Integrative QTL analysis of gene expression and chromatin accessibility identifies multi-tissue patterns of genetic regulation.

Gene transcription profiles across tissues are largely defined by the activity of regulatory elements, most of which correspond to regions of accessible chromatin. Regulatory element activity is in turn modulated by genetic variation, resulting in variable transcription rates across individuals. The interplay of these factors, however, is poorly understood. Here we characterize expression and chromatin state dynamics across three tissues-liver, lung, and kidney-in 47 strains of the Collaborative Cross (CC) mouse population, examining the regulation of these dynamics by expression quantitative trait loci (eQTL) and chromatin QTL (cQTL). QTL whose allelic effects were consistent across tissues were detected for 1,101 genes and 133 chromatin regions. Also detected were eQTL and cQTL whose allelic effects differed across tissues, including local-eQTL for Pik3c2g detected in all three tissues but with distinct allelic effects. Leveraging overlapping measurements of gene expression and chromatin accessibility on the same mice from multiple tissues, we used mediation analysis to identify chromatin and gene expression intermediates of eQTL effects. Based on QTL and mediation analyses over multiple tissues, we propose a causal model for the distal genetic regulation of Akr1e1, a gene involved in glycogen metabolism, through the zinc finger transcription factor Zfp985 and chromatin intermediates. This analysis demonstrates the complexity of transcriptional and chromatin dynamics and their regulation over multiple tissues, as well as the value of the CC and related genetic resource populations for identifying specific regulatory mechanisms within cells and tissues.

Death doula working practices and models of care: the views of death doula training organisations.

BACKGROUND: The role of death doula has emerged in recent years, arguably as a result of overwhelming demands on carers, healthcare professionals and service providers in end-of-life care. Death doulas work independently without governing oversight and enact the role in various ways. The main driver of this evolving role is the organisations that train them. The aim of this study was to examine death doula training organisations' views with regard to DD business models, incorporating the death doula role into other existing models of care, and role enactment. METHODS: An electronic survey was administered to 15 death doula training organisations in 5 countries asking additionally that they disseminate the survey. Responses were received from 13 organisations, based in Australia (n = 4), the US (n = 4), Canada (n = 2), the UK (n = 1), Sweden (n = 1) and New Zealand (n = 1). This paper provides the qualitative findings from four open-text questions posed within the survey related to models of care. RESULTS: Qualitative data analysis was inductive, themes were determined in relation to: (1) standardised business model for death doulas, (2) death doulas incorporated into existing models of care or existing funding options, (3) death doulas who volunteer their services rather than charge money, and (4) role specialisation such as has occurred with birth doulas. CONCLUSIONS: The death doula role has the potential to be formally recognised in the future under national registration schemes, accompanied by death doula training required via certification. Until such time the death doula role will continue to evolve much as the birth doula role has, organically and unstructured. How and if death doulas are incorporated into existing models of health or social care remains to be seen as the organisations that train them push for independence, flexibility and fiscal independence.

Assessing the current and desired levels of training and applied experiences in chronic disease prevention of students during medical school.

INTRODUCTION: Chronic diseases account for approximately 70% of deaths in the U.S. annually. Though physicians are uniquely positioned to provide behavior change counseling for chronic disease prevention, they often lack the necessary training and self-efficacy. This study examined medical student interest in receiving chronic disease prevention training as a formal part of their education as part of an effort to enhance their ability to provide guidance to patients in the future. METHODS: A 23-question, online survey was sent to all undergraduate medical students enrolled in a large medical education program. The survey assessed medical student interest in receiving training related to chronic disease prevention. Survey topics included student awareness of primary prevention programs, perceived importance of receiving training and applied experience in chronic disease prevention, and preferences for how and when to receive this training. RESULTS: Of 793 eligible medical students, 432 completed the survey (54.5%). Overall, 92.4% of students reported receiving formal training in physical activity, public health, nutrition, obesity, smoking cessation, and chronic diseases was of "very high" or "high" importance. Despite this level of importance, students most frequently reported receiving no or 1-5 h of formal training in a number of topics, including physical activity (35.4% and 47.0%, respectively) and nutrition (16.9% and 56.3%, respectively). The level of importance given to public health training was significantly greater across degree type (p = 0.0001) and future specialty (p = 0.03) for MD/MPH students and those interested in primary care, respectively. CONCLUSIONS: While medical students perceive chronic disease prevention as an important topic, most reported receiving little to no formal training. To address the growing prevalence of chronic disease across our society, programs schools should place greater emphasis on integrating training in physical activity, nutrition, and obesity-related content into the medical education curriculum.

