text:
To assess blood vessel stability in inflammatory synovial tissue (ST) and to examine neural cell adhesion molecule (NCAM), oxidative DNA damage, and hypoxia in vivo.
To assess blood vessel stability in inflammatory synovial tissue (ST) and to examine neural cell adhesion molecule (NCAM), oxidative DNA damage, and hypoxia in vivo.
Macroscopic vascularity and ST oxygen levels were determined in vivo in patients with inflammatory arthritis who were undergoing arthroscopy. Vessel maturity/stability was quantified in matched ST samples by dual immunofluorescence staining for factor VIII (FVIII)/α-smooth muscle actin (α-SMA). NCAM and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) were examined by immunohistochemistry. Angiogenesis was assessed in vitro, using human dermal endothelial cells (HDECs) in a Matrigel tube formation assay.
A significant number of immature vessels (showing no pericyte recruitment) was observed in tissue from patients with inflammatory arthritis (P < 0.001), in contrast to osteoarthritic and normal tissue, which showed complete recruitment of pericytes. Low in vivo PO2 levels in the inflamed joint (median [range] 22.8 [3.2–54.1] mm Hg) were inversely related to increased macroscopic vascularity (P < 0.04) and increased microscopic expression of FVIII and α-SMA (P < 0.04 and P < 0.03, respectively). A significant proportion of vessels showed focal expression of NCAM and strong nuclear 8-oxodG expression, implicating a loss of EC–pericyte contact and increased DNA damage, levels of which were inversely associated with low in vivo PO2 (P = 0.04 for each comparison). Circulating cells were completely negative for 8-oxodG. Exposure of HDEC to 3% O2 (reflecting mean ST in vivo measurements) significantly increased EC tube formation (P < 0.05).
Our findings indicate the presence of unstable vessels in inflamed joints associated with hypoxia, incomplete EC–pericyte interactions, and increased DNA damage. These changes may further contribute to persistent hypoxia in the inflamed joint to further drive this unstable microenvironment.
Inflammatory arthritides are chronic progressive diseases that are characterized by proliferation of the synovial tissue (ST), leading to the degradation of articular cartilage and subchondral bone. Angiogenesis is an early event in the inflammatory joint that is important in enabling activated monocytes to enter the synovium and expand it into a pannus via endothelial cells (ECs) by active recruitment (1, 2), resulting in cartilage degradation and bone destruction. Previous studies have demonstrated increased angiogenesis and distinct vascular morphology in the synovial membrane (SM) of inflammatory arthritis during early disease (3), which is associated with increased differential expression of proangiogenic factors in synovial fluid (SF) and ST (4, 5).
ECs receive cues from proinflammatory molecules that initiate mitosis, migration, and organization of primitive angiotubes (6–8), leading to the formation of a mature vasculature. Vascular endothelial growth factor (VEGF) is a main angiogenic "on" switch, which acts early in vascular morphogenesis, stimulating EC proliferation and migration. However, in the presence or absence of angiopoietin 1/2 (Ang-1/2), placenta growth factor, platelet-derived growth factor (PDGF), or transforming growth factor β1 (TGFβ1), blood vessels may undergo further remodeling, resulting in either immature or mature, stable vessels (6, 9, 10). The acquisition of a pericyte layer ends the "plastic" state, stabilizing the vessel (6, 11, 12). Vessel stability is also dependent on EC–pericyte interactions and perivascular extracellular matrix (ECM) components, such as the immunoglobulin neural cell adhesion molecule (NCAM). NCAM deficiency results in an unstable EC–pericyte interaction and vessel survival (11, 13, 14). This process is dependent on cell survival signals, which may influence nuclear instability events, such as telomere length shortening induced by high levels of oxidative stress (15).
Hypoxia is defined as cellular demand for molecular oxygen exceeding vascular supply, leading to bioenergetic crisis. Increases in uniform blood flow in the pannus fail to restore tissue oxygen levels, causing chronic, persistent cell infiltration and invasion. Previous studies have shown that the oxygen level in rheumatoid arthritis (RA) SF is reduced compared with the level in normal controls, and low oxygen levels have been described in tenosynovium in patients with tendon rupture (16–18). Hypoxia-inducible factor 1α (HIF-1α), which is a key transcription factor in the cellular response to hypoxic conditions, is also up-regulated in RA synovium (19), and in vitro, it is involved in angiogenesis, migration, cell survival pathways, reactive oxygen species (ROS), glycolysis, and matrix degradation (16, 18, 20, 21).
Oxidative stress occurs when a disturbance develops in the balance between the production of ROS and antioxidant defenses. Alterations in mitochondrial oxygen sensing can result in increased release of ROS, coupled with a compromised antioxidant defense system (22). Excessive production of ROS can damage biologic molecules, including DNA, lipids, and proteins. The DNA adduct 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) is formed by the reaction of the OH radical with the DNA guanine base. It is a promutagenic lesion that mispairs with adenine, leading to GC to TA transversions. This oxidative DNA damage is repaired primarily by base excision repair pathways incorporating the glycosylates OGG1, MYH, and NUDT1 (16, 23). Disturbance of this system can lead to oxidative damage, which is associated with many pathologic conditions, such as atherosclerosis, diabetes mellitus, and cancer (24, 25). However, the pathophysiologic role of oxidative damage in inflammatory arthritis remains unclear. Previous studies have shown that SF T cells have decreased levels of the antioxidant glutathione (26) and that oxidative conditions in RA ST are associated with a higher incidence of p53 mutations (27).
In this study, we quantified blood vessel maturity and stability, in vivo PO2 levels, and the level of oxidative damage in the inflamed ST. Furthermore, we examined the relationship of vascularity, blood vessel stability, and DNA damage to the level of oxygen in the inflamed tissue measured using a novel PO2 probe.
Patients with active inflammatory arthritis (RA or psoriatic arthritis [PsA]) or osteoarthritis (OA) were recruited from rheumatology clinics prior to starting therapy with biologic agents. Healthy control subjects were also recruited. The majority of the patients had never taken disease-modifying antirheumatic drugs or steroids. Twelve patients were taking methotrexate, 1 patient was taking sulfasalazine, and 1 patient was taking azathioprine. Patients were diagnosed as having RA according to the American College of Rheumatology (formerly, the American Rheumatism Association) criteria (28) and as having PsA according to previously defined criteria (29). The study was approved by the St. Vincent's University Hospital Medical Research and Ethics Committee, and all patients provided fully informed written consent. Clinical assessments included tender and swollen joint counts, rheumatoid factor status, anti–cyclic citrullinated peptide (anti-CCP) antibody status, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Disease Activity Score in 28 joints (DAS28), and global health, by visual analog scale (VAS). Arthroscopy of the inflamed knee was performed under local anesthetic using a Wolf 2.7-mm needle arthroscope, as previously described (3). SM vascularity was assessed macroscopically by direct visualization and quantified as validated previously (3), using a VAS (0–100 mm).
A Licox combined PO2 and temperature probe (CC1.P1; Integra Life Sciences, Plainsboro, NJ) was used to obtain PO2 levels. Following the first biopsy, the novel Licox PO2 probe (Integra Life Sciences) was introduced via a 22-gauge needle and positioned into the biopsy pocket under direct visualization, allowing direct tissue PO2 (tPO2; mm Hg) measurements in the SM sublining layer. Biopsy specimens were then obtained and embedded in OCT compound (Tissue-Tek; Sakura, Zoeterwoude, The Netherlands) or embedded in paraffin for immunohistochemical analysis.
Seven-micrometer OCT sections were placed on glass slides coated with 2% 3-aminopropyltriethoxysilane (Sigma-Aldrich Ireland, Dublin, Ireland) and dried overnight at room temperature. Sections were stored at −80°C until required for staining. Tissue sections were allowed to reach room temperature, fixed in acetone for 10 minutes, and air dried. Nonspecific binding was blocked using 10% casein in phosphate buffered saline (PBS) for 10 minutes at room temperature. Slides were washed in PBS for 5 minutes. To examine the maturity of blood vessels, the presence of immature and mature blood vessels was assessed. Dual immunofluorescence staining was initially performed for factor VIII (FVIII)/α-smooth muscle actin (α-SMA; a pericyte marker, indicating vessel maturity). Slides were coincubated with a primary antibody against rabbit anti-FVIII and mouse anti–α-SMA (Dako, Glostrup, Denmark) and an appropriate IgG isotype-matched control for 1 hour in a humidified chamber. Immunofluorescent sections were washed in PBS for 5 minutes and incubated with a Cy2/Cy3-conjugated secondary antibody (Jackson Immuno- Research, Suffolk, UK) for 30 minutes. Slides were washed in PBS for 5 minutes and counterstained with 4′,6-diamidino-2-phenylindole (DAPI) nuclear stain (1:1,000; Sigma, St. Louis, MO) for 10 minutes. Sections were mounted with anti-fade (Molecular Probes, Eugene, OR) and assessed by immunofluorescence microscopy. Fluorescent images were captured using a confocal microscope using a multi-track filter program for Cy2, Cy3, and DAPI excitations and emissions. Images were processed using LSM imaging software (Zeiss, Oberkochen, Germany). In a subgroup of patients, serial sections were stained with a primary antibody against mouse anti-FVIII and rabbit anti–lymphatic vessel endothelial marker 1 (anti–LYVE-1; Abcam, Cambridge, UK) to differentiate lymphatic from pan vessels.
We also examined blood vessel maturity using another double staining kit (EnVision G2 double-stain system, catalog no. K5361; Dako). This protocol was carried out according to the recommendations of the manufacturer, and positive staining was detected using diaminobenzidine/permanent red secondary antibodies. Blood vessel maturity was quantified by the number of blood vessels per high-power field (hpf) coexpressing FVIII/α-SMA compared with those expressing only FVIII. Five random fields were analyzed.
For NCAM expression, cryostat sections were allowed to reach room temperature, fixed in acetone for 10 minutes, and air dried as described above. Staining with 8-oxodG was performed on paraffin-embedded sections. Sections were baked at 90°C for 30 minutes, deparaffinized in xylene, and rehydrated in alcohols and deionized water. Antigen retrieval was performed using 1,500 ml of citrate solution. This solution was heated in a pressure cooker with the lid off for 20 minutes in an 800V microwave. Slides were placed in a pressure cooker with the lid sealed and were heated at full power until the pressure valve popped (5–7 minutes). Slides were removed from the pressure cooker once the pressure had equalized and were washed in PBS and 0.05% Tween 20 for 5 minutes. For both cryostat and paraffin sections, nonspecific binding was blocked using 10% casein in PBS for 10 minutes at room temperature. A routine 3-stage immunoperoxidase labeling technique incorporating avidin–biotin–immunoperoxidase complex (Dako) was used. The sections were incubated with primary antibodies against mouse monoclonal NCAM (Dako) and mouse monoclonal 8-oxodG (Genox, Baltimore, MD) at room temperature. Separate sections were incubated with a relevant isotype-matched monoclonal antibody as a negative control. Endogenous peroxidase activity was quenched by adding 3% H2O2 for 7 minutes, followed by addition of a rabbit/mouse horseradish peroxidase solution for 30 minutes. Color was developed in solution containing diaminobenzidine tetrahydrochloride (Sigma), 0.5% H2O2 in PBS buffer (pH 7.6). Slides were counterstained with hematoxylin and mounted.
For NCAM and 8-oxodG expression on blood vessels, slides were analyzed by 3 blinded observers (MB, JO, and UF) using an established semiquantitative scoring method with a scale ranging from 0–4, where 0 = no staining, 1 = <25% staining, 2 = 25–50% staining, 3 = 50–75% staining, and 4 = >75% staining (4, 5). NCAM staining was performed in a single run on the same day to control for peroxidase staining variability, and blood vessels were assessed for the percentage of staining and the strength (intensity) of staining in all vessels in the entire section (24). Then, in 5 hpf of tissue sections, we determined the percentage of individual blood vessels showing staining of NCAM in focal, discrete cells and the percentage showing NCAM staining as intact, continuous expression by adjacent cells. For 8-oxodG, blood vessels were assessed for cytoplasmic intensity, percentage of blood vessel with cytoplasmic staining, nuclear intensity, percentage of blood vessel with nuclear staining, and percentage of blood vessel stained for 8-oxodG in whole tissue, as previously described (24).
Matrigel (Becton Dickinson, Franklin Lakes, NJ) basement membrane matrix was used to examine HDEC tube formation. Matrigel (50 μl) was plated in 96-well culture plate slides after thawing on ice and allowed to polymerize at 37°C in a 5% CO2 humidified atmosphere for 1 hour. HDECs were removed from culture, trypsinized, and resuspended at 4 × 104 cells/ml in full-strength EGM growth medium. Three hundred microliters of cell suspension was added to each chamber and incubated under either normoxic conditions or exposed to 3% hypoxia for 24 hours at 37°C in a 5% CO2 humidified atmosphere. EC tubule formation was assessed using phase-contrast microscopy and photographed. A connecting branch between 2 discrete ECs was counted as 1 tube. The tube analysis was determined from 5 sequential fields (magnification × 40) focusing on the surface of the Matrigel.
SPSS, version 11 for Windows was used for statistical analysis. The nonparametric Wilcoxon signed rank test, Spearman's correlation coefficient, and the Kruskal-Wallis test were used for analysis. P values less than 0.05 were considered significant. Results are expressed as the median and range unless specified otherwise.
Forty-three subjects were recruited prior to starting therapy with biologic agents (21 patients with RA, 12 patients with PsA, 8 patients with OA, and 2 normal controls). Synovial tPO2 levels were recorded in 34 subjects. The median age of the cohort of patients with inflammatory arthritis (patients with RA and patients with PsA) was 52.37 years (range 27.26–80.22 years), and the clinical characteristics obtained for these patients included the tender joint count (median 5 [range 0–28]), swollen joint count (median 5 [range 0–19]), ESR (median 25 mm/hour [range 2–80 mm/hour]), CRP level (median 21 mg/liter [range 4–99 mg/liter]), DAS28 (median 4.11 [range 2.84–6.89]), global health, by VAS (median 46 mm [range 3–84 mm]), and disease duration (median 42 months [range 5–564 months]). Anti-CCP antibodies were found in 32.3% of these patients at a median titer of 15.6 (range 0.8–250). The OA patients in this cohort had a median age of 56.2 years (range 44–84 years) and a median disease duration of 12 months (range 1–192 months), and they were negative for rheumatoid factor and anti-CCP antibodies.
