Dupilumab-induced eosinophilia in patients with diffuse type 2 chronic rhinosinusitis.

BACKGROUND Dupilumab, a monoclonal anti-IL-4Rα antibody, is approved for several type 2 mediated inflammatory diseases like asthma, atopic dermatitis, and diffuse type 2 chronic rhinosinusitis (CRS). Clinical studies had reported a transient increase in blood eosinophils during dupilumab therapy. This study aimed to assess the impact of elevated blood eosinophils on clinical outcome and to investigate the cause of high blood eosinophil levels under dupilumab therapy. METHODS Patients suffering from diffuse type 2 CRS treated with dupilumab were examined on days 0, 28, 90, and 180 after therapy start. Sino-Nasal-Outcome-Test Score (SNOT-22), Total Nasal Polyp Score (TNPS), and blood samples were collected. Cytokine measurements and proteomics analysis were conducted. Flow cytometry analysis measured receptor expression on eosinophils. RESULTS Sixty-eighty patients were included. Baseline eosinophilia ≥0.3G/L was observed in 63.2% of patients, and in 30.9% of patients, eosinophils increased by ≥0.5G/L under dupilumab. Subjects with eosinophilia ≥0.3G/L at baseline had the best SNOT-22 mean change compared to no eosinophilia. Eosinophil elevation during dupilumab therapy had no impact on clinical scores. The eosinophil adhesion molecule VCAM-1 decreased significantly during therapy in all patients. The chemokine receptor CXCR4 was significantly down- and IL-4 upregulated in subjects with eosinophil increase. CONCLUSION Our findings suggest that increased eosinophils in type 2 CRS are associated with a good clinical response to dupilumab. Patients with elevated IL-4 at baseline developed dupilumab-induced transient eosinophilia. We identified the downregulation of VCAM-1 and surface markers CD49d and CXCR4 on eosinophils as possible explanations of dupilumab-induced eosinophilia

Exploring the effects of human-centered AI explanations on trust and reliance

Transparency is widely regarded as crucial for the responsible real-world deployment of artificial intelligence (AI) and is considered an essential prerequisite to establishing trust in AI. There are several approaches to enabling transparency, with one promising attempt being human-centered explanations. However, there is little research into the effectiveness of human-centered explanations on end-users' trust. What complicates the comparison of existing empirical work is that trust is measured in different ways. Some researchers measure subjective trust using questionnaires, while others measure objective trust-related behavior such as reliance. To bridge these gaps, we investigated the effects of two promising human-centered post-hoc explanations, feature importance and counterfactuals, on trust and reliance. We compared these two explanations with a control condition in a decision-making experiment (N = 380). Results showed that human-centered explanations can significantly increase reliance but the type of decision-making (increasing a price vs. decreasing a price) had an even greater influence. This challenges the presumed importance of transparency over other factors in human decision-making involving AI, such as potential heuristics and biases. We conclude that trust does not necessarily equate to reliance and emphasize the importance of appropriate, validated, and agreed-upon metrics to design and evaluate human-centered AI

Topical NSAIDs for chronic musculoskeletal pain: systematic review and meta-analysis

A previous systematic review reported that topical NSAIDs were effective in relieving pain in chronic conditions like osteoarthritis and tendinitis. More trials, a better understanding of trial quality and bias, and a reclassification of certain drugs necessitate a new review. Studies were identified by searching electronic databases, and writing to manufacturers. We identified randomised, double blind trials comparing topical NSAID with either placebo or another active treatment, in adults with chronic pain. The primary outcome was a reduction in pain of approximately 50% at two weeks, and secondary outcomes were local and systemic adverse events and adverse event-related withdrawals. Relative benefit and number-needed-to-treat (NNT), and relative harm and number-needed-to-harm (NNH) were calculated, and the effects of trial quality, validity and size, outcome reported, and condition treated, were examined by sensitivity analyses. Twelve new trials were added to 13 trials from a previous review. Fourteen double blind placebo-controlled trials had information from almost 1,500 patients. Topical NSAID was significantly better than placebo with relative benefit 1.9 (95% confidence interval 1.7 to 2.2), NNT 4.6 (95% confidence interval 3.8 to 5.9). Results were not affected by trial quality, validity or size, outcome reported, or condition treated. Three trials with 764 patients comparing a topical with an oral NSAID found no difference in efficacy. Local adverse events (6%), systemic adverse events (3%), or the numbers withdrawing due to an adverse event were the same for topical NSAID and placebo. Topical NSAIDs were effective and safe in treating chronic musculoskeletal conditions for two weeks. Larger and longer trials are necessary to fully elucidate the place of topical NSAIDs in clinical practice

Crowdsourcing hypothesis tests: Making transparent how design choices shape research results

To what extent are research results influenced by subjective decisions that scientists make as they design studies? Fifteen research teams independently designed studies to answer fiveoriginal research questions related to moral judgments, negotiations, and implicit cognition. Participants from two separate large samples (total N > 15,000) were then randomly assigned to complete one version of each study. Effect sizes varied dramatically across different sets of materials designed to test the same hypothesis: materials from different teams renderedstatistically significant effects in opposite directions for four out of five hypotheses, with the narrowest range in estimates being d = -0.37 to +0.26. Meta-analysis and a Bayesian perspective on the results revealed overall support for two hypotheses, and a lack of support for three hypotheses. Overall, practically none of the variability in effect sizes was attributable to the skill of the research team in designing materials, while considerable variability was attributable to the hypothesis being tested. In a forecasting survey, predictions of other scientists were significantly correlated with study results, both across and within hypotheses. Crowdsourced testing of research hypotheses helps reveal the true consistency of empirical support for a scientific claim.</div

