Guidelines for establishing a cytometry laboratory.

The purpose of this document is to provide guidance for establishing and maintaining growth and development of flow cytometry shared resource laboratories. While the best practices offered in this manuscript are not intended to be universal or exhaustive, they do outline key goals that should be prioritized to achieve operational excellence and meet the needs of the scientific community. Additionally, this document provides information on available technologies and software relevant to shared resource laboratories. This manuscript builds on the work of Barsky et al. 2016 published in Cytometry Part A and incorporates recent advancements in cytometric technology. A flow cytometer is a specialized piece of technology that require special care and consideration in its housing and operations. As with any scientific equipment, a thorough evaluation of the location, space requirements, auxiliary resources, and support is crucial for successful operation. This comprehensive resource has been written by past and present members of the International Society for Advancement of Cytometry (ISAC) Shared Resource Laboratory (SRL) Emerging Leaders Program https://isac-net.org/general/custom.asp?page=SRL-Emerging-Leaders with extensive expertise in managing flow cytometry SRLs from around the world in different settings including academia and industry. It is intended to assist in establishing a new flow cytometry SRL, re-purposing an existing space into such a facility, or adding a flow cytometer to an individual lab in academia or industry. This resource reviews the available cytometry technologies, the operational requirements, and best practices in SRL staffing and management.

Nurse facilitated 5000 m running at Parkrun improves vulnerable adolescent health in a high deprivation area: A matched pair randomized control trial.

OBJECTIVE: To examine the effect of weekly nurse facilitated 5000 m running at Parkrun on markers of health in vulnerable adolescents from a high deprivation area. DESIGN: A matched pair randomized control trial. SAMPLE: Twenty-five adolescents aged 13-18, 90% identifying as Maori/Pasifika ethnicity. INTERVENTION: The intervention (INT) group participated in 6-10 Parkruns within 10 weeks, and a control group (CON) participated in one Parkrun only. A nurse facilitated the intervention offering support and encouragement at each Parkrun. MEASUREMENTS: Pre- and post-intervention testing sessions for cardiorespiratory fitness (CRF), glycated hemoglobin, body mass index (BMI), skeletal muscle mass (SMM), body fat, and hand grip strength (STR) were conducted. RESULTS: Parkrun improved CRF (F = 5.308, p = 0.035) and 5000 m time (t = 2.850, p = 0.019) by 5.5 ± 4.9 min (11.2%). Parkrun conferred a large beneficial effect on CRF (η2 = 0.249) a moderate beneficial effect on glycated hemoglobin levels (η2 = 0.119), and small beneficial effects upon SMM (η2 = 0.037) and body fat (η2 = 0.017). CONCLUSION: A weekly dose of nurse facilitated Parkrun can be recommended as a simple, accessible intervention that confers multiple beneficial effects on markers for health in adolescents from a high deprivation area.

Sex Disparity in Cause-Specific and All-Cause Mortality Among Incident Dialysis Patients.

RATIONALE & OBJECTIVE: Early mortality rates of female patients receiving dialysis have been, at times, observed to be higher than rates among male patients. The differences in cause-specific mortality between male and female incident dialysis patients with kidney failure are not well understood and were the focus of this study. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Incident patients who had initiated dialysis in Australia and New Zealand in 1998-2018. EXPOSURE: Sex. OUTCOMES: Cause-specific and all-cause mortality while receiving dialysis, censored for kidney transplant. ANALYTICAL APPROACH: Adjusted cause-specific proportional hazards models, focusing on the first 5 years following initiation of dialysis. RESULTS: Among 53,414 patients (20,876 [39%] female) followed for a median period of 2.8 (IQR, 1.3-5.2) years, 27,137 (51%) died, with the predominant cause of death attributed to cardiovascular disease (18%), followed by dialysis withdrawal (16%). Compared with male patients, female patients were more likely to die in the first 5 years after dialysis initiation (adjusted hazard ratio [AHR], 1.08 [95% CI, 1.05-1.11]). Even though female patients experienced a lower risk of cardiovascular disease-related mortality (AHR, 0.93 [95% CI, 0.89-0.98]) than male patients, they experienced a greater risk of infection-related (AHR, 1.20 [95% CI, 1.10-1.32]) and dialysis withdrawal-related (AHR, 1.19 [95% CI, 1.13-1.26]) mortality. LIMITATIONS: Possibility of residual and unmeasured confounders. CONCLUSIONS: Compared with male patients, female patients had a higher risk of all-cause mortality in the first 5 years after dialysis initiation, a difference driven by higher rates of mortality from infections and dialysis withdrawals. These findings may inform the study of sex differences in mortality in other geographic settings.

