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.

Variant angina in an 11 year old boy.

Variant angina is a syndrome in which ischemic cardiac pain occurs with ST segment elevation. The syndrome is due at least in part to coronary vasospasm. Although well documented in adults, there are no known reports of this syndrome in children. The clinical, electrocardiographic and echocardiographic findings in an 11 year old boy with variant angina are reported.

Improved prediction of peak left ventricular pressure by echocardiography in children with aortic stenosis.

Prediction of peak left ventricular pressure by echocardiography in children with aortic stenosis assumes that wall stress is normal. The recent finding that stress is subnormal in many children with aortic stenosis and elevated ejection performance requires reevaluation of this noninvasive technique. By using M-mode echocardiography, left ventricular end-diastolic dimension and wall thickness and left ventricular shortening fraction were measured in 27 children with aortic stenosis undergoing left ventricular pressure measurement by cardiac catheterization. Similar echocardiographic measurements and systolic blood pressure determinations by the cuff method were obtained from 29 normal children. Peak circumferential wall stress and shortening fraction were calculated from the echocardiographic and pressure data. It was found that stress was inversely proportional to shortening fraction for all patients with aortic stenosis (p less than 0.001, r = -0.86). In a subgroup of patients with a shortening fraction of less than 0.40, stress was 262 +/- 20 mm Hg, similar to 280 +/- 30 mm Hg in the normal group but greater than 205 +/- 27 mm Hg in patients with a shortening fraction of 0.40 or greater (p less than 0.001). In patients with aortic stenosis, the ratio of left ventricular end-diastolic wall thickness to cavity dimension predicted peak left ventricular pressure moderately well (r = 0.83, standard error of the estimate [SEE] = 23). The stress-shortening fraction relation was used to estimate stress and correct this ratio in patients with diminished stress and a shortening fraction greater than or equal to 0.40. This yielded a significantly improved correlation (r = 0.93, SEE = 15, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular wall stress and function in childhood coarctation of the aorta.

Unlike most adults with compensated pressure overload of the left ventricle, children with moderate to severe aortic stenosis exhibit pronounced left ventricular muscle hypertrophy, enhanced ejection performance and diminished wall stress. To determine whether these findings are present in other forms of left ventricular pressure overload in children, left ventricular mechanics were studied by catheterization in 14 children with coarctation of the aorta (average peak gradient 39 +/- 17 mm Hg) and in 10 normal children. Ejection fraction and mean velocity of circumferential fiber shortening in the coarctation group (0.74 +/- 0.09 and 1.71 +/- 0.43 circumferences/s, respectively) were significantly higher than in normal subjects (0.65 +/- 0.05 and 1.27 +/- 0.26 circumferences/s, respectively) (p = 0.008), but the ranges for both groups overlapped. End-systolic stress in children with coarctation (77 +/- 20 dynes X 10(3)/cm2) was less than in normal children (121 +/- 24 dynes X 10(3)/cm2) (p less than 0.001), again with overlap of the ranges for both groups. The ratio of end-systolic stress to end-systolic volume index, an estimate of contractile function, was similar in both groups. Relations between severity of obstruction (left ventricular peak systolic pressure, coarctation gradient) and end-systolic stress and between stress and ejection performance were present within the coarctation group. Comparison of these data with those found in children with moderate to severe aortic stenosis shows a similar but less pronounced response to pressure overload due to coarctation of the aorta.

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.

Left ventricular wall stress in compensated aortic stenosis in children.

It is known that children with aortic stenosis (AS) frequently have supernormal indexes of left ventricular (LV) pump function and remain compensated for many years. Factors causing this increase in pump performance have not been elucidated. A study was done on LV mechanics in 11 children with AS (aortic valve area 0.5 +/- 0.3 cm2/m2) and 10 normal subjects. The ejection fraction in the AS group (0.88 +/- 0.08) was significantly higher than in normal subjects (0.64 +/- 0.08, p less than 0.001). The mean velocity of fiber shortening was also higher in AS patients (1.80 +/- 0.35 circ/s) than in normal subjects (1.22 +/- 0.21 circ/s, p less than 0.001). The end-systolic volume index in patients with AS (9 +/- 8 ml/m2) was much lower than in normal subjects (27 +/- 8 ml/m2). LV mass in patients with AS was 180 +/- 58 g/m2 compared with 96 +/- 9 in normal subjects. LV wall stress was reduced throughout the cardiac cycle in patients with AS. Peak stress in patients with AS was 238 +/- 51 dynes/cm2 X 10(3) versus 439 +/- 85 in normal subjects. The end-systolic stress-end-systolic volume index ratio, an indicator of contractile state, was not elevated in patients with AS. It is suggested that diminished wall stress in concert with normal contractile function permits the supernormal pump function seen at rest in children with AS.

Dilatation of the descending aorta: a radiologic and echocardiographic diagnostic sign in arteriovenous malformations in neonates and young infants.

Eleven infants with arteriovenous malformations were admitted to St. Christopher's Hospital for Children between 1970 and 1978. Dilatation of the descending aorta was seen in the chest roentgenogram in 8 of the 11 patients. Echocardiography used in the two most recent cases revealed approximation of the descending aorta to the posterior left atrial and left ventricular wall in association with generalized cardiomegaly. The most frequently reported radiologic findings in infants with arteriovenous malformations are cardiomegaly, increased pulmonary vasculature and a widened superior mediastinum. These findings can accompany other congenital malformations of the heart, but the radiographic and echocardiographic findings of a dilated descending aorta appear to be more specifically associated with arteriovenous malformations in the neonate and infant.

