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Tricuspid atresia with common arterial trunk is a very rare association in complex CHD. This association has even more infrequently been documented concomitantly with interrupted aortic arch. We present the diagnosis and initial surgical management of an infant with a fetal diagnosis of tricuspid atresia and common arterial trunk, with additional postnatal finding of interrupted aortic arch with interruption between the left common carotid and left subclavian artery. Due to the infant’s small size, she was initially palliated with bilateral pulmonary artery bands and a ductal stent. This was followed by septation of the common arterial trunk and interrupted aortic arch repair and 4 mm right subclavian artery to main pulmonary artery shunt placement at two months of age. She was discharged home on day of life 81.
An interatrial communication is present in most neonates. The majority are considered the “normal” patency of the oval foramen, while a minority are abnormal atrial septal defects. Differentiation between the two with transthoracic echocardiography may be challenging, and no generally accepted method of classification is presently available. We aimed to develop and determine the reliability of a new classification of interatrial communications in newborns.
Methods and Results:
An algorithm was developed based on echocardiographic criteria from 495 newborns (median age 11[8;13] days, 51.5% females). The algorithm defines three main categories: patency of the oval foramen, atrial septal defect, and no interatrial communication as well as several subtypes. We found an interatrial communication in 414 (83.6%) newborns. Of these, 386 (93.2%) were categorised as patency of the oval foramen and 28 (6.8%) as atrial septal defects.
Echocardiograms from another 50 newborns (median age 11[8;13] days, 36.0% female), reviewed by eight experts in paediatric echocardiography, were used to assess the inter- and intraobserver variation of classification of interatrial communications into patency of the oval foramen and atrial septal defect, with and without the use of the algorithm. Review with the algorithm gave a substantial interobserver agreement (kappa = 0.66), and an almost perfect intraobserver agreement (kappa = 0.82). Without the use of the algorithm, the interobserver agreement between experienced paediatric cardiologists was low (kappa = 0.20).
Conclusion:
A new algorithm for echocardiographic classification of interatrial communications in newborns produced almost perfect intraobserver and substantial interobserver agreement. The algorithm may prove useful in both research and clinical practice.
We honour a great man and a true giant. Lodewyk H.S. van Mierop (March 31, 1927 – October 17, 2021), known as Bob, was not only a Paediatric Cardiologist but also a dedicated Scientist. He made many significant and ground-breaking contributions to the fields of cardiac anatomy and embryology. He was devoted as a teacher, spending many hours with medical students, Residents, and Fellows, all of whom appreciated his regularly scheduled educational sessions. Those of us who were fortunate to know and spend time with him will always remember his great mind, his willingness to share his knowledge, and his ability to encourage spirited and fruitful discussions. His life was most productive, and he will long be remembered by many through his awesome and exemplary scientific contributions.
His legacy continues to influence the current and future generations of surgeons and all providers of paediatric and congenital cardiac care through the invaluable archive he established at University of Florida in Gainesville: The University of Florida van Mierop Heart Archive. Undoubtedly, with these extraordinary contributions to the fields of cardiac anatomy and embryology, which were way ahead of his time, Professor van Mierop was a true giant in Paediatric Cardiology. The invaluable archive he established at University of Florida in Gainesville, The University of Florida van Mierop Heart Archive, has been instrumental in teaching medical students, Residents, Medical Fellows, and Surgical Fellows. Only a handful of similar archives exist across the globe, and these archives are the true legacy of giants such as Dr. van Mierop. We have an important obligation to leave no stone unturned to continue to preserve these archives for the future generations of surgeons, physicians, all providers of paediatric and congenital cardiac care, and, most importantly, our patients.
Paediatric residents are often taught cardiac anatomy with two-dimensional images of heart specimens, or via imaging such as echocardiography or computed tomography. This study aimed to determine if the use of a structured, interactive, teaching session using heart specimens with CHD would be effective in teaching the concepts of cardiac anatomy.
