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Historically, the majority of patients with complement-mediated atypical hemolytic uremic syndrome (CaHUS) progress to end-stage kidney disease (ESKD). Single-arm trials of eculizumab with a short follow-up suggested efficacy. We prove, for the first time to our knowledge, in a genotype matched CaHUS cohort that the 5-year cumulative estimate of ESKD-free survival improved from 39.5% in a control cohort to 85.5% in the eculizumab-treated cohort (hazard ratio, 4.95; 95% confidence interval [CI], 2.75-8.90; P = .000; number needed to treat, 2.17 [95% CI, 1.81-2.73]). The outcome of eculizumab treatment is associated with the underlying genotype. Lower serum creatinine, lower platelet count, lower blood pressure, and younger age at presentation as well as shorter time between presentation and the first dose of eculizumab were associated with estimated glomerular filtration rate >60 ml/min at 6 months in multivariate analysis. The rate of meningococcal infection in the treated cohort was 550 times greater than the background rate in the general population. The relapse rate upon eculizumab withdrawal was 1 per 9.5 person years for patients with a pathogenic mutation and 1 per 10.8 person years for those with a variant of uncertain significance. No relapses were recorded in 67.3 person years off eculizumab in those with no rare genetic variants. Eculizumab was restarted in 6 individuals with functioning kidneys in whom it had been stopped, with no individual progressing to ESKD. We demonstrated that biallelic pathogenic mutations in RNA-processing genes, including EXOSC3, encoding an essential part of the RNA exosome, cause eculizumab nonresponsive aHUS. Recessive HSD11B2 mutations causing apparent mineralocorticoid excess may also present with thrombotic microangiopathy.
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Síndrome Hemolítico Urémico Atípico , Fallo Renal Crónico , Microangiopatías Trombóticas , Humanos , Preescolar , Síndrome Hemolítico Urémico Atípico/tratamiento farmacológico , Síndrome Hemolítico Urémico Atípico/genética , Recuento de Plaquetas , Proteínas del Sistema Complemento , Estudios de Cohortes , Fallo Renal Crónico/genéticaRESUMEN
The generation of the components that make up the embryonic body axis, such as the spinal cord and vertebral column, takes place in an anterior-to-posterior (head-to-tail) direction. This process is driven by the coordinated production of various cell types from a pool of posteriorly-located axial progenitors. Here, we review the key features of this process and the biology of axial progenitors, including neuromesodermal progenitors, the common precursors of the spinal cord and trunk musculature. We discuss recent developments in the in vitro production of axial progenitors and their potential implications in disease modelling and regenerative medicine.
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Biología , Tipificación del Cuerpo , Gastrulación/fisiología , Estratos Germinativos/embriología , Animales , Ectodermo/embriología , Endodermo/embriología , Regulación del Desarrollo de la Expresión Génica , Estratos Germinativos/inervación , Humanos , Técnicas In Vitro , Mesodermo/embriología , Mesodermo/inervación , Músculo Esquelético , Células MadreRESUMEN
AIM: The aim of the study was to evaluate a person-centred model of clinical supervision to enhance person-centredness. DESIGN: Experimental, quantitative. METHODS: One hundred and three New Graduates were supported to reflect through a person-centred lens (July-December 2020). Evaluation was undertaken at 6 months using: the Manchester Clinical Supervision Scale-26 (effectiveness of supervision) and the Person-centred Practice Inventory (measures attributes of the nurse/midwife, the care environment and person-centred processes). Due to participation difficulties, scores were calculated by attendance rates using descriptive and inferential statistics. RESULTS: Regular attendees scored higher on the supervision's effectiveness; however, this did not reach efficacy. 'Finding time' to attend contributed to low scores. Supervision scored well on its supportive function when attended. Many New Graduates perceived a decline in their care environment. Attendance aside, New Graduates averaged an increased in their person-centred attributes and processes. Greater participation was found in those who scored higher at baseline on their person-centred attributes and processes, and this higher scoring continued at 6 months than those who attended less. CONCLUSION: New Graduates who perceive themselves as person-centred and reflective at baseline are more likely to attend a person-centred clinical supervision and score higher at 6 months than those who attended less often. New Graduates found support within supervision during challenging times. IMPLICATIONS FOR PRACTICE FOR PROFESSIONAL AND/OR PATIENT CARE: For successful implementation of Person-centred Clinical Supervision, New Graduates need support to attend, as attendance supports them to begin seeing value in the process. IMPACT: This intervention kept person-centred practice at the forefront of New Graduates reflection, in a time of extreme change. The research has implications for nursing and midwifery management with the imperative to deliver person-centred care and create the person-centred cultures for staff to feel supported and empowered. REPORTING METHOD: Transparent Evaluation of Non-randomized Designs (TREND). PATIENT OF PUBLIC CONTRIBUTION: No patient or public contribution. CONTRIBUTION TO WIDER COMMUNITY: New Graduates grow their person-centredness over their transitioning year; however, this can be enhanced with regular clinical supervision underpinned by person-centred theory. Clinical supervisors can provide support to New Graduates when the environment is challenged.
