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text:
The Sacred lyre : comprising poems, devotional, moral and preceptive : including many original pieces, with an introduction and a copious index.
Glasgow : R. Griffin, 1828.
Christian poetry, English.
Added t.p. with engraving.
Second edition includes "Table of first lines".
xxii, 360 p. :
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domain: artistic


text:
What people call “practices” I like to think of as experiments.
What happens if I do this? If I stay with it for a while? What do I notice?
This helps me have a more open mind and also approach it with interest and curiosity.
It becomes more open, interesting, fun, and enjoyable.
For instance, what happens if I do ho’oponopno towards (images of) myself at different ages? How is it if I start at birth (or before) and go along the timeline to today (or even later), staying with each age for a while – perhaps even days – until there is a shift towards genuine love towards myself at that age. How is it to include others in my life at the different ages? How is it to include my parents, friends, teachers, and others? How is it to include even those my mind has made into an “enemy”, however subtly?

domain: psychology


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Internal Medicine Opportunity in Mississippi
Company: Necnic Group, LLC
Posted on: September 22, 2022
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text:
Joint arthropathy secondary to recurrent hemarthroses remains a debilitating complication of hemophilia despite the use of prophylactic factor concentrates. Increased vascularity and neoangiogenesis have been implicated in the progression of musculoskeletal disorders and tumor growth. We hypothesized that de novo blood vessel formation could play a major role in the pathogenesis of hemophilic joint disease (HJD). We observed a 4-fold elevation in proangiogenic factors (vascular endothelial growth factor-A [VEGF-A], stromal cell–derived factor-1, and matrix metalloprotease-9) and proangiogenic macrophage/monocyte cells (VEGF+/CD68+ and VEGFR1+/CD11b+) in the synovium and peripheral blood of HJD subjects along with significantly increased numbers of VEGFR2+/AC133+ endothelial progenitor cells and CD34+/VEGFR1+ hematopoietic progenitor cells. Sera from HJD subjects induced an angiogenic response in endothelial cells that was abrogated by blocking VEGF, whereas peripheral blood mononuclear cells from HJD subjects stimulated synovial cell proliferation, which was blocked by a humanized anti-VEGF antibody (bevacizumab). Human synovial cells, when incubated with HJD sera, could elicit up-regulation of HIF-1α mRNA with HIF-1α expression in the synovium of HJD subjects, implicating hypoxia in the neoangiogenesis process. Our results provide evidence of local and systemic angiogenic response in hemophilic subjects with recurrent hemarthroses suggesting a potential to develop surrogate biologic markers to identify the onset and progression of hemophilic synovitis.
Hemophilic joint disease (HJD) secondary to recurrent hemarthroses is one of the most disabling and expensive complications of severe hemophilia A or B (X-linked recessive disorders with < 1% factor VIII/IX [FVIII/FIX] activity).1,2 Clinical and subclinical hemarthroses during childhood can result in the development of synovitis, which is characterized by villous formation, increased vascularity, and chronic inflammatory cells, resulting in hypertrophied synovium,2,3 resultant joint arthropathy, and destructive arthritis.4 Although synovitis and joint arthropathy can be minimized by the prophylactic infusion of factor concentrates, which is the standard of care in the developed world, prophylaxis is unaffordable in the developing world. Moreover, the dose, timing, schedule, and duration of prophylaxis are topics of ongoing debate.5 In the presence of active synovitis, prophylaxis may not stop further joint deterioration, necessitating the use of procedures, such as isotopic and arthroscopic synovectomy.6,7 Alternatively, the selective implementation of these strategies would require a more sensitive tool for detecting synovitis than is currently possible with clinical surveillance or plain radiographs. Magnetic resonance imaging (MRI) can detect both synovial and cartilage changes resulting from recurrent hemarthroses,8 unlike plain radiographs, which detect only advanced bony changes associated with joint arthropathy.2 However, MRI is expensive and requires sedation in younger children, limiting its utility for routine monitoring of synovitis. A better understanding of the pathogenesis of HJD might make it possible to identify surrogate biologic markers to indicate the onset of synovitis to aid in treatment decisions, such as prophylaxis and synovectomy.
The pathogenesis of HJD is not well defined. Villous formation after a single hemarthrosis resulting from acid phosphatase and cathepsin D-induced synovial inflammation,2 cartilage damage from long-lasting inhibition of proteoglycan synthesis,9 and abrogated synovial apoptosis via iron-dependent increase in MDM2 expression and MYC-C amplification have been reported.10-12 Neoangiogenesis is a critical factor in processes, such as tumor growth and inflammatory arthritis.13 Vascular endothelial growth factor (VEGF), the principal signaling molecule in angiogenesis, can be induced by hypoxia and certain cytokines through interaction with its receptors, VEGFR1 and VEGFR2.14-16 The synovitic pannus in other joint diseases that share histologic similarities with HJD have enhanced oxygen demand and show evidence of de novo blood vessel formation, including endothelialization of the synovium.2 Endothelialization may occur as a result of mature endothelial cell migration or through the recruitment of bone marrow (BM)–derived endothelial progenitor cells (EPCs) and hematopoietic progenitor cells (HPCs) from the peripheral circulation.17 Importantly, proliferating synovium can secrete chemocytokines, such as VEGF, that might promote recruitment of endothelial cells (ECs) to sites of active angiogenesis.18 In other joint diseases, such as rheumatoid arthritis and osteoarthritis, VEGF expression in the serum has been correlated with disease activity.18 Colocalization of HIF-1α and VEGF emphasizes the role of hypoxia in the up-regulation of angiogenesis in rheumatoid joint diseases.19 Because of the observed vascularity in human HJD2,3 and experimental murine models of hemophilic synovitis,20 we hypothesized that neoangiogenesis could play a major role in the development of synovitis secondary to recurrent hemarthroses. We observed potent proangiogenic mediators, circulating HPCs and EPCs in HJD synovium, and peripheral blood of HJD subjects. Collectively, our data suggest that cells of the early and late myeloid lineage can induce proangiogenic mediators contributing to neoangiogenesis associated with hemophilic synovitis.
Subjects and samples
This is a single-institution study where plasma samples were prospectively collected after Institutional Review Board approval from Weill Cornell Medical College, with informed consent obtained in compliance with the Declaration of Helsinki. Subjects with severe (FVIII/IXc: 0.01%), moderate (FVIII/ IXc: 2%-5%), and mild (FVIII/ IXc: 5%-25%) factor activity and a history of more than 2 hemarthroses in a joint composed the prospectively studied cohort of experimental subjects. A retrospective cohort of subjects who had MRIs of joints performed to determine eligibility for isotopic synovectomy also had plasma analyzed for VEGF-A levels. Early joint disease in this retrospective cohort was defined as less than or equal to the median of 20 lifetime hemarthroses, no x-ray evidence of joint arthropathy, but with MRI evidence of synovitis. Advanced joint disease was defined as more than 20 lifetime hemarthroses and x-ray evidence of joint arthropathy. All subjects had baseline x-rays 6 months to 2 years from enrollment on the study, depending on their bleeding history. Two control groups were established. Group A, the bleeding disorders control group, was composed of subjects with FVIII/ IX, XI activity levels between 0.05 and 0.25 U/dL, and rarer homozygous factor I, V, X, and XIII deficiencies who had a history of non-joint-related bleeding but no hemarthroses. Group B was composed of normal healthy persons without a history of joint bleeds. Experimental subjects were screened to ensure that they had not had a joint bleed less than 4 weeks before blood sampling to maximize bleed resolution potential, and they had last infused with factor concentrates more than 72 hours before blood draw to mitigate effects of factor concentrates on the relevant studies. Both subjects and guardians signed informed consent and assent forms. Peripheral blood samples were collected in ethylenediaminetetraacetic acid, serum separator tubes, and PAXgene Blood RNA tubes (PreAnalytiX/QIAGEN). Within 2 hours of collection, ethylenediaminetetraacetic acid and serum separator tube samples were centrifuged at 1000g for 15 minutes. Platelet-poor plasma aliquots were then stored at −80°C. Samples were analyzed within 4 to 8 weeks of collection. A random subset of samples was rerun for sample storage and interassay control, which varied for VEGF-A by 15.4 pg/mL (1.16 ± 0.08 seconds). Plasma samples from rheumatoid arthritis subjects were used as positive controls to determine assay sensitivity.
Primary cultures of human synovial fibroblast cells were a generous gift from Dr Katalin Mikecz (Rush University) and were cultured as described.11 Functionally validated primary ECs (BD Biosciences) were cultured with Clonetics EGM-2 endothelial growth medium (Cambrex). All experiments with ECs (second to fourth passages) and synovial cells (fourth to 15th passages) did not display discernable morphologic changes before each assay. Testing for bacterial, fungal, and mycoplasma contamination was done routinely.
ECs were incubated with plasma from HJD subjects and controls for 22 hours, and morphology was assessed. This time point was used based on a time course experiment (t = 2, 6, 12, 22, 32, and 40 hours) in which t = 22 hours morphologically acceptable “tube formation” was observed with recombinant VEGF.
Matrigel tube assay and effect of inhibitors.
ECs were preincubated with or without VEGF blocking peptide in Dulbecco modified Eagle medium (DMEM; 5 μg/mL, 1 hour, 37°C), washed twice with phosphate-buffered saline (PBS) or ECs in DMEM + 10% fetal bovine serum (FBS) or DMEM + 2.5% serum from HJD were seeded into Matrigel-coated 96-well plates (Angiogenesis System Endothelial Tubule formation plates, BD Biosciences) at a density of 48 000 cells/well (12 hours, 37°C). At the end of the incubation period, ECs were observed for any morphologic changes at 10×, 20×, and 40× magnification, and images were taken using Roper Scientific CoolSnap Camera. Morphologic changes were quantified using MetaMorph Imaging Systems where analysis of total tube length, mean tube length, and the total number of branch points was performed.21
ECs (1 × 105) were serum-starved for 12 hours and placed into 8-μm pore size Transwell inserts, which were then placed into 24-well plates and allowed to migrate for 4 hours. Plasma from HJD subjects, DMEM alone, VEGF (1 μg/mL), anti-VEGF antibody (5 μg/mL), or anti-stromal cell–derived factor-1 (SDF-1) antibody (10 μg/mL) was placed into the lower chamber of a modified Boyden chamber as described.22 Cells in the lower chamber and the under surface of the membrane were trypsinized and counted in a blinded fashion by 2 independent observers.