LoL, Why Do You Even Play? Validating the Motives for Online Gaming Questionnaire in the Context of League of Legends

Motives are essential concepts in understanding a playerâEurotms experience in video games. We report and describe the analysis of a widely used questionnaire to measure playersâEurotm motives in video games, the Motives for Online Gaming Questionnaire (MOGQ). The present research aimed to investigate the psychometric quality of the MOGQ in the context of League of Legends (LoL). The MOGQ is a 27-item self-report scale designed to measure the motives for playing online games. To this end, 256 participants completed an online survey asking about their experiences and motives to play LoL. Results of confirmatory and exploratory factor analyses indicate weaknesses in the original 7-factor model. By removing five conspicuous items from the original 7-factor model, we propose an alternative 22-item version of the MOGQ. Additional confirmatory and exploratory factor analyses results indicate that the 22-item version of the MOGQ is more suitable in the context of LoL than the original 27-item questionnaire. However, further investigation into the quality of this alternative version compared to the original questionnaire is needed

Independent Validation of the Video Game Dispositional Flow Scale With League of Legends Players

Flow is a highly influential concept across many research domains. Because of the close links between enjoyment and flow, it is also a central concept in game research. Accordingly, many measurement instruments in the form of questionnaires have been developed to measure flow in video games. However, limited independent validation work has been carried out to date. In this project, we evaluated the recently developed Video Game Dispositional Flow Scale (VGDFS) in the context of League of Legends. An online survey posted on the online community reddit.com yielded a sample of N = 140. Confirmatory factor analysis did not support the originally proposed structure. Subsequent exploratory factor analysis resulted in inconclusive findings. Convergent validity with other questionnaires for the measurement of interest, enjoyment, and flow could be demonstrated in our data, although with unusually high correlations between the VGDFS and another flow measure. For divergent validity, correlations with questionnaires for the measurement of boredom and trait anxiety in the hypothesized direction could be found. Findings suggest that the VGDFS needs further evaluation in different video game contexts while also hinting at measurement problems possibly related to conceptual issues with flow

The esterase-like activity of serum albumin may be due to cholinesterase contamination.

PURPOSE: The "esterase-like activity" of human serum albumin (HSA) is described in the literature, but a contamination of commercially available HSA preparations by plasma cholinesterase is conceivable in some cases. The purpose of the present work was to examine this hypothesis. METHODS: The hydrolytic activity of HSA and its inhibition by physostigmine were measured fluorimetrically by monitoring the hydrolysis of the ester substrate moxisylyte. Affinity chromatography was used to separate cholinesterase and HSA. The cholinesterase activity in the eluted fractions was assessed using Ellman's reagent and butyrylthiocholine as substrate. RESULTS: A significant variation in the esterase-like activity of different albumin batches was observed. This activity was strongly inhibited by physostigmine, a well-known inhibitor of cholinesterase. Affinity chromatography led to a complete separation between HSA and the esterase activity, which was found exclusively in the cholinesterase fraction. CONCLUSIONS: The apparent esterase-like activity of HSA toward moxisylyte and butyrylthiocholine was due to a contamination by cholinesterase. With these substrates, HSA showed a total lack of esterase-like activity

TrustDiff: Development and Validation of a Semantic Differential for User Trust on the Web

Trust is an essential factor in many social interactions involving uncertainty. In the context of online services and websites, the problems of anonymity and lack of control make trust a vital element for successful e-commerce. Despite trust having received sustained attention, there is a need for validated questionnaires that can be readily applied in different contexts and for various products. We, therefore, report the development and validation of the TrustDiff scale, a semantic differential that measures user trust on three dimensions. Compared to Likert-type scales, semantic differentials have advantages when it comes to measuring multidimensional constructs in different contexts. Using 10 items, the TrustDiff semantic differential measures user perceptions of the Benevolence, Integrity, and Competence of an online vendor. The scale was investigated in three independent studies with over 1,000 participants and shows good structural validity, high reliability, and correlates expectedly with related scales. As a test of criterion validity, the TrustDiff scale showed significant differences on all subscales in a study involving a manipulated website

Transparency in Measurement Reporting: A Systematic Literature Review of CHI PLAY

Measuring theoretical concepts, so-called constructs, is a central challenge of Player Experience research. Building on recent work in HCI and psychology, we conducted a systematic literature review to study the transparency of measurement reporting. We accessed the ACM Digital Library to analyze all 48 full papers published at CHI PLAY 2020, of those, 24 papers used self-report measurements and were included in the full review. We assessed specifically, whether researchers reported What, How and Why they measured. We found that researchers matched their measures to the construct under study and that administrative details, such as number of points on a Likert-type scale, were frequently reported. However, definitions of the constructs to be measured and justifications for selecting a particular scale were sparse. Lack of transparency in these areas threaten the validity of singular studies, but further compromise the building of theories and accumulation of research knowledge in meta-analytic work. This work is limited to only assessing the current transparency of measurement reporting at CHI PLAY 2020, however we argue this constitutes a fair foundation to assess potential pitfalls. To address these pitfalls, we propose a prescriptive model of a measurement selection process, which aids researchers to systematically define their constructs, specify operationalizations, and justify why these measures were chosen. Future research employing this model should contribute to more transparency in measurement reporting. The research was funded through internal resources. All materials are available on https://osf.io/4xz2v/