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COVID-19 , Atención Dirigida al Paciente , Humanos , Femenino , Adulto , Masculino , SARS-CoV-2 , Partería/educación , Competencia Clínica , Enfermeras Obstetrices/psicología , Enfermeras Obstetrices/educación , Supervisión de Enfermería , EmbarazoRESUMEN
The head-tail axis in birds and mammals develops from a growth zone in the tail-end, which contains the node. This growth zone then forms the tailbud. Labelling experiments have shown that while many cells leave the node and tailbud to contribute to axial (notochord, floorplate) and paraxial (somite) structures, some cells remain resident in the node and tailbud. Could these cells be resident axial stem cells? If so, do the node and tailbud represent an instructive stem cell niche that specifies and maintains these stem cells? Serial transplantation and single cell labelling studies support the existence of self-renewing stem cells and heterotopic transplantations suggest that the node can instruct such self-renewing behaviour. However, only single cell manipulations can reveal whether self-renewing behaviour occurs at the level of a cell population (asymmetric or symmetric cell divisions) or at the level of single cells (asymmetric divisions only). We combine data on resident cells in the node and tailbud and review it in the context of axial development in chick and mouse, summarising our current understanding of axial stem cells and their niche and highlighting future directions of interest.
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Somitos , Células Madre , Animales , División Celular , Mamíferos , Mesodermo , Ratones , NotocordaRESUMEN
AIMS: To explore whether clinical supervision has an influence on person-centred practice. BACKGROUND: The ability to deliver person-centred care and the ability to engage in reflective practice are two key skills expected of nurses. Person-centred care shifts nurses thinking from the patient's disease state to their personhood. Clinical supervision has been proposed as a place to explore person-centred care. Person-centred practice extends person-centredness to enhance healthful relationships between care providers, services users and their significant others. METHODS: An integrative literature was conducted with the key words 'clinical supervision' and 'person-centredness' within CINAHL, Medline, PsychInfo and Google Scholar. The PRISMA statement was used to report the identification, selection, appraisal and synthesis of articles and PRISMA diagram reports the selection process. The Mixed Methods Appraisal Tool was used to appraise the articles, followed by a thematic analysis. The Template for Intervention Description and Replication was used to explore the concept of clinical supervision. RESULTS: Twelve articles met the inclusion criteria. Person-centredness and clinical supervision are not universally defined concepts. Clinical supervision in this context was mainly an adjunct to educative programmes. Clinical supervision has a positive influence on participants' person-centred attributes, but the influence on others is less clear. The clinical supervisor's qualities are pivotal to supervisions' success. CONCLUSIONS: Clinical supervision is a common reflective strategy used to explore nursing practice, yet as a strategy to enhance person-centred practices, is under-researched. Participants can experience person-centredness when their supervisor has person-centred attributes, an important aspect in delivering person-centred care. RELEVANCE TO CLINICAL PRACTICE: This review identified a gap in the literature between two common nursing concepts 'clinical supervision' and 'person-centred care/practices'. There is a need to conduct further research into the combination of these concepts to seek ways to embed person-centredness into health care and everyday nursing practice.