Representative images of dual staining for FVIII and α-SMA are shown in Figure 1. Sections from patients with inflammatory arthritis demonstrated a mixture of immature vessels, vessels acquiring pericytes, and stable vessels, which showed close alignment of ECs and pericytes. In OA and normal control tissue, all vessels had acquired pericytes and thus had undergone full maturation and stabilization. Immature and mature vessels were also identified and confirmed using immunohistochemistry (Figure 2A). In a subgroup of patients, we observed expression of FVIII independently of the lymphatic marker LYVE-1, which confirmed that the immature vessels were not lymphatics (Figure 2B). There was a significant difference between the number of vessels expressing FVIII and the number of vessels expressing FVIII/α-SMA in inflamed tissue (P < 0.001) (Figure 2C). In contrast, there was no significant difference between the number of blood vessels expressing FVIII and those expressing FVIII/α-SMA in OA or normal control tissue, suggesting vessel stabilization.
NCAM expression was demonstrated in ∼25–50% of vessels in the inflamed synovial joint. The expression pattern of NCAM varied in the inflamed ST (Figure 3A). Some blood vessels showed focal expression of NCAM, suggesting incomplete pericyte–EC interaction and unstable vessels, while others were entirely surrounded by NCAM-positive cells, suggesting a fully intact wall and mature vessels. NCAM expression was intact in OA tissue. The percentage of patients showing focal NCAM expression was significantly greater than the percentage showing intact NCAM expression, with 69% of ST samples displaying focal expression and 31% displaying nearly complete blood vessel expression (P < 0.001), suggesting that the majority of vessels remained unstable (Figure 3B). The number of NCAM-positive blood vessels in the entire section was significantly correlated with DAS28 (r = 0.498, P = 0.013), demonstrating a direct relationship between NCAM expression and disease severity. In a subgroup of patients, we performed NCAM and FVIII staining in serial sections to demonstrate colocalization of NCAM on FVIII-positive blood vessels. (Additional information is available from the corresponding author upon request.)
Increased levels of oxidative DNA damage were demonstrated in the synovial joint tissue. Figure 3C shows representative images of immunohistochemical staining for 8-oxodG expression around blood vessels in the synovium. The pattern of 8-oxodG staining was both nuclear and cytoplasmic, with minimal expression in OA tissue. Higher nuclear 8-oxodG expression was found compared with cytoplasmic staining (Figure 3D); however, this difference did not reach statistical significance. Figure 3C shows strong nuclear expression of 8-oxodG in blood vessels, in contrast to cells that accumulated in the lumen, which were negative for 8-oxodG, suggesting that oxidative damage is induced within the ST microenvironment.
We quantified PO2 in ST using the novel Licox probe, and found low levels of PO2 in the SM, with a median value of 22.8 mm Hg (range 3.2–54.1), consistent with median ambient oxygen tensions of 3.2% (range 0.45–7.7%). Figures 4A and B show representative images of macroscopic vascularity and microscopic vascular expression in patients with low, medium, and high in vivo PO2 measurements (<10, 10–35, and >35 mm Hg, respectively), demonstrating an inverse relationship. At low tPO2, there was an increase in macroscopic vascularity, with blood vessels demonstrating a tortuous pattern of vascular morphology (elongated with an increased diameter). At medium tPO2 levels, an increase in blood vessels was also observed; however, vessels appeared more regularly shaped. Finally, in patients with high tPO2 levels, a minimal number of blood vessels was observed.
At the microscopic level, low tPO2 was associated with a significant increase in the number of blood vessels as compared with medium and high PO2 levels, where the number of vessels was significantly reduced (Figure 4B). When patients were grouped according to tPO2 levels of <20 mm Hg versus >20 mm Hg, lower tPO2 levels were significantly associated with increased numbers of vessels expressing FVIII (P < 0.04) and α-SMA (P < 0.03) (Figures 4C and D). There was no difference in the percentage of blood vessels coexpressing FVIII and α-SMA between patients with PO2 <20 mm Hg and those with PO2 >20 mm Hg, suggesting that low oxygen tension induces new vessel growth and acquisition of pericytes simultaneously.
Figures 5A and B show that low tPO2 levels were associated with increased vessel NCAM expression compared with medium and high tPO2 levels, where NCAM had a focal expression pattern. When NCAM levels were examined in patients with tPO2 <20 mm Hg and those with tPO2 >20 mm Hg, there was a significant increase in NCAM expression with low PO2 (Figure 5B). Figures 5C and D show 8-oxodG expression in samples from patients with high, medium, and low tPO2 levels. Lower tPO2 levels were associated with high 8-oxodG expression as compared with medium or high tPO2 levels. When 8-oxodG levels were examined in patients with tPO2 <20 mm Hg and those with tPO2 >20 mm Hg, there was a significant increase in 8-oxodG expression with low tPO2 (Figure 5D), an effect which was significant when nuclear and cytoplasmic expression were analyzed separately (P < 0.01) (data not shown). Interestingly, no association between tPO2 and sublining or lining layer expression of 8-oxodG was demonstrated. Expression of blood vessel 8-oxodG further contributes to the unstable environment.
Significant inverse correlations were also demonstrated between the in vivo tPO2 level and macroscopic vascularity (r = −0.4, P = 0.004), between the tPO2 level and NCAM expression (r = −0.44, P = 0.04), and between the tPO2 level and nuclear and cytoplasmic expression of 8-oxodG (r = −0.42, P = 0.04 and r = −0.44, P = 0.03, respectively). There was no significant correlation between FVIII and NCAM expression, further confirming dysfunctional vessels. There was a significant inverse correlation of the tPO2 level with the DAS28 (r = −0.439, P < 0.05) and the CRP level (r = −0.35, P < 0.05). Patients with tortuous blood vessel patterns had a significant increase in microscopic vascularity as compared with those with vessels with straight regular branching vessels (P < 0.05). Patients with tortuous blood vessel patterns also had a lower median ambient oxygen level of 2.6% (range 0.83–7%) compared with 3.3% (range 0.43–7.3%) in patients with straight regular branching vessels. This difference, however, was not significant.
Induction of HDEC tube formation on Matrigel matrices plated in 96-well culture plates was assessed under normoxic and 3% hypoxic conditions (reflecting the median level measured in vivo in the joint). Connecting branches and tube-like structures formed after 24 hours (Figures 6A and B). Cells incubated in 3% hypoxia showed a significant increase in tube formation. The mean ± SEM number of HDEC tubules formed increased from 9.8 ± 0.9 (normoxia) to 18 ± 1.4 (3% hypoxia; P < 0.05) (Figure 6C).
Angiogenesis is an early event and is highly dysregulated in inflammatory disorders, such as arthritis, psoriasis, and inflammatory bowel disease, and in many cancers. Activation and dysfunction of ECs and pericytes in these conditions are critically dependent on blood vessel maturity/stability and survival to preserve the integrity of newly formed vessels (6, 7). This study is the first to show the presence of both immature and mature blood vessels in the inflamed synovium, with <50% of these vessels expressing NCAM, which was predominantly focal, suggesting that endothelial–pericyte interactions are not intact. In addition, this is the first study to demonstrate nuclear and cytoplasmic expression of 8-oxodG in the perivascular regions of the synovium. The evidence of DNA damage further supports the notion of an unstable vascular environment. Furthermore, we demonstrated that in vivo measures of tPO2 in the inflamed joint were inversely correlated with macroscopic vascularity and microscopic blood vessel stability, NCAM expression, and DNA oxidative damage. Finally, HDECs exposed in vitro to PO2 levels that reflected those measured in the joint showed a significant increase in angiogenic tube formation.
In this study, we demonstrated the presence of both immature and mature vessels in the inflamed synovium, with a significant proportion of vessels not having recruited supporting pericytes, which are essential for functional vascular patterning, diameter regulation, and vessel stabilization (12, 30, 31). This is in contrast to OA and normal ST, in which intact pericyte layers were observed. Furthermore, we demonstrated a direct relationship between low tPO2 levels in the joint and macroscopic vascularity, microscopic vessel number, pericyte recruitment, and NCAM expression. This implies that in a hypoxic environment, synovial vessels are in a constant state of remodeling, and although many have recruited pericytes, vessels are still in an unstable state.
Pericyte recruitment and NCAM expression are critical for vessel stability in normal tissue. Acquisition of a pericyte layer ends the "plastic" state, thus stabilizing the vessel, as was demonstrated in OA and normal tissue in the present study. In pathologic states, pericyte coverage varies dramatically and is thought to be dysfunctional (32), with pericyte–EC contact constantly changing during the course of vessel development. This results in a deficiency in the ability of pericytes to mediate vascular stability. In cancer models, inhibition of VEGF results in regression of immature vessels, while vessels that are covered by pericytes remain (33), which is consistent with the results of studies showing that pericyte coverage is positively correlated with retinal vessel protection (34). Conversely, studies have also shown that retinal vessels abundantly covered by pericytes undergo regression when VEGF is suppressed. Therefore, the mere presence of pericytes on the vessel does not confer stability and thus protection against regression and may depend on EC–pericyte alignment through the regulation of ECM molecules, such as NCAM (35). NCAM deficiency results in blood vessel leakage, inhibition of pericyte recruitment, and continued vessel growth (13, 14), an effect that may be mediated through altering the deposition of ECM molecules or by affecting PDGF-B (36, 37).
Dysregulated angiogenesis is well recognized as one of the critical mechanisms involved in the progression of inflammation in arthritis. Previous studies have demonstrated increased angiogenesis and distinct vascular morphology in the SM in inflammatory arthritis (1, 3, 4). ECs lining synovial blood vessels express integrins, such as αvβ3, early in blood vessel formation, and later express adhesion molecules and Ki-67, which are markers of EC adhesion and proliferation (1, 38, 39). Activation, proliferation, and migration of ECs is fundamental for enabling activated monocytes to enter the SM via active recruitment, supporting the synovial pannus as it grows over the cartilage, eroding into bone, causing destruction and related disability (40). Dysfunctional vessels result in increased fenestration and leakiness, abnormal morphology, and overexpression of specific molecules that sustain abnormal growth. Thus, synovial expression of EC αvβ3 integrin and many proangiogenic/antiangiogenic growth factors such as VEGF, Ang-2, Ang-1, PDGF, and TGFβ1 (4, 5), coupled with the data from this study, suggests that synovial vessels are in a constant state of simultaneous formation, regression, and maturation.
This is a crucial finding in terms of implications for treatment, in particular the potential for clinical responsiveness in these patients. In vitro and in vivo cancer biology data have suggested that combination therapy targeting both the EC and pericyte may more efficiently inhibit blood vessel growth than therapy targeting either alone. Furthermore, for treatment to be most effective, synovial vessels should be targeted early in the disease process. This is consistent with previous studies demonstrating that synovial vascular development occurs before lining layer proliferation or leukocyte infiltration (41), as well as clinical studies demonstrating a window of opportunity in early arthritis during which therapy with biologic agents may be most effective (42).
We also demonstrated that low tPO2 levels were associated with increased macroscopic and microscopic vascularity. We observed a wide range of tPO2 levels within the joint that were inversely correlated with vascularity, vessel stability, and oxidative damage, further strengthening the hypothesis of an unstable synovial microenvironment. Furthermore, we found no association between NCAM expression and vascularity, suggesting that vessel stability is deficient. We showed that recapitulating the in vivo ST hypoxia levels in vitro leads to induction of angiogenic tube formation. Our data are consistent with previous morphometric studies showing that although there is an increase in blood vessel number, the expanding synovium increases at a greater rate, reflecting a greater metabolic turnover of the invasive pannus. Thus, the tissue remains hypoxic (43). Taken together, these data suggest that the neovascular network is dysfunctional in inflammatory arthritis, which results in failure to restore ST oxygen homeostasis, and the joint becomes a profoundly hypoxic environment.
The potential role of hypoxia in the inflamed joint is supported by several in vitro studies. HIF-1α expression has been demonstrated in ST and in synovial cells, and hypoxia induces key angiogenic growth factors (VEGF and angiopoietins), chemokines (monocyte chemotactic protein 1, IL-8, and CCL20), and matrix metalloproteinase 1 (MMP-1), MMP-3, and MMP-9 and down-regulates IL-10 (18). Increased metabolic activity in the synovial joint with increased glycolytic metabolism has been demonstrated previously. Oxygen levels in RA SF are reduced compared with levels in normal control SF, and low oxygen levels have been described in tenosynovium in patients with tendon rupture (16–18). Finally, in animal models, HIF-1α is localized to areas of hypoxia in the joint, with synovial expression of hypoxia markers positively correlating with synovitis at the preclinical stage, suggesting a possible role for hypoxia before the activation of the inflammatory response.
We demonstrated strong expression of 8-oxodG around ST blood vessels, indicating increased oxidative DNA damage. This has not been documented previously. Interestingly, we observed that 8-oxodG staining is predominantly expressed by cells within the SM, but not in cells within the blood vessel lumen, which suggests that cells do not become damaged until after they enter the SM microenvironment. This is consistent with several studies suggesting that the initiating factor for oxidative damage is in the local microenvironment (44). Increased oxidative enzymes and production of ROS have been demonstrated in the sera and SF of RA patients (45, 46) and in the inflamed joint (16). Oxidative damage to hyaluronic acid and lipid peroxidation products have also been demonstrated in RA ST (47). ROS may induce cartilage damage by up-regulating matrix degradation (48) and mediate EC activation and angiogenesis (49). Furthermore, oxidative damage can modulate the abnormal expression of adhesion molecules, including NCAM, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1, which influence both vessel stability and leukocyte migration (50). This suggests that oxidative damage is closely associated with the synovial perivascular environment and may directly influence vessel stability.
In conclusion, these data demonstrate for the first time the presence of mature and immature vessels in the inflamed joint synovium. NCAM deficiency and oxidative DNA damage in a perivascular distribution indicates that although pericyte acquisition may occur, many vessels remain in a plastic state. The relationship between tPO2 levels, increased vascularity, NCAM expression, and pericyte recruitment suggests that profound hypoxia may not only increase angiogenesis and vessel instability, but may also account for the persistence of inflammation.
All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. Dr. Fearon had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study conception and design. Kennedy, Ng, Taylor, O'Sullivan, Veale, Fearon.
Acquisition of data. Kennedy, Ng, Biniecka, Saber, Veale, Fearon.
Analysis and interpretation of data. Kennedy, Ng, Biniecka, Taylor, O'Sullivan, Veale, Fearon.


