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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.
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.
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.
Horseweed is a problematic weed to control, especially in no-tillage production. Increasing cases of herbicide resistance have exacerbated the problem, necessitating alternative control options and an integrated weed management approach. Field experiments were conducted to evaluate horseweed suppression from fall-planted cover crop monocultures and mixtures as well as two fall-applied residual herbicide treatments. Prior to cover crop termination, horseweed density was reduced by 88% to 96% from cover crops. At cover crop termination in late spring, cereal rye biomass was 7,671 kg ha–1, which was similar to cereal rye–containing mixtures (7,720 kg ha–1) but greater than legumes in monoculture (3,335 kg ha–1). After cover crops were terminated in late spring using a roller crimper, corn and soybeans were planted and horseweed was evaluated using density counts, visible ratings, and biomass collection until harvest. Forage radish winterkilled, offering no competition in late winter or biomass to contribute to horseweed suppression after termination. Excluding forage radish in monoculture, no difference in horseweed suppression was detected between cereal rye–containing cover crops and legumes (crimson clover and hairy vetch) in monoculture. Likewise, horseweed suppression was similar between monocultures and mixtures, with the exception of one site-year in which mixtures provided better suppression. In this experiment, the cover crop treatments performed as well as or better than the fall-applied residual herbicides, flumioxazin+paraquat and metribuzin+chlorimuron-ethyl. These results indicate that fall-planted cover crops are a viable option to suppress horseweed and can be an effective part of an integrated weed management program. Furthermore, cover crop mixtures can be used to gain the benefits of legume or brassica cover crop species without sacrificing horseweed suppression.
OBJECTIVES/SPECIFIC AIMS: The purpose of the study was to describe patient characteristics associated with subsequent development of bowel ischemia. Primary outcomes were survival to discharge, 30-day and 1-year survival in patients with LVAD who subsequently develop bowel ischemia. Secondary outcomes included characteristics of patients who survive to discharge after bowel ischemia and those who do not. These included markers of patient condition prior to surgical/endoscopic intervention such as lactate levels, ICU admission, ventilator dependence, vasopressor and renal replacement requirements, as well as presence of sepsis. Of these, we predicted that lactate levels and white blood cell count would be significantly elevated pre- and post-operatively in patients who do not recover from bowel ischemic event. We used Mann-Whitney U Test to examine lactate levels between the two groups as our sample size was <30 and therefore necessitated the use of non-parametric testing. METHODS/STUDY POPULATION: In this single-center retrospective study, we analyzed all patients who underwent durable, CF-LVAD implantation at Duke University Medical Center (DUMC) between January 2008 and November 2018. Patients were screened using CPT codes for abdominal surgical exploration or ICD codes for intestinal vascular insufficiency. Final cohort was selected with confirmed diagnosis of intestinal ischemia based on surgical exploration or endoscopic intervention. Patient characteristics including pre-LVAD comorbidities, indication for LVAD implant, and clinical picture prior to bowel ischemic event were collected. Specific characteristics related to bowel ischemia were summarized, including diagnostic imaging, time from imaging study to operative intervention, and intraoperative details. Patient outcomes including survival to discharge, 30-day-, and 1-year survival were summarized. Patients were stratified based on survival to discharge status. Continuous variables were reported as median and interquartile range and compared using Mann-Whitney U test. Categorical variables were reported as proportions and compared using Fisher’s exact test as appropriate. RESULTS/ANTICIPATED RESULTS: A total of 754 patients underwent durable, CF-LVAD implant at DUMC, of which 21 subsequently developed intestinal ischemia (incidence 2.8%). The majority were male (81%) and treated as destination therapy (76.2%). Ten patients (50%) survived to discharge (one remains hospitalized). The proportions of patients receiving HeartMate II (60% vs. 50%, p=1.0), HeartMate III (20% vs. 10%, p=1.0), and HeartWare (20% vs. 40%, p=0.6) were not significantly different between patients who survived to discharge and patients who did not. Median time from LVAD implant to diagnosis of bowel ischemia did not vary significantly between the patient groups (11.5 days, IQR 34.75 vs. 16.5 days, IQR 173.8; p=0.40), nor