Recall Study Research Articles

Incidence of dementia in the German Heinz Nixdorf Recall study over 20 years.

The aim of the study was to estimate the population-based dementia incidence in Germany over a period of two decades. We analyzed data from 4814 participants of the population-based Heinz Nixdorf Recall study (49.8% men, 45-75 years at baseline period 2000-2003), who have been monitored for the occurrence of cognitive decline and dementia. We calculated the cumulative incidence of dementia and its major subtypes and the incidence rate per 1000 person-years over two decades. During a median follow-up of 18.2 (Q1-Q3: 11.3-20.6) years, a total of 298 participants (6.2%) developed dementia (22.1% Alzheimer´s disease, 23.5% vascular dementia, 15.1% mixed dementia, 9.1% other dementia, 30.2% unspecified). The overall incidence rate was 3.9 per 1000 person-years. Our study is the only current population-based study in Germany that estimates the incidence of dementia. In order to reduce the high proportion of unspecific dementia diagnoses, diagnostics urgently need to be improved. New data on the incidence of dementia in Germany in participants ≥45 years of age.Participants have been monitored for dementia incidence over two decades.The overall incidence in our cohort was 3.9 per 1000 person-years.Many patients had unspecific dementia diagnoses in their medical records.Further diagnostic evaluation should be available for all dementia patients.

Socioeconomic position interacts with the genetic effect of a CRP gene common variant to influence C-reactive protein values.

C-Reactive Protein (CRP) values are partly determined by variation at the CRP gene locus, but also influenced by socioeconomic position (SEP) and related lifestyle factors. As gene-by-SEP interactions have been suggested for traits associated with CRP and SEP (e.g., BMI, coronary artery disease), the aim of this study was to investigate the strength of a possible interaction between a CRP gene common variant (rs4287174) and SEP in their joint influence on CRP levels in a population-based study sample. Single nucleotide polymorphism rs4287174 was genotyped in 4065 participants (aged 45-75 years) of the Heinz Nixdorf Recall study, a population-based prospective cohort. SEP indicators (education and income), risk factors (i.e., body mass index (BMI), total cholesterol, diabetes mellitus, coronary artery calcification, current smoking, hypertension, diet, no exercise) and blood serum CRP (mg/dl) were assessed at study baseline. Interaction analysis was based on linear regression and on stratified analyses (genetic effect stratified by SEP and vice versa) adjusted for age and sex using loge(CRP + 1) as dependent variable. Low SEP and rs4287174 T allele were both associated with higher CRP values. The strongest genetic effect was observed in the lowest educational group (≤ 10 years of education) with an exp(β) indicating 1.058-fold (95%-CI: 1.018; 1.100) average CRP values per additional T allele, while in the highest educational group (≥ 18 years) the association was considerably less strong (exp(β): 1.005 (95%-CI: 0.975; 1.037)). After including rs4287174-by-education interaction terms in the regression analysis, interaction was indicated suggesting stronger genetic effects on CRP in low SEP groups (exp(βinteraction): 1.056 (95%-CI: 1.005; 1.108); p = 0.029). The observed interaction did not seem to be substantially mediated by the risk factors included in the analysis. No indication for rs4287174-by-income interaction was observed. Results imply that genetic effects of the CRP locus are modified by education as an indicator of life course SEP.

Use of Estonian Biobank data and participant recall to improve Wilson's disease management.

Population-based biobanks enable genomic screening to support initiatives that prevent disease onset or slow its progression and to estimate the prevalence of genetic diseases in the population. Wilson's disease (WD) is a rare genetic copper-accumulation disorder for which timely intervention is crucial, as treatment is readily available. We studied WD in the Estonian Biobank population to advance patient screening, swift diagnosis, and subsequent treatment. Combined analysis of genotype and phenotype data from electronic health records (EHRs) consolidated at the Estonian biobank led to the identification of 17 individuals at high risk of developing WD, who were recalled for further examination and deep phenotyping. All recall study participants, regardless of phenotype, age, and prior WD diagnosis, had low serum ceruloplasmin and copper levels, and 87% also exhibited signs of early to late neurodegeneration. The p.His1069Gln variant in ATP7B, a prevalent pathogenic mutation, showed a striking four- to five-fold enrichment in Estonians compared with other populations. Based on our analysis of genetic and nationwide health registry data, we estimate that WD remains underdiagnosed and undertreated in Estonia. Our study demonstrates that personalized medicine, implemented with the collaboration of medical professionals, has the potential to reduce the healthcare burden by facilitating the accurate diagnosis of rare genetic diseases. To our knowledge, this report is the first to describe a large-scale national biobank-based study of WD.

