Scale dependence of fractal dimension in deterministic and stochastic Lorenz-63 systems.

Many natural systems show emergent phenomena at different scales, leading to scaling regimes with signatures of deterministic chaos at large scales and an apparently random behavior at small scales. These features are usually investigated quantitatively by studying the properties of the underlying attractor, the compact object asymptotically hosting the trajectories of the system with their invariant density in the phase space. This multi-scale nature of natural systems makes it practically impossible to get a clear picture of the attracting set. Indeed, it spans over a wide range of spatial scales and may even change in time due to non-stationary forcing. Here, we combine an adaptive decomposition method with extreme value theory to study the properties of the instantaneous scale-dependent dimension, which has been recently introduced to characterize such temporal and spatial scale-dependent attractors in turbulence and astrophysics. To provide a quantitative analysis of the properties of this metric, we test it on the well-known low-dimensional deterministic Lorenz-63 system perturbed with additive or multiplicative noise. We demonstrate that the properties of the invariant set depend on the scale we are focusing on and that the scale-dependent dimensions can discriminate between additive and multiplicative noise despite the fact that the two cases have exactly the same stationary invariant measure at large scales. The proposed formalism can be generally helpful to investigate the role of multi-scale fluctuations within complex systems, allowing us to deal with the problem of characterizing the role of stochastic fluctuations across a wide range of physical systems.

Evaluation of Winter Ticks (Dermacentor albipictus) Collected from North American Elk (Cervus canadensis) in an Area of Chronic Wasting Disease Endemicity for Evidence of PrPCWD Amplification Using Real-Time Quaking-Induced Conversion Assay.

Chronic wasting disease (CWD) is a progressive and fatal spongiform encephalopathy of deer and elk species, caused by a misfolded variant of the normal prion protein. Horizontal transmission of the misfolded CWD prion between animals is thought to occur through shedding in saliva and other forms of excreta. The role of blood in CWD transmission is less clear, though infectivity has been demonstrated in various blood fractions. Blood-feeding insects, including ticks, are known vectors for a range of bacterial and viral infections in animals and humans, though to date, there has been no evidence for their involvement in prion disease transmission. In the present study, we evaluated winter ticks (Dermacentor albipictus) collected from 136 North American elk (Cervus canadensis) in an area where CWD is endemic for evidence of CWD prion amplification using the real-time quaking-induced conversion assay (RT-QuIC). Although 30 elk were found to be CWD positive (22%) postmortem, amplifiable prions were found in just a single tick collected from an elk in advanced stages of CWD infection, with some evidence for prions in ticks collected from elk in mid-stage infection. These findings suggest that further investigation of ticks as reservoirs for prion disease may be warranted. IMPORTANCE This study reports the first finding of detectable levels of prions linked to chronic wasting disease in a tick collected from a clinically infected elk. Using the real-time quaking-induced conversion assay (RT-QuIC), "suspect" samples were also identified; these suspect ticks were more likely to have been collected from CWD-positive elk, though suspect amplification was also observed in ticks collected from CWD-negative elk. Observed levels were at the lower end of our detection limits, though our findings suggest that additional research evaluating ticks collected from animals in late-stage disease may be warranted to further evaluate the role of ticks as potential vectors of chronic wasting disease.

Fingerprint of volcanic forcing on the ENSO-Indian monsoon coupling.

Coupling of the El Niño-Southern Oscillation (ENSO) and Indian monsoon (IM) is central to seasonal summer monsoon rainfall predictions over the Indian subcontinent, although a nonstationary relationship between the two nonlinear phenomena can limit seasonal predictability. Radiative effects of volcanic aerosols injected into the stratosphere during large volcanic eruptions (LVEs) tend to alter ENSO evolution; however, their impact on ENSO-IM coupling remains unclear. Here, we investigate how LVEs influence the nonlinear behavior of the ENSO and IM dynamical systems using historical data, 25 paleoclimate reconstructions, last-millennium climate simulations, large-ensemble targeted climate sensitivity experiments, and advanced analysis techniques. Our findings show that LVEs promote a significantly enhanced phase-synchronization of the ENSO and IM oscillations, due to an increase in the angular frequency of ENSO. The results also shed innovative insights into the physical mechanism underlying the LVE-induced enhancement of ENSO-IM coupling and strengthen the prospects for improved seasonal monsoon predictions.

