Exploring a revised interprofessional learning curriculum in undergraduate health education programs at Linköping University.

BACKGROUND: Interprofessional education aiming at providing competencies require evaluation in order to ensure that outcomes match the needs and ambitions. Health professionals today need a broad range of skills and competencies in order to provide high quality care, including interprofessional competence. Linköping University has been a pioneer in interprofessional learning for decades and this study provides one example of how a curriculum revision can be carried out. The aim of this study was to study the intentions and outcomes of a revised interprofessional learning curriculum in health professions education programs. METHODS: This was a qualitative study, including documents (n = 143) and complementary interviews with key individuals (n = 4). Data included syllabuses, study guides, educational program plans, supervisor guides, and interview transcripts. A qualitative document analysis and a content analysis with a directed approach was used, applying a theoretical framework for curriculum development that guided the analysis. RESULTS: The analysis resulted in one overarching theme named "A planned, lived, and attended curriculum" including four main categories inspired by a theoretical framework. The findings demonstrate a variety of aspects relating to the why and how of curriculum revision. The introduction of a programme director in interprofessional learning, with a mandate equal to respective program directors, seemed to contribute to legitimacy. Further, the partnership between the university and the healthcare sector had an impact on the curriculum revision, in that healthcare had a say in the revision regarding what suggestions to implement or not. The expectations of the teachers involved were high, although clear support structures seemed to be lacking. CONCLUSIONS: This study has identified some of the important links between teachers, organizational prerequisites, and healthcare when revising an existing fully integrated curriculum in interprofessional learning for health professions education programs. The aim of this curriculum revision was to legitimize and provide education that is up to date with current healthcare needs and to provide students with competencies to collaborate in teams to ensure patient safety. When redesigning a curriculum there seems to be a fine balance between pedagogical innovation and pragmatism. This study identified that the links provided between organizational support structures and the expectations on teachers were not aligned.

Hearing and Functioning in Everyday Life Questionnaire: Psychometric Evaluation and Revision.

PURPOSE: The aim of the current study was to explore the construct validity and internal consistency reliability of the International Classification of Functioning, Disability and Health (ICF)-based original English version of the Hearing and Functioning in Everyday Life Questionnaire (HFEQ) and to revise the HFEQ based on the results. METHOD: This study used a cross-sectional survey design. The data were collected using an online survey. Adults with self-reported hearing disability (n = 513) from the United States were included. The ICF components of body functions, activity and participation, and environmental factors were tested as the underlying structure of the HFEQ using confirmatory factor analysis and then adjusted by triangulation with previous content validation. RESULTS: The results of the current study confirmed the ICF components of body functions, activity and participation, and environmental factors as underlying constructs of the HFEQ. However, after triangulation with previous content validation, fine adjustments were made. The revised version of the HFEQ includes two removed items and a fine-tuned factor structure. CONCLUSION: The results confirm that the structure of the HFEQ aligns with the ICF, and the overall results indicate that HFEQ has acceptable construct validity and internal consistency.

Folded Alpha Helical Putative New Proteins from Apilactobacillus kunkeei.

The emergence of new proteins is a central question in biology. Most tertiary protein folds known to date appear to have an ancient origin, but it is clear from bioinformatic analyses that new proteins continuously emerge in all organismal groups. However, there is a paucity of experimental data on new proteins regarding their structure and biophysical properties. We performed a detailed phylogenetic analysis and identified 48 putative open reading frames in the honeybee-associated bacterium Apilactobacillus kunkeei for which no or few homologs could be identified in closely-related species, suggesting that they could be relatively new on an evolutionary time scale and represent recently evolved proteins. Using circular dichroism-, fluorescence- and nuclear magnetic resonance (NMR) spectroscopy we investigated six of these proteins and show that they are not intrinsically disordered, but populate alpha-helical dominated folded states with relatively low thermodynamic stability (0-3 kcal/mol). The NMR and biophysical data demonstrate that small new proteins readily adopt simple folded conformations suggesting that more complex tertiary structures can be continuously re-invented during evolution by fusion of such simple secondary structure elements. These findings have implications for the general view on protein evolution, where de novo emergence of folded proteins may be a common event.

Social Insurance Literacy Among the Sick-listed-A Study of Clients' Comprehension and Self-Rated System Comprehensibility of the Sickness Insurance System.

