Unconscious activation of negative emotional memories increases pain unpleasantness.

OBJECTIVE: The influence of unconscious emotional processes on pain remains poorly understood. The present study tested whether cues to forgotten unpleasant images might amplify pain (i.e., in the absence of conscious recall). METHODS: 72 healthy female adults (19 to 34 years) performed an adapted Think/No-think paradigm (T/NT) using 72 combinations of neutral face images (cues) paired with 36 neutral & 36 unpleasant images. After completion of the T/NT task, cues associated with forgotten neutral or unpleasant images were identified. Cues to either neutral or unpleasant images from the NT condition were then presented in randomized order while participants received intermediate-level thermal pain stimulation on the left hand. Ratings of both pain intensity and unpleasantness were acquired after each trial. RESULTS: Mean pain unpleasantness ratings were greater during presentation of cues to forgotten negative vs. neutral images (5.52 [SD = 2.06] vs. 5.23 [SD = 2.10]; p = 0.02). This pattern was also present when comparing cues to remembered negative vs. neutral images (5.62 [SD = 1.94] vs. 5.04 [SD = 1.90]; p < .001). Mean pain intensity ratings were higher for cues to negative vs. neutral images when remembered (5.48 [SD = 1.79] vs. 5.00 [SD = 1.69]; p < .001), but not when forgotten (5.27 [SD = 1.96] vs. 5.16 [SD = 1.93]; p = 0.30). CONCLUSIONS: Using an adapted T/NT-Pain paradigm, this study demonstrated that cues to non-recallable (but potentially unconsciously activated) negative emotional memories amplify pain unpleasantness, similar to known effects of conscious negative emotions.

FSFI score and timing of tubal ligation in patients: preliminary results of an online survey.

INTRODUCTION: Tubal ligation is the most common contraceptive method worldwide. Apart from a very low pearl index and anxiety relief, other benefits are not commonly recognised. In young patients, there is the post-operative risk of regretting the decision with the need for In-Vitro-Fertilisation or refertilising surgery. Positive side effects have not been widely published. In our study we investigated the change in the female sexual function index score after tubal ligation. MATERIAL AND METHOD: In this survey the FSFI score of participants around the time of the tubal ligation was compared with the FSFI score of intermediate and long-term time distance to the ligation. RESULTS: The data indicate an increase in younger women seeking information on permanent contraception and whilst the FSFI score of the early group indicates a risk of female sexual dysfunction, the intermediate and long-term FSFI scores are comparable to published control groups. DISCUSSION: Besides the obvious benefit of a low pearl index, tubal ligation may contribute to reduce the risk of female sexual dysfunction in the mid and long term. Informed consent is essential for the surgeon and patient to weigh up the risks and benefits individually including possible future perspectives on family planning.

Measurement of the nociceptive flexion reflex threshold in critically ill patients - a randomized observational pilot study.

BACKGROUND: Pain detection and treatment is a major challenge in the care of critically ill patients, rendered more complex by the need to take into consideration the risk of insufficient or excessive analgesia. The nociceptive flexion reflex threshold (NFRT) has become the established basis for measuring the level of analgesia in the perioperative context. However, it remains unclear whether NFRT measurement can be usefully applied to mechanically ventilated, analgosedated critically ill patients who are unable to communicate. Therefore, the aim of the present study was to investigate whether there is an association between the NFRT measurement and the Behavioral Pain Scale (BPS) in critically ill, analgosedated, and mechanically ventilated patients and whether the NFRT measurement can also detect potential excessive analgesia. METHODS: This prospective, observational, randomized single-center pilot study included patients admitted to the surgical Intensive Care Unit of University Hospital Ulm, Germany, all of whom were analgosedated and intubated. Major exclusion criteria were defined as the need for the administration of neuromuscular blocking agents or neurological diseases associated with peripheral nerve conduction restriction. Initial NFRT and BPS measurements were conducted within 12 h after admission. A structured pain assessment was performed at least twice daily until extubation throughout the observation period thereafter (Group A: BPS + NFRT, Group B: BPS). RESULTS: 114 patients were included in the study. NFRT is associated negatively with BPS. NFRT was almost twice as high in patients with a Richmond Agitation Sedation Scale (RASS) score of -5 than in patients with a RASS score ≥ -4 (RASS -5 - NFRT: 59.40 vs. RASS -4 - NFRT: 29.00, p < 0.001). CONCLUSIONS: NFRT measurement is associated negatively with the BPS in critically ill patients. NFRT measurement provides guidance for the evaluation of nociceptive processes in patients with RASS scores ≤ -4, in whom analgesia level is often difficult to assess. However, in order to identify excessive analgesia and derive therapeutic consequences, it is necessary to gradually decrease analgesics and sedatives until a stimulus threshold is reached at which the patient does not feel pain. TRIAL REGISTRATION: Retrospectively registered in the German Clinical Trials Register, registration number DRKS00021149, date of registration: March 26, 2020. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00021149 .

