Context Matters: Memories of Prior Times

It’s not just the answer to the question Do you love me? that determines the fate of two people. When the answer takes too long, even a positive response can induce negative emotions. This highlights our ability to track, and the importance of tracking the passage of time. In this thesis, I demonstrate that the perception of a duration is influenced by previous experiences (the “Typing…” message in a WhatsApp group with one’s parents just takes an eternity after just having chatted with friends) and that this finding is a highly robust phenomenon. To counter a number of implausible assumptions in existing mathematical models of how memory is involved in the perception of time, I propose an extension to these mathematical Bayesian models of timing that implements a more realistic memory representation. Additionally, in a series of experiments in healthy aged populations and patients diagnosed with amnestic mild cognitive impairment (aMCI), I show that the temporal memory effects are directly linked to memory proficiency: the more memory is clinically affected - for example due to the early stages of Alzheimer’s - the more one relies on earlier experiences instead of on the currently perceived duration. This paradoxical finding could potentially be used as an indirect yet sensitive measure to track declining memory before aMCI, a precursor to Alzheimer’s, is officially diagnosed

1-s Productions: A Validation of an Efficient Measure of Clock Variability

Objective: Clock variance is an important statistic in many clinical and developmental studies. Existing methods require a large number of trials for accurate clock variability assessment, which is problematic in studies using clinical or either young or aged participants. Furthermore, these existing methods often implicitly convolute clock and memory processes, making it difficult to disentangle whether the clock or memory system are driving the observed deviations. Here we assessed whether 20 repeated productions of a well-engrained interval (1 s), a task that does not incorporate memory updating nor the processing of feedback, could provide an accurate assessment of clock variability.Method: Sixty-eight undergraduate students completed two tasks: a 1-s production task in which they were asked to produce a 1-s duration by ending a tone by a keypress, and a multi-duration reproduction task. Durations presented in the reproduction task were tones lasting 1.17, 1.4 and 1.68 s. No feedback was presented in either task, and the order of presentation was counterbalanced between participants.Results: The observed central tendency in the reproduction task was better explained by models including the measures of clock variability derived from the 1-s production task than by models without it. Three clock variability measures were calculated for each participant [standard deviation, root mean squared residuals (RMSRs) from an estimated linear slope, and RMSR scaled by mean production duration]. The model including the scaled RMSR was preferred over the alternative models, and no notable effects of the order of task presentation were observed. These results suggest that: (1) measures of variability should account for drift; (2) the presentation of another timing task before a 1-s production task did not influence the assessment of the clock variability; and (3) the observed variability adheres to the scalar property and predicts temporal performance, and is thus a usable index of clock variability.Conclusion: This study shows that just 20 repeated productions of 1 s provide a reliable index of clock variability. As administering this task is fast and easy, it could prove to be useful in a large variety of developmental and clinical populations

Keeping Bystanders Active:Resuscitating Resuscitation Skills

Introduction: Sufficient CPR skills in the general population are essential to make them active bystanders and contribute to an effective chain of survival in cardiac arrest emergencies. However, having a large proportion of the population regularly retrained is practically infeasible. Objective: The aim of this study was to assess and retrain cardiopulmonary resuscitation (CPR) skills of individuals who received (limited) CPR training several months to years prior. Method: Ninety-nine German adults in a possession of a driver's license were asked to perform CPR on a Laerdal Resusci Anne (R) QCPR manikin (Laerdal, Stavanger, Norway). After initial assessment, participants watched an instructional video and completed short, isolated compression, and ventilation practice with live feedback. CPR competency was assessed again after retraining and after a retention interval of 45 min. Results: Our results indicate that only 2% of participants managed to reach the performance criteria set by the European Resuscitation Council Guidelines, with most failing to reach even the lowest levels of performance. This corroborates earlier observations that CPR skills have deteriorated almost completely after a long retention interval, calling into question "one-and-done" certification of this basic life-saving. However, we also demonstrated that performance strikingly increased after watching a 6-min instructional video and a short opportunity for isolated practice. This increase in performance was stable over 45 min with 96% of participants meeting performance levels specified in the Guidelines. Closer inspection of the isolated compression practice data suggests that performance was very high at the start of the practice already, indicating that short refresher videos might suffice to change bystanders that would not have initiated CPR due to lack of knowledge into active first responders. Conclusion: We suggest that short refresher trainings could be an effective and affordable means of improving basic lifesaving skills to increase the effective contribution of bystanders during emergencies

Within-Subject Performance on a Real-Life, Complex Task and Traditional Lab Experiments:Measures of Word Learning, Raven Matrices, Tapping, and CPR

In this data report, we describe a three-session experiment spanning six months. Several well-controlled laboratory tasks (Word Learning, Raven Matrices, and Tapping) and Cardiopulmonary Resuscitation (CPR), a complex but well-defined real-world task, were administered. Data are reported from 50 participants for the first session, 40 for the second, and 34 for the third. CPR is a useful domain for studying real-world performance inside the laboratory because clear performance standards can be applied to quantifying learners’ proficiency covering both the first steps that need to be taken prior to the initiation of CPR (declarative knowledge) as well as the compressions and ventilations themselves (procedural skill). This research resulted in a rich dataset with a range of different measures for all participants. For all tasks, the complete set of raw data are made available along with relevant aggregate performance scores (see https://osf.io/m8bxe/). The raw data in particular will enable other researchers to explore potential analyses and modeling beyond the scope of our own. The details of the data collection protocol and available data are documented here to facilitate this process

