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Tina S Gambling1 †, Andrew F Long2 1School of Healthcare Sciences, Cardiff University, Cardiff, UK; 2School of Health Care, University of Leeds, Leeds, UK†Tina S Gambling passed away on November 23, 2020.Correspondence: Andrew F Long Email a.f.long@btinternet.comAbstract: Hip dysplasia is a significant public health issue, representing the single largest cause for total hip arthroplasty in young adults. To gain insight into patient concerns and the impact of hip dysplasia on young adults, we developed a patient-centred outcome measure, the ‘Quality of Life Impact and Concerns’ (QoLI&C) measure. This short report provides additional evidence on test–retest reliability and suggests refinements to the measure to enhance its research and clinical utility.Keywords: acetabular dysplasia, developmental dysplasia of the hip, paediatric hip conditions, test–retest reliability, psychometric validation

Andrew F Long,1 Tina Gambling21School of Healthcare, Faculty of Health and Social Care, University of Leeds, Leeds, UK; 2School of Health Sciences, College of Biomedical and Life Sciences, Cardiff University, Cardiff, Wales, UKCorrespondence: Andrew F LongSchool of Healthcare, Health Systems Research, University of Leeds, Baines Wing, Leeds LS2 9UT, UKEmail a.f.long@btinternet.comPurpose: To explore the question of ‘how to evaluate a qualitative patient-centred outcome measure’, comprising predominantly open-ended items, including perhaps emojis, story writing and/or pictures, in a way that does not compromise the strictures of the qualitative paradigm, doing so in a credible and authoritative manner. The paper aims to promote debate and discussion in the measurement validation community.Methods: Comprehensive literature review of three electronic databases (PubMed; SCOPUS; Web of Science/Knowledge) and searches of three outcome-focused journals.Results: The vast majority (>90%) of the papers only used qualitative methods in the initial, in particular, content validation of a measure and then used (quantitative) psychometric validation procedures. The remaining papers comprised articles that were either methodologically or methods focused and the role of qualitative research. A number of key issues are raised, inter alia: giving primacy to the patient’s perspective; exploring the meaning and interpretation respondents place on the concept and possible items in a measure; prioritising maximising meaningful discrimination from the respondent’s perspective; ensuring face and content validity and relevance of items in the item content pool; and using appropriate qualitative methods, for example, concept elicitation, “think-aloud” and cognitive interviews and expert respondent panels/judges. This approach is applied to validate a child-friendly outcome measure for children with Perthes disease, a paediatric hip condition presenting primarily amongst male children aged 5-8 years.Conclusions: The core messages are to: (i) not force validation of a qualitative outcome measure into psychometric validation; but (ii) retain full adherence to the principles of the qualitative paradigm and employ procedures drawn from that paradigm. In this manner, primary emphasis would lie on issues of meaningfulness, face and content validity, the meaning of item and measure scores to respondents and, for a child-friendly measure, the child-friendliness of the measure.Keywords: qualitative validation, outcome measure, psychometric validation, qualitative paradigm, Perthes disease, child-friendly measure