Ignorance can be trustworthy: The effect of social self-awareness on trust.

Much research has found self-awareness to be associated with positive qualities, but we explore cases in which self-awareness sends a negative signal to others. Specifically, we propose that when a target person appears to be high in social self-awareness-that is, the person seems to accurately know what others think of them-observers infer that the target's actions are more intentional because the target is acting while seeming to know what others think of their actions. Because perceived intent is the key input to trust judgments, perceived self-awareness impacts observers' trust toward the target but does so differently depending on whether the target behaves in ways that positively or negatively impact others. When the target behaves in positive ways, exhibiting high (relative to low) self-awareness should increase trust as the positive behaviors will be interpreted as conveying stronger positive intentions toward others. However, for negative behaviors, exhibiting self-awareness should decrease trust, as it should convey stronger negative intent toward others. Across six studies (N = 4,707) using online experiments, a recall study paradigm, and live interactions in a laboratory setting, we find support for this framework. We also show that when we constrain the extent to which people can infer a target's intentions toward others from their behaviors-by reducing the target's control over their own behavior or by reducing the impact of the target's actions on others-the effect of self-awareness on trust attenuates. Our findings suggest that self-awareness, though often considered a desirable quality, does not universally increase others' trust. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Gender‐ and age‐specific association of known type 2 diabetes mellitus on incident mild cognitive impairment five years later: Results from the population‐based Heinz Nixdorf Recall Study

Gender‐ and age‐specific association of known type 2 diabetes mellitus on incident mild cognitive impairment five years later: Results from the population‐based Heinz Nixdorf Recall Study

Abstract 4134911: Coronary Artery Calcium Predicts Cardiovascular Events in Individuals with Controlled Atherosclerotic Risk Factors: A Multi-Cohort Study

Background: There is residual risk of atherosclerotic cardiovascular disease (ASCVD) that remains despite adequate risk factor (RF) control. Coronary artery calcium (CAC) has demonstrated value in ASCVD risk stratification. We evaluated the value of CAC in identifying residual risk of ASCVD events among those with traditional RF control. Methods: Participants without clinical ASCVD were pooled from the Multi-Ethnic Study of Atherosclerosis, Heinz Nixdorf Recall Study, Framingham Heart Study, and Jackson Heart Study. RF control was classified as “guideline-concordant” and “optimal” (Figure 1). Participants were stratified by the number of controlled RFs at baseline and CAC score (CAC = 0, 1-99, ≥100). Cox proportional hazards models examined the association between CAC and incident ASCVD events. Results: The study included 14,780 individuals (mean age 58 years (SD: 11), 54% female, 59% White, 27% Black, 50% CAC = 0). Over a median follow-up of 14.6 years, there were 1,441 incident ASCVD events. The distribution of CAC and ASCVD event incidence is shown in Panel A; 10% of those with 3 optimal RFs and 19% of those with 3 guideline-concordant RFs controlled had CAC > 100. The rate of ASCVD events decreased with more RFs controlled and increased with higher CAC. Overall, optimal RF control was associated with lower ASCVD event rates compared to guideline-concordant control. At every level of RF control, CAC > 100 was associated with increased HRs for incident ASCVD (Panel B). Those with CAC ≥ 100 and controlled RFs experienced ASCVD rates numerically comparable to or exceeding those with uncontrolled RFs but CAC = 0 (Panel A). Adjusted HR (95% CI) for ASCVD events with CAC > 100 compared to CAC = 0 was 5.0 (2.0, 12.9) in optimal RF control and 3.7 (2.6, 5.4) in guideline-concordant RF control. Conclusion: There is significant heterogeneity in residual ASCVD risk among those with optimal or guideline-concordant traditional RF control and CAC can help identify this risk. Irrespective of RF control, a higher CAC burden was associated with increased ASCVD risk. Future studies could use CAC testing to identify those with higher residual ASCVD risk despite effective traditional RF control to target for novel therapies.

