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The air gap technique (AGT) is an approach to radiation dose optimisation during fluoroscopy where an “air gap” is used in place of an anti-scatter grid to reduce scatter irradiation. The AGT is effective in adults but remains largely untested in children. Effects are expected to vary depending on patient size and the amount of scatter irradiation produced.
Fluoroscopy and cineangiography were performed using a Phillips Allura Fluoroscope on tissue simulation anthropomorphic phantoms representing a neonate, 5-year-old, and teenager. Monte Carlo simulations were then used to estimate effective radiation dose first using a standard recommended imaging approach and then repeated using the AGT. Objective image quality assessments were performed using an image quality phantom.
Effective radiation doses for the neonate and 5-year-old phantom increased consistently (2–92%) when the AGT was used compared to the standard recommended imaging approaches in which the anti-scatter grid is removed at baseline. In the teenage phantom, the AGT reduced effective doses by 5–59%, with greater dose reductions for imaging across the greater thoracic dimension of lateral projection. The AGT increased geometric magnification but with no detectable change in image blur or contrast differentiation.
The AGT is an effective approach for dose reduction in larger patients, particularly for lateral imaging. Compared to the current dose optimisation guidelines, the technique may be harmful in smaller children where scatter irradiation is minimal.
While echocardiographic parameters are used to quantify ventricular function in infants with single ventricle physiology, there are few data comparing these to invasive measurements. This study correlates echocardiographic measures of diastolic function with ventricular end-diastolic pressure in infants with single ventricle physiology prior to superior cavopulmonary anastomosis.
Data from 173 patients enrolled in the Pediatric Heart Network Infant Single Ventricle enalapril trial were analysed. Those with mixed ventricular types (n = 17) and one outlier (end-diastolic pressure = 32 mmHg) were excluded from the analysis, leaving a total sample size of 155 patients. Echocardiographic measurements were correlated to end-diastolic pressure using Spearman’s test.
Median age at echocardiogram was 4.6 (range 2.5–7.4) months. Median ventricular end-diastolic pressure was 7 (range 3–19) mmHg. Median time difference between the echocardiogram and catheterisation was 0 days (range −35 to 59 days). Examining the entire cohort of 155 patients, no echocardiographic diastolic function variable correlated with ventricular end-diastolic pressure. When the analysis was limited to the 86 patients who had similar sedation for both studies, the systolic:diastolic duration ratio had a significant but weak negative correlation with end-diastolic pressure (r = −0.3, p = 0.004). The remaining echocardiographic variables did not correlate with ventricular end-diastolic pressure.
In this cohort of infants with single ventricle physiology prior to superior cavopulmonary anastomosis, most conventional echocardiographic measures of diastolic function did not correlate with ventricular end-diastolic pressure at cardiac catheterisation. These limitations should be factored into the interpretation of quantitative echo data in this patient population.
This study aimed to estimate the number of new cancer cases attributable to diet among adults aged 30–84 years in France in 2015, where convincing or probable evidence of a causal association exists, and, in a secondary analysis, where at least limited but suggestive evidence of a causal association exists. Cancer cases attributable to diet were estimated assuming a 10-year latency period. Dietary intake data were obtained from the 2006 French National Nutrition and Health Survey. Counterfactual scenarios of dietary intake were based on dietary guidelines. Corresponding risk relation estimates were obtained from meta-analyses, cohort studies and one case–control study. Cancer incidence data were obtained from the French Network of Cancer Registries. Nationally, unfavourable dietary habits led to 16 930 new cancer cases, representing 5·4 % of all new cancer cases. Low intake of fruit and dietary fibre was the largest contributor to this burden, being responsible for 4787 and 4389 new cancer cases, respectively. If this is expanded to dietary component and cancer pairs with at least limited but suggestive evidence of a causal association, 36 049 new cancer cases, representing 11·6 % of all new cancer cases, were estimated to be attributable to diet. These findings suggest that unfavourable dietary habits lead to a substantial number of new cancer cases in France; however, there is a large degree of uncertainty as to the number of cancers attributable to diet, including through indirect mechanisms such as obesity, and therefore additional research is needed to determine how diet affects cancer risk.