text:
Home /
Our Sources / About Us
/ FAQs /
Advanced Search
Not what you're
looking for? Try an advanced search.
Official citation and/or docket number and footnotes (if any) for this case available with purchase.
Learn more about what you receive with purchase of this case.
United States District Court, N.D. Illinois, Eastern Division
July 22, 2004.
AMI DIAMONDS COMPANY, an Illinois corporation, Plaintiff,
HANOVER INSURANCE COMPANY, Defendant.
This matter is before the court on Plaintiff A.M.I. Diamonds
Company's ("AMI") motion for summary judgment, Defendant Hanover
Insurance Company's ("Hanover") motion for summary judgment, and
Plaintiff AMI's motion to strike. For the reasons below, we deny
AMI's motion for summary judgment, grant Hanover's motion for
summary judgment, and deny AMI's motion to strike as moot.
AMI is an Illinois corporation that is in the business of
wholesaling loose, finished diamonds to retail jewelers. Hanover
is a Massachusetts corporation that is in the business of issuing
Jewelers' Block policies of insurance. In return for valuable
consideration by AMI, Hanover issued to AMI a Jewelers' Block
Policy of insurance insuring against risks of physical loss or damage to
property insured under the policy during the time period of
November 1, 2002 to November 1, 2003.
On or about November 8, 2002, AMI's sales representative, Maged
Soliman ("Soliman") was traveling in Arlington Heights, Illinois
making business calls in furtherance of the business of AMI. Mr.
Soliman was carrying approximately $150,000.00 worth of finished
diamonds belonging to AMI in a briefcase. After calling on a
retail jeweler and client of AMI, Soliman drove to a gas station
to use the telephone to call AMI's business manager at AMI's
downtown office to inform him of his whereabouts and to obtain
instructions as to the next retail store he should visit. Soliman
pulled into a designated parking space adjacent to the telephone.
The diamonds were contained in the briefcase and was situated
between the driver's seat and the passenger's seat. Soliman had
to step outside the car to reach the telephone. He leaned on the
door of the driver's side of the car while speaking to the
business manager on the telephone. He then hung up the phone, and
opened the car door to re-enter.
At this time, a Hispanic woman from the passenger side of a
maroon minivan diverted Soliman's attention by calling him and
asking for help. The minivan was approximately five feet from
where Mr. Soliman's car was parked. He asked her what she needed,
and the woman replied that she needed directions.
Mr. Soliman proceeded to walk the five feet to the minivan,
stood at the passenger side of the minivan, and turned at an
angle so as to keep his own car in sight. The woman persisted in
her purported need for assistance in reading the map, and then she dropped the map to the ground where Soliman was
standing. As he bent to pick it up, Soliman observed a white car
near his vehicle. Instantly, Mr. Soliman knew he was being set
up, and that the woman in the maroon minivan was a decoy to lure
him away from his car.
Soliman then ran the few steps back to his car and the white
car sped away. Soliman then saw that his briefcase containing the
diamonds was gone. He looked up and saw the maroon minivan
speeding away as well. Soliman then alleged that he became crazy,
and jumped into his car to try and chase the minivan, to no
avail. He then returned to the gas station where he exclaimed
that he had been robbed, and then called 911. The Arlington
Heights police took Soliman to the Chicago Police Station at
O'Hare Airport and showed him pictures of known Columbian
nationals who specialize in jewelry theft to see if Soliman could
identify any of them. He could not. The diamonds were never
AMI submitted a claim for coverage for the stolen diamonds to
Hanover under its Jewelers' Block Policy. Four months later,
Hanover denied coverage, asserting three separate provisions of
the Policy in support of its position. First, Hanover asserted
the "unexplained loss mysterious disappearance" exclusion,
stating that, because Soliman did not actually see anyone take
the diamonds from his car, and because there were no signs of a
forcible entry, the loss was "unexplained". Second, Hanover
contended that, pursuant to the "in or upon" exclusion clause,
Soliman was not "in" or "upon" the vehicle at the time the loss
occurred. Finally, Hanover claimed that, pursuant to the
"personal conveyance clause", the diamonds were not in Mr. Soliman's "close personal custody" and "under his direct
control "at the time of the theft.
As a result, AMI brought three counts against Hanover. Count I
seeks a declaratory judgment that Hanover is obligated to
indemnify AMI with respect to the loss of over $150,000.00 worth
of goods and merchandise covered under the Jewelers' Block Policy
of insurance issued by Hanover to AMI. Count II asserts a claim
for breach of contract as to the Jewelers' Block Policy issued by
Hanover to AMI, and Count III is for damages for vexatious and
unreasonable conduct under Section 155 of the Illinois Insurance
Summary judgment is appropriate when the record reveals that
there is no genuine issue as to any material fact and the moving
party is entitled to judgment as a matter of law. Fed.R.Civ.P.
56(c)). In seeking a grant of summary judgment the moving party
must identify "those portions of `the pleadings, depositions,
answers to interrogatories, and admissions on file, together with
the affidavits, if any,' which it believes demonstrate the
absence of a genuine issue of material fact." Celotex Corp. v.
Catrett, 477 U.S. 317, 323 (1986) (quoting Fed.R.Civ.P.
56(c)). This initial burden may be satisfied by presenting
specific evidence on a particular issue or by pointing out "an
absence of evidence to support the non-moving party's case."
Id. at 325. Once the movant has met this burden, the non-moving
party cannot simply rest on the allegations or denials in the pleadings, but, "by
affidavits or as otherwise provided for in [Rule 56], must set
forth specific facts showing that there is a genuine issue for
trial." Fed.R.Civ.P. 56(e). A "genuine issue" in the context
of a motion for summary judgment is not simply a "metaphysical
doubt as to the material facts." Matsushita Elec. Indus. Co.,
Ltd. v. Zenith Radio Corp, 475 U.S. 574, 586 (1986). Rather, a
genuine issue of material fact exists when "the evidence is such
that a reasonable jury could return a verdict for the nonmoving
party." Anderson v. Liberty Lobby, Inc., 477 U.S. 242, 248
(1986); Insolia v. Phillip Morris, Inc., 216 F.3d 596, 599
(7th Cir. 2000). The court must consider the record as a
whole, in a light most favorable to the non-moving party, and
draw all reasonable inferences that favor the non-moving party.
Anderson, 477 U.S. at 255; Bay v. Cassens Transport Co.,
212 F.3d 969, 972 (7th Cir. 2000).
I. Declaratory Judgment (Count I)
Count I of the complaint seeks a declaratory judgment that
Hanover is obligated to indemnify AMI with respect to the loss of
over $150,000.00 worth of goods and merchandise covered under the
Jewelers' Block Policy of insurance issued by Hanover to AMI A. In or Upon the Vehicle Exclusion
Under exclusion 5(I) of AMI's policy AMI was not covered under
the policy for property lost while in a vehicle "unless at the
time the loss occur[red] there [wa]s actually in or upon such
vehicle, the insured, or a permanent employee of the
Insured. . . ." AMI argues that Soliman was upon the vehicle at
the time the theft occurred. This court does not agree. AMI
refers to E.M.M.I. Inc. v. Zurich American Insurance Co.,
84 P.3d 385, 393 (Cal. 2004), to construe the meaning of "upon." In
E.M.M.I., the court held that the "upon" requirement is
satisfied when the insured is in close proximity to the vehicle
and attending to it. E.M.M.I. v. Zurich American Insurance Co.,
84 P.3d 385, 393 (Cal. 2004). Therefore, according to AMI,
because Soliman was in close proximity of the car, he was upon
it, and as a result, the "in or upon" exclusion clause does not
apply. However, Hanover argues that it is well settled in
Illinois that under a Jewelers' Block Policy, an insured can only
defeat an "in or upon" vehicle exclusion if its jewelry was lost
and if at the time of the loss a permanent employee of the
plaintiff or person whose duty it was to attend to the vehicle
was actually in or upon such vehicle. Bliss Ring Co. v. Globe
and Rutgers Fire Insurance Co., 7 Ill. App.2d 523, 531 (Ill.App.
Ct. 1955). We agree. Furthermore, according to Hanover, courts
have routinely held that the "in or upon such vehicle" exclusion
of a Jewelers' Block Policy is unambiguous and must be strictly
construed that someone must be actually in the vehicle at the
time of the loss for the coverage to apply. Silverman v. Lloyd's
Underwriters, 422 F. Supp. 89, 90 (S.D.N.Y. 1976); Wieband
Jewelry Corporation v. Sun Insurance Company of New York, 619 N.Y.S.2d 339, 339 (N.Y. App. Div. 1994).
AMI admits pursuant to Local Rule 56.1 that Soliman was not in
or upon the car when the diamonds were stolen. He also indicates
this in his own 56.1 statement of facts. Some of AMI's 56.1
responses are evasive denials in regards to some facts relating
to this issue and AMI attempts to avoid admitting or denying
facts by raising evidentiary objections that are not meritorious.
See Jankovich v. Exelon Corp., 2003 WL 260714, at *5 (N.D. Ill.
2003) (indicating that evasive denials that do not directly
oppose an assertion are improper and thus the contested fact is
deemed to be admitted pursuant to Local Rule 56.1). AMI admits
pursuant to Local Rule 56.1 that Soliman walked away from his car
before the jewelry was stolen. (RHSF 14, 16). AMI also states
this in its own 56.1 statement of facts. (AMI SF 34-40). Under
the plain meaning of the language in Exclusion 5(I) of the
policy, AMI's loss is not afforded coverage because AMI's agent
and/or employee was not "actually in or upon" his vehicle at the
time that AMI claims the jewelry was missing. AMI attempts to
introduce a variety of red herrings arguing that at one point he
was leaning on his car and that he did not intend to abandon his
car. However, the admitted fact is that he walked away from his
car and left the diamonds unattended in the car. (RHSF 14, 16)
Regardless of the period of time he left the diamonds, Soliman
engaged in exactly the type of conduct that is described in the
exclusion provision. B. Personal Custody Exclusion
An endorsement in AMI's policy states that the policy does not
cover losses incurred "when in transit unless the property
insured is in the close personal custody and under the direct
control of a Director or Employee of the Assured's Firm and/sales
representatives, commission salesmen or selling agents. . . ."
AMI argues that the diamonds were in Soliman's close personal
custody and under his direct control at the time of the theft.
However, clearly the jewelry was not in Soliman's close personal
custody at the time of the loss. Soliman admits that he was duped
into approaching the woman and that the diamonds were taken while
he was preoccupied with her. (RHSF 14, 15, 16) (AMI SF 34-40).
Thus, Soliman in no way, shape, or form had the diamonds in his
"personal custody" or under his "direct control." Therefore, we
grant Hanover's motion for summary judgment on the declaratory
judgment claim.
II Breach of Contract Claim (Count II)
Count II of the complaint alleges that Hanover breached the
contract of the Jewelers' Block Policy. However, because no
reasonable trier of fact could conclude other than that Soliman's
conduct fell within the exclusion clauses of the contract, AMI is
not entitled to coverage under the contract. Therefore, Hanover
did not breach the contract with AMI by refusing to pay for its
loss. Therefore, we grant Hanover's motion for summary judgment
on the breach of contract claim. (Count II).
III. Vexatious and Unreasonable Conduct Claim (Count III)
Count III is for damages for vexatious and unreasonable conduct
under Section 155 of the Illinois Insurance Code. Section 155 of
the Illinois Insurance Code provides for the award of attorney
fees in cases where the insurer caused "an unreasonable delay in
settling a claim, and it appears to the court that such action or
delay is vexatious and unreasonable." 215 ILCS 5/155(1); Mobile
Oil Corporation v. Maryland Casualty Company, 681 N.E.2d 552,
558 (Ill.App. Ct. 1997). According to AMI, Hanover's denial of
coverage in this case is a striking example of the type of
conduct Section 155 of the Insurance Code is intended to deter.
However, as Hanover asserts, in determining if an insurer is
guilty of vexatious and unreasonable conduct, the court must look
at the "totality of the circumstances." Spearman Industries,
Inc. v. Paul Fire and Marine Insurance Co., 138 F. Supp.2d 1088,
1102 (N.D. Ill. 2001). An insurer is not guilty of vexatious and
unreasonable conduct if:" (1) there is a bona fide dispute
concerning the scope and application of the insurance coverage,
(2) the insurer asserts a legitimate policy defense, (3) the
claim presents a genuine legal or factual issue regarding
coverage, or (4) the insurer takes a reasonable legal position on
an unsettled issue of law." Id. According to Hanover, in the
instant case it conducted a thorough investigation of the claim
and determined that AMI was not entitled to insurance coverage
under the policy based on several exclusions. Hanover retained an investigator, immediately upon
AMI submitting the insurance claim, who investigated the claim
for several months. AMI contends that Hanover engaged in a
"fabrication of evidence to support is [sic] decision to deny
coverage. . . ." (Ans. HSJ 15). However, there is no evidence
that Hanover fabricated evidence. There is every indication, that
even if Hanover accepted AMI's version of the facts as indicated
in their 56.1 statement of facts, that the exclusion provisions
applied and that AMI was not entitled to coverage. There is
insufficient evidence for a reasonable trier of fact to conclude
that Hanover engaged in vexatious and unreasonable conduct.
Therefore, we grant Hanover's motion for summary judgment on the
vexatious and unreasonable conduct claim (Count III).
Based on the foregoing analysis, we deny AMI's motion for
summary judgment and grant Hanover's motion for summary judgment.
In addition, we deny AMI's motion to strike as moot.
© 1992-2004 VersusLaw Inc.
Our website includes the main text of the court's opinion but does not include the
docket number, case citation or footnotes. Upon purchase, docket numbers and/or
citations allow you to research a case further or to use a case in a legal proceeding.
Footnotes (if any) include details of the court's decision.
Official citation and/or docket number and footnotes (if any) for this case available with purchase.
Learn more about what you receive with purchase of this case.
LRC, Inc. About Us