did the median time from diagnosis to surgical intervention (264.5 minutes, IQR 497.8 vs. 323 minutes, IQR 440, p=0.82). In the 48 hours leading to diagnosis and intervention, renal replacement therapy (50% vs. 0%, p=0.033) was more prevalent in patients who did not survive to discharge. Differences in pre- and post-operative lactate levels were not significantly different in patient groups. A similar pattern of diagnostic study preference emerged from both groups, with CT being the most common (76.2%) followed by KUB (42.9%). Upper endoscopy/colonoscopy was performed in 7 patients (33.3%), of which 5 also had operative exploration. A total of 19 patients underwent abdominal exploration (90.5%). Nine had large bowel resection (42.9%) while 14 had small bowel resection (66.7% with average 75cm removed). Overall survival at 1-year was 33%. For those making it to discharge (n=10), one year survival was 60%. DISCUSSION/SIGNIFICANCE OF IMPACT: This is the first institutional study to our knowledge to describe intestinal ischemia in patients receiving CF-LVAD therapy. Intestinal ischemia in patients receiving CF-LVAD therapy is associated with high mortality and morbidity. Diagnosis of bowel ischemia should be considered in patients presenting with clinical symptoms of bowel ischemia in addition to requirement of renal replacement therapy. Imaging modalities used were dependent on the clinical situation and were not always necessary prior to intervention. Further investigation is warranted to identify predictors of this morbid complication.
Biological invasions are one of the grand challenges facing society, as exotic species introductions continue to rise and can result in dramatic changes to native ecosystems and economies. The scale of the “biological invasions crisis” spans from hyperlocal to international, involving a myriad of actors focused on mitigating and preventing biological invasions. However, the level of engagement among stakeholders and opportunities to collaboratively solve invasives issues in transdisciplinary ways is poorly understood. The Biological Invasions: Confronting a Crisis workshop engaged a broad group of actors working on various aspects of biological invasions in Virginia, USA—researchers, Extension personnel, educators, local, state, and federal agencies, nongovernmental organizations, and land managers—to discuss their respective roles and how they interact with other groups. Through a series of activities, it became clear that despite shared goals, most groups are not engaging with one another, and that enhanced communication and collaboration among groups is key to designing effective solutions. There is strong support for a multistakeholder coalition to affect change in policy, public education/engagement, and solution design. Confronting the biological invasions crisis will increasingly require engagement among stakeholders.
Historians and some scholars of international relations have long argued that historical contingencies play a critical role in the evolution of the international system, but have not explained whether they do so to a greater extent than in other domains or why such differences may exist. The authors address these lacunae by identifying stable differences between war and other policy domains that render the evolution of the international system more subject to chance events than those other domains. The selection environment of international politics has produced tightly integrated organizations (militaries) as the domain’s key players to a much greater degree than other policy domains. Because there are few players, no law of large numbers holds, and because militaries are tightly integrated, microshocks can reverberate up to macro-organizational levels. The anarchic character of the international system amplifies the impact of these shocks. The authors explore these phenomena in a range of historical examples.
Optimising short- and long-term outcomes for children and patients with CHD depends on continued scientific discovery and translation to clinical improvements in a coordinated effort by multiple stakeholders. Several challenges remain for clinicians, researchers, administrators, patients, and families seeking continuous scientific and clinical advancements in the field. We describe a new integrated research and improvement network – Cardiac Networks United – that seeks to build upon the experience and success achieved to-date to create a new infrastructure for research and quality improvement that will serve the needs of the paediatric and congenital heart community in the future. Existing gaps in data integration and barriers to improvement are described, along with the mission and vision, organisational structure, and early objectives of Cardiac Networks United. Finally, representatives of key stakeholder groups – heart centre executives, research leaders, learning health system experts, and parent advocates – offer their perspectives on the need for this new collaborative effort.
Subglacial hydrology plays a key role in many glaciological processes, including ice dynamics via the modulation of basal sliding. Owing to the lack of an overarching theory, however, a variety of model approximations exist to represent the subglacial drainage system. The Subglacial Hydrology Model Intercomparison Project (SHMIP) provides a set of synthetic experiments to compare existing and future models. We present the results from 13 participating models with a focus on effective pressure and discharge. For many applications (e.g. steady states and annual variations, low input scenarios) a simple model, such as an inefficient-system-only model, a flowline or lumped model, or a porous-layer model provides results comparable to those of more complex models. However, when studying short term (e.g. diurnal) variations of the water pressure, the use of a two-dimensional model incorporating physical representations of both efficient and inefficient drainage systems yields results that are significantly different from those of simpler models and should be preferentially applied. The results also emphasise the role of water storage in the response of water pressure to transient recharge. Finally, we find that the localisation of moulins has a limited impact except in regions of sparse moulin density.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
The Appalachian region of the United States is home to the largest temperate deciduous forest in the world, though surface mining has caused significant forest loss. Many former coal mines are now dominated by invasive plants, which often inhibit establishment of desirable species, especially slower-growing native trees. Autumn-olive (Elaeagnus umbellata Thunb.) is a nonnative, nitrogen-fixing shrub that was historically planted on former coalfields, but now impedes reclamation. To better understand the influence of E. umbellata management practices on hardwood establishment, we evaluated two common management practices: cutting and cut stump herbicide treatment. Planted native tree species, including black cherry (Prunus serotina Ehrh.), pin oak (Quercus palustris Münchh.), and red maple (Acer rubrum L.), were monitored for survival and performance over two growing seasons following E. umbellata removal. In each plot, we also measured plant-available nitrate (NO3−) and ammonium (NH4+) in soils using ionic exchange membranes. At the end of the first growing season, native tree survival was high, and the presence or absence of E. umbellata had little effect on tree survival or growth, despite the higher plant-available nitrate where E. umbellata was present. By the end of the second growing season, native tree survival dropped to 20% to 60% and varied among E. umbellata treatments. Survival was highest when E. umbellata was cut and treated with herbicide, though tree growth was similar across all treatments without E. umbellata. When establishing native trees to replace E. umbellata, cutting and herbicide application treatment of the invader resulted in the highest overall efficacy (100% control), though the most cost-effective method may be to simply cut mature stands despite regrowth, as this resulted in equivalent native tree growth over 2 yr. While this allowed E. umbellata regeneration, it provided sufficient invader control to allow initial tree establishment. Cutting and herbicide application treatment resulted in less E. umbellata regeneration and appears to provide greater assurance that established trees will persist over the long term.
Measurements in the infrared wavelength domain allow direct assessment of the physical state and energy balance of cool matter in space, enabling the detailed study of the processes that govern the formation and evolution of stars and planetary systems in galaxies over cosmic time. Previous infrared missions revealed a great deal about the obscured Universe, but were hampered by limited sensitivity.
SPICA takes the next step in infrared observational capability by combining a large 2.5-meter diameter telescope, cooled to below 8 K, with instruments employing ultra-sensitive detectors. A combination of passive cooling and mechanical coolers will be used to cool both the telescope and the instruments. With mechanical coolers the mission lifetime is not limited by the supply of cryogen. With the combination of low telescope background and instruments with state-of-the-art detectors SPICA provides a huge advance on the capabilities of previous missions.
SPICA instruments offer spectral resolving power ranging from R ~50 through 11 000 in the 17–230 μm domain and R ~28.000 spectroscopy between 12 and 18 μm. SPICA will provide efficient 30–37 μm broad band mapping, and small field spectroscopic and polarimetric imaging at 100, 200 and 350 μm. SPICA will provide infrared spectroscopy with an unprecedented sensitivity of ~5 × 10−20 W m−2 (5σ/1 h)—over two orders of magnitude improvement over what earlier missions. This exceptional performance leap, will open entirely new domains in infrared astronomy; galaxy evolution and metal production over cosmic time, dust formation and evolution from very early epochs onwards, the formation history of planetary systems.