Values, Perspectives, and Experiences of Indigenous Maori Regarding Kidney Transplantation: A Qualitative Interview Study in Aotearoa/New Zealand.

RATIONALE & OBJECTIVE: In Aotearoa/New Zealand, Indigenous Maori experience inequitable delivery of kidney transplantation despite disproportionately higher rates of kidney failure. This study describes Maori patients' and families' values, perspectives, and experiences related to kidney transplantation. STUDY DESIGN: Qualitative interview study. SETTING & PARTICIPANTS: We conducted 40 in-depth interviews of 40 Maori: 8 who had received a transplant, 20 with chronic kidney disease (which included 10 on the deceased donor transplant list, 9 who were interested in transplantation and not currently waitlisted or who were ineligible for waitlisting, and 1 who was not interested in transplantation), 4 live-kidney donors, and 8 family members including 6 who had experiences with donor assessment. ANALYTICAL APPROACH: Data were analyzed inductively to generate themes and a conceptual framework. RESULTS: We identified 5 major themes: actively seeking a kidney transplant; evolving attitudes toward traditional values and practices; being confronted by interpersonal and systemic racism; poor information and communication; and challenged by social determinants of health. LIMITATIONS: Participants were recruited nationally through patient advocacy organizations and 1 regional kidney service. Potential participants unrelated to these groups or region could not be included. CONCLUSIONS: Maori participants were highly motivated to seek kidney transplantation and were inspired by positive experiences through donating and receiving a kidney. However, they faced barriers including social determinants, racism, and lack of information that impacted both direct experiences of transplantation and access to transplantation services.

Temporal changes and risk factors for death from early withdrawal within 12 months of dialysis initiation-a cohort study.

BACKGROUND: Mortality risk is high soon after dialysis initiation in patients with kidney failure, and dialysis withdrawal is a major cause of early mortality, attributed to psychosocial or medical reasons. The temporal trends and risk factors associated with cause-specific early dialysis withdrawal within 12 months of dialysis initiation remain uncertain. METHODS: Using data from the Australia and New Zealand Dialysis and Transplant Registry, we examined the temporal trends and risk factors associated with mortality attributed to early psychosocial and medical withdrawals in incident adult dialysis patients in Australia between 2005 and 2018 using adjusted competing risk analyses. RESULTS: Of 32 274 incident dialysis patients, 3390 (11%) experienced death within 12 months post-dialysis initiation. Of these, 1225 (36%) were attributed to dialysis withdrawal, with 484 (14%) psychosocial withdrawals and 741 (22%) medical withdrawals. These patterns remained unchanged over the past two decades. Factors associated with increased risk of death from early psychosocial and medical withdrawals were older age, dialysis via central venous catheter, late referral and the presence of cerebrovascular disease; obesity and Asian ethnicity were associated with decreased risk. Risk factors associated with early psychosocial withdrawals were underweight and higher socioeconomic status. Presence of peripheral vascular disease, chronic lung disease and cancers were associated with early medical withdrawals. CONCLUSIONS: Death from dialysis withdrawal accounted for >30% of early deaths in kidney failure patients initiated on dialysis and remained unchanged over the past two decades. Several shared risk factors were observed between mortality attributed to early psychosocial and medical withdrawals.