subset: commoncrawl


text:
Play: Unity 3D Cars
Related Games
Description: Unity 3D Cars
Description: Unity 3D Cars it's a new cool Unity 3D car games where you test a simulator of the latest super cars like Ferrari, Nisan GTR and other awesome ones. Test the cars by driving them from inside or outside just adjust the camera view with the keyboard C and enjoy high speed and drifting wheels. Have fun here on brightestgames.com with new unity 3D car games, racing and monster truck game everyday. Be the best driver from this new Unity 3D Cars and drive your dream car like you one it.
Tags: unity 3d cars, racing, cars, unity 3d, 3d game, unity 3d cars games, unity 3d cars games, racing, stimulation, new 3d car games, unity cars
New racing games, shooting games, car games, bike games and sport games are added weekly! Unity 3D Cars Games


text:
Joolz Day Studio Nursery Bag - Noir
Item Ref: 200070
Mouseover image to zoom or click here for full image
The Joolz Day Studio Nursery Bag perfectly compliments the Joolz Day Studio, providing stylish and functional storage for those baby essentials.
- Details
Beautifully complimenting the Joolz Day Studio, the Nursery Bag is stunningly stylish and provdes ample storage for all the essentials.
- Adjustable shoulder strap.
- Straps to attach the Joolz Nursery Bag to the Joolz.
- Includes changing mat.
- Internal pockets.
- 2 insulated outer pockets.
- Reviews
Customer Reviews (0)
- Warranty


text:
Herbal Body Moisturizer For a Real Skin Trip! Exquisitely smooth moisturizer made with 100% Pure Organic Hemp Seed and Avocado Oil that fortify and support your skins hydration and nourishment leaving it looking and feeling its very best. Since the beginning of time, Hemp Seed Oil has been used as the cure all for skin ailments and conditioning. As one of nature's richest sources of essential fatty acids and key amino acids, it's been proven to be vital for healthy skin condition. The results- pure, inhibited richness that leaves your skin sensual, soft and silky smooth.
|Company Name
|123 Hair And Beauty
|Shop Name
|123 Hair And Beauty
|Shop Address
|Mickledore Coach House BB4 8RS Rawtentstall
|Shop Phone Number
|Shop Email Address


