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The spinel ZnFe 2 O 4 specimens were obtained via a hydrothermal and a ceramic method, respectively, and their structural and magnetic properties were comparatively studied. It was found that all the specimens exhibited a single-phase and mixed spinel structure. The magnetism of specimens synthesized via the hydrothermal method is obviously better than that of specimen prepared via the ceramic method. This can be ascribed to the different occupancy of Fe ions resulted from the loss of Zn during the hydrothermal process. [ABSTRACT FROM AUTHOR]

Mechanistic hypothesis linking the mechanical and topographical variation to AFSC differentiation via YAP activation. YAP mediates cell differentiation in concern with FAs assembly through integrin to maintain the integrity of actin fiber cytoskeleton. This triggers YAP nuclear shuttling. In the nucleus, YAP helps transcribe the tendon/ligament-related genes encoding for proteins participating in AFSC differentiation. Annulus fibrosus (AF) tissue engineering has attracted increasing attention as a promising therapy for degenerative disc disease (DDD). However, regeneration of AF still faces many challenges due to the tremendous complexity of this tissue and lack of in-depth understanding of the structure-function relationship at cellular level within AF is highly required. In light of the fact that AF is composed of various types of cells and has gradient mechanical, topographical and biochemical features along the radial direction. In this study, we aimed to achieve directed differentiation of AF-derived stem cells (AFSCs) by mimicking the mechanical and topographical features of native AF tissue. AFSCs were cultured on four types of electrospun poly(ether carbonate urethane)urea (PECUU) scaffolds with various stiffness and fiber size (soft, small size; stiff, small size; soft, large size and stiff, large size). The results show that with constant fiber size, the expression level of the outer AF (oAF) phenotypic marker genes in AFSCs increased with the scaffold stiffness, while that of inner AF (iAF) phenotypic marker genes showed an opposite trend. When scaffold stiffness was fixed, the expression of oAF phenotypic marker genes in AFSCs increased with fiber size. While the expression of iAF phenotypic marker genes decreased. Such substrate stiffness- and topography-dependent changes of AFSCs was in accordance with the genetic and biochemical distribution of AF tissue from the inner to outer regions. Further, we found that the Yes-associated protein (YAP) was translocated to the nucleus in AFSCs cultured with increasing stiffness and fiber size of scaffolds, yet it remained mostly phosphorylated and cytosolic in cells on soft scaffolds with small fiber size. Inhibition of YAP down-regulated the expression of tendon/ligament-related genes, whereas expression of the cartilage-related genes was upregulated. The results illustrate that matrix stiffness is a potent regulator of AFSC differentiation. Moreover, we reveal that fiber size of scaffolds induced changes in cell adhesions and determined cell shape, spreading area, and extracellular matrix expression. In all, both mechanical property and topography features of scaffolds regulate AFSC differentiation, possibly through a YAP-dependent mechanotransduction mechanism. Physical cues such as mechanical properties, topographical and geometrical features were shown to profoundly impact the growth and differentiation of cultured stem cells. Previously, we have found that the differentiation of annulus fibrosus-derived stem cells (AFSCs) could be regulated by the stiffness of scaffold. In this study, we fabricated four types of poly(ether carbonate urethane)urea (PECUU) scaffolds with controlled stiffness and fiber size to explore the potential of induced differentiation of AFSCs. We found that AFSCs are able to present different gene expression patterns simply as a result of the stiffness and fiber size of scaffold material. This work has, for the first time, demonstrated that larger-sized and higher-stiffness substrates increase the amount of vinculin assembly and activate YAP signaling in pre-differentiated AFSCs. The present study affords an in-depth comprehension of materiobiology, and be helpful for explain the mechanism of YAP mechanosensing in AF in response to biophysical effects of materials. [ABSTRACT FROM AUTHOR]

