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Motives motivate human behavior. Most behaviors are driven by more than one motive, yet it is unclear how different motives interact and how such motive combinations affect the neural computation of the behaviors they drive. To answer this question, we induced two prosocial motives simultaneously (multi-motive condition) and separately (single motive conditions). After the different motive inductions, participants performed the same choice task in which they allocated points in favor of the other person (prosocial choice) or in favor of themselves (egoistic choice). We used fMRI to assess prosocial choice-related brain responses and drift diffusion modeling to specify how motive combinations affect individual components of the choice process. Our results showed that the combination of the two motives in the multi-motive condition increased participants’ choice biases prior to the behavior itself. On the neural level, these changes in initial prosocial bias were associated with neural responses in the bilateral dorsal striatum. In contrast, the efficiency of the prosocial decision process was comparable between the multi-motive and the single-motive conditions. These findings provide insights into the computation of prosocial choices in complex motivational states, the motivational setting that drives most human behaviors.
Background: Although being considered as a rarely observed HIV-1 protease mutation in clinical isolates, the L76V-prevalence increased 1998-2008 in some European countries most likely due to the approval of Lopinavir, Amprenavir and Darunavir which can select L76V. Beside an enhancement of resistance, L76V is also discussed to confer hypersusceptibility to the drugs Atazanavir and Saquinavir which might enable new treatment strategies by trying to take advantage of particular mutations. Results: Based on a cohort of 47 L76V-positive patients, we examined if there might exist a clinical advantage for L76V-positive patients concerning long-term success of PI-containing regimens in patients with limited therapy options. Genotypic- and phenotypic HIV-resistance tests from 47 mostly multi-resistant, L76V-positive patients throughout Germany were accomplished retrospectively 1999-2009. Five genotype-based drug-susceptibility predictions received from online interpretation-tools for Atazanavir, Saquinavir, Amprenavir and Lopinavir, were compared to phenotype-based predictions that were determined by using a recombinant virus assay along with a Virtual Phenotype™(Virco). The clinical outcome of the L76V-adapted follow-up therapy was determined by monitoring viral load for 96 weeks. Conclusions: In this analysis, the mostly used interpretation systems overestimated the L76V-mutation concerning Atazanavir- and SQV resistance. In fact, a clear benefit in drug susceptibility for these drugs was observed in phenotype analysis after establishment of L76V. More importantly, long-term therapy success was significantly higher in patients receiving Atazanavir and/or Saquinavir plus one L76V-selecting drug compared to patients without L76V-selecting agents (p = 0.002). In case of L76V-occurrence ATV and/or SQV may represent encouraging options for patients in deep salvage situations.
A novel thiazol‐based ratiometric dye for the detection of local pH values is synthesized, and its properties are characterized by a combination of optical spectroscopy, solid‐state NMR and DNP (dynamic nuclear polarization)‐enhanced solid‐state NMR. This novel dye covers a completely different sensitivity range with its acidic pKa value of 3.5 compared to other established dyes for ratiometric pH detection, such as SNARF. The dye is grafted to the surfaces of mesoporous silica materials, which enables, for the first time, direct in situ measurements of the local pH values in silica mesopores by a simple UV‐vis spectroscopy method. The obtained results, which are in good agreement with previous indirect techniques, indicate a background electrolyte‐dependent pKa shift of at least one pH unit under nanoconfined conditions compared to the pKa of the dye in bulk solution.
Acute physical activity has been repeatedly shown to improve various cognitive functions. However, there have been no investigations comparing the effects of exercise during verbal encoding versus exercise prior to encoding on long-term memory performance. In this current psychoneuroendocrinological study we aim to test whether light to moderate ergometric bicycling during vocabulary encoding enhances subsequent recall compared to encoding during physical rest and encoding after being physically active. Furthermore, we examined the kinetics of brain-derived neurotrophic factor (BDNF) in serum which has been previously shown to correlate with learning performance. We also controlled for the BDNF val66met polymorphism. We found better vocabulary test performance for subjects that were physically active during the encoding phase compared to sedentary subjects. Post-hoc tests revealed that this effect was particularly present in initially low performers. BDNF in serum and BDNF genotype failed to account for the current result. Our data indicates that light to moderate simultaneous physical activity during encoding, but not prior to encoding, is beneficial for subsequent recall of new items.
Non-standard errors
(2021)
In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in sample estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty: non-standard errors. To study them, we let 164 teams test six hypotheses on the same sample. We find that non-standard errors are sizeable, on par with standard errors. Their size (i) co-varies only weakly with team merits, reproducibility, or peer rating, (ii) declines significantly after peer-feedback, and (iii) is underestimated by participants.
