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**Background:** For patients with locally advanced or metastatic urothelial carcinoma (la/mUC), prognosis is poor and effective treatment options are limited. Erdafitinib is an oral fibroblast growth factor receptor (FGFR) kinase inhibitor approved by the FDA for the treatment of adults with la/mUC harboring FGFR alterations whose disease progressed following at least 1 prior line of therapy, including a PD-1 or PD-L(1) inhibitor, based on the phase 3, randomized THOR trial (NCT03390504, Cohort 1). **Objective:** To compare the efficacy and safety of erdafitinib vs enfortumab vedotin-ejfv (EV) in the absence of head-to-head comparison via an anchored matching-adjusted indirect comparison (MAIC). **Methods:** An anchored MAIC was conducted according to the National Institute for Health and Care Excellence Decision Support Unit guidance, with physician’s choice of chemotherapy (docetaxel/paclitaxel and vinflunine) as the common comparator. Individual patient data from THOR were adjusted to match published key eligibility criteria and average baseline characteristics of EV-301, such as Bellmunt risk score, liver or visceral metastases, primary site, among others. Erdafitinib was then indirectly compared with EV using the relative treatment effects for the reweighted THOR population and those published for EV-301. **Results:** After matching, the effective sample size for THOR was 126 patients. The MAIC-recalculated hazard ratio (95% credible interval) for erdafitinib vs EV was 0.92 (0.54, 1.57) for overall survival and 0.93 (0.55, 1.56) for progression-free survival, yielding Bayesian probabilities of erdafitinib being better than EV of 62.1% and 60.5%, respectively. For response outcomes, the MAIC-recalculated risk ratio was 1.49 (0.56, 3.90) for confirmed objective response rate and 2.89 (0.27, 30.33) for confirmed complete response with probabilities of 72.6% and 81.3% for erdafitinib being better than EV, respectively. For safety, MAIC-yielded risk ratios of 1.09 (0.99, 1.21) for any treatment-related adverse events, 0.86 (0.57, 1.28) for grade 3+ TRAEs, and 1.02 (0.98, 1.06) for any treatment-emergent adverse events. **Conclusion:** The MAIC indicates comparable efficacy of erdafitinib vs EV for overall survival and progression-free survival, with erdafitinib showing a higher probability of achieving deep responses. While erdafitinib is associated with slightly more adverse events compared with EV, these events seem to be less severe.

Abstract Aims To outline the extent to which practice owners in Dutch oral healthcare practices (OHPs) use a directive and supportive leadership styles, to map out which goals practice owners in Dutch OHPs consider most important when choosing collaboration within the practice and to identify the reasons why oral healthcare professionals choose to engage in collaborative practice. Materials and methods A survey involving 802 general dental practitioners, dental hygienists, and prevention assistants was conducted. The questionnaire covered, among other subjects, leadership styles and reasons for collaboration. Data analysis included descriptive statistics, chi-square tests, one-way ANOVA, linear regression, and logistic regression. Results Compared to employees, practice owners ascribe to themselves more characteristics of both directive and supportive leadership. The most frequently mentioned reasons for choosing a practice form that involves collaboration were the possibilities to provide the best care and the desire to focus on prevention. Healthcare providers chose to work in a collaborative practice for several reasons, which were associated with profession, age and gender. Conclusions The degree of directive and supportive leadership among practice owners in dental care practices in the Netherlands showed a strong correlation. The most frequently mentioned reasons for choosing collaboration were related to healthcare content.

Background: Communication difficulties are common in people with dementia, and often present from an early stage. However, direct treatment options for people with dementia that positively influence their daily communication are scarce. Aims: To evaluate the potential impact and feasibility of a personalized logopaedic intervention. Methods & Procedures: A total of 40 community-dwelling persons with dementia and their caregivers were recruited. Five experienced speech and language therapists (SLTs) delivered the six-session Com-mens intervention at home. Com-mens aims to improve positive communication between people with dementia and their primary caregivers and comprises five elements: interactive history-taking, dynamic observational assessment, education about the consequences of dementia on communication, development and use of personalized communication tools, use motivational, and person-centred strategies by the SLT. We conducted a single-group mixed-methods pilot study with five measurements: baseline, directly after intervention, and at 3, 6 and 9 months follow-up. Semi-structured interviews and questionnaires for Experienced Communication in Dementia, quality of life, psychological well-being and caregiver burden were conducted. Process evaluation was performed by interviewing participants, drop-outs, SLTs and other stakeholders. Outcomes & Results: A total of 32 dyads completed the intervention. Repeated measures analyses revealed no significant changes over time. In the interviews, participants reported a positive impact on their feelings, increased communication skills and better coping with the diagnosis. Participants would recommend the intervention to others. Facilitators were timely delivery, personalized content and adequate reimbursement. Barriers were unfamiliarity with Com-mens among referrers, an overburdened caregiver or disrupted family relationships. Conclusions & Implications: This newly developed logopaedic intervention is feasible and has a perceived positive impact on both people with dementia and their caregivers, which is confirmed by a stable pattern over a period of 1 year. Future comparative studies are needed to test the effectiveness of personalized interventions in this patient population.

