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Nordic twin studies have played a critical role in understanding cancer etiology and elucidating the nature of familial effects on site-specific cancers. The NorTwinCan consortium is a collaborative effort that capitalizes on unique research advantages made possible through the Nordic system of registries. It was constructed by linking the population-based twin registries of Denmark, Finland, Norway and Sweden to their country-specific national cancer and cause-of-death registries. These linkages enable the twins to be followed many decades for cancer incidence and mortality. To date, two major linkages have been conducted: NorTwinCan I in 2011–2012 and NorTwinCan II in 2018. Overall, there are 315,413 eligible twins, 57,236 incident cancer cases and 58 years of follow-up, on average. In the initial phases of our work, NorTwinCan established the world’s most comprehensive twin database for studying cancer, developed novel analytical approaches tailored to address specific research considerations within the context of the Nordic data and leveraged these models and data in research publications that provide the most accurate estimates of heritability and familial risk of cancers reported in the literature to date. Our findings indicate an excess familial risk for nearly all cancers and demonstrate that the incidence of cancer among twins mirrors the rate in the general population. They also revealed that twin concordance for cancer most often manifests across, rather than within, cancer sites, and we are currently focusing on the analysis of these cross-cancer associations.
The interfacial behaviour of surfactant-laden drops squeezing through tight constrictions in a uniform far-field flow is modelled with respect to capillary number, drop-to-medium viscosity ratio and surfactant contamination. The surfactant is treated as insoluble and non-diffusive, and drop surface tension is related to surfactant concentration by a linear equation of state. The constriction is formed by three solid spheres held rigidly in space. A characteristic aspect of this confined and contaminated multiphase system is the rapid development of steep surfactant-concentration gradients during the onset of drop squeezing. The interplay between two physical effects of surfactant, namely the greater interface deformability due to decreased surface tension and interface immobilization due to Marangoni stresses, results in particularly rich drop-squeezing dynamics. A three-dimensional boundary-integral algorithm is used to describe drop hydrodynamics, and accurate treatment of close squeezing and trapped states is enabled by advanced singularity subtraction techniques. Surfactant transport and hydrodynamics are coupled via the surface convection equation (or convection–diffusion equation, if artificial diffusion is included), the interfacial stress balance and a solid-particle contribution based on the Hebeker representation. For extreme conditions, such as drop-to-medium viscosity ratios significantly less than unity, it is found that upwind-biased methods are the only stable approaches for modelling surfactant transport. Two distinct schemes, upwind finite volume and flow-biased least squares, are found to provide results in close agreement, indicating negligible numerical diffusion. Surfactant transport is enhanced by low drop-to-medium viscosity ratios, at which extremely sharp concentration gradients form during various stages of the squeezing process. The presence of surfactant, even at low degrees of contamination, significantly decreases the critical capillary number for droplet trapping, due to the accumulation of surfactant at the downwind pole of the drop and its subsequent elongation. Increasing the degree of contamination significantly affects surface mobility and further decreases the critical capillary number as well as drop squeezing times, up to a threshold above which the addition of surfactant negligibly affects squeezing dynamics.
To develop a physiological data-driven model for early identification of impending cardiac arrest in neonates and infants with cardiac disease hospitalised in the cardiovascular ICU.
We performed a single-institution retrospective cohort study (11 January 2013–16 September 2015) of patients ≤1 year old with cardiac disease who were hospitalised in the cardiovascular ICU at a tertiary care children’s hospital. Demographics and diagnostic codes of cardiac arrest were obtained via the electronic health record. Diagnosis of cardiac arrest was validated by expert clinician review. Minute-to-minute physiological monitoring data were recorded via bedside monitors. A generalized linear model was used to compute a minute by minute risk score. Training and test data sets both included data from patients who did and did not develop cardiac arrest. An optimal risk-score threshold was derived based on the model’s discriminatory capacity for impending arrest versus non-arrest. Model performance measures included sensitivity, specificity, accuracy, likelihood ratios, and post-test probability of arrest.
The final model consisting of multiple clinical parameters was able to identify impending cardiac arrest at least 2 hours prior to the event with an overall accuracy of 75% (sensitivity = 61%, specificity = 80%) and observed an increase in probability of detection of cardiac arrest from a pre-test probability of 9.6% to a post-test probability of 21.2%.
Our findings demonstrate that a predictive model using physiologic monitoring data in neonates and infants with cardiac disease hospitalised in the paediatric cardiovascular ICU can identify impending cardiac arrest on average 17 hours prior to arrest.
Recent years have seen an exponential increase in the variety of healthcare data captured across numerous sources. However, mechanisms to leverage these data sources to support scientific investigation have remained limited. In 2013 the Pediatric Heart Network (PHN), funded by the National Heart, Lung, and Blood Institute, developed the Integrated CARdiac Data and Outcomes (iCARD) Collaborative with the goals of leveraging available data sources to aid in efficiently planning and conducting PHN studies; supporting integration of PHN data with other sources to foster novel research otherwise not possible; and mentoring young investigators in these areas. This review describes lessons learned through the development of iCARD, initial efforts and scientific output, challenges, and future directions. This information can aid in the use and optimisation of data integration methodologies across other research networks and organisations.