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Relaciones Enfermero-Paciente , Atención Dirigida al Paciente , Humanos , Atención Dirigida al Paciente/métodos , PersoneidadRESUMEN
AIMS AND OBJECTIVES: To evaluate the influence of an ageing simulation intervention on qualified acute care nurses' empathy towards older people. BACKGROUND: Life expectancy is increasing globally with an increased incidence of older people accessing healthcare services. As such, it is essential for qualified nurses within hospital settings to connect with older people by establishing healthful relationships. Empathy is an essential component of healthful nurse-patient relationships. Fortunately, empathy can be taught through education. DESIGN: A convergent mixed-methods design was utilised. METHODS: Nurses (N = 95) undertook an 8-hour ageing simulation intervention. Data were collected from April 2019 to May 2020 across three time points: before the intervention (T0); immediately after (T1) and at three months follow-up (T2). A mix of convenience (intervention) and purposeful (follow-up) sampling techniques were utilised. Quantitative data were collected via the Interpersonal Reactivity Index survey (n = 86) and analysed using repeat measures ANOVA to compare mean scores across time points. Qualitative data were collected via debriefing discussions (N = 95) and focus groups (n = 38), and analysed using a systematic thematic analysis method. Data convergence occurred during the interpretation phase. Study reported with the TREND checklist. RESULTS: Primarily, when quantitative and qualitative findings were merged they confirmed each others' empathy outcomes. Quantitative results showed a statistically significant increase in affective and cognitive empathy levels among nurses post-intervention. Qualitative findings expanded on quantitative results and revealed an increase in nurses' affective, cognitive and behavioural empathy represented in themes 'enhancing my empathy', 'impact of ageing', 'from self to others' and 'person-centred moments'. CONCLUSIONS: This study adds empirical evidence how a mixed-methods design can be used to evaluate the influence of an ageing simulation intervention on nurses' empathy levels. RELEVANCE TO CLINICAL PRACTICE: Ageing simulation interventions are a suitable experiential educational approach to improve acute care nurses' affective, cognitive and behavioural empathy towards older people.
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Empatía , Enfermeras y Enfermeros , Humanos , Anciano , Grupos Focales , Relaciones Enfermero-Paciente , EnvejecimientoRESUMEN
BACKGROUND: Australia has been confronted with a severe nursing deficit, making it difficult to maintain a strong healthcare workforce capable of meeting the mounting demands of healthcare organizations. AIMS: This study aimed to understand how personal and organizational resources influence career optimism and job-related affective well-being of Australian nurses during a pandemic using the Conservation of Resource Theory. METHODS: A cross-sectional online survey was emailed to 123 Australian nurses from January to February 2021. The survey consisted of self-reported measures, including mindfulness, career optimism, job-related affective well-being, personal and job resources measures, and the Dirty Dozen scale. Correlations, independent sample t-test, and a series of hierarchical regressions were conducted on the cross-sectional data with SPSS Version 27. The STROBE checklist was used to report the results. RESULTS: Findings suggested that mindfulness, perceived supervisor support, and job autonomy were significant predictors of job-related well-being, whereas mindfulness, perceived supervisor support, and opportunities for professional growth contributed more to career optimism of nurses during a health crisis. Male nurses in this study reported significantly higher mindfulness, career optimism, and job-related well-being levels than female nurses. LINKING EVIDENCE TO ACTION: Developing mindfulness among nurses, allocating organizational resources to facilitate more supervisor support, and providing job autonomy may enhance career optimism and job-related well-being of nursing staff who work in disruptive and high-demand work environments such as those experienced during the COVID-19 health crisis. Supervisors should also facilitate and encourage nurses to reflect and be mindful of their behaviors with their peers and patients which can help to reduce exploitative or arrogant behaviors in the workplace.
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The elongating mouse anteroposterior axis is supplied by progenitors with distinct tissue fates. It is not known whether these progenitors confer anteroposterior pattern to the embryo. We have analysed the progenitor population transcriptomes in the mouse primitive streak and tail bud throughout axial elongation. Transcriptomic signatures distinguish three known progenitor types (neuromesodermal, lateral/paraxial mesoderm and notochord progenitors; NMPs, LPMPs and NotoPs). Both NMP and LPMP transcriptomes change extensively over time. In particular, NMPs upregulate Wnt, Fgf and Notch signalling components, and many Hox genes as progenitors transit from production of the trunk to the tail and expand in number. In contrast, the transcriptome of NotoPs is stable throughout axial elongation and they are required for normal axis elongation. These results suggest that NotoPs act as a progenitor niche whereas anteroposterior patterning originates within NMPs and LPMPs.