Exploring rural and remote patients' experiences of health services for kidney disease in Aotearoa New Zealand: An in-depth interview study.

AIMS: People with chronic kidney disease (CKD) living in rural communities have increased risks of death, morbidity, hospitalization and poorer quality of life compared with people with CKD living in urban areas. This study explores the experiences and perceptions of rural and remote patients and families in relation to accessing health services for kidney disease in Aotearoa New Zealand. METHODS: We conducted an In-depth interview study. We purposively sampled adult patients with CKD and their caregivers who lived further than 100 km (62 miles) or more than 1 h drive from their nearest dialysis or transplant centre. Qualitative data were analyzed inductively to generate themes, subthemes and a conceptual framework. RESULTS: Of 35 participants, including 26 patients and nine caregivers, 51% were female, 71% travelled between 1 and 3 h to their nearest renal unit, and the remainder, between 3 and 6 h. We identified five themes and related subthemes: intense psychological impact of rurality; pressure of extended periods away from home; services not designed for rural and remote living; suffering from financial losses; and poor communication. CONCLUSION: Rural and remote patients with CKD and their caregivers face the added challenges of separation from family, social and community support and financial burden, which can have profound consequences on their psychological and physical well-being and that of their families.

Shared Resource Laboratory Operations: Changes Made During Initial Global COVID-19 Lockdown of 2020.

Undoubtedly, the global pandemic caused by the SARS-CoV-2 virus has had a significant impact on Shared Resource Laboratories (SRL) operations worldwide. Unlike other crises (e.g., natural disasters, acts of war, or terrorism) which often result in a sudden and sustained cessation of scientific research usually affecting one or two cities at a time, this impact is being seen simultaneously in every SRL worldwide albeit to a varying degree. The alterations to SRL operations caused by the COVID-19 pandemic can generally be divided into three categories: (1) complete shutdown, (2) partial shutdown, and (3) uninterrupted operations. In many cases, SRLs that remained partially or fully operational during the initial wave of global infections saw a concurrent increase in COVID-19-related research coming through their facilities. This forced SRLs to make rapid adjustments to core operations at the same time as infectious disease experts were still developing recommendations for the safety of frontline medical workers. Although many SRLs already had contingency plans in place, this pandemic has highlighted the importance of having such plans for continuity of service, if possible, during a crisis. Immediate changes have occurred in the way SRLs operate due to potential virus transmission and in line with this new "Best Practices" have been established, that is,social distancing, remote working, and technology-based meetings and training. Many of these changes are likely to be in place for some time with the threat of further waves of infections toward the end of 2020 and into 2021. Some of these best practices, such as having many training resources recorded and available online, are likely to remain long-term. Although many changes have been made in haste, these will alter the future operations of SRLs. In addition, we have learnt how to deal with future crises that may be encountered in the workplace. © 2020 The Authors. Cytometry Part A published by Wiley Periodicals LLC. on behalf of International Society for Advancement of Cytometry.

Patient-reported outcome measures for life participation in peritoneal dialysis: a systematic review.

BACKGROUND: Patients receiving peritoneal dialysis (PD) endure an ongoing regimen of daily fluid exchanges and are at risk of potentially life-threatening complications and debilitating symptoms that can limit their ability to participate in life activities. The aim of the study was to identify the characteristics, content and psychometric properties of measures for life participation used in research in PD. METHODS: We searched MEDLINE, Embase, PsychInfo, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and the Cochrane Central Register of Controlled Trials from inception to May 2020 for all studies that reported life participation in patients on PD. The characteristics, dimensions of life participation and psychometric properties of these measures were extracted and analyzed. RESULTS: Of the 301 studies included, 17 (6%) were randomized studies and 284 (94%) were nonrandomized studies. Forty-two different measures were used to assess life participation. Of these, 23 (55%) were used in only one study. Fifteen (36%) measures were specifically designed to assess life participation, while 27 (64%) measures assessed broader constructs, such as quality of life, but included questions on life participation. The 36-Item Short Form Health Survey and Kidney Disease Quality of Life Short Form were the most frequently used measures [122 (41%) and 86 (29%) studies, respectively]. Eight (19%) measures had validation data to support their use in patients on PD. CONCLUSIONS: The many measures currently used to assess life participation in patients receiving PD vary in their characteristics, content and validation. Further work to pilot and validate potential measures is required to establish a core patient-reported outcome measure to assess life participation in patients receiving PD.