Methods:
The interest amongst paediatric residents of a cardiac anatomy session using heart specimens was assessed initially by circulating a survey. Next, four major cardiac lesions were identified to be of interest: atrial septal defect, ventricular septal defect, tetralogy of Fallot, and transposition. A list of key structures and anatomic concepts for these lesions was developed, and appropriate specimens demonstrating these features were identified by a cardiac morphologist. A structured, interactive, teaching session was then held with the paediatric residents using the cardiac specimens. The same 10-question assessment was administered at the beginning and end of the session.
Results:
The initial survey demonstrated that all the paediatric residents had an interest in a cardiac anatomy teaching session. A total of 24 participated in the 2-hour session. The median pre-test score was 45%, compared to a median post-test score of 90% (p < 0.01). All paediatric residents who completed a post-session survey indicated that the session was a good use of educational time and contributed to increasing their knowledge base. They expressed great interest in future sessions.
Conclusion:
A 2-hour hands-on cardiac anatomy teaching session using cardiac specimens can successfully highlight key anatomic concepts for paediatric residents.
Monoclonal antibody therapeutics to treat coronavirus disease (COVID-19) have been authorized by the US Food and Drug Administration under Emergency Use Authorization (EUA). Many barriers exist when deploying a novel therapeutic during an ongoing pandemic, and it is critical to assess the needs of incorporating monoclonal antibody infusions into pandemic response activities. We examined the monoclonal antibody infusion site process during the COVID-19 pandemic and conducted a descriptive analysis using data from 3 sites at medical centers in the United States supported by the National Disaster Medical System. Monoclonal antibody implementation success factors included engagement with local medical providers, therapy batch preparation, placing the infusion center in proximity to emergency services, and creating procedures resilient to EUA changes. Infusion process challenges included confirming patient severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity, strained staff, scheduling, and pharmacy coordination. Infusion sites are effective when integrated into pre-existing pandemic response ecosystems and can be implemented with limited staff and physical resources.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Results
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
Conclusions
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
We report the strawberry blossom weevil, Anthonomus rubi (Herbst, 1795) (Coleoptera: Curculionidae), a species native to Europe, Asia, and North Africa, as established in British Columbia, Canada. This is the first report of A. rubi in North America. We provide a diagnosis of the species and compare it with other species of the genus Anthonomus Germar in Canada. This species is a pest of plants in Rosaceae Jussieu, including economically important berries such as strawberries (Fragaria Linnaeus) and raspberries (Rubus idaeus Linnaeus), and of native berries of importance to Indigenous peoples in Canada. Female weevils oviposit eggs inside developing flower buds and sever flower stalks, facilitating larval development inside damaged buds and thus reducing fruit yields. Surveys to confirm the presence of A. rubi conducted in 2020 found the weevil to be well established in cultivated and wild hosts throughout the Greater Vancouver area and Fraser Valley, British Columbia. At least one species of parasitoid wasp in the genus Pteromalus Swederus (Hymenoptera: Pteromalidae) has been found in association with A. rubi in the province. Future investigations are required to understand the biology of A. rubi in its new range, assess its impact on berries, and develop management strategies.
Balloon valvuloplasty and surgical aortic valvotomy have been the treatment mainstays for congenital aortic stenosis in children. Choice of intervention often differs depending upon centre bias with limited relevant, comparative literature.
Objectives:
This study aims to provide an unbiased, contemporary matched comparison of these balloon and surgical approaches.
Methods:
Retrospective analysis of patients with congenital aortic valve stenosis who underwent balloon valvuloplasty (Queensland Children’s Hospital, Brisbane) or surgical valvotomy (Royal Children’s Hospital, Melbourne) between 2005 and 2016. Patients were excluded if pre-intervention assessment indicated ineligibility to either group. Propensity score matching was performed based on age, weight, and valve morphology.
Results:
Sixty-five balloon patients and seventy-seven surgical patients were included. Overall, the groups were well matched with 18 neonates/25 infants in the balloon group and 17 neonates/28 infants in the surgical group. Median age at balloon was 92 days (range 2 days – 18.8 years) compared to 167 days (range 0 days – 18.1 years) for surgery (rank-sum p = 0.08). Mean follow-up was 5.3 years. There was one late balloon death and two early surgical deaths due to left ventricular failure. There was no significant difference in freedom from reintervention at latest follow-up (69% in the balloon group and 70% in the surgical group, p = 1.0).
