Acute Onset of Impaired Consciousness: Diagnostic Evaluation in the Emergency Department.

BACKGROUND: Mortality in patients with acute onset of impaired consciousness is high: as many as 10% do not survive. The spectrum of differential diagnoses is wide, and more than one underlying condition is found in one-third of all cases. In this article, we describe a structured approach to patients with acute onset of impaired consciousness in the emergency department. METHODS: This review is based on pertinent articles retrieved by a selective search of PubMed and on the AWMF guidelines on the most common causes of impairment of consciousness. RESULTS: Impairments of consciousness are classified as quantitative (reduced wakefulness) or qualitative (abnormal content of consciousness). Of all such cases, 45-50% have a primary neurological cause, and approximately 20% are of metabolic or infectious origin. Some cases are due to intoxications, cardiovascular disorders, or psychiatric disorders. Important warning signs ("red flags") in acute onset of impaired consciousness are a hyperacute onset, pupillomotor disturbances, focal neurologic deficits, meningismus, headache, tachycardia and tachypnea (with or without fever), muscle contractions, and skin abnormalities. Patients with severely impaired consciousness should be initially treated in the shock room according to the ABCDE scheme. CONCLUSION: Acute onset of impaired consciousness is a medical emergency. Red flags must be rapidly recognized and treatment initiated immediately. Patients with severely impaired consciousness of new onset and uncertain cause, status epilepticus, lack of protective reflexes, or a new, acute neurologic deficit should be admitted via the resuscitation room.

Evaluation of Pulmonary Nodules by Radiologists vs. Radiomics in Stand-Alone and Complementary CT and MRI.

Increased attention has been given to MRI in radiation-free screening for malignant nodules in recent years. Our objective was to compare the performance of human readers and radiomic feature analysis based on stand-alone and complementary CT and MRI imaging in classifying pulmonary nodules. This single-center study comprises patients with CT findings of pulmonary nodules who underwent additional lung MRI and whose nodules were classified as benign/malignant by resection. For radiomic features analysis, 2D segmentation was performed for each lung nodule on axial CT, T2-weighted (T2w), and diffusion (DWI) images. The 105 extracted features were reduced by iterative backward selection. The performance of radiomics and human readers was compared by calculating accuracy with Clopper-Pearson confidence intervals. Fifty patients (mean age 63 +/- 10 years) with 66 pulmonary nodules (40 malignant) were evaluated. ACC values for radiomic features analysis vs. radiologists based on CT alone (0.68; 95%CI: 0.56, 0.79 vs. 0.59; 95%CI: 0.46, 0.71), T2w alone (0.65; 95%CI: 0.52, 0.77 vs. 0.68; 95%CI: 0.54, 0.78), DWI alone (0.61; 95%CI:0.48, 0.72 vs. 0.73; 95%CI: 0.60, 0.83), combined T2w/DWI (0.73; 95%CI: 0.60, 0.83 vs. 0.70; 95%CI: 0.57, 0.80), and combined CT/T2w/DWI (0.83; 95%CI: 0.72, 0.91 vs. 0.64; 95%CI: 0.51, 0.75) were calculated. This study is the first to show that by combining quantitative image information from CT, T2w, and DWI datasets, pulmonary nodule assessment through radiomics analysis is superior to using one modality alone, even exceeding human readers' performance.

Bioactive adrenomedullin and interleukin-6 in COVID-19: potential biomarkers of acute kidney injury and critical illness.

BACKGROUND: The aim of this study was to investigate whether bioactive adrenomedullin (bio-ADM) and interleukin-6 (IL-6) are related to acute kidney injury (AKI) and severe illness in COVID-19 patients. METHODS: 153 patients with COVID-19 admitted to the emergency department (ED) were included. Blood samples were collected from each patient at admission. Bio-ADM and IL-6, as well as DPP3 and routinely measured markers were evaluated regarding the endpoints AKI (22/128 hospitalized patients) and a composite endpoint of admission to intensive care unit and/or in-hospital death (n = 26/153 patients). RESULTS: Bio-ADM and IL-6 were significantly elevated in COVID-19 patients with AKI compared to COVID-19 patients without AKI (each p < 0.001). According to ROC analyses IL-6 and bio-ADM had the largest AUC (0.84 and 0.81) regarding the detection of AKI. Furthermore, bio-ADM and IL-6 were significantly elevated in COVID-19 patients reaching the composite endpoint (each p < 0.001). Regarding the composite endpoint ROC analysis showed an AUC of 0.89 for IL-6 and 0.83 for bio-ADM in COVID-19 patients. In the multivariable logistic model bio-ADM and IL-6 presented as independent significant predictors regarding both endpoints AKI and the composite endpoint in COVID-19 patients (as well as creatinine regarding the composite endpoint; each p < 0.05), opposite to leukocytes, C-reactive protein (CRP) and dipeptidyl peptidase 3 (DPP3; each p = n.s.). CONCLUSION: Elevated levels of bio-ADM and IL-6 are associated with AKI and critical illness in patients with COVID-19. Therefore, both biomarkers may be potential tools in risk stratification in COVID-19 patients at presentation in the ED.

