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Background Patients with congenitally corrected transposition of the great arteries (ccTGA) with intact ventricular septum (IVS) or d-looped transposition of the great arteries (DTGA) with IVS post atrial switch operation often develop left ventricular dysfunction after anatomical repair despite prior retraining of the morphologically left ventricle (mLV) using pulmonary artery banding (PAB). We examined histopathological changes in such mLV. Methods Capillary density, myocyte diameter, and interstitial fibrous area in the mLV were retrospectively evaluated in postmortem or explanted heart specimens obtained from patients with ccTGA/IVS or DTGA/IVS post atrial switch operation after PAB for retraining and compared with those of patients with normal cardiac anatomy, ccTGA/IVS or DTGA/IVS without PAB, and ccTGA or DTGA with high mLV pressure using generalized estimating equations models. Results Adjusting for age, capillary density in four patients with ccTGA/IVS or DTGA/IVS after PAB was ∼20% lower than that in eight patients with normal cardiac anatomy (3149 ± 863 / um2 vs 3978 ± 1206 /um2 (mean, SD); p = 0.039), while myocyte diameter was ∼50% larger (16.2 ± 4.0 um vs 11.7 ± 2.4 um (mean, SD); p Conclusions We observed significant cardiomyocyte hypertrophy but lower capillary density in patients with ccTGA/IVS or DTGA/IVS after PAB for retraining compared to normal controls. This suggests inadequate capillary growth is a potential pathological basis for mLV dysfunction occurring after retraining or anatomical repair.

Introduction Previous research has shown that patients from historically marginalized groups in the United States tend to have poorer outcomes after joint replacement surgery and that they are less likely to receive joint replacement surgery at high-volume hospitals. However, little is known regarding how this group of patients chooses their joint replacement surgeon. The purpose of this study was to understand the factors influencing the choice of joint replacement surgeon amongst a diverse group of patients. Methods Semi-structured interviews were conducted with Medicare patients who underwent a hip or knee replacement within the last 24 months (N = 38) at an academic and community hospital. Interviews were audio recorded, transcribed and verified for accuracy. Transcripts were reviewed using iterative content analysis to extract key themes related to how respondents chose their joint replacement surgeon. Results and discussion MD referral/recommendation appears to be the strongest factor influencing joint replacement surgeon choice. Other key considerations are hospital reputation and surgeon attributes—including operative experience, communication skills, and participation in shared decision-making. Gender/ethnicity of a surgeon, industry payments to surgeons, number of publications and cost did not play a large role in surgeon choice. Conclusion and clinical relevance The process of choosing a joint replacement surgeon is a complex decision-making process with several factors at play. Despite growing availability of information regarding surgeons, patients largely relied on referrals for choosing their joint replacement surgeon regardless of ethnicity. Referring physicians need to ensure that patients are able to access hospital and surgeon outcomes, operative volume, and industry-payment information to learn more about their orthopedic surgeons in order to make an informed choice.

Fluoride exposure is associated with later pubertal development and decreased testosterone production in adolescent and adult males. However, its effects on female reproductive health and pubertal development are unclear. Therefore, we examined associations of fluoride exposure with reproductive health outcomes among adolescent girls and women in the United States. Participants were from The National Health and Nutrition Examination Surveys (2013 to 2016), aged 16–19 and identified as female. There were 524 and 460 participants with measures of plasma fluoride and household tap water fluoride respectively, who had at least one reproductive health outcome examined, and complete covariate data. We applied covariate adjusted survey-weighted linear or logistic regression to examine associations of fluoride exposure with age of menarche, menstrual cycle regularity, or serum sex steroid hormone levels. Median interquartile range (IQR) water and plasma fluoride concentrations were 0.48 (0.53) mg/L and 0.34 (0.30) µmol/L respectively. An IQR increase in water fluoride was associated with a 3.3 month earlier first menstrual period (B = − 0.28, 95%CI − 0.54, − 0.02, p = 0.05). Additionally, we observed a significant interaction between plasma fluoride and race/ethnicity in association with age of menarche (p = 0.01). Among Non-Hispanic Black adolescents, each IQR increase in plasma fluoride was associated with a 5-month earlier age of menarche (B = − 0.42, 95%CI − 0.61, − 0.23, p

Substantial progress has been made in the standardization of nomenclature for paediatric and congenital cardiac care. In 1936, Maude Abbott published her Atlas of Congenital Cardiac Disease, which was the first formal attempt to classify congenital heart disease. The International Paediatric and Congenital Cardiac Code (IPCCC) is now utilized worldwide and has most recently become the paediatric and congenital cardiac component of the Eleventh Revision of the International Classification of Diseases (ICD-11). The most recent publication of the IPCCC was in 2017. This manuscript provides an updated 2021 version of the IPCCC.The International Society for Nomenclature of Paediatric and Congenital Heart Disease (ISNPCHD), in collaboration with the World Health Organization (WHO), developed the paediatric and congenital cardiac nomenclature that is now within the eleventh version of the International Classification of Diseases (ICD-11). This unification of IPCCC and ICD-11 is the IPCCC ICD-11 Nomenclature and is the first time that the clinical nomenclature for paediatric and congenital cardiac care and the administrative nomenclature for paediatric and congenital cardiac care are harmonized. The resultant congenital cardiac component of ICD-11 was increased from 29 congenital cardiac codes in ICD-9 and 73 congenital cardiac codes in ICD-10 to 318 codes submitted by ISNPCHD through 2018 for incorporation into ICD-11. After these 318 terms were incorporated into ICD-11 in 2018, the WHO ICD-11 team added an additional 49 terms, some of which are acceptable legacy terms from ICD-10, while others provide greater granularity than the ISNPCHD thought was originally acceptable. Thus, the total number of paediatric and congenital cardiac terms in ICD-11 is 367. In this manuscript, we describe and review the terminology, hierarchy, and definitions of the IPCCC ICD-11 Nomenclature. This article, therefore, presents a global system of nomenclature for paediatric and congenital cardiac care that unifies clinical and administrative nomenclature.The members of ISNPCHD realize that the nomenclature published in this manuscript will continue to evolve. The version of the IPCCC that was published in 2017 has evolved and changed, and it is now replaced by this 2021 version. In the future, ISNPCHD will again publish updated versions of IPCCC, as IPCCC continues to evolve.

Bei On-Machine Measurements werden Bauteile direkt mit dem Messtastersystem der Maschine gemessen. So wird im Vergleich zur Messung per KMG (Koordinatenmessgeräte) der Aufwand zur dimensionellen Bauteilprüfung und einer anschließenden Korrektur fehlerhafter Bauteile erheblich reduziert. Es wird eine Dateninfrastruktur vorgestellt, welche die aus der Maschine stammenden Daten annotiert speichert. Mithilfe der gesammelten Daten kann die Maßhaltigkeit des Bauteils automatisch erkannt werden.**

Purpose: Report relevance of molecular groups to clinicopathologic features, germline SMARCB1/SMARCA4 alterations (GLA), and survival of children with atypical teratoid rhabdoid tumor (ATRT) treated in two multi-institutional clinical trials. Materials and Methods: Seventy-four participants with newly diagnosed ATRT were treated in two trials: infants (SJYC07: age < 3 years; n = 52) and children (SJMB03: age 3–21 years; n = 22), using surgery, conventional chemotherapy (infants), or dose-dense chemotherapy with autologous stem cell rescue (children), and age- and risk-adapted radiotherapy [focal (infants) and craniospinal (CSI; children)]. Molecular groups ATRT-MYC (MYC), ATRT-SHH (SHH), and ATRT-TYR (TYR) were determined from tumor DNA methylation profiles. Results: Twenty-four participants (32%) were alive at time of analysis at a median follow-up of 8.4 years (range, 3.1–14.1 years). Methylation profiling classified 64 ATRTs as TYR (n = 21), SHH (n = 30), and MYC (n = 13), SHH group being associated with metastatic disease. Among infants, TYR group had the best overall survival (OS; P = 0.02). However, outcomes did not differ by molecular groups among infants with nonmetastatic (M0) disease. Children with M0 disease and Conclusions: Among infants, those with ATRT-TYR had the best OS. ATRT-SHH was associated with metastases and consequently with inferior outcomes. Children with nonmetastatic ATRT benefit from postoperative CSI and adjuvant chemotherapy.

