The Importance of Distrust in AI

In recent years the use of Artificial Intelligence (AI) has become increasingly prevalent in a growing number of fields. As AI systems are being adopted in more high-stakes areas such as medicine and finance, ensuring that they are trustworthy is of increasing importance. A concern that is prominently addressed by the development and application of explainability methods, which are purported to increase trust from its users and wider society. While an increase in trust may be desirable, an analysis of literature from different research fields shows that an exclusive focus on increasing trust may not be warranted. Something which is well exemplified by the recent development in AI chatbots, which while highly coherent tend to make up facts. In this contribution, we investigate the concepts of trust, trustworthiness, and user reliance. In order to foster appropriate reliance on AI we need to prevent both disuse of these systems as well as overtrust. From our analysis of research on interpersonal trust, trust in automation, and trust in (X)AI, we identify the potential merit of the distinction between trust and distrust (in AI). We propose that alongside trust a healthy amount of distrust is of additional value for mitigating disuse and overtrust. We argue that by considering and evaluating both trust and distrust, we can ensure that users can rely appropriately on trustworthy AI, which can both be useful as well as fallible.Comment: This preprint has not undergone peer review or any post-submission improvements or corrections. The version of records of this contribution is published in Explainable Artificial Intelligence First World Conference, xAI 2023, Lisbon, Portugal, July 26-28, 2023, Proceedings, Part III (CCIS, volume 1903) and is available at https://doi.org/10.1007/978-3-031-44070-

Longitudinal hypothalamic-pituitary-adrenal axis trait and state effects in recurrent depression

SummaryBackgroundHypothalamic–pituitary–adrenal (HPA)-axis hyperactivity has been observed in (recurrent) major depressive disorder (MDD), although inconsistently and mainly cross-sectional. Longitudinal studies clarifying state-trait issues are lacking. We aimed to determine whether HPA-axis (hyper)activity in recurrent MDD is: (I) reflecting a persistent trait; (II) influenced by depressive state; (III) associated with stress or previous episodes; (IV) associated with recurrence; and (V) influenced by cognitive therapy.MethodsWe included 187 remitted highly recurrent MDD-patients (mean number of previous episodes: 6.3), participating in a randomized-controlled-trial investigating the preventive effect of additional cognitive therapy on recurrence. In an add-on two-staged patient-control and prospective-cohort design, we first cross-sectionally compared patients’ salivary morning and evening cortisol concentrations with 72 age- and sex-matched controls, and subsequently longitudinally followed-up the patients with repeated measures after three months and two years.ResultsPatients had higher cortisol concentrations than controls (p<.001), which did not change by MDD-episodes during follow-up. HPA-axis activity had no relation with daily hassles or childhood life events. Cortisol concentrations were lower in patients with more previous episodes (p=.047), but not associated with recurrence(s) during follow-up. Finally, randomly assigned cognitive therapy at study-entry enhanced cortisol declines over the day throughout the two-year follow-up (p=.052).ConclusionsOur results indicate that remitted recurrent MDD-patients have a persistent trait of increased cortisol concentrations, irrespective of stress. In combination with our finding that patients’ cortisol concentrations do not change during new MDD-episodes (and thus not represent epiphenomenal or state-effects), our results support that hypercortisolemia fulfills the state-independence criterion for an endophenotype for recurrent depression

Statistical Methodological Issues in Handling of Fatty Acid Data: Percentage or Concentration, Imputation and Indices

Basic aspects in the handling of fatty acid-data have remained largely underexposed. Of these, we aimed to address three statistical methodological issues, by quantitatively exemplifying their imminent confounding impact on analytical outcomes: (1) presenting results as relative percentages or absolute concentrations, (2) handling of missing/non-detectable values, and (3) using structural indices for data-reduction. Therefore, we reanalyzed an example dataset containing erythrocyte fatty acid-concentrations of 137 recurrently depressed patients and 73 controls. First, correlations between data presented as percentages and concentrations varied for different fatty acids, depending on their correlation with the total fatty acid-concentration. Second, multiple imputation of non-detects resulted in differences in significance compared to zero-substitution or omission of non-detects. Third, patients’ chain length-, unsaturation-, and peroxidation-indices were significantly lower compared to controls, which corresponded with patterns interpreted from individual fatty acid tests. In conclusion, results from our example dataset show that statistical methodological choices can have a significant influence on outcomes of fatty acid analysis, which emphasizes the relevance of: (1) hypothesis-based fatty acid-presentation (percentages or concentrations), (2) multiple imputation, preventing bias introduced by non-detects; and (3) the possibility of using (structural) indices, to delineate fatty acid-patterns thereby preventing multiple testing

Observer variability of absolute and relative thrombus density measurements in patients with acute ischemic stroke

Introduction: Thrombus density may be a predictor for acute ischemic stroke treatment success. However, only limited data on observer variability for thrombus density measurements exist. This study assesses the variability and bias of four common thrombus density measurement methods by expert and non-expert observers. Methods: For 132 consecutive patients with acute ischemic stroke, three experts and two trained observers determined thrombus density by placing three standardized regions of interest (ROIs) in the thrombus and corresponding contralateral arterial segment. Subsequently, absolute and relative thrombus densities were determined using either one or three ROIs. Intraclass correlation coefficient (ICC) was determined, and Bland–Altman analysis was performed to evaluate interobserver and intermethod agreement. Accuracy of the trained observer was evaluated with a reference expert observer using the same statistical analysis. Results: The highest interobserver agreement was obtained for absolute thrombus measurements using three ROIs (ICCs ranging from 0.54 to 0.91). In general, interobserver agreement was lower for relative measurements, and for using one instead of three ROIs. Interobserver agreement of trained non-experts and experts was similar. Accuracy of the trained observer measurements was comparable to the expert interobserver agreement and was better for absolute measurements and with three ROIs. The agreement between the one ROI and three ROI methods was good. Conclusion: Absolute thrombus density measurement has superior interobserver agreement compared to relative density measurement. Interobserver variation is smaller when multiple ROIs are used. Trained non-expert observers can accurately and reproducibly assess absolute thrombus densities using three ROIs

Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

A. Palotie on työryhmän Schizophrenia Working Grp Psychiat jäsen.We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P = 1 x 10(-4)) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P = 8.4 x 10(-7)). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.Peer reviewe

Multicriteria optimization enables less experienced planners to efficiently produce high quality treatment plans in head and neck cancer radiotherapy

Objectives: To demonstrate that novice dosimetry planners efficiently create clinically acceptable IMRT plans for head and neck cancer (HNC) patients using a commercially available multicriteria optimization (MCO) system. Methods: Twenty HNC patients were enrolled in this in-silico comparative planning study. Per patient, novice planners with less experience in dosimetry planning created an IMRT plan using an MCO system (RayStation). Furthermore, a conventionally planned clinical IMRT plan was available (Pinnacle(3)). All conventional IMRT and MCO-plans were blind-rated by two expert radiation-oncologists in HNC, using a 5-point scale (1-5 with 5 the highest score) assessment form comprising 10 questions. Additionally, plan quality was reported in terms of planning time, dosimetric and normal tissue complication probability (NTCP) comparisons. Inter-rater reliability was derived using the intra-class correlation coefficient (ICC). Results: In total, the radiation-oncologists rated 800 items on plan quality. The overall plan score indicated no differences between both planning techniques (conventional IMRT: 3.8 +/- 1.2 vs. MCO: 3.6 +/- 1.1, p = 0.29). The inter-rater reliability of all ratings was 0.65 (95% CI: 0.57-0.71), indicating substantial agreement between the radiation-oncologists. In 93% of cases, the scoring difference of the conventional IMRT and MCO-plans was one point or less. Furthermore, MCO-plans led to slightly higher dose uniformity in the therapeutic planning target volume, to a lower integral body dose (13.9 +/- 4.5 Gy vs. 12.9 +/- 4.0 Gy, p <0.001), and to reduced dose to the contra-lateral parotid gland (28.1 +/- 11.8 Gy vs. 23.0 +/- 11.2 Gy, p <0.002). Consequently, NTCP estimates for xerostomia reduced by 8.4 +/- 7.4% (p <0.003). The hands-on time of the conventional IMRT planning was approximately 205 min. The time to create an MCO-plan was on average 43 +/- 12 min. Conclusions: MCO planning enables novice treatment planners to create high quality IMRT plans for HNC patients. Plans were created with vastly reduced planning times, requiring less resources and a short learning curve

Socio-economic and environmental factors influence energy utilization in Brazilian breast-fed infants

Energy intake recommendations for infants are based on data from industrialized countries. FAO/WHO/UNU expressed the need for studies on total energy expenditure (TEE) and basal metabolic rate from developing countries covering current and changing lifestyles. For this observational study, 65 infants of differing socioeconomic status (SES) (n = 32 middle SES, n = 33 low SES) were selected in Pelotas, southern Brazil, aiming to: 1) compare TEE, minimum observable energy expenditure (MOEE), activity energy expenditure (AEE) between breast-fed infants 8.7 mo of age from middle and low SES; and 2) investigate the effect of potential mediating factors on TEE and AEE. TEE and total body water were measured with doubly labeled water, MOEE with respiration calorimetry, breast milk intake using the dose-to-the-mother deuterium-oxide turnover method, food intake using 1-d food weighing, and prevalence of overweight using BMI Z-scores. TEE adjusted for ethnicity was 257 (95% CI 232-281) kJ/(kg(.)d) in middle SES infants vs. 318 (95%CI 294-342) kJ/(kg(.)d) in low SES infants (P = 0.001). MOEE did not differ between groups and the difference in TEE was therefore attributed to AEE (P = 0.008). The effect of SES on AEE was mediated by the number of persons per bedroom (crowding). Prevalence of overweight tended to be higher in middle SES infants (P = 0.054) than in low SES infants. The difference in TEE and AEE between SES groups emphasizes the importance of an accurate description of the SES of any population in which TEE is studied and questions the extent to which TEE data from middle-class infants in transitional countries should be considered normative