Evolution of a minimal cell.

Possessing only essential genes, a minimal cell can reveal mechanisms and processes that are critical for the persistence and stability of life1,2. Here we report on how an engineered minimal cell3,4 contends with the forces of evolution compared with the Mycoplasma mycoides non-minimal cell from which it was synthetically derived. Mutation rates were the highest among all reported bacteria, but were not affected by genome minimization. Genome streamlining was costly, leading to a decrease in fitness of greater than 50%, but this deficit was regained during 2,000 generations of evolution. Despite selection acting on distinct genetic targets, increases in the maximum growth rate of the synthetic cells were comparable. Moreover, when performance was assessed by relative fitness, the minimal cell evolved 39% faster than the non-minimal cell. The only apparent constraint involved the evolution of cell size. The size of the non-minimal cell increased by 80%, whereas the minimal cell remained the same. This pattern reflected epistatic effects of mutations in ftsZ, which encodes a tubulin-homologue protein that regulates cell division and morphology5,6. Our findings demonstrate that natural selection can rapidly increase the fitness of one of the simplest autonomously growing organisms. Understanding how species with small genomes overcome evolutionary challenges provides critical insights into the persistence of host-associated endosymbionts, the stability of streamlined chassis for biotechnology and the targeted refinement of synthetically engineered cells2,7-9.

Analysis of the yearly transition function in measles disease modeling.

Globally, there were an estimated 9.8 million measles cases and 207 500 measles deaths in 2019. As the effort to eliminate measles around the world continues, modeling remains a valuable tool for public health decision-makers and program implementers. This study presents a novel approach to the use of a yearly transition function that formulates mathematically the vaccine schedules for different age groups while accounting for the effects of the age of vaccination, the timing of vaccination, and disease seasonality on the yearly number of measles cases in a country. The methodology presented adds to an existing modeling framework and expands its analysis, making its utilization more adjustable for the user and contributing to its conceptual clarity. This article also adjusts for the temporal interaction between vaccination and exposure to disease, applying adjustments to estimated yearly counts of cases and the number of vaccines administered that increase population immunity. These new model features provide the ability to forecast and compare the effects of different vaccination timing scenarios and seasonality of transmission on the expected disease incidence. Although the work presented is applied to the example of measles, it has potential relevance to modeling other vaccine-preventable diseases.

Genome-wide surveillance of transcription errors in response to genotoxic stress.

Mutagenic compounds are a potent source of human disease. By inducing genetic instability, they can accelerate the evolution of human cancers or lead to the development of genetically inherited diseases. Here, we show that in addition to genetic mutations, mutagens are also a powerful source of transcription errors. These errors arise in dividing and nondividing cells alike, affect every class of transcripts inside cells, and, in certain cases, greatly exceed the number of mutations that arise in the genome. In addition, we reveal the kinetics of transcription errors in response to mutagen exposure and find that DNA repair is required to mitigate transcriptional mutagenesis after exposure. Together, these observations have far-reaching consequences for our understanding of mutagenesis in human aging and disease, and suggest that the impact of DNA damage on human physiology has been greatly underestimated.

Early detection and intervention for young children with early developmental disabilities in Western Uganda: a mixed-methods evaluation.

BACKGROUND: Early support for children with developmental disabilities is crucial but frequently unavailable in low-resource settings. We conducted a mixed-methods evaluation to assess the feasibility, acceptability, and impact of a programme of early detection and intervention for young children with developmental disabilities in Western Uganda. METHODS: Early child development training for healthcare workers (HCWs) was implemented in three rural districts, and attendance was tracked. HCW knowledge and confidence were assessed pre-/post-intervention, and referral numbers tracked to evaluate impact. Facilitators were trained and mentored to deliver a participatory, group, early intervention programme (EIP) for young children with developmental disabilities and their families. Facilitators were tracked as they were identified, trained, and delivered the intervention, and attendance of families was tracked. Pre-/post-intervention assessments evaluated changes in family quality of life (PedsQL 2.0, Family Impact Module), and child nutritional outcomes. Focus group discussions with stakeholders also assessed feasibility, acceptability and impact. RESULTS: Overall, 93 HCWs from 45 healthcare facilities received training. In the pre-/post-evaluation, median knowledge and confidence scores increased significantly (from 4.0 to 7.0 and from 2.7 to 4.7, respectively (p < 0.001)). HCWs reported feeling empowered to refer and offer care for families with a young child with disability. Referral rates increased significantly from 148 to 251 per annum (70%; p = 0.03). Eleven EIP facilitators were trained, and all delivered the intervention; 84 families were enrolled, of which 78% attended at least 6 out of 10 modules. Amongst those with paired pre-/post-intervention data (n = 48), total family quality of life scores increased significantly (21%, p < 0.001). Improvements were seen across all domains of quality of life, with the largest impacts on emotional functioning and social functioning (p < 0.001). The programme was acceptable to caregivers and facilitators. Caregivers reported improved knowledge, family relationships, hope, emotional wellbeing, and reduced self-stigma. CONCLUSIONS: A programme of early detection and intervention for children with early developmental disabilities and their families was feasible and acceptable in a rural community-based Ugandan setting. HCW training positively impacted knowledge, confidence, attitudes, and referral rates. Families enrolled to the EIP reported significant improvements in quality of life. Important programmatic barriers identified included geographical spread, poverty, gender inequality, and stigma.

