TY  - JOUR
A1  - Kaminski, Jakob A.
A1  - Schlagenhauf, Florian
A1  - Rapp, Michael A.
A1  - Awasthi, Swapnil
A1  - Ruggeri, Barbara
A1  - Deserno, Lorenz
A1  - Banaschewski, Tobias
A1  - Bokde, Arun L. W.
A1  - Bromberg, Uli
A1  - Büchel, Christian
A1  - Quinlan, Erin Burke
A1  - Desrivieres, Sylvane
A1  - Flor, Herta
A1  - Frouin, Vincent
A1  - Garavan, Hugh
A1  - Gowland, Penny
A1  - Ittermann, Bernd
A1  - Martinot, Jean-Luc
A1  - Martinot, Marie-Laure Paillere
A1  - Nees, Frauke
A1  - Orfanos, Dimitri Papadopoulos
A1  - Paus, Tomas
A1  - Poustka, Luise
A1  - Smolka, Michael N.
A1  - Fröhner, Juliane H.
A1  - Walter, Henrik
A1  - Whelan, Robert
A1  - Ripke, Stephan
A1  - Schumann, Gunter
A1  - Heinz, Andreas
T1  - Epigenetic variance in dopamine D2 receptor
BT  - a marker of IQ malleability?
JF  - Translational Psychiatry
N2  - Genetic and environmental factors both contribute to cognitive test performance. A substantial increase in average intelligence test results in the second half of the previous century within one generation is unlikely to be explained by genetic changes. One possible explanation for the strong malleability of cognitive performance measure is that environmental factors modify gene expression via epigenetic mechanisms. Epigenetic factors may help to understand the recent observations of an association between dopamine-dependent encoding of reward prediction errors and cognitive capacity, which was modulated by adverse life events. The possible manifestation of malleable biomarkers contributing to variance in cognitive test performance, and thus possibly contributing to the "missing heritability" between estimates from twin studies and variance explained by genetic markers, is still unclear. Here we show in 1475 healthy adolescents from the IMaging and GENetics (IMAGEN) sample that general IQ (gIQ) is associated with (1) polygenic scores for intelligence, (2) epigenetic modification of DRD2 gene, (3) gray matter density in striatum, and (4) functional striatal activation elicited by temporarily surprising reward-predicting cues. Comparing the relative importance for the prediction of gIQ in an overlapping subsample, our results demonstrate neurobiological correlates of the malleability of gIQ and point to equal importance of genetic variance, epigenetic modification of DRD2 receptor gene, as well as functional striatal activation, known to influence dopamine neurotransmission. Peripheral epigenetic markers are in need of confirmation in the central nervous system and should be tested in longitudinal settings specifically assessing individual and environmental factors that modify epigenetic structure.
Y1  - 2018
U6  - https://doi.org/10.1038/s41398-018-0222-7
SN  - 2158-3188
VL  - 8
PB  - Nature Publ. Group
CY  - New York
ER  - 
TY  - JOUR
A1  - Gellert, Paul
A1  - Häusler, Andreas
A1  - Suhr, Ralf
A1  - Gholami, Maryam
A1  - Rapp, Michael A.
A1  - Kuhlmey, Adelheid
A1  - Nordheim, Johanna
T1  - Testing the stress-buffering hypothesis of social support in couples coping with early-stage dementia
JF  - PLoS one
N2  - Purpose:
To test whether the negative relationship between perceived stress and quality of life (Hypothesis 1) can be buffered by perceived social support in patients with dementia as well as in caregivers individually (Hypothesis 2: actor effects) and across partners (Hypothesis 3: partner effects and actor-partner effects).

Method:
A total of 108 couples (N = 216 individuals) comprised of one individual with early-stage dementia and one caregiving partner were assessed at baseline and one month apart. Moderation effects were investigated by applying linear mixed models and actor-partner interdependence models.

Results:
Although the stress-quality of life association was more pronounced in caregivers (beta = -.63, p<.001) compared to patients (beta= -.31, p<.001), this association was equally moderated by social support in patients (beta = .14, p<.05) and in the caregivers (beta =.13, p<.05). From one partner to his or her counterpart, the partner buffering and actor-partner-buffering effect were not present. 

Conclusion:
The stress-buffering effect has been replicated in individuals with dementia and caregivers but not across partners. Interventions to improve quality of life through perceived social support should not only focus on caregivers, but should incorporate both partners.
Y1  - 2018
U6  - https://doi.org/10.1371/journal.pone.0189849
SN  - 1932-6203
VL  - 13
IS  - 1
PB  - PLoS
CY  - San Fransisco
ER  - 
TY  - GEN
A1  - Garbusow, Maria
A1  - Sommer, C.
A1  - Nebe, S.
A1  - Sebold, Miriam
A1  - Kuitunen-Paul, Sören
A1  - Wittchen, H. U.
A1  - Smolka, M.
A1  - Zimmermann, U.
A1  - Rapp, Michael A.
A1  - Huys, Q.
A1  - Schlagenhauf, Florian
A1  - Heinz, A.
T1  - Pavlovian-instrumental transfer in the course of alcohol use disorder
T2  - European psychiatry : the journal of the Association of European Psychiatrists
N2  - Background: Pavlovian processes are thought to play an important role in the development, maintenance and relapse of alcohol dependence, possibly by influencing and usurping on- going thought and behavior. The influence of Pavlovian stimuli on on-going behavior is paradigmatically measured by Pavlovian-to-instrumental-transfer (PIT) tasks. These involve multiple stages and are complex. Whether increased PIT is involved in human alcohol
dependence is uncertain. We therefore aimed to establish and validate a modified PIT paradigm that would be robust, consistent, and tolerated by healthy controls as well as by patients suffering from alcohol dependence, and to explore whether alcohol dependence is associated with enhanced Pavlovian-Instrumental transfer.

Methods: 32 recently detoxified alcohol-dependent patients and 32 age and gender matched healthy controls performed a PIT task with instrumental go/no-go approach behaviours. The task involved both Pavlovian stimuli associated with monetary rewards and losses, and images of drinks.

Results: Both patients and healthy controls showed a robust and temporally stable PIT effect. Strengths of PIT effects to drug-related and monetary conditioned stimuli were highly correlated. Patients more frequently showed a PIT effect and the effect was stronger in response to aversively conditioned CSs (conditioned suppression), but there was no group difference in response to appetitive CSs.

Conclusion: The implementation of PIT has favorably robust properties in chronic alcohol- dependent patients and in healthy controls. It shows internal consistency between monetary and drug-related cues. The findings support an association of alcohol dependence with an increased propensity towards PIT.
Y1  - 2018
SN  - 0924-9338
SN  - 1778-3585
VL  - 48
SP  - S546
EP  - S546
PB  - Elsevier
CY  - ISSY-LES-MOULINEAUX
ER  - 
TY  - JOUR
A1  - Heissel, Andreas
A1  - Pietrek, Anou F.
A1  - Schwefel, Melanie
A1  - Abula, Kahar
A1  - Wilbertz, Gregor
A1  - Heinzel, Stephan
A1  - Rapp, Michael A.
T1  - STEP.De study
BT  - a multicentre cluster-randomised effectiveness trial of exercise therapy for patients with depressive symptoms in healthcare services : study protocol
JF  - BMJ open
N2  - Introduction Although exercise therapy has widely been shown to be an efficacious treatment modality for depression, evidence for its effectiveness and cost efficiency is lacking. The Sport/Exercise Therapy for Depression study is a multicentre cluster-randomised effectiveness trial that aims to compare the effectiveness and cost efficiency of exercise therapy and psychotherapy as antidepressant treatment. <br /> Methods and analysis 480 patients (aged 18-65) with an International Classification of Diseases diagnosis associated with depressive symptoms are recruited. Up to 30 clusters (psychotherapists) are randomly assigned to allocate patients to either an exercise or a psychotherapy treatment as usual in a 2: 1 ratio. The primary outcome (depressive symptoms) and the secondary outcomes (work and social adjustment, quality of life) will be assessed at six measurement time points (t0: baseline, t1: 8 weeks after treatment initiation, t2: 16 weeks after treatment initiation, t3/ 4/5: 2, 6, 12 months after treatment). Linear regression analyses will be used for the primary endpoint data analysis. For the secondary endpoints, mixed linear and logistic regression models with fixed and random factors will be added. For the cost efficiency analysis, expenditures in the 12 months before and after the intervention and the outcome difference will be compared between groups in a multilevel model. Recruitment start date was 1 July 2018 and the planned recruitment end date is 31 December 2020. <br /> Ethics and dissemination The study protocol was approved by the ethics committee of the University of Potsdam (No. 17/2018) and the Freie Universitat Berlin (No. 206/2018) and registered in the ISRCTN registry. Informed written consent will be obtained from all participants. The study will be reported in accordance with the Consolidated Standards of Reporting Trials and the Recommendations for Interventional Trials statements. The results will be published in peer-reviewed academic journals and disseminated to the public.
Y1  - 2020
U6  - https://doi.org/10.1136/bmjopen-2019-036287
SN  - 2044-6055
VL  - 10
IS  - 4
PB  - BMJ Publishing Group
CY  - London
ER  - 
TY  - JOUR
A1  - Schulze, Susanne
A1  - Merz, Sibille
A1  - Thier, Anne
A1  - Tallarek, Marie
A1  - König, Franziska
A1  - Uhlenbrock, Greta
A1  - Nübling, Matthias
A1  - Lincke, Hans-Joachim
A1  - Rapp, Michael A.
A1  - Spallek, Jacob
A1  - Holmberg, Christine
T1  - Psychosocial burden in nurses working in nursing homes during the Covid-19 pandemic
BT  - a cross-sectional study with quantitative and qualitative data
JF  - BMC health services research
N2  - Background The Covid-19 pandemic led to increased work-related strain and psychosocial burden in nurses worldwide, resulting in high prevalences of mental health problems. Nurses in long-term care facilities seem to be especially affected by the pandemic. Nevertheless, there are few findings indicating possible positive changes for health care workers. Therefore, we investigated which psychosocial burdens and potential positive aspects nurses working in long-term care facilities experience during the Covid-19 pandemic. Methods We conducted a mixed-methods study among nurses and nursing assistants working in nursing homes in Germany. The survey contained the third German version of the Copenhagen Psychosocial Questionnaire (COPSOQ III). Using Welch's t-tests, we compared the COPSOQ results of our sample against a pre-pandemic reference group of geriatric nurses from Germany. Additionally, we conducted semi-structured interviews with geriatric nurses with a special focus on psychosocial stress, to reach a deeper understanding of their experiences on work-related changes and burdens during the pandemic. Data were analysed using thematic coding (Braun and Clarke). Results Our survey sample (n = 177) differed significantly from the pre-pandemic reference group in 14 out of 31 COPSOQ scales. Almost all of these differences indicated negative changes. Our sample scored significantly worse regarding the scales 'quantitative demands', 'hiding emotions', 'work-privacy conflicts', 'role conflicts', 'quality of leadership', 'support at work', 'recognition', 'physical demands', 'intention to leave profession', 'burnout', 'presenteeism' and 'inability to relax'. The interviews (n = 15) revealed six main themes related to nurses' psychosocial stress: 'overall working conditions', 'concern for residents', 'management of relatives', 'inability to provide terminal care', 'tensions between being infected and infecting others' and 'technicisation of care'. 'Enhanced community cohesion' (interviews), 'meaning of work' and 'quantity of social relations' (COPSOQ III) were identified as positive effects of the pandemic. Conclusions Results clearly illustrate an aggravation of geriatric nurses' situation and psychosocial burden and only few positive changes due to the Covid-19 pandemic. Pre-existing hardships seem to have further deteriorated and new stressors added to nurses' strain. The perceived erosion of care, due to an overemphasis of the technical in relation to the social and emotional dimensions of care, seems to be especially burdensome to geriatric nurses.
KW  - COPSOQ
KW  - Nurses
KW  - Nursing home
KW  - Psychosocial burden
KW  - Mixed-methods study
KW  - Covid-19
Y1  - 2022
U6  - https://doi.org/10.1186/s12913-022-08333-3
SN  - 1472-6963
VL  - 22
IS  - 1
PB  - BMC
CY  - London
ER  - 
TY  - JOUR
A1  - Förstner, Bernd Rainer
A1  - Böttger, Sarah Jane
A1  - Moldavski, Alexander
A1  - Bajbouj, Malek
A1  - Pfennig, Andrea
A1  - Manook, Andre
A1  - Ising, Marcus
A1  - Pittig, Andre
A1  - Heinig, Ingmar
A1  - Heinz, Andreas
A1  - Mathiak, Klaus
A1  - Schulze, Thomas G.
A1  - Schneider, Frank
A1  - Kamp-Becker, Inge
A1  - Meyer-Lindenberg, Andreas
A1  - Padberg, Frank
A1  - Banaschewski, Tobias
A1  - Bauer, Michael
A1  - Rupprecht, Rainer
A1  - Wittchen, Hans-Ulrich
A1  - Rapp, Michael A.
A1  - Tschorn, Mira
T1  - The associations of positive and negative valence systems, cognitive systems and social processes on disease severity in anxiety and depressive disorders
JF  - Frontiers in psychiatry
N2  - Background   Anxiety and depressive disorders share common features of mood dysfunctions. This has stimulated interest in transdiagnostic dimensional research as proposed by the Research Domain Criteria (RDoC) approach by the National Institute of Mental Health (NIMH) aiming to improve the understanding of underlying disease mechanisms. The purpose of this study was to investigate the processing of RDoC domains in relation to disease severity in order to identify latent disorder-specific as well as transdiagnostic indicators of disease severity in patients with anxiety and depressive disorders. 