Peripheral blood mononuclear cells (PBMCs) were isolated from subjects with HJD and controls using Ficoll-Paque, washed twice with 1× PBS, and frozen (−80°C, up to 3 days). Synovial cells were seeded (10 000 cells/well) into a 24-well plate and incubated with proliferation media for 24 hours. For the experiment, PBMCs and THP-1 (macrophage cell lines used as a positive control) were concentrated by spinning down and removing the freezing media, washed with 1× PBS, and resuspended in 1 mL of DMEM with or without 1% FBS. To determine whether PBMCs from the HJD subjects and controls had an effect on synovial proliferation, PBMCs or THP-1 (10 000 cells/well) was added to synovial cells and incubated for 48 hours and counted in a blinded fashion by 2 independent observers. For proliferation blocking experiments, synovial cells were treated with bevacuzimab (Avastin); VEGF inhibitor (0.25 mg/mL in DMEM with or without 1% FBS; Genentech) was a generous gift from Dr S. Modak (Memorial Sloan-Kettering Cancer Center, New York, NY) followed by PBMCs and THP-1 cells and incubated for 48 hours. Cells were washed twice with 1× PBS, trypsinized, and counted in a blinded fashion using a hemocytometer. This concentration of bevacuzimab was determined by a dose inhibition experiment using elimination by Trypan blue.
Histologic sections of hemophilic synovium obtained after synovectomy/loose body removal/replacement (experimental), and surgically obtained synovium without a specific pathology (control) were a generous gift from Dr E. DiCarlo (Hospital for Special Surgery, New York, NY). Paraffin sections of synovium were processed using avidin/biotin enzyme complex system (Vector Laboratories) as described.23 The following primary antibodies were used: c-Kit (clone YB5.B8), CD11b (clone CBRM1/5), and VEGF-A (polyclonal) (eBioscience); VEGFR1/flt-1 (clone FB5, Imclone Systems); CD68 (clone PG-M1, Dako North America); matrix metalloprotease-9 (MMP-9; clone 56-2A4) and HIF-1α (clone H1α67; Calbiochem); and SDF-1α (clone 79018; R&D Systems). Sections were incubated with primary antibodies (2 μg/mL, 4°C, 12 hours) followed by appropriate secondary antibody (2 μg/mL, 21°C, 30 minutes), and developed with 0.02% 3-3-diaminobenzamidine tetrahydrochloride (DAB) or immunofluorescence as previously described.24 Serial sections (cryostat; Leica) were mounted with Vectashield containing DAPI (4,6-diamidino-2-phenylindole), and visualized with an ultraviolet fluorescent microscope (Nikon Eclipse E800) with a Retiga camera (Q Imaging) through IP Lab Version 3.65a imaging software (Scanalytics). Imaging medium/solution used was Vectashield containing DAPI and Permount for paraffin-embedded sections. Images were captured by a Nikon Eclipse microscope. The numeric apertures of the objective lens are as follows: 4×/0.13, 10×/0.3, 20×/0.75, 40×/0.75, 40× oil/1.3, 100× oil/1.4. Controls were hemophilic synovium incubated with nonimmune IgG or normal synovium, as detailed in “Subjects and samples.”
Measurement of plasma cytokine expression
VEGF, SDF-1, and MMP-9 concentrations from plasma of experimental and control groups A and B were measured with specific ELISA kits (R&D Systems) per the manufacturer's instructions.
Mononuclear cells were isolated from peripheral blood samples of experimental and control groups A and B via separation with Ficoll. Fluorescein isothiocyanate (FITC)–, phycoerythrin (PE)–, and allophycocyanin (APC)–labeled antibodies, namely, anti-VEGFR1 and VEGFR2 APC-conjugated mouse IgG1 (R&D Systems), PE-conjugated CD133/CD34/CD45 and FITC-conjugated CD11b (Miltenyi Biotec), and CD45APC and CD45 FITC (BD Biosciences PharMingen), were used. Three antibody triplet combinations (anti-hVEGFR1 APC /CD34 PE/CD45 FITC, anti-hVEGFR2 APC/CD133 PE/CD45 FITC, and anti-VEGFR1 APC/CD11b FITC/CD45 PE) and one negative control were used for flow cytometry analysis on each sample processed (each containing 1 × 106 cells). Flow cytometry was performed on a dual argon and diode laser FACSCalibur system (BD Biosciences). All data acquisition and analysis were performed using CELLQuest software Version 7.5.3 (BD Biosciences) and FlowJo software Version 7.2.5 (TreeStar). Live gates were set to exclude cell debris, and 100 000 cellular events were acquired. To prevent spectral overlap, compensation was performed before running samples.
RNA isolation from peripheral blood samples of experimental and control groups A and B was accomplished using the RNAqueous-4PCR Kit (Ambion). cDNA was synthesized in a 20-μL reaction volume via reagents and protocol included with the iScript cDNA Synthesis Kit (Bio-Rad). Quantification of mRNA transcripts using iTaq SYBR Green Supermix with Rox (Bio-Rad), and 30 ng cDNA for VEGFR1, VEGFR2, and β-actin using the standard procedures with 40 cycles of denaturation for 2 minutes at 50°C, annealing for 10 minutes at 95°C, and extension for 15 seconds at 95°C was carried out. Expression of target genes was normalized to β-actin expression.RNA isolation from synovial cell cultures (after exposure to serum from HJD subjects or control sera for 6 hours) was carried out as above, with similar thermacycler conditions. Primers for VEGFR1, VEGFR2, CXCR4, and HIF-1α were designed using Primer Quest and purchased from Integrated DNA Technologies. Forward and reverse primers, respectively, were 5′-TGCGAGCTCCGGCTTTC-3′ and 5′-AAACCGTCAGAATCCTCTTC-3′ (VEGFR1); 5′-CCCAAGCCAAGCCTTAAGTG-3′ and 5′-TCCAGTACTCTCCAAAGCAAGGT-3′ (VEGFR2) and 5′-TGCCACATCATCACCA TATAGAGA-3′and 5′-TCCTTTTCCTGCTCTGTTTGG-3′ (HIF-1-α); 5′ ACT GTT GTC TGA AAC CCA TCC-3′ and 5′-CGT GCT GGG CAG AGG TTT TA-3′ (CXCR4). All polymerase chain reaction (PCR) was performed on an ABI PRISM 7700 analytical thermal cycler, according to the manufacturer's recommendations.
Descriptive statistics were used to define subjects' characteristics. Results were expressed as mean plus or minus SD or SEM of at least 3 experiments performed in duplicate. Categorical variables were compared using the 2-tailed Student t test. A P value less than .05 was considered significant. Analyses were also performed using the program GraphPad Prism Version 3.0 (Strata Corporation). Power calculations were not performed to determine patient/sample population size because this was a single-institution pilot study, and we used all available samples of subjects enrolled on the study.
HJD synovium expresses proangiogenic mediators and myeloid cells
We examined hemophilic synovium for expression of VEGF-A, a principal mediator of angiogenesis. Immunohistochemical examination of 14 specimens using antihuman VEGF antibody showed localization of VEGF-A to vascular endothelial cells, perivascular tissue, and synoviocytes in the lining and sublining regions (Figure 1A). As expected, normal human synovium (n = 11) showed minimal VEGF-A staining (Figure 1D). Because mobilization of EPCs and proangiogenic HPCs from the BM requires activation of MMPs, particularly MMP-9, and because SDF-1α has been shown to potently promote the migration and activation of mononuclear cells, including HPCs,25,26 we stained HJD and control synovium for these mediators. We observed that MMP-9 (Figure 1B) and SDF-1α (Figure 1C), were highly expressed in the vascular endothelium, with moderate expression in synovial cells in the lining and sublining regions of the hemophilic synovium (n = 12). Previously, cells of monocyte/macrophage lineage have been reported to be involved in clearing breakdown products after hemarthroses in hemophilic synovium.2,3 To further characterize whether monocytes/macrophages of myeloid lineage were expressed in the synovium, we stained 12 hemophilic and 10 control synovial specimens for CD68 and CD11b, well-characterized markers of the same. We observed that hemophilic (Figure 1E), but not control (Figure 1G), synovium had increased numbers of CD68+ (Figure 1E,G) and CD11b+ (Figure 1F) cells, suggesting the involvement of myeloid cells in synovial pathology. Furthermore, CD68 staining colocalized with VEGF (Figure 1K) in hemophilic synovium (n = 12), suggesting that macrophages may be involved in synovial angiogenesis. In addition, CD11b+ cells coexpressed VEGFR1 (Figure 1I) (n = 10), and a subset also expressed the early HPC marker c-kit (Figure 1J; n = 11), demonstrating the presence of proangiogenic mediators and myeloid progenitor cells in HJD synovium.
Angiogenic factors are up-regulated in the plasma of HJD subjects
In addition to the observed up-regulation of VEGF-A, SDF-1, and MMP-9 in the synovium, we sought to determine their expression in the peripheral blood of experimental and control group A and B subjects. Experimental subjects had sustained a median of 10 (range, 6 to > 20) bleeds into a joint over a median of 7 years (range, 3-43 years) and 36% (FVIII deficiency 32% 3 times a week, FIX deficiency 4% twice a week) were being treated with prophylactic factor concentrates. The white blood cell counts, along with monocyte counts, were within normal limits at the time of these blood draws. Enzyme-linked immunosorbent assays performed on plasma from this prospective cohort of HJD subjects revealed 4-fold elevated levels of VEGF-A (n = 76), MMP-9 (n = 25), and SDF-1α (n = 46) compared with control group A (VEGF, n = 41; MMP-9, n = 28; SDF-1α, n = 17) and control group B subjects (VEGF-A, n = 26; MMP-9, n = 18; SDF-1α, n = 16) (Figure 2A-C). Notably, subjects with HJD and elevated VEGF-A levels had increased expression of VEGFR1 mRNA (Figure 2D).
In the retrospective HJD cohort (described in “Methods”), we observed that 10 subjects with early joint disease had a 10-fold increase in VEGF-A levels (mean ± SEM, 227.7 ± 33.4 pg/mL) compared with 13 subjects with advanced joint disease, who had levels of VEGF-A at 22.4 ± 1.2 pg/mL (n = 13, P < .001). These data suggested that neoangiogenesis in HJD might occur locally in the synovium with the presence of angiogenic mediators in the peripheral blood.
Circulating levels of HPCs expressing VEGFR1 and CXCR4 are increased in peripheral blood of HJD subjects
VEGF and SDF-1α, both observed in HJD synovium, exert their peripheral effects through their receptors VEGFR1, VEGFR2 (VEGF), and CXCR4 (SDF-1α), respectively.14,15,26 Using quantitative PCR, we observed that VEGFR1 (Figure 3A) and CXCR4 (Figure 3B) mRNA levels were increased in the peripheral blood of HJD subjects. Furthermore, a larger number of VEGFR1+/CD11b+ cells in the peripheral blood of 16 HJD subjects were observed on flow cytometry compared with 19 controls: control group A (n = 12) and control group B (n = 7) (Figure 3C). In addition, HPCs expressing CD34/VEGFR1, markers of early myeloid cells, were increased 4-fold in 48 HJD subjects compared with both control group A (n = 26) and control group B (n = 16; Figure 3D). Moreover, PBMCs from 17 HJD subjects stimulated a 2.5-fold increase in proliferation of normal human synovial cells (Figure 3E) that could be abrogated by bevacizumab (Avastin), a VEGF inhibitor (Figure 3F). These results provided data for association of immature HPCs as a possible source of localized proangiogenic growth factors eliciting synovial proliferation.
Endothelialization occurs in HJD synovium
Endothelialization, as occurs in neoangiogenesis with recruitment of BM-derived HPCs and EPCs, is a vital process during tumor growth and progression.27,28 HJD synovium, known to be highly vascularized, expressed VEGFR2, an EPC marker (Figure 4A). VEGFR2 mRNA levels were increased in the peripheral blood of HJD subjects compared with controls (control groups A and B) as quantified by quantitative PCR (Figure 4B). Furthermore, we observed increased VEGFR2+/AC133+ early EPCs in the peripheral blood of 14 HJD subjects (P < .01), compared with 12 controls (7 control group A and 5 control group B) by flow cytometry (Figure 4C). Taken together, these results provided evidence for endothelialization and proangiogenic cell mobilization in HJD subjects with synovitis.
Hemophilic plasma elicits an angiogenic response from ECs that is VEGF-dependent