Natural Death Versus Known Date-Of-Death: A Qualitative Study of Views on Voluntary Assisted Dying in an Online Course About Death.

The study aimed to describe views on Voluntary Assisted Dying (VAD), gleaned through qualitative analysis of participant responses to a set activity, run during the 2018 'Dying2Learn' Massive Open Online Course (MOOC). Data from 508 participants, most of whom identified as health professionals, were analysed using thematic content analysis, and themes generated. A large proportion of participants discussed their personal views related to VAD, specifically around choice, control, dignity, palliative care and dying at home, medical intervention, societal factors, the impact on those left behind, laws and regulations, dying 'naturally', advance care directives, and being in pain. In this study, participants had many different views on the act itself, often divisive, but also with common concepts such as respecting the choices and decisions of others.

Impact of the COVID-19 Pandemic on Funerals: Experiences of Participants in the 2020 Dying2Learn Massive Open Online Course.

A Massive-Open-Online-Course (MOOC) on death and dying (Dying2Learn) was offered in 2020, designed to build conversations about death as a natural part of life. In week 1, the content focused on how today's society engages with death through the language we use, humour, public mourning and funerals. This study investigated 2020 MOOC participants' responses to an online activity reflecting on funerals and memorials during the time of COVID-19. From this activity, n = 204 responses were analysed qualitatively. Themes included the positives and negatives of virtual funeral attendance (e.g. opportunity to have a way to participate when travel barriers existed, versus a sense of impersonal voyeurism); and the challenges related to the inability to physically comfort the bereaved due to physical distancing requirements. Comments made as part of this MOOC activity provide a unique insight into the community's experience of funeral changes necessitated by COVID-19, with important implications for the grieving process.

Baseline malaria prevalence and care-seeking behaviours in rural Madagascar prior to a trial to expand malaria community case management to all ages.

BACKGROUND: Integrated community case management of malaria, pneumonia, and diarrhoea can reduce mortality in children under five years (CU5) in resource-poor countries. There is growing interest in expanding malaria community case management (mCCM) to older individuals, but limited empirical evidence exists to guide this expansion. As part of a two-year cluster-randomized trial of mCCM expansion to all ages in southeastern Madagascar, a cross-sectional survey was conducted to assess baseline malaria prevalence and healthcare-seeking behaviours. METHODS: Two enumeration areas (EAs) were randomly chosen from each catchment area of the 30 health facilities (HFs) in Farafangana district designated for the mCCM age expansion trial; 28 households were randomly selected from each EA for the survey. All household members were asked about recent illness and care-seeking, and malaria prevalence was assessed by rapid diagnostic test (RDT) among children < 15 years of age. Weighted population estimates and Rao-Scott chi-squared tests were used to examine illness, care-seeking, malaria case management, and malaria prevalence patterns. RESULTS: Illness in the two weeks prior to the survey was reported by 459 (6.7%) of 8050 respondents in 334 of 1458 households surveyed. Most individuals noting illness (375/459; 82.3%) reported fever. Of those reporting fever, 28.7% (112/375) sought care; this did not vary by participant age (p = 0.66). Most participants seeking care for fever visited public HFs (48/112, 46.8%), or community healthcare volunteers (CHVs) (40/112, 31.0%). Of those presenting with fever at HFs or to CHVs, 87.0% and 71.0%, respectively, reported being tested for malaria. RDT positivity among 3,316 tested children < 15 years was 25.4% (CI: 21.5-29.4%) and increased with age: 16.9% in CU5 versus 31.8% in 5-14-year-olds (p < 0.0001). Among RDT-positive individuals, 28.4% of CU5 and 18.5% of 5-14-year-olds reported fever in the two weeks prior to survey (p = 0.044). CONCLUSIONS: The higher prevalence of malaria among older individuals coupled with high rates of malaria testing for those who sought care at CHVs suggest that expanding mCCM to older individuals may substantially increase the number of infected individuals with improved access to care, which could have additional favorable effects on malaria transmission.

Breast cancer in neurofibromatosis 1: survival and risk of contralateral breast cancer in a five country cohort study.

