Investigating people's attitudes towards participating in longitudinal health research: an intersectionality-informed perspective.

BACKGROUND: Increasing evidence suggests that participation proportions in longitudinal health research vary according to sex/gender, age, social class, or migration status. Intersectionality scholarship purports that such social categories cannot be understood in isolation and makes visible the co-dependent nature of the social determinants of health and illness. This paper uses an intersectionality-informed approach in order to expand the understanding of why people participate in health research, and the impact of intersecting social structures and experiences on these attitudes. METHODS: A sample of 80 respondents who had previously either accepted or declined an invitation to participate in the German National Cohort (NAKO) participated in our interview study. Interviews were semi-structured and contained both narrative elements and more structured probes. Data analysis proceeded in two steps: first, the entire data set was analysed thematically (separately for participants and non-participants); second, key themes were compared across self-reported sex/gender, age group and migration status to identify differences and commonalities. RESULTS: Respondents' attitudes towards study participation can be categorised into four themes: wanting to make a contribution, seeking personalised health information, excitement and feeling chosen, and seeking social recognition. Besides citing logistical challenges, non-participants narrated adverse experiences with or attitudes towards science and the healthcare system that deterred them from participating. A range of social experiences and cultural value systems shaped such attitudes; in particular, this includes the cultural authority of science as an arbiter of social questions, transgressing social categories and experiences of marginalisation. Care responsibilities, predominantly borne by female respondents, also impacted upon the decision to take part in NAKO. DISCUSSION: Our findings suggest that for participants, health research constitutes a site of distinction in the sense of making a difference and being distinct or distinguishable, whereas non-participants inhabited an orientation towards science that reflected their subjective marginalisation through science. No clear relationship can thereby be presumed between social location and a particular attitude towards study participation; rather, such attitudes transgress and challenge categorical boundaries. This challenges the understanding of particular populations as more or less disadvantaged, or as more or less inclined to participate in health research.

Statistical Analysis in the German National Cohort (NAKO) - Specific Aspects and General Recommendations.

The German National Cohort (NAKO) is an ongoing, prospective multicenter cohort study, which started recruitment in 2014 and includes more than 205,000 women and men aged 19-74 years. The study data will be available to the global research community for analyses. Although the ultimate decision about the analytic methods will be made by the respective investigator, in this paper we provide the basis for a harmonized approach to the statistical analyses in the NAKO. We discuss specific aspects of the study (e.g., data collection, weighting to account for the sampling design), but also give general recommendations which may apply to other large cohort studies as well.

Cross-Sectional and Longitudinal Associations Between Psychosocial Well-Being and Cardiometabolic Markers in European Children and Adolescents.

OBJECTIVE: Research examining aspects of positive mental health as potential predictors of cardiometabolic health in young populations is scarce. We investigated the associations between psychosocial well-being and waist circumference (WAIST), blood pressure (BP), the homeostasis model assessment for insulin resistance, triglycerides, and high-density lipoprotein cholesterol considering life-style factors as mediators. METHODS: Data of European children and adolescents participating in the baseline (2007/2008), first follow-up (FU1; 2009/2010) and second follow-up (FU2; 2013/2014) examinations of the IDEFICS/I.Family study were used (ncross-sectional = 6519; nlongitudinal = 1393). A psychosocial well-being score was calculated from 16 items on emotional well-being, self-esteem, and social relationships (0-48 points). Cardiometabolic markers were transformed to age- and sex-specific and, in case of BP, also height-specific z scores. Life-style factors included diet, physical activity, sleep, and electronic media use. Applying path analysis, we obtained unstandardized estimates of direct and indirect effects of well-being on cardiometabolic markers. RESULTS: Cross-sectionally, well-being score showed a negative direct and a negative indirect effect through life-style factors on WAIST z score (estimate per 4-point increase, -0.051 [p = .001] and -0.014 [p < .001], respectively). Longitudinally, positive changes in well-being score between baseline and FU1 and between FU1 and FU2, respectively, demonstrated negative indirect effects through life-style factorsFU2 on WAIST z scoreFU2. Both cross-sectionally and longitudinally, higher levels of well-being showed lowering indirect effects on homeostasis model assessment, BP, and triglyceride z scores and an increasing indirect effect on high-density lipoprotein cholesterol z score through both life-style factors and WAIST z score. CONCLUSIONS: These results supported our hypothesis that a healthier life-style may be one mechanism through which higher well-being is linked with lower abdominal obesity and fewer other cardiometabolic disorders in young populations. TRIAL REGISTRATION: Pan-European IDEFICS/I.Family children cohort, ISRCTN registry number: ISRCTN62310987 (http://www.isrctn.com/ISRCTN62310987).