Summary Background Pregnancy is associated with deteriorations in maternal bone strength and heightened susceptibility to bone fractures. We aimed to investigate whether ambient particulate matter (PM)2·5 concentrations were associated with bone strength during pregnancy. Methods In this longitudinal cohort study, we analysed longitudinal data from women participating in the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) cohort in Mexico City, Mexico. Eligible women were aged 18 years or older, at less than 20 weeks' gestation at the time of recruitment, planning to stay in Mexico City for the next 3 years, without heart or kidney disease, did not use steroids or anti-epileptic drugs, were not daily consumers of alcohol, and had access to a telephone. Daily ambient PM2·5 concentrations were estimated from a spatio-temporal model that was based on the individual's address. Trabecular bone strength was measured using quantitative ultrasound from the radius of the middle finger and cortical bone strength from the proximal phalanx of the middle finger, during the second trimester, third trimester, and 1 and 6 months post partum. Bone strength T scores were modelled with PM2·5 concentrations using linear mixed models and distributed lag models. Findings Adjusting for multiple exposure windows, each 10 ug/m3 increase in PM2·5 exposure concentrations in the first trimester was associated with a 0·18 SD decrease (95% CI −0·35 to −0·01; p=0·033) in ultrasound speed-of-sound (SOS) T score of trabecular bone strength from the second trimester until 6 months post partum. Similarly, each 10 μg/m3 increase in third trimester PM2·5 exposure was associated with a 0·18 SD decrease (–0·36 to −0·01; p=0·044) in the SOS T score of trabecular bone strength from the third trimester until 6 months post partum. PM2·5 exposure in the first month post partum was associated with a 0·20 SD decline (–0·39 to −0·01; p=0·043) in cortical bone strength until 6 months post partum. Interpretation Ambient PM2·5 exposure during and after pregnancy was associated with diminished trabecular and cortical bone strength. Early pregnancy PM2·5 exposure was associated with a greater decline in bone strength later during pregnancy. Late pregnancy and early post-partum exposures adversely affected the post-partum bone strength recovery. Technological and policy solutions to reduce PM2·5 pollution could improve public health by reducing bone fracture risk. Funding US National Institute of Environmental Health Sciences.

Bicuspid aortic valve (BAV) is one of the most common congenital heart defects in children, adolescents and adults. BAV can occur as an isolated lesion or in association with other congenital heart defects, such as coarctation of the aorta or genetic syndromes like Turner syndrome. Although the majority of long term complications associated with BAV manifest later in life, children and adolescents may present with early onset valvular dysfunction or dilation of the aorta. BAV is a heterogeneous disease with a wide array of presentations at various ages, depending on the degree of aortic valve dysfunction, aortic dilation and presence of associated lesions. Aortic valve stenosis and/or regurgitation are the primary indications for intervention in children and adolescents with BAV. Although a majority of young patients with BAV also have some aortic dilation, interventions on the aorta are very rare during this time frame. Children and adolescents with BAV benefit from comprehensive assessment of their risk profile to determine follow-up surveillance intervals, sports recommendations, and timing of surgical intervention. The morphologic phenotype of BAV is important to identify, as it may predict future complications and prognosis.

Uncontrolled environmental conditions often impact manufacturing processes and lead to product quality fluctuations. For machine tools, thermal influences are a major limitation to the volumetric performance. Climate controls for the shop floor, and machines, or thermally stable structural designs are economically not feasible, promoting control-based compensation as a possible solution. Since the relationship between disturbing quantities and effects are complex and specific to each machine, appropriate modelling is a critical requirement. The authors describe an approach for developing hybrid models, superposing white-box model knowledge, and machine learning. The overall effort can be optimized by combining and balancing different modelling methods, like designing the physical model part and training intelligent algorithms. A general model structure allows a continuous integration of different white-box and black-box model components. The authors integrate self-developed smart sensors into a demonstrator machine tool to test and validate the performance of the approach.

There is a critical need for sensitive biomarkers of renal disease and progression. Micro(mi)RNAs are attractive as next-generation biomarkers in kidney disease, particularly as urine miRNAs can inform kidney function and cellular integrity. This review summarizes recent epidemiologic and toxicologic advances using urinary miRNAs and exosomal miRNAs as novel biomarkers of chemical exposure and of kidney damage and disease. Urine miRNA biomarkers offer improved stability over protein in stored samples, relative ease of collection and quantitation, and conserved sequence homology across species. Particularly in the case of emergent environmental health threats such as chronic kidney disease of unknown origin, urinary miRNAs hold promise as biomarkers of disease and/or exposure. We present evidence to address scientific knowledge gaps, comment on the relevance of urine-derived miRNAs in environmental health research, and discuss limitations and recommendations for future directions needed to advance miRNA biomarker strategies.

Background: Exposure to lead (Pb) during the early life stages has been associated with the development of metabolic syndrome (MetS). Longitudinal studies of Pb exposure in critical developmental windows in children are limited.Methods: Our study included 601 mother–child dyads from the PROGRESS (Programming Research in Obesity, Growth, Environment and Social Stressors) birth cohort. Blood lead levels (BLLs) were assessed during the second and third gestational trimesters, in cord blood at delivery, and at ages 1, 2, and 4 years. Bone lead levels in the patella and tibia were assessed at 1 month postpartum and evaluated in separate models. To account for cumulative exposure (prenatal, postnatal, and cumulative), we dichotomized the BLLs at each stage visit and determined the following: “higher” if a BLL was at least once above the median (HPb) and “lower” if all BLLs were below the median (LPb). We analyzed fasting glucose, HbA1c, triglycerides (TGs), total cholesterol (TC), high-density lipoprotein cholesterol (cHDL), low-density lipoprotein cholesterol (cLDL), body mass index, waist circumference (WC), body fat percentage, and systolic (SBP) and diastolic blood pressure (DBP) at two study visits between 6 and 12 years of age and created cutoff points based on the clinical guidelines for each indicator. Mixed effects models were used to analyze each outcome longitudinally for each BLL score, adjusting for child's sex, size for gestational age, child's age, maternal parity, mother's age, and socioeconomic status.Results: We observed associations for HPb exposure and TC in all stages (OR = 0.53, 95%CI = 0.32–0.86) and postnatally (OR = 0.59, 95%CI = 0.36–0.94) and for prenatal HPb and TGs (OR = 0.65, 95%CI = 0.44–0.95). HPb at all stages was associated with WC (OR = 0.27, 95%CI = 0.08–0.86), BMI (OR = 0.33, 95%CI = 0.11–0.99), SBP (OR = 0.53, 95%CI = 0.32–0.85), and DBP (OR = 0.57, 95%CI = 0.34–0.95). Pb levels in the patella were associated with cHDL (OR = 1.03, 95%CI = 1.00–1.07) and those in the tibia with TGs (OR = 0.95, 95%CI = 0.91–0.99).Conclusion: Early life exposure to Pb may alter early indicators of MetS. A follow-up of these children will allow for more definition on the impact of longer-term exposures.

