Distribution Of Degeneration Research Articles

New Specifications for Exponential Random Graph Models

The most promising class of statistical models for expressing structural properties of social networks observed at one moment in time is the class of exponential random graph models (ERGMs), also known as p* models. The strong point of these models is that they can represent a variety of structural tendencies, such as transitivity, that define complicated dependence patterns not easily modeled by more basic probability models. Recently, Markov chain Monte Carlo (MCMC) algorithms have been developed that produce approximate maximum likelihood estimators. Applying these models in their traditional specification to observed network data often has led to problems, however, which can be traced back to the fact that important parts of the parameter space correspond to nearly degenerate distributions, which may lead to convergence problems of estimation algorithms, and a poor fit to empirical data. This paper proposes new specifications of exponential random graph models. These specifications represent structural properties such as transitivity and heterogeneity of degrees by more complicated graph statistics than the traditional star and triangle counts. Three kinds of statistics are proposed: geometrically weighted degree distributions, alternating k-triangles, and alternating independent two-paths. Examples are presented both of modeling graphs and digraphs, in which the new specifications lead to much better results than the earlier existing specifications of the ERGM. It is concluded that the new specifications increase the range and applicability of the ERGM as a tool for the statistical analysis of social networks.

Relativistic quantum plasma dispersion functions

Relativistic quantum plasma dispersion functions are defined and the longitudinal and transverse response functions for an electron (plus positron) gas are written in terms of them. The dispersion is separated into Landau-damping, pair-creation and dissipationless regimes. Explicit forms are given for the RQPDFs in the cases of a completely degenerate distribution and a nondegenerate thermal (J\"uttner) distribution. Particular emphasis is placed on the relation between dissipation and dispersion, with the dissipation treated in terms of the imaginary parts of RQPDFs. Comparing the dissipation calculated in this way with the existing treatments leads to the identification of errors in the literature, which we correct. We also comment on a controversy as to whether the dispersion curves in a superdense plasma pass through the region where pair creation is allowed.

White Matter Alterations in Cerebral Amyloid Angiopathy Measured by Diffusion Tensor Imaging

Cerebral amyloid angiopathy (CAA) represents beta-amyloid deposition in the small- and medium-sized vessels of the brain and meninges. CAA contributes to altered vessel function and is associated with white matter damage, cognitive impairment, and most salient, hemorrhagic stroke. We used diffusion tensor imaging to evaluate the anatomic distribution of white matter degeneration in participants diagnosed with advanced CAA. Diffusion tensor imaging was obtained from 11 participants diagnosed with CAA-related intracerebral hemorrhage and 13 matched healthy control participants. Fractional anisotropy (FA) and diffusivity maps were compared using voxel based t test and region-of-interest analyses. FA was reduced in CAA in temporal white matter and in the splenium of the corpus callosum (P<0.001 with approximately 17% reduction in temporal white matter and 15% reduction in the splenium). FA was marginally increased in CAA in the posterior limb of the internal capsule and subthalamic gray matter regions (approximately 7% increase in subthalamic gray). FA changes were bilateral, remained significant in cluster analysis controlling for multiple comparisons, and did not depend on the hemisphere of the cerebral hemorrhage. Diffusivity was not substantially altered. These findings suggest that a pattern of regional brain tissue degeneration is a characteristic feature of advanced CAA.

Inference on Survival Data with Covariate Measurement Error – An Imputation‐based Approach

Abstract. We propose a new method for fitting proportional hazards models with error‐prone covariates. Regression coefficients are estimated by solving an estimating equation that is the average of the partial likelihood scores based on imputed true covariates. For the purpose of imputation, a linear spline model is assumed on the baseline hazard. We discuss consistency and asymptotic normality of the resulting estimators, and propose a stochastic approximation scheme to obtain the estimates. The algorithm is easy to implement, and reduces to the ordinary Cox partial likelihood approach when the measurement error has a degenerate distribution. Simulations indicate high efficiency and robustness. We consider the special case where error‐prone replicates are available on the unobserved true covariates. As expected, increasing the number of replicates for the unobserved covariates increases efficiency and reduces bias. We illustrate the practical utility of the proposed method with an Eastern Cooperative Oncology Group clinical trial where a genetic marker, c‐myc expression level, is subject to measurement error.