Automatic vs. Human Recognition of Pain Intensity from Facial Expression on the X-ITE Pain Database.

Prior work on automated methods demonstrated that it is possible to recognize pain intensity from frontal faces in videos, while there is an assumption that humans are very adept at this task compared to machines. In this paper, we investigate whether such an assumption is correct by comparing the results achieved by two human observers with the results achieved by a Random Forest classifier (RFc) baseline model (called RFc-BL) and by three proposed automated models. The first proposed model is a Random Forest classifying descriptors of Action Unit (AU) time series; the second is a modified MobileNetV2 CNN classifying face images that combine three points in time; and the third is a custom deep network combining two CNN branches using the same input as for MobileNetV2 plus knowledge of the RFc. We conduct experiments with X-ITE phasic pain database, which comprises videotaped responses to heat and electrical pain stimuli, each of three intensities. Distinguishing these six stimulation types plus no stimulation was the main 7-class classification task for the human observers and automated approaches. Further, we conducted reduced 5-class and 3-class classification experiments, applied Multi-task learning, and a newly suggested sample weighting method. Experimental results show that the pain assessments of the human observers are significantly better than guessing and perform better than the automatic baseline approach (RFc-BL) by about 1%; however, the human performance is quite poor due to the challenge that pain that is ethically allowed to be induced in experimental studies often does not show up in facial reaction. We discovered that downweighting those samples during training improves the performance for all samples. The proposed RFc and two-CNNs models (using the proposed sample weighting) significantly outperformed the human observer by about 6% and 7%, respectively.

Immunogenic stress and death of cancer cells: Contribution of antigenicity vs adjuvanticity to immunosurveillance.

Cancer cells are subjected to constant selection by the immune system, meaning that tumors that become clinically manifest have managed to subvert or hide from immunosurveillance. Immune control can be facilitated by induction of autophagy, as well as by polyploidization of cancer cells. While autophagy causes the release of ATP, a chemotactic signal for myeloid cells, polyploidization can trigger endoplasmic reticulum stress with consequent exposure of the "eat-me" signal calreticulin on the cell surface, thereby facilitating the transfer of tumor antigens into dendritic cells. Hence, both autophagy and polyploidization cause the emission of adjuvant signals that ultimately elicit immune control by CD8+ T lymphocytes. We investigated the possibility that autophagy and polyploidization might also affect the antigenicity of cancer cells by altering the immunopeptidome. Mass spectrometry led to the identification of peptides that were presented on major histocompatibility complex (MHC) class I molecules in an autophagy-dependent fashion or that were specifically exposed on the surface of polyploid cells, yet lost upon passage of such cells through immunocompetent (but not immunodeficient) mice. However, the preferential recognition of autophagy-competent and polyploid cells by the innate and cellular immune systems did not correlate with the preferential recognition of such peptides in vivo. Moreover, vaccination with such peptides was unable to elicit tumor growth-inhibitory responses in vivo. We conclude that autophagy and polyploidy increase the immunogenicity of cancer cells mostly by affecting their adjuvanticity rather than their antigenicity.

[Reconciliation of Family and Work Life in the Department of Gynecology and Obstetrics - Systematic Assessment in Different Occupational Groups of a German University Hospital]. / "Zur Vereinbarkeit von Beruf und Familie bei Beschäftigten einer Universitätsfrauenklinik" ­ Auswertung einer systematischen Berufsgruppen-übergreifenden Befragung.