Conception and prospective multicentric validation of a Robotic Surgery Training Curriculum (RoSTraC) for surgical residents: from simulation via laboratory training to integration into the operation room.

There is a lack of training curricula and educational concepts for robotic-assisted surgery (RAS). It remains unclear how surgical residents can be trained in this new technology and how robotics can be integrated into surgical residency training. The conception of a training curriculum for RAS addressing surgical residents resulted in a three-step training curriculum including multimodal learning contents: basics and simulation training of RAS (step 1), laboratory training on the institutional robotic system (step 2) and structured on-patient training in the operating room (step 3). For all three steps, learning content and video tutorials are provided via cloud-based access to allow self-contained training of the trainees. A prospective multicentric validation study was conducted including seven surgical residents. Transferability of acquired skills to a RAS procedure were analyzed using the GEARS score. All participants successfully completed RoSTraC within 1 year. Transferability of acquired RAS skills could be demonstrated using a RAS gastroenterostomy on a synthetic biological organ model. GEARS scores concerning this procedure improved significantly after completion of RoSTraC (17.1 (±5.8) vs. 23.1 (±4.9), p < 0.001). In step 3 of RoSTraC, all participants performed a median of 12 (range 5-21) RAS procedures on the console in the operation room. RoSTraC provides a highly standardized and comprehensive training curriculum for RAS for surgical residents. We could demonstrate that participating surgical residents acquired fundamental and advanced RAS skills. Finally, we could confirm that all surgical residents were successfully and safely embedded into the local RAS team.

[Prehospital treatment of polytrauma : Ongoing challenge in prehospital emergency services]. / Präklinische Polytraumaversorgung : Beständige Herausforderung im präklinischen Rettungswesen.

Tscherne was the first to define the term polytrauma in 1966 as "multiple injuries to different regions of the body sustained simultaneously, with at least one injury or the combination of these injuries being life-threatening". This definition highlights the essential pathophysiological paradigm of polytrauma, with the life-threating characteristics resulting from injuries to multiple organ systems. The treatment of polytrauma patients begins at the scene of the accident. Important life-saving initial interventions can already be carried out on site through targeted measures and expertise of the emergency medical service team, thus improving patient survival. The advanced trauma life support/prehospital trauma life support (ATLS/PHTLS) concept is the worldwide gold standard. As prehospital treatment of severely injured patients is not routine for most emergency teams, concepts and emergency interventions must be regularly trained. This is the prerequisite for safe and effective emergency treatment in this time-critical situation.

In Vivo Measurement of Rat Brain Water Content at 9.4 T MR Using Super-Resolution Reconstruction: Validation With Ex Vivo Experiments.

BACKGROUND: Given that changes in brain water content are often correlated with disease, investigating water content non-invasively and in vivo could lead to a better understanding of the pathogenesis of several neurologic diseases. PURPOSE: To adapt a super-resolution-based technique, previously developed for humans, to the rat brain and report in vivo high-resolution (HR) water content maps in comparison with ex vivo wet/dry methods. STUDY TYPE: Prospective. ANIMAL MODEL: Eight healthy male Wistar rats. FIELD STRENGTH/SEQUENCE: 9.4-T, multi-echo gradient-echo (mGRE) sequence. ASSESSMENT: Using super-resolution reconstruction (SRR), a HR mGRE image (200 µm isotropic) was reconstructed from three low-resolution (LR) orthogonal whole-brain images in each animal, which was followed by water content mapping in vivo. The animals were subsequently sacrificed, the brains excised and divided into five regions (front left, front right, middle left, middle right, and cerebellum-brainstem regions), and the water content was measured ex vivo using wet/dry measurements as the reference standard. The water content values of the in vivo and ex vivo methods were then compared for the whole brain and also for the different regions separately. STATISTICAL TESTS: Friedman's non-parametric test was used to test difference between the five regions, and Pearson's correlation coefficient was used for correlation between in vivo and ex vivo measurements. A P-value <0.05 was considered statistically significant. RESULTS: Water content values derived from in vivo MR measurements showed strong correlations with water content measured ex vivo at a regional level (r = 0.902). Different brain regions showed significantly different water content values. Water content values were highest in the frontal brain, followed by the midbrain, and lowest in the cerebellum and brainstem regions. DATA CONCLUSION: An in vivo technique to achieve HR isotropic water content maps in the rat brain using SRR was adopted in this study. The MRI-derived water content values obtained using the technique showed strong correlations with water content values obtained using ex vivo wet/dry methods. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 1.

