Detection of linear IgE deposits in bullous pemphigoid and mucous membrane pemphigoid: a useful clue for diagnosis

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease of the skin associated with IgG autoantibodies to BP180 and BP230, while mucous membrane pemphigoid (MMP) comprises a heterogeneous group of autoimmune blistering diseases characterized by a predominant mucous membrane involvement and scarring tendency associated with an autoantibody response to various autoantigens, including BP180. While the pathogenicity of IgG autoantibodies to BP180 has been demonstrated in BP, the role of IgE autoantibodies in mediating tissue damage in BP and MMP is unclear.

Linear sclerodermic lupus erythematosus, a distinct variant of linear morphea and chronic cutaneous lupus erythematous

Overlap syndromes represent disorders that combine diagnostic criteria of two or more different connective tissue diseases.

Uniqueness of the Embedding Continuous Convolution Semigroup of a Gaussian Probability Measure on the Affine Group and an Application in Mathematical Finance

Let {μ(i)t}t≥0 ( i=1,2 ) be continuous convolution semigroups (c.c.s.) of probability measures on Aff(1) (the affine group on the real line). Suppose that μ(1)1=μ(2)1 . Assume furthermore that {μ(1)t}t≥0 is a Gaussian c.c.s. (in the sense that its generating distribution is a sum of a primitive distribution and a second-order differential operator). Then μ(1)t=μ(2)t for all t≥0 . We end up with a possible application in mathematical finance.

Reproducibility and accuracy of linear measurements on dental models derived from cone-beam computed tomography compared with digital dental casts.

INTRODUCTION The aim of this study was to determine the reproducibility and accuracy of linear measurements on 2 types of dental models derived from cone-beam computed tomography (CBCT) scans: CBCT images, and Anatomodels (InVivoDental, San Jose, Calif); these were compared with digital models generated from dental impressions (Digimodels; Orthoproof, Nieuwegein, The Netherlands). The Digimodels were used as the reference standard. METHODS The 3 types of digital models were made from 10 subjects. Four examiners repeated 37 linear tooth and arch measurements 10 times. Paired t tests and the intraclass correlation coefficient were performed to determine the reproducibility and accuracy of the measurements. RESULTS The CBCT images showed significantly smaller intraclass correlation coefficient values and larger duplicate measurement errors compared with the corresponding values for Digimodels and Anatomodels. The average difference between measurements on CBCT images and Digimodels ranged from -0.4 to 1.65 mm, with limits of agreement values up to 1.3 mm for crown-width measurements. The average difference between Anatomodels and Digimodels ranged from -0.42 to 0.84 mm with limits of agreement values up to 1.65 mm. CONCLUSIONS Statistically significant differences between measurements on Digimodels and Anatomodels, and between Digimodels and CBCT images, were found. Although the mean differences might be clinically acceptable, the random errors were relatively large compared with corresponding measurements reported in the literature for both Anatomodels and CBCT images, and might be clinically important. Therefore, with the CBCT settings used in this study, measurements made directly on CBCT images and Anatomodels are not as accurate as measurements on Digimodels.

On degeneracy and invariances of random fields paths with applications in Gaussian process modelling

We study pathwise invariances and degeneracies of random fields with motivating applications in Gaussian process modelling. The key idea is that a number of structural properties one may wish to impose a priori on functions boil down to degeneracy properties under well-chosen linear operators. We first show in a second order set-up that almost sure degeneracy of random field paths under some class of linear operators defined in terms of signed measures can be controlled through the two first moments. A special focus is then put on the Gaussian case, where these results are revisited and extended to further linear operators thanks to state-of-the-art representations. Several degeneracy properties are tackled, including random fields with symmetric paths, centred paths, harmonic paths, or sparse paths. The proposed approach delivers a number of promising results and perspectives in Gaussian process modelling. In a first numerical experiment, it is shown that dedicated kernels can be used to infer an axis of symmetry. Our second numerical experiment deals with conditional simulations of a solution to the heat equation, and it is found that adapted kernels notably enable improved predictions of non-linear functionals of the field such as its maximum.

Accuracy of linear measurements using three imaging modalities: two lateral cephalograms and one 3D model from CBCT data