Architectures and Buffering for All-Optical Packet-Switched Cross-Connects

This paper considers the performance of an all-optical packet-switched cross-connect. All-optical header processing and all-optical routing are implemented in the cross-connect architectures. The main metric considered to measure the performance is the packet loss ratio for the buffering. This is influenced primarily by three factors. The first is the cross-connect architecture: feedback or feed-forward buffering, incorporating wavelength domain contention resolution. The second is the selection of the fibre delay line distribution: degenerate or non-degenerate distributions. And the third is the traffic load together with the traffic model used for the performance analysis: a Poisson distribution or a self-similar model. It is shown that the optimal implementation of a feedback buffer requires a technique such as overflow buffering as well as the superior performance of an all-optical switch in order to maintain signal quality through multiple recirculations.

Degeneration in dysplastic hips

Hip dysplasia is considered pre-osteoarthritic, causing degeneration in young individuals. To determine the pattern of degenerative change in moderate to severely dysplastic hips in young patients. One hundred and ninety-three consecutively-referred younger patients with hip pain believed to be caused by hip dysplasia constituted the study cohort. The average age was 35.5 years (range, 15-61 years). They were examined by close-cut transverse pelvic and knee computed tomography and antero-posterior radiographs (CT). We identified 197 hips with moderate to severe dysplasia, and 78 hips with normal morphology in the study cohort, whilst 111 hip joints were borderline dysplastic according to preset definitions. Comparative analyses of anatomy and distribution of degeneration between dysplastic and normal hips in the study cohort were performed. In dysplastic hips the anterior acetabular sector angle was significantly and inversely associated to femoral anteversion (p < 0.001). The center-edge (CE) angle, the acetabular angle (AA), and the acetabular depth ratio (ADR) were significantly interrelated (p < 0.001; correlation coefficients ranging from -0.8 to 0.7). Fifty-one hips were subluxated (24R/27L). There were no cases of complete dislocation. The formation of subchondral cysts or osteophytes in dysplastic hips was significantly associated with reduced minimum joint space width (p ranging from 0.005 to 0.02). However, in 67 hips with acetabular cysts, only 6 hips had minimum joint space widths = 2.0 mm (8.9%) in the coronal plane. In 96 cases with acetabular cysts found in the sagittal plane, 43 cases had minimum joint space widths = 2.0 mm (44.7%). Bony rim detachment at the site of labral insertion was recorded in 30 hips. Twenty-three of these were dysplastic (p = 0.01). Degeneration was most often found in the anterolateral part of the dysplastic hip joints. Most cysts were located above the transition zone between the bony and the fibrocartilaginous acetabulum, and we found a significantly- increased number of cases with avulsed bony fragments at the antero-lateral labral insertion in dysplastic hips compared to normal hips. It seems likely that the early degenerative process in dysplastic hips originates at the watershed zone between the acetabular labrum and the acetabular cartilage in response to subluxation and femoroacetabular impingement.

Solution to the Siegel Paradox

The Siegel Paradox in international finance arises because the equilibrium conditions in foreign exchange markets violate Jensen's Inequality. This paper shows that in the original risk-neutral framework (Siegel, 1972), or more accurately a rational representative-agent setting, the paradox does not exist because the conditional probability distribution of the expected spot rate follows a degenerate distribution. When this overlooked condition is incorporated, Jensen's Inequality holds with equality and the paradox vanishes. However, the paradox may still exist when rational agents are heterogeneous and form expectations independently and differently. The result of this paper has implications for both theoretical and empirical studies in international finance.

Degenerative disc disease as a cause of back pain in the thalassaemic population: a case-control study using MRI and plain radiographs

