Performance of a deep convolutional neural network for MRI-based vertebral body measurements and insufficiency fracture detection.

OBJECTIVES: The aim is to validate the performance of a deep convolutional neural network (DCNN) for vertebral body measurements and insufficiency fracture detection on lumbar spine MRI. METHODS: This retrospective analysis included 1000 vertebral bodies in 200 patients (age 75.2 ± 9.8 years) who underwent lumbar spine MRI at multiple institutions. 160/200 patients had ≥ one vertebral body insufficiency fracture, 40/200 had no fracture. The performance of the DCNN and that of two fellowship-trained musculoskeletal radiologists in vertebral body measurements (anterior/posterior height, extent of endplate concavity, vertebral angle) and evaluation for insufficiency fractures were compared. Statistics included (a) interobserver reliability metrics using intraclass correlation coefficient (ICC), kappa statistics, and Bland-Altman analysis, and (b) diagnostic performance metrics (sensitivity, specificity, accuracy). A statistically significant difference was accepted if the 95% confidence intervals did not overlap. RESULTS: The inter-reader agreement between radiologists and the DCNN was excellent for vertebral body measurements, with ICC values of > 0.94 for anterior and posterior vertebral height and vertebral angle, and good to excellent for superior and inferior endplate concavity with ICC values of 0.79-0.85. The performance of the DCNN in fracture detection yielded a sensitivity of 0.941 (0.903-0.968), specificity of 0.969 (0.954-0.980), and accuracy of 0.962 (0.948-0.973). The diagnostic performance of the DCNN was independent of the radiological institution (accuracy 0.964 vs. 0.960), type of MRI scanner (accuracy 0.957 vs. 0.964), and magnetic field strength (accuracy 0.966 vs. 0.957). CONCLUSIONS: A DCNN can achieve high diagnostic performance in vertebral body measurements and insufficiency fracture detection on heterogeneous lumbar spine MRI. KEY POINTS: • A DCNN has the potential for high diagnostic performance in measuring vertebral bodies and detecting insufficiency fractures of the lumbar spine.

Soil pH, nitrogen, phosphatase and urease activities in response to cover crop species, termination stage and termination method.

The best management options for cover cropping are largely unknown, including the growth patterns of cover crop (CC) species, optimum termination stages and termination methods. A greenhouse experiment was conducted to explore the following: (i) Effect of two termination stages (vegetative and flowering) on the chemical composition (N and C:N) of four CCs; (ii) Short-term impacts of living CCs and residues on soil pH, total N, urease and phosphatase activities at the two termination stages, and under two termination methods (slash and spray). Species tested as CCs were, vetch (Vicia dasycarpa L.), field pea (Pisum sativum L.), oats (Avena sativa L.), rye (Secale cereal L.) and a control (no CC). The experiment was set up in a randomized block design with three replications. Soil was sampled at kill and one year after CC kill. Delaying termination from vegetative till flowering stage decreased N in the tissue of P. sativum, A. sativa, V. dasycarpa and S. cereal by 59%, 65%, 44% and 56%, respectively, while their C:N ratios increased. Cover crop presence had no effect on soil pH. Living CCs had no significant effect on soil N concentration. The activities of urease and phosphatase were stimulated by all the living CC species. Unlike urease, all CC residues had a positive impact on phosphatase activity at one year. Only P. sativum and V. dasycarpa residues increased soil N concentration in the short-term. Compared to flowering, termination at vegetative stage improved soil N concentrations and phosphatase activity at both sampling times. Termination method had no effect on soil N, urease and phosphatase activity at one year. The significant interaction (P < 0.05) of sampling time, CC and termination stage effects on soil N concentration and phosphatase activity observed in this study indicates that these management approaches can optimize CC benefits and improve soil chemical and biological properties.

Long-term chipping and failure rates of implant-supported and combined tooth-implant-supported metal-ceramic and ceramic fixed dental prostheses: A cohort study.