Background For the developing kidney, the prenatal period may represent a critical window of vulnerability to environmental insults resulting in permanent nephron loss. Given that the majority of nephron formation is complete in the 3rd trimester, we set out to test whether 1) prenatal lead exposure is associated with decreased preadolescent kidney function and 2) whether preadolescent obesity acts synergistically with early life lead exposure to reduce kidney function. Methods Our study included 453 mother–child pairs participating in the PROGRESS birth cohort. We assessed prenatal blood lead levels (BLLs) in samples collected in the 2nd and 3rd trimesters and at delivery, as well as tibial and patellar bone lead measures assessed one-month postpartum. Preadolescent estimated glomerular filtration rate (eGFR) was derived from serum levels of creatinine and/or cystatin C measured at age 8–12 years. We applied linear regression to assess the relationship between prenatal bone and BLL with preadolescent eGFR, and adjusted for covariates including age, sex, BMI z-score, indoor tobacco smoke exposure, and socioeconomic status. We also examined sex-specific associations and tested for effect modification by BMI status. Results We observed null associations between prenatal lead exposure and eGFR. However, in interaction analyses we found that among overweight children, there was an inverse association between BLL (assessed at 2nd and 3rd trimester and at delivery) and preadolescent eGFR. For example, among overweight participants, a one ln-unit increase in 2nd trimester BLL was associated with a 10.5 unit decrease in cystatin C-based eGFR (95% CI: −18.1, −2.8; p = 0.008). Regardless of lead exposure, we also observed null relationships between BMI z-score and eGFR overall, as well as among overweight participants. However, among participants with preadolescent obesity, we observed a significant 5.9-unit decrease in eGFR. We observed no evidence of sex-specific effects. Conclusions Our findings, if confirmed in other studies, suggest a complex interplay between the combined adverse effects of adiposity and perinatal lead exposure as they relate to adolescent kidney function. Future studies will assess kidney function and adiposity trajectories through adolescence to better understand environmental risk factors for kidney function decline.

Deficiency or excess exposure to manganese (Mn), an essential mineral, may have potentially adverse health effects. The kidneys are a major organ of Mn site-specific toxicity because of their unique role in filtration, metabolism, and excretion of xenobiotics. We hypothesized that Mn concentrations were associated with poorer blood pressure (BP) and kidney parameters such as estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), and albumin creatinine ratio (ACR). We conducted a cross-sectional analysis of 1931 healthy U.S. adolescents aged 12–19 years participating in National Health and Nutrition Examination Survey cycles 2013–2014, 2015–2016, and 2017–2018. Blood and urine Mn concentrations were measured using inductively coupled plasma mass spectrometry. Systolic and diastolic BP were calculated as the average of available readings. eGFR was calculated from serum creatinine using the Bedside Schwartz equation. We performed multiple linear regression, adjusting for age, sex, body mass index, race/ethnicity, and poverty income ratio. We observed null relationships between blood Mn concentrations with eGFR, ACR, BUN, and BP. In a subset of 691 participants, we observed that a 10-fold increase in urine Mn was associated with a 16.4 mL/min higher eGFR (95% Confidence Interval: 11.1, 21.7). These exploratory findings should be interpreted cautiously and warrant investigation in longitudinal studies.

BACKGROUND AND AIM: Air pollution exposure, especially particulate matter ≤ 2.5 μm in diameter (PM2.5), is associated with poorer kidney function in adults and children. Perinatal exposure may occu...

Exposure to metals including lead (Pb), cadmium (Cd), and arsenic (As), may impair kidney function as individual toxicants or in mixtures. However, no single medium is ideal to study multiple metals simultaneously. We hypothesized that multi-media biomarkers (MMBs), integrated indices combining information across biomarkers, are informative of adverse kidney function. Levels of Pb, Cd, and As were quantified in blood and urine in 4–6-year-old Mexican children (n = 300) in the PROGRESS longitudinal cohort study. We estimated the mixture effects of these metals, using weighted quantile sum regression (WQS) applied to urine biomarkers (Umix), blood biomarkers (Bmix), and MMBs, on the cystatin C-based estimated glomerular filtration rate (eGFR) and serum cystatin C assessed at 8–10 years of age, adjusted for covariates. Quartile increases in Umix and the MMB mixture were associated with 2.5% (95%CI: 0.1, 5.0) and 3.0% (95%CI: 0.2, 5.7) increased eGFR and −2.6% (95% CI: −5.1%, −0.1%) and −3.3% (95% CI: −6.5%, −0.1%) decreased cystatin C, respectively. Weights indicate that the strongest contributors to the associations with eGFR and serum cystatin C were Cd and Pb, respectively. MMBs detected mixture effects distinct from associations with individual metals or media-type, highlighting the benefits of incorporating information from multiple exposure media in mixtures analyses.

Dehnmessstreifen werden meist eingesetzt, um kurzfristige kraft- und momentenabhängige Dehnungen zu messen. Die thermische Dehnung des Bauteils lässt sich dabei typischerweise nicht zuverlässig messen, da sich der Dehnmessstreifen unter Temperatur ebenfalls verformt. Der hier beschriebene Smart Sensor soll für absolute Verformungsmessung jedoch entsprechend die absolute Dehnung messen, das heißt sowohl mechanische als auch thermische Dehnung. Dieser Beitrag beschreibt den Aufbau und die Validierung eines kostengünstig herstellbaren Bluetooth-Dehnungssensors, bei dem als temperaturinvariante Referenz ein Bauteil aus kohlefaserverstärktem Kunststoff genutzt wird. Strain gauges are mostly used to measure short-term force and torque-dependent strain. Thereby the thermal strain of the component is mostly a disturbing effect. The following Smart Sensor is explicitly intended to measure the absolute strain for absolute deformation measurements. The article describes the design and validation of a bluetooth strain sensor that can be manufactured at low cost using a carbon fiber reinforced plastic component as a temperature-invariant reference.

Marine microplastic (plastic particles smaller than 5 mm in length) pollution is a recognized and growing threat to the environment. Microplastic particle estimates number in the trillions and are under sampled in ecosystems worldwide (Eriksen et al. 2014, Zhao et al. 2019). Sources of microplastics include manufactured particles (fibers, beads, industrial abrasives) or microplastics generated from breakdown of larger plastics through mechanical, photochemical, or biologically mediated degradation (Schwarz et al. 2019). Little is known about the fate or effect of microplastics on marine environments thus emphasizing the importance of scientific research. The University of Georgia Skidaway Institute of Oceanography (UGA SkIO) and Marine Extension and Georgia Sea Grant (UGA MAREX) are mapping the distribution and abundance of microplastics in Georgia’s coastal waters. There are many challenges to studying microplastic abundances, including intensive sampling and measurement efforts on a temporal and spatial scale that require trained personnel. Volunteer-based research is well suited for studying microplastic pollution. We have developed a successful volunteer-based monitoring program to assist with research efforts. We have established partnerships with environmental programs and groups including the UGA MAREX volunteer program, and the Satilla, Altamaha and Ogeechee Riverkeepers to assist with monitoring efforts. Everyone involved understands the critical importance of proper research technique, strict protocols and training in order to obtain “believable” data. Our research to date suggests that a dedicated, trained group of scientists and volunteers can provide the mechanism for conducting detailed studies of microplastics on a local to regional scale.

