Age-related changes in time perception:The impact of naturalistic environments and retrospective judgements on timing performance

Reduced timing abilities have been reported in older adults and are associated with pathological cognitive decline. However, time perception experiments often lack ecological validity. Especially the reduced complexity of experimental stimuli and the participants’ awareness of the time-related nature of the task can influence lab-assessed timing performance and thereby conceal age-related differences. An approximation of more naturalistic paradigms can provide important information about age-related changes in timing abilities. To determine the impact of higher ecological validity on timing experiments, we implemented a paradigm that allowed us to test (1) the effect of embedding the to-be-timed stimuli within a naturalistic visual scene and (2) the effect of retrospective time judgements, which are more common in real life than prospective judgements. The results show that compared with out-of-context stimuli, younger adults benefit from a naturalistic embedding of stimuli (reflected in higher precision and less errors), whereas the performance of older adults is reduced when confronted with naturalistic stimuli. Differences between retrospective and prospective time judgements were not modulated by age. We conclude that, potentially driven by difficulties in suppressing temporally irrelevant environmental information, the contextual embedding of naturalistic stimuli can affect the degree to which age influences the performance in time perception tasks

Temporal context effects are associated with cognitive status in advanced age

The perception of temporal intervals changes during the life-span, and especially older adults demonstrate specific impairments of timing abilities. Recently, we demonstrated that timing performance and cognitive status are correlated in older adults, suggesting that timing tasks can serve as a behavioral marker for the development of dementia. Easy-to-administer and retest-capable timing tasks therefore have potential as diagnostic tools for tracking cognitive decline. However, before being tested in a clinical cohort study, a further validation and specification of the original findings is warranted. Here we introduce several modifications of the original task and investigated the effects of temporal context on time perception in older adults (> 65 years) with low versus high scores in the Montreal Cognitive Assessment survey (MoCA) and a test of memory functioning. In line with our previous work, we found that temporal context effects were more pronounced with increasing memory deficits, but also that these effects are stronger for realistic compared to abstract visual stimuli. Furthermore, we show that two distinct temporal contexts influence timing behavior in separate experimental blocks, as well as in a mixed block in which both contexts are presented together. These results replicate and extend our previous findings. They demonstrate the stability of the effect for different stimulus material and show that timing tasks can reveal valuable information about the cognitive status of older adults. In the future, these findings could serve as a basis for the development of a diagnostic tool for pathological cognitive decline at an early, pre-clinical stage

Reducing the tendency for chronometric counting in duration discrimination tasks

Chronometric counting is a prevalent issue in the study of human time perception as it reduces the construct validity of tasks and can conceal existing timing deficits. Several methods have been proposed to prevent counting strategies, but the factors promoting those strategies in specific tasks are largely uninvestigated. Here, we modified a classical two-interval duration discrimination task in two aspects that could affect the tendency to apply counting strategies. We removed the pause between the two intervals and changed the task instructions: Participants decided whether a short event occurred in the first or in the second half of a reference duration. In Experiment 1, both classical and modified task versions were performed under timing conditions, in which participants were asked not to count, and counting conditions, in which counting was explicitly instructed. The task modifications led to (i) a general decrease in judgment precision, (ii) a shift of the point of subjective equality, and (iii) a counting-related increase in reaction times, suggesting enhanced cognitive effort of counting during the modified task version. Precision in the two task versions was not differently affected by instructed counting. Experiment 2 demonstrates that—in the absence of any counting-related instructions—participants are less likely to engage in spontaneous counting in the modified task version. These results enhance our understanding of the two-interval duration discrimination task and demonstrate that the modifications tested here—although they do not significantly reduce the effectiveness of instructed counting—can diminish the spontaneous tendency to adopt counting strategies

PET/CT Imaging for Personalized Management of Infectious Diseases

Positron emission tomography combined with computed tomography (PET/CT) is a nuclear imaging technique which is increasingly being used in infectious diseases. Because infection foci often consume more glucose than surrounding tissue, most infections can be diagnosed with PET/CT using 2-deoxy-2-[18F]fluoro-D-glucose (FDG), an analogue of glucose labeled with Fluorine-18. In this review, we discuss common infectious diseases in which FDG-PET/CT is currently applied including bloodstream infection of unknown origin, infective endocarditis, vascular graft infection, spondylodiscitis, and cyst infections. Next, we highlight the latest developments within the field of PET/CT, including total body PET/CT, use of novel PET radiotracers, and potential future applications of PET/CT that will likely lead to increased capabilities for patient-tailored treatment of infectious diseases