BACKGROUND The aim of this study was to evaluate the accuracy of linear measurements on three imaging modalities: lateral cephalograms from a cephalometric machine with a 3 m source-to-mid-sagittal-plane distance (SMD), from a machine with 1.5 m SMD and 3D models from cone-beam computed tomography (CBCT) data. METHODS Twenty-one dry human skulls were used. Lateral cephalograms were taken, using two cephalometric devices: one with a 3 m SMD and one with a 1.5 m SMD. CBCT scans were taken by 3D Accuitomo® 170, and 3D surface models were created in Maxilim® software. Thirteen linear measurements were completed twice by two observers with a 4 week interval. Direct physical measurements by a digital calliper were defined as the gold standard. Statistical analysis was performed. RESULTS Nasion-Point A was significantly different from the gold standard in all methods. More statistically significant differences were found on the measurements of the 3 m SMD cephalograms in comparison to the other methods. Intra- and inter-observer agreement based on 3D measurements was slightly better than others. LIMITATIONS Dry human skulls without soft tissues were used. Therefore, the results have to be interpreted with caution, as they do not fully represent clinical conditions. CONCLUSIONS 3D measurements resulted in a better observer agreement. The accuracy of the measurements based on CBCT and 1.5 m SMD cephalogram was better than a 3 m SMD cephalogram. These findings demonstrated the linear measurements accuracy and reliability of 3D measurements based on CBCT data when compared to 2D techniques. Future studies should focus on the implementation of 3D cephalometry in clinical practice.

VMC++ versus BEAMnrc: a comparison of simulated linear accelerator heads for photon beams

BEAMnrc, a code for simulating medical linear accelerators based on EGSnrc, has been bench-marked and used extensively in the scientific literature and is therefore often considered to be the gold standard for Monte Carlo simulations for radiotherapy applications. However, its long computation times make it too slow for the clinical routine and often even for research purposes without a large investment in computing resources. VMC++ is a much faster code thanks to the intensive use of variance reduction techniques and a much faster implementation of the condensed history technique for charged particle transport. A research version of this code is also capable of simulating the full head of linear accelerators operated in photon mode (excluding multileaf collimators, hard and dynamic wedges). In this work, a validation of the full head simulation at 6 and 18 MV is performed, simulating with VMC++ and BEAMnrc the addition of one head component at a time and comparing the resulting phase space files. For the comparison, photon and electron fluence, photon energy fluence, mean energy, and photon spectra are considered. The largest absolute differences are found in the energy fluences. For all the simulations of the different head components, a very good agreement (differences in energy fluences between VMC++ and BEAMnrc <1%) is obtained. Only a particular case at 6 MV shows a somewhat larger energy fluence difference of 1.4%. Dosimetrically, these phase space differences imply an agreement between both codes at the <1% level, making VMC++ head module suitable for full head simulations with considerable gain in efficiency and without loss of accuracy.

REGULATION OF WHOLE-BODY ENERGY HOMEOSTASIS WITH GROWTH HORMONE REPLACEMENT THERAPY AND ENDURANCE EXERCISE

We hypothesized that network analysis is useful to expose coordination between whole body and myocellular levels of energy metabolism and can identify entities that underlie skeletal muscle's contribution to growth hormone-stimulated lipid handling and metabolic fitness. We assessed 112 metabolic parameters characterizing metabolic rate and substrate handling in tibialis anterior muscle and vascular compartment at rest, after a meal and exercise with growth hormone replacement therapy (GH-RT) of hypopituitary patients (n = 11). The topology of linear relationships (| r | ≥ 0.7, P ≤ 0.01) and mutual dependencies exposed the organization of metabolic relationships in three entities reflecting basal and exercise-induced metabolic rate, triglyceride handling, and substrate utilization in the pre- and postprandial state, respectively. GH-RT improved aerobic performance (+5%), lean-to-fat mass (+19%), and muscle area of tibialis anterior (+2%) but did not alter its mitochondrial and capillary content. Concomitantly, connectivity was established between myocellular parameters of mitochondrial lipid metabolism and meal-induced triglyceride handling in serum. This was mediated via the recruitment of transcripts of muscle lipid mobilization (LIPE, FABP3, and FABP4) and fatty acid-sensitive transcription factors (PPARA, PPARG) to the metabolic network. The interdependence of gene regulatory elements of muscle lipid metabolism reflected the norm in healthy subjects (n = 12) and distinguished the regulation of the mitochondrial respiration factor COX1 by GH and endurance exercise. Our observations validate the use of network analysis for systems medicine and highlight the notion that an improved stochiometry between muscle and whole body lipid metabolism, rather than alterations of single bottlenecks, contributes to GH-driven elevations in metabolic fitness.

Uniform approach to linear and nonlinear interrelation patterns in multivariate time series

Currently, a variety of linear and nonlinear measures is in use to investigate spatiotemporal interrelation patterns of multivariate time series. Whereas the former are by definition insensitive to nonlinear effects, the latter detect both nonlinear and linear interrelation. In the present contribution we employ a uniform surrogate-based approach, which is capable of disentangling interrelations that significantly exceed random effects and interrelations that significantly exceed linear correlation. The bivariate version of the proposed framework is explored using a simple model allowing for separate tuning of coupling and nonlinearity of interrelation. To demonstrate applicability of the approach to multivariate real-world time series we investigate resting state functional magnetic resonance imaging (rsfMRI) data of two healthy subjects as well as intracranial electroencephalograms (iEEG) of two epilepsy patients with focal onset seizures. The main findings are that for our rsfMRI data interrelations can be described by linear cross-correlation. Rejection of the null hypothesis of linear iEEG interrelation occurs predominantly for epileptogenic tissue as well as during epileptic seizures.