Methods   Within the German research network for mental disorders, 895 participants (n = 476 female, n = 602 anxiety disorder, n = 257 depressive disorder) were recruited for the Phenotypic, Diagnostic and Clinical Domain Assessment Network Germany (PD-CAN) and included in this cross-sectional study. We performed incremental regression models to investigate the association of four RDoC domains on disease severity in patients with affective disorders: Positive (PVS) and Negative Valance System (NVS), Cognitive Systems (CS) and Social Processes (SP). 

Results   The results confirmed a transdiagnostic relationship for all four domains, as we found significant main effects on disease severity within domain-specific models (PVS: & beta; = -0.35; NVS: & beta; = 0.39; CS: & beta; = -0.12; SP: & beta; = -0.32). We also found three significant interaction effects with main diagnosis showing a disease-specific association. 

Limitations   The cross-sectional study design prevents causal conclusions. Further limitations include possible outliers and heteroskedasticity in all regression models which we appropriately controlled for. 

Conclusion   Our key results show that symptom burden in anxiety and depressive disorders is associated with latent RDoC indicators in transdiagnostic and disease-specific ways.
KW  - Research Domain Criteria
KW  - depression
KW  - anxiety disoders
KW  - disease severity
KW  - transdiagnostic
KW  - RDoC
Y1  - 2023
U6  - https://doi.org/10.3389/fpsyt.2023.1161097
SN  - 1664-0640
VL  - 14
PB  - Frontiers Research Foundation
CY  - Lausanne
ER  - 
TY  - GEN
A1  - Sebold, Miriam
A1  - Garbusow, Maria
A1  - Nebe, S.
A1  - Sundmacher, L.
A1  - Kuitunen-Paul, Sören
A1  - Wittchen, H. U.
A1  - Smolka, M.
A1  - Zimmermann, U.
A1  - Rapp, Michael A.
A1  - Huys, Q.
A1  - Schlagenhauf, Florian
A1  - Heinz, A.
T1  - From goals to habits in alcohol dependence
BT  - association with treatment outcome and cognitive bias modification training
T2  - European psychiatry : the journal of the Association of European Psychiatrists
Y1  - 2018
SN  - 0924-9338
SN  - 1778-3585
VL  - 48
SP  - S274
EP  - S274
PB  - Elsevier
CY  - Paris
ER  - 
TY  - JOUR
A1  - Garbusow, Maria
A1  - Nebe, Stephan
A1  - Sommer, Christian
A1  - Kuitunen-Paul, Sören
A1  - Sebold, Miriam
A1  - Schad, Daniel
A1  - Friedel, Eva
A1  - Veer, Ilya M.
A1  - Wittchen, Hans-Ulrich
A1  - Rapp, Michael A.
A1  - Ripke, Stephan
A1  - Walter, Henrik
A1  - Huys, Quentin J. M.
A1  - Schlagenhauf, Florian
A1  - Smolka, Michael N.
A1  - Heinz, Andreas
T1  - Pavlovian-To-Instrumental Transfer and Alcohol Consumption in Young Male Social Drinkers
BT  - Behavioral, Neural and Polygenic Correlates
JF  - Journal of Clinical Medicine
N2  - In animals and humans, behavior can be influenced by irrelevant stimuli, a phenomenon called Pavlovian-to-instrumental transfer (PIT). In subjects with substance use disorder, PIT is even enhanced with functional activation in the nucleus accumbens (NAcc) and amygdala. While we observed enhanced behavioral and neural PIT effects in alcohol-dependent subjects, we here aimed to determine whether behavioral PIT is enhanced in young men with high-risk compared to low-risk drinking and subsequently related functional activation in an a-priori region of interest encompassing the NAcc and amygdala and related to polygenic risk for alcohol consumption. A representative sample of 18-year old men (n = 1937) was contacted: 445 were screened, 209 assessed: resulting in 191 valid behavioral, 139 imaging and 157 genetic datasets. None of the subjects fulfilled criteria for alcohol dependence according to the Diagnostic and Statistical Manual of Mental Disorders-IV-TextRevision (DSM-IV-TR). We measured how instrumental responding for rewards was influenced by background Pavlovian conditioned stimuli predicting action-independent rewards and losses. Behavioral PIT was enhanced in high-compared to low-risk drinkers (b = 0.09, SE = 0.03, z = 2.7, p < 0.009). Across all subjects, we observed PIT-related neural blood oxygen level-dependent (BOLD) signal in the right amygdala (t = 3.25, p(SVC) = 0.04, x = 26, y = -6, z = -12), but not in NAcc. The strength of the behavioral PIT effect was positively correlated with polygenic risk for alcohol consumption (r(s) = 0.17, p = 0.032). We conclude that behavioral PIT and polygenic risk for alcohol consumption might be a biomarker for a subclinical phenotype of risky alcohol consumption, even if no drug-related stimulus is present. The association between behavioral PIT effects and the amygdala might point to habitual processes related to out PIT task. In non-dependent young social drinkers, the amygdala rather than the NAcc is activated during PIT; possible different involvement in association with disease trajectory should be investigated in future studies.
KW  - Pavlovian-to-instrumental transfer
KW  - amygdala
KW  - alcohol
KW  - polygenic risk
KW  - high risk drinkers
Y1  - 2019
U6  - https://doi.org/10.3390/jcm8081188
SN  - 2077-0383
VL  - 8
IS  - 8
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Jacob, Louis
A1  - Rapp, Michael A.
A1  - Kostev, Karel
T1  - Long-term use of benzodiazepines in older patients in Germany
BT  - a retrospective analysis
JF  - Therapeutic Advances in Psychopharmacology
N2  - Background: The purpose of this study was to analyze the prevalence of long-term benzodiazepine use in older adults treated in general and neuropsychiatric practices in Germany. Methods: This study included 32,182 patients over the age of 65 years who received benzodiazepine prescriptions for the first time between January 2010 and December 2014 in general and neuropsychiatric practices in Germany. Follow up lasted until July 2016. The main outcome measure was the proportion of patients treated with benzodiazepines for >6 months. Results: The proportion of patients with benzodiazepine therapy for >6 months increased with age (65-70 years: 12.3%; 71-80 years: 15.5%; 81-90 years: 23.7%; >90 years: 31.6%) but did not differ significantly between men (15.5%) and women (17.1%). The proportion of patients who received benzodiazepines for >6 months was higher among those with sleep disorders (21.1%), depression (20.8%) and dementia (32.1%) than among those with anxiety (15.5%). By contrast, this proportion was lower among people diagnosed with adjustment disorders (7.7%) and back pain (3.8%). Conclusion: Overall, long-term use of benzodiazepines is common in older people, particularly in patients over the age of 80 and in those diagnosed with dementia, sleep disorders, or depression.
KW  - benzodiazepines
KW  - Germany
KW  - long-term use
KW  - older people
KW  - risk factors
Y1  - 2017
U6  - https://doi.org/10.1177/2045125317696454
SN  - 2045-1253
SN  - 2045-1261
VL  - 7
IS  - 6/7
SP  - 191
EP  - 200
PB  - Sage Publ.
CY  - London
ER  - 
TY  - JOUR
A1  - Sebold, Miriam
A1  - Chen, Hao
A1  - Önal, Aleyna
A1  - Kuitunen-Paul, Sören
A1  - Mojtahedzadeh, Negin
A1  - Garbusow, Maria
A1  - Nebe, Stephan
A1  - Wittchen, Hans-Ulrich
A1  - Huys, Quentin J. M.
A1  - Schlagenhauf, Florian
A1  - Rapp, Michael A.
A1  - Smolka, Michael N.
A1  - Heinz, Andreas
T1  - Stronger prejudices are associated with decreased model-based control
JF  - Frontiers in psychology
N2  - Background: 
Prejudices against minorities can be understood as habitually negative evaluations that are kept in spite of evidence to the contrary. Therefore, individuals with strong prejudices might be dominated by habitual or "automatic" reactions at the expense of more controlled reactions. Computational theories suggest individual differences in the balance between habitual/model-free and deliberative/model-based decision-making.

Methods: 
127 subjects performed the two Step task and completed the blatant and subtle prejudice scale.

Results: 
By using analyses of choices and reaction times in combination with computational modeling, subjects with stronger blatant prejudices showed a shift away from model-based control. There was no association between these decision-making processes and subtle prejudices.

Conclusion: 
These results support the idea that blatant prejudices toward minorities are related to a relative dominance of habitual decision-making. This finding has important implications for developing interventions that target to change prejudices across societies.
KW  - subtle and blatant prejudice
KW  - immigrant
KW  - social behavior;
KW  - decision-making
KW  - computational modeling
KW  - reinforcement learning
Y1  - 2022
U6  - https://doi.org/10.3389/fpsyg.2021.767022
SN  - 1664-1078
VL  - 12
PB  - Frontiers Research Foundation
CY  - Lausanne
ER  - 
TY  - JOUR
A1  - Jara Muñoz, Julius
A1  - Melnick, Daniel
A1  - Li, Shaoyang
A1  - Socquet, Anne
A1  - Cortés-Aranda, Joaquín
A1  - Brill, Dominik
A1  - Strecker, Manfred
T1  - The cryptic seismic potential of the Pichilemu blind fault in Chile revealed by off-fault geomorphology
JF  - Nature Communications
N2  - The first step towards assessing hazards in seismically active regions involves mapping capable faults and estimating their recurrence times. While the mapping of active faults is commonly based on distinct geologic and geomorphic features evident at the surface, mapping blind seismogenic faults is complicated by the absence of on-fault diagnostic features. Here we investigated the Pichilemu Fault in coastal Chile, unknown until it generated a Mw 7.0 earthquake in 2010. The lack of evident surface faulting suggests activity along a partly-hidden blind fault. We used off-fault deformed marine terraces to estimate a fault-slip rate of 0.52 ± 0.04 m/ka, which, when integrated with satellite geodesy suggests a 2.12 ± 0.2 ka recurrence time for Mw~7.0 normal-faulting earthquakes. We propose that extension in the Pichilemu region is associated with stress changes during megathrust earthquakes and accommodated by sporadic slip during upper-plate earthquakes, which has implications for assessing the seismic potential of cryptic faults along convergent margins and elsewhere.
Y1  - 2022
U6  - https://doi.org/10.1038/s41467-022-30754-1
SN  - 2041-1723
VL  - 13
PB  - Springer Nature
CY  - London
ER  - 
TY  - JOUR
A1  - De Freitas, Jessica K.
A1  - Johnson, Kipp W.
A1  - Golden, Eddye
A1  - Nadkarni, Girish N.
A1  - Dudley, Joel T.
A1  - Böttinger, Erwin
A1  - Glicksberg, Benjamin S.
A1  - Miotto, Riccardo
T1  - Phe2vec
BT  - Automated disease phenotyping based on unsupervised embeddings from electronic health records
JF  - Patterns
N2  - Robust phenotyping of patients from electronic health records (EHRs) at scale is a challenge in clinical informatics. Here, we introduce Phe2vec, an automated framework for disease phenotyping from EHRs based on unsupervised learning and assess its effectiveness against standard rule-based algorithms from Phenotype KnowledgeBase (PheKB). Phe2vec is based on pre-computing embeddings of medical concepts and patients' clinical history. Disease phenotypes are then derived from a seed concept and its neighbors in the embedding space. Patients are linked to a disease if their embedded representation is close to the disease phenotype. Comparing Phe2vec and PheKB cohorts head-to-head using chart review, Phe2vec performed on par or better in nine out of ten diseases. Differently from other approaches, it can scale to any condition and was validated against widely adopted expert-based standards. Phe2vec aims to optimize clinical informatics research by augmenting current frameworks to characterize patients by condition and derive reliable disease cohorts.
Y1  - 2021
U6  - https://doi.org/10.1016/j.patter.2021.100337
SN  - 2666-3899
VL  - 2
IS  - 9
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Grdseloff, Nastasja
A1  - Boulday, Gwenola
A1  - Roedel, Claudia J.
A1  - Otten, Cecile
A1  - Vannier, Daphne Raphaelle
A1  - Cardoso, Cecile
A1  - Faurobert, Eva
A1  - Dogra, Deepika
A1  - Tournier-Lasserve, Elisabeth
A1  - Abdelilah-Seyfried, Salim
T1  - Impaired retinoic acid signaling in cerebral cavernous malformations
JF  - Scientific reports
N2  - The capillary-venous pathology cerebral cavernous malformation (CCM) is caused by loss of CCM1/Krev interaction trapped protein 1 (KRIT1), CCM2/MGC4607, or CCM3/PDCD10 in some endothelial cells. Mutations of CCM genes within the brain vasculature can lead to recurrent cerebral hemorrhages. Pharmacological treatment options are urgently needed when lesions are located in deeply-seated and in-operable regions of the central nervous system. Previous pharmacological suppression screens in disease models of CCM led to the discovery that treatment with retinoic acid improved CCM phenotypes. This finding raised a need to investigate the involvement of retinoic acid in CCM and test whether it has a curative effect in preclinical mouse models. Here, we show that components of the retinoic acid synthesis and degradation pathway are transcriptionally misregulated across disease models of CCM. We complemented this analysis by pharmacologically modifying retinoic acid levels in zebrafish and human endothelial cell models of CCM, and in acute and chronic mouse models of CCM. Our pharmacological intervention studies in CCM2-depleted human umbilical vein endothelial cells (HUVECs) and krit1 mutant zebrafish showed positive effects when retinoic acid levels were increased. However, therapeutic approaches to prevent the development of vascular lesions in adult chronic murine models of CCM were drug regiment-sensitive, possibly due to adverse developmental effects of this hormone. A treatment with high doses of retinoic acid even worsened CCM lesions in an adult chronic murine model of CCM. This study provides evidence that retinoic acid signaling is impaired in the CCM pathophysiology and suggests that modification of retinoic acid levels can alleviate CCM phenotypes.
KW  - Developmental biology
KW  - Molecular medicine
Y1  - 2023
U6  - https://doi.org/10.1038/s41598-023-31905-0
SN  - 2045-2322
VL  - 13
IS  - 1
PB  - Nature Portfolio
CY  - Berlin
ER  - 
TY  - JOUR
A1  - Smith, Taylor
A1  - Boers, Niklas
T1  - Global vegetation resilience linked to water availability and variability
JF  - Nature Communications
N2  - Quantifying the resilience of vegetated ecosystems is key to constraining both present-day and future global impacts of anthropogenic climate change. Here we apply both empirical and theoretical resilience metrics to remotely-sensed vegetation data in order to examine the role of water availability and variability in controlling vegetation resilience at the global scale. We find a concise global relationship where vegetation resilience is greater in regions with higher water availability. We also reveal that resilience is lower in regions with more pronounced inter-annual precipitation variability, but find less concise relationships between vegetation resilience and intra-annual precipitation variability. Our results thus imply that the resilience of vegetation responds differently to water deficits at varying time scales. In view of projected increases in precipitation variability, our findings highlight the risk of ecosystem degradation under ongoing climate change. 