Moderation of alcohol consumption as a recommendation in European hypertension management guidelines: a survey on awareness, screening and implementation among European physicians

Objectives: Moderation of alcohol consumption is included as a class I, level of evidence A recommendation in the current European guidelines for the management of hypertension. We investigated its awareness and self-reported implementation among European physicians across different specialties and workplaces. Design and setting: A cross-sectional survey study conducted in two annual German meetings (German Society of Cardiology and the German Society of Internal Medicine) and two annual European meetings (European Society of Hypertension and European Society Cardiology) in 2015. Participants: 1064 physicians attending the European meetings were interviewed including 52.1% cardiologists, 29.2% internists and 8.8% general practitioners. Main outcome measures: Physician screening of alcohol consumption, awareness and self-implementation of the recommendation of the current European guidelines about moderation of alcohol consumption for the management of hypertension. Results: Overall, 81.9% of physicians reported to generally quantify alcohol consumption in patients with hypertension. However, only 28.6% and 14.5% of participants reported screening alcohol consumption in their patients with newly detected or treatment-resistant hypertension. Physicians recommended a maximum alcohol intake of 13.1 +/- 11.7 g/day for women (95% CI 12.3 to 13.8) and 19.9 +/- 15.6 g/day for men (95% CI 18.8 to 20.9). In case of moderate to high alcohol consumption, 10.3% would manage only hypertension without addressing alcohol consumption, while 3.7% of the physicians would do so in case of alcohol dependence (p<0.001). Conclusions: The average amount of alcohol intake per day recommended by European physicians in this survey was in agreement with the guidelines. The low number of physicians that screen for alcohol consumption in patients with newly detected and with treatment-resistant hypertension indicates an important deficit in the management of hypertension

Timing deficiencies in amnestic Mild Cognitive Impairment:Disentangling clock and memory processes

Interval timing performance in cognitive decline is typically characterized by decreased accuracy, precision, or both. One explanation for this decreased performance is a larger clock time variability. However, memory deficiencies associated with cognitive decline might also affect temporal performance in two alternative ways: First, memory deficiencies could lead to reduced encoding of just perceived durations, and thus a stronger reliance on the memory traces of previous experiences (the “prior”), yielding less precise reproductions of the most current experiences. Second, memory deficiencies could hamper the storage of perceived intervals, thus resulting in less influence of the prior. Here, we present data of 15 patients with amnestic Mild Cognitive Impairment (aMCI) and 44 healthy, aged controls, the latter split in two groups based on memory performance. All participants were tested on a temporal production task to assess clock time variability and a multi-duration reproduction task to assess the influence of memory traces reflecting current and previous experiences. Patients with aMCI showed the strongest regression towards the mean in a multi-duration reproduction task, followed by low-performing healthy controls and high-performing healthy controls, respectively. As no difference was observed between the groups in terms of clock time variability, and clock variability did not statistically contribute to the observed regression, this increased central tendency effect was not attributable to clock noise. We therefore, in line with the first explanation, conclude that memory deficiencies result in a stronger (relative) reliance on the prior

comparison of methadone and levomethadone in long-term treatment

Background This study aimed to investigate the development of opioid tolerance in patients receiving long-term methadone maintenance treatment (MMT). Methods A region-wide cross-sectional study was performed focusing on dosage and duration of treatment. Differences between racemic methadone and levomethadone were examined. All 20 psychiatric hospitals and all 110 outpatient clinics in Berlin licensed to offer MMT were approached in order to reach patients under MMT fulfilling the DSM IV criteria of opiate dependence. In the study, 720 patients treated with racemic methadone or levomethadone gave information on the dosage of treatment. Out of these, 679 patients indicated the duration of MMT. Results Treatment with racemic methadone was reported for 370 patients (54.5 %), with levomethadone for 309 patients (45.5 %). Mean duration of MMT was 7.5 years. We found a significant correlation between dosage and duration of treatment, both in a conjoint analysis for the two substances racemic methadone and levomethadone and for each substance separately. These effects remained significant when only patients receiving MMT for 1 year or longer were considered, indicating proceeding tolerance development in long-term treatment. When correlations were compared between racemic methadone and levomethadone, no significant difference was found. Conclusions Our data show a tolerance development under long-term treatment with both racemic methadone and levomethadone. Tolerance development did not differ significantly between the two substances