We present a heuristic argument based on Honda–Tate theory against many conjectures in ‘unlikely intersections’ over the algebraic closure of a finite field; notably, we conjecture that every abelian variety of dimension 4 is isogenous to a Jacobian. Using methods of additive combinatorics, we answer a related question of Chai and Oort where the ambient Shimura variety is a power of the modular curve.
Background: Supratentorial ventricular hemangioblastoma (HB) associated with Von Hippel Lindau (VHL) are extremely rare. Due to their vascularity and location, their management can be difficult. Methods: A 35 year old female with VHL, has been followed for 25 years with multiple intracranial and spinal tumours. Surgical removal was carried out on one large cystic and solid posterior fossa lesion. In addition, she underwent adrenalectomy for pheochromocytoma. There were no pancreatic or renal lesions. On serial follow up for years, a left frontal ventricular lesion showed increasing size with clinical signs of increased ICP and marked hydrocephalus, requiring shunting procedures, which were carried out 11 years ago. She has been clinically stable since. Results: Hemangioblastomas of the CNS are rare and account for 2% of primary CNS tumours. Supratentorial location is estimated at 4% for sporadic and 13% for HB associated with VHL. The lateral ventricular location is extremely rare. Review of the literature revealed a total of 9 cases of supratentorial ventricular location. The majority of the lesions are associated with VHL and they are solid and vascular lesions. In our cases there was a cystic component. Conclusions: If removal is contemplated, angiography with possible preoperative embolization may be required.
Background: Leptomeningeal dissemination of hemangioblastomas (HB), whether sporadic or associated with Von Hippel Lindau (VHL), are extremely rare. Very scanty literature is available. Methods: A 36 year old female with VHL and stable pancreatic, adrenal and renal lesions was operated upon 4 years ago for a large symptomatic cervicomedullary cystic and solid tumor. 2 years after surgery the tumour recurred and further removal was unsuccessful due to medullary adhesions. Radiation was given to the posterior fossa area and to several small nodules over the cauda equina resulting in severe pain. Serial follow up imaging revealed diffuse leptomeningeal dissemination increasing in size of the suprasellar region, ambient cistern and Sylvian fissures. Clinically, she has been stable with small dose of steroids and VP shunt insertion for papilledema. Results: Review of the literature consists of 2 series of 7 and 21 patients each with leptomeningeal dissemination involving sporadic HB and VHL associated HB. Leptomeningeal dissemination is estimated at about 4.3%. It is postulated that the tumour starts in the Pia and spreads in an extra medullary fashion throughout the subarachnoid spaces. Conclusions: Long term recurrence has been noted raising the question of aggressive treatment with some drug therapy related to angiogenesis is postulated.
An internationally approved and globally used classification scheme for the diagnosis of CHD has long been sought. The International Paediatric and Congenital Cardiac Code (IPCCC), which was produced and has been maintained by the International Society for Nomenclature of Paediatric and Congenital Heart Disease (the International Nomenclature Society), is used widely, but has spawned many “short list” versions that differ in content depending on the user. Thus, efforts to have a uniform identification of patients with CHD using a single up-to-date and coordinated nomenclature system continue to be thwarted, even if a common nomenclature has been used as a basis for composing various “short lists”. In an attempt to solve this problem, the International Nomenclature Society has linked its efforts with those of the World Health Organization to obtain a globally accepted nomenclature tree for CHD within the 11th iteration of the International Classification of Diseases (ICD-11). The International Nomenclature Society has submitted a hierarchical nomenclature tree for CHD to the World Health Organization that is expected to serve increasingly as the “short list” for all communities interested in coding for congenital cardiology. This article reviews the history of the International Classification of Diseases and of the IPCCC, and outlines the process used in developing the ICD-11 congenital cardiac disease diagnostic list and the definitions for each term on the list. An overview of the content of the congenital heart anomaly section of the Foundation Component of ICD-11, published herein in its entirety, is also included. Future plans for the International Nomenclature Society include linking again with the World Health Organization to tackle procedural nomenclature as it relates to cardiac malformations. By doing so, the Society will continue its role in standardising nomenclature for CHD across the globe, thereby promoting research and better outcomes for fetuses, children, and adults with congenital heart anomalies.