2020 to April 2021. The intervention group received the FutureMe intervention, a physical activity and food purchase tracking mobile phone app that uses a future-self avatar as the primary interface and provides participants with personalized food basket analysis and shopping tips. The control group received a conventional text- and graphic-based primary interface intervention. We pioneered a novel system to track nutrition by leveraging digital receipts from loyalty card data and analyzing food purchases in a fully automated way. Data were consolidated in 4-week intervals, and nonparametric tests were conducted to test for within- and between-group differences. ResultsWe recruited 167 participants, and 95 eligible participants were randomized into either the intervention (n=42) or control group (n=53). The median age was 44 years (IQR 19), and the gender ratio was balanced (female 52/95, 55%). Attrition was unexpectedly high with only 30 participants completing the intervention, negatively impacting the statistical power. The FutureMe intervention led to small statistically insignificant increases in physical activity (median +242 steps/day) and small insignificant improvements in the nutritional quality of food purchases (median −1.28 British Food Standards Agency Nutrient Profiling System Dietary Index points) at the end of the intervention. Intrinsic motivation significantly increased (P=.03) in the FutureMe group, but decreased in the control group. Outcome expectancy directionally increased in the FutureMe group, but decreased in the control group. Leveraging loyalty card data to track the nutritional quality of food purchases was found to be a feasible and accepted fully automated nutrition tracking system. ConclusionsPreventative future-self avatar mHealth interventions promise to encourage improvements in physical activity and food purchasing behavior in healthy population groups. A full-powered RCT is needed to confirm this preliminary evidence and to investigate how future-self avatars might be modified to reduce attrition, overcome present bias, and promote sustainable behavior change. Trial RegistrationClinicalTrials.gov NCT04505124; https://clinicaltrials.gov/ct2/show/NCT04505124
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- 2022
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11. A novel role for GalNAc-T2 dependent glycosylation in energy homeostasis
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Cristy R.C. Verzijl, Federico Oldoni, Natalia Loaiza, Justina C. Wolters, Antoine Rimbert, E. Tian, Weiming Yang, Dicky Struik, Marieke Smit, Niels J. Kloosterhuis, Amy J. Fernandez, Nadine L. Samara, Kelly G. Ten Hagen, Kruti Dalal, Aliona Chernish, Peggy McCluggage, Lawrence A. Tabak, Johan W. Jonker, and Jan Albert Kuivenhoven
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Glycosylation ,Genetic disorder ,Energy metabolism ,Adipose tissue ,Insulin signaling ,Internal medicine ,RC31-1245 - Abstract
Objective: GALNT2, encoding polypeptide N-acetylgalactosaminyltransferase 2 (GalNAc-T2), was initially discovered as a regulator of high-density lipoprotein metabolism. GalNAc-T2 is known to exert these effects through post-translational modification, i.e., O-linked glycosylation of secreted proteins with established roles in plasma lipid metabolism. It has recently become clear that loss of GALNT2 in rodents, cattle, nonhuman primates, and humans should be regarded as a novel congenital disorder of glycosylation that affects development and body weight. The role of GALNT2 in metabolic abnormalities other than plasma lipids, including insulin sensitivity and energy homeostasis, is poorly understood. Methods: GWAS data from the UK Biobank was used to study variation in the GALNT2 locus beyond changes in high-density lipoprotein metabolism. Experimental data were obtained through studies in Galnt2−/− mice and wild-type littermates on both control and high-fat diet. Results: First, we uncovered associations between GALNT2 gene variation, adiposity, and body mass index in humans. In mice, we identify the insulin receptor as a novel substrate of GalNAc-T2 and demonstrate that Galnt2−/− mice exhibit decreased adiposity, alterations in insulin signaling and a shift in energy substrate utilization in the inactive phase. Conclusions: This study identifies a novel role for GALNT2 in energy homeostasis, and our findings suggest that the local effects of GalNAc-T2 are mediated through posttranslational modification of the insulin receptor.
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- 2022
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12. Evolution, geographic spreading, and demographic distribution of Enterovirus D68.
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Emma B Hodcroft, Robert Dyrdak, Cristina Andrés, Adrian Egli, Josiane Reist, Diego García Martínez de Artola, Julia Alcoba-Flórez, Hubert G M Niesters, Andrés Antón, Randy Poelman, Marijke Reynders, Elke Wollants, Richard A Neher, and Jan Albert
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Immunologic diseases. Allergy ,RC581-607 ,Biology (General) ,QH301-705.5 - Abstract
Worldwide outbreaks of enterovirus D68 (EV-D68) in 2014 and 2016 have caused serious respiratory and neurological disease. We collected samples from several European countries during the 2018 outbreak and determined 53 near full-length genome ('whole genome') sequences. These sequences were combined with 718 whole genome and 1,987 VP1-gene publicly available sequences. In 2018, circulating strains clustered into multiple subgroups in the B3 and A2 subclades, with different phylogenetic origins. Clusters in subclade B3 emerged from strains circulating primarily in the US and Europe in 2016, though some had deeper roots linking to Asian strains, while clusters in A2 traced back to strains detected in East Asia in 2015-2016. In 2018, all sequences from the USA formed a distinct subgroup, containing only three non-US samples. Alongside the varied origins of seasonal strains, we found that diversification of these variants begins up to 18 months prior to the first diagnostic detection during a EV-D68 season. EV-D68 displays strong signs of continuous antigenic evolution and all 2018 A2 strains had novel patterns in the putative neutralizing epitopes in the BC- and DE-loops. The pattern in the BC-loop of the USA B3 subgroup had not been detected on that continent before. Patients with EV-D68 in subclade A2 were significantly older than patients with a B3 subclade virus. In contrast to other subclades, the age distribution of A2 is distinctly bimodal and was found primarily among children and in the elderly. We hypothesize that EV-D68's rapid evolution of surface proteins, extensive diversity, and high rate of geographic mixing could be explained by substantial reinfection of adults. Better understanding of evolution and immunity across diverse viral pathogens, including EV-D68 and SARS-CoV-2, is critical to pandemic preparedness in the future.
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- 2022
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13. Replication in Human Intestinal Enteroids of Infectious Norovirus from Vomit Samples
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Marie Hagbom, Jenny Lin, Tina Falkeborn, Lena Serrander, Jan Albert, Johan Nordgren, and Sumit Sharma
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norovirus ,infectivity ,vomit ,human intestinal enteroids ,Norwalk virus ,viruses ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
A typical clinical symptom of human norovirus infection is projectile vomiting. Although norovirus RNA and viral particles have been detected in vomitus, infectivity has not yet been reported. We detected replication-competent norovirus in 25% of vomit samples with a 13-fold to 714-fold increase in genomic equivalents, confirming infectious norovirus.
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- 2021
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14. Massive and rapid COVID-19 testing is feasible by extraction-free SARS-CoV-2 RT-PCR
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Ioanna Smyrlaki, Martin Ekman, Antonio Lentini, Nuno Rufino de Sousa, Natali Papanicolaou, Martin Vondracek, Johan Aarum, Hamzah Safari, Shaman Muradrasoli, Antonio Gigliotti Rothfuchs, Jan Albert, Björn Högberg, and Björn Reinius
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Science - Abstract
SARS-CoV-2 infection is widely diagnosed by RT-PCR, but RNA extraction is a bottleneck for fast and cheap diagnosis. Here, the authors develop protocols to perform RT-PCR directly on heat-inactivated subject samples or samples lysed with readily available detergents and benchmark performance against 597 clinically diagnosed patient samples.
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- 2020
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15. Lecithin:cholesterol acyltransferase: symposium on 50 years of biomedical research from its discovery to latest findings
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Kaare R. Norum, Alan T. Remaley, Helena E. Miettinen, Erik H. Strøm, Bruno E.P. Balbo, Carlos A.T.L. Sampaio, Ingrid Wiig, Jan Albert Kuivenhoven, Laura Calabresi, John J. Tesmer, Mingyue Zhou, Dominic S. Ng, Bjørn Skeie, Sotirios K. Karathanasis, Kelly A. Manthei, and Kjetil Retterstøl
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HDL cholesterol ,lipoprotein ,cardiovascular heart disease ,lipoprotein X ,Biochemistry ,QD415-436 - Abstract
LCAT converts free cholesterol to cholesteryl esters in the process of reverse cholesterol transport. Familial LCAT deficiency (FLD) is a genetic disease that was first described by Kaare R. Norum and Egil Gjone in 1967. This report is a summary from a 2017 symposium where Dr. Norum recounted the history of FLD and leading experts on LCAT shared their results. The Tesmer laboratory shared structural findings on LCAT and the close homolog, lysosomal phospholipase A2. Results from studies of FLD patients in Finland, Brazil, Norway, and Italy were presented, as well as the status of a patient registry. Drs. Kuivenhoven and Calabresi presented data from carriers of genetic mutations suggesting that FLD does not necessarily accelerate atherosclerosis. Dr. Ng shared that LCAT-null mice were protected from diet-induced obesity, insulin resistance, and nonalcoholic fatty liver disease. Dr. Zhou presented multiple innovations for increasing LCAT activity for therapeutic purposes, whereas Dr. Remaley showed results from treatment of an FLD patient with recombinant human LCAT (rhLCAT). Dr. Karathanasis showed that rhLCAT infusion in mice stimulates cholesterol efflux and suggested that it could also enhance cholesterol efflux from macrophages. While the role of LCAT in atherosclerosis remains elusive, the consensus is that a continued study of both the enzyme and disease will lead toward better treatments for patients with heart disease and FLD.