Abstract: Although intradiscal cement leakage is a common complication of spine augmentation, the effects of cement leakage into the intervertebral disc (IVD) have not been well investigated. This study aimed to determine the effects of cement leakage on IVD degeneration in rabbits. Poly(methyl methacrylate) (PMMA) particles were injected into lumbar discs of rabbits using 26G needles. Tissue effects were assessed using disc height, sagittal T2-weighted images, histology and immunohistochemistry. The results showed that stimulation with PMMA particles significantly reduced disc height compared with that in the sham-operation group at 3weeks after injection. The mean signal intensity of the operated discs showed little to no changes among all groups at 3weeks post-operation. After 6weeks, the signal intensity of the PMMA-injected group decreased by 22% compared with that in the sham-operation group. Histological and quantitative immunohistochemical examination indicated phenotypic tissue changes from cartilaginous tissue into fibrotic tissue, with apparent degeneration in the PMMA group. Additionally, more collagen type II-containing tissues, but fewer matrix metalloproteinase-7-positive cells or apoptotic cells, were detected in the sham-operation group. The PMMA particle-induced degeneration rate was slower than that of the degeneration group, whereas the histologic data showed no difference in the progression of degeneration between the two groups. These data suggest that PMMA particles can moderately accelerate disc degeneration compared with the 18G needle puncture model. In conclusion, intradiscal injection of PMMA particles induced significant IVD degeneration in vivo. Therefore, further study of the adverse effects of PMMA leakage on IVD degeneration is required. [Copyright &y& Elsevier]

Abstract: Particle-wear-induced inflammatory osteolysis remains a major problem for the long-term success of total joint arthroplasty. Previous studies have demonstrated that cyclooxygenase-2 (COX-2) is expressed abundantly in the tissue around a failed implant. However, the role of COX-2 in the development of particle-wear-induced osteoclastogenesis remains unclear. The aim of the study was to test the hypothesis that Dynastat, a COX-2 inhibitor, ameliorates particle-wear-induced inflammatory osteoclastogenesis through the down-regulation of the receptor activators of nuclear factor-κB (RANK) and nuclear factor-κB ligand (RANKL) expression in a murine osteolysis model. Titanium (Ti) particles were introduced into established air pouches in BALB/c mice, followed by the implantation of calvaria bone from syngeneic littermates. Dynastat was given to mice intraperitoneally 2days before the introduction of Ti particles and maintained until the mice were sacrificed. Pouch tissues were collected 14days after Ti inoculation for molecular and histological analysis. The results showed that Dynastat has more impact on Ti-particle-induced prostaglandin E2 expression and less on the expression of interleukin-1β and tumor necrosis factor-α. Dynastat inhibited Ti-particle-induced osteoclastogenesis by reducing the gene activation of RANK and RANKL, and diminishing the RANKL expression in Ti-particle-charged pouches. Dynastat markedly reduced the number of tartrate-resistant acid-phosphatase-positive cells in pouch tissues stimulated by Ti particles. In conclusion, this study provides evidence that Dynastat can markedly inhibit Ti-particle-induced osteoclastogenesis by the down-regulation of RANK/RANKL in a murine air pouch model, and is a promising therapeutic candidate for the treatment of inflammatory osteolysis induced by wear particles. [Copyright &y& Elsevier]

Abstract: Nineteen patients with post-traumatic osteoporotic vertebral osteonecrosis were treated using percutaneous balloon kyphoplasty. The anterior and middle vertebral heights, as well as the kyphotic angle, were measured using a standing lateral radiograph before surgery, 2 days after surgery and at the final follow-up. At the same time points, a visual analog scale and the Oswestry Disability Index were used to evaluate pain status and functional activity, respectively. The mean follow-up was 24.7 months (range: 7–36 months). Statistically significant improvements were observed between the preoperative and postoperative assessments for each evaluated measure (p <0.05). There were no statistically significant differences between the postoperative and final follow-up assessments (p >0.05). Asymptomatic cement leakage into the intervertebral disc occurred in three patients. This study suggests that balloon kyphoplasty is a safe and effective procedure for treating this disease entity. [Copyright &y& Elsevier]

Abstract: Autogenous bone grafting has traditionally been considered the “gold standard” for spinal fusion. However, the associated morbidity and limitations of autogenous bone grafts have prompted the search for bone graft alternatives, such as a bioabsorbable-calcified triglyceride (BCT). We aimed to assess the capability of BCT in a rat spinal fusion model. Thirty-six Sprague-Dawley rats underwent lumbar fusion surgery: Group 1 rats were implanted with an autograft from the iliac crest; Group 2 rats were implanted with BCT; and Group 3 rats were implanted with BCT and autograft. In Group 2, 66.7% of rats and in Group 3, 83.3% of rats, were judged to have undergone complete fusion. Only 25% of rats in Group 1 showed bridging bone from the transverse processes with some gaps. Our study demonstrated that osteoconductive BCT is a promising autograft extender when applied as an adjunct to spinal fusion. [Copyright &y& Elsevier]

