scholarly journals CFTR Modulators: Does One Dose Fit All?

2021 ◽  
Vol 11 (6) ◽  
pp. 458
Author(s):  
Renske van der Meer ◽  
Erik B. Wilms ◽  
Harry G.M. Heijerman
Keyword(s):  
Cystic Fibrosis ◽  
Drug Exposure ◽  
Individual Effect ◽  
Group Level ◽  
Improve Treatment ◽  
Exposure Response ◽  
Pharmacokinetic Properties ◽  
Dosing Regimens ◽  
The Individual ◽  
Cftr Modulators

For many people with cystic fibrosis (pwCF), CFTR modulators will be the cornerstone of their treatment. These modulators show robust treatment effects at group level in pwCF with specific mutations. The individual effect however, is variable. In this review we will explain reasons for reconsideration of dosing regimens of CFTR modulating therapy in order to improve treatment response and prevent side effects. Since the effect of a drug depends on pharmacodynamics and pharmacokinetics, pharmacodynamics and pharmacokinetic properties of CFTR modulators will be discussed. Pharmacokinetic-pharmacodynamic relationships will be used to gain insight in dosage response and exposure response relationships. To understand the cause of variation in drug exposure, pharmacokinetic properties that may change due to CF disease will be explained. We show that with current insight, there are conceivable situations that give reason for reconsideration of dosing regimens, however many questions need to be unravelled.

QUALITY OF INDIVIDUAL AND GROUP LEVEL INTERVENTIONS FOR FIRST EPISODE PSYCHOSIS AT THE TERTIARY PSYCHIATRIC HOSPITAL IN UGANDA.

2020 ◽  
Author(s):  
Emmanuel Kiiza Mwesiga ◽  
Noeline Nakasujja ◽  
Lawrence Nankaba ◽  
Juliet Nakku ◽  
Seggane Musisi
Keyword(s):  
Psychiatric Hospital ◽  
Psychotic Disorders ◽  
First Episode Psychosis ◽  
First Episode ◽  
Group Level ◽  
Group Interventions ◽  
Episode Psychosis ◽  
Essential Components ◽  
The Individual

Introduction: Individual and group level interventions have the largest effect on outcomes in patients with the first episode of psychosis. The quality of these individual and group level interventions provided to first-episode psychosis patients in Uganda is unclear.Methods: The study was performed at Butabika National Psychiatric Teaching and referral hospital in Uganda. A retrospective chart review of recently discharged adult in-patients with the first episode of psychosis was first performed to determine the proportion of participants who received the different essential components for individual and group level interventions. From the different proportions, the quality of the services across the individual and group interventions was determined using the first-Episode Psychosis Services Fidelity Scale (FEPS-FS). The FEPS-FS assigns a grade of 1-5 on a Likert scale depending on the proportion of patients received the different components of the intervention. Results: The final sample included 156 first-episode psychosis patients. The median age was 27 years [IOR (24-36)] with 55% of participants of the female gender. 13 essential components across the individual and group interventions were assessed and their quality quantified. All 13 essential components had poor quality with the range of scores on the FEPS-FS of 1-3. Only one essential component assessed (use of single antipsychotics) had moderate quality.Discussion: Among current services at the National psychiatric hospital of Uganda, the essential for individual and group level interventions for psychotic disorders are of low quality. Further studies are required on how the quality of these interventions can be improved.

Reply to Connor and Evers (2020): Critique of the Bias of Crowds Model Simply Restates the Model

2020 ◽  
Author(s):  
Keith Payne ◽  
Heidi A. Vuletich ◽  
Kristjen B. Lundberg
Keyword(s):  
Implicit Bias ◽  
Group Level ◽  
Systemic Racism ◽  
Individual Level ◽  
The Core ◽  
Psychological Science ◽  
Implicit Biases ◽  
The Individual