INTRODUCTION: Sickness insurance systems and their processes have been studied in terms of transparency, comprehensibility and fairness, highlighting the importance of just procedures that make sense to clients. Related research demonstrates differences between groups of clients, pointing towards a social gradient. The concept of social insurance literacy and the Social Insurance Literacy Questionnaire (SILQ) was recently developed and serves as a measure for client's ability to obtain, understand and act on information in a sickness insurance system, relating to the comprehensibility of the information that the system provides. OBJECTIVE: The purpose of this study was to investigate social insurance literacy among clients on sick leave and its associations with perceived justice, being granted sickness benefits and background factors. METHODS: This was a questionnaire study with clients on sick leave in Sweden. In the selection process 3993 clients were invited, of which 1173 recently had their sickness benefits withdrawn. Those who answered the SILQ (n = 1152) also answered a perceived justice measure and accepted sharing register data from the Swedish Social Insurance Agency. Data were analyzed through regression analysis. RESULTS: The findings demonstrate that clients' perceptions of system comprehensibility and the status of their sick leave case was significantly associated with perceived justice, and being granted sickness benefits, while their individual abilities to obtain, understand, and act on information had lesser influence. CONCLUSIONS: The system's ability to provide understandable information seems more important than clients' abilities to comprehend it. From a client perspective, a just system seems to be related to their experiences of the sick leave process (i,e., whether they had an ongoing or closed case) rather than their skills to obtain the correct information.

Ischemic Stroke Temporally Associated With New-Onset Atrial Fibrillation: A Population-Based Registry-Linkage Study.

BACKGROUND: Limited data exist on the temporal relationship between new-onset atrial fibrillation (AF) and ischemic stroke and its impact on patients' clinical characteristics and mortality. METHODS: A population-based registry-linkage database includes all patients with new-onset AF in Finland from 2007 to 2018. Ischemic stroke temporally associated with AF (ISTAF) was defined as an ischemic stroke occurring within ±30 days from the first AF diagnosis. Clinical factors associated with ISTAF were studied with logistic regression and 90-day survival with Cox proportional hazards analysis. RESULTS: Among 229 565 patients with new-onset AF (mean age, 72.7 years; 50% female), 204 774 (89.2%) experienced no ischemic stroke, 12 209 (5.3%) had past ischemic stroke >30 days before AF, and 12 582 (5.8%) had ISTAF. The annual proportion of ISTAF among patients with AF decreased from 6.0% to 4.8% from 2007 to 2018. Factors associated positively with ISTAF were higher age, lower education level, and alcohol use disorder, whereas vascular disease, heart failure, chronic kidney disease cancer, and psychiatric disorders were less probable with ISTAF. Compared with patients without ischemic stroke and those with past ischemic stroke, ISTAF was associated with ≈3-fold and 1.5-fold risks of death (adjusted hazard ratios, 2.90 [95% CI, 2.76-3.04] and 1.47 [95% CI, 1.39-1.57], respectively). The 90-day survival probability of patients with ISTAF increased from 0.79 (95% CI, 0.76-0.81) in 2007 to 0.89 (95% CI, 0.87-0.91) in 2018. CONCLUSIONS: ISTAF depicts the prominent temporal clustering of ischemic strokes surrounding AF diagnosis. Despite having fewer comorbidities, patients with ISTAF had worse, albeit improving, survival than patients with a history of or no ischemic stroke. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04645537. URL: https://www.encepp.eu; Unique identifier: EUPAS29845.

Temporal Relation Between Myocardial Infarction and New-Onset Atrial Fibrillation: Results from a Nationwide Registry Study.

Myocardial infarction (MI) and atrial fibrillation (AF) are commonly seen in the same patient. In this study, we evaluated the temporal relations and prognosis of MI and AF. This is a substudy of the nationwide registry-based Finnish Anticoagulation in Atrial Fibrillation (FinACAF) study, comprising all Finnish patients with new-onset AF from 2010 to 2017. Patients with MI and AF were divided into groups depending on the temporal relation between the disease onsets: (1) MI before AF (MIAF), and (4) no MI. The 1-year mortality in the groups were studied with the Cox proportional hazards model. Of the 153,207 patients with new-onset AF (mean age 72.7 years, 50.0% women), 16,265 (10.6%) were diagnosed with MI. Altogether, 8,889 (54.7%) of the patients with MI were in the MIAF group. Of all MIs, 42.2% were diagnosed within 1 year from new-onset AF. The MI>AF group had the worst survival, with an adjusted hazard ratio for death of 3.08 (confidence interval [CI] 2.89 to 3.27) compared with patients without MI. For the MI

The Social Insurance Literacy Questionnaire (SILQ): Development and Psychometric Evaluation.