Dipeptidyl-peptidase 3 and IL-6: potential biomarkers for diagnostics in COVID-19 and association with pulmonary infiltrates.

Coronavirus SARS-CoV-2 spread worldwide, causing a respiratory disease known as COVID-19. The aim of the present study was to examine whether Dipeptidyl-peptidase 3 (DPP3) and the inflammatory biomarkers IL-6, CRP, and leucocytes are associated with COVID-19 and able to predict the severity of pulmonary infiltrates in COVID-19 patients versus non-COVID-19 patients. 114 COVID-19 patients and 35 patients with respiratory infections other than SARS-CoV-2 were included in our prospective observational study. Blood samples were collected at presentation to the emergency department. 102 COVID-19 patients and 28 non-COVID-19 patients received CT imaging (19 outpatients did not receive CT imaging). If CT imaging was available, artificial intelligence software (CT Pneumonia Analysis) was used to quantify pulmonary infiltrates. According to the median of infiltrate (14.45%), patients who obtained quantitative CT analysis were divided into two groups (> median: 55 COVID-19 and nine non-COVID-19, ≤ median: 47 COVID-19 and 19 non-COVID-19). DPP3 was significantly elevated in COVID-19 patients (median 20.85 ng/ml, 95% CI 18.34-24.40 ng/ml), as opposed to those without SARS-CoV-2 (median 13.80 ng/ml, 95% CI 11.30-17.65 ng/ml; p < 0.001, AUC = 0.72), opposite to IL-6, CRP (each p = n.s.) and leucocytes (p < 0.05, but lower levels in COVID-19 patients). Regarding binary logistic regression analysis, higher DPP3 concentrations (OR = 1.12, p < 0.001) and lower leucocytes counts (OR = 0.76, p < 0.001) were identified as significant and independent predictors of SARS-CoV-2 infection, as opposed to IL-6 and CRP (each p = n.s.). IL-6 was significantly increased in patients with infiltrate above the median compared to infiltrate below the median both in COVID-19 (p < 0.001, AUC = 0.78) and in non-COVID-19 (p < 0.05, AUC = 0.81). CRP, DPP3, and leucocytes were increased in COVID-19 patients with infiltrate above median (each p < 0.05, AUC: CRP 0.82, DPP3 0.70, leucocytes 0.67) compared to infiltrate below median, opposite to non-COVID-19 (each p = n.s.). Regarding multiple linear regression analysis in COVID-19, CRP, IL-6, and leucocytes (each p < 0.05) were associated with the degree of pulmonary infiltrates, as opposed to DPP3 (p = n.s.). DPP3 showed the potential to be a COVID-19-specific biomarker. IL-6 might serve as a prognostic marker to assess the extent of pulmonary infiltrates in respiratory patients.

Principles and Applications of CF2X Moieties as Unconventional Halogen Bond Donors in Medicinal Chemistry, Chemical Biology, and Drug Discovery.

As an orthogonal principle to the established (hetero)aryl halides, we herein highlight the usefulness of CF2X (X = Cl, Br, or I) moieties. Using tool compounds bearing CF2X moieties, we study their chemical/metabolic stability and their logP/solubility, as well as the role of XB in their small molecular crystal structures. Employing QM techniques, we analyze the observed interactions, provide insights into the conformational flexibilities and preferences in the potential interaction space. For their application in molecular design, we characterize their XB donor capacities and its interaction strength dependent on geometric parameters. Implementation of CF2X acetamides into our HEFLibs and biophysical evaluation (STD-NMR/ITC), followed by X-ray analysis, reveals a highly interesting binding mode for fragment 23 in JNK3, featuring an XB of CF2Br toward the P-loop, as well as chalcogen bonds. We suggest that underexplored chemical space combined with unconventional binding modes provides excellent opportunities for patentable chemotypes for therapeutic intervention.