STATEMENT OF PROBLEM: Combined tooth-implant-supported fixed dental prostheses have been associated with an increased risk of long-term failure. Furthermore, high chipping rates have been reported for ceramic fixed dental prostheses. However, clinical data are sparse. PURPOSE: The purpose of this observational cohort study was to evaluate the chipping and failure rates of metal-ceramic and ceramic implant-supported and combined tooth-implant-supported fixed dental prostheses. MATERIAL AND METHODS: Four hundred thirty-four fixed dental prostheses placed in 324 patients (mean age: 60.8 years) were selected from a prospective clinical long-term study comprising 213 implant-supported fixed dental prostheses, 66 implant-supported cantilever fixed dental prostheses, and 155 tooth-implant-supported fixed dental prostheses. Metal-ceramic fixed dental prostheses (n=260) were fabricated with a high noble metal alloy (n=225) or Co-Cr base metal alloy (n=35) frameworks. Ceramic fixed dental prostheses (n=174) were all zirconia based and had monolithic (n=68), completely veneered (n=43), or partially veneered frameworks (n=63). Kaplan-Meier curves were used to estimate the survival probability and the chipping-free survival rate of the fixed dental prostheses. RESULTS: During the observation period of 0.5 to 12.6 years (mean: 4.26 years), 17 fixed dental prostheses failed because of implant failure (n=6), tooth loss (n=5), major chipping (n=5), or abutment screw loosening (n=1). Survival probability was 96% after 5 years and 91% after 10 years. Cox regression analysis showed that age, sex, fixed dental prosthesis location, type of fixed dental prosthesis support, and fixed dental prosthesis material had no significant effect on fixed dental prosthesis failure. Chipping (n=61) was significantly affected by the framework material and type of veneer (P=.001). After 5 years, the greatest incidence of chipping (39%) was observed for zirconia fixed dental prostheses with a complete veneer compared with an 18% incidence of chipping for metal-ceramic fixed dental prostheses with a high noble metal framework. A lower incidence of chipping was observed for zirconia fixed dental prostheses with a partial veneer or monolithic design. CONCLUSIONS: Implant-implant-supported and combined tooth-implant-supported fixed dental prostheses have promising long-term survival rates. Chipping seems to occur less frequently in monolithic or partially veneered fixed dental prostheses than in fixed dental prostheses with complete veneers.

Effect of Increased Lactate Dehydrogenase A Activity and Aerobic Glycolysis on the Proinflammatory Profile of Autoimmune CD8+ T Cells in Rheumatoid Arthritis.

OBJECTIVE: CD8+ T cells contribute to rheumatoid arthritis (RA) by releasing proinflammatory and cytolytic mediators, even in a challenging hypoxic and nutrient-poor microenvironment such as the synovial membrane. This study was undertaken to explore the mechanisms through which CD8+ T cells meet their metabolic demands in the blood and synovial membrane of patients with RA. METHODS: Purified blood CD8+ T cells from patients with RA, patients with psoriatic arthritis (PsA), and patients with spondyloarthritis (SpA), as well as healthy control subjects, and CD8+ T cells from RA synovial membrane were stimulated in medium containing 13 C-labeled metabolic substrates in the presence or absence of metabolic inhibitors, under conditions of normoxia or hypoxia. The production of metabolic intermediates was quantified by 1 H-nuclear magnetic resonance. The expression of metabolic enzymes, transcription factors, and immune effector molecules was assessed at both the messenger RNA (mRNA) and protein levels. CD8+ T cell functional studies were performed. RESULTS: RA blood CD8+ T cells met their metabolic demands through aerobic glycolysis, production of uniformly 13 C-enriched lactate in the RA blood (2.6 to 3.7-fold higher than in patients with SpA, patients with PsA, and healthy controls; P < 0.01), and induction of glutaminolysis. Overexpression of Warburg effect-linked enzymes in all RA CD8+ T cell subsets maintained this metabolic profile, conferring to the cells the capacity to proliferate under hypoxia and low-glucose conditions. In all RA CD8+ T cell subsets, lactate dehydrogenase A (LDHA) was overexpressed at the mRNA level (P < 0.03 versus controls; n = 6 per group) and protein level (P < 0.05 versus controls; n = 17 RA patients, n = 9 controls). In RA blood, inhibition of LDHA with FX11 led to reductions in lipogenesis, migration and proliferation of CD8+ T cells, and CD8+ T cell effector functions, while production of reactive oxygen species was increased by 1.5-fold (P < 0.03 versus controls). Following inhibition of LDHA with FX11, RA CD8+ T cells lost their capacity to induce healthy B cells to develop a proinflammatory phenotype. Similar metabolic alterations were observed in RA CD8+ T cells from the synovial membrane. CONCLUSION: Remodeling glucose and glutamine metabolism in RA CD8+ T cells by targeting LDHA activity can reduce the deleterious inflammatory and cytolytic contributions of these cells to the development of autoimmunity.

Long-term performance of implant-supported metal-ceramic and all-ceramic single crowns.