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Tipificación del Cuerpo/fisiología , Embrión de Mamíferos/embriología , Mesodermo/embriología , Notocorda/embriología , Transducción de Señal/fisiología , Animales , Embrión de Mamíferos/citología , Mesodermo/citología , Ratones , Ratones Transgénicos , Notocorda/citología , Línea Primitiva/citología , Línea Primitiva/embriología , Receptores Notch/genética , Receptores Notch/metabolismoRESUMEN
SCN2A-related disorders include intellectual disability, autism spectrum disorder, seizures, episodic ataxia, and schizophrenia. In this study, the phenotype-genotype association in SCN2A-related disorders was further delineated by collecting detailed clinical and molecular characteristics. Using previously proposed genotype-phenotype hypotheses based on variant function and position, the potential of phenotype prediction from the variants found was examined. Patients were identified through the Deciphering Developmental Disorders study and gene matching strategies. Phenotypic information and variant interpretation evidence were collated. Seventeen previously unreported patients and five patients who had been previously reported (but with minimal phenotypic and segregation data) were included (10 males, 12 females; median age 10.5 years). All patients had developmental delays and the majority had intellectual disabilities. Seizures were reported in 15 of 22 (68.2%), four of 22 (18.2%) had autism spectrum disorder and no patients were reported with episodic ataxia. The majority of variants were de novo. One family had presumed gonadal mosaicism. The correlation of the use of sodium channel-blocking antiepileptic drugs with phenotype or genotype was variable. These data suggest that variant type and position alone can provide some predictive information about the phenotype in a proportion of cases, but more precise assessment of variant function is needed for meaningful phenotype prediction.
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Trastorno del Espectro Autista , Discapacidad Intelectual , Trastorno del Espectro Autista/genética , Niño , Femenino , Humanos , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/genética , Masculino , Canal de Sodio Activado por Voltaje NAV1.2/genética , Fenotipo , Convulsiones/genéticaRESUMEN
AIM: Explore how nurses and midwives use patient experience data collected from a mobile health app to influence the development of person-centred practice. DESIGN: Participatory action research, underpinned by the Person-Centred Nursing Framework and Practice Development principles. METHODS: Six clinical units in a large health district engaged in three action cycles from 2018 to 2020 using a mobile health app. Nursing/midwifery staff on the units (N = 177) utilized data collected via the app to evaluate and improve person-centred practice. A pre-post survey using the PCPI-S was conducted to evaluate staff perceptions of person-centredness. Data from the surveys (n = 101 in 2018 and n = 102 in 2020) and 17 semi-structured interviews were used to understand the influence working with these data had on person-centred practice. The Guidelines for Best Practices in the Reporting of Participatory Action Research have been used to report this study. RESULTS: Improvements in person-centred practice were noted across both data sets. There was a statistically significant increase in two domains of the PCPI-S in the independent t-test and across all three domains in the paired t-test results. Thematic analysis resulted in the identification of six themes: Getting everyone on board, once we understood, keeping on track, there's a person in the bed, knowing you're doing a good job and improving over time. CONCLUSION: Engaging with the data collected from the app in a facilitated and collaborative way results in increases in person-centredness. IMPACT: This study provides insight into how nurses and midwives used data from a mHealth app to evaluate and improve person-centred practice. Utilizing the data generated by the app resulted in increased person-centredness amongst staff and changes to practice and culture. Nursing and midwifery teams who are supported to engage with patient experience data in an action-oriented way will see person-centred practice improvements, affecting patients and staff.