Tina Gambling,1 Andrew F Long21School of Healthcare Sciences, College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK; 2School of Healthcare, University of Leeds, Leeds, UKPurpose: To develop and validate a patient-centered, evaluative outcome measure to assess patient-significant and identified impacts of the three pediatric hip conditions (the “Quality of Life, Concerns and Impact Measure” (QoLC&I)), for use by patients and clinicians in discussions over treatment options and the evaluation of treatment and post-operative rehabilitation.Patients and methods: The measure was developed through a qualitative study, via two web-based forums (patient narratives, n=84) and one specialist orthopedic adult hip clinic (conducting interviews, n=38). The draft (1) measure was piloted in an asynchronous web-based discussion group forum; following revision, it was piloted with a group of clinicians and patients to assess its patient and clinical utility, face and content validity. The final, refined prototype measure (QoLC&I, draft 3) was subjected to psychometric evaluation.Results: A total of 230 patients provided useable data for the psychometric analysis: 70% (160) had a confirmed diagnosis of Developmental Dysplasia of the Hip, 15% (35) Perthes, 11% (26) Slipped Upper Femoral Epiphyses; 4% (9) PHC not stated. The scale showed good acceptability (few missing items, good spread, low floor/ceiling effects), relevance (76% stating they would find the measure useful in their discussions with clinicians), and good internal consistency (Cronbach’s α=0.98; average ICC=0.98). Hypotheses on convergent validity (with the General Health Questionnaire, to measure depression, and the International Hip Outcome Tool Short Form, to measure quality of life) and divergent validity (with the General Self-Efficacy Scale, to measure coping) were confirmed.Conclusion: The 64-item QoL&CI measure is a practical and valid measure addressing areas of clinical and patient significance and has potential value to assist patients and clinicians in discussions about treatment choices and treatment progress. Future research will address further psychometric testing (test–retest validity and responsiveness to change), in additional sites, and embedding the measure into clinical practice.Keywords: Developmental Dysplasia of the Hip, Perthes disease, Slipped Upper Femoral Epiphyses, psychology, osteoarthritis

Abstract Background Interest is increasing in the application of standardised outcome measures in clinical practice. Measures designed for use in research may not be sufficiently precise to be used in monitoring individual patients. However, little is known about how clinicians and in particular, multidisciplinary teams, score patients using these measures. This paper explores the challenges faced by multidisciplinary teams in allocating scores on standardised outcome measures in clinical practice. Methods Qualitative case study of an inpatient neurorehabilitation team who routinely collected standardised outcome measures on their patients. Data were collected using non participant observation, fieldnotes and tape recordings of 16 multidisciplinary team meetings during which the measures were recited and scored. Eleven clinicians from a range of different professions were also interviewed. Data were analysed used grounded theory techniques. Results We identified a number of instances where scoring the patient was 'problematic'. In 'problematic' scoring, the scores were uncertain and subject to revision and adjustment. They sometimes required negotiation to agree on a shared understanding of concepts to be measured and the guidelines for scoring. Several factors gave rise to this problematic scoring. Team members' knowledge about patients' problems changed over time so that initial scores had to be revised or dismissed, creating an impression of deterioration when none had occurred. Patients had complex problems which could not easily be distinguished from each other and patients themselves varied in their ability to perform tasks over time and across different settings. Team members from different professions worked with patients in different ways and had different perspectives on patients' problems. This was particularly an issue in the scoring of concepts such as anxiety, depression, orientation, social integration and cognitive problems. Conclusion From a psychometric perspective these problems would raise questions about the validity, reliability and responsiveness of the scores. However, from a clinical perspective, such characteristics are an inherent part of clinical judgement and reasoning. It is important to highlight the challenges faced by multidisciplinary teams in scoring patients on standardised outcome measures but it would be unwarranted to conclude that such challenges imply that these measures should not be used in clinical practice for decision making about individual patients. However, our findings do raise some concerns about the use of such measures for performance management.