Reconciliation of family and work life is an important topic for employees. Due to common work in shifts within the health care sector, this is even more essential for health care workers and has great implications in work satisfaction and individuals ́ health. Within all employees of the department of OB/GYN of the German university hospital Ulm, an anonymous and voluntary survey on compatibility of work and family was performed in the summer of 2017. The questionnaires consisted of established and newly designed tools to assess reconciliation of family/work life as well as work-family (WFC) and family-work conflict (FWC). Return rate of questionnaires was 63% (n=136). Physicians (n=33), nurses (n=53), and midwives (n=31) were grouped together as "medical staff" (n=115). There was no significant difference between employees with (n=73) or without children (n=59) regarding WFC and FWC. The group of nurses/midwives and the group of physicians had a significantly higher inter-role conflict (p<0.001) than the group of administrative staff. A negative correlation with "work satisfaction" was found for WFC and FWC. The group of nurses/midwives has significantly higher inter-role conflicts than the administrative staff. Especially the negative correlation of work satisfaction and inter-role conflicts shows the enormous need for improvement in sufficient compatibility of work and family life of employees in the health care sector. This needs to be addressed quickly and effectively as there is an alarming deficit of nurses and midwives in the German health care system.

Optimization in Detection of Antigen-Specific T Cells Through Differentially Labeled MHC Multimers.

A large variety of fluorescent molecules are used on a regular basis to tag major histocompatibility complex (MHC) multimers for detection of antigen-specific T cells. We have evaluated the way in which the choice of fluorescent label can impact the detection of MHC multimer binding T cells in an exploratory proficiency panel where detection of MHC multimer binding T cells was assessed across 16 different laboratories. We found that the staining index (SI) of the multimer reagent provided the best direct correlation with the value of a given fluorochrome for T cell detection studies. The SI is dependent on flow cytometer settings and chosen antibody panel; hence, the optimal fluorochrome selection may differ from lab to lab. Consequently, we describe a strategy to evaluate performance of the detection channels and optimize the SI for selected fluorescent molecules. This approach can easily be used to test and optimize fluorescence detection in relation to MHC multimer staining and in general, for antibody-based identification of rare cell populations. © 2019 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.

[Challenges of the COVID-19 pandemic in gastrointestinal endoscopy: expectations and implementation of recommendations]. / Gastrointestinale Endoskopie in Zeiten der COVID-19-Pandemie: Umsetzung von Empfehlungen und Erwartungen für die Zukunft.

INTRODUCTION: The COVID-19 pandemic represents a major challenge for health care systems worldwide. Recent data suggests an increased risk for personnel of gastrointestinal (GI) endoscopy units for SARS-CoV-2 infections. Several societies have provided recommendations for the current situation, but their feasibility is unclear and real-world data on preparedness of endoscopy units are lacking. AIMS & METHODS: A web-based survey among German GI-endoscopy heads was conducted from April 1 to April 7, 2020. It comprised 33 questions based on the ESGE (European Society of Gastrointestinal Endoscopy) recommendations and was distributed electronically by the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS). RESULTS: Of 551 completed surveys, 202 (37 %) endoscopy units cancelled less than 40 % of their procedures. Small-volume units (< 4000 procedures/year) cancelled significantly less procedures than high-volume units (> 4000). Complete spatial separation of high-risk patients was possible in only 17 %. Most units systematically identified patients at risk (91 %) and used risk adapted personal protective equipment (PPE, 85 %). For the future, shortages in PPE (83 %), staff (69 %) and relevant financial losses (80 %) were expected. CONCLUSIONS: Recommendations on structural measures were only partially fulfilled and cancellations of procedures were heterogeneous. Clear definitions of indications to perform endoscopies during such a pandemic are needed. Further, structural recommendations should be adapted and strategies to compensate financial losses need to be developed.

[Survey: Why did you become a gastroenterologist?] / Umfrage: Was hat Sie dazu bewogen, die Gastroenterologie als Fachgebiet auszuwählen?