PURPOSE: For clients to understand social insurance decisions and processes, information from authorities needs to be comprehensible, and clients need sufficient individual abilities. These dimensions are captured by the concept social insurance literacy, which has been operationalized into a measure, the Social Insurance Literacy Questionnaire (SILQ). The aim of this study was to describe the development of the SILQ and evaluate its psychometric properties using Rasch measurement theory. METHODS: The development of the SILQ included a Delphi study and cognitive interviews. A preliminary version, divided on four scales corresponding to the domains of the concept (obtaining information, understanding information, acting on information, and system comprehensibility) was psychometrically evaluated according to Rasch measurement theory, in a survey to a stratified random sample of people on sick leave (n = 1151) sent out in the fall of 2020. RESULTS: Overall, the items in the final version of the SILQ demonstrated good fit to the Rasch model, and the response scale worked as intended. Unidimensionality was supported for all scales, but minor problems with local dependency was detected for three items. The person separation was 0.80 for the Obtain scale, 0.82 for the Understand scale, 0.68 for the Act scale, and 0.81 for the System scale. Corresponding ordinal alpha values were 0.91, 0.91, 0.86, and 0.91, respectively. CONCLUSION: This study is a first step toward exploring literacy in the social insurance field. The SILQ covers individual abilities and systems' comprehensibility, and the results show that it has acceptable psychometric properties.

Patient-Reported Outcome Measures for Hearing Aid Benefit and Satisfaction: Content Validity and Readability.

PURPOSE: Numerous patient-reported outcome measures (PROMs) are available to measure hearing aid benefit and satisfaction. It is unclear to what extent currently available PROMs on hearing aid outcomes, often developed decades ago, meet current guidelines for good content validity and readability. This study evaluated the content validity and readability of PROMs that focus on perceived hearing aid benefit and/or satisfaction. METHOD: A literature review was conducted to identify eligible instruments. Content validity evaluation included mapping extracted questionnaire items to the World Health Organization's International Classification of Functioning, Disability and Health (ICF) framework. In addition, study design in content validity methodology was evaluated using the COnsensus-based Standards for the selection of health Measurement INstruments study design checklist for PROM instruments. Readability was estimated using the Simple Measure of Gobbledygook measure. RESULTS: Thirteen questionnaires were identified and evaluated. Item content focused primarily on the components of environmental factors as well as activity limitations and participation restrictions with less emphasis on body functions and personal factors. The content validity methodology analysis revealed an underuse or lack of reporting of a qualitative methodology in assessing patient and professional perspectives. All the included questionnaires exceeded the recommended sixth-grade reading level. CONCLUSIONS: The categories covered by hearing aid PROMs vary considerably, with no single instrument comprehensively covering all the key ICF components. Future development of hearing aid outcome measures should consider a mixed methodology approach for improved content validity and ensure an appropriate reading level.

Intrinsically Disordered Flanking Regions Increase the Affinity of a Transcriptional Coactivator Interaction across Vertebrates.

Interactions between two proteins are often mediated by a disordered region in one protein binding to a groove in a folded interaction domain in the other one. While the main determinants of a certain interaction are typically found within a well-defined binding interface involving the groove, recent studies show that nonspecific contacts by flanking regions may increase the affinity. One example is the coupled binding and folding underlying the interaction between the two transcriptional coactivators NCOA3 (ACTR) and CBP, where the flanking regions of an intrinsically disordered region in human NCOA3 increases the affinity for CBP. However, it is not clear whether this flanking region-mediated effect is a peculiarity of this single protein interaction or if it is of functional relevance in a broader context. To further assess the role of flanking regions in the interaction between NCOA3 and CBP, we analyzed the interaction across orthologs and paralogs (NCOA1, 2, and 3) in human, zebra fish, and ghost shark. We found that flanking regions increased the affinity 2- to 9-fold in the six interactions tested. Conservation of the amino acid sequence is a strong indicator of function. Analogously, the observed conservation of increased affinity provided by flanking regions, accompanied by moderate sequence conservation, suggests that flanking regions may be under selection to promote the affinity between NCOA transcriptional coregulators and CBP.

Symptoms of eating disorders and low energy availability in recreational active female runners.