OBJECTIVE: To explore the way that patient-centred care is realised within a tele-carer behavioural change intervention. METHOD: In-depth, semi-structured interviews undertaken at years 1 and 3 with a purposively selected sample from the intervention group within a 3-year randomised controlled trial (RCT) of a telephone-based education and support for persons with type 2 diabetes, and interviews with the non-medically trained tele-carers and supervising diabetes specialist nurse. RESULTS: A four-phased flow of the patient-centred interactions was identified, which evolved over the process of the intervention. Initially, attention centred on building a picture for and of the patient and assessing their knowledge base. Later, focus moved towards understanding diabetes from the patient's perspective and advice-giving became more individualised. Throughout, the interaction dynamics varied for patients. CONCLUSION: This study provides insight into the development of patient-centred behaviours over time and the influence of patients on tele-carer communication styles. PRACTICE IMPLICATION: When adopting a patient-centred approach, tele-carers need to be flexible and recognise that patients vary in their knowledge, skills and psychological adaption to diabetes. Continuity of care and consistent contact is pivotal to patients being able to move through the various phases of their illness trajectory and make the transition towards improved self-care management. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The objective of this study was to explore client perceptions of the short-term and longer-term effects of shiatsu. DESIGN: The study design was a prospective, 6-month observational, pragmatic study. SETTING: There were 85 shiatsu practitioners in three countries involved in the study: Austria, Spain, and the United Kingdom. SUBJECTS: There were 948 clients receiving shiatsu from 1 of these practitioners. INTERVENTIONS: Shiatsu as delivered by the practitioner in routine practice. OUTCOME MEASURES: The outcomes measures were symptom severity, changes in health care use (baseline, 3 and 6 months), shiatsu-specific effects, uptake of advice (3 and 6 months), achieved expectations and occurrence of adverse events (4-6 days after first session, 3 and 6 months). RESULTS: Six hundred and thirty-three (633) clients provided full follow-up data (a response rate of 67%). A typical shiatsu user was female, in her 40s, in paid employment, and had used shiatsu before. At 'first-ever' use, the most typical reason for trying shiatsu was 'out of curiosity.' At 'today's' session, the dominant reason was health maintenance. The most mentioned symptom groups were problems with 'muscles, joints, or body structure,' 'tension/stress,' and 'low energy/fatigue.' Symptom scores improved significantly over the 6 months (all symptom groups, Austria and the United Kingdom; two symptom groups, Spain), with moderate effect sizes (0.66-0.77) for 'tension or stress' and 'body structure problems' (Austria, the United Kingdom), and small effect sizes (0.32-0.47) for the other symptom groups (Spain, 0.28-0.43 for four groups). Previous users reported significant symptom improvement from 'first ever' to baseline with moderate effect sizes. Across countries, substantial proportions (> or = 60%) agreed or agreed strongly with shiatsu-specific benefits. At 6 months, 77%-80% indicated that they had made changes to their lifestyle as a result of having shiatsu, and reductions in the use of conventional medicine (16%-22%) and medication (15%-34%). Ten (10) adverse events were reported by 9 clients (1.4%); none of these clients ceased shiatsu. CONCLUSIONS: Clients receiving shiatsu reported improvements in symptom severity and changes in their health-related behaviour that they attributed to their treatment, suggestive of a role for shiatsu in maintaining and enhancing health. [ABSTRACT FROM AUTHOR]

Background and objective: An economic analysis of telemedicine support to improve glycemic control in patients with type 2 diabetes mellitus, illustrating the use of an analytic framework that efficiently combines telemedicine program findings with published estimates of treatment cost effectiveness.Method: The Pro-Active Call Centre Treatment Support (PACCTS) trial compared tailored, protocol-driven call-center support with usual care as methods to manage glycemic control in 591 patients with diabetes in Salford, UK. Economic analysis of the trial describes the cost of delivering telemedicine support and level of improved glycemic control achieved in patients. These findings are linked to current best evidence for the long-term cost effectiveness of treatment to help inform whether the provision of call-center support to improve glycemic control should become routine health policy.Results: Under trial conditions, the cost effectiveness of the PACCTS intervention was estimated to be [pounds]43 400/quality-adjusted life-year (QALY) [2003 costings]. Under routine-use call-center conditions (a full caseload of patients with moderate to poor glycemic control) cost effectiveness was estimated to be lower at [pounds]33 700/QALY. Set against a threshold of [pounds]30 000/QALY, Monte Carlo simulation suggests the probability of PACCTS being cost-effective in routine use is 29%.Discussion: Despite being received well by patients and healthcare professionals alike, telemedicine support solely to achieve improved glycemic control in patients with type 2 diabetes was found to be borderline cost effective. Major uncertainties that could change this result include the underlying cost effectiveness of improved glycemic control, which is currently imprecisely known. Research is ongoing in patients with type 2 diabetes to extend call-center support to improve blood pressure and lipid management, where if similar improvements are obtained, the call center should prove highly cost effective. The novel analytic approach illustrated provides a clear framework for thinking about the design and analysis of behavioral change policies for healthcare. [ABSTRACT FROM AUTHOR]