The aim of this study was to test our observation that back pain in thalassemic patients could be caused by premature and extensive lumbar degenerative disc disease, when compared to non-thalassemic patients with back pain. Sixteen thalassemic patients with their sex- and age-matched controls were recruited into the study, 12 with thalassemia major, and 4 with thalassemia intermedia. Both the thalassemia patients and control subjects suffered from back pain, which was subjective rather than measured/pain scored. All subjects underwent magnetic resonance (MR) imaging of the lumbar spine, and 11 of the cases and 8 controls had lumbar spine radiographs. Each lumbar disc was scored for radiographic appearances and MR features of disc degeneration and disc protrusion. Proportion values for these parameters and median scores were derived at each disc level, and were analyzed and compared. There was a statistically-significant difference between proportion values of cases and controls for the MR features (P value=0.01, n=16) and the radiographic features (P value=0.01, n=11 cases, n=8 controls) of disc degeneration. The median disc level scores for the thalassemic group were uniformly high across all lumbar discs, and at all levels except at L 4/5. The control group conversely demonstrated a predilection for disc degeneration at L4/5 level. The distribution of lumbar disc degeneration in thalassemic patients with back pain is more extensive, severe and multi-level in nature compared to matched controls, and disc degeneration should be considered as a significant cause of back pain in this population group.

Copulas, degenerate distributions and quantile tests in competing risk problems

It is well known that, given observable data for a competing risk problem, there is always an independent model consistent with the data. It has been pointed out, however, that this independent model does not necessarily have to be one with proper marginals. One purpose of this paper is to explore the extent to which one might try to use the non-parametric assumption that the marginals are proper in order to test whether or not independence holds. This will lead us naturally to a closely related estimation problem—how we estimate the marginals given that a certain quantile of one variable is reached at the same time as a given quantile of the other variable. The problem will be considered using the copula-based approach of Zheng and Klein. Two different methods are discussed. One is a non-parametric maximum likelihood method. The other is a consistent estimator, called the bilinear adjustment estimator, that can be computed quickly and which thus lends itself more readily to simulation methods such as bootstrapping. The ultimate objective of the work in this paper is to provide an additional analytical tool to understand the effectiveness of preventive maintenance. Preventive maintenance censors component failure data and thus provides an important example of competing risk within the reliability area.

Enhanced Shutoff of Phototransduction in Transgenic Mice Expressing Palmitoylation-deficient Rhodopsin*♦

Palmitoylation is a reversible, post-translational modification observed in a number of G-protein-coupled receptors. To gain a better understanding of its role in visual transduction, we produced transgenic knock-in mice that expressed a palmitoylation-deficient rhodopsin (Palm(-/-)). The mutant rhodopsin was expressed at wild-type levels and showed normal cellular localization to rod outer segments, indicating that neither rhodopsin stability nor its intracellular trafficking were compromised. But Palm(-/-) rods had briefer flash responses and reduced sensitivity to flashes and to steps of light. Upon exposure to light, rhodopsin became phosphorylated at a faster rate in mutant than in wild-type retinas. Since quench of rhodopsin begins with its phosphorylation, these results suggest that palmitoylation may modulate rod photoreceptor sensitivity by permitting rhodopsin to remain active for a longer period.

Method for three-dimensional visualization of neurodegeneration in cupric-silver stained serial rat brain slices

The spatial distribution of neurodegeneration in brains is difficult to visualize when working from 2-D serial slices. In studies where repetitive operant behavior measurements are made over several weeks following organic solvent exposure, definitive evidence of degeneration in brain structures may have been significantly cleared by the time the tissue is prepared histologically. The only remaining evidence that injury has occurred may be nothing more than neuronal and cellular debris. By choosing stains that are specific for this type of residual and/or indicative of specific pathology, a 3-D representation of the spatial distribution of the neuronal and cellular debris fields within the organ can be highlighted and displayed. We present a method for visualizing the spatial distribution of neuronal degeneration that can result from low-level organic solvent exposure scenarios. A cupric-silver stain highly specific for neuronal degeneration is used to identify neuronal debris fields in 73 serial slices of brains of rodents that were exposed to toluene vapors. Serial brain sections stained with cupric-silver are scanned at 600 dpi using a gray-scale protocol. Using commercially available software, scans are assembled into 3-D images showing both topographical and internal anatomical details. The reassembled images are further processed into stereo pairs. Gray-scale scans are compared to the original sections to establish gray-scale ranges for healthy and damaged tissue and artifact staining.

Application of Catastrophe Theory for Multimodal Distributions Statistical Analysis

This work considers the application of catastrophe theory methods (classification of smooth mappings) to the construction of analytical models of objects and processes based on statistical data. Multimodal one-dimensional statistical distributions are compared to catastrophe models of corank 1, i.e., the $A_N$ series catastrophes. We also propose methods for the calculation of a type $A_N$ catastrophe's parameters (the moment method and the maximum likelihood method), and their modifications applicable to the cases of multimodal and degenerate quasi-unimodal distributions. We provide the results of numeric experiments on constructing statistical catastrophe models for random processes.

