TY  - JOUR
A1  - Dörk, Thilo
A1  - Peterlongo, Peter
A1  - Mannermaa, Arto
A1  - Bolla, Manjeet K.
A1  - Wang, Qin
A1  - Dennis, Joe
A1  - Ahearn, Thomas
A1  - Andrulis, Irene L.
A1  - Anton-Culver, Hoda
A1  - Arndt, Volker
A1  - Aronson, Kristan J.
A1  - Augustinsson, Annelie
A1  - Beane Freeman, Laura E.
A1  - Beckmann, Matthias W.
A1  - Beeghly-Fadiel, Alicia
A1  - Behrens, Sabine
A1  - Bermisheva, Marina
A1  - Blomqvist, Carl
A1  - Bogdanova, Natalia V.
A1  - Bojesen, Stig E.
A1  - Brauch, Hiltrud
A1  - Brenner, Hermann
A1  - Burwinkel, Barbara
A1  - Canzian, Federico
A1  - Chan, Tsun L.
A1  - Chang-Claude, Jenny
A1  - Chanock, Stephen J.
A1  - Choi, Ji-Yeob
A1  - Christiansen, Hans
A1  - Clarke, Christine L.
A1  - Couch, Fergus J.
A1  - Czene, Kamila
A1  - Daly, Mary B.
A1  - dos-Santos-Silva, Isabel
A1  - Dwek, Miriam
A1  - Eccles, Diana M.
A1  - Ekici, Arif B.
A1  - Eriksson, Mikael
A1  - Evans, D. Gareth
A1  - Fasching, Peter A.
A1  - Figueroa, Jonine
A1  - Flyger, Henrik
A1  - Fritschi, Lin
A1  - Gabrielson, Marike
A1  - Gago-Dominguez, Manuela
A1  - Gao, Chi
A1  - Gapstur, Susan M.
A1  - García-Closas, Montserrat
A1  - García-Sáenz, José A.
A1  - Gaudet, Mia M.
A1  - Giles, Graham G.
A1  - Goldberg, Mark S.
A1  - Goldgar, David E.
A1  - Guenél, Pascal
A1  - Haeberle, Lothar
A1  - Haimann, Christopher A.
A1  - Håkansson, Niclas
A1  - Hall, Per
A1  - Hamann, Ute
A1  - Hartman, Mikael
A1  - Hauke, Jan
A1  - Hein, Alexander
A1  - Hillemanns, Peter
A1  - Hogervorst, Frans B. L.
A1  - Hooning, Maartje J.
A1  - Hopper, John L.
A1  - Howell, Tony
A1  - Huo, Dezheng
A1  - Ito, Hidemi
A1  - Iwasaki, Motoki
A1  - Jakubowska, Anna
A1  - Janni, Wolfgang
A1  - John, Esther M.
A1  - Jung, Audrey
A1  - Kaaks, Rudolf
A1  - Kang, Daehee
A1  - Kapoor, Pooja Middha
A1  - Khusnutdinova, Elza
A1  - Kim, Sung-Won
A1  - Kitahara, Cari M.
A1  - Koutros, Stella
A1  - Kraft, Peter
A1  - Kristensen, Vessela N.
A1  - Kwong, Ava
A1  - Lambrechts, Diether
A1  - Le Marchand, Loic
A1  - Li, Jingmei
A1  - Lindström, Sara
A1  - Linet, Martha
A1  - Lo, Wing-Yee
A1  - Long, Jirong
A1  - Lophatananon, Artitaya
A1  - Lubiński, Jan
A1  - Manoochehri, Mehdi
A1  - Manoukian, Siranoush
A1  - Margolin, Sara
A1  - Martinez, Elena
A1  - Matsuo, Keitaro
A1  - Mavroudis, Dimitris
A1  - Meindl, Alfons
A1  - Menon, Usha
A1  - Milne, Roger L.
A1  - Mohd Taib, Nur Aishah
A1  - Muir, Kenneth
A1  - Mulligan, Anna Marie
A1  - Neuhausen, Susan L.
A1  - Nevanlinna, Heli
A1  - Neven, Patrick
A1  - Newman, William G.
A1  - Offit, Kenneth
A1  - Olopade, Olufunmilayo I.
A1  - Olshan, Andrew F.
A1  - Olson, Janet E.
A1  - Olsson, Håkan
A1  - Park, Sue K.
A1  - Park-Simon, Tjoung-Won
A1  - Peto, Julian
A1  - Plaseska-Karanfilska, Dijana
A1  - Pohl-Rescigno, Esther
A1  - Presneau, Nadege
A1  - Rack, Brigitte
A1  - Radice, Paolo
A1  - Rashid, Muhammad U.
A1  - Rennert, Gad
A1  - Rennert, Hedy S.
A1  - Romero, Atocha
A1  - Ruebner, Matthias
A1  - Saloustros, Emmanouil
A1  - Schmidt, Marjanka K.
A1  - Schmutzler, Rita K.
A1  - Schneider, Michael O.
A1  - Schoemaker, Minouk J.
A1  - Scott, Christopher
A1  - Shen, Chen-Yang
A1  - Shu, Xiao-Ou
A1  - Simard, Jaques
A1  - Slager, Susan
A1  - Smichkoska, Snezhana
A1  - Southey, Melissa C.
A1  - Spinelli, John J.
A1  - Stone, Jennifer
A1  - Surowy, Harald
A1  - Swerdlow, Anthony J.
A1  - Tamimi, Rulla M.
A1  - Tapper, William J.
A1  - Teo, Soo H.
A1  - Terry, Mary Beth
A1  - Toland, Amanda E.
A1  - Tollenaar, Rob A. E. M.
A1  - Torres, Diana
A1  - Torres-Mejía, Gabriela
A1  - Troester, Melissa A.
A1  - Truong, Thérèse
A1  - Tsugane, Shoichiro
A1  - Untch, Michael
A1  - Vachon, Celine M.
A1  - van den Ouweland, Ans M. W.
A1  - van Veen, Elke M.
A1  - Vijai, Joseph
A1  - Wendt, Camilla
A1  - Wolk, Alicja
A1  - Yu, Jyh-Cherng
A1  - Zheng, Wei
A1  - Ziogas, Argyrios
A1  - Ziv, Elad
A1  - Dunnig, Alison
A1  - Pharaoh, Paul D. P.
A1  - Schindler, Detlev
A1  - Devilee, Peter
A1  - Easton, Douglas F.
T1  - Two truncating variants in FANCC and breast cancer risk
JF  - Scientific Reports
N2  - Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44–1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.
KW  - oncology
KW  - risk factors
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-222838
VL  - 9
ER  - 
TY  - JOUR
A1  - Manchia, Mirko
A1  - Adli, Mazda
A1  - Akula, Nirmala
A1  - Arda, Raffaella
A1  - Aubry, Jean-Michel
A1  - Backlund, Lena
A1  - Banzato, Claudio E. M.
A1  - Baune, Bernhard T.
A1  - Bellivier, Frank
A1  - Bengesser, Susanne
A1  - Biernacka, Joanna M.
A1  - Brichant-Petitjean, Clara
A1  - Bui, Elise
A1  - Calkin, Cynthia V.
A1  - Cheng, Andrew Tai Ann
A1  - Chillotti, Caterina
A1  - Cichon, Sven
A1  - Clark, Scott
A1  - Czerski, Piotr M.
A1  - Dantas, Clarissa
A1  - Del Zompo, Maria
A1  - DePaulo, J. Raymond
A1  - Detera-Wadleigh, Sevilla D.
A1  - Etain, Bruno
A1  - Falkai, Peter
A1  - Frisén, Louise
A1  - Frye, Mark A.
A1  - Fullerton, Jan
A1  - Gard, Sébastien
A1  - Garnham, Julie
A1  - Goes, Fernando S.
A1  - Grof, Paul
A1  - Gruber, Oliver
A1  - Hashimoto, Ryota
A1  - Hauser, Joanna
A1  - Heilbronner, Urs
A1  - Hoban, Rebecca
A1  - Hou, Liping
A1  - Jamain, Stéphane
A1  - Kahn, Jean-Pierre
A1  - Kassem, Layla
A1  - Kato, Tadafumi
A1  - Kelsoe, John R.
A1  - Kittel-Schneider, Sarah
A1  - Kliwicki, Sebastian
A1  - Kuo, Po-Hsiu
A1  - Kusumi, Ichiro
A1  - Laje, Gonzalo
A1  - Lavebratt, Catharina
A1  - Leboyer, Marion
A1  - Leckband, Susan G.
A1  - López Jaramillo, Carlos A.
A1  - Maj, Mario
A1  - Malafosse, Alain
A1  - Martinsson, Lina
A1  - Masui, Takuya
A1  - Mitchell, Philip B.
A1  - Mondimore, Frank
A1  - Monteleone, Palmiero
A1  - Nallet, Audrey
A1  - Neuner, Maria
A1  - Novák, Tomás
A1  - O'Donovan, Claire
A1  - Ösby, Urban
A1  - Ozaki, Norio
A1  - Perlis, Roy H.
A1  - Pfennig, Andrea
A1  - Potash, James B.
A1  - Reich-Erkelenz, Daniela
A1  - Reif, Andreas
A1  - Reininghaus, Eva
A1  - Richardson, Sara
A1  - Rouleau, Guy A.
A1  - Rybakowski, Janusz K.
A1  - Schalling, Martin
A1  - Schofield, Peter R.
A1  - Schubert, Oliver K.
A1  - Schweizer, Barbara
A1  - Seemüller, Florian
A1  - Grigoroiu-Serbanescu, Maria
A1  - Severino, Giovanni
A1  - Seymour, Lisa R.
A1  - Slaney, Claire
A1  - Smoller, Jordan W.
A1  - Squassina, Alessio
A1  - Stamm, Thomas
A1  - Steele, Jo
A1  - Stopkova, Pavla
A1  - Tighe, Sarah K.
A1  - Tortorella, Alfonso
A1  - Turecki, Gustavo
A1  - Wray, Naomi R.
A1  - Wright, Adam
A1  - Zandi, Peter P.
A1  - Zilles, David
A1  - Bauer, Michael
A1  - Rietschel, Marcella
A1  - McMahon, Francis J.
A1  - Schulze, Thomas G.
A1  - Alda, Martin
T1  - Assessment of Response to Lithium Maintenance Treatment in Bipolar Disorder: A Consortium on Lithium Genetics (ConLiGen) Report
JF  - PLoS ONE
N2  - Objective: The assessment of response to lithium maintenance treatment in bipolar disorder (BD) is complicated by variable length of treatment, unpredictable clinical course, and often inconsistent compliance. Prospective and retrospective methods of assessment of lithium response have been proposed in the literature. In this study we report the key phenotypic measures of the "Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder" scale currently used in the Consortium on Lithium Genetics (ConLiGen) study. 
Materials and Methods: Twenty-nine ConLiGen sites took part in a two-stage case-vignette rating procedure to examine inter-rater agreement [Kappa (\(\kappa\))] and reliability [intra-class correlation coefficient (ICC)] of lithium response. Annotated first-round vignettes and rating guidelines were circulated to expert research clinicians for training purposes between the two stages. Further, we analyzed the distributional properties of the treatment response scores available for 1,308 patients using mixture modeling. 
Results: Substantial and moderate agreement was shown across sites in the first and second sets of vignettes (\(\kappa\) = 0.66 and \(\kappa\) = 0.54, respectively), without significant improvement from training. However, definition of response using the A score as a quantitative trait and selecting cases with B criteria of 4 or less showed an improvement between the two stages (\(ICC_1 = 0.71\) and \(ICC_2 = 0.75\), respectively). Mixture modeling of score distribution indicated three subpopulations (full responders, partial responders, non responders). 
Conclusions: We identified two definitions of lithium response, one dichotomous and the other continuous, with moderate to substantial inter-rater agreement and reliability. Accurate phenotypic measurement of lithium response is crucial for the ongoing ConLiGen pharmacogenomic study.
KW  - age
KW  - observer agreement
KW  - prophylactic lithium
KW  - mapping susceptibility genes
KW  - mood disorders
KW  - onset
KW  - association
KW  - reliability
KW  - morality
KW  - illness
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130938
VL  - 8
IS  - 6
ER  - 
TY  - JOUR
A1  - Rayner, Christopher
A1  - Coleman, Jonathan R. I.
A1  - Purves, Kirstin L.
A1  - Hodsoll, John
A1  - Goldsmith, Kimberley
A1  - Alpers, Georg W.
A1  - Andersson, Evelyn
A1  - Arolt, Volker
A1  - Boberg, Julia
A1  - Bögels, Susan
A1  - Creswell, Cathy
A1  - Cooper, Peter
A1  - Curtis, Charles
A1  - Deckert, Jürgen
A1  - Domschke, Katharina
A1  - El Alaoui, Samir
A1  - Fehm, Lydia
A1  - Fydrich, Thomas
A1  - Gerlach, Alexander L.
A1  - Grocholewski, Anja
A1  - Hahlweg, Kurt
A1  - Hamm, Alfons
A1  - Hedman, Erik
A1  - Heiervang, Einar R.
A1  - Hudson, Jennifer L.
A1  - Jöhren, Peter
A1  - Keers, Robert
A1  - Kircher, Tilo
A1  - Lang, Thomas
A1  - Lavebratt, Catharina
A1  - Lee, Sang-hyuck
A1  - Lester, Kathryn J.
A1  - Lindefors, Nils
A1  - Margraf, Jürgen
A1  - Nauta, Maaike
A1  - Pané-Farré, Christiane A.
A1  - Pauli, Paul
A1  - Rapee, Ronald M.
A1  - Reif, Andreas
A1  - Rief, Winfried
A1  - Roberts, Susanna
A1  - Schalling, Martin
A1  - Schneider, Silvia
A1  - Silverman, Wendy K.
A1  - Ströhle, Andreas
A1  - Teismann, Tobias
A1  - Thastum, Mikael
A1  - Wannemüller, Andre
A1  - Weber, Heike
A1  - Wittchen, Hans-Ulrich
A1  - Wolf, Christiane
A1  - Rück, Christian
A1  - Breen, Gerome
A1  - Eley, Thalia C.
T1  - A genome-wide association meta-analysis of prognostic outcomes following cognitive behavioural therapy in individuals with anxiety and depressive disorders
JF  - Translational Psychiatry
N2  - Major depressive disorder and the anxiety disorders are highly prevalent, disabling and moderately heritable. Depression and anxiety are also highly comorbid and have a strong genetic correlation (r(g) approximate to 1). Cognitive behavioural therapy is a leading evidence-based treatment but has variable outcomes. Currently, there are no strong predictors of outcome. Therapygenetics research aims to identify genetic predictors of prognosis following therapy. We performed genome-wide association meta-analyses of symptoms following cognitive behavioural therapy in adults with anxiety disorders (n = 972), adults with major depressive disorder (n = 832) and children with anxiety disorders (n = 920; meta-analysis n = 2724). We (h(SNP)(2)) and polygenic scoring was used to examine genetic associations between therapy outcomes and psychopathology, personality and estimated the variance in therapy outcomes that could be explained by common genetic variants learning. No single nucleotide polymorphisms were strongly associated with treatment outcomes. No significant estimate of h(SNP)(2) could be obtained, suggesting the heritability of therapy outcome is smaller than our analysis was powered to detect. Polygenic scoring failed to detect genetic overlap between therapy outcome and psychopathology, personality or learning. This study is the largest therapygenetics study to date. Results are consistent with previous, similarly powered genome-wide association studies of complex traits.
KW  - Human behaviour
KW  - Personalized medicine
KW  - Prognostic markers
KW  - Psychiatric disorders
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225048
VL  - 9
IS  - 150
ER  - 
TY  - JOUR
A1  - Gabriel, Katharina M. A.
A1  - Jírů-Hillmann, Steffi
A1  - Kraft, Peter
A1  - Selig, Udo
A1  - Rücker, Victoria
A1  - Mühler, Johannes
A1  - Dötter, Klaus
A1  - Keidel, Matthias
A1  - Soda, Hassan
A1  - Rascher, Alexandra
A1  - Schneider, Rolf
A1  - Pfau, Mathias
A1  - Hoffmann, Roy
A1  - Stenzel, Joachim
A1  - Benghebrid, Mohamed
A1  - Goebel, Tobias
A1  - Doerck, Sebastian
A1  - Kramer, Daniela
A1  - Haeusler, Karl Georg
A1  - Volkmann, Jens
A1  - Heuschmann, Peter U.
A1  - Fluri, Felix
T1  - Two years' experience of implementing a comprehensive telemedical stroke network comprising in mainly rural region: the Transregional Network for Stroke Intervention with Telemedicine (TRANSIT-Stroke)
JF  - BMC Neurology
N2  - Background 
Telemedicine improves the quality of acute stroke care in rural regions with limited access to specialized stroke care. We report the first 2 years' experience of implementing a comprehensive telemedical stroke network comprising all levels of stroke care in a defined region. 

