Phylogenomics and the rise of the angiosperms.

Angiosperms are the cornerstone of most terrestrial ecosystems and human livelihoods1,2. A robust understanding of angiosperm evolution is required to explain their rise to ecological dominance. So far, the angiosperm tree of life has been determined primarily by means of analyses of the plastid genome3,4. Many studies have drawn on this foundational work, such as classification and first insights into angiosperm diversification since their Mesozoic origins5-7. However, the limited and biased sampling of both taxa and genomes undermines confidence in the tree and its implications. Here, we build the tree of life for almost 8,000 (about 60%) angiosperm genera using a standardized set of 353 nuclear genes8. This 15-fold increase in genus-level sampling relative to comparable nuclear studies9 provides a critical test of earlier results and brings notable change to key groups, especially in rosids, while substantiating many previously predicted relationships. Scaling this tree to time using 200 fossils, we discovered that early angiosperm evolution was characterized by high gene tree conflict and explosive diversification, giving rise to more than 80% of extant angiosperm orders. Steady diversification ensued through the remaining Mesozoic Era until rates resurged in the Cenozoic Era, concurrent with decreasing global temperatures and tightly linked with gene tree conflict. Taken together, our extensive sampling combined with advanced phylogenomic methods shows the deep history and full complexity in the evolution of a megadiverse clade.

To explore the factors that impact on patient concordance with venous leg ulcer management using compression therapy.

It is understood that intervention for venous leg ulcer (VLU) management is more successful the sooner compression is applied, yet healing rates of VLUs are falling and recurrence rates increasing. This literature review seeks to explore the factors affecting patient concordance with compression therapy to manage VLU. Of the literature searched, 14 articles were identified and four themes of reasons for non-concordance emerged: education; pain/discomfort; physical limitations; and psychosocial issues. The reasons for non-concordance are vast and complex; district nurses must explore these reasons to help improve the alarming rates of non-concordance. A personalised approach is necessary to meet individual needs. High risks of ulcer recurrence are noted and a greater understanding of the chronic nature of ulceration should be conveyed. Follow-up care and building trust is linked with higher rates of concordance. Further research is needed within district nursing as the majority of venous ulceration is managed within the community.

The challenges homeless people face when accessing end-of-life care: what district nurses need to know.

People experiencing homelessness have poorer physical and mental health compared with the rest of the population. Mortality rates are significantly higher, yet there is a dearth in suitable places for the delivery of palliative and end-of-life (EOL) care. Homeless people are being failed by the current healthcare system. The stigma associated with being homeless negatively impacts these marginalised people, affecting care given from healthcare professionals (HCP). Services are often inflexible and have little tolerance for substance misuse. District Nurses (DN) are often experienced EOL care practitioners and well-placed to give person-centred care with a focus on collaborative decision-making. However, many homeless people die without input from DNs or specialist palliative support. It is important to understand why this is happening to address what can be done to help.

1. Vaginal breech birth--the phoenix arising from the ashes.

Vaginal breech birth all but disappeared from UK maternity units after the publication of the Term Breech Trial (Hannah et al 2000). However, mounting evidence does not support caesarean section as the safest mode of birth for the baby or the mother when the baby is presenting breech. But the intervening years have depleted the attending professional's skills. We describe our personal journey to regaining them, learning better ones and introducing safe choice for women. This article is the first in a series which examines the practice and evidence base for the care of women and babies aspiring to experience a safe breech birth.

Estimating the alcohol-related burden of child maltreatment among Maori in Aotearoa, New Zealand.