After observing that proangiogenic mediators are up-regulated in the plasma of HJD subjects, we speculated whether these mediators might aid in maintaining increased vascularity in the HJD synovium. We hypothesized that the plasma from HJD subjects may contain angiogenic stimuli to promote neoangiogenesis in the synovium. In a functional in vitro assay,29 the plasma from 18 HJD subjects, unlike 12 control group A subjects, elicited a marked angiogenic response from ECs. The morphologic changes of capillary-like tubular structure formation, cord-like processes connecting cellular nodes, increased tube length, and branchpoints of tubular nodes demonstrated the angiogenic capacity of HJD plasma (Figure 5C,E,F). Moreover, the increased total tube length and the number of branch points of tubular nodes could be almost completely abrogated by a VEGF-blocking peptide (P < .001), suggesting that this process was VEGF-dependent (Figure 5D-F).
Migration of ECs is VEGF-A– and SDF-1α–dependent
Previous studies have reported that neoangiogenesis requires migration of ECs.30 As we observed increased expression of the proangiogenic mediators VEGF-A and SDF-1α in the synovium and peripheral blood of HJD subjects, we reasoned that these molecules may be critical for proangiogenic cell recruitment and migration. Chemotaxis of ECs was increased in response to HJD plasma. A VEGF-blocking peptide decreased chemotaxis by 50% (± 2.6%, SEM), whereas an anti-SDF-1α antibody reduced it by 60% (± 3.4%, SEM, P < .01). Interestingly, there was no additive effect of a combined blockade of VEGF and SDF-1α (Figure 5G), suggesting that both VEGF and SDF-1α act through a common pathway to promote endothelial migration.
Sera from HJD subjects induce expression of HIF-1α–in synovial cells
Hypoxia has been shown to induce angiogenic mediators.31 To determine the angiogenic trigger in the HJD synovium, we decided to investigate the role of HIF-1α previously shown to induce SDF-1α during progenitor cell trafficking,31 in the angiogenic process. Human synovial cells were incubated with sera from 16 HJD or 14 (8 group A and 6 group B) control subjects for 6 hours. After the incubation, mRNA was extracted and subjected to quantitative PCR analysis. We observed that there was a significant up-regulation in the mRNA signal for HIF-1α from synovial cells incubated with serum from HJD subjects (Figure 6A). HIF-1α was overexpressed in HJD synovium (n = 8) compared with control synovium (n = 6; Figure 6B-E). These data indicated that HJD sera could potentially stimulate synovial cells to produce HIF-1α and mobilize HPCs and EPCs to the synovium.
HJD secondary to recurrent hemarthroses is composed of synovial neovascularization and bony arthropathy.2-4 Previous work has suggested the role of iron and cytokines in the pathogenesis of HJD.7-9 Observing that the hemophilic synovium is not only hyperproliferative but also highly vascular,2,3 we embarked on a study to examine human blood and synovium from subjects with HJD, hypothesizing that angiogenic mediators may play a role in the pathogenesis of HJD.
In the present study, we observed that angiogenic mediators were expressed in the peripheral blood and synovium of pediatric and adult subjects with hemophilia. Our results suggest that cells of early and late myeloid lineage produced by, or acting in concert with, macrophages/monocytes of hematopoietic progenitor cell origin in HJD subjects could play a pathogenetic role in the development of hemophilic synovitis. Early pathologic features of hemophilia have been well elucidated in both hemophilic dogs32 and in an experimental murine model of hemophilic synovitis.20 Fourteen days after a single massive hemarthroses, vascular synovial hyperplasia with inflammatory cell infiltrate and irregularity of cartilage and pannus formation were observed.20 However, the signals responsible for synovial proliferation and hypertrophy are not well understood, and no large systematic studies have been carried out in patients with hemophilia. Other investigators have reported iron-induced abrogation of synovial apoptosis via MDM2 up-regulation in vitro in the pathophysiology of HJD.11 We postulated that the introduction of blood components, including endothelial cells capable of producing cytokines and angiogenic growth factors, may disrupt the homeostatic balance, thus favoring villous hypertrophy and increased vascularity.
Our data confirm the vascular nature of human hemophilic synovium and observe the up-regulation of proangiogenic mediators VEGF-A, MMP-9, and SDF-1α, as well as the transcription factor HIF-1α in hemophilic synovitis. Moreover, we observed that VEGF-A colocalized with CD68, a well-characterized macrophage marker in humans.33 It is unclear whether these are resident macrophages, type A synoviocytes,34 which were activated in response to hemarthroses, or recruited monocytes/macrophages from the BM, or a combination of all 3. Furthermore, when we incubated normal human synovial cells (which display fibroblast-like morphology, presumably type B synoviocytes) with PBMCs, we observed that PBMCs containing BM-derived HPCs and EPCs from HJD subjects, but not control subjects, stimulated synovial proliferation that could be abrogated by a VEGF inhibitor. Thus, macrophages and HPCs, mobilized from the BM, may be a potential source of VEGF in the synovium. These data further suggest that the hemophilic synovium has undergone alteration of the microenvironment with alteration of the extracellular matrix, release of chemoattractants, leading to neovascularization. The increased expression of both hematopoietic (CD34+/VEGFR1+) and endothelial progenitor (VEGFR2+/AC133+) cells in the peripheral blood of HJD subjects suggests that these BM-derived cells may be recruited to the hemophilic synovium by HIF-1α to stimulate neoangiogenesis. HIF-1α is a transcription factor induced by hypoxia, previously shown to be involved in progenitor cell trafficking.31 Hypoxic conditions are possibly created in the joint after the initial bleed followed by synovial proliferation stimulated by iron or other mediators, consequently contributing to neoangiogenesis. The subsequent local and systemic mobilization of proangiogenic mediators in response to hypoxia could promote and maintain neovascularization in the hemophilic joint.
We found evidence of both localized (synovial) and systemic (peripheral blood) mediators of neoangiogenesis, suggesting a mechanism for the development of a highly vascularized joint and leading to persistent joint damage. Subjects with inherited bleeding disorders other than hemophilia typically bleed into the skin, mucus membranes, and muscles, whereas hemophilic subjects tend to bleed into their knees, ankles, and elbows. The findings of elevated levels of VEGF-A in the peripheral blood of subjects with HJD and increased expression of VEGF-A in the synovium suggested that this elevation of VEGF-A levels in HJD subjects may be specific to the pathogenesis of joint arthropathy. In other arthritides, including osteoarthritis and rheumatoid arthritis, serum VEGF levels have been directly correlated with disease activity.18 Unfortunately, because of limitations of synovium sample procurement, we could not demonstrate mRNA expression of these angiogenic mediators in the synovium, which may have further strengthened evidence for a VEGF-induced cascade leading to synovitis.
Measurement of serum VEGF levels has proven useful in evaluating the disease severity, more rapid disease progression,35 and response to treatment in both rat collagen-induced arthritis and patients with ovarian cancer.36,37 In HJD subjects, elevated VEGF-A levels as well as levels of circulating hematopoietic and endothelial progenitor cells may signify the onset and progression of synovitis. In support of this hypothesis, we observed a 10-fold increase in plasma VEGF-A levels in a retrospective cohort of hemophilic subjects with active synovitis diagnosed by MRI, compared with subjects with advanced joint arthropathy. Interestingly, in this retrospective cohort, subjects with joint arthropathy demonstrated VEGF-A levels similar to control subjects (data not shown). This finding suggests that VEGF-A levels could rise during the phase of active synovitis playing a role in synovitis initiation and progression, and fall after progression to chronic synovitis, characterized by a predominance of fibrous tissue and decreased vascularity. Therefore, VEGF-A levels along with the presence of circulating HPCs and EPCs may serve as surrogate biologic markers for active synovitis. As our results have demonstrated the blockade of VEGF-induced synovial cell proliferation, VEGF inhibition may also be an effective treatment strategy in preventing synovial proliferation.
Apart from VEGF-A, levels of MMP-9 and SDF-1α were also up-regulated 4-fold in HJD subjects (prospective cohort). SDF-1 binding to CXCR4 triggers chemotaxis, and the up-regulation of the cell surface integrins and MMPs (eg, MMP-9) is necessary for cell migration and trafficking.38 Moreover, increased MMP-9 activity has also been reported to mediate SDF-1α–stimulated transendothelial migration of hematopoietic cell types.39 We hypothesized that SDF-1α and VEGF-A may play similar roles in progenitor cell recruitment into the hemophilic synovium. HJD sera could induce endothelial cell migration and tube formation, which was almost completely abrogated by a VEGF-blocking peptide (Figure 5). Likewise, transwell migration of endothelial cells was stimulated by HJD sera and inhibited 50% to 60% by antibodies to VEGF-A and SDF-1α (Figure 5). These data provided further functional evidence for the role of proangiogenic factors in the pathogenesis of HJD. In addition, it suggested that blockade of local chemokine signaling may abrogate the cellular infiltration causing hypervascularity characteristic of hemophilic synovitis.
The exact mechanisms by which bleeding into the joint leads to changes within the synovium have not been well elucidated. Here we have shown that hypoxia induced by recurrent hemarthroses in hemophilia through synovial proliferation potentially induces synovial angiogenesis and infiltration of BMD cells of monocyte/macrophage origin in hemophilic synovitis. Elevated levels of angiogenic mediators in hemophilic subjects could signify the presence of active synovitis, and our observations suggest that neoangiogenesis mediated by BMD-cell recruitment and infiltration could play a pathogenetic role in hemophilic synovitis. Future prospective studies that use an angiogenic profile (including VEGF-A, SDF-1, MMP-9, and progenitor cells) may help better delineate the temporal and etiologic role of angiogenesis in hemophilic synovitis.
An Inside Blood analysis of this article appears at the front of this issue.
The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked “advertisement” in accordance with 18 USC section 1734.
The authors thank Scott Kerns for help with imaging and graphics, Dr Edward DiCarlo for synovium samples, Simon Meas for technical support with the flow cytometry, and all our study subjects for enrolling in the study.
This work was supported by Hemophilia of Georgia Foundation (S.S.A.), Doris Duke Charitable Foundation, Hope Street Kids, ASCO, Butler Foundation, Michael Cuccione Foundation (R.N.K.); National Foundation for Cancer Research, Hartwell Foundation, Malcolm Hewitt Wiener Foundation, Nancy C. and Daniel P. Paduano Foundation, American Hellenic Educational Progressive Foundation, Charles and Meryl Witmer Family Foundation, Stavros S. Niarchos Foundation, and Champalimaud Foundation (D.L.); and Susan G. Komen for the Cure (R.N.K., D.L.), Children's Cancer and Blood Foundation Laboratories, and the A. P. Alexander Family donation for hemophilia research.
Contribution: S.S.A. and R.N.K. designed the research and wrote and edited the manuscript; D.M. performed the flow studies, immunofluorescence, and immunohistochemistry; O.T.F. performed the quantitative PCR, migration, and proliferation studies; D.L. helped plan and edit the paper; and D.D. helped in clinical data correlation and prepared the manuscript.
Conflict-of-interest disclosure: The authors declare no competing financial interests.
Correspondence: Suchitra S. Acharya, Cohen Children's Medical Center of New York, Pediatric Hematology/Oncology/BMT, 269-01 76th Ave, Suite 255, New Hyde Park, NY 11040; e-mail: email@example.com.
S.S.A. and R.N.K. contributed equally to this study.