text:
Oreck DutchTech Canister Vacuum DTX1400 Reviews
- Other Vacuums:
- Average: 4.2
- High: 5.0
- Type:
- Canister Vacuums
- Brand:
- Oreck
- Model:
Read 2 Reviews
REVIEW SNAPSHOT®by PowerReviews
Reviewed by 2 customers
Sort by
Comments about Oreck DutchTech Canister Vacuum:
This is great vacuum. It is an Oreck so it will last forever. The vacuum is great for all types of floors. I use it on hardwood, bathroom tile and carpet. It has great suction and does not loose suction until the bag gets very full.
The canister has to be pulled around and that is the only bad thing about the vacuum. The carpet attachment and the hard floor attachment are very easy to push around and then can go pretty much anywhere.
Ease of Maintenance
Never have had a problem with the vacuum except changing the bag. So Maintenance is very easy.
Suction Performance
Really great. There is even an adjustment to change the power level.
Works on every type of floor. You can even use the hose to vacuum cobwebs off the ceiling.
It is sleek and holds all the attachments inside it.
It is an oreck so the durability is great. It is suppose to last a lifetime or until you get bored with it and want a new one or a different model.
Comments about Oreck DutchTech Canister Vacuum:
The dutchtech vacuum has alot of power and has a three year warranty. It is easy to use and has quiet mode which has come in handy. Just before the three year warranty expired, the light on it went out. It was an electrical problem. The vacuum came back from repairs with new scratches, a used brush and little things broken on it that weren't broken before. We made a stink and it took a long time to get it sorted out, but they finally decided to give us a vacuum that had been returned by someone within the thirty day trial period. they did not renew the 3 year contract. We are happy with our vacuum and we love that you can attach an optional hepa filter. there is also a filter in the bag area. we never have dust come out of our vacuum. it also comes with a hard floor attachment, and three other attachments.


text:
Need a birthday gift, hostess gift, or just an appreciation gift for a friend or something for you at home spa day? Look no further! Kesh Beauty is now offering all three of their signature Argan Oils in a Gift Set Trio. With countless uses for the skin and hair from head to toe—and a beautiful bottle you'll want to display—Kesh Beauty's 100% organic cold- pressed Moroccan argan oils take the guesswork out of gifting.
Kesh Beauty uses only the highest quality, natural ingredients, and their argan oils are certified 100% organic by the U.S. National Organic Program. Their unique spray dispensers minimize waste by delivering the perfect dose, while preventing contamination so our preservative-free argan oils stay fresher, longer. Imported directly from a cooperative in Southern Morocco, Kesh Beauty's argan oils are extracted from the fresh kernels of the Argan fruit tree using the same ancient techniques that have been passed down from generation to generation.
PURE: 100% organic cold-pressed argan oil
ROSE ESSENCE: 100% organic cold-pressed argan oil with rose essential oil
ORANGE BLOSSOM ESSENCE: 100% organic cold-pressed argan oil with orange blossom essential oil
50 ml (1.7 oz) per bottle
Artisan goods preserve culture & tradition by continuing to handcraft high-quality goods. We believe the past should inform our progress forward.Artisan
Eco-Friendly goods approach production with the earth in mind. This includes low impact dyes & new textiles like modal, tencel, soy & hemp.Eco Friendly
Fair Trade goods offer fair wages & safe conditions for makers worldwide. Together we are investing in community with trade, not aid.Fair Trade
Made in USA goods are crafted in the United States with safe conditions & fair wages. Local production helps America move forward.Made in USA
Organic goods use no harmful toxins from seed to wear. Eliminating toxins is better for you & the environment we live in.Organic
Recycled goods expand the life for elements that make our stuff. Textiles, buttons, zippers, plastics that would otherwise be in landfills.Recycled
Vegan goods have no animals or animal by-products used in the creation or testing before it reaches you. We believe in safety for all involved.Vegan
Zero Waste goods maximize what we can make with the resources we have. From reusing water to pattern making, nothing goes to waste.Zero Waste
Ingredients: 100% organic cold-pressed argan oil with rose essential oil


text:
Black Satin Rhinestone Crystal Embellished Small Clutch Handbag
Have questions? Or looking for something specific?
Clutch has silver toned chain link strap. Rhinestone crystal kiss lock closure. One interior open pocket. Comes with dust bag. Retails for $3,095.
Join our mailing list to access a first look at our fabulous finds!
Your E-mail id is successfully added into our Newsletter mail list


text:
Clinical, scanographic and histological aspects of cerebral tumours in children in Yaoundé, Cameroon [Aspects cliniques, scanographiques et histologiques des tumeurs cérébrales de l'enfant à Yaoundé, Cameroun]
Mbonda E.,Unite de neuropediatrie |
Siaka C.L.,Unite de neuropediatrie |
De Paul Djientcheu V.,Service de Neurochirurgie |
Nguefack S.,Unite de neuropediatrie |
And 5 more authors.
Schweizer Archiv fur Neurologie und Psychiatrie | Year: 2011
Cerebral tumours in children occur in approximately 2.5 cases per 100 000 inhabitants every year in developed countries, however, they remain misunderstood in subSaharan Africa, where there is a problem with diagnosis and treatment. The objective of this retrospective work was to illustrate the clinical, scanographic and histological aspects of cerebral tumours in children in Yaoundé. Children who have had their cerebral tumours operated on were included, the age of whom varied between 0 and over 15 years. In all cases, the working diagnosis was made using scanography and the confirmed diagnosis was determined using histology. Cerebral tumours in children (42 cases) represented 35.29% of all cerebral tumours (119 cases). Intracranial hypertension represented the most frequent method of discovery (88.09%) followed by cerebellar syndrome (37.5%). The subtentorial position was the most frequent and represented 54.76% of cases. Cerebral tumours in children are frequent in Yaoundé. The subtentorial position was most frequently encountered. Astrocytoma was the most frequent type in the histology. The diagnosis essentially rests on computed tomography which enables the histological diagnosis to be targeted in 71.43% of cases and the tumour to be located. Source
Eyssartier E.,Service de chirurgie pediatrique viscerale |
Villemagne T.,Service de chirurgie pediatrique viscerale |
Maurin L.,Service de Radiologie et Imagerie Medicale |
Machet M.C.,Service dAnatomie et de Cytologie Pathologiques |
Lardy H.,Service de chirurgie pediatrique viscerale
Journal of Pediatric Urology | Year: 2013
Lipoblastomas are rare benign mesenchymal tumors of fetal white fat tissue appearing most commonly in children under 3 years of age, and usually affecting the extremities. Only nine cases of intrascrotal lipoblastoma have been reported to our knowledge, and although they are benign, in one case an orchidectomy was performed. We describe two new cases of intrascrotal lipoblastoma, and review the literature. Source
Eyssartier E.,Service de chirurgie pediatrique viscerale |
Ang P.,Unite de Specialites Pediatriques |
Bonnemaison E.,Unite de Specialites Pediatriques |
Gibertini I.,Unite de Specialites Pediatriques |
And 9 more authors.
Pediatric Pulmonology | Year: 2014
Primary endobronchial tumors are rare in children and they include a broad spectrum of lesions. The aim of this study was to determine the characteristic features, treatments and outcomes of these tumors. We report a retrospective analysis of all patients treated for endobronchial tumor in nine French hospitals between 1990 and 2010 and a comparison of the results with those reported in the medical literature. Twelve tumors were reported: five low grade muco epidermoid carcinomas, two inflammatory myofibroblastic tumors, two hemangiomas, one anaplastic large cell lymphoma, one carcinoid tumor, and one juvenile xanthogranuloma. The mean age of the patients was 7.5 ± 3.5 years. The most common sign revealing the disease was persistent atelectasis or recurrent pneumonia (eight cases). The other revealing signs were a persistent bronchospasm (three cases) and hemoptysis (one case). The clinical presentation, biology, serum tumor markers, and chest X-ray abnormalities were not specific to a particular histological diagnosis. Chest CT scan revealed the presence of an endobronchial tumor in 11 cases. Nine tumors could be diagnosed from a biopsy obtained by video endoscopy. Complete surgical resection was performed in seven patients. Bronchoscopic removal was performed in five cases and was successful in three. There were no deaths. Endobronchial tumors are rare in childhood and their histology is diverse. Chest CT scan and per-endoscopic endobronchial biopsies are required for diagnosis, when possible. Surgical or endoscopic treatment should be discussed by a multidisciplinary team. Despite the multiple etiologies, the prognosis of these tumors is good if diagnosis is early and if resection is complete. Long-term recurrences have been described, so long-term follow-up of these children is recommended. © 2014 Wiley Periodicals, Inc. Source
Evaluating pediatric patient dose during computed tomography in two University Teaching Hospitals in Yaoundé - Cameroun [Ivaluation de la dose patient en scanographie pédiatrique dans deux hôpitaux universitaires à Yaoundé Cameroun]
Ongolo-Zogo P.,University of Yaounde I |
Mpeke Mokubangele C.,University of Yaounde I |
Moifo B.,University of Yaounde I |
Gonsu Fotsin J.,Service de Radiologie et Imagerie Medicale
Radioprotection | Year: 2012
The practices related to patient radiation protection are poorly documented in sub-Saharan Africa because of the lack and/or weak enforcement of the related legislative and regulatory frameworks. This study investigates the justification and optimization of pediatric CT scans in two university teaching hospitals in Yaoundé in Cameroon. 171 CT scans in pediatric patients below 15 years of age performed during one trimester were surveyed. The data collection form was adapted from a dosimetric assessment sheet from the French Institut de radioprotection et de sureté nucléaire. The guidelines were those of the Société française de radiologie and the Société francophone d'imagerie pédiatrique et prénatale. Each CT scan was assessed and the CT dose index and dose length product were compared with the Diagnostic Reference Levels (DRLs) of the above-mentioned guidelines. While all the CT exams were justified, protocols were not readily available and varied amongst teams and units. The tension conformed in 87.7% of cases and 15.2% of DLPs were higher than the DRL for thoracic and abdominal CT scans performed under helical mode and brain CT scans performed sequentially. Readily available optimal CT protocols for children are urgent to improve upon the pediatric CT practices in these two units with a high turn-over rate of technologists and radiology residents. © 2012 EDP Sciences. Source
Preoperative angiographic CT-scan imaging for perforator flaps transfer. Clinical applications in an emergency unit of reconstructive surgery: Case report [Intérêt de l'angio-TDM dans la chirurgie des lambeaux perforants. Applications dans une unité de chirurgie plastique et reconstructrice. À propos de quatre cas cliniques]
Bosc R.,Service de chirurgie plastique |
Hivelin M.,Service de chirurgie plastique |
Benjoar M.-D.,Service de chirurgie plastique |
Pigneur F.,Service de Radiologie et Imagerie Medicale |
Lantieri L.,Service de chirurgie plastique
Annales de Chirurgie Plastique et Esthetique | Year: 2010
Our experience of the deep inferior epigastric artery perforator flap has led us to perform systematically an abdominal CT-scan for the pretherapeutic checking. This exam gives us a precise vascular mapping of musculocutaneous and septocutaneous perforators artery of the flap, may enable a better orientation in the dissection and reduce the surgery time. We have enlarged the indication of this exam to the members flaps who needs the dissection of a musculocutaneous or a septocutaneous perforators vessels: Nakajima's et al. classification [1]. The mapping of perforating vessels on 3D reconstruction pictures helps us to planify the vascular cutaneous autologous grafts. © 2009 Elsevier Masson SAS. Source