INTRODUCTION: The specific support of medical students is indispensable in gastroenterology. The aim of this study was to identify factors that influenced members of the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS) to choose their specialty. METHODS: Using an online survey all members of the DGVS were invited to assess the following factors: earliest time point of the decision to become a gastroenterologist, important role models and mentors, important course contents and teaching methods, the role of the doctoral thesis and other influencing aspects of the specialty gastroenterology. The evaluation included an additional subgroup analysis involving work experience (≤ 8, 9-29, ≥ 30 years) and working place (university hospital, community-based hospital, private practice). RESULTS: 1358 participants representing 24.2 % of the DGVS-members took part in the survey. Physicians with ≤ 8 years of work experience decided in 62.5 % during medical school to become a gastroenterologist compared to 37.1 % of the physicians with a work experience of ≥ 9 years (p < 0.001). Senior physicians were regarded as important role models and mentors by 40.8 % of the participants. Doctoral supervisors were regarded as important mentors that influenced the selection of the specialty by 42.8 % of the participants that completed their doctoral thesis in gastroenterology. Hands-on courses like sonography were regarded as important course contents by 42.2 % of the participants. Interventional medicine in particular endoscopy and the diversity of gastroenterology were rated as important in the selection process for the specialty. CONCLUSION: The decision to become a gastroenterologist is mainly made during medical school. The main influencing role models and mentors are senior physicians. Hands-on training in ultrasound and endoscopy were regarded as important course contents and teaching methods.

IMA901, a multipeptide cancer vaccine, plus sunitinib versus sunitinib alone, as first-line therapy for advanced or metastatic renal cell carcinoma (IMPRINT): a multicentre, open-label, randomised, controlled, phase 3 trial.

BACKGROUND: In a phase 2 study in patients with metastatic renal cell carcinoma, overall survival was associated with T-cell responses against IMA901, a vaccine consisting of ten tumour-associated peptides. In this phase 3 trial, we aimed to determine the clinical effect of adding IMA901 to sunitinib, the standard first-line treatment in metastatic renal cell carcinoma with postulated favourable immunomodulatory effects. METHODS: The IMPRINT study is an open-label, randomised, controlled, phase 3 trial done at 124 clinical sites in 11 countries. HLA-A*02-positive patients (aged ≥18 years) with treatment-naive, histologically confirmed metastatic or locally advanced (or both) clear-cell renal cell carcinoma were randomly assigned (3:2) to receive sunitinib plus up to ten intradermal vaccinations of IMA901 (4·13 mg) and granulocyte macrophage colony-stimulating factor (75 µg), with one dose of cyclophosphamide (300 mg/m2) 3 days before the first vaccination, or to receive sunitinib alone. Sunitinib (50 mg) was given orally once daily, with each cycle defined as 4 weeks on treatment followed by 2 weeks off treatment, until progression of disease as determined by the investigator, death, or withdrawal of consent. Block randomisation (block size five) was done centrally using an interactive web response system, stratified by prognostic risk, geographical region, and previous nephrectomy. Patients and investigators were not masked to treatment allocation. The primary endpoint was overall survival from randomisation until death of any cause as determined by the investigator, analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01265901. FINDINGS: Between Dec 22, 2010, and Dec 15, 2012, we screened 1171 patients, of whom 339 were randomly assigned to receive sunitinib plus IMA901 (n=204) or sunitinib monotherapy (n=135). Patients had a median follow-up of 33·27 months (IQR 29·92-35·64). Median overall survival did not differ significantly between the groups (33·17 months [95% CI 27·81-41·36] in the sunitinib plus IMA901 group vs not reached [33·67-not reached] in the sunitinib monotherapy group; hazard ratio 1·34 [0·96-1·86]; p=0·087). 116 (57%) of 202 patients in the sunitinib plus IMA901 group and 62 (47%) of 132 in the sunitinib group had grade 3 or worse adverse events, the most common of which were hypertension, neutropenia, and anaemia in both groups, and mild-to-moderate transient injection-site reactions (eg, erythema, pruritus) were the most frequent IMA901-related side-effect in the sunitinib plus IMA901 group. Serious adverse events leading to death occurred in four (2%) patients (one respiratory failure and circulatory collapse [possibly related to sunitinib], one oesophageal varices haemorrhage [possibly related to sunitinib], one cardiac arrest [possibly related to sunitinib], and one myocardial infarction) and eight (6%) patients in the sunitinib group (one case each of renal failure, oesophageal varices haemorrhage, circulatory collapse, wound infection, ileus, cerebrovascular accident [possibly treatment related], and sepsis). INTERPRETATION: IMA901 did not improve overall survival when added to sunitinib as first-line treatment in patients with metastatic renal cell carcinoma. The magnitude of immune responses needs to be improved before further development of IMA901 in this disease is indicated. FUNDING: Immatics Biotechnologies.