INTRODUCTION: To assesses the alcohol-related burden of child maltreatment among Maori in Aotearoa New Zealand. We compared the risk of child maltreatment among Maori (0-17 years) exposed to parents with alcohol-related hospitalisation or mental health/addiction service use. We also conducted a sensitivity analysis to estimate the number of cases of maltreatment that could be attributed to alcohol among Maori. METHODS: A cohort study of 16,617 Maori aged 0-17 and their parents from 2000 to 2017 was conducted using the Statistics New Zealand Integrated Data Infrastructure. A Bayesian piecewise exponential model estimated the risk of time to first child maltreatment event. This analysis used data from child protection, hospital, mortality and police records, and specifically focused on the risk associated with exposure to parents with an alcohol-attributable hospitalisation or mental health/addiction service use event. Potential confounders for both parents and Maori (0-17 years) were included. We calculated a population-attributable fraction to estimate the proportion of maltreatment cases that could be attributed to alcohol in 2017. RESULTS: Results showed a 65% increased risk for young Maori exposed to parents with heavy alcohol use. We estimated 17% of substantiated child maltreatment among Maori could be attributed to parental hazardous alcohol consumption. DISCUSSION AND CONCLUSIONS: Severe or hazardous alcohol consumption among parents is a risk factor for child maltreatment among Maori. Maori alcohol consumption and harm are symptomatic of wider inequities related, among other things, to the ongoing effects of colonisation, as well as gaps in the regulation of alcohol sales.

Quantifying alcohol-attributable disability-adjusted life years to others than the drinker in Aotearoa/New Zealand: A modelling study based on administrative data.

BACKGROUND AND AIMS: Quantifying the health burden of alcohol has largely focused upon harm to drinkers, which is an underestimate. There is a growing literature on alcohol's harm to others (HTO), but it lacks the systematic transfer of HTO into a comparative risk assessment framework. This study calculated disability-adjusted life years (DALYs) for fetal alcohol spectrum disorder (FASD), interpersonal violence and traffic injury due to another's drinking. DESIGN: This study is a disease burden analysis, using modelling of DALYs for New Zealand in 2018. SETTING AND PARTICIPANTS: The study took place among the Aotearoa/New Zealand population in 2018. MEASUREMENTS: The involvement of others' drinking was obtained from prevalence, alcohol-attributable fraction studies and administrative data. Disability weights (DW) for FASD were adapted from fetal alcohol syndrome (FAS) weights using a Beta-Pert probability distribution; for interpersonal injury, DWs used hospital events linked with injury compensation; for traffic injury, DWs used hospital events. Populations were stratified by ethnicity, age group and gender. A descriptive comparison was made with a previous estimate of DALYs for drinkers. FINDINGS: In 2018, 78 277 healthy life years were lost in Aotearoa/New Zealand due to alcohol's HTO. The main contributor (90.3%) was FASD, then traffic crashes (6.3%) and interpersonal violence (3.4%). The indigenous population, Maori, was impacted at a higher rate (DALYs among Maori were 25 per 1000 population; among non-Maori 15 per 1000 population). The burden of HTO was greater than that to drinkers (DALYs HTO = 78 277; DALYs drinkers = 60 174). CONCLUSIONS: Disability from fetal alcohol spectrum disorder (FASD) appears to be a major contributor to alcohol's harm to others in Aotearoa/New Zealand. Taking FASD into account, the health burden of harm to others is larger than harm to the drinker in Aotearoa/New Zealand, and ethnicity differences show inequity in harm to others. Quantification of the burden of harm informs the value of implementing effective alcohol policies and should include the full range of harms.

Measurement and Incorporation of Laryngeal Motion Using cine-MRI on an MR-Linear Accelerator to Generate Radiation Therapy Plans for Early-stage Squamous Cell Cancers of the Glottis.