Objectives: This retrospective, cross-sectional study aimed to investigate symptoms of eating disorders (EDs) and low energy availability (LEA) among recreational female runners. Methods: Females (18-39 years) (n=89) participating in running group sessions organised by running clubs and companies were recruited via social media and completed an anonymous online survey compromising the Eating Disorder Examination Questionnaire (EDE-Q) and Low Energy Availability in Females Questionnaire (LEAF-Q). An EDE-Q global score ≥2.3 and a LEAF-Q total score ≥8 (in combination with an injury score≥2 and/or menstruation dysfunction score≥4) were used to categorise subjects as having symptoms of EDs and LEA, respectively. Results: Among the subjects fulfilling the age criteria (n=85), 18% (n=15) had symptoms of EDs and 19% (n=16) had symptoms of LEA. Of those with symptoms of EDs, 13% (n=2) had concomitant symptoms of LEA. The higher the EDE-Q dietary restraint score, the higher the gastrointestinal problem score (r=0.23, p=0.04), otherwise no other associations were found between EDE-Q global or subscale scores and LEAF-Q scores. Conclusion: Our results indicate that symptoms of EDs and LEA are frequent among adult females at all athletic levels, including the recreational level. Hence, to prevent the negative health consequences of EDs and LEA, preventative initiatives are also needed in recreational running communities.

Hearing and Functioning in Everyday Life Questionnaire: Development and Validation of an ICF-Based Instrument.

OBJECTIVES: Self-assessment instruments are commonly used in audiological rehabilitation. However, several studies highlight the lack of multidimensionality in existing outcome measures, with the consequence that they only partially capture aspects of functioning in everyday life for people living with hearing loss. This study aimed to develop and investigate the content validity of a self-assessment instrument based on the validated Brief International Classification of Functioning, Disability, and Health Core Set for Hearing Loss. DESIGN: The design was a two-part instrument development study. The first part focused on the item-generation process of the instrument, named the Hearing and Functioning in Everyday Life Questionnaire (HFEQ) during an experts' workshop. The second part focused on international content validation of the instrument using group interviews. Strategic sampling was used and 30 adults with hearing loss from India, South Africa, and the United States participated in the group interviews. RESULTS: The expert's workshop resulted in the first version of the HFEQ containing 30 items. The results from group interviews show that the content of the HFEQ was considered to be valid concerning its relevance, comprehensiveness, and comprehensibility. A majority (73%) of the HFEQ items were perceived by the participants as relevant and easy to comprehend. For the remaining 27% of the items, the content was perceived to be relevant in all countries, but some terms and expressions were reported to require rewording or clearer examples. These modifications will be made in the next step of the development process. CONCLUSION: Content validation of the HFEQ demonstrates promising results, with participants perceiving the content as relevant and comprehensible. Further psychometric validation is required to investigate other psychometric properties, such as construct validity and reliability. The HFEQ has the potential to become a valuable new instrument for assessing everyday functioning in people with hearing loss in audiological rehabilitation and in research.

Challenges of primary health care leadership during the COVID-19 pandemic in Sweden: a qualitative study of managers' experiences.

PURPOSE: At the outbreak of the COVID-19 pandemic, health care was at the centre of the crisis. New demands made existing organizational practices and services obsolete. Primary health care had a great deal of responsibility for COVID-19-related care. The pandemic demanded effective leadership to manage the new difficulties. This paper aims to explore experiences and perceptions of managers in primary health care in relation to their efforts to manage the COVID-19 crisis in their everyday work. DESIGN/METHODOLOGY/APPROACH: The authors used a qualitative approach based on 14 semi-structured interviews with managers in primary health care from four regions in Sweden. The interviews were conducted during September to December 2020. Data were analysed using conventional qualitative content analysis. FINDINGS: Data analysis yielded three categories: lonely in decision-making; stretched to the limit; and proud to have coped. The participants felt lonely in their decision-making, and they were stretched to the limit of their own and the organization's capacity. The psychosocial working conditions in primary care worsened considerably during the pandemic because demands on leaders increased while their ability to control the work situation decreased. However, they also expressed pride that they and their employees had managed the situation by being flexible and having a common focus. ORIGINALITY/VALUE: Looking ahead and using lessons learnt, and apart from making wise decisions under pressure, an important implication for primary health-care leaders is to not underestimate the power of acknowledging the virtues of humanity and justice during a crisis. Continuing professional education for leaders focusing on crisis leadership could help prepare leaders for future crises.

Disordered Regions Flanking the Binding Interface Modulate Affinity between CBP and NCOA.

