The feasibility of radiolabeling for human serum albumin (HSA) adsorption studies

Human serum albumin (HSA) was labeled in various ways and with different radioactive labels (Technetium-99m and Iodine-125). Characterization with electrophoresis on polyacryl gel and immunoelectrophoresis did not reveal differences between labeled and nonlabeled HSA. The release of the label from labeled proteins in phosphate buffer (pH 7.4) was studied as a function of time. 125I-labeled proteins were stable and 99mTc-labeled proteins showed different stabilities depending on the labeling method which was used. The adsorption behavior of labeled HSA and HSA onto polystyrene (PS) and silicon rubber (SR) was studied by using two methods. It appeared that all labeled HSA compounds showed a preferential adsorption onto PS (and SR) substrates. The 99mTc-labeled HSA showed a high value of the preferential adsorption factor (φ 1). The φ value for 125I-labeled HSA was about 1.4. It was also shown that φ was dependent on the kind of substrate used. The methods developed to determine preferential adsorption of labeled proteins compared to their nonlabeled analogs are also generally applicable for different types of compounds

Customer experience: conceptualization, measurement, and application in omnichannel environments

Managing customer experiences has become a key strategic priority for service research and management. Yet researchers and managers lack a customer experience (CX) measure that applies to the different experience partners, touchpoints, and journey stages in the omnichannel environments of today’s service industries. Without such a common measure, empirical research on CX remains fragmented, and service companies continue to struggle to improve customer interactions in customer journeys. To address this shortcoming, this article proposes an omnichannel-capable measurement of CX that applies to different customer interactions in the omnichannel environment. With seven studies, the authors develop and validate a six-dimensional, 18-item CX scale. The proposed CX scale overcomes the fragmentation of existing scales in service research and provides a valid measure that can be used consistently for various customer interactions in omnichannel environments. This article details how the proposed CX scale can monitor and compare CX for different interactions in customer journeys (i.e., pain-point analysis), as well as improve CX features and their marketing outcomes (i.e., CX profiling). By overcoming the existing fragmentation in available scales and providing a common omnichannel CX measure, this CX scale establishes an empirical foundation for developing CX knowledge and advancing related service research

Metacognitive and cognitive-behavioral interventions for psychosis: new developments

This review describes four cognitive approaches for the treatment of schizophrenia: cognitive-behavioral therapy for psychosis (CBTp), metacognitive therapy, metacognitive training, and metacognitive reflection insight therapy (MERIT). A central reference point of our review is a seminal paper by James Flavell, who introduced the term metacognition ("cognition about cognition"). In a way, every psychotherapeutic approach adopts a metacognitive perspective when therapists reflect with clients about their thoughts. Yet, the four approaches map onto different components of metacognition. CBTp conveys some "metacognitive knowledge" (eg, thoughts are not facts) but is mainly concerned with individual beliefs. Metacognitive therapy focuses on unhelpful metacognitive beliefs about thinking styles (eg, thought suppression). Metacognitive training brings distorted cognitive biases to the awareness of patients; a central goal is the reduction of overconfidence. MERIT focuses on larger senses of identity and highlights metacognitive knowledge about oneself and other persons. For CBTp and metacognitive training, meta-analytic evidence supports their efficacy; single studies speak for the effectiveness of MERIT and metacognitive therapy.

The P2X3 receptor antagonist filapixant in patients with refractory chronic cough: a randomized controlled trial

BACKGROUND: P2X3 receptor antagonists seem to have a promising potential for treating patients with refractory chronic cough. In this double-blind, randomized, placebo-controlled study, we investigated the efficacy, safety, and tolerability of the novel selective P2X3 receptor antagonist filapixant (BAY1902607) in patients with refractory chronic cough. METHODS: Following a crossover design, 23 patients with refractory chronic cough (age: 60.4 ± 9.1 years) received ascending doses of filapixant in one period (20, 80, 150, and 250 mg, twice daily, 4-days-on/3-days-off) and placebo in the other. The primary efficacy endpoint was the 24-h cough frequency on Day 4 of each dosing step. Further, subjective cough severity and health-related quality of life were assessed. RESULTS: Filapixant at doses ≥ 80 mg significantly reduced cough frequency and severity and improved cough health-related quality of life. Reductions in 24-h cough frequency over placebo ranged from 17% (80 mg dose) to 37% (250 mg dose), reductions over baseline from 23% (80 mg) to 41% (250 mg) (placebo: 6%). Reductions in cough severity ratings on a 100-mm visual analog scale ranged from 8 mm (80 mg) to 21 mm (250 mg). No serious or severe adverse events or adverse events leading to discontinuation of treatment were reported. Taste-related adverse events occurred in 4%, 13%, 43%, and 57% of patients treated with filapixant 20, 80, 150, and 250 mg, respectively, and in 12% treated with placebo. CONCLUSIONS: Filapixant proved to be efficacious, safe, and-apart from the occurrence of taste disturbances, especially at higher dosages-well tolerated during the short therapeutic intervention. Clinical trial registration EudraCT, eudract.ema.europa.eu, 2018-000129-29; ClinicalTrials.gov, NCT03535168