PURPOSE: Neurofibromatosis 1 (NF1) is an autosomal dominant condition caused by pathogenic variants of the NF1 gene. A markedly increased risk of breast cancer is associated with NF1. We have determined the breast cancer survival and risk of contralateral breast cancer in NF1. METHODS: We included 142 women with NF1 and breast cancer from five cohorts in Europe and 335 women without NF1 screened for other familial breast cancers. Risk of contralateral breast cancer and death were assessed by Kaplan-Meier analysis with delayed entry. RESULTS: One hundred forty-two women with NF1 were diagnosed for breast cancer at a median age of 46.9 years (range 27.0-84.3 years) and then followed up for 1235 person-years (mean = 8.70 years). Twelve women had contralateral breast cancer with a rate of 10.5 per 1000 years. Cumulative risk for contralateral breast cancer was 26.5% in 20 years. Five and 10-year all-cause survival was 64.9% (95% confidence interval [CI] = 54.8-76.8) and 49.8% (95%CI = 39.3-63.0). Breast cancer-specific 10-year survival was 64.2% (95% CI = 53.5-77.0%) compared with 91.2% (95% CI = 87.3-95.2%) in the non-NF1 age-matched population at increased risk of breast cancer. CONCLUSION: Women with NF1 have a substantial contralateral breast cancer incidence and poor survival. Early start of breast cancer screening may be a way to improve the survival.

Correction: Breast cancer in neurofibromatosis 1: survival and risk of contralateral breast cancer in a five country cohort study.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Perceived fatigue in children and young adults with neurofibromatosis type 1.

AIM: This study describes the prevalence and severity of perceived fatigue in a young neurofibromatosis type 1 (NF1) population. METHODS: Ethical approval was obtained and NF1 affected Individuals aged 2-18 years from the Manchester's NF1 clinic invited along with any unaffected siblings. The PedsQL Multidimensional Fatigue Scale Parental and child report was used. This validated measure explores cognitive, physical and sleep/rest domains on a 0-100 scale. Higher scores indicate less fatigue. Fatigue scores in affected children were compared to unaffected siblings after adjusting for age, sex and Index of Multiple Deprivation and with published population standards using z-scores. RESULTS: A total of 286 families were invited and 75 affected and 16 siblings participated. There were significant differences between NF1 and controls in the aggregated fatigue core (child report 55 ± 19 vs. 75 (14), P < 0.001; parent 54 ± 20 vs. 73 ± 18, P = 0.001) and the three sub-domains: cognitive (child 48 ± 27 vs. 75 ± 23, P < 0.001), physical (child 59 ± 19 vs. 82 ± 14, P < 0.001) and sleep/rest (child 59 ± 19 vs. 71 ± 15, P = 0.018). Similar differences were seen when compared with published controls (aggregated child z-score -1.9 ± 1.4, P < 0.001; parent -3.2 ± 1.8, P < 0.001). Prevalence of severe fatigue indicated by scores <2 standard deviation below published means for healthy controls were also higher for children with NF on both parent and child reports. Agreement between child and parent reports were limited as is frequently seen in the literature. CONCLUSION: This study suggests that children with NF1 are affected by perceived fatigue when compared with healthy children who do not have NF1.

Can Exposure to Online Conversations About Death and Dying Influence Death Competence? An Exploratory Study Within an Australian Massive Open Online Course.

A Massive Open Online Course, Dying2Learn, was designed to foster community death conversations and strengthen community awareness of palliative care and death as a normal process. This exploratory study used a pre-post prospective design to determine if participation in Dying2Learn and exposure to online conversations about death and dying resulted in any significant influence on death competence in 134 participants who completed the Coping-with-Death-Scale both at the beginning and end of the course in 2016. Death competence refers to a range of attitudes and capabilities people have for dealing with death. Results at the end of the course indicated that engagement in Dying2Learn led to significant improvements in death competence scores over time (medium-to-large effect size). The positive impact was greater for those who completed more of the course, and effectiveness did not depend on sociodemographic characteristics. In conclusion, this study found that an online learning platform in the form of a Massive Open Online Course could engage community members in meaningful social discussion about death and dying, and that exposure to these conversations was beneficial for all participants regardless of previous exposure to death. Further exploration is required to determine whether this change in death competence will have an impact on participant's behavior in the community regarding death conversations and preparedness.

Population-Based Analysis of DNA Damage and Epigenetic Effects of 1,3-Butadiene in the Mouse.