text:
Today's Baltimore wedding venue, the American Visionary Art Museum, has to be one of the most awesome and unique locations in our area. Kristin and Laura chose it for their Jewish wedding ceremony, captured by Kelly Prizel Photography, and really let the one-of-a-kind aspects it offers shine through with their simple palette and decor. If you want a great place to take photos before and after your wedding, this is it! They had a legal ceremony in Washington DC the day before their wedding in Baltimore. They took full advantage of the museum's quirky backdrops in the daytime, before standing under their handmade chuppah and tying the knot. Check back later for more handmade goodness at the fun reception that followed!
From Kristin and Laura: We chose a modern black and white color scheme and tried to let the art and beauty of the venue shine through. For our evening ceremony in the wildflower garden, we kept the details simple and focused on lighting and our homemade chuppah.
Kristin's father constructed the chuppah and used Laura's great grandmother's shawl for the covering. We began with a ketubah signing, then had a jewish ceremony after sunset. Kristin broke the glass!
One of our favorite memories is when our Rabbi asked everyone to affirm our marriage, and the whole crowd burst out into cheers and applause. We were surprised and grateful for this outpouring for love. Following the ceremony, we practiced a yiccud (fifteen minutes alone as newlyweds). This was one of the most emotional moments of the day for both of us.
The following Washington, DC area wedding vendors contributed to Kristin and Laura's wedding:
Venue: American Visionary Art Museum
Caterer: Absolutely Perfect Catering
Floral Designer: Local Color Flowers
Photographer: Kelly Prizel Photography
Band: Junkyard Saints
Cakes: Sugarbakers
Ice Cream Cart: Ben and Jerry's DC Scoop Shop
Lighting: Particle Wave Creative
Kristin's Dress and Hairpiece: Stephanie James Couture
Laura's Dress: Amy Kuschel
Don't forget to visit our vendor guide for more fabulous Washington, DC area wedding professionals or our real wedding gallery for more beautiful Washington, DC area weddings!
Photo Credits: Kelly Prizel Photography


text:
Check in from 14h / Check out prior to 11h
Scottish Inns Boone (North Carolina): Find photos, reviews, information, amenities and compare prices for 2 stars hotels in Boone, United States.
Scottish Inns Boone is situated in Boone and is close to the area's well-known attractions.
Hotel description
Guests staying at the hotel can enjoy a unique dining experience at the in-house restaurant, conveniently based for those who want to stay close by when looking for a bite to eat. A wide variety of dining options are also found in the surrounding area.
Scottish Inns Boone provides easy access to Tweetsie Railroad Theme Park and Appalachian State University. Julian Price Memorial Park is within an easy car ride from the hotel.
Hotel features
Availability and Prices
Booking Site
Room Type
Per room
Per night
Per night
Users who viewed Scottish Inns Boone (North Carolina) also viewed these 2 stars Boone hotels:
The Lodge Hotel Boone (North Carolina)
3600 Heavenly Mtn Dr , Boone
3600 Heavenly Mtn Dr , Boone
Highland Hills Motel and Cabins Boone
2748 Highway 105 South, Boone
2748 Highway 105 South, Boone
Greene's Motel
1377 Blowing Rock Road, Boone
1377 Blowing Rock Road, Boone
Search hotels
based on
0 reviews
Nearest hotels
- Holiday Inn Express Boone
11 m
- Fairfield Inn & Suites Boone
173 m
- Greene's Motel
870 m


text:
- Anonyme
- Autriche, Femme, 25-30
- Nomade novice
- 1 revue
we made our reservation for a private four bed room 2 months in advance. but when we arrived our room was not available. we received a three bed room with an extra matress and four using the bathroom we had to cross the patio.
- Anonyme
- Angleterre, Femme, 18-24
- Nomade novice
- 3 Avis
The main owner was very nice, but the directions for reaching the location were too confusing. Especially considering it is in the Medina. I highly recommend that if you go you get picked up since it is too confusing to find the first time on your own. Also, Marrakech being so hot in the peak of summer and there being no fans or AC made this a bit difficult to handle.
Les applications mobiles d'Hostelworld
Réservez facilement grâce à la nouvelle application mobile Hostelworld.


text:
Blade Gallentine/Corbis
We've been conjecturing about life on Mars for centuries. In popular culture, the concept of intelligent life on Mars was championed by astronomer Percival Lowell in the late 1800s and his theories on the Martian canals. Science fiction writers -- always game for some reckless conjecture -- took up the banner from there.
Perhaps the most famous Martians in the history of sci-fi and popular culture, the invaders in H.G. Wells' 1898 novel "War of the Worlds," have since spawned dozens of films, TV shows, comic books and one very famous radio drama.
Wikimedia Commons
Telescopic observations of Mars in the late 19th and early 20th centuries appeared to show long surface lines that some believed were man-made (well, Martian-made) irrigation canals. Italian astronomer Giovanni Schiaparelli made this map of Mars from his notes on the telescope images.
Wikimedia Commons
Science fiction writers often depicted Martians as an advanced humanoid race intent on conquering Earth. In "Flash Gordon's Trip To Mars" (1938), Azura Queen of Mars subjugates her own Martian people. Ray Bradbury would later conceive of a kinder, gentler race in "The Martian Chronicles."
ohn Springer Collection/Corbis
Space explorer stories were a regular staple in the pulp fiction magazines of the early 1900s, and Edgar Rice Burroughs was another author to speculate at length on Mars' inhabitants. His Martians included the six-limbed, green-skinned Tharks and humanoid Red Martians.
Science Picture Co./Corbis
The so-called Grey Alien is a kind of archetype image of an extraterrestrial -- not necessarily from Mars -- that has arisen from fictional depictions, alleged alien abduction stories and conjecture on what an advanced race of beings would look like.
Roger Ressmeyer/NASA/Corbis
On July 25, 1976, NASA's Viking 1 orbiter captured the above image on the surface of Mars' Cydonia region. The infamous "Face on Mars" prompted decades of speculation, although scientists have long dismissed the image as an example of pareidolia; e.g. seeing shapes in the clouds, or Jesus in your toast.
Warner Bros.
Legendary Looney Tunes animator Chuck Jones created the character of Marvin the Martian in 1948 as a foil for Bugs Bunny. As devotees of Saturday morning cartoons know, Marvin is forever plotting to destroy the Earth by way of his Illudium Q-36 Explosive Space Modulator. Apparently, we obstruct his view of Venus.
Bureau L.A. Collection/Sygma/Corbis
Director Tim Burton played around with B-movie tropes and pop art notions of Martians in his 1996 film "Mars Attacks!" Brian De Palma followed up a few years later with "Mission to Mars," a huge critical and commercial bomb. (Although the French critics liked it -- really.)
Bureau L.A. Collection/Sygma/Corbis
As is its eternal wont, pop culture is constantly recycling its own ideas -- Martians included. In 1999, Christopher Lloyd starred as the titular alien in director Donald Petrie's reboot of the 1960s TV show "My Favorite Martian," which was itself inspired by earlier pulp sci-fi stories.
If a microorganism were found on Mars, would anyone care?
NASA scientists announced on March 12 that the Red Planet could have supported ancient life — though they don't yet have evidence that it did. A sample of rock drilled by the Curiosity rover revealed conditions that could have supported ancient microbes at some point in the distant past.
The news of even potential life made headlines, and there's no doubt the discovery of actual microbial life on Mars would, too. But the impact of finding life on another world might not be as Earth-shattering as one might think, experts say. That's mainly because the life probably wouldn't be asking to be taken to our leader.
PHOTOS: Top 10 Places To Find Alien Life
"People don't get excited about microorganisms," said Chris McKay, an astrobiologist at NASA Ames Research Center in Moffett Field, Calif.
Life on Mars?
For scientists, Mars life would be a big deal, McKay told LiveScience. Even more paradigm-altering would be to find that life on Mars originated independently.
It's plausible that Mars and Earth exchanged material in their early days, and that life found on Mars could have arisen from the same source as life on Earth. Such a discovery would be intriguing, McKay said, but "not as profound as finding that there's life on Mars and finding that it represents a second genesis."
"If we find on Mars evidence for a second genesis, that changes everything," he said. (Photos: Curiosity Finds Habitable Martian Site)
13 Ways to Hunt Intelligent Aliens
Life evolving twice in the same solar system would suggest that life is common throughout the universe, McKay explained. Such a discovery would be huge for biologists, who would suddenly have an entirely new type of biology to study.
McKay doesn't envision any major shifts in philosophy among the public in response to such a discovery, though. The discovery of microorganisms on another planet wouldn't necessarily spur the need to re-evaluate humanity's place in the universe, for example.
"I would put it along the lines of the discovery of the Higgs boson," McKay said, referring to the particle theorized to explain where other particles get their mass. "It would be that sort of level of event. It would be out in the public and people would be like, 'Oh, wow,' but mostly it would be something that scientists would get into."
Physicists announced last week they had confirmed the newfound particle discovered with experiments in the Large Hadron Collider was indeed a Higgs boson, with other physicists expressing their excitement and exhilaration of the discovery.
Life versus life
Indeed, some data suggests that even the discovery of intelligent extraterrestrials wouldn't shake human society beyond its ability to cope. One survey of more than 1,300 religious individuals released in 2011 found that believers were extremely confident that the discovery of intelligent aliens wouldn't shake their faith. (7 Theories on the Origin of Life)
"Theologians and religious leaders who have looked at this, it's surprising to me that they have so little to say — almost as if it's not interesting," said Ted Peters, a theologian at Pacific Lutheran Theological Seminary in Berkeley, Calif., who led the study.
Mars microbial life would be unlikely to have much of a theological impact, Peters told LiveScience. Most religious traditions hold that life is the creation of God, but don't commit to an exact explanation of how God did it. Life's origin could happen through chemistry multiple times throughout the solar system and not conflict with these worldviews, Peters said.
The discovery of intelligent life somewhere in the universe would be far more theologically significant, Peters said. Such a discovery could throw open fundamentally spiritual questions, he said: Are the aliens spiritual? Do they have a sense of morality, empathy or love?
VIDEO: Curiosity Rover Finds Possible Life on Mars
Intelligent aliens could also provide answers about the evolution of religious belief, Peters said. Some scientists hold that religion is a primitive way of explaining the world, and that science will replace it, he said. If super-intelligent aliens were to both embrace science and God, it might disprove that evolutionary theory.
Discovering intelligent life would also be scientifically valuable, above and beyond any discovery that microbes evolved on Mars, McKay said. There are three big steps that get you to a species like humans: The origin of life, the evolution of complex life such as plants and animals, and, finally, the development of intelligence.
"We don't have any expectation that, on Mars, life did the other two steps," beyond possibly originating, McKay said. "Communicating with extraterrestrial intelligence takes us to the end of that comparison, so we immediately know that all three steps occurred."
More from LiveScience.com:
5 Mars Myths and Misconceptions
Science Fact or Fantasy? 20 Imaginary Worlds
UFO Quiz: What's Really Out There
This article originally appeared on LiveScience.com. Copyright 2013 LiveScience, a TechMediaNetwork company. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.