Loss of CFHR5 function reduces the risk for age-related macular degeneration.

Age-related macular degeneration (AMD) is a prevalent cause of vision loss in the elderly with limited therapeutic options. A single chromosomal region around the complement factor H gene (CFH) is reported to explain nearly 25% of genetic AMD risk. Here, we used association testing, statistical finemapping and conditional analyses in 12,495 AMD cases and 461,686 controls to deconvolute four major CFH haplotypes that convey protection from AMD. We show that beyond CFH, two of these are explained by Finn-enriched frameshift and missense variants in the CFH modulator CFHR5. We demonstrate through a FinnGen sample recall study that CFHR5 variant carriers exhibit dose-dependent reductions in serum levels of the CFHR5 gene product FHR-5 and two functionally related proteins at the locus. Genetic reduction in FHR-5 correlates with higher preserved activities of the classical and alternative complement pathways. Our results propose therapeutic downregulation of FHR-5 as promising to prevent or treat AMD.

The person behind the therapist: a recall study on significant events that contribute to therapists' personal and professional development.

This study explores the interconnexion between personal and professional development in therapist growth. This research examines a self-integrated perspective on training, by looking at the equal importance of nurturing personal development alongside professional skills cultivation. The study uses the concept of Significant Events (SE) which was originally developed to understand client change processes and applies the concept to investigate the development of the person-of-the-therapist. SE is events that are experienced in the therapy process and that are experienced by the client as being helpful or hindering for therapeutic change. Similar to the process of therapy, professional development is not a linear process of acquiring skills and knowledge but a discontinuous process that is driven by SE. The goal is to explore transformative moments in therapists' development. 281 participants completed an online questionnaire, evaluating: i) ) personal events (physical and mental health, interpersonal relationships, exploring the world, losses and deaths), ii) professional events (training, clinical experiences, relationship with colleagues, challenges due to work position), and iii) hybrid events where personal and professional aspects intertwine (personal therapy and societal context inducing insecurity). Findings suggest a more integrated self in personal and professional development. The study contributes to ongoing discussions on professional development, revealing the interplay between personal and professional spheres of therapists.

Sex-Specific Differences in Serum Kallikrein-8 (KLK8): An Exploratory Study.

There are indications for sex-specific differences regarding the association between kallikrein-8 (KLK8) and cognitive impairment in early stages of Alzheimer's disease for which KLK8 may be an early blood-based biomarker. These may be due to different levels of sex hormones. To correctly interpret KLK8 blood concentrations, sex-specific analyses are needed. The aim of our exploratory study was to investigate sex-specific differences in blood-based KLK8 in participants of the population-based Heinz Nixdorf Recall study with different cognitive status and the association between KLK8 and sex hormones. In 290 participants (45% women, 69.7±7.4 years (mean±SD)) we investigated sex-specific serum KLK8 differences between cognitively unimpaired (CU, 43%) and cognitively impaired (CI) participants and the association between KLK8 and dehydroepiandrosteronsulfate (DHEAS), estradiol and testosterone, using adjusted multiple linear regression. The mean±SD KLK8 was similar for CU men (808.1±729.6 pg/ml) and women (795.9±577.7 pg/ml); adjusted mean-difference [95%-CI]: -95.3 [-324.1;133.5] pg/ml. KLK8 was lower in CI women (783.5±498.7 pg/ml) than men (1048.4±829 pg/ml); -261 [-493.1; -29] pg/ml. In men but not women, there was a weak indication for a positive slope between estradiol (11.9 [-0.4;24.3] pg/ml) and DHEAS (1.4 [-0.5;3.3] pg/ml) with KLK8, while testosterone had no impact. The results suggested a different role for KLK8 in the development of cognitive impairment in men and women, potentially influenced by sex hormones. To use blood KLK8 as an early biomarker, further research on hormonal regulation of KLK8 expression is needed as a part of the investigation of the KLK8 involvement in cognitive impairment and Alzheimer's disease pathology.

Understanding self-forgiveness in emotion-focused therapy: An interpersonal process recall study with men in recovery from addiction.

Understanding self-forgiveness in emotion-focused therapy: An interpersonal process recall study with men in recovery from addiction.