BACKGROUND: Arrhythmogenic cardiomyopathy (ACM) is a variably penetrant disease increasingly identified in young patients. OBJECTIVES: This study sought to describe the diverse phenotype, genotype, and outcomes in pediatric and adolescent patients. METHODS: Records from 1999 to 2016 were reviewed for individuals age

Objectives To report our experience with fetal diagnosis of right aortic arch (RAA) variants based on the ductus arteriosus (DA) anatomy and brachiocephalic vessel branching pattern in relation to the trachea, and to establish whether the echocardiographic 'V-shaped' or 'U-shaped' appearance of the junction between the DA and aortic arch (AA) in the fetal upper mediastinal view is sufficiently accurate for assessment of fetal AA anatomy. Methods This was a retrospective study of pregnancies with a prenatal diagnosis of fetal RAA that had postnatal confirmation of AA anatomy, referred to our tertiary center during 2011-2017. Prenatal and postnatal medical records, including echocardiographic and computed tomography (CT)/magnetic resonance imaging (MRI) scan reports, were reviewed, and cardiac and extracardiac abnormalities and the results of genetic testing were recorded. Results Of 55 consecutive pregnancies with a prenatal diagnosis of fetal RAA, six were lost to follow-up, one was terminated and three were excluded due to lack of postnatal confirmation of AA anatomy. Of the remaining 45 pregnancies, AA anatomy was assessed postnatally by CT in 39, by MRI in one and by direct examination at cardiac surgery in five. A U-shaped appearance was found in 37/45 (82.2%) patients, all of which had a complete vascular ring (CVR). Of these 37 patients, on postnatal confirmation, 21 (56.8%) had RAA with Kommerell's diverticulum, left posterior ductus arteriosus (LPDA) and aberrant left subclavian artery (ALSA) (RAA/LPDA/ALSA), 11 (29.7%) had a double AA (DAA), four (10.8%) had RAA with Kommerell's diverticulum, LPDA and mirror-image (MI) branching (RAA/LPDA/MI), and one (2.7%) had RAA with Kommerell's diverticulum, LPDA and aberrant left innominate artery (ALIA) (RAA/LPDA/ALIA). A V-shaped appearance was found in 3/45 (6.7%) patients, all of which had RAA with right DA not forming a CVR and MI branching. In the 5/45 (11.1%) fetuses with neither U- nor V-shaped appearance, RAA with left anterior DA arising from the left innominate artery and MI branching, not forming a CVR, was found. Twelve (26.7%) fetuses had a congenital heart defect (CHD). RAA forming a CVR (U-shaped appearance) was associated with a septal defect in 6/37 (16.2%) fetuses, while RAA not forming a CVR (V-shaped appearance or no U- or V-shaped appearance) was associated with major CHD in 6/8 (75.0%) fetuses. Conclusions In fetuses with RAA, V-shaped appearance of the junction between the DA and AA indicates only that the transverse AA and DA run together on the same side of the thorax (trachea) while a U-shaped appearance is always a sign of a CVR. Among fetuses with a CVR, RAA/LPDA/MI is more frequent than described previously. Finally, RAA forming a CVR is not usually associated with complex CHD, as opposed to RAA not forming a CVR. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Objective: To determine whether prenatal sex hormones from maternal saliva are associated with birth weight-for-gestational age. Study Design: We measured salivary progesterone, testosterone, estradiol, dehydroepiandrosterone (DHEA) and cortisone in 504 pregnant women in a Mexico City cohort in the. We performed linear and modified Poisson regression to examine associations of log-transformed hormones with birth weight-for-gestational age z-scores and the risk of small-for-gestational age (SGA) and large-for-gestational age (LGA) adjusting for maternal age, sex, BMI, parity, smoking, education and socioeconomic status. Results: 15% of infants were SGA and 2% were LGA. Each interquartile range increment in testosterone/estradiol ratio was associated with a 0.12 decrement in birth weight-for-gestational age z-score (95% CI: −0.27, −0.02) and a 50% higher risk of SGA versus appropriate-for-gestational age (AGA) (95% CI: 1.13, 1.99). Conclusion: Higher salivary testosterone/estradiol ratios may affect fetal growth, and identifying the predictors of hormone levels may be important to optimizing fetal growth.

Objectives This study sought to evaluate for the presence of and characterize the interdigitating and entrapped myocardium within cardiac fibromas (CF) and correlate tissue findings with symptoms and surgical outcomes. Background The mechanism of ventricular tachycardia (VT) in CF is unclear. The authors hypothesized that CF harbor tongues of interdigitating myocardium, which could be a substrate for episodes of arrhythmia analogous to peri-infarct zones. Methods A total of 29 patients (14 boys) with CF were identified; all subjects had undergone at least partial tumor resection. A semiquantitative grading system was used to assess the degree of myocardial interdigitation and entrapment, myocyte morphology (hematoxylin and eosin stain and immunohistochemical stain for desmin), tumor collagen density, and cellularity (trichrome stain). The subjects’ ages at presentation, types of arrhythmia, and responses to surgery were correlated with histology. Results CF consistently demonstrated interdigitating and entrapped myocardium, and the extent correlated negatively with age at surgery, as did cellularity, whereas collagen increased with age. Median age at arrhythmia recognition was 8 months. Sustained VT was present in 18 of 29 patients (62%), and 5 of 6 patients with prenatally diagnosed conditions developed VT before 8 months. All 8 patients who experienced cardiac arrest had clinically significant arrhythmia events. Sustained arrhythmia episodes correlated with more diffuse myocyte interdigitation. Ten patients had abnormal karyotype: chromosomes 9 (n = 3) and 3 (n = 1) deletions; isolated translocations: t(4;13), t(5;11) and t(1;9); and undefined aberrations (n = 3). All patients who underwent complete resection were cured of arrhythmias, whereas 2 of 14 patients who had subtotal resections had recurrence, with resolution following re-resection in 1 patient. Conclusions Interdigitating myocardium represents a potential histopathologic substrate for VT and cardiac arrest in CF, which may also explain the occasional recurrence of arrhythmia following incomplete resection.