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- 2020
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16. Low Detection Rates of Genetic FH in Cohort of Patients With Severe Hypercholesterolemia in the United Arabic Emirates
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Antoine Rimbert, Hinda Daggag, Peter Lansberg, Adam Buckley, Martijn Viel, Roan Kanninga, Lennart Johansson, Robin P. F. Dullaart, Richard Sinke, Alia Al Tikriti, Jan Albert Kuivenhoven, and Maha Taysir Barakat
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familial hypercholestelemia ,genetics ,screening ,prevalence ,United Arab Emirates (UAE) ,Genetics ,QH426-470 - Abstract
Background: Programs to screen for Familial hypercholesterolemia (FH) are conducted worldwide. In Western societies, these programs have been shown to be cost-effective with hit/detection rates of 1 in 217–250. Thus far, there is no published data on genetic FH in the Gulf region. Using United Arab Emirates as a proxy for the Gulf region, we assessed the prevalence of genetically confirmed FH in the Emirati population sample.Materials and Methods: We recruited 229 patients with LDL-C >95th percentile and employed a customized next generation sequencing pipeline to screen canonical FH genes (LDLR, APOB, PCSK9, LDLRAP1).Results: Participants were characterized by mean total cholesterol and low-density lipoprotein cholesterol (LDL-c) of 6.3 ± 1.1 and 4.7 ± 1.1 mmol/L respectively. Ninety-six percent of the participants were using lipid-lowering medication with mean corrected LDL-c values of 10.0 ± 3.0 mmol/L 15 out of 229 participants were found to suffer from genetically confirmed FH. Carriers of causal genetic variants for FH had higher on-treatment LDL-c compared to those without causal variants (5.7 ± 1.5 vs 4.7 ± 1.0; p = 3.7E-04). The groups did not differ regarding high-density lipoprotein cholesterol, triglycerides, body mass index, blood pressure, glucose, and glycated haemoglobin.Conclusion: This study reveals a low 7% prevalence of genetic FH in Emiratis with marked hypercholesterolemia as determined by correcting LDL-c for the use of lipid-lowering treatment. The portfolio of mutations identified is, to a large extent, unique and includes gene duplications. Our findings warrant further studies into origins of hypercholesterolemia in these patients. This is further supported by the fact that these patients are also characterized by high prevalence of type 2 diabetes (42% in the current study cohort) which already puts them at an increased risk of atherosclerotic cardiovascular disease. These results may also be useful in public health initiatives for FH cascade screening programs in the UAE and maybe the Gulf region.
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- 2022
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17. Association of Ischemic Core Imaging Biomarkers With Post-Thrombectomy Clinical Outcomes in the MR CLEAN Registry
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Miou S. Koopman, Jan W. Hoving, Manon Kappelhof, Olvert A. Berkhemer, Ludo F. M. Beenen, Wim H. van Zwam, Hugo W. A. M. de Jong, Jan Willem Dankbaar, Diederik W. J. Dippel, Jonathan M. Coutinho, Henk A. Marquering, Bart J. Emmer, Charles B. L. M. Majoie, for the MR CLEAN Registry Investigators, Aad van der Lugt, Yvo B. W. E. M. Roos, Robert J. van Oostenbrugge, Jelis Boiten, Jan Albert Vos, Ivo G. H. Jansen, Maxim J. H. L. Mulder, Robert-Jan B. Goldhoorn, Kars C. J. Compagne, Josje Brouwer, Sanne J. den Hartog, Wouter H. Hinsenveld, Bob Roozenbeek, Adriaan C. G. M. van Es, Wouter J. Schonewille, Marieke J. H. Wermer, Marianne A. A. van Walderveen, Julie Staals, Jeannette Hofmeijer, Jasper M. Martens, Geert J. Lycklama à Nijeholt, Sebastiaan F. de Bruijn, Lukas C. van Dijk, H. Bart van der Worp, Rob H. Lo, Ewoud J. van Dijk, Hieronymus D. Boogaarts, J. de Vries, Paul L. M. de Kort, Julia van Tuijl, Jo P. Peluso, Puck Fransen, Jan S. P. van den Berg, Boudewijn A. A. M. van Hasselt, Leo A. M. Aerden, René J. Dallinga, Maarten Uyttenboogaart, Omid Eschgi, Reinoud P.H. Bokkers, Tobien H. C. M. L. Schreuder, Roel J. J. Heijboer, Koos Keizer, Lonneke S. F. Yo, Heleen M. den Hertog, Emiel J. C. Sturm, Paul J. A. M. Brouwers, Marieke E. S. Sprengers, Sjoerd F. M. Jenniskens, René van den Berg, Albert J. Yoo, Alida A. Postma, Stefan D. Roosendaal, Bas F. W. van der Kallen, Ido R. van den Wijngaard, Joost Bot, Pieter-Jan van Doormaal, Anton Meijer, Elyas Ghariq, Reinoud P. H. Bokkers, Marc P. van Proosdij, G. Menno Krietemeijer, Rob Lo, Dick Gerrits, Wouter Dinkelaar, Auke P. A. Appelman, Bas Hammer, Sjoert Pegge, Anouk van der Hoorn, Saman Vinke, H. Zwenneke Flach, Hester F. Lingsma, Naziha el Ghannouti, Martin Sterrenberg, Wilma Pellikaan, Rita Sprengers, Marjan Elfrink, Michelle Simons, Marjolein Vossers, Joke de Meris, Tamara Vermeulen, Annet Geerlings, Gina van Vemde, Tiny Simons, Gert Messchendorp, Nynke Nicolaij, Hester Bongenaar, Karin Bodde, Sandra Kleijn, Jasmijn Lodico, Hanneke Droste, Maureen Wollaert, Sabrina Verheesen, D. Jeurrissen, Erna Bos, Yvonne Drabbe, Michelle Sandiman, Nicoline Aaldering, Berber Zweedijk, Jocova Vervoort, Eva Ponjee, Sharon Romviel, Karin Kanselaar, Denn Barning, Esmee Venema, Vicky Chalos, Ralph R. Geuskens, Tim van Straaten, Saliha Ergezen, Roger R. M. Harmsma Daan Muijres, Anouk de Jong, Anna M. M. Boers, J. Huguet, P. F. C. Groot, Marieke A. Mens, Katinka R. van Kranendonk, Kilian M. Treurniet, Manon L. Tolhuisen, Heitor Alves, Annick J. Weterings, Eleonora L. F. Kirkels, Lieve M. Schupp, Eva J. H. F. Voogd, Sabine Collette, Adrien E. D. Groot, Natalie E. LeCouffe, Praneeta R. Konduri, Haryadi Prasetya, Nerea Arrarte- Terreros, and Lucas A. Ramos
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CT perfusion (CTP) ,ischemic core ,thrombectomy ,stroke ,alberta stroke program early CT score (ASPECTS) ,collaterals ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Background: A considerable proportion of acute ischemic stroke patients treated with endovascular thrombectomy (EVT) are dead or severely disabled at 3 months despite successful reperfusion. Ischemic core imaging biomarkers may help to identify patients who are more likely to have a poor outcome after endovascular thrombectomy (EVT) despite successful reperfusion. We studied the association of CT perfusion-(CTP), CT angiography-(CTA), and non-contrast CT-(NCCT) based imaging markers with poor outcome in patients who underwent EVT in daily clinical practice.Methods: We included EVT-treated patients (July 2016–November 2017) with an anterior circulation occlusion from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry with available baseline CTP, CTA, and NCCT. We used multivariable binary and ordinal logistic regression to analyze the association of CTP ischemic core volume, CTA-Collateral Score (CTA-CS), and Alberta Stroke Program Early CT Score (ASPECTS) with poor outcome (modified Rankin Scale score (mRS) 5-6) and likelihood of having a lower score on the mRS at 90 days.Results: In 201 patients, median core volume was 13 (IQR 5-41) mL. Median ASPECTS was 9 (IQR 8-10). Most patients had grade 2 (83/201; 42%) or grade 3 (28/201; 14%) collaterals. CTP ischemic core volume was associated with poor outcome [aOR per 10 mL 1.02 (95%CI 1.01–1.04)] and lower likelihood of having a lower score on the mRS at 90 days [aOR per 10 mL 0.85 (95% CI 0.78–0.93)]. In multivariable analysis, neither CTA-CS nor ASPECTS were significantly associated with poor outcome or the likelihood of having a lower mRS.Conclusion: In our population of patients treated with EVT in daily clinical practice, CTP ischemic core volume is associated with poor outcome and lower likelihood of shift toward better outcome in contrast to either CTA-CS or ASPECTS.
