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The conditional extremes framework allows for event-based stochastic modeling of dependent extremes, and has recently been extended to spatial and spatio-temporal settings. After standardizing the marginal distributions and applying an appropriate linear normalization, certain non-stationary Gaussian processes can be used as asymptotically-motivated models for the process conditioned on threshold exceedances at a fixed reference location and time. In this work, we adapt existing conditional extremes models to allow for the handling of large spatial datasets. This involves specifying the model for spatial observations at d locations in terms of a latent m≪d dimensional Gaussian model, whose structure is specified by a Gaussian Markov random field. We perform Bayesian inference for such models for datasets containing thousands of observation locations using the integrated nested Laplace approximation, or INLA. We explain how constraints on the spatial and spatio-temporal Gaussian processes, arising from the conditioning mechanism, can be implemented through the latent variable approach without losing the computationally convenient Markov property. We discuss tools for the comparison of models via their posterior distributions, and illustrate the flexibility of the approach with gridded Red Sea surface temperature data at over 6,000 observed locations. Posterior sampling is exploited to study the probability distribution of cluster functionals of spatial and spatio-temporal extreme episodes.

Certain fish and amphibians retain a robust capacity for cardiac regeneration throughout life, but the same is not true of the adult mammalian heart. Whether the capacity for cardiac regeneration is absent in mammals or whether it exists and is switched off early after birth has been unclear. We found that the hearts of 1-day-old neonatal mice can regenerate after partial surgical resection, but this capacity is lost by 7 days of age. This regenerative response in 1-day-old mice was characterized by cardiomyocyte proliferation with minimal hypertrophy or fibrosis, thereby distinguishing it from repair processes. Genetic fate mapping indicated that the majority of cardiomyocytes within the regenerated tissue originated from preexisting cardiomyocytes. Echocardiography performed 2 months after surgery revealed that the regenerated ventricular apex had normal systolic function. Thus, for a brief period after birth, the mammalian heart appears to have the capacity to regenerate.

We recently identified a brief time period during postnatal development when the mammalian heart retains significant regenerative potential after amputation of the ventricular apex. However, one major unresolved question is whether the neonatal mouse heart can also regenerate in response to myocardial ischemia, the most common antecedent of heart failure in humans. Here, we induced ischemic myocardial infarction (MI) in 1-d-old mice and found that this results in extensive myocardial necrosis and systolic dysfunction. Remarkably, the neonatal heart mounted a robust regenerative response, through proliferation of preexisting cardiomyocytes, resulting in full functional recovery within 21 d. Moreover, we show that the miR-15 family of microRNAs modulates neonatal heart regeneration through inhibition of postnatal cardiomyocyte proliferation. Finally, we demonstrate that inhibition of the miR-15 family from an early postnatal age until adulthood increases myocyte proliferation in the adult heart and improves left ventricular systolic function after adult MI. We conclude that the neonatal mammalian heart can regenerate after myocardial infarction through proliferation of preexisting cardiomyocytes and that the miR-15 family contributes to postnatal loss of cardiac regenerative capacity.

Collecting large-scale population data on dietary intake is challenging, particularly when resources and funding are constrained. Technology offers the potential to develop novel ways of collecting large amounts of dietary information while making it easier, more convenient, intuitive, and engaging for users. INTAKE24 is an online multiple pass 24 h dietary recall tool developed for use in national food and nutrition surveys. The development of INTAKE24 was a four-stage iterative process of user interaction and evaluation with the intended end users, 11–24 years old. A total of 80 11–24 years old took part in the evaluation, 20 at each stage. Several methods were used to elicit feedback from the users including, ‘think aloud’, ‘eye tracking’, semi-structured interviews, and a system usability scale. Each participant completed an interviewer led recall post system completion. Key system developments generated from the user feedback included a ‘flat’ interface, which uses only a single interface screen shared between all of the various activities (e.g., free text entry, looking up foods in the database, portion size estimation). Improvements to the text entry, search functionality, and navigation around the system were also influenced through feedback from users at each stage. The time to complete a recall using INTAKE24 almost halved from the initial prototype to the end system, while the agreement with an interviewer led recall improved. Further developments include testing the use of INTAKE24 with older adults and translation into other languages for international use. Our future aim is to validate the system with recovery biomarkers.

Online self-reported 24-h dietary recall systems promise increased feasibility of dietary assessment. Comparison against interviewer-led recalls established their convergent validity; however, reliability and criterion-validity information is lacking. The validity of energy intakes (EI) reported using Intake24, an online 24-h recall system, was assessed against concurrent measurement of total energy expenditure (TEE) using doubly labelled water in ninety-eight UK adults (40–65 years). Accuracy and precision of EI were assessed using correlation and Bland–Altman analysis. Test–retest reliability of energy and nutrient intakes was assessed using data from three further UK studies where participants (11–88 years) completed Intake24 at least four times; reliability was assessed using intra-class correlations (ICC). Compared with TEE, participants under-reported EI by 25 % (95 % limits of agreement −73 % to +68 %) in the first recall, 22 % (−61 % to +41 %) for average of first two, and 25 % (−60 % to +28 %) for first three recalls. Correlations between EI and TEE were 0·31 (first), 0·47 (first two) and 0·39 (first three recalls), respectively. ICC for a single recall was 0·35 for EI and ranged from 0·31 for Fe to 0·43 for non-milk extrinsic sugars (NMES). Considering pairs of recalls (first two v. third and fourth recalls), ICC was 0·52 for EI and ranged from 0·37 for fat to 0·63 for NMES. EI reported with Intake24 was moderately correlated with objectively measured TEE and underestimated on average to the same extent as seen with interviewer-led 24-h recalls and estimated weight food diaries. Online 24-h recall systems may offer low-cost, low-burden alternatives for collecting dietary information.