Simple Summary: Acute myeloid leukemia (AML) is a genetically heterogeneous disease. Clinical phenotypes of frequent mutations and their impact on patient outcome are well established. However, the role of rare mutations often remains elusive. We retrospectively analyzed 1529 newly diagnosed and intensively treated AML patients for mutations of BCOR and BCORL1. We report a distinct co-mutational pattern that suggests a role in disease progression rather than initiation, especially affecting mechanisms of DNA-methylation. Further, we found loss-of-function mutations of BCOR to be independent markers of poor outcomes in multivariable analysis. Therefore, loss-of-function mutations of BCOR need to be considered for AML management, as they may influence risk stratification and subsequent treatment allocation.
Abstract: Acute myeloid leukemia (AML) is characterized by recurrent genetic events. The BCL6 corepressor (BCOR) and its homolog, the BCL6 corepressor-like 1 (BCORL1), have been reported to be rare but recurrent mutations in AML. Previously, smaller studies have reported conflicting results regarding impacts on outcomes. Here, we retrospectively analyzed a large cohort of 1529 patients with newly diagnosed and intensively treated AML. BCOR and BCORL1 mutations were found in 71 (4.6%) and 53 patients (3.5%), respectively. Frequently co-mutated genes were DNTM3A, TET2 and RUNX1. Mutated BCORL1 and loss-of-function mutations of BCOR were significantly more common in the ELN2017 intermediate-risk group. Patients harboring loss-of-function mutations of BCOR had a significantly reduced median event-free survival (HR = 1.464 (95%-Confidence Interval (CI): 1.005–2.134), p = 0.047), relapse-free survival (HR = 1.904 (95%-CI: 1.163–3.117), p = 0.01), and trend for reduced overall survival (HR = 1.495 (95%-CI: 0.990–2.258), p = 0.056) in multivariable analysis. Our study establishes a novel role for loss-of-function mutations of BCOR regarding risk stratification in AML, which may influence treatment allocation.
Background: The combination of intermediate-dose cytarabine plus mitoxantrone (IMA) can induce high complete remission rates with acceptable toxicity in elderly patients with acute myeloid leukemia (AML). We present the final results of a randomized-controlled trial comparing IMA with the standard 7 + 3 induction regimen consisting of continuous infusion cytarabine plus daunorubicin (DA).
Patients and methods: Patients with newly diagnosed AML >60 years were randomized to receive either intermediate-dose cytarabine (1000 mg/m2 twice daily on days 1, 3, 5, 7) plus mitoxantrone (10 mg/m2 days 1–3) (IMA) or standard induction therapy with cytarabine (100 mg/m2 continuously days 1–7) plus daunorubicin (45 mg/m2 days 3–5) (DA). Patients in complete remission after DA received intermediate-dose cytarabine plus amsacrine as consolidation treatment, whereas patients after IMA were consolidated with standard-dose cytarabine plus mitoxantrone.
Results: Between February 2005 and October 2009, 485 patients were randomized; 241 for treatment arm DA and 244 for IMA; 76% of patients were >65 years. The complete response rate after DA was 39% [95% confidence interval (95% CI): 33–45] versus 55% (95% CI: 49–61) after IMA (odds ratio 1.89, P = 0.001). The 6-week early-death rate was 14% in both arms. Relapse-free survival curves were superimposable in the first year, but separated afterwards, resulting in 3-year relapse-free survival rates of 29% versus 14% in the DA versus IMA arms, respectively (P = 0.042). The median overall survival was 10 months in both arms (P = 0.513).
Conclusion: The dose escalation of cytarabine in induction therapy lead to improved remission rates in the elderly AML patients. This did not translate into a survival advantage, most likely due to differences in consolidation treatment. Thus, effective consolidation strategies need to be further explored. In combination with an effective consolidation strategy, the use of intermediate-dose cytarabine in induction may improve curative treatment for elderly AML patients.