The Bias of Crowds model (Payne, Vuletich, & Lundberg, 2017) argues that implicit bias varies across individuals and across contexts. It is unreliable and weakly associated with behavior at the individual level. But when aggregated to measure context-level effects, the scores become stable and predictive of group-level outcomes. We concluded that the statistical benefits of aggregation are so powerful that researchers should reconceptualize implicit bias as a feature of contexts, and ask new questions about how implicit biases relate to systemic racism. Connor and Evers (2020) critiqued the model, but their critique simply restates the core claims of the model. They agreed that implicit bias varies across individuals and across contexts; that it is unreliable and weakly associated with behavior at the individual level; and that aggregating scores to measure context-level effects makes them more stable and predictive of group-level outcomes. Connor and Evers concluded that implicit bias should be considered to really be noisily measured individual construct because the effects of aggregation are merely statistical. We respond to their specific arguments and then discuss what it means to really be a feature of persons versus situations, and multilevel measurement and theory in psychological science more broadly.

The Epistemology of Groups

2020 ◽  
Author(s):  
Jennifer Lackey
Keyword(s):  
Group Level ◽  
Social Significance ◽  
Individual Group ◽  
Key Concepts ◽  
Normative Requirements ◽  
Group Members ◽  
The Individual ◽  
Belief Justification ◽  
In Virtue Of ◽  
Trump Administration

Groups are often said to bear responsibility for their actions, many of which have enormous moral, legal, and social significance. The Trump Administration, for instance, is said to be responsible for the U.S.’s inept and deceptive handling of COVID-19 and the harms that American citizens have suffered as a result. But are groups subject to normative assessment simply in virtue of their individual members being so, or are they somehow agents in their own right? Answering this question depends on understanding key concepts in the epistemology of groups, as we cannot hold the Trump Administration responsible without first determining what it believed, knew, and said. Deflationary theorists hold that group phenomena can be understood entirely in terms of individual members and their states. Inflationary theorists maintain that group phenomena are importantly over and above, or otherwise distinct from, individual members and their states. It is argued that neither approach is satisfactory. Groups are more than their members, but not because they have “minds of their own,” as the inflationists hold. Instead, this book shows how group phenomena—like belief, justification, and knowledge—depend on what the individual group members do or are capable of doing while being subject to group-level normative requirements. This framework, it is argued, allows for the correct distribution of responsibility across groups and their individual members.

scholarly journals Examining the Effects of Three Group-Level Metacognitive Scaffoldings on In-Service Teachers’ Knowledge Building

2021 ◽  
pp. 073563312110308
Author(s):  
Fan Ouyang ◽  
Si Chen ◽  
Yuqin Yang ◽  
Yunqing Chen
Keyword(s):  
Small Groups ◽  
Mixed Method ◽  
Peer Interactions ◽  
Knowledge Building ◽  
Group Level ◽  
Question Asking ◽  
Individual Level ◽  
The Individual ◽  
Task Oriented ◽  
Metacognitive Scaffolding

Group-level metacognitive scaffolding is critical for productive knowledge building. However, previous research mainly focuses on the individual-level metacognitive scaffoldings in helping learners improve knowledge building, and little effort has been made to develop group-level metacognitive scaffolding (GMS) for knowledge building. This research designed three group-level metacognitive scaffoldings of general, task-oriented, and idea-oriented scaffoldings to facilitate in-service teachers’ knowledge building in small groups. A mixed method is used to examine the effects of the GMSs on groups’ knowledge building processes, performances, and perceptions. Results indicate a complication of the effects of GMSs on knowledge building. The idea-oriented scaffolding has potential to facilitate question-asking and perspective-proposing inquiry through peer interactions; the general scaffolding does not necessarily lessen teachers’ idea-centered explanation and elaboration on the individual level; the task-oriented scaffolding has the worst effect. Pedagogical and research implications are discussed to foster knowledge building with the support of GMSs.

scholarly journals Which Analysis Approach Is Adequate to Leverage Clinical Microdialysis Data? A Quantitative Comparison to Investigate Exposure and Reponse Exemplified by Levofloxacin

