B_s Mixing and B Hadron Lifetimes at CDF

We present the CDF results using 1.0 fb^{-1} of data on the mixing frequency measurement in the B_s system and the lifetime measurements of several B hadrons. We obtain \Delta m_s=17.77 +- 0.1 +- 0.07 ps^{-1} and c\tau(\Lambda_b)=473.8 +- 23.1 +- 3.5 \mu m. The later one is more than 3 sigma above the world average, but in reasonable agreement with HQE calculations.Comment: submitted to EPS2007 proceeding

Search for Rare b-hadron Decays at CDF

We report on searches for B^0_s to \mu^+ \mu^-, B^0_d to \mu^+ \mu^- decays and b to s \mu^+\mu^- transitions in exclusive decays of B mesons. Using 2 fb^{-1} of data collected by the CDF II detector we find upper limits on the branching fractions B(B^0_s to \mu^+ \mu^-) < 5.8 x 10^{-8} and B(B^0_d to \mu^+ \mu^-) < 1.8 x 10^{-8} at 95% confidence level. Using 924 pb^{-1} of data we measure the branching fractions B(B^+ to \mu^+ \mu^- K^+) = (0.60 \pm 0.15 \pm 0.04) x 10^{-6}, B(B^0_d to \mu^+ \mu^- K^{*0}) = (0.82 \pm 0.31 \pm 0.10) x 10^{-6} and the limit B(B^0_s to \mu^+ \mu^- phi)/B(B^0_s to J/\psi\phi) < 2.61(2.30) x 10^{-3} at 95(90)% confidence level.Comment: 3 pages, 5 figures, conference proceedings to the 2007 Europhysics Conference on High Energy Physics (Manchester, July 2007

Attention-dependent modulation of neural activity in primary sensorimotor cortex

Although motor tasks at most times do not require much attention, there are findings that attention can alter neuronal activity not only in higher motor areas but also within the primary sensorimotor cortex. However, these findings are equivocal as attention effects were investigated only in either the dominant or the nondominant hand; attention was operationalized either as concentration (i.e., attention directed to motor task) or as distraction (i.e., attention directed away from motor task), the complexity of motor tasks varied and almost no left-handers were studied. Therefore, in this study, both right- and left-handers were investigated with an externally paced button press task in which subjects typed with the index finger of the dominant, nondominant, or both hands. We introduced four different attention levels: attention-modulation-free, distraction (counting backward), concentration on the moving finger, and divided concentration during bimanual movement. We found that distraction reduced neuronal activity in both contra- and ipsilateral primary sensorimotor cortex when the nondominant hand was tapping in both handedness groups. At the same time, distraction activated the dorsal frontoparietal attention network and deactivated the ventral default network. We conclude that difficulty and training status of both the motor and cognitive task, as well as usage of the dominant versus the nondominant hand, are crucial for the presence and magnitude of attention effects on sensorimotor cortex activity. In the case of a very simple button press task, attention modulation is seen for the nondominant hand under distraction and in both handedness groups

Why complex human phenotypes need complex data analytics - insights from fields of molecular and cognitive neuroscience

Epidemiological research investigates the natural occurring variation of complex traits and the covariance between these traits in the general population. By doing so, epidemiological research is an important tool to understand influential factors on complex traits such as neuropsychiatric diseases and related phenotypes. However, epidemiological studies are challenged by interpretational difficulties and are often limited to inferential data analysis especially when based on a cross-sectional design. Different strategies exist to optimize the impact generated by such inferential data analyses. One strategy is to increase the depth of information by adding intermediate related traits, which is especially done in the field of genetics. However, complex covariance pattern typically underlie the relation between e.g. genotype, intermediate phenotype and primary phenotype of interest, which have to be resolved. In this situation, more complex analytical strategies might help to identify the most plausible model of relationship. The downside of these more comprehensive analytical models lies in the increase of model complexity, that might result in a less stable outcome. Finding a good balance between model complexity and analytical simplicity is a major challenge when performing combined analyses with several complex phenotypes. In the current thesis I presented three different works dealing with complex analytical strategies. The main goal behind all three of them was not to build up comprehensive theoretical frameworks, but to perform more preparatory analytical steps. The meta-analysis validated and extended a genetic association finding of the single nucleotide polymorphism rs17070145 with human memory performance by accumulating information of about 6 years of research performed worldwide. The heritability analysis verified that a common SNP-chip array is an appropriate dataset to perform more complex genetic analysis with human working memory performance measurements. The analysis of common epigenetic variation validates the DNA CpG methylation dataset in the context of complex analyses in mentally healthy young adults. Additionally, when comparing the three analyses, they also shed light on the varying complexity of putative intermediate phenotypes in human research. This knowledge can be used to build up comprehensive theoretical models and complex statistical analyses that combine several complex phenotypes