Purpose: Swallow-related motion of the larynx is most significant in the cranio-caudal directions and of` short duration. Conventional target definition for radical radiation therapy includes coverage of the whole larynx. This study longitudinally examined respiration- and swallow-related laryngeal motions using cine-magnetic resonance imaging. We further analyzed the dosimetry to organs at risk by comparing 3D-conformal radiation therapy (3D-CRT), volumetric modulated arc therapy (VMAT), and intensity modulated radiation therapy (IMRT) techniques. Methods: Fifteen patients with T1-2 N0 glottic squamous cell carcinomas were prospectively recruited for up to 3 cine-MRI scans on the Elekta Unity MR-Linear accelerator, at the beginning, middle, and end of a course of radical radiation therapy. Swallow frequency and motion of the hyoid bone, cricoid and thyroid cartilages, and vocal cords were recorded during swallow and rest. Adapted treatment volumes consisted of gross tumor volume + 0.5-1 cm to a clinical target volume with an additional internal target volume (ITV) for personalized resting-motion. Swallow-related motion was deemed infrequent and was not accounted for in the ITV. We compared radiation therapy plans for 3D-CRT (whole larynx), VMAT (whole larynx), and VMAT and IMRT (ITV for resting motion). Results: Resting- and swallow-related motions were most prominent in the cranio-caudal plane. There were no significant changes in the magnitude of motion over the course of radiation therapy. There was a trend of a progressive reduction in the frequency of swallow. Treatment of partial larynx volumes with intensity modulated methods significantly reduced the dose to carotid arteries, compared with treatment of whole larynx volumes. Robustness analysis demonstrated that when accounting for intrafraction swallow, the total dose delivered to the ITV/planning target volume was maintained at above 95%. Conclusions: Swallow-related motions are infrequent and accounting for resting motion in an ITV is sufficient. VMAT/IMRT techniques that treat more conformal targets can significantly spare critical organs at risk such as the carotid arteries and thyroid gland, potentially reducing the risk of carotid artery stenosis-related complications and other long-term complications.

Medication management in patients with dysphagia: a service evaluation.

The administration of medicines to patients with dysphagia presents substantial challenges to patient safety. Within stroke services, where up to half of patients may experience dysphagia, ensuring safe medication management is particularly challenging. This article describes how best practice within one stroke unit is being achieved by means of a knowledge-to-action service improvement project, ongoing education and training, and the input of a specialist dysphagia practitioner.

Evaluation of therapeutic radiographer contouring for magnetic resonance image guided online adaptive prostate radiotherapy.

BACKGROUND AND PURPOSE: The implementation of MRI-guided online adaptive radiotherapy has facilitated the extension of therapeutic radiographers' roles to include contouring, thus releasing the clinician from attending daily treatment. Following undergoing a specifically designed training programme, an online interobserver variability study was performed. MATERIALS AND METHODS: 117 images from six patients treated on a MR Linac were contoured online by either radiographer or clinician and the same images contoured offline by the alternate profession. Dice similarity coefficient (DSC), mean distance to agreement (MDA), Hausdorff distance (HD) and volume metrics were used to analyse contours. Additionally, the online radiographer contours and optimised plans (n = 59) were analysed using the offline clinician defined contours. After clinical implementation of radiographer contouring, target volume comparison and dose analysis was performed on 20 contours from five patients. RESULTS: Comparison of the radiographers' and clinicians' contours resulted in a median (range) DSC of 0.92 (0.86 - 0.99), median (range) MDA of 0.98 mm (0.2-1.7) and median (range) HD of 6.3 mm (2.5-11.5) for all 117 fractions. There was no significant difference in volume size between the two groups. Of the 59 plans created with radiographer online contours and overlaid with clinicians' offline contours, 39 met mandatory dose constraints and 12 were acceptable because 95 % of the high dose PTV was covered by 95 % dose, or the high dose PTV was within 3 % of online plan. A clinician blindly reviewed the eight remaining fractions and, using trial quality assurance metrics, deemed all to be acceptable. Following clinical implementation of radiographer contouring, the median (range) DSC of CTV was 0.93 (0.88-1.0), median (range) MDA was 0.8 mm (0.04-1.18) and HD was 5.15 mm (2.09-8.54) respectively. Of the 20 plans created using radiographer online contours overlaid with clinicians' offline contours, 18 met the dosimetric success criteria, the remaining 2 were deemed acceptable by a clinician. CONCLUSION: Radiographer and clinician prostate and seminal vesicle contours on MRI for an online adaptive workflow are comparable and produce clinically acceptable plans. Radiographer contouring for prostate treatment on a MR-linac can be effectively introduced with appropriate training and evaluation. A DSC threshold for target structures could be implemented to streamline future training.