Importance of Blood Glucose Management Before 18F-FDG PET/CT in 322 Patients with Bacteremia of Unknown Origin

We investigated the effects of blood glucose levels on the performance of 18F-FDG PET/CT for detecting an infection focus in patients with bacteremia. Methods: A total of 322 consecutive patients with bacteremia who underwent 18F-FDG PET/CT between 2010 and 2021 were included. Logistic regression analysis was performed to evaluate the association between finding a true-positive infection focus on 18FFDG PET/CT and blood glucose level, type of diabetes, and use of hypoglycemic medication. C-reactive protein, leukocyte count, duration of antibiotic treatment, and type of isolated bacteria were considered as well. Results: Blood glucose level (odds ratio, 0.76 per unit increase; P=,0.001) was significantly and independently associated with 18F-FDG PET/CT outcome. In patients with a blood glucose level between 3.0 and 7.9mmol/L (54-142mg/dL), the true-positive detection rate of 18F-FDG PET/CT varied between 61% and 65%, whereas in patients with a blood glucose level between 8.0 and 10.9mmol/L (144-196mg/dL), the true-positive detection rate decreased to 30%- 38%. In patients with a blood glucose level greater than 11.0mmol/L (200mg/dL), the true-positive detection rate was 17%. In addition to C-reactive protein (odds ratio, 1.004 per point increase; P = 0.009), no other variables were independently associated with 18F-FDG PET/CT outcome. Conclusion: In patients with moderate to severe hyperglycemia, 18F-FDG PET/CT was much less likely to identify the focus of infection than in normoglycemic patients. Although current guidelines recommend postponing 18F-FDG PET/CT only in cases of severe hyperglycemia with glucose levels greater than 11mmol/L (200mg/dL), a lower blood glucose threshold seems to be more appropriate in patients with bacteremia of unknown origin and other infectious diseases.</p

Is Therapeutic Drug Monitoring Relevant for Antidepressant Drug Therapy? Implications From a Systematic Review and Meta-Analysis With Focus on Moderating Factors

Inter-individual differences in antidepressant drug concentrations attained in blood may limit the efficacy of pharmacological treatment of depressive disorders. Therapeutic drug monitoring (TDM) enables to determine drug concentrations in blood and adjust antidepressant dosage accordingly. However, research on the underlying assumption of TDM, association between concentration and clinical effect, has yielded ambiguous results for antidepressants. It has been proposed that this ambiguity may be caused by methodological shortcomings in studies investigating the concentration-effect relationship. Guidelines recommend the use of TDM in antidepressant treatment as expert opinion. This reflects the lack of research, particularly systematic reviews and meta-analyses of randomized controlled trials, on the relationship between concentration and effect as well as on the benefits of the use of TDM in clinical practice. In this study, a systematic review and meta-analysis of randomized controlled trials has been performed to investigate the relationship between antidepressant concentration, efficacy, and side effects. It is the first meta-analytical approach to this subject and additionally considers methodological properties of primary studies as moderators of effect in quantitative analysis. Our results identified methodological shortcomings, namely the use of a flexible dose design and the exclusion of concentrations in lower- or subtherapeutic ranges, which significantly moderate the relationship between antidepressant concentration and efficacy. Such shortcomings obscure the evidence base of using TDM in clinical practice to guide antidepressant drug therapy. Further research should consider these findings to determine the relationship between concentration and efficacy and safety of antidepressant treatments, especially for newer antidepressants.Peer Reviewe

Methode zur Untersuchung des dynamischen Verhaltens von Netzhautgefässen

This paper offers various approches to destine the changing of the diameter of human relatinal vessel. The focus is rather on the approches than on the physiological discussion of the results. The source signal has particular properties thus a costly signal preprocessing is necessary. This approches will be explained and discussed. The final transformation in the freqency domain is based on a common DFT algorithm. The calculated results will be compared