Toward harmonized phenotyping of human myeloid-derived suppressor cells by flow cytometry: results from an interim study.

There is an increasing interest for monitoring circulating myeloid-derived suppressor cells (MDSCs) in cancer patients, but there are also divergences in their phenotypic definition. To overcome this obstacle, the Cancer Immunoguiding Program under the umbrella of the Association of Cancer Immunotherapy is coordinating a proficiency panel program that aims at harmonizing MDSC phenotyping. After a consultation period, a two-stage approach was designed to harmonize MDSC phenotype. In the first step, an international consortium of 23 laboratories immunophenotyped 10 putative MDSC subsets on pretested, peripheral blood mononuclear cells of healthy donors to assess the level of concordance and define robust marker combinations for the identification of circulating MDSCs. At this stage, no mandatory requirements to standardize reagents or protocols were introduced. Data analysis revealed a small intra-laboratory, but very high inter-laboratory variance for all MDSC subsets, especially for the granulocytic subsets. In particular, the use of a dead-cell marker altered significantly the reported percentage of granulocytic MDSCs, confirming that these cells are especially sensitive to cryopreservation and/or thawing. Importantly, the gating strategy was heterogeneous and associated with high inter-center variance. Overall, our results document the high variability in MDSC phenotyping in the multicenter setting if no harmonization/standardization measures are applied. Although the observed variability depended on a number of identified parameters, the main parameter associated with variation was the gating strategy. Based on these findings, we propose further efforts to harmonize marker combinations and gating parameters to identify strategies for a robust enumeration of MDSC subsets.

Cryopreservation of MHC multimers: Recommendations for quality assurance in detection of antigen specific T cells.

Fluorescence-labeled peptide-MHC class I multimers serve as ideal tools for the detection of antigen-specific T cells by flow cytometry, enabling functional and phenotypical characterization of specific T cells at the single cell level. While this technique offers a number of unique advantages, MHC multimer reagents can be difficult to handle in terms of stability and quality assurance. The stability of a given fluorescence-labeled MHC multimer complex depends on both the stability of the peptide-MHC complex itself and the stability of the fluorochrome. Consequently, stability is difficult to predict and long-term storage is generally not recommended. We investigated here the possibility of cryopreserving MHC multimers, both in-house produced and commercially available, using a wide range of peptide-MHC class I multimers comprising virus and cancer-associated epitopes of different affinities presented by various HLA-class I molecules. Cryopreservation of MHC multimers was feasible for at least 6 months, when they were dissolved in buffer containing 5-16% glycerol (v/v) and 0.5% serum albumin (w/v). The addition of cryoprotectants was tolerated across three different T-cell staining protocols for all fluorescence labels tested (PE, APC, PE-Cy7 and Quantum dots). We propose cryopreservation as an easily implementable method for stable storage of MHC multimers and recommend the use of cryopreservation in long-term immunomonitoring projects, thereby eliminating the variability introduced by different batches and inconsistent stability.

Harmonisation of short-term in vitro culture for the expansion of antigen-specific CD8(+) T cells with detection by ELISPOT and HLA-multimer staining.

Ex vivo ELISPOT and multimer staining are well-established tests for the assessment of antigen-specific T cells. Many laboratories are now using a period of in vitro stimulation (IVS) to enhance detection. Here, we report the findings of a multi-centre panel organised by the Association for Cancer Immunotherapy Immunoguiding Program to investigate the impact of IVS protocols on the detection of antigen-specific T cells of varying ex vivo frequency. Five centres performed ELISPOT and multimer staining on centrally prepared PBMCs from 3 donors, both ex vivo and following IVS. A harmonised IVS protocol was designed based on the best-performing protocol(s), which was then evaluated in a second phase on 2 donors by 6 centres. All centres were able to reliably detect antigen-specific T cells of high/intermediate frequency both ex vivo (Phase I) and post-IVS (Phase I and II). The highest frequencies of antigen-specific T cells ex vivo were mirrored in the frequencies following IVS and in the detection rates. However, antigen-specific T cells of a low/undetectable frequency ex vivo were not reproducibly detected post-IVS. Harmonisation of the IVS protocol reduced the inter-laboratory variation observed for ELISPOT and multimer analyses by approximately 20 %. We further demonstrate that results from ELISPOT and multimer staining correlated after (P < 0.0001 and R (2) = 0.5113), but not before IVS. In summary, IVS was shown to be a reproducible method that benefitted from method harmonisation.