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|Rickenbacker International Corporation - Forum|
|Page 1 of 1|
|Author:||Guggs [ Mon Feb 27, 2006 5:55 pm ]|
|Post subject:||Rickenbacker Europe?|
I'm living in switzerland and I'm looking for a Rickenbacker.. I didnt find any Store with Rickenbacker Knobs/Pickups etc.. only finished Guitars/Bass
My dreammodel is the 660 Rick, but its too expansive for me... Thats why I'm looking for a 620 Model (jetglo).. I would like to buy the "TV-knobs"? looking like a cateye + 2 toaster pickups (if needed)
I dont really know the difference between the Hi-Gain and Toaster pickups... I play mostly Beatles-style music..
Want a very clean (glassy) sound.. Can u tell me the difference (sound) of those pickups? And may be a store with knobs/pickups anywhere in Europe?
|Author:||doctorno [ Mon Feb 27, 2006 8:04 pm ]|
|Post subject:||Re: Rickenbacker Europe?|
Guggs, you will hardly find a store that carries Rickenbacker spare parts in Europe (except for the UK maybe). But US dealers are allowed to send Rickenbacker spare parts and strings to international customers, now. So I recommend to send an e-mail to a few American dealers and ask, whether they can ship these things to you. You find the US dealers on this website.
If you e-mail me at email@example.com I might be able to give you some further advice where to get the oven-knobs, a 620 a.s.o.
Viele Grüße in die Schweiz!
|Page 1 of 1||All times are UTC - 8 hours|
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domain: hobby