Methods 
The TRANSIT-Stroke network covers a mainly rural region in north-western Bavaria (Germany). All hospitals providing acute stroke care in this region participate in TRANSIT-Stroke, including four hospitals with a supra-regional certified stroke unit (SU) care (level III), three of those providing teleconsultation to two hospitals with a regional certified SU (level II) and five hospitals without specialized SU care (level I). For a two-year-period (01/2015 to 12/2016), data of eight of these hospitals were available; 13 evidence-based quality indicators (QIs) related to processes during hospitalisation were evaluated quarterly and compared according to predefined target values between level-I- and level-II/III-hospitals. 

Results 
Overall, 7881 patients were included (mean age 74.6 years +/- 12.8; 48.4% female). In level-II/III-hospitals adherence of all QIs to predefined targets was high ab initio. In level-I-hospitals, three patterns of QI-development were observed: a) high adherence ab initio (31%), mainly in secondary stroke prevention; b) improvement over time (44%), predominantly related to stroke specific diagnosis and in-hospital organization; c) no clear time trends (25%). Overall, 10 out of 13 QIs reached predefined target values of quality of care at the end of the observation period. 

Conclusion 
The implementation of the comprehensive TRANSIT-Stroke network resulted in an improvement of quality of care in level-I-hospitals.
KW  - pilot project
KW  - care tempis
KW  - ischemic stroke
KW  - thrombolysis
KW  - areas
KW  - time
KW  - hospitals
KW  - mortality
KW  - outcomes
KW  - quality
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229214
VL  - 20
ER  - 
TY  - JOUR
A1  - Schoffer, Olaf
A1  - Schülein, Stefanie
A1  - Arand, Gerlinde
A1  - Arnholdt, Hans
A1  - Baaske, Dieter
A1  - Bargou, Ralf C.
A1  - Becker, Nikolaus
A1  - Beckmann, Matthias W.
A1  - Bodack, Yves
A1  - Böhme, Beatrix
A1  - Bozkurt, Tayfun
A1  - Breitsprecher, Regine
A1  - Buchali, Andre
A1  - Burger, Elke
A1  - Burger, Ulrike
A1  - Dommisch, Klaus
A1  - Elsner, Gudrun
A1  - Fernschild, Karin
A1  - Flintzer, Ulrike
A1  - Funke, Uwe
A1  - Gerken, Michael
A1  - Göbel, Hubert
A1  - Grobe, Norbert
A1  - Gumpp, Vera
A1  - Heinzerling, Lucie
A1  - Kempfer, Lana Raffaela
A1  - Kiani, Alexander
A1  - Klinkhammer-Schalke, Monika
A1  - Klöcking, Sabine
A1  - Kreibich, Ute
A1  - Knabner, Katrin
A1  - Kuhn, Peter
A1  - Lutze, Stine
A1  - Mäder, Uwe
A1  - Maisel, Tanja
A1  - Maschke, Jan
A1  - Middeke, Martin
A1  - Neubauer, Andreas
A1  - Niedostatek, Antje
A1  - Opazo-Saez, Anabelle
A1  - Peters, Christoph
A1  - Schell, Beatrice
A1  - Schenkirsch, Gerhard
A1  - Schmalenberg, Harald
A1  - Schmidt, Peter
A1  - Schneider, Constanze
A1  - Schubotz, Birgit
A1  - Seide, Anika
A1  - Strecker, Paul
A1  - Taubenheim, Sabine
A1  - Wackes, Matthias
A1  - Weiß, Steffen
A1  - Welke, Claudia
A1  - Werner, Carmen
A1  - Wittekind, Christian
A1  - Wulff, Jörg
A1  - Zettl, Heike
A1  - Klug, Stefanie J.
T1  - Tumour stage distribution and survival of malignant melanoma in Germany 2002-2011
JF  - BMC Cancer
N2  - Background

Over the past two decades, there has been a rising trend in malignant melanoma incidence worldwide. In 2008, Germany introduced a nationwide skin cancer screening program starting at age 35. The aims of this study were to analyse the distribution of malignant melanoma tumour stages over time, as well as demographic and regional differences in stage distribution and survival of melanoma patients.

Methods

Pooled data from 61 895 malignant melanoma patients diagnosed between 2002 and 2011 and documented in 28 German population-based and hospital-based clinical cancer registries were analysed using descriptive methods, joinpoint regression, logistic regression and relative survival.

Results

The number of annually documented cases increased by 53.2% between 2002 (N = 4 779) and 2011 (N = 7 320). There was a statistically significant continuous positive trend in the proportion of stage UICC I cases diagnosed between 2002 and 2011, compared to a negative trend for stage UICC II. No trends were found for stages UICC III and IV respectively. Age (OR 0.97, 95% CI 0.97–0.97), sex (OR 1.18, 95% CI 1.11–1.25), date of diagnosis (OR 1.05, 95% CI 1.04–1.06), ‘diagnosis during screening’ (OR 3.24, 95% CI 2.50–4.19) and place of residence (OR 1.23, 95% CI 1.16–1.30) had a statistically significant influence on the tumour stage at diagnosis. The overall 5-year relative survival for invasive cases was 83.4% (95% CI 82.8–83.9%).