Vegetation dynamics depend on both the amount of precipitation and its variability over time. Here, the authors show that vegetation resilience is greater where water availability is higher and where precipitation is more stable from year to year.
Y1  - 2023
U6  - https://doi.org/10.1038/s41467-023-36207-7
SN  - 2041-1723
VL  - 14
IS  - 1
PB  - Springer Nature
CY  - London
ER  - 
TY  - JOUR
A1  - Falkenhagen, Undine
A1  - Knöchel, Jane
A1  - Kloft, Charlotte
A1  - Huisinga, Wilhelm
T1  - Deriving mechanism-based pharmacodynamic models by reducing quantitative systems pharmacology models
BT  - an application to warfarin
JF  - CPT: Pharmacometrics & Systems Pharmacology
N2  - Quantitative systems pharmacology (QSP) models integrate comprehensive qualitative and quantitative knowledge about pharmacologically relevant processes. We previously proposed a first approach to leverage the knowledge in QSP models to derive simpler, mechanism-based pharmacodynamic (PD) models. Their complexity, however, is typically still too large to be used in the population analysis of clinical data. Here, we extend the approach beyond state reduction to also include the simplification of reaction rates, elimination of reactions, and analytic solutions. We additionally ensure that the reduced model maintains a prespecified approximation quality not only for a reference individual but also for a diverse virtual population. We illustrate the extended approach for the warfarin effect on blood coagulation. Using the model-reduction approach, we derive a novel small-scale warfarin/international normalized ratio model and demonstrate its suitability for biomarker identification. Due to the systematic nature of the approach in comparison with empirical model building, the proposed model-reduction algorithm provides an improved rationale to build PD models also from QSP models in other applications.
Y1  - 2023
U6  - https://doi.org/10.1002/psp4.12903
SN  - 2163-8306
VL  - 12
IS  - 4
SP  - 432
EP  - 443
PB  - Wiley
CY  - Hoboken
ER  - 
TY  - JOUR
A1  - Datta, Suparno
A1  - Sachs, Jan Philipp
A1  - Freitas da Cruz, Harry
A1  - Martensen, Tom
A1  - Bode, Philipp
A1  - Morassi Sasso, Ariane
A1  - Glicksberg, Benjamin S.
A1  - Böttinger, Erwin
T1  - FIBER
BT  - enabling flexible retrieval of electronic health records data for clinical predictive modeling
JF  - JAMIA open
N2  - Objectives: 
The development of clinical predictive models hinges upon the availability of comprehensive clinical data. Tapping into such resources requires considerable effort from clinicians, data scientists, and engineers. Specifically, these efforts are focused on data extraction and preprocessing steps required prior to modeling, including complex database queries. A handful of software libraries exist that can reduce this complexity by building upon data standards. However, a gap remains concerning electronic health records (EHRs) stored in star schema clinical data warehouses, an approach often adopted in practice. In this article, we introduce the FlexIBle EHR Retrieval (FIBER) tool: a Python library built on top of a star schema (i2b2) clinical data warehouse that enables flexible generation of modeling-ready cohorts as data frames. 

Materials and Methods: 
FIBER was developed on top of a large-scale star schema EHR database which contains data from 8 million patients and over 120 million encounters. To illustrate FIBER's capabilities, we present its application by building a heart surgery patient cohort with subsequent prediction of acute kidney injury (AKI) with various machine learning models. 

Results:
Using FIBER, we were able to build the heart surgery cohort (n = 12 061), identify the patients that developed AKI (n = 1005), and automatically extract relevant features (n = 774). Finally, we trained machine learning models that achieved area under the curve values of up to 0.77 for this exemplary use case.

Conclusion: 
FIBER is an open-source Python library developed for extracting information from star schema clinical data warehouses and reduces time-to-modeling, helping to streamline the clinical modeling process.
KW  - databases
KW  - factual
KW  - electronic health records
KW  - information storage and
KW  - retrieval
KW  - workflow
KW  - software/instrumentation
Y1  - 2021
U6  - https://doi.org/10.1093/jamiaopen/ooab048
SN  - 2574-2531
VL  - 4
IS  - 3
PB  - Oxford Univ. Press
CY  - Oxford
ER  - 
TY  - JOUR
A1  - Cope, Justin L.
A1  - Baukmann, Hannes A.
A1  - Klinger, Jörn E.
A1  - Ravarani, Charles N. J.
A1  - Böttinger, Erwin
A1  - Konigorski, Stefan
A1  - Schmidt, Marco F.
T1  - Interaction-based feature selection algorithm outperforms polygenic risk score in predicting Parkinson’s Disease status
JF  - Frontiers in genetics
N2  - Polygenic risk scores (PRS) aggregating results from genome-wide association studies are the state of the art in the prediction of susceptibility to complex traits or diseases, yet their predictive performance is limited for various reasons, not least of which is their failure to incorporate the effects of gene-gene interactions. Novel machine learning algorithms that use large amounts of data promise to find gene-gene interactions in order to build models with better predictive performance than PRS. Here, we present a data preprocessing step by using data-mining of contextual information to reduce the number of features, enabling machine learning algorithms to identify gene-gene interactions. We applied our approach to the Parkinson's Progression Markers Initiative (PPMI) dataset, an observational clinical study of 471 genotyped subjects (368 cases and 152 controls). With an AUC of 0.85 (95% CI = [0.72; 0.96]), the interaction-based prediction model outperforms the PRS (AUC of 0.58 (95% CI = [0.42; 0.81])). Furthermore, feature importance analysis of the model provided insights into the mechanism of Parkinson's disease. For instance, the model revealed an interaction of previously described drug target candidate genes TMEM175 and GAPDHP25. These results demonstrate that interaction-based machine learning models can improve genetic prediction models and might provide an answer to the missing heritability problem.
KW  - epistasis
KW  - machine learning
KW  - feature selection
KW  - parkinson's disease
KW  - PPMI (parkinson's progression markers initiative)
Y1  - 2021
U6  - https://doi.org/10.3389/fgene.2021.744557
SN  - 1664-8021
VL  - 12
PB  - Frontiers Media
CY  - Lausanne
ER  - 
TY  - JOUR
A1  - Lewkowicz, Daniel
A1  - Böttinger, Erwin
A1  - Siegel, Martin
T1  - Economic evaluation of digital therapeutic care apps for unsupervised treatment of low back pain
BT  - Monte Carlo Simulation
JF  - JMIR mhealth and uhealth
N2  - Background: 
Digital therapeutic care (DTC) programs are unsupervised app-based treatments that provide video exercises and educational material to patients with nonspecific low back pain during episodes of pain and functional disability. German statutory health insurance can reimburse DTC programs since 2019, but evidence on efficacy and reasonable pricing remains scarce. This paper presents a probabilistic sensitivity analysis (PSA) to evaluate the efficacy and cost-utility of a DTC app against treatment as usual (TAU) in Germany. 

Objective: 
The aim of this study was to perform a PSA in the form of a Monte Carlo simulation based on the deterministic base case analysis to account for model assumptions and parameter uncertainty. We also intend to explore to what extent the results in this probabilistic analysis differ from the results in the base case analysis and to what extent a shortage of outcome data concerning quality-of-life (QoL) metrics impacts the overall results. 

Methods: 
The PSA builds upon a state-transition Markov chain with a 4-week cycle length over a model time horizon of 3 years from a recently published deterministic cost-utility analysis. A Monte Carlo simulation with 10,000 iterations and a cohort size of 10,000 was employed to evaluate the cost-utility from a societal perspective. Quality-adjusted life years (QALYs) were derived from Veterans RAND 6-Dimension (VR-6D) and Short-Form 6-Dimension (SF-6D) single utility scores. Finally, we also simulated reducing the price for a 3-month app prescription to analyze at which price threshold DTC would result in being the dominant strategy over TAU in Germany. 

Results: 
The Monte Carlo simulation yielded on average a euro135.97 (a currency exchange rate of EUR euro1=US $1.069 is applicable) incremental cost and 0.004 incremental QALYs per person and year for the unsupervised DTC app strategy compared to in-person physiotherapy in Germany. The corresponding incremental cost-utility ratio (ICUR) amounts to an additional euro34,315.19 per additional QALY. DTC yielded more QALYs in 54.96% of the iterations. DTC dominates TAU in 24.04% of the iterations for QALYs. Reducing the app price in the simulation from currently euro239.96 to euro164.61 for a 3-month prescription could yield a negative ICUR and thus make DTC the dominant strategy, even though the estimated probability of DTC being more effective than TAU is only 54.96%.