Metabolism of 1,3-butadiene, a known human and rodent carcinogen, results in formation of reactive epoxides, a key event in its carcinogenicity. Although mice exposed to 1,3-butadiene present DNA adducts in all tested tissues, carcinogenicity is limited to liver, lung, and lymphoid tissues. Previous studies demonstrated that strain- and tissue-specific epigenetic effects in response to 1,3-butadiene exposure may influence susceptibly to DNA damage and serve as a potential mechanism of tissue-specific carcinogenicity. This study aimed to investigate interindividual variability in the effects of 1,3-butadiene using a population-based mouse model. Male mice from 20 Collaborative Cross strains were exposed to 0 or 635 ppm 1,3-butadiene by inhalation (6 h/day, 5 days/week) for 2 weeks. We evaluated DNA damage and epigenetic effects in target (lung and liver) and nontarget (kidney) tissues of 1,3-butadiene-induced carcinogenesis. DNA damage was assessed by measuring N-7-(2,3,4-trihydroxybut-1-yl)-guanine (THB-Gua) adducts. To investigate global histone modification alterations, we evaluated the trimethylation and acetylation of histones H3 and H4 across tissues. Changes in global cytosine DNA methylation were evaluated from the levels of methylation of LINE-1 and SINE B1 retrotransposons. We quantified the degree of variation across strains, deriving a chemical-specific human variability factor to address population variability in carcinogenic risk, which is largely ignored in current cancer risk assessment practice. Quantitative trait locus mapping identified four candidate genes related to chromatin remodeling whose variation was associated with interstrain susceptibility. Overall, this study uses 1,3-butadiene to demonstrate how the Collaborative Cross mouse population can be used to identify the mechanisms for and quantify the degree of interindividual variability in tissue-specific effects that are relevant to chemically induced carcinogenesis.

Malaria case management commodity supply and use by community health workers in Mozambique, 2017.

BACKGROUND: Community health workers (CHWs) provide preventive care and integrated community case management (iCCM) to people with low healthcare access worldwide. CHW programmes have helped reduce mortality in myriad countries, but little data on malaria supply chain management has been shared. This project evaluated the current composition, use, and delivery of malaria iCCM kit commodities in Mozambique-rapid diagnostic tests (RDTs) and artemether-lumefantrine (AL) treatments-to better tailor existing resources to the needs of CHWs in diverse practice settings. METHODS: Health facilities in Maputo (low malaria burden), Inhambane (moderate), and Nampula (high) Provinces were selected using probability proportionate to the number of CHWs at each facility. All CHWs and their supervisors at selected facilities were interviewed using a structured questionnaire to document experiences with kit commodities. Data were analysed to assess CHW commodity stock levels by province and season. RESULTS: In total, 216 CHWs and 56 supervisors were interviewed at 56 health facilities. CHWs reported receiving an average of 6.7 kits in the last year, although they are intended to receive kits monthly. One-tenth of CHWs reported receiving kits with missing RDTs, and 28% reported lacking some AL treatments. Commodity use was highest in the rainy season. Stockouts were reported by CHWs in all provinces, more commonly in the rainy season. Facility-level stockouts of RDTs or some AL formulation in the past year were reported by 66% of supervisors. Use of CHW kit materials by health facilities was reported by 43% of supervisors; this was most common at facilities experiencing stockouts. CONCLUSIONS: Variations in geographic and seasonal malaria commodity needs should be considered in CHW kit distribution planning in Mozambique. Improvements in provision of complete, monthly CHW kits are needed in parallel with improvements in the broader commodity system strengthening. The findings of this evaluation can help other CHW programmes determine best practices for management of iCCM supply chains.

Sex-specific differences in genotoxic and epigenetic effects of 1,3-butadiene among mouse tissues.

Exposure to environmental chemicals has been shown to have an impact on the epigenome. One example is a known human carcinogen 1,3-butadiene which acts primarily by a genotoxic mechanism, but also disrupts the chromatin structure by altering patterns of cytosine DNA methylation and histone modifications. Sex-specific differences in 1,3-butadiene-induced genotoxicity and carcinogenicity are well established; however, it remains unknown whether 1,3-butadiene-associated epigenetic alterations are also sex dependent. Therefore, we tested the hypothesis that inhalational exposure to 1,3-butadiene will result in sex-specific epigenetic alterations. DNA damage and epigenetic effects of 1,3-butadiene were evaluated in liver, lung, and kidney tissues of male and female mice of two inbred strains (C57BL/6J and CAST/EiJ). Mice were exposed to 0 or 425 ppm of 1,3-butadiene by inhalation (6 h/day, 5 days/week) for 2 weeks. Strain- and tissue-specific differences in 1,3-butadiene-induced DNA adducts and crosslinks were detected in the liver, lung and kidney; however, significant sex-specific differences in DNA damage were observed in the lung of C57BL/6J mice only. In addition, we assessed expression of the DNA repair genes and observed a marked upregulation of Mgmt in the kidney in female C57BL/6J mice. Sex-specific epigenetic effects of 1,3-butadiene exposure were evident in alterations of cytosine DNA methylation and histone modifications in the liver and lung in both strains. Specifically, we observed a loss of cytosine DNA methylation in the liver and lung of male and female 1,3-butadiene-exposed C57BL/6J mice, whereas hypermethylation was found in the liver and lung in 1,3-butadiene-exposed female CAST/EiJ mice. Our findings suggest that strain- and sex-specific effects of 1,3-butadiene on the epigenome may contribute to the known differences in cancer susceptibility.