Socio-economic disparity, access to care and patient-relevant outcomes after kidney allograft failure.

Social disparity is a major impediment to optimal health outcomes after kidney transplantation. In this study, we aimed to define the association between socio-economic status (SES) disparities and patient-relevant outcomes after kidney allograft failure. Using data from the Australia and New Zealand Dialysis and Transplant registry, we included patients with failed first-kidney allografts in Australia between 2005 and 2017. The association between residential postcode-derived SES in quintiles (quintile 1-most disadvantaged areas, quintile 5-most advantaged areas) with uptake of home dialysis (peritoneal or home haemodialysis) within the first 12-months post-allograft failure, repeat transplantation and death on dialysis were examined using competing-risk analysis. Of 2175 patients who had experienced first allograft failure, 417(19%) and 505(23%) patients were of SES quintiles 1 and 5, respectively. Compared to patients of quintile 5, quintile 1 patients were less likely to receive repeat transplants (adjusted subdistributional hazard ratio [SHR] 0.70,95%CI 0.55-0.89) and were more likely to die on dialysis (1.37 [1.04-1.81]), but there was no association with the uptake of home dialysis (1.02 [0.77-1.35]). Low SES may have a negative effect on outcomes post-allograft failure and further research is required into how best to mitigate this. However, small-scale variation within SES cannot be accounted for in this study.

Tracking the embryonic stem cell transition from ground state pluripotency.

Mouse embryonic stem (ES) cells are locked into self-renewal by shielding from inductive cues. Release from this ground state in minimal conditions offers a system for delineating developmental progression from naïve pluripotency. Here, we examine the initial transition process. The ES cell population behaves asynchronously. We therefore exploited a short-half-life Rex1::GFP reporter to isolate cells either side of exit from naïve status. Extinction of ES cell identity in single cells is acute. It occurs only after near-complete elimination of naïve pluripotency factors, but precedes appearance of lineage specification markers. Cells newly departed from the ES cell state display features of early post-implantation epiblast and are distinct from primed epiblast. They also exhibit a genome-wide increase in DNA methylation, intermediate between early and late epiblast. These findings are consistent with the proposition that naïve cells transition to a distinct formative phase of pluripotency preparatory to lineage priming.

Cell investigation into the biocompatibility of adult human dermal fibroblasts with PCL nanofibers/TiO2 nanotubes on the surface of Ti-30Ta alloy for biomedical applications.

The polymer poly(ε-caprolactone) (PCL) has been used in the biomaterial field for its relatively inexpensive price and suitability for modification. Also, its chemical and biological properties are desirable for biomedical applications. The electrospinning process has been used for producing polymer fibers of PCL due in large part to an increased interest in nanoscale properties and technologies. Moreover, the use of biocompatible polymers for the viability of cell growth is a promising alternative to improve osseointegration. Characterization techniques such as scanning electron microscopy and contact angle were used for analyses of samples. Adult human dermal fibroblasts (neonatal) were utilized to evaluate the biocompatibility of the association of the electrospinning process of the biocompatible polymer (PCL) with TiO2 nanotubes on the Ti-30Ta alloy surface. The results of this study showed a favorable response for adhesion on the surface. This promising material is due to the modulation of the biological response.

Understanding the experiences, perspectives and values of indigenous women around smoking cessation in pregnancy: systematic review and thematic synthesis of qualitative studies.