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Partería , Atención Dirigida al Paciente , Femenino , Investigación sobre Servicios de Salud , Humanos , Atención Dirigida al Paciente/métodos , Embarazo , Encuestas y CuestionariosRESUMEN
AIMS AND OBJECTIVES: To explore how nurses and midwives engage with patient experience data collected via a mobile health app to inform person-centred practice improvements. BACKGROUND: A large amount of data is collected in healthcare, yet there is limited evidence outlining how nursing and midwifery staff utilise patient experience data to inform person-centred quality and safety improvements. METHODS: This study utilised action research, underpinned by Practice Development methodology and has been reported using the SQUIRE 2.0 checklist. Six clinical units (medical short stay, acute medical, surgical, oncology/haematology, day surgery and maternity) in a large health district in Australia engaged in three cycles of data collection using a mobile health app. The app captured patient experience data relating to the person-centred KPIs developed and tested by McCance et al. (2012). Staff used the data to develop and evaluate person-centred practice. RESULTS: A number of improvements in scores and practice occurred through engaging with the data in a cyclical way. All six clinical units saw an improvement in four or more of the KPIs in the patient survey results from cycle one to cycle three, with two clinical units improving in all eight. On average across the six units, there was also an increase in time nurses/midwives were visible to their patients, an increase in clinical documentation reflecting the patients' needs and what was important to them, an increase in positive comments and a decrease in negative comments in patient stories. CONCLUSION: This study shows that collecting and utilising data from the person-centred KPIs in a collaborative and cyclical way lead to enhanced patient experience and the development and implementation of person-centred quality and safety improvements. RELEVANCE TO CLINICAL PRACTICE: Capturing and utilising data that are meaningful to nursing/midwifery teams in a cyclical, action-orientated approach result in person-centred practice improvements that enhance the experience of those that are receiving and delivering patient care.
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Partería , Embarazo , Humanos , Femenino , Atención Dirigida al Paciente/métodos , Encuestas y Cuestionarios , Evaluación del Resultado de la Atención al Paciente , AustraliaRESUMEN
AIM: The aim is to understand current research into the impact of undergraduate nursing education on the development of professional values. BACKGROUND: Values are evident in the professional standards for nurses and the guidelines and healthcare policies of many countries. These professional values guide decisions and behaviour and are recognised as an essential component in the professions ability to provide safe and professional care. This literature review presents the current research on the impact of education on professional values in undergraduate nurse education. DESIGN: An integrative review of the findings was conducted to provide insight into the current research on the professional value development in undergraduate nurses. DATA SOURCES: CINAHL, PubMed and Scopus. REVIEW METHODS: A literature search was undertaken within defined date parameters 2010-2021 using a systematic approach. The Preferred Reporting Items for Systematic Reviews and Meta-analysis guide PRISMA was used to guide and illustrate the process. Papers were assessed for quality using the Mixed Methods Appraisal Tool. RESULTS: Two distinct areas of inquiry were identified. (a) Changes in professional values as an outcome of undergraduate nursing education or (b) changes in professional values as an outcome of specifically designed educational content. These areas were further explored to better understand the influences of undergraduate education on students' professional values. CONCLUSION: There is a lack of evidence in the literature to support the premise that professional values develop in line with academic year progression; however, there is strong evidence to support the inclusion of explicit learning in undergraduate education that engages students in education specifically designed to explore and develop professional values.
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Bachillerato en Enfermería , Estudiantes de Enfermería , Competencia Clínica , Bachillerato en Enfermería/métodos , Humanos , AprendizajeRESUMEN
The identification of transcription factor (TF) binding sites in the genome is critical to understanding gene regulatory networks (GRNs). While ChIP-seq is commonly used to identify TF targets, it requires specific ChIP-grade antibodies and high cell numbers, often limiting its applicability. DNA adenine methyltransferase identification (DamID), developed and widely used in Drosophila, is a distinct technology to investigate protein-DNA interactions. Unlike ChIP-seq, it does not require antibodies, precipitation steps, or chemical protein-DNA crosslinking, but to date it has been seldom used in mammalian cells due to technical limitations. Here we describe an optimized DamID method coupled with next-generation sequencing (DamID-seq) in mouse cells and demonstrate the identification of the binding sites of two TFs, POU5F1 (also known as OCT4) and SOX2, in as few as 1000 embryonic stem cells (ESCs) and neural stem cells (NSCs), respectively. Furthermore, we have applied this technique in vivo for the first time in mammals. POU5F1 DamID-seq in the gastrulating mouse embryo at 7.5 d post coitum (dpc) successfully identified multiple POU5F1 binding sites proximal to genes involved in embryo development, neural tube formation, and mesoderm-cardiac tissue development, consistent with the pivotal role of this TF in post-implantation embryo. This technology paves the way to unprecedented investigation of TF-DNA interactions and GRNs in specific cell types of limited availability in mammals, including in vivo samples.