Angiostrongylus cantonensis is a pathogenic nematode and the cause of neuroangiostrongyliasis, an eosinophilic meningitis more commonly known as rat lungworm disease. Transmission is thought to be primarily due to ingestion of infective third stage larvae (L3) in gastropods, on produce, or in contaminated water. The gold standard to determine the effects of physical and chemical treatments on the infectivity of A. cantonensis L3 larvae is to infect rodents with treated L3 larvae and monitor for infection, but animal studies are laborious and expensive and also raise ethical concerns. This study demonstrates propidium iodide (PI) to be a reliable marker of parasite death and loss of infective potential without adversely affecting the development and future reproduction of live A. cantonensis larvae. PI staining allows evaluation of the efficacy of test substances in vitro, an improvement upon the use of lack of motility as an indicator of death. Some potential applications of this assay include determining the effectiveness of various anthelmintics, vegetable washes, electromagnetic radiation and other treatments intended to kill larvae in the prevention and treatment of neuroangiostrongyliasis.
To evaluate the association between novel pre- and post-operative biomarker levels and 30-day unplanned readmission or mortality after paediatric congenital heart surgery.
Children aged 18 years or younger undergoing congenital heart surgery (n = 162) at Johns Hopkins Hospital from 2010 to 2014 were enrolled in the prospective cohort. Collected novel pre- and post-operative biomarkers include soluble suppression of tumorgenicity 2, galectin-3, N-terminal prohormone of brain natriuretic peptide, and glial fibrillary acidic protein. A model based on clinical variables from the Society of Thoracic Surgery database was developed and evaluated against two augmented models.
Unplanned readmission or mortality within 30 days of cardiac surgery occurred among 21 (13%) children. The clinical model augmented with pre-operative biomarkers demonstrated a statistically significant improvement over the clinical model alone with a receiver-operating characteristics curve of 0.754 (95% confidence interval: 0.65–0.86) compared to 0.617 (95% confidence interval: 0.47–0.76; p-value: 0.012). The clinical model augmented with pre- and post-operative biomarkers demonstrated a significant improvement over the clinical model alone, with a receiver-operating characteristics curve of 0.802 (95% confidence interval: 0.72–0.89; p-value: 0.003).
Novel biomarkers add significant predictive value when assessing the likelihood of unplanned readmission or mortality after paediatric congenital heart surgery. Further exploration of the utility of these novel biomarkers during the pre- or post-operative period to identify early risk of mortality or readmission will aid in determining the clinical utility and application of these biomarkers into routine risk assessment.
Major transitions in trilobite ontogeny have historically been defined based on the number and distribution of trunk segments, and articulation between the trunk and cephalon. This study documents additional morphological change across the meraspid-holaspid transition on the Ordovician phacopid trilobite Calyptaulax strasburgensis. An extensive dataset of silicified cranidia and pygidia collected from the mid-Ordovician Edinburg Formation of Virginia was subjected to a series of multivariate analyses, with a primary focus on the intersections and termini of furrows. Multivariate regression of partial warp scores demonstrates statistically significant change in allometric growth patterns over the course of development. These changes are concentrated in earlier instars, but are coincident in cranidia and pygidia. This sharp decrease in the rate of allometry, present in both tagmata, is expressed as significant breakpoints derived from a segmented regression, with the largest portion of allometric change found in the pre-breakpoint individuals. The term holeidos is proposed to describe the completion of form during trilobite development, independent of the completion of the thorax. The most dramatic change in shape during this period of ontogeny includes lateral glabellar expansion through deflection of the axial and palpebral furrows, possibly reflecting a change in the feeding habit during later development. Other morphological changes include the development of a more angular appearance to the anterior portion of the glabella, and anterior migration of the pygidial anterior margin. The appearance of these growth patterns in Calyptaulax extends the temporal range of these changes, some of which have only been documented in Devonian phacopids.
Using existing data from clinical registries to support clinical trials and other prospective studies has the potential to improve research efficiency. However, little has been reported about staff experiences and lessons learned from implementation of this method in pediatric cardiology.
We describe the process of using existing registry data in the Pediatric Heart Network Residual Lesion Score Study, report stakeholders’ perspectives, and provide recommendations to guide future studies using this methodology.
The Residual Lesion Score Study, a 17-site prospective, observational study, piloted the use of existing local surgical registry data (collected for submission to the Society of Thoracic Surgeons-Congenital Heart Surgery Database) to supplement manual data collection. A survey regarding processes and perceptions was administered to study site and data coordinating center staff.
Survey response rate was 98% (54/55). Overall, 57% perceived that using registry data saved research staff time in the current study, and 74% perceived that it would save time in future studies; 55% noted significant upfront time in developing a methodology for extracting registry data. Survey recommendations included simplifying data extraction processes and tailoring to the needs of the study, understanding registry characteristics to maximise data quality and security, and involving all stakeholders in design and implementation processes.