text:
I have been double posting here, back and forth from my blog to here and I'm going to stop. I have a blog and if you want to see what I write about EVERY DAY this year, then come on by and take a peek. http://crbh-ruminations.blogspot.com
Recent Posts by CRB-H
Recent Posts
Follow BlogHer
Most Popular
No Mess Rice Recipes
We asked our bloggers to craft some recipes from the different Success® Rice flavors and tell us about it. Check out their ideas and you could win a $100 Visa gift card! Read more
Guilt Free Meals
Lean Pockets have no artificial flavors, a good source of protein & have 100% real cheese. Read our bloggers posts where they will tell you their guilt free experiences with Lean Pockets. Plus get a chance to win $100! Read more


text:
Privacy Policy | Terms & Conditions
October 20, 2016
Expires On December 30, 2016
Enter with Steamy Kitchen for your chance to win an iPad Mini.
More from Apple »
© 2012 - 2016 Free.ca All rights reserved.
© adjump 2011
All Rights Reserved
No part of this website or any of its contents may be reproduced, copied, modified or adapted without adjump's prior written consent.


text:
AL752BBISSHVLHD 24" 5.5 Cu. Ft. Capacity Compact Refrigerator Automatic Defrost Adjustable Glass Shelves Adjustable Thermostat ADA Compliant: Stainless
Home > Appliances Connection > Appliances > Refrigerators > Compact Refrigerator
|SUMMIT39s AL750BI series features built-in capable all-refrigerators designed to fit under lower ADA compliant counters
$25 Off Appliances Connection Coupon Code - Use SAVE25 at checkout on select purchases for a limited time.
Only $1,025.00 at AppliancesConnection.com


text:
Preschool Worksheets and Printables
Preschool is a great time to introduce your kids to worksheets to prepare them for elementary school. These preschool worksheets include fun themes and visuals to inspire a love of learning. Use these worksheets to teach them about letters, number recognition, counting shapes, and more. To start with a specific subject, try our preschool math worksheets.
Key Preschool Skills:Preschool Sight Words
- Filter Results
- Holidays & Seasons
- Winter (30)
- Hanukkah (4)
- Kwanzaa (1)
- Christmas (73)
- New Year (6)
- Martin Luther King (2)
- Chinese New Year (3)
- Valentine's Day (30)
- St. Patrick's Day (10)
- Spring (7)
- Passover (3)
- Easter (24)
- Asian Pacific American Heritage Month (1)
- Cinco de Mayo (3)
- Mother's Day (8)
- Summer (14)
- Graduation (2)
- Father's Day (1)
- July 4th/Independence Day (26)
- Back to School (9)
- Fall (14)
- Labor Day (4)
- Hispanic Heritage Month (1)
- Halloween (55)
- Veterans Day (1)
- Thanksgiving (28)
- Earth Day (16)
- Summer Olympics (1)
- Birthdays (23)
- The Holiday Season (18)
Current Filters (2,699 results):
What Doesn't Belong at School?
Backpack, ice cream cone, pencil, scissors: One of these objects is not an essential school item. Preschoolers identify the object that does not belong.
Practice Tracing the Letter F
First, kids trace lines on this prekindergarten writing worksheet to strengthen the fine motor skills needed to form the letter F. Then they trace the letter F!
Get Ready for Reading: All About the Letter H
Prepare your preschooler for reading readiness by getting her familiar with the letter H. This worksheet will do the trick!
D Is For...
Help your preschooler learn the alphabet and practice letter D sounds all while having fun and coloring!
C is for Caterpillar
C is for caterpillar on this alphabet coloring page. Can you and your child come up with other animals' names that start with C?
Classification of Living Things
Can your budding learner tell which of these items are living things? As she colors each picture, she'll decide if it grows and takes in air, water, or energy.
Tracing Numbers: 6
Kids color six sharks and trace the number 6 several times to practice counting, identifying, and writing numbers on this prekindergarten math worksheet.
Match the Shapes
Oh, what a mix-up! With this worksheet, your child matches mixed-up shapes together.
Tracing Letters: A
This alphabet worksheet introduces kids to the letter A and lets them practice tracing letters!
Trace the Squares
How many squares are in this building? Help your student build fine motor skills with this tracing worksheet.
Nikola Tesla Hidden Code
Nikola Tesla was a smart, smart man. Your preschooler needs maybe 0.3 percent of Tesla's intelligence to find the hidden code.
Domino Addition!
Counting and number writing practice are all-in as your child works on her additions skills with this domino dots page!
Cut Out Shapes
Kids cut out pictures to put silly, mixed-up shapes back together on this prekindergarten math worksheet.
Your Five Senses: Matching 4
Get your child thinking about the five senses with this worksheet that gets her to consider taste, touch, sight, smell, and hearing.
I Is For...
Help your preschooler learn the alphabet and practice letter I sounds all while having fun and coloring!
Pond Life Coloring Page
Preschoolers are sure to love coloring this pond life coloring page that's full of happy frogs, flitting dragonflies, and one cheerful turtle.
Beginning Sounds Coloring: Sounds Like Pumpkin
Ease your child into phonics with this coloring page that asks him to color the things that begin with the letter P.
Get Ready for Reading: All About the Letter S
She, saw, sun ... No, it's not a tongue twister, it's a preschool worksheet all about the letter "S."
The Color Orange
Is orange a color or a delicious fruit? Learn all about the color orange with a fun project, where your child can create her own color book!
The Five Senses!
In this worksheet, your child will check off which of the five senses he'd use to interact with each object pictured.
Practice Tracing the Letter J
First, kids trace lines on this prekindergarten writing worksheet to strengthen the fine motor skills needed to form the letter J. Then they trace the letter J!
Dinosaur Alphabet
D is for dinosaur! These dinosaur alphabet flashcards are perfect for getting little ones excited about learning their ABCs.
Get Ready for Reading: All About the Letter M
Want to teach your preschooler the letters of the alphabet? Help her get to know the letter M with a handful of activities all about this captivating consonant.
Using Preschool Worksheets at Home or in ClassThe preschool years go from 3 to 5 years of age, prior to the start of Kindergarten or the formal classroom environment of first grade. The preschool years represent a unique developmental window where kids are growing out of toddlerhood and are very receptive to both formal learning and informal learning through play. Some preschoolers have spent most of their time at home with parents or caretakers, while others have been in a daycare or school environment part or full time. In any of these scenarios, preschool worksheets can help 3, 4, or 5 year olds grow accustomed to using writing tools and paper to learn new concepts.
Try these tips to create an educational and engaging environment for your child while using printable preschool worksheets:


text:
Wanna join the discussion?! Login to your Long distance hiking trails forum accountor Register a new forum account. Or Connect via Facebook
Very well, we have some writers.
Good luck to you all.
Like the sentence ". The game is over. Or we win or fade away.
Because what is good for our area.
The last writer asked something I think is worth to look at (Russian/English translation).
Anyway recommend to transfer to General Forum.
And again, lots of luck to you and to all the writers.
Congratulations yagil! Definitely going to buy this week.
What's the next step? The book for
Yagil successfully , even lustily at the end of the dissertation, or have you already done? If so then good luck with the rest of the way. I will attend to you in joy so much as one writer rather than a shelf at home.
If we tell the wonderful writers Forum, my first book in two responses:
Yankale17 39240.4355324074
And the back cover also (forgive the quality of the forum rules that need to be met.)
Ashreichm mate, really good for you all.
Rose and I wish I still win the Sapir Prize for literature.
Yagil mate, good luck. Also several g too!!!
יענק'לה, said a first book (which, by the way, I know I would buy it after I finish the book of toren) came more him?
Organise a sale to Forum members with dedications.
If Ma approves course.


text:
Watch Beyond Beauty: Taiwan from Above (2013) Free Online
Beyond Beauty: Taiwan from Above
IMDB Link:
Rating: 8.0/10 (423 votes)
Director: Po-lin Chi
Writer: Chi-chuan Tsui (screenplay), Chi-chuan Tsui
Stars: Cing-Soong Lai, Nien-Jen Wu, Nolay Piho, Xiang Hong
Runtime: 93 min
Rated: N/A
Year: 2013
Genre: Documentary, Drama
Quality: HD
Language: Chinese, Mandarin
Released: 01 Nov 2013
|Plot: A documentary that documents Taiwan from an aerial perspective. It offers viewers a glimpse of Taiwan's natural beauty as well as the effect of human activities and urbanization to our environment.
Promoted Content
Watch Beyond Beauty: Taiwan from Above (2013) - Alternative Servers
|Version 2
|Version 3


text:
Minnie Mouse Halloween Plush Ornament
now $9.99
reg. $12.99, you save: 23%
Costumed as a happy Halloween Witch, this soft Minnie ornament will stir-up some good voodoo for you as she hangs around the house all through the spooky season! See more
It's added to your bag!
Not eligible for in-store reservation.
Magic in the details...
Created especially for Walt Disney World Resort and Disneyland Resort
- Soft, padded Minnie figure
- Felt texture
- Embroidered detailing
- Satin bow and and ribbon on hat
- Satin loop for hanging
- Beans in bottom
- Part of the Disney Parks Plush Ornament Collection, each item sold separately
The bare necessities
- Polyester / polystyrene beads
- 8 1/2'' H (hat tip to heel)
- Ribbon hangs 3'' L
- Imported
Most items ordered via Standard Delivery will arrive within 7-9 business days, personalized items within 9-11 business days. Exceptions include items shipped from locations other than our main warehouse. Express Delivery is available for an extra charge.


text:
Jason Derulo and Daphne Joy have apparently split up. The R&B star and the model had been together for months; both had history of high-profile relationships and seemed to be doing fine but things are reportedly over after less than a year.
TMZ reports that it was Joy who decided it was time to part ways.
Derulo and 50 Cent's ex started dating last year and "went public" at the People's Choice Awards this past January. In March, Derulo talked about their relationship and gushed about how the two of them enjoyed simple pleasures.
"I love the simple things," the 26-year old told People.com "I like just kicking back and getting that one-on-one time, watching a movie at the house, or she (Daphne) cooks dinner. She's an unbelievable cook!"
Derulo and Joy began dating a little over a year after he split with fellow R&B star Jordin Sparks. That was a high-profile relationship that had lasted three years, and the breakup was highly scrutinized at the time. Derulo admitted in 2015 that he was frustrated with constantly being asked about what happened between the former couple.
"I understand why people ask but it's a bit weird," he said. "The strange part is it's like a prolonged break-up. Instead of it being over and moving on, it keeps on going and going. That's the strange part."
Joy is the mother of Fiddy's 3-year-old son, Sire Jackson.


text:
South Carolina Scrapple
Total Time
Prep 0 mins
Cook 0 mins
Ingredients Nutrition
- Select three pounds of bony pieces of pork. For each pound of meat use a quart of water and simmer until the meat drops from the bone. Remove the meat from bones carefully being certain to get all the small pieces.
- Bring the remaining broth to boiling point, adding sufficient water to make two cups.
- Slowly add two cups of corn meal and cook until the mixture becomes a thick mush, stirring constantly.
- Chop the meat and put it in the pot; also add salt, pepper and the juice of an onion.
- Cook for two minutes, stirring constantly.
- Pour the hot scrapple into a dampened oblong pan.
- Let stand until cold and firm.
- Slice and brown in hot skillet. If the scrapple is rich with fat, no more fat is required for frying.