BACKGROUND: The prevalence of smoking during pregnancy among indigenous women approaches 50% and is associated with sudden infant death, pregnancy loss, preterm delivery, low birth weight, and anatomical deformity. This study aims to synthesise qualitative studies by reporting experiences, perceptions, and values of smoking cessation among pregnant indigenous women to inform potential interventions. METHOD: A highly-sensitive search of MEDLINE, Embase, PsychINFO, and CINAHL, in conjunction with analysis of Google Scholar and reference lists of related studies was conducted in March 2018. We utilised two methods (thematic synthesis and an indigenous Maori analytical framework) in parallel to analyse data. Completeness of reporting in studies was evaluated using the Consolidated Criteria for Reporting Qualitative Studies (COREQ) framework. RESULTS: We included seven studies from Australia and New Zealand involving 250 indigenous women. Three themes were identified. Realising well-being and creating agency included giving the best start to baby, pride in being a healthy mum, female role models, and family support. Understanding the drivers for smoking included the impact of stress and chaos that hindered prioritisation of self-care, the social acceptability of smoking, guilt and feeling judged, and inadequate information about the risks of smoking. Indigenous women strongly preferred culturally responsive approaches to smoking cessation, placing value on programs designed specifically for and by indigenous people, that were accessible, and provided an alternative to smoking. CONCLUSION: Future interventions and smoking cessation programmes might be more effective and acceptable to indigenous women and families when they harness self-agency and the desire for a healthy baby, recognise the high value of indigenous peer involvement, and embed a social focus in place of smoking as a way to maintain community support and relationships. Development and evaluation of smoking cessation programs for pregnant indigenous women and families is warranted.

Experiences, perspectives and values of Indigenous peoples regarding kidney transplantation: systematic review and thematic synthesis of qualitative studies.

BACKGROUND: Kidney transplantation is considered best practice treatment for end stage kidney disease (ESKD), however Indigenous patients are substantially less likely to receive either a deceased or live donor kidney transplant than non-Indigenous patients. We describe Indigenous peoples' experiences and perspectives including traditional values around kidney transplantation to inform international transplant programs. METHODS: We conducted a systematic review of qualitative studies involving Indigenous adults who have experience with or perceptions of kidney transplantation. We searched MEDLINE, Embase, PsychINFO, and CINAHL, in conjunction with analysis of Google Scholar and reference lists of related studies till July 2019. We utilised thematic synthesis to analyse data. Completeness of reporting in studies was evaluated using the Consolidated Criteria for Reporting Qualitative Studies (COREQ) framework. RESULTS: Eight studies involving 225 Indigenous participants were included. Five themes were identified: strong desire for transplantation (seeking normality and freedom from dialysis, wanting to reduce burden of disease within community); lack of partnership in shared decision-making (receiving inadequate information, ineffective communication); barriers to live kidney donation (difficulty asking, apprehension about impact on donor, avoiding additional financial burden and fear of complications); cultural considerations (influence of traditional values and beliefs, reconciling traditional values with pragmatic need); and experiencing lack of cultural competence in clinical care (struggling with prejudice and ignorance, mistrust of clinicians and health system). CONCLUSION: Indigenous participants had a strong desire for a kidney transplant and recognised the need for more readily available kidney transplants for others in their communities with ESKD. However, they faced prejudice and a lack of cultural competence by health workers as well as wider barriers to transplantation in systems that did not support effective and culturally appropriate delivery of information and care. Traditional cultural values also influenced decisions regarding kidney transplantation but such values were moderated when considering transplantation. Transplantation programs need to identify and mitigate barriers, such as the financial burden, promote cultural safety and incorporate traditional values into the promotion of transplantation in order to address inequitable transplantation rates. REGISTRATION: Not applicable.

Children's experiences and expectations of kidney transplantation: A qualitative interview study.