Conclusions

No distinct changes in the distribution of malignant melanoma tumour stages among those aged 35 and older were seen that could be directly attributed to the introduction of skin cancer screening in 2008.
"
KW  - Malignant melanoma
KW  - TNM staging
KW  - Survival analysis
KW  - Skin cancer screening
KW  - Stage distribution
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164544
VL  - 16
IS  - 936
ER  - 
TY  - JOUR
A1  - Sommer, Kim K.
A1  - Amr, Ali
A1  - Bavendiek, Udo
A1  - Beierle, Felix
A1  - Brunecker, Peter
A1  - Dathe, Henning
A1  - Eils, Jürgen
A1  - Ertl, Maximilian
A1  - Fette, Georg
A1  - Gietzelt, Matthias
A1  - Heidecker, Bettina
A1  - Hellenkamp, Kristian
A1  - Heuschmann, Peter
A1  - Hoos, Jennifer D. E.
A1  - Kesztyüs, Tibor
A1  - Kerwagen, Fabian
A1  - Kindermann, Aljoscha
A1  - Krefting, Dagmar
A1  - Landmesser, Ulf
A1  - Marschollek, Michael
A1  - Meder, Benjamin
A1  - Merzweiler, Angela
A1  - Prasser, Fabian
A1  - Pryss, Rüdiger
A1  - Richter, Jendrik
A1  - Schneider, Philipp
A1  - Störk, Stefan
A1  - Dieterich, Christoph
T1  - Structured, harmonized, and interoperable integration of clinical routine data to compute heart failure risk scores
JF  - Life
N2  - Risk prediction in patients with heart failure (HF) is essential to improve the tailoring of preventive, diagnostic, and therapeutic strategies for the individual patient, and effectively use health care resources. Risk scores derived from controlled clinical studies can be used to calculate the risk of mortality and HF hospitalizations. However, these scores are poorly implemented into routine care, predominantly because their calculation requires considerable efforts in practice and necessary data often are not available in an interoperable format. In this work, we demonstrate the feasibility of a multi-site solution to derive and calculate two exemplary HF scores from clinical routine data (MAGGIC score with six continuous and eight categorical variables; Barcelona Bio-HF score with five continuous and six categorical variables). Within HiGHmed, a German Medical Informatics Initiative consortium, we implemented an interoperable solution, collecting a harmonized HF-phenotypic core data set (CDS) within the openEHR framework. Our approach minimizes the need for manual data entry by automatically retrieving data from primary systems. We show, across five participating medical centers, that the implemented structures to execute dedicated data queries, followed by harmonized data processing and score calculation, work well in practice. In summary, we demonstrated the feasibility of clinical routine data usage across multiple partner sites to compute HF risk scores. This solution can be extended to a large spectrum of applications in clinical care.
KW  - medical informatics initiative
KW  - HiGHmed
KW  - medical data integration center
KW  - clinical routine data
KW  - heart failure
KW  - risk prediction scores
KW  - semantic interoperability
KW  - openEHR
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-275239
SN  - 2075-1729
VL  - 12
IS  - 5
ER  - 
TY  - JOUR
A1  - Arlt, Wiebke
A1  - Biehl, Michael
A1  - Taylor, Angela E.
A1  - Hahner, Stefanie
A1  - Libé, Rossella
A1  - Hughes, Beverly A.
A1  - Schneider, Petra
A1  - Smith, David J.
A1  - Stiekema, Han
A1  - Krone, Nils
A1  - Porfiri, Emilio
A1  - Opocher, Giuseppe
A1  - Bertherat, Jerôme
A1  - Mantero, Franco
A1  - Allolio, Bruno
A1  - Terzolo, Massimo
A1  - Nightingale, Peter
A1  - Shackleton, Cedric H. L.
A1  - Bertagna, Xavier
A1  - Fassnacht, Martin
A1  - Stewart, Paul M.
T1  - Urine Steroid Metabolomics as a Biomarker Tool for Detecting Malignancy in Adrenal Tumors
JF  - The Journal of Clinical Endocrinology & Metabolism
N2  - Context:
Adrenal tumors have a prevalence of around 2% in the general population. Adrenocortical carcinoma (ACC) is rare but accounts for 2–11% of incidentally discovered adrenal masses. Differentiating ACC from adrenocortical adenoma (ACA) represents a diagnostic challenge in patients with adrenal incidentalomas, with tumor size, imaging, and even histology all providing unsatisfactory predictive values.

Objective:
Here we developed a novel steroid metabolomic approach, mass spectrometry-based steroid profiling followed by machine learning analysis, and examined its diagnostic value for the detection of adrenal malignancy.

Design:
Quantification of 32 distinct adrenal derived steroids was carried out by gas chromatography/mass spectrometry in 24-h urine samples from 102 ACA patients (age range 19–84 yr) and 45 ACC patients (20–80 yr). Underlying diagnosis was ascertained by histology and metastasis in ACC and by clinical follow-up [median duration 52 (range 26–201) months] without evidence of metastasis in ACA. Steroid excretion data were subjected to generalized matrix learning vector quantization (GMLVQ) to identify the most discriminative steroids.

Results:
Steroid profiling revealed a pattern of predominantly immature, early-stage steroidogenesis in ACC. GMLVQ analysis identified a subset of nine steroids that performed best in differentiating ACA from ACC. Receiver-operating characteristics analysis of GMLVQ results demonstrated sensitivity = specificity = 90% (area under the curve = 0.97) employing all 32 steroids and sensitivity = specificity = 88% (area under the curve = 0.96) when using only the nine most differentiating markers.

Conclusions:
Urine steroid metabolomics is a novel, highly sensitive, and specific biomarker tool for discriminating benign from malignant adrenal tumors, with obvious promise for the diagnostic work-up of patients with adrenal incidentalomas.
KW  - adrenal cortex hormones
KW  - urine
KW  - adrenal cortex neoplasms
KW  - mass spectrometry
KW  - metabolomics
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-154682
VL  - 96
IS  - 12
SP  - 3775
EP  - 3784
ER  - 
TY  - JOUR
A1  - Seydelmann, Nora
A1  - Liu, Dan
A1  - Krämer, Johannes
A1  - Drechsler, Christiane
A1  - Hu, Kai
A1  - Nordbeck, Peter
A1  - Schneider, Andreas
A1  - Störk, Stefan
A1  - Bijnens, Bart
A1  - Ertl, Georg
A1  - Wanner, Christoph
A1  - Weidemann, Frank
T1  - High-Sensitivity Troponin: A Clinical Blood Biomarker for Staging Cardiomyopathy in Fabry Disease
JF  - Journal of the American Heart Association
N2  - Background
High‐sensitivity troponin (hs‐TNT), a biomarker of myocardial damage, might be useful for assessing fibrosis in Fabry cardiomyopathy. We performed a prospective analysis of hs‐TNT as a biomarker for myocardial changes in Fabry patients and a retrospective longitudinal follow‐up study to assess longitudinal hs‐TNT changes relative to fibrosis and cardiomyopathy progression.

Methods and Results
For the prospective analysis, hs‐TNT from 75 consecutive patients with genetically confirmed Fabry disease was analyzed relative to typical Fabry‐associated echocardiographic findings and total myocardial fibrosis as measured by late gadolinium enhancement (LE) on magnetic resonance imaging. Longitudinal data (3.9±2.0 years), including hs‐TNT, LE, and echocardiographic findings from 58 Fabry patients, were retrospectively collected. Hs‐TNT level positively correlated with LE (linear correlation coefficient, 0.72; odds ratio, 32.81 [95% CI, 3.56–302.59]; P=0.002); patients with elevated baseline hs‐TNT (>14 ng/L) showed significantly increased LE (median: baseline, 1.9 [1.1–3.3] %; follow‐up, 3.2 [2.3–4.9] %; P<0.001) and slightly elevated hs‐TNT (baseline, 44.7 [30.1–65.3] ng/L; follow‐up, 49.1 [27.6–69.5] ng/L; P=0.116) during follow‐up. Left ventricular wall thickness and EF of patients with elevated hs‐TNT were decreased during follow‐up, indicating potential cardiomyopathy progression.

Conclusions
hs‐TNT is an accurate, easily accessible clinical blood biomarker for detecting replacement fibrosis in patients with Fabry disease and a qualified predictor of cardiomyopathy progression. Thus, hs‐TNT could be helpful for staging and follow‐up of Fabry patients.
KW  - biomarker
KW  - cardiomyopathy
KW  - fabry disease
KW  - myocardial fibrosis
KW  - troponin T
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165682
VL  - 5
IS  - e002839
ER  - 
TY  - JOUR
A1  - Magyar, Attila
A1  - Wagner, Martin
A1  - Thomas, Phillip
A1  - Malsch, Carolin
A1  - Schneider, Reinhard
A1  - Störk, Stefan
A1  - Heuschmann, Peter U
A1  - Leyh, Rainer G
A1  - Oezkur, Mehmet
T1  - HO-1 concentrations 24 hours after cardiac surgery are associated with the incidence of acute kidney injury: a prospective cohort study
JF  - International Journal of Nephrology and Renovascular Disease
N2  - Background: 
Acute kidney injury (AKI) is a serious complication after cardiac surgery that is associated with increased mortality and morbidity. Heme oxygenase-1 (HO-1) is an enzyme synthesized in renal tubular cells as one of the most intense responses to oxidant stress linked with protective, anti-inflammatory properties. Yet, it is unknown if serum HO-1 induction following cardiac surgical procedure involving cardiopulmonary bypass (CPB) is associated with incidence and severity of AKI.

Patients and methods: 
In the present study, we used data from a prospective cohort study of 150 adult cardiac surgical patients. HO-1 measurements were performed before, immediately after and 24 hours post-CPB. In univariate and multivariate analyses, the association between HO-1 and AKI was investigated.

Results: 
AKI with an incidence of 23.3% (35 patients) was not associated with an early elevation of HO-1 after CPB in all patients (P=0.88), whereas patients suffering from AKI developed a second burst of HO-1 24 hours after CBP. In patients without AKI, the HO-1 concentrations dropped to baseline values (P=0.031). Furthermore, early HO-1 induction was associated with CPB time (P=0.046), while the ones 24 hours later lost this association (P=0.219).