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

Conceptually plausible Bayesian inference in interval timing

In a world that is uncertain and noisy, perception makes use of optimization procedures that rely on the statistical properties of previous experiences. A well-known example of this phenomenon is the central tendency effect observed in many psychophysical modalities. For example, in interval timing tasks, previous experiences influence the current percept, pulling behavioural responses towards the mean. In Bayesian observer models, these previous experiences are typically modelled by unimodal statistical distributions, referred to as the prior. Here, we critically assess the validity of the assumptions underlying these models and propose a model that allows for more flexible, yet conceptually more plausible, modelling of empirical distributions. By representing previous experiences as a mixture of lognormal distributions, this model can be parametrized to mimic different unimodal distributions and thus extends previous instantiations of Bayesian observer models. We fit the mixture lognormal model to published interval timing data of healthy young adults and a clinical population of aged mild cognitive impairment patients and age-matched controls, and demonstrate that this model better explains behavioural data and provides new insights into the mechanisms that underlie the behaviour of a memory-affected clinical population

Migration of Acanthamoeba through Legionella biofilms is regulated by the bacterial Lqs-LvbR network, effector proteins and the flagellum

The environmental bacterium Legionella pneumophila causes the pneumonia Legionnaires' disease. The opportunistic pathogen forms biofilms and employs the Icm/Dot type IV secretion system (T4SS) to replicate in amoebae and macrophages. A regulatory network comprising the Legionella quorum sensing (Lqs) system and the transcription factor LvbR controls bacterial motility, virulence and biofilm architecture. Here we show by comparative proteomics that in biofilms formed by the L. pneumophila ΔlqsR or ΔlvbR regulatory mutants the abundance of proteins encoded by a genomic 'fitness island', metabolic enzymes, effector proteins and flagellar components (e.g. FlaA) varies. ∆lqsR or ∆flaA mutants form 'patchy' biofilms like the parental strain JR32, while ∆lvbR forms a 'mat-like' biofilm. Acanthamoeba castellanii amoebae migrated more slowly through biofilms of L. pneumophila lacking lqsR, lvbR, flaA, a functional Icm/Dot T4SS (∆icmT), or secreted effector proteins. Clusters of bacteria decorated amoebae in JR32, ∆lvbR or ∆icmT biofilms but not in ∆lqsR or ∆flaA biofilms. The amoeba-adherent bacteria induced promoters implicated in motility (PflaA ) or virulence (PsidC , PralF ). Taken together, the Lqs-LvbR network (quorum sensing), FlaA (motility) and the Icm/Dot T4SS (virulence) regulate migration of A. castellanii through L. pneumophila biofilms, and - apart from the T4SS - govern bacterial cluster formation on the amoebae

Benefits of Adaptive Learning Transfer From Typing-Based Learning to Speech-Based Learning

Memorising vocabulary is an important aspect of formal foreign-language learning. Advances in cognitive psychology have led to the development of adaptive learning systems that make vocabulary learning more efficient. One way these computer-based systems optimize learning is by measuring learning performance in real time to create optimal repetition schedules for individual learners. While such adaptive learning systems have been successfully applied to word learning using keyboard-based input, they have thus far seen little application in word learning where spoken instead of typed input is used. Here we present a framework for speech-based word learning using an adaptive model that was developed for and tested with typing-based word learning. We show that typing- and speech-based learning result in similar behavioral patterns that can be used to reliably estimate individual memory processes. We extend earlier findings demonstrating that a response-time based adaptive learning approach outperforms an accuracy-based, Leitner flashcard approach in learning efficiency (demonstrated by higher average accuracy and lower response times after a learning session). In short, we show that adaptive learning benefits transfer from typing-based learning, to speech based learning. Our work provides a basis for the development of language learning applications that use real-time pronunciation assessment software to score the accuracy of the learner’s pronunciations. We discuss the implications for our approach for the development of educationally relevant, adaptive speech-based learning applications

A global data-driven census of Salmonella small proteins and their potential functions in bacterial virulence.

Small proteins are an emerging class of gene products with diverse roles in bacterial physiology. However, a full understanding of their importance has been hampered by insufficient genome annotations and a lack of comprehensive characterization in microbes other than Escherichia coli. We have taken an integrative approach to accelerate the discovery of small proteins and their putative virulence-associated functions in Salmonella Typhimurium. We merged the annotated small proteome of Salmonella with new small proteins predicted with in silico and experimental approaches. We then exploited existing and newly generated global datasets that provide information on small open reading frame expression during infection of epithelial cells (dual RNA-seq), contribution to bacterial fitness inside macrophages (Transposon-directed insertion sequencing), and potential engagement in molecular interactions (Grad-seq). This integrative approach suggested a new role for the small protein MgrB beyond its known function in regulating PhoQ. We demonstrate a virulence and motility defect of a Salmonella ΔmgrB mutant and reveal an effect of MgrB in regulating the Salmonella transcriptome and proteome under infection-relevant conditions. Our study highlights the power of interpreting available 'omics' datasets with a focus on small proteins, and may serve as a blueprint for a data integration-based survey of small proteins in diverse bacteria