Burgess Hill Town Development -
There have been some theories as to what is going to happen to Cyprus Road car park within the big town centre redevelopment.
What's Going To
Happen To Cyprus Road Car Park?
Let's take a look at what was proposed/rumoured and
at what plan is now the most likely to come to fruition
The early theory and fear was that a Sainsbury Supermarket was going to swallow up the entire plot of land including the demolition of the Orion Cinema, Cyprus Hall and some other buildings along Cyprus Road.
Shops transferred from the Martlets
In November 2011, NewRiver Retail - Owners of the Martlets, released a presentation document for their investors (Click to download). Part of their plan was to put a supermaket where Lidl is currently located, the size of the supermarket would cover the footprint of the multistorey car park and many of the existing shops. In addition they planned to install other larger retail units. To make room for this redevelopment the smaller shops in the Martlets were going to be relocated to Cyprus Road Car Park.
A Block of Flats
After kicking the Town Council up their backside, they finally published the minutes of April's Annual Town Meeting. Included was information from NewRiver Retail where they reveal that they no longer have plans to develop Cyprus Road Car Park. This ties in with the Mid Sussex District Plan which has land at the rear of Cyprus Road earmarked for a large block of flats. MSDC have always said that they'd be happy to include land they own in any development as long as it gives them a good financial return. A block of flats = ££££ and enables them to keep the current car park open - which as we all know is a great source of revenue.
What of the Cinema?
On Facebook a few local residents have reported that Cllr Andrew Barrett-Miles revealed to them that the Orion Cinema has a new five year lease. This would make sense if a block of flats at the rear of Cyprus Road car park is the chosen development option.
However, a very reliable source has told Burgess Hill Uncovered that a Mid Sussex District Council Cabinet member has said that talks are taking place to bring a multiplex Cinema next to the Triangle leisure centre. In February 2011 we reported that the 'Mid Sussex Better Lives Advisory Group' had met to discuss development options - some of which were plain daft. Cllr Andrew Barrett-Miles himself told Burgess Hill Uncovered that a survey of the Dunstall Ward residents had a cinema as one of the favoured options for the land.
It's good to share. Especially to your Burgess Hill friends!
What do you think to the proposed developments?
If our information is correct, do you think a block of flats in the town centre is a good idea? If big shops come to the Martlets where will all the small shops go? Will they just disappear?
Are you pleased that the Orion could be around for another 5 years?
Is land by the Triangle leisure centre the best place for a multiplex cinema when the intention of the grand developments is to bring more people into the town centre?