Application and comparison of classification algorithms for recognition of Alzheimer's disease in electrical brain activity (EEG)

The early detection of subjects with probable Alzheimer's disease (AD) is crucial for effective appliance of treatment strategies. Here we explored the ability of a multitude of linear and non-linear classification algorithms to discriminate between the electroencephalograms (EEGs) of patients with varying degree of AD and their age-matched control subjects. Absolute and relative spectral power, distribution of spectral power, and measures of spatial synchronization were calculated from recordings of resting eyes-closed continuous EEGs of 45 healthy controls, 116 patients with mild AD and 81 patients with moderate AD, recruited in two different centers (Stockholm, New York). The applied classification algorithms were: principal component linear discriminant analysis (PC LDA), partial least squares LDA (PLS LDA), principal component logistic regression (PC LR), partial least squares logistic regression (PLS LR), bagging, random forest, support vector machines (SVM) and feed-forward neural network. Based on 10-fold cross-validation runs it could be demonstrated that even tough modern computer-intensive classification algorithms such as random forests, SVM and neural networks show a slight superiority, more classical classification algorithms performed nearly equally well. Using random forests classification a considerable sensitivity of up to 85% and a specificity of 78%, respectively for the test of even only mild AD patients has been reached, whereas for the comparison of moderate AD vs. controls, using SVM and neural networks, values of 89% and 88% for sensitivity and specificity were achieved. Such a remarkable performance proves the value of these classification algorithms for clinical diagnostics.

Effect of disodium monofluorophosphate, calcium and vitamin D supplementation on bone mineral density in patients chronically treated with glucocorticosteroids: a prospective, randomized, double-blind study

To study the effect of fluoride on bone mineral density (BMD) in patients treated chronically with glucocorticosteroids, 15 subjects (renal grafted, n = 12; skin disease, n = 1; broncho pulmonary disorder, n = 1; Crohn's disease, n = 1) were prospectively studied in a double-blinded manner and randomly allocated either to group 1 (n = 8) receiving 13.2 mg/day fluoride given as disodium monofluorophosphate (MFP) supplemented with calcium (1,000 mg/day) and 25-hydroxyvitamin D (calcifediol) (50 micrograms/day), or to group 2 (n = 7) receiving Cas+ calcifediol alone. An additional group of 14 renal transplant patients treated chronically with glucocorticosteroids but exempt of specific therapeutic intervention for bone disease was set up as historical controls. BMD was measured by dual-energy X-ray absorptiometry (DXA, Hologic QDR 1000) performed at months 0, 6 and 12 for groups 1 and 2 (lumbar spine, total upper femur, diaphysis and epiphysis of distal tibia), or 11-31 months apart with calculation of linear yearly changes for the historical cohort. Lumbar BMD tended to rise in groups 1 and 2, and to fall in group 3, the change reaching statistical significance (p < 0.05) in group 1, thus leading to a significant difference between groups 1 and 3 (p < 0.05). At upper femur, tibial diaphysis and tibial epiphysis, no significant change in BMD occurred in any of the groups. In conclusion, lumbar BMD rises more after a mild dosis of fluoride given as MFP and combined to calcium and calcifediol than on Ca+ calcifediol alone, without changes in BMD at the upper femur or distal tibia.

Analysis of Pressure Head-Flow Loops of Pulsatile Rotodynamic Blood Pumps

The clinical importance of pulsatility is a recurring topic of debate in mechanical circulatory support. Lack of pulsatility has been identified as a possible factor responsible for adverse events and has also demonstrated a role in myocardial perfusion and cardiac recovery. A commonly used method for restoring pulsatility with rotodynamic blood pumps (RBPs) is to modulate the speed profile, synchronized to the cardiac cycle. This introduces additional parameters that influence the (un)loading of the heart, including the timing (phase shift) between the native cardiac cycle and the pump pulses, and the amplitude of speed modulation. In this study, the impact of these parameters upon the heart-RBP interaction was examined in terms of the pressure head-flow (HQ) diagram. The measurements were conducted using a rotodynamic Deltastream DP2 pump in a validated hybrid mock circulation with baroreflex function. The pump was operated with a sinusoidal speed profile, synchronized to the native cardiac cycle. The simulated ventriculo-aortic cannulation showed that the level of (un)loading and the shape of the HQ loops strongly depend on the phase shift. The HQ loops displayed characteristic shapes depending on the phase shift. Increased contribution of native contraction (increased ventricular stroke work [WS ]) resulted in a broadening of the loops. It was found that the previously described linear relationship between WS and the area of the HQ loop for constant pump speeds becomes a family of linear relationships, whose slope depends on the phase shift.