RESUME Objectif Aider les medecins qui pratiquent la chirurgie gynecologique dans leur processus decisionnel relatif aux indications benignes de l'hysterectomie. Public cible Medecins, y compris gynecologues, obstetriciens, medecins de famille, chirurgiens generalistes, urgentologues; infirmieres, y compris les infirmieres autorisees et les infirmieres praticiennes; apprentis en medecine, y compris etudiants de medecine, residents, stagiaires (fellows); et autres fournisseurs de soins de sante. Population cible Femmes adultes (18 ans et plus) qui devront subir une hysterectomie pour une indication gynecologie benigne. Options La presente directive clinique examine les differentes voies d'abord de l'hysterectomie et l'utilite des interventions chirurgicales concomitantes. Donnees probantes Pour la presente directive clinique, des recherches ont ete effectuees dans les bases de donnees PubMed, Medline et Cochrane Library pour trouver des etudes pertinentes. Les recherches ont ete effectuees parmi les publications des cinq dernieres annees (2012-2017) au moyen des termes de recherche MeSH suivants ainsi que leurs variations : vaginal hysterectomy, laparoscopic hysterectomy, robotic hysterectomy, laparoscopically assisted vaginal hysterectomy, total laparoscopic hysterectomy, standard vaginal hysterectomy et total vaginal hysterectomy. Methodes de validation Le contenu et les recommandations ont ete rediges et acceptes par les auteurs principaux et membres du comite de pratique clinique – gynecologie. Le conseil d'administration de la Societe des obstetriciens et gynecologues du Canada a approuve la version definitive aux fins de publication. La qualite des donnees probantes utilisees dans le present document a ete evaluee au moyen des criteres du cadre methodologique GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) (tableau 1, tableau 2). Le resume des conclusions est disponible sur demande. Avantages, prejudices et couts Bien que l'hysterectomie soit commune, la pratique chirurgicale varie grandement chez les medecins specialises en gynecologie. La presente directive expose les facteurs pre- et perioperatoires a prendre en compte pour ameliorer la qualite des soins prodigues aux femmes qui doivent subir une chirurgie pour une affection gynecologique benigne. Mise a jour de la directive clinique La presente directive clinique de la Societe des obstetriciens et gynecologues du Canada sera automatiquement passee en revue cinq ans apres sa publication. Les auteurs peuvent toutefois proposer une autre date de reevaluation s'ils croient qu'une periode de cinq ans est trop courte ou trop longue en fonction de leurs connaissances du sujet a titre d'experts en la matiere. Promoteurs La presente directive clinique a ete elaboree au moyen de ressources financees par la Societe des obstetriciens et gynecologues du Canada. Declarations condensees 1La technicite correspond a la proportion des hysterectomies realisees par voie d'abord a effraction minimale (laparoscopique, assistee par laparoscopie et vaginale). L'indice de technicite eleve est lie a une amelioration de la qualite chirurgicale et des soins a la patiente (elevee). 2Les voies d'abord de l'hysterectomie a effraction minimale sont liees a moins de complications perioperatoires que la laparotomie (elevee). 3Les hopitaux et chirurgiens qui traitent un grand nombre de patientes sont les plus susceptibles de detenir un indice de technicite eleve et un taux plus faible de complications (elevee). 4Les protocoles de chirurgie d'un jour pour l'hysterectomie a effraction minimale sont rentables, n'augmentent pas les taux de complications ni de readmission et sont lies a un taux eleve de satisfaction des patientes (moyenne). 5Le risque de traumas des voies urinaires est comparable entre les differentes voies d'approche chirurgicales de l'hysterectomie (moyenne). 6La laparotomie ou la mini-laparotomie peut etre indiquee comme solution de remplacement dans des cas precis en fonction de facteurs propres a la patiente, des indications chirurgicales et des pathologies sous-jacentes (moyenne). 7Le risque de dehiscence de la tranche vaginale est rare et n'est pas lie au choix du materiel de suture ni a la voie de fermeture (moyenne). 8L'hysterectomie supracervicale n'a pas demontre qu'elle peut preserver la fonction sexuelle, diminuer le risque de prolapsus des organes pelviens, ni reduire l'incidence du trauma des voies urinaires par rapport a l'hysterectomie totale (moyenne). 9Chez les femmes qui presentent des fibromyomes uterins, un traitement medicamenteux preoperatoire a l'acetate de leuprolide ou a l'acetate d'ulipristal peut reduire la taille des myomes, diminuer les saignements et corriger l'anemie. Les risques et avantages du traitement medicamenteux doivent etre abordes avant l'intervention (elevee). 10La preparation mecanique systematique des intestins n'est pas necessaire avant une chirurgie gynecologique pour une maladie benigne (elevee). 11L'ablation des ovaires normaux lors d'une hysterectomie reduit le risque de cancer de l'ovaire, mais peut entrainer des repercussions sur la sante. L'ovariectomie bilaterale peut provoquer une manifestation aigue de symptomes menopausiques chez les femmes non menopausees; elle n'a demontre aucun avantage de survie en l'absence d'une predisposition genetique au cancer de l'ovaire (elevee). 12L'hysterectomie seule affecte la reserve ovarienne (elevee). 13La salpingectomie prophylactique lors de l'hysterectomie devrait diminuer l'incidence des cas de cancer de l'ovaire grave de haut grade (faible). 14Il n'y a aucune donnee probante solide a l'appui de la suspension systematique aux utero-sacrees ou de la voute vaginale lors de l'hysterectomie chez les femmes qui ne presentent pas de prolapsus des organes pelviens (faible). Recommandations 1Pour les indications gynecologiques benignes, l'hysterectomie devrait se faire de preference par voie d'abord vaginale ou laparoscopique (forte, elevee). 2Pour realiser une hysterectomie, la voie d'abord vaginale est toujours l'option privilegiee, mais la chirurgie laparoscopique est une option de remplacement (forte, moyenne). 3La correction preoperatoire de l'anemie (hemoglobine a 4L'antibioprophylaxie preoperatoire et les mesures pour reduire le risque de thromboembolie veineuse sont recommandees pour toutes les patientes qui doivent subir une hysterectomie (forte, elevee). 5Il est important de conseiller les femmes sur les risques et avantages de l'ablation des ovaires lors de l'hysterectomie. Cette discussion doit aborder le risque de cancer de l'ovaire et les repercussions sur la sante a long terme relativement a une menopause precoce (forte, moyenne). 6La salpingectomie prophylactique peut etre envisagee lors de l'hysterectomie, mais la voie d'abord chirurgicale ne devrait pas etre modifiee pour cette seule fin (forte, faible). 7Comme le trauma des voies urinaires est une complication connue de l'hysterectomie, les cliniciens ne doivent pas hesiter a effectuer des examens supplementaires lorsqu'ils suspectent un trauma. Il convient, pour les chirurgiens qui pratiquent l'hysterectomie, d'avoir acces a la cystoscopie diagnostique, individuellement ou sur consultation, pour examiner la vessie et evaluer l'integrite ureterale (forte, moyenne). 8Pour les patientes atteintes d'endometriose qui prevoient de subir une hysterectomie, l'excision complete des lesions endometriosiques doit etre effectuee au moment de l'intervention (forte, moyenne).

BACKGROUND: Trace metal concentrations may affect cardio-metabolic risk, but the role of prenatal exposure is unclear. We examined: 1) the relationship between blood metal concentrations during pregnancy and child cardio-metabolic risk factors; 2) overall effects of metals mixture (essential vs. nonessential); and 3) interactions between metals. METHODS: We measured 11 metals in maternal 2(nd) trimester whole blood in a prospective birth cohort in Mexico City. In children 4–6 years old, we measured body mass index (BMI), percent body fat, and blood pressure (N=609); and plasma hemoglobin A1C (HbA1c) , non-high density lipoprotein (HDL) cholesterol, triglycerides, leptin, and adiponectin (N=411). We constructed cardio-metabolic component scores using age- and sex-adjusted z-scores and averaged five scores to create a global risk score. We estimated linear associations of each metal with individual z-scores and used Bayesian Kernel Machine Regression to assess metal mixtures and interactions. RESULTS: Higher total metals were associated with lower HbA1c, leptin, and systolic blood pressure, and with higher adiponectin and non-HDL cholesterol. We observed no interactions between metals. Higher selenium was associated with lower triglycerides in linear (β=−1.01 z-score units per 1 unit ln(Se), 95%CI = −1.84; −0.18) and Bayesian Kernel Machine Regression models. Manganese was associated with decreased HbA1c in linear models (β = −0.32 and 95% CI: −0.61, −0.03). Antimony and arsenic were associated with lower leptin in Bayesian Kernel Machine Regression models. Essential metals were more strongly associated with cardio-metabolic risk than were nonessential metals. CONCLUSIONS: Low essential metals during pregnancy were associated with increased cardio-metabolic risk factors in childhood.

Funding Acknowledgements Type of funding sources: None. OnBehalf Centre for Heart Rhythm Disorders Background Education is critical to empower individuals to self-monitor and manage their condition. Significant variability exists in the provision of education for atrial fibrillation (AF), whilst individual patient factors including health literacy and education level attainment may impact on knowledge levels. Objective assessment of knowledge may help to target education to areas of need, and result in improved patient outcomes. Objective To describe the development and validation of a knowledge questionnaire for AF. Methods A multidisciplinary expert team of healthcare professionals developed the questionnaire, in conjunction with consumers, with question content based upon areas deemed most critical to AF and related self-management. The multiple choice questionnaire consists of 20 items, each worth 5 points, to give a total score out of 100. The questionnaire assesses five domains specific to AF: general knowledge, complications, medications, risk factors and action. The questionnaire was developed in English. The questionnaire was tested on 10 randomly selected patients with AF for face validity and 19 healthcare professionals for content validity. The final version was completed by 454 individuals with AF. Exploratory factor analysis was used to determine construct validity with factor loadings of 0.40 and above considered acceptable. Reliability was assessed using Cronbach’s alpha, with a value greater than 0.7 acceptable. Results Face and content validity were considered acceptable, after minor changes to wording. The cohort of 454 individuals with AF had a mean age of 66.9 ± 12 years and 43% were female. Mean (SD) total score was 57.7 ± 15.8. Exploratory factor analysis was undertaken using the principal components method. This resulted in a Kaiser–Meyer–Olkin Measure of Sampling Adequacy of .64 and a Bartlett"s Test of Sphericity being significant at 0.00. Seven factors were selected and analysed using principal component analysis with varimax rotation. All items loaded on one of the seven factors. Internal consistency demonstrated a Cronbach’s alpha of 0.65. Conclusion The Atrial Fibrillation Knowledge Questionnaire is a valid measure to assess knowledge in individuals with AF.