The amount of data generated in qualitative research can be difficult to manage. In this paper Tracey Williamson and Andrew Long discuss how the use of data displays can improve data management and also how the process can help to make the routes from raw data to research findings in qualitative research more transparent. Data displays can take several forms but share the benefit of helping to condense large amounts of data into more manageable forms. They can also help to convey information in a visually stimulating format where presentation time or column space may be limited. [ABSTRACT FROM AUTHOR]

This paper applies a theory-driven approach to explore why the use of patient-reported outcome (PRO) measures in clinical practice, in particular, health-related quality of life (HRQoL) instruments, has little or no apparent influence on clinical decision making. A theory-driven approach involves combining knowledge of whether and how an intervention works. It is argued that such an approach is currently lacking within the literature evaluating the effectiveness of feeding back HRQoL information to clinicians. The paper identifies a number of mechanisms that might give rise to the expected outcomes that are currently implicit within the design of the intervention and hypotheses specified within the trials evaluating the use of HRQoL measures in clinical practice. It then examines how far current clinical practice matches these mechanisms and in doing so, a number of possible explanations for the lack of impact of HRQoL on clinical decision making are reviewed. The influence of HRQoL information on clinical decision making depends on a large number of factors related to the design of the intervention, patients' and clinicians' desire to discuss HRQoL issues within the consultation and the legitimacy that clinicians give to HRQoL instruments. To date, knowledge of how the feedback of HRQoL information to clinicians might improve doctor-patient communication or clinical decision making has yet to sufficiently inform an assessment of whether these aspects of patient care are improved. The paper concludes by specifying how the feedback of HRQoL information to clinicians might be modified to maximise its impact on clinical decision making. [ABSTRACT FROM AUTHOR]

Objective: To examine patients' views of the acceptability of and satisfaction with telephone care center support provided to improve blood glucose control in type 2 diabetes.Research Design and Methods: The Pro-Active Call-Center Treatment Support (PACCTS) Trial randomized patients from 47 general practices in a deprived urban area in northwest England to usual care or to proactive call center support in addition to usual care. Satisfaction with care was assessed in all 591 patients at baseline and the end of the study using the Diabetes Satisfaction and Treatment Questionnaire (DTSQ). Acceptability was assessed in 394 intervention patients after at least three proactive calls from the call center and at the end of the trial. A purposive sample of 25 patients took part in in-depth semistructured interviews.Results: The response rates to the questionnaires were 79% (DTSQ) and 65% (acceptability). Persons receiving the intervention continued to report high levels of satisfaction with their treatment (95% CI 32.3-33.2 at 1 year), and >90% strongly agreed or agreed that the telecarer approach was acceptable. Qualitative comments pointed to the importance of a personalized service; increased feelings of well-being, including confidence and self-control; help with problem-solving; and patients developing rapport and a strong bond with the telecarers.Conclusions: A personalized PACCTS approach is acceptable to patients. A service giving priority to the interpersonal dimension leads to increased commitment from patients to improve long-term glycemic control. [ABSTRACT FROM AUTHOR]