Management of chronic wasting disease in ranched elk: conclusions from a longitudinal three-year study.

Chronic wasting disease is a fatal, horizontally transmissible prion disease of cervid species that has been reported in free-ranging and farmed animals in North America, Scandinavia, and Korea. Like other prion diseases, CWD susceptibility is partly dependent on the sequence of the prion protein encoded by the host's PRNP gene; it is unknown if variations in PRNP have any meaningful effects on other aspects of health. Conventional diagnosis of CWD relies on ELISA or IHC testing of samples collected post-mortem, with recent efforts focused on antemortem testing approaches. We report on the conclusions of a study evaluating the role of antemortem testing of rectal biopsies collected from over 570 elk in a privately managed herd, and the results of both an amplification assay (RT-QuIC) and conventional IHC among animals with a several PRNP genotypes. Links between PRNP genotype and potential markers of evolutionary fitness, including pregnancy rates, body condition, and annual return rates were also examined. We found that the RT-QuIC assay identified significantly more CWD positive animals than conventional IHC across the course of the study, and was less affected by factors known to influence IHC sensitivity - including follicle count and PRNP genotype. We also found that several evolutionary markers of fitness were not adversely correlated with specific PRNP genotypes. While the financial burden of the disease in this herd was ultimately unsustainable for the herd owners, our scientific findings and the hurdles encountered will assist future CWD management strategies in both wild and farmed elk and deer.

Cross-validation of the RT-QuIC assay for the antemortem detection of chronic wasting disease in elk.

Chronic wasting disease is a progressively fatal, horizontally transmissible prion disease affecting several members of the cervid species. Conventional diagnosis relies on ELISA or IHC evaluation using tissues collected post-mortem; however, recent research has focused on newly developed amplification techniques using samples collected antemortem. The present study sought to cross-validate the real-time quaking-induced conversion assay (RT-QuIC) evaluation of rectal biopsies collected from an elk herd with endemic CWD, assessing both binary positive/negative test results as well as relative rates of amplification between laboratories. We found that results were correlative in both categories across all laboratories performing RT-QuIC, as well as to conventional IHC performed at a national reference laboratory. A significantly higher number of positive samples were identified using RT-QuIC, with results seemingly unhindered by low follicle counts. These findings support the continued development and implementation of amplification assays in the diagnosis of prion diseases of veterinary importance, targeting not just antemortem sampling strategies, but post-mortem testing approaches as well.

Disentangling different types of El Niño episodes by evolving climate network analysis.

Complex network theory provides a powerful toolbox for studying the structure of statistical interrelationships between multiple time series in various scientific disciplines. In this work, we apply the recently proposed climate network approach for characterizing the evolving correlation structure of the Earth's climate system based on reanalysis data for surface air temperatures. We provide a detailed study of the temporal variability of several global climate network characteristics. Based on a simple conceptual view of red climate networks (i.e., networks with a comparably low number of edges), we give a thorough interpretation of our evolving climate network characteristics, which allows a functional discrimination between recently recognized different types of El Niño episodes. Our analysis provides deep insights into the Earth's climate system, particularly its global response to strong volcanic eruptions and large-scale impacts of different phases of the El Niño Southern Oscillation.

Computational radiology in skeletal radiography.

Recent years have brought rapid developments in computational image analysis in musculo-skeletal radiology. Meanwhile the algorithms have reached a maturity that makes initial clinical use feasible. Applications range from joint space measurement to erosion quantification, and from fracture detection to the assessment of alignment angles. Current results of computational image analysis in radiography are very promising, but some fundamental issues remain to be clarified, among which the definition of the optimal trade off between automatization and operator-dependency, the integration of these tools into clinical work flow and last not least the proof of incremental clinical benefit of these methods.

[Measurement instead of scoring in rheumatology: new quantitative imaging and processing methods in radiology]. / Messen statt scoren in der Rheumatologie : Neue quantitative Bildgebungs- und -verarbeitungsmethoden der Radiologie.

Many radiological methods to statistically evaluate progression of rheumatic diseases have been presented in recent years. This review article explains their basics as well as the background to the development of "imaging biomarkers" and their potential application in rheumatology.