Percentile indices for assessing changes in heavy precipitation events

Many climate studies assess trends and projections in heavy precipitation events using precipitation percentile (or quantile) indices. Here we investigate three different percentile indices that are commonly used. We demonstrate that these may produce very different results and thus require great care with interpretation. More specifically, consideration is given to two intensity-based indices and one frequency-based index, namely (a) all-day percentiles, (b) wet-day percentiles, and (c) frequency indices based on the exceedance of a percentile threshold. Wet-day percentiles are conditionally computed for the subset of wet events (with precipitation exceeding some threshold, e.g. 1 mm/d for daily precipitation). We present evidence that this commonly used methodology can lead to artifacts and misleading results if significant changes in the wet-day frequency are not accounted for. Percentile threshold indices measure the frequency of exceedance with respect to a percentile-based threshold. We show that these indices yield an assessment of changes in heavy precipitation events that is qualitatively consistent with all-day percentiles, but there are substantial differences in quantitative terms. We discuss the reasons for these effects, present a theoretical assessment, and provide a series of examples using global and regional climate models to quantify the effects in typical applications. Application to climate model output shows that these considerations are relevant to a wide range of typical climate-change applications. In particular, wet-day percentiles generally yield different results, and in most instances should not be used for the impact-oriented assessment of changes in heavy precipitation events

The association between reduced knee joint proprioception and medial meniscal abnormalities using MRI in knee osteoarthritis: results from the Amsterdam osteoarthritis cohort.

BACKGROUND: Osteoarthritis (OA) of the knee is characterized by pain and activity limitations. In knee OA, proprioceptive accuracy is reduced and might be associated with pain and activity limitations. Although causes of reduced proprioceptive accuracy are divergent, medial meniscal abnormalities, which are highly prevalent in knee OA, have been suggested to play an important role. No study has focussed on the association between proprioceptive accuracy and meniscal abnormalities in knee OA. OBJECTIVE: To explore the association between reduced proprioceptive accuracy and medial meniscal abnormalities in a clinical sample of knee OA subjects. METHODS: Cross-sectional study in 105 subjects with knee OA. Knee proprioceptive accuracy was assessed by determining the joint motion detection threshold in the knee extension direction. The knee was imaged with a 3.0 T magnetic resonance (MR) scanner. Number of regions with medial meniscal abnormalities and the extent of abnormality in the anterior and posterior horn and body were scored according to the Boston-Leeds Osteoarthritis Knee Score (BLOKS) method. Multiple regression analyzes were used to examine whether reduced proprioceptive accuracy was associated with medial meniscal abnormalities in knee OA subjects. RESULTS: Mean proprioceptive accuracy was 2.9degree + 1.9degree. Magnetic resonance imaging (MRI)-detected medial meniscal abnormalities were found in the anterior horn (78%), body (80%) and posterior horn (90%). Reduced proprioceptive accuracy was associated with both the number of regions with meniscal abnormalities (P < 0.01) and the extent of abnormality (P = 0.02). These associations were not confounded by muscle strength, joint laxity, pain, age, gender, body mass index (BMI) and duration of knee complaints. CONCLUSION: This is the first study showing that reduced proprioceptive accuracy is associated with medial meniscal abnormalities in knee OA. The study highlights the importance of meniscal abnormalities in understanding reduced proprioceptive accuracy in persons with knee OA. Copyright 2013 Osteoarthritis Research Society International. All rights reserve

Training specialists to write appropriate reply letters to general practitioners about patients with medically unexplained physical symptoms; A cluster-randomized trial.

Objective: To evaluate effects of a communication training for specialists on the quality of their reply letters to general practitioners (GPs) about patients with medically unexplained physical symptoms (MUPS). Methods: Before randomization, specialists included ≤3 MUPS patients in a multi-center cluster-randomized trial. In 14 h of MUPS-specific communication training, 2.5 h focused on reply letters. Letters were discussed with regard to reporting and answering GPs' referral questions and patients' questions, and to reporting findings, explaining MUPS with perpetuating factors and giving advice. After the training, all doctors again included ≤3 MUPS patients. Reply letters to GPs were assessed for quality and blindly rated on a digital scale. Results: We recruited 478 MUPS patients and 123 specialists; 80% of the doctors wrote ≥1 reply letters, 285 letters were assessed. Trained doctors reported (61% versus 37%, OR=2.55, F(1281)=6.60, pgroup*time=.01) and answered (63% versus 33%, OR=3.31, F(1281)=5.36, pgroup*time=.02) patients' questions more frequently than untrained doctors. Conclusion: Training improves reply letters with regard to patients' questions, but not with regard to the following: GPs' referral questions, somatic findings, additional testing, explaining, and advice. Practice implications: Training specialists to write appropriate reply letters needs more focus on explanation and advice