Conclusion: 
The association of the second HO-1 burst 24 hours after CBP might help to distinguish between the causality of AKI in patients undergoing CBP, thus helping to adapt patient stratification and management.
KW  - acute kidney injury
KW  - cardiac surgery
KW  - heme oxygenase-1
KW  - cardiopulmonary bypass
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177250
VL  - 12
ER  - 
TY  - JOUR
A1  - Rabinowitz, Mitchell
A1  - Ornstein, Peter A.
A1  - Folds-Bennett, Trisha H.
A1  - Schneider, Wolfgang
T1  - Age-related differences in speed of processing: Unconfounding age and experience
N2  - No abstract available
KW  - Psychologie
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62223
ER  - 
TY  - JOUR
A1  - Doerck, Sebastian
A1  - Goebel, Kerstin
A1  - Weise, Gesa
A1  - Schneider-Hohendorf, Tilman
A1  - Reinhardt, Michael
A1  - Hauff, Peter
A1  - Schwab, Nicholas
A1  - Linker, Ralf
A1  - Maeurer, Mathias
A1  - Meuth, Sven G.
A1  - Wiendl, Heinz
T1  - Temporal Pattern of ICAM-I Mediated Regulatory T Cell Recruitment to Sites of Inflammation in Adoptive Transfer Model of Multiple Sclerosis
N2  - Migration of immune cells to the target organ plays a key role in autoimmune disorders like multiple sclerosis (MS). However, the exact underlying mechanisms of this active process during autoimmune lesion pathogenesis remain elusive. To test if pro-inflammatory and regulatory T cells migrate via a similar molecular mechanism, we analyzed the expression of different adhesion molecules, as well as the composition of infiltrating T cells in an in vivo model of MS, adoptive transfer experimental autoimmune encephalomyelitis in rats. We found that the upregulation of ICAM-I and VCAM-I parallels the development of clinical disease onset, but persists on elevated levels also in the phase of clinical remission. However, the composition of infiltrating T cells found in the developing versus resolving lesion phase changed over time, containing increased numbers of regulatory T cells (FoxP3) only in the phase of clinical remission. In order to test the relevance of the expression of cell adhesion molecules, animals were treated with purified antibodies to ICAM-I and VCAM-I either in the phase of active disease or in early remission. Treatment with a blocking ICAM-I antibody in the phase of disease progression led to a milder disease course. However, administration during early clinical remission aggravates clinical symptoms. Treatment with anti-VCAM-I at different timepoints had no significant effect on the disease course. In summary, our results indicate that adhesion molecules are not only important for capture and migration of pro-inflammatory T cells into the central nervous system, but also permit access of anti-inflammatory cells, such as regulatory T cells. Therefore it is likely to assume that intervention at the blood brain barrier is time dependent and could result in different therapeutic outcomes depending on the phase of CNS lesion development.
KW  - Multiple Sklerose
Y1  - 2010
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68565
ER  - 
TY  - JOUR
A1  - Rivero, Olga
A1  - Reif, Andreas
A1  - Sanjuan, Julio
A1  - Molto, Maria D.
A1  - Kittel-Schneider, Sarah
A1  - Najera, Carmen
A1  - Toepner, Theresia
A1  - Lesch, Klaus-Peter
T1  - Impact of the AHI1 Gene on the Vulnerability to Schizophrenia: A Case-Control Association Study
N2  - Background: The Abelson helper integration-1 (AHI1) gene is required for both cerebellar and cortical development in humans. While the accelerated evolution of AHI1 in the human lineage indicates a role in cognitive (dys)function, a linkage scan in large pedigrees identified AHI1 as a positional candidate for schizophrenia. To further investigate the contribution of AHI1 to the susceptibility of schizophrenia, we evaluated the effect of AHI1 variation on the vulnerability to psychosis in two samples from Spain and Germany. Methodology/Principal Findings: 29 single-nucleotide polymorphisms (SNPs) located in a genomic region including the AHI1 gene were genotyped in two samples from Spain (280 patients with psychotic disorders; 348 controls) and Germany (247 patients with schizophrenic disorders; 360 controls). Allelic, genotypic and haplotype frequencies were compared between cases and controls in both samples separately, as well as in the combined sample. The effect of genotype on several psychopathological measures (BPRS, KGV, PANSS) assessed in a Spanish subsample was also evaluated. We found several significant associations in the Spanish sample. Particularly, rs7750586 and rs911507, both located upstream of the AHI1 coding region, were found to be associated with schizophrenia in the analysis of genotypic (p = 0.0033, and 0.031,respectively) and allelic frequencies (p = 0.001 in both cases). Moreover, several other risk and protective haplotypes were detected (0.006,p,0.036). Joint analysis also supported the association of rs7750586 and rs911507 with the risk for schizophrenia. The analysis of clinical measures also revealed an effect on symptom severity (minimum P value = 0.0037). Conclusions/Significance: Our data support, in agreement with previous reports, an effect of AHI1 variation on the susceptibility to schizophrenia in central and southern European populations.
KW  - Schizophrenie
KW  - Abelson helper integration-1 (AHI1)
Y1  - 2010
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68501
ER  - 
TY  - JOUR
A1  - Schneider, Peter
T1  - SIRT Was Given Short Shrift
JF  - Deutsches Ärzteblatt International
N2  - No abstract available.
KW  - heptacellular carcinoma
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-119564
VL  - 111
IS  - 26
ER  - 
TY  - JOUR
A1  - Kittel-Schneider, Sarah
A1  - Kenis, Gunter
A1  - Schek, Julia
A1  - van den Hove, Daniel
A1  - Prickaerts, Jos
A1  - Lesch, Klaus-Peter
A1  - Steinbusch, Harry
A1  - Reif, Andreas
T1  - Expression of monoamine transporters, nitric oxide synthase 3, and neurotrophin genes in antidepressant-stimulated astrocytes
JF  - Frontiers in Psychiatry
N2  - Background: There is increasing evidence that glial cells play a role in the pathomechanisms of mood disorders and the mode of action of antidepressant drugs. 
Methods: To examine whether there is a direct effect on the expression of different genes encoding proteins that have been implicated in the pathophysiology of affective disorders, primary astrocyte cell cultures from rats were treated with two different antidepressant drugs, imipramine and escitalopram, and the RNA expression of brain-derived neurotrophic factor (Bdnf), serotonin transporter (5Htt), dopamine transporter (Dat), and endothelial nitric oxide synthase (Nos3) was examined. 
Results: Stimulation of astroglial cell culture with imipramine, a tricyclic antidepressant, led to a significant increase of the Bdnf RNA level whereas treatment with escitalopram did not. In contrast, 5Htt was not differentially expressed after antidepressant treatment. Finally, neither Dat nor Nos3 RNA expression was detected in cultured astrocytes. 
Conclusion: These data provide further evidence for a role of astroglial cells in the molecular mechanisms of action of antidepressants.
KW  - monoamine transporters
KW  - BDNF
KW  - geneexpression
KW  - astrocytes
KW  - glia
KW  - depression
KW  - antidepressant
KW  - mechanismofaction
KW  - nitricoxidesynthase
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-123627
VL  - 3
ER  - 
TY  - JOUR
A1  - Schaeffer, Evelin L.
A1  - Kühn, Franziska
A1  - Schmitt, Angelika
A1  - Gattaz, Wagner F.
A1  - Gruber, Oliver
A1  - Schneider-Axmann, Thomas
A1  - Falkai, Peter
A1  - Schmitt, Andrea
T1  - Increased cell proliferation in the rat anterior cingulate cortex following neonatal hypoxia: relevance to schizophrenia
JF  - Journal of Neural Transmission
N2  - As a consequence of obstetric complications, neonatal hypoxia has been discussed as an environmental factor in the pathophysiology of schizophrenia. However, the biological consequences of hypoxia are unclear. The neurodevelopmental hypothesis of schizophrenia suggests that the onset of abnormal brain development and neuropathology occurs perinatally, whereas symptoms of the disease appear in early adulthood. In our animal model of chronic neonatal hypoxia, we have detected behavioral alterations resembling those known from schizophrenia. Disturbances in cell proliferation possibly contribute to the pathophysiology of this disease. In the present study, we used postnatal rats to investigate cell proliferation in several brain areas following neonatal hypoxia. Rats were repeatedly exposed to hypoxia (89 % N2, 11 % O2) from postnatal day (PD) 4–8. We then evaluated cell proliferation on PD 13 and 39, respectively. These investigations were performed in the anterior cingulate cortex (ACC), caudate-putamen (CPU), dentate gyrus, and subventricular zone. Rats exposed to hypoxia exhibited increased cell proliferation in the ACC at PD 13, normalizing at PD 39. In other brain regions, no alterations have been detected. Additionally, hypoxia-treated rats showed decreased CPU volume at PD 13. The results of the present study on the one hand support the assumption of chronic hypoxia influencing transient cell proliferation in the ACC, and on the other hand reveal normalization during ageing.
KW  - schizophrenia
KW  - cell proliferation
KW  - rat
KW  - anterior cingulate cortex
KW  - neonatal hypoxia
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-125890
VL  - 120
IS  - 1
ER  - 
TY  - JOUR
A1  - Maier, Sebastian
A1  - Gold, Peter
A1  - Forchel, Alfred
A1  - Gregersen, Niels
A1  - Mork, Jesper
A1  - Höfling, Sven
A1  - Schneider, Christian
A1  - Kamp, Martin
T1  - Bright single photon source based on self-aligned quantum dot-cavity systems
JF  - Optics Express
N2  - We report on a quasi-planar quantum-dot-based single-photon source that shows an unprecedented high extraction efficiency of 42% without complex photonic resonator geometries or post-growth nanofabrication. This very high efficiency originates from the coupling of the photons emitted by a quantum dot to a Gaussian shaped nanohill defect that naturally arises during epitaxial growth in a self-aligned manner. We investigate the morphology of these defects and characterize the photonic operation mechanism. Our results show that these naturally arising coupled quantum dot-defects provide a new avenue for efficient (up to 42% demonstrated) and pure (g(2)(0) value of 0.023) single-photon emission.
KW  - photon statistics
KW  - quantum communications
KW  - resonators
KW  - quantum-well -wire and -dot devices
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-119801
SN  - 1094-4087
VL  - 22
IS  - 7
ER  - 
TY  - JOUR
A1  - Marenholz, Ingo
A1  - Esparza-Gordillo, Jorge
A1  - Rüschendorf, Franz
A1  - Bauerfeind, Anja
A1  - Strachan, David P.
A1  - Spycher, Ben D.
A1  - Baurecht, Hansjörg
A1  - Magaritte-Jeannin, Patricia
A1  - Sääf, Annika
A1  - Kerkhof, Marjan
A1  - Ege, Markus
A1  - Baltic, Svetlana
A1  - Matheson, Melanie C.
A1  - Li, Jin
A1  - Michel, Sven
A1  - Ang, Wei Q.
A1  - McArdle, Wendy
A1  - Arnold, Andreas
A1  - Homuth, Georg
A1  - Demenais, Florence
A1  - Bouzigon, Emmanuelle
A1  - Söderhäll, Cilla
A1  - Pershagen, Göran
A1  - de Jongste, Johan C.
A1  - Postma, Dirkje S.
A1  - Braun-Fahrländer, Charlotte
A1  - Horak, Elisabeth
A1  - Ogorodova, Ludmila M.
A1  - Puzyrev, Valery P.
A1  - Bragina, Elena Yu
A1  - Hudson, Thomas J.
A1  - Morin, Charles
A1  - Duffy, David L.
A1  - Marks, Guy B.
A1  - Robertson, Colin F.
A1  - Montgomery, Grant W.
A1  - Musk, Bill
A1  - Thompson, Philip J.
A1  - Martin, Nicholas G.
A1  - James, Alan
A1  - Sleiman, Patrick
A1  - Toskala, Elina
A1  - Rodriguez, Elke
A1  - Fölster-Holst, Regina
A1  - Franke, Andre
A1  - Lieb, Wolfgang
A1  - Gieger, Christian
A1  - Heinzmann, Andrea
A1  - Rietschel, Ernst
A1  - Keil, Thomas
A1  - Cichon, Sven
A1  - Nöthen, Markus M.
A1  - Pennel, Craig E.
A1  - Sly, Peter D.
A1  - Schmidt, Carsten O.
A1  - Matanovic, Anja
A1  - Schneider, Valentin
A1  - Heinig, Matthias
A1  - Hübner, Norbert
A1  - Holt, Patrick G.
A1  - Lau, Susanne
A1  - Kabesch, Michael
A1  - Weidinger, Stefan
A1  - Hakonarson, Hakon
A1  - Ferreira, Manuel A. R.
A1  - Laprise, Catherine
A1  - Freidin, Maxim B.
A1  - Genuneit, Jon
A1  - Koppelman, Gerard H.
A1  - Melén, Erik
A1  - Dizier, Marie-Hélène
A1  - Henderson, A. John
A1  - Lee, Young Ae
T1  - Meta-analysis identifies seven susceptibility loci involved in the atopic march
JF  - Nature Communications
N2  - 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.
KW  - chromosome 11Q13
KW  - risk
KW  - genomewide association
KW  - hay fever
KW  - birth cohort
KW  - filaggrin mutations
KW  - food allergy
KW  - juvenile myoclonic epilepsy
KW  - childhood asthma
KW  - dermatitis
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-139835
VL  - 6
IS  - 8804
ER  - 
TY  - JOUR
A1  - Schneider, Peter
T1  - Paradigm Shift
JF  - Deutsches Ärzteblatt International
N2  - No abstract available.
KW  - osteoporosis
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-128858
VL  - 110
IS  - 22
ER  - 
TY  - THES
A1  - Schneider, Volkmar Peter Josef
T1  - Retrospektive Studie über die Ergebnisse nach Implantation von autolysiertem, Antigen-extrahiertem, allogenem Knochen
T1  - Retrospective study about results after implantation of autolyzed, antigen-extracted, allogenic bone
N2  - Im Rahmen der von der Datenbank bone97 erfassten Zeitraums dieser Studie wurde an der Klinik und Poliklinik für Mund-, Kiefer-, Gesichtschirurgie der Universität Würzburg zwischen März 1990 und März 2002 in 1073 Fällen bei 794 Patienten (421 männlich und 373 weiblich) autolysierter, Antigen extrahierter, allogener Knochen (AAA-Knochen) in den Kiefer- und Gesichtsbereich implantiert. In 97 Fällen wurde zwischen einzelnen Applikationsformen kombiniert, so dass insgesamt 1278 Präparate eingesetzt wurden. Das verwendete Knochenmaterial stammt aus Multiorganspendern. Das Herstellungsverfahren beinhaltet unter anderem die teilweise oder vollständige Demineralisation von kortikalem Knochen sowie dessen Chemosterilisation. Durch die Konservierung seiner physiologischerweise in der Knochenmatrix lokalisierten Bone Morphogenetic Proteins (BMPs) besitzt AAA-Knochen osteoinduktive Eigenschaften. Der Spenderknochen wurde als Chip (60,9%), als Pulver (mit unterschiedlicher Partikelgröße) (37,4%) sowie als Kalottenchip (1,3%) implantiert. Die häufigste Diagnose, die zur Implantation von AAA-Knochen führte, war die Diagnose Kieferdefekt (259) gefolgt von Zysten (147) und Mittelgesichtshypoplasien (115). Die Liste der Therapieformen wird von der Zystenauffüllung angeführt (147), gefolgt von der Kieferdefektauffüllung (142) und der Mittelgesichtsaugmentation (118). Hierbei lag der Zugang in 63,47% der Fälle intraoral und in 36,53% der Fälle extraoral. Im Laufe des Zeitraums der Nachuntersuchungen kam es zu 44 Implantatverlusten, dies entspricht etwa 3,44%, im Mittel nach 328,52 Tagen. Es traten bei 111 Präparaten Dehiszensen (8,69%)und bei 30 Präparaten Pus (2,35%) auf. Weder die Resuspension der Implantate noch die peri- und postoperativ durchgeführte Antibiose hatten Einfluss auf die Komplikationsrate.
N2  - From March 1990 to March 2002 AAA-bone were implanted in 1073 casts in 794 patients at the Klinik und Poliklinik für Mund-, Kiefer-, Gesichtschirurgie of the University of Würzburg.
KW  - AAA-Knochen
KW  - allogen
KW  - Knochenersatz
KW  - Knochentransplantat
KW  - AAA-bone
KW  - allogenic
KW  - bonegraft
KW  - bonetransplantation
Y1  - 2005
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-15828
ER  - 
TY  - THES
A1  - Schneider, Volkmar Peter Josef
T1  - Methodik der Mittelgesichtsdistraktion bei kraniofacialen Syndromen
T1  - Method of Distraction of the Middleface of Patients with Craniofacial Syndrom
N2  - Die craniofacialen Fehlbildungen sind genetisch bedingte Störungen, die schon vor der Geburt klinisch bemerkbar werden. Dazu gehören in erster Linie die folgenden vier Syndrome: Apert-, Pfeiffer-, Crouzon- und das Saethre-Chotzen-Syndrom. Alle fünf beinhalten Fehlbildungen des Kopf- und Mittelgesichtsbereiches und des Bewegungsapparates. Um die Mittelgesichtshypoplasie zu behandeln sind in den letzten 100 Jahren multiple Ansätze weiterentwickelt worden. Mit der hier vorgestellten Behandlungsmethode wird durch Modifikationen an verschiedenen Punkten des momentan üblichen, etablierten Behandlungskonzeptes versucht, einen Fortschritt zu erzielen. So wird schon in der für die Therapie äußerst wichtige Planungsphase die Operation durch Simulation am Organmodell und praeoperative Anfertigung von individuellen Metallplatten weitestmöglich vorbereitet. Hierfür wird das bisher verbreitete sehr teure Stereolithographieverfahren durch die weitaus kostengünstigere Methode des 3D-Drucks ersetzt. Die Möglichkeiten der Distraktion werden in der hier vorgestellten Methode durch die Kombination eines selbstentwickelten Schädelfixationsbogens mit einem Mandibulardistraktor ausgeweitet. In der herkömmlichen Form bietet der im Handel zu erhaltende Distraktor nur die Möglichkeit, in einer Ebene zu distrahieren, welche in der im Vorfeld der Operation stattfindenden Planung durch die Vektorfestlegung der beiden ansetzenden Zugkräfte festgelegt wird. Durch die Kombination des unseres Schädelfixationsbogens mit dem Mandibuladistraktor Multi-Guide-IITM der Firma Stryker hat man durch einen zusätzlichen Vektor die Möglichkeit, in drei Dimensionen zu distrahieren. Auf einen primären Verschluss des offenen Bisses wird aufgrund der möglichen ästhetischen Nachteile und der hohen Rezidivgefahr bewusst verzichtet. Stattdessen wird von vorneherein eine klassische Oberkiefer-Umstellungs-Osteotomie in der Le-Fort-I-Ebene, eventuell gepaart mit einer Umstellungsosteotomie im Unterkiefer, für den Zeitpunkt der Metallentfernung eingeplant. Die vorliegende Arbeit zeigt, dass durch die Verbesserung des herkömmlichen Behandlungskonzepts gleichzeitig an mehreren Ansatzpunkten die Chancen auf ein funktionell und ästhetisch befriedigendes Ergebnis gesteigert werden können.
N2  - The craniofacial syndroms force an interdisziplinary treatment. This dissertation describes the treatment protocol of the Universtity of Würzburg of craniofacial deformations of the midface and compares it with different international treatment methods.
KW  - Kraniofaziale
KW  - Appert
KW  - Distraktion
KW  - Crouzon
KW  - Craniofacial
KW  - Appert
KW  - Distraction
KW  - Crouzon
Y1  - 2006
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-20931
ER  - 
TY  - JOUR
A1  - Grimm, Oliver
A1  - Weber, Heike
A1  - Kittel-Schneider, Sarah
A1  - Kranz, Thorsten M.
A1  - Jacob, Christian P.
A1  - Lesch, Klaus-Peter
A1  - Reif, Andreas
T1  - Impulsivity and Venturesomeness in an Adult ADHD Sample: Relation to Personality, Comorbidity, and Polygenic Risk
JF  - Frontiers in Psychiatry
N2  - While impulsivity is a basic feature of attention-deficit/hyperactivity disorder (ADHD), no study explored the effect of different components of the Impulsiveness (Imp) and Venturesomeness (Vent) scale (IV7) on psychiatric comorbidities and an ADHD polygenic risk score (PRS). We used the IV7 self-report scale in an adult ADHD sample of 903 patients, 70% suffering from additional comorbid disorders, and in a subsample of 435 genotyped patients. Venturesomeness, unlike immediate Impulsivity, is not specific to ADHD. We consequently analyzed the influence of Imp and Vent also in the context of a PRS on psychiatric comorbidities of ADHD. Vent shows a distinctly different distribution of comorbidities, e.g., less anxiety and depression. PRS showed no effect on different ADHD comorbidities, but correlated with childhood hyperactivity. In a complementary analysis using principal component analysis with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition ADHD criteria, revised NEO Personality Inventory, Imp, Vent, and PRS, we identified three ADHD subtypes. These are an impulsive–neurotic type, an adventurous–hyperactive type with a stronger genetic component, and an anxious–inattentive type. Our study thus suggests the importance of adventurousness and the differential consideration of impulsivity in ADHD. The genetic risk is distributed differently between these subtypes, which underlines the importance of clinically motivated subtyping. Impulsivity subtyping might give insights into the organization of comorbid disorders in ADHD and different genetic background.
KW  - impulsivity
KW  - ADHD
KW  - polygenic risk score
KW  - venturesomeness
KW  - substance abuse disorder
KW  - attention
KW  - hyperactivity
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-219751
SN  - 1664-0640
VL  - 11
ER  - 
TY  - JOUR
A1  - Pittig, Andre
A1  - Heinig, Ingmar
A1  - Goerigk, Stephan
A1  - Thiel, Freya
A1  - Hummel, Katrin
A1  - Scholl, Lucie
A1  - Deckert, Jürgen
A1  - Pauli, Paul
A1  - Domschke, Katharina
A1  - Lueken, Ulrike
A1  - Fydrich, Thomas
A1  - Fehm, Lydia
A1  - Plag, Jens
A1  - Ströhle, Andreas
A1  - Kircher, Tilo
A1  - Straube, Benjamin
A1  - Rief, Winfried
A1  - Koelkebeck, Katja
A1  - Arolt, Volker
A1  - Dannlowski, Udo
A1  - Margraf, Jürgen
A1  - Totzeck, Christina
A1  - Schneider, Silvia
A1  - Neudeck, Peter
A1  - Craske, Michelle G.
A1  - Hollandt, Maike
A1  - Richter, Jan
A1  - Hamm, Alfons
A1  - Wittchen, Hans-Ulrich
T1  - Efficacy of temporally intensified exposure for anxiety disorders: A multicenter randomized clinical trial
JF  - Depression and Anxiety
N2  - Background

The need to optimize exposure treatments for anxiety disorders may be addressed by temporally intensified exposure sessions. Effects on symptom reduction and public health benefits should be examined across different anxiety disorders with comorbid conditions.

Methods

This multicenter randomized controlled trial compared two variants of prediction error-based exposure therapy (PeEx) in various anxiety disorders (both 12 sessions + 2 booster sessions, 100 min/session): temporally intensified exposure (PeEx-I) with exposure sessions condensed to 2 weeks (n = 358) and standard nonintensified exposure (PeEx-S) with weekly exposure sessions (n = 368). Primary outcomes were anxiety symptoms (pre, post, and 6-months follow-up). Secondary outcomes were global severity (across sessions), quality of life, disability days, and comorbid depression.

Results

Both treatments resulted in substantial improvements at post (PeEx-I: d\(_{within}\) = 1.50, PeEx-S: d\(_{within}\) = 1.78) and follow-up (PeEx-I: d\(_{within}\) = 2.34; PeEx-S: d\(_{within}\) = 2.03). Both groups showed formally equivalent symptom reduction at post and follow-up. However, time until response during treatment was 32% shorter in PeEx-I (median = 68 days) than PeEx-S (108 days; TR\(_{PeEx-I}\)-I = 0.68). Interestingly, drop-out rates were lower during intensified exposure. PeEx-I was also superior in reducing disability days and improving quality of life at follow-up without increasing relapse.

Conclusions

Both treatment variants focusing on the transdiagnostic exposure-based violation of threat beliefs were effective in reducing symptom severity and disability in severe anxiety disorders. Temporally intensified exposure resulted in faster treatment response with substantial public health benefits and lower drop-out during the exposure phase, without higher relapse. Clinicians can expect better or at least comparable outcomes when delivering exposure in a temporally intensified manner.
KW  - randomized controlled trial
KW  - anxiety disorders
KW  - exposure therapy
KW  - intensified treatment
KW  - public health
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-257331
VL  - 38
IS  - 11
ER  - 
TY  - JOUR
A1  - Willeke, Kristina
A1  - Janson, Patrick
A1  - Zink, Katharina
A1  - Stupp, Carolin
A1  - Kittel-Schneider, Sarah
A1  - Berghöfer, Anne
A1  - Ewert, Thomas
A1  - King, Ryan
A1  - Heuschmann, Peter U.
A1  - Zapf, Andreas
A1  - Wildner, Manfred
A1  - Keil, Thomas
T1  - Occurrence of mental illness and mental health risks among the self-employed: a systematic review
JF  - International Journal of Environmental Research and Public Health
N2  - We aimed to systematically identify and evaluate all studies of good quality that compared the occurrence of mental disorders in the self-employed versus employees. Adhering to the Cochrane guidelines, we conducted a systematic review and searched three major medical databases (MEDLINE, Web of Science, Embase), complemented by hand search. We included 26 (three longitudinal and 23 cross-sectional) population-based studies of good quality (using a validated quality assessment tool), with data from 3,128,877 participants in total. The longest of these studies, a Swedish national register evaluation with 25 years follow-up, showed a higher incidence of mental illness among the self-employed compared to white-collar workers, but a lower incidence compared to blue-collar workers. In the second longitudinal study from Sweden the self-employed had a lower incidence of mental illness compared to both blue- and white-collar workers over 15 years, whereas the third longitudinal study (South Korea) did not find a difference regarding the incidence of depressive symptoms over 6 years. Results from the cross-sectional studies showed associations between self-employment and poor general mental health and stress, but were inconsistent regarding other mental outcomes. Most studies from South Korea found a higher prevalence of mental disorders among the self-employed compared to employees, whereas the results of cross-sectional studies from outside Asia were less consistent. In conclusion, we found evidence from population-based studies for a link between self-employment and increased risk of mental illness. Further longitudinal studies are needed examining the potential risk for the development of mental disorders in specific subtypes of the self-employed.
KW  - incidence
KW  - mental disorders
KW  - mental health
KW  - mental illness
KW  - prevalence
KW  - self-employed
KW  - small business
KW  - systematic review
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-245085
SN  - 1660-4601
VL  - 18
IS  - 16
ER  - 
TY  - JOUR
A1  - Padberg, Inken
A1  - Knispel, Petra
A1  - Zöllner, Susanne
A1  - Sieveking, Meike
A1  - Schneider, Alice
A1  - Steinbrink, Jens
A1  - Heuschmann, Peter U.
A1  - Wellwood, Ian
A1  - Meisel, Andreas
T1  - Social work after stroke: identifying demand for support by recording stroke patients' and carers' needs in different phases after stroke
JF  - BMC Neurology
N2  - Background

Previous studies examining social work interventions in stroke often lack information on content, methods and timing over different phases of care including acute hospital, rehabilitation and out-patient care. This limits our ability to evaluate the impact of social work in multidisciplinary stroke care.

We aimed to quantify social-work-related support in stroke patients and their carers in terms of timing and content, depending on the different phases of stroke care.

Methods

We prospectively collected and evaluated data derived from a specialized “Stroke-Service-Point” (SSP); a “drop in” center and non-medical stroke assistance service, staffed by social workers and available to all stroke patients, their carers and members of the public in the metropolitan region of Berlin, Germany.

Results

Enquiries from 257 consenting participants consulting the SSP between March 2010 and April 2012 related to out-patient and in-patient services, therapeutic services, medical questions, medical rehabilitation, self-help groups and questions around obtaining benefits. Frequency of enquiries for different topics depended on whether patients were located in an in-patient or out-patient setting. The majority of contacts involved information provision. While the proportion of male and female patients with stroke was similar, about two thirds of the carers contacting the SSP were female.

Conclusion

The social-work-related services provided by a specialized center in a German metropolitan area were diverse in terms of topic and timing depending on the phase of stroke care. Targeting the timing of interventions might be important to increase the impact of social work on patient’s outcome.
KW  - Social support
KW  - Stroke
KW  - Rehabilitation
KW  - Social work
KW  - Patient-centered care
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164691
VL  - 16
IS  - 111
ER  - 
TY  - JOUR
A1  - Köping, Maria
A1  - Shehata-Dieler, Wafaa
A1  - Schneider, Dieter
A1  - Cebulla, Mario
A1  - Oder, Daniel
A1  - Müntze, Jonas
A1  - Nordbeck, Peter
A1  - Wanner, Christoph
A1  - Hagen, Rudolf
A1  - Schraven, Sebastian P.
T1  - Characterization of vertigo and hearing loss in patients with Fabry disease
JF  - Orphanet Journal of Rare Diseases
N2  - Background
Fabry Disease (FD) is an X-linked hereditary lysosomal storage disorder which leads to a multisystemic intralysosomal accumulation of globotriaosylceramid (Gb3). Besides prominent renal and cardiac organ involvement, patients commonly complain about vestibulocochlear symptoms like high-frequency hearing loss, tinnitus and vertigo. However, comprehensive data especially on vertigo remain scarce. The aim of this study was to examine the prevalence and characteristics of vertigo and hearing loss in patients with FD, depending on renal and cardiac parameters and get hints about the site and the pattern of the lesions.

Methods
Single-center study with 57 FD patients. Every patient underwent an oto-rhino-laryngological examination as well as videonystagmography and vestibular evoked myogenic potentials (VEMPs) and audiological measurements using pure tone audiometry and auditory brainstem response audiometry (ABR). Renal function was measured by eGFR, cardiac impairment was graduated by NYHA class.

Results
More than one out of three patients (35.1%) complained about hearing loss, 54.4% about vertigo and 28.1% about both symptom. In 74% a sensorineural hearing loss of at least 25 dB was found, ABR could exclude any retrocochlear lesion. Caloric testing showed abnormal values in 71.9%, VEMPs were pathological in 68%. A correlation between the side or the shape of hearing loss and pathological vestibular testing could not be revealed.