In the fall of 2020, two teacher educators conducted a qualitative study to better understand how 14 female undergraduate, early childhood education teacher candidates completing student teaching at a large public university in a Midwestern state, navigated student teaching during a global pandemic. Analyzing data from transcripts of regularly submitted teaching reflections, we examined how these novice educators perceived and reacted to this situation, to determine the influence of this unique event on their professional growth. Findings revealed that while some elements of student teaching appeared similar to the experience of candidates completing student teaching in earlier times, these candidates' experience was colored by the unavoidable challenges of a global pandemic, including altered instructional experiences, professional interactions, student relationships, and pedagogical options. Because candidates student teaching during the pandemic had such different experiences than their earlier counterparts, a traditional menu of learning opportunities and mentoring will likely be insufficient to meet their varied development requirements as new teachers. It will be critical to scrutinize the skills, knowledge base, and emotional perspectives of each early career educator and to create individualized development and support plans that build on the unique opportunities and challenges they will carry into their first teaching positions.

IntroductionPeople with dementia and their carers experience social stigma and often refrain from social participation. Significant improvement might be achieved by creating Dementia Friendly communities (DFCs) for which dementia friendly initiatives (DFIs) are needed. DFIs are developed by a variation of stakeholders. However, people with dementia and their carers are often unrepresented herein. This study aims to get insight into the perspectives of stakeholders (e.g., health- and social care professionals, volunteers, people with dementia and their carers) about the involvement of people with dementia and their carers during the development and sustainment of DFIs.MethodsDescriptive qualitative study, using a co-research design with a carer as co-researcher. Nineteen semi-structured interviews with stakeholders, including people with dementia and their carers, were performed. Inductive content analysis took place using Atlas Ti.ResultsFour themes were found: 1) the involvement of people with dementia and their carers is important for both people with dementia and their carers and other stakeholders; 2) personal character traits, life histories, and associated emotions evoke the need for involvement; 3) involvement requires an open, responsive stance and building relationships; and 4) the estimation of one’s own and others’ capacities influences perspectives on involvement. As such, practice what you preach means actively adopting an open, responsive approach and acknowledging the unique abilities and backgrounds of people with dementia and their carers. It emphasizes the importance of actually living by the values you advocate for.ConclusionCentral to perspectives on involving people with dementia and their carers is the emphasis on working relationally, differing from service-led and pre-structured patient and public involvement (PPI). Working relationally calls for organizational shifts aligned with a rights-based perspective to avoid tokenism, and promotion of user-led organizations with genuine partnerships. Creative methods, problem-solving, and communication skills are essential for the development and sustainment of inclusive, supportive, person-centered DFIs. Future studies should explore the long-term impact of the involvement and working relationally on the well-being of people with dementia and their carers.

An increasingly relevant functional measurement is a liquid biopsy to assist in the diagnosis of cancers. The existing approach for liquid biopsy is to utilize microfluidic chips for the isolation of circulating tumor cells (CTCs) or exosomes or extracellular vesicles (EV) from patient samples, and then for the analysis of the cargo contained inside the CTCs, exosomes or EVs. However, such an analysis does not provide a real-time liquid biopsy, since there is a long delay between the time of sample collection and the results from the analysis. Microfluidic chip-formats also provide the capability to mimic tissue functions from the analysis of small numbers of cells cultured in the chip. Analysis of the secreted molecules from such cells could provide a measurement of the secretome, which could be analogous to a liquid biopsy. A 3D structural organization of cells in microfluidic chips is usually in the form of organoids or spheroids. The analysis of organoids or spheroids is well-adapted for immunohistochemistry or ELISA-type identification of surface markers, but not for real-time analysis of secreted molecules since the fluid and molecules in the interior volume of the organoid or spheroid is not accessible in real-time. We have recently proposed an alternative novel design for a microfluidic chip format comprising 3D micro-niches that provide a real-time analysis of secretions produced directly from small numbers of cells. The microfluidic chip with 3D micro-niches then analyses the secretions from these monolayers in real-time (“secretome”). The microfluidic chip includes electronic biosensors that provide real-time measurement of secreted molecules. This short review concludes with a proposition for the means to utilize this novel microfluidic chip to function as a real-time and quantifiable diagnostic screening device to differentiate cancerous cells from healthy cells.