Effect of supplement crude protein concentration on milk production over the main grazing season and on nitrogen excretion in late-lactation grazing dairy cows.

The objectives of this study are to evaluate the effects of (1) a potential interaction between supplement crude protein (CP) concentration and differing cow genotypes on milk production, (2) differing cow genotypes on milk production, and (3) decreasing the supplement CP concentration on milk production and N excretion during the main grazing season within a spring-calving herd. A 2 × 2 factorial arrangement experiment, with 2 feeding strategies [14%; n = 30 (lower CP; LCP) and 18%; n = 28 (higher CP; HCP) CP concentrate supplements] offered at varying levels according to pasture availability and days in milk (DIM) was conducted over the main grazing season from April 3 to September 3, 2019, at University College Dublin Lyons Farm. Cows were also grouped into 2 genotype groups: lower milk genotype; n = 30 [LM; milk kg predicted transmitting ability (PTA): 45 ± 68.6 (mean ± SD); fat kg PTA: 10 ± 4.9; and protein kg PTA: 7 ± 2.3] and higher milk genotype; n = 28 [HM; milk kg PTA: 203 ± 55.0; fat kg PTA: 13 ± 3.8; and protein kg PTA: 10 ± 2.4]. A total of 46 multiparous and 12 primiparous (total; 58) Holstein Friesian dairy cows were blocked on parity and balanced on DIM, body condition score, and Economic Breeding Index. Cows were offered a basal diet of grazed perennial ryegrass pasture. The N partitioning study took place from August 25 to 30, 2019 (187 ± 15.2 DIM). No interactions were observed for any milk production or milk composition parameter. No effect of supplement CP concentration was observed for any total accumulated milk production, daily milk production, or milk composition parameter measured. The HM cows had increased daily milk yield (+1.9 kg), fat and protein (+0.15 kg), and energy-corrected milk (+1.7 kg), compared with the LM cows. Furthermore, HM cows had decreased milk protein concentration (-0.1%) compared with LM cows. For the N partitioning study, cows offered LCP had increased pasture dry matter intake (PDMI; +0.9 kg/d), dietary N intake (+0.022 kg/d), feces N excretion (+0.016 kg/d), and decreased N partitioning to milk (-2%), and N utilization efficiency (-2.3%). In conclusion, offering cows LCP had no negative influence on milk production or milk composition over the main grazing season where high pasture quality was maintained. However, any potential negative effects of offering LCP on milk production may have been offset by the increased PDMI. Furthermore, offering cows LCP decreased N utilization efficiency due to the higher PDMI and feed N intake associated with cows on this treatment in our study.

SARS-CoV-2 Testing and Patient Waiting Times in the Emergency Department.

Aim Emergency Departments (EDs) were impacted early in the coronavirus disease 2019 (COVID-19) pandemic, with high attendance numbers. EDs relied upon SARS-CoV-2 reverse-transcriptase polymerase chain reaction (RT-PCR) tests to triage patients and facilitate admission to appropriate wards, meaning positive patients were isolated as early as possible. In October 2020, we introduced a 24-hour SARS-CoV-2 testing service. We examined the impact of this on patient experience times (PETs) in the ED, and on healthcare-associated (HA) COVID-19 infections. Methods Data on PETs before and after the introduction of 24-hour testing were available from the ED. HA COVID-19 infections were reported weekly to the Health Services Executive as a key performance indicator. Results Mean PET prior to the pandemic was 20 hours and dropped to 10 and 13 hours respectively in the first and second wave. A surge in case numbers and ED attendances during the third wave was not reflected in a rise in PETs, with a mean PET of 11 hours, significantly below pre-pandemic levels. HA-COVID-19 infections remained stable between wave one and three (83 v 92). Conclusion The introduction of 24-hour SARS-CoV-2 testing in our ED contributed to a reduction in PETs, facilitated appropriate patient placement at ward level, and kept HA-COVID-19 infections at acceptably low levels.