Cardiopulmonary interaction during partial liquid ventilation in surfactant-treated preterm lambs.

UNLABELLED: Gas ventilation following instillation of perfluorochemical (PFC) liquid, partial liquid ventilation (PLV), improves gas exchange and pulmonary mechanics in neonatal animals and humans with severe respiratory distress. The effect of PLV on cardiac contractility, performance, pulmonary blood flow and ductal shunt has not been fully described. To this end, we evaluated these indices of cardiopulmonary function in eight conventionally gas ventilated, surfactant-treated premature lambs (125 days gestation) before and during PLV. Animals were instrumented with central venous and aortic lines. Serial evaluation of arterial blood chemistry/pressure, and pulmonary mechanics was performed; cardiac contractility, performance, pulmonary blood flow and ductal shunts were serially assessed by echocardiography. As compared to conventional gas ventilation, during PLV there was a significant decrease in left ventricular meridian (22.5+/-6.6 SE vs 8.1+/-1.4 SE g/cm2, P < 0.02) and circumferential wall stress (54.1+/-16.5 vs 24.4+/-3.8 SE g/cm2, P < 0.04) at end systole. The fall in wall stress at end systole was associated with a significant decrease in left ventricular internal diameter (1.2+/-0.05 SE vs 1.04+/-0.045 SE cm; P < 0.01). There were no significant changes in heart rate, systemic arterial and central venous pressures, systemic vascular resistance, left ventricular shortening and ejection fractions during PLV. The decrease in wall stress was associated with a significant decrease in mean airway pressures (15.9+/-1.1 SE vs 9.9+/-0.2 SE cmH2O; P < 0.05) and ostensibly a change in intrathoracic pressures during PLV. There were no significant differences in blood flows (pre vs during PLV; ml/min/kg): pulmonary (226+/-62 SE vs 293+/-65 SE), aortic (237+/-36 SE vs 204+/-21 SE), and left to right ductal (119+/-25 SE vs 105.5+/-26 SE) measured before and during PLV. CONCLUSION: Cardiac output and pulmonary blood flow do not change significantly during PLV and therefore do not appear to contribute to improved gas exchange. This stable cardiac performance occurs at lower wall stress and thereby more advantageous energetic conditions.

Multifocal mesenchymal hamartoma of the chest wall in infancy.

The authors report on an infant who had multifocal mesenchymal hamartoma of the right posterior chest wall. The tumors were found incidentally, on a chest radiograph, during routine evaluation for upper respiratory tract infection. Resection of both lesions with chest wall reconstruction was performed, with a good result. Only 46 cases of this unusual tumor have been reported previously, and only two of them were multifocal.

Sudden death in childhood due to right ventricular dysplasia: report of two cases.

Two cases of sudden death due to arrhythmogenic right ventricular dysplasia (ARVD) occurring in the pediatric age group are described. One of the subjects, at the age of 7 years, is believed to be the youngest child in whom ARVD has been diagnosed at autopsy. The clinical and pathological characteristics of ARVD are discussed.

Potential to involve multiple effector cells with human recombinant interleukin-2 and antiganglioside monoclonal antibodies in a canine malignant melanoma immunotherapy model.

Human tumors originating from neuroectodermal cells such as malignant melanoma and neuroblastoma express high levels of disialogangliosides GD2 and GD3, making these antigens ideal for targeting by monoclonal antibodies (Mabs). The purpose of this study was to investigate expression and targeting of gangliosides on canine melanoma. Using immunohistochemical methods, we analyzed the expression of disialogangliosides GD2 and GD3 on canine oral malignant melanomas with murine Mabs 14.G2a and R24 that recognize GD2 and GD3 disialogangliosides, respectively, on human tumors. We also assessed the ability of Mab 14.G2a (and its mouse-human chimera, ch 14.18) to mediate antibody-dependent cellular cytotoxicity (ADCC) in vitro against a canine malignant melanoma cell line with human recombinant interleukin-2 (IL-2) activated canine peripheral blood lymphocytes (PBL), or canine neutrophil effector cells. Our data show that Mabs 14.G2a and R24 recognized fresh frozen canine oral melanoma. Mabs 14.G2a or ch 14.18, or IL-2, potentiated lysis of the canine malignant melanoma cell line by canine PBL. The killing effect observed using the combination of either Mab with IL-2 was additive. Mab 14.G2a mediated potent ADCC of canine melanoma by canine neutrophils. These studies indicate that disialogangliosides are expressed on fresh canine melanoma cells. Mabs reactive with these antigens can target and trigger tumor killing by multiple canine effector populations and IL-2 can potentiate these effects by canine lymphocytes. Thus, canine oral malignant melanoma, a spontaneously occurring, metastatic cancer in the dog, may be a relevant animal model to investigate combination immunotherapy using antitumor Mab and IL-2.

