Technique, pharmacokinetics, toxicity, and efficacy of intratumoral etanidazole and radiotherapy for treatment of spontaneous feline oral squamous cell carcinoma

International Nuclear Information System (INIS)

Evans, S.M.; LaCreta, F.; Helfand, S.; VanWinkle, T.; Curran, W.J. Jr.; Brown, D.Q.; Hanks, G.

1991-01-01

The histologic appearance, locoregional recurrence, and rate/site of metastases of spontaneous feline oral squamous cell carcinoma are similar to head and neck cancer in humans. A feasibility study of intratumoral Etanidazole, a hypoxic cell sensitizer, and radiation therapy were instituted in this model. Eleven cats with feline squamous cell carcinoma were treated with intratumoral Etanidazole and radiation therapy. Total Etanidazole doses were 1.5-24.0 gms/m2 (0.5-6.9 gms). The tumor partial response rate was 100% (11/11); the median volume regression was 70%. All cats have died as a result of tumor recurrence or tumor-related complications. Median survival was 116 days. Ten cats have been autopsied. Non-necrotic and necrotic tumor cells were identified at the treatment site in all cats. Pharmacokinetic studies were performed in six cats. Following intravenous infusion, the plasma elimination of the Etanidazole was biexponential. The systemic availability following intratumoral administration was 61.2 +/- 21.1%. Peak plasma Etanidazole levels were observed 14 minutes following intratumoral injection, after which elimination was biexponential. Thirty minutes following intratumoral Etanidazole administration, tumor Etanidazole levels were 62.8% of plasma levels. Feline squamous cell carcinoma appears to be a useful model of human head and neck cancer. Cats tolerate substantial doses of intratumoral and intravenous Etanidazole. Etanidazole and radiation therapy cause rapid regression, but not cure, of feline squamous cell carcinoma. There is a similarity between the intravenous kinetics of Etanidazole in humans and cats. Further studies in this model are planned

Optimising intratumoral treatment of head and neck squamous cell carcinoma models with the diterpene ester Tigilanol tiglate.

Science.gov (United States)

Barnett, Catherine M E; Broit, Natasa; Yap, Pei-Yi; Cullen, Jason K; Parsons, Peter G; Panizza, Benedict J; Boyle, Glen M

2018-04-18

The five-year survival rate for patients with head and neck squamous cell carcinoma (HNSCC) has remained at ~50% for the past 30 years despite advances in treatment. Tigilanol tiglate (TT, also known as EBC-46) is a novel diterpene ester that induces cell death in HNSCC in vitro and in mouse models, and has recently completed Phase I human clinical trials. The aim of this study was to optimise efficacy of TT treatment by altering different administration parameters. The tongue SCC cell line (SCC-15) was identified as the line with the lowest efficacy to treatment. Subcutaneous xenografts of SCC-15 cells were grown in BALB/c Foxn1 nu and NOD/SCID mice and treated with intratumoral injection of 30 μg TT or a vehicle only control (40% propylene glycol (PG)). Greater efficacy of TT treatment was found in the BALB/c Foxn1 nu mice compared to NOD/SCID mice. Immunohistochemical analysis indicated a potential role of the host's innate immune system in this difference, specifically neutrophil infiltration. Neither fractionated doses of TT nor the use of a different excipiant led to significantly increased efficacy. This study confirmed that TT in 40% PG given intratumorally as a single bolus dose was the most efficacious treatment for a tongue SCC mouse model.

CT analysis of intratumoral gas formation after hepatic tumor embolization

International Nuclear Information System (INIS)

Kim, Hyun Sook; Ahn, In Oak; Kim, Hyung Jin; Lee, Goo; Chung, Sung Hoon

1994-01-01

To evaluate the prevalence and the patterns of sterile gas shown at computed tomography(CT) after transarterial embolization(TAE) for primary hepatic tumor. Among 102 patients who performed TAE for hepatoma, thirty-four in whom follow-up CT was underwent constituted the basis of our study. At CT, we evaluated the patterns and locations of intratumoral gas. We also reviewed the clinical data to exclude an infectious origin of intratumoral gas. Of 34 patients, intratumoral gas was detected in 11 patients(32%), in all of whom Gelfoam was used as an embolic material. The initial tumor size measured at pre-TAE CT was larger in patients with intratumoral gas than in patients without it(p < 0.005). No specific patterns or locations of intratumoral gas were noted on CT scans. No patients had clinical signs and symptoms that suggested infection. Intratumoral gas formation without clinical evidence of infection is not an infrequent finding after TAE for hepatoma, especially when Gelfoam is used and when the tumor is larger in size. This finding may be a part of postinfarction syndrome and should not be misinterpreted as an postprocedural abscess formation

Different thallium-201 single-photon emission tomographic patterns in benign and aggressive meningiomas

International Nuclear Information System (INIS)

Tedeschi, E.; Soricelli, A.; Brunetti, A.; Romano, M.; Bucciero, A.; Iaconetta, G.; Alfieri, A.; Postiglione, A.; Salvatore, M.

1996-01-01

To evaluate the possibility of preoperatively obtaining an index of aggressiveness for intracranial meningiomas, we prospectively studied 22 patients with computed tomographic or magnetic resonance imaging evidence of meningeal tumour, using single-photon emission tomography (SPET) of the brain and thallium-201 ( 201 Tl). On a brain-dedicated SPET scanner, a rapid acquisition protocol with early, short scans was started simultaneously with the intravenous administration of 111 MBq 201 Tl, covering the initial intratumoral distribution of the tracer. Twenty minutes post injection, a delayed SPET scan was also obtained. On the reconstructed and attenuation-corrected images we calculated the 201 Tl concentration in tumour and normal contralateral brain tissue, and compared intratumoral tracer concentration in the initial and the final part of the rapid acquisition protocol. Benign and malignant meningiomas were classified as such based on histological examination. In malignant lesions, the ratio of the 201 Tl concentration at 2-4 min post injection to that at 14-16 min was found to be significantly higher than in non-aggressive neoplasms (mean±1 SD: 1.14±0.31 and 0.56±0.13, respectively, P 201 Tl concentration values at 2-4 and at 14-16 min. Our findings suggest that the comparative assessment of intratumoral 201 Tl concentration at 2-4 and at 14-16 min post injection could provide a fast, simple method to differentiate preoperatively intracranial meningiomas with different biological behaviour. (orig.). With 3 figs., 1 tab

Bronchoscopic intratumoral injection of tranexamic acid to prevent excessive bleeding during multiple forceps biopsies of lesions with a high risk of bleeding: a prospective case series

International Nuclear Information System (INIS)