Interobserver variation of clinical oncologists compared to therapeutic radiographers (RTT) prostate contours on T2 weighted MRI.

The implementation of MRI-guided online adaptive radiotherapy has enabled extension of therapeutic radiographers' roles to include contouring. An offline interobserver variability study compared five radiographers' and five clinicians' contours on 10 MRIs acquired on a MR-Linac from 10 patients. All contours were compared to a "gold standard" created from an average of clinicians' contours. The median (range) DSC of radiographers' and clinicians' contours compared to the "gold standard" was 0.91 (0.86-0.96), and 0.93 (0.88-0.97) respectively illustrating non-inferiority of the radiographers' contours to the clinicians. There was no significant difference in HD, MDA or volume size between the groups.

Bladder filling in patients undergoing prostate radiotherapy on a MR-linac: The dosimetric impact.

The implementation of adaptive radiotherapy for prostate cancer compensates for inter-fraction motion, at the penalty of increased time in room. The subsequent increase in bladder filling may impact dosimetry, which we have investigated on ten patients treated on the MR-linac. Patients drank water before treatment, to achieve a bladder volume of 200-300 cm3. Bladder and bowel were re-outlined offline on 140 images and plans recalculated. All mandatory bladder dose constraints and 99.1% of bowel constraints were achieved at time of treatment, despite varying bladder volumes and varying adherence to original bladder filling guidance.

Online adaptive radiotherapy for head and neck cancers on the MR linear Accelerator: Introducing a novel modified Adapt-to-Shape approach.

INTRODUCTION: The Elekta Unity MR-Linac (MRL) has enabled adaptive radiotherapy (ART) for patients with head and neck cancers (HNC). Adapt-To-Shape-Lite (ATS-Lite) is a novel Adapt-to-Shape strategy that provides ART without requiring daily clinician presence to perform online target and organ at risk (OAR) delineation. In this study we compared the performance of our clinically-delivered ATS-Lite strategy against three Adapt-To-Position (ATP) variants: Adapt Segments (ATP-AS), Optimise Weights (ATP-OW), and Optimise Shapes (ATP-OS). METHODS: Two patients with HNC received radical-dose radiotherapy on the MRL. For each fraction, an ATS-Lite plan was generated online and delivered and additional plans were generated offline for each ATP variant. To assess the clinical acceptability of a plan for every fraction, twenty clinical goals for targets and OARs were assessed for all four plans. RESULTS: 53 fractions were analysed. ATS-Lite passed 99.9% of mandatory dose constraints. ATP-AS and ATP-OW each failed 7.6% of mandatory dose constraints. The Planning Target Volumes for 54 Gy (D95% and D98%) were the most frequently failing dose constraint targets for ATP. ATS-Lite median fraction times for Patient 1 and 2 were 40 mins 9 s (range 28 mins 16 s - 47 mins 20 s) and 32 mins 14 s (range 25 mins 33 s - 44 mins 27 s), respectively. CONCLUSIONS: Our early data show that the novel ATS-Lite strategy produced plans that fulfilled 99.9% of clinical dose constraints in a time frame that is tolerable for patients and comparable to ATP workflows. Therefore, ATS-Lite, which bridges the gap between ATP and full ATS, will be further utilised and developed within our institute and it is a workflow that should be considered for treating patients with HNC on the MRL.

Dosimetric comparison of automatically propagated prostate contours with manually drawn contours in MRI-guided radiotherapy: A step towards a contouring free workflow?

