Ludwig-Maximilians-Universität München
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Aerobic exercise therapy in severe mental disorders: from methods to underlying mechanisms
No full textBound on the excess charge of generalized Thomas-Fermi-Weizsäcker functionals
No full textWe bound the number of electrons Q that an atom can bind in excess of neutrality for density functionals generalizing the classical Thomas-Fermi-Weizsäcker functional: instead of the classical power 5/3 more general powers p are considered. For 3/2 < p < 2 we prove the excess charge conjecture, i.e., that Q is uniformly bounded in the atomic number Z. The case p = 3/2 is critical: the behavior changes from a uniform bound in Z to a linear bound at the critical coupling of the nonlinear term. We also improve the linear bound for all p ≥ 6/5
A Contemporary Look at Methodological Shifts and Publication Trends in the Business Informatics Community
No full textThis study explores recent trends in the adoption of research methods and publication practices within the Business Informatics (Wirtschaftsinformatik, WI) community in German-speaking countries, taking into account the various research paradigms in the Information Systems (IS) discipline. A scientometric analysis of more than 1,800 peer-reviewed journal articles by WI professors from 2010 to 2020 reveals two key findings. First, research methods from positivist, interpretive, and constructivist paradigms have been adopted in a balanced manner, reflecting progress and maturity within the WI community. Second, a trend toward increased publication in international IS journals was observed, with constructivist research notably well represented. These findings indicate a growing presence of the WI community in international IS journals while maintaining methodological diversity
Aligning NLP Models with Target Population Perspectives using PAIR: Population-Aligned Instance Replication
Get PDFModels trained on crowdsourced annotations may not reflect population views, if those who work as annotators do not represent the broader population. In this paper, we propose PAIR: Population-Aligned Instance Replication, a post-processing method that adjusts training data to better reflect target population characteristics without collecting additional annotations. Using simulation studies on offensive language and hate speech detection with varying annotator compositions, we show that non-representative pools degrade model calibration while leaving accuracy largely unchanged. PAIR corrects these calibration problems by replicating annotations from underrepresented annotator groups to match population proportions. We conclude with recommendations for improving the representativity of training data and model performance
Ein Review und Leitfaden für die adäquate und interdisziplinäre (sozial-)medizinische Versorgung von Menschen mit einem Down-Syndrom und einer dementiellen Entwicklung
Get PDFQuantitative Susceptibility Mapping of Deep Grey Matter in MS: Association With Clinical Scores and Brain Volume Measures
Get PDFBackground
Changes in quantitative susceptibility mapping (QSM) of the deep grey matter (DGM) in multiple sclerosis (MS) are thought to reflect tissue damage invisible in conventional magnetic resonance imaging (MRI) sequences, such as iron-related neurodegeneration.
Objective
To explore the associations of clinical scores and MRI-based volumes with QSM values in the DGM (thalamus, putamen, caudate, and pallidum) in a large cohort of people with MS, and to assess the predictive value of QSM values for clinical outcomes after three years.
Methods
A total of 771 MS patients (clinically isolated syndrome (CIS): n = 35, relapsing-remitting: n = 637, progressive: n = 63) were scanned at 3T with T1-weighted, T2-FLAIR, and QSM sequences. All patients were included in the cross-sectional analyses examining the relationship of DGM QSM values with MRI variables and clinical scores. Normalized brain volume (NBV) was computed using SIENAX, while total lesion volume (TLV) was derived from the lesion segmentation tool, LST-AI. Clinical scores included the expanded disability status scale (EDSS), timed 25 foot walk (T25FW), Nine Hole Peg Test (9HPT), symbol digit modalities test (SDMT), and fatigue scale for motor and cognitive functions (FSMC). In the longitudinal analyses, only clinical scores were included, with various sample sizes across different clinical scores (NEDSS = 396, NT25Fw = 284, N9HPT = 284, NSDMT = 165, NFSMC = 288). These analyses evaluated the predictive value of baseline DGM QSM values for follow-up clinical scores; these associations were compared to those of corresponding regional DGM volumes.
Results
At baseline, after adjusting for confounding factors, higher QSM values in the basal ganglia were significantly associated with greater TLV (β = 0.14 – 0.17; p < 0.001), higher clinical severity (EDSS: β = 0.13 – 0.19, p < 0.001), worse dexterity (NHPT: β = 0.14 – 0.16, p = 0.02), and lower cognitive functioning (SDMT: β = –0.13 – –0.15, p = 0.03). In contrast, lower thalamic QSM values were associated with greater TLV (β = –0.07; p = 0.03). Unlike regional volumes, DGM QSM values did not predict clinical outcomes at follow-up.