Objective: To determine whether Pro-Active Call Center Treatment Support (PACCTS), using trained nonmedical telephonists supported by specially designed software and a diabetes nurse, can effectively improve glycemic control in type 2 diabetes.Research Design and Methods: A randomized controlled implementation trial of 1-year duration was conducted in Salford, U.K. The trial comprised 591 randomly selected individuals with type 2 diabetes. By random allocation, 197 individuals were assigned to the usual care (control) group and 394 to the PACCTS (intervention) group. Lifestyle advice and drug treatment in both groups followed local guidelines. PACCTS patients were telephoned according to a protocol with the frequency of calls proportional to the last HbA(1c) level. The primary outcome was absolute reduction in HbA(1c), and the secondary outcome was the proportion of patients reducing HbA(1c) by at least 1%.Results: A total of 332 patients (84%) in the PACCTS group and 176 patients (89%) in the control group completed the study. Final HbA(1c) values were available in 374 patients (95%) in the PACCTS group and 180 patients (92%) in the usual care group. Compared with usual care, HbA(1c) improved by 0.31% (95% CI 0.11-0.52, P = 0.003) overall in the PACCTS patients. For patients with baseline HbA(1c) >7%, the improvement increased to 0.49% (0.21-0.77, P < 0.001), whereas in patients with baseline HbA(1c) <7% there was no change. The difference in the proportions of patients achieving a >/=1% reduction in HbA(1c) significantly favored the PACCTS intervention: 10% (4-16, P < 0.001) overall and 15% (7-24, P < 0.001) for patients with baseline HbA(1c) >7%.Conclusions: In an urban Caucasian trial population with blood glucose HbA(1c) >7%, PACCTS facilitated significant improvement in glycemic control. Further research should extend the validity of findings to rural communities and other ethnic groups, as well as to smoking and lipid and blood pressure control. [ABSTRACT FROM AUTHOR]

This article identifies that the introduction of the support worker role in the critical care team facilitates flexibility when organizing and managing patient care. Qualified nurses' time can be used more effectively, enhancing the quality of the patient care delivered. Aspects of the qualified nurses' workload in critical care can be shared and delegated successfully to unqualified staff. It is our view that staffing levels in critical care environments need to be reviewed with more flexible working practices to meet the current and future demands of critical care. There is a need for national consensus amongst qualified nurses to clarify and define the role of the support worker and develop a critical care competency framework to standardize training. To ensure proficiency, adequate training and appropriate accountability, support workers require regulation by a nationally recognized body. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to develop further a diary originally devised to measure the impact of multiple sclerosis (MS) as part of a cost utility study of beta interferon, and to evaluate its reliability, validity, and responsiveness in an outpatient sample of people with MS.Methods: The original diary was further developed using qualitative and quantitative methods to ensure that it addressed the views of people with MS. The psychometric properties of the MS Symptom and Impact Diary (MSSID) were evaluated in a sample of 77 people who completed the MSSID daily for 12 weeks. Internal and test-retest reliability, discriminant and convergent validity, and responsiveness were assessed using traditional psychometric methods.Results: The MSSID formed three, internally consistent scales that measured mobility, fatigue, and the overall impact of MS. The test-retest reliability of the mobility scale was adequate for individual comparisons (ICC>0.90) and the fatigue and overall impact scales were adequate for group comparisons (ICC>0.70). The MSSID was able to distinguish between clinical groups depending on clinical course, indoor ambulation status, and relapse status. It demonstrated associations with other single point instruments in the expected direction. Compared with single point instruments, its responsiveness was similar or better, especially in detecting short term improvements in functioning.Conclusions: The MSSID may provide a useful complement to currently available instruments to measure the outcomes of MS within clinical trials. Further research is needed to explore its feasibility in the context of a randomised controlled trial and its utility for clinicians. [ABSTRACT FROM AUTHOR]

Effective rehabilitation depends on multiple inputs from a variety of skilled multi-professional team members. This paper explores perceptions of the nurse's role within the multi-professional rehabilitation team and challenges for effective team working. It draws on findings from a 2-year qualitative study exploring the role of the nurse within rehabilitation. Substantial differences in the nurse's role were evident, depending on their and others' perceptions, especially in relation to the nurse's carry-on role. Many nurses felt their contributions were not valued and others desired greater reciprocity within the team. Blurring of role boundaries could bring benefits to clients but also led to professional tensions and rivalry. [ABSTRACT FROM AUTHOR]

AIM OF THE STUDY/PAPER: To identify the contribution of the nurse within the multi-professional rehabilitation team. BACKGROUND: The requirement for nurses to work effectively within the multi-professional rehabilitation team is increasingly important with the higher incidence of chronic disease, growing numbers of older people and enhanced survival from major trauma. METHODS: A 2-year qualitative investigation was undertaken centred on three contrasting condition case studies (fractured neck of femur, rheumatoid arthritis and stroke). Clients were theoretically sampled, with their 'rehabilitation pathway' through different services providing the window through which the nurse's contribution was explored. Multiple methods and points of data collection were used, including observation, face to face interviews (clients, carers and staff) and record review. To enhance generalisability, a series of national expert workshops were undertaken with four groups: users, carers and carers' organizations; nurses; members of the multi-professional team; and educationalists. FINDINGS: Six interlinked roles for the nurse were identified: assessment, co-ordination and communication, technical and physical care, therapy integration and therapy carry-on, emotional support, and involving the family. Of particular significance is the creation of a supportive environment for rehabilitation to occur. Some nurses undertook aspects of all of these roles at any one time while others were only involved in one or two areas. While nurses expressed a desire to integrate therapy into their care delivery, the actual achievement of this goal was variable. CONCLUSIONS: Key elements of the nurse's contribution within rehabilitation should aim to maximize client choice to enhance independent living in the client's future environment. At a nursing educational policy level the nurse needs to have a full understanding of the principles and models of rehabilitation. At a practice level, the nurse's role must be valued and recognized, by nurses themselves and other team members. [ABSTRACT FROM AUTHOR]

This paper explores how multidisciplinary teams (MDTs) balance encoded knowledge, in the form of standardised outcome measurement, with tacit knowledge, in the form of intuitive judgement, clinical experience and expertise, in the process of clinical decision making. The paper is based on findings from a qualitative case study of a multidisciplinary in-patient neurorehabilitation team in one UK NHS trust who routinely collected standardised outcome measures. Data were collected using non-participant observation of 16 MDT meetings and semi-structured interviews with 11 practitioners representing different professional groups. Our analysis suggests that clinicians drew on tacit knowledge to supplement, adjust or dismiss 'the scores' in making judgements about a patients' likely progress in rehabilitation, their change (or lack of) during therapy and their need for support on discharge. In many cases, the scores accorded with clinicians' tacit knowledge of the patient, and were used to reinforce this opinion, rather than determine it. In other cases, the scores, in particular the Barthel Index, provided a partial picture of the patient and in these circumstances, clinicians employed tacit knowledge to fill in the gaps. In some cases, the scores and tacit knowledge diverged and clinicians preferred to rely on their clinical experience and intuition and adjusted or downplayed the accuracy of the scores. We conclude that there are limits to the advantages of quantifying and standardising assessments of health within routine clinical practice and that standardised outcome measures can support, rather than determine clinical judgement. Tacit knowledge is essential to produce and interpret this form of encoded knowledge and to balance its significance against other information about the patient in making decisions about patient care. [ABSTRACT FROM AUTHOR]

Microtubule doublets (MTDs) comprise an incomplete microtubule (B-tubule) attached to the side of a complete cylindrical microtubule. These compound microtubules are conserved in cilia across the tree of life; however, the mechanisms by which MTDs form and are maintained in vivo remain poorly understood. Here, we identify microtubule-associated protein 9 (MAP9) as an MTD-associated protein. We demonstrate that C. elegans MAPH-9, a MAP9 homolog, is present during MTD assembly and localizes exclusively to MTDs, a preference that is in part mediated by tubulin polyglutamylation. We find that loss of MAPH-9 causes ultrastructural MTD defects, including shortened and/or squashed B-tubules with reduced numbers of protofilaments, dysregulated axonemal motor velocity, and perturbed cilia function. Because we find that the mammalian ortholog MAP9 localizes to axonemes in cultured mammalian cells and mouse tissues, we propose that MAP9/MAPH-9 plays a conserved role in regulating ciliary motors and supporting the structure of axonemal MTDs., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Patient-derived organoids and cellular spheroids recapitulate tissue physiology with remarkable fidelity. We investigated how engagement with a reconstituted basement membrane in three dimensions (3D) supports the polarized, stress resilient tissue phenotype of mammary epithelial spheroids. Cells interacting with reconstituted basement membrane in 3D had reduced levels of total and actin-associated filamin and decreased cortical actin tension that increased plasma membrane protrusions to promote negative plasma membrane curvature and plasma membrane protein associations linked to protein secretion. By contrast, cells engaging a reconstituted basement membrane in 2D had high cortical actin tension that forced filamin unfolding and endoplasmic reticulum (ER) associations. Enhanced filamin-ER interactions increased levels of PKR-like ER kinase effectors and ER-plasma membrane contact sites that compromised calcium homeostasis and diminished cell viability. Consequently, cells with decreased cortical actin tension had reduced ER stress and survived better. Consistently, cortical actin tension in cellular spheroids regulated polarized basement membrane membrane deposition and sensitivity to exogenous stress. The findings implicate cortical actin tension-mediated filamin unfolding in ER function and underscore the importance of tissue mechanics in organoid homeostasis., (© 2022 The Authors.)

Multiciliated cells are considered terminally differentiated, yet tissues bearing them are remodeled during development and after injury. In this issue of Developmental Cell, Tasca et al. (2021) show that multiciliated epithelial cells are lost via two different Notch-dependent processes, apoptosis and transdifferentiation, during developmental remodeling of the Xenopus epidermis., (Copyright © 2021 Elsevier Inc. All rights reserved.)

At cell division, the mammalian kinetochore binds many spindle microtubules that make up the kinetochore-fiber. To segregate chromosomes, the kinetochore-fiber must be dynamic and generate and respond to force. Yet, how it remodels under force remains poorly understood. Kinetochore-fibers cannot be reconstituted in vitro, and exerting controlled forces in vivo remains challenging. Here, we use microneedles to pull on mammalian kinetochore-fibers and probe how sustained force regulates their dynamics and structure. We show that force lengthens kinetochore-fibers by persistently favoring plus-end polymerization, not by increasing polymerization rate. We demonstrate that force suppresses depolymerization at both plus and minus ends, rather than sliding microtubules within the kinetochore-fiber. Finally, we observe that kinetochore-fibers break but do not detach from kinetochores or poles. Together, this work suggests an engineering principle for spindle structural homeostasis: different physical mechanisms of local force dissipation by the k-fiber limit force transmission to preserve robust spindle structure. These findings may inform how other dynamic, force-generating cellular machines achieve mechanical robustness., (© 2020 Long et al.)

Aims: To identify a suite of the key physical, emotional, and social outcomes to be employed in clinical practice and research concerning Perthes' disease in children., Methods: The study follows the guidelines of the COMET-Initiative (Core Outcome Measures in Effectiveness Trials). A systematic review of the literature was performed to identify a list of outcomes reported in previous studies, which was supplemented by a qualitative study exploring the experiences of families affected by Perthes' disease. Collectively, these outcomes formed the basis of a Delphi survey (two rounds), where 18 patients with Perthes' disease, 46 parents, and 36 orthopaedic surgeons rated each outcome for importance. The International Perthes Study Group (IPSG) (Dallas, Texas, USA (October 2018)) discussed outcomes that failed to reach any consensus (either 'in' or 'out') before a final consensus meeting with representatives of surgeons, patients, and parents., Results: In total, 23 different outcome domains were identified from the systematic review, and a further ten from qualitative interviews. After round one of the Delphi survey, participants suggested five further outcome domains. A total of 38 outcomes were scored in round two of the Delphi. Among these, 16 outcomes were scored over the prespecified 70% threshold for importance (divided into six main categories: adverse events; life impact; resource use; pathophysiological manifestations; death; and technical considerations). Following the final consensus meeting, 14 outcomes were included in the final Core Outcome Set (COS)., Conclusion: Core Outcome Sets (COSs) are important to improve standardization of outcomes in clinical research and to aid communication between patients, clinicians, and funding bodies. The results of this study should be a catalyst to develop high-quality clinical research in order to determine the optimal treatments for children with Perthes' disease. Cite this article: Bone Joint J 2020;102-B(5):611-617.