text:
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domain: design


text:
Record Company Signs 'American Idol''s Pia Toscano
By Paige Feigenbaum
Pia Toscano's early "American Idol" elimination may have been a blessing in disguise. The overnight singing sensation has been offered a recording contract, according to Us Weekly.
Interscope Records scooped up the burgeoning star. A source told the mag that the label "starting [Thursday] night right after the show, Interscope told her they wanted her and first thing [Friday] morning Interscope…started calling every top songwriter and producer in town to get an album together and rush release it." "Idol" mentor Jimmy Iovine is chairman of Interscope.
Has Pia signed on the dotted line yet? The source said, "Papers are being finalized. It's basically a done deal. She's signing. They rushed everything, but she's so excited."
Pia's elimination caught America off guard, but executive producer Nigel Lythgoe was not taken by surprise. He told Yahoo, "I know the [voting] results, so I know she was never a frontrunner."
To avoid such upsets in future "Idol" seasons, Nigel said they'll consider tweaking the show's format. Using the model of his other reality competition "So You Think You Can Dance," "America votes for the bottom three and then the judges decide who goes home…I think that will be thought about."
The "American Idol" contestants still campaigning for the title will sing another tune Wednesday night on Fox.

domain: news


Dancing With the Stars is paying tribute to one of their own.
MORE: 'Brady Bunch' Star Florence Henderson Dead at 82
Host Tom Bergeron took to social media ahead of Monday’s season 24 premiere to share a photo of a star dedicated to the late Florence Henderson, who died in November 2016.
“A lovely addition to our ballroom in memory of a lovely lady. @dancingabc #dwts,” Bergeron captioned the image on the dance floor.
The Brady Bunch actress, who competed on season 11, died from heart failure and was at a DWTS show taping supporting former co-star Maureen McCormick, just three days before her death at age 82.
McCormick opened up to ET at the time about her close relationship with her TV mom.
MORE: 'Brady Bunch' Star Maureen McCormick Makes Emotional 'DWTS' Debut, Florence Henderson Cheers Her On
"She was an incredible example of how to life your life," McCormick told ET's Nancy O'Dell. "She was that sweet. She really was. She was the loveliest of ladies."
"Florence played our mother on the show, but I always felt like she was more of a sister,” she added.
“She was so young at heart, and just a really good friend," she added.
For more on Monday’s DWTS premiere, including the show’s biggest ballroom bombshells, watch below:


text:
By Jim Groh
Broomfield Veterans Memorial Museum
More than 3,000 miles separate Colorado from Hawaii, yet the reverberations of the explosions that rocked that tropical paradise 80 years ago were felt here in the Centennial State in terms of 32 young lives lost on that fateful “day of infamy.”
In commemoration of them, the Broomfield Veterans Memorial Museum will open a new exhibit today and host a Coffee-and-Conversation presentation about the event on Saturday, Dec. 11.
The exhibit explores the causes and consequences of Japan’s Dec. 7, 1941, attack on U.S. Army and Navy facilities in Hawaii, as well as the simultaneous attacks against U.S. military interests on Wake Island and in the Philippines. A 20-foot-long timeline highlights the significant events leading up to the attack. The centerpiece of the exhibit is a large model of the USS Arizona, created by local model shipbuilder Jerry Gavaldon.
The Arizona blew up when a Japanese bomb penetrated her forward ammunition magazine and detonated, killing 1,177 of her crew, including 22 men from Colorado. Posters honor two sets of brothers who died — Francis and Norman Morse of Denver and Homer and Edmon Jones of Montrose.
Other posters pay homage to the other 20 Coloradans who lost their lives aboard the USS Oklahoma, Nevada, Utah, and West Virginia. And some tell the stories of Don Stratton and James Downing, who survived, along with Albert “Pete” Peterson, who swam from the burning West Virginia to Ford Island. Peterson’s uniform is on display, as well as a model of a Japanese “Zero” fighter plane. Daniel T. Griffin of Colorado Springs is considered the first Coloradan — and possibly even the first American — killed on Dec. 7 when his PBY Catalina “Flying Boat” was shot down by the Japanese air armada.
In his Dec. 8, 1941, request to Congress for a declaration of war on the Empire of Japan, President Franklin D. Roosevelt called the raid an “unprovoked and dastardly attack.” Yet the seeds of war had been planted many years earlier. The raid was the result of the Japanese militarists who in the 1930s and 1940s set their nation on a course of conquest in Asia in order to obtain the oil, rubber and minerals that their resource-starved nation required. They believed that by knocking out the powerful U.S. Pacific Fleet that lay at anchor in Pearl Harbor they could continue their conquests without American interference.
The massive Japanese flotilla that consisted of six aircraft carriers, 420 warplanes and numerous support craft reached a point some 250 miles from Hawaii without being detected. When the two-wave attack (a third wave was called off) was finished pummeling the U.S. Pacific Fleet and flew back to their carriers, the jubilant Japanese were convinced that they had crippled American power in the Pacific and would have free rein for months to come.
Despite the tragedy, fortune smiled on the Americans; none of the eight U.S. aircraft carriers that the Japanese had hoped to sink in Pearl Harbor were in Hawaiian waters. They were either at sea on training maneuvers or in U.S. ports undergoing repairs. Nevertheless, the raid was costly. The attack killed 2,403 Americans, including 68 civilians, and destroyed or damaged 21 U.S. Navy ships, including eight battleships. Aircraft losses were 188 planes destroyed and 159 damaged. The raid also caused Nazi Germany to declare war on the United States.
The Japanese lost 55 airmen and nine submariners. The fleet returned to Japan without being spotted.
The crippled American fleet didn’t remain crippled for long. Working around the clock, shipyards managed to repair most of the damaged ships and enabled them to take the war to the enemy where they would, as the patriotic posters urged, “Avenge Pearl Harbor.” Within four months, a carrier-mounted raid by 16 B-25 Mitchell bombers struck back at Tokyo and other Japanese cities, beginning the process of avenging Pearl Harbor.
The Coffee-and-Conversation presentation about the Pearl Harbor attack will be on Saturday, Dec. 11 at 10 a.m. in the museum’s presentation room. The exhibit is expected to be up through February 2022.
The Broomfield Veterans Memorial Museum is free and open to the public on Thursdays from 10 a.m. to 2 p.m. and Saturdays from 9 a.m. to 3 p.m.. The museum is located at 12 Garden Center, on the north side of Midway, about a quarter-mile east of Wadsworth (287). For more information, go to broomfieldveterans.org or call 303-460-6801.