Recognition memory performance can be estimated based on brain activation networks

Recognition memory is an essential ability for functioning in everyday life. Establishing robust brain networks linked to recognition memory performance can help to understand the neural basis of recognition memory itself and the interindividual differences in recognition memory performance.; We analysed behavioural and whole-brain fMRI data from 1'410 healthy young adults during the testing phase of a picture-recognition task. Using independent component analysis (ICA), we decomposed the fMRI contrast for previously seen vs. new (old-new) pictures into networks of brain activity. This was done in two independent samples (training sample: N = 645, replication sample: N = 665). Next, we investigated the relationship between the identified brain networks and interindividual differences in recognition memory performance by conducting a prediction analysis. We estimated the prediction accuracy in a third independent sample (test sample: N = 100).; We identified 12 robust and replicable brain networks using two independent samples. Based on the activity of those networks we could successfully estimate interindividual differences in recognition memory performance with high accuracy in a third independent sample (r = 0.5, p = 1.29 × 10; -07; ).; Given the robustness of the ICA decomposition as well as the high prediction estimate, the identified brain networks may be considered as potential biomarkers of recognition memory performance in healthy young adults and can be further investigated in the context of health and disease

Human cerebellum and corticocerebellar connections involved in emotional memory enhancement

Emotional information is better remembered than neutral information. Extensive evidence indicates that the amygdala and its interactions with other cerebral regions play an important role in the memory-enhancing effect of emotional arousal. While the cerebellum has been found to be involved in fear conditioning, its role in emotional enhancement of episodic memory is less clear. To address this issue, we used a whole-brain functional MRI approach in 1,418 healthy participants. First, we identified clusters significantly activated during enhanced memory encoding of negative and positive emotional pictures. In addition to the well-known emotional memory-related cerebral regions, we identified a cluster in the cerebellum. We then used dynamic causal modeling and identified several cerebellar connections with increased connection strength corresponding to enhanced emotional memory, including one to a cluster covering the amygdala and hippocampus, and bidirectional connections with a cluster covering the anterior cingulate cortex. The present findings indicate that the cerebellum is an integral part of a network involved in emotional enhancement of episodic memory

Exhaustive search for epistatic effects on the human methylome

Studies assessing the existence and magnitude of epistatic effects on complex human traits provide inconclusive results. The study of such effects is complicated by considerable increase in computational burden, model complexity, and model uncertainty, which in concert decrease model stability. An additional source introducing significant uncertainty with regard to the detection of robust epistasis is the biological distance between the genetic variation and the trait under study. Here we studied CpG methylation, a genetically complex molecular trait that is particularly close to genomic variation, and performed an exhaustive search for two-locus epistatic effects on the CpG-methylation signal in two cohorts of healthy young subjects. We detected robust epistatic effects for a small number of CpGs (N = 404). Our results indicate that epistatic effects explain only a minor part of variation in DNA-CpG methylation. Interestingly, these CpGs were more likely to be associated with gene-expression of nearby genes, as also shown by their overrepresentation in DNase I hypersensitivity sites and underrepresentation in CpG islands. Finally, gene ontology analysis showed a significant enrichment of these CpGs in pathways related to HPV-infection and cancer

Common epigenetic variation in a European population of mentally healthy young adults