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- 2022
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18. Probabilistic classification of anti‐SARS‐CoV‐2 antibody responses improves seroprevalence estimates
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Xaquin Castro Dopico, Sandra Muschiol, Nastasiya F Grinberg, Soo Aleman, Daniel J Sheward, Leo Hanke, Marcus Ahl, Linnea Vikström, Mattias Forsell, Jonathan M Coquet, Gerald McInerney, Joakim Dillner, Gordana Bogdanovic, Ben Murrell, Jan Albert, Chris Wallace, and Gunilla B Karlsson Hedestam
- Subjects
antibody responses ,antibody testing ,COVID‐19 ,probability ,SARS‐CoV‐2 ,serology ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Abstract Objectives Population‐level measures of seropositivity are critical for understanding the epidemiology of an emerging pathogen, yet most antibody tests apply a strict cutoff for seropositivity that is not learnt in a data‐driven manner, leading to uncertainty when classifying low‐titer responses. To improve upon this, we evaluated cutoff‐independent methods for their ability to assign likelihood of SARS‐CoV‐2 seropositivity to individual samples. Methods Using robust ELISAs based on SARS‐CoV‐2 spike (S) and the receptor‐binding domain (RBD), we profiled antibody responses in a group of SARS‐CoV‐2 PCR+ individuals (n = 138). Using these data, we trained probabilistic learners to assign likelihood of seropositivity to test samples of unknown serostatus (n = 5100), identifying a support vector machines‐linear discriminant analysis learner (SVM‐LDA) suited for this purpose. Results In the training data from confirmed ancestral SARS‐CoV‐2 infections, 99% of participants had detectable anti‐S and ‐RBD IgG in the circulation, with titers differing > 1000‐fold between persons. In data of otherwise healthy individuals, 7.2% (n = 367) of samples were of uncertain serostatus, with values in the range of 3‐6SD from the mean of pre‐pandemic negative controls (n = 595). In contrast, SVM‐LDA classified 6.4% (n = 328) of test samples as having a high likelihood (> 99% chance) of past infection, 4.5% (n = 230) to have a 50–99% likelihood, and 4.0% (n = 203) to have a 10–49% likelihood. As different probabilistic approaches were more consistent with each other than conventional SD‐based methods, such tools allow for more statistically‐sound seropositivity estimates in large cohorts. Conclusion Probabilistic antibody testing frameworks can improve seropositivity estimates in populations with large titer variability.
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- 2022
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19. Airway antibodies emerge according to COVID-19 severity and wane rapidly but reappear after SARS-CoV-2 vaccination
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Alberto Cagigi, Meng Yu, Björn Österberg, Julia Svensson, Sara Falck-Jones, Sindhu Vangeti, Eric Åhlberg, Lida Azizmohammadi, Anna Warnqvist, Ryan Falck-Jones, Pia C. Gubisch, Mert Ödemis, Farangies Ghafoor, Mona Eisele, Klara Lenart, Max Bell, Niclas Johansson, Jan Albert, Jörgen Sälde, Deleah D. Pettie, Michael P. Murphy, Lauren Carter, Neil P. King, Sebastian Ols, Johan Normark, Clas Ahlm, Mattias N. Forsell, Anna Färnert, Karin Loré, and Anna Smed-Sörensen
- Subjects
COVID-19 ,Immunology ,Medicine - Abstract
Understanding the presence and durability of antibodies against SARS-CoV-2 in the airways is required to provide insights into the ability of individuals to neutralize the virus locally and prevent viral spread. Here, we longitudinally assessed both systemic and airway immune responses upon SARS-CoV-2 infection in a clinically well-characterized cohort of 147 infected individuals representing the full spectrum of COVID-19 severity, from asymptomatic infection to fatal disease. In addition, we evaluated how SARS-CoV-2 vaccination influenced the antibody responses in a subset of these individuals during convalescence as compared with naive individuals. Not only systemic but also airway antibody responses correlated with the degree of COVID-19 disease severity. However, although systemic IgG levels were durable for up to 8 months, airway IgG and IgA declined significantly within 3 months. After vaccination, there was an increase in both systemic and airway antibodies, in particular IgG, often exceeding the levels found during acute disease. In contrast, naive individuals showed low airway antibodies after vaccination. In the former COVID-19 patients, airway antibody levels were significantly elevated after the boost vaccination, highlighting the importance of prime and boost vaccinations for previously infected individuals to obtain optimal mucosal protection.
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- 2021
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20. Dynamics and Management of Restored Forests in Post-Mining Sites with Respect to Their Recreation Value: A Matrix Growth Model
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Jan Melichar, Emil Cienciala, Jan Albert, Markéta Braun Kohlová, Vojtěch Máca, and Petr Pavelčík
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forest reclamation ,open-cast mining restoration ,discrete growth model ,spontaneous succession ,thinning ,attractiveness for recreation ,Plant ecology ,QK900-989 - Abstract
Afforestation has been a popular restoration procedure for spoil heaps in the sites affected by coal open-cast mining in the Czech Republic. Forest replantation is a frequent restoration variant when spoil heaps are recovered, but unreclaimed sites are often left to spontaneous succession. Studies on the dynamics of such restored forests are missing, and the evidence of restored forests with respect to their recreation value is also sporadic. To study the dynamics and management of restored forests—both replanted and recovered by spontaneous succession—on spoil heaps, we used a matrix growth model, which accounts for harvest, artificial and natural regeneration, and recreation value of these forest stands. The model calibration was performed on data from 250 inventory plots distributed across the Velká Podkrušnohorská spoil heap and the Matyáš spoil heap in the Sokolov brown-coal mining area. The growth model was applied on six restored forest types to simulate—over 65 years with a 10-year cutting cycle—the effect of various management regimes of thinning on their recreation value and aboveground biomass (AGB). The results indicate that initial planting density and stand type have an effect on the dynamics of restored forest stands in the short-term horizon. Applying the thinning management resulted in an increase in recreation value for all types of restored stands, while AGB decreased.
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- 2022
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21. Use of plasma metabolomics to analyze phenotype-genotype relationships in young hypercholesterolemic females
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Xiang Zhang, Antoine Rimbert, Willem Balder, Aeilko Having Zwinderman, Jan Albert Kuivenhoven, Geesje Margaretha Dallinga-Thie, and Albert Kornelis Groen
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hypercholesterolemia ,triglyceride ,low density lipoprotein ,genetics ,metabolomics ,Biochemistry ,QD415-436 - Abstract
Hypercholesterolemia is characterized by high plasma LDL cholesterol and often caused by genetic mutations in LDL receptor (LDLR), APOB, or proprotein convertase subtilisin/kexin type 9 (PCSK9). However, a substantial proportion of hypercholesterolemic subjects do not have any mutations in these canonical genes, leaving the underlying pathobiology to be determined. In this study, we investigated to determine whether combining plasma metabolomics with genetic information increases insight in the biology of hypercholesterolemia. For this proof of concept study, we combined plasma metabolites from 119 hypercholesterolemic females with genetic information on the LDL canonical genes. Using hierarchical clustering, we identified four subtypes of hypercholesterolemia, which could be distinguished along two axes represented by triglyceride and large LDL particle concentration. Subjects with mutations in LDLR or APOB preferentially clustered together, suggesting that patients with defects in the LDLR pathway show a distinctive metabolomics profile. In conclusion, we show the potential of using metabolomics to segregate hypercholesterolemic subjects into different clusters, which may help in targeting genetic analysis.
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- 2018
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22. Inferring transmission heterogeneity using virus genealogies: Estimation and targeted prevention.