Applications and future directions for optical coherence tomography in dermatology.

Optical coherence tomography (OCT) is a noninvasive optical imaging method that can generate high-resolution en face and cross-sectional images of the skin in vivo to a maximum depth of 2 mm. While OCT holds considerable potential for noninvasive diagnosis and disease monitoring, it is poorly understood by many dermatologists. Here we aim to equip the practising dermatologist with an understanding of the principles of skin OCT and the potential clinical indications. We begin with an introduction to the technology and discuss the different modalities of OCT including angiographic (dynamic) OCT, which can image cutaneous blood vessels at high resolution. Next we review clinical applications. OCT has been most extensively investigated in the diagnosis of keratinocyte carcinomas, particularly basal cell carcinoma. To date, OCT has not proven sufficiently accurate for the robust diagnosis of malignant melanoma; however, the evaluation of abnormal vasculature with angiographic OCT is an area of active investigation. OCT, and in particular angiographic OCT, also shows promise in monitoring the response to therapy of inflammatory dermatoses, such as psoriasis and connective tissues disease. We additionally discuss a potential role for artificial intelligence in improving the accuracy of interpretation of OCT imaging data.

Opportunities for the application of real-time bacterial cell analysis using flow cytometry for the advancement of sterilization microbiology.

Medical devices provide critical care and diagnostic applications through patient contact. Sterility assurance level (SAL) may be defined as the probability of a single viable micro-organism occurring on an item after a sterilization process. Sterilization microbiology often relies upon using an overkill validation method where a 12-log reduction in recalcitrant bacterial endospore population occurs during the process that exploits conventional laboratory-based culture media for enumeration. This timely review explores key assumptions underpinning use of conventional culture-based methods in sterilization microbiology. Consideration is given to how such methods may limit the ability to fully appreciate the inactivation kinetics of a sterilization process such as vaporized hydrogen peroxide (VH2O2) sterilization, and consequently design efficient sterilization processes. Specific use of the real-time flow cytometry (FCM) is described by way of elucidating the practical relevance of these limitation factors with implications and opportunities for the sterilization industry discussed. Application of FCM to address these culture-based limitation factors will inform real-time kinetic inactivation modelling and unlock potential to embrace emerging opportunities for pharma, medical device and sterilization industries including potentially disruptive applications that may involve reduced usage of sterilant.

The effect of malaria control on Plasmodium falciparum in Africa between 2000 and 2015.

Since the year 2000, a concerted campaign against malaria has led to unprecedented levels of intervention coverage across sub-Saharan Africa. Understanding the effect of this control effort is vital to inform future control planning. However, the effect of malaria interventions across the varied epidemiological settings of Africa remains poorly understood owing to the absence of reliable surveillance data and the simplistic approaches underlying current disease estimates. Here we link a large database of malaria field surveys with detailed reconstructions of changing intervention coverage to directly evaluate trends from 2000 to 2015, and quantify the attributable effect of malaria disease control efforts. We found that Plasmodium falciparum infection prevalence in endemic Africa halved and the incidence of clinical disease fell by 40% between 2000 and 2015. We estimate that interventions have averted 663 (542-753 credible interval) million clinical cases since 2000. Insecticide-treated nets, the most widespread intervention, were by far the largest contributor (68% of cases averted). Although still below target levels, current malaria interventions have substantially reduced malaria disease incidence across the continent. Increasing access to these interventions, and maintaining their effectiveness in the face of insecticide and drug resistance, should form a cornerstone of post-2015 control strategies.

A survey analysis of farmer practices and perceptions of zero-grazing on Irish dairy farms.