Problem-based learning in American medical education: an overview.

The recent trend toward problem-based learning (PBL) in American medical education amounts to one of the most significant changes since the Flexner report motivated global university affiliation. In PBL, fundamental knowledge is mastered by the solving of problems, so basic information is learned in the same context in which it will be used. Also, the PBL curriculum employs student initiative as a driving force and supports a system of student-faculty interaction in which the student assumes primary responsibility for the process. The first PBL medical curriculum in North America was established at McMaster University in Toronto in 1969. The University of New Mexico was the first to adopt a medical PBL curriculum in the United States, and Mercer University School of Medicine in Georgia was the first U.S. medical school to employ PBL as its only curricular offering. Many interpretations of the basic PBL plan are in use in North American medical schools. Common features include small-group discussions of biomedical problems, a faculty role as facilitator, and the student's relative independence from scheduled lectures. The advantages of PBL are perceived as far outweighing its disadvantages, and the authors conclude that eventually it will see wider use at all levels of education.

Cerebral rhinocele, hydrocephalus, and cleft lip and palate in infants with cardiac fibroma.

Cardiac transplantation was performed in two infants with unresectable fibromas of the myocardium. In one patient, lip surgery was also required for unilateral cleft lip and palate. At autopsy, communicating hydrocephalus of mild to moderate degree was found in both cases. In the patient with facial clefts, there was also a large, ipsilateral cyst, or rhinocele, of the olfactory lobe. This unusual lesion, which seems to represent a previously unreported malformation, was apparently formed by segmental dilatation of a persistent olfactory ventricle. Cerebral or cranial anomalies are thought to be rare in cases of cardiac fibroma; however, macrocephaly was present in five patients. Furthermore, presenting abnormalities among previously reported cases included hydrocephalus in one case, and cleft lip and palate in another. These and other findings suggest that, at least in some cases, cardiac fibroma is a manifestation of a more extensive developmental disorder.

Problem-based learning: an assessment of its feasibility and cost.

As our knowledge of human biology becomes more complex and the medical school applicant pool declines, there is ample reason to consider an alternative to the conventional medical curriculum. Many authorities feel that a format incorporating problem-based learning (PBL) would be more appropriate and effective. The problem-based medical curriculum is one in which facts and principles are learned in the context of a clinical problem. Problem-based medical education began as a revision of the McMaster University medical curriculum in 1969 and was instituted in the United States as a problem-based experimental track at the University of New Mexico School of Medicine in 1979. The first completely integrated, totally problem-based, McMaster-type, medical curriculum in the United States began operation in 1982 with the establishment of Mercer University School of Medicine. Many years of experience at these three institutions have shown that the problem-based curriculum works well. Several medical schools throughout the world are either practicing PBL or investigating the feasibility of adopting it. A comparison of the costs (in faculty time) of problem-based and conventional pathology programs suggests that the PBL curriculum is quite feasible for schools with a class size of 60 or less and may be so for many schools and programs with classes of less than 100.

Alterations in left ventricular geometry, wall stress, and ejection performance after correction of congenital aortic stenosis.