DNA methylation represents an important link between structural genetic variation and complex phenotypes. The study of genome-wide CpG methylation and its relation to traits relevant to psychiatry has become increasingly important. Here, we analyzed quality metrics of 394,043 CpG sites in two samples of 568 and 319 mentally healthy young adults. For 25% of all CpGs we observed medium to large common epigenetic variation. These CpGs were overrepresented in open sea and shore regions, as well as in intergenic regions. They also showed a strong enrichment of significant hits in association analyses. Furthermore, a significant proportion of common DNA methylation is at least partially genetically driven and thus may be observed similarly across tissues. These findings could be of particular relevance for studies of complex neuropsychiatric traits, which often rely on proxy tissues

Sex-dependent dissociation between emotional appraisal and memory: a large-scale behavioral and fMRI study

Extensive evidence indicates that women outperform men in episodic memory tasks. Furthermore, women are known to evaluate emotional stimuli as more arousing than men. Because emotional arousal typically increases episodic memory formation, the females' memory advantage might be more pronounced for emotionally arousing information than for neutral information. Here, we report behavioral data from 3398 subjects, who performed picture rating and memory tasks, and corresponding fMRI data from up to 696 subjects. We were interested in the interaction between sex and valence category on emotional appraisal, memory performances, and fMRI activity. The behavioral results showed that females evaluate in particular negative (p &lt; 10(-16)) and positive (p = 2 × 10(-4)), but not neutral pictures, as emotionally more arousing (pinteraction &lt; 10(-16)) than males. However, in the free recall females outperformed males not only in positive (p &lt; 10(-16)) and negative (p &lt; 5 × 10(-5)), but also in neutral picture recall (p &lt; 3.4 × 10(-8)), with a particular advantage for positive pictures (pinteraction &lt; 4.4 × 10(-10)). Importantly, females' memory advantage during free recall was absent in a recognition setting. We identified activation differences in fMRI, which corresponded to the females' stronger appraisal of especially negative pictures, but no activation differences that reflected the interaction effect in the free recall memory task. In conclusion, females' valence-category-specific memory advantage is only observed in a free recall, but not a recognition setting and does not depend on females' higher emotional appraisal

Mobilisation of critically ill patients receiving norepinephrine: a retrospective cohort study

Background: Mobilisation and exercise intervention in general are safe and feasible in critically ill patients. For patients requiring catecholamines, however, doses of norepinephrine safe for mobilisation in the intensive care unit (ICU) are not defined. This study aimed to describe mobilisation practice in our hospital and identify doses of norepinephrine that allowed a safe mobilisation. Methods: We conducted a retrospective single-centre cohort study of 16 ICUs at a university hospital in Germany with patients admitted between March 2018 and November 2021. Data were collected from our patient data management system. We analysed the effect of norepinephrine on level (ICU Mobility Scale) and frequency (units per day) of mobilisation, early mobilisation (within 72 h of ICU admission), mortality, and rate of adverse events. Data were extracted from free-text mobilisation entries using supervised machine learning (support vector machine). Statistical analyses were done using (generalised) linear (mixed-effect) models, as well as chi-square tests and ANOVAs. Results: A total of 12,462 patients were analysed in this study. They received a total of 59,415 mobilisation units. Of these patients, 842 (6.8%) received mobilisation under continuous norepinephrine administration. Norepinephrine administration was negatively associated with the frequency of mobilisation (adjusted difference -0.07 mobilisations per day; 95% CI - 0.09, - 0.05; p 0.1). Higher compared to lower doses of norepinephrine did not lead to a significant increase in adverse events in our practice (p > 0.1). We identified that mobilisation was safe with up to 0.20 mu g/kg/min norepinephrine for out-of-bed (IMS >= 2) and 0.33 mu g/kg/min for in-bed (IMS 0-1) mobilisation. Conclusions: Mobilisation with norepinephrine can be done safely when considering the status of the patient and safety guidelines. We demonstrated that safe mobilisation was possible with norepinephrine doses up to 0.20 mu g/kg/min for out-of-bed (IMS >= 2) and 0.33 mu g/kg/min for in-bed (IMS 0-1) mobilisation