PURPOSE: To evaluate failure rates and incidence of chipping for metal-ceramic and all-ceramic implant-supported single crowns (SCs). METHODS: Six hundred and fifty-two implant-supported SCs placed in 404 patients (mean age: 57.8 years; 193 male; mean SCs per patient: 1.6) were evaluated up to 12.8 years. The frameworks of the SCs were made from Au alloys (n = 319), CoCr (n = 37), zirconia (n = 286), or lithium disilicate (n = 10). Full-coverage ceramic veneers were placed on 319 Au SCs, 34 CoCr SCs, and 92 zirconia SCs. One hundred and fifty-two monolithic zirconia SCs were not veneered. A partial veneer was placed on the buccal surface only of a further 42 zirconia SCs. RESULTS: A total of 26 failures were caused by loss of implants (n = 6), ceramic fractures and chipping (n = 15), loosening of the abutment (n = 4), or swallowing of a de-cemented SC (n = 1). Kaplan-Meier analysis revealed a probability of survival of 96% after five years and 92% after 10 years. A greater incidence of failure was observed for lithium disilicate and zirconia SCs than for metal-ceramic SCs (p < .05). Separate analysis of the most frequent complication, chipping (n = 61), revealed that zirconia and lithium disilicate frameworks were significant risk factors for chipping (p < 0.05). Furthermore, a significantly greater incidence of chipping was observed for SCs with full-coverage veneers than for monolithic zirconia SCs and for SCs with partial veneers (p < .05). CONCLUSION: Avoidance of full-coverage veneers significantly improves the clinical performance of implant-supported crowns, primarily reduces the incidence of chipping.

Fracture resistance of zirconia-based all-ceramic crowns after bur adjustment.

Intra-oral grinding is often required to optimize occlusion of all-ceramic restorations. The effect of burs of different grit size on the fracture resistance of veneered zirconia crowns was investigated in this study. Forty-eight standardized zirconia copings were produced. The ceramic veneer was designed with a positive ellipsoidal defect on the palatal aspect of the crowns. To simulate adjustment of dental restorations by burs, this palatal defect was removed by use of three different diamond-coated burs with grit sizes 46, 107, or 151 µm (fine, medium, or coarse, respectively). Each different grit size of bur was used to grind 16 crowns. All crowns were then polished and surface roughness was measured. Half of the specimens underwent thermomechanical aging (10,000 thermocycles between 6.5°C and 60°C) and 1.2 million cycles of chewing simulation (F = 108 N). A linear regression model was computed to test the effect of aging and grinding grit size at a level of significance of α = 0.05. Fracture loads increased with decreasing grit size. Grit size and aging had a significant effect on the fracture resistance of the crowns. Use of fine and coarse burs for intra-oral adjustments resulted in different fracture resistance of veneered zirconia crowns. Coarse burs should be avoided in the final stage of grinding before polishing.

Rapid Monte Carlo simulation of detector DQE(f).

PURPOSE: Performance optimization of indirect x-ray detectors requires proper characterization of both ionizing (gamma) and optical photon transport in a heterogeneous medium. As the tool of choice for modeling detector physics, Monte Carlo methods have failed to gain traction as a design utility, due mostly to excessive simulation times and a lack of convenient simulation packages. The most important figure-of-merit in assessing detector performance is the detective quantum efficiency (DQE), for which most of the computational burden has traditionally been associated with the determination of the noise power spectrum (NPS) from an ensemble of flood images, each conventionally having 10(7) - 10(9) detected gamma photons. In this work, the authors show that the idealized conditions inherent in a numerical simulation allow for a dramatic reduction in the number of gamma and optical photons required to accurately predict the NPS. METHODS: The authors derived an expression for the mean squared error (MSE) of a simulated NPS when computed using the International Electrotechnical Commission-recommended technique based on taking the 2D Fourier transform of flood images. It is shown that the MSE is inversely proportional to the number of flood images, and is independent of the input fluence provided that the input fluence is above a minimal value that avoids biasing the estimate. The authors then propose to further lower the input fluence so that each event creates a point-spread function rather than a flood field. The authors use this finding as the foundation for a novel algorithm in which the characteristic MTF(f), NPS(f), and DQE(f) curves are simultaneously generated from the results of a single run. The authors also investigate lowering the number of optical photons used in a scintillator simulation to further increase efficiency. Simulation results are compared with measurements performed on a Varian AS1000 portal imager, and with a previously published simulation performed using clinical fluence levels. RESULTS: On the order of only 10-100 gamma photons per flood image were required to be detected to avoid biasing the NPS estimate. This allowed for a factor of 10(7) reduction in fluence compared to clinical levels with no loss of accuracy. An optimal signal-to-noise ratio (SNR) was achieved by increasing the number of flood images from a typical value of 100 up to 500, thereby illustrating the importance of flood image quantity over the number of gammas per flood. For the point-spread ensemble technique, an additional 2× reduction in the number of incident gammas was realized. As a result, when modeling gamma transport in a thick pixelated array, the simulation time was reduced from 2.5 × 10(6) CPU min if using clinical fluence levels to 3.1 CPU min if using optimized fluence levels while also producing a higher SNR. The AS1000 DQE(f) simulation entailing both optical and radiative transport matched experimental results to within 11%, and required 14.5 min to complete on a single CPU. CONCLUSIONS: The authors demonstrate the feasibility of accurately modeling x-ray detector DQE(f) with completion times on the order of several minutes using a single CPU. Convenience of simulation can be achieved using GEANT4 which offers both gamma and optical photon transport capabilities.

