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Abstract Passive acoustic recorders have emerged as powerful tools for ecological monitoring. However, effective monitoring is not simply an act of recording sounds. To have meaning for conservation and management, acoustic monitoring needs to be properly planned and analyzed to yield high quality information. Here, we provide a set of considerations for the design of an effective acoustic monitoring program. We argue that such a program, has the following attributes: (1) has established appropriate partnerships with landowners, Traditional Owners, researchers, or other relevant stakeholders, (2) is based on clear objectives and questions, (3) is explicit in its target sound signals, (4) has considered in‐field sensor placement for a range of factors, including experimental design, statistical power, background noise, and potential impacts on human privacy and animal disturbance, (5) has a justified recording schedule and periodicity, (6) has methods to process sound data in line with objectives, and (7) has protocols for permanent data storage and access. Acoustic monitoring is increasingly used in large‐scale programs and will be important in addressing global biodiversity targets and new biodiversity markets. It is critical that new monitoring programs are designed to effectively and efficiently capture data that address pertinent and emerging issues in conservation.

Abstract Objectives Behçet’s disease is a rare, chronic, incurable, multisystemic disease. It causes significant morbidity, with patients experiencing symptoms including mucous membrane ulcers, and joint pain and swelling. It is an important cause of avoidable blindness due to ocular involvement. The aetiology is unknown. The aims were to identify population prevalence of Behçet’s disease in Wales in comparison to other endemic and non-endemic regions, and provide an epidemiological profile of a case series of adult patients. This is the first analysis of data from the Adult Rare Diseases Surveillance Registry for Wales, established in 2020 as part of the COVID-19 pandemic response. Results Between 1995 and 2020, 347 adults and 5 children were recorded in Wales with a diagnosis of Behçet’s disease. Population prevalence was calculated as 11.1 per 100,000 population. Of the adult cases, 76.9% were female, and 6.6% died before the end of the study period. When comparing genders, there were no statistically significant differences in age at diagnosis, mortality or socioeconomic status. There was no evidence that the age at which cases were diagnosed had changed over time. Survival analyses showed no significant differences in durations of survival between genders or individuals residing in different WIMD 2019 quintiles. Age at diagnosis was the only factor significantly and independently associated with poorer durations of survival (p

Introduction Linking healthcare data sets can create valuable resources for research, particularly when investigating rare exposures or outcomes. However, across Europe, the permissions processes required to access data can be complex. This paper documents the processes required by the EUROlinkCAT study investigators to research the health and survival of children with congenital anomalies in Europe.Methods Eighteen congenital anomaly registries in 14 countries provided information on all the permissions required to perform surveillance of congenital anomalies and to link their data on live births with available vital statistics and healthcare databases for research. Small number restrictions imposed by data providers were also documented.Results The permissions requirements varied substantially, with certain registries able to conduct congenital anomaly surveillance as part of national or regional healthcare provision, while others were required to obtain ethics approvals or informed consent. Data linkage and analysis for research purposes added additional layers of complexity for registries, with some required to obtain several permissions, including ethics approvals to link the data. Restrictions relating to small numbers often resulted in a registry’s data on specific congenital anomalies being unusable.Conclusion The permissions required to obtain and link data on children with congenital anomalies varied greatly across Europe. The variation and complexity present a significant obstacle to the use of such data, especially in large data linkage projects. Furthermore, small number restrictions severely limited the research that could be performed for children with specific rare congenital anomalies.

Abstract Fauna surveys are traditionally manual, and hence limited in scale, expensive and labour‐intensive. Low‐cost hardware and storage mean that acoustic recording now has the potential to efficiently build scale in terrestrial fauna surveys, both spatially and temporally. With this aim, we have constructed the Australian Acoustic Observatory. It provides a direct and permanent record of terrestrial soundscapes through continuous recording across Australian ecoregions, including those periodically subject to fire and flood, when manual surveys are dangerous or impossible. The observatory comprises 360 permanent listening stations deployed across Australia. Groups of four sensors are deployed at each of 90 sites, placed strategically across ecoregions, to provide representative datasets of soundscapes. Each station continuously records sound, resulting in year‐round data collection. All data are made freely available under an open access licence. The Australian Acoustic Observatory is the world's first terrestrial acoustic observatory of this size. It provides continental‐scale environmental monitoring of unparalleled spatial extent, temporal resolution and archival stability. It enables new approaches to understanding ecosystems, long‐term environmental change, data visualization and acoustic science that will only increase in scientific value over time, particularly as others replicate the design in other parts of the world.