Participants who were difficult to recruit at baseline are less likely to complete a follow-up questionnaire - results from the German National Cohort.

BACKGROUND: With declining response proportions in population-based research the importance of evaluating the effectiveness of measures aimed at improving response increases. We investigated whether an additional flyer with information about the study influences participation in a follow-up questionnaire and the time participants take to send back filled questionnaire. METHODS: In a trial embedded within the German National Cohort we compared responses to invitations for a follow-up questionnaire either including a flyer with information about the cohort study or not including it. Outcomes of interest were participation in the follow-up (yes vs. no) and time to response (in days). We analyzed paradata from baseline recruitment to account for differences in recruitment history between participants. RESULTS: Adding a flyer to invitations did neither influence the likelihood of participation in the follow-up (OR 0.94, 95% CI: 0.80, 1.11), nor the time it took participants to return completed questionnaires (ß̂ = 1.71, 95% CI: - 1.01, 4.44). Subjects who, at baseline, needed to be reminded before eventually participating in examinations and subjects who scheduled three or more appointments until eventually completing baseline examinations were less likely to complete the follow-up questionnaire and, if they did, took more time to complete questionnaires. CONCLUSIONS: Evaluating the effectiveness of measures aimed at increasing response can help to improve the allocation of usually limited resources. Characteristics of baseline recruitment can influence response to follow-up studies and therefore information about recruitment history (i.e., paradata) might prove useful to tailor follow-up recruitments to those who were difficult to recruit during baseline. To this end, however, it is necessary to routinely and meticulously collect paradata during recruitment.

[The baseline assessment of the German National Cohort (NAKO Gesundheitsstudie): participation in the examination modules, quality assurance, and the use of secondary data]. / Die Basiserhebung der NAKO Gesundheitsstudie: Teilnahme an den Untersuchungsmodulen, Qualitätssicherung und Nutzung von Sekundärdaten.

BACKGROUND: The German National Cohort (NAKO) is an interdisciplinary health study aimed at elucidating causes for common chronic diseases and detecting their preclinical stages. This article provides an overview of design, methods, participation in the examinations, and their quality assurance based on the midterm baseline dataset (MBD) of the recruitment. METHODS: More than 200,000 women and men aged 20-69 years derived from random samples of the German general population were recruited in 18 study centers (2014-2019). The data collection comprised physical examinations, standardized interviews and questionnaires, and the collection of biomedical samples for all participants (level 1). At least 20% of all participants received additional in-depth examinations (level 2), and 30,000 received whole-body magnet resonance imaging (MRI). Additional information will be collected through secondary data sources such as medical registries, health insurances, and pension funds. This overview is based on the MBD, which included 101,839 participants, of whom 11,371 received an MRI. RESULTS: The mean response proportion was 18%. The participation in the examinations was high with most of the modules performed by over 95%. Among MRI participants, 96% completed all 12 MRI sequences. More than 90% of the participants agreed to the use of complementary secondary and registry data. DISCUSSION: Individuals selected for the NAKO were willing to participate in all examinations despite the time-consuming program. The NAKO provides a central resource for population-based epidemiologic research and will contribute to developing innovative strategies for prevention, screening and prediction of chronic diseases.