Long-term administration of IgG2a anti-NK1.1 monoclonal antibody ameliorates lupus-like disease in NZB/W mice in spite of an early worsening induced by an IgG2a-dependent BAFF/BLyS production.

The role of natural killer (NK) T cells in the development of lupus-like disease in mice is still controversial. We treated NZB/W mice with anti-NK1.1 monoclonal antibodies (mAbs) and our results revealed that administration of either an irrelevant immunoglobulin G2a (IgG2a) mAb or an IgG2a anti-NK1.1 mAb increased the production of anti-dsDNA antibodies in young NZB/W mice. However, the continuous administration of an anti-NK1.1 mAb protected aged NZB/W mice from glomerular injury, leading to prolonged survival and stabilization of the proteinuria. Conversely, the administration of the control IgG2a mAb led to an aggravation of the lupus-like disease. Augmented titres of anti-dsDNA in NZB/W mice, upon IgG2a administration, correlated with the production of BAFF/BLyS by dendritic, B and T cells. Treatment with an anti-NK1.1 mAb reduced the levels of interleukin-16, produced by T cells, in spleen cell culture supernatants from aged NZB/W. Adoptive transfer of NK T cells from aged to young NZB/W accelerated the production of anti-dsDNA in recipient NZB/W mice, suggesting that NK T cells from aged NZB/W are endowed with a B-cell helper activity. In vitro studies, using purified NK T cells from aged NZB/W, showed that these cells provided helper B-cell activity for the production of anti-dsDNA. We concluded that NK T cells are involved in the progression of lupus-like disease in mature NZB/W mice and that immunoglobulin of the IgG2a isotype has an enhancing effect on antibody synthesis due to the induction of BAFF/BLyS, and therefore have a deleterious effect in the NZB/W mouse physiology.

Potentiation of immunological tolerance induction in adult mice by co-administration of pooled normal IgG and oral tolerogens: a potential therapeutic approach for autoimmune diseases.

Oral tolerance can be defined as the inability of an adult animal to produce specific antibodies or cellular immune responses upon conventional immunization, after oral antigenic administration. Recently, the oral administration of antigens has gained renewed interest because of the possibility of inducing tolerance in nonimmunized adult animals and, consequently, opening up the theoretical possibility of preventing or treating diseases caused by malfunction of the immune system. This strategy has been proven to be useful in the prevention of allergic and autoimmune diseases in rodents, as well as in the amelioration of certain autoimmune diseases in humans. Although there is experimental and clinical evidence for the usefulness of oral tolerance in medical practice, the mechanisms responsible for this phenomenon are still poorly understood, and the results obtained are not always satisfactory. Herein, we show that the thymus is required for the induction and maintenance of oral tolerance, providing evidence that it is not a pure form of clonal deletion-based peripheral tolerance. Oral tolerance could therefore depend on the formation and release to the periphery of regulatory T cells, such as gammadelta or alphabeta T cells, by the thymus. This finding may have profound implications for the treatment of autoimmune diseases, since most of them are associated with thymic hypofunction. On the other hand, due to so far unknown mechanisms, the intraperitoneal co-administration of normal IgG to mice orally treated with tolerogen leads to a sustained and intense immunological tolerance, both in euthymic and thymectomized mice, including those of the lupus erythematosus-prone NZB x NZW lineage. This approach for inducing and maintaining tolerance in thymus-deficient conditions is discussed and put forth herein as a new evidence-based proposition for the therapy of autoimmune diseases.