Objectives Education outcomes predict life chances; however disabilities and concurrent learning difficulties are often barriers to school performance. Low educational achievement is also linked with socio-economic deprivation. We aimed to quantify the association of these factors with education outcomes by ages 12 and 17 for children in Wales (UK). Approach We linked health, socio-economic and education data for children born after 1997 in Wales, registered with any one of 17 isolated congenital anomalies. Children were included if they had known education outcomes at ages 12 (n=9,223) and 17 (n=4524). A reference population comprised children born similarly but without anomalies, also having education records at 12 (n=261,827) and 17 (n=4,524). Multinomial logistic regressions determined the likelihood of attainment in compulsory subjects by age 12 and of attaining five GCSE qualifications by age 17. We adjusted for socio-economic status by using free school meal eligibility (household deprivation) and area-based indices of deprivation. Results We identified 14 and 11 isolated anomalies that reduced the likelihood of achieving educational standards by ages 12 and 17 respectively. Educational achievements were lower for children with Down syndrome, Turner syndrome, hydrocephalus and limb reduction defects, particularly at age 12, indicating that children with anomalies may catch-up with their peers. While children with anomalies were less likely to achieve five GCSEs by age 17, there was no difference in the grades of those who did so. Deprivation, particularly at household level, further reduced the likelihood of education success. At age 17, household deprivation reduced 3-fold the odds of achieving any five GCSEs grades A*-C. Conclusions Children with congenital anomalies from the most deprived communities and households are at particular risk of low education achievement. To realise their potential, these children should be identified from medical records at an early age and offered targeted educational support as soon as possible and at every opportunity.

Abstract Accurate, reproducible diagnoses can be difficult to make in haemato‐oncology due to multi‐parameter clinical data, complex diagnostic criteria and time‐pressured environments. We have designed a decision tree application (DTA) that reflects WHO diagnostic criteria to support accurate diagnoses of myeloid malignancies. The DTA returned the correct diagnoses in 94% of clinical cases tested. The DTA maintained a high level of accuracy in a second validation using artificially generated clinical cases. Optimisations have been made to the DTA based on the validations, and the revised version is now publicly available for use at http://bit.do/ADAtool.

The ever-changing nature of the power industry will require the implementation of hybrid energy systems. Integration of tightly coupled components in hybrids often involves the diversion of exhaust gas flow. An innovative smart material actuation technology is proposed to replace traditional electro-mechanical actuated valve mechanisms with lighter and less expensive actuators. A shape memory alloy (SMA) spring-actuated valve was designed for high-temperature service to demonstrate the promise of smart materials in control valve applications. With SMA springs only generating a maximum force of 3.2 N, an innovative valve design was necessary. To demonstrate the concept, a 3-inch Nominal Pipe Size valve was designed, and 3D printed using the stereolithography technique. Increasing the electrical current to actuate the SMA springs reduced actuation time. The maximum current of 10 A produced the lowest actuation time of 2.85 s, with an observed maximum stroke rate of more than 100 stroke completion %/s (considering actuation open/close as 100% stroke) at the midrange. The final assembly of the valve was estimated to provide a cost reduction of more than 30% and a weight reduction of more than 80% compared to the other available automatic valves in the present market.

The major design parameters of SOFC have great impacts on the net electrical efficiency of SOFC/GT hybrid systems. The influence of the SOFC operating temperature and fuel utilization on the net efficiency of a pressurized solid oxide fuel cell gas turbine hybrid system was studied in this paper. The system model was combined a 1D SOFC model, which included a lumped equilibrium steam methane reformer model in the Simulink, with a gas turbine recuperated cycle model in Ebsilon®. A system design point study was established to observe the coupling impacts of SOFC operating temperature and fuel utilization on the system performance. Thirty design cases of SOFC operating temperatures (635 °C–835 °C) over a range of SOFC fuel utilization(45%–90%) were evaluated. The optimal SOFC fuel utilization shifted from 65% to 55% when the SOFC operating temperature decreased from 835 °C to 635 °C. The maximal(minimal) system efficiency was 74%(49%) at 65%(90%) SOFC fuel utilization with operating SOFC at 835 °C(635 °C). The results show that high operating temperature leads to the high efficiency of the entire hybrid system, but high fuel utilization might cause a decrease in system efficiency.

Background: Myelofibrosis (MF) is a blood cancer associated with splenomegaly, blood count abnormalities, reduced life expectancy and high prevalence of disease-associated symptoms. Current treatment options for MF are diverse, with limited data on management strategies in real-world practice in the United Kingdom. Methods: The REALISM UK study was a multi-center, retrospective, non-interventional study, which documented the early management of patients with MF. The primary endpoint was the time from diagnosis to active treatment. Discussion: Two hundred patients were included (63% [ n = 126/200] with primary MF; 37% [ n = 74/200] with secondary MF). Symptoms and prognostic scores at diagnosis were poorly documented, with infrequent use of patient reported outcome measures. ‘Watch and wait’ was the first management strategy for 53.5% ( n = 107/200) of patients, while the most commonly used active treatments were hydroxycarbamide and ruxolitinib. Only 5% of patients proceeded to allogeneic transplant. The median (IQR) time to first active treatment was 46 days (0–350); patients with higher risk disease were prescribed active treatment sooner. Conclusion: These results provide insight into real-world clinical practice for patients with MF in the United Kingdom. Despite the known high prevalence of disease-associated symptoms in MF, symptoms were poorly documented. Most patients were initially observed or received hydroxycarbamide, and ruxolitinib was used as first-line management strategy in only a minority of patients. Plain Language Summary Background: Myelofibrosis is a rare blood cancer associated with symptoms that can seriously affect a patient’s daily life, such as enlarged spleen and decreased white and red blood cells. Although several treatments are available for patients with myelofibrosis, it is not clear which ones clinicians use most frequently. Methods: We aimed to review which treatments are usually given to patients with myelofibrosis in the UK, by collecting information from the medical records of 200 patients with myelofibrosis treated in different centres across the UK. Results: The results showed that the symptoms patients experienced were not always written down in the medical records. Similarly, clinical scores based on patient characteristics (which clinicians use to try to predict if a patient will respond to treatment well or not) were also missing from the medical records. Clinicians also rarely asked patients to complete questionnaires that try to measure the impact of myelofibrosis and its treatment on their health. The most common approach for patients with myelofibrosis in the UK was ‘watch and wait’, which over half of patients received. The most common drugs used for treatment were hydroxycarbamide and ruxolitinib; only a very small proportion of patients received a bone marrow transplant. On average, patients waited for 46 days before receiving a treatment, although patients considered to have a more aggressive type of disease received treatment sooner. Conclusion: The results of this study suggest that medical records can be missing key information, which is needed to decide which is the best way to treat a patient with myelofibrosis. They also suggest that clinicians in the UK prefer observation to treatment for a large number of patients with myelofibrosis. This could mean that the approach used for many patients with myelofibrosis does not help them to control symptoms that have an impact on their daily lives.

High rates of biodiversity loss caused by human-induced changes in the environment require new methods for large scale fauna monitoring and data analysis. While ecoacoustic monitoring is increasingly being used and shows promise, analysis and interpretation of the big data produced remains a challenge. Computer-generated acoustic indices potentially provide a biologically meaningful summary of sound, however, temporal autocorrelation, difficulties in statistical analysis of multi-index data and lack of consistency or transferability in different terrestrial environments have hindered the application of those indices in different contexts. To address these issues we investigate the use of time-series motif discovery and random forest classification of multi-indices through two case studies. We use a semi-automated workflow combining time-series motif discovery and random forest classification of multi-index (acoustic complexity, temporal entropy, and events per second) data to categorize sounds in unfiltered recordings according to the main source of sound present (birds, insects, geophony). Our approach showed more than 70% accuracy in label assignment in both datasets. The categories assigned were broad, but we believe this is a great improvement on traditional single index analysis of environmental recordings as we can now give ecological meaning to recordings in a semi-automated way that does not require expert knowledge and manual validation is only necessary for a small subset of the data. Furthermore, temporal autocorrelation, which is largely ignored by researchers, has been effectively eliminated through the time-series motif discovery technique applied here for the first time to ecoacoustic data. We expect that our approach will greatly assist researchers in the future as it will allow large datasets to be rapidly processed and labeled, enabling the screening of recordings for undesired sounds, such as wind, or target biophony (insects and birds) for biodiversity monitoring or bioacoustics research.

Background: Hypoplastic Left Heart Syndrome (HLHS) is a severe congenital heart defect (CHD) characterised by the underdevelopment of the left side of the heart with varying levels of hypoplasia of the left atrium, mitral valve, left ventricle, aortic valve and aortic arch. In the UK, age 12 survival for cases born between 1991 and 1993 was 21%. UK survival estimates corresponding to cases born between 2000 and 2015 were improved at 56%, but survival was examined up to age five only. Contemporary long-term survival estimates play a crucial role in counselling parents following diagnosis. The aim of this study was to report survival estimates up to age 15 for children born with HLHS or hypoplastic left ventricle with additional CHD in England and Wales between 1998 and 2012.Methods: Cases of HLHS notified to four congenital anomaly registers in England and Wales during 1998–2012, matched to Office for National Statistics mortality information, were included. Kaplan-Meier survival estimates to age 15 were reported. Cox regression models were fitted to examine risk factors for mortality.Results: There were 244 cases of HLHS and 99 cases of hypoplastic left ventricle co-occurring with other CHD, with traced survival status. Kaplan-Meier survival estimates for HLHS were 84.4% at age 1 week, 76.2% at 1 month, 63.5% at age 1 year, 58.6% at age 5 years, 54.6% at age 10 years, and 32.6% to age 15 years. The Kaplan-Meier survival estimates for cases of hypoplastic left ventricle co-occurring with additional CHD were 90.9% at age 1 week, 84.9% at 1 month, 73.7% at age 1 year, 67.7% to age 5 years, 59.2% to age 10 years, and 40.3% to age 15 years. Preterm birth (p = 0.007), low birth weight (p = 0.005), and female sex (p = 0.01) were associated with mortality.Conclusions: We have shown that prognosis associated with HLHS in the twenty first century exceeds that of many previous population-based studies, likely due to improvements in intensive care technologies and advances in surgical techniques over the last few decades.

Rare pathogenic copy number variants (CNVs) are genetic rearrangements that have been associated with an increased risk for congenital heart disorders (CHDs). However, the association of CNVs with atypical brain development, leading to neurodevelopmental disorders (NDDs), in the presence of CHDs remains unclear. We attempted to explore this association by establishing the prevalence and burden of CNVs associated with CHD in a Welsh population and by studying the effect of rare CNVs associated with CHDs in mediating the risk of NDDs. Toward this goal, we analyzed data from the Congenital Anomaly Register for Wales (CARIS), referred from hospitals in Wales between 1998 and 2018, which included 1,113 subjects in total. Of these, 785 subjects were included in the study following application of the exclusion criteria, and a total of 28 rare CNVs associated with CHD were analyzed. The findings from this cohort study identified 22q11.2 deletion as the most prominent CNV across the cohort. Our data demonstrates that the survival rate of the cohort after 3 years was 99.9%, and mortality fell significantly between 1 and 2 years and between 2 and 3 years [F(1,27) = 10, p = 0.0027; F(1,27) = 5.8, p = 0.0222]. Importantly, the data set revealed a positive correlation between the incidence of congenital heart disease and the incidence of neurodevelopmental abnormalities in patients with CNVs across the whole cohort [95% CI (0.4062, 0.8449), p < 0.0001, r = 0.6829]. Additionally, we identified significant CNVs that result in the co-morbidity of CHD and NDD and show that septal defects and global developmental delay are major congenital defects. Further research should identify a common molecular mechanism leading to the phenotypic comorbidity of CHDs and NDDs, arising from a common CNV, which can have an implication for improving risk classification and for fetal neuroprotection strategies in the affected children and in precision medicine.

Objective: Thirty years ago it was demonstrated that folic acid taken before pregnancy and in early pregnancy reduced the risk of a neural tube defect (NTD). Despite Public Health Initiatives across Europe recommending that women take 0.4 mg folic acid before becoming pregnant and during the first trimester, the prevalence of NTD pregnancies has not materially decreased in the EU since 1998, in contrast to the dramatic fall observed in the USA. This study aimed to estimate the number of NTD pregnancies that would have been prevented if flour had been fortified with folic acid in Europe from 1998 as it had been in the USA.Design and Setting: The number of NTD pregnancies from 1998 to 2017 that would have been prevented if folic acid fortification had been implemented in the 28 countries who were members of the European Union in 2019 was predicted was predicted using data on NTD prevalence from 35 EUROCAT congenital anomaly registries and literature searches for population serum folate levels and folic acid supplementation.Results: From 1998 to 2017 an estimated 95,213 NTD pregnancies occurred amongst 104 million births in the 28 countries in the EU, a prevalence of 0.92 per 1,000 births. The median serum folate level in Europe over this time period was estimated to be 14.1 μg/L. There is a lack of information about women taking folic acid supplements before becoming pregnant and during the first trimester of pregnancy, with one meta-analysis indicating that around 25% of women did so. An estimated 14,600 NTD pregnancies may have been prevented if the European countries had implemented fortification at the level adopted by the USA in 1998 and 25% of women took folic acid supplements. An estimated 19,500 NTD pregnancies would have been prevented if no women took folic acid supplements.Conclusions: This study suggests that failure to implement mandatory folic acid fortification in the 28 European countries has caused, and continues to cause, neural tube defects to occur in almost 1,000 pregnancies every year.

Introduction Congenital anomalies (CAs) are a major cause of infant mortality, childhood morbidity and long-term disability. Over 130 000 children born in Europe every year will have a CA. This paper describes the EUROlinkCAT study, which is investigating the health and educational outcomes of children with CAs for the first 10 years of their lives.Methods and analysis EUROCAT is a European network of population-based registries for the epidemiological surveillance of CAs. EUROlinkCAT is using the EUROCAT infrastructure to support 22 EUROCAT registries in 14 countries to link their data on births with CAs to mortality, hospital discharge, prescription and educational databases. Once linked, each registry transforms their case data into a common data model (CDM) format and they are then supplied with common STATA syntax scripts to analyse their data. The resulting aggregate tables and analysis results are submitted to a central results repository (CRR) and meta-analyses are performed to summarise the results across all registries. The CRR currently contains data on 155 594 children with a CA followed up to age 10 from a population of 6 million births from 1995 to 2014.Ethics The CA registries have the required ethics permissions for routine surveillance and transmission of anonymised data to the EUROCAT central database. Each registry is responsible for applying for and obtaining additional ethics and other permissions required for their participation in EUROlinkCAT.Dissemination The CDM and associated documentation, including linkage and standardisation procedures, will be available post-EUROlinkCAT thus facilitating future local, national and European-level analyses to improve healthcare. Recommendations to improve the accuracy of routinely collected data will be made.Findings will provide evidence to inform parents, health professionals, public health authorities and national treatment guidelines to optimise diagnosis, prevention and treatment for these children with a view to reducing health inequalities in Europe.

Introduction The challenges in identifying a cohort of people with a rare condition can be addressed by routinely collected, population-scale electronic health record (eHR) data, which provide large volumes of data at a national level. This paper describes the challenges of accurately identifying a cohort of children with Cystic Fibrosis (CF) using eHR and their validation against the UK CF Registry. Objectives To establish a proof of principle and provide insight into the merits of linked data in CF research and the benefits of access to multiple data sources. In particular, the UK CF Registry data, and to demonstrate the opportunity it represents as a resource for future CF research. Method Three eHR data sources were used to identify children with CF born in Wales between 1st January 1998 and 31st August 2015 within the Secure Anonymised Information Linkage (SAIL) Databank. The UK CF Registry was later acquired by SAIL and linked to the eHR cohort to validate the cases and explore the reasons for misclassifications. Results We identified 352 children with CF in the three eHR data sources. This was greater than expected based on historical incidence rates in Wales. Subsequent validation using the UK CF Registry found that 257 (73%) of these were true cases. Over 98% of individuals identified as CF cases in all three eHR data sources were confirmed as true cases; but this was only the case for 19.8% of those identified in a single data source. Conclusion Identifying health conditions in eHR data can be challenging, so data quality assurance and validation is important or the merit of the research is undermined. This retrospective review identifies some of the challenges in identifying CF cases and demonstrates the benefits of linking cases across multiple data sources to improve quality.

ObjectivesTo explore associations between exposures to medicines prescribed for asthma and their discontinuation in pregnancy and preterm birth [MethodsDesign. A population-based cohort study. Setting. The Secure Anonymised Information Linkage [SAIL] databank in Wales, linking maternal primary care data with infant outcomes. Population. 107,573, 105,331, and 38,725 infants born 2000-2010 with information on premature birth, SGA and breastfeeding respectively, after exclusions. Exposures. maternal prescriptions for asthma medicines or their discontinuation in pregnancy. Methods. Odds ratios for adverse pregnancy outcomes were calculated for the exposed versus the unexposed population, adjusted for smoking, parity, age and socio-economic status.ResultsPrescriptions for asthma, whether continued or discontinued during pregnancy, were associated with birth atConclusionsPrescription of asthma medicines before or during pregnancy was associated with higher prevalence of adverse perinatal outcomes, particularly if prescriptions were discontinued during pregnancy. Women discontinuing medicines during pregnancy could be identified from prescription records. The impact of targeting close monitoring and breastfeeding support warrants exploration.

BackgroundChronic kidney disease (CKD) is a growing contributor to the global burden of noncommunicable diseases. Early diagnosis and treatment can reduce the severity of kidney damage and the need for dialysis or transplantation. It is not known whether mild-to-moderate renal pelvis dilatation (RPD) identified at 18-20 weeks gestation is an early indicator of renal pathology. The aim of this follow-up to the Welsh Study of Mothers and Babies was to assess the risk of hospital admission in children with mild-to-moderate antenatal RPD compared with children without this finding. We also examined how the natural history of the RPD (whether the dilatation persists in later pregnancy or postpartum) or its characteristics (unilateral versus bilateral) changed the risk of hospital admission.Methods/findingsThis population-based cohort study included singleton babies born in Wales between January 1, 2009, and December 31, 2011 (n = 22,045). We linked ultrasound scan data to routinely available data on hospital admissions from the Patient Episode Database for Wales (PEDW). The outcome was a hospital admission for urinary tract causes (defined by an expert study steering group) in the first three years of life. We used Cox regression to model time to first hospital admission, according to whether there was evidence of RPD at the fetal anomaly scan (FAS) and/or evidence of dilatation in later investigations, adjusting for other predictors of admission. We used multiple imputation with chained equations to impute values for missing data. We included 21,239 children in the analysis. The risk of at least one hospital admission was seven times greater in those with RPD (n = 138) compared with those without (n = 21,101, conditional hazard ratio [cHR] 7.23, 95% confidence interval [CI] 4.31-12.15, p < 0.001). The risk of hospital admission was higher in children with RPD at the FAS and later dilatation (cHR 25.13, 95% CI 13.26-47.64, p < 0.001) and in children without RPD at the FAS who had later dilatation (cHR 62.06, 95% CI 41.10-93.71, p < 0.001) than in children without RPD (n = 21,057). Among children with RPD at the FAS but no dilatation in later pregnancy or postpartum, we did not find an association with hospital admissions (cHR 2.16, 95% CI 0.69-6.75, p = 0.185), except when the initial dilatation was bilateral (cHR 4.77, 95% CI 1.17-19.47, p = 0.029). Limitations of the study include small numbers in subgroups (meaning that these results should be interpreted with caution), that less severe outcomes (such as urinary tract infections [UTIs] managed in the community or in outpatients) could not be included in our analysis, and that obtaining records of radiological investigations later in pregnancy and postpartum was challenging. Our conclusions were consistent after conducting sensitivity analyses to account for some of these limitations.ConclusionsIn this large population-based study, children with RPD at the FAS had higher rates of hospital admissions when there was persistent dilatation in later pregnancy or postpartum. Our results can be used to improve counselling of parents and develop care pathways for antenatal screening programmes, including protocols for reporting and further investigation of RPD.

ObjectivesTo explore associations between exposure to antidepressants, their discontinuation, depression [medicated or unmediated] and preterm birth [MethodsDesign: A population-based cohort study. Setting: The Secure Anonymised Information Linkage [SAIL] databank in Wales, linking maternal primary care data with infant outcomes. Participants: 107,573, 105,331, and 38,725 infants born 2000-2010 with information on prematurity, SGA and breastfeeding respectively, after exclusions. Exposures: Maternal antidepressant prescriptions in trimesters 2 or 3, discontinuation after trimester 1, recorded diagnosis of depression [medicated or unmediated] in pregnancy. Methods: Odds ratios for adverse pregnancy outcomes were calculated, adjusted for smoking, parity, socio-economic status, and depression.ResultsExclusive formula feeding at 6-8 weeks was associated with prescriptions in trimesters 2 or 3 for any antidepressants (adjusted odds ratio [aOR] 0.81, 95% confidence intervals 0.67-0.98), SSRIs [aOR 0.77, 0.62-0.95], particularly higher doses [aOR 0.45, 0.23-0.86], discontinuation of antidepressants or SSRIs after trimester 1 (aOR 0.70, 0.57-0.83 and 0.66, 0.51-0.87), diagnosis of depression aOR 0.76 [0.70-0.82), particularly if medicated (aOR 0.70, 0.58-0.85), rather than unmedicated (aOR 0.87, 0.82-0.92). Preterm birth at ImplicationsExposure to antidepressants or depression increased risks of exclusive formula feeding at 6-8 weeks, and prescription of antidepressants was associated with SGA

Ruminants are significant contributors to the livestock generated component of the greenhouse gas, methane (CH4). The CH4 is primarily produced by the rumen microbes. Although the composition of the diet and animal intake amount have the largest effect on CH4 production and yield (CH4 production/dry matter intake, DMI), the host also influences CH4 yield. Shorter rumen feed mean retention time (MRT) is associated with higher dry matter intake and lower CH4 yield, but the molecular mechanism(s) by which the host affects CH4 production remain unclear. We integrated rumen wall transcriptome data and CH4 phenotypes from two independent experiments conducted with sheep in Australia (AUS, n = 62) and New Zealand (NZ, n = 24). The inclusion of the AUS data validated the previously identified clusters and gene sets representing rumen epithelial, metabolic and muscular functions. In addition, the expression of the cell cycle genes as a group was consistently positively correlated with acetate and butyrate concentrations (p < 0.05, based on AUS and NZ data together). The expression of a group of metabolic genes showed positive correlations in both AUS and NZ datasets with CH4 production (p < 0.05) and yield (p < 0.01). These genes encode key enzymes in the ketone body synthesis pathway and included members of the poorly characterized aldo-keto reductase 1C (AKR1C) family. Several AKR1C family genes appear to have ruminant specific evolution patterns, supporting their specialized roles in the ruminants. Combining differential gene expression in the rumen wall muscle of the shortest and longest MRT AUS animals (no data available for the NZ animals) with correlation and network analysis, we identified a set of rumen muscle genes involved in cell junctions as potential regulators of MRT, presumably by influencing contraction rates of the smooth muscle component of the rumen wall. Higher rumen expression of these genes, including SYNPO (synaptopodin, p < 0.01) and NEXN (nexilin, p < 0.05), was associated with lower CH4 yield in both AUS and NZ datasets. Unlike the metabolic genes, the variations in the expression of which may reflect the availability of rumen metabolites, the muscle genes are currently our best candidates for causal genes that influence CH4 yield.

Introduction Cystic fibrosis (CF) is the most common life-limiting inherited disease in white populations, with most patients dying prematurely from respiratory failure. As it is rare, it is important to reduce misclassification. We therefore aimed to assess how well CF children could be identified across routine data in Wales. Objectives and Approach Data from the Secure Anonymised Information Linkage (SAIL) databank, identified children with CF from 1998 to 2016, within hospital, General Practice (GP), and the Welsh Congenital Abnormality Register (CARIS), which uses new born screening to identify congenital abnormalities, including CF. The International Classification of Diseases (ICD10) E84 was used to identify CF children in both hospital and CARIS data, with READ codes used in the GP data (approximately 80% coverage of Wales). The data was linked using anonymised linking fields and matching rates analysed, as unmatched records in linked data can reduce the utility of the data for epidemiological studies. Results 352 cases were identified in total, with 158 matched across all three datasets over an 18 year period (9-19 cases per year). The Welsh rate from the disease registry is 12–14. Since CF is a severely debilitating condition, a greater match was expected. This prompted further investigation of cases which appeared in only one dataset, as these seemed least likely to be true cases. In the ‘CARIS only’ data, 79% of the admissions, were found coded for respiratory, digestive and health complications not for an E84 CF condition. In the 43 cases in ‘GP only’ data, and the 19 in ‘hospital only’ data the events indicated the possible late presentation of CF by older children or children with very mild CF phenotypes. Conclusion/Implications Cases of rare diseases like CF can be identified in routine data. Linking across multiple datasets, particularly with specialist datasets like CARIS, help identify potentially misclassified cases. This increases confidence in the data. Future work will include the CF registry, permitting checks against a gold standard data resource.

BACKGROUND:Surveillance of congenital anomalies is important to identify potential teratogens. METHODS:This study analysed the prevalence of 61 congenital anomaly subgroups (excluding chromosomal) in 25 population-based EUROCAT registries (1980-2012). Live births, fetal deaths and terminations of pregnancy for fetal anomaly were analysed with multilevel random-effects Poisson regression models. RESULTS:Seventeen anomaly subgroups had statistically significant trends from 2003-2012; 12 increasing and 5 decreasing. CONCLUSIONS:The annual increasing prevalence of severe congenital heart defects, single ventricle, atrioventricular septal defects and tetralogy of Fallot of 1.4% (95% CI: 0.7% to 2.0%), 4.6% (1.0% to 8.2%), 3.4% (1.3% to 5.5%) and 4.1% (2.4% to 5.7%) respectively may reflect increases in maternal obesity and diabetes (known risk factors). The increased prevalence of cystic adenomatous malformation of the lung [6.5% (3.5% to 9.4%)] and decreased prevalence of limb reduction defects [-2.8% (-4.2% to -1.5%)] are unexplained. For renal dysplasia and maternal infections, increasing trends may be explained by increased screening, and deceases in patent ductus arteriosus at term and increases in craniosynostosis, by improved follow up period after birth and improved diagnosis. For oesophageal atresia, duodenal atresia/stenosis and ano-rectal atresia/stenosis recent changes in prevalence appeared incidental when compared with larger long term fluctuations. For microcephaly and congenital hydronephrosis trends could not be interpreted due to discrepancies in diagnostic criteria. The trends for club foot and syndactyly disappeared once registries with disparate results were excluded. No decrease in neural tube defects was detected, despite efforts at prevention through folic acid supplementation.

Coupling a solid oxide fuel cell (SOFC) with a gas turbine provides a substantial increment in system efficiency compared to the separate technologies, which can potentially introduce economic benefits and favor an early market penetration of fuel cells. Currently, the economic viability of such systems is limited by fuel cell short lifetime due to a progressive performance degradation that leads to cell failure. Mitigating these phenomena would have a significant impact on system economic feasibility. In this study, the lifetime of a standalone, atmospheric SOFC system was compared to a pressurized SOFC gas turbine hybrid and an economic analysis was performed. In both cases, the power production was required to be constant over time, with significantly different results for the two systems in terms of fuel cell operating life, system efficiency, and economic return. In the hybrid system, an extended fuel cell lifetime is achieved while maintaining high system efficiency and improving economic performance. In this work, the optimal power density was determined for the standalone fuel cell in order to have the best economic performance. Nevertheless, the hybrid system showed better economic performance, and it was less affected by the stack cost.