Urinary N-Terminal Pro-Brain Natriuretic Peptide Predicts Acute Kidney Injury and Severe Disease in COVID-19.

INTRODUCTION: The ongoing COVID-19 pandemic is placing an extraordinary burden on our health care system with its limited resources. Accurate triage of patients is necessary to ensure medical care for those most severely affected. In this regard, biomarkers could contribute to risk evaluation. The aim of this prospective observational clinical study was to assess the relationship between urinary N-terminal pro-brain natriuretic peptide (NT-proBNP) and acute kidney injury (AKI) as well as severe disease in patients with COVID-19. METHODS: 125 patients treated with an acute respiratory infection in the emergency department of the University Hospital Regensburg were analyzed. These patients were divided into a COVID-19 cohort (n = 91) and a cohort with infections not caused by severe acute respiratory syndrome-coronavirus-2 (n = 34). NT-proBNP was determined from serum and fresh urine samples collected in the emergency department. Clinical endpoints were the development of AKI and a composite one consisting of AKI, intensive care unit admission, and in-hospital death. RESULTS: 11 (12.1%) COVID-19 patients developed AKI during hospitalization, whereas 15 (16.5%) reached the composite endpoint. Urinary NT-proBNP was significantly elevated in COVID-19 patients who suffered AKI or reached the composite endpoint (each p < 0.005). In a multivariate regression analysis adjusted for age, chronic kidney disease, chronic heart failure, and arterial hypertension, urinary NT-proBNP was identified as independent predictor of AKI (p = 0.017, OR = 3.91 [CI: 1.28-11.97] per standard deviation [SD]), as well as of the composite endpoint (p = 0.026, OR 2.66 [CI: 1.13-6.28] per SD). CONCLUSION: Urinary NT-proBNP might help identify patients at risk for AKI and severe disease progression in COVID-19.

Synthesis of Amino Acids Bearing Halodifluoromethyl Moieties and Their Application to p53-Derived Peptides Binding to Mdm2/Mdm4.

Introduction: Therapeutic peptides are a significant class of drugs in the treatment of a wide range of diseases. To enhance their properties, such as stability or binding affinity, they are usually chemically modified. This includes, among other techniques, cyclization of the peptide chain by bridging, modifications to the backbone, and incorporation of unnatural amino acids. One approach previously established, is the use of halogenated aromatic amino acids. In principle, they are thereby enabled to form halogen bonds (XB). In this study, we focus on the -R-CF2X moiety (R = O, NHCO; X = Cl, Br) as an uncommon halogen bond donor. These groups enable more spatial variability in protein-protein interactions. The chosen approach via Fmoc-protected building blocks allows for the incorporation of these modified amino acids in peptides using solid-phase peptide synthesis. Results and Discussion: Using a competitive fluorescence polarization assay to monitor binding to Mdm4, we demonstrate that a p53-derived peptide with Lys24Nle(εNHCOCF2X) exhibits an improved inhibition constant Ki compared to the unmodified peptide. Decreasing Ki values observed with the increasing XB capacity of the halogen atoms (F ≪ Cl < Br) indicates the formation of a halogen bond. By reducing the side chain length of Nle(εNHCOCF2X) to Abu(γNHCOCF2X) as control experiments and through quantum mechanical calculations, we suggest that the observed affinity enhancement is related to halogen bond-induced intramolecular stabilization of the α-helical binding mode of the peptide or a direct interaction with His54 in human Mdm4.

Endoscopic vacuum-assisted closure therapy for leakage of the lower gastrointestinal tract: multicenter experiences.