Conclusions:
Contemporary analysis of balloon aortic valvuloplasty and surgical aortic valvotomy shows no difference in overall reintervention rates in the medium term. Balloon valvuloplasty performs well across all age groups, achieving delay or avoidance of surgical intervention.
In this paper, we describe the system design and capabilities of the Australian Square Kilometre Array Pathfinder (ASKAP) radio telescope at the conclusion of its construction project and commencement of science operations. ASKAP is one of the first radio telescopes to deploy phased array feed (PAF) technology on a large scale, giving it an instantaneous field of view that covers $31\,\textrm{deg}^{2}$ at $800\,\textrm{MHz}$. As a two-dimensional array of 36$\times$12 m antennas, with baselines ranging from 22 m to 6 km, ASKAP also has excellent snapshot imaging capability and 10 arcsec resolution. This, combined with 288 MHz of instantaneous bandwidth and a unique third axis of rotation on each antenna, gives ASKAP the capability to create high dynamic range images of large sky areas very quickly. It is an excellent telescope for surveys between 700 and $1800\,\textrm{MHz}$ and is expected to facilitate great advances in our understanding of galaxy formation, cosmology, and radio transients while opening new parameter space for discovery of the unknown.
Manuscripts pertaining to paediatric cardiology and CHD have been published in a variety of different journals. Some of these journals are journals dedicated to paediatric cardiology, while others are focused on adult cardiology. Historically, it has been considered that manuscripts published in journals devoted to adult cardiology have greater citation potential. Our objective was to compare citation performance between manuscripts related to paediatric cardiology and CHD published in paediatric as opposed to adult cardiology journals.
Methods:
We identified manuscripts related to paediatric cardiology and CHD published in five journals of interest during 2014. Of these journals, two were primarily concerned with adult cardiology, while the other three focused on paediatric cardiology. The number of citations for these identified manuscripts was gathered from Google Scholar. We compared the number of citations (median, mean, and 25th, 75th, 90th, and 95th percentiles), the potential for citation, and the h-index for the identified manuscripts.
Results:
We identified a total of 828 manuscripts related to paediatric cardiology and congenital heart as published in the 5 journals during 2014. Of these, 783 (95%) were published in journals focused on paediatric cardiology, and the remaining 45 (5%) were published in journals focused on adult cardiology. The median number of citations was 41 in the manuscripts published in the journals focused on adult cardiology, as opposed to 7 in journals focused on paediatric cardiology (p < 0.001). The h-index, however, was greater for the journals dedicated to paediatric cardiology (36 versus 27).
Conclusion:
Approximately one-twentieth of the work relating to paediatric cardiology and CHD is published in journals that focus predominantly on adult cardiology. The median number of citations is greater when manuscripts concerning paediatric cardiology and CHD are published in these journals focused on adult cardiology. The h-index, however, is higher when the manuscripts are published in journals dedicated to paediatric cardiology. While such publications in journals that focus on adult cardiology tend to generate a greater number of citations than those achieved for works published in specialised paediatric cardiology journals, the potential for citation is no different between the journals. Due to the drastically lower number of manuscripts published in journals dedicated to adult cardiology, however, median performance is different.
Glacier basal motion is responsible for the majority of ice flux on fast-flowing glaciers, enables rapid changes in glacier motion and provides the means by which glaciers shape alpine landscapes. In an effort to enhance our understanding of basal motion, we investigate the evolution of glacier velocity and ice-marginal lake stage on Kennicott Glacier, Alaska, during the spring–summer transition, a time when subglacial drainage is undergoing rapid change. A complicated record of > 50 m fill-and-drain sequences on a hydraulically-connected ice-marginal lake likely reflects the punctuated establishment of efficient subglacial drainage as the melt season begins. The rate of change of lake stage generally correlates with diurnal velocity maxima, both in timing and magnitude. At the seasonal scale, the up-glacier progression of enhanced summer basal motion promotes uniformity of daily glacier velocity fluctuations throughout the 10 km study reach, and results in diurnal velocity patterns suggesting increasingly efficient meltwater delivery to and drainage from the subglacial channel system. Our findings suggest the potential of using an ice-marginal lake as a proxy for subglacial water pressure, and show how widespread basal motion affects bulk glacier behavior.