High brittleness and lack osteogenesis are two major limitations of calcium phosphate cement (CPC) in application in bone defect reconstruction. Here we prepared a composite calcium phosphate cement by mixing N-acetyl cysteine loaded silk fibroin solution with α-tricalcium phosphate. In vitro cytology experiment revealed that SF-NAC/α-TCP could significantly increase the activity of exocrine ALP and up-regulated expression of bone-related genes. However, NAC up-regulated gene expression could be significantly suppressed by DKK1. We propose that NAC functioning as osteogenic factor by activating the Wnt/β-catenin signaling pathway may be the possible mechanism of up-regulation of osteogenic genes. Bone regeneration in vivo shown in a rat femur defect was enhanced by the addition of NAC in SF/α-TCP. In addition, the combination intensity of cement-bone interface was improved. The combination SF-NAC/α-TCP might be developed into a promising tool for bone tissue repair in the clinic. [ABSTRACT FROM AUTHOR]

[Display omitted] • Constituents of different varieties of matcha varies significantly. • Qualitative and quantitative analysis of matcha by Vis-NIR is superior than NIR. • HSI realized the visualization of main constituents in matcha. • RF feature selection can reduce the dimension of spectra and with good results. • Raw spectra perform better than processed spectral effects. Matcha, made from different tea leaves as raw material, exhibits diverse aromas and flavors. Therefore, there is an urgent need for a rapid, non-destructive method to assess the quality of matcha to ensure that these different characteristics are accurately assessed without compromising the integrity of the product. In this study, hyperspectral imaging technology (HSI) combined with machine learning methods enabled the first visual in situ assessment of matcha quality. The physicochemical contents of matcha were determined chemically. Qualitative and quantitative detection models for different types and grades were developed using HSI (containing Vis-NIR and NIR band). The results showed that hyperspectral data in the Vis-NIR were better than in the NIR band. The accuracy of XGBoost in modelling the classification of matcha grades reached 98.10 %. After feature selection using the random forest (RF) method, partial least squares regression (PLSR) was built to predicted the quality of matcha, which showed high prediction accuracy (test set R p 2 > 0.95). The model uses HSI to visually visualize spatial variations in constitutions (catechins, free amino acids, caffeine, soluble proteins, and soluble sugars) to show compositional differences between different types of matcha, providing a rapid non-destructive method for comprehensive assessment of matcha quality. [ABSTRACT FROM AUTHOR]

Background Balloon kyphoplasty (BKP) is an effective method for osteoporotic vertebral compression fractures. However osteoporotic spinal fractures with middle column compromise are mentioned as a relative contraindication to BKP. Thus we investigated the safety and efficacy of BKP in the treatment of osteoporotic spinal fractures with middle column compromise but without neurological deficit. Methods In this retrospective study, 45 patients who suffered osteoporotic fractures with middle column compromise but without neurological deficits were treated by BKP from May 2007 to December 2010. The final follow-ups were finished during the time of July 2011–September 2011. The mean follow-up period was 20.2 months. The height of the compromised vertebral body, the kyphotic angle and spinal canal compromise were measured before surgery, one day after surgery, and at the final follow-up. A visual analogue scale (VAS) and the Oswestry disability index (ODI) were chosen to evaluate pain and functional activity. Results The mean VAS and ODI scores improved significantly from pre- to post-operation ( p < 0.05), and this improvement was sustained at the final follow-up. The mean anterior vertebral body height ratio improved from 57.6% ± 11.8% preoperatively to 86.2% ± 12.2% postoperatively ( p < 0.05), so did the mean middle vertebral body height ratio. The kyphotic angle improved from 16.3° ± 3.7° preoperatively to 9.3° ± 2.6° postoperatively ( p < 0.05). At final follow-up, BKP stabilised vertebral height and prevented further kyphotic deformity. While there were no differences in spinal canal compromise between pre-operation and one day after surgery ( p > 0.05), there was a significant difference from the measurement at the final follow-up ( p < 0.05). Conclusion BKP is a safe and effective method for osteoporotic spinal fractures with middle column compromise but without neurological deficit. Spontaneous remodelling of the spinal canal also occurs after BKP. [ABSTRACT FROM AUTHOR]