During the COVID-19 pandemic, laboratory research was not possible in different educational programs at Delft University of Technology and Erasmus University Medical Center due to the taken measures. Therefore, a team of faculty from both institutions developed an alternative transdisciplinary research group project that was fully performed online. The overall project was named the Corona Research Super Project. This project provided an opportunity for students to fulfil the requirements for their degree while complying with the guidelines of the University, Medical Center, and government. It also gave them an opportunity to participate in something that felt meaningful during a stressful time since all sub-projects contributed to developing knowledge on the current COVID-19 pandemic. This article describes the process of setting up this educational project, the resources provided to the students, and the format of transdisciplinary work. Furthermore, it also provides a theoretical view on how to think about research projects when you cannot be side by side in a laboratory and how to make this into meaningful research education. By sharing our experience of setting up this program in unprecedented times and providing a format, we hope that other universities will use this approach to develop comparable transdisciplinary educational programs. We believe that these sorts of programs are essential for in depth transdisciplinary training of scientists of the future

The aims of this study were to investigate the relationship between self-reported preventive and curative orientations of general dental practitioners (GDPs) and the oral healthcare services (OHS) they provided to patients under 18-years-old. And in addition, to determine which patient, GDP, and dental practice characteristics predicted the provision of preventive and curative care. GDPs in the Netherlands using dental software program Exquise (>2,000) were invited to participate in this study voluntarily. Participants completed a web-based questionnaire on characteristics of themselves, their dental practices, and on 20 hypothetical clinical situations concerning caries management. Based on their responses GDPS were classified for their preventive orientation, and their curative orientation. Data on the OHS provided to their young patients over the period 2013-2017 were automatically extracted from the patient files. Based on the annual frequency of provided care to regular patients over a period of 4 or 5 years, this was converted into 3 longitudinal care patterns regarding prevention and 3 longitudinal care patterns regarding curative care. Multinomial logistic regression analyses were conducted with a multilevel approach to correct for dental practices. The 37 participating GDPs provided data for 16,229 young patients. There was not a significant relationship between self-reported preventive orientations and preventive care patterns. The self-reported middle curative orientation was a predictor of the care pattern 'curative treatment(s) in 1 year' (OR 1.23 compared to nu curative treatments; 95% CI 1.02-1.48). The self-reported high curative orientation was a predictor of 'curative treatments in several years' (OR 1.90; 95% CI 1.27-2.85). Common characteristics predicting (p

General dental practitioners (GDPs) differ in the preventive and curative care they provide to their young patients. This may be related to variation in the caries risk of patients, but also to differing opinions among GDPs about 'proper care'. Longitudinal data offers the possibility to make care patterns of GDPs comparable and to reveal possible treatment variation between GDPs. GDPs who participated in this study delivered data on the oral healthcare services (OHS) they provided to young patients during the period 2013-2017. Subsequently, data from patients who received regular OHS for 4 to 5 years were used in the analyses. Based on this, longitudinal preventive and curative care patterns were distinguished. Patients were divided into 3 preventive care patterns: no prevention, occasional prevention, and regular prevention. Furthermore, 3 curative care patterns were distinguished: no curation, curation in 1 year, and curation in several years. These care patterns were then combined. In addition, patients were classified into caries risk categories based on the caries-related treatments they received over a 2-year period: low (no procedures), elevated (1 procedure), and high (2 or more procedures). The caries risk based on the first 2 years and the last 2 years in the dataset were combined into a longitudinal caries risk profile. The most frequent combined care pattern (35.8%) was no curation and occasional or regular prevention. The most common longitudinal caries risk profile was low at beginning and end (45.2%). Dental practices varied considerably in the distribution of curative and preventive care patterns. Thereby, no relationship was shown between curative care patterns and provided preventive care. There was also a large spread in the provided OHS within the various caries risk profiles. These diversities indicated treatment variation between GDPs, which is unwarranted if less or more care is provided than necessary.

Background: Machine learning is becoming a common tool in monitoring emotion. However, methodological studies of the processing pipeline are scarce, especially ones using subjective appraisals as ground truth. New method: A novel protocol was used to induce cognitive load and physical discomfort, and emotional dimensions (arousal, valence, and dominance) were reported after each task. The performance of five common ML models with a versatile set of features (physiological features, task performance data, and personality trait) was compared in binary classification of subjectively assessed emotions. Results: The psychophysiological responses proved the protocol was successful in changing the mental state from baseline, also the cognitive and physical tasks were different. The optimization and performance of ML models used for emotion detection were evaluated. Additionally, methods to account for imbalanced classes were applied and shown to improve the classification performance. Comparison with existing method(s): Classification of human emotional states often assumes the states are determined by the stimuli. However, individual appraisals vary. None of the past studies have classified subjective emotional dimensions with a set of features including biosignals, personality and behavior. Conclusion: Our data represent a typical setup in affective computing utilizing psychophysiological monitoring: N is low compared to number of features, inter-individual variability is high, and class imbalance cannot be avoided. Our observations are a) if possible, include features representing physiology, behavior and personality, b) use simple models and limited number of features to improve interpretability, c) address the possible imbalance, d) if the data size allows, use nested cross-validation.