Evaluation of effects of selected factors on inter-vertebral fusion—a simulation study

This study simulated the effects of inter-vertebral disc degeneration and bone density distribution on the structural stiffness and strength provided by inter-vertebral fusion. Based on the original and redistributed bone density distributions, the effects of selected factors, including contact area between device/graft and vertebral endplates, endplate conditions, and bone growth capacity were evaluated using a factorial design of experiment. The simulation results suggested that the degeneration of inter-vertebral disc significantly affected the bone density and density distribution in adjacent vertebrae. The mechanical strength immediately after instrumentation is the worst case of device/graft subsidence. After that procedure, bone will adapt itself to the changed loading conditions and therefore reduce the risk of subsidence. A deficiency in structural stiffness immediately after instrumentation could be the “worst-case scenario” depending on the combinations of selected factors. The simulation results demonstrated that the contact area and initial bone density distribution should be considered jointly while estimating the risk of device/graft subsidence. The endplate condition is a secondary factor on the subsidence risk, compared with the contact area and initial bone density distribution.

Differences in the topographical distribution of articular cartilage degeneration between equine metacarpo- and metatarsophalangeal joints.

The equine metacarpophalangeal (MCP) and metatarsophalangeal (MTP) joints, although having virtually the same geometrical appearance, differ in the prevalence of joint pathologies, such as osteochondral fragmentation, and in biomechanical behaviour. The recently developed cartilage degeneration index (CDI) technique offers a possibility to assess quantitatively differences in cartilage degeneration between these joints and to compare these with known differences in biomechanics and clinical observations. To compare the topographical distribution of articular cartilage degeneration across the proximal articular surface of the proximal phalanx (P1) in the equine fore- and hindlimb. In 24 distal hindlimbs from 24 horses, articular cartilage degeneration of the proximal articular surface of P1 was quantified using the CDI. Overall CDI value (CDI(P1)) and CDI values of 6 areas of interest were determined: the medial dorsal surface (mds), lateral dorsal surface (lds), medial central fovea (mcf), lateral central fovea (lcf), medial plantar surface (mps) and lateral plantar surface (lps). The joints were divided into 4 equally sized groups of increasing CDI(P1) values. From an existing CDI database of MCP joints, 24 joints were selected with matching CDI(P1) values to the MTP joints and CDI values for the same areas of interest were determined. In both the MCP and MTP joints, highest CDI values were determined at the dorsal articular surfaces. Values were not significantly different between fore- and hindlimbs. In contrast to the MCP joint, CDI values at the plantar joint margin were significantly higher compared to CDI values in the central sites in the MTP joint. CDI values for the plantar surfaces of P1 were significantly higher than those for the palmar surfaces in the forelimb in joints with advanced stages of OA; and values for the central regions of P1 were significantly lower in the hindlimb compared with the forelimb in joints with severe OA. In both fore- and hindlimbs, initial cartilage degeneration started at the dorsal articular margin of P1. There was a major difference in the spread of cartilage degeneration; in the forelimb both the central and palmar parts are about equally involved, whereas in the hindlimb the plantar parts were significantly more and the central parts significantly less involved. These differences can be linked to differences in biomechanical loading reported elsewhere. This study supports the hypothesis that differences in biokinematics between fore- and hindlimbs are associated with differences in the development of cartilage degeneration and other joint pathologies such as osteochondral fragmentation in the MCP and MTP joints. This information is indispensable for a better understanding of the dynamic nature and progression of these joint disorders and may be of help when monitoring the effects of therapeutic interventions and preventative measures.

Prevalence of age-related macular degeneration in the United States.