Limited self-renewal potency of cartilage impedes the repair and regeneration at the site of damage. Investigating small-molecule compounds to boost chondrogenesis has yielded the dawn. However, the durability and targeting of current drug delivery and the adaptive integration for cartilage defects are not addressed. Herein, we fabricated a dynamic hydrogel based on the coordination between metal ions and collagen and then supramolecularly enveloped with a chondro-inductive factor kartogenin (KGN) via cyclodextrin (CD). The self-recovery and injectability of dynamic hydrogel enabled minimally invasive and precise treatment of cartilage injury assisted by continuous KGN administration. The hydrogel could significantly promote the expression of cartilage matrix components (type II collagen and aggrecan) in articular chondrocytes without affecting cell proliferation or migration in vitro. Mechanistically, the protective effects depended on enhancing chondrocyte mitochondrial function and intracellular antioxidant properties. In situ hydrogel injection strengthened cartilage regenerative potential and facilitated the reconstruction of subchondral bone following full-thickness defects in vivo. This study revealed that the dynamic chondrogenic hydrogel could benefit cartilage repair via mitochondrial reinforcement, acting as a novel therapeutic strategy for refractory cartilage damage. [ABSTRACT FROM AUTHOR]

Aseptic loosening is associated with the development of wear debris-induced peri-implant osteolytic bone disease caused by an increased osteoclastic bone resorption and decreased osteoblastic bone formation. However, no effective measures for the prevention and treatment of peri-implant osteolysis currently exist. The aim of this study was to determine whether lithium chloride (LiCl), a selective inhibitor of glycogen synthetase kinase 3 beta (GSK-3β), mitigates wear debris-induced osteolysis in a murine calvarial model of osteolysis. GSK-3β is activated by titanium (Ti) particles, and implantation of Ti particles on the calvarial surface in C57BL/6 mice resulted in osteolysis caused by an increase in the number of osteoclasts and a decrease in the number of osteoblasts. Mice implanted with Ti particles were gavage-fed LiCl (50 or 200 mg kg −1 d −1 ), 6 days per week for 2 weeks. The LiCl treatment significantly inhibited GSK-3β activity and increased β-catenin and axin-2 expression in a dose-dependent manner, dramatically mitigating the Ti particle-induced suppression of osteoblast numbers and the expression of bone formation markers. Finally, we demonstrated that inhibition of GSK-3β suppresses osteoclast differentiation and reduces the severity of Ti particle-induced osteolysis. The results of this study indicate that Ti particle-induced osteolysis is partly dependent on GSK-3β and, therefore, the canonical Wnt signaling pathway. This suggests that selective inhibitors of GSK-3β such as LiCl may help prevent and treat wear debris-induced osteolysis. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA), characterized by cartilage erosion, synovium inflammation, and subchondral bone remodeling, is a common joint degenerative disease worldwide. OA pathogenesis is regulated by multiple predisposing factors, including imbalanced matrix metabolism, aberrant inflammatory response, and excessive oxidative stress. Moreover, melatonin has been implicated in development of several degenerative disorders owing to its potent biological functions. With regards to OA, melatonin reportedly promotes synthesis of cartilage matrix, inhibition of chondrocyte apoptosis, attenuation of inflammatory response, and suppression of matrix degradation by regulating the TGF-β, MAPK, or NF-κB signaling pathways. Notably, melatonin has been associated with amelioration of oxidative damage by restoring the OA-impaired intracellular antioxidant defense system in articular cartilage. Findings from preliminary application of melatonin or melatonin-loaded biomaterials in animal models have affirmed its potential anti-arthritic effects. Herein, we summarize the anti-arthritic effects of melatonin on OA cartilage and demonstrate that melatonin has potential therapeutic efficacy in treating OA. Melatonin reverses the progression of OA and boosts cartilage recovery at multiple dimensions. At the organismal level, intra-articular injection of melatonin suppresses arthritis development and promotes cartilage regeneration. At the tissue level, melatonin modulates cartilage erosion, synovial inflammation, subchondral bone remodeling, and thus impedes cartilage degeneration. At the cellular level, chondrocyte apoptosis, inflammatory cytokines (e.g., IL-1β or TNF-α), anabolic/catabolic activities (e.g., MMPs or ADAMTS versus COLII or ACAN), and oxidative stress status are harmonized by melatonin treatment. At the organelle level, melatonin preserves matrix metabolic and redox equilibrium via enhancement of mitochondrial function, regulation of sirtuins activities, scavenging of free radicals as well as reinforcement of antioxidant properties (e.g., SOD, CAT, or GPX), through targeting the MAPK, NF-κB, TGF-β, NRF2, or FOXO signaling pathways. [Display omitted] • Melatonin protects articular chondrocytes from OA-induced cellular apoptosis. • Melatonin improves cartilage ECM synthesis and suppresses catabolic metabolism. • Melatonin maintains redox homeostasis via regulating oxidant–antioxidant balance. • Melatonin regulates the activities of NAD+-dependent deacylases sirtuins. • Intra-articular delivery of melatonin-laden biomaterials ameliorates cartilage degeneration. [ABSTRACT FROM AUTHOR]