Zero-grazing (ZG; the mechanical harvesting and feeding of fresh grass) is increasingly used in grass-based milk production systems alongside conventional grazing. It allows farmers to supply fresh grass from land parcels that are outside of the main grazing block during seasonal shortages and periods when climatic conditions limit animal grazing opportunities. The objective of this study was to establish an understanding of current ZG practices on Irish dairy farms, to capture farmer perceptions on the implementation of this management practice, and to identify farmer knowledge requirements on ZG. An online survey was distributed and completed by 130 dairy farmers who use or have used ZG. Zero-grazing was used alongside conventional grazing by 92% of respondents. These farms were particularly fragmented, with between 1 and 14 separate land blocks. Respondents felt ZG helped them overcome fragmentation, increase grass use, and extend grass feeding in spring and autumn. However, extra cost and time input associated with ZG were recognized as key challenges. The majority of respondents rated current technical information available on ZG in the Republic of Ireland as "poor" or "very poor," and knowledge deficits were identified in the areas of cost analysis, grass management and productivity, cow productivity, cow health and nutrition, and soil fertility.

The effect of nutritional management in early lactation and dairy cow genotype on milk production, metabolic status, and uterine recovery in a pasture-based system.

High levels of milk production coupled with low feed intake cause negative energy balance in early lactation, especially in the first month postpartum (PP). Therefore, specific nutritional management at this time may improve nutritional and metabolic status with the possibility of contrasting genotypes responding differently. Thus, the objective of this study was to compare the effects of nutritional management strategies and dairy cow genotype on milk production, metabolic status, and some fertility parameters during early lactation in a pasture-based system. Sixty Holstein Friesian cows were blocked on parity and genotype [low-fertility high-milk (LFHM) and high-fertility low-milk (HFLM)] and were randomly assigned to 1 of 2 treatments in a 2 × 2 factorial arrangement, in a randomized complete block design based on calving date, previous 305-d milk yield, and precalving body condition score (BCS). The nutritional management treatments were: (1) ad libitum access to fresh pasture plus an allowance of 3 kg of concentrates per day (CTR, n = 30); and (2) ab libitum access to a tailored total mixed ration (TMR, n = 30). These diets were offered for the first 30 d PP. Following the first 30 d PP, cows fed TMR joined the CTR treatment and were managed similarly until 100 d PP. Blood samples were taken at d 7, 14, 21, and 28 PP to determine metabolic status. Milk samples for composition analysis were collected weekly and BCS assessed every 2 wk. Genotype had a significant effect on milk output, whereas LFHM had increased fat (+0.28 kg/d) and fat-plus-protein (+0.17 kg/d) yield in the first 30 d PP compared with HFLM cows. The LFHM group also exhibited higher protein and lactose yields over the first 100 d PP. Nutritional management did create significant differences in milk composition in the first 30 d: TMR cows had lower protein, milk urea nitrogen, and casein concentration and higher lactose concentration than CTR cows. Over the first 100 d PP, TMR cows had higher fat-plus-protein and lactose yields. Feeding TMR reduced concentrations of nonesterified fatty acids (-0.12 mmol/L) and ß-hydroxybutyric acid (-0.10 mmol/L) compared with the CTR group. Cows fed TMR had smaller BCS losses from calving to 60 d PP. There was no effect of any treatment on uterine recovery. Cows in the LFHM group demonstrated greater milk production in the first 30 and 100 d in milk. These results demonstrate that feeding cows a TMR for the first month of lactation has positive effects on milk output, metabolic status, and BCS profile.

Mitigation policies, community mobility, and COVID-19 case counts in Australia, Japan, Hong Kong, and Singapore.

OBJECTIVES: The objective of the study was to characterize the timing and trends of select mitigation policies, changes in community mobility, and coronavirus disease 2019 (COVID-19) epidemiology in Australia, Japan, Hong Kong, and Singapore. STUDY DESIGN: Prospective abstraction of publicly available mitigation policies obtained from media reports and government websites. METHODS: Data analyzed include seven kinds of mitigation policies (mass gathering restrictions, international travel restrictions, passenger screening, traveler isolation/quarantine, school closures, business closures, and domestic movement restrictions) implemented between January 1 and April 26, 2020, changes in selected measures of community mobility assessed by Google Community Mobility Reports data, and COVID-19 epidemiology in Australia, Japan, Hong Kong, and Singapore. RESULTS: During the study period, community mobility decreased in Australia, Japan, and Singapore; there was little change in Hong Kong. The largest declines in mobility were seen in places that enforced mitigation policies. Across settings, transit-associated mobility declined the most and workplace-associated mobility the least. Singapore experienced an increase in cases despite the presence of stay-at-home orders, as migrant workers living in dormitories faced challenges to safely quarantine. CONCLUSIONS: Public policies may have different impacts on mobility and transmission of severe acute respiratory coronavirus-2 transmission. When enacting mitigation policies, decision makers should consider the possible impact of enforcement measures, the influence on transmission of factors other than movement restrictions, and the differential impact of mitigation policies on subpopulations.