Development and body mass inversely affect children's brain activation in dorsolateral prefrontal cortex during food choice.

Childhood obesity is a rising problem caused in part by unhealthy food choices. Food choices are based on a neural value signal encoded in the ventromedial prefrontal cortex, and self-control involves modulation of this signal by the dorsolateral prefrontal cortex (dlPFC). We determined the effects of development, body mass (BMI Cole score) and body mass history on the neural correlates of healthy food choice in children. 141 children (aged 10-17y) from Germany, Hungary and Sweden were scanned with fMRI while performing a food choice task. Afterwards health and taste ratings of the foods were collected. In the food choice task children were asked to consider the healthiness or tastiness of the food or to choose naturally. Overall, children made healthier choices when asked to consider healthiness. However, children who had a higher weight gain per year chose less healthy foods when considering healthiness but not when choosing naturally. Pubertal development stage correlated positively while current body mass correlated negatively with dlPFC activation when accepting foods. Pubertal development negatively and current body mass positively influenced the effect of considering healthiness on activation of brain areas involved in salience and motivation. In conclusion, children in earlier stages of pubertal development and children with a higher body weight exhibited less activation in the dlPFC, which has been implicated in self-control during food choice. Furthermore, pubertal development and body mass influenced neural responses to a health cue in areas involved in salience and motivation. Thus, these findings suggest that children in earlier stages of pubertal development, children with a higher body mass gain and children with overweight may possibly be less susceptible to healthy eating interventions that rely on self-control or that highlight health aspects of food.

Impact of the intervention program "JolinchenKids - fit and healthy in daycare" on energy balance related-behaviors: results of a cluster controlled trial.

BACKGROUND: The purpose of this study was to evaluate the multi-component health promotion program, JolinchenKids - fit and healthy in daycare, designed to promote physical activity (PA), healthy eating, and mental wellbeing among 3- to 6-year-old preschoolers. METHODS: For this cluster controlled trial, 62 daycare facilities (DFs) from thirteen different federal states in Germany were recruited (31 intervention, 31 control DFs). Outcome measures were children's habitual PA, fruits and vegetable consumption, consumption of unsweetened beverages and snacks with parents as raters. Study nurses assessed children's body composition and motor skills. Data was collected at baseline and 12 months later. To track adherence to the implementation of intervention modules at individual DF groups, an implementation calendar was used from baseline to follow-up. Linear mixed models were used to investigate effects for survey, group and their interaction at the individual level while accounting for clustering. RESULTS: Samples of 831 (baseline) and 641 (follow-up) children aged 4.3 ± 0.8 and 5.2 ± 0.8 years were analysed. More than half of the intervention DFs chose the nutrition or PA module for the first year of implementation while an implementation level of > 50% was only achieved in less than a third. A significant intervention effect (survey × group interaction) was found for the standing long jump favouring children at intervention DFs (ß = 3.08; 95% Confidence interval [CI]: (0.09; 6.07)). No significant intervention effects were found for time spent on PA, total screen time, dietary habits, and body composition, i.e. body-mass-index and percentage of body fat. CONCLUSIONS: Participation in JolinchenKids - fit and healthy in daycare led to improvements in some indicators for motor skills. However, other health outcomes and behaviours were not affected by program participation over the course of 1 year. TRIAL REGISTRATION: German Clinical Trials Register DRKS00011065 (Date of registration 16-09-2016).

Auditory and audio-visual processing in patients with cochlear, auditory brainstem, and auditory midbrain implants: An EEG study.