TWINGEN: protocol for an observational clinical biobank recall and biomarker cohort study to identify Finnish individuals with high risk of Alzheimer’s disease

IntroductionA better understanding of the earliest stages of Alzheimer’s disease (AD) could expedite the development or administration of treatments. Large population biobanks hold the promise to identify individuals at an...

Take Me Out of the Loop

Abstract: Three studies examined whether people feel better when self-excluding from group conversations about negative, rather than positive, information and whether people feel worse when included in group conversations about negative, rather than positive, information. Participants ( N = 665) completed a retrospective recall (Study 1) and imagined scenarios (Studies 2 and 3). Participants generally reported feeling worse when they were included in groups discussing negative, rather than positive, information. They also reported feeling better when they self-excluded from groups discussing negative, rather than positive, information, particularly negative gossip. Negative gossip also led participants to have a high desire to self-exclude from the group, and this was mediated by mood. These findings suggest there are certain circumstances where people prefer to self-exclude from groups.

Can glucose facilitate fear exposure? Randomized, placebo-controlled trials on the effects of glucose administration on fear extinction processes

Previous studies showed that glucose has beneficial effects on memory function and can enhance contextual fear learning. To derive potential therapeutic interventions, further research is needed regarding the effects of glucose on fear extinction. In two experimental studies with healthy participants (Study 1: N = 68, 39 females; Study 2: N = 89, 67 females), we investigated the effects of glucose on fear extinction learning and its consolidation. Participants completed a differential fear conditioning paradigm consisting of acquisition, extinction, and return of fear tests: reinstatement, and extinction recall. US-expectancy ratings, skin conductance response (SCR), and fear potentiated startle (FPS) were collected. Participants were pseudorandomized and double-blinded to one of two groups: They received either a drink containing glucose or saccharine 20 min before (Study 1) or immediately after extinction (Study 2). The glucose group showed a significantly stronger decrease in differential FPS during extinction (Study 1) and extinction recall (Study 2). Additionally, the glucose group showed a significantly lower contextual anxiety at test of reinstatement (Study 2). Our findings provide first evidence that glucose supports the process of fear extinction, and in particular the consolidation of fear extinction memory, and thus has potential as a beneficial adjuvant to extinction-based treatments.Registered through the German Clinical Trials Registry (https://www.bfarm.de/EN/BfArM/Tasks/German-Clinical-Trials-Register/_node.html; Study 1: DRKS00010550; Study 2: DRKS00018933).

Effects of perceived illegitimacy of interrupting tasks on employees’ cognitive and affective experiences: the mediating role of stress appraisals

ABSTRACT Employees are frequently interrupted when doing their work, sometimes with tasks that seem unreasonable or unnecessary. Drawing on stress-as-offence-to-self and stress appraisal theories, we expected that perceived illegitimacy of an interrupting task is detrimental to employees’ affective (i.e., anxiety, fatigue, vitality) and cognitive (i.e., task focus, attention residue) reactions to an interruption, because such interruptions are appraised as more of a hindrance and less of a challenge. To test this, we first used a within-persons recall study, where participants (N = 144) recalled two interrupting tasks, one perceived as legitimate, and one illegitimate. As expected, perceived illegitimacy of the interrupting task was associated with more anxiety and less task focus, because of more hindrance appraisal. Perceived illegitimacy also was associated with less vitality, task focus, and more attention residue, because of less challenge appraisal. Second, using a between-persons manipulation of an interrupting task in a work simulation (N = 231), perceived illegitimacy was associated with more anxiety, fatigue, attention residue, and less task focus, because of more hindrance appraisal. Furthermore, participants performed worse on the interrupting task because of more hindrance appraisal and less task focus. Overall, interrupting tasks perceived as illegitimate can be more negatively impacting, because such interruptions are appraised as hindering.

Epidemiology and Prognostic Implications of Coronary Artery Calcium in Asymptomatic Individuals With Prediabetes: A Multicohort Study.