Evidence demonstrates that participation in regular physical activity (PA) reduces the risk of morbidity and mortality. However, current PA guidelines are focused on weekly accumulation of 150 min of moderate intensity PA as a threshold. Although recent developments of this guidance have discussed the merits of short bouts of physical activity, guidance that sets large behavioural goals for PA has not been successful in supporting the public to become sufficiently physically active and a ‘one-size fits all’ approach to PA guidelines may not be optimal. A complementary ‘whole day’ approach to PA promotion (i.e. incorporating PA throughout the day) that could motivate the population to be more physically active, is a concept we have called ‘Snacktivity™’. The Snacktivity™ approach promotes small or ‘bite’ size bouts (e.g. 2–5 min) of PA accumulated throughout the whole day. Snacktivity™ is consistent with the small change approach which suggest that behaviour change and habit formation are best achieved through gradual building of task self-efficacy, celebrating small successes. Snacktivity™ also offers opportunities to “piggyback” on to existing behaviours/habits, using them as prompts for Snacktivity™. Moreover, small behaviour changes are easier to initiate and maintain than larger ones. A plethora of evidence supports the hypothesis that Snacktivity may be a more acceptable and effective way to help the public reach, or exceed current PA guidelines. This paper outlines the evidence to support the Snacktivity™ approach and the mechanisms by which it may increase population levels of physical activity. Future research directions for Snacktivity™ are also outlined.

Funding Acknowledgements Type of funding sources: None. Background There is a lack of consensus guidelines regarding the continuation of anticoagulant therapy following cavotricuspid isthmus (CTI) ablation for typical atrial flutter. This is despite a significant number of patients developing new-onset atrial fibrillation (AF) following the procedure. Furthermore, a summary of Kaplan-Meier estimates for drug-free, arrhythmia-free survival has never been reported. Purpose To estimate the incidence of drug-free, new-onset AF stratified by rhythm monitoring strategy in patients undergoing CTI ablation for isolated typical atrial flutter. Methods PubMed, Embase and MEDLINE databases were searched to identify relevant studies. Only studies where anti-arrhythmic drugs were discontinued post-ablation and that accounted for patient censoring by reporting results in the form of time to event data were included. Data was extracted from published Kaplan-Meier curves using a digitizing software and confidence intervals for the survivor function were estimated based on the number at risk at the time point of interest. Results were pooled in a random effects model using the DerSimonian-Laird estimator. Results Thirteen relevant studies incorporating 1712 patients (79 % male, mean age 63.2 +/-11.2 years, LVEF 55.2 +/-10.8%) were identified. The estimated freedom from new-onset atrial fibrillation was 89.7% (95% CI: 80.3-90.1%) at 1 year and 86.2% (95% CI: 78.4-94.0%) at 2 years in patients undergoing predominantly symptom –based monitoring, 74.6% (95%CI: 67.0-82.3%) at 1 year and 69.5% (95%CI: 63.5-75.6%) at 2 years in patients undergoing regular clinic follow-up with periodic Holter monitoring and 51.4% (95% CI: 41.8-61.0%) at 1 year and 22.7% (95% CI: 8.7% - 36.6%) at 2 years in patients with implantable loop recorders. Conclusion With the advent of implantable loop recorders, it is apparent that most patients with isolated atrial flutter manifest new-onset AF following CTI ablation and the merits of discontinuing anticoagulation must be carefully considered in this population. Symptom-based monitoring likely severely underestimates the incidence of new-onset AF and may lead to adverse outcomes, particularly in patients with a high risk of stroke.

Funding Acknowledgements Type of funding sources: None. Background Sudden cardiac death (SCD) during physical exercise is uncommon but devastating. Purpose We aimed to determine risk factors, causes and circumstances of sports and exercise-related SCD in the young in Australia. Methods We retrospectively reviewed the National Coronial Information System (NCIS) registry for deaths in Australia relating to cardiovascular disease (CVD) in cases aged 10 to 35 years between 2000-2016. Included cases had been undertaking sports or physical exercise at time of event. We collected baseline demographics and circumstances of death including location, type of physical exercise, whether the event was witnessed, and engagement of bystander cardiopulmonary resuscitation (CPR) and automated external defibrillator (AED) use prior to ambulance arrival. Results Over a 17-year period, 1,925 SCD cases were identified of which 110 cases (6%) related to sports/physical exercise were included in final analysis. Median age was 27 years (interquartile range [IQR] 21-32 years) with most being male (92%). Median BMI was 27 kg/m2 (IQR, 23-30) with 13 cases (12%) occurring in active athletes. Most common causes were coronary artery disease (CAD; 37%) and sudden arrhythmic death syndrome (SADS; 20%). Australian Rules Football (24%), running/jogging (14%) and soccer (14%) were the most frequently practiced at time of event. Prior symptoms were present in 39% (chest pain 37%, presyncope/syncope 26%). Most were witnessed (87%) with bystander CPR in 70%. AED use prior to ambulance arrival was 8%. Conclusions This study demonstrates the high occurrence of CAD and SADS in exercise-related SCD in the young. Although events were commonly witnessed, an AED was seldom used prior to ambulance arrival highlighting an important opportunity to improve outcomes in the post-arrest chain of survival.

Study Objective An isthmocele is a cesarean scar site defect with a depth of >2mm and can lead to both obstetric and gynecologic complications. The primary objective was to evaluate the feasibility of a study protocol comparing different cesarean section closure techniques amongst our own patients/physicians, with the ultimate goal of a larger scale randomized controlled trial (RCT). Secondary objectives included isthmocele incidence, measurements on postoperative ultrasound, and adverse surgical outcomes related to suture technique. Design A single-center parallel-group pilot RCT comparing locked vs. unlocked first-layer uterine closure. Outpatient transvaginal ultrasound to evaluate isthmocele formation was performed at least six months postoperatively. Setting Operating room and outpatient ultrasound clinic. Patients or Participants All term pregnant patients >18 years old undergoing a primary caesarean section were eligible. Exclusion criteria included previous uterine hysterotomy, known uterine anomalies, active labour, and maternal bleeding and/or connective tissue disorders. Interventions Locked or unlocked closure of the first uterine layer. Measurements and Main Results Forty-one subjects were randomized, and 23 completed the follow-up ultrasound, with 12 in the locked group and 11 in the unlocked group. Barriers to feasibility included hesitance to participate in research during pregnancy, difficulty attending follow-up ultrasound with a newborn, and mainly Covid-19 pandemic related delays in study activities and fear of potential exposures. Isthmocele was present in 10/12 patients receiving locked closure, and in 11/11 of the unlocked group. Mean sagittal depth was 0.36 cm and 0.40 cm in the locked vs. unlocked groups, respectively. Sagittal adjacent myometrial thickness was 1.03 cm in the locked group, and 1.12 cm in the unlocked group. No adverse outcomes were noted with either surgical technique. Conclusion The study design is feasible outside of the pandemic setting. A larger trial is needed to determine differences regarding isthmocele rates and measurements between groups.

Naloxone is a medication with a largely benign safety profile that is frequently administered in the emergency department to patients presenting with altered mental status. Ventricular tachycardia has been reported after naloxone administration in adult patients with prior use of opiate or sympathomimetic medications. However, no such reports exist in the pediatric population or in patients who have no known history of opiate or sympathomimetic medication use. We describe a case of ventricular tachycardia after naloxone administration in a 17-year-old male with no known prior use of opiate or sympathomimetic agents who presented to the emergency department with altered mental status of unknown etiology. Emergency physicians may wish to prepare for prompt treatment of ventricular arrythmias when administering naloxone to pediatric patients presenting with altered mental status.