There is substantial variability in speech recognition ability across patients with cochlear implants (CIs), auditory brainstem implants (ABIs), and auditory midbrain implants (AMIs). To better understand how this variability is related to central processing differences, the current electroencephalography (EEG) study compared hearing abilities and auditory-cortex activation in patients with electrical stimulation at different sites of the auditory pathway. Three different groups of patients with auditory implants (Hannover Medical School; ABI: n = 6, CI: n = 6; AMI: n = 2) performed a speeded response task and a speech recognition test with auditory, visual, and audio-visual stimuli. Behavioral performance and cortical processing of auditory and audio-visual stimuli were compared between groups. ABI and AMI patients showed prolonged response times on auditory and audio-visual stimuli compared with NH listeners and CI patients. This was confirmed by prolonged N1 latencies and reduced N1 amplitudes in ABI and AMI patients. However, patients with central auditory implants showed a remarkable gain in performance when visual and auditory input was combined, in both speech and non-speech conditions, which was reflected by a strong visual modulation of auditory-cortex activation in these individuals. In sum, the results suggest that the behavioral improvement for audio-visual conditions in central auditory implant patients is based on enhanced audio-visual interactions in the auditory cortex. Their findings may provide important implications for the optimization of electrical stimulation and rehabilitation strategies in patients with central auditory prostheses. Hum Brain Mapp 38:2206-2225, 2017. © 2017 Wiley Periodicals, Inc.

Selective modulation of interhemispheric functional connectivity by HD-tACS shapes perception.

Oscillatory neuronal synchronization between cortical areas has been suggested to constitute a flexible mechanism to coordinate information flow in the human cerebral cortex. However, it remains unclear whether synchronized neuronal activity merely represents an epiphenomenon or whether it is causally involved in the selective gating of information. Here, we combined bilateral high-density transcranial alternating current stimulation (HD-tACS) at 40 Hz with simultaneous electroencephalographic (EEG) recordings to study immediate electrophysiological effects during the selective entrainment of oscillatory gamma-band signatures. We found that interhemispheric functional connectivity was modulated in a predictable, phase-specific way: In-phase stimulation enhanced synchronization, anti-phase stimulation impaired functional coupling. Perceptual correlates of these connectivity changes were found in an ambiguous motion task, which strongly support the functional relevance of long-range neuronal coupling. Additionally, our results revealed a decrease in oscillatory alpha power in response to the entrainment of gamma band signatures. This finding provides causal evidence for the antagonistic role of alpha and gamma oscillations in the parieto-occipital cortex and confirms that the observed gamma band modulations were physiological in nature. Our results demonstrate that synchronized cortical network activity across several spatiotemporal scales is essential for conscious perception and cognition.

Consequences of an Extended Recruitment on Participation in the Follow-Up of a Child Study: Results from the German IDEFICS Cohort.

BACKGROUND: Declining response proportions in population-based studies are often countered by extended recruitment efforts at baseline that may, however, result in higher attrition in a subsequent follow-up. This study analysed the effect of extended recruitment efforts on attrition at the first follow-up of a child cohort. METHODS: We used paradata (i.e. information about the process of data collection) from the German IDEFICS cohort investigating dietary- and life style-induced health effects on children to quantify recruitment effort and classify respondents as completing the recruitment early vs. late for baseline and follow-up separately. Multilevel logistic regression models were used to investigate the association between recruitment effort and attrition at follow-up (loss to follow-up) adjusted for sociodemographic and health related variables. RESULTS: Individuals who were late respondents at baseline and early respondents at the follow-up had a higher chance of attrition (odds ratio 1.65, 95% confidence interval (CI) 1.19, 2.28) as compared to other groups. An investigation of reasons for non-participation revealed that members of this group were more likely to be not reachable by phone. CONCLUSIONS: An extended recruitment effort at baseline of a child cohort study is not per se associated with a higher chance of attrition at follow-up. Much care should be taken to collect valid telephone numbers.

Design and methods for a cluster-controlled trial conducted at sixty-eight daycare facilities evaluating the impact of "JolinchenKids - Fit and Healthy in Daycare", a program for health promotion in 3- to 6-year-old children.