The spindle generates force to segregate chromosomes at cell division. In mammalian cells, kinetochore-fibers connect chromosomes to the spindle. The dynamic spindle anchors kinetochore-fibers in space and time to move chromosomes. Yet, how it does so remains poorly understood as we lack tools to directly challenge this anchorage. Here, we adapt microneedle manipulation to exert local forces on the spindle with spatiotemporal control. Pulling on kinetochore-fibers reveals the preservation of local architecture in the spindle-center over seconds. Sister, but not neighbor, kinetochore-fibers remain tightly coupled, restricting chromosome stretching. Further, pulled kinetochore-fibers pivot around poles but not chromosomes, retaining their orientation within 3 μm of chromosomes. This local reinforcement has a 20 s lifetime, and requires the microtubule crosslinker PRC1. Together, these observations indicate short-lived, specialized reinforcement in the spindle center. This could help protect chromosome attachments from transient forces while allowing spindle remodeling, and chromosome movements, over longer timescales., Competing Interests: PS, AL, SD No competing interests declared, (© 2020, Suresh et al.)

The kinetochore drives chromosome segregation at cell division. It acts as a physical link between chromosomes and dynamic microtubules, and as a signaling hub detecting and processing microtubule attachments to control anaphase onset. The mammalian kinetochore is a large macromolecular machine that forms a dynamic interface with the many microtubules that it binds. While we know most of the kinetochore's component parts, how they work together to give rise to its robust functions remains poorly understood. Here we highlight recent findings that shed light on this question, driven by an expanding physical and molecular toolkit. We present emerging principles that underlie the kinetochore's robust microtubule grip, such as redundancy, specialization, and dynamicity, and present signal processing principles that connect this microtubule grip to robust computation. Throughout, we identify open questions, and define simple engineering concepts that provide insight into kinetochore function., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The kinetochore links chromosomes to dynamic spindle microtubules and drives both chromosome congression and segregation. To do so, the kinetochore must hold on to depolymerizing and polymerizing microtubules. At metaphase, one sister kinetochore couples to depolymerizing microtubules, pulling its sister along polymerizing microtubules [1, 2]. Distinct kinetochore-microtubule interfaces mediate these behaviors: active interfaces transduce microtubule depolymerization into mechanical work, and passive interfaces generate friction as the kinetochore moves along microtubules [3, 4]. Despite a growing understanding of the molecular components that mediate kinetochore binding [5-7], we do not know how kinetochores physically interact with polymerizing versus depolymerizing microtubule bundles, and whether they use the same mechanisms and regulation to do so. To address this question, we focus on the mechanical role of the essential load-bearing protein Hec1 [8-11] in mammalian cells. Hec1's affinity for microtubules is regulated by Aurora B phosphorylation on its N-terminal tail [12-15], but its role at the interface with polymerizing versus depolymerizing microtubules remains unclear. Here we use laser ablation to trigger cellular pulling on mutant kinetochores and decouple sisters in vivo, and thereby separately probe Hec1's role on polymerizing versus depolymerizing microtubules. We show that Hec1 tail phosphorylation tunes friction along polymerizing microtubules and yet does not compromise the kinetochore's ability to grip depolymerizing microtubules. Together, the data suggest that kinetochore regulation has differential effects on engagement with growing and shrinking microtubules. Through this mechanism, the kinetochore can modulate its grip on microtubules over mitosis and yet retain its ability to couple to microtubules powering chromosome movement., (Copyright © 2017 Elsevier Ltd. All rights reserved.)