Conclusion
DGM QSM values are robustly associated with MS severity and TLV cross-sectionally. However, our large-scale longitudinal analysis suggests that DGM QSM values lack prognostic value for short-term clinical progression in early-stage MS
Soluble VCAM-1 May Serve as a Pharmacodynamic CSF Marker to Monitor BACE2 Activity in Non-Human Primates
Get PDFIL6 genetic perturbation mimicking IL-6 inhibition is associated with lower cardiometabolic risk
Get PDFHuman genetics supports a causal involvement of IL-6 signaling in atherosclerotic cardiovascular disease, prompting the clinical development of anti-IL-6 therapies. Genetic evidence has historically focused on IL6R missense variants, but emerging cardiovascular treatments target IL-6, not its receptor, questioning the translatability of genetic findings. Here we develop a genetic instrument for IL-6 signaling downregulation comprising IL6 locus variants that mimic the effects of the anti-IL-6 antibody ziltivekimab and use it to predict the effects of IL-6 inhibition on cardiometabolic and safety endpoints. Similar to IL6R, we found that genetically downregulated IL-6 signaling via IL6 perturbation is associated with lower lifetime risks of coronary artery disease, peripheral artery disease and ischemic atherosclerotic stroke in individuals of European and East Asian ancestry. Unlike IL6R missense variants linked to bacterial infections, the IL6 instrument was associated with lower risk of pneumonia hospitalization. Our data suggest that IL-6 inhibition can reduce cardiovascular risk without major unexpected safety concerns
Connectivity as a universal predictor of tau progression in atypical Alzheimer’s disease
Get PDFThe link between regional tau load and clinical manifestation of Alzheimer’s disease (AD) highlights the importance of characterizing spatial tau distribution across disease variants. In typical (memory-predominant) AD, the spatial progression of tau pathology mirrors the functional connections from temporal lobe epicentres. However, given the limited spatial heterogeneity of tau in typical AD, atypical (non-amnestic-predominant) AD variants with distinct tau patterns provide a key opportunity to investigate the universality of connectivity as a scaffold for tau progression.
In this large-scale, multicentre study across 14 international sites, we included cross-sectional tau-PET data from 320 individuals with atypical AD (n = 139 posterior cortical atrophy/PCA-AD; n = 103 logopenic variant primary progressive aphasia/lvPPA-AD; n = 35 behavioural variant AD/bvAD; n = 43 corticobasal syndrome/CBS-AD), with a subset of individuals (n = 78) having longitudinal tau-PET data. Additionally, as an independent sample, we included regional post-mortem tau stainings from 93 atypical AD patients from two sites (n = 19 PCA-AD, n = 32 lvPPA-AD, n = 23 bvAD, n = 19 CBS-AD). Gaussian mixture modelling was used to harmonize different tau-PET tracers by transforming tau-PET standardized uptake value ratios to tau positivity probabilities (a uniform scale ranging from 0% to 100%). Using linear regression, we assessed whether brain regions with stronger resting-state functional MRI-based functional connectivity, derived from healthy elderly controls in the Alzheimer’s Disease Neuroimaging Initiative (ADNI), showed greater covariance in cross-sectional and longitudinal tau-PET and post-mortem tau pathology. Furthermore, we examined whether functional connectivity of tau-PET epicentres (i.e. the top 5% of regions with the highest baseline tau load) and tau-PET accumulation epicentres (i.e. the top 5% of regions with the highest tau accumulation rates) was associated with cross-sectional and longitudinal tau patterns.
Our findings show that tau-PET epicentres aligned with clinical variants, e.g. a visual network predominant pattern in PCA-AD (‘visual AD’) and left-hemispheric temporal predominance, particularly within the language network, in lvPPA-AD (‘language AD’). Moreover, more strongly functionally connected regions showed correlated concurrent tau-PET levels (confirmed with post-mortem data) and tau-PET accumulation rates. The functional connectivity profile of tau-PET epicentres and accumulation epicentres corresponded to tau-PET progression patterns, with higher tau-PET levels and accumulation rates in functionally close regions, and lower tau-PET levels and accumulation rates in functionally distant regions.
Our data are consistent with the hypothesis that tau propagation occurs along functional connections originating from local epicentres, across all AD clinical variants. Since tau proteinopathy is a major driver of neurodegeneration and cognitive decline, this finding may advance personalized medicine and participant-specific end points in clinical trials