A novel naloxone training compared with current recommended training in an overdose simulation.

OBJECTIVES: The aim of this study was to determine if a novel naloxone training program with a focus on situational stress management yields better results than the currently recommended state training in a simulated overdose response. METHODS: Students were randomized to receive either the state training or a novel training developed by the Wilkes University Nesbitt School of Pharmacy. After their respective training, each student individually completed a live simulated overdose response with an added stressor of a panicked bystander. A checklist was used to evaluate students during the simulation, and the results were compared. RESULTS: The average grade for the novel training students was 89% compared with 64% for the state training students (P < 0.001). There was no statistically significant difference in time to complete the simulation. CONCLUSION: Students who underwent the novel training received the state training. The novel training appears to be effective in preparing students to manage a live opioid overdose.

Correlates of perceived death competence: What role does meaning-in-life and quality-of-life play?

OBJECTIVE: Understanding factors that are associated with more adaptive death attitudes and competencies can inspire future health-promoting palliative care strategies and inform approaches to training and development for health professionals. The potential importance of meaning, purpose, quality, and values in life for promoting adaptive death attitudes has been highlighted, but there is limited research in this area, particularly in relation to death competence. The purpose of this cross-sectional study was to develop an understanding of demographic and life-related factors associated with perceived death competence, such as meaning in life and quality of life. METHOD: During the course enrollment period of a Massive-Online-Open-Course about death and dying, 277 participants completed questionnaires on death competence, meaning in life, quality of life, and sociodemographic background. RESULT: Findings indicated that greater presence of meaning in life, quality of life, age, death experience, and carer experience were each statistically significant unique predictors of death competence scores. Life-related variables were more strongly associated with death competence than demographic variables. Bereavement experience and experience caring for the dying was associated with greater death competence, but there were no differences on death competence between health professionals and the general community. Above all other factors, the presence of meaning in life was the strongest predictor of higher perceived competence in coping with death. SIGNIFICANCE OF RESULTS: The findings demonstrate important interconnections between our attitudes about life and death. Knowledge of factors associated with poorer death competence may help identify those at risk of greater distress when facing death, and might prove useful additions to bereavement risk assessments. Understanding factors associated with greater death competence in health professionals and volunteers may help predict or prevent burnout and compassion fatigue, and help identify who would benefit from additional training and support. Future longitudinal studies including both health professionals and the general community are needed to determine the effect adaptive attitudes toward meaning in life can potentially have on bolstering subsequent adaptive coping and competence regarding death and dying.

Tissue- and strain-specific effects of a genotoxic carcinogen 1,3-butadiene on chromatin and transcription.

Epigenetic effects of environmental chemicals are under intense investigation to fill existing knowledge gaps between environmental/occupational exposures and adverse health outcomes. Chromatin accessibility is one prominent mechanism of epigenetic control of transcription, and understanding of the chemical effects on both could inform the causal role of epigenetic alterations in disease mechanisms. In this study, we hypothesized that baseline variability in chromatin organization and transcription profiles among various tissues and mouse strains influence the outcome of exposure to the DNA damaging chemical 1,3-butadiene. To test this hypothesis, we evaluated DNA damage along with comprehensive quantification of RNA transcripts (RNA-seq), identification of accessible chromatin (ATAC-seq), and characterization of regions with histone modifications associated with active transcription (ChIP-seq for acetylation at histone 3 lysine 27, H3K27ac). We collected these data in the lung, liver, and kidney of mice from two genetically divergent strains, C57BL/6J and CAST/EiJ, that were exposed to clean air or to 1,3-butadiene (~600 ppm) for 2 weeks. We found that tissue effects dominate differences in both gene expression and chromatin states, followed by strain effects. At baseline, xenobiotic metabolism was consistently more active in CAST/EiJ, while immune system pathways were more active in C57BL/6J across tissues. Surprisingly, even though all three tissues in both strains harbored butadiene-induced DNA damage, little transcriptional effect of butadiene was observed in liver and kidney. Toxicologically relevant effects of butadiene in the lung were on the pathways of xenobiotic metabolism and inflammation. We also found that variability in chromatin accessibility across individuals (i.e., strains) only partially explains the variability in transcription. This study showed that variation in the basal states of epigenome and transcriptome may be useful indicators for individuals or tissues susceptible to genotoxic environmental chemicals.