Background and Aims: Osteosarcoma is the most frequent malignant bone tumor with a peak incidence in the second and third decades of life. Survivin, a member of the IAP family of proteins, is overexpressed in osteosarcomas and plays an important role in protecting cells from apoptosis. Here we investigated the anti-cancer effects of downregulating survivin by shRNA vector pSUPER-sh in combination with chemotherapeutic drugs on human osteosarcoma cells. Methods: Expression of survivin was detected by Western blot. The effects of pSUPER-sh and chemotherapeutic drugs on osteosarcoma cell lines Saos-2 and U2OS by cell viability assay and its underlying mechanisms were analyzed by flow cytometry and caspase-3 activity assay. Results: Downregulated survivin could significantly induce apoptosis of osteosarcoma cell lines Saos-2 and U2OS. The effect probably resulted from downregulation of survivin induced by pSUPER-sh. Importantly, we found that the downregulation of survivin by pSUPER-sh could enhance the anticancer effects of chemotherapies such as etoposide, cisplatin and doxorubicin through decreasing mitochondrial membrane potentials and increasing caspase-3 activity. Conclusions: Downregulated survivin by pSUPER-sh could markedly induce apoptosis of osteosarcoma cells lines and pSUPER-sh may be a promising adjuvant in osteosarcoma chemotherapy. [Copyright &y& Elsevier]

Abstract: Background: Osteoporotic compression fractures (OVCFs) commonly occur in aged people, and as much as one-third of these fractures progress to chronic pain. Kyphoplasty (KP) is proved to be efficacious for pain relief and vertebral height restoration in chronic OVCFs, but there is still no data available about the clinical and radiographical outcomes compared by unipedicular and bipedicular KP in treating chronic painful OVCFs. Purpose: To assess the clinical and radiographical outcomes in treating chronic painful OVCFs compared by unipedicular and bipedicular KP. Methods: Fifty-eight patients with a total of sixty-six chronic painful OVCFs were enroled in our study. They were randomly allocated into two groups: group I (n =33) was treated with unipedicular KP and group II (n =25) with bipedicular KP. The operation times for each group were recorded and compared. Preoperative and postoperative of visual analogue scores (VAS) and oswestry disability index (ODI) scores were compared 2 weeks after surgery within each group and between groups. The radiographic outcomes were evaluated by the restoration rate (RR) in the most compressed point of the vertebral bodies. Results: Significant improvement on the VAS, ODI scores and RR was noted in each group (p <0.001), and there is no significant difference existing in clinical outcomes between the two groups. The mean operation time for each vertebra in group I was significantly shorter than in group II (p <0.001). But the RR in group II was higher than in group I (p =0.041). Conclusion: Both unipedicular kyphoplasty and bipedicular kyphoplasty can achieve satisfactory clinical and radiographic outcomes in treating the chronic painful OVCFs and the operation time is shorter in unipedicular kyphoplasty. However, the bipedicular kyphoplasty is more efficacious in height restoration. [Copyright &y& Elsevier]