The polarization state of isolated attosecond pulses generated by high-order harmonic generation can now be manipulated at will. The development opens the door for a multitude of ultrafast experiments to investigate chiral media.

Abstract Objectives: To identify evidence from comparative studies on the effects of involving users in the delivery and evaluation of mental health services. Data sources: English language articles published between January 1966 and October 2001 found by searching electronic databases. Study selection: Systematic review of randomised controlled trials and other comparative studies of involving users in the delivery or evaluation of mental health services. Data extraction:Patterns of delivery of services by employees who use or who used to use the service and professional employees and the effects on trainees, research, or clients of mental health services. Results: Five randomised controlled trials and seven other comparative studies were identified. Half of the studies considered involving users in managing cases. Involving users as employees of mental health services led to clients having greater satisfaction with personal circumstances and less hospitalisation. Providers of services who had been trained by users had more positive attitudes toward users. Clients reported being less satisfied with services when interviewed by users. Conclusions: Users can be involved as employees, trainers, or researchers without detrimental effect. Involving users with severe mental disorders in the delivery and evaluation of services is feasible.

Heart transplant for adults following Donation after Circulatory Death (DCD) is well established in many parts of the world, including the United Kingdom (UK). Small child DCD hearts have now been recovered in the UK and internationally utilising novel technologies. Despite these recent advances, extension of this practice to pediatric cardiac transplantation has been slow and difficult despite the severe shortage of donors for children leading to a high number of deaths annually of children waiting for heart transplant. This is in direct contrast with the thriving UK programme of adult DCD heart transplant and pediatric DCD donation for non-cardiac organs. There has been insufficient action in addressing this inequality thus far. Barriers to development of a pediatric cardiac DCD programme are multifaceted: ethical concerns, technological paucity, financial and logistical hurdles. We describe the background, live issues, current developments and how we are driving resources toward a sustainable DCD programme for small children in the UK to provide valuable insights to other countries of the elements and principles at play. This is a call to responsible bodies to take urgent and achievable actions to establish an equitable paediatric DCD cardiac programme for donors, recipients and their families.

Background Pediatric applications of non-invasive brain stimulation using transcranial direct current stimulation (tDCS) have demonstrated its safety with few adverse events reported. Remotely monitored tDCS, as an adjuvant intervention to rehabilitation, may improve quality of life for children with cerebral palsy (CP) through motor function improvements, reduced treatment costs, and increased access to tDCS therapies. Our group previously evaluated the feasibility of a remotely monitored mock tDCS setup in which families and children successfully demonstrated the ability to follow tDCS instructional guidance. Methods and design Here, we designed a protocol to investigate the feasibility, safety, and tolerability of at-home active transcranial direct current stimulation in children with CP with synchronous supervision from laboratory investigators. Ten participants will be recruited to participate in the study for 5 consecutive days with the following sessions: tDCS setup practice on day 1, sham tDCS on day 2, and active tDCS on days 3-5. Sham stimulation will consist of an initial 30-second ramp up to 1.5 mA stimulation followed by a 30-second ramp down. Active stimulation will be delivered at 1.0 - 1.5 mA for 20 minutes and adjusted based on child tolerance. Feasibility will be evaluated via photographs of montage setup and the quality of stimulation delivery. Safety and tolerability will be assessed through an adverse events survey, the Box and Blocks Test (BBT) motor assessment, and a setup ease/comfort survey. Discussion We expect synchronous supervision of at-home teleneuromodulation to be tolerable and safe with increasing stimulation quality over repeated sessions when following a tDCS setup previously determined to be feasible. The findings will provide opportunity for larger clinical trials exploring efficacy and illuminate the potential of remotely monitored tDCS in combination with rehabilitation interventions as a means of pediatric neurorehabilitation. This will demonstrate the value of greater accessibility of non-invasive brain stimulation interventions and ultimately offer the potential to improve care and quality of life for children and families with CP. Trial Registration October 8, 2021( https://clinicaltrials.gov/ct2/show/NCT05071586 )

Dietary assessment is important for monitoring and evaluating population intakes. Online tools can reduce the level of participant burden and the time taken to complete records, compared with other methods. The study aimed to field test an online dietary recall tool (Intake24) to test the suitability for collecting dietary information in Scottish national surveys and to develop the system based on feedback and emerging issues. Previous Scottish Health Survey participants, aged 11+ years, were invited to complete Intake24 and provide feedback about it. Of those who agreed to take part, 60% completed at least one recall. Intake24 was found to be user-friendly, enjoyable to use, and easy to follow and understand. Users agreed they would like to use Intake24 often, (44% compared with 15% who disagreed) and >75% felt the system accurately captured their dietary intakes. The main challenge reported was finding foods within the database. Of those completing fewer recalls than requested, the majority reported that they believed they had completed the required number or reported not receiving emails requesting they complete a further recall. Intake24 was found to be a user-friendly tool allowing dietary assessment without interviewer presence. Feedback indicated the method for recall reminders needs to be refined and tailored.