domain: history


A blood pressure machine has many names such as blood pressure meter or the blood pressure gauge and sometimes also known as blood pressure monitor. The medical name for this device is however sphygmomanometer. This device is usually made up of cuff that is inflatable, which can collapse and release the artery which is under it in a very controlled aspect. Another device which is known as mercury manometer is used with the blood pressure machine in order to measure the pressure. This device is always used to determine the pressure at which blood flows. There are majorly two types of these blood pressure machines. One is the manual machine and the second is the digital machine. The manual blood pressure machine makes use of stethoscope.
However, manual and digital machines both are used by doctors and consumers at home. These machines vary in accuracies and the conveniences varies. The manual blood pressure machine is used in such cases where the practitioner is very much trained because this require accuracy. The manual blood pressure machines which uses mercury are standard and people have been using it for over quite time. But one must learn how to read the measurements from the manual blood pressure machine and the manual blood pressure machines are only used for measuring the systolic pressure.
In digital blood pressure machine, the mechanism is different form other. It makes use of oscillometer measurements and the calculations of these are electronic. These kinds of machine could use both either the manual or automatic inflation and unlike manual blood pressure machine it can be used to measure both the systolic and diastolic pressure. The major reason why these blood pressure machines are more famous than the manual blood pressure machines is their convenience to use. No special kind of training is required in reading the measurement from the digital blood pressure machine. Even someone with no knowledge could use these to check the blood pressure. Another major reason of the popularity of these blood pressure machines is that these could even work in an environment where there is a chance of noise that is there is an chance of some error. not only this digital machine just measure the blood pressure but it also make use of microprocessors which help in measuring the heart rate and pulse rate as well. The accuracy of the digital blood pressure machine is much more than the manual blood pressure machine.


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Lord Mayor appointed as the Women’s first Philanthropy Ambassador
The Royal Women’s Hospital is delighted to welcome the Lord Mayor of Melbourne, Sally Capp as the hospital’s inaugural Philanthropy Ambassador.
Well-known for her passion for all-things Melbourne and her commitment to supporting people in need, Ms Capp says she is honoured to be continuing her long-standing association with the 166-year-old hospital in this new capacity.
“The Women’s has a long and proud history as Australia’s first and most respected specialist hospital for women and newborns – it holds a special place in the hearts of Melburnians,” Ms Capp said.
“The hospital has been providing world-class care and support to the women and babies of Melbourne for well over a century. Today, it is still providing compassionate care, undertaking life-saving research and supporting women and families who need it most,” she said.
“Philanthropic support for a specialist hospital like the Women’s is critical to ensuring it can continue to meet the diverse and growing needs of our community.
"Donors can have a huge impact on the wellbeing of Victorian women and newborns by investing in high impact research, supporting programs that provide wrap-around care for patients and funding vital equipment and infrastructure.”
Seeing first-hand the impact of philanthropy
Ms Capp visited some of the hospital’s key service areas that have received support from generous philanthropists.
- The Pauline Gandel Women's Imaging Centre which provides radiology and ultrasound services to diagnose and treat maternity and gynaecological issues in women and assist in the diagnosis of fetal and newborn disorders. The centre was established in 2008 thanks to the leadership and generous support of Gandel Foundation. The Women’s has a long-standing relationship with Gandel Foundation which more recently led to the establishment of the Gandel Simulation Service in partnership with The University of Melbourne Medical School
- The Women’s Newborn Intensive Care Unit (NICU), which cares for up to 2,000 babies from across Victoria each year. The Barr Family Foundation has generously funded the introduction of a Family Integrated Care model, which will enable parents and families to take a more active role in caring for their premature babies while they are in the NICU.
- The Women’s Fertility Preservation service which specialises in providing care for patients who have cancer or another health issue that puts their fertility at risk. To ensure regional and rural patients across Australia can benefit from this service, the Sony Foundation Australia generously provides funding to the National Ovarian and Testicular Tissue Transport and Cryopreservation Service.
During her visit, Ms Capp met some of the hospital’s staff and was struck by the impact that philanthropic support can have.
“It was great to hear first-hand from the Women’s dedicated staff about the positive difference that philanthropic donations are making, and will continue to make, in patients’ lives and health outcomes,” Ms Capp said.
The Women's CEO and Board Chair thrilled
The Women’s CEO Professor Sue Matthews and Board Chair Cath Bowtell were thrilled to welcome Ms Capp to the Women’s in her new role.
“We’re so pleased Sally is now officially our Philanthropy Ambassador. We have so many ambitions and ideas to improve healthcare and health outcomes for women in our community. We’ve been leaders in our field for decades but we can’t always realise our dreams without the support of visionary philanthropists,” said Professor Matthews.
“It’s great that Sally will be helping us to partner with the many generous donors and supporters within our own community. It means we can collaborate with them to create something really special.”


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I know Ender's Game
is a classic and highly acclaimed YA science fiction novel, but I just can't bring myself to read it. Maybe I would have felt differently if I had discovered this novel back when I was a young adult; I could have read it on purely its own merits and, as I understand, its merits are very strong. But I didn't. And as an adult, any feeling I have for this novel is shadowed by my distaste and dislike for Card.
While Card is welcome to have his personal views, those views strongly influence my view of him. I find myself so discomforted by his statements, I find an authority figure spouting those views so wrong
, I have difficulty articulating my opinion. But it yields to the same result: Card's personal views have so colored my feelings of him that I cannot divorce myself of my feelings sufficiently to permit me to read his works with even the smallest sense of enjoyment.


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PROVO, Utah – After a weekend in Texas, the No. 39 BYU men’s tennis team returns home to host conference opponent No. 47 San Diego on Saturday at 1:30 p.m. in the BYU Indoor Tennis Courts.
The Cougars (11-4, 1-0 West Coast Conference) face just their second league opponent of the season when the Toreros (6-3, 0-0 WCC) come to Provo.
Patrick Kawka and Francis Sargeant, the No. 50 nationally ranked doubles team, is 10-4 in 2013, including a 5-2 mark in the month of February.
Sophomore Keaton Cullimore has won three consecutive singles matches and has won six of his last seven.
BYU’s No. 3 duo of Cullimore and John Pearce also has a 10-4 record on the season.
San Diego’s Clarke Spinosa, who plays at the No. 3 singles position, is ranked No. 82 nationally and Uros Petronijevic is ranked No. 112. The Toreros are coming off a recent 6-1 loss to No. 2 USC.
Saturday’s match is the Y Game for the year. Admission is free.
Aaron Sorenson is the tennis sports information director at BYU.
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Panel should represent city
Published: Thursday, December 9, 2010 at 10:17 a.m.
Last Modified: Thursday, December 9, 2010 at 10:17 a.m.
I read your article “Panel’s makeup sparks debate in Thibodaux.” Although I am not a resident of Thibodaux, it is my hometown, and it disheartens me when I read articles like this one. I respect Mayor-elect Tommy Eschete’s comment, “I wasn’t looking at color. I was trying to get people from the community who know the workings of law enforcement and city government.” However, the point that many members of the “minority community” were making is that if there are six members of a selection panel, those members should be representative of the community the chief will serve. If blacks make up 34 percent of Thibodaux’s population, theoretically two members should be black. Someone on the selection panel should also be female. And, like Charles Mosley suggested, “There are no citizens on it. Everyone on it is from the aristocracy.” So, let us rise above seeing this as purely a race issue. Residents should be active participants in the political process, and they should certainly expect that their interests are taken into consideration when key leadership appointments are made. I appreciate that Mr. Eschete wants to be transparent in this process; but, he, too, should strive for a representative sample in terms of this selection committee.
Per the article, I was most disturbed by Mr. Eschete’s assertion that “the minority community has their representative on the council who will have the opportunity to vote on the selection,” referring to Councilwoman-elect Constance Thompson-Johnson. Perhaps this comment was taken out of context, but from the way it was written, it is terribly unfortunate that anyone, especially the mayor-elect, would suggest that all African-Americans in Thibodaux are represented by one council member — even if a large number (though certainly not all) of Thibodaux’s African-Americans reside in a small geographic area. Council members cannot ignore the interests of the whole community because their decisions, in aggregate, affect everyone. And my guess is that Mr. Eschete would not have been elected had it not been for at least a portion of the registered black voters in Thibodaux.
Finally, when we think of the often-tumultuous relationship between law enforcement and African-Americans, I would hope that Eschete seeks to ensure that his next police chief will work with the community to drive down crime and build citizen involvement. A selection panel that represents diverse viewpoints and life experiences would be a first step in the right direction.
Reader comments posted to this article may be published in our print edition. All rights reserved. This copyrighted material may not be re-published without permission. Links are encouraged.