Conclusions:
Decision-makers should be cautious when considering the reimbursement of DTC apps since no significant treatment effect was found, and the probability of cost-effectiveness remains below 60% even for an infinite willingness-to-pay threshold. More app-based studies involving the utilization of QoL outcome parameters are urgently needed to account for the low and limited precision of the available QoL input parameters, which are crucial to making profound recommendations concerning the cost-utility of novel apps.
KW  - cost-utility analysis
KW  - cost
KW  - probabilistic sensitivity analysis
KW  - Monte Carlo simulation
KW  - low back pain
KW  - pain
KW  - economic
KW  - cost-effectiveness
KW  - Markov model
KW  - digital therapy
KW  - digital health app
KW  - mHealth
KW  - mobile health
KW  - health app
KW  - mobile app
KW  - orthopedic
KW  - QUALY
KW  - DALY
KW  - quality-adjusted life years
KW  - disability-adjusted life years
KW  - time horizon
KW  - veteran
KW  - statistics
Y1  - 2023
U6  - https://doi.org/10.2196/44585
SN  - 2291-5222
VL  - 11
PB  - JMIR Publications
CY  - Toronto
ER  - 
TY  - JOUR
A1  - Konigorski, Stefan
A1  - Wernicke, Sarah
A1  - Slosarek, Tamara
A1  - Zenner, Alexander M.
A1  - Strelow, Nils
A1  - Ruether, Darius F.
A1  - Henschel, Florian
A1  - Manaswini, Manisha
A1  - Pottbäcker, Fabian
A1  - Edelman, Jonathan A.
A1  - Owoyele, Babajide
A1  - Danieletto, Matteo
A1  - Golden, Eddye
A1  - Zweig, Micol
A1  - Nadkarni, Girish N.
A1  - Böttinger, Erwin
T1  - StudyU: a platform for designing and conducting innovative digital N-of-1 trials
JF  - Journal of medical internet research
N2  - N-of-1 trials are the gold standard study design to evaluate individual treatment effects and derive personalized treatment strategies.  Digital tools have the potential to initiate a new era of N-of-1 trials in terms of scale and scope, but fully functional platforms are not yet available. 
Here, we present the open source StudyU platform, which includes the StudyU Designer and StudyU app. 
With the StudyU Designer, scientists are given a collaborative web application to digitally specify, publish, and conduct N-of-1 trials. 
The StudyU app is a smartphone app with innovative user-centric elements for participants to partake in trials published through the StudyU Designer to assess the effects of different interventions on their health. 
Thereby, the StudyU platform allows clinicians and researchers worldwide to easily design and conduct digital N-of-1 trials in a safe manner. 
We envision that StudyU can change the landscape of personalized treatments both for patients and healthy individuals, democratize and personalize evidence generation for self-optimization and medicine, and can be integrated in clinical practice.
KW  - digital interventions
KW  - N-of-1 trial
KW  - SCED
KW  - single-case experimental design
KW  - web application
KW  - mobile application
KW  - app
KW  - digital health
Y1  - 2022
U6  - https://doi.org/10.2196/35884
SN  - 1439-4456
SN  - 1438-8871
VL  - 24
IS  - 7
PB  - Healthcare World
CY  - Richmond, Va.
ER  - 
TY  - JOUR
A1  - Woutersen, Amber
A1  - Jardine, Phillip E.
A1  - Giovanni Bogota-Angel, Raul
A1  - Zhang, Hong-Xiang
A1  - Silvestro, Daniele
A1  - Antonelli, Alexandre
A1  - Gogna, Elena
A1  - Erkens, Roy H. J.
A1  - Gosling, William D.
A1  - Dupont-Nivet, Guillaume
A1  - Hoorn, Carina
T1  - A novel approach to study the morphology and chemistry of pollen in a phylogenetic context, applied to the halophytic taxon Nitraria L.(Nitrariaceae)
JF  - PeerJ
N2  - Nitraria is a halophytic taxon (i.e., adapted to saline environments) that belongs to the plant family Nitrariaceae and is distributed from the Mediterranean, across Asia into the south-eastern tip of Australia. This taxon is thought to have originated in Asia during the Paleogene (66-23 Ma), alongside the proto-Paratethys epicontinental sea. The evolutionary history of Nitraria might hold important clues on the links between climatic and biotic evolution but limited taxonomic documentation of this taxon has thus far hindered this line of research. Here we investigate if the pollen morphology and the chemical composition of the pollen wall are informative of the evolutionary history of Nitraria and could explain if origination along the proto-Paratethys and dispersal to the Tibetan Plateau was simultaneous or a secondary process. To answer these questions, we applied a novel approach consisting of a combination of Fourier Transform Infrared spectroscopy (FTIR), to determine the chemical composition of the pollen wall, and pollen morphological analyses using Light Microscopy (LM) and Scanning Electron Microscopy (SEM). We analysed our data using ordinations (principal components analysis and non-metric multidimensional scaling), and directly mapped it on the Nitrariaceae phylogeny to produce a phylomorphospace and a phylochemospace. Our LM, SEM and FTIR analyses show clear morphological and chemical differences between the sister groups Peganum and Nitraria. Differences in the morphological and chemical characteristics of highland species (Nitraria schoberi, N. sphaerocarpa, N. sibirica and N. tangutorum) and lowland species (Nitraria billardierei and N. retusa) are very subtle, with phylogenetic history appearing to be a more important control on Nitraria pollen than local environmental conditions. Our approach shows a compelling consistency between the chemical and morphological characteristics of the eight studied Nitrariaceae species, and these traits are in agreement with the phylogenetic tree. Taken together, this demonstrates how novel methods for studying fossil pollen can facilitate the evolutionary investigation of living and extinct taxa, and the environments they represent.
KW  - FTIR
KW  - LM
KW  - SEM
KW  - Paratethys
KW  - Tibet
KW  - Sporopollenin
KW  - Mediterranean
KW  - Steppe-desert
KW  - Australia
KW  - Palynology
Y1  - 2018
U6  - https://doi.org/10.7717/peerj.5055
SN  - 2167-8359
VL  - 6
PB  - PeerJ Inc.
CY  - London
ER  - 
TY  - JOUR
A1  - Vaid, Akhil
A1  - Somani, Sulaiman
A1  - Russak, Adam J.
A1  - De Freitas, Jessica K.
A1  - Chaudhry, Fayzan F.
A1  - Paranjpe, Ishan
A1  - Johnson, Kipp W.
A1  - Lee, Samuel J.
A1  - Miotto, Riccardo
A1  - Richter, Felix
A1  - Zhao, Shan
A1  - Beckmann, Noam D.
A1  - Naik, Nidhi
A1  - Kia, Arash
A1  - Timsina, Prem
A1  - Lala, Anuradha
A1  - Paranjpe, Manish
A1  - Golden, Eddye
A1  - Danieletto, Matteo
A1  - Singh, Manbir
A1  - Meyer, Dara
A1  - O'Reilly, Paul F.
A1  - Huckins, Laura
A1  - Kovatch, Patricia
A1  - Finkelstein, Joseph
A1  - Freeman, Robert M.
A1  - Argulian, Edgar
A1  - Kasarskis, Andrew
A1  - Percha, Bethany
A1  - Aberg, Judith A.
A1  - Bagiella, Emilia
A1  - Horowitz, Carol R.
A1  - Murphy, Barbara
A1  - Nestler, Eric J.
A1  - Schadt, Eric E.
A1  - Cho, Judy H.
A1  - Cordon-Cardo, Carlos
A1  - Fuster, Valentin
A1  - Charney, Dennis S.
A1  - Reich, David L.
A1  - Böttinger, Erwin
A1  - Levin, Matthew A.
A1  - Narula, Jagat
A1  - Fayad, Zahi A.
A1  - Just, Allan C.
A1  - Charney, Alexander W.
A1  - Nadkarni, Girish N.
A1  - Glicksberg, Benjamin S.
T1  - Machine learning to predict mortality and critical events in a cohort of patients with COVID-19 in New York City: model development and validation
JF  - Journal of medical internet research : international scientific journal for medical research, information and communication on the internet ; JMIR
N2  - Background:
COVID-19 has infected millions of people worldwide and is responsible for several hundred thousand fatalities. The COVID-19 pandemic has necessitated thoughtful resource allocation and early identification of high-risk patients. However, effective methods to meet these needs are lacking.

Objective:
The aims of this study were to analyze the electronic health records (EHRs) of patients who tested positive for COVID-19 and were admitted to hospitals in the Mount Sinai Health System in New York City; to develop machine learning models for making predictions about the hospital course of the patients over clinically meaningful time horizons based on patient characteristics at admission; and to assess the performance of these models at multiple hospitals and time points. 

Methods:
We used Extreme Gradient Boosting (XGBoost) and baseline comparator models to predict in-hospital mortality and critical events at time windows of 3, 5, 7, and 10 days from admission. Our study population included harmonized EHR data from five hospitals in New York City for 4098 COVID-19-positive patients admitted from March 15 to May 22, 2020. The models were first trained on patients from a single hospital (n=1514) before or on May 1, externally validated on patients from four other hospitals (n=2201) before or on May 1, and prospectively validated on all patients after May 1 (n=383). Finally, we established model interpretability to identify and rank variables that drive model predictions.

Results:
Upon cross-validation, the XGBoost classifier outperformed baseline models, with an area under the receiver operating characteristic curve (AUC-ROC) for mortality of 0.89 at 3 days, 0.85 at 5 and 7 days, and 0.84 at 10 days. XGBoost also performed well for critical event prediction, with an AUC-ROC of 0.80 at 3 days, 0.79 at 5 days, 0.80 at 7 days, and 0.81 at 10 days. In external validation, XGBoost achieved an AUC-ROC of 0.88 at 3 days, 0.86 at 5 days, 0.86 at 7 days, and 0.84 at 10 days for mortality prediction. Similarly, the unimputed XGBoost model achieved an AUC-ROC of 0.78 at 3 days, 0.79 at 5 days, 0.80 at 7 days, and 0.81 at 10 days. Trends in performance on prospective validation sets were similar. At 7 days, acute kidney injury on admission, elevated LDH, tachypnea, and hyperglycemia were the strongest drivers of critical event prediction, while higher age, anion gap, and C-reactive protein were the strongest drivers of mortality prediction. 

Conclusions:
We externally and prospectively trained and validated machine learning models for mortality and critical events for patients with COVID-19 at different time horizons. These models identified at-risk patients and uncovered underlying relationships that predicted outcomes.
KW  - machine learning
KW  - COVID-19
KW  - electronic health record
KW  - TRIPOD
KW  - clinical
KW  - informatics
KW  - prediction
KW  - mortality
KW  - EHR
KW  - cohort
KW  - hospital
KW  - performance
Y1  - 2020
U6  - https://doi.org/10.2196/24018
SN  - 1439-4456
SN  - 1438-8871
VL  - 22
IS  - 11
PB  - Healthcare World
CY  - Richmond, Va.
ER  - 
TY  - JOUR
A1  - Döll, Stefanie
A1  - Djalali Farahani-Kofoet, Roxana
A1  - Zrenner, Rita
A1  - Henze, Andrea
A1  - Witzel, Katja
T1  - Tissue-specific signatures of metabolites and proteins in asparagus roots and exudates
JF  - Horticulture research
N2  - Comprehensive untargeted and targeted analysis of root exudate composition has advanced our understanding of rhizosphere processes. However, little is known about exudate spatial distribution and regulation. We studied the specific metabolite signatures of asparagus root exudates, root outer (epidermis and exodermis), and root inner tissues (cortex and vasculature). The greatest differences were found between exudates and root tissues. In total, 263 non-redundant metabolites were identified as significantly differentially abundant between the three root fractions, with the majority being enriched in the root exudate and/or outer tissue and annotated as 'lipids and lipid-like molecules' or 'phenylpropanoids and polyketides'. Spatial distribution was verified for three selected compounds using MALDI-TOF mass spectrometry imaging. Tissue-specific proteome analysis related root tissue-specific metabolite distributions and rhizodeposition with underlying biosynthetic pathways and transport mechanisms. The proteomes of root outer and inner tissues were spatially very distinct, in agreement with the fundamental differences between their functions and structures. According to KEGG pathway analysis, the outer tissue proteome was characterized by a high abundance of proteins related to 'lipid metabolism', 'biosynthesis of other secondary metabolites' and 'transport and catabolism', reflecting its main functions of providing a hydrophobic barrier, secreting secondary metabolites, and mediating water and nutrient uptake. Proteins more abundant in the inner tissue related to 'transcription', 'translation' and 'folding, sorting and degradation', in accord with the high activity of cortical and vasculature cell layers in growth- and development-related processes. In summary, asparagus root fractions accumulate specific metabolites. This expands our knowledge of tissue-specific plant cell function.
Y1  - 2021
U6  - https://doi.org/10.1038/s41438-021-00510-5
SN  - 2052-7276
SN  - 2662-6810
VL  - 8
IS  - 1
PB  - Nanjing Agricultural Univ.
CY  - Nanjing
ER  - 
TY  - JOUR
A1  - Toumoulin, Agathe
A1  - Tardif-Becquet, Delphine
A1  - Donnadieu, Yannick
A1  - Licht, Alexis
A1  - Ladant, Jean-Baptiste
A1  - Kunzmann, Lutz
A1  - Dupont-Nivet, Guillaume
T1  - Evolution of continental temperature seasonality from the Eocene greenhouse to the Oligocene icehouse
BT  - a model-data comparison
JF  - Climate of the past : an interactive open access journal of the European Geosciences Union
N2  - At the junction of greenhouse and icehouse climate states, the Eocene-Oligocene Transition (EOT) is a key moment in Cenozoic climate history. While it is associated with severe extinctions and biodiversity turnovers on land, the role of terrestrial climate evolution remains poorly resolved, especially the associated changes in seasonality. Some paleobotanical and geochemical continental records in parts of the Northern Hemisphere suggest the EOT is associated with a marked cooling in winter, leading to the development of more pronounced seasons (i.e., an increase in the mean annual range of temperature, MATR). However, the MATR increase has been barely studied by climate models and large uncertainties remain on its origin, geographical extent and impact. In order to better understand and describe temperature seasonality changes between the middle Eocene and the early Oligocene, we use the Earth system model IPSL-CM5A2 and a set of simulations reconstructing the EOT through three major climate forcings: pCO(2) decrease (1120, 840 and 560 ppm), the Antarctic ice-sheet (AIS) formation and the associated sea-level decrease. Our simulations suggest that pCO(2) lowering alone is not sufficient to explain the seasonality evolution described by the data through the EOT but rather that the combined effects of pCO(2) , AIS formation and increased continentality provide the best data-model agreement.pCO(2) decrease induces a zonal pattern with alternating increasing and decreasing seasonality bands particularly strong in the northern high latitudes (up to 8 degrees C MATR increase) due to sea-ice and surface albedo feedback. Conversely, the onset of the AIS is responsible for a more constant surface albedo yearly, which leads to a strong decrease in seasonality in the southern midlatitudes to high latitudes (> 40 degrees S). Finally, continental areas that emerged due to the sea-level lowering cause the largest increase in seasonality and explain most of the global heterogeneity in MATR changes (1MATR) patterns. The Delta MATR patterns we reconstruct are generally consistent with the variability of the EOT biotic crisis intensity across the Northern Hemisphere and provide insights on their underlying mechanisms.
Y1  - 2022
U6  - https://doi.org/10.5194/cp-18-341-2022
SN  - 1814-9324
SN  - 1814-9332
VL  - 18
IS  - 2
SP  - 341
EP  - 362
PB  - Copernicus
CY  - Göttingen
ER  - 
TY  - JOUR
A1  - König, Johanna
A1  - Block, Andrea
A1  - Becker, Mathias
A1  - Fenske, Kristin
A1  - Hertel, Johannes
A1  - Van der Auwera, Sandra
A1  - Zymara, Kathleen
A1  - Voelzke, Henry
A1  - Freyberger, Harald Jürgen
A1  - Grabe, Hans Joergen
T1  - Assessment of subjective emotional valence and long-lasting impact of life events
BT  - development and psychometrics of the Stralsund Life Event List (SEL)
JF  - BMC Psychiatry
N2  - Background: Life events (LEs) are associated with future physical and mental health. They are crucial for understanding the pathways to mental disorders as well as the interactions with biological parameters. However, deeper insight is needed into the complex interplay between the type of LE, its subjective evaluation and accompanying factors such as social support. The "Stralsund Life Event List" (SEL) was developed to facilitate this research. 
Methods: The SEL is a standardized interview that assesses the time of occurrence and frequency of 81 LEs, their subjective emotional valence, the perceived social support during the LE experience and the impact of past LEs on present life. Data from 2265 subjects from the general population-based cohort study "Study of Health in Pomerania" (SHIP) were analysed. Based on the mean emotional valence ratings of the whole sample, LEs were categorized as "positive" or "negative". For verification, the SEL was related to lifetime major depressive disorder (MDD; Munich Composite International Diagnostic Interview), childhood trauma (Childhood Trauma Questionnaire), resilience (Resilience Scale) and subjective health (SF-12 Health Survey). 
Conclusions: The SEL is a valid instrument that enables the analysis of the number and frequency of LEs, their emotional valence, perceived social support and current impact on life on a global score and on an individual item level. Thus, we can recommend its use in research settings that require the assessment and analysis of the relationship between the occurrence and subjective evaluation of LEs as well as the complex balance between distressing and stabilizing life experiences.
KW  - Positive life events
KW  - Negative life events
KW  - General population
KW  - Emotional valence
KW  - Depressive disorder
Y1  - 2018
U6  - https://doi.org/10.1186/s12888-018-1649-3
SN  - 1471-244X
VL  - 18
PB  - BioMed Central
CY  - London
ER  - 
TY  - JOUR
A1  - Herrmann, Matthias L.
A1  - Boden, Cindy
A1  - Maurer, Christoph
A1  - Kentischer, Felix
A1  - Mennig, Eva
A1  - Wagner, Sören
A1  - Conzelmann, Lars O.
A1  - Förstner, Bernd R.
A1  - Rapp, Michael A.
A1  - von Arnim, Christine A. F.
A1  - Denkinger, Michael
A1  - Eschweiler, Gerhard W.
A1  - Thomas, Christine
T1  - Anticholinergic drug exposure increases the risk of delirium in older patients undergoing elective surgery
JF  - Frontiers in medicine
N2  - IntroductionPostoperative delirium (POD) is a common and serious adverse event of surgery in older people. Because of its great impact on patients' safety and quality of life, identification of modifiable risk factors could be useful. Although preoperative medication intake is assumed to be an important modifiable risk factor, the impact of anticholinergic drugs on the occurrence of POD seems underestimated in elective surgery. The aim of this study was to investigate the association between preoperative anticholinergic burden and POD. We hypothesized that a high preoperative anticholinergic burden is an independent, potentially modifiable predisposing and precipitating factor of POD in older people. MethodsBetween November 2017 and April 2019, 1,470 patients of 70 years and older undergoing elective orthopedic, general, cardiac, or vascular surgery were recruited in the randomized, prospective, multicenter PAWEL trial. Anticholinergic burden of a sub-cohort of 899 patients, who did not receive a multimodal intervention for preventing POD, was assessed by two different tools at hospital admission: The established Anticholinergic Risk Scale (ARS) and the recently developed Anticholinergic Burden Score (ABS). POD was detected by confusion assessment method (CAM) and a validated post discharge medical record review. Logistic regression analyses were performed to evaluate the association between anticholinergic burden and POD. ResultsPOD was observed in 210 of 899 patients (23.4%). Both ARS and ABS were independently associated with POD. The association persisted after adjustment for relevant confounding factors such as age, sex, comorbidities, preoperative cognitive and physical status, number of prescribed drugs, surgery time, type of surgery and anesthesia, usage of heart-lung-machine, and treatment in intensive care unit. If a patient was taking one of the 56 drugs listed in the ABS, risk for POD was 2.7-fold higher (OR = 2.74, 95% CI = 1.55-4.94) and 1.5-fold higher per additional point on the ARS (OR = 1.54, 95% CI = 1.15-2.02). ConclusionPreoperative anticholinergic drug exposure measured by ARS or ABS was independently associated with POD in older patients undergoing elective surgery. Therefore, identification, discontinuation or substitution of anticholinergic medication prior to surgery may be a promising approach to reduce the risk of POD in older patients.
KW  - delirium
KW  - acute encephalopathy
KW  - surgery
KW  - anticholinergic
KW  - geriatric
KW  - postoperative
Y1  - 2022
U6  - https://doi.org/10.3389/fmed.2022.871229
SN  - 2296-858X
VL  - 9
PB  - Frontiers Media
CY  - Lausanne
ER  - 
TY  - JOUR
A1  - Haugk, Charlotte
A1  - Jongejans, Loeka L.
A1  - Mangelsdorf, Kai
A1  - Fuchs, Matthias
A1  - Ogneva, Olga
A1  - Palmtag, Juri
A1  - Mollenhauer, Gesine
A1  - Mann, Paul J.
A1  - Overduin, P. Paul
A1  - Grosse, Guido
A1  - Sanders, Tina
A1  - Tuerena, Robyn E.
A1  - Schirrmeister, Lutz
A1  - Wetterich, Sebastian
A1  - Kizyakov, Alexander
A1  - Karger, Cornelia
A1  - Strauss, Jens
T1  - Organic matter characteristics of a rapidly eroding permafrost cliff in NE Siberia (Lena Delta, Laptev Sea region)
JF  - Biogeosciences
N2  - Organic carbon (OC) stored in Arctic permafrost represents one of Earth's largest and most vulnerable terrestrial carbon pools. Amplified climate warming across the Arctic results in widespread permafrost thaw. Permafrost deposits exposed at river cliffs and coasts are particularly susceptible to thawing processes. Accelerating erosion of terrestrial permafrost along shorelines leads to increased transfer of organic matter (OM) to nearshore waters. However, the amount of terrestrial permafrost carbon and nitrogen as well as the OM quality in these deposits is still poorly quantified. We define the OM quality as the intrinsic potential for further transformation, decomposition and mineralisation. Here, we characterise the sources and the quality of OM supplied to the Lena River at a rapidly eroding permafrost river shoreline cliff in the eastern part of the delta (Sobo-Sise Island). Our multi-proxy approach captures bulk elemental, molecu- lar geochemical and carbon isotopic analyses of Late Pleistocene Yedoma permafrost and Holocene cover deposits, discontinuously spanning the last similar to 52 kyr. We showed that the ancient permafrost exposed in the Sobo-Sise cliff has a high organic carbon content (mean of about 5 wt %). The oldest sediments stem from Marine Isotope Stage (MIS) 3 interstadial deposits (dated to 52 to 28 cal ka BP) and are overlaid by last glacial MIS 2 (dated to 28 to 15 cal ka BP) and Holocene MIS 1 (dated to 7-0 cal ka BP) deposits. The relatively high average chain length (ACL) index of n-alkanes along the cliff profile indicates a predominant contribution of vascular plants to the OM composition. The elevated ratio of isoand anteiso-branched fatty acids (FAs) relative to mid- and long-chain (C >= 20) n-FAs in the interstadial MIS 3 and the interglacial MIS 1 deposits suggests stronger microbial activity and consequently higher input of bacterial biomass during these climatically warmer periods. The overall high carbon preference index (CPI) and higher plant fatty acid (HPFA) values as well as high C/N ratios point to a good quality of the preserved OM and thus to a high potential of the OM for decomposition upon thaw. A decrease in HPFA values downwards along the profile probably indicates stronger OM decomposition in the oldest (MIS 3) deposits of the cliff. The characterisation of OM from eroding permafrost leads to a better assessment of the greenhouse gas potential of the OC released into river and nearshore waters in the future.
Y1  - 2022
U6  - https://doi.org/10.5194/bg-19-2079-2022
SN  - 1726-4170
SN  - 1726-4189
VL  - 19
IS  - 7
SP  - 2079
EP  - 2094
PB  - Copernicus
CY  - Göttingen
ER  - 
TY  - JOUR
A1  - Voglimacci-Stephanopoli, Joëlle
A1  - Wendleder, Anna
A1  - Lantuit, Hugues
A1  - Langlois, Alexandre
A1  - Stettner, Samuel
A1  - Schmitt, Andreas
A1  - Dedieu, Jean-Pierre
A1  - Roth, Achim
A1  - Royer, Alain
T1  - Potential of X-band polarimetric synthetic aperture radar co-polar phase difference for arctic snow depth estimation
JF  - Cryosphere
N2  - Changes in snowpack associated with climatic warming has drastic impacts on surface energy balance in the cryosphere. Yet, traditional monitoring techniques, such as punctual measurements in the field, do not cover the full snowpack spatial and temporal variability, which hampers efforts to upscale measurements to the global scale. This variability is one of the primary constraints in model development. In terms of spatial resolution, active microwaves (synthetic aperture radar - SAR) can address the issue and outperform methods based on passive microwaves. Thus, high-spatial-resolution monitoring of snow depth (SD) would allow for better parameterization of local processes that drive the spatial variability of snow. The overall objective of this study is to evaluate the potential of the TerraSAR-X (TSX) SAR sensor and the wave co-polar phase difference (CPD) method for characterizing snow cover at high spatial resolution. Consequently, we first (1) investigate SD and depth hoar fraction (DHF) variability between different vegetation classes in the Ice Creek catchment (Qikiqtaruk/Herschel Island, Yukon, Canada) using in situ measurements collected over the course of a field campaign in 2019; (2) evaluate linkages between snow characteristics and CPD distribution over the 2019 dataset; and (3) determine CPD seasonality considering meteorological data over the 2015-2019 period. SD could be extracted using the CPD when certain conditions are met. A high incidence angle (>30 circle) with a high topographic wetness index (TWI) (>7.0) showed correlation between SD and CPD (R2 up to 0.72). Further, future work should address a threshold of sensitivity to TWI and incidence angle to map snow depth in such environments and assess the potential of using interpolation tools to fill in gaps in SD information on drier vegetation types.
Y1  - 2022
U6  - https://doi.org/10.5194/tc-16-2163-2022
SN  - 1994-0416
SN  - 1994-0424
VL  - 16
IS  - 6
SP  - 2163
EP  - 2181
PB  - Copernicus
CY  - Göttingen
ER  - 
TY  - JOUR
A1  - Agthe, Maria
A1  - Kayser, Daniela Niesta
A1  - Schwarz, Sascha
A1  - Maner, Jon K.
T1  - Antecedents of the red-romance effect
BT  - men's attractiveness and women's fertility
JF  - PLOS ONE / Public Library of Science
N2  - The color red has been implicated in a variety of social processes, including those involving mating. While previous research suggests that women sometimes wear red strategically to increase their attractiveness, the replicability of this literature has been questioned. The current research is a reasonably powered conceptual replication designed to strengthen this literature by testing whether women are more inclined to display the color red 1) during fertile (as compared with less fertile) days of the menstrual cycle, and 2) when expecting to interact with an attractive man (as compared with a less attractive man and with a control condition). Analyses controlled for a number of theoretically relevant covariates (relationship status, age, the current weather). Only the latter hypothesis received mixed support (mainly among women on hormonal birth control), whereas results concerning the former hypothesis did not reach significance. Women (N = 281) displayed more red when expecting to interact with an attractive man; findings did not support the prediction that women would increase their display of red on fertile days of the cycle. Findings thus suggested only mixed replicability for the link between the color red and psychological processes involving romantic attraction. They also illustrate the importance of further investigating the boundary conditions of color effects on everyday social processes.
Y1  - 2023
U6  - https://doi.org/10.1371/journal.pone.0284035
SN  - 1932-6203
VL  - 18
IS  - 4
PB  - PLOS
CY  - San Fransisco
ER  - 
TY  - JOUR
A1  - Schmicker, Marlen
A1  - Frühling, Insa
A1  - Menze, Inga
A1  - Glanz, Wenzel
A1  - Müller, Patrick
A1  - Noesselt, Toemme
A1  - Müller, Notger Germar
T1  - The potential role of gustatory function as an early diagnostic marker for the risk of alzheimer's disease in subjective cognitive decline
JF  - Journal of Alzheimer's disease reports : JADR
N2  - Background: Patients with subjective cognitive decline (SCD) report memory deterioration and are at an increased risk of converting to Alzheimer's disease (AD) although psychophysical testing does not reveal any cognitive deficit. 

Objective: Here, gustatory function is investigated as a potential predictor for an increased risk of progressive cognitive decline indicating higher AD risk in SCD. 

Methods: Measures of smell and taste perception as well as neuropsychological data were assessed in patients with subjective cognitive decline (SCD): Subgroups with an increased likelihood of the progression to preclinical AD (SCD+) and those with a lower likelihood (SCD-) were compared to healthy controls (HC), patients with mild cognitive impairment and AD patients. The Sniffin' Sticks test contained 12 items with different qualities and taste was measured with 32 taste stripes (sweet, salty, bitter, sour) of different concentration. 

Results: Only taste was able to distinguish between HC/SCD- and SCD+ patients.

Conclusion: This study provides a first hint of taste as a more sensitive marker than smell for detecting preclinical AD in SCD. Longitudinal observation of cognition and pathology are necessary to further evaluate taste perception as a predictor of pathological objective decline in cognition.
KW  - Alzheimer's disease
KW  - dementia
KW  - diagnostic marker
KW  - early diagnosis
KW  - subjective cognitive decline
KW  - taste
Y1  - 2023
U6  - https://doi.org/10.3233/ADR220092
SN  - 2542-4823
VL  - 7
IS  - 1
SP  - 249
EP  - 262
PB  - IOS Press
CY  - Clifton, VA
ER  - 
TY  - JOUR
A1  - Xiong, Yingquan
A1  - Delic, Denis
A1  - Zeng, Shufei
A1  - Chen, Xin
A1  - Chu, Chang
A1  - Hasan, Ahmed A.
A1  - Krämer, Bernhard K.
A1  - Klein, Thomas
A1  - Yin, Lianghong
A1  - Hocher, Berthold
T1  - Regulation of SARS CoV-2 host factors in the kidney and heart in rats with 5/6 nephrectomy-effects of salt, ARB, DPP4 inhibitor and SGLT2 blocker
JF  - BMC nephrology
N2  - Background Host factors such as angiotensin-converting enzyme 2 (ACE2) and the transmembrane protease, serine-subtype-2 (TMPRSS2) are important factors for SARS-CoV-2 infection. Clinical and pre-clinical studies demonstrated that RAAS-blocking agents can be safely used during a SARS-CoV-2 infection but it is unknown if DPP-4 inhibitors or SGLT2-blockers may promote COVID-19 by increasing the host viral entry enzymes ACE2 and TMPRSS2. Methods We investigated telmisartan, linagliptin and empagliflozin induced effects on renal and cardiac expression of ACE2, TMPRSS2 and key enzymes involved in RAAS (REN, AGTR2, AGT) under high-salt conditions in a non-diabetic experimental 5/6 nephrectomy (5/6 Nx) model. In the present study, the gene expression of Ace2, Tmprss2, Ren, Agtr2 and Agt was assessed with qRT-PCR and the protein expression of ACE2 and TMPRSS2 with immunohistochemistry in the following experimental groups: Sham + normal diet (ND) + placebo (PBO); 5/6Nx + ND + PBO; 5/6Nx + high salt-diet (HSD) + PBO; 5/6Nx + HSD + telmisartan; 5/6Nx + HSD + linagliptin; 5/6Nx + HSD + empagliflozin. Results In the kidney, the expression of Ace2 was not altered on mRNA level under disease and treatment conditions. The renal TMPRSS2 levels (mRNA and protein) were not affected, whereas the cardiac level was significantly increased in 5/6Nx rats. Intriguingly, the elevated TMPRSS2 protein expression in the heart was significantly normalized after treatment with telmisartan, linagliptin and empagliflozin. Conclusions Our study indicated that there is no upregulation regarding host factors potentially promoting SARS-CoV-2 virus entry into host cells when the SGLT2-blocker empagliflozin, telmisartan and the DPP4-inhibitor blocker linagliptin are used. The results obtained in a preclinical, experimental non-diabetic kidney failure model need confirmation in ongoing interventional clinical trials.
KW  - SARS CoV-2 host factors
KW  - 5/6 nephrectomy
KW  - High-salt diet
KW  - ARB
KW  - DPP4 inhibitor
KW  - SGLT2 blocker
Y1  - 2022
U6  - https://doi.org/10.1186/s12882-022-02747-1
SN  - 1471-2369
VL  - 23
IS  - 1
PB  - Springer Nature
CY  - London
ER  - 
TY  - JOUR
A1  - Shams, Boshra
A1  - Wang, Ziqian
A1  - Roine, Timo
A1  - Aydogan, Dogu Baran
A1  - Vajkoczy, Peter
A1  - Lippert, Christoph
A1  - Picht, Thomas
A1  - Fekonja, Lucius Samo
T1  - Machine learning-based prediction of motor status in glioma patients using diffusion MRI metrics along the corticospinal tract
JF  - Brain communications
N2  - Shams et al. report that glioma patients' motor status is predicted accurately by diffusion MRI metrics along the corticospinal tract based on support vector machine method, reaching an overall accuracy of 77%. They show that these metrics are more effective than demographic and clinical variables. 

Along tract statistics enables white matter characterization using various diffusion MRI metrics. These diffusion models reveal detailed insights into white matter microstructural changes with development, pathology and function. Here, we aim at assessing the clinical utility of diffusion MRI metrics along the corticospinal tract, investigating whether motor glioma patients can be classified with respect to their motor status. We retrospectively included 116 brain tumour patients suffering from either left or right supratentorial, unilateral World Health Organization Grades II, III and IV gliomas with a mean age of 53.51 +/- 16.32 years. Around 37% of patients presented with preoperative motor function deficits according to the Medical Research Council scale. At group level comparison, the highest non-overlapping diffusion MRI differences were detected in the superior portion of the tracts' profiles. Fractional anisotropy and fibre density decrease, apparent diffusion coefficient axial diffusivity and radial diffusivity increase. To predict motor deficits, we developed a method based on a support vector machine using histogram-based features of diffusion MRI tract profiles (e.g. mean, standard deviation, kurtosis and skewness), following a recursive feature elimination method. Our model achieved high performance (74% sensitivity, 75% specificity, 74% overall accuracy and 77% area under the curve). We found that apparent diffusion coefficient, fractional anisotropy and radial diffusivity contributed more than other features to the model. Incorporating the patient demographics and clinical features such as age, tumour World Health Organization grade, tumour location, gender and resting motor threshold did not affect the model's performance, revealing that these features were not as effective as microstructural measures. These results shed light on the potential patterns of tumour-related microstructural white matter changes in the prediction of functional deficits.
KW  - machine learning
KW  - support vector machine
KW  - tractography
KW  - diffusion MRI;
KW  - corticospinal tract
Y1  - 2022
U6  - https://doi.org/10.1093/braincomms/fcac141
SN  - 2632-1297
VL  - 4
IS  - 3
PB  - Oxford University Press
CY  - Oxford
ER  - 
TY  - JOUR
A1  - de Carvalho Souza, Alyson Matheus
A1  - Barrocas, Roberta
A1  - Fischer, Martin H.
A1  - Arnaud, Emanuel
A1  - Moeller, Korbinian
A1  - Rennó-Costa, César
T1  - Combining virtual reality and tactile stimulation to investigate embodied finger-based numerical representations
JF  - Frontiers in psychology / Frontiers Research Foundation
N2  - Finger-based representation of numbers is a high-level cognitive strategy to assist numerical and arithmetic processing in children and adults. It is unclear whether this paradigm builds on simple perceptual features or comprises several attributes through embodiment. Here we describe the development and initial testing of an experimental setup to study embodiment during a finger-based numerical task using Virtual Reality (VR) and a low-cost tactile stimulator that is easy to build. Using VR allows us to create new ways to study finger-based numerical representation using a virtual hand that can be manipulated in ways our hand cannot, such as decoupling tactile and visual stimuli. The goal is to present a new methodology that can allow researchers to study embodiment through this new approach, maybe shedding new light on the cognitive strategy behind the finger-based representation of numbers. In this case, a critical methodological requirement is delivering precisely targeted sensory stimuli to specific effectors while simultaneously recording their behavior and engaging the participant in a simulated experience. We tested the device's capability by stimulating users in different experimental configurations. Results indicate that our device delivers reliable tactile stimulation to all fingers of a participant's hand without losing motion tracking quality during an ongoing task. This is reflected by an accuracy of over 95% in participants detecting stimulation of a single finger or multiple fingers in sequential stimulation as indicated by experiments with sixteen participants. We discuss possible application scenarios, explain how to apply our methodology to study the embodiment of finger-based numerical representations and other high-level cognitive functions, and discuss potential further developments of the device based on the data obtained in our testing.
KW  - virtual reality
KW  - numerical cognition
KW  - finger counting
KW  - embodied cognition
KW  - cognitive science
KW  - virtual environment
Y1  - 2023
U6  - https://doi.org/10.3389/fpsyg.2023.1119561
SN  - 1664-1078
VL  - 14
PB  - Frontiers Research Foundation
CY  - Lausanne
ER  - 
TY  - JOUR
A1  - Stübler, Sabine
A1  - Kloft, Charlotte
A1  - Huisinga, Wilhelm
T1  - Cell-level systems biology model to study inflammatory bowel diseases and their treatment options
JF  - CPT: pharmacometrics & systems pharmacology
N2  - To help understand the complex and therapeutically challenging inflammatory bowel diseases (IBDs), we developed a systems biology model of the intestinal immune system that is able to describe main aspects of IBD and different treatment modalities thereof. The model, including key cell types and processes of the mucosal immune response, compiles a large amount of isolated experimental findings from literature into a larger context and allows for simulations of different inflammation scenarios based on the underlying data and assumptions. In the context of a large and diverse virtual IBD population, we characterized the patients based on their phenotype (in contrast to healthy individuals, they developed persistent inflammation after a trigger event) rather than on a priori assumptions on parameter differences to a healthy individual. This allowed to reproduce the enormous diversity of predispositions known to lead to IBD. Analyzing different treatment effects, the model provides insight into characteristics of individual drug therapy. We illustrate for anti-TNF-alpha therapy, how the model can be used (i) to decide for alternative treatments with best prospects in the case of nonresponse, and (ii) to identify promising combination therapies with other available treatment options.
Y1  - 2023
U6  - https://doi.org/10.1002/psp4.12932
SN  - 2163-8306
VL  - 12
IS  - 5
SP  - 690
EP  - 705
PB  - Nature Publ. Group
CY  - London
ER  - 
TY  - JOUR
A1  - Kaya, Mustafa Yücel
A1  - Dupont-Nivet, Guillaume
A1  - Frieling, Joost
A1  - Fioroni, Chiara
A1  - Rohrmann, Alexander
A1  - Altıner, Sevinç Özkan
A1  - Vardar, Ezgi
A1  - Tanyas, Hakan
A1  - Mamtimin, Mehmut
A1  - Zhaojie, Guo
T1  - The Eurasian epicontinental sea was an important carbon sink during the Palaeocene-Eocene thermal maximum
JF  - Communications earth and environment
N2  - The Palaeocene-Eocene Thermal Maximum (ca. 56 million years ago) offers a primary analogue for future global warming and carbon cycle recovery. Yet, where and how massive carbon emissions were mitigated during this climate warming event remains largely unknown. Here we show that organic carbon burial in the vast epicontinental seaways that extended over Eurasia provided a major carbon sink during the Palaeocene-Eocene Thermal Maximum. We coupled new and existing stratigraphic analyses to a detailed paleogeographic framework and using spatiotemporal interpolation calculated ca. 720–1300 Gt organic carbon excess burial, focused in the eastern parts of the Eurasian epicontinental seaways. A much larger amount (2160–3900 Gt C, and when accounting for the increase in inundated shelf area 7400–10300 Gt C) could have been sequestered in similar environments globally. With the disappearance of most epicontinental seas since the Oligocene-Miocene, an effective negative carbon cycle feedback also disappeared making the modern carbon cycle critically dependent on the slower silicate weathering feedback.
Y1  - 2022
U6  - https://doi.org/10.1038/s43247-022-00451-4
SN  - 2662-4435
VL  - 3
IS  - 1
PB  - Springer Nature
CY  - London
ER  - 
TY  - JOUR
A1  - van Soest, Heleen L.
A1  - Aleluia Reis, Lara
A1  - Baptista, Luiz Bernardo
A1  - Bertram, Christoph
A1  - Després, Jacques
A1  - Drouet, Laurent
A1  - den Elzen, Michel
A1  - Fragkos, Panagiotis
A1  - Fricko, Oliver
A1  - Fujimori, Shinichiro
A1  - Grant, Neil
A1  - Harmsen, Mathijs
A1  - Iyer, Gokul
A1  - Keramidas, Kimon
A1  - Köberle, Alexandre C.
A1  - Kriegler, Elmar
A1  - Malik, Aman
A1  - Mittal, Shivika
A1  - Oshiro, Ken
A1  - Riahi, Keywan
A1  - Roelfsema, Mark
A1  - van Ruijven, Bas
A1  - Schaeffer, Roberto
A1  - Silva Herran, Diego
A1  - Tavoni, Massimo
A1  - Ünlü, Gamze
A1  - Vandyck, Toon
A1  - van Vuuren, Detlef P.
T1  - Global roll-out of comprehensive policy measures may aid in bridging emissions gap
JF  - Nature communications
N2  - Closing the emissions gap between Nationally Determined Contributions (NDCs) and the global emissions levels needed to achieve the Paris Agreement’s climate goals will require a comprehensive package of policy measures. National and sectoral policies can help fill the gap, but success stories in one country cannot be automatically replicated in other countries. They need to be adapted to the local context. Here, we develop a new Bridge scenario based on nationally relevant, short-term measures informed by interactions with country experts. These good practice policies are rolled out globally between now and 2030 and combined with carbon pricing thereafter. We implement this scenario with an ensemble of global integrated assessment models. We show that the Bridge scenario closes two-thirds of the emissions gap between NDC and 2 °C scenarios by 2030 and enables a pathway in line with the 2 °C goal when combined with the necessary long-term changes, i.e. more comprehensive pricing measures after 2030. The Bridge scenario leads to a scale-up of renewable energy (reaching 52%–88% of global electricity supply by 2050), electrification of end-uses, efficiency improvements in energy demand sectors, and enhanced afforestation and reforestation. Our analysis suggests that early action via good-practice policies is less costly than a delay in global climate cooperation.
KW  - climate-change mitigation
KW  - climate-change policy
Y1  - 2021
U6  - https://doi.org/10.1038/s41467-021-26595-z
VL  - 12
IS  - 1
PB  - Nature Publishing Group UK
CY  - London
ER  - 
TY  - JOUR
A1  - Ehrig, Lukas
A1  - Wagner, Ann-Christin
A1  - Wolter, Heike
A1  - Correll, Christoph U.
A1  - Geisel, Olga
A1  - Konigorski, Stefan
T1  - FASDetect as a machine learning-based screening app for FASD in youth with ADHD
JF  - npj Digital Medicine
N2  - Fetal alcohol-spectrum disorder (FASD) is underdiagnosed and often misdiagnosed as attention-deficit/hyperactivity disorder (ADHD). Here, we develop a screening tool for FASD in youth with ADHD symptoms. To develop the prediction model, medical record data from a German University outpatient unit are assessed including 275 patients aged 0-19 years old with FASD with or without ADHD and 170 patients with ADHD without FASD aged 0-19 years old. We train 6 machine learning models based on 13 selected variables and evaluate their performance. Random forest models yield the best prediction models with a cross-validated AUC of 0.92 (95% confidence interval [0.84, 0.99]). Follow-up analyses indicate that a random forest model with 6 variables - body length and head circumference at birth, IQ, socially intrusive behaviour, poor memory and sleep disturbance - yields equivalent predictive accuracy. We implement the prediction model in a web-based app called FASDetect - a user-friendly, clinically scalable FASD risk calculator that is freely available at https://fasdetect.dhc-lab.hpi.de.
KW  - Medical research
KW  - Psychiatric disorders
Y1  - 2023
U6  - https://doi.org/10.1038/s41746-023-00864-1
SN  - 2398-6352
VL  - 6
IS  - 1
PB  - Macmillan Publishers Limited
CY  - Basingstoke
ER  - 
TY  - JOUR
A1  - Slosarek, Tamara
A1  - Ibing, Susanne
A1  - Schormair, Barbara
A1  - Heyne, Henrike
A1  - Böttinger, Erwin
A1  - Andlauer, Till
A1  - Schurmann, Claudia
T1  - Implementation and evaluation of personal genetic testing as part of genomics analysis courses in German universities
JF  - BMC Medical Genomics
N2  - Purpose
Due to the increasing application of genome analysis and interpretation in medical disciplines, professionals require adequate education. Here, we present the implementation of personal genotyping as an educational tool in two genomics courses targeting Digital Health students at the Hasso Plattner Institute (HPI) and medical students at the Technical University of Munich (TUM).