Recognition motifs that mediate protein-protein interactions are usually embedded within longer intrinsically disordered regions. While binding interfaces involving the recognition motif in such interactions are well studied, less is known about the role of disordered regions flanking the motifs. The interaction between the transcriptional co-activators NCOA3 (ACTR) and CBP is mediated by coupled binding and folding of the two domains CID and NCBD. Here, we used circular dichroism and kinetics to directly quantify the contribution of the adjacent flanking regions of CID to its interaction with NCBD. Using N- and C-terminal combinatorial variants we found that the flanking regions promote binding in an additive fashion while retaining a large degree of disorder in the complex. Experiments at different ionic strengths demonstrated that the increase in affinity is not mediated by electrostatic interactions from the flanking regions. Instead, site-directed mutagenesis and molecular dynamics simulations suggest that binding is promoted by short-lived non-specific hydrophobic contacts between the flanking regions and NCBD. Our findings are consistent with highly frustrated interactions outside of the canonical binding interface resulting in a slightly energetically favorable fuzzy binding. Modulation of affinity via flanking regions could represent a general mechanism for functional regulation by intrinsically disordered protein regions.

The dynamic properties of a nuclear coactivator binding domain are evolutionarily conserved.

Evolution of proteins is constrained by their structure and function. While there is a consensus that the plasticity of intrinsically disordered proteins relaxes the structural constraints on evolution there is a paucity of data on the molecular details of these processes. The Nuclear Coactivator Binding Domain (NCBD) from CREB-binding protein is a protein interaction domain, which contains a hydrophobic core but is not behaving as a typical globular domain, and has been described as 'molten-globule like'. The highly dynamic properties of NCBD makes it an interesting model system for evolutionary structure-function investigation of intrinsically disordered proteins. We have here compared the structure and biophysical properties of an ancient version of NCBD present in a bilaterian animal ancestor living around 600 million years ago with extant human NCBD. Using a combination of NMR spectroscopy, circular dichroism and kinetics we show that although NCBD has increased its thermodynamic stability, it has retained its dynamic biophysical properties in the ligand-free state in the evolutionary lineage leading from the last common bilaterian ancestor to humans. Our findings suggest that the dynamic properties of NCBD have been maintained by purifying selection and thus are important for its function, which includes mediating several distinct protein-protein interactions.

Validation of the International Classification of Functioning, Disability and Health (ICF) core sets from 2001 to 2019 - a scoping review.

Objective: To investigate and summarize the literature on the validation of International Classification of Functioning, Disability and Health (ICF) core sets from 2001 to 2019 and explore what research methods have been used when validating ICF core sets.Methods: The current study is a scoping review using a structured literature search.Results: In total, 66 scientific articles were included, of which 23 ICF core sets were validated. Most validation studies were conducted in Europe using a quantitative methodology and were validated from the perspective of patients. Analysis methods differed considerably between the studies, and most ICF core sets were validated only once for a single target population or from a single perspective. The comprehensive core sets were validated more often than the brief core sets, and core sets for stroke and low back pain were validated most often.Conclusion: The results of the current study show that only 66% of the existing ICF core sets are validated. Many of the validation studies are conducted in a European context and from a single perspective. More validation studies of ICF core sets from the perspective of both patients and professionals are needed.Implications for rehabilitationICF core sets aim to facilitate assessments in clinical settings and research.Validation studies indicate in general that the ICF core sets are valid and relevant for patients and professionals in the specific areas explored and thus can be used in rehabilitation settings.To improve the quality of ICF core sets, more validation studies are needed for ICF core sets not yet tested and for ICF core sets that have been validated only in one study or for one specific population or target group.

Examining the consequences of tinnitus using the multidimensional perspective.

BACKGROUND: Tinnitus is one of the most frequent chronic conditions in adults with wide range of consequences. AIMS/OBJECTIVES: The aim of the current study was to determine the problems and life effects reported by individuals with tinnitus using the International Classification of Functioning, Disability and Health (ICF) framework. MATERIAL AND METHODS: The study used a cross-sectional survey design. A total of 344 individuals with tinnitus completed a series of questionnaires. The responses to open-ended questions were linked to ICF categories. RESULTS: Activity limitations and participation restrictions were most dominant consequence of tinnitus followed by effect on the body function with limited emphasis on the contextual factors. Frequently reported responses to body function involved emotional functions (b152), attention function (b140), and sleep functions (b134). Commonly reported responses to activity limitations and participation restrictions were recreation and leisure (d920), conversation (d350), communicating with-receiving-spoken messages (d310), listening (d115), and remunerative employment (d850). Sound intensity (e2500) and sound quality (e2501) were the frequently reported responses to environmental factors. Coping styles, past and present experiences, and lifestyle were the most frequently occurring personal factors. CONCLUSIONS AND SIGNIFICANCE: The study highlighted some key influencing factors of tinnitus in different ICF domains which can be helpful in rehabilitation planning.