domain: sociology


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TrialSite has covered the rise of research and development in the El Paso region thanks in part to the Medical Center of the Americas Foundation (MCS), a TrialSite partner actively facilitating and supporting the conditions for research expansion in this community of nearly 1 million people. Most recently, the University of Texas at El Paso (UTEP) received a portion of a major $142 million research grant from the Cancer Prevention and Research Institute of Texas (CPRIT). Specifically, Dr. Xuijun “James” Li and his research team were given the High Impact/High-Risk Research Award in the amount of $249,999 for their study in ovarian cancer biomarkers. According to the Cancer Prevention and Research Institute of Texas, Marc Cox was also awarded $5,881,734 for his UTEP partnership with UTMDACC for the study of Hispanic cancer disparities.
First, there is Dr. Li’s research targeting ovarian cancer. This cancer represents the second most common gynecological cancer in the United States, reports Professor Li. The American Cancer Society says that in 2021 alone, 21,410 will receive a new diagnosis of ovarian cancer, and 13,770 will die from ovarian cancer, giving...
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Today marks the retirement of Lomar Machine Repair’s Frank Cirino.
Cirino established Lomar Machine Repair in 1993 as a service provider, growing to import and sell international machine tool brands. Since then, Cirino and his family grew Lomar into a team of qualified service technicians and a multi-line machine distributor providing support to hundreds of customers.
“It is with mixed feelings that Ferro Technique and Lomar Machine Repair announces the retirement of Frank Cirino. For almost 30 years Frank and Lomar have provided the industry with top notch service and sales to the Windsor area and beyond,” commented Matt Fleming, president of Ferro Technique. “The entire Ferro Technique and Lomar team wish Frank the very best and look forward to seeing what the future has in store for he and his family.”
In 2020 Cirino began succession planning for his eventual retirement to ensure both Lomar’s customers and employees would continue the legacy he has built.
“Ferro Technique and Lomar Machine Repair will continue to maintain the customer first mission that Frank started,” added Fleming.
Cirino will also continue to consult Ferro and Lomar.


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Indianapolis doctors perform intensive surgery on boy for free
Two Peyton Manning Children's Hospital surgeons recently gave one little boy a new skull and a new life - free of charge.
The Pettelliers were busy conducting theological mission work in Zimbabwe when they noticed something was wrong with their youngest son, Liam. They discovered the 2-year-old suffered from craniosyntosis, a rare skull deformation that requires intense reconstructive surgery."He was actually behind in all areas of development including language and again we thought, 'How are we gonna get help for Liam in the middle of Africa?'" said Liam's mother Kayle.
After South African doctors couldn't perform the operation, the family turned to St. Vincent pediatric surgeons for help.
On January 22, Liam underwent a four-hour surgery under the care of pediatric surgeons Drs. Jason Blocksom and Ronald Young. The pair completed the procedure successfully and, along with the hospital, wrote off all medical bills to provide the surgery at no cost.
Little Liam got a new skull. His missionary parents, who already spent so much of their time giving back to others, finally got a little back themselves.
"For someone giving that type of service, I felt it was the least I could do to offer my time to serve them," said Dr. Young.
The doctors now say Liam is healthy and recovering well. The family returns to their missionary work in Africa later this week.


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U.S. Rep. John Grotberg (R., Ill.), who has been seriously ill since January, will be transferred in about two weeks from the National Institutes of Health in Bethesda, Md., to the Rehabilitation Institute of Chicago.
But aides to Grotberg, who was nominated in the March primary election for a second term in Congress, still haven`t asked him if he wants to run for re-election.
``That specific question hasn`t been asked,`` said Steve Trossman, the congressman`s press secretary. ``It hasn`t been discussed.``
Grotberg, 61, suffered a heart attack in January after undergoing experimental cancer therapy and was in a coma for nearly six weeks.
Trossman said Grotberg will undergo physical and occupational therapy in the Rehabilitation Institute to strengthen his muscles.
``No date has been set for the move,`` he said. ``It will be sometime within the next two weeks.``
Grotberg was the only candidate listed on the GOP ballot in the March 18 primary, although a De Kalb man mounted a write-in campaign.
If the congressman stays in the race, he will face Kane County Coroner Mary Lou Kearns, of St. Charles, the winner of the Democratic nomination.
Trossman said Grotberg has been watching television news programs.
Grotberg fell into a coma after undergoing a third round of experimental cancer treatment in the National Institutes of Health, a government research facility. The congressman has suffered from cancer for more than a decade.
Doctors reported the therapy was partially successful. But an artery through which Grotberg was receiving the cell and protein injections became infected, setting off a chain of medical events leading to the coma.
Trossman said no testing has been undertaken to determine if the congressman experienced any brain damage from the prolonged coma or if the cancer has spread.
``That will have to wait until he can speak,`` Trossman said.


Wave Farm and the Bard College Conservatory of Music join the John Cage Trust in presenting Reality Radio
Wave Farm and the Bard College Conservatory of Music join the John Cage Trust in presenting Reality Radio, a four-month durational project spanning February to May 2015 featuring a continuous audio surveillance feed from the Bard College Percussion Studio headed by Sō Percussion. Reality Radio positions those who move throughout the studio – students, professors, administrators, visitors, even maintenance crews – in the role of performer, with listening audiences as ever present observers. In conjunction with Reality Radio, Wave Farm’s WGXC 90.7-FM will feature a series of special live broadcasts: February 7, March 7, April 25, and May 23, 2015.
Vocal Arts Program graduate Faylotte Crayton receives fellowship for Marlboro Music Festival
Soprano Faylotte Crayton '12 has received a fellowship to attend the Marlboro Music Festival during the summer of 2015. While in the graduate Vocal Arts Program at Bard Ms. Crayton was in the voice studio of Edith Bers.


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In another example of the limitations of direct sales a company in the UK has been ordered to pay redress for misselling complex products. This statement is telling:
In a statement, First Direct told the newspaper: “We have carried out a review of the investments that some of our customers hold or have held on our self-select investment platforms and have found that some of them should not have been available.
“This is because they are defined as ‘complex’ and not appropriate for a self-select investment service without assessing a customer’s knowledge and experience for appropriateness. We are currently in touch with the customers affected and are working with them to ensure they will be compensated for any loss as appropriate.”

domain: economics