Methods
We compared and evaluated the courses and the students ' perceptions on the course setup using questionnaires.

Results
During the course, students changed their attitudes towards genotyping (HPI: 79% [15 of 19], TUM: 47% [25 of 53]). Predominantly, students became more critical of personal genotyping (HPI: 73% [11 of 15], TUM: 72% [18 of 25]) and most students stated that genetic analyses should not be allowed without genetic counseling (HPI: 79% [15 of 19], TUM: 70% [37 of 53]). Students found the personal genotyping component useful (HPI: 89% [17 of 19], TUM: 92% [49 of 53]) and recommended its inclusion in future courses (HPI: 95% [18 of 19], TUM: 98% [52 of 53]).

Conclusion
Students perceived the personal genotyping component as valuable in the described genomics courses. The implementation described here can serve as an example for future courses in Europe.
KW  - Genomics education
KW  - Personal genotyping
KW  - Personalized medicine
Y1  - 2023
U6  - https://doi.org/10.1186/s12920-023-01503-0
SN  - 1755-8794
VL  - 16
IS  - 1
PB  - BMC
CY  - London
ER  - 
TY  - JOUR
A1  - Gisch, Ulrike Alexandra
A1  - Robert, Margaux
A1  - Berlin, Noemi
A1  - Nebout, Antoine
A1  - Etile, Fabrice
A1  - Teyssier, Sabrina
A1  - Andreeva, Valentina A.
A1  - Hercberg, Serge
A1  - Touvier, Mathilde
A1  - Peneau, Sandrine
T1  - Mastery is associated with weight status, food intake, snacking, and eating disorder symptoms in the NutriNet-Sante cohort study
JF  - Frontiers in Nutrition
N2  - Mastery is a psychological resource that is defined as the extent to which individuals perceive having control over important circumstances of their lives. Although mastery has been associated with various physical and psychological health outcomes, studies assessing its relationship with weight status and dietary behavior are lacking. The aim of this cross-sectional study was to assess the relationship between mastery and weight status, food intake, snacking, and eating disorder (ED) symptoms in the NutriNet-Sante cohort study. Mastery was measured with the Pearlin Mastery Scale (PMS) in 32,588 adults (77.45% female), the mean age was 50.04 (14.53) years. Height and weight were self-reported. Overall diet quality and food group consumption were evaluated with >= 3 self-reported 24-h dietary records (range: 3-27). Snacking was assessed with an ad-hoc question. ED symptoms were assessed with the Sick-Control-One-Fat-Food Questionnaire (SCOFF). Linear and logistic regression analyses were conducted to assess the relationship between mastery and weight status, food intake, snacking, and ED symptoms, controlling for sociodemographic and lifestyle characteristics. Females with a higher level of mastery were less likely to be underweight (OR: 0.88; 95%CI: 0.84, 0.93), overweight [OR: 0.94 (0.91, 0.97)], or obese [class I: OR: 0.86 (0.82, 0.90); class II: OR: 0.76 (0.71, 0.82); class III: OR: 0.77 (0.69, 0.86)]. Males with a higher level of mastery were less likely to be obese [class III: OR: 0.75 (0.57, 0.99)]. Mastery was associated with better diet quality overall, a higher consumption of fruit and vegetables, seafood, wholegrain foods, legumes, non-salted oleaginous fruits, and alcoholic beverages and with a lower consumption of meat and poultry, dairy products, sugary and fatty products, milk-based desserts, and sweetened beverages. Mastery was also associated with lower snacking frequency [OR: 0.89 (0.86, 0.91)] and less ED symptoms [OR: 0.73 (0.71, 0.75)]. As mastery was associated with favorable dietary behavior and weight status, targeting mastery might be a promising approach in promoting healthy behaviors.
KW  - mastery
KW  - locus of control
KW  - weight status
KW  - diet quality
KW  - food group consumption
KW  - snacking
KW  - eating disorder symptoms
KW  - large population
Y1  - 2022
U6  - https://doi.org/10.3389/fnut.2022.871669
SN  - 2296-861X
VL  - 9
PB  - Frontiers Media
CY  - Lausanne
ER  - 
TY  - JOUR
A1  - Kretzschmar, Mirjam E.
A1  - Ashby, Ben
A1  - Fearon, Elizabeth
A1  - Overton, Christopher E.
A1  - Panovska-Griffiths, Jasmina
A1  - Pellis, Lorenzo
A1  - Quaife, Matthew
A1  - Rozhnova, Ganna
A1  - Scarabel, Francesca
A1  - Stage, Helena B.
A1  - Swallow, Ben
A1  - Thompson, Robin N.
A1  - Tildesley, Michael J.
A1  - Villela, Daniel Campos
T1  - Challenges for modelling interventions for future pandemics
JF  - Epidemics
N2  - Mathematical modelling and statistical inference provide a framework to evaluate different non-pharmaceutical and pharmaceutical interventions for the control of epidemics that has been widely used during the COVID-19 pandemic. In this paper, lessons learned from this and previous epidemics are used to highlight the challenges for future pandemic control. We consider the availability and use of data, as well as the need for correct parameterisation and calibration for different model frameworks. We discuss challenges that arise in describing and distinguishing between different interventions, within different modelling structures, and allowing both within and between host dynamics. We also highlight challenges in modelling the health economic and political aspects of interventions. Given the diversity of these challenges, a broad variety of interdisciplinary expertise is needed to address them, combining mathematical knowledge with biological and social insights, and including health economics and communication skills. Addressing these challenges for the future requires strong cross disciplinary collaboration together with close communication between scientists and policy makers.
KW  - Mathematical models
KW  - Pandemics
KW  - Pharmaceutical interventions
KW  - Non-pharmaceutical interventions
KW  - Policy support
Y1  - 2022
U6  - https://doi.org/10.1016/j.epidem.2022.100546
SN  - 1755-4365
SN  - 1878-0067
VL  - 38
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - GEN
A1  - Bilgen, Isa
T1  - Our dignity in your hands
T2  - Verfassungsblog : on matters constitutional
Y1  - 2024
UR  - https://verfassungsblog.de/our-dignity-in-your-hands/
U6  - https://doi.org/10.17176/20240204-004255-0
SN  - 2366-7044
PB  - Max Steinbeis Verfassungsblog gGmbH
CY  - Berlin
ER  - 
TY  - GEN
A1  - Bilgen, Isa
T1  - Unsere Würde in Euren Händen
T2  - Verfassungsblog : on matters constitutional
Y1  - 2024
UR  - https://verfassungsblog.de/unsere-wurde-in-euren-handen/
U6  - https://doi.org/10.17176/20240204-004217-0
SN  - 2366-7044
PB  - Max Steinbeis Verfassungsblog gGmbH
CY  - Berlin
ER  - 
TY  - JOUR
A1  - Seroussi, Helene
A1  - Nowicki, Sophie
A1  - Simon, Erika
A1  - Abe-Ouchi, Ayako
A1  - Albrecht, Torsten
A1  - Brondex, Julien
A1  - Cornford, Stephen
A1  - Dumas, Christophe
A1  - Gillet-Chaulet, Fabien
A1  - Goelzer, Heiko
A1  - Golledge, Nicholas R.
A1  - Gregory, Jonathan M.
A1  - Greve, Ralf
A1  - Hoffman, Matthew J.
A1  - Humbert, Angelika
A1  - Huybrechts, Philippe
A1  - Kleiner, Thomas
A1  - Larourl, Eric
A1  - Leguy, Gunter
A1  - Lipscomb, William H.
A1  - Lowry, Daniel
A1  - Mengel, Matthias
A1  - Morlighem, Mathieu
A1  - Pattyn, Frank
A1  - Payne, Anthony J.
A1  - Pollard, David
A1  - Price, Stephen F.
A1  - Quiquet, Aurelien
A1  - Reerink, Thomas J.
A1  - Reese, Ronja
A1  - Rodehacke, Christian B.
A1  - Schlegel, Nicole-Jeanne
A1  - Shepherd, Andrew
A1  - Sun, Sainan
A1  - Sutter, Johannes
A1  - Van Breedam, Jonas
A1  - van de Wal, Roderik S. W.
A1  - Winkelmann, Ricarda
A1  - Zhang, Tong
T1  - initMIP-Antarctica
BT  - an ice sheet model initialization experiment of ISMIP6
JF  - The Cryosphere : TC ; an interactive open access journal of the European Geosciences Union
N2  - Ice sheet numerical modeling is an important tool to estimate the dynamic contribution of the Antarctic ice sheet to sea level rise over the coming centuries. The influence of initial conditions on ice sheet model simulations, however, is still unclear. To better understand this influence, an initial state intercomparison exercise (initMIP) has been developed to compare, evaluate, and improve initialization procedures and estimate their impact on century-scale simulations. initMlP is the first set of experiments of the Ice Sheet Model Intercomparison Project for CMIP6 (ISMIP6), which is the primary Coupled Model Intercomparison Project Phase 6 (CMIP6) activity focusing on the Greenland and Antarctic ice sheets. Following initMlP-Greenland, initMlP-Antarctica has been designed to explore uncertainties associated with model initialization and spin-up and to evaluate the impact of changes in external forcings. Starting from the state of the Antarctic ice sheet at the end of the initialization procedure, three forward experiments are each run for 100 years: a control run, a run with a surface mass balance anomaly, and a run with a basal melting anomaly beneath floating ice. This study presents the results of initMlP-Antarctica from 25 simulations performed by 16 international modeling groups. The submitted results use different initial conditions and initialization methods, as well as ice flow model parameters and reference external forcings. We find a good agreement among model responses to the surface mass balance anomaly but large variations in responses to the basal melting anomaly. These variations can be attributed to differences in the extent of ice shelves and their upstream tributaries, the numerical treatment of grounding line, and the initial ocean conditions applied, suggesting that ongoing efforts to better represent ice shelves in continental-scale models should continue.
Y1  - 2019
U6  - https://doi.org/10.5194/tc-13-1441-2019
SN  - 1994-0416
SN  - 1994-0424
VL  - 13
IS  - 5
SP  - 1441
EP  - 1471
PB  - Copernicus
CY  - Göttingen
ER  - 
TY  - JOUR
A1  - Reese, Ronja
A1  - Albrecht, Torsten
A1  - Mengel, Matthias
A1  - Asay-Davis, Xylar
A1  - Winkelmann, Ricarda
T1  - Antarctic sub-shelf melt rates via PICO
JF  - The Cryosphere : TC ; an interactive open access journal of the European Geosciences Union
N2  - Ocean-induced melting below ice shelves is one of the dominant drivers for mass loss from the Antarctic Ice Sheet at present. An appropriate representation of sub-shelf melt rates is therefore essential for model simulations of marine-based ice sheet evolution. Continental-scale ice sheet models often rely on simple melt-parameterizations, in particular for long-term simulations, when fully coupled ice-ocean interaction becomes computationally too expensive. Such parameterizations can account for the influence of the local depth of the ice-shelf draft or its slope on melting. However, they do not capture the effect of ocean circulation underneath the ice shelf. Here we present the Potsdam Ice-shelf Cavity mOdel (PICO), which simulates the vertical overturning circulation in ice-shelf cavities and thus enables the computation of sub-shelf melt rates consistent with this circulation. PICO is based on an ocean box model that coarsely resolves ice shelf cavities and uses a boundary layer melt formulation. We implement it as a module of the Parallel Ice Sheet Model (PISM) and evaluate its performance under present-day conditions of the Southern Ocean. We identify a set of parameters that yield two-dimensional melt rate fields that qualitatively reproduce the typical pattern of comparably high melting near the grounding line and lower melting or refreezing towards the calving front. PICO captures the wide range of melt rates observed for Antarctic ice shelves, with an average of about 0.1 ma(-1) for cold sub-shelf cavities, for example, underneath Ross or Ronne ice shelves, to 16 ma(-1) for warm cavities such as in the Amundsen Sea region. This makes PICO a computationally feasible and more physical alternative to melt parameterizations purely based on ice draft geometry.
Y1  - 2018
U6  - https://doi.org/10.5194/tc-12-1969-2018
SN  - 1994-0416
SN  - 1994-0424
VL  - 12
IS  - 6
SP  - 1969
EP  - 1985
PB  - Copernicus
CY  - Göttingen
ER  - 
TY  - JOUR
A1  - Reese, Ronja
A1  - Winkelmann, Ricarda
A1  - Gudmundsson, Gudmundur Hilmar
T1  - Grounding-line flux formula applied as a flux condition in numerical simulations fails for buttressed Antarctic ice streams
JF  - The Cryosphere : TC ; an interactive open access journal of the European Geosciences Union
N2  - Currently, several large-scale ice-flow models impose a condition on ice flux across grounding lines using an analytically motivated parameterisation of grounding-line flux. It has been suggested that employing this analytical expression alleviates the need for highly resolved computational domains around grounding lines of marine ice sheets. While the analytical flux formula is expected to be accurate in an unbuttressed flow-line setting, its validity has hitherto not been assessed for complex and realistic geometries such as those of the Antarctic Ice Sheet. Here the accuracy of this analytical flux formula is tested against an optimised ice flow model that uses a highly resolved computational mesh around the Antarctic grounding lines. We find that when applied to the Antarctic Ice Sheet the analytical expression provides inaccurate estimates of ice fluxes for almost all grounding lines. Furthermore, in many instances direct application of the analytical formula gives rise to unphysical complex-valued ice fluxes. We conclude that grounding lines of the Antarctic Ice Sheet are, in general, too highly buttressed for the analytical parameterisation to be of practical value for the calculation of grounding-line fluxes.
Y1  - 2018
U6  - https://doi.org/10.5194/tc-12-3229-2018
SN  - 1994-0416
SN  - 1994-0424
VL  - 12
IS  - 10
SP  - 3229
EP  - 3242
PB  - Copernicus
CY  - Göttingen
ER  - 
TY  - JOUR
A1  - Albrecht, Torsten
A1  - Winkelmann, Ricarda
A1  - Levermann, Anders
T1  - Glacial-cycle simulations of the Antarctic Ice Sheet with the Parallel Ice Sheet Model (PISM)
BT  - Part 1: boundary conditions and climatic forcing
JF  - The Cryosphere : TC ; an interactive open access journal of the European Geosciences Union