What is AI? Applications of artificial intelligence to dermatology.

In the past, the skills required to make an accurate dermatological diagnosis have required exposure to thousands of patients over many years. However, in recent years, artificial intelligence (AI) has made enormous advances, particularly in the area of image classification. This has led computer scientists to apply these techniques to develop algorithms that are able to recognize skin lesions, particularly melanoma. Since 2017, there have been numerous studies assessing the accuracy of algorithms, with some reporting that the accuracy matches or surpasses that of a dermatologist. While the principles underlying these methods are relatively straightforward, it can be challenging for the practising dermatologist to make sense of a plethora of unfamiliar terms in this domain. Here we explain the concepts of AI, machine learning, neural networks and deep learning, and explore the principles of how these tasks are accomplished. We critically evaluate the studies that have assessed the efficacy of these methods and discuss limitations and potential ethical issues. The burden of skin cancer is growing within the Western world, with major implications for both population skin health and the provision of dermatology services. AI has the potential to assist in the diagnosis of skin lesions and may have particular value at the interface between primary and secondary care. The emerging technology represents an exciting opportunity for dermatologists, who are the individuals best informed to explore the utility of this powerful novel diagnostic tool, and facilitate its safe and ethical implementation within healthcare systems.

A retrospective review of pregnancies on biologics for the treatment of dermatological conditions.

Psoriasis often first presents in young adulthood, with the average age of diagnosis in women being 28 years, thus in the prime reproductive years. In addition, approximately 50% of pregnancies worldwide are unplanned. Although biologic therapies have revolutionized the treatment of moderate-to-severe psoriasis, there are no controlled studies of biologics in pregnant women. The increasing use of these agents in women of childbearing age highlights the need to further assess their safety during pregnancy. Postmarketing experience regarding the safety of these drugs is accumulating and being published, with largely reassuring results. We present our real-world experience of 17 pregnancies occurring in women on treatment with biologic agents for dermatological conditions to further add to the body of knowledge.

Smoking cessation in elective surgical patients offered free nicotine patches at listing: a pilot study.

Free nicotine patches may promote pre-operative smoking cessation. Smokers (≥ 10 cigarettes.day-1 ) awaiting non-urgent surgery were randomly assigned (3:1) to an offer of free nicotine patches or a control group who were not offered free nicotine patches. The suggested regimen lasted 5 weeks, with patch strength decreasing incrementally after 3 and 4 weeks. The primary outcome was smoking abstinence for ≥ 4 weeks, as self-reported by participants on the day of surgery, including, where possible, corroboration using exhaled carbon monoxide testing. Out of 600 included smokers, 447 (74.5%) were randomly assigned to an offer of pre-operative nicotine patches, with 175 (39.1%) of these accepting the offer and 56 (12.5%) using patches for ≥ 3 weeks. Out of 396 participants offered nicotine patches who were included for analysis, 36 (9.1%) quit smoking for ≥ 4 weeks before surgery as compared with 8 (5.9%) controls, OR 1.5 [95%CI 0.7-3.2], p = 0.300. Sixty-three (15.9%) quit smoking for 24 h before surgery as compared with 15 (11.1%) controls, OR 1.4 [95%CI 0.8-2.4], p = 0.200. Participants offered nicotine patches were more likely to engage in a cessation attempt lasting more than 24 h, 46 (11.6%) vs. 5 (3.7%), OR 3.4 [95%CI 1.8-8.8], p = 0.010. Out of 78 participants who quit smoking by the day of surgery and were followed up at 6 months, 46 (59%) had relapsed. Offering free nicotine patches stimulated interest in quitting compared with controls, but our protocol had limited effectiveness.

Herb species inclusion in grazing swards for dairy cows-A systematic review and meta-analysis.