Cardiac Fibromas are primary cardiac tumours more common in children than in adults. Surgical intervention is often not required except in the case of limited cardiac output or significant arrhythmia burden. We present a symptomatic 3-month-old infant who had successful surgical intervention for a giant right ventricle fibroma found on prenatal imaging.
To evaluate long-term efficacy of deutetrabenazine in patients with tardive dyskinesia (TD) by examining response rates from baseline in Abnormal Involuntary Movement Scale (AIMS) scores. Preliminary results of the responder analysis are reported in this analysis.
Background
In the 12-week ARM-TD and AIM-TD studies, the odds of response to deutetrabenazine treatment were higher than the odds of response to placebo at all response levels, and there were low rates of overall adverse events and discontinuations associated with deutetrabenazine.
Method
Patients with TD who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12mg/day, titrating up to a maximum total daily dose of 48mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration and a long-term maintenance phase. The cumulative proportion of AIMS responders from baseline was assessed. Response was defined as a percent improvement from baseline for each patient from 10% to 90% in 10% increments. AlMS score was assessed by local site ratings for this analysis.
Results
343 patients enrolled in the extension study (111 patients received placebo in the parent study and 232 patients received deutetrabenazine). At Week 54 (n=145; total daily dose [mean±standard error]: 38.1±0.9mg), 63% of patients receiving deutetrabenazine achieved ≥30% response, 48% of patients achieved ≥50% response, and 26% achieved ≥70% response. At Week 80 (n=66; total daily dose: 38.6±1.1mg), 76% of patients achieved ≥30% response, 59% of patients achieved ≥50% response, and 36% achieved ≥70% response. Treatment was generally well tolerated.
Conclusions
Patients who received long-term treatment with deutetrabenazine achieved response rates higher than those observed in positive short-term studies, indicating clinically meaningful long-term treatment benefit.
Presented at: American Academy of Neurology Annual Meeting; April 21–27, 2018, Los Angeles, California, USA.
Funding Acknowledgements: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel.
To evaluate the long-term safety and tolerability of deutetrabenazine in patients with tardive dyskinesia (TD) at 2years.
Background
In the 12-week ARM-TD and AIM-TD studies, deutetrabenazine showed clinically significant improvements in Abnormal Involuntary Movement Scale scores compared with placebo, and there were low rates of overall adverse events (AEs) and discontinuations associated with deutetrabenazine.
Method
Patients who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12mg/day, titrating up to a maximum total daily dose of 48mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration period and a long-term maintenance phase. Safety measures included incidence of AEs, serious AEs (SAEs), and AEs leading to withdrawal, dose reduction, or dose suspension. Exposure-adjusted incidence rates (EAIRs; incidence/patient-years) were used to compare AE frequencies for long-term treatment with those for short-term treatment (ARM-TD and AIM-TD). This analysis reports results up to 2 years (Week106).
Results
343 patients were enrolled (111 patients received placebo in the parent study and 232 received deutetrabenazine). There were 331.4 patient-years of exposure in this analysis. Through Week 106, EAIRs of AEs were comparable to or lower than those observed with short-term deutetrabenazine and placebo, including AEs of interest (akathisia/restlessness [long-term EAIR: 0.02; short-term EAIR range: 0–0.25], anxiety [0.09; 0.13–0.21], depression [0.09; 0.04–0.13], diarrhea [0.06; 0.06–0.34], parkinsonism [0.01; 0–0.08], somnolence/sedation [0.09; 0.06–0.81], and suicidality [0.02; 0–0.13]). The frequency of SAEs (EAIR 0.15) was similar to those observed with short-term placebo (0.33) and deutetrabenazine (range 0.06–0.33) treatment. AEs leading to withdrawal (0.08), dose reduction (0.17), and dose suspension (0.06) were uncommon.