Exploring Interactions in the Sickness Insurance System in Terms of Power and Trust.

Purpose Activation policies and efforts to reduce sick leave rates has influenced sickness insurance systems in Western countries, which has led to social security being more connected with work and attempts to expose malingering among the sickness absent. The aim of this study was to explore how power and trust are expressed by clients and stakeholders within the Swedish sickness insurance system. Methods This was a longitudinal qualitative study based on semi structured interviews and case files from 31 clients on sick leave in Sweden. Data was analyzed using a thematic analysis. Results The main theme 'Acts of power and distrust' illustrates how stakeholders' express suspicions towards each other, and how clients need to demonstrate desire and efforts to return to work which other stakeholders verified. Conclusions The clients desire to prove themselves able to contribute to society was prominent in this study and power relations need to be acknowledged, in particular between client and the SIA. Further, to preserve citizens trust in the system, the system needs to demonstrate trust also in the clients.

Social validity of work ability evaluations and official decisions within the sickness insurance system: A client perspective.

BACKGROUND: Studies of the social validity of work ability evaluations are rare, although the concept can provide valuable information about the acceptability, comprehensibility and importance of procedures. OBJECTIVE: The aim of this study was to explore clients' perceptions of social validity of work ability evaluations and the following official decisions concerning sickness benefits within the Swedish sickness insurance system. METHODS: This was a longitudinal qualitative study based on interviews with 30 clients on sick leave, analyzed through deductive content analysis. RESULTS: Clients' understanding of the evaluation was dependent on whether the specific tests were perceived as clearly related to the clients' situation and what information they received. For a fair description of their work ability, clients state that the strict structure in the evaluation is not relevant to everyone. CONCLUSION: The work ability evaluations indicate low acceptability due to lack of individual adaptation, the comprehensibility varied depending on the applicability of the evaluation and information provided, while the dimension 'importance' indicated as higher degree of social validity. The official decision about sickness benefits however was considered unrelated to the evaluation results, lacking solid arguments and sometimes contradictory to other stakeholders' recommendations indicating poor social validity.

Emergencies in freestanding ambulatory surgery centre.

PURPOSE OF REVIEW: Ambulatory surgery is increasing, more procedures as well as more complex procedures are transferred to ambulatory surgery. Patients of all ages including elderly and more fragile are nowadays scheduled for ambulatory surgery. Enhanced recovery after surgery (ERAS) protocols are now developed for further facilitating readily recovery, ambulation, and discharge. Thus, to secure safety, a vigilant planning and preparedness for adverse events and emergencies is mandatory. RECENT FINDINGS: Proper preoperative assessment, preparation/optimization and collaboration between anaesthetist and surgeon to plan for the optimal perioperative handling has become basic to facilitate well tolerated perioperative course. Standard operating procedures for rare emergencies must be in place. These SOPs should be trained and retrained on a regular basis to secure safety. Check lists and cognitive aids are tools to help improving safety. Audit and analysis of adverse outcomes and deviations is likewise of importance to continuously analyse and implement corrective activity plans whenever needed. SUMMARY: The present review will provide an oversight of aspects that needs to be acknowledged around planning handling of rare but serious emergencies to secure quality and safety of care in freestanding ambulatory settings.

Kinetic Methods of Deducing Binding Mechanisms Involving Intrinsically Disordered Proteins.

There are multiple examples of protein-protein interactions involving one intrinsically disordered protein region binding to an ordered protein domain in a coupled binding and folding reaction. Similarly to protein folding studies, much effort has been devoted to understanding the mechanisms of such coupled binding and folding reactions. In this chapter, we describe how kinetics can be used to assess binding mechanisms with focus on fluorescence-monitored stopped-flow experiments. The approach can be applied more generally to any protein interaction with or without a coupled conformational change and to other kinetic techniques. Determining binding mechanisms is a great challenge and while "proving" a mechanism may be futile, it is possible to deduce the simplest scenarios, which are consistent with experimental data.