To describe the epidemiology and prognostic value of coronary artery calcium (CAC) in individuals with prediabetes. We pooled participants free of clinical atherosclerotic cardiovascular disease (ASCVD) from four prospective cohorts: the Multi-Ethnic Study of Atherosclerosis, Heinz Nixdorf Recall Study, Framingham Heart Study, and Jackson Heart Study. Two definitions were used for prediabetes: inclusive (fasting plasma glucose [FPG] ≥100 to <126 mg/dL and hemoglobin A1c [HbA1c] ≥5.7% to <6.5%, if available, and no glucose-lowering medications) and restrictive (FPG ≥110 to <126 mg/dL and HbA1c ≥5.7% to <6.5%, if available, among participants not taking glucose-lowering medications). The study included 13,376 participants (mean age 58 years; 54% women; 57% White; 27% Black). The proportions with CAC ≥100 were 17%, 22%, and 37% in those with euglycemia, prediabetes, and diabetes, respectively. Over a median (25th-75th percentile) follow-up time of 14.6 (interquartile range 7.8-16.4) years, individuals with prediabetes and CAC ≥100 had a higher unadjusted 10-year incidence of ASCVD (13.4%) than the overall group of those with diabetes (10.6%). In adjusted analyses, using the inclusive definition of prediabetes, compared with euglycemia, the hazard ratios (HRs) for ASCVD were 0.79 (95% CI 0.62, 1.01) for prediabetes and CAC 0, 0.70 (0.54, 0.89) for prediabetes and CAC 1-99, 1.54 (1.27, 1.88) for prediabetes and CAC ≥100, and 1.64 (1.39, 1.93) for diabetes. Using the restrictive definition, the HR for ASCVD was 1.63 (1.29, 2.06) for prediabetes and CAC ≥100. CAC ≥100 is frequent among individuals with prediabetes and identifies a high ASCVD risk subgroup in which the adjusted ASCVD risk is similar to that in individuals with diabetes.

Aggregation of type-2 diabetes, prediabetes, and metabolic syndrome in German couples

We aimed to examine the concordance of type-2 diabetes, prediabetes and the metabolic syndrome in couples. In cross-sectional analyses, we used data from 1173 couples with index persons from the Heinz Nixdorf Recall Study (2011–2015), a population-based cohort study in Western Germany, and partners from the associated Heinz Nixdorf Multigeneration Study (2013–2016). Mean age (standard deviation) was 67.2 (6.6) years in index persons, and 67.8 (7.7) years in partners. The exposure was the presence of diabetes, prediabetes or metabolic syndrome in index persons, the outcome was the presence of the same health status in partners. Diabetes was defined by either self-reported diagnosis, intake of antidiabetic drugs or insulin, or HbA1c ≥ 6.5%. If the index person had prediabetes or diabetes, the partner was 1.46 (95% CI 1.07–2.00) times more likely to have diabetes than partners of index persons without the condition in the crude model (adjusted model: 1.33 (0.97–1.83)). For self-reported diabetes and for the metabolic syndrome, the corresponding prevalence ratios were 1.33 (0.90–1.97) and 1.17 (1.03–1.32), respectively (adjusted models: 1.23 (0.77–1.94), 1.04 (0.91–1.18)). In German couples, there was weak to moderate concordance of type-2 diabetes, prediabetes and the metabolic syndrome in crude, but poor concordance in adjusted models.

Synergism between coexisting eye diseases and sex in increasing the prevalence of the dry eye syndrome

The aim was to investigate prevalence of dry eye syndrome (DES) in a population-based sample in Germany. The association between coexisting eye diseases and DES was also of interest. We recontacted participants of the Heinz Nixdorf Recall study between 2018 and 2021 by postal questionnaire that included the Women’s Health Study questionnaire on DES. We estimated prevalence of DES and examined DES-associated factors among 2095 participants aged 62–91 years. We performed interaction analyses between sex and coexisting eye diseases in relation to the DES prevalence and performed bias analyses to examine the robustness of the results. The DES prevalence was 31.5% (34–36% after correction for potential non-response bias, 24.1% after correction for outcome misclassification) and it was almost 2.1-times higher in women than in men (women 42.3%, men 20.4%). Among DES subjects, 70.3% had received treatment in the previous 12 months. There was synergism between female sex and coexisting eye diseases (cataract, glaucoma, macular degeneration) in terms of DES prevalence. The extrapolated numbers of patients aged 62–91 years with DES in Germany are 1.1–1.3 million men and 6.1–6.8 million women. The observed synergism may be explained by differences in ocular physiology, subjective perception and response behavior. Women with eye diseases (cataract, glaucoma, macula degeneration) appear to have a markedly higher susceptibility to suffer from DES than men, so that a diagnostic workup of DES symptoms is particularly justified in women with these eye diseases.