To estimate the prevalence and distribution of age-related macular degeneration (AMD) in the United States by age, race/ethnicity, and gender. Summary prevalence estimates of drusen 125 microm or larger, neovascular AMD, and geographic atrophy were prepared separately for black and white persons in 5-year age intervals starting at 40 years. The estimated rates were based on a meta-analysis of recent population-based studies in the United States, Australia, and Europe. These rates were applied to 2000 US Census data and to projected US population figures for 2020 to estimate the number of the US population with drusen and AMD. The overall prevalence of neovascular AMD and/or geographic atrophy in the US population 40 years and older is estimated to be 1.47% (95% confidence interval, 1.38%-1.55%), with 1.75 million citizens having AMD. The prevalence of AMD increased dramatically with age, with more than 15% of the white women older than 80 years having neovascular AMD and/or geographic atrophy. More than 7 million individuals had drusen measuring 125 microm or larger and were, therefore, at substantial risk of developing AMD. Owing to the rapidly aging population, the number of persons having AMD will increase by 50% to 2.95 million in 2020. Age-related macular degeneration was far more prevalent among white than among black persons. Age-related macular degeneration affects more than 1.75 million individuals in the United States. Owing to the rapid aging of the US population, this number will increase to almost 3 million by 2020.

ON THE ROBUSTNESS OF HYPOTHESIS TESTING BASED ON FULLY MODIFIED VECTOR AUTOREGRESSION WHEN SOME ROOTS ARE ALMOST ONE

This paper proves that the fully modified vector autoregression (FM-VAR) estimator has second-order bias effects when some roots are local to unity. These bias effects are shown to result in potentially severe size distortions in FM-VAR testing when the hypothesis involves near unit root variables. In addition, the paper reveals that with the FM-VAR method near unit roots become estimated as exact unit roots with convergence speed faster than the order of the sample size. Also this result implies problems for FM-VAR testing, as such “hyperconsistent†estimates give rise to degenerate limit distributions under the null hypothesis.I am grateful to Pentti Saikkonen, Jim Stock, Markku Lanne, Jukka Nyblom, and three referees for very helpful comments on earlier drafts. This paper is a part of the research program of the Research Unit on Economic Structures and Growth (RUESG) at the Department of Economics at the University of Helsinki. Financial support from the ASLA Fulbright, the YrjA¶ Jahnsson Foundation, and the Finnish Cultural Foundation is gratefully acknowledged. The usual disclaimer applies.

Latency to onset of status epilepticus determines molecular mechanisms of seizure-induced cell death

The molecular mechanisms mediating degeneration in response to neuronal insults, including damage evoked by prolonged seizure activity, show substantial variability across laboratories and injury models. Here we investigate the extent to which the proportion of cell death occurring by apoptotic vs. necrotic mechanisms may be shifted by changing the temporal parameters of the insult. In initial studies with continuous seizures (status epilepticus, SE), signs of apoptotic degeneration were most clearly observed when SE occurred following a long latency (>86 min) after injection of kainic acid as compared with a short-latency SE (<76 min). Therefore, in this study we directly compared short- with long-latency SE for the expression of molecular markers for apoptosis and necrosis in an especially vulnerable brain region (rhinal cortex). Molecular markers of apoptosis (DNA fragmentation, cleavage of ICAD, an inhibitor of “caspase-activated DNase” (CAD), and prevalence of a caspase-generated fragment of α-spectrin) were detected following long-latency SE. Short-latency SE resulted in expression of predominantly necrotic features of cell death, such as “non-ladder” pattern of genomic DNA degradation, prevalence of a calpain-generated α-spectrin fragment, and absence of ICAD cleavage. Silver staining revealed no significant difference in the extent and spatial distribution of degeneration between long- or short-latency SE. These data indicate that the latency to onset of SE determines the extent to which apoptotic or necrotic mechanisms contribute to the degeneration following SE. The presence of a long latency period, during which multiple brief seizure episodes may occur, favors the occurrence of apoptotic cell death. It is possible that the absence of such “preconditioning” period in short-latency SE favors predominantly necrotic profile.

Quantification and age-related distribution of articular cartilage degeneration in the equine fetlock joint.