A systematic review and meta-analysis were conducted to estimate the effect of herb species on milk production and urinary nitrogen (UN) excretion from grazing dairy cows. Grazing swards consisting of herb species grown with either a grass species or a grass and legume (multispecies swards) were compared with non-herb-containing swards consisting of a grass species grown as a monoculture or grass-legume swards (simple swards). A literature search was completed using the online databases CAB Direct, Web of Science, and Google Scholar, using the search strategy "dairy cow", "herb OR forb OR phorb", and "grazing". Milk production data, variance, and sample size were required for eligibility. In all, 116 studies were identified. Following eligibility screening, 11 papers from 6 journals, published between 2006 and 2018, were available for analysis. Studies were from New Zealand (N = 7), Australia (N = 3), and the United States (N = 1). The population was either Holstein Friesian or Holstein Friesian × Jersey dairy cows, with a range in mean daily milk yield (MY) from 12.1 kg to 34.7 kg (mean = 18.6 kg). A total of 25 comparisons were used for milk production analysis, with 324 and 284 cows included in multispecies and simple sward groups respectively. Data analysis was conducted in R using a random effects, robust variance estimation model (R Foundation for Statistical Computing, Vienna, Austria). Heterogeneity was reported using the I2 statistic. Milk production was significantly increased. Analysis of MY resulted in a weighted mean difference (WMD) of +1.20 kg/d (95% CI = 0.90, 1.49; I2 = 4%). Fat and protein kg were also significantly increased (WMD +0.06 kg/d; CI = 0.01, 0.11). Urinary nitrogen excretion was estimated from milk urea nitrogen when reported (n = 6). A WMD of -28.1 g of N/d (95% CI = -81.1, 24.9) was generated, with heterogeneity high among studies (I2 = 75%). This meta-analysis shows the potential benefits of multispecies swards. Although we saw no significant difference in UN excretion, an increase in milk production was found.

Parents' and healthcare professionals' experiences of care after stillbirth in low- and middle-income countries: a systematic review and meta-summary.

BACKGROUND: Stillbirth has a profound impact on women, families, and healthcare workers. The burden is highest in low- and middle-income countries (LMICs). There is need for respectful and supportive care for women, partners, and families after bereavement. OBJECTIVE: To perform a qualitative meta-summary of parents' and healthcare professionals' experiences of care after stillbirth in LMICs. SEARCH STRATEGY: Search terms were formulated by identifying all synonyms, thesaurus terms, and variations for stillbirth. Databases searched were AMED, EMBASE, MEDLINE, PsychINFO, BNI, CINAHL. SELECTION CRITERIA: Qualitative, quantitative, and mixed method studies that addressed parents' or healthcare professionals' experience of care after stillbirth in LMICs. DATA COLLECTION AND ANALYSIS: Studies were screened, and data extracted in duplicate. Data were analysed using the Sandelowski meta-summary technique that calculates frequency and intensity effect sizes (FES/IES). MAIN RESULTS: In all, 118 full texts were screened, and 34 studies from 17 countries were included. FES range was 15-68%. Most studies had IES 1.5-4.5. Women experience a broad range of manifestations of grief following stillbirth, which may not be recognised by healthcare workers or in their communities. Lack of recognition exacerbates negative experiences of stigmatisation, blame, devaluation, and loss of social status. Adequately developed health systems, with trained and supported staff, are best equipped to provide the support and information that women want after stillbirth. CONCLUSIONS: Basic interventions could have an immediate impact on the experiences of women and their families after stillbirth. Examples include public education to reduce stigma, promoting the respectful maternity care agenda, and investigating stillbirth appropriately. TWEETABLE ABSTRACT: Reducing stigma, promoting respectful care and investigating stillbirth have a positive impact after stillbirth for women and families in LMICs.

PARENTS 2 study: consensus report for parental engagement in the perinatal mortality review process.