Modern CNC machine tools provide lookup tables to enhance the machine tool’s precision but the generation of table entries can be a demanding task. In this paper, the coefficients of the 25 cubic polynomial functions used to generate the LUTs entries for a five-axis machine tool are obtained by solving a linear system incorporating a Vandermonde expansion of the nominal control jacobian. The necessary volumetric errors within the working volume are predicted from the machine’s geometric errors estimated by the indirect error identification method based on the on-machine touch probing measurement of a reconfigurable uncalibrated master ball artifact (RUMBA). The proposed scheme is applied to a small Mitsubishi M730 CNC machine. Two different error models are used for modeling the erroneous machine tool, one estimating mainly inter-axis errors and the other including numerous intra-axis errors. The table-based compensation is validated through additional on-machine measurements. Experimental tests demonstrate a significant reduction in volumetric errors and in the effective machine error parameters. The LUTs reduce most of the dominant machine error parameters. It is concluded that although being effective in correcting some geometric errors, the generated LUTs cannot compensate for some axis misalignments such as EB(OX)A and EB(OX)Z. The root-mean-square of the translational volumetric errors is improved from 87.3, 75.4, and 71.5 µm down to 24.8, 18.8, and 22.1 µm in the X-, Y-, and Z-directions, respectively.

Bilateral ligation of the anterior division of the internal iliac arteries can be a lifesaving intervention for severe pelvic hemorrhage. The procedure results in decreased pelvic perfusion and promotes coagulation. The classical method of internal iliac artery ligation involved extensive retroperitoneal dissection with complete circumferential isolation of the vessel to allow the passage of a suture around the artery. This can be surgically challenging and fraught with risks of inadvertent injury to the surrounding iliac veins. We propose a contemporary technique that requires limited dissection of the anterior division of the internal iliac artery. A few millimeters of space is created on either side of the artery by spreading right-angle forceps parallel to the vessel. The artery is occluded by 2 large vascular clips. Because circumferential vessel dissection is not necessary with this technique, there is limited disruption of the delicate underlying internal iliac vein. In addition, this approach may decrease the risk of inadvertent injury to the adjacent external iliac vein. By showcasing the ease of our approach to internal iliac artery ligation, we hope to empower surgeons with an alternative approach to this lifesaving procedure.

Background There is a growing burden of hospitalizations due to atrial fibrillation (AF). The implications of hospitalisation to the individual with AF has not been well characterized. Purpose To characterise the consequences of presenting to hospital with AF. Methods Individuals presenting to the emergency department (ED) of three hospitals in South Australia from March 2013 to February 2014 with a primary diagnosis of AF were enrolled. Based on coding and individual electronic medical record review all re-presentations over follow up were characterised as: 1) AF related; 2) cardiovascular related (excluding AF); or 3) all other causes. Mortality over follow up was also determined. Results The study cohort comprised of 437 individuals with an AF related index presentation. Mean age was 69±15 years and 49.9% were male. Individuals were followed for a mean of 3.7±0.4 years. There were 2304 unplanned presentations over follow up. The percentage of the study cohort who presented to the ED or were admitted to hospital over follow up is detailed in Figure 1. Compared to individuals who did not have a hospital admission for AF over follow up, those who were readmitted for AF were more likely to be hypertensive (63.2% vs 49.3%, p Conclusions A hospital presentation with a primary diagnosis of AF identifies individuals at high risk of repeat hospitalisations and death. Urgent studies are needed to improve management of this high-risk cohort. Figure 1. Repeat hospital presentations in AF Funding Acknowledgement Type of funding source: None

Background The health benefits of extensive endurance training have been debated due to the report of myocardial fibrosis (MF), arrhythmias and temporary post-race cardiac impairment in middle-aged and veteran athletes. The extent of these changes is unknown in elite young athletes. Purpose To assess the prevalence of MF and its structural, functional and electrical impact in highly trained young endurance athletes (YA, 15–23 years) as compared to middle-aged athletes (MA, 30–50 years). We hypothesised that MF would be more frequent in MA and associated with more structural, functional and electrical abnormalities. Methods We prospectively assessed 197 YA and 34 MA. All had ECG, maximal oxygen consumption (VO2max) testing, cardiac magnetic resonance imaging (CMR), echocardiography and 24h-holter. Indexed left ventricular and right ventricular end diastolic volume (LVEDVi, RVEDVi), ejection fraction (LVEF, RVEF), left ventricular mass (LVMi), and MF defined as delayed gadolinium enhancement were assessed by CMR. LV and RV free wall strain (LVSL, RVfwSL) were assessed by 2D speckle tracking echocardiography. Ventricular premature beats (VPB) and non-sustained ventricular tachycardia (nsVT) were assessed by 24h-holter. Results YA and MA (18±2 vs 38±5 years [p MF+ MA(A) and YA(B) as well as MF− MA(C) and YA(D) had similar structural remodelling (LVEDVi 110±14 vs 118±14 vs 113±19 vs 110±16 mL/m2; RVEDVi 120±14 vs 128±17 vs 117±19 vs 125±23mL/m2; LVMi 77±11 vs 83±14 vs 81±14 vs 77±15g/m2, p>0.05). LVEF, LVSL and RVSL were similar (59±3 vs 58±5 vs 61±6 vs 58±6%; −18.8±2 vs −18.8±2 vs −19.8±2 vs −19.3±2%; −26.3±2.4 vs −24.4±2.4; −26.3±3 vs −25.8±3.5% respectively, p>0.05). LVEF 100VPB/24h (12.5 vs 5 vs 11.1 vs 5.1%, p=0.42). 2 athletes had nsVT, both in D. All had similar exercise capacity (% predicted VO2max 157±26 vs 152±15 vs 147±24 vs 158±32%; p=0.11). Conclusion Hinge-point fibrosis was more prevalent in MA, possibly due to repeated hemodynamic stress during exercise, but is not associated with structural, functional or electrical consequences. Figure 1. Cardiac remodelling in elite athletes Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Fonds voor Wetenschappelijk Onderzoek (FWO)

Background Stroke is one of the most devastating complications of atrial fibrillation (AF) and is associated with poor patient outcomes. Recent registry data has demonstrated improved use of stroke prevention therapy with the advent of direct-acting oral anticoagulants, but little data exists in the Australian health care setting. Purpose To examine the use of oral anticoagulant therapy in a cohort of individuals presenting to the emergency department (ED) due to AF. Methods A total of 437 consecutive individuals who presented to the ED with a primary diagnosis of AF to three tertiary hospitals in our city in South Australia between March 2013 and March 2014 were included. Data were collected retrospectively from electronic medical record review. CHA2DS2-VASc and HAS-BLED scores were calculated and any documented contraindications to the use of oral anticoagulation (OAC) taken in to consideration. Results Mean age was 69±15 years and 49.9% were male. A total of 244 (55.8%) individuals had a prior diagnosis of AF at index presentation. 179 (73.4%) of these individuals recorded a CHA2DS2-VASc score of ≥2. A total of 124 of these individuals were appropriately anticoagulated (69.3%) whilst 37 individuals were not treated with OAC and did not have a documented contraindication (20.7%). Anticoagulation status was unknown in 18 individuals due to a lack of documentation (10.0%). A CHA2DS2-VASc score of 0 was recorded in 25 individuals with a prior diagnosis of AF at index presentation with 3 individuals (12%) inappropriately overtreated with OAC. The remaining 193 individuals (44.2%) presented with a first episode of AF. In 129 (66.8%) of these individuals a CHA2DS2-VASc score of ≥2 was recorded and only 10 individuals had a documented contraindication to the use of OAC. In 119 (61.7%) individuals there were no documented contraindications to the use of OAC. In 74 (62.2%) of these presentations OAC was not commenced, whilst in 45 (37.8%) individuals OAC was prescribed. Conclusions Significant opportunity exists to improve the use of stroke prevention therapy in AF. Despite repeated opportunities to commence this therapy within the hospital setting, it remains frequently underutilised in individuals at high risk of stroke. Funding Acknowledgement Type of funding source: None

Advances in virtual reality have made it possible for clinicians and trainees to interact with 3D renderings of hearts with congenital heart disease in 3D stereoscopic vision. No study to date has assessed whether this technology improved instruction compared to standard 2D interfaces. The purpose of this study was to assess whether stereoscopic virtual reality improves congenital heart disease anatomy education. Subjects in a prospective, blinded, randomized trial completed a pre-test assessing factual and visuospatial knowledge of common atrioventricular canal and were randomized to an intervention or control group based on their score. The intervention group used a 3D virtual reality (VR) headset to visualize a lecture with 3D heart models while the control group used a desktop (DT) computer interface with the same models. Subjects took a post-test and provided subjective feedback. 51 subjects were enrolled, 24 in the VR group & 27 in the DT group. The median score difference for VR subjects was 12 (IQR 9–13.3), compared to 10 (IQR 7.5–12) in the DT group. No difference in score improvement was found (p = 0.11). VR subjects’ impression of the ease of use of their interface was higher than DT subjects (median 8 vs 7, respectively, p = 0.01). VR subjects’ impression of their understanding of the subject matter was higher than desktop subjects (median 7 vs 5, respectively, p = 0.01). There was no statistically significant difference in the knowledge acquisition observed between the stereoscopic virtual reality group and the monoscopic desktop-based group. Participants in virtual reality reported a better learning experience and self-assessment suggesting virtual reality may increase learner engagement in understanding congenital heart disease.