Conclusions
Hearing loss and vertigo show a high prevalence in FD. While hearing loss seems due to a cochlear lesion, peripheral vestibular as well as central nervous pathologies cause vertigo. Thus, both the site of lesion and the pathophysiological patterns seem to differ.
KW  - Fabry disease
KW  - vertigo
KW  - VEMP
KW  - cardiomyopathy
KW  - chronic kidney disease
KW  - lysosomal storage disorder
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-222818
VL  - 13
ER  - 
TY  - JOUR
A1  - Weidemann, Frank
A1  - Maier, Sebastian K. G.
A1  - Störk, Stefan
A1  - Brunner, Thomas
A1  - Liu, Dan
A1  - Hu, Kai
A1  - Seydelmann, Nora
A1  - Schneider, Andreas
A1  - Becher, Jan
A1  - Canan-Kühl, Sima
A1  - Blaschke, Daniela
A1  - Bijnens, Bart
A1  - Ertl, Georg
A1  - Wanner, Christoph
A1  - Nordbeck, Peter
T1  - Usefulness of an implantable loop recorder to detect clinically relevant arrhythmias in patients with advanced fabry cardiomyopathy
JF  - The American Journal of Cardiology
N2  - Patients with genetic cardiomyopathy that involves myocardial hypertrophy often develop clinically relevant arrhythmias that increase the risk of sudden death. Consequently, guidelines for medical device therapy were established for hypertrophic cardiomyopathy, but not for conditions with only anecdotal evidence of arrhythmias, like Fabry cardiomyopathy. Patients with Fabry cardiomyopathy progressively develop myocardial fibrosis, and sudden cardiac death occurs regularly. Because 24-hour Holier electrocardiograms (ECGs) might not detect clinically important arrhythmias, we tested an implanted loop recorder for continuous heart rhythm surveillance and determined its impact on therapy. This prospective study included 16 patients (12 men) with advanced Fabry cardiomyopathy, relevant hypertrophy, and replacement fibrosis in "loco typico." No patients previously exhibited clinically relevant arrhythmias on Holier ECGs. Patients received an implantable loop recorder and were prospectively followed with telemedicine for a median of 1.2 years (range 0.3 to 2.0 years). The primary end point was a clinically meaningful event, which required a therapy change, captured with the loop recorder. Patients submitted data regularly (14 +/- 11 times per month). During follow-up, 21 events were detected (including 4 asystole, i.e., ECG pauses >= 3 seconds) and 7 bradycardia events; 5 episodes of intermittent atrial fibrillation (>3 minutes) and 5 episodes of ventricular tachycardia (3 sustained and 2 nonsustained). Subsequently, as defined in the primary end point, 15 events leaded to a change of therapy. These patients required therapy with a pacemaker or cardioverter defibrillator implantation and/or anticoagulation therapy for atrial fibrillation. In conclusion, clinically relevant arrhythmias that require further device and/or medical therapy are often missed with Holier ECGs in patients with advanced stage Fabry cardiomyopathy, but they can be detected by telemonitoring with an implantable loop recorder.
KW  - Cardiovascular magnetic-resonance
KW  - Coronary artery disease
KW  - Ventricular-arrhythmias
KW  - Task force
KW  - Management
KW  - Enzyme replacement therapy
KW  - Hypertrophic cardiomyopathy
KW  - Myocardial fibrosis
KW  - Guidelines
KW  - Manifestation
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-188093
VL  - 118
IS  - 2
ER  - 
TY  - JOUR
A1  - Latifi, Hooman
A1  - Holzwarth, Stefanie
A1  - Skidmore, Andrew
A1  - Brůna, Josef
A1  - Červenka, Jaroslav
A1  - Darvishzadeh, Roshanak
A1  - Hais, Martin
A1  - Heiden, Uta
A1  - Homolová, Lucie
A1  - Krzystek, Peter
A1  - Schneider, Thomas
A1  - Starý, Martin
A1  - Wang, Tiejun
A1  - Müller, Jörg
A1  - Heurich, Marco
T1  - A laboratory for conceiving Essential Biodiversity Variables (EBVs)—The ‘Data pool initiative for the Bohemian Forest Ecosystem’
JF  - Methods in Ecology and Evolution
N2  - Effects of climate change‐induced events on forest ecosystem dynamics of composition, function and structure call for increased long‐term, interdisciplinary and integrated research on biodiversity indicators, in particular within strictly protected areas with extensive non‐intervention zones. The long‐established concept of forest supersites generally relies on long‐term funds from national agencies and goes beyond the logistic and financial capabilities of state‐ or region‐wide protected area administrations, universities and research institutes.
We introduce the concept of data pools as a smaller‐scale, user‐driven and reasonable alternative to co‐develop remote sensing and forest ecosystem science to validated products, biodiversity indicators and management plans. We demonstrate this concept with the Bohemian Forest Ecosystem Data Pool, which has been established as an interdisciplinary, international data pool within the strictly protected Bavarian Forest and Šumava National Parks and currently comprises 10 active partners. We demonstrate how the structure and impact of the data pool differs from comparable cases.
We assessed the international influence and visibility of the data pool with the help of a systematic literature search and a brief analysis of the results. Results primarily suggest an increase in the impact and visibility of published material during the life span of the data pool, with highest visibilities achieved by research conducted on leaf traits, vegetation phenology and 3D‐based forest inventory.
We conclude that the data pool results in an efficient contribution to the concept of global biodiversity observatory by evolving towards a training platform, functioning as a pool of data and algorithms, directly communicating with management for implementation and providing test fields for feasibility studies on earth observation missions.
KW  - bohemian forest ecosystem
KW  - data pool
KW  - forest ecosystem science
KW  - remote sensing
KW  - remote sensing‐enabled essential biodiversity variables
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-262743
VL  - 12
IS  - 11
ER  - 
TY  - JOUR
A1  - Brevik, Erlend J
A1  - van Donkelaar, Marjolein M. J.
A1  - Weber, Heike
A1  - Sánchez-Mora, Cristina
A1  - Jacob, Christian
A1  - Rivero, Olga
A1  - Kittel-Schneider, Sarah
A1  - Garcia-martinez, Iris
A1  - Aebi, Marcel
A1  - van Hulzen, Kimm
A1  - Cormand, Bru
A1  - Ramos-Quiroga, Josep A
A1  - Lesch, Klaus-Peter
A1  - Reif, Andreas
A1  - Ribases, Marta
A1  - Franke, Barbara
A1  - Posserud, Maj-Britt
A1  - Johansson, Stefan
A1  - Lundervold, Astri J.
A1  - Haavik, Jan
A1  - Zayats, Tetyana
T1  - Genome-wide analyses of aggressiveness in attention-deficit hyperactivity disorder
JF  - American Journal of Medical Genetics Part B-Neuropsychiatric Genetics
N2  - Aggressiveness is a behavioral trait that has the potential to be harmful to individuals and society. With an estimated heritability of about 40%, genetics is important in its development. We performed an exploratory genome-wide association (GWA) analysis of childhood aggressiveness in attention deficit hyperactivity disorder (ADHD) to gain insight into the underlying biological processes associated with this trait. Our primary sample consisted of 1,060 adult ADHD patients (aADHD). To further explore the genetic architecture of childhood aggressiveness, we performed enrichment analyses of suggestive genome-wide associations observed in aADHD among GWA signals of dimensions of oppositionality (defiant/vindictive and irritable dimensions) in childhood ADHD (cADHD). No single polymorphism reached genome-wide significance (P<5.00E-08). The strongest signal in aADHD was observed at rs10826548, within a long noncoding RNA gene (beta = -1.66, standard error (SE) = 0.34, P = 1.07E-06), closely followed by rs35974940 in the neurotrimin gene (beta = 3.23, SE = 0.67, P = 1.26E-06). The top GWA SNPs observed in aADHD showed significant enrichment of signals from both the defiant/vindictive dimension (Fisher's P-value = 2.28E-06) and the irritable dimension in cADHD (Fisher's P-value = 0.0061). In sum, our results identify a number of biologically interesting markers possibly underlying childhood aggressiveness and provide targets for further genetic exploration of aggressiveness across psychiatric disorders.
KW  - Large multicenter ADHD
KW  - Antisocial behavior
KW  - Diagnostic approach
KW  - Rating scale
KW  - Gene
KW  - Deficit/hyperactivity disorder
KW  - Susceptibility loci
KW  - Conduct disorder
KW  - Association
KW  - Adult
KW  - ADHD
KW  - Aggression
KW  - GWAS
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-188116
VL  - 171B
IS  - 5
ER  - 
TY  - JOUR
A1  - Oezkur, Mehmet
A1  - Magyar, Attila
A1  - Thomas, Phillip
A1  - Stork, Tabea
A1  - Schneider, Reinhard
A1  - Bening, Constanze
A1  - Störk, Stefan
A1  - Heuschmann, Peter U.
A1  - Leyh, Rainer G.
A1  - Wagner, Martin
T1  - TIMP-2*IGFBP7 (Nephrocheck®) Measurements at Intensive Care Unit Admission After Cardiac Surgery are Predictive for Acute Kidney Injury Within 48 Hours
JF  - Kidney & Blood Pressure Research
N2  - Background/Aims: 
Acute kidney injury (AKI) is a postoperative complication after cardiac surgery with a high impact on mortality and morbidity. Nephrocheck® [TIMP-2*IGFBP7] determines markers of tubular stress, which occurs prior to tubular damage. It is unknown at which time-point [TIMP-2*IGFBP7] measurement should be performed to ideally predict AKI. We investigated the association of [TIMP-2*IGFBP7] at various time-points with the incidence of AKI in patients undergoing elective cardiac surgery including cardio-pulmonary bypass. 
Methods: In a prospective cohort study, serial blood and urine samples were collected from 150 patients: pre-operative, at ICU-admission, 24h and 48h post-surgery. AKI was defined as Serum-Creatinine rise >0.3 mg/dl within 48hrs. Urinary [TIMP-2*IGFBP7] was measured at pre-operative, ICU-admission and 24h post-surgery; medical staff was kept blinded to these results. 
Results: A total of 35 patients (23.5%) experienced AKI, with a higher incidence in those with high [TIMP-2*IGFBP7] values at ICU admission (57.1% vs. 10.1%, p<0.001). In logistic regression [TIMP-2*IGFBP7] at ICU admission was independently associated with the occurrence of AKI (Odds Ratio 11.83; p<0.001, C-statistic= 0.74) after adjustment for EuroSCORE II and CBP-time. 
Conclusions: Early detection of elevated [TIMP-2*IGFBP7] at ICU admission was strongly predictive for postoperative AKI and appeared to be more precise as compared to subsequent measurements.
KW  - postoperativ
KW  - Akutes Nierenversagen
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-157988
VL  - 42
ER  - 
TY  - JOUR
A1  - Janson, Patrick
A1  - Willeke, Kristina
A1  - Zaibert, Lisa
A1  - Budnick, Andrea
A1  - Berghöfer, Anne
A1  - Kittel-Schneider, Sarah
A1  - Heuschmann, Peter U.
A1  - Zapf, Andreas
A1  - Wildner, Manfred
A1  - Stupp, Carolin
A1  - Keil, Thomas
T1  - Mortality, morbidity and health-related outcomes in informal caregivers compared to non-caregivers: a systematic review
JF  - International Journal of Environmental Research and Public Health
N2  - A systematic overview of mental and physical disorders of informal caregivers based on population-based studies with good methodological quality is lacking. Therefore, our aim was to systematically summarize mortality, incidence, and prevalence estimates of chronic diseases in informal caregivers compared to non-caregivers. Following PRISMA recommendations, we searched major healthcare databases (CINAHL, MEDLINE and Web of Science) systematically for relevant studies published in the last 10 years (without language restrictions) (PROSPERO registration number: CRD42020200314). We included only observational cross-sectional and cohort studies with low risk of bias (risk scores 0–2 out of max 8) that reported the prevalence, incidence, odds ratio (OR), hazard ratio (HR), mean- or sum-scores for health-related outcomes in informal caregivers and non-caregivers. For a thorough methodological quality assessment, we used a validated checklist. The synthesis of the results was conducted by grouping outcomes. We included 22 studies, which came predominately from the USA and Europe. Informal caregivers had a significantly lower mortality than non-caregivers. Regarding chronic morbidity outcomes, the results from a large longitudinal German health-insurance evaluation showed increased and statistically significant incidences of severe stress, adjustment disorders, depression, diseases of the spine and pain conditions among informal caregivers compared to non-caregivers. In cross-sectional evaluations, informal caregiving seemed to be associated with a higher occurrence of depression and of anxiety (ranging from 4 to 51% and 2 to 38%, respectively), pain, hypertension, diabetes and reduced quality of life. Results from our systematic review suggest that informal caregiving may be associated with several mental and physical disorders. However, these results need to be interpreted with caution, as the cross-sectional studies cannot determine temporal relationships. The lower mortality rates compared to non-caregivers may be due to a healthy-carer bias in longitudinal observational studies; however, these and other potential benefits of informal caregiving deserve further attention by researchers.
KW  - cohort studies
KW  - longitudinal studies
KW  - cross-sectional studies
KW  - family caregivers
KW  - informal caregiving
KW  - mental health
KW  - physical health
KW  - population-based studies
KW  - systematic review
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-275219
SN  - 1660-4601
VL  - 19
IS  - 10
ER  - 
TY  - JOUR
A1  - McNeill, Rhiannon V.
A1  - Ziegler, Georg C.
A1  - Radtke, Franziska
A1  - Nieberler, Matthias
A1  - Lesch, Klaus‑Peter
A1  - Kittel‑Schneider, Sarah
T1  - Mental health dished up — the use of iPSC models in neuropsychiatric research
JF  - Journal of Neural Transmission
N2  - Genetic and molecular mechanisms that play a causal role in mental illnesses are challenging to elucidate, particularly as there is a lack of relevant in vitro and in vivo models. However, the advent of induced pluripotent stem cell (iPSC) technology has provided researchers with a novel toolbox. We conducted a systematic review using the PRISMA statement. A PubMed and Web of Science online search was performed (studies published between 2006–2020) using the following search strategy: hiPSC OR iPSC OR iPS OR stem cells AND schizophrenia disorder OR personality disorder OR antisocial personality disorder OR psychopathy OR bipolar disorder OR major depressive disorder OR obsessive compulsive disorder OR anxiety disorder OR substance use disorder OR alcohol use disorder OR nicotine use disorder OR opioid use disorder OR eating disorder OR anorexia nervosa OR attention-deficit/hyperactivity disorder OR gaming disorder. Using the above search criteria, a total of 3515 studies were found. After screening, a final total of 56 studies were deemed eligible for inclusion in our study. Using iPSC technology, psychiatric disease can be studied in the context of a patient’s own unique genetic background. This has allowed great strides to be made into uncovering the etiology of psychiatric disease, as well as providing a unique paradigm for drug testing. However, there is a lack of data for certain psychiatric disorders and several limitations to present iPSC-based studies, leading us to discuss how this field may progress in the next years to increase its utility in the battle to understand psychiatric disease.
KW  - hiPSC
KW  - iPSC
KW  - stem cells
KW  - mental disorders
KW  - affective disorders
KW  - ADHD
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235666
SN  - 0300-9564
VL  - 127
ER  - 
TY  - JOUR
A1  - Sitter, Magdalena
A1  - Schlesinger, Tobias
A1  - Reinhold, Ann-Kristin
A1  - Scholler, Axel
A1  - Heymann, Christian von
A1  - Welfle, Sabine
A1  - Bartmann, Catharina
A1  - Wöckel, Achim
A1  - Kleinschmidt, Stefan
A1  - Schneider, Sven
A1  - Gottschalk, André
A1  - Greve, Susanne
A1  - Wermelt, Julius Z.
A1  - Wiener, Roland
A1  - Schulz, Frank
A1  - Chappell, Daniel
A1  - Brunner, Maya
A1  - Neumann, Claudia
A1  - Meybohm, Patrick
A1  - Kranke, Peter
T1  - COVID-19 in der geburtshilflichen Anästhesie: Prospektive Erfassung von SARS-CoV-2-Infektionen zum Zeitpunkt der Geburt sowie des peripartalen Verlaufs SARS-CoV-2-positiver Schwangerer
JF  - Der Anaesthesist
N2  - Hintergrund
Im Rahmen der Pandemie des SARS-CoV-2-Virus erlangte das Patientenkollektiv der Schwangeren früh Aufmerksamkeit. Initial wurde angesichts sich früh abzeichnender Krankheitsfälle bei jüngeren Patienten mit einem erheblichen Aufkommen peripartal zu betreuender, COVID-19-positiver Schwangerer gerechnet.
Ziel der Arbeit
Diese Arbeit vermittelt einen Einblick in die SARS-CoV-2-Infektionszahlen im Rahmen der geburtshilflichen Anästhesie zu Beginn der Pandemie sowie während der zweiten Infektionswelle in Deutschland.
Methoden
Über das COALA-Register (COVID-19 related Obstetric Anaesthesia Longitudinal Assessment-Registry) wurden sowohl von März bis Mai 2020 als auch von Oktober 2020 bis Februar 2021 in Deutschland und der Schweiz wöchentlich prospektiv Daten zu Verdachts- und bestätigten SARS-CoV-2-Fällen bei Schwangeren zum Zeitpunkt der Geburt erhoben. Betrachtet wurden die Verteilung dieser auf die Anzahl der Geburten, Zentren und Erhebungswochen sowie mütterliche Charakteristika und Krankheitsverläufe.
Ergebnisse
Neun Zentren haben im Verlauf 44 SARS-CoV-2-positive Schwangere zum Zeitpunkt der Geburt bei 7167 Geburten (0,6 %) gemeldet (3 Fälle auf 2270 Geburten (0,4 %) und 41 Fälle auf 4897 Geburten (0,8 %)). Berichtet wurden 2 schwere COVID-19-Verläufe (n = 1 mit Todesfolge nach ECMO, n = 1 mit ECMO überlebt). Bei 28 (68 %) Patientinnen verlief die Infektion asymptomatisch. Ein Neugeborenes wurde im Verlauf positiv auf SARS-CoV‑2 getestet.
Schlussfolgerung
Mithilfe des Registers konnte das Auftreten von Fällen zu Beginn der Pandemie zeitnah eingeschätzt werden. Es traten sporadisch Verdachtsfälle bzw. bestätigte Fälle auf. Aufgrund fehlender flächendeckender Testung muss aber von einer Dunkelziffer asymptomatischer Fälle ausgegangen werden. Während der zweiten Infektionswelle wurden 68 % asymptomatische Fälle gemeldet. Jedoch kann es bei jungen, gesunden Patientinnen ohne das Vorliegen typischer Risikofaktoren zu schwerwiegenden Verläufen kommen.
KW  - ECMO-Therapie
KW  - Geburtshilfe
KW  - Geburtshilfliche Intensivmedizin
KW  - COVID-19-Pademie
KW  - Infektionswellen
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-264878
SN  - 1432-055X
VL  - 71
IS  - 6
ER  - 
TY  - JOUR
A1  - Schmitt, Andrea
A1  - Tatsch, Laura
A1  - Vollhardt, Alisa
A1  - Schneider-Axmann, Thomas
A1  - Raabe, Florian J.
A1  - Roell, Lukas
A1  - Heinsen, Helmut
A1  - Hof, Patrick R.
A1  - Falkai, Peter
A1  - Schmitz, Christoph
T1  - Decreased oligodendrocyte number in hippocampal subfield CA4 in schizophrenia: a replication study
JF  - Cells
N2  - Hippocampus-related cognitive deficits in working and verbal memory are frequent in schizophrenia, and hippocampal volume loss, particularly in the cornu ammonis (CA) subregions, was shown by magnetic resonance imaging studies. However, the underlying cellular alterations remain elusive. By using unbiased design-based stereology, we reported a reduction in oligodendrocyte number in CA4 in schizophrenia and of granular neurons in the dentate gyrus (DG). Here, we aimed to replicate these findings in an independent sample. We used a stereological approach to investigate the numbers and densities of neurons, oligodendrocytes, and astrocytes in CA4 and of granular neurons in the DG of left and right hemispheres in 11 brains from men with schizophrenia and 11 brains from age- and sex-matched healthy controls. In schizophrenia, a decreased number and density of oligodendrocytes was detected in the left and right CA4, whereas mean volumes of CA4 and the DG and the numbers and density of neurons, astrocytes, and granular neurons were not different in patients and controls, even after adjustment of variables because of positive correlations with postmortem interval and age. Our results replicate the previously described decrease in oligodendrocytes bilaterally in CA4 in schizophrenia and point to a deficit in oligodendrocyte maturation or a loss of mature oligodendrocytes. These changes result in impaired myelination and neuronal decoupling, both of which are linked to altered functional connectivity and subsequent cognitive dysfunction in schizophrenia.
KW  - schizophrenia
KW  - hippocampus
KW  - CA4
KW  - dentate gyrus
KW  - postmortem
KW  - stereology
KW  - oligodendrocyte
KW  - neuron
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-290360
SN  - 2073-4409
VL  - 11
IS  - 20
ER  - 
TY  - JOUR
A1  - Schulmeyer, Carla E.
A1  - Fasching, Peter A.
A1  - Häberle, Lothar
A1  - Meyer, Julia
A1  - Schneider, Michael
A1  - Wachter, David
A1  - Ruebner, Matthias
A1  - Pöschke, Patrik
A1  - Beckmann, Matthias W.
A1  - Hartmann, Arndt
A1  - Erber, Ramona
A1  - Gass, Paul
T1  - Expression of the immunohistochemical markers CK5, CD117, and EGFR in molecular subtypes of breast cancer correlated with prognosis
JF  - Diagnostics
N2  - Molecular-based subclassifications of breast cancer are important for identifying treatment options and stratifying the prognosis in breast cancer. This study aimed to assess the prognosis relative to disease-free survival (DFS) and overall survival (OS) in patients with triple-negative breast cancer (TNBC) and other subtypes, using a biomarker panel including cytokeratin 5 (CK5), cluster of differentiation 117 (CD117), and epidermal growth factor receptor (EGFR). This cohort–case study included histologically confirmed breast carcinomas as cohort arm. From a total of 894 patients, 572 patients with early breast cancer, sufficient clinical data, and archived tumor tissue were included. Using the immunohistochemical markers CK5, CD117, and EGFR, two subgroups were formed: one with all three biomarkers negative (TBN) and one with at least one of those three biomarkers positive (non-TBN). There were significant differences between the two biomarker subgroups (TBN versus non-TBN) in TNBC for DFS (p = 0.04) and OS (p = 0.02), with higher survival rates (DFS and OS) in the non-TBN subgroup. In this study, we found the non-TBN subgroup of TNBC lesions with at least one positive biomarker of CK5, CD117, and/or EGFR, to be associated with longer DFS and OS.
KW  - early breast cancer
KW  - therapy
KW  - prognosis
KW  - CK5
KW  - CD117
KW  - EGFR
KW  - triple-negative breast cancer
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304987
SN  - 2075-4418
VL  - 13
IS  - 3
ER  - 
TY  - JOUR
A1  - Holländer, Olivia
A1  - Schwender, Kristina
A1  - Böhme, Petra
A1  - Fleckhaus, Jan
A1  - Haas, Cordula
A1  - Han, Yang
A1  - Heidorn, Frank
A1  - Klein-Unseld, Rachel
A1  - Lichtenwald, Julia
A1  - Naue, Jana
A1  - Neubauer, Jacqueline
A1  - Poetsch, Micaela
A1  - Schneider, Peter M.
A1  - Wagner, Wolfgang
A1  - Vennemann, Marielle
T1  - Forensische DNA-Methylierungsanalyse
T1  - Forensic DNA methylation analysis : First technical collaborative exercise by the working group on molecular age estimation of the German Society of Legal Medicine
BT  - Erster, technischer Ringversuch der Arbeitsgruppe „Molekulare Altersschätzung“ der Deutschen Gesellschaft für Rechtsmedizin
JF  - Rechtsmedizin
N2  - Die quantitative Analyse der relativen DNA-Methylierung gilt als eine der vielversprechendsten Methoden der molekularen Altersschätzung. Viele Studien der letzten Jahre identifizierten geeignete Positionen im Genom, deren DNA-Methylierung sich altersabhängig verändert. Für den Einsatz dieser Methode in der Routine- bzw. Fallarbeit ist es von großer Bedeutung, angewandte Analysetechniken zu validieren. Als ein Teilaspekt dieser Validierung sollte die Vergleichbarkeit der Analyseergebnisse zur DNA-Methylierung mithilfe der Mini- und Pyrosequenzierung zwischen verschiedenen Laboren evaluiert werden. Die Arbeitsgruppe „Molekulare Altersschätzung“ der Deutschen Gesellschaft für Rechtsmedizin (DGRM) führte hierzu den ersten, technischen Ringversuch durch, der 4 Positionen in den Genen PDE4C, EDARADD, SST und KLF14 umfasste. Diese Marker waren in vorangegangenen Studien als altersabhängige Biomarker charakterisiert worden. Am Ringversuch nahmen 12 Labore teil, wobei jedes die Wahl zwischen der Minisequenzierung und/oder der Pyrosequenzierung für die quantitative Methylierungsanalyse hatte. Jedem teilnehmenden Labor wurden Blut- und Speichelproben von 3 Personen unterschiedlichen Alters übersandt. Die Wahl der Reagenzien für die Probenbearbeitung wurde den Teilnehmern freigestellt.