Background: The prostate demonstrates inter- and intra- fractional changes and thus adaptive radiotherapy would be required to ensure optimal coverage. Daily adaptive radiotherapy for MRI-guided radiotherapy can be both time and resource intensive when structure delineation is completed manually. Contours can be auto-generated on the MR-Linac via a deformable image registration (DIR) based mapping process from the reference image. This study evaluates the performance of automatically generated target structure contours against manually delineated contours by radiation oncologists for prostate radiotherapy on the Elekta Unity MR-Linac. Methods: Plans were generated from prostate contours propagated by DIR and rigid image registration (RIR) for forty fractions from ten patients. A two-dose level SIB (simultaneous integrated boost) IMRT plan is used to treat localised prostate cancer; 6000 cGy to the prostate and 4860 cGy to the seminal vesicles. The dose coverage of the PTV 6000 and PTV 4860 created from the manually drawn target structures was evaluated with each plan. If the dose objectives were met, the plan was considered successful in covering the gold standard (clinician-delineated) volume. Results: The mandatory PTV 6000 dose objective (D98% > 5580 cGy) was met in 81 % of DIR plans and 45 % of RIR plans. The SV were mapped by DIR only and for all the plans, the PTV 4860 dose objective met the optimal target (D98% > 4617 cGy). The plans created by RIR led to under-coverage of the clinician-delineated prostate, predominantly at the apex or the bladder-prostate interface. Conclusion: Plans created from DIR propagation of prostate contours outperform those created from RIR propagation. In approximately 1 in 5 DIR plans, dosimetric coverage of the gold standard PTV was not clinically acceptable. Thus, at our institution, we use a combination of DIR propagation of contours alongside manual editing of contours where deemed necessary for online treatments.

Kids in the city study: research design and methodology.

BACKGROUND: Physical activity is essential for optimal physical and psychological health but substantial declines in children's activity levels have occurred in New Zealand and internationally. Children's independent mobility (i.e., outdoor play and traveling to destinations unsupervised), an integral component of physical activity in childhood, has also declined radically in recent decades. Safety-conscious parenting practices, car reliance and auto-centric urban design have converged to produce children living increasingly sedentary lives. This research investigates how urban neighborhood environments can support or enable or restrict children's independent mobility, thereby influencing physical activity accumulation and participation in daily life. METHODS/DESIGN: The study is located in six Auckland, New Zealand neighborhoods, diverse in terms of urban design attributes, particularly residential density. Participants comprise 160 children aged 9-11 years and their parents/caregivers. Objective measures (global positioning systems, accelerometers, geographical information systems, observational audits) assessed children's independent mobility and physical activity, neighborhood infrastructure, and streetscape attributes. Parent and child neighborhood perceptions and experiences were assessed using qualitative research methods. DISCUSSION: This study is one of the first internationally to examine the association of specific urban design attributes with child independent mobility. Using robust, appropriate, and best practice objective measures, this study provides robust epidemiological information regarding the relationships between the built environment and health outcomes for this population.

An environmentally friendly alternative to single-use plastics for radiotherapy bladder preparation.

More than 60,000 plastic cups were used annually for bladder preparation in one radiotherapy centre. As an alternative, patients were provided with a specifically designed reusable water bottle, aiming to reduce waste and improve bladder filling compliance. Cup usage and bladder volume at treatment were calculated pre- and post-implementation. Bladder volume was measured as a percentage of the planned volume and grouped for analysis. Cup usage halved from 12,000 cups to 6000 cups. Percentage of bladder volumes in the optimal group increased from 47% to 54%. The introduction of water bottles reduced plastic cup usage and increased bladder filling compliance.

Constructing a new role for family carers and volunteers providing care towards the end of life: an action research approach exploring a new model of hospice care.

The objective of this study was to understand the conceptualisation and development of a novel way of providing end-of-life care in a Cottage Hospice setting, with a focus on the role of family carers and volunteers within this care model. A participatory action research design enabled a situational analysis, together with change processes. The study setting was a hospice in the South of England, and its network of wider associates in the local health economy. Participants were purposively sampled to provide relevant information. Data collection (2017-2018) included documents (e.g., meeting minutes) and interviews (individual and group) with external (e.g., GPs) and internal (e.g., staff, managers, volunteers, patients, family carers) stakeholders. These were followed by action cycles conducted by a core action group which explored issues related to family and young carers, the relationship between the main and Cottage Hospices and workforce engagement with the change process. Iterative, inductive, thematic analysis was followed by axial coding facilitated within NVivo. Twenty-six individual and eight follow-up interviews, two group interviews and five discrete action cycles were completed. At the core was a focus on disruption of the norm of professionally provided and mediated care, with three main themes: imagining the future of Cottage Hospice (growing demand, a home-like space, innovative roles for families and volunteers); developing the role of family caregivers (making agreements, meeting needs, social inclusion and the 'unknown' expectations) and quality and safety issues (negative perceptions, personalised care and volunteer roles). Change was viewed as both a threat and an opportunity. Cottage Hospice represents the possibility of a truly new way of meeting the needs of dying people and their families, and could act as a template for progressive service developments elsewhere.

Development and results of a patient-reported treatment experience questionnaire on a 1.5 T MR-Linac.

INTRODUCTION: With the implementation of new radiotherapy technology, it is imperative that patient experience is investigated alongside efficacy and outcomes. This paper presents the development of a specifically designed validated questionnaire and a first report of international multi-institutional preliminary patient experience of MRI-guided adaptive radiotherapy (MRgART) on the 1.5 T MR-Linac (MRL). METHODS: A patient experience questionnaire was developed and validated before being distributed to the Elekta MRL Consortium, to gather first patient-reported experience from participating centres worldwide. The final version of the questionnaire contains 18 questions covering a range of themes and was scored on a Likert scale of 0-3. Responses were post-processed so that a score of 0 represents a negative response and 3 represents the most favourable response. These results were analysed for patient-reported experience of treatment on the MRL. Results were also analysed for internal consistency of the questionnaire using Chronbach's Alpha and the questionnaire contents were validated for relevance using content validity indexes (CVI). RESULTS: 170 responses were received from five centres, representing patients with a wide range of tumour treatment sites from four different countries. MRgART was well tolerated with an 84% favourable response across all questions and respondents. When analysed by theme, all reported the highest percentage of results in the favourable categories (2 and 3). Internal consistency in the questionnaire was high (Cronbach's α = 0.8) and the item-level CVI for each question was 0.78 or above and the Scale-level CVI was 0.93, representing relevant content. CONCLUSION: The developed questionnaire has been validated as relevant and appropriate for use in reporting experience of patients undergoing treatment on the MRL. The overall patient-reported experience and satisfaction from multiple centres within the Elekta MRL Consortium was consistently high. These results can reinforce user confidence in continuing to expand and develop MRL use in adaptive radiotherapy.

Kaupapa Maori Action Research to improve heart disease services in Aotearoa, New Zealand.

Action Research can be a powerful tool for change and improvement in health services for indigenous people when utilised within an appropriate framework. The project Maori Utilisation & Experience of Ischaemic Heart Disease Management illustrates this convergence in its use of Kaupapa Maori Action Research methods in its efforts to improve the health and well-being of Maori within the northern region of Aotearoa/New Zealand. We outline the research processes and outcomes obtained through the application of 'by Maori for Maori' approaches to understanding Maori pathways and barriers to care for ischaemic heart disease. Maori understandings of their illness and experiences of treatment, and healthcare providers' perspectives on care of Maori with ischaemic heart disease, were combined into Maori-led actions to improve service provision. The paper examines critical factors in an action research approach to health service innovations and implications for efforts to reduce entrenched health disparities.

Laser-free pelvic alignment in an online adaptive radiotherapy environment.

The MR-Linac (MRL) provides a novel treatment modality that enables online adaptive treatments, but also creates new challenges for patient positioning in a laser-free environment. The accuracy and duration of prostate patient set-up on the MRL using two different methods for patient alignment was determined to establish standard of practice on the MRL. Differences in set-up accuracy were significant in the longitudinal direction and are accounted for in online plan adaption. Both methods recorded similar set-up times. The vendor recommended alignment method involves less manipulation of the patient and will be adopted as the standard positioning method for prostate and other pelvic patients on the MRL in future.