AIM: Kidney transplantation offers improved quality of life and life expectancy compared with dialysis for children. This study aims to understand the experiences and expectations of children during the kidney transplantation process to inform clinical care. METHODS: Face-to-face, semi-structured interviews were conducted with 13 children and adolescents aged between 7 and 17 years in New Zealand who had received a kidney transplantation. Findings were conceptualized using thematic analysis with inductive coding. RESULTS: Three major themes were identified: transplant as the goal (the only real treatment and escaping dialysis); dealing with negative emotions (coping with anxiety and fear, guilt for siblings and burden of parent as donor); and enhancing understanding and knowledge (individualised education and reassurance from peer support). CONCLUSION: Children and adolescents view transplantation as freedom from dialysis and return to a more normal life. Children focus on the positive aspects of transplantation to reduce anxiety and be reassured in the face of uncertainty. Complex emotions arise when thinking about their donor. Children recognize transplantation is not a return to full health and actively seek out ways to self-manage their care, while remaining anxious about their future.

Palbociclib synergizes with BRAF and MEK inhibitors in treatment naïve melanoma but not after the development of BRAF inhibitor resistance.

Increased CDK4 activity occurs in the majority of melanomas and CDK4/6 inhibitors in combination with BRAF and MEK inhibitors are currently in clinical trials for the treatment of melanoma. We hypothesize that the timing of the addition of CDK4/6 inhibitors to the current BRAF and MEK inhibitor regime will impact on the efficacy of this triplet drug combination. The efficacy of BRAF, MEK and CDK4/6 inhibitors as single agents and in combination was assessed in human BRAF mutant cell lines that were treatment naïve, BRAF inhibitor tolerant or had acquired resistance to BRAF inhibitors. Xenograft studies were then performed to test the in vivo efficacy of the BRAF and CDK4/6 inhibitor combination. Melanoma cells that had developed early reversible tolerance or acquired resistance to BRAF inhibition remained sensitive to palbociclib. In drug-tolerant cells, the efficacy of the combination of palbociclib with BRAF and/or MEK inhibitors was equivalent to single agent palbociclib. Similarly, acquired BRAF inhibitor resistance cells lost efficacy to the palbociclib and BRAF combination. In contrast, upfront treatment of melanoma cells with palbociclib in combination with BRAF and/or MEK inhibitors induced either cell death or senescence and was superior to a BRAF plus MEK inhibitor combination. In vivo palbociclib plus BRAF inhibitor induced rapid and sustained tumor regression without the development of therapy resistance. In summary, upfront dual targeting of CDK4/6 and mutant BRAF signaling enables tumor cells to evade resistance to monotherapy and is required for robust and sustained tumor regression. Melanoma patients whose tumors have acquired resistance to BRAF inhibition are less likely to have favorable responses to subsequent treatment with the triplet combination of BRAF, MEK and CDK4/6 inhibitors.

"Who matters most?": Clinician perspectives of influence and recommendation on home dialysis uptake.

AIM: There is little research exploring the association between clinicians' behaviours and home dialysis uptake. This paper aims to better understand the influence of clinicians on home dialysis modality recommendations and uptake. METHODS: Online survey of all NZ renal units to determine the influence of individuals within pre-dialysis teams. We used the self-declaration scale of influence to rate the identified member's perceived influence on decision-making. We used this measure of 'decisional power' to compare the perceived influence of pre-dialysis nurses with nephrologists using both parametric and non-parametric methods. We developed a generalized linear model to investigate the relationship between the influence of nephrologists and pre-dialysis nurses with home dialysis uptake by individual centre using additional data from Australian and New Zealand Dialysis and Transplant Registry (ANZDATA). Finally, respondents rated the importance of a list of patient and service-level factors in recommendations for home dialysis. RESULTS: Data suggest the nephrologists are the most influential member of the pre-dialysis team. This contrasts with perceptions of survey respondents who view pre-dialysis nurses as most influential. Nephrologists' recommendations are likely to be a successful way of increasing home dialysis. A single point increase in nephrologist decisional power is associated with a 6.1% increase in the prevalence of home dialysis. CONCLUSION: The decisional power around home dialysis in NZ sits with nephrologists. It is therefore critical that nephrologists exercise their decisional power in advocating home dialysis and address reasons why they may not recommend home dialysis to well-suited and appropriate patients.