The contribution of a MOOC to community discussions around death and dying.

BACKGROUND: Advances in medicine have helped many to live longer lives and to be able to meet health challenges. However death rates are anticipated to increase given the ageing population and chronic disease progression. Being able to talk about death is seen to be important in normalising death as part of life and supporting preparedness for death. Massive Open Online Courses (MOOCs) provide opportunities for the community to engage in collaborative learning. A 5 week MOOC was developed covering four main topics (language and humour, representations of death, medicalisation of dying, and digital dying) aiming: To enable participants to openly and supportively discuss and learn about issues around living, death and dying, To explore the normally unheard opinions and views of Australians around death and dying, and To determine what effect online learning and discussions offered through the MOOC had on participants' feelings and attitudes towards death and dying. METHODS: Data was captured on engagement rates in the various MOOC activities. Death Attitudes were measured by five items representing the MOOC's learning objectives and completed at enrolment and conclusion. MOOC Satisfaction was measured with six items at the end of the MOOC. Descriptive statistics were produced for each variable and Chi-Square Tests of Independence assessed the extent of the relationship between categorical variables. Socio-demographic variables were examined as predictors of the outcome variables of MOOC engagement, MOOC satisfaction, and death attitudes. Ethical approval was received from Flinders University Social and Behavioural Research Ethics Committee (Project No. 7247). RESULTS: One thousand one hundred fifty six people enrolled in the Dying2Learn MOOC with 895 participating in some way. Enrolees were primarily female (92.1%). Age ranged from 16 to 84 (mean = 49.5, SD = 12.3). MOOC satisfaction scores were high. Responses to the experience of participating in the MOOC were very positive, with mean scores ranging from 4.3 to 4.6 (aligning with agreement and strong agreement to statements on the value of participating). Death Attitudes were positive at commencement but increased significantly following participation. CONCLUSIONS: The Dying2Learn MOOC provided an environment that enabled open and supportive discussion around death and dying and influenced attitudinal change.

The Oxytocin Product Correlates with Total Oxytocin Received during Labor: A Research Methods Study.

OBJECTIVE: Total dose of oxytocin received during labor is an important variable in studies of human labor but is difficult to calculate. We sought to identify a surrogate measure for total dose of oxytocin received. STUDY DESIGN: For each subject receiving oxytocin during labor, the oxytocin total dose received in labor was calculated as the area under the curve. Maximal oxytocin infusion rate, total duration of oxytocin infusion, and the product of both, defined as the oxytocin product, were then each correlated with the total dose of oxytocin received using the Pearson's correlation coefficient. RESULTS: Oxytocin dosing data were available from 402 women at Duke and 6,907 women from Pithagore6. The two variables alone, or combined as the oxytocin product, demonstrated a high correlation with the oxytocin total dose (r > 0.7), with the oxytocin product demonstrating the highest (r > 0.9). This was true whether labor was induced or augmented and whether delivery was vaginal or cesarean. CONCLUSION: The oxytocin product, composed of two easily obtained variables, demonstrated a very high correlation with total oxytocin dose received in labor and represents a simple and accurate surrogate for total dose of oxytocin received during labor. The oxytocin product can be used in clinical studies in which oxytocin dose is an important variable.

Never say die: death euphemisms, misunderstandings and their implications for practice.

BACKGROUND: A Massive Open Online Course (MOOC) on death and dying was conducted to open the dialogue around death and dying. In one activity, participants were asked to engage with language and to think of alternative words (or euphemisms) that are used to describe death. AIM: To reflect from a nursing perspective how language enables and sometimes disguises important messages and conversations. METHODS: Four hundred and seventy one participants provided 3053 euphemisms. FINDINGS: Euphemisms were varied, with many providing commentary on their purpose and use. DISCUSSION: As a society we have become quite creative in the use of euphemisms, but need to be mindful of misunderstandings and misinterpretations which can cause embarrassment and distress in clinical situations. CONCLUSION: This paper describes some of the euphemisms that were provided, examining why they are used and how their use can be easily misconstrued in daily life and in clinical practice.