The ventricular assist device is being increasingly used as a “bridge-to-transplant” option in children with heart failure who have failed medical management. Care for this medically complex population must be optimised, including through concomitant pharmacotherapy. Pharmacokinetic/pharmacodynamic alterations affecting pharmacotherapy are increasingly discovered in children supported with extracorporeal membrane oxygenation, another form of mechanical circulatory support. Similarities between extracorporeal membrane oxygenation and ventricular assist devices support the hypothesis that similar alterations may exist in ventricular assist device-supported patients. We conducted a literature review to assess the current data available on pharmacokinetics/pharmacodynamics in children with ventricular assist devices. We found two adult and no paediatric pharmacokinetic/pharmacodynamic studies in ventricular assist device-supported patients. While mechanisms may be partially extrapolated from children supported with extracorporeal membrane oxygenation, dedicated investigation of the paediatric ventricular assist device population is crucial given the inherent differences between the two forms of mechanical circulatory support, and pathophysiology that is unique to these patients. Commonly used drugs such as anticoagulants and antibiotics have narrow therapeutic windows with devastating consequences if under-dosed or over-dosed. Clinical studies are urgently needed to improve outcomes and maximise the potential of ventricular assist devices in this vulnerable population.
Cardiac rhabdomyomas are the most common tumours in children and are typically seen in association with the tuberous sclerosis complex. Although benign and often associated with spontaneous regression, in rare circumstances surgical resection is indicated to relieve obstruction or other mass-related effects. Recent clinical trials have demonstrated the benefits of mammalian target of rapamycin inhibitors for the treatment of other tumour sub-types associated with tuberous sclerosis. Here we report rapid regression of several massive cardiac rhadomyomas in two neonates with the use of the mammalian target of rapamycin inhibitor sirolimus.
While a long history of experimental data shows that aerial thermal images can reveal a wide range of both surface and subsurface archaeological features, technological hurdles have largely prevented more widespread use of this promising prospecting method. However, recent advances in the sophistication of thermal cameras, the reliability of commercial drones, and the growing power of photogrammetric software packages are revolutionizing archaeologists' ability to collect, process, and analyze aerial thermal imagery. This paper provides an overview of the theory behind aerial thermography in archaeology, as well as a discussion of an emerging set of methods developed by the authors for undertaking successful surveys. Summarizing investigations at archaeological sites in North America, the Mediterranean, and the Near East, our results illustrate some contexts in which aerial thermography is very effective, as well as cases in which ground cover, soil composition, or the depth and character of archaeological features present challenges. In addition, we highlight novel approaches for filtering out noise caused by vegetation, as well as methods for improving feature visibility using radiometric thermal imagery.
The aim of this study was to describe previously unrecognised or under-recognised adverse events associated with Melody® valve implantation.
In rare diseases and conditions, it is typically not feasible to conduct large-scale safety trials before drug or device approval. Therefore, post-market surveillance mechanisms are necessary to detect rare but potentially serious adverse events.
We reviewed the United States Food and Drug Administration’s Manufacturer and User Facility Device Experience (MAUDE) database and conducted a structured literature review to evaluate adverse events associated with on- and off-label Melody® valve implantation. Adverse events were compared with those described in the prospective Investigational Device Exemption and Post-Market Approval Melody® transcatheter pulmonary valve trials.
We identified 631 adverse events associated with “on-label” Melody® valve implants and 84 adverse events associated with “off-label” implants. The most frequent “on-label” adverse events were similar to those described in the prospective trials including stent fracture (n=210) and endocarditis (n=104). Previously unrecognised or under-recognised adverse events included stent fragment embolisation (n=5), device erosion (n=4), immediate post-implant severe valvar insufficiency (n=2), and late coronary compression (n=2 cases at 5 days and 3 months after implantation). Under-recognised adverse events associated with off-label implantation included early valve failure due to insufficiency when implanted in the tricuspid position (n=7) and embolisation with percutaneous implantation in the mitral position (n=5).
Post-market passive surveillance does not demonstrate a high frequency of previously unrecognised serious adverse events with “on-label” Melody® valve implantation. Further study is needed to evaluate safety of “off-label” uses.
Previous studies have identified risk factors for femoral arterial thrombosis after paediatric cardiac catheterisation, but none of them have evaluated the clinical and economic significance of this complication at the population level. Therefore, we examined the national prevalence and economic impact of femoral arterial thrombosis after cardiac catheterisation in children.
Patients⩽18 years of age who underwent cardiac catheterisation were identified in the 2003–2009 Kids’ Inpatient Database. Patients were stratified by age as follows: <1 year of age or 1–18 years of age. The primary outcome was arterial thrombosis of the lower extremity during the same hospitalisation as cardiac catheterisation. Propensity score matching was used to determine the impact of femoral arterial thrombosis on hospital length of stay, cost, and mortality.