2021 ◽  
Author(s):  
David Busse ◽  
André Schaeftlein ◽  
Alexander Solms ◽  
Luis Ilia ◽  
Robin Michelet ◽  
...  
Keyword(s):  
Drug Exposure ◽  
Visual Predictive Check ◽  
Model Performance ◽  
Compartmental Analysis ◽  
Community Acquired Pneumonia ◽  
Target Site ◽  
Clinical Pharmacokinetics ◽  
Time Integral ◽  
Dosing Regimens ◽  
Therapeutic Decision Making

Abstract Purpose Systematic comparison of analysis methods of clinical microdialysis data for impact on target-site drug exposure and response. Methods 39 individuals received a 500 mg levofloxacin short-term infusion followed by 24-h dense sampling in plasma and microdialysate collection in interstitial space fluid (ISF). ISF concentrations were leveraged using non-compartmental (NCA) and compartmental analysis (CA) via (ii) relative recovery correction at midpoint of the collection interval (midpoint-NCA, midpoint-CA) and (ii) dialysate-based integrals of time (integral-CA). Exposure and adequacy of community-acquired pneumonia (CAP) therapy via pharmacokinetic/pharmacodynamic target-attainment (PTA) analysis were compared between approaches. Results Individual AUCISF estimates strongly varied for midpoint-NCA and midpoint-CA (≥52.3%CV) versus integral-CA (≤32.9%CV) owing to separation of variability in PK parameters (midpoint-CA = 46.5%–143%CVPK, integral-CA = 26.4%–72.6%CVPK) from recovery-related variability only in integral-CA (41.0%–50.3%CVrecovery). This also led to increased variability of AUCplasma for midpoint-CA (56.0%CV) versus midpoint-NCA and integral-CA (≤33.0%CV), and inaccuracy of predictive model performance of midpoint-CA in plasma (visual predictive check). PTA analysis translated into 33% of evaluated patient cases being at risk of incorrectly rejecting recommended dosing regimens at CAP-related epidemiological cut-off values. Conclusions Integral-CA proved most appropriate to characterise clinical pharmacokinetics- and microdialysis-related variability. Employing this knowledge will improve the understanding of drug target-site PK for therapeutic decision-making.

Discovery of CFTR modulators for the treatment of cystic fibrosis

2021 ◽  
pp. 1-17
Author(s):  
Miquéias Lopes-Pacheco ◽  
Nicoletta Pedemonte ◽  
Guido Veit
Keyword(s):  
Cystic Fibrosis ◽  
Cftr Modulators

scholarly journals Comparative physical activity as a global question to assess physical activity among university students

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Katharina Diehl ◽  
Alessia Brassat ◽  
Jennifer Hilger-Kolb
Keyword(s):  
Physical Activity ◽  
University Students ◽  
Online Survey ◽  
Group Level ◽  
Comparative Measurement ◽  
Cross Sectional ◽  
Physically Active ◽  
Comparative Optimism ◽  
Individual Assessment ◽  
The Individual

Abstract Background To assess physical activity (PA), a comparative measurement – evaluating one’s own PA compared to others – may be an appropriate method. In previous studies, the use of comparative measurements led to an effect known as unrealistic comparative optimism (UCO) – people being unrealistically optimistic about their behavior. Our aim was to use this comparative measurement in university students to quantify the prevalence of UCO at the group level and to draw conclusions on its validity. Methods We used data from the Nutrition and Physical Activity in Adolescence Study (NuPhA), a cross-sectional online survey that included only self-reports (n = 689). To assess PA among students, they were asked to rate their PA level compared to that of their same-aged fellow students. In addition, we used the Godin-Shephard leisure-time PA questionnaire and other questions on PA for comparisons. We used bivariate and cluster-based analyses to identify potential UCO. Results We found that UCO at the group level led to an uneven distribution, with a higher proportion of students who rated themselves as being more physically active than average. However, the individual assessment of PA with a single and simple comparative question seemed to be valid. Discussion A global single comparative question seems useful for studies where PA is measured as a covariate in university students.

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