text:
Doctor insights on:
Macular Hole
What is a macular hole?
Retinal break: A macular hole is a type of detachment of the retinal in the center of the vision. Many are spontaneous and some related to trauma. It causes a lowering of the central acuity and commonly is progressive unless treated. Treatment is done by retinal surgeons , is somewhat complex but commonly can reverse the process. ...Read moreSee 1 more doctor answer
Can you tell me about macular hole?
Fixable: A macular hole represents an opening of the central vision area of the vision tissue (retina) that develops. It is usually associated with a decline in visual acuity and 'funny' "scrunched up" vision centrally. Having surgery to repair the macular hole has greater than 90% success rate, and the vision is usually dramatically improved compared to be fore surgery, but not as good as it was. ...Read moreSee 1 more doctor answer
How much time will a macular hole take to heal?
Depends: Without intervention (surgery), anything but what is called a "Stage 1" macular hole will not heal. If it is a "Stage 1" macular hole, it will go away in about 50% of the time over weeks to months. If it is a "Stage 2-4" macular hole, surgery will be required, and vision recovery after surgery takes weeks to a few months. An evaluation by a competent retina specialist might be helpful. ...Read moreSee 1 more doctor answer
A friend was diagnosed w/ a macular hole a few months ago. On a later visit, the hole apparently disappeared. Is this normal and any repercussions?
Rare: Rarely, macular holes can resolve on their own. This usually occurs with recent onset, small holes. It would not be expected to have a negative effect, or present any disadvantage. ...Read moreSee 2 more doctor answers
What to do if I have a macular hole. how long can I wait until surgery?
Depends: First, it would be unusual for a 33 year old to have a macular hole. If there is one indeed, on average, surgery sooner results in better vision outcomes. However, waiting a few weeks should make difference. ...Read more
The day after vitrectomy for a macular hole, the gas dissipated to less than half the amount it should be. Why?
See a retina special: Ask your retina specialist. Different gases of different concentrations are chosen by your retinal surgeon (based on how long he or she wants it to last) and injected into the eye. ...Read moreSee 2 more doctor answers
I had consulted 2 surgeons prior to a projected macular hole surgery; one will be using C3F8 and the other SF6. Whats the difference of the two types?
See below: C3F8 gas lasts longer than SF6 gas before dissolving away on its own. Usually SF6 gas is used unless there are other compelling reasons to use the longer-acting gas, like peripheral retinal pathology. Ask your retina specialist. ...Read moreSee 1 more doctor answer
Can you recommend any alternative treatments for macular hole other than surgery.?
Macular hole: For early stage lamellar or full thickness macular holes, intervitreal injections of steroid or a vitreolysis agent can be of some benefit. For most macular holes, surgery is yourbest option. ...Read moreSee 2 more doctor answers
What's a detached retina and macular hole?
Retinal detachemnt: Retinal detachment is a detachment of the retina from the inside of the eye. The portion of retina that is detached leaves the vision completely black in the detached area. Retinal detachment is usually caused by a peripheral hole/tear of the retina. A macular hole is a hole in the center of the macula, the portion responsible for central vision causing varying degrees of loss. ...Read moreSee 2 more doctor answers
Went to the eye dr. He said my vision was 20/400. What does that mean. I had macular hole surgery last year in my rt. eye.
Poor eyesight : 20/400 vision means that you see at 20 feet what others can see at 400 feet. There are many people with 20/400 vision. However, they can be corrected to 20/20 with glasses or contacts. If your vision is 20/400 and cannot be corrected, it means you have poor eyesight and are legally blind. ...Read more
- Talk to a doctor live online for free
- Lamellar macular hole treatment
- Treatments for macular hole
- Stages of macular hole
- Ask a doctor a question free online
- Full thickness macular hole
- Lamellar macular hole
- Macular hole surgery recovery equipment
- How do i take care of a boil after it has popped and left behind a small hole?
- Alternative treatments for macular hole


text:
Lara Croft Wallpaper
#TombRaider #LaraCroft Para más información sobre #Videojuegos, Suscríbete a nuestra página web: http://legiondejugadores.com/ y síguenos en Twitter https://twitter.com/LegionJugadores
lara croft tomb raider | lara-croft-tomb-raider-2012-screenshot-cg
Lara Croft, Tomb Raider. I completed it, what a well paced and well made game it is, a very satisfying play through.
Lara Croft - Rise of the tomb raider
sometimes I like to imagine myself as the heroine of a story, but then reality gets in the way.. :)
Rise Of The Tomb Raider | www.fabuloussavers.com/games-desktop-wallpapers.shtml
this woman has evolved into a warrior, and brought legions of teenaged girls with her.
Tomb Raider - beautiful, brutal and at times deeply disturbing. One of the best games of the last decade.
Tomb Raider Lara Croft
Tomb Raider Mais


text:
STATE BANK OF INDIA RTGS HO Branch in TAMNAR - Address, IFSC, MICR Code
SBIN0012142MICR Code
TAMNAR VILLAGEContact
TAMNAR VILLAGEVILLEGE TAMNARPO TAMNARDISTRAIGARH CGDISTRAIGARH496107City
What is IFSC Code of STATE BANK OF INDIA situated at TAMNAR VILLAGE- RTGS-HO?
IFSC Code of STATE BANK OF INDIA situated at TAMNAR VILLAGE - RTGS-HO is
What is the meaning of IFSC Code, MICR Codes in Banking industry?
IFSC or Indian Financial System Code is the code allocated to all banks branches. Bank branches use this code to participate in RTGS and NEFT transactions.
What is the significance of IFSC Code and how we can use it?
IFSC Code is a 11 digit code and we can use this code to communicate between different branches of different banks. Upon receiving the request for fund transfer it is easy for a bank to identify the payee branch. First four characters are code of bank, last six digits are branch code and fifth character is left 0, for any future use.


text:
Cobalt houston for sale on US's largest classifieds sites (98 results)
Used 2006 Chevrolet Cobalt For Sale
2006 Chevy Cobalt Clean - $3500I need to sale my very good clean car , It\'s working very well; the motor, transmission, Cold A/c, Heather, radio, good inspection and registration, very clean in and outside, clean blue title. Great carmiles: 1036234 cylinder-GAS SAVERDrives smoothFor more info call me...
2008 Chevrolet Cobalt 189K clean title
Used 2006 Chevrolet Cobalt For Sale
Used 2006 Chevrolet Cobalt For Sale
CASH PRICE $3,500 WILL FINANCE Contact 713-73-7202 runs and drive like new The front windshield is in excellent condition. The paint is in great shape and condition. No dings are visible on this vehicle. This vehicle comes with a great of tires The inter...
Used 2007 Chevrolet Cobalt For Sale
Used 2009 Chevrolet Cobalt LT
Used 2009 Chevrolet Cobalt LT
Visit Success Auto Sales online at successautosales.net to see more pictures of this vehicle or call us at (888) 612-3230 today to schedule your test drive. We will BUY your Vehicle! Top Dollar Paid! Call today for a FREE appraisal! Committed to Customer Satisfaction for 12 years! On duty mechanics to...
Used 2009 Chevrolet Cobalt LT
CLEANT TITLE,Air conditioning, Power steering, Power windows, Tilt steering wheel, Drive type front-wheel, Engine liters 2.2, Cylinder configuration I-4, Engine displacement 2.2 L, Wheelbase 2,624mm (103.3"), Towing capacity 454kg (1,000lbs), Fully automatic headlights Speak Spanish: Puede llamar...
Used 2009 Chevrolet Cobalt LS
Cobalt LS, 4D Sedan, ECOTEC 2.2L I4 MPI DOHC, FWD, and Summit White. Get ready to ENJOY! Best color! Looking for a superb deal on a wonderful-looking 2009 Chevrolet Cobalt? Well, we've got it! New Car Test Drive called it ...the quietest, stiffest, strongest, most refined small car it has ever built, ...
Used 2009 Chevrolet Cobalt LS
ONE OWNER! 130 POINT INSPECTED! NEW OIL, AIR, AND FUEL FILTERS! THIS VEHICLE IS READY TO GO. FREE CARFAX AVAILABLE. NO HIDDEN FEES OR DEALER ADDENDUMS!!! JUST THAT GREAT MAC HAIK FEELING! DON'T MISS THIS GREAT DEAL. CALL NOW!!! At Mac Haik Ford we are the winner of the prestigious Presidents Award, Fo...
Used 2009 Chevrolet Cobalt SS Turbocharged
Come check us out Monday through Friday 8:00am-6:00pm and Saturdays 9:00am-4:00pm. Come find your dream car today!
Year: 2009, Make: Chevrolet, Model: Cobalt SS Turbocharged
2005 Chevy Cobalt* Financing Available* Clean Title
2010 Chevrolet Cobalt Sedan LT
2010 Chevrolet Cobalt Coupe LT Coupe
!!!HEAD CURTAIN SIDE AIRBAGS***REMOTE KEYLESS ENTRY***CD-MP3 PLAYER!!! - This 2010 Chevrolet Cobalt 2dr LT Coupe features a 2.2L L4 MPI DOHC 16V 4cyl Gasoline engine. It is equipped with a Automatic transmission. The vehicle is Silver Ice Metallic with a Ebony Cloth interior. It is offered with the re...
*Vehicle Photos* Please visit http://www.bridgestoneauto.com/vehicles/2007-chevrolet-cobalt--59 for quality photos. (Please cut & paste the address above in your browsers address bar) *Vehicles Options* Vin: 1G1AK15FX77372053 Make: Chevrolet Model: Cobalt Year: 2007 ...
Year: 2007, Make: Chevrolet, Model: Cobalt ls coupe
2010 Chevrolet Cobalt 4 Dr. Sedan - Excellent Car Fax - One Owner
2010 Chevrolet Cobalt ! Excellent Carfax ! Looks and Drives New ! Lots of Options ! One Owner ! Godfathers Auto Sales is offering this gas miser four door accident free sedan, well below market value. We offer a free 3 month/3000 mile limited warranty with extented coverage available. This garaged k...


text:
BROOKLYN - Pier 1 officially opened Monday in Brooklyn Bridge Park and many hope it will help revive the downtown area.
The park features views of the Manhattan skyline and could be the setting for a new wine bar. Officials say the 85-acre, $350 million project is slated to be complete by 2012.
When complete the park could feature a boating area, skating rink, biking path and several new restaurants.


text:
CPG18V - Cordless Grease Gun 18V
Supplier: Jack Sealey Ltd | Brand: SEALEY | Product: CPG18V
Share this product
Details of CPG18V
o High power, professional, cordless grease gun, developing 8000psi.
o Ideal for in-field lubrication where power and speed are required.
o Suitable for 400g cartridges, manual or bulk filling.
o Features LCD battery condition indicator, air bleed and heavy-duty aluminium pressure head.
o Supplied with 18V 1.7Ah battery and mains charger.
o Supplied in carry-case.
Barcode: 5051747484641
Warranty: 1 Year
6.5 Kg
Copy the link below to feature this product in a forum post: