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OBJECTIVES Early right-sided heart failure (RHF) was seen in 22% of recipients of a left ventricular assist device (LVAD) in the European Registry for Patients with Mechanical Circulatory Support (EUROMACS). However, the optimal treatment of post-LVAD RHF is not well known. Levosimendan has proven to be effective in patients with cardiogenic shock and in those with end-stage heart failure. We sought to evaluate the efficacy of levosimendan on post-LVAD RHF and 30-day and 1-year mortality. METHODS The EUROMACS Registry was used to identify adults with mainstream continuous-flow LVAD implants who were treated with preoperative levosimendan compared to a propensity matched control cohort. RESULTS In total, 3661 patients received mainstream LVAD, of which 399 (11%) were treated with levosimendan pre-LVAD. Patients given levosimendan had a higher EUROMACS RHF score [4 (2– 5.5) vs 2 (2– 4); P CONCLUSIONS In this analysis of the EUROMACS registry, we found no evidence for an association between levosimendan and early RHF or death, albeit patients taking levosimendan had much higher risk profiles. For a definitive conclusion, a multicentre, randomized study is warranted.

Background Since the outbreak of COVID-19 in December 2019, there have been more than 115 million cases worldwide (1). Symptoms of COVID-19 vary widely and the spectrum of clinical presentation has yet to be fully characterised (2). Many countries have detailed their early experience with COVID-19, with a focus on the clinical characteristics of the disease. However, to our knowledge, there has been no such study detailing symptoms in the Irish population. Aim Our aim is to describe COVID-19 symptoms in the Irish population at the beginning of the COVID-19 pandemic and compare symptoms between those reporting positive and negative test results. Method A Web page MyCovidSymptoms.ie was created by researchers at the National University of Ireland, Galway, in April 2020 to investigate COVID-19 symptoms in Ireland. The Web page invited participants to self-report RT-PCR test outcome data (positive, negative, untested), temperature and a range of symptoms (cough, shortness of breath, fatigue, loss of taste, loss of smell). Results One hundred and twenty-three Irish participants who had a RT-PCR test for COVID-19 logged their symptoms. Eighty-four patients reported that they tested positive for COVID-19, and 39 patients reported a negative COVID-19 test. In our cohort of respondents with a positive COVID-19 test, 49/84 (58%) respondents reported a cough. Of the 39 respondents with a negative COVID-19 test, 17 (44%) reported having a cough. The distribution of temperature was similar in both those with and without COVID-19. Levels of self-reported fatigue were high in both groups with 65/84 (77%) of COVID-19-positive patients reporting fatigue and 30/39 (77%) of those who were COVID-19-negative reporting fatigue. New symptoms emerging at the time of data collection included loss of taste and smell. We demonstrated a higher proportion of loss of smell (p = 0.02) and taste (p = 0.01) in those reporting a positive result, compared to those reporting a negative result. Conclusion These data represents an early picture of the clinical characteristics of COVID-19 in an Irish population. It also highlights the potential use of self-reported data globally as a powerful tool in helping with the pandemic.

Background Digital Contact Tracing is seen as a key tool in reducing the propagation of Covid-19. But it requires high uptake and continued participation across the population to be effective. To achieve sufficient uptake/participation, health authorities should address, and thus be aware of, user concerns. Aim This work manually analyzes user reviews of the Irish Heath Service Executive’s (HSE) Contact Tracker app, to identify user concerns and to lay the foundations for subsequent, large-scale, automated analyses of reviews. While this might seem tightly scoped to the Irish context, the HSE app provides the basis for apps in many jurisdictions in the USA and Europe. Methods Manual analysis of (1287) user reviews from the Google/Apple playstores was performed, to identify the aspects of the app that users focused on, and the positive/negative sentiment expressed. Results The findings suggest a largely positive sentiment towards the app, and that users thought it handled data protection and transparency aspects well. But feedback suggests that users would appreciate more targeted feedback on the incidence of the virus, and facilities for more proactive engagement, like notifications that prompt users to submit their health status daily. Finally, the analysis suggests that the “android battery” issue and the backward-compatibility issue with iPhones seriously impacted retention/uptake of the app respectively. Conclusion The HSE have responded to the public’s desire for targeted feedback in newer versions, but should consider increasing the app’s proactive engagement. The results suggest they should also raise the backward compatibility issue, regarding older iPhones, with Apple.

Background Contact tracing remains a critical part of controlling COVID-19 spread. Many countries have developed novel software applications (Apps) in an effort to augment traditional contact tracing methods. Aim Conduct a national survey of the Irish population to examine barriers and levers to the use of a contact tracing App. Methods Adult participants were invited to respond via an online survey weblink sent via e-mail and messaging Apps and posted on our university website and on popular social media platforms, prior to launch of the national App solution. Results A total of 8088 responses were received, with all 26 counties of the Republic of Ireland represented. Fifty-four percent of respondents said they would definitely download a contact-tracing App, while 30% said they would probably download a contact tracing App. Ninety-five percent of respondents identified at least one reason for them to download such an App, with the most common reasons being the potential for the App to help family members and friends and a sense of responsibility to the wider community. Fifty-nine percent identified at least one reason not to download the App, with the most common reasons being fear that technology companies or the government might use the App technology for greater surveillance after the pandemic. Conclusion The Irish citizens surveyed expressed high levels of willingness to download a public health–backed App to augment contact tracing. Concerns raised regarding privacy and data security will be critical if the App is to achieve the large-scale adoption and ongoing use required for its effective operation.

ObjectiveTo determine the incidence, clinical correlates and exposure risk of medical encounters during community-based physical activity events in the UK.MethodsAn analysis of medical data from weekly, community-based physical activity events (parkrun) at 702 UK locations over a 6-year period (29 476 294 participations between 2014 and 2019) was conducted in order to define the incidence and clinical correlates of serious life-threatening, non-life-threatening and fatal medical encounters.Results84 serious life-threatening encounters (overall incidence rate=0.26/100 000 participations) occurred including 18 fatalities (0.056/100 000 participations). Statistical modelling revealed that the probabilities of serious life-threatening encounters were exceptionally low, however, male sex, increasing age, slower personal best parkrun time and less prior running engagement/experience (average number of runs per year and number of years as a parkrun participant) were associated with increased probability of serious life-threatening encounters. These were largely accounted for by cardiac arrest (48/84, 57%) and acute coronary syndromes (20/84, 24%). Non-life-threatening medical encounters were mainly attributed to tripping or falling, with a reported incidence of 39.2/100 000 participations.ConclusionsSerious life-threatening and fatal medical encounters associated with parkrun participation are extremely rare. In the context of a global public health crisis due to inactivity, this finding underscores the safety and corollary public health value of community running/walking events as a strategy to promote physical activity.

Background and Objectives: Thyroid nodules are lumps of solid or liquid-filled tumors that form inside the thyroid gland, which can be malignant or benign. Our aim was to test whether the described features of the Thyroid Imaging Reporting and Data System (TI-RADS) could improve radiologists’ decision making when integrated into a computer system. In this study, we developed a computer-aided diagnosis system integrated into multiple-instance learning (MIL) that would focus on benign–malignant classification. Data were available from the Universidad Nacional de Colombia. Materials and Methods: There were 99 cases (33 Benign and 66 malignant). In this study, the median filter and image binarization were used for image pre-processing and segmentation. The grey level co-occurrence matrix (GLCM) was used to extract seven ultrasound image features. These data were divided into 87% training and 13% validation sets. We compared the support vector machine (SVM) and artificial neural network (ANN) classification algorithms based on their accuracy score, sensitivity, and specificity. The outcome measure was whether the thyroid nodule was benign or malignant. We also developed a graphic user interface (GUI) to display the image features that would help radiologists with decision making. Results: ANN and SVM achieved an accuracy of 75% and 96% respectively. SVM outperformed all the other models on all performance metrics, achieving higher accuracy, sensitivity, and specificity score. Conclusions: Our study suggests promising results from MIL in thyroid cancer detection. Further testing with external data is required before our classification model can be employed in practice.

DNA methylation (DNAm) is known to play a pivotal role in childhood health and development, but a comprehensive characterization of genome-wide DNAm trajectories across this age period is currently lacking. We have therefore performed a series of epigenome-wide association studies in 5019 blood samples collected at multiple time-points from birth to late adolescence from 2348 participants of two large independent cohorts. DNAm profiles of autosomal CpG sites (CpGs) were generated using the Illumina Infinium HumanMethylation450 BeadChip. Change over time was widespread, observed at over one-half (53%) of CpGs. In most cases, DNAm was decreasing (36% of CpGs). Inter-individual variation in linear trajectories was similarly widespread (27% of CpGs). Evidence for non-linear change and inter-individual variation in non-linear trajectories was somewhat less common (11 and 8% of CpGs, respectively). Very little inter-individual variation in change was explained by sex differences (0.4% of CpGs) even though sex-specific DNAm was observed at 5% of CpGs. DNAm trajectories were distributed non-randomly across the genome. For example, CpGs with decreasing DNAm were enriched in gene bodies and enhancers and were annotated to genes enriched in immune-developmental functions. In contrast, CpGs with increasing DNAm were enriched in promoter regions and annotated to genes enriched in neurodevelopmental functions. These findings depict a methylome undergoing widespread and often non-linear change throughout childhood. They support a developmental role for DNA methylation that extends beyond birth into late adolescence and has implications for understanding life-long health and disease. DNAm trajectories can be visualized at http://epidelta.mrcieu.ac.uk.

ObjectivesThe menstrual cycle can affect sports participation and exercise performance. There are very few data on specific menstrual cycle symptoms (symptoms during various phases of the cycle, not only during menstruation) experienced by exercising women. We aimed to characterise the most common symptoms, as well as the number and frequency of symptoms, and evaluate whether menstrual cycle symptoms are associated with sporting outcomes.Methods6812 adult women of reproductive age (mean age: 38.3 (8.7) years) who were not using combined hormonal contraception were recruited via the Strava exercise app user database and completed a 39-part survey. Respondents were from seven geographical areas, and the questions were translated and localised to each region (Brazil, n=892; France, n=1355; Germany, n=839; Spain, n=834; UK and Ireland, n=1350; and USA, n=1542). The survey captured exercise behaviours, current menstrual status, presence and frequency of menstrual cycle symptoms, medication use for symptoms, perceived effects of the menstrual cycle on exercise and work behaviours, and history of hormonal contraception use. We propose a novel Menstrual Symptom index (MSi) based on the presence and frequency of 18 commonly reported symptoms (range 0–54, where 54 would correspond to all 18 symptoms each occurring very frequently).ResultsThe most prevalent menstrual cycle symptoms were mood changes/anxiety (90.6%), tiredness/fatigue (86.2%), stomach cramps (84.2%) and breast pain/tenderness (83.1%). After controlling for body mass index, training volume and age, the MSi was associated with a greater likelihood of missing or changing training (OR=1.09 (CI 1.08 to 1.10); p≤0.05), missing a sporting event/competition (OR=1.07 (CI 1.06 to 1.08); p≤0.05), absenteeism from work/academia (OR=1.08 (CI 1.07 to 1.09); p≤0.05) and use of pain medication (OR=1.09 (CI 1.08 to 1.09); p≤0.05).ConclusionMenstrual cycle symptoms are very common in exercising women, and women report that these symptoms compromise their exercise participation and work capacity. The MSi needs to be formally validated (psychometrics); at present, it provides an easy way to quantify the frequency of menstrual cycle symptoms.

Low energy availability (EA) is suspected to be the underlying cause of both the Female Athlete Triad and the more recently defined syndrome, Relative Energy Deficiency in Sport (RED-S). The International Olympic Committee (IOC) defined RED-S as a syndrome of health and performance impairments resulting from an energy deficit. While the importance of adequate EA is generally accepted, few studies have attempted to understand whether low EA is associated with the health and performance consequences posited by the IOC.ObjectiveThe purpose of this cross-sectional study was to examine the association of low EA with RED-S health and performance consequences in a large clinical population of female athletes.MethodsOne thousand female athletes (15–30 years) completed an online questionnaire and were classified as having low or adequate EA. The associations between low EA and the health and performance factors listed in the RED-S models were evaluated using chi-squared test and the odds ratios were evaluated using binomial logistic regression (pResultsAthletes with low EA were more likely to be classified as having increased risk of menstrual dysfunction, poor bone health, metabolic issues, haematological detriments, psychological disorders, cardiovascular impairment and gastrointestinal dysfunction than those with adequate EA. Performance variables associated with low EA included decreased training response, impaired judgement, decreased coordination, decreased concentration, irritability, depression and decreased endurance performance.ConclusionThese findings demonstrate that low EA measured using self-report questionnaires is strongly associated with many health and performance consequences proposed by the RED-S models.

Background: DNA methylation levels are known to vary over time, and modelling these trajectories is crucial for our understanding of the biological relevance of these changes over time. However, due to the computational cost of fitting multilevel models across the epigenome, most trajectory modelling efforts to date have focussed on a subset of CpG sites identified through epigenome-wide association studies (EWAS) at individual time-points. Methods: We propose using linear regression across the repeated measures, estimating cluster robust standard errors using a sandwich estimator, as a less computationally intensive strategy than multilevel modelling. We compared these two longitudinal approaches, as well as three approaches based on EWAS (associated at baseline, at any time-point, and at all time-points), for identifying epigenetic change over time related to an exposure using simulations and by applying them to blood DNA methylation profiles from the Accessible Resource for Integrated Epigenomics Studies (ARIES). Results: Restricting association testing to EWAS at baseline identified a less complete set of associations than performing EWAS at each time-point or applying the longitudinal modelling approaches to the full dataset. Linear regression models with cluster robust standard errors identified similar sets of associations with almost identical estimates of effect as the multilevel models, while also being 74 times more efficient. Both longitudinal modelling approaches identified comparable sets of CpG sites in ARIES with an association with prenatal exposure to smoking (>70% agreement). Conclusions: Linear regression with cluster robust standard errors is an appropriate and efficient approach for longitudinal analysis of DNA methylation data.

BackgroundAccurate grading at the time of diagnosis if fundamental to risk stratification and treatment decision making in patients with prostate cancer. Whilst previous studies have demonstrated significant pathological upgrading and downgrading following radical prostatectomy (RP), these were based on historical cohorts and do not reflect contemporary patient selection and management practices. The aim of this national, multicentre observational study was to characterise contemporary rates and risk factors for pathological upgrading after RP in the United Kingdom (UK).MethodsAll RP entries on the British Association of Urological Surgeons (BAUS) Radical Prostatectomy Registry database of prospectively entered cases undertaken between January 2011 and December 2016 were extracted. Those patients with full preoperative PSA, clinical stage, needle biopsy and subsequent RP pathological grade information were included. Upgrade was defined as any increase in Gleason grade from initial needle biopsy to pathological assessment of the entire surgical specimen. Statistical analysis and multivariate logistic regression were undertaken using R version 3.5 (R Foundation for Statistical Computing, Vienna, Austria).ResultsA total of 17,598 patients met full inclusion criteria. Absolute concordance between initial biopsy and pathological grade was 58.9% (n= 10,364), whilst upgrade and downgrade rates were 25.5% (n= 4489) and 15.6% (n= 2745) respectively. Upgrade rate was highest in those with D’Amico low risk compared with intermediate and high-risk disease (55.7% versus 19.1 and 24.3% respectively,P< 0.001). Although rates varied between year of surgery and geographical regions, these differences were not significant after adjusting for other preoperative diagnostic variables using multivariate logistic regression.ConclusionsPathological upgrading after RP in the UK is lower than expected when compared with other large contemporary series, despite operating on a generally higher risk patient cohort. As new diagnostic techniques that may reduce rates of pathological upgrading become more widely utilised, this study provides an important benchmark against which to measure future performance.

AimsTo evaluate temporal trends of acute coronary syndromes (ACS) treated via percutaneous coronary intervention (PCI) throughout the COVID-19 outbreak in a European healthcare system affected but not overwhelmed by COVID-19-related pathology.Methods and resultsWe performed a retrospective multicentre analysis of the rates of PCI for the treatment of ACS within the period 2 months pre and post the first confirmed COVID-19 case in Ireland, as well as comparing PCI for ST-elevation myocardial infarction (STEMI) with the corresponding period in 2019. During the 2020 COVID-19 period (29 February–30 April 2020), there was a 24% decline in PCI for overall ACS (incidence rate ratio (IRR) 0.76; 95% CI 0.65 to 0.88; pConclusionThis study demonstrates a significant reduction in PCI procedures for the treatment of ACS since the COVID-19 outbreak in Ireland. The reasons for this decline are still unclear but patients need to be encouraged to seek medical attention when cardiac symptoms appear, in order to avoid incremental cardiac morbidity and mortality due to a reduction in coronary revascularisation for the treatment of ACS.

ObjectivesOur aim was to investigate the association of epigenetic age and physical capability in later life. Having a higher epigenetic than chronological age (known as age acceleration (AA)) has been found to be associated with an increased rate of mortality. Similarly, physical capability has been proposed as a marker of ageing due to its consistent associations with mortality.SettingThe MRC National Survey of Health and Development (NSHD) cohort study.ParticipantsWe used data from 790 women from the NSHD who had DNA methylation data available.DesignEpigenetic age was calculated using buccal cell (n=790) and matched blood tissue (n=152) from 790 female NSHD participants. We investigated the association of AA at age 53 with changes in physical capability in women from ages 53 to 60–64. Regression models of change in each measure of physical capability on AA were conducted. Secondary analysis focused on the relationship between AA and smoking, alcohol, body mass index (BMI) and socioeconomic position.Outcome measuresThree objective measures of physical capability were used: grip strength, standing balance time and chair rise speed.ResultsEpigenetic age was lower than chronological age (mean 53.4) for both blood (50.3) and buccal cells (42.8). AA from blood was associated with a greater decrease in grip strength from ages 53 to 60–64 (0.42 kg decrease per year of AA, 95% CI 0.03, 0.82 kg; p=0.03, n=152), but no associations were observed with standing balance time or chair rise speed. Current smoking and lower BMI were associated with lower epigenetic age from buccal cells.ConclusionsWe found evidence that AA in blood is associated with a greater decrease in grip strength in British females aged between 53 and 60–64, but no association with standing balance time or chair rise speed was found.

Objectives Adult sagittal posture is established during childhood and adolescence. A flattened or hypercurved spine is associated with poorer musculoskeletal health in adulthood. Although anthropometry from birth onwards is expected to be a key influence on sagittal posture design, this has never been assessed during childhood. Our aim was to estimate the association between body size throughout childhood with sagittal postural patterns at age 7. Design Prospective cohort study. Setting and participants A subsample of 1029 girls and 1101 boys taking part in the 7-year-old follow-up of the birth cohort Generation XXI (Porto, Portugal) was included. We assessed the associations between anthropometric measurements (weight, height and body mass index) at birth, 4 and 7 years of age and postural patterns at age 7. Postural patterns were defined using latent profile analysis, a probabilistic model-based technique which allows for simultaneously including anthropometrics as predictors of latent profiles by means of logistic regression. Results Postural patterns identified were sway, flat and "neutral to hyperlordotic"in girls, and "sway to neutral", flat and hyperlordotic in boys; with flat and hyperlordotic postures representing a straightened and a rounded spine, respectively. In both girls and boys, higher weight was associated with lower odds of a flat pattern compared with a sway/"sway to neutral"pattern, with stronger associations at older ages: for example, ORs were 0.68 (95% CI 0.53 to 0.88) per SD increase in birth weight and 0.36 (95% CI 0.19 to 0.68) per SD increase in weight at age 7 in girls, with similar findings in boys. Boys with higher ponderal index at birth were more frequently assigned to the hyperlordotic pattern (OR=1.44 per SD;p=0.043). Conclusions Our findings support a prospective sculpting role of body size and therefore of load on musculoskeletal spinopelvic structures, with stronger associations as children get older. Generation XXI was funded by FEDER through the Operational Programme Competitiveness and Internationalization and by national funds through the FCT - Fundação para a Ciência e a Tecnologia via grants POCI-01-0145-FEDER-016838 and POCI-01-0145-FEDER-016837, under the projects PTDC/DTP-EPI/1687/2014 and PTDC/DTP-EPI/3306/2014. Support by Administração Regional de Saúde Norte (Ministry of Health), Fundação Calouste Gulbenkian and Unidade de Investigação em Epidemiologia - Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (POCI-01-0145-FEDER-006862; UID/DTP/04750/2013) is also acknowledged. Araújo FA and Lucas R were supported by grants SFRH/BD/85398/2012 and SFRH/ BPD/88729/2012, co-funded by FCT and the POPH/FSE.

Aims To look at the incidence of tip margin involvement in skin excisions for basal cell carcinomas (BCCs) and to examine if any factors might be used to predict margin involvement. Methods and results All reports of BCCs by a single dermatopathologist were reviewed and 793 excisions were included from 642 patients. Whether there was BCC in the tip and whether this tip was involved were recorded together with macroscopic and microscopic factors based on the Royal College of Pathologists’ (RCPath) dataset. Statistical analysis was carried out to determine associations between these factors and tip involvement. In 43 (5%) specimens the tip margin was involved and in 35 (4%) cases the peripheral lateral margin was involved. Risk factors for tip margin involvement were a lesion that was non-discernible macroscopically and most importantly, involvement of a peripheral lateral margin. Conclusions The incidence of tip margin involvement is small and it appears unnecessary to embed the tips unless the lesion is non-discernible macroscopically or if the peripheral lateral margin is involved.

The concept of applying constraints on individual sources to a small fraction of the public dose limit has been deemed inappropriate when shielding the medical X-ray sources. This represents a broad-based consensus of medical physics and radiological societies in the United States, and the report series on the shielding design for medical X-ray sources (including dental, X-ray imaging and therapeutic X ray) from the National Council on Radiation Protection and Measurements (NCRP) utilises 1 mSv y(-1) as a source control limit. In the present study, the rationale for such a conclusion is discussed, and a somewhat critical look at the current model of radiation protection of the public is made.

The shielding of positron emission tomography (PET) and PET/CT (computed tomography) facilities presents special challenges. The 0.511 MeV annihilation photons associated with positron decay are much higher energy than other diagnostic radiations. As a result, barrier shielding may be required in floors and ceilings as well as adjacent walls. Since the patient becomes the radioactive source after the radiopharmaceutical has been administered, one has to consider the entire time that the subject remains in the clinic. In this report we present methods for estimating the shielding requirements for PET and PET/CT facilities. Information about the physical properties of the most commonly used clinical PET radionuclides is summarized, although the report primarily refers to fluorine-18. Typical PET imaging protocols are reviewed and exposure rates from patients are estimated including self-attenuation by body tissues and physical decay of the radionuclide. Examples of barrier calculations are presented for controlled and noncontrolled areas. Shielding for adjacent rooms with scintillation cameras is also discussed. Tables and graphs of estimated transmission factors for lead, steel, and concrete at 0.511 MeV are also included. Meeting the regulatory limits for uncontrolled areas can be an expensive proposition. Careful planning with the equipment vendor, facility architect, and a qualified medical physicist is necessary to produce a cost effective design while maintaining radiation safety standards.

A survey of modern medical institutions has been performed to measure the workload and primary beam use factors used in diagnostic x-ray installations in comparison to those suggested in Report 49 of the NCRP. Seven types of radiology installations were investigated, namely general radiographic rooms, general fluoroscopic and radiographic rooms (fluoroscopic and radiographic tubes surveyed separately), chest radiographic rooms, mammographic suites, and cardiac and peripheral angiographic suites. The radiologic technique (kVp and mAs) for each exposure performed on a total of 2396 patients was recorded either manually or by a commercially-available invasive electronic sensing system. Additionally, the direction of the primary beam during the exposure was recorded. The kVp distribution of the workload data was determined and normalized per patient for each of the seven types of installations. The total average workload per patient surveyed in each type of installation is 2.5, 13, 1.5, 0.22, 6.7, 160, and 64 mA min per patient for the above installation types. For general radiographic rooms the primary beam was directed at the floor for 69% of the total workload, with the remaining 21.5%, 6.5% and 1.6% of the workload directed toward three walls. When multiplied by the average number of patients examined weekly in each type of installation, the mean weekly workloads observed are 270, 230, 35, 44, 320, 3100, and 1400 mA min for the above-listed types of installations. Additionally, a significant fraction of the observed workloads occur at potentials much less than the kVp values typically assumed for radiation shielding.

Background: Statistical models that use an individual’s DNA methylation levels to estimate their age (known as epigenetic clocks) have recently been developed, with 96% correlation found between epigenetic and chronological age. We postulate that differences between estimated and actual age [age acceleration (AA)] can be used as a measure of developmental age in early life. Methods: We obtained DNA methylation measures at three time points (birth, age 7 years and age 17 years) in 1018 children from the Avon Longitudinal Study of Parents and Children (ALSPAC). Using an online calculator, we estimated epigenetic age, and thus AA, for each child at each time point. We then investigated whether AA was prospectively associated with repeated measures of height, weight, body mass index (BMI), bone mineral density, bone mass, fat mass, lean mass and Tanner stage. Results: Positive AA at birth was associated with higher average fat mass [1321 g per year of AA, 95% confidence interval (CI) 386, 2256 g] from birth to adolescence (i.e. from age 0–17 years) and AA at age 7 was associated with higher average height (0.23 cm per year of AA, 95% CI 0.04, 0.41 cm). Conflicting evidence for the role of AA (at birth and in childhood) on changes during development was also found, with higher AA being positively associated with changes in weight, BMI and Tanner stage, but negatively with changes in height and fat mass. Conclusions: We found evidence that being ahead of one’s epigenetic age acceleration is related to developmental characteristics during childhood and adolescence. This demonstrates the potential for using AA as a measure of development in future research.

A Monte Carlo simulation was performed to characterize the spatial and energy distribution of bremsstrahlung radiation from β point sources important to radioimmunotherapy (RIT). Using the EGS4 Monte Carlo code, the isotropic emission and transport of monoenergetic 0.1‐, 0.5‐, 1.0‐, 2.0‐, and 3.0‐MeV electrons and 3 2P and 9 0Y β particles was simulated in an infinite, homogeneous H2O phantom. The probability of bremsstrahlung production for each Monte Carlo‐simulated electron step was accumulated in energy intervals not exceeding 5 keV and stored as a function of radial position. To validate this scheme, the EGS4 code was tested in the continuous slowing down approximation (csda) mode, with resulting radiation yields seen to agree with values in ICRU Report No. 37 (ICRU, Bethesda, MD, 1984) to better than 1.6%. The radiation yield calculated with the simulation of secondary particles is seen to be 3%–5% greater than the csda yield. The photon energy distributions are characterized by a typically broad bremsstrahlung spectrum with the probability of photon generation decreasing with radial distance. In the energy range 0.05–0.511 MeV, the probability for bremsstrahlung production from 9 0Y (2.76×10− 2 decay− 1) is twice that from 3 2P (1.35×10− 2 decay− 1). When passed through 10 cm of H2O and put upon a standard NaI scintillation camera, count rates of 2.3×10− 6 and 1.2×10− 6 counts s− 1 Bq− 1 are estimated from point sources of 9 0Y and 3 2P. These results predict the inherent spatial resolution limitation and provide the initial data required for modeling and analyzing the scatter, attenuation, and image formation processes in quantitative imaging of bremsstrahlung for RIT dosimetry.

The EGS4 Monte Carlo code has been used to simulate the emission and energy deposition in H2O about point sources of monoenergetic electrons and radionuclides of potential use in radioimmunotherapy. The radiations studied were 0.05, 0.1, 0.5, 1.0, 2.0, and 3.0 MeV monoenergetic electrons and 32P, 67Cu, 90Y, 105Rh, 131I, 153Sm, 186Re, and 188Re beta particles and conversion and Auger electrons. Ten batches of 10,000 electrons (or 10,000 radionuclide decays) each were started isotropically at a point in an infinite homogeneous H2O phantom. The parameter-reduced electron-step transport algorithm (PRESTA) version of the EGS4 Monte Carlo code was used to follow these and their progeny, scoring the energy deposited in thin spherical shells. The scaled dose kernels are calculated and compared to kernels available in the literature. These previously published kernels either completely ignore secondary electrons or are based on a Monte Carlo code which improperly sampled the Landau energy straggling distribution.

Equations are derived and the results of numerical calculations shown that illustrate the effect of counting system deadtime on measured thyroid uptake of radioiodine. It is predicted that the observed uptake is higher than the true uptake due to system deadtime. This is shown for both paralyzing and nonparalyzing deadtime. The effect of increasing the administered activity is shown to increase the measured uptake, in a manner predicted by the paralyzable and nonparalyzable deadtime models.

Diels–Alder addition of olefins to trichloro- and trifluoro-1,2,4-triazines gives, via loss of nitrogen, intermediate dihydropyridines, which undergo a variety of further pericyclic reactions.

The use of orthochromatic x‐ray film in a Wisconsin kVp Test Cassette calibrated with RP film has been evaluated. It is found that orthochromatic film usage in the test cassette will lead to overestimates of the x‐ray tube peak potential for 3φ and 1φ radiographic beams and 3φ mammographic beams. The magnitude of this error ranges from 0.5 to 3.5 kVp, depending on the cassette type, cassette region, and x‐ray tube potential waveform.

Aims There is increasing evidence of Gleason score (GS) drift in prostatic core biopsies during the last two decades. The ProtecT study is a randomized controlled study and provides an excellent cohort to study the effect of time, prostate-specific antigen (PSA) level, perineural invasion, tumour length and age on GS. Methods and results The ProtecT study recruited men in the United Kingdom between 1999 and 2010. The Gleason scores were grouped into four categories ≤3 + 3, 3 + 4, 4 + 3 and ≥4 + 4 for analysis. Data from England between 2000 and 2012 were also available. A total of 3282 biopsies containing cancer were analysed. For each year of the ProtecT study, the odds of being diagnosed with a higher GS category increased by 4.9%. Higher GS was also associated with perineural invasion, increasing tumour length, age and PSA level. While biopsy GS from England was incomplete, it also showed a marked decrease in GS five and six tumours during the same period. Conclusion There was GS drift from 3 + 3 to 3 + 4 with time in the ProtecT study, but there appeared to be no significant change in percentage of GS 4 + 3 or higher. This drift was less dramatic when compared to GS in the rest of England.