N2  - Simulations of the glacial-interglacial history of the Antarctic Ice Sheet provide insights into dynamic threshold behavior and estimates of the ice sheet's contributions to global sea-level changes for the past, present and future. However, boundary conditions are weakly constrained, in particular at the interface of the ice sheet and the bedrock. Also climatic forcing covering the last glacial cycles is uncertain, as it is based on sparse proxy data. <br /> We use the Parallel Ice Sheet Model (PISM) to investigate the dynamic effects of different choices of input data, e.g., for modern basal heat flux or reconstructions of past changes of sea level and surface temperature. As computational resources are limited, glacial-cycle simulations are performed using a comparably coarse model grid of 16 km and various parameterizations, e.g., for basal sliding, iceberg calving, or for past variations in precipitation and ocean temperatures. In this study we evaluate the model's transient sensitivity to corresponding parameter choices and to different boundary conditions over the last two glacial cycles and provide estimates of involved uncertainties. We also discuss isolated and combined effects of climate and sea-level forcing. Hence, this study serves as a "cookbook" for the growing community of PISM users and paleo-ice sheet modelers in general. <br /> For each of the different model uncertainties with regard to climatic forcing, ice and Earth dynamics, and basal processes, we select one representative model parameter that captures relevant uncertainties and motivates corresponding parameter ranges that bound the observed ice volume at present. The four selected parameters are systematically varied in a parameter ensemble analysis, which is described in a companion paper.
Y1  - 2020
U6  - https://doi.org/10.5194/tc-14-599-2020
SN  - 1994-0416
SN  - 1994-0424
VL  - 14
IS  - 2
SP  - 599
EP  - 632
PB  - Copernicus
CY  - Göttingen
ER  - 
TY  - JOUR
A1  - Kreuzer, Moritz
A1  - Reese, Ronja
A1  - Huiskamp, Willem Nicholas
A1  - Petri, Stefan
A1  - Albrecht, Torsten
A1  - Feulner, Georg
A1  - Winkelmann, Ricarda
T1  - Coupling framework (1.0) for the PISM (1.1.4) ice sheet model and the MOMS (5.1.0) ocean model via the PICO ice shelf cavity model in an Antarctic domain
JF  - Geoscientific model development : an interactive open access journal of the European Geosciences Union
N2  - The past and future evolution of the Antarctic Ice Sheet is largely controlled by interactions between the ocean and floating ice shelves. To investigate these interactions, coupled ocean and ice sheet model configurations are required. Previous modelling studies have mostly relied on high-resolution configurations, limiting these studies to individual glaciers or regions over short timescales of decades to a few centuries. We present a framework to couple the dynamic ice sheet model PISM (Parallel Ice Sheet Model) with the global ocean general circulation model MOM5 (Modular Ocean Model) via the ice shelf cavity model PICO (Pots-dam Ice-shelf Cavity mOdel). As ice shelf cavities are not resolved by MOM5 but are parameterized with the PICO box model, the framework allows the ice sheet and ocean components to be run at resolutions of 16 km and 3 degrees respectively. This approach makes the coupled configuration a useful tool for the analysis of interactions between the Antarctic Ice Sheet and the global ocean over time spans of the order of centuries to millennia. In this study, we describe the technical implementation of this coupling framework: sub-shelf melting in the ice sheet component is calculated by PICO from modelled ocean temperatures and salinities at the depth of the continental shelf, and, vice versa, the resulting mass and energy fluxes from melting at the ice-ocean interface are transferred to the ocean component. Mass and energy fluxes are shown to be conserved to machine precision across the considered component domains. The implementation is computationally efficient as it introduces only minimal overhead. Furthermore, the coupled model is evaluated in a 4000 year simulation under constant present-day climate forcing and is found to be stable with respect to the ocean and ice sheet spin-up states. The framework deals with heterogeneous spatial grid geometries, varying grid resolutions, and timescales between the ice and ocean component in a generic way; thus, it can be adopted to a wide range of model set-ups.
Y1  - 2021
U6  - https://doi.org/10.5194/gmd-14-3697-2021
SN  - 1991-959X
SN  - 1991-9603
VL  - 14
IS  - 6
SP  - 3697
EP  - 3714
PB  - Copernicus
CY  - Göttingen
ER  - 
TY  - JOUR
A1  - Zeitz, Maria
A1  - Haacker, Jan M.
A1  - Donges, Jonathan
A1  - Albrecht, Torsten
A1  - Winkelmann, Ricarda
T1  - Dynamic regimes of the Greenland Ice Sheet emerging from interacting melt-elevation and glacial isostatic adjustment feedbacks
JF  - Earth system dynamics
N2  - The stability of the Greenland Ice Sheet under global warming is governed by a number of dynamic processes and interacting feedback mechanisms in the ice sheet, atmosphere and solid Earth. 
Here we study the long-term effects due to the interplay of the competing melt-elevation and glacial isostatic adjustment (GIA) feedbacks for different temperature step forcing experiments with a coupled ice-sheet and solid-Earth model. 
Our model results show that for warming levels above 2 degrees C, Greenland could become essentially ice-free within several millennia, mainly as a result of surface melting and acceleration of ice flow. These ice losses are mitigated, however, in some cases with strong GIA feedback even promoting an incomplete recovery of the Greenland ice volume. We further explore the full-factorial parameter space determining the relative strengths of the two feedbacks: our findings suggest distinct dynamic regimes of the Greenland Ice Sheets on the route to destabilization under global warming - from incomplete recovery, via quasi-periodic oscillations in ice volume to ice-sheet collapse. 
In the incomplete recovery regime, the initial ice loss due to warming is essentially reversed within 50 000 years, and the ice volume stabilizes at 61 %-93 % of the present-day volume. For certain combinations of temperature increase, atmospheric lapse rate and mantle viscosity, the interaction of the GIA feedback and the melt-elevation feedback leads to self-sustained, long-term oscillations in ice-sheet volume with oscillation periods between 74 000 and over 300 000 years and oscillation amplitudes between 15 %-70 % of present-day ice volume. 
This oscillatory regime reveals a possible mode of internal climatic variability in the Earth system on timescales on the order of 100 000 years that may be excited by or synchronized with orbital forcing or interact with glacial cycles and other slow modes of variability. Our findings are not meant as scenario-based near-term projections of ice losses but rather providing insight into of the feedback loops governing the "deep future" and, thus, long-term resilience of the Greenland Ice Sheet.
Y1  - 2022
U6  - https://doi.org/10.5194/esd-13-1077-2022
SN  - 2190-4979
SN  - 2190-4987
VL  - 13
IS  - 3
SP  - 1077
EP  - 1096
PB  - Copernicus Publ.
CY  - Göttingen
ER  - 
TY  - JOUR
A1  - Albrecht, Torsten
A1  - Winkelmann, Ricarda
A1  - Levermann, Anders
T1  - Glacial-cycle simulations of the Antarctic Ice Sheet with the Parallel Ice Sheet Model (PISM)
BT  - part 2: parameter ensemble analysis
JF  - The Cryosphere : TC ; an interactive open access journal of the European Geosciences Union
N2  - The Parallel Ice Sheet Model (PISM) is applied to the Antarctic Ice Sheet over the last two glacial cycles (approximate to 210 000 years) with a resolution of 16 km. An ensemble of 256 model runs is analyzed in which four relevant model parameters have been systematically varied using full-factorial parameter sampling. Parameters and plausible parameter ranges have been identified in a companion paper (Albrecht et al., 2020) and are associated with ice dynamics, climatic forcing, basal sliding and bed deformation and represent distinct classes of model uncertainties. The model is scored against both modern and geologic data, including reconstructed grounding-line locations, elevation-age data, ice thickness, surface velocities and uplift rates. An aggregated score is computed for each ensemble member that measures the overall model-data misfit, including measurement uncertainty in terms of a Gaussian error model (Briggs and Tarasov, 2013). The statistical method used to analyze the ensemble simulation results follows closely the simple averaging method described in Pollard et al. (2016). 
This analysis reveals clusters of best-fit parameter combinations, and hence a likely range of relevant model and boundary parameters, rather than individual best-fit parameters. The ensemble of reconstructed histories of Antarctic Ice Sheet volumes provides a score-weighted likely range of sea-level contributions since the Last Glacial Maximum (LGM) of 9.4 +/- 4.1m (or 6.5 +/- 2.0 x 10(6) km(3)), which is at the upper range of most previous studies. The last deglaciation occurs in all ensemble simulations after around 12 000 years before present and hence after the meltwater pulse 1A (MWP1a). Our ensemble analysis also provides an estimate of parametric uncertainty bounds for the present-day state that can be used for PISM projections of future sea-level contributions from the Antarctic Ice Sheet.
Y1  - 2020
U6  - https://doi.org/10.5194/tc-14-633-2020
SN  - 1994-0416
SN  - 1994-0424
VL  - 14
IS  - 2
SP  - 633
EP  - 656
PB  - Copernicus Publ.
CY  - Göttingen
ER  - 
TY  - JOUR
A1  - Schlemm, Tanja
A1  - Feldmann, Johannes
A1  - Winkelmann, Ricarda
A1  - Levermann, Anders
T1  - Stabilizing effect of melange buttressing on the marine ice-cliff instability of the West Antarctic Ice Sheet
JF  - The Cryosphere : TC ; an interactive open access journal of the European Geosciences Union
N2  - Owing to global warming and particularly high regional ocean warming, both Thwaites and Pine Island Glaciers in the Amundsen region of the Antarctic Ice Sheet could lose their buttressing ice shelves over time. We analyse the possible consequences using the parallel ice sheet model (PISM), applying a simple cliff-calving parameterization and an ice melange-buttressing model. We find that the instantaneous loss of ice-shelf buttressing, due to enforced ice-shelf melting, initiates grounding-line retreat and triggers marine ice sheet instability (MISI). As a consequence, the grounding line progresses into the interior of the West Antarctic Ice Sheet and leads to a sea level contribution of 0.6 m within 100 a. By subjecting the exposed ice cliffs to cliff calving using our simplified parameterization, we also analyse marine ice cliff instability (MICI). In our simulations it can double or even triple the sea level contribution depending on the only loosely constrained parameter that determines the maximum cliff-calving rate. The speed of MICI depends on this upper bound of the calving rate, which is given by the ice melange buttressing the glacier. However, stabilization of MICI may occur for geometric reasons. Because the embayment geometry changes as MICI advances into the interior of the ice sheet, the upper bound on calving rates is reduced and the progress of MICI is slowed down. Although we cannot claim that our simulations bear relevant quantitative estimates of the effect of ice-melange buttressing on MICI, the mechanism has the potential to stop the instability. Further research is needed to evaluate its role for the past and future evolution of the Antarctic Ice Sheet.
Y1  - 2022
U6  - https://doi.org/10.5194/tc-16-1979-2022
SN  - 1994-0416
SN  - 1994-0424
VL  - 16
IS  - 5
SP  - 1979
EP  - 1996
PB  - Copernicus
CY  - Göttingen
ER  - 
TY  - JOUR
A1  - Feldmann, Johannes
A1  - Reese, Ronja
A1  - Winkelmann, Ricarda
A1  - Levermann, Anders
T1  - Shear-margin melting causes stronger transient ice discharge than ice-stream melting in idealized simulations
JF  - The Cryosphere : TC ; an interactive open access journal of the European Geosciences Union
N2  - Basal ice-shelf melting is the key driver of Antarctica's increasing sea-level contribution. In diminishing the buttressing force of the ice shelves that fringe the ice sheet, the melting increases the ice discharge into the ocean.
Here we contrast the influence of basal melting in two different ice-shelf regions on the time-dependent response of an isothermal, inherently buttressed ice-sheet-shelf system. In the idealized numerical simulations, the basal-melt perturbations are applied close to the grounding line in the ice-shelf's (1) ice-stream region, where the ice shelf is fed by the fastest ice masses that stream through the upstream bed trough and (2) shear margins, where the ice flow is slower.
The results show that melting below one or both of the shear margins can cause a decadal to centennial increase in ice discharge that is more than twice as large compared to a similar perturbation in the ice-stream region. We attribute this to the fact that melt-induced ice-shelf thinning in the central grounding-line region is attenuated very effectively by the fast flow of the central ice stream. In contrast, the much slower ice dynamics in the lateral shear margins of the ice shelf facilitate sustained ice-shelf thinning and thereby foster buttressing reduction.
Regardless of the melt location, a higher melt concentration toward the grounding line generally goes along with a stronger response. Our results highlight the vulnerability of outlet glaciers to basal melting in stagnant, buttressing-relevant ice-shelf regions, a mechanism that may gain importance under future global warming.
Y1  - 2022
U6  - https://doi.org/10.5194/tc-16-1927-2022
SN  - 1994-0416
SN  - 1994-0424
VL  - 16
IS  - 5
SP  - 1927
EP  - 1940
PB  - Copernicus
CY  - Göttingen
ER  -