BACKGROUND: The prevention of overweight and obesity during infancy is a highly relevant public health topic given the significant impact of childhood obesity on acute and chronic diseases, general health, and well-being in later stages of life. Apart from the family setting, daycare facilities (DFs) represent a key setting for health promotion among children under the age of six years. "JolinchenKids - Fit and Healthy in Daycare" is a multi-component program promoting physical activity (PA), healthy eating, and mental well-being in 3- to 6-year-old preschoolers at DFs, originally designed by the German health insurance AOK. To evaluate program effectiveness, a cluster-controlled trial involving 68 DFs is currently conducted. The objective of this article is to describe the background, study design, and aims of this trial. METHODS/DESIGN: Sixty-eight DFs across Germany will be recruited to take part in the study, half of them serving as intervention DFs and half of them as delayed intervention control DFs (which receive the program upon completion of the study). At each DF, height, weight, and body composition, as well as motor skills, will be assessed in twenty 3- to 6-year-old children. Children's eating and PA habits, and mental well-being will be assessed via parental questionnaires. A subsample of children (i.e., at 24 DFs which are randomly selected within a geographic region) will be asked to wear accelerometers at their wrists to objectively measure PA over the course of seven days. To compare changes in body composition, motor skills, eating and PA habits, and mental well-being of children at intervention DFs with those observed among children at delayed intervention control DFs over one year, all measurements will take place at baseline and twelve months after the launch of the program at all DFs. DISCUSSION: This study investigates the influence of a health promotion program in the daycare setting on various outcomes, including body composition and objectively measured PA, in a nationwide sample of 3- to 6-year-old preschoolers. This study will provide evidence regarding the effectiveness of a multi-component program for health promotion in this setting and may provide insights into new strategies for preventing obesity in early life. TRIAL REGISTRATION: German Clinical Trials Register DRKS00011065 (Date of registration 16-09-2016).

Further evidence for the role of pregnancy-induced hypertension and other early life influences in the development of ADHD: results from the IDEFICS study.

The aim of this study is to investigate whether in addition to established early risk factors other, less studied pre-, peri-, and postnatal influences, like gestational hypertension or neonatal respiratory disorders and infections, may increase a child's risk of developing attention-deficit/hyperactivity disorders (ADHD). In the IDEFICS study more than 18,000 children, aged 2-11.9 years, underwent extensive medical examinations supplemented by parental questionnaires on pregnancy and early childhood. The present analyses are restricted to children whose parents also completed a supplementary medical questionnaire (n = 15,577), including the question whether or not the child was ever diagnosed with ADHD. Multilevel multivariable logistic regression was used to assess the association between early life influences and the risk of ADHD. Our study confirms the well-known association between maternal smoking during pregnancy and a child's risk of ADHD. In addition, our study showed that children born to mothers younger than 20 years old were 3-4 times more likely to develop ADHD as compared to children born to mothers aged 25 years and older. Moreover, we found that children whose mothers suffered from pregnancy-induced hypertension had an approximately twofold risk of ADHD (OR 1.95; 95% CI 1.09-3.48). This also holds true for infections during the first 4 weeks after birth (OR 2.06; 95% CI 1.05-4.04). In addition, although not statistically significant, we observed a noticeable elevated risk estimate for neonatal respiratory disorders (OR 1.76; 95% CI 0.91-3.41). Hence, we recommend that these less often studied pre-, peri, and postnatal influences should get more attention when considering early indicators or predictors for ADHD in children. However, special study designs such as genetically sensitive designs may be needed to derive causal conclusions.

Time-frequency analysis of event-related potentials: a brief tutorial.