Similarities and differences of emotions in human-machine and human-human interactions: what kind of emotions are relevant for future companion systems?

Cognitive-technical intelligence is envisioned to be constantly available and capable of adapting to the user's emotions. However, the question is: what specific emotions should be reliably recognised by intelligent systems? Hence, in this study, we have attempted to identify similarities and differences of emotions between human-human (HHI) and human-machine interactions (HMI). We focused on what emotions in the experienced scenarios of HMI are retroactively reflected as compared with HHI. The sample consisted of N = 145 participants, who were divided into two groups. Positive and negative scenario descriptions of HMI and HHI were given by the first and second groups, respectively. Subsequently, the participants evaluated their respective scenarios with the help of 94 adjectives relating to emotions. The correlations between the occurrences of emotions in the HMI versus HHI were very high. The results do not support the statement that only a few emotions in HMI are relevant.

High immune response rates and decreased frequencies of regulatory T cells in metastatic renal cell carcinoma patients after tumor cell vaccination.

Our previously reported phase I clinical trial with the allogeneic gene-modified tumor cell line RCC-26/CD80/IL-2 showed that vaccination was well tolerated and feasible in metastatic renal cell carcinoma (RCC) patients. Substantial disease stabilization was observed in most patients despite a high tumor burden at study entry. To investigate alterations in immune responses that might contribute to this effect, we performed an extended immune monitoring that included analysis of reactivity against multiple antigens, cytokine/chemokine changes in serum and determination of the frequencies of immune suppressor cell populations, including natural regulatory T cells (nTregs) and myeloid-derived suppressor cell subsets (MDSCs). An overall immune response capacity to virus-derived control peptides was present in 100% of patients before vaccination. Vaccine-induced immune responses to tumor-associated antigens occurred in 75% of patients, demonstrating the potent immune stimulatory capacity of this generic vaccine. Furthermore, some patients reacted to peptide epitopes of antigens not expressed by the vaccine, showing that epitope-spreading occurred in vivo. Frequencies of nTregs and MDSCs were comparable to healthy donors at the beginning of study. A significant decrease of nTregs was detected after vaccination (p = 0.012). High immune response rates, decreased frequencies of nTregs and a mixed T helper 1/T helper 2 (T(H)1/T(H)2)-like cytokine pattern support the applicability of this RCC generic vaccine for use in combination therapies.

Exploiting the glioblastoma peptidome to discover novel tumour-associated antigens for immunotherapy.

Peptides presented at the cell surface reflect the protein content of the cell; those on HLA class I molecules comprise the critical peptidome elements interacting with CD8 T lymphocytes. We hypothesize that peptidomes from ex vivo tumour samples encompass immunogenic tumour antigens. Here, we uncover >6000 HLA-bound peptides from HLA-A*02(+) glioblastoma, of which over 3000 were restricted by HLA-A*02. We prioritized in-depth investigation of 10 glioblastoma-associated antigens based on high expression in tumours, very low or absent expression in healthy tissues, implication in gliomagenesis and immunogenicity. Patients with glioblastoma showed no T cell tolerance to these peptides. Moreover, we demonstrated specific lysis of tumour cells by patients' CD8(+) T cells in vitro. In vivo, glioblastoma-specific CD8(+) T cells were present at the tumour site. Overall, our data show the physiological relevance of the peptidome approach and provide a critical advance for designing a rational glioblastoma immunotherapy. The peptides identified in our study are currently being tested as a multipeptide vaccine (IMA950) in patients with glioblastoma.

Immersive medium for early clinical exposure - knowledge acquisition, spatial orientation and the unexpected role of annotation in 360° VR photos.