An NLP-based framework for early identification of design reliability issues from heterogeneous automotive lifecycle data

Natural Language Processing is increasingly used in different areas of design and product development with varied objectives, from enhancing productivity to embedding resilience into systems. In this paper, we introduce a framework that draws on NLP algorithms and expert knowledge for the automotive engineering domain, to extract actionable insight for system reliability improvement from data available from the operational phase of the system. Specifically, we are looking at the systematic exploration and exploitation of automotive heterogeneous data sources, including both closed-source (such as warranty records) and open-source (e.g., social networks, chatrooms, recall systems) data, to extract and classify information about faults, with predictive capability for early detection of issues. We present a preliminary NLP-based framework for enhancing system knowledge representation to increase the effectiveness and robustness of information extraction from data, and discuss the temporal alignment of data sources and insight to improve prediction ability. We demonstrate the effectiveness of the proposed framework using real-world automotive data in a recall study for a vehicle lighting system and a particular manufacturer: four recall campaigns were identified leading to corrective actions by the warranty experts.

Advanced Parkinson’s Disease Detection: A comprehensive artificial intelligence approach utilizing clinical assessment and neuroimaging samples

Medical experts are utilizing neuroimaging and clinical assessments to enhance the early identification of Parkinson’s disease. The current research initiative offers ways to identify Parkinson’s disease using machine learning and transfer learning. To carry out this, we extracted 7500 MRI images from 2022 and 2023 and 12 clinical assessment records from 2010 to 2023 from the well-known Parkinson’s Progression Marker Initiative (PPMI) database. Then, we applied machine and transfer learning approaches using clinical assessment records and MRI images, respectively. To identify Parkinson’s Disease (PD) using samples from clinical assessments, four distinct resampling techniques were employed. Subsequently, three machine learning models were applied to train on these resample records, and the recall score was analyzed. A hybrid of SMOTE and ENN proved to be the most effective approach for handling all of the imbalanced data, according to the recall study. Later, four different feature selection methods were used to find the top 10 features using these new samples. Lastly, we trained and validated the model using nine machine-learning algorithms. We also used explainable AI techniques like LIME and SHAP to interpret clinical assessment records. The extra tree classifier outperformed the others in terms of accuracy, reaching 98.44% using the tree-based feature selection technique. In addition to examining clinical assessment samples, this study investigated Parkinson’s disease using neuroimaging data. In pursuit of this objective, four pre-trained architectures were employed to analyze MRI images through two distinct approaches. The first approach involved utilizing the convolutional layer while replacing the remaining two layers with a customized Artificial Neural Network (ANN). Subsequently, training and evaluation are performed using our MRI samples, followed by analyzing significant weights using a LIME interpretable explainer. The second approach employs an improvisational technique without directly replacing the last layer. Instead, we predicted the weights of our MRI samples using the knowledge of the pre-trained model and stored them. Finally, CNN architecture was utilized for Parkinson’s disease detection, achieving an optimal accuracy of 85.08% with the implementation of DenseNet169 and CNN.

The interpersonal costs of revealing others' secrets

People often keep relevant information secret from others. For example, an employee might keep a coworker's plan to quit without giving notice secret from their manager, or someone might keep a friend's affair secret from their friend's spouse. In this article, we identify a critical but overlooked factor that determines whether an actor will disclose secret information they know about another person: Impression management concerns about how other people will judge their decision to disclose or keep the secret. We conceptualize secret-keeping as social decisions that involve the focal actor (who could keep or disclose a secret), the partner (the focus of the secret), the audience (interested in learning the secret information), and external observers (who may observe if the focal actor disclosed the secret). Across four pre-registered studies, including real-world judgments of secret-keeping dilemmas (field data from a Reddit community; N = 332), a recall study (N = 200), and controlled experiments (N = 624), we describe how impression management concerns influence secret-keeping decisions. We find that focal actors are often judged harshly for disclosing others' secrets, even when the audience could derive substantial benefits from learning the information and even when observers judge disclosure to be more moral than keeping a secret. Focal actors are heavily influenced by impression management concerns and routinely keep partners' secrets from an audience who could benefit from the information. Taken together, impression management concerns act as significant impediments to the flow of information, advancing our understanding of both information flows within groups and secret-keeping dilemmas.