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Genoma/genética , Factor 3 de Transcripción de Unión a Octámeros/genética , Factores de Transcripción SOXB1/genética , Factores de Transcripción/genética , Animales , Sitios de Unión/genética , Células Madre Embrionarias/metabolismo , Redes Reguladoras de Genes/genética , Ratones , Células-Madre Neurales/metabolismo , Metiltransferasa de ADN de Sitio Específico (Adenina Especifica)/genéticaRESUMEN
AIM: To implement and evaluate a co-designed staff well-being programme. BACKGROUND: Working in health care can be physically and psychologically demanding. The job demands-resources model indicates job resources moderate the impact of job demands on staff well-being. Well-being initiatives introduced by organisations improve staff commitment, and reduce absences and incidents. METHODS: A qualitative descriptive design was applied. In 2019, within an Australian local health district, 232 health care professionals across eight hospitals and two community settings attended a six-week well-being programme, which included a variety of self-care strategies, for example mindfulness. Nine 1-hr focus groups were completed 2-4 weeks post-programme. Data were analysed using thematic analysis to explore participants' thoughts and experiences. RESULTS: Participants experienced joy from workshops and guilt for leaving peers with their workload. Participants developed strong interpersonal relationships with workshop attendees within a 'safe well-being space'. Broader impacts expressed by participants were; learnt coping mechanisms and proactive self-care practices and can be easily embedded into daily routines. Participants shared their 'toolkit' with colleagues, family and friends, positively impacting the well-being of people around them. CONCLUSION: Participants encouraged by their new well-being 'toolkit' engaged with colleagues, better managed stressors and shared learnings. IMPLICATIONS FOR NURSING MANAGEMENT: Building well-being capability within a health organisation requires nursing management to make staff well-being a strategic priority, use a co-design approach and embed coping mechanisms at the grassroots levels.
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Personal de Salud , Autocuidado , Australia , Grupos Focales , Humanos , Recursos HumanosRESUMEN
Recessive mutations in diacylglycerol kinase epsilon (DGKE) display genetic pleiotropy, with pathological features reported as either thrombotic microangiopathy or membranoproliferative glomerulonephritis (MPGN), and clinical features of atypical hemolytic uremic syndrome (aHUS), nephrotic syndrome or both. Pathophysiological mechanisms and optimal management strategies have not yet been defined. In prospective and retrospective studies of aHUS referred to the United Kingdom National aHUS service and prospective studies of MPGN referred to the National Registry of Rare Kidney Diseases for MPGN we defined the incidence of DGKE aHUS as 0.009/million/year and so-called DGKE MPGN as 0.006/million/year, giving a combined incidence of 0.015/million/year. Here, we describe a cohort of sixteen individuals with DGKE nephropathy. One presented with isolated nephrotic syndrome. Analysis of pathological features reveals that DGKE mutations give an MPGN-like appearance to different extents, with but more often without changes in arterioles or arteries. In 15 patients presenting with aHUS, ten had concurrent substantial proteinuria. Identified triggering events were rare but coexistent developmental disorders were seen in six. Nine with aHUS experienced at least one relapse, although in only one did a relapse of aHUS occur after age five years. Persistent proteinuria was seen in the majority of cases. Only two individuals have reached end stage renal disease, 20 years after the initial presentation, and in one, renal transplantation was successfully undertaken without relapse. Six individuals received eculizumab. Relapses on treatment occurred in one individual. In four individuals eculizumab was withdrawn, with one spontaneously resolving aHUS relapse occurring. Thus we suggest that DGKE-mediated aHUS is eculizumab non-responsive and that in individuals who currently receive eculizumab therapy it can be safely withdrawn. This has important patient safety and economic implications.