Die Ergebnisse der Minisequenzierung zeigten systematische Abweichungen zwischen den Laboren, die am ehesten auf die Verwendung unterschiedlicher Reagenzien und Analyseplattformen zurückzuführen sein können. Die Resultate der Pyrosequenzierung hingegen wiesen nicht auf systematische Abweichungen zwischen den Laboren hin, hier zeigte sich jedoch die Tendenz einer markerabhängigen Abweichung. Darüber hinaus konnten Unterschiede hinsichtlich technischer Probleme zwischen Laboren mit mehr Erfahrung in der jeweiligen Sequenzierungsmethode und Laboren mit weniger Erfahrung festgestellt werden. Sowohl die Beobachtung von systematischen als auch die von markerabhängigen Abweichungen lässt den Schluss zu, dass eine Übertragung von Analysemethoden zwischen Laboren grundsätzlich möglich ist, eine Anpassung des jeweiligen Modells zur Altersschätzung jedoch notwendig sein kann.
N2  - Quantitative analysis of relative DNA methylation is currently one of the most promising methods of molecular age estimation. In recent years numerous studies identified potential DNA methylation markers showing age-dependent changes in their relative methylation state. For routine application of this method validation is an important prerequisite. One aspect of validation is the degree of comparability of analytical data between laboratories. The working group on molecular age estimation of the German Society for Legal Medicine (DGRM) conducted a first technical proficiency test comprising four age estimation markers within the genes PDE4C, EDARADD, SST and KLF14. These positions were previously characterized as age-dependent biomarkers. A total of 12 laboratories participated using pyrosequencing and/or minisequencing techniques for quantitative analysis of DNA methylation. Each laboratory received blood and buccal swab samples from three individuals of different ages. Laboratories were free in their choice of reagents and material for sequencing.

Minisequencing results showed systematic deviations between laboratories, which are believed to originate from differing reagents and sequencing platforms. The results of pyrosequencing did not show clear signs of systematic deviation but did show differences in the comparability between markers. Different levels of technical problems were reported, which correlated with the amount of experience with the sequencing technology.

Both systematic and specific differences between analytical data produced in different laboratory settings lead to the conclusion that while it is generally possible to transfer an age estimation method to another laboratory, a mathematical model for age estimation might need to be adjusted accordingly.
KW  - DNA-Methylierung
KW  - Pyrosequenzierung
KW  - Minisequenzierung
KW  - Ergebnisreproduzierbarkeit
KW  - Laborleistungstests
KW  - DNA methylation
KW  - minisequencing
KW  - pyrosequencing
KW  - reproducibility of results
KW  - laboratory proficiency testing
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-307131
SN  - 0937-9819
SN  - 1434-5196
VL  - 31
IS  - 3
ER  - 
TY  - JOUR
A1  - Naue, Jana
A1  - Pfeifer, Manuel
A1  - Augustin, Christa
A1  - Becker, Julia
A1  - Fleckhaus, Jan
A1  - Grabmüller, Melanie
A1  - Han, Yang
A1  - Heidorn, Frank
A1  - Hollaender, Olivia
A1  - Klein-Unseld, Rachel
A1  - Kulstein, Galina
A1  - Lichtenwald, Julia
A1  - Neubauer, Jacqueline
A1  - Suarez, Philippe
A1  - Haas, Cordula
A1  - Schneider, Peter M.
A1  - Vennemann, Marielle
A1  - Böhme, Petra
T1  - Forensische DNA-Methylierungsanalyse
T1  - Forensic DNA methylation analysis : Second technical collaborative exercise by the working group on “molecular age estimation” of the German Society of Legal Medicine
BT  - Zweiter, technischer Ringversuch der Arbeitsgruppe „Molekulare Altersschätzung“ der Deutschen Gesellschaft für Rechtsmedizin
JF  - Rechtsmedizin
N2  - Mit der Entdeckung altersabhängiger epigenetischer Veränderungen, der DNA-Methylierung (DNAm), hat sich eine neue Möglichkeit aufgezeigt, das Alter eines Individuums zu schätzen. Die Methode wurde intensiv erforscht und ihre Anwendung in der forensischen Fallarbeit durch die Aktualisierung des § 81e der Strafprozessordnung (StPO) in Deutschland reguliert. Zur Untersuchung des DNAm-Grades müssen neue Techniken etabliert und validiert werden. Dies macht die Prüfung der Vergleichbarkeit von Messergebnissen aus verschiedenen forensischen Laboren erforderlich.

Hierzu führte die Arbeitsgruppe „Molekulare Altersschätzung“ der Deutschen Gesellschaft für Rechtsmedizin (DGRM) im Winter 2019/2020 den 2. Ringversuch (RV) zur quantitativen DNAm-Analyse mithilfe der Mini- und der Pyrosequenzierung durch. Dieser basierte auf den Erfahrungen des 1. RV 2018/2019, dessen Ergebnisse in dieser Ausgabe ebenfalls vorgestellt werden. Die aktuelle Studie umfasst Analyseergebnisse aus 12 Laboren (ingesamt 14 teilnehmende Labore), von denen einige beide Methoden angewandt haben. Zusätzlich führten 4 Labore eine Altersschätzung an den RV-Proben mit eigenen Markerkombinationen und Modellen durch. Da diese auf unterschiedlichen Referenzdaten und Markerkombinationen beruhen, erfolgte kein qualitativer Vergleich der Modelle, sondern das grundsätzliche Potenzial der Methodik wurde verdeutlicht. Ziele des RV waren die Evaluierung der Vergleichbarkeit der DNAm-Messungen und die Bewertung möglicher Einflussfaktoren, wie Extraktionsmethode und verwendetes Gerät.

Die Ergebnisse zeigen, dass sich die gemessenen DNAm-Werte der untersuchten Marker sowohl zwischen Mini- und Pyrosequenzierung als auch innerhalb der jeweiligen Methode zwischen den Laboren unterscheiden können, sodass mit Schwankungen gerechnet werden muss.
N2  - With the discovery of age-related epigenetic changes DNA methylation (DNAm) has shown new possibilities for the estimation of the age of an individual. The method has been intensively researched and its application in forensic casework is regulated by an amendment of § 81e of the German Code of Criminal Procedures (StPO). To investigate the degree of DNAm new techniques must be established and validated. This necessitates investigation of the comparability of measurement results from different forensic laboratories.

In winter 2019/2020 the molecular age estimation working group of the German Society of Legal Medicine (DGRM) conducted a second proficiency test to investigate this comparability using minisequencing and pyrosequencing for quantitative analysis of DNAm. This was based on the experience from the first proficiency test in 2018/2019, the results of which are presented in this edition of the journal. The current study includes the results of DNAm analysis from 12 laboratories (in total 14 participating laboratories), some of which have used both methods. In addition, four laboratories performed an age estimation using their own marker combinations and models. As these are based on different reference data and marker combinations, no qualitative comparison of the models was done but the fundamental potential of the methodology was clarified. The aim of the interlaboratory comparison was to evaluate the comparability of the DNAm measurements and to assess possible influencing factors, such as the extraction method and the device used.

The results showed that the measured DNAm values of the investigated markers can differ between minisequencing and pyrosequencing as well as within the respective method between laboratories, so that fluctuations are to be expected.
KW  - Epigenetik
KW  - Biomarker
KW  - Minisequenzierung
KW  - Pyrosequenzierung
KW  - Laborleistungstests
KW  - epigenetics
KW  - biomarker
KW  - minisequencing
KW  - pyrosequencing
KW  - laboratory proficiency testing
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-307129
SN  - 0937-9819
SN  - 1434-5196
VL  - 31
IS  - 3
ER  -