OBJECTIVE: The PARENTS 1 study (Parents' Active Role and ENgagement in The review of their Stillbirth/perinatal death) found that parents would endorse the opportunity to give feedback into the perinatal mortality review (PNMR) process. In subsequent focus groups, healthcare professionals were positive about parental engagement, although they considered that there may be significant challenges. The objective of this study was to develop core principles and recommendations for parental engagement in PNMR in the UK. METHODS: A two-round Delphi technique was followed to reach consensus on core principles for parental engagement in the PNMR process; Round 1 included a national consensus workshop and Round 2 an online questionnaire. The consensus meeting was attended by a national panel of stakeholders (clinical and academic experts, parent advocates, managers and commissioners) in stillbirth and neonatal and bereavement care. To develop recommendations for parental engagement, participants discussed four key areas comprising: communication with parents, including receiving feedback; the format of the PNMR meeting; the parental engagement pathway; and challenging aspects of engaging with parents in reviews. Content analysis was conducted to generate recommendations from the meeting for a subsequent anonymous web-based survey. Attendees of the consensus workshop and members of the PARENTS 2 Project Advisory Board were asked to rank recommendations using a 9-point Likert scale from 1 (not important) to 9 (critically important). It had been agreed a priori, in compliance with established Grading of Recommendations, Assessment, Development and Evaluation (GRADE) criteria, that 'consensus' would be achieved if over 70% of participants scored the principle as 'critical' (score of 7-9) and fewer than 15% scored the principle as 'not important' (score of 1-3). Principles for which consensus was achieved were included in the core recommendations. RESULTS: Of the 29 invited stakeholders, 22 participated in the consensus meeting and 25 (86% response rate) in the subsequent online questionnaire in June 2017. Consensus was agreed on 12 core principles. Of the 25 participants, 96% agreed that a face-to-face explanation of the PNMR process was of critical importance, 72% considered that parents should be offered the opportunity to nominate a suitable advocate, 92% believed that responses to parents' comments should be formally documented, 96% indicated that it was vital for action plans to be translated into lessons learnt and that this process should be monitored, and 100% of stakeholders voted that a plain-English summary should be produced for the parents following the meeting. There was good agreement on a further seven principles. CONCLUSIONS: Key national stakeholders were unanimously supportive of parental engagement in the PNMR process and agreed on core principles to make this process feasible, meaningful and robust. A 6-month pilot of parental engagement in the PNMR process (PARENTS 2 study) in two UK units took place after the consensus on core principles. In collaboration with the National Perinatal Epidemiology Unit, the findings will inform the national standardized PNMR tool. © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

The effect of concentrate supplementation type on milk production, dry matter intake, rumen fermentation, and nitrogen excretion in late-lactation, spring-calving grazing dairy cows.

In Ireland, milk is primarily produced using a spring-calving grass-based system, with the use of concentrate supplementation mainly when pasture availability and quality are reduced. In the autumn, when cows are in late lactation, reduced pasture productivity results in reduced milk yield and altered milk composition. Nitrogen utilization efficiency also reduces as lactation progresses. Concentrate supplementation has been found to increase milk production and reduce nitrogen (N) excretion, as high-N grass is usually replaced by a lower-N supplement; however, there is a paucity of information with regard to the optimum type of supplementation in late lactation. Therefore, the objective of this research is to investigate the effect of different concentrate supplementation types, based on barley or maize, on milk production, dry matter intake (DMI), rumen fermentation, and N excretion in late-lactation, spring-calving, grazing dairy cows. Thirty-six Holstein Friesian dairy cows were blocked on days in milk (185 DIM) and balanced for parity, pre-experimental milk yield, milk composition, and body condition score. Cows were randomly assigned to 1 of 3 dietary treatments in a randomized complete block design (n = 12). The 3 treatments consisted of a perennial ryegrass-based pasture-only (PO) treatment and pasture plus either of 2 supplementary concentrates, based on barley (PB) or maize (PM). The diets were fed for a 14-d acclimatization period and then for a further 63-d experimental period. Cows offered PO had a lower daily milk yield (15.1 kg) than PB (18.2 kg) or PM (16.8 kg). Similarly, PO had lower daily milk solids yield (1.46 kg) than PB or PM (1.68 and 1.53 kg, respectively). Cows offered PB had a greater milk yield and higher fat and protein yields than those offered PM. Offering PB increased total DMI (19.5 kg) compared with PO (17.7 kg), and milk response to concentrates was also greater for PB compared with PM (1.21 vs. 0.71 kg of milk per kg of concentrate). Cows offered PB had increased N in milk compared with PO. In conclusion, concentrate supplementation based on barley or maize resulted in increased milk and milk solids yield compared with offering PO. Cows offered barley had a greater response to concentrates and increased milk and milk solids yield in comparison to maize and showed increased N partitioning in milk compared with PO. A barley-based concentrate increased total DMI compared with PO.