Event-related potentials (ERPs) reflect cognitive processes and are usually analyzed in the so-called time domain. Additional information on cognitive functions can be assessed when analyzing ERPs in the frequency domain and treating them as event-related oscillations (EROs). This procedure results in frequency spectra but lacks information about the temporal dynamics of EROs. Here, we describe a method-called time-frequency analysis-that allows analyzing both the frequency of an ERO and its evolution over time. In a brief tutorial, the reader will learn how to use wavelet analysis in order to compute time-frequency transforms of ERP data. Basic steps as well as potential artifacts are described. Rather than in terms of formulas, descriptions are in textual form (written text) with numerous figures illustrating the topics. Recommendations on how to present frequency and time-frequency data in journal articles are provided. Finally, we briefly review studies that have applied time-frequency analysis to mismatch negativity paradigms. The deviant stimulus of such a paradigm evokes an ERO in the theta frequency band that is stronger than for the standard stimulus. Conversely, the standard stimulus evokes a stronger gamma-band response than does the deviant. This is interpreted in the context of the so-called match-and-utilization model.

Antiphasic 40 Hz oscillatory current stimulation affects bistable motion perception.

When viewing ambiguous stimuli, conscious perception alternates spontaneously between competing interpretations of physically unchanged stimulus information. As one possible neural mechanism underlying the perceptual switches, it has been suggested that neurons dynamically change their pattern of synchronized oscillatory activity in the gamma band (30-80 Hz). In support of this hypothesis, there is correlative evidence from human electroencephalographic (EEG) studies for gamma band modulations during ambiguous perception. To establish a causal role of gamma band oscillations in the current study, we applied transcranial alternating current stimulation (tACS) at 40 Hz over occipital-parietal areas of both hemispheres during the presentation of bistable apparent motion stimuli that can be perceived as moving either horizontally or vertically. In this paradigm, the switch between horizontal and vertical apparent motion is likely to involve a change in interhemispheric functional coupling. We examined gamma tACS effects on the durations of perceived horizontal and vertical motion as well as on interhemispheric EEG coherence and found a decreased proportion of perceived horizontal motion together with an increase of interhemispheric gamma band coherence. In a control experiment using 6 Hz tACS, we did not observe any stimulation effects on behavior or coherence. Furthermore, external stimulation at 40 Hz was only effective when applied with 180° phase difference between hemispheres (anti-phase), as compared to in-phase stimulation with 0° phase difference. These findings suggest that externally desynchronizing gamma oscillations between hemispheres impairs interhemispheric motion integration and in turn biases conscious experience of bistable apparent motion.

The Use of Machine Translation for Outreach and Health Communication in Epidemiology and Public Health: Scoping Review.

BACKGROUND: Culturally and linguistically diverse groups are often underrepresented in population-based research and surveillance efforts, leading to biased study results and limited generalizability. These groups, often termed "hard-to-reach," commonly encounter language barriers in the public health (PH) outreach material and information campaigns, reducing their involvement with the information. As a result, these groups are challenged by 2 effects: the medical and health knowledge is less tailored to their needs, and at the same time, it is less accessible for to them. Modern machine translation (MT) tools might offer a cost-effective solution to PH material language accessibility problems. OBJECTIVE: This scoping review aims to systematically investigate current use cases of MT specific to the fields of PH and epidemiology, with a particular interest in its use for population-based recruitment methods. METHODS: PubMed, PubMed Central, Scopus, ACM Digital Library, and IEEE Xplore were searched to identify articles reporting on the use of MT in PH and epidemiological research for this PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews)-compliant scoping review. Information on communication scenarios, study designs and the principal findings of each article were mapped according to a settings approach, the World Health Organization monitoring and evaluation framework and the service readiness level framework, respectively. RESULTS: Of the 7186 articles identified, 46 (0.64%) were included in this review, with the earliest study dating from 2009. Most of the studies (17/46, 37%) discussed the application of MT to existing PH materials, limited to one-way communication between PH officials and addressed audiences. No specific article investigated the use of MT for recruiting linguistically diverse participants to population-based studies. Regarding study designs, nearly three-quarters (34/46, 74%) of the articles provided technical assessments of MT from 1 language (mainly English) to a few others (eg, Spanish, Chinese, or French). Only a few (12/46, 26%) explored end-user attitudes (mainly of PH employees), whereas none examined the legal or ethical implications of using MT. The experiments primarily involved PH experts with language proficiencies. Overall, more than half (38/70, 54% statements) of the summarizing results presented mixed and inconclusive views on the technical readiness of MT for PH information. CONCLUSIONS: Using MT in epidemiology and PH can enhance outreach to linguistically diverse populations. The translation quality of current commercial MT solutions (eg, Google Translate and DeepL Translator) is sufficient if postediting is a mandatory step in the translation workflow. Postediting of legally or ethically sensitive material requires staff with adequate content knowledge in addition to sufficient language skills. Unsupervised MT is generally not recommended. Research on whether machine-translated texts are received differently by addressees is lacking, as well as research on MT in communication scenarios that warrant a response from the addressees.