Among the 11,497 paediatric cardiac catheterisations identified, 4558 catheterisations (39.6%) were performed in children <1 year of age. This age group experienced a higher prevalence of reported femoral arterial thrombosis, compared with children aged 1–18 years (1.3 versus 0.3%, p<0.001). After matching, femoral arterial thrombosis in children <1 year of age was associated with similar mortality (5.4 versus 1.8%, p=0.28), length of stay (8 versus 5 days, p=0.11), and total hospital cost ($27,135 versus $28,311, p=0.61), compared with absence of thrombosis.
Femoral arterial thrombosis is especially prevalent in children <1 year of age undergoing cardiac catheterisation. Clinicians should be vigilant in monitoring femoral arterial patency in neonates and infants after cardiac catheterisation.
Studies have demonstrated that the effects of two well-known predictors of adolescent substance use, family monitoring and antisocial peers, are not static but change over the course of adolescence. Moreover, these effects may differ for different groups of youth. The current study uses time-varying effect modeling to examine the changes in the association between family monitoring and antisocial peers and marijuana use from ages 11 to 19, and to compare these associations by gender and levels of behavioral disinhibition. Data are drawn from the Raising Healthy Children study, a longitudinal panel of 1,040 youth. The strength of association between family monitoring and antisocial peers and marijuana use was mostly steady over adolescence, and was greater for girls than for boys. Differences in the strength of the association were also evident by levels of behavioral disinhibition: youth with lower levels of disinhibition were more susceptible to the influence of parents and peers. Stronger influence of family monitoring on girls and less disinhibited youth was most evident in middle adolescence, whereas the stronger effect of antisocial peers was significant during middle and late adolescence. Implications for the timing and targeting of marijuana preventive interventions are discussed.
National organisations in several countries have recently released more restrictive guidelines for infective endocarditis prophylaxis, including the American Heart Association 2007 guidelines. Initial studies demonstrated no change in infective endocarditis rates over time; however, a recent United Kingdom study suggested an increase; current paediatric trends are unknown.
Children (<18 years) hospitalised with infective endocarditis at 29 centres participating in the Pediatric Health Information Systems Database from 2003 to 2014 were eligible for inclusion. Our primary analysis focussed on infective endocarditis most directly related to the change in guidelines and included community-acquired cases in those >5 years of age. Interrupted time series analysis was used to evaluate rates over time indexed to total hospitalisations.
A total of 841 cases were identified. The median age was 13 years (interquartile range 9–15 years). In the pre-guideline period, there was a slight increase in the rate of infective endocarditis by 0.13 cases/10,000 hospitalisations per semi-annual period. In the post-guideline period, the rate of infective endocarditis increased by 0.12 cases/10,000 hospitalisations per semi-annual period. There was no significant difference in the rate of change in the pre- versus post-guidelines period (p=0.895). Secondary analyses in children >5 years of age with CHD and in children hospitalised with any type of infective endocarditis at any age revealed similar results.
We found no significant change in infective endocarditis hospitalisation rates associated with revised prophylaxis guidelines over 11 years across 29 United States children’s hospitals.
The aim of the study was to evaluate the trends in respiratory syncytial virus-related hospitalisations and associated outcomes in children with haemodynamically significant heart disease in the United States of America.
The Kids’ Inpatient Databases (1997–2012) were used to estimate the incidence of respiratory syncytial virus hospitalisation among children ⩽24 months with or without haemodynamically significant heart disease. Weighted multivariable logistic regression and chi-square tests were used to evaluate the trends over time and factors associated with hospitalisation, comparing eras before and after publication of the 2003 American Academy of Pediatrics palivizumab immunoprophylaxis guidelines. Secondary outcomes included in-hospital mortality, morbidity, length of stay, and cost.
Overall, 549,265 respiratory syncytial virus-related hospitalisations were evaluated, including 2518 (0.5%) in children with haemodynamically significant heart disease. The incidence of respiratory syncytial virus hospitalisation in children with haemodynamically significant heart disease decreased by 36% when comparing pre- and post-palivizumab guideline eras versus an 8% decline in children without haemodynamically significant heart disease (p<0.001). Children with haemodynamically significant heart disease had higher rates of respiratory syncytial virus-associated mortality (4.9 versus 0.1%, p<0.001) and morbidity (31.5 versus 3.5%, p<0.001) and longer hospital length of stay (17.9 versus 3.9 days, p<0.001) compared with children without haemodynamically significant heart disease. The mean cost of respiratory syncytial virus hospitalisation in 2009 was $58,166 (95% CI:$46,017, $70,315).
These data provide stakeholders with a means to evaluate the cost–utility of various immunoprophylaxis strategies.