Abstract Background The Observable Movement Quality scale for patients with low back pain (OMQ-LBP) is a newly developed measurement instrument for use in primary care settings of physical and exercise therapists to assess movement quality (MQ) of patients with low back pain (LBP). Objective This study aims to determine validity, reliability and feasibility of the OMQ-LBP. The OMQ-LBP consists of a standardized movement circuit (performed twice) consisting of five daily activities problematic for LBP patients, which are scored with an 11-item observation list. Methods Construct validity was determined by testing seven hypotheses on associations between constructs (n = 85 patients with LBP) and four hypotheses on known group differences (n = 85 patients with LBP and n = 63 healthy controls; n = 35 matched participant-patients having VAS-pain ≥ 20 mm during and/or after both circuits and healthy controls). Internal consistency was analyzed with Cronbach’s alpha (n = 85 patients with LBP). For inter- and intra-rater reliability Intraclass Correlation Coefficient (ICC) values were examined (n = 14 therapists: seven primary care physical therapists and seven exercise therapists). Additionally, content validity and feasibility were determined using thematic analysis of a brief interview with participants, patients (n = 38) and therapists (n = 14). Results After Bonferroni correction 2/7 associations between constructs and 2/4 significant group differences were confirmed. Cronbach’s alpha was 0,79. The ICC-values of interrater reliability of the OMQ-LBP total score and the duration score were 0.56 and 0.99 and intra-rater reliability 0.82 and 0,93, respectively. Thematic analysis revealed five themes. Three themes elucidate that both patients and therapists perceived the content of the OMQ-LBP as valid. The fourth theme exhibits that OMQ-LBP provides a clear and unambiguous language for MQ in patients with LBP. Theme 5 depicts that the OMQ-LBP seems feasible, but video recording is time-consuming. Conclusions The OMQ-LBP is a promising standardized observational assessment of MQ during the five most problematic daily activities in patients with LBP. It is expected that uniform and objective description and evaluation of MQ add value to clinical reasoning and facilitate uniform communication with patients and colleagues.

RESUMENA partir de los resultados obtenidos de los ensayos en modelo de las turbinas de Salto Grande, se observó que, debido a la incertidumbre con que se miden las diferentes magnitudes significativas en la operación de la central hidroeléctrica, el rendimiento de la turbina sería menor que el correspondiente a la combinatoria, es decir, al que resultaría de la combinación óptima de ángulo de pala y apertura del distribuidor. Se consideraron reducciones en la incertidumbre del salto neto de 50 cm a menos de 1 cm y en la medición del ángulo de pala de 0.4° a 0.11°. En virtud de estas reducciones de la incertidumbre de la medición, el rendimiento mínimo de cada turbina se incrementaría hasta en 0.78%, mientras que el rendimiento medio podría hacerlo hasta en 0.39%. Estos incrementos en el rendimiento podrían dar lugar a un aumento en el orden de los 3,5 millones de dólares en el ingreso anual de producción, siendo los principales aportes la reducción de la incertidumbre en la medición del salto neto y del ángulo de pala. Puesto que el error aleatorio en la medición del ángulo de pala del rotor podría ser elevado, incluso reduciendo la incertidumbre en el salto se podría tener rendimientos aún menores a los estimados previamente. En caso de reducir la incertidumbre en la fijación del ángulo de pala entre 1 ° y 0.1 ° se podría esperar un incremento en los ingresos, por venta al sistema de margen izquierda, de 1.4%.

Increasingly alarmed by instructional mandates more founded on journalistic rhetoric and popular opinion than on research findings or practitioner expertise, researchers gathered survey data from teachers to better understand the status of K-2 phonics instruction. Data demonstrate that the overwhelming majority of these K-2 teachers teach phonics, rely on a published curriculum, and teach phonics in systematic and explicit ways. These findings contradict media assertions that reading classrooms are largely devoid of phonics instruction and that teachers fail to include phonics as an important element of their reading instruction. Implications include calls for researchers to explore what teachers can share that helps us better understand what happens in the name of classroom phonics instruction and for decision makers to assume an informed stance before mandating instructional practices based on a narrow understanding of the needs of young readers and the teachers who support them.