Zamani, Adil

2014-01-01

Significant bleeding may occur following endobronchial forceps biopsy or brushing of necrotic or hypervascular tumors in the airways. In some cases, methods such as endobronchial instillation of iced saline lavage and epinephrine may fail to control bleeding. The present study evaluated the efficacy and safety of a new bronchoscopic technique using intratumoral injection of tranexamic acid (IIT) for control of bleeding during forceps biopsy in patients with endobronchial tumors with a high risk of bleeding. The study was a prospective case series carried out in a single center. Bronchoscopic IIT was performed in those patients who had endoscopically visible tumoral lesions with persistent active bleeding following the first attempt at bronchoscopic sampling. Tranexamic acid (TEA) was injected through a 22-gauge Wang cytology needle into the lesion in nominal doses of 250–500 mg. After 2–3 minutes, multiple forceps biopsy specimens were obtained from the lesion. Of the 57 consecutive patients included in the study, 20 patients (35.1%) underwent bronchoscopic IIT. The first attempt in 18 patients was endobronchial forceps biopsy (EBB), and because of a high risk of bleeding, the first attempt for the remaining two patients, who were on continuous dual antiplatelet therapy (aspirin and clopidogrel), employed endobronchial needle aspiration (EBNA) as a precautionary measure. Following IIT, subsequent specimens were obtained using EBB in all patients. Multiple forceps biopsy specimens (3–10) were obtained from the lesions (8 necrotic and 12 hypervascular) without incurring active bleeding. The following histopathologic diagnoses were made: squamous cell carcinoma (n = 14), adenocarcinoma (n = 2), small-cell lung cancer (n = 3), and malignant mesenchymal tumor (n = 1). No side effects of TEA were observed. Bronchoscopic IIT is a useful and safe technique for controlling significant bleeding from a forceps biopsy procedure and can be considered as a pre

Therapeutic Endoscopic Ultrasonography: Intratumoral Injection for Pancreatic Adenocarcinoma

Directory of Open Access Journals (Sweden)

Lawrence A. Shirley

2013-01-01

Full Text Available Pancreatic adenocarcinoma is an aggressive disease that has poor outcomes despite maximal traditional therapies. Thus, treatment of this cancer demands innovative strategies to be used in addition to standing therapies in order to provide new avenues of care. Here, we describe the technique of using endoscopic ultrasound in order to directly inject both novel and conventional therapies into pancreatic tumors. We detail the rationale behind this strategy and the many benefits it provides. We then describe our technique in detail, including our experience injecting the AdV-tk adenoviral vector to create an in situ vaccine effect.

Intratumor and Intertumor Heterogeneity in Melanoma

Directory of Open Access Journals (Sweden)

Tomasz M. Grzywa

2017-12-01

Full Text Available Melanoma is a cancer that exhibits one of the most aggressive and heterogeneous features. The incidence rate escalates. A high number of clones harboring various mutations contribute to an exceptional level of intratumor heterogeneity of melanoma. It also refers to metastases which may originate from different subclones of primary lesion. Such component of the neoplasm biology is termed intertumor and intratumor heterogeneity. These levels of tumor heterogeneity hinder accurate diagnosis and effective treatment. The increasing number of research on the topic reflects the need for understanding limitation or failure of contemporary therapies. Majority of analyses concentrate on mutations in cancer-related genes. Novel high-throughput techniques reveal even higher degree of variations within a lesion. Consolidation of theories and researches indicates new routes for treatment options such as targets for immunotherapy. The demand for personalized approach in melanoma treatment requires extensive knowledge on intratumor and intertumor heterogeneity on the level of genome, transcriptome/proteome, and epigenome. Thus, achievements in exploration of melanoma variety are described in details. Particularly, the issue of tumor heterogeneity or homogeneity given BRAF mutations is discussed.

Mass Spectrometry Imaging for the Investigation of Intratumor Heterogeneity.

Science.gov (United States)

Balluff, B; Hanselmann, M; Heeren, R M A

2017-01-01

One of the big clinical challenges in the treatment of cancer is the different behavior of cancer patients under guideline therapy. An important determinant for this phenomenon has been identified as inter- and intratumor heterogeneity. While intertumor heterogeneity refers to the differences in cancer characteristics between patients, intratumor heterogeneity refers to the clonal and nongenetic molecular diversity within a patient. The deciphering of intratumor heterogeneity is recognized as key to the development of novel therapeutics or treatment regimens. The investigation of intratumor heterogeneity is challenging since it requires an untargeted molecular analysis technique that accounts for the spatial and temporal dynamics of the tumor. So far, next-generation sequencing has contributed most to the understanding of clonal evolution within a cancer patient. However, it falls short in accounting for the spatial dimension. Mass spectrometry imaging (MSI) is a powerful tool for the untargeted but spatially resolved molecular analysis of biological tissues such as solid tumors. As it provides multidimensional datasets by the parallel acquisition of hundreds of mass channels, multivariate data analysis methods can be applied for the automated annotation of tissues. Moreover, it integrates the histology of the sample, which enables studying the molecular information in a histopathological context. This chapter will illustrate how MSI in combination with statistical methods and histology has been used for the description and discovery of intratumor heterogeneity in different cancers. This will give evidence that MSI constitutes a unique tool for the investigation of intratumor heterogeneity, and could hence become a key technology in cancer research. © 2017 Elsevier Inc. All rights reserved.

Intratumor and Intertumor Heterogeneity in Melanoma.

Science.gov (United States)

Grzywa, Tomasz M; Paskal, Wiktor; Włodarski, Paweł K

2017-12-01

Melanoma is a cancer that exhibits one of the most aggressive and heterogeneous features. The incidence rate escalates. A high number of clones harboring various mutations contribute to an exceptional level of intratumor heterogeneity of melanoma. It also refers to metastases which may originate from different subclones of primary lesion. Such component of the neoplasm biology is termed intertumor and intratumor heterogeneity. These levels of tumor heterogeneity hinder accurate diagnosis and effective treatment. The increasing number of research on the topic reflects the need for understanding limitation or failure of contemporary therapies. Majority of analyses concentrate on mutations in cancer-related genes. Novel high-throughput techniques reveal even higher degree of variations within a lesion. Consolidation of theories and researches indicates new routes for treatment options such as targets for immunotherapy. The demand for personalized approach in melanoma treatment requires extensive knowledge on intratumor and intertumor heterogeneity on the level of genome, transcriptome/proteome, and epigenome. Thus, achievements in exploration of melanoma variety are described in details. Particularly, the issue of tumor heterogeneity or homogeneity given BRAF mutations is discussed. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

MALDI-imaging guided microproteomics workflow for biomarker discovery of intra-tumor heterogeneity

OpenAIRE

Alberts, Deborah; Longuespée, Rémi; Smargiasso, Nicolas; Mazzucchelli, Gabriel; Baiwir, Dominique; DELVENNE, Philippe; Pamelard, Fabien; Picard de Meller, Gael; De Pauw, Edwin

2016-01-01

Introduction A single tumoral tissue can bear phenotypically different cell populations. This phenomenon called intra-tumor heterogeneity can lead to differential behaviors regarding metastasis seeding and therapy resistance [Zardavas et al., Nature Rev. Clin. Onc. 2015]. MALDI imaging has proven its efficiency for revealing hidden molecular features offering an insight into distinct cellular regions based on their molecular content. Further, proteomics applied to these regions could allo...

Intratumoral Heterogeneous F 18 Fluorodeoxyglucose Uptake Corresponds with Glucose Transporter 1 and Ki-67 Expression in a Case of Krukenberg Tumor: Localization of Intratumoral Hypermetabolic Focus by Fused PET/MR

International Nuclear Information System (INIS)

Im, Hyung Jun; Kim, Youg il; Kim, Woo Ho; Kim, Seung Hyup; Kang, Keon Wook

2011-01-01

The expression of glucose transporters (Glut 1, Glut 3), Hexokinase II, and Ki-67 has been proposed to explain intratumoral heterogeneous F-18 fluorodeoxyglucose (FDG) uptake. We report a case of Krukenberg tumor with intratumoral heterogeneous FDG uptake which corresponded well with the expression tomography (PET)/magnetic resonance (MR) imaging was helpful for localizing the metabolically active area in the tumor specimen. This report elucidates the relationship between the intratumoral heterogeneous FDG uptake and biologic heterogeneity, and shows the usefulness of PET/MR in research on intratumoral heterogeneity.

Erratum: PDGF-BB induces intratumoral lymphangiogenesis and promotes lymphatic metastasis

DEFF Research Database (Denmark)

Cao, R.H.; Bjorndahl, M.A.; Religa, P.

2006-01-01

This corrects the article "PDGF-BB induces intratumoral lymphangiogenesis and promotes lymphatic metastasis", Cancer Cell, 2004, vol. 6(4), pg 333-45.......This corrects the article "PDGF-BB induces intratumoral lymphangiogenesis and promotes lymphatic metastasis", Cancer Cell, 2004, vol. 6(4), pg 333-45....

Cost-Utility of a Single-Injection Combined Corticosteroid-Hyaluronic Acid Formulation vs a 2-Injection Regimen of Sequential Corticosteroid and Hyaluronic Acid Injections.

Science.gov (United States)

Belzile, Etienne L; Deakon, Robert T; Vannabouathong, Christopher; Bhandari, Mohit; Lamontagne, Martin; McCormack, Robert

2017-01-01

Research has shown early and sustained relief with a combination therapy of a corticosteroid (CS) and hyaluronic acid (HA) in knee osteoarthritis (OA) patients. This can be administered via a single injection containing both products or as separate injections. The former may be more expensive when considering only product cost, but the latter incurs the additional costs and time of a second procedure. The purpose of this study was to compare the cost-utility of the single injection with the 2-injection regimen. The results of this analysis revealed that the single-injection formulation of a CS and HA may be cost-effective, assuming a willingness-to-pay of $50 000 per quality-adjusted life year gained, for symptomatic relief of OA symptoms. This treatment may also be more desirable to patients who find injections to be inconvenient or unpleasant.

Imaging-documented repeated intratumoral hemorrhage in vestibular schwannoma: a case report

NARCIS (Netherlands)

Mandl, E. S.; Vandertop, W. P.; Meijer, O. W. M.; Peerdeman, S. M.

2009-01-01

Intratumoral hemorrhage in vestibular schwannomas is rare. Symptoms often have an acute onset and include headache, nausea, vomiting, vertigo, and depressed consciousness. Intratumoral hemorrhage is probably caused by vascular fragility associated with tumor characteristics and growth. With

Inter- and intratumoral heterogeneity of BCL2 correlates with IgH expression and prognosis in follicular lymphoma

International Nuclear Information System (INIS)

Barreca, A; Martinengo, C; Annaratone, L; Righi, L; Chiappella, A; Ladetto, M; Demurtas, A; Chiusa, L; Stacchini, A; Crosetto, N; Oudenaarden, A van; Chiarle, R

2014-01-01

Most follicular lymphomas (FLs) are genetically defined by the t(14;18)(q32;q21) translocation that juxtaposes the BCL2 gene to the immunoglobulin heavy chain (IgH) 3' regulatory regions (IgH-3'RRs). Despite this recurrent translocation, FL cases are heterogeneous in terms of intratumoral clonal diversity for acquired mutations and variations in the tumor microenvironment. Here we describe an additional mechanism that contributes to inter- and intratumoral heterogeneity in FLs. By applying a novel single-molecule RNA fluorescence-based in situ hybridization (FISH) technique to detect mRNA molecules of BCL2 and IgH in single cells, we found marked heterogeneity in the number of BCL2 mRNA transcripts within individual lymphoma cells. Moreover, BCL2 mRNA molecules correlated with IgH mRNA molecules in individual cells both in t(14;18) lymphoma cell lines and in patient samples. Consistently, a strong correlation between BCL2 and IgH protein levels was found in a series of 205 primary FL cases by flow cytometry and immunohistochemistry. Inter- and intratumoral heterogeneity of BCL2 expression determined resistance to drugs commonly used in FL treatment and affected overall survival of FL patients. These data demonstrate that BCL2 and IgH expressions are heterogeneous and coregulated in t(14;18)-translocated cells, and determine the response to therapy in FL patients

Primary central nervous system lymphoma: is absence of intratumoral hemorrhage a characteristic finding on MRI?

Science.gov (United States)

Sakata, Akihiko; Okada, Tomohisa; Yamamoto, Akira; Kanagaki, Mitsunori; Fushimi, Yasutaka; Dodo, Toshiki; Arakawa, Yoshiki; Takahashi, Jun C; Miyamoto, Susumu; Togashi, Kaori

2015-06-01

Previous studies have shown that intratumoral hemorrhage is a common finding in glioblastoma multi-forme, but is rarely observed in primary central nervous system lymphoma. Our aim was to reevaluate whether intratumoral hemorrhage observed on T2-weighted imaging (T2WI) as gross intratumoral hemorrhage and on susceptibility-weighted imaging as intratumoral susceptibility signal can differentiate primary central nervous system lymphoma from glioblastoma multiforme. A retrospective cohort of brain tumors from August 2008 to March 2013 was searched, and 58 patients (19 with primary central nervous system lymphoma, 39 with glioblastoma multiforme) satisfied the inclusion criteria. Absence of gross intratumoral hemorrhage was examined on T2WI, and an intratumoral susceptibility signal was graded using a 3-point scale on susceptibility-weighted imaging. Results were compared between primary central nervous system lymphoma and glioblastoma multiforme, and values of P central nervous system lymphoma and 23 patients (59%) with glioblastoma multiforme. Absence of gross intratumoral hemorrhage could not differentiate between the two disorders (P = 0.20). However, intratumoral susceptibility signal grade 1 or 2 was diagnostic of primary central nervous system lymphoma with 78.9% sensitivity and 66.7% specificity (P central nervous system lymphoma from glioblastoma multiforme. However, specificity in this study was relatively low, and primary central nervous system lymphoma cannot be excluded based solely on the presence of an intratumoral susceptibility signal.

Voltage controlled nano-injection system for single-cell surgery

Science.gov (United States)

Seger, R. Adam; Actis, Paolo; Penfold, Catherine; Maalouf, Michelle; Vilozny, Boaz; Pourmand, Nader

2015-01-01

Manipulation and analysis of single cells is the next frontier in understanding processes that control the function and fate of cells. Herein we describe a single-cell injection platform based on nanopipettes. The system uses scanning microscopy techniques to detect cell surfaces, and voltage pulses to deliver molecules into individual cells. As a proof of concept, we injected adherent mammalian cells with fluorescent dyes. PMID:22899383

Two injection digital block versus single subcutaneous palmar injection block for finger lacerations.

Science.gov (United States)

Okur, O M; Şener, A; Kavakli, H Ş; Çelik, G K; Doğan, N Ö; Içme, F; Günaydin, G P

2017-12-01

We aimed to compare two digital nerve block techniques in patients due to traumatic digital lacerations. This was a randomized-controlled study designed prospectively in the emergency department of a university-based training and research hospital. Randomization was achieved by sealed envelopes. Half of the patients were randomised to traditional (two-injection) digital nerve block technique while single-injection digital nerve block technique was applied to the other half. Score of pain due to anesthetic infiltration and suturing, onset time of total anesthesia, need for an additional rescue injection were the parameters evaluated with both groups. Epinephrin added lidocaine hydrochloride preparation was used for the anesthetic application. Visual analog scale was used for the evaluation of pain scores. Outcomes were compared by using Mann-Whitney U test and Student t-test. Fifty emergency department patients ≥18 years requiring digital nerve block were enrolled in the study. Mean age of the patients was 33 (min-max: 19-86) and 39 (78 %) were male. No statistically significant difference was found between the two groups in terms of our main parameters; anesthesia pain score, suturing pain score, onset time of total anesthesia and rescue injection need. Single injection volar digital nerve block technique is a suitable alternative for digital anesthesias in emergency departments.

Intratumoral Vasculopathy in Leiomyoma Treated With Tranexamic Acid.

Science.gov (United States)

Kudose, Satoru; Krigman, Hannah R

2017-07-01

Although intravascular thrombi and infarct-type necrosis have been reported in leiomyomas following tranexamic acid therapy, intratumoral vasculopathy resembling acute atherosis has not been reported to date in patients without exposure to gonadotropin receptor agonist. We describe a case of intratumoral vasculopathy resembling acute atherosis in a leiomyoma in a 49-year-old woman, with hereditary hemorrhagic telangiectasia and menorrhagia, treated with tranexamic acid. The patient had no exposure to gonadotropin receptor agonists. Pathologic examination of the hysterectomy specimen showed a 5.7-cm submucosal leiomyoma containing multiple arteries with fibrinoid change accompanied with abundant subintimal foamy macrophages and occasional luminal thrombi. The vascular media showed scant lymphocytic inflammation without necrosis. The leiomyoma contained numerous mast cells and edematous areas. Vessels outside of the leiomyoma showed neither fibrinoid changes nor inflammation. The patient is alive and well with no signs of systemic vasculitis. We demonstrate that intratumoral vasculopathy resembling acute atherosis may be seen in leiomyomas from patients taking tranexamic acid and postulate that this change results in vascular thrombosis, tumoral edema, and infarct-type necrosis.

Intratumoral chemotherapy for lung cancer: re-challenge current targeted therapies

Directory of Open Access Journals (Sweden)

Hohenforst-Schmidt W

2013-07-01

through passive transport within the tumor. Recent advances have enhanced the diffusion of pharmaceuticals through active transport by using pharmaceuticals designed to target the genome of tumors. In the present study, five patients with non-small cell lung cancer epidermal growth factor receptor (EGFR negative stage IIIa–IV International Union Against Cancer 7 (UICC-7, and with Eastern Cooperative Oncology Group (ECOG 2 scores were administered platinum-based doublet chemotherapy using combined intratumoral-regional and intravenous route of administration. Cisplatin analogues were injected at 0.5%–1% concentration within the tumor lesion and proven malignant lymph nodes according to pretreatment histological/cytological results and the concentration of systemic infusion was decreased to 70% of a standard protocol. This combined intravenous plus intratumoral-regional chemotherapy is used as a first line therapy on this short series of patients. To the best of our knowledge this is the first report of direct treatment of involved lymph nodes with cisplatin by endobronchial ultrasound drug delivery with a needle without any adverse effects. The initial overall survival and local response are suggestive of a better efficacy compared to established doublet cisplatin–based systemic chemotherapy in (higher standard concentrations alone according to the UICC 7 database expected survival. An extensive search of the literature was performed to gather information of previously published literature of intratumoral chemo-drug administration and formulation for this treatment modality. Our study shows a favorable local response, more than a 50% reduction, for a massive tumor mass after administration of five sessions of intratumoral chemotherapy plus two cycles of low-dose intravenous chemotherapy according to our protocol. These encouraging results (even in very sick ECOG 2 patients with central obstructive non-small cell lung cancer having a worse prognosis and quality of

Cycloamylose-nanogel drug delivery system-mediated intratumor silencing of the vascular endothelial growth factor regulates neovascularization in tumor microenvironment.

Science.gov (United States)

Fujii, Hidetaka; Shin-Ya, Masaharu; Takeda, Shigeo; Hashimoto, Yoshihide; Mukai, Sada-atsu; Sawada, Shin-ichi; Adachi, Tetsuya; Akiyoshi, Kazunari; Miki, Tsuneharu; Mazda, Osam

2014-12-01

RNAi enables potent and specific gene silencing, potentially offering useful means for treatment of cancers. However, safe and efficient drug delivery systems (DDS) that are appropriate for intra-tumor delivery of siRNA or shRNA have rarely been established, hindering clinical application of RNAi technology to cancer therapy. We have devised hydrogel polymer nanoparticles, or nanogel, and shown its validity as a novel DDS for various molecules. Here we examined the potential of self-assembled nanogel of cholesterol-bearing cycloamylose with spermine group (CH-CA-Spe) to deliver vascular endothelial growth factor (VEGF)-specific short interfering RNA (siVEGF) into tumor cells. The siVEGF/nanogel complex was engulfed by renal cell carcinoma (RCC) cells through the endocytotic pathway, resulting in efficient knockdown of VEGF. Intra-tumor injections of the complex significantly suppressed neovascularization and growth of RCC in mice. The treatment also inhibited induction of myeloid-derived suppressor cells, while it decreased interleukin-17A production. Therefore, the CH-CA-Spe nanogel may be a feasible DDS for intra-tumor delivery of therapeutic siRNA. The results also suggest that local suppression of VEGF may have a positive impact on systemic immune responses against malignancies. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Single-needle temporomandibular joint arthrocentesis with hyaluronic acid injections. Preliminary data after a five-injection protocol.

Science.gov (United States)

Manfredini, D; Guarda-Nardini, L; Ferronato, G

2009-10-01

The classical technique for temporomandibular joint (TMJ) arthrocentesis provides a double access to the joint space, which may lead to patient's postoperatory discomfort. For this reason, a less invasive, single-needle approach has been recently described, and the present investigation reports findings on a case series of patients with TMJ osteoarthritis treated with hyaluronic acid injections following a single needle arthrocentesis. METHODS. Fourteen consecutive patients with a diagnosis of TMJ osteoarthritis according to the Research Diagnostic Criteria for Temporo-mandibular Disorders were treated with a cycle of five weekly injections of hyaluronic acid after arthrocentesis. A number of subjective (pain at rest and mastication, masticatory efficiency, functional limitation, subjective efficacy of treatment, tolerability of treatment) and objective (maximum assisted and unassited mouth opening, protrusive and laterotrusive movements) outcome variables were assessed before and after the treatment period. At the end of the five-injection protocol, significant improvements were showed in almost all the subjective outcome variables. Tolerability of the treatment was good on a four-point ordinal scale since the time of the first injection. The present investigation suggested that the single needle technique for TMJ hyaluronic injection following arthrocentesis in osteoarthritic joints may have promising applications in the clinical setting, which have to be confirmed with future studies.

Surgical and survival outcomes of lung cancer patients with intratumoral lung abscesses.

Science.gov (United States)

Yamanashi, Keiji; Okumura, Norihito; Takahashi, Ayuko; Nakashima, Takashi; Matsuoka, Tomoaki

2017-05-26

Intratumoral lung abscess is a secondary lung abscess that is considered to be fatal. Therefore, surgical procedures, although high-risk, have sometimes been performed for intratumoral lung abscesses. However, no studies have examined the surgical outcomes of non-small cell lung cancer patients with intratumoral lung abscesses. The aim of this study was to investigate the surgical and survival outcomes of non-small cell lung cancer patients with intratumoral lung abscesses. Eleven consecutive non-small cell lung cancer patients with intratumoral lung abscesses, who had undergone pulmonary resection at our institution between January 2007 and December 2015, were retrospectively analysed. The post-operative prognoses were investigated and prognostic factors were evaluated. Ten of 11 patients were male and one patient was female. The median age was 64 (range, 52-80) years. Histopathologically, 4 patients had Stage IIA, 2 patients had Stage IIB, 2 patients had Stage IIIA, and 3 patients had Stage IV tumors. The median operative time was 346 min and the median amount of bleeding was 1327 mL. The post-operative morbidity and mortality rates were 63.6% and 0.0%, respectively. Recurrence of respiratory infections, including lung abscesses, was not observed in all patients. The median post-operative observation period was 16.1 (range, 1.3-114.5) months. The 5-year overall survival rate was 43.3%. No pre-operative, intra-operative, or post-operative prognostic factors were identified in the univariate analyses. Surgical procedures for advanced-stage non-small cell lung cancer patients with intratumoral lung abscesses, although high-risk, led to satisfactory post-operative mortality rates and acceptable prognoses.

Mathematical modeling analysis of intratumoral disposition of anticancer agents and drug delivery systems.

Science.gov (United States)

Popilski, Hen; Stepensky, David

2015-05-01

Solid tumors are characterized by complex morphology. Numerous factors relating to the composition of the cells and tumor stroma, vascularization and drainage of fluids affect the local microenvironment within a specific location inside the tumor. As a result, the intratumoral drug/drug delivery system (DDS) disposition following systemic or local administration is non-homogeneous and its complexity reflects the differences in the local microenvironment. Mathematical models can be used to analyze the intratumoral drug/DDS disposition and pharmacological effects and to assist in choice of optimal anticancer treatment strategies. The mathematical models that have been applied by different research groups to describe the intratumoral disposition of anticancer drugs/DDSs are summarized in this article. The properties of these models and of their suitability for prediction of the drug/DDS intratumoral disposition and pharmacological effects are reviewed. Currently available mathematical models appear to neglect some of the major factors that govern the drug/DDS intratumoral disposition, and apparently possess limited prediction capabilities. More sophisticated and detailed mathematical models and their extensive validation are needed for reliable prediction of different treatment scenarios and for optimization of drug treatment in the individual cancer patients.

Ultrasound-Guided Single-Injection Infraclavicular Block Versus Ultrasound-Guided Double-Injection Axillary Block: A Noninferiority Randomized Controlled Trial.

Science.gov (United States)

Boivin, Ariane; Nadeau, Marie-Josée; Dion, Nicolas; Lévesque, Simon; Nicole, Pierre C; Turgeon, Alexis F

2016-01-01

Single-injection ultrasound-guided infraclavicular block is a simple, reliable, and effective technique. A simplified double-injection ultrasound-guided axillary block technique with a high success rate recently has been described. It has the advantage of being performed in a superficial and compressible location, with a potentially improved safety profile. However, its effectiveness in comparison with single-injection infraclavicular block has not been established. We hypothesized that the double-injection ultrasound-guided axillary block would show rates of complete sensory block at 30 minutes noninferior to the single-injection ultrasound-guided infraclavicular block. After approval by our research ethics committee and written informed consent, adults undergoing distal upper arm surgery were randomized to either group I, ultrasound-guided single-injection infraclavicular block, or group A, ultrasound-guided double-injection axillary block. In group I, 30 mL of 1.5% mepivacaine was injected posterior to the axillary artery. In group A, 25 mL of 1.5% mepivacaine was injected posteromedial to the axillary artery, after which 5 mL was injected around the musculocutaneous nerve. Primary outcome was the rate of complete sensory block at 30 minutes. Secondary outcomes were the onset of sensory and motor blocks, surgical success rates, performance times, and incidence of complications. All outcomes were assessed by a blinded investigator. The noninferiority of the double-injection ultrasound-guided axillary block was considered if the limits of the 90% confidence intervals (CIs) were within a 10% margin of the rate of complete sensory block of the infraclavicular block. At 30 minutes, the rate of complete sensory block was 79% in group A (90% CI, 71%-85%) compared with 91% in group I (90% CI, 85%-95%); the upper limit of CI of group A is thus included in the established noninferiority margin of 10%. The rate of complete sensory block was lower in group A (proportion

Efficacy of a single ultrasound-guided injection for the treatment of hip osteoarthritis.

LENUS (Irish Health Repository)

Atchia, Ismaël

2011-01-01

Intra-articular injection is effective for osteoarthritis, but the best single injection strategy is not known, nor are there established predictors of response. The objectives of this study were to assess and predict response to a single ultrasound-guided injection in moderate to severe hip osteoarthritis.

Presence of intratumoral neutrophils is an independent prognostic factor in localized renal cell carcinoma

DEFF Research Database (Denmark)

Jensen, Hanne Krogh; Donskov, Frede; Marcussen, Niels

2009-01-01

: The intratumoral neutrophils ranged from zero to 289 cells/mm(2) tumor tissue. The presence of intratumoral neutrophils was statistically significantly associated with increasing tumor size, low hemoglobin, high creatinine, and CA IX

Intra-tumor heterogeneity in head and neck cancer and its clinical implications

Directory of Open Access Journals (Sweden)

Edmund A. Mroz

2016-06-01

Full Text Available The presence of heritable differences among cancer cells within a tumor, called intra-tumor genetic heterogeneity, has long been suspected of playing a role in poor responses to therapy. Research over the past decade has documented the existence of such heterogeneity within tumors of individual patients and documented its potential clinical significance. The research methods for identifying this heterogeneity were not, however, readily adaptable to widespread clinical application. After a brief review of this background, we describe the development of a measure of intra-tumor genetic heterogeneity, based on whole-exome sequencing of individual tumor samples, that could be applied to biopsy specimens in a clinical setting. This measure has now been used in head and neck squamous cell carcinoma (HNSCC to document, for the first time, a relation of high intra-tumor genetic heterogeneity to shorter overall survival in a large, multi-institutional study. The implications of heterogeneity for research and clinical care thus now need to be addressed. Keywords: Head and neck squamous cell carcinoma, Intra-tumor genetic heterogeneity, Next-generation sequencing, Targeted therapy

Current status of intratumoral therapy for glioblastoma.

Science.gov (United States)

Mehta, Ankit I; Linninger, Andreas; Lesniak, Maciej S; Engelhard, Herbert H

2015-10-01

With emerging drug delivery technologies becoming accessible, more options are expected to become available to patients with glioblastoma (GBM) in the near future. It is important for clinicians to be familiar with the underlying mechanisms and limitations of intratumoral drug delivery, and direction of recent research efforts. Tumor-adjacent brain is an extremely complex living matrix that creates challenges with normal tissue intertwining with tumor cells. For convection-enhanced delivery (CED), the role of tissue anisotropy for better predicting the biodistribution of the infusate has recently been studied. Computational predictive methods are now available to better plan CED therapy. Catheter design and placement—in addition to the agent being used—are critical components of any protocol. This paper overviews intratumoral therapies for GBM, highlighting key anatomic and physiologic perspectives, selected agents (especially immunotoxins), and some new developments such as the description of the glymphatic system.

Increasing energy efficiency of a gasoline direct injection engine through optimal synchronization of single or double injection strategies

International Nuclear Information System (INIS)

Costa, Michela; Sorge, Ugo; Allocca, Luigi

2012-01-01

Highlights: ► Advantages of split injection in a GDI engine are studied through numerical simulation. ► At high load and speed, rich conditions, split injection does not improve engine performance. ► At moderate load and speed, lean conditions, double injection improves charge stratification. ► Optimal double injection increases work, reduces HC and increases NO. - Abstract: The greatest fuel efficiency advantages of gasoline direct injection (GDI) engines are achieved under the so-called mixed mode boosting, where mixture characteristics are properly adapted to the specific working condition. In particular, in the medium range of load and speed, overall lean mixtures are suitable of being used in the so-called direct injection stratified charge operation. Present paper reports the results of numerical optimization analyses aimed at increasing the energetic efficiency of a GDI engine equipped with a high pressure multi-hole injector under both single and double injection events. In moderate-load moderate-speed lean conditions, the single or double injection synchronization in the working cycle is effected through a procedure that couples a 3D numerical model of the in-cylinder processes with an optimization tool. The choice of both the start of the injection events and the time of spark advance is realized to maximize the engine work. The optimal double injection solution is shown to increase the engine energy efficiency with respect to the case injection is realized in one shot, thus confirming that split injections improve the quality of the charge stratification under lean operation. The effect on the major pollutants is also discussed.

The experimental study on the radioimmunotherapy of the hepatoma in nude mice model with intratumoral injection of 131I-human anti-HBsAg Fab

International Nuclear Information System (INIS)

Luo Rongcheng; Wu Guichen; Han Huanxing; You Changxuan; Ding Xuemei; Li Aimin; Wang Chuanbin; Zhang Mingjiang

2001-01-01

Objective: To study the therapeutic efficacy of radioimmunotherapy of 131 I-human anti-HBsAg Fab via different routes of administration. Methods: The human hepatoma bearing nude mice we reinjected with 131 I-human anti-HBsAg Fab intra-tumor (IT) and intra-peritoneum (IP). Biodistribution was measured on the 5th day. The tumor growth inhibition rate was determined by measurement of tumor volume. Results: In the IT-treated mice, tumor uptake of 131 I-human anti-HBsAg Fab was four-fold greater than in the IP-treated mice, and normal organ uptake was half of that in the IP-treated mice. At the 3rd week after the infusion, the tumor growth inhibition rate in IT-treated mice was higher than that in the IP-treated mice. Conclusions: Intratumoral administration of 131 I-human anti-HBsAg Fab makes high level of radioactivity retained in tumor with significantly lower radioactivity retained in normal tissues, and provides a more effective regional therapy

Comparison of circulating and intratumoral regulatory T cells in patients with renal cell carcinoma.

Science.gov (United States)

Asma, Gati; Amal, Gorrab; Raja, Marrakchi; Amine, Derouiche; Mohammed, Chebil; Amel, Ben Ammar Elgaaied

2015-05-01

The clear evidence that tumor-infiltrating lymphocytes (TIL) exists in the tumor microenvironment raises the question why renal cell carcinoma (RCC) progresses. Numerous studies support the implication of CD4(+)CD25(high) regulatory T (Treg) cells in RCC development. We aimed in this study to characterize the phenotype and function of circulating and intratumoral Treg cells of RCC patient in order to evaluate their implication in the inhibition of the local antitumor immune response. Our results demonstrate that the proportion of Treg in TIL was, in average, similar to that found in circulating CD4(+) T cells of patients or healthy donors. However, intratumoral Treg exhibit a marked different phenotype when compared with the autologous circulating Treg. A higher CD25 mean level, HLA-DR, Fas, and GITR, and a lower CD45RA expression were observed in intratumoral Treg, suggesting therefore that these cells are effector in the tumor microenvironment. Additionally, intratumoral Treg showed a higher inhibitory function on autologous CD4(+)CD25(-) T cells when compared with circulating Treg that may be explained by an overexpression of FoxP3 transcription factor. These findings suggest that intratumoral Treg could be major actors in the impairment of local antitumor immune response for RCC patients.

O4.04‘FROM THE CORE TO BEYOND THE MARGIN’: A GENOMIC PICTURE OF GLIOBLASTOMA INTRATUMOR HETEROGENEITY

Science.gov (United States)

Aubry, M.; de Tayrac, M.; Etcheverry, A.; Clavreul, A.; Saikali, S.; Menei, P.; Mosser, J.

2014-01-01

expression and methylation levels was significantly higher than in the whole genome. This indicated that their abnormal expression might be linked to cis-acting epimutations in their promoter. We also evidenced that a single tumor can harbor different transcriptional GB subtypes depending on its spatial architecture. Results were validated on published data (Sottoriva et al., PNAS, 2013). CONCLUSION: Our study confirms that GBs are highly diverse at the three molecular levels, but not randomly so. GB intratumor heterogeneity is an important issue for the potential use of GB molecular subclasses in predictive algorithms and clinical trial stratification. We also evidenced a strong epigenetic determination of GB intratumor heterogeneity.

Cystic craniopharyngioma: intratumoral chemotherapy with alpha interferon

Directory of Open Access Journals (Sweden)

Patrícia Alessandra Dastoli

2011-02-01

Full Text Available OBJECTIVE: To assess whether the cystic craniopharyngiomas can be controlled with the use of intratumoral applications of interferon alpha. METHOD: Nineteen patients with the diagnosis of cystic craniopharyngioma were treated with intratumoral chemotherapy with interferon alpha from January 2002 to April 2006. All patients underwent placement of an intracystic catheter connected to an Ommaya reservoir. Through this reservoir were made applications during chemotherapy cycles. Each cycle corresponded to application of 3,000,000 units of interferon alpha three times per week on alternate days totalizing 36,000,000 units. Response to treatment was evaluated by calculating the tumor volume on MRI control after one, three and six months after the end of each cycle. Patients who developed worsening of symptoms or who had insignificant reduction in tumor volume during follow-up underwent repeat cycle chemotherapy. RESULTS: Four patients received four cycles of chemotherapy, three patients received three cycles, six patients received two cycles and six patients received one. The lower percentage of reduction in tumor volume was 60% and the bigger reduction was 98.37%. Eleven patients had a reduction greater than 90%. Five patients had a tumor reduction between 75 and 90% and in three patients the tumors were reduced by less than 75%. No deaths occurred during treatment and side effects of interferon alpha were well tolerated. No treatment was discontinued. Follow-up after the last application ranged from one year and five months to three years and nine months. CONCLUSION: The intratumoral chemotherapy with interferon alpha decreases the volume of cystic craniopharyngiomas and so far can be considered a new therapeutic alternative.

Overview on Clinical Relevance of Intra-Tumor Heterogeneity.

Science.gov (United States)

Stanta, Giorgio; Bonin, Serena

2018-01-01

Today, clinical evaluation of tumor heterogeneity is an emergent issue to improve clinical oncology. In particular, intra-tumor heterogeneity (ITH) is closely related to cancer progression, resistance to therapy, and recurrences. It is interconnected with complex molecular mechanisms including spatial and temporal phenomena, which are often peculiar for every single patient. This review tries to describe all the types of ITH including morphohistological ITH, and at the molecular level clonal ITH derived from genomic instability and nonclonal ITH derived from microenvironment interaction. It is important to consider the different types of ITH as a whole for any patient to investigate on cancer progression, prognosis, and treatment opportunities. From a practical point of view, analytical methods that are widely accessible today, or will be in the near future, are evaluated to investigate the complex pattern of ITH in a reproducible way for a clinical application.

Overview on Clinical Relevance of Intra-Tumor Heterogeneity

Directory of Open Access Journals (Sweden)

Giorgio Stanta

2018-04-01

Full Text Available Today, clinical evaluation of tumor heterogeneity is an emergent issue to improve clinical oncology. In particular, intra-tumor heterogeneity (ITH is closely related to cancer progression, resistance to therapy, and recurrences. It is interconnected with complex molecular mechanisms including spatial and temporal phenomena, which are often peculiar for every single patient. This review tries to describe all the types of ITH including morphohistological ITH, and at the molecular level clonal ITH derived from genomic instability and nonclonal ITH derived from microenvironment interaction. It is important to consider the different types of ITH as a whole for any patient to investigate on cancer progression, prognosis, and treatment opportunities. From a practical point of view, analytical methods that are widely accessible today, or will be in the near future, are evaluated to investigate the complex pattern of ITH in a reproducible way for a clinical application.

Intratumoral heterogeneity of Ki67 expression in early breast cancers exceeds variability between individual tumours

NARCIS (Netherlands)

Focke, Cornelia M.; Decker, Thomas; van Diest, Paul J.

2016-01-01

Aims: Regional differences in proliferative activity are commonly seen within breast cancers, but little is known on the extent of intratumoral heterogeneity of Ki67 expression. Our aim was to study the intratumoral heterogeneity of Ki67 expression in early breast cancers and its association with

Amplitude Noise Suppression and Orthogonal Multiplexing Using Injection-Locked Single-Mode VCSEL

DEFF Research Database (Denmark)

Lyubopytov, Vladimir; von Lerber, Tuomo; Lassas, Matti

2017-01-01

We experimentally demonstrate BER reduction and orthogonal modulation using an injection locked single-mode VCSEL. It allows us suppressing an amplitude noise of optical signal and/or double the capacity of an information channel.......We experimentally demonstrate BER reduction and orthogonal modulation using an injection locked single-mode VCSEL. It allows us suppressing an amplitude noise of optical signal and/or double the capacity of an information channel....

Cluster endophthalmitis following multiple intravitreal bevacizumab injections from a single use vial

Directory of Open Access Journals (Sweden)

Perwez Khan

2016-01-01

Full Text Available The risk of endophthalmitis is always a concern when an intraocular procedure is performed. Intravitreal injection is a frequently used method for therapeutic management of many diseases, affecting the posterior segment of the eye. Hence, it is important to assess the risk of complications, especially endophthalmitis. Most studies conducted concentrate on risk assessment from single use from single drug vial. The present article reports the occurrence of cluster endophthalmitis following multiple intravitreal bevacizumab injections from a single vial. Intravitreal injection of bevacizumab was administered to eight eyes of eight patients. Administered dose was prepared from single 4-ml vial of bevacizumab and was injected in the eye, after patient preparation and under aseptic conditions. The procedure was repeated for the remaining patients, thereby imparting multiple pricks in the same vial. Four of the eight patients reported to the hospital on the 3rd day after injection with complaints of pain, watering, and diminution of vision. Two patients reported the following day with similar complaints. Two patients who did not report by the 4th day were contacted and recalled for an examination. All the patients were thoroughly examined using slit lamp biomicroscopy and indirect ophthalmoscopy. Six out of eight were clinically diagnosed to have endophthalmitis and were administered intravitreal antibiotics. The present report highlights possibility of microbial contamination of the drug vial or during compounding process. However, from the present incident, we are encouraged to stay vigilant and wary of contamination

Expression of connective tissue growth factor and interleukin-11 in intratumoral tissue is associated with poor survival after curative resection of hepatocellular carcinoma.

Science.gov (United States)

Xiang, Zuo-Lin; Zeng, Zhao-Chong; Fan, Jia; Tang, Zhao-You; Zeng, Hai-Ying

2012-05-01

In the present study, we evaluated the prognostic value of intratumoral and peritumoral expression of connective tissue growth factor (CTGF), transforming growth factor-beta 1 (TGF-β1), and interleukin-11 (IL-11) in patients with hepatocellular carcinoma (HCC) after curative resection. Expression of CTGF, TGF-β1, and IL-11 was assessed by immunohistochemical staining of tissue microarrays containing paired tumor and peritumoral liver tissue from 290 patients who had undergone hepatectomy for histologically proven HCC. The prognostic value of these and other clinicopathologic factors were evaluated. The median follow-up time was 54.3 months (range, 4.3-118.3 months). High intratumoral CTGF expression was associated with vascular invasion (P = 0.015), intratumoral IL-11 expression correlated with higher tumor node metastasis (TNM) stage (P = 0.009), and peritumoral CTGF overexpression correlated with lack of tumor encapsulation (P = 0.031). Correlation analysis of these proteins revealed that intratumoral CTGF and IL-11 correlated with high intratumoral TGF-β1 expression (r = 0.325, P < 0.001; and r = 0.273, P < 0.001, respectively). TNM stage (P < 0.001), high intratumoral CTGF levels (P = 0.010), and intratumoral IL-11 expression (P = 0.015) were independent prognostic factors for progression-free survival (PFS). Vascular invasion (P = 0.032), TNM stage (P < 0.001), high intratumoral CTGF levels (P = 0.036), and intratumoral IL-11 expression (P = 0.013) were independent prognostic factors for overall survival (OS). High intratumoral CTGF and intratumoral IL-11 expression were associated with PFS and OS after hepatectomy, and the combination of intratumoral CTGF with IL-11 may be predictive of survival.

Ultrasound-guided single-penetration dual-injection block for leg and foot surgery

DEFF Research Database (Denmark)

Børglum, Jens; Johansen, Karina; Christensen, Karen Margrethe

2014-01-01

We describe a new approach to blocking the sciatic and saphenous nerves in the proximal thigh (level of the lesser trochanter or immediately below) using a single-penetration dual-injection (SPEDI) technique. The popliteal-sciatic approach necessitates repositioning of the leg exposing the poplit......We describe a new approach to blocking the sciatic and saphenous nerves in the proximal thigh (level of the lesser trochanter or immediately below) using a single-penetration dual-injection (SPEDI) technique. The popliteal-sciatic approach necessitates repositioning of the leg exposing...... the popliteal fossa and an extra injection for the saphenous nerve (SAN) block at the midthigh level. We introduce an alternative, effective, and possibly faster method....

Ambiguity in measuring matrix diffusion with single-well injection/recovery tracer tests

Science.gov (United States)

Lessoff, S.C.; Konikow, Leonard F.

1997-01-01

Single-well injection/recovery tracer tests are considered for use in characterizing and quantifying matrix diffusion in dual-porosity aquifers. Numerical modeling indicates that neither regional drift in homogeneous aquifers, nor heterogeneity in aquifers having no regional drift, nor hydrodynamic dispersion significantly affects these tests. However, when drift is coupled simultaneously with heterogeneity, they can have significant confounding effects on tracer return. This synergistic effect of drift and heterogeneity may help explain irreversible flow and inconsistent results sometimes encountered in previous single-well injection/recovery tracer tests. Numerical results indicate that in a hypothetical single-well injection/recovery tracer test designed to demonstrate and measure dual-porosity characteristics in a fractured dolomite, the simultaneous effects of drift and heterogeneity sometimes yields responses similar to those anticipated in a homogeneous dual-porosity formation. In these cases, tracer recovery could provide a false indication of the occurrence of matrix diffusion. Shortening the shut-in period between injection and recovery periods may make the test less sensitive to drift. Using multiple tracers having different diffusion characteristics, multiple tests having different pumping schedules, and testing the formation at more than one location would decrease the ambiguity in the interpretation of test data.

Experimental study on ultrasound-guided intratumoral injection of "Star-99" in treatment of hepatocellular carcinoma of nude mice

Institute of Scientific and Technical Information of China (English)

Li-Wu Lin; Xiao-Dong Lin; Yi-Mi He; Shang-Da Gao; En-Sheng Xue

2003-01-01

AIM: To investigate the anti-cancer effect and the immunological mechanism of ultrasound-guided intratumoral injection of Chinese medicine "Star-99" in hepatocellular carcinoma (HCC) of nude mice.METHODS: Twenty-eight human hepatocellular carcinoma SMMC-7721 transplanted nude mice, 14 of hypodermically implanted and 14 of orthotopic liver transplanted, were randomly divided into three groups of which 14 mice with Star-99, and 7 with ethanol and saline respectively. Ten days after the transplantation the medicines were injected into the tumors of all the nude mice once every 5 days.After 4 injections the nude mice were killed. The diameters of three dimension of the tumors were measured by high frequency ultrasound before and after the treatment and the tumor growth indexes* (TGI) were calculated.Radioimmunoassay was used to detect the serum levels of interleukin-2 (IL-2) and tumor necrosis factor (TNF)-alpha.The tumor tissues were sent for flow cytometry (FCM) DNA analysis. Apoptotic cells were visualized by TUNEL assay.All the experiments were carried out by double blind method. zRESULTS: The TGI of Star-99 group (0.076±0.024) was markedly lower than that of the saline group (4.654±1.283)(P＜0.01). It also seemed to be lower than that of the ethanol group (0.082±0.028), but not significantly different (P＞0.05).Serum levels of IL-2 and TNF-α were markedly higher than those of ethanol group and saline groups (P＜0.05). The mean apoptotic index (AI: percentage of TUNEL signal positive cells)in Star-99 group (48.98±5.09 %) was significantly higher than that of the ethanol group (11.95±2.24 %) and the saline group (10.48±3.85 %) (P＜0.01). FCM DNA analysis showed that the appearance rate of the apoptosis peak in Srar-99group was 92.9 %, markedly higher than that of the ethanol group (14.3 %) and the saline group (0.0 %) (P＜0.01).Correlation (r=0.499, P＜0.05) was found between AI and serum level of TNF-α.CONCLUSION: Star-99 has an effect on the

Arterial spin-labeling assessment of normalized vascular intratumoral signal intensity as a predictor of histologic grade of astrocytic neoplasms.

Science.gov (United States)

Furtner, J; Schöpf, V; Schewzow, K; Kasprian, G; Weber, M; Woitek, R; Asenbaum, U; Preusser, M; Marosi, C; Hainfellner, J A; Widhalm, G; Wolfsberger, S; Prayer, D

2014-03-01

Pulsed arterial spin-labeling is a noninvasive MR imaging perfusion method performed with the use of water in the arterial blood as an endogenous contrast agent. The purpose of this study was to determine the inversion time with the largest difference in normalized intratumoral signal intensity between high-grade and low-grade astrocytomas. Thirty-three patients with gliomas, histologically classified as low-grade (n = 7) or high-grade astrocytomas (n = 26) according to the World Health Organization brain tumor classification, were included. A 3T MR scanner was used to perform pulsed arterial spin-labeling measurements at 8 different inversion times (370 ms, 614 ms, 864 ms, 1114 ms, 1364 ms, 1614 ms, 1864 ms, and 2114 ms). Normalized intratumoral signal intensity was calculated, which was defined by the signal intensity ratio of the tumor and the contralateral normal brain tissue for all fixed inversion times. A 3-way mixed ANOVA was used to reveal potential differences in the normalized vascular intratumoral signal intensity between high-grade and low-grade astrocytomas. The difference in normalized vascular intratumoral signal intensity between high-grade and low-grade astrocytomas obtained the most statistically significant results at 370 ms (P = .003, other P values ranged from .012-.955). The inversion time by which to differentiate high-grade and low-grade astrocytomas by use of normalized vascular intratumoral signal intensity was 370 ms in our study. The normalized vascular intratumoral signal intensity values at this inversion time mainly reflect the labeled intra-arterial blood bolus and therefore could be referred to as normalized vascular intratumoral signal intensity. Our data indicate that the use of normalized vascular intratumoral signal intensity values allows differentiation between low-grade and high-grade astrocytomas and thus may serve as a new, noninvasive marker for astrocytoma grading.

Intra-tumor heterogeneity in breast cancer has limited impact on transcriptomic-based molecular profiling.

Science.gov (United States)

Karthik, Govindasamy-Muralidharan; Rantalainen, Mattias; Stålhammar, Gustav; Lövrot, John; Ullah, Ikram; Alkodsi, Amjad; Ma, Ran; Wedlund, Lena; Lindberg, Johan; Frisell, Jan; Bergh, Jonas; Hartman, Johan

2017-11-29

Transcriptomic profiling of breast tumors provides opportunity for subtyping and molecular-based patient stratification. In diagnostic applications the specimen profiled should be representative of the expression profile of the whole tumor and ideally capture properties of the most aggressive part of the tumor. However, breast cancers commonly exhibit intra-tumor heterogeneity at molecular, genomic and in phenotypic level, which can arise during tumor evolution. Currently it is not established to what extent a random sampling approach may influence molecular breast cancer diagnostics. In this study we applied RNA-sequencing to quantify gene expression in 43 pieces (2-5 pieces per tumor) from 12 breast tumors (Cohort 1). We determined molecular subtype and transcriptomic grade for all tumor pieces and analysed to what extent pieces originating from the same tumors are concordant or discordant with each other. Additionally, we validated our finding in an independent cohort consisting of 19 pieces (2-6 pieces per tumor) from 6 breast tumors (Cohort 2) profiled using microarray technique. Exome sequencing was also performed on this cohort, to investigate the extent of intra-tumor genomic heterogeneity versus the intra-tumor molecular subtype classifications. Molecular subtyping was consistent in 11 out of 12 tumors and transcriptomic grade assignments were consistent in 11 out of 12 tumors as well. Molecular subtype predictions revealed consistent subtypes in four out of six patients in this cohort 2. Interestingly, we observed extensive intra-tumor genomic heterogeneity in these tumor pieces but not in their molecular subtype classifications. Our results suggest that macroscopic intra-tumoral transcriptomic heterogeneity is limited and unlikely to have an impact on molecular diagnostics for most patients.

Injection molded nanofluidic chips: Fabrication method and functional tests using single-molecule DNA experiments

DEFF Research Database (Denmark)

Utko, Pawel; Persson, Karl Fredrik; Kristensen, Anders

2011-01-01

We demonstrate that fabrication of nanofluidic systems can be greatly simplified by injection molding of polymers. We functionally test our devices by single-molecule DNA experiments in nanochannels.......We demonstrate that fabrication of nanofluidic systems can be greatly simplified by injection molding of polymers. We functionally test our devices by single-molecule DNA experiments in nanochannels....

Optimal sampling strategies to assess inulin clearance in children by the inulin single-injection method

NARCIS (Netherlands)

van Rossum, Lyonne K.; Mathot, Ron A. A.; Cransberg, Karlien; Vulto, Arnold G.

2003-01-01

Glomerular filtration rate in patients can be determined by estimating the plasma clearance of inulin with the single-injection method. In this method, a single bolus injection of inulin is administered and several blood samples are collected. For practical and convenient application of this method

Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing

DEFF Research Database (Denmark)

Gerlinger, Marco; Rowan, Andrew J.; Horswell, Stuart

2012-01-01

.RESULTS: Phylogenetic reconstruction revealed branched evolutionary tumor growth, with 63 to 69% of all somatic mutations not detectable across every tumor region. Intratