A national pilot of donation after circulatory death (DCD) heart transplantation within the United Kingdom.

BACKGROUND: The United Kingdom (UK) was one of the first countries to pioneer heart transplantation from donation after circulatory death (DCD) donors. To facilitate equity of access to DCD hearts by all UK heart transplant centers and expand the retrieval zone nationwide, a Joint Innovation Fund (JIF) pilot was provided by NHS Blood and Transplant (NHSBT) and NHS England (NHSE). The activity and outcomes of this national DCD heart pilot program are reported. METHODS: This is a national multi-center, retrospective cohort study examining early outcomes of DCD heart transplants performed across 7 heart transplant centers, adult and pediatric, throughout the UK. Hearts were retrieved using the direct procurement and perfusion (DPP) technique by 3 specialist retrieval teams trained in ex-situ normothermic machine perfusion. Outcomes were compared against DCD heart transplants before the national pilot era and against contemporaneous donation after brain death (DBD) heart transplants, and analyzed using Kaplan-Meier analysis, chi-square test, and Wilcoxon's rank-sum. RESULTS: From September 7, 2020 to February 28, 2022, 215 potential DCD hearts were offered of which 98 (46%) were accepted and attended. There were 77 potential donors (36%) which proceeded to death within 2 hours, with 57 (27%) donor hearts successfully retrieved and perfused ex situ and 50 (23%) DCD hearts going on to be transplanted. During this same period, 179 DBD hearts were transplanted. Overall, there was no difference in the 30-day survival rate between DCD and DBD (94% vs 93%) or 90 day survival (90% vs 90%) respectively. There was a higher rate of ECMO use post-DCD heart transplants compared to DBD (40% vs 16%, p = 0.0006), and DCD hearts in the pre pilot era, (17%, p = 0.002). There was no difference in length of ICU stay (9 DCD vs 8 days DBD, p = 0.13) nor hospital stay (28 DCD vs 27 DBD days, p = 0.46). CONCLUSION: During this pilot study, 3 specialist retrieval teams were able to retrieve DCD hearts nationally for all 7 UK heart transplant centers. DCD donors increased overall heart transplantation in the UK by 28% with equivalent early posttransplant survival compared with DBD donors.

Adult heart procurement following circulatory determined death from a donor on venous-venous extracorporeal membrane oxygenation: A case report.

Donation after circulatory death in the context of heart transplants is attracting interest and becoming popular in clinical practice. Activity is growing in the United Kingdom, Australia, and the United States. We believe that a prolonged warm ischemic time (time from asystole to reperfusion of the heart on an ex vivo perfusion system) is a primary indicator of adverse outcomes. However, 1.5 liters of blood must be retrieved from the right atrium following sternotomy prolonging warm ischemic time. The patient in the following case report was supported by veno-venous extra-corporeal membrane oxygenation following drowning, further complicated by aspiration-related lung failure. Following circulatory death and a mandatory five-minute stand-off period, 1.5 liters of blood was drained from the circuit as sternotomy began. Surgeons then proceeded to direct procurement of the heart, aiming for least functional warm ischemic time. Following standard implantation, the patient's postoperative recovery has been unremarkable to date.

Estimates of Quality-Adjusted Life-Year Loss for Injuries in the United States.

PURPOSE: The goal of this study is to develop an approach for estimating nationally representative quality-adjusted life-year (QALY) loss from injury and poisoning conditions using data collected in the Medical Expenditure Panel Survey (MEPS) and the National Health Interview Survey (NHIS). METHODS: This study uses data from the 2002-2015 NHIS and MEPS surveys. Injuries were identified in the MEPS medical events file and through self-reporting of medical conditions. We restricted our model to 163,731 adults, for which we predict a total of 294,977 EQ-5D scores using responses to the self-administered questionnaire. EQ-5D scores were modeled using age, sex, comorbidities, and binary indicators of the presence and duration of injury at the time of the health status questionnaire. These models consider nonlinearity over time during the first 3 y following the injury event. RESULTS: Injuries are identified in MEPS using medical events that provide a reasonable proxy for the date of injury occurrence. Health-related quality of life (HRQL) decrements can be estimated using binary indicators of injury during different time periods. When grouped into 29 injury categories, most categories were statistically significant predictors of HRQL scores in the first year after injury. For these groups of injuries, mean first-year QALY loss estimates range from 0.005 (sprains and strains of joints and adjacent muscles, n = 7067) to 0.109 (injury to nerves and spinal cord, n = 71). Fewer estimates are significant in the second and third years after injury, which may reflect a return to baseline HRQL. CONCLUSION: This research presents both a framework for estimating QALY loss for short-lived medical conditions and nationally representative, community-based HRQL scores associated with a wide variety of injury and poisoning conditions. HIGHLIGHTS: This research provides a catalog of nationally representative, preference-based EQ-5D score decrements associated with surviving a large set of injuries, based on patient-reported health status.Mean first-year QALY loss estimates range from 0.005 (sprains and strains of joints and adjacent muscles, n = 7067) to 0.109 (injury to nerves and spinal cord, n = 71).This article presents a novel methodology for assessing quality-of-life impacts for acute conditions by calculating the time elapsed between injury and health status elicitation. Researchers may explore adapting these methods to study other short-lived conditions and health states, such as COVID-19 or chemotherapy.

Identifying transformational space for transdisciplinarity: using art to access the hidden third.

A challenge for transdisciplinary sustainability science is learning how to bridge diverse worldviews among collaborators in respectful ways. A temptation in transdisciplinary work is to focus on improving scientific practices rather than engage research partners in spaces that mutually respect how we learn from each other and set the stage for change. We used the concept of Nicolescu's "Hidden Third" to identify and operationalize this transformative space, because it focused on bridging "objective" and "subjective" worldviews through art. Between 2014 and 2017, we explored the engagement of indigenous peoples from three inland delta regions in Canada and as a team of interdisciplinary scholars and students who worked together to better understand long-term social-ecological change in those regions. In working together, we identified five characteristics associated with respectful, transformative transdisciplinary space. These included (1) establishing an unfiltered safe place where (2) subjective and objective experiences and (3) different world views could come together through (4) interactive and (5) multiple sensory experiences. On the whole, we were more effective in achieving characteristics 2-5-bringing together the subjective and objective experiences, where different worldviews could come together-than in achieving characteristic 1-creating a truly unfiltered and safe space for expression. The novelty of this work is in how we sought to change our own engagement practices to advance sustainability rather than improving scientific techniques. Recommendations for sustainability scientists working in similar contexts are provided.

Bridging science and traditional knowledge to assess cumulative impacts of stressors on ecosystem health.

Cumulative environmental impacts driven by anthropogenic stressors lead to disproportionate effects on indigenous communities that are reliant on land and water resources. Understanding and counteracting these effects requires knowledge from multiple sources. Yet the combined use of Traditional Knowledge (TK) and Scientific Knowledge (SK) has both technical and philosophical hurdles to overcome, and suffers from inherently imbalanced power dynamics that can disfavour the very communities it intends to benefit. In this article, we present a 'two-eyed seeing' approach for co-producing and blending knowledge about ecosystem health by using an adapted Bayesian Belief Network for the Slave River and Delta region in Canada's Northwest Territories. We highlight how bridging TK and SK with a combination of field data, interview transcripts, existing models, and expert judgement can address key questions about ecosystem health when considerable uncertainty exists. SK indicators (e.g., bird counts, mercury in fish, water depth) were graded as moderate, whereas TK indicators (e.g., bird usage, fish aesthetics, changes to water flow) were graded as being poor in comparison to the past. SK indicators were predominantly spatial (i.e., comparing to other locations) while the TK indicators were predominantly temporal (i.e., comparing across time). After being populated by 16 experts (local harvesters, Elders, governmental representatives, and scientists) using both TK and SK, the model output reported low probabilities that the social-ecological system is healthy as it used to be. We argue that it is novel and important to bridge TK and SK to address the challenges of environmental change such as the cumulative impacts of multiple stressors on ecosystems and the services they provide. This study presents a critical social-ecological tool for widening the evidence-base to a more holistic understanding of the system dynamics of multiple environmental stressors in ecosystems and for developing more effective knowledge-inclusive partnerships between indigenous communities, researchers and policy decision-makers. This represents new transformational empirical insights into how wider knowledge discourses can contribute to more effective adaptive co-management governance practices and solutions for the resilience and sustainability of ecosystems in Northern Canada and other parts of the world with strong indigenous land tenure.

Fathers' Leave and Fathers' Involvement: Evidence from Four OECD Countries.

In recent years, several OECD countries have taken steps to promote policies encouraging fathers to spend more time caring for young children, thereby promoting a more gender equal division of care work. Evidence, mainly for the United States and United Kingdom, has shown fathers taking some time off work around childbirth are more likely to be involved in childcare related activities than fathers who do not take time off. This paper conducts a first cross-national analysis on the association between fathers' leave taking and fathers' involvement when children are young. It uses birth cohort data of children born around 2000 from four OECD countries: Australia, Denmark, the United Kingdom and the United States. Results show that the majority of fathers take time off around childbirth independent of the leave policies in place. In all countries, except Denmark, important socio-economic differences between fathers who take leave and those who do not are observed. In addition, fathers who take leave, especially those taking two weeks or more, are more likely to carry out childcare related activities when children are young. This study adds to the evidence that suggests that parental leave for fathers is positively associated with subsequent paternal involvement.

The effect of opponent type on human performance in a three-alternative choice task.

Adult participants played computerised games of "Paper Scissors Rock". Participants in one group were told that they were playing against the computer, and those in the other group were told that they were playing against another participant in the adjacent room. The participant who won the most games would receive a $50 prize. For both groups however, the opponent's responses (paper, scissors, or rock) were generated by the computer, and the distribution of these responses was varied across four blocks of 126 trials. Results were analysed using the generalised matching law for the three possible pairs of alternatives (paper vs. scissors, paper vs. rock, and scissors vs. rock) across all participants in each group. Overall, significantly higher estimates of sensitivity to the distribution of opponent's responses were obtained from participants who were told their opponent was a computer compared to participants who were told their opponent was another participant. While adding to the existing literature showing that the generalised matching law is an adequate descriptor of human three-alternative choice behaviour, these findings show that external factors such as perceived opponent type can affect the efficacy of reinforcer contingencies on human behaviour. This suggests that generalising the results from tasks performed against a computer to real-life human-to-human interactions warrants some caution.

Social and emotional outcomes of Australian children from Indigenous and culturally and linguistically diverse backgrounds.

OBJECTIVES: 1) profile the living environments and 2) examine the social and emotional outcomes of Australian children from Indigenous and cultural and linguistically diverse (CALD) backgrounds at school entry. METHOD: Secondary analysis of cross-sectional data collected in Wave 1 of the Longitudinal Study of Australian Children (n=4,735). Child mental-health outcomes were measured using parent report of the Strengths and Difficulties Questionnaire (SDQ). RESULTS: Significant differences in family and neighbourhood characteristics, including parental income, maternal education, maternal parenting quality and neighbourhood safety, were found in children of Indigenous and CALD backgrounds compared to the reference group of Australian-born, English-speaking children. After controlling for family and neighbourhood characteristics, significant differences in parent-reported SDQ total difficulties were found for Indigenous children. Significant differences in emotional difficulties and peer problems subscales were found for children with overseas-born mothers regardless of English proficiency. CONCLUSIONS: Children from Indigenous and CALD backgrounds experience poorer mental health outcomes at school entry than their Australian-born English-speaking peers. They are also more likely to be exposed to risk factors for poor child mental-health outcomes within their family and neighbourhood environments.

Intimate partner violence in older women: what home healthcare clinicians should know.

Older women can be victims of intimate partner violence (IPV), and home healthcare clinicians should know what they can do. Although there is no instrument specific to screening for IPV in older women within the home environment, home healthcare clinicians can use currently available resources and lobby for better resources to screen for and serve older women who may be victims of IPV. Forensic nursing education can provide additional skills to identify possible victims of violence, gather evidence, document findings, and provide treatment and referrals.

Which mothers wean their babies prematurely from full breastfeeding? An Australian cohort study.

AIM: To identify the maternal and infant characteristics associated with an early transition from full breastfeeding to complementary or no breastfeeding during the first 2 months of life in a large, representative cohort of Australian infants. METHOD: Multinomial logistic modelling was performed on data for infants with complete breastfeeding and sociodemographic data (N = 4679) including maternal age, education, smoking, employment, pregnancy and birth outcomes. RESULTS: Ninety-one percent of women initiated breastfeeding. Sixty-nine percent of infants were being fully breastfed at 1 month, and 59% were fully breastfed at 2 months. Maternal characteristics - age less than 25 years, smoking in pregnancy, early full-time postnatal employment and less educational attainment - were associated with early breastfeeding cessation. Infant factors - multiple birth, caesarean birth, infant or first birth - were associated with a transition to complementary breastfeeding in the first postnatal month. CONCLUSION: Breastfeeding duration is substantially affected by breastfeeding outcomes in the first postpartum month. The first month is an important window for evidence-based interventions to improve rates of full breastfeeding in groups of women identified as at risk of early breastfeeding cessation.

Shear-induced variability in the United States Pharmacopeia Apparatus 2: modifications to the existing system.

The hydrodynamics within the United States Pharmacopeia Apparatus 2 have been shown to be highly non-uniform with a potential to yield substantial variability in dissolution rate measurements. Through the use of readily available engineering tools, several geometric modifications to the device were evaluated in this study. Specifically, we examined the influence of impeller clearance, agitator type (radial and axial), and vessel geometry (PEAK vessel) on the fluid flow properties and their relation to measured dissolution rates. Increasing the impeller clearance was observed to exacerbate the heterogeneity in shear and would likely result in greater variability in dissolution measurements. Altering the impeller type was shown to yield changes in the hydrodynamic behavior; however, the overall properties and problems with the test remain the same. Use of the PEAK vessel was observed to reduce shear heterogeneity in the regions where tablets are most likely to visit during testing; however, higher shear rates may result in the inability to discriminate between true differences in dissolution rates.

Hydrodynamics-induced variability in the USP apparatus II dissolution test.

The USP tablet dissolution test is an analytical tool used for the verification of drug release processes and formulation selection within the pharmaceutical industry. Given the strong impact of this test, it is surprising that operating conditions and testing devices have been selected empirically. In fact, the flow phenomena in the USP test have received little attention in the past. An examination of the hydrodynamics in the USP apparatus II shows that the device is highly vulnerable to mixing problems that can affect testing performance and consistency. Experimental and computational techniques reveal that the flow field within the device is not uniform, and dissolution results can vary dramatically with the position of the tablet within the vessel. Specifically, computations predict sharp variations in the shear along the bottom of the vessel where the tablet is most likely to settle. Experiments in which the tablet location was carefully controlled reveal that the variation of shear within the testing device can affect the measured dissolution rate.

Delayed rRNA processing results in significant ribosome biogenesis and functional defects.

mof6-1 was originally isolated as a recessive mutation in Saccharomyces cerevisiae which promoted increased efficiencies of programmed -1 ribosomal frameshifting and rendered cells unable to maintain the killer virus. Here, we demonstrate that mof6-1 is a unique allele of the histone deacetylase RPD3, that the deacetylase function of Rpd3p is required for controlling wild-type levels of frameshifting and virus maintenance, and that the closest human homolog can fully complement these defects. Loss of the Rpd3p-associated histone deacetylase function, either by mutants of rpd3 or loss of the associated gene product Sin3p or Sap30p, results in a delay in rRNA processing rather than in an rRNA transcriptional defect. This results in production of ribosomes having lower affinities for aminoacyl-tRNA and diminished peptidyltransferase activities. We hypothesize that decreased rates of peptidyl transfer allow ribosomes with both A and P sites occupied by tRNAs to pause for longer periods of time at -1 frameshift signals, promoting increased programmed -1 ribosomal frameshifting efficiencies and subsequent loss of the killer virus. The frameshifting defect is accentuated when the demand for ribosomes is highest, suggesting that rRNA posttranscriptional modification is the bottleneck in ribosome biogenesis.

The 9-A solution: how mRNA pseudoknots promote efficient programmed -1 ribosomal frameshifting.

There is something special about mRNA pseudoknots that allows them to elicit efficient levels of programmed -1 ribosomal frameshifting. Here, we present a synthesis of recent crystallographic, molecular, biochemical, and genetic studies to explain this property. Movement of 9 A by the anticodon loop of the aminoacyl-tRNA at the accommodation step normally pulls the downstream mRNA a similar distance along with it. We suggest that the downstream mRNA pseudoknot provides resistance to this movement by becoming wedged into the entrance of the ribosomal mRNA tunnel. These two opposing forces result in the creation of a local region of tension in the mRNA between the A-site codon and the mRNA pseudoknot. This can be relieved by one of two mechanisms; unwinding the pseudoknot, allowing the downstream region to move forward, or by slippage of the proximal region of the mRNA backwards by one base. The observed result of the latter mechanism is a net shift of reading frame by one base in the 5' direction, that is, a -1 ribosomal frameshift.