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Síndrome Hemolítico Urémico Atípico , Diacilglicerol Quinasa , Síndrome Hemolítico Urémico Atípico/tratamiento farmacológico , Síndrome Hemolítico Urémico Atípico/epidemiología , Síndrome Hemolítico Urémico Atípico/genética , Preescolar , Diacilglicerol Quinasa/genética , Humanos , Estudios Prospectivos , Estudios Retrospectivos , Reino UnidoRESUMEN
The deluge of single-cell data obtained by sequencing, imaging and epigenetic markers has led to an increasingly detailed description of cell state. However, it remains challenging to identify how cells transition between different states, in part because data are typically limited to snapshots in time. A prerequisite for inferring cell state transitions from such snapshots is to distinguish whether transitions are coupled to cell divisions. To address this, we present two minimal branching process models of cell division and differentiation in a well-mixed population. These models describe dynamics where differentiation and division are coupled or uncoupled. For each model, we derive analytic expressions for each subpopulation's mean and variance and for the likelihood, allowing exact Bayesian parameter inference and model selection in the idealised case of fully observed trajectories of differentiation and division events. In the case of snapshots, we present a sample path algorithm and use this to predict optimal temporal spacing of measurements for experimental design. We then apply this methodology to an in vitro dataset assaying the clonal growth of epiblast stem cells in culture conditions promoting self-renewal or differentiation. Here, the larger number of cell states necessitates approximate Bayesian computation. For both culture conditions, our inference supports the model where cell state transitions are coupled to division. For culture conditions promoting differentiation, our analysis indicates a possible shift in dynamics, with these processes becoming more coupled over time.
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Diferenciación Celular , División Celular , Células Madre Embrionarias/fisiología , Algoritmos , Teorema de Bayes , Modelos Biológicos , ProbabilidadRESUMEN
Atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy (C3G) are associated with dysregulation and overactivation of the complement alternative pathway. Typically, gene analysis for aHUS and C3G is undertaken in small patient numbers, yet it is unclear which genes most frequently predispose to aHUS or C3G. Accordingly, we performed a six-center analysis of 610 rare genetic variants in 13 mostly complement genes (CFH, CFI, CD46, C3, CFB, CFHR1, CFHR3, CFHR4, CFHR5, CFP, PLG, DGKE, and THBD) from >3500 patients with aHUS and C3G. We report 371 novel rare variants (RVs) for aHUS and 82 for C3G. Our new interactive Database of Complement Gene Variants was used to extract allele frequency data for these 13 genes using the Exome Aggregation Consortium server as the reference genome. For aHUS, significantly more protein-altering rare variation was found in five genes CFH, CFI, CD46, C3, and DGKE than in the Exome Aggregation Consortium (allele frequency < 0.01%), thus correlating these with aHUS. For C3G, an association was only found for RVs in C3 and the N-terminal C3b-binding or C-terminal nonsurface-associated regions of CFH In conclusion, the RV analyses showed nonrandom distributions over the affected proteins, and different distributions were observed between aHUS and C3G that clarify their phenotypes.
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Síndrome Hemolítico Urémico Atípico/genética , Complemento C3/genética , Factor H de Complemento/genética , Vía Alternativa del Complemento/genética , Glomerulonefritis Membranoproliferativa/genética , Síndrome Hemolítico Urémico Atípico/patología , Complemento C3/metabolismo , Vía Alternativa del Complemento/fisiología , Femenino , Frecuencia de los Genes/genética , Predisposición Genética a la Enfermedad/genética , Glomerulonefritis Membranoproliferativa/patología , Humanos , Masculino , Mutación Missense/genéticaRESUMEN
OBJECTIVE: The aim of the study was to evaluate a technological solution in the form of an App to implement and measure person-centredness in nursing. The focus was to enhance the knowledge transfer of a set of person-centred key performance indicators and the corresponding measurement framework used to inform improvements in the experience of care. DESIGN: The study used an evaluation approach derived from the work of the Medical Research Council to assess the feasibility of the App and establish the degree to which the App was meeting the aims set out in the development phase. Evaluation data were collected using focus groups (n = 7) and semi-structured interviews (n = 7) to capture the impact of processes experienced by participating sites. SETTING: The study was conducted in the UK and Australia in two organizations, across 11 participating sites. PARTICIPANTS: 22 nurses from 11 sites in two large health care organizations were recruited on a voluntary basis. INTERVENTION: Implementing the KPIs and measurement framework via the APP through two cycles of data collection. MAIN OUTCOME MEASURES: The main outcome was to establish feasibility in the use of the App. RESULTS: The majority of nurse/midwife participants found the App easy to use. There was broad consensus that the App was an effective method to measure the patient experience and generated clear, concise reports in real time. CONCLUSIONS: The implementation of the person-centred key performance indicators using the App enhanced the generation of meaningful data to evidence patient experience across a range of different clinical settings.
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Atención Dirigida al Paciente , Australia , Grupos Focales , HumanosRESUMEN
AIMS AND OBJECTIVES: To assess the impact of the proactive organisational resource allocation in terms of a 6-week well-being initiative to support public healthcare professionals' workplace engagement, well-being and job satisfaction. BACKGROUND: Burnout of healthcare professionals can be a major cost to the Australian economy and public healthcare sector. According to the social exchange theory, when healthcare professionals perceive that their organisation proactively allocates resources to caring for its employees, then they are more likely to reciprocate and become more engaged in their work roles. DESIGN: The study used a pre- and postsurvey of healthcare professionals who participated in the well-being initiative. METHODS: Between February-June 2019, 172 healthcare professionals were surveyed before and after a well-being initiative. The survey included questions on workplace engagement, workplace well-being and job satisfaction. Paired t tests were used to determine whether the difference between before and after averages was significant. The TREND statement was used to ensure the quality reporting of this study. RESULTS: The well-being initiative had a positive impact on the healthcare professionals involved in the initiative. Nursing staff benefitted the most from the well-being initiative, while the full-time staff members and highly experienced demonstrated an increase in engagement. CONCLUSION: Well-being initiatives can be a targeted strategy to help alleviate burnout amongst healthcare professionals and build a mutually beneficial relationship between management and employees. RELEVANCE TO CLINICAL PRACTICE: This study shows how implementing a staff well-being initiative increases workplace engagement, which benefits both the individual and the organisation.
Asunto(s)
Agotamiento Profesional , Cuidadores , Personal de Salud , Australia , Agotamiento Profesional/prevención & control , Atención a la Salud , Humanos , Satisfacción en el Trabajo , Salud Pública , Lugar de TrabajoRESUMEN
AIM AND OBJECTIVES: To explore the thoughts and experiences of aged care nurses following participation in an ageing-suit simulation intervention. BACKGROUND: Globally, people are living longer, and for nurses, there are increasing challenges to meet the needs of the higher numbers of older people in hospital. Educating nurses to understand the ageing process and the experiences of older people in hospital is crucial to addressing these challenges. Ageing-suits were identified as a possible approach to assist with these educational needs. DESIGN: This study adopted a qualitative descriptive design. METHOD: A convenience sample of nurses (n = 15) were selected from a single aged care ward. Volunteered nurses participated in a four-hour ageing-suit simulation session. Their immediate thoughts and experiences were explored via postsimulation debriefs, and three 30-to 50-min follow-up focus groups were conducted at 3 months to explore perceptions on the impact of their experience on clinical practices. The data were analysed with the Braun and Clarke's six-step thematic analysis method. To ensure quality reporting of this study, the COREQ checklist was utilised (see Appendix S1). RESULTS: Data analysis generated three main themes. Nurses in the study highlighted that the experience of the ageing-suit resulted in "it feels real" (theme 1) and helped them in "enhancing understanding" (theme 2) about older people and their practices and supported a process of "changing me" (theme 3). CONCLUSION: Ageing-suits are emerging as a promising innovative educational approach for aged care nurses to gain insight into the challenges of ageing and subsequently making changes to themselves and their individualised practices towards older people. Future research is required to determine whether this educational approach is useful for a broader population of healthcare professionals. RELEVANCE TO CLINICAL PRACTICE: Ageing-suits were identified as a worthwhile educational approach for aged care nurses to improve their specialised clinical practices with older people.