International Society for Advancement of Cytometry (ISAC) flow cytometry shared resource laboratory (SRL) best practices.

The purpose of this document is to define minimal standards for a flow cytometry shared resource laboratory (SRL) and provide guidance for best practices in several important areas. This effort is driven by the desire of International Society for the Advancement of Cytometry (ISAC) members in SRLs to define and maintain standards of excellence in flow cytometry, and act as a repository for key elements of this information (e.g. example SOPs/training material, etc.). These best practices are not intended to define specifically how to implement these recommendations, but rather to establish minimal goals for an SRL to address in order to achieve excellence. It is hoped that once these best practices are established and implemented they will serve as a template from which similar practices can be defined for other types of SRLs. Identification of the need for best practices first occurred through discussions at the CYTO 2013 SRL Forum, with the most important areas for which best practices should be defined identified through several surveys and SRL track workshops as part of CYTO 2014. © 2016 International Society for Advancement of Cytometry.

Patient and caregiver values, beliefs and experiences when considering home dialysis as a treatment option: a semi-structured interview study.

BACKGROUND: Home dialysis can offer improved quality of life and economic benefits compared with facility dialysis. Yet the uptake of home dialysis remains low around the world, which may be partly due to patients' lack of knowledge and barriers to shared and informed decision-making. We aimed to describe patient and caregiver values, beliefs and experiences when considering home dialysis, to inform strategies to align policy and practice with patients' needs. METHODS: Semi-structured interviews with adult patients with chronic kidney disease Stage 4-5D (on dialysis <1 year) and their caregivers, recruited from three nephrology centres in New Zealand. Transcripts were analysed thematically. RESULTS: In total, 43 patients [pre-dialysis (n = 18), peritoneal dialysis (n = 13), home haemodialysis (n = 4) and facility haemodialysis (n = 9)] and 9 caregivers participated. We identified five themes related to home dialysis: lacking decisional power (complexity of information, limited exposure to home dialysis, feeling disempowered, deprived of choice, pressure to choose), sustaining relationships (maintaining cultural involvement, family influence, trusting clinicians, minimizing social isolation), reducing lifestyle disruption (sustaining employment, avoiding relocation, considering additional expenses, seeking flexible schedules, creating free time), gaining confidence in choice (guarantee of safety, depending on professional certainty, reassurance from peers, overcoming fears) and maximizing survival. CONCLUSIONS: To engage and empower patients and caregivers to consider home dialysis, a stronger emphasis on the development of patient-focused educational programmes and resources is suggested. Pre-dialysis and home dialysis programmes that address health literacy and focus on cultural and social values may reduce fears and build confidence around decisions to undertake home dialysis. Financial burdens may be minimized through provision of reimbursement programmes, employment support and additional assistance for patients, particularly those residing in remote areas.

Germline potential of parthenogenetic haploid mouse embryonic stem cells.

Haploid embryonic stem cells (ESCs) have recently been derived from parthenogenetic mouse embryos and offer new possibilities for genetic screens. The ability of haploid ESCs to give rise to a wide range of differentiated cell types in the embryo and in vitro has been demonstrated. However, it has remained unclear whether haploid ESCs can contribute to the germline. Here, we show that parthenogenetic haploid ESCs at high passage have robust germline competence enabling the production of transgenic mouse strains from genetically modified haploid ESCs. We also show that differentiation of haploid ESCs in the embryo correlates with the gain of a diploid karyotype and that diploidisation is the result of endoreduplication and not cell fusion. By contrast, we find that a haploid karyotype is maintained when differentiation to an extra-embryonic fate is forced by induction of Gata6.