The equine fetlock joint has the largest number of traumatic and degenerative lesions of all joints of the appendicular skeleton. To gain insight into the distribution of cartilage degeneration across the articular surface in relation to age in order better to understand the dynamic nature and progression of osteoarthritis (OA). That there would be a specific age-related distribution pattern of cartilage degeneration in the equine metacarpophalangeal joint. The proximal articular cartilage surfaces of the first phalanges (P1) of 73 slaughter horses (age range 0.4-23 years) with different stages of osteoarthritis were scored semiquantitatively on a 0 to 5 scale and also assessed quantitatively using the cartilage degeneration index (CDI(P1)), which ranges from 0 to 100%. Furthermore, CDI values were determined for special areas of interest; medial dorsal surface (CDI(mds)), lateral dorsal surface (CDI(lds)), medial central fovea (CDI(mcf)) and lateral central fovea (CDI(lcf)). Correlations were calculated for CDI(P1) values and CDI values at the specific areas of interest with macroscopic scores and with age. There was a high correlation between the semiquantitative macroscopic score and the quantitative CDI(P1) values (r = 0.92; P < 0.001). A macroscopic score of 0 (i.e. no obvious cartilage degeneration) corresponded with a CDI(P1) mean +/- s.e. value of 25 +/- 2.8% and a macroscopic score of 5 (i.e. severe cartilage degeneration in localised areas) with a mean +/- s.e. value of 38.1 +/- 7.9%. There was a moderate but highly significant correlation between the CDI(P1) value and the age of the horses (r = 0.41; P < 0.001). Highest CDI values were calculated for the medial dorsal surface (from 10.6 +/- 2.8% at macroscopic Grade 0 to 63.1 +/- 8.4% at Grade 5). At the lateral dorsal surface, these values were 5.9 +/- 1.4% and 47.2 +/- 10.4%, respectively. The CDI(mcf) and CDI(lcf) were significantly lower (P < 0.05) than the CDI(mds) and CDI(lds) at all grades. The CDI(mcf) ranged from 1.0 +/- 2.9% at Grade 0 to 43.7 +/- 9.1% at Grade 5; laterally, these values were 1.5 +/- 2.6% and 15.2 +/- 6.2%, respectively. CDI grading increased from lateral to medial and from central to dorsal. This specific distribution pattern confirms the heterogeneous nature of the OA process and strongly supports an important role for biomechanical loading, superimposed on age-related changes, in the spread of the disorder over the joint. Knowledge of the development of OA across the articular surface is essential for understanding the dynamic nature and progression of the disease and can form a basis for improvements in diagnostic and therapeutic approaches to degenerative joint disease.

Inference on Clustered Survival Data Using Imputed Frailties

This article proposes a new method for fitting frailty models to clustered survival data that is intermediate between the fully parametric and nonparametric maximum likelihood estimation approaches. A parametric form is assumed for the baseline hazard, but only for the purpose of imputing the unobserved frailties. The regression coefficients are then estimated by solving an estimating equation that is the average of the partial likelihood score with respect to the conditional distribution of frailties given the observed data. We prove consistency and asymptotic normality of the resulting estimators and give associated closedform estimators of their variance. The algorithm is easy to implement and reduces to the ordinary Cox partial likelihood approach when the frailties have a degenerate distribution. Simulations indicate high efficiency and robustness of the resulting estimates. We apply our new approach to a study with clustered survival data on asthma in children in east Boston.

Acetabular rim degeneration: a constant finding in the aged hip.

During recent years the acetabular labrum has gained increased interest because its degeneration frequently is found in association with early osteoarthritis of the hip. To determine spatial distribution of labral degeneration in the aged hip and to identify the pathologic features triggering this event, an anatomic postmortem and an intraoperative in vivo study were done in 30 cadavers (range, 60-90 years) and in 18 elderly patients (range, 69-97 years) who had hemiarthroplasty for displaced femoral neck fractures. In both groups, no gross anatomic or radiographic abnormalities suggesting advanced osteoarthritis were present. All cadaveric acetabuli (30 of 30) revealed labrum and cartilage damage. Labrum damage (17 of 18) and cartilage lesions (16 of 18) occurred less frequently and were smaller in the elderly patients. Peripheral joint degeneration was most frequent at the superior acetabular rim close to the anterior inferior iliac spine. More centrally localized cartilage lesions were present in 47% of cadavers and in 28% of patients. The majority of femurs (cadavers) (80%) showed reduced narrowing at the anteromedial femoral head-neck junction causing impingement against the corresponding acetabular rim or squeezing of this area into the joint during flexion, whereas the femoral head cartilage appeared normal in all but one hip. Acetabular rim degeneration is a constant finding in the aged hip, which seems to be triggered by femoroacetabular impingement.