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Yunjun Zhang, Thomas Leitner, Jan Albert, and Tom Britton
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Biology (General) ,QH301-705.5 - Abstract
Spread of HIV typically involves uneven transmission patterns where some individuals spread to a large number of individuals while others to only a few or none. Such transmission heterogeneity can impact how fast and how much an epidemic spreads. Further, more efficient interventions may be achieved by taking such transmission heterogeneity into account. To address these issues, we developed two phylogenetic methods based on virus sequence data: 1) to generally detect if significant transmission heterogeneity is present, and 2) to pinpoint where in a phylogeny high-level spread is occurring. We derive inference procedures to estimate model parameters, including the amount of transmission heterogeneity, in a sampled epidemic. We show that it is possible to detect transmission heterogeneity under a wide range of simulated situations, including incomplete sampling, varying levels of heterogeneity, and including within-host genetic diversity. When evaluating real HIV-1 data from different epidemic scenarios, we found a lower level of transmission heterogeneity in slowly spreading situations and a higher level of heterogeneity in data that included a rapid outbreak, while R0 and Sackin's index (overall tree shape statistic) were similar in the two scenarios, suggesting that our new method is able to detect transmission heterogeneity in real data. We then show by simulations that targeted prevention, where we pinpoint high-level spread using a coalescence measurement, is efficient when sequence data are collected in an ongoing surveillance system. Such phylogeny-guided prevention is efficient under both single-step contact tracing as well as iterative contact tracing as compared to random intervention.
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- 2020
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23. Potential impact of seasonal forcing on a SARS-CoV-2 pandemic
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Richard A. Neher, Robert Dyrdak, Valentin Druelle, Emma B. Hodcroft, and Jan Albert
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COVID19 ,Epidemiology ,pandemic prepardness ,seasonality ,Medicine - Abstract
A novel coronavirus (SARS-CoV-2) first detected in Wuhan, China, has spread rapidly since December 2019, causing more than 100,000 confirmed infections and 4000 fatalities (as of 10 March 2020). The outbreak has been declared a pandemic by the WHO on Mar 11, 2020. Here, we explore how seasonal variation in transmissibility could modulate a SARS-CoV-2 pandemic. Data from routine diagnostics show a strong and consistent seasonal variation of the four endemic coronaviruses (229E, HKU1, NL63, OC43) and we parameterise our model for SARS-CoV-2 using these data. The model allows for many subpopulations of different size with variable parameters. Simulations of different scenarios show that plausible parameters result in a small peak in early 2020 in temperate regions of the Northern Hemisphere and a larger peak in winter 2020/2021. Variation in transmission and migration rates can result in substantial variation in prevalence between regions. While the uncertainty in parameters is large, the scenarios we explore show that transient reductions in the incidence rate might be due to a combination of seasonal variation and infection control efforts but do not necessarily mean the epidemic is contained. Seasonal forcing on SARS-CoV-2 should thus be taken into account in the further monitoring of the global transmission. The likely aggregated effect of seasonal variation, infection control measures, and transmission rate variation is a prolonged pandemic wave with lower prevalence at any given time, thereby providing a window of opportunity for better preparation of health care systems.
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- 2020
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24. Late presentation of Torsades de Pointes related to fluoxetine following a multiple drug overdose
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Jan Albert Nicolaas Groot, Leonore ten Bokum, and Hubertus Laurentius Antonius van den Oever
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Fluoxetine ,Risperidone ,Depression ,Overdose ,QTc prolongation ,Torsades de Pointes ,Medical emergencies. Critical care. Intensive care. First aid ,RC86-88.9 - Abstract
Abstract Background Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) commonly used in the treatment of depression. While most intoxications with SSRI’s have favorable outcomes and do not require interventions other than strict observation of vital signs and heart rhythm, clinicians should be aware of the life-threatening complications that may occur. Case presentation A 61-year-old woman presented to the emergency department after an intentional multiple drug overdose. Upon examination, she was somnolent with stable respiration and hemodynamics. Electrocardiography showed a prolonged QTc interval of 503 ms. The patient was admitted to the ICU for cardiopulmonary monitoring. During admission, the patient remained stable and showed improved neurologic function over time. After 22 h, a second ECG showed normalization of the QTc interval to 458 ms. However, 36 to 40 h after admission, our patient developed recurrent episodes of Torsades de Pointes (TdP) with loss of cardiac output, leading to cardiopulmonary resuscitation. Spontaneous circulation was restored after intravenous administration of magnesium sulphate. Retrospective serum analysis revealed fluoxetine concentrations of 2700 mcg/l. Conclusion Most intoxications with selective serotonin reuptake inhibitors (SSRI) have favorable outcomes and do not require medical interventions other than strict cardiopulmonary observation. However, higher doses have been associated with QTc interval prolongation, TdP, serotonin syndrome, and death. This case illustrates that life-threatening complications may occur late in the course of hospital admission. Even though overdoses with SSRI’s generally result in few fatalities, clinicians should be aware of the life-threatening clinical manifestations that may occur. Despite being an imperfect predictor of imminent TdP, continuous monitoring of cardiac rhythm is strongly recommended when either cardiac or non-cardiac symptoms are present.
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- 2018
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25. Mechanism of Unusual Isosymmetric Order-Disorder Phase Transition in [Dimethylhydrazinium]Mn(HCOO)3 Hybrid Perovskite Probed by Vibrational Spectroscopy
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Jan Albert Zienkiewicz, Edyta Kucharska, and Maciej Ptak
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hybrid perovskite ,phase transition ,order-disorder ,dimethylhydrazinium cation ,Technology ,Electrical engineering. Electronics. Nuclear engineering ,TK1-9971 ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Microscopy ,QH201-278.5 ,Descriptive and experimental mechanics ,QC120-168.85 - Abstract
[DMHy]Mn(HCOO)3 (DMHy+ = dimethylhydrazinium cation) is an example of an organic–inorganic hybrid adopting perovskite-like architecture with the largest organic cation used so far in the synthesis of formate-based hybrids. This compound undergoes an unusual isosymmetric phase transition at 240 K on heating. The mechanism of this phase transition has a complex nature and is mainly driven by the ordering of DMHy+ cations and accompanied by a significant distortion of the metal–formate framework in the low temperature (LT) phase. In this work, the Density Functional Theory (DFT) calculations and factor group analysis are combined with experimental temperature-dependent IR and Raman studies to unequivocally assign the observed vibrational modes and shed light on the details of the occurring structural changes. The spectroscopic data show that this first-order phase transition has a highly dynamic nature, which is a result of balanced interplay combining re-arrangement of the hydrogen bonds and ordering of DMHy+ cations. The tight confinement of organic cations forces simultaneous steric deformation of formate ions and the MnO6 octahedra.
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- 2021
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26. Pressure and Argumentation in Public Controversies
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Jan Albert van Laar and Erik C. W. Krabbe
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Logic ,BC1-199 - Abstract
When can exerting pressure in a public controversy promote reasonable outcomes, and when is it rather a hindrance? We show how negotiation and persuasion dialogue can be intertwined. Then, we examine in what ways one can in a public controversy exert pressure on others through sanctions or rewards. Finally, we discuss from the viewpoints of persuasion and negotiation whether and, if so, how pressure hinders the achievement of a reasonable outcome.
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- 2019
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27. A Single-Stranded Oligonucleotide Inhibits Toll-Like Receptor 3 Activation and Reduces Influenza A (H1N1) Infection
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Candice Poux, Aleksandra Dondalska, Joseph Bergenstråhle, Sandra Pålsson, Vanessa Contreras, Claudia Arasa, Peter Järver, Jan Albert, David C. Busse, Roger LeGrand, Joakim Lundeberg, John S. Tregoning, and Anna-Lena Spetz
- Subjects
influenza A ,TLR3 ,single-stranded oligonucleotides ,human monocyte-derived dendritic cells (MoDC) ,mice ,cytokines ,Immunologic diseases. Allergy ,RC581-607 - Abstract
The initiation of an immune response is dependent on the activation and maturation of dendritic cells after sensing pathogen associated molecular patterns by pattern recognition receptors. However, the response needs to be balanced as excessive pro-inflammatory cytokine production in response to viral or stress-induced pattern recognition receptor signaling has been associated with severe influenza A virus (IAV) infection. Here, we use an inhibitor of Toll-like receptor (TLR)3, a single-stranded oligonucleotide (ssON) with the capacity to inhibit certain endocytic routes, or a TLR3 agonist (synthetic double-stranded RNA PolyI:C), to evaluate modulation of innate responses during H1N1 IAV infection. Since IAV utilizes cellular endocytic machinery for viral entry, we also assessed ssON's capacity to affect IAV infection. We first show that IAV infected human monocyte-derived dendritic cells (MoDC) were unable to up-regulate the co-stimulatory molecules CD80 and CD86 required for T cell activation. Exogenous TLR3 stimulation did not overcome the IAV-mediated inhibition of co-stimulatory molecule expression in MoDC. However, TLR3 stimulation using PolyI:C led to an augmented pro-inflammatory cytokine response. We reveal that ssON effectively inhibited PolyI:C-mediated pro-inflammatory cytokine production in MoDC, notably, ssON treatment maintained an interferon response induced by IAV infection. Accordingly, RNAseq analyses revealed robust up-regulation of interferon-stimulated genes in IAV cultures treated with ssON. We next measured reduced IAV production in MoDC treated with ssON and found a length requirement for its anti-viral activity, which overlapped with its capacity to inhibit uptake of PolyI:C. Hence, in cases wherein an overreacting TLR3 activation contributes to IAV pathogenesis, ssON can reduce this signaling pathway. Furthermore, concomitant treatment with ssON and IAV infection in mice resulted in maintained weight and reduced viral load in the lungs. Therefore, extracellular ssON provides a mechanism for immune regulation of TLR3-mediated responses and suppression of IAV infection in vitro and in vivo in mice.
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- 2019
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28. Hybrid repair of a large pseudoaneurysm of the proximal right subclavian artery in a Marfan patient
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Emma van der Weijde, MD, Jan Albert Vos, MD, and Robin H. Heijmen, MD, PhD
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Surgery ,RD1-811 ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
A pseudoaneurysm of the proximal right subclavian artery is rare and most commonly caused by penetrating or blunt trauma. We report a case of a Marfan patient with a large iatrogenic pseudoaneurysm of the right subclavian artery, induced by a puncture lesion during central venous catheter placement for an elective endovascular thoracic aortic procedure. The patient was successfully treated with a hybrid approach, which consisted of endovascular coiling and balloon occlusion of the adjacent vessels, followed by open surgical exploration and uneventful closure of the puncture hole with the use of bovine pericardium-reinforced sutures.
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- 2017
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29. CCC- and WASH-mediated endosomal sorting of LDLR is required for normal clearance of circulating LDL
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Paulina Bartuzi, Daniel D. Billadeau, Robert Favier, Shunxing Rong, Daphne Dekker, Alina Fedoseienko, Hille Fieten, Melinde Wijers, Johannes H. Levels, Nicolette Huijkman, Niels Kloosterhuis, Henk van der Molen, Gemma Brufau, Albert K. Groen, Alison M. Elliott, Jan Albert Kuivenhoven, Barbara Plecko, Gernot Grangl, Julie McGaughran, Jay D. Horton, Ezra Burstein, Marten H. Hofker, and Bart van de Sluis
- Subjects
Science - Abstract
Low density lipoprotein receptor (LDLR) is crucial for cholesterol homeostasis. Here, the authors show that components of the CCC-protein complex, CCDC22 and COMMD1, facilitate the endosomal sorting of LDLR and that mutations in these genes cause hypercholesterolemia in dogs and mice, providing new insights into regulation of cholesterol homeostasis.
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- 2016
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30. Norms and Practices of Public Argumentation
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van Laar, Jan Albert and Zenker, Frank
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- 2024
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31. Norms of Public Argumentation and the Ideals of Correctness and Participation
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Zenker, Frank, van Laar, Jan Albert, Cepollaro, B., Gâţă, A., Hinton, M., King, C. G., Larson, B., Lewiński, M., Lumer, C., Oswald, S., Pichlak, M., Scott, B. D., Urbański, M., and Wagemans, J. H. M.
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- 2024
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32. Estimating time of HIV-1 infection from next-generation sequence diversity.
- Author
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Vadim Puller, Richard Neher, and Jan Albert
- Subjects
Biology (General) ,QH301-705.5 - Abstract
Estimating the time since infection (TI) in newly diagnosed HIV-1 patients is challenging, but important to understand the epidemiology of the infection. Here we explore the utility of virus diversity estimated by next-generation sequencing (NGS) as novel biomarker by using a recent genome-wide longitudinal dataset obtained from 11 untreated HIV-1-infected patients with known dates of infection. The results were validated on a second dataset from 31 patients. Virus diversity increased linearly with time, particularly at 3rd codon positions, with little inter-patient variation. The precision of the TI estimate improved with increasing sequencing depth, showing that diversity in NGS data yields superior estimates to the number of ambiguous sites in Sanger sequences, which is one of the alternative biomarkers. The full advantage of deep NGS was utilized with continuous diversity measures such as average pairwise distance or site entropy, rather than the fraction of polymorphic sites. The precision depended on the genomic region and codon position and was highest when 3rd codon positions in the entire pol gene were used. For these data, TI estimates had a mean absolute error of around 1 year. The error increased only slightly from around 0.6 years at a TI of 6 months to around 1.1 years at 6 years. Our results show that virus diversity determined by NGS can be used to estimate time since HIV-1 infection many years after the infection, in contrast to most alternative biomarkers. We provide the regression coefficients as well as web tool for TI estimation.
- Published
- 2017
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33. Tweeting dignity: A practical theological reflection on Twitter’s normative function
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Jan Albert Van den Berg
- Subjects
Social media ,practical theology ,dignity speech ,interdisciplinary ,politics ,Twitter ,normativity ,empirical research ,The Bible ,BS1-2970 ,Practical Theology ,BV1-5099 - Abstract
Social media makes an important contribution to a rapidly changing world in which various domains of meaning are described anew. The evolving nature and dynamic character of social media therefore provides for a rich praxis terrain with which to interact from a practical theological orientation. More specifically associated with the theme of this contribution, the social media sphere also provides an excellent space not only to rethink but also to reenact expressions of dignity in society. The research is facilitated from a practical theological orientation, with particular focus on a normative dimension as embodied in aspects of dignity. Through the use of an interdisciplinary approach and methodology, some contours of dignity specifically associated with South African politics as well as the so-called Charlie Hebdo attacks in 2015 in Paris expressed on the social media platform, Twitter, are described and discussed. From this empirical analysis, description and discussion, a practical theological reflection is offered in which aspects of dignity associated with a normativity function are described. Some practical theological perspectives contributing to future relevant tweeting on dignity are also formulated and provided in conclusion.
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- 2017
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34. Correction: Viral genetic variation accounts for a third of variability in HIV-1 set-point viral load in Europe.
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François Blanquart, Chris Wymant, Marion Cornelissen, Astrid Gall, Margreet Bakker, Daniela Bezemer, Matthew Hall, Mariska Hillebregt, Swee Hoe Ong, Jan Albert, Norbert Bannert, Jacques Fellay, Katrien Fransen, Annabelle J Gourlay, M Kate Grabowski, Barbara Gunsenheimer-Bartmeyer, Huldrych F Günthard, Pia Kivelä, Roger Kouyos, Oliver Laeyendecker, Kirsi Liitsola, Laurence Meyer, Kholoud Porter, Matti Ristola, Ard van Sighem, Guido Vanham, Ben Berkhout, Paul Kellam, Peter Reiss, Christophe Fraser, and BEEHIVE collaboration
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Biology (General) ,QH301-705.5 - Abstract
[This corrects the article DOI: 10.1371/journal.pbio.2001855.].
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- 2017
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35. Viral genetic variation accounts for a third of variability in HIV-1 set-point viral load in Europe.
- Author
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François Blanquart, Chris Wymant, Marion Cornelissen, Astrid Gall, Margreet Bakker, Daniela Bezemer, Matthew Hall, Mariska Hillebregt, Swee Hoe Ong, Jan Albert, Norbert Bannert, Jacques Fellay, Katrien Fransen, Annabelle J Gourlay, M Kate Grabowski, Barbara Gunsenheimer-Bartmeyer, Huldrych F Günthard, Pia Kivelä, Roger Kouyos, Oliver Laeyendecker, Kirsi Liitsola, Laurence Meyer, Kholoud Porter, Matti Ristola, Ard van Sighem, Guido Vanham, Ben Berkhout, Paul Kellam, Peter Reiss, Christophe Fraser, and BEEHIVE collaboration
- Subjects
Biology (General) ,QH301-705.5 - Abstract
HIV-1 set-point viral load-the approximately stable value of viraemia in the first years of chronic infection-is a strong predictor of clinical outcome and is highly variable across infected individuals. To better understand HIV-1 pathogenesis and the evolution of the viral population, we must quantify the heritability of set-point viral load, which is the fraction of variation in this phenotype attributable to viral genetic variation. However, current estimates of heritability vary widely, from 6% to 59%. Here we used a dataset of 2,028 seroconverters infected between 1985 and 2013 from 5 European countries (Belgium, Switzerland, France, the Netherlands and the United Kingdom) and estimated the heritability of set-point viral load at 31% (CI 15%-43%). Specifically, heritability was measured using models of character evolution describing how viral load evolves on the phylogeny of whole-genome viral sequences. In contrast to previous studies, (i) we measured viral loads using standardized assays on a sample collected in a strict time window of 6 to 24 months after infection, from which the viral genome was also sequenced; (ii) we compared 2 models of character evolution, the classical "Brownian motion" model and another model ("Ornstein-Uhlenbeck") that includes stabilising selection on viral load; (iii) we controlled for covariates, including age and sex, which may inflate estimates of heritability; and (iv) we developed a goodness of fit test based on the correlation of viral loads in cherries of the phylogenetic tree, showing that both models of character evolution fit the data well. An overall heritability of 31% (CI 15%-43%) is consistent with other studies based on regression of viral load in donor-recipient pairs. Thus, about a third of variation in HIV-1 virulence is attributable to viral genetic variation.
- Published
- 2017
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36. Long‐Term Follow‐up of the PADI Trial: Percutaneous Transluminal Angioplasty Versus Drug‐Eluting Stents for Infrapopliteal Lesions in Critical Limb Ischemia
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Marlon I. Spreen, Jasper M. Martens, Bob Knippenberg, Lukas C. van Dijk, Jean‐Paul P. M. de Vries, Jan Albert Vos, Gert Jan de Borst, Evert‐Jan P. A. Vonken, Okker D. Bijlstra, Jan J. Wever, Randolph G. Statius van Eps, Willem P. Th. M. Mali, and Hendrik van Overhagen
- Subjects
critical limb ischemia ,drug‐eluting stent ,endovascular treatment ,peripheral artery disease ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
BackgroundClinical outcomes reported after treatment of infrapopliteal lesions with drug‐eluting stents (DESs) have been more favorable compared with percutaneous transluminal angioplasty with a bailout bare metal stent (PTA‐BMS) through midterm follow‐up in patients with critical limb ischemia. In the present study, long‐term results of treatment of infrapopliteal lesions with DESs are presented. Methods and ResultsAdults with critical limb ischemia (Rutherford category ≥4) and infrapopliteal lesions were randomized to receive PTA‐BMS or DESs with paclitaxel. Long‐term follow‐up consisted of annual assessments up to 5 years after treatment or until a clinical end point was reached. Clinical end points were major amputation (above ankle level), infrapopliteal surgical or endovascular reintervention, and death. Preserved primary patency (≤50% restenosis) of treated lesions was an additional morphological end point, assessed by duplex sonography. In total, 74 limbs (73 patients) were treated with DESs and 66 limbs (64 patients) were treated with PTA‐BMS. The estimated 5‐year major amputation rate was lower in the DES arm (19.3% versus 34.0% for PTA‐BMS; P=0.091). The 5‐year rates of amputation‐ and event‐free survival (survival free from major amputation or reintervention) were significantly higher in the DES arm compared with PTA‐BMS (31.8% versus 20.4%, P=0.043; and 26.2% versus 15.3%, P=0.041, respectively). Survival rates were comparable. The limited available morphological results showed higher preserved patency rates after DESs than after PTA‐BMS at 1, 3, and 4 years of follow‐up. ConclusionsBoth clinical and morphological long‐term results after treatment of infrapopliteal lesions in patients with critical limb ischemia are improved with DES compared with PTA‐BMS. Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00471289.
- Published
- 2017
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37. Inference of Transmission Network Structure from HIV Phylogenetic Trees.
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Federica Giardina, Ethan Obie Romero-Severson, Jan Albert, Tom Britton, and Thomas Leitner
- Subjects
Biology (General) ,QH301-705.5 - Abstract
Phylogenetic inference is an attractive means to reconstruct transmission histories and epidemics. However, there is not a perfect correspondence between transmission history and virus phylogeny. Both node height and topological differences may occur, depending on the interaction between within-host evolutionary dynamics and between-host transmission patterns. To investigate these interactions, we added a within-host evolutionary model in epidemiological simulations and examined if the resulting phylogeny could recover different types of contact networks. To further improve realism, we also introduced patient-specific differences in infectivity across disease stages, and on the epidemic level we considered incomplete sampling and the age of the epidemic. Second, we implemented an inference method based on approximate Bayesian computation (ABC) to discriminate among three well-studied network models and jointly estimate both network parameters and key epidemiological quantities such as the infection rate. Our ABC framework used both topological and distance-based tree statistics for comparison between simulated and observed trees. Overall, our simulations showed that a virus time-scaled phylogeny (genealogy) may be substantially different from the between-host transmission tree. This has important implications for the interpretation of what a phylogeny reveals about the underlying epidemic contact network. In particular, we found that while the within-host evolutionary process obscures the transmission tree, the diversification process and infectivity dynamics also add discriminatory power to differentiate between different types of contact networks. We also found that the possibility to differentiate contact networks depends on how far an epidemic has progressed, where distance-based tree statistics have more power early in an epidemic. Finally, we applied our ABC inference on two different outbreaks from the Swedish HIV-1 epidemic.
- Published
- 2017
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38. Arguments that take Counterconsiderations into Account
- Author
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Jan Albert van Laar
- Subjects
counterconsideration, conductive argument, dialogue, refutation ,Logic ,BC1-199 - Abstract
This paper examines arguments that take counter- considerations into account, and it does so from a dialogical point of view. According to my account, a counterconsideration is part of a critical reaction from a real or imagined opponent, and an arguer may take it into account in his argument in at least six fully responsive ways. Conductive arguments (or: pro and con arguments, balance of con-siderations arguments) will be characterized as one of these types. In this manner, the paper aims to show how conducive, and related kinds of argument can be understood dialogically.
- Published
- 2014
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- View/download PDF
39. Establishment and stability of the latent HIV-1 DNA reservoir
- Author
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Johanna Brodin, Fabio Zanini, Lina Thebo, Christa Lanz, Göran Bratt, Richard A Neher, and Jan Albert
- Subjects
HIV ,cure ,evolution ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
HIV-1 infection cannot be cured because the virus persists as integrated proviral DNA in long-lived cells despite years of suppressive antiretroviral therapy (ART). In a previous paper (Zanini et al, 2015) we documented HIV-1 evolution in 10 untreated patients. Here we characterize establishment, turnover, and evolution of viral DNA reservoirs in the same patients after 3–18 years of suppressive ART. A median of 14% (range 0–42%) of the DNA sequences were defective due to G-to-A hypermutation. Remaining DNA sequences showed no evidence of evolution over years of suppressive ART. Most sequences from the DNA reservoirs were very similar to viruses actively replicating in plasma (RNA sequences) shortly before start of ART. The results do not support persistent HIV-1 replication as a mechanism to maintain the HIV-1 reservoir during suppressive therapy. Rather, the data indicate that DNA variants are turning over as long as patients are untreated and that suppressive ART halts this turnover.
- Published
- 2016
- Full Text
- View/download PDF
40. Characterization of Binding of Magnetic Nanoparticles to Rolling Circle Amplification Products by Turn-On Magnetic Assay
- Author
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Sobhan Sepehri, Björn Agnarsson, Teresa Zardán Gómez de la Torre, Justin F. Schneiderman, Jakob Blomgren, Aldo Jesorka, Christer Johansson, Mats Nilsson, Jan Albert, Maria Strømme, Dag Winkler, and Alexei Kalaboukhov
- Subjects
magnetic nanoparticle ,bioassay ,differential homogenous magnetic assay ,immobilization ,binding kinetics ,rolling circle amplification product ,Biotechnology ,TP248.13-248.65 - Abstract
The specific binding of oligonucleotide-tagged 100 nm magnetic nanoparticles (MNPs) to rolling circle products (RCPs) is investigated using our newly developed differential homogenous magnetic assay (DHMA). The DHMA measures ac magnetic susceptibility from a test and a control samples simultaneously and eliminates magnetic background signal. Therefore, the DHMA can reveal details of binding kinetics of magnetic nanoparticles at very low concentrations of RCPs. From the analysis of the imaginary part of the DHMA signal, we find that smaller MNPs in the particle ensemble bind first to the RCPs. When the RCP concentration increases, we observe the formation of agglomerates, which leads to lower number of MNPs per RCP at higher concentrations of RCPs. The results thus indicate that a full frequency range of ac susceptibility observation is necessary to detect low concentrations of target RCPs and a long amplification time is not required as it does not significantly increase the number of MNPs per RCP. The findings are critical for understanding the underlying microscopic binding process for improving the assay performance. They furthermore suggest DHMA is a powerful technique for dynamically characterizing the binding interactions between MNPs and biomolecules in fluid volumes.
- Published
- 2019
- Full Text
- View/download PDF
41. In vivo tissue cholesterol efflux is reduced in carriers of a mutation in APOA1[S]
- Author
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Adriaan G. Holleboom, Lily Jakulj, Remco Franssen, Julie Decaris, Menno Vergeer, Joris Koetsveld, Jayraz Luchoomun, Alexander Glass, Marc K. Hellerstein, John J.P. Kastelein, G. Kees Hovingh, Jan Albert Kuivenhoven, Albert K. Groen, Scott M. Turner, and Erik S.G. Stroes
- Subjects
reverse cholesterol transport ,high density lipoprotein ,genetics ,fecal sterol excretion ,Biochemistry ,QD415-436 - Abstract
Atheroprotection by high density lipoprotein (HDL) is considered to be mediated through reverse cholesterol transport (RCT) from peripheral tissues. We investigated in vivo cholesterol fluxes through the RCT pathway in patients with low plasma high density lipoprotein cholesterol (HDL-c) due to mutations in APOA1. Seven carriers of the L202P mutation in APOA1 (mean HDL-c: 20 ± 19 mg/dl) and seven unaffected controls (mean HDL-c: 54 ± 11 mg/dl, P < 0.0001) received a 20 h infusion of 13C2-cholesterol (13C-C). Enrichment of plasma and erythrocyte free cholesterol and plasma cholesterol esters was measured. With a three-compartment SAAM-II model, tissue cholesterol efflux (TCE) was calculated. TCE was reduced by 19% in carriers (4.6 ± 0.8 mg/kg/h versus 5.7 ± 0.7 mg/kg/h in controls, P = 0.02). Fecal 13C recovery and sterol excretion 7 days postinfusion did not differ significantly between carriers and controls: 21.3 ± 20% versus 13.3 ± 6.3% (P = 0.33), and 2,015 ± 1,431 mg/day versus 1456 ± 404 mg/day (P = 0.43), respectively. TCE is reduced in carriers of mutations in APOA1, suggesting that HDL contributes to efflux of tissue cholesterol in humans. The residual TCE and unaffected fecal sterol excretion in our severely affected carriers suggest, however, that non-HDL pathways contribute to RCT significantly.
- Published
- 2013
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42. Cohorte GEFA-HT-UY (GEnotipo, Fenotipo y Ambiente de la HiperTensión Arterial en UruguaY)
- Author
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Leonella Luzardo, Inés Lujambio, Mariana Sottolano, Alicia Da Rosa, Sebastián Robaina, Federico Arce, María Márquez, Valentina Agorrody, Carlos Américo, Mariela Garau, Nadia Krul, Ana Carina Ríos, Lucía Florio, Alicia Olascoaga, Óscar Noboa, Jan Albert Staessen, and José Boggia
- Subjects
hipertensión ,estudios de cohortes ,factores de riesgo ,enfermedades cardiovasculares ,enfermedades renales ,Medicine ,Medicine (General) ,R5-920 - Abstract
Introducción: la hipertensión arterial esencial es el resultado de complejas interacciones entre el genotipo, el fenotipo y el ambiente. El estudio GEFA-HT-UY busca analizar el papel de diferentes rasgos fenotípicos cardiovasculares y renales y su relación con factores genéticos y ambientales en una muestra aleatoria de una zona de Montevideo. Material y método: estudio de cohorte poblacional, observacional y analítico que inició su diseño y programación en 2011 y la recolección de datos en abril de 2012. La muestra consiste en 150 familias (aproximadamente 450 sujetos), seleccionados de forma aleatoria entre los habitantes de un área geográfica delimitada de Montevideo. Las determinaciones basales incluyen el registro de antecedentes médicos de relevancia, medidas antropométricas, determinaciones de presión arterial en domicilio, en consultorio, automonitoreo de presión arterial y monitoreo ambulatorio de presión arterial periférico y central. Se realiza registro electrocardiográfico, ecocardiográfico y de rigidez arterial. Se recogen muestras de sangre y orina para determinaciones bioquímicas con especial énfasis en los factores de riesgo cardiovascular y de enfermedad renal crónica y la evidencia de daño de órgano blanco. Durante el seguimiento se pesquisará la incidencia de nuevos eventos cardiovasculares y renales. Resultados: el objetivo de esta publicación es comunicar el protocolo, de todas formas se presentan los resultados de los primeros 36 sujetos que ya lo han completado. Discusión: el seguimiento de la cohorte aportará datos relevantes y originales sobre la hipertensión arterial y su relación con el desarrollo de enfermedad cardiovascular y renal.
- Published
- 2013
43. LCAT deficiency in mice is associated with a diminished adrenal glucocorticoid function
- Author
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Menno Hoekstra, Suzanne J.A. Korporaal, Ronald J. van der Sluis, Veronica Hirsch-Reinshagen, Andrea E. Bochem, Cheryl L. Wellington, Theo J.C. Van Berkel, Jan Albert Kuivenhoven, and Miranda Van Eck
- Subjects
lecithin:cholesterol acyltransferase ,glucocorticoids ,cholesteryl esters ,Biochemistry ,QD415-436 - Abstract
In vitro studies have suggested that HDL and apoB-containing lipoproteins can provide cholesterol for synthesis of glucocorticoids. Here we assessed adrenal glucocorticoid function in LCAT knockout (KO) mice to determine the specific contribution of HDL-cholesteryl esters to adrenal glucocorticoid output in vivo. LCAT KO mice exhibit an 8-fold higher plasma free cholesterol-to-cholesteryl ester ratio (P < 0.001) and complete HDL-cholesteryl ester deficiency. ApoB-containing lipoprotein and associated triglyceride levels are increased in LCAT KO mice as compared with C57BL/6 control mice (44%; P < 0.05). Glucocorticoid-producing adrenocortical cells within the zona fasciculata in LCAT KO mice are devoid of neutral lipids. However, adrenal weights and basal corticosterone levels are not significantly changed in LCAT KO mice. In contrast, adrenals of LCAT KO mice show compensatory up-regulation of genes involved in cholesterol synthesis (HMG-CoA reductase; 516%; P < 0.001) and acquisition (LDL receptor; 385%; P < 0.001) and a marked 40–50% lower glucocorticoid response to adrenocorticotropic hormone exposure, endotoxemia, or fasting (P < 0.001 for all). In conclusion, our studies show that HDL-cholesteryl ester deficiency in LCAT KO mice is associated with a 40–50% lower adrenal glucocorticoid output. These findings further highlight the important novel role for HDL as cholesterol donor for the synthesis of glucocorticoids by the adrenals.
- Published
- 2013
- Full Text
- View/download PDF
44. Middelloopbaan-ontwikkeling deur spirituele lewenstylafrigting: Verkennende teoretiese perspektiewe
- Author
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Madelein C. Fourie and Jan Albert van den Berg
- Subjects
interdissiplinêre gesprek ,‘postfoundational’ praktiese teologie ,middelloopbaanontwikkeling ,spirituele intelligensie ,lewenstylafrigting ,interdisciplinary dialogue ,postfoundational practical theology ,middle-career development ,spiritual intelligence ,The Bible ,BS1-2970 ,Practical Theology ,BV1-5099 - Abstract
Middle-career development through spiritual lifestyle coaching: Preliminary theoretical perspectives. This study bases itself in the epistemological and methodological development of a broad and interdisciplinary dialogue where various voices in the form of different domains converse in order to establish an integrated whole. The research contributes to the actual corporative question regarding spirituality in the workplace, specifically aimed at the individual in the middle-career phase. This phase is characterised as a re-evaluation period aimed at personal and professional growth. A shift in emphasis to the meaning and sense of work is linked to spiritual intelligence as spirituality can be described and understood as a type of intelligence. The study shows that the middle-career experience provides opportunity for an altered future view. Lifestyle coaching serves as facilitating process and offers guidance in answering existential questions which are included in the spiritual. The probable outcome promises to add meaning as a manifesting component in a dynamic and transforming life strategy.
- Published
- 2013
45. How Much Do We Know about Drug Resistance Due to PrEP Use? Analysis of Experts' Opinion and Its Influence on the Projected Public Health Impact.
- Author
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Dobromir T Dimitrov, Marie-Claude Boily, Timothy B Hallett, Jan Albert, Charles Boucher, John W Mellors, Deenan Pillay, and David A M C van de Vijver
- Subjects
Medicine ,Science - Abstract
Randomized controlled trials reported that pre-exposure prophylaxis (PrEP) with tenofovir and emtricitabine rarely selects for drug resistance. However, drug resistance due to PrEP is not completely understood. In daily practice, PrEP will not be used under the well-controlled conditions available in the trials, suggesting that widespread use of PrEP can result in increased drug resistance.We surveyed expert virologists with questions about biological assumptions regarding drug resistance due to PrEP use. The influence of these assumptions on the prevalence of drug resistance and the fraction of HIV transmitted resistance was studied with a mathematical model. For comparability, 50% PrEP-coverage of and 90% per-act efficacy of PrEP in preventing HIV acquisition are assumed in all simulations.Virologists disagreed on the following: the time until resistance emergence (range: 20-180 days) in infected PrEP users with breakthrough HIV infections; the efficacy of PrEP against drug-resistant HIV (25%-90%); and the likelihood of resistance acquisition upon transmission (10%-75%). These differences translate into projections of 0.6%- 1% and 3.5%-6% infected individuals with detectable resistance 10 years after introducing PrEP, assuming 100% and 50% adherence, respectively. The rate of resistance emergence following breakthrough HIV infection and the rate of resistance reversion after PrEP use is discontinued, were the factors identified as most influential on the expected resistance associated with PrEP. Importantly, 17-23% infected individuals could virologically fail treatment as a result of past PrEP use or transmitted resistance to PrEP with moderate adherence.There is no broad consensus on quantification of key biological processes that underpin the emergence of PrEP-associated drug resistance. Despite this, the contribution of PrEP use to the prevalence of the detectable drug resistance is expected to be small. However, individuals who become infected despite the use of PrEP should be closely monitored due to higher risk of virological failure when initiating antiretroviral treatment in the future.
- Published
- 2016
- Full Text
- View/download PDF
46. The Use of Heparin during Endovascular Peripheral Arterial Interventions: A Synopsis
- Author
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Arno M. Wiersema, Christopher Watts, Alexandra C. Durran, Michel M. P. J. Reijnen, Otto M. van Delden, Frans L. Moll, and Jan Albert Vos
- Subjects
Medicine ,Science - Abstract
A large variety exists for many aspects of the use of heparin as periprocedural prophylactic antithrombotics (PPAT) during peripheral arterial interventions (PAI). This variation is present, not only within countries, but also between them. Due to a lack of (robust) data, no systematic review on the use of heparin during PAI could be justified. A synopsis of all available literature on heparin during PAI describes that heparin is used on technical equipment to reduce the thrombogenicity and in the flushing solution with saline. Heparin could have a cumulative anticoagulant effect when used in combination with ionic contrast medium. No level-1 evidence exists on the use of heparin. A measurement of actual anticoagulation status by means of an activated clotting time should be mandatory.
- Published
- 2016
- Full Text
- View/download PDF
47. Frequent Respiratory Viral Infections in Children with Febrile Neutropenia - A Prospective Follow-Up Study.
- Author
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Martina Söderman, Samuel Rhedin, Thomas Tolfvenstam, Maria Rotzén-Östlund, Jan Albert, Kristina Broliden, and Anna Lindblom
- Subjects
Medicine ,Science - Abstract
OBJECTIVE:Febrile neutropenia is common in children undergoing chemotherapy for the treatment of malignancies. In the majority of cases, the cause of the fever is unknown. Although respiratory viruses are commonly associated with this condition, the etiologic significance of this finding remains unclear and is therefore the subject of this study. STUDY DESIGN:Nasopharyngeal aspirates were collected during 87 episodes of febrile neutropenia in children age 0-18 years, being treated at a children's oncology unit between January 2013 and June 2014. Real-time polymerase chain reaction was used to determine the presence of 16 respiratory viruses. Follow-up samples were collected from children who tested positive for one or more respiratory viruses. Rhinoviruses were genotyped by VP4/VP2 sequencing. Fisher's exact test and Mann-Whitney U test were used for group comparisons. RESULTS:At least one respiratory virus was detected in samples from 39 of 87 episodes of febrile neutropenia (45%), with rhinoviruses the most frequently detected. Follow-up samples were collected after a median of 28 days (range, 9-74 days) in 32 of the 39 virus-positive episodes. The respiratory viral infection had resolved in 25 episodes (78%). The same virus was detected at follow-up in one coronavirus and six rhinovirus episodes. Genotyping revealed a different rhinovirus species in two of the six rhinovirus infections. CONCLUSION:The frequency of respiratory viral infections in this group of patients suggests an etiologic role in febrile neutropenia. However, these findings must be confirmed in larger patient cohorts.
- Published
- 2016
- Full Text
- View/download PDF
48. Vertical stratification and microhabitat selection by the Great Capricorn Beetle (Cerambyx cerdo) (Coleoptera: Cerambycidae) in open-grown, veteran oaks
- Author
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Jan ALBERT, Michal PLATEK, and Lukas CIZEK
- Subjects
cerambycidae ,cerambyx cerdo ,dead wood ,natura 2000 ,quercus ,saproxylic ,longhorned beetle ,xylophagous ,woodland ,Zoology ,QL1-991 - Abstract
The great capricorn beetle or Cerambyx longicorn (Cerambyx cerdo, Linnaeus, 1758) is an internationally protected umbrella species representing the highly diverse and endangered fauna associated with senescent oaks. For the conservation and monitoring of populations of C. cerdo it is important to have a good knowledge of its microhabitat requirements. We investigated determinants and patterns of C. cerdo distribution within individual old, open-grown oaks. Trees inhabited by this species were climbed, and the number of exit holes and environmental variables recorded at two sites in the Czech Republic. Distribution of exit holes in relation to height above the ground, trunk shading by branches, orientation in terms of the four cardinal directions, diameter, surface and volume of inhabited tree parts were investigated. This study revealed that the number of exit holes in the trunks of large open-grown oaks was positively associated with the diameter of the trunk and openness and negatively with height above the ground, and the effects of diameter and openness changed with height. The number of exit holes in the surface of a trunk was also associated with the cardinal orientation of the surface. Approximately half of both C. cerdo populations studied developed less than 4 m and approximately a third less than 2 m above the ground. This indicates that most C. cerdo develop near the ground. Active management that prevents canopy closure is thus crucial for the survival of C. cerdo and searching for exit holes is an effective method of detecting sites inhabited by this species.
- Published
- 2012
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49. Forward individualized medicine from personal genomes to interactomes
- Author
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Xiang eZhang, Jan Albert Kuivenhoven, and Albert K. Groen
- Subjects
personalized medicine ,Interactome ,Integrative Genomics ,genome-scale metabolic models ,gene regulatory networks (GRN) ,Network medicine ,Physiology ,QP1-981 - Abstract
When considering the variation in the genome, transcriptome, proteome and metabolome, and their interaction with the environment, every individual can be rightfully considered as a unique biological entity. Individualized medicine promises to take this uniqueness into account to optimize disease treatment and thereby improve health benefits for every patient. The success of individualized medicine relies on a precise understanding of the genotype-phenotype relationship. Although omics technologies advance rapidly, there are several challenges that need to be overcome: Next generation sequencing can efficiently decipher genomic sequences, epigenetic changes, and transcriptomic variation in patients, but it does not automatically indicate how or whether the identified variation will cause pathological changes. This is likely due to the inability to account for 1) the consequences of gene-gene and gene-environment interactions, and 2) (post)transcriptional as well as (post)translational processes that eventually determine the concentration of key metabolites. The technologies to accurately measure changes in these latter layers are still under development, and such measurements in humans are also mainly restricted to blood and circulating cells. Despite these challenges, it is already possible to track dynamic changes in the human interactome in healthy and diseased states by using the integration of multi-omics data. In this review, we evaluate the potential value of current major bioinformatics and systems biology-based approaches, including genome wide association studies, epigenetics, gene regulatory and protein-protein interaction networks, and genome-scale metabolic modeling. Moreover, we address the question whether integrative analysis of personal multi-omics data will help understanding of personal genotype-phenotype relationships.
- Published
- 2015
- Full Text
- View/download PDF
50. Population genomics of intrapatient HIV-1 evolution
- Author
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Fabio Zanini, Johanna Brodin, Lina Thebo, Christa Lanz, Göran Bratt, Jan Albert, and Richard A Neher
- Subjects
HIV-1 ,deep sequencing ,evolution ,reversion ,fitness landscapes ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
Many microbial populations rapidly adapt to changing environments with multiple variants competing for survival. To quantify such complex evolutionary dynamics in vivo, time resolved and genome wide data including rare variants are essential. We performed whole-genome deep sequencing of HIV-1 populations in 9 untreated patients, with 6-12 longitudinal samples per patient spanning 5-8 years of infection. The data can be accessed and explored via an interactive web application. We show that patterns of minor diversity are reproducible between patients and mirror global HIV-1 diversity, suggesting a universal landscape of fitness costs that control diversity. Reversions towards the ancestral HIV-1 sequence are observed throughout infection and account for almost one third of all sequence changes. Reversion rates depend strongly on conservation. Frequent recombination limits linkage disequilibrium to about 100bp in most of the genome, but strong hitch-hiking due to short range linkage limits diversity.
- Published
- 2015
- Full Text
- View/download PDF
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