Following the inaugural Australian Association for Environmental Education (AAEE) research symposium in November 2014, we — a group of emerging researchers in Environmental Education/Sustainability Education (EE/SE) — commenced an online collaboration to identify and articulate our responses to the main themes of the symposium. Identifying as #aaeeer, our discussions coalesced into four main areas that we felt captured not only some of our current research interests, but also ‘under-explored’ areas that need further attention and that also held the potential for meaningful and ‘dangerous’ contributions to EE/SE research and practice. These themes were: (1) uncertain futures, (2) traditional knowledges for the future, (3) community EE/SE, and (4) the rise of the digital, explorations of which we present in this article. By no means intended to capture all that is worth researching in this field, these themes, and this article, are deliberately presented by #aaeeer to spark discussions, as well as showcase an example of online collaboration between researchers in a number of countries.
Recent regulatory initiatives in the United States of America and Europe have transformed the paediatric clinical trials landscape by significantly increasing capital investment and paediatric trial volume. The purpose of this manuscript was to review the impact of these initiatives on the paediatric cardiovascular trials landscape when compared with other paediatric sub-specialties. We also evaluate factors that may have contributed to the success or failure of recent major paediatric cardiovascular trials so as to inform the optimal design and conduct of future trials in the field.
In the United States alone, ∼14,000 children are hospitalised annually with acute heart failure. The science and art of caring for these patients continues to evolve. The International Pediatric Heart Failure Summit of Johns Hopkins All Children’s Heart Institute was held on February 4 and 5, 2015. The 2015 International Pediatric Heart Failure Summit of Johns Hopkins All Children’s Heart Institute was funded through the Andrews/Daicoff Cardiovascular Program Endowment, a philanthropic collaboration between All Children’s Hospital and the Morsani College of Medicine at the University of South Florida (USF). Sponsored by All Children’s Hospital Andrews/Daicoff Cardiovascular Program, the International Pediatric Heart Failure Summit assembled leaders in clinical and scientific disciplines related to paediatric heart failure and created a multi-disciplinary “think-tank”. The purpose of this manuscript is to summarise the lessons from the 2015 International Pediatric Heart Failure Summit of Johns Hopkins All Children’s Heart Institute, to describe the “state of the art” of the treatment of paediatric cardiac failure, and to discuss future directions for research in the domain of paediatric cardiac failure.
Sildenafil is frequently prescribed to children with single ventricle heart defects. These children have unique hepatic physiology with elevated hepatic pressures, which may alter drug pharmacokinetics. We sought to determine the impact of hepatic pressure on sildenafil pharmacokinetics in children with single ventricle heart defects.
A population pharmacokinetic model was developed using data from 20 single ventricle children receiving single-dose intravenous sildenafil during cardiac catheterisation. Non-linear mixed effect modelling was used for model development, and covariate effects were evaluated based on estimated precision and clinical significance.
The analysis included a median (range) of 4 (2–5) pharmacokinetic samples per child. The final structural model was a two-compartment model for sildenafil with a one-compartment model for des-methyl-sildenafil (active metabolite), with assumed 100% sildenafil to des-methyl-sildenafil conversion. Sildenafil clearance was unaffected by hepatic pressure (clearance=0.62 L/hour/kg); however, clearance of des-methyl-sildenafil (1.94×(hepatic pressure/9)−1.33 L/hour/kg) was predicted to decrease ~7-fold as hepatic pressure increased from 4 to 18 mmHg. Predicted drug exposure was increased by ~1.5-fold in subjects with hepatic pressures ⩾10 versus <10 mmHg (median area under the curve=533 versus 792 µg*h/L).
Elevated hepatic pressure delays clearance of the sildenafil metabolite – des-methyl-sildenafil – and increases drug exposure. We speculate that this results from impaired biliary clearance. Hepatic pressure should be considered when prescribing sildenafil to children. These data demonstrate the importance of pharmacokinetic assessments in patients with unique cardiovascular physiology that may affect drug metabolism.