Mild COVID-19 infection associated with post-COVID-19 condition after 3 months - a questionnaire survey.

INTRODUCTION: The coronavirus disease 2019 (COVID-19), caused by infection with SARS-CoV-2, can lead to post-COVID-19 condition, a secondary syndrome of persistent and new post-acute symptoms, but evidence on this syndrome is still scarce. METHODS: In a questionnaire survey, residents of the city of Bremen (Germany) with verified SARS-CoV-2 infection were invited to answer questions (online questionnaire or interview) concerning symptoms experienced at the time of infection and at the time of questionnaire completion at least three months later. Main outcome of the analysis was the presence of a post-COVID-19 condition at the time of the interview, defined as the presence of at least two of three leading symptoms: fatigue, breathing difficulties, or cognitive problems. RESULTS: A post-COVID-19 condition was more likely to be reported if respondents had, at the time of infection, suffered from fatigue (OR 1.75; 95% CI: 1.00, 3.06), breathing difficulties (OR 4.02; 95% CI: 2.80, 5.77), cognitive symptoms (OR 2.98; 95% CI: 1.48, 6.02), or head- & bone aches (OR 2.06; 95% CI: 1.25, 3.42). The odds of developing a post-COVID-19 condition increased with the number of symptoms at infection. Females were more likely to report a post-COVID-19 condition (OR 1.54; 95% CI: 1.05, 2.24). Analyzing only non-hospitalized respondents changed results only slightly. CONCLUSION: Our study adds to growing evidence that even a mild course of COVID-19 poses a risk for developing a post-COVID-19 condition. Females and those with initial symptoms including fatigue, breathing difficulties, and cognitive symptoms seem more likely to also experience post COVID-19 symptoms several months after infection.KEY MESSAGESEven a mild course of COVID-19 poses a risk for developing a post-COVID-19 condition.Females seem more likely to develop a post-COVID-19 condition.Those with initial symptoms including fatigue, breathing difficulties, and cognitive symptoms seem more likely to develop a post-COVID-19 condition.

Multiple imputation of missing data under missing at random: compatible imputation models are not sufficient to avoid bias if they are mis-specified.

OBJECTIVES: Epidemiological studies often have missing data, which are commonly handled by multiple imputation (MI). Standard (default) MI procedures use simple linear covariate functions in the imputation model. We examine the bias that may be caused by acceptance of this default option and evaluate methods to identify problematic imputation models, providing practical guidance for researchers. STUDY DESIGN AND SETTING: Using simulation and real data analysis, we investigated how imputation model mis-specification affected MI performance, comparing results with complete records analysis (CRA). We considered scenarios in which imputation model mis-specification occurred because (i) the analysis model was mis-specified or (ii) the relationship between exposure and confounder was mis-specified. RESULTS: Mis-specification of the relationship between outcome and exposure, or between exposure and confounder, can cause biased CRA and MI estimates (in addition to any bias in the full-data estimate due to analysis model mis-specification). MI by predictive mean matching can mitigate model mis-specification. Methods for examining model mis-specification were effective in identifying mis-specified relationships. CONCLUSION: When using MI methods that assume data are MAR, compatibility between the analysis and imputation models is necessary, but not sufficient to avoid bias. We propose a step-by-step procedure for identifying and correcting mis-specification of imputation models.