Use of existing registry data was perceived to save time and promote efficiency. Consideration must be given to the upfront investment of time and resources needed. Ongoing efforts focussed on automating and centralising data management may aid in further optimising this methodology for future studies.
Background: Cervical sponylotic myelopathy (CSM) may present with neck and arm pain. This study investiagtes the change in neck/arm pain post-operatively in CSM. Methods: This ambispective study llocated 402 patients through the Canadian Spine Outcomes and Research Network. Outcome measures were the visual analogue scales for neck and arm pain (VAS-NP and VAS-AP) and the neck disability index (NDI). The thresholds for minimum clinically important differences (MCIDs) for VAS-NP and VAS-AP were determined to be 2.6 and 4.1. Results: VAS-NP improved from mean of 5.6±2.9 to 3.8±2.7 at 12 months (P<0.001). VAS-AP improved from 5.8±2.9 to 3.5±3.0 at 12 months (P<0.001). The MCIDs for VAS-NP and VAS-AP were also reached at 12 months. Based on the NDI, patients were grouped into those with mild pain/no pain (33%) versus moderate/severe pain (67%). At 3 months, a significantly high proportion of patients with moderate/severe pain (45.8%) demonstrated an improvement into mild/no pain, whereas 27.2% with mild/no pain demonstrated worsening into moderate/severe pain (P <0.001). At 12 months, 17.4% with mild/no pain experienced worsening of their NDI (P<0.001). Conclusions: This study suggests that neck and arm pain responds to surgical decompression in patients with CSM and reaches the MCIDs for VAS-AP and VAS-NP at 12 months.
Background: In preparation for July 2019 rollout of competency-based design (CBD) in Canadian neurosurgery residency training, the University of Calgary launched a pilot-program of five representative EPAs using the One45 program. Our study objectives were to examine the uptake of CBD with residents and faculty and to quantify CBD implementation barriers. Methods: Phase one of the One45-based CBD pilot-program launched on November 1st, 2018 and ended on January 8th, 2019, after which a questionnaire was sent to each participating resident. The questionnaire examined number of EPAs initiated, measures of favourability, importance, ease of use, and barriers encountered. Results: Results obtained from the survey show 93.8% response rate (15/16 residents). 66.7% of residents feel that CBD is moderately important or higher to their education. Over the 10 study weeks, there were only 8 completed EPAs (expected was 50), five of which were completed by a single resident. Major expressed barriers of implementation of CBD were time involved (50.0%) and technical unfamiliarity with the platform itself (50.0%). Conclusions: This study demonstrates the critical importance of piloting a CBD program prior to official implementation as immediate buy-in was significantly slower than anticipated. Technical and time barriers exist which need to be rectified in advance of July 2019.
This study examined the intermediate role job satisfaction and organizational commitment play between leaders' perceived use of power and followers' performance. Based on a sample of 365 cadets at the U.S. Air Force Academy, this study found followers' job satisfaction and commitment mediated the positive relationships between their leaders' use of expert, referent, and reward power and the followers' organizational citizenship behavior. Further, while the use of legitimate or coercive power were both related negatively to followers' in-role job performance, these relationships were not mediated by the followers' job satisfaction or organizational commitment. This study then discusses the practical implications of these findings, highlights its theoretical contributions toward understanding power's direct and indirect relationships with performance in the leadership dynamic, and recommends future research avenues to leverage and build upon these findings.
The Nordic countries have comprehensive, population-based health and medical registries linkable on individually unique personal identity codes, enabling complete long-term follow-up. The aims of this study were to describe the NorTwinCan cohort established in 2010 and assess whether the cancer mortality and incidence rates among Nordic twins are similar to those in the general population. We analyzed approximately 260,000 same-sexed twins in the nationwide twin registers in Denmark, Finland, Norway and Sweden. Cancer incidence was determined using follow-up through the national cancer registries. We estimated standardized incidence (SIR) and mortality (SMR) ratios with 95% confidence intervals (CI) across country, age, period, follow-up time, sex and zygosity. More than 30,000 malignant neoplasms have occurred among the twins through 2010. Mortality rates among twins were slightly lower than in the general population (SMR 0.96; CI 95% [0.95, 0.97]), but this depends on information about zygosity. Twins have slightly lower cancer incidence rates than the general population, with SIRs of 0.97 (95% CI [0.96, 0.99]) in men and 0.96 (95% CI [0.94, 0.97]) in women. Testicular cancer occurs more often among male twins than singletons (SIR 1.15; 95% CI [1.02, 1.30]), while cancers of the kidney (SIR 0.82; 95% CI [0.76, 0.89]), lung (SIR 0.89; 95% CI [0.85, 0.92]) and colon (SIR 0.90; 95% CI [0.87, 0.94]) occur less often in twins than in the background population. Our findings indicate that the risk of cancer among twins is so similar to the general population that cancer risk factors and estimates of heritability derived from the Nordic twin registers are generalizable to the background populations.