tbuckley/cabot-search huggingface dataset:
Abstract A35: Immunological characterization of Imprime PGG® and an anti-EGFR antibody combination treatment for cancer
Authors: Mary A. Antonysamy, Christine Dudney, Yumi Yokoyama
Journal: Clinical Cancer Research (2010)

Abstract More promising antitumor strategies utilize combination therapies, with each strategy targeting a separate aspect of oncogenesis. Imprime PGG® (Imprime PGG) is a soluble beta-1,3/1,6 glucose polymer being developed as an adjunct to monoclonal antibody (MAb) therapy for cancer. Imprime PGG, a pathogen- associated molecular pattern isolated from the cell wall of S. cerevisiae, has shown therapeutic antitumor and survival-enhancing effects when combined with an antitumor MAb in several in vivo syngeneic and xenogeneic tumor models. Here, we evaluated and characterized the antitumor activity and functional synergy of Imprime PGG in combination with an anti-EGFR MAb, cetuximab, in two different cancers, using an EGFR+ human pancreatic tumor line, MiaPaCa-2, and an EGFR+ human ovarian tumor line, SKOV-3. The objectives of this study were: (1) Evaluate the ability of cetuximab to activate complement as measured by iC3b opsonization on tumor cells (measured by flow cytometry using a FITC anti-human iC3b MAb); (2) Characterize tumor cells for expression of the complement regulatory proteins (CRP) CD46, CD55 and CD59 (measured by flow cytometry using fluorescently-labeled CRP-specific antibodies); (3) Evaluate tumor cytolysis following treatment with cetuximab +/- Imprime PGG in the absence and presence of human peripheral blood mononuclear cells (PBMC) (using the MTT colorimetric assay); and (4) Assess the ability of cetuximab +/- Imprime PGG to induce cytokines when tumor cells were cultured with human PBMC. Key findings include: (1) in vitro cetuximab does not induce iC3b deposition on SKOV-3 and MiaPaCa-2 tumor cells over that seen with fresh serum alone. (2) Both tumor cell lines expressed all CRPs but each to a variable extent. (3) Cetuximab did not induce CDC but did induce ADCC in the presence of PBMC, and Imprime PGG further enhanced cetuximab-induced cytolysis under these conditions. (4) The combination of cetuximab and Imprime PGG inhibited the secretion of VEGF in tumor cell/PBMC co-cultures compared to levels observed with either agent alone. These studies demonstrate antitumor synergy of Imprime PGG when combined with cetuximab that may be mediated by modulation of the tumor microenvironment. Overall, the data indicate synergy between Imprime PGG and cetuximab in vitro in inducing antitumor activity in both pancreatic and ovarian tumor cells and provide rationale for such combination strategy for therapy in cancer. Citation Information: Clin Cancer Res 2010;16(14 Suppl):A35.
369 PHENOTYPIC AND EXPRESSION QUANTITATIVE TRAIT LOCI (P/EQTLS) AFFECTING LIVER FIBROSIS BY GENOME-WIDE ASSOCIATION ANALYSIS IN RECOMBINANT INBRED MOUSE LINES
Authors: R. Hall, R. Müllenbach, S. Huss, R. Alberts, K. Schughart, K. Hochrath, S.N. Weber, R.W. Williams, F. Lammert
Journal: Journal of Hepatology (2012)
The murdered child and his killers
Authors: D Kaplun, R Reich
Journal: American Journal of Psychiatry (1976)

The authors studied 112 cases of child homicide in New York City in 1968-1969 to identify contributing social and psychiatric factors and to determine the fate of the surviving siblings and the degree of involvement of the city's social agencies with the families. There was a pattern of long-term familial child maltreatment extending to the siblings and continuing after the murders. The victims were usually illegitimate preschoolers; the assailants, usually the mothers or their paramours, had backgrounds of assaultiveness and social deviance and killed in impulsive rage. Reports of sexual abuse of victims or of suicide or psychosis among assailants were rare. The authors present case illustrations and offer guidelines for improved prevention by psychiatrists and social workers.
661 ULTRASONOGRAPHIC (US) SCREENING OF HEPATOCELLULAR CARCINOMA (HCC) IN COMPENSATED CIRRHOSIS DUE TO HEPATITIS C VIRUS (HCV) IMPROVES SURVIVAL: A MODELING APPROACH
Authors: A. Mourad, S. Deuffic-Burban, T. Renault-Vantroys, N. Ganne-Carrié, I. Rosa, A.M. Bouvier, G. Launoy, S. Cattan, A. Louvet, S. Dharancy, J.C. Trinchet, Y. Yazdanpanah, P. Mathurin
Journal: Journal of Hepatology (2013)
A Preliminary Study of Long-Term Treatment with Interferon Gamma-1b and Low-Dose Prednisolone in Patients with Idiopathic Pulmonary Fibrosis
Authors: Rolf Ziesche, Elisabeth Hofbauer, Karin Wittmann, Ventzislav Petkov, Lutz-Henning Block
Journal: New England Journal of Medicine (1999)

Patients with idiopathic pulmonary fibrosis have progressive scarring of the lung and usually die within four to five years after symptoms develop. Treatment with oral glucocorticoids is often ineffective. We conducted an open, randomized trial of treatment with a combination of interferon gamma-1b, which has antifibrotic properties, and an oral glucocorticoid.
FRI0266 The mechanism of umbilical cord mesenchymal stem cells in the upregulation of regulatory t cells by tgf-b1 in systemic lupus erythematosus
Authors: L. Sun, L. Lu, D. Wang, X. Li
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> The aim of this study is to investigate the mechanism of umbilical cord mesenchymal stem cells (UC-MSC) in the upregulation of peripheral regulatory T cells in patients with systemic lupus erythematosus (SLE). <h3>Methods</h3> Peripheral blood mononuclear cells (PBMC) from 20 SLE patients and normal controls were co-cultured with UC-MSC at different ratios respectively for 72 hours, and the proportions of CD4<sup>+</sup>CD25<sup>+</sup>Foxp3<sup>+</sup>regulatory T cells were analyzed by flow cytometry. PBMC and serum from active SLE patients and normal controls were used to stimulate UC-MSC, TGF-β1 mRNA expressions on UC-MSC were detected by real-time fluorescence quantitative polymerase chain reaction (real-time PCR). Supernatant TGF-β1 levels were determined by enzyme-linked immunesorbent assay (ELISA). The TGF-β1 small interfering RNA (siRNA) was used to interfere TGF-β1 expression on UC-MSC, then to determine its effect on the regulation of SLE Treg cells. TGF-β1 inhibitor was added in the culture system of UC-MSC and PBMC from active SLE patients, to observe its role on the upregulation of Treg cells by UC-MSC. <h3>Results</h3> UC-MSC could dose-dependently upregulate peripheral CD4<sup>+</sup>CD25<sup>+</sup>Foxp3<sup>+</sup>Treg proportion in SLE patients, which was not depended on cell-cell contact. UC-MSC had no regulatory effect on Treg cells in normal controls. Compared with the non-stimulated group and normal PBMC stimulated group, PBMC from SLE patients significantly promoted TGF-β1 mRNA expression on UC-MSC (relative gene expression was 1.00 ± 0.09,1.95 ± 0.62,4.20 ± 2.34, respectively, both <i>P</i>&lt;0.05). Supernatant TGF-β1 levels were significantly elevated in the presence of SLE PBMC. Serum of SLE patients (5%) enhanced TGF-β1mRNAexpression on UC-MSC (12.19 ± 4.49), significantly higher than fetal bovine serum cultured group (1.33 ± 0.06, <i>P</i>&lt;0.01) and normal individuals serum cultured group (2.53 ± 0.72, <i>P</i>&lt;0.01). Additionally, TGF-β1 siRNA interfered UC-MSC failed to upregulate Treg cells in SLE patients (SLE PBMC + TGF-β1siRNA UC-MSC group 2.33% ± 0.99% <i>vs.</i>SLE PBMC group 1.80%±0.65%, <i>P</i>&gt;0.05). Furthermore, TGF-β1 specific inhibitor SB431542 significantly inhibited the regulatory role of UC-MSC on Treg cells in SLE patients (SLE PBMC+UC-MSC+SB431542 group 4.58%±2.10% <i>vs.</i> SLE PBMC+UC-MSC group 7.85%±3.54%, <i>P</i>&lt;0.05). <h3>Conclusions</h3> Immune microenvironment in SLE patients can significantly stimulate TGF-β1 expression on UC-MSC, which plays an important role in the upregulation of Treg cells in patients. This study provides a new mechanism for the regulation of Treg cells by UC-MSC and treatment for SLE patients. <b>Disclosure of Interest</b>: None Declared
AB0639 The Prevalence of Cardiac Arrhythmias and Conduction Defects in Patients with Systemic Sclerosis
Authors: R. Alekperov, E. Cheremukhina, R. Alekperov, D. Novikova, L. Ananyeva
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> To study a frequency of cardiac arrhythmias and conduction disturbances by standard ECG and 24-hour Holter monitoring (HM) <h3>Methods</h3> Eighty pts with systemic sclerosis (SSc) (28 – diffuse, and 52 – limited form), age 21-80y (52±11), and disease duration of 1-36y (9,8±8,6). All pts underwent standard ECG and 24-hour HM <h3>Results</h3> By standard ECG cardiac arrhythmias were found in 14 patients (17%), including premature supraventricular beats (PSVB) in 10 (13%) patients and premature ventricular beats (PVB) in 7 (9%) of them. Conduction disorders were seen in 28 (35%) patients, including right bundle branch block in 7 (9%) patients, left bundle branch block in 16 (20%), and combined right and left bundles branch block in 5 (6%) from 80 pts. By HM, PSVB were found in 74 (93%) patients, and PVB in 52 (65%). Twenty nine (36%) patients showed grade III, IVA, IVB or V of ventricular arrhythmias, according to Lown9s classification. There also were atrioventricular block of 1st grade in 1 case, and 2nd grade – in 2 patients. Twenty one patients had coronary artery disease (CAD) and there weren9t any differences of arrhythmias9 frequency between patients with or without CAD. Arrhythmias in group of patients under 50 year and in group of older patients were found in 10 from 28 (35%) patient and in 34 from 52 (65%) patients, respectively (p=0,001). There weren9t any associations of the frequency of arrhythmias with duration of disease and clinical forms of SSc. The frequency of cardiac arrhythmias didn9t differ between patients group with disease duration lesser 5 years and in patients with disease duration greater than 5 years. <h3>Conclusions</h3> Cardiac arrhythmias and conduction abnormalities are common in patients with SSc and are revealed significantly often by HM in comparison with standard ECG <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5182
FDG PET/CT in Acute Tumefactive Multiple Sclerosis Occurring in a Case of Chronic Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Aisheng Dong, Mingjun Gao, Yang Wang, Lei Gao, Changjing Zuo
Journal: Clinical Nuclear Medicine (2016)

Tumefactive multiple sclerosis refers to the presentation of large demyelinating lesions (≥2 cm in diameter) mimicking brain tumors clinically and radiologically. We present the MRI and FDG PET/CT findings in a case with tumefactive multiple sclerosis, who had chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Head MRI showed 7 cerebral lesions with incomplete ring enhancement. All but one lesion had size more than 2 cm. All these demyelinating lesions showed increased uptake at the rims of the lesions with central hypometabolism. Stereotactic brain biopsy of the right frontal lesion revealed extensive macrophage and lymphocyte infiltration.
Molecular profile of Epstein–Barr virus infection in HHV-8-positive primary effusion lymphoma
Authors: L Fassone, K Bhatia, M Gutierrez, D Capello, A Gloghini, R Dolcetti, D Vivenza, V Ascoli, FLo Coco, L Pagani, G Dotti, A Rambaldi, M Raphael, U Tirelli, G Saglio, IT Magrath, A Carbone, G Gaidano
Journal: Leukemia (2000)
Abstract 408: Intermittent hypoxia effect on osteoclastogenesis stimulated by neuroblastoma cells
Authors: Vasantha Kumar Bhaskara, Indra Mohanam, Jasti S. Rao, Sanjeeva Mohanam
Journal: Cancer Research (2012)

Abstract Neuroblastoma is the most common extracranial pediatric solid tumor that is derived from the developing sympathetic nervous system and results from the improper differentiation of neural crest cells. Neuroblastomas show a tremendous clinical heterogeneity ranging from benign ganglioneuromas to highly aggressive immature tumors. Hypoxia is a common feature of solid tumors and is associated with their malignant phenotype. Intermittent hypoxia (IH) which is characterized by cyclic periods of hypoxia and reoxygenation, occurs in tumor cells that are dependent on tumor blood vessels having intermittent perfusion fluctuations in blood flow. The occurrence of IH episodes varies significantly in rapidly growing malignant tumors. Bone is one of the target organs of metastasis in advanced neuroblastoma. To invade the bone, tumor cells produce osteoclast-activating factors that increase bone resorption by the osteoclast. The present study focuses on how IH-conditioned neuroblastoma cells modulate the differentiation of osteoclasts. IH-conditioned cells were derived by exposing tumor cells to 10 repeated cycles of hypoxia followed by reoxygenation. In order to assess the role of HIF-1α overexpression in osteolysis, we stably transfected human neuroblastoma cells with an expression vector containing a HIF-1α cDNA. Additionally, cells were stably transfected with a plasmid expressing HIF-1α shRNA or luciferase shRNA and selected in neomycin. The expression of HIF-1α protein was analyzed by western blotting in IH-conditioned and stable transfectants of neuroblastoma cells. Changes in gene expression were determined by real-time PCR for IL-8, MCP-1α, PTHrP, CXCR-4 and RANKL and the expression of osteoclastogenic factors was found increased in IH-conditioned and HIF-1α protein overexpressing cells. Conditioned medium collected from IH-conditioned and HIF-1α cDNA overexpressing neuroblastoma cells has shown enhanced osteoclast formation capabilities in the tartrate-resistant acid phosphatase (TRAP) assay. IH-conditioned and HIF-1α protein overexpressing neuroblastoma cells secrete increased amounts of VEGF protein, which has been found to promote osteoclast activity. Calcium-sensing receptor (CaR) plays a pivotal role in osteoclast differentiation. We found enhanced expression of CaR in RAW 264.7 (osteoclast precursors) cells treated with conditioned medium collected from IH-conditioned and HIF-1α protein overexpressing neuroblastoma cells compared with the control. Thus, IH was found to enhance osteolytic capabilities of neuroblastoma cells in vitro in part through HIF-1α protein stabilization. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 408. doi:1538-7445.AM2012-408
ENDOVASCULAR RECANALIZATION OF SUPERFICIAL FEMORAL ARTERY CHRONIC TOTAL OCCLUSIONS: A MULTI-DISCIPLINARY, SINGLE CENTER EXPERIENCE
Authors: Aparna C. Swaminathan, Yuliya Lokhnygina, David Kopin, Michael Miller, Mitchell Cox, James Mills, Lawrence Crawford, Manesh Patel, William Jones
Journal: Journal of the American College of Cardiology (2015)
SAT0344 Intravenous Bisphosphonate Reduces Rapidly Pain in Complex Regional Pain Syndrome (CRPS)
Authors: F. Bartoli, G. Fiori, F. Peruzzi, G. Guidi, S. Pfanner, M. Ceruso, M. Matucci Cerinic
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The treatment of CRPS remains controversial, but multidisciplinary and interdisciplinary approaches is mandatory to prevent long-standing or permanent disability. Bisphosphonates, apart from their antiresorptive activity, have been shown to have an analgesic or anti-inflammatory effect. Bisphosphonate therapy has been suggested for the therapy for CRPS. <h3>Objectives</h3> to evaluate the efficacy of intravenous bisphosphonates in reducing pain in patients with CRPS. <h3>Methods</h3> 52 patients (14 males and 38 females; mean age 64.3±8 years) diagnosed with CRPS of carpal and metacarpals bones (confirmed by clinical, x-ray and MRI) from two to six weeks, previously treated with non-steroidal anti-inflammatory drugs (NSAID), calcium, Vitamin D, physical therapy. All patients were treated with iv clodronate 300 mg/day for 2 weeks, followed by im clodronate 200 mg/weekly for 3 months. Pain scale (VAS 0-100) and joint examination were performed before, after two weeks and after 3 months of clodronate therapy. X-ray and MRI were performed at the diagnosis and after 3 months. <h3>Results</h3> Clodronate reduced pain significantly (p=0.0001) after two weeks of therapy (87.7±8 mm <i>vs</i> 15.7±4 mm). After 3 months, a further reduction of pain (10.4±3 mm) was found (p&lt;0.001). After two weeks of therapy reduction of pain was associated also to a reduction of hyperhidrosis, edema and joint stiffness. X-ray showed a stability of radiological features, and MRI a significant reduction of bone oedema. No adverse events were reported. <h3>Conclusions</h3> Iv clodronate achieves a rapid reduction of pain in patients with CRPS. Early intervention and reduction of pain is associated with a rapid clinical and imaging improvement, may prevent long-standing disability. <h3>References</h3> Tran de QH, Duong S, Bertini P, Finlayson RJ. Treatment of complex regional pain syndrome: a review of the evidence. Can J Anaesth. 2010 Feb;57(2):149-66. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4175
Abstract 1489: Function of Rho kinases on HCC tumor growth and metastasis
Authors: Ying Wu, Pamela M. Whalen, Jean Yu Wang, Gary Li, David Pocalyko, Yuli Wang
Journal: Cancer Research (2011)

Abstract The Rho/ROCK (Rho-associated protein kinase) pathway has been found to be frequently upregulated in hepatocellular carcinoma (HCC). Clinico-pathological research has shown that increased RhoA and ROCK2 expression are associated with the presence of tumor microsatellite formation. RhoA is over expressed in 69% of HCC, and high RhoA levels are correlated with poor survival. ROCK2 protein level is upregulated in 54% of HCC, and its expression is associated with intrahepatic metastasis. The ROCK2 knockdown by short hairpin (sh)RNA leads to significant reduction of tumor formation. These observations suggest that Rho/ROCK pathway could be a potential therapeutic target for the treatment of liver cancer. Down-regulation of the Rho/ROCK pathway may inhibit tumor metastasis. However, the role of ROCK1 in HCC metastasis is still not clear. In order to dissect out the roles of ROCK1 and ROCK2 in liver tumor formation and metastasis, we used the shRNAmir- lentiviral system to knockdown ROCK1, ROCK2, and ROCK1/ROCK2 in HCC cell lines. The RNA and protein levels of ROCK1 and ROCK2 were significantly reduced in HCC cell lines that expressed shRNAs targeting ROCK1 and ROCK2. Orthotopically implanted HCC cells carrying shRNA targeted at ROCK1 and ROCK2 either alone or in combination were examined for tumor induction in mice. Our data showed that tumor growth was significantly reduced in those mice inoculated with cells expressing shRNAs. In addition, fewer tumor nodules as compared to the control (Non-target shRNA control) group were seen in those mice. Using qRT-PCR, we confirmed that the decreased ROCK activity was associated with the reduction of ROCK1 and ROCK2 RNA levels in mouse liver samples. Conclusion: our results indicate that both ROCK1 and ROCK2 are important for HCC tumor growth. Moreover, we demonstrated that ROCK1 played a more significant role than ROCK2 in HCC intrahepatic metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1489. doi:10.1158/1538-7445.AM2011-1489
COMPARISON OF IN-STENT THROMBUS IMMEDIATELY AFTER PERCUTANEOUS CORONARY INTERVENTION FOR ACUTE CORONARY SYNDROME BETWEEN PATIENTS PRETREATED WITH PRASUGREL VERSUS CLOPIDOGREL BY USING OPTICAL COHERENCE TOMOGRAPHY
Authors: Yosuke Katayama, Takashi Kubo, Yasushi Ino, Yoshiki Matsuo, Yasutsugu Shiono, Takashi Yamano, Akira Taruya, Tsuyoshi Nishiguchi, Keisuke Satogami, Kuninobu Kashiyama, Akio Kuroi, Makoto Orii, Tomoyuki Yamaguchi, Atsushi Tanaka, Takeshi Hozumi, Takashi Akasaka
Journal: Journal of the American College of Cardiology (2016)
Thin-Basement-Membrane Nephropathy in Adults with Persistent Hematuria
Authors: Anton T.M.G. Tiebosch, Peter M. Frederik, Peter J.C. van Breda Vriesman, Jaap M.V. Mooy, Henk van Rie, Theo W.M. van de Wiel, Johannes Wolters, Ewald Zeppenfeldt
Journal: New England Journal of Medicine (1989)

Thin-basement-membrane nephropathy, also called benign recurrent hematuria, is characterized by diffuse thinning of the glomerular basement membrane and by hematuria. To determine the incidence of thin-basement-membrane nephropathy among patients with idiopathic hematuria, we conducted a prospective study in the nephrology units of three large hospitals in the Netherlands. Eighty normotensive adults without azotemia underwent renal biopsy because of recurrent macroscopic hematuria (n = 26) or persistent microscopic hematuria (n = 54). Idiopathic IgA nephropathy was found in 27 of the 80 patients. Light microscopical examination showed that 42 patients had normal renal tissue. The remaining 11 patients had mesangioproliferative glomerulonephritis (n = 5), interstitial nephritis (n = 3), or focal global glomerulosclerosis (n = 3). Tissue from the 42 patients whose renal biopsy specimens were normal when examined with light microscopy was analyzed morphometrically with electron microscopy to determine the thickness of the glomerular basement membrane. Two subsets of patients were identified by this analysis. In 18, thin-basement-membrane nephropathy was found (mean basement-membrane thickness [+/- SE], 191 +/- 28 nm; normal, 350 +/- 43 nm); all but one of these 18 patients had microscopic hematuria, which persisted during follow-up (median duration, 50 months). (Of the 54 patients who presented with microscopic hematuria, 17 [31 percent] had thin-basement-membrane nephropathy.) The thickness of the glomerular basement membrane was normal in the other 24 patients (361 +/- 69 nm); during follow-up, hematuria disappeared in all 13 of these patients who had macroscopic hematuria, and hematuria resolved in 5 of the 11 patients who had microscopic hematuria. We conclude that in patients with persistent microscopic hematuria, the incidence of thin-basement-membrane nephropathy is similar to that of idiopathic IgA nephropathy. Morphometric analysis of the thickness of the glomerular basement membrane should be included in the workup of adults with persistent microscopic hematuria that is not of urologic origin.
Frequency of biopsies (BX) and colposcopy (CP) of intraepitelial lesions (IL) in the cervical cancer screening program (CCSP)
Authors: S. Holgado, M. Sanchez Segura, J. J. Zarba, C. Monroy, C. Lorente, A. Elias
Journal: Journal of Clinical Oncology (2006)

11000 Background: Cervical cancer is a public health problem in developing countries that can be prevent by screening programs. The loss of patients with PAP smears with IL is one of the main concern in the CCSP. The objectives of this study were establish the frequency of IL in the CCSP of Tucumán and determine the frequency of BX and CP in patients with IL within the program. Methods: Data was taken from the clinic-epidemiological charts of CCSP, and pathology reports of 29,169 cytologies (CX) done in women entered in CCSP of Tucumán between 1997 and 2004 The PAP smears were done and informed following Bethesda system and centralized in Hospital Centro de Salud: Zenón Santillán of Tucumán. Results: 2% of the CX were IL. In the beginning of program in 1997 in HSIL and LSIL a BX was performed in 22% and 18% of patients respectively and in 2004 BX was performed in 61% and 25% respectively. There were no data of CP before 2001 but in 2001 a CP was performed in HSIL and LSIL in 21% and 9% and in 2004 CP was performed in 43% and 14% respectively. Conclusion: The percentage of BX and CP performed in IL patients included in the CCSP, increased in the last year of program achieving a 60% and 43% in HSIL which is quite acceptable in a developing country. No significant financial relationships to disclose.