@article{WilsonAmblerLeeetal.2019, author = {Wilson, Duncan and Ambler, Gareth and Lee, Keon-Joo and Lim, Jae-Sung and Shiozawa, Masayuki and Koga, Masatoshi and Li, Linxin and Lovelock, Caroline and Chabriat, Hugues and Hennerici, Michael and Wong, Yuen Kwun and Mak, Henry Ka Fung and Prats-S{\´a}nchez, Luis and Mart{\´i}nez-Dome{\~n}o, Alejandro and Inamura, Shigeru and Yoshifuji, Kazuhisa and Arsava, Ethem Murat and Horstmann, Solveig and Purrucker, Jan and Lam, Bonnie Yin Ka and Wong, Adrian and Kim, Young Dae and Song, Tae-Jin and Schrooten, Maarten and Lemmens, Robin and Eppinger, Sebastian and Gattringer, Thomas and Uysal, Ender and Tanriverdi, Zeynep and Bornstein, Natan M and Ben Assayag, Einor and Hallevi, Hen and Tanaka, Jun and Hara, Hideo and Coutts, Shelagh B and Hert, Lisa and Polymeris, Alexandros and Seiffge, David J and Lyrer, Philippe and Algra, Ale and Kappelle, Jaap and Salman, Rustam Al-Shahi and J{\"a}ger, Hans R and Lip, Gregory Y H and Mattle, Heinrich P and Panos, Leonidas D and Mas, Jean-Louis and Legrand, Laurence and Karayiannis, Christopher and Phan, Thanh and Gunkel, Sarah and Christ, Nicolas and Abrigo, Jill and Leung, Thomas and Chu, Winnie and Chappell, Francesca and Makin, Stephen and Hayden, Derek and Williams, David J and Kooi, M Eline and van Dam-Nolen, Dianne H K and Barbato, Carmen and Browning, Simone and Wiegertjes, Kim and Tuladhar, Anil M and Maaijwee, Noortje and Guevarra, Christine and Yatawara, Chathuri and Mendyk, Anne-Marie and Delmaire, Christine and K{\"o}hler, Sebastian and van Oostenbrugge, Robert and Zhou, Ying and Xu, Chao and Hilal, Saima and Gyanwali, Bibek and Chen, Christopher and Lou, Min and Staals, Julie and Bordet, R{\´e}gis and Kandiah, Nagaendran and de Leeuw, Frank-Erik and Simister, Robert and van der Lugt, Aad and Kelly, Peter J and Wardlaw, Joanna M and Soo, Yannie and Fluri, Felix and Srikanth, Velandai and Calvet, David and Jung, Simon and Kwa, Vincent I H and Engelter, Stefan T and Peters, Nils and Smith, Eric E and Yakushiji, Yusuke and Necioglu Orken, Dilek and Fazekas, Franz and Thijs, Vincent and Heo, Ji Hoe and Mok, Vincent and Veltkamp, Roland and Ay, Hakan and Imaizumi, Toshio and Gomez-Anson, Beatriz and Lau, Kui Kai and Jouvent, Eric and Rothwell, Peter M and Toyoda, Kazunori and Bae, Hee-Yoon and Marti-Fabregas, Joan and Werring, David J}, title = {Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies}, series = {The Lancet Neurology}, volume = {18}, journal = {The Lancet Neurology}, organization = {Microbleeds International Collaborative Network}, doi = {10.1016/S1474-4422(19)30197-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-233710}, pages = {653-665}, year = {2019}, abstract = {Background Cerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrombotic drugs. We therefore aimed to establish whether a large burden of cerebral microbleeds or particular anatomical patterns of cerebral microbleeds can identify ischaemic stroke or transient ischaemic attack patients at higher absolute risk of intracranial haemorrhage than ischaemic stroke. Methods We did a pooled analysis of individual patient data from cohort studies in adults with recent ischaemic stroke or transient ischaemic attack. Cohorts were eligible for inclusion if they prospectively recruited adult participants with ischaemic stroke or transient ischaemic attack; included at least 50 participants; collected data on stroke events over at least 3 months follow-up; used an appropriate MRI sequence that is sensitive to magnetic susceptibility; and documented the number and anatomical distribution of cerebral microbleeds reliably using consensus criteria and validated scales. Our prespecified primary outcomes were a composite of any symptomatic intracranial haemorrhage or ischaemic stroke, symptomatic intracranial haemorrhage, and symptomatic ischaemic stroke. We registered this study with the PROSPERO international prospective register of systematic reviews, number CRD42016036602. Findings Between Jan 1, 1996, and Dec 1, 2018, we identified 344 studies. After exclusions for ineligibility or declined requests for inclusion, 20 322 patients from 38 cohorts (over 35 225 patient-years of follow-up; median 1·34 years [IQR 0·19-2·44]) were included in our analyses. The adjusted hazard ratio [aHR] comparing patients with cerebral microbleeds to those without was 1·35 (95\% CI 1·20-1·50) for the composite outcome of intracranial haemorrhage and ischaemic stroke; 2·45 (1·82-3·29) for intracranial haemorrhage and 1·23 (1·08-1·40) for ischaemic stroke. The aHR increased with increasing cerebral microbleed burden for intracranial haemorrhage but this effect was less marked for ischaemic stroke (for five or more cerebral microbleeds, aHR 4·55 [95\% CI 3·08-6·72] for intracranial haemorrhage vs 1·47 [1·19-1·80] for ischaemic stroke; for ten or more cerebral microbleeds, aHR 5·52 [3·36-9·05] vs 1·43 [1·07-1·91]; and for ≥20 cerebral microbleeds, aHR 8·61 [4·69-15·81] vs 1·86 [1·23-2·82]). However, irrespective of cerebral microbleed anatomical distribution or burden, the rate of ischaemic stroke exceeded that of intracranial haemorrhage (for ten or more cerebral microbleeds, 64 ischaemic strokes [95\% CI 48-84] per 1000 patient-years vs 27 intracranial haemorrhages [17-41] per 1000 patient-years; and for ≥20 cerebral microbleeds, 73 ischaemic strokes [46-108] per 1000 patient-years vs 39 intracranial haemorrhages [21-67] per 1000 patient-years). Interpretation In patients with recent ischaemic stroke or transient ischaemic attack, cerebral microbleeds are associated with a greater relative hazard (aHR) for subsequent intracranial haemorrhage than for ischaemic stroke, but the absolute risk of ischaemic stroke is higher than that of intracranial haemorrhage, regardless of cerebral microbleed presence, antomical distribution, or burden.}, language = {en} } @article{MarenholzEsparzaGordilloRueschendorfetal.2015, author = {Marenholz, Ingo and Esparza-Gordillo, Jorge and R{\"u}schendorf, Franz and Bauerfeind, Anja and Strachan, David P. and Spycher, Ben D. and Baurecht, Hansj{\"o}rg and Magaritte-Jeannin, Patricia and S{\"a}{\"a}f, Annika and Kerkhof, Marjan and Ege, Markus and Baltic, Svetlana and Matheson, Melanie C. and Li, Jin and Michel, Sven and Ang, Wei Q. and McArdle, Wendy and Arnold, Andreas and Homuth, Georg and Demenais, Florence and Bouzigon, Emmanuelle and S{\"o}derh{\"a}ll, Cilla and Pershagen, G{\"o}ran and de Jongste, Johan C. and Postma, Dirkje S. and Braun-Fahrl{\"a}nder, Charlotte and Horak, Elisabeth and Ogorodova, Ludmila M. and Puzyrev, Valery P. and Bragina, Elena Yu and Hudson, Thomas J. and Morin, Charles and Duffy, David L. and Marks, Guy B. and Robertson, Colin F. and Montgomery, Grant W. and Musk, Bill and Thompson, Philip J. and Martin, Nicholas G. and James, Alan and Sleiman, Patrick and Toskala, Elina and Rodriguez, Elke and F{\"o}lster-Holst, Regina and Franke, Andre and Lieb, Wolfgang and Gieger, Christian and Heinzmann, Andrea and Rietschel, Ernst and Keil, Thomas and Cichon, Sven and N{\"o}then, Markus M. and Pennel, Craig E. and Sly, Peter D. and Schmidt, Carsten O. and Matanovic, Anja and Schneider, Valentin and Heinig, Matthias and H{\"u}bner, Norbert and Holt, Patrick G. and Lau, Susanne and Kabesch, Michael and Weidinger, Stefan and Hakonarson, Hakon and Ferreira, Manuel A. R. and Laprise, Catherine and Freidin, Maxim B. and Genuneit, Jon and Koppelman, Gerard H. and Mel{\´e}n, Erik and Dizier, Marie-H{\´e}l{\`e}ne and Henderson, A. John and Lee, Young Ae}, title = {Meta-analysis identifies seven susceptibility loci involved in the atopic march}, series = {Nature Communications}, volume = {6}, journal = {Nature Communications}, number = {8804}, doi = {10.1038/ncomms9804}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-139835}, year = {2015}, abstract = {Eczema often precedes the development of asthma in a disease course called the 'atopic march'. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time; rs9357733 located in EFHC1 on chromosome 6p12.3 (OR 1.27; P = 2.1 x 10(-8)) and rs993226 between TMTC2 and SLC6A15 on chromosome 12q21.3 (OR 1.58; P = 5.3 x 10(-9)). Additional susceptibility loci identified at genome-wide significance are FLG (1q21.3), IL4/KIF3A (5q31.1), AP5B1/OVOL1 (11q13.1), C11orf30/LRRC32 (11q13.5) and IKZF3 (17q21). We show that predominantly eczema loci increase the risk for the atopic march. Our findings suggest that eczema may play an important role in the development of asthma after eczema.}, language = {en} } @article{Franz2022, author = {Franz, David J.}, title = {Moral responsibility for self-deluding beings}, series = {Philosophia}, volume = {50}, journal = {Philosophia}, number = {4}, issn = {0048-3893}, doi = {10.1007/s11406-022-00469-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324871}, pages = {1791-1807}, year = {2022}, abstract = {In this article, I argue for four theses. First, libertarian and compatibilist accounts of moral responsibility agree that the capability of practical reason is the central feature of moral responsibility. Second, this viewpoint leads to a reasons-focused account of human behavior. Examples of human action discussed in debates about moral responsibility suggest that typical human actions are driven primarily by the agent's subjective reasons and are sufficiently transparent for the agent. Third, this conception of self-transparent action is a questionable idealization. As shown by psychological research on self-assessment, motivated reasoning, and terror management theory, humans oftentimes have only a limited understanding of their conduct. Self-deception is rather the rule than the exception. Fourth, taking the limited self-transparency of practical reason seriously leads to a socially contextualized conception of moral responsibility.}, language = {en} } @article{VonaMazaheriLinetal.2021, author = {Vona, Barbara and Mazaheri, Neda and Lin, Sheng-Jia and Dunbar, Lucy A. and Maroofian, Reza and Azaiez, Hela and Booth, Kevin T. and Vitry, Sandrine and Rad, Aboulfazl and R{\"u}schendorf, Franz and Varshney, Pratishtha and Fowler, Ben and Beetz, Christian and Alagramam, Kumar N. and Murphy, David and Shariati, Gholamreza and Sedaghat, Alireza and Houlden, Henry and Petree, Cassidy and VijayKumar, Shruthi and Smith, Richard J. H. and Haaf, Thomas and El-Amraoui, Aziz and Bowl, Michael R. and Varshney, Gaurav K. and Galehdari, Hamid}, title = {A biallelic variant in CLRN2 causes non-syndromic hearing loss in humans}, series = {Human Genetics}, volume = {140}, journal = {Human Genetics}, number = {6}, issn = {1432-1203}, doi = {10.1007/s00439-020-02254-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-267740}, pages = {915-931}, year = {2021}, abstract = {Deafness, the most frequent sensory deficit in humans, is extremely heterogeneous with hundreds of genes involved. Clinical and genetic analyses of an extended consanguineous family with pre-lingual, moderate-to-profound autosomal recessive sensorineural hearing loss, allowed us to identify CLRN2, encoding a tetraspan protein, as a new deafness gene. Homozygosity mapping followed by exome sequencing identified a 14.96 Mb locus on chromosome 4p15.32p15.1 containing a likely pathogenic missense variant in CLRN2 (c.494C > A, NM_001079827.2) segregating with the disease. Using in vitro RNA splicing analysis, we show that the CLRN2 c.494C > A variant leads to two events: (1) the substitution of a highly conserved threonine (uncharged amino acid) to lysine (charged amino acid) at position 165, p.(Thr165Lys), and (2) aberrant splicing, with the retention of intron 2 resulting in a stop codon after 26 additional amino acids, p.(Gly146Lysfs*26). Expression studies and phenotyping of newly produced zebrafish and mouse models deficient for clarin 2 further confirm that clarin 2, expressed in the inner ear hair cells, is essential for normal organization and maintenance of the auditory hair bundles, and for hearing function. Together, our findings identify CLRN2 as a new deafness gene, which will impact future diagnosis and treatment for deaf patients.}, language = {en} } @article{Franz2022, author = {Franz, David J.}, title = {Is Applied Ethics Morally Problematic?}, series = {Journal of Academic Ethics}, volume = {20}, journal = {Journal of Academic Ethics}, issn = {1572-8544}, doi = {10.1007/s10805-021-09417-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-269095}, pages = {359-374}, year = {2022}, abstract = {This paper argues that applied ethics can itself be morally problematic. As illustrated by the case of Peter Singer's criticism of social practice, morally loaded communication by applied ethicists can lead to protests, backlashes, and aggression. By reviewing the psychological literature on self-image, collective identity, and motivated reasoning three categories of morally problematic consequences of ethical criticism by applied ethicists are identified: serious psychological discomfort, moral backfiring, and hostile conflict. The most worrisome is moral backfiring: psychological research suggests that ethical criticism of people's central moral convictions can reinforce exactly those attitudes. Therefore, applied ethicists unintentionally can contribute to a consolidation of precisely those social circumstances that they condemn to be unethical. Furthermore, I argue that the normative concerns raised in this paper are not dependent on the commitment to one specific paradigm in moral philosophy. Utilitarianism, Aristotelian virtue ethics, and Rawlsian contractarianism all provide sound reasons to take morally problematic consequences of ethical criticism seriously. Only the case of deontological ethics is less clear-cut. Finally, I point out that the issues raised in this paper provide an excellent opportunity for further interdisciplinary collaboration between applied ethics and social sciences. I also propose strategies for communicating ethics effectively.}, language = {en} }