The use of AI in knowledge dense domains, e.g., chemistry, medicine, biology, etc. - is extremely promising, but often suffers from slow deployment and adaptation to different tasks. We propose a methodology to quickly capture the intent and expertise of a domain expert in order to train personalized AI models for specific tasks. Specifically we focus on the domain of polymer materials design and discovery: it often takes 10 years or more to design, synthesize, test, and introduce a new polymer material into the market. One way to accelerate up the design of polymer materials is through the use of computational methods to design the material, such as combinatorial screening, generative models, inverse design, etc. The drawback of these methods is that they generate a large number of candidates for new molecules, which then need to be manually reviewed by subject matter experts who select only a dozen for further investigation. Our solution is a human-in-the-loop methodology where we rank the candidates according to a utility function that is learned via the continued interaction with the subject matter experts, but which is also constrained by specific chemical knowledge. We prove the viability of our proposed methodology in a polymer production lab and we (i) evaluate against datasets of polymers previously produced in the lab as well as (ii) producing several novel materials that are undergoing experimental development, and (iii) quantitatively show that standard synthetic accessibility scores do not inform about patterns of SME decisions.

Cadmium (Cd) is a toxic metal associated with adverse health effects, including kidney injury or disease. The aims of this study were to estimate dietary Cd exposure during childhood, and to evaluate the association of early-life dietary Cd with biomarkers of glomerular kidney function in 9-year-old Mexican children. Our study included 601 children from the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) cohort with up to five follow-up food frequency questionnaires from 1 to 9 years of age; and 480 children with measures of serum creatinine, cystatin C, and blood nitrogen urea (BUN), as well as 9-year-old estimated glomerular filtration rate. Dietary Cd was estimated through food composition tables. Multiple linear regression models were used to analyze the association between 1 and 9 years, cumulative dietary Cd, and each kidney parameter. Dietary Cd exposure increased with age and exceeded the tolerable weekly intake (TWI = 2.5 µg/kg body weight) by 16–64% at all ages. Early-life dietary Cd exposure was above the TWI and we observed inverse associations between dietary Cd exposure and kidney function parameters. Additional studies are needed to assess kidney function trajectories through adolescence. Identifying preventable risk factors including environmental exposures in early life can contribute to decreasing the incidence of adult kidney disease.

A main prerequisite to applications in the Internet of Production is the integration of sensor data into an interconnected infrastructure, which in turn requires expert knowledge of sensor implementation as well as of network architecture design and communication protocols. To reduce complexity in this concern, the authors propose the SensOr Interfacing Language (SOIL), a domain-specific programming language for sensor interface definition and exchange of metrological data. Based on a meta-model, the functional interface can be designed without prior knowledge of the underlying communication details. It is composed of instances of components, parameters, functions and measurements as core elements of SOIL. Subsequently, the interface is automatically defined on protocol level and its software implementation is generated, leaving only the hardware-specific implementation to the developer. The domain-specific language is prototyped and evaluated by implementing and integrating interfaces for a virtual laser tracker and a distributed temperature measurement system, confirming the envisaged benefits.

Background The right ventricle (RV) often fails when functioning as the systemic ventricle, but the cause is not understood. We tested the hypothesis that myofiber organization is abnormal in the failing systemic right ventricle. Methods We used diffusion-weighted cardiovascular magnetic resonance imaging to examine 3 failing hearts explanted from young patients with a systemic RV and one structurally normal heart with postnatally acquired RV hypertrophy for comparison. Diffusion compartment imaging was computed to separate the free diffusive component representing free water from an anisotropic component characterizing the orientation and diffusion characteristics of myofibers. The orientation of each anisotropic compartment was displayed in glyph format and used for qualitative description of myofibers and for construction of tractograms. The helix angle was calculated across the ventricular walls in 5 locations and displayed graphically. Scalar parameters (fractional anisotropy and mean diffusivity) were compared among specimens. Results The hypertrophied systemic RV has an inner layer, comprising about 2/3 of the wall, composed of hypertrophied trabeculae and an epicardial layer of circumferential myofibers. Myofibers within smaller trabeculae are aligned and organized with parallel fibers while larger, composite bundles show marked disarray, largely between component trabeculae. We observed a narrow range of helix angles in the outer, compact part of the wall consistent with aligned, approximately circumferential fibers. However, there was marked variation of helix angle in the inner, trabecular part of the wall consistent with marked variation in fiber orientation. The apical whorl was disrupted or incomplete and we observed myocardial whorls or vortices at other locations. Fractional anisotropy was lower in abnormal hearts while mean diffusivity was more variable, being higher in 2 but lower in 1 heart, compared to the structurally normal heart. Conclusions Myofiber organization is abnormal in the failing systemic RV and might be an important substrate for heart failure and arrhythmia. It is unclear if myofiber disorganization is due to hemodynamic factors, developmental problems, or both.

Pregnancy is characterized by high bone remodeling and might be a window of susceptibility to the toxic effects of metals on bone tissue. The aim of this study was to assess associations between metals in blood [lead (Pb), cadmium (Cd)and arsenic (As)] and bone remodeling during pregnancy. We studied pregnant woman from the PROGRESS Cohort (Programming Research in Obesity, Growth, and Environment and Social Stress). We measured concentrations of metals in blood and obtained measures of bone remodeling by quantitative ultrasound (QUS) at the radius in the second and third trimester of pregnancy. To account for chronic lead exposure, we measured lead in tibia and patella one-month postpartum with K-shell X-ray fluorescence. We assessed cross-sectional and longitudinal associations between multiple-metal concentrations and QUS z-scores using linear regression models and linear mixed models adjusted for potential confounders. Third trimester blood Cd concentrations were marginal associated with lower QUS z-scores [-0.16 (95% CI: −0.33, 0.007); P-Value = 0.06]. Mixed models showed that blood Cd was longitudinally and marginally associated with an average of −0.10 z-score (95% CI: −0.21, 0.002; P-Value = 0.06) over the course of pregnancy. Associations for Pb and As were all inverse however none reached significance. Additionally, bone Pb concentrations in patella, an index of cumulative exposure, were significantly associated with −0.06 z-score at radius (95% CI: −0.10, −0.01; P-Value = 0.03) during pregnancy. Pb and Cd blood levels are associated with lower QUS distal radius z-scores in pregnant women. Bone Pb concentrations in patella were negatively associated with z-score at radius showing the long-term effects of Pb on bone tissue. However, we cannot exclude the possibility of reverse causality for patella Pb and radius z-score associations. Our results support the importance of reducing women’s metal exposure during pregnancy, as metals exposure during pregnancy may have consequences for bone strength later in life. The main finding of our study is the association between Cd blood levels and radius z-score during pregnancy. Bone lead in patella was also negatively associated with radius z-scores.