ABSTRACT Objectives 9.4% of pregnant women in Wales are prescribed medicines for asthma. Prescription of asthma medicines in early pregnancy is associated with increased prevalence of congenital anomalies (aOR 1.20, 1.08 - 1.34). The literature offers less consensus on more common adverse outcomes: premature delivery (

ABSTRACT Objectives The All Wales Perinatal Survey (AWPS) collects mortality data on perinatal, neonatal and infant mortality in Wales up to a year of age. The Congenital Anomaly Register and Information Service (CARIS) collects clinical data on all congenital anomalies in foeti, infants and children in Wales. This was the first attempt to link the AWPS and CARIS databases. Approach The AWPS database coded stillbirths, terminations and deaths by the clinic-pathologic classification until 2012, assigning each case a survey number. The CARIS database started collecting data from 1998. Thus, the common period between 1998 and 2012 (15 years) was chosen for this study. Using CARIS as the main dataset, AWPS data were matched against the CARIS database using NHS numbers, along with soft linking on date of birth, maternal date of birth, and postcode. The unique AWPS survey number and coding was then added to the matched record within the CARIS dataset. This final ‘linked’ dataset was used to look at trend data. Results Between 1998 and 2012 a total of 20,574 cases were recorded in the CARIS database. After excluding cases where no gestation or date of death were recorded, and including deaths between >19 weeks’ gestation up to 365 days after birth, there were 1306 foetal losses/terminations, 231 stillbirths, and 662 livebirths (total 2,199) records left in the CARIS database who died with congenital anomalies. In the comparable period, using the same criteria, there were 6,909 records identified in the AWPS database. Of those, 1,765 had a recorded lethal congenital anomaly. By using the above criteria, a total of 2,039 cases in the CARIS database were linked to the AWPS database. 241 cases in the CARIS database and 151 cases in the AWPS database could not be linked by the above methods. Analysing the CARIS cases alone showed that consistently more than 80% of foeti are live-born, and survive. Chromosomal (22%), cardiovascular (21%) and brain (15%) anomalies are the most common congenital anomalies in the linked cases, which contribute to infant mortality. This pattern has remained largely unchanged over the study period. Conclusion Using NHS numbers and soft linking, the majority of CARIS cases were linked to AWPS cases. Although both these databases should closely reflect each other, missing cases suggest there is scope for improvement in data collection. Sharing of data could also improve the quality of both databases.

We report a rare case of cutaneous Legionella longbeachae infection in a patient receiving long-term corticosteroids for immune thrombocytopenia. Such infections cannot be identified by using Legionella urinary antigen testing but are commonly seen after exposure to commercial potting compost, particularly in immunocompromised patients.

Hypothesised associations between in utero exposure to selective serotonin reuptake inhibitors (SSRIs) and congenital anomalies, particularly congenital heart defects (CHD), remain controversial. We investigated the putative teratogenicity of SSRI prescription in the 91 days either side of first day of last menstrual period (LMP).Three population-based EUROCAT congenital anomaly registries- Norway (2004-2010), Wales (2000-2010) and Funen, Denmark (2000-2010)-were linked to the electronic healthcare databases holding prospectively collected prescription information for all pregnancies in the timeframes available. We included 519,117 deliveries, including foetuses terminated for congenital anomalies, with data covering pregnancy and the preceding quarter, including 462,641 with data covering pregnancy and one year either side. For SSRI exposures 91 days either side of LMP, separately and together, odds ratios with 95% confidence intervals (ORs, 95%CI) for all major anomalies were estimated. We also explored: pausing or discontinuing SSRIs preconception, confounding, high dose regimens, and, in Wales, diagnosis of depression. Results were combined in meta-analyses. SSRI prescription 91 days either side of LMP was associated with increased prevalence of severe congenital heart defects (CHD) (as defined by EUROCAT guide 1.3, 2005) (34/12,962 [0.26%] vs. 865/506,155 [0.17%] OR 1.50, 1.06-2.11), and the composite adverse outcome of 'anomaly or stillbirth' (473/12962, 3.65% vs. 15829/506,155, 3.13%, OR 1.13, 1.03-1.24). The increased prevalence of all major anomalies combined did not reach statistical significance (3.09% [400/12,962] vs. 2.67% [13,536/506,155] OR 1.09, 0.99-1.21). Adjusting for socio-economic status left ORs largely unchanged. The prevalence of anomalies and severe CHD was reduced when SSRI prescriptions were stopped or paused preconception, and increased when >1 prescription was recorded, but differences were not statistically significant. The dose-response relationship between severe CHD and SSRI dose (meta-regression OR 1.49, 1.12-1.97) was consistent with SSRI-exposure related risk. Analyses in Wales suggested no associations between anomalies and diagnosed depression.The additional absolute risk of teratogenesis associated with SSRIs, if causal, is small. However, the high prevalence of SSRI use augments its public health importance, justifying modifications to preconception care.