Abstract: Osteolysis and subsequent aseptic loosening are the most common causes of failure of total joint arthroplasty. Osteolysis is initiated by inflammatory response to wear debris, resulting in localized, osteoclastic peri-implant bone loss. However, there were no effective measures for prevention and treatment of periprosthetic osteolysis. The aim of the current study was to determine whether CB2 selective antagonist (AM630) inhibits wear debris-induced osteolysis in a murine osteolysis model. Titanium (Ti) particles were introduced into established air pouches on BALB/c mice, followed by implantation of calvaria bone from syngeneic littermates. AM630 was given to mice intraperitoneally 2 days before Ti particles introduction and maintained until the sacrifice of the mice. Mice without drug treatment, as well as mice injected with saline alone, were included. Each group contains 10 mice. Pouch tissues were harvested 14 days after bone implantation for histological and molecular analysis. Ti particles stimulation significantly increased CB2 expression. However, less CB2 was observed in AM630 treatment group. AM630 inhibited Ti particle-induced osteolysis associated gene activity of RANK, RANKL and CPK, and diminished RANKL expression in Ti particle stimulated pouches. AM630 markedly reduced the number of TRAP+ cells in pouch tissues. In conclusion, this study provides the evidence that blockage of CB2 with AM630 can markedly reduce Ti particle induced osteolysis in a murine air pouch model. This finding points to the possibility that CB2 selective antagonists like AM630 may have potential value for prevention and treatment of wear particle induced osteolysis. [Copyright &y& Elsevier]

Three-dimension (3D)-printed bioscaffolds are precise and personalized for bone regeneration. However, customized 3D scaffolds may activate the immune response in vivo and consequently impede bone formation. In this study, with layer-by-layer deposition and electrospinning technology to control the physical structure, 3D-printed PCL scaffolds with PLLA electrospun microfibrous (3D-M-EF) and nanofibrous (3D-N-EF) composites were constructed, and their immunomodulatory effect and the subsequent osteogenic effects were explored. Compared to 3D-N-EF scaffolds, 3D-M-EF scaffolds polarized more RAW264.7 cells toward alternatively activated macrophages (M2), as demonstrated by increased M2 and deceased classically activated macrophage (M1) phenotypic marker expression in the cells. In addition, the 3D-M-EF scaffolds shifted RAW264.7 cells to the M2 phenotype through PI3K/AKT signaling and enhanced VEGF and BMP-2 expression. Conditional medium from the RAW264.7 cells seeded in 3D-M-EF scaffolds promoted osteogenesis of MC3T3-E1 cells. Furthermore, in vivo study of repairing rat calvarial defects, the 3D-M-EF scaffolds increased the polarization of M2 macrophages, enhanced angiogenesis, and accelerated new bone formation. Collectively, our data suggested that well-designed 3D-M-EF scaffolds are favorable for osteogenesis through regulation of M2 polarization. Therefore, it is potential to utilize the physical structure of 3D-printed scaffolds to manipulate the osteoimmune environment to promote bone regeneration. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic, inflammatory, synovitis-dominated systemic disease with unknown etiology. RA is characterized by the involvement of multiple affected joints, symmetry, and invasive arthritis of the limbs, which can lead to joint deformity, cartilage destruction, and loss of function. Cannabinoid receptor 2 (CB 2) has potent immunomodulatory and anti-inflammatory effects and is predominantly expressed in non-neuronal tissues. In the current study, the role of CB 2 in the process of inflammatory bone erosion in RA was examined. The selective agonist or high-affinity ligand of CB 2 (4-quinolone-3-carboxamides CB2 agonist, 4Q3C CB 2 agonist, 4Q3C) significantly reduced the severity of arthritis, decreased histopathological findings, and markedly reduced bone erosion in collagen-induced arthritis (CIA) mice. In addition, 4Q3C prevented an increase in the nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG) ratio and inhibited the formation of osteoclasts in CIA mice. Furthermore, the expression of tumor necrosis factor-alpha, interleukin-1β, cyclooxygenase-2, and inducible nitric oxide synthase was lower in 4Q3C-treated CIA mice than in control CIA mice. Micro-computed tomography corroborated the finding that 4Q3C reduced joint destruction. These data clearly indicate that the CB 2 -selective agonist, 4Q3C, may have anti-inflammatory and anti-osteoclastogenesis effects in RA and may be considered to be a novel treatment for RA. [ABSTRACT FROM AUTHOR]