Children with congenital aortic stenosis have "excessive" left ventricular hypertrophy with reduced resting systolic wall stress that allows for supernormal ejection performance. If aortic stenosis is uncorrected, this pattern persists until adulthood. The effect of removing the aortic pressure gradient on left ventricular hypertrophy and wall stress in children with congenital aortic stenosis is unknown. To test the hypothesis that removal of the stimulus for hypertrophy by aortic valve replacement or repair would normalize left ventricular mass and wall stress, we measured left ventricular ejection performance, wall stress, and contractile function in seven patients at cardiac catheterization before and 36 +/- 7 months after surgical correction of congenital aortic stenosis. After aortic valve replacement or repair, the aortic valve gradient fell from 87 +/- 12 to 7 +/- 4 mm Hg, and peak left ventricular pressure fell from 187 +/- 14 to 128 +/- 8 mm Hg. Left ventricular ejection fraction decreased postoperatively from 86 +/- 4% to 74 +/- 4% (p less than 0.001), whereas velocity of circumferential fiber shortening decreased from 2.15 +/- 0.15 to 1.6 +/- 0.11 (p less than 0.002). Left ventricular mass remained unchanged preoperatively (121 +/- 14 g/m2) and postoperatively (121 +/- 16 g/m2), but wall thickness (h) decreased in relation to ventricular radius (r) (h/r = 0.55 +/- 0.05 preoperatively, 0.36 +/- 0.02 postoperatively; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Ectopic automatic atrial tachycardia in children: clinical characteristics, management and follow-up.

Ectopic automatic atrial tachycardia, an uncommon type of supraventricular tachycardia in children and adults, has been reported to be resistant to medical therapy, and surgical or cryoblation has been recommended. This report describes 10 infants and children (median age 6 months; range birth to 7.5 years) with automatic atrial tachycardia and their management and follow-up. Digoxin alone was unsuccessful in controlling tachycardia in all 10 patients but decreased the tachycardia rate by 5 to 20% in 8. Intravenous (0.1 mg/kg body weight per dose) and oral propranolol successfully suppressed tachycardia in three of five patients and oral propranolol successfully controlled tachycardia in two of five other patients. Class I antiarrhythmic agents--quinidine (three patients), procainamide (four patients) and phenytoin (three patients)--did not control tachycardia in any patients but made the tachycardia rate worse in three patients. Intravenous (5 mg/kg per dose) and oral amiodarone suppressed tachycardia in three of four patients and oral amiodarone suppressed it in another patient. Thus, intravenous propranolol and amiodarone were effective in acutely suppressing automatic ectopic atrial tachycardia and predicted the response to long-term oral therapy. One patient had persistent tachycardia after surgical ablation of the high right atrial ectopic focus, and another patient had unsuccessful catheter ablation of the high right atrial ectopic focus (25 J). During follow-up (10 to 28 months), ectopic atrial tachycardia resolved completely in four patients and was well controlled in four patients.

Pediatric heart transplantation at St. Christopher's Hospital for Children.

Heart transplantation has become the standard of care for patients with end-stage heart failure. The efficacy and therapeutic advantages of transplantation in the pediatric population have not been fully determined. Between March 1985 and September 1986, nine pediatric heart transplantations were performed; the ages ranged from 39 days to 19 years; weight ranged from 2.3 to 100 kg. The underlying disease was acquired cardiomyopathy (four patients); cardiomyopathy caused by congenital mitral valve disease (two patients); unresectable fibroma of the left ventricle in a newborn (one patient); hypoplastic left heart syndrome (one patient); and hypertrophic obstructive cardiomyopathy (one patient). Initial immunosuppression therapy consisted of cyclosporine, prednisone, and antithymocyte globulin. Recently, newer protocols have evolved through experience. Seven patients survived the perioperative period and had follow-up from 1 to 19 months, for a total of 41 transplant months. Rejection occurred at a rate of 1.4 episodes per month in children compared with 0.8 episodes per month in our adult patients. There was no statistical difference in the number, severity, or timing of rejection episodes in the pediatric versus adult population. Major complications included cyclosporine-induced seizures in two patients, mild hypertension in two, five infectious episodes (three bacterial and two viral), and three late deaths. All children who survived are in New York Heart Association functional class I with no developmental delays. This series is heavily weighted with children (33% less than age 1 year). Early results demonstrate that pediatric and infant heart transplantation is technically practical. Improved results are to be expected with additional experience and further modification of adult protocols to assure patient growth and minimize the high infection rate.

Postoperative evaluation of complex congenital heart disease by magnetic resonance imaging.

This study suggests that the use of MRI together with echocardiography may reduce the need for serial cardiac catheterizations in the postoperative care of children with complex congenital heart disease.