The paper reports on the fourth (2010) season of fieldwork of the Cyrenaican Prehistory Project, and on further results of analyses of artefacts and organic materials collected in the 2009 season. Ground-based LiDar has provided both an accurate 3D scan of the Haua Fteah cave and information on the cave's morphometry or origins. The excavations in the cave focussed on Middle Palaeolithic or Middle Stone Age ‘Pre-Aurignacian’ layers below the base of the Middle Trench beside the McBurney Deep Sounding (Trench D) and on Final Palaeolithic ‘Oranian’ layers beside the upper part of the Middle Trench (Trench M). Although McBurney referred to the upper part of the Deep Sounding as more or less sterile, the 2010 excavations found evidence for small-scale but regular human presence in the form of stone artefacts and debitage, though given the sedimentary context the latter are unlikely to represent in situ knapping. The excavations of Trench M extended from the basal Capsian layers investigated in 2009 through Oranian layers to the transition with the Dabban Upper Palaeolithic. Some 17,000 lithic pieces have been studied from the Capsian and Oranian layers excavated in Trench M, in an area measuring less than 2 m by 1 m by 1.1 m deep, along with numerous animal bones, molluscs, and macrobotanical remains, as well as occasional shell beads. Preliminary studies of the lithics, bones, molluscs, and plant remains are revealing the changing character of late Pleistocene (Oranian) and early Holocene (Capsian) occupation in the Haua Fteah. Alongside the work in the Haua Fteah, the project continued its assessment of the Quaternary and archaeological sequences of the Cyrenaican coastland and completed a transect survey of surface lithic materials and their landform contexts from the pre-desert across the Gebel Akhdar to the coast, with a new focus on the al-Marj basin. Significant differences are emerging in patterns of Middle Palaeolithic and later hominin occupation and palaeodemography.
Metal organic chemical vapor deposition, as well as material and basic device properties of nitride-based high electron mobility transistor structures on (111) silicon substrates varying in diameter from 4 to 8 inch were studied using in-situ and ex-situ characterization techniques. All substrates used for the growth of the nitride structures in this study were of SEMI standard thicknesses. The total thickness of the nitride structures was in the range of 1.5 – 5 µm. It is reported that nitride structures can be grown on 4, 6 and 8 inch diameter substrates with very similar post-growth wafer shape, material and device characteristics. It is also shown that their crystal quality, 2DEG transport properties and isolation blocking voltages can be improved by increasing nitride structure thickness while maintaining post-growth wafer bow and warp less than 50 µm. The maximum thickness of nitride structures that can be successfully grown on 8 inch diameter SEMI standard substrates seems to be limited to about 4.5 µm due to plastic deformation of Si. Blocking voltages of more than 700 V were achieved using 4.5 µm thick nitride-based high electron mobility transistor structures grown on 8 inch Si substrate.
Fall-weaned calves entering the feedlot experience a variety of psychological and physical stressors, including maternal separation, transportation, social mixing, restraint, and dietary changes. Mixing calves from multiple sources also exposes them to respiratory pathogens at a time when maternal immunity has waned. Using an experimental bovine respiratory disease (BRD) challenge, we analyzed the effects of specific stressors on clinical disease and immune responses following bovine herpes virus (BHV-1/IBR) infection of naïve calves. Transportation stress was compared to either abrupt weaning plus transportation or transportation following a two-step weaning process. Transportation alone significantly (P < 0.05) increased BHV-1 shedding in nasal secretions despite elevated interferon-gamma production in the upper respiratory tract. In contrast, abrupt weaning and transportation, significantly (P < 0.05) increased serum haptoglobin on day 3 post-infection (PI) and blood leukocyte tumor necrosis factor α secretion on day 5 PI. These systemic responses were reduced by instituting a two-step weaning process 4 days prior to transportation and BHV-1 infection. In conclusion, these observations are consistent with earlier studies implicating weaning and transportation as stressors contributing to BRD severity and mortality. Current studies also revealed that different stressors or combination of stressors have distinct effects on host responses to viral infection in naïve calves.
Understanding the nutritional demands on serving military personnel is critical to inform training schedules and dietary provision. Troops deployed to Afghanistan face austere living and working environments. Observations from the military and those reported in the British and US media indicated possible physical degradation of personnel deployed to Afghanistan. Therefore, the present study aimed to investigate the changes in body composition and nutritional status of military personnel deployed to Afghanistan and how these were related to physical fitness. In a cohort of British Royal Marines (n 249) deployed to Afghanistan for 6 months, body size and body composition were estimated from body mass, height, girth and skinfold measurements. Energy intake (EI) was estimated from food diaries and energy expenditure measured using the doubly labelled water method in a representative subgroup. Strength and aerobic fitness were assessed. The mean body mass of volunteers decreased over the first half of the deployment ( − 4·6 (sd 3·7) %), predominately reflecting fat loss. Body mass partially recovered (mean +2·2 (sd 2·9) %) between the mid- and post-deployment periods (P< 0·05). Daily EI (mean 10 590 (sd 3339) kJ) was significantly lower than the estimated daily energy expenditure (mean 15 167 (sd 1883) kJ) measured in a subgroup of volunteers. However, despite the body mass loss, aerobic fitness and strength were well maintained. Nutritional provision for British military personnel in Afghanistan appeared sufficient to maintain physical capability and micronutrient status, but providing appropriate nutrition in harsh operational environments must remain a priority.