Auditory event-related response in visual cortex modulates subsequent visual responses in humans.

Growing evidence from electrophysiological data in animal and human studies suggests that multisensory interaction is not exclusively a higher-order process, but also takes place in primary sensory cortices. Such early multisensory interaction is thought to be mediated by means of phase resetting. The presentation of a stimulus to one sensory modality resets the phase of ongoing oscillations in another modality such that processing in the latter modality is modulated. In humans, evidence for such a mechanism is still sparse. In the current study, the influence of an auditory stimulus on visual processing was investigated by measuring the electroencephalogram (EEG) and behavioral responses of humans to visual, auditory, and audiovisual stimulation with varying stimulus-onset asynchrony (SOA). We observed three distinct oscillatory EEG responses in our data. An initial gamma-band response around 50 Hz was followed by a beta-band response around 25 Hz, and a theta response around 6 Hz. The latter was enhanced in response to cross-modal stimuli as compared to either unimodal stimuli. Interestingly, the beta response to unimodal auditory stimuli was dominant in electrodes over visual areas. The SOA between auditory and visual stimuli--albeit not consciously perceived--had a modulatory impact on the multisensory evoked beta-band responses; i.e., the amplitude depended on SOA in a sinusoidal fashion, suggesting a phase reset. These findings further support the notion that parameters of brain oscillations such as amplitude and phase are essential predictors of subsequent brain responses and might be one of the mechanisms underlying multisensory integration.

Gamma in motion: pattern reversal elicits stronger gamma-band responses than motion.

Previous studies showed higher gamma-band responses (GBRs, ≈40 Hz) of the electroencephalogram (EEG) for moving compared to stationary stimuli. However, it is unclear whether this modulation by motion reflects a special responsiveness of the GBR to the stimulus feature "motion," or whether GBR enhancements of similar magnitude can be elicited also by a salient change within a static stimulus that does not include motion. Therefore, we measured the EEG of healthy subjects watching stationary square wave gratings of high contrast that either started to move or reversed their black and white pattern shortly after their onset. The strong contrast change of the pattern reversal represented a salient but motionless change within the grating that was compared to the onset of the stationary grating and the motion onset. Induced and evoked GBRs were analyzed for all three display conditions. In order to assess the influence of fixational eye movements on the induced GBRs, we also examined the time courses of microsaccade rates during the three display conditions. Amplitudes of both evoked and induced GBRs were stronger for pattern reversal than for motion onset. There was no significant amplitude difference between the onsets of the stationary and moving gratings. However, mean frequencies of the induced GBR were ~10 Hz higher in response to the onsets of moving compared to stationary gratings. Furthermore, the modulations of the induced GBR did not parallel the modulations of microsaccade rate, indicating that our induced GBRs reflect neuronal processes. These results suggest that, within the gamma-band range, the encoding of moving gratings in early visual cortex is primarily based on an upward frequency shift, whereas contrast changes within static gratings are reflected by amplitude enhancement.

On quantifying multisensory interaction effects in reaction time and detection rate.

Both mean reaction time (RT) and detection rate (DR) are important measures for assessing the amount of multisensory interaction occurring in crossmodal experiments, but they are often applied separately. Here we demonstrate that measuring multisensory performance using either RT or DR alone misses out on important information. We suggest an integration of RT and DR into a single measure of multisensory performance: the first index (MRE*) is based on an arithmetic combination of RT and DR, the second (MPE) is constructed from parameters derived from fitting a sequential sampling model to RT and DR data simultaneously. Our approach is illustrated by data from two audio-visual experiments. In the first, a redundant targets detection experiment using stimuli of different intensity, both measures yield similar pattern of results supporting the "principle of inverse effectiveness". The second experiment, introducing stimulus onset asynchrony and differing instructions (focused attention vs. redundant targets task) further supports the usefulness of both indices. Statistical properties of both measures are investigated via bootstrapping procedures.