Background and study aims Only a few studies are available regarding endoscopic vacuum-assisted closure (E-VAC) therapy for the post-surgery leakage of the lower gastrointestinal tract. Patients and methods In this multicenter German study, we retrospectively analyzed patients treated with E-VAC therapy due to post-surgery leakage of the lower gastrointestinal tract from 2000-2020 at Hannover Medical School, University Medical Center Schleswig-Holstein, Campus Luebeck, and Robert Koch Hospital Gehrden. Results Overall, 147 patients were included in this study. Most patients had undergone tumor resections of the lower gastrointestinal tract (n = 88; 59.9 %). Median time to diagnosis of leakage was 10 days (interquartile range [IQR] 6-19). Median duration of E-VAC therapy was 14 days (IQR 8-27). Increase of C-reactive protein (CRP) levels significantly correlated with first diagnosis of leakage ( P  < 0.001). E-VAC therapy led to closure or complete epithelialization of leakage in the majority of patients (n = 122; 83.0 %) and stoma reversal was achieved in 60.0 %. Stoma reversal was significantly more often achieved in patients with CRP levels ≤ 100 mg/L at first diagnosis compared to patients with CRP levels > 100 mg/L (78.4 % vs. 52.7 %; P  = 0.012). Odds ratio for failure of stoma reversal was 3.36 in cases with CRP values > 100 mg/L ( P  = 0.017). In total, leakage- and/ or E-VAC therapy-associated complications occurred in 26 patients (17.7 %). Minor complications included recurrent E-VAC dislocations and subsequent stenosis. Overall, 14 leakage- or E-VAC-associated deaths were observed most often due to sepsis. Conclusions E-VAC therapy due to post-surgery leakage of the lower gastrointestinal tract is safe and effective. High levels of CRP are a negative predictor of E-VAC therapy success.

Long-term functional outcome after tubular laparoscopic sigmoid resection for diverticular disease.

PURPOSE: Sigmoid resection for diverticular disease is a frequent surgical procedure in the Western world. However, long-term bowel function after sigmoid resection has been poorly described in the literature. This study aims to assess the long-term bowel function after tubular sigmoid resection with preservation of inferior mesenteric artery (IMA) for diverticular disease. METHODS: We retrospectively identified patients who underwent sigmoid resection for diverticular disease between 2002 and 2012 at a tertiary referral center in northern Germany. Using well-validated questionnaires, bowel function was assessed for fecal urgency, incontinence, and obstructed defecation. The presence of bowel dysfunction was compared to baseline characteristics and perioperative outcome. RESULTS: Two hundred and thirty-eight patients with a mean age of 59.2 ± 10 years responded to our survey. The follow-up was conducted 117 ± 32 months after surgery. At follow-up, 44 patients (18.5%) had minor LARS (LARS 21-29) and 35 (15.1%) major LARS (LARS ≥ 30-42), 35 patients had moderate-severe incontinence (CCIS ≥ 7), and 2 patients (1%) had overt obstipation (CCOS ≥ 15). The multivariate analysis showed that female gender was the only prognostic factor for long-term incontinence (CCIS ≥ 7), and ASA score was the only preoperative prognostic factor for the presence of major LARS at follow-up. CONCLUSION: Sigmoid resection for diverticular disease can be associated with long-term bowel dysfunction, even with tubular dissection and preservation of IMA. These findings suggest intercolonic mechanisms of developing symptoms of bowel dysfunction after disruption of the colorectal continuity that are so far summarized as "sigmoidectomy syndrome."

Artificial Intelligence for Clinical Interpretation of Bedside Chest Radiographs.

Background Supine chest radiography for bedridden patients in intensive care units (ICUs) is one of the most frequently ordered imaging studies worldwide. Purpose To evaluate the diagnostic performance of a neural network-based model that is trained on structured semiquantitative radiologic reports of bedside chest radiographs. Materials and Methods For this retrospective single-center study, children and adults in the ICU of a university hospital who had been imaged using bedside chest radiography from January 2009 to December 2020 were reported by using a structured and itemized template. Ninety-eight radiologists rated the radiographs semiquantitatively for the severity of disease patterns. These data were used to train a neural network to identify cardiomegaly, pulmonary congestion, pleural effusion, pulmonary opacities, and atelectasis. A held-out internal test set (100 radiographs from 100 patients) that was assessed independently by an expert panel of six radiologists provided the ground truth. Individual assessments by each of these six radiologists, by two nonradiologist physicians in the ICU, and by the neural network were compared with the ground truth. Separately, the nonradiologist physicians assessed the images without and with preliminary readings provided by the neural network. The weighted Cohen κ coefficient was used to measure agreement between the readers and the ground truth. Results A total of 193 566 radiographs in 45 016 patients (mean age, 66 years ± 16 [SD]; 61% men) were included and divided into training (n = 122 294; 64%), validation (n = 31 243; 16%), and test (n = 40 029; 20%) sets. The neural network exhibited higher agreement with a majority vote of the expert panel (κ = 0.86) than each individual radiologist compared with the majority vote of the expert panel (κ = 0.81 to ≤0.84). When the neural network provided preliminary readings, the reports of the nonradiologist physicians improved considerably (aided vs unaided, κ = 0.87 vs 0.79, respectively; P < .001). Conclusion A neural network trained with structured semiquantitative bedside chest radiography reports allowed nonradiologist physicians improved interpretations compared with the consensus reading of expert radiologists. © RSNA, 2022 Supplemental material is available for this article. See also the editorial by Wielpütz in this issue.

Revisiting a challenging p53 binding site: a diversity-optimized HEFLib reveals diverse binding modes in T-p53C-Y220C.

The cellular tumor antigen p53 is a key component in cell cycle control. The mutation Y220C heavily destabilizes the protein thermally but yields a druggable crevice. We have screened the diversity-optimized halogen-enriched fragment library against T-p53C-Y220C with STD-NMR and DSF to identify hits, which we validated by 1H,15N-HSQC NMR. We could identify four hits binding in the Y220C cleft, one hit binding covalently and four hits binding to an uncharacterized binding site. Compound 1151 could be crystallized showing a flip of C220 and thus opening subsite 3. Additionally, 4482 was identified to alkylate cysteines. Data shows that the diversity-optimized HEFLib leads to multiple diverse hits. The identified scaffolds can be used to further optimize interactions with T-p53C-Y220C and increase thermal stability.

Screening of a Halogen-Enriched Fragment Library Leads to Unconventional Binding Modes.

We conceived the Halogen-Enriched Fragment Library (HEFLib) to investigate the potential of halogen bonds in the early stages of drug discovery. As the number of competitive interactions increases with ligand size, we reasoned that a binding mode relying on halogen bonding is more likely for fragments than highly decorated molecules. Thus, fragments could feature unexplored binding modes. We screened the HEFLib against the human kinase DYRK1a and verified micromolar binding fragments via isothermal titration calorimetry (ITC). The crystal structure of one fragment revealed a noncanonical binding mode, despite the fragment's classical hinge binding motif. In addition, the fragment occupies a secondary binding site. Both binding modes feature a halogen bond, which we evaluated by ab initio calculations. Structure-affinity relationship (SAR) from a set of analogues improves the affinity, provides a promising fragment-growth vector, and highlights the benefits and applicability of halogen bonds in early lead development.

Discovery of Ircinianin Lactones B and C-Two New Cyclic Sesterterpenes from the Marine Sponge Ircinia wistarii.

Two new ircinianin-type sesterterpenoids, ircinianin lactone B and ircinianin lactone C (7 and 8), together with five known entities from the ircinianin compound family (1, 3-6) were isolated from the marine sponge Ircinia wistarii. Ircinianin lactones B and C (7 and 8) represent new ircinianin terpenoids with a modified oxidation pattern. Despite their labile nature, the structures could be established using a combination of spectroscopic data, including HRESIMS and 1D/2D NMR techniques, as well as computational chemistry and quantum-mechanical calculations. In a broad screening approach for biological activity, the class-defining compound ircinianin (1) showed moderate antiprotozoal activity against Plasmodium falciparum (IC50 25.4 µM) and Leishmania donovani (IC50 16.6 µM).

A Compliance-Reactance Framework for Evaluating Human-Robot Interaction.

When do we follow requests and recommendations and which ones do we choose not to comply with? This publication combines definitions of compliance and reactance as behaviours and as affective processes in one model for application to human-robot interaction. The framework comprises three steps: human perception, comprehension, and selection of an action following a cue given by a robot. The paper outlines the application of the model in different study settings such as controlled experiments that allow for the assessment of cognition as well as observational field studies that lack this possibility. Guidance for defining and measuring compliance and reactance is outlined and strategies for improving robot behaviour are derived for each step in the process model. Design recommendations for each step are condensed into three principles on information economy, adequacy, and transparency. In summary, we suggest that in order to maximise the probability of compliance with a cue and to avoid reactance, interaction designers should aim for a high probability of perception, a high probability of comprehension and prevent negative affect. Finally, an example application is presented that uses existing data from a laboratory experiment in combination with data collected in an online survey to outline how the model can be applied to evaluate a new technology or interaction strategy using the concepts of compliance and reactance as behaviours and affective constructs.