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.

Palliative repair of transposition of the great arteries with criss-cross heart: ventricular septal defect and hypoplastic right (systemic) ventricle.

Four cases of palliative Mustard or Senning repair for transposition of the great arteries (TGA) with ventricular septal defect (VSD), hypoplastic right ventricle, and superior-inferior ventricular configuration are presented. The palliative Mustard procedure-a Mustard repair without VSD closure-is usually reserved for patients with pulmonary vascular obstructive disease (PVOD). In such cases, VSD closure would result in left ventricular failure. Each of our four patients had normal or only slightly elevated pulmonary resistance (1.0 to 5.2 Wood units). However, in each case a hypoplastic right ventricle precluded VSD closure. All four patients had transposition-like hemodynamics with unfavorable streaming to the great arteries, despite the fact that two patients had a levo arterial configuration. In each case, the ventricular relationship included a hypoplastic, superior right ventricle with a horizontal ventricular septum-the so-called "upstairs-downstairs" or "superior-inferior" heart. All patients had previous balloon atrial septostomy or open septectomy to improve atrial mixing. Two patients had previous pulmonary artery banding because of increased pulmonary flow. All four patients remain survivors of the palliative Mustard or Senning repair, which was performed at 10 months, 5 1/2, 12, and 16 years. In each case, there was a marked improvement of symptomatology with a decrease of hemoglobin (mean 21.1 gm/dl preoperatively to 15.3 gm/dl postoperatively) and an increase of arterial oxygen saturation (mean 78 vol % preoperatively to 93 vol % postoperatively). This is the first palliative Mustard or Senning repairs in patients with TGA, VSD, and hypoplastic right ventricle without PVOD. The procedure produces gratifying palliation for these patients.

Preservation of pathology specimens by silicone plastination. An innovative adjunct to pathology education.

The authors have used the process of plastination to preserve gross anatomic specimens for teaching purposes. A specimen is fixed in 10% buffered formalin and dehydrated in increasing grades of ethanol. Thereafter it is saturated with methylene chloride and then impregnated in vacuo at -20 degrees C with silicone rubber. Final steps involve drainage and exposure to a curing agent. The total time required is approximately 16 weeks. The finished plastinated specimen is dry to the touch, odorless, and nontoxic, yet it maintains its original shape and, in many cases, is reasonably close in color and consistency. It resists deterioration and can be stored at room temperature indefinitely. The authors have found plastinated specimens to be superior to those preserved in formalin for teaching anatomic pathology to undergraduate medical students.

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.

Advances in noninvasive evaluation of congenital anomalies of the thoracic aorta.

Two-dimensional echocardiography, Doppler ultrasound, and magnetic resonance imaging (MRI) have greatly enhanced the noninvasive diagnosis of congenital anomalies of the thoracic aorta. Both sonic and magnetic resonance techniques can obviate preoperative invasive studies, and both provide an excellent means of follow-up. Ultrasound will likely remain the most valuable modality in neonates, while MRI promises to make an important contribution in older children and adults.

Magnetic resonance imaging of rerouted pulmonary blood flow.

Correction of structural defects of the heart associated with cyanotic heart disease often requires rerouting of systemic venous return into the pulmonary arteries and pulmonary venous return into the ventricles. Preliminary experience suggests that magnetic resonance imaging, through its superior depiction of the resultant complex anatomy, provides important supplemental information to echocardiography. Together, these noninvasive techniques may lessen the present need for repeat catheterization in children with surgically corrected cyanotic heart disease.

Hyperplasia of palmar plates and macrodactyly in a young child.

A case is reported of a young girl who presented with macrodactyly of the right middle finger and tumour masses on the palmar side of both interphalangeal joints. The lesions were fibrocartilaginous and appeared to be hyperplastic palmar plates. The macrodactyly and the hyperplasia of the palmar plates were attributed to trauma.

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.

[Annoyance and loudness measurements in auditory fatigue and recovery under different sound exposures]. / Lästigkeits- und Lautheitseinstufungen bei Hörermüdung und deren Rückbildung unter verschiedenen Lärmbelastungen.

In the course of two experimental studies the individual evaluations of noise annoyance during sound exposure were compared with the experimental auditory fatigue (TTS) and the recovery functions. In both studies, in fourteen young men with normal hearing capacity, a temporary threshold shift was built up and then the subjects were submitted during the recovery period to different second-noise levels (narrow band noise and white noise). The loudness estimations and the evaluations of noise annoyance were scaled at the same points as TTS was measured. The poststimulatory recovery of hearing was significantly delayed, even at noise levels of 65 and 75 db. The evaluations of loudness and noise annoyance corresponded well with the recovery of hearing. In the first experiment, the mean values of noise annoyance ratings increased after 16 min of the second noise exposure, in spite of a further decrement of auditory fatigue. In the second experiment, the mean values of noise annoyance ratings remained almost unchanged during the secondary noise exposure. Regarding individual evaluations, however, the noise annoyance ratings of half of the subjects increased whereas the other half decreased. These results are interpreted as a habituation respectively a sensitization process.