Conclusions
These results confirm the safety outcomes seen in the ARM-TD and AIM-TD parent studies, demonstrating that deutetrabenazine is well tolerated for long-term use in TD patients.
Presented at: American Academy of Neurology Annual Meeting; April 21–27, 2018, Los Angeles, California,USA
Funding Acknowledgements: Funding: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel
Aortic arch anomalies are rare congenital cardiovascular malformations. We present a case of a 9-year-old asymptomatic boy with an unusual, unknown arch anomaly.
Vegetable and grain amaranths represent a vital source of micronutrients and protein in Asia and Africa. However, various foliar lepidopteran pests and stem-mining weevils hinder amaranth production. Insect-resistant cultivars can enhance the productivity of this crop. Here, we report on the performances of amaranth varieties screened for their resistance to insect pests under the field conditions at The World Vegetable Center stations in Asia and sub-Saharan Africa. We conducted two preliminary screening trials with a total of 263 entries from around the world in Taiwan and a third preliminary screening trial with 49 African-indigenous entries in Tanzania. Promising entries from these preliminary trials were collectively evaluated in an advanced screening trial in Tanzania, to identify lines resistant to foliar and stem-boring pests in East Africa. Four entries exhibited moderate resistance to foliar pests: TZ51 and TZ53 (Amaranthus cruentus), TZ34 (A. dubius) and TZ39 (Amaranthus sp.). Five entries showed moderate resistance to stem weevils: TZ06 and TZ27 (A. cruentus), TZ52 (A. graecizans), TZ59 (A. palmeri) and TZ07 (Amaranthus sp.). Lepidopteran pests affecting leaves were reared to adulthood and identified as Spoladea recurvalis (Crambidae), Spodoptera exigua (Noctuidae) and Spodoptera littoralis (Noctuidae). Stem weevil larvae were also reared and identified as: Neocleonus sannio Herbst, Gasteroclisus pr. rhomboidalis Boheman, Hypolixus pr. haerens Boheman and Baradine sp. (Curculionidae). These results highlight key amaranth pests in East Africa and identify insect-resistant entries that will be useful in breeding programmes and resistance studies.
OBJECTIVES/SPECIFIC AIMS: More partial nephrectomies are performed every year as a surgical treatment for kidney cancer. However, this procedure remains technically challenging. Surgeons require a substantial number of cases before their performance plateaus. No established practice mode exists; thus, there is a need for training models to simulate real tumor excisions and kidney suturing. In this study, we seek to validate these silicone models using multiple simulations with urologists of different training levels. METHODS/STUDY POPULATION: We created silicone renal tumor models using 3D printed molds of a patient’s kidney with a mass. Medical students, urology residents, fellows, and attending surgeons are recruited to perform simulated partial nephrectomies on these models. Four trials are performed with a da Vinci surgical robot on 2 different days. We are evaluating surgeon performance and improvement using validated measures as well as operation-specific metrics. Operation-specific metrics include renal artery clamp time and surgical margins. Validated measures of self-assessed operative demand (NASA TLX) and reviewer-assessed surgical performance (GEARS) are also recorded across trials. RESULTS/ANTICIPATED RESULTS: The preliminary results of 2 medical students, 10 urology residents, 3 endourology fellows, and 2 attending urologists are reported here. Model face validity was evaluated on a 0–100 sliding scale anchored at unrealistic and realistic. Mean results thus far are 77.7 for overall feel, 82.7 for needle driving, 75.6 for cutting, and 73.2 for visual representation. Between trials 1 and 4 there was a mean reduction of 3.26 minutes in renal artery clamp time, and a 75% reduction in positive margins. There was a reduced incidence of positive surgical margins with advanced training stage. Fellows, residents, and medical students had positive tumor margins in 25%, 50%, and 75% of their trials, respectively. We expect to recruit 15 additional subjects for this study. Upon completion of data acquisition, more robust statistical comparisons and measures will be reported. DISCUSSION/SIGNIFICANCE OF IMPACT: Face validity measures indicate the model adequately represents reality. Preliminary data suggest improved surgical performance over the course of the training and better performance in urologists of higher training levels. This model may have potential for broader application and integration into minimally invasive surgery training programs.