Aim: 360° VR photos could be a low-threshold possibility to increase early clinical exposure. Apart from granting insights into local routines and premises, the medium should facilitate knowledge acquisition and spatial orientation depending on its design. This assumption, however, is not yet substantiated empirically. Thus, three hypotheses were tested in consideration of Mayer's modality principle: 1) Providing 360° VR photos as visual reference improves retention and comprehension of information. 2) The annotation of text boxes in 360° VR photos compromises spatial orientation and presence. 3) Annotated audio commentary is superior to annotated text boxes in terms of cognitive load and knowledge acquisition. Methods: Using head-mounted displays, students of human (N=53) and dental medicine (N=8) completed one of three virtual tours through a surgical unit, which were created with 360° VR photos. In the first two variants, information about the facilities, medical devices and clinical procedures was annotated either as text boxes or audio commentary comprising 67 words on average (SD=6.67). In the third variant, the same information was given separately on a printed handout before the virtual tour. Taking user experience and individual learner characteristics into account, differences between conditions were measured regarding retention, comprehension, spatial orientation, cognitive load, and presence. Results: Concerning retention and comprehension of information, annotated text boxes outperformed annotated audio commentary and the handout condition. Although annotated audio commentary exhibited the lowest knowledge test scores, students preferred listening over reading. Students with an interest in VR and 360° media reported higher levels of enjoyment and presence. Regarding spatial orientation and presence, no significant group differences were found. Conclusions: 360° VR photos can convey information and a sense of spatial orientation effectively in the same learning scenario. For students, their use is both enjoyable and instructive. Unexpectedly, the ideal mode of annotation is not dictated by Mayer's modality principle. For information like in this study, annotated text boxes are better for knowledge acquisition than the subjectively preferred audio commentary. This finding is probably contingent on the length and the quality of the annotated text. To identify boundary conditions and to validate the findings, more research is required on the design and educational use of 360° VR photos.

The impact of analgesic on EMG and other biosignals in a postoperative setting.

Background: In the clinical context, the assessment of pain in patients with inadequate communication skills is standardly performed externally by trained medical staff. Automated pain recognition (APR) could make a significant contribution here. Hereby, pain responses are captured using mainly video cams and biosignal sensors. Primary, the automated monitoring of pain during the onset of analgesic sedation has the highest relevance in intensive care medicine. In this context, facial electromyography (EMG) represents an alternative to recording facial expressions via video in terms of data security. In the present study, specific physiological signals were analyzed to determine, whether a distinction can be made between pre-and post-analgesic administration in a postoperative setting. Explicitly, the significance of the facial EMG regarding the operationalization of the effect of analgesia was tested. Methods: N = 38 patients scheduled for surgical intervention where prospectively recruited. After the procedure the patients were transferred to intermediate care. Biosignals were recorded and all doses of analgesic sedations were carefully documented until they were transferred back to the general ward. Results: Almost every biosignal feature is able to distinguish significantly between 'before' and 'after' pain medication. We found the highest effect sizes (r = 0.56) for the facial EMG. Conclusion: The results of the present study, findings from research based on the BioVid and X-ITE pain datasets, staff and patient acceptance indicate that it would now be appropriate to develop an APR prototype.

Automated Electrodermal Activity and Facial Expression Analysis for Continuous Pain Intensity Monitoring on the X-ITE Pain Database.

This study focuses on improving healthcare quality by introducing an automated system that continuously monitors patient pain intensity. The system analyzes the Electrodermal Activity (EDA) sensor modality modality, compares the results obtained from both EDA and facial expressions modalities, and late fuses EDA and facial expressions modalities. This work extends our previous studies of pain intensity monitoring via an expanded analysis of the two informative methods. The EDA sensor modality and facial expression analysis play a prominent role in pain recognition; the extracted features reflect the patient's responses to different pain levels. Three different approaches were applied: Random Forest (RF) baseline methods, Long-Short Term Memory Network (LSTM), and LSTM with the sample-weighting method (LSTM-SW). Evaluation metrics included Micro average F1-score for classification and Mean Squared Error (MSE) and intraclass correlation coefficient (ICC [3, 1]) for both classification and regression. The results highlight the effectiveness of late fusion for EDA and facial expressions, particularly in almost balanced datasets (Micro average F1-score around 61%, ICC about 0.35). EDA regression models, particularly LSTM and LSTM-SW, showed superiority in imbalanced datasets and outperformed guessing (where the majority of votes indicate no pain) and baseline methods (RF indicates Random Forest classifier (RFc) and Random Forest regression (RFr)). In conclusion, by integrating both modalities or utilizing EDA, they can provide medical centers with reliable and valuable insights into patients' pain experiences and responses.