Die vorliegende, von Studierenden der Fachhochschule für Bibliothekswesen in Frankfurt am Main erstellte Projektarbeit befaßt sich mit Fragen, Aspekten und Möglichkeiten der Flexibilisierung von Arbeitszeiten und Arbeitsformen in Bibliotheken. Im ersten Teil der Arbeit werden die wichtigsten Arbeitsteilzeitmodelle vorgestellt und deren Vorteile für Arbeitgeber und nehmer herausgearbeitet. Anschließend erfolgt eine durch Graphiken und Tabellen veranschaulichte Untersuchung von drei ausgewählte Universitätsbibliotheken (Gießen, Marburg, Mainz) in bezug auf bereits existierende Arbeitszeitflexibilisierung. Ein Ausblick geht der Frage nach, ob die dargestellten Teilzeitmodelle für Bibliotheken notwendig und ausreichend sind. Der zweite Themenkomplex befaßt sich mit der Telearbeit als einer innovativen Arbeitsform in Bibliotheken. Ausgehend von einer Begriffsbestimung werden verschiedene Formen der Telearbeit sowie deren Vor und Nachteile geschildert. Es wird erläutert, welche Bedingungen an den Telearbeiter und seinen Arbeitsplatz geknüpft sind, welche rechtlichen Voraussetzungen erfüllt werden müssen, welche finanziellen Aspekte eine Rolle spielen und welche Anwendungsmöglichkeiten für Telearbeit in Bibliotheken bestehen. An drei konkreten Beispielen wird dann geschildert, wie Telearbeit in Bibliotheken bereits verwirklicht wurde. Abschließend wird der Frage nachgegangen, welche Perspektiven der Einsatz von Telearbeit in Bibliotheken hat. Der dritte Abschnitt der Ausarbeitung stellt das bibliothekarische Call Center als neue Form einer benutzerorientierten Einrichtung vor. Zielsetzungen und Dienstleistungsformen des Call Centers werden ebenso abgehandelt wie Aspekte der Planung, Einrichtung und Arbeitsplatzergonomie sowie des Einsatzes von Telearbeit. Anhand des Beispiels der Zentral und Landesbibliothek Berlin wird schließlich dokumentiert, wie sich ein bibliothekarisches Call Center in der Praxis bereits bewährt hat.
Aim: Assessment of the effect of nonsurgical periodontal therapy on haematological parameters in patients with grades B (BP) and C periodontitis (CP).
Methods: Eight BP and 46 CP patients received full-mouth periodontal debridement within 48 h, if positive for Aggregatibacter actinomycetemcomitans with adjunctive systemic antibiotics (4 BP, 17 CP). Clinical data were collected prior and 12 weeks after periodontal therapy. Blood was sampled prior to and 1 day as well as 6 and 12 weeks after the first SD visit. Erythrocyte count, haemoglobin value, haematocrit (HCT), mean erythrocyte volume (MCV), mean corpuscular haemoglobin (MCH), MCH concentration (MCHC), platelets (PLT) and heat shock protein 27 (Hsp27) were assessed.
Results: Both groups showed significant clinical improvement (p < 0.05). Using univariate analysis, MCV was noticeably lower in CP than BP at all examinations, HCT only at baseline. For CP, MCHC was noticeably higher 12 weeks after SD than at baseline and 1 day (p ≤ 0.005) and Hsp27 increased noticeably at 1 day (p < 0.05). Repeated measures analysis of variance revealed African origin to be associated with lower MCV and female sex with lower MCHC.
Conclusion: Based on multivariate analysis, periodontal diagnosis (BP/CP) was not associated with haematological parameters measured in this study or serum Hsp27. In CP, nonsurgical periodontal therapy improved MCHC 12 weeks after SD. Also in CP Hsp27 was increased 1 day after SD.
Electroencephalography (EEG) represents a widely established method for assessing altered and typically developing brain function. However, systematic studies on EEG data quality, its correlates, and consequences are scarce. To address this research gap, the current study focused on the percentage of artifact-free segments after standard EEG pre-processing as a data quality index. We analyzed participant-related and methodological influences, and validity by replicating landmark EEG effects. Further, effects of data quality on spectral power analyses beyond participant-related characteristics were explored. EEG data from a multicenter ADHD-cohort (age range 6 to 45 years), and a non-ADHD school-age control group were analyzed (ntotal = 305). Resting-state data during eyes open, and eyes closed conditions, and task-related data during a cued Continuous Performance Task (CPT) were collected. After pre-processing, general linear models, and stepwise regression models were fitted to the data. We found that EEG data quality was strongly related to demographic characteristics, but not to methodological factors. We were able to replicate maturational, task, and ADHD effects reported in the EEG literature, establishing a link with EEG-landmark effects. Furthermore, we showed that poor data quality significantly increases spectral power beyond effects of maturation and symptom severity. Taken together, the current results indicate that with a careful design and systematic quality control, informative large-scale multicenter trials characterizing neurophysiological mechanisms in neurodevelopmental disorders across the lifespan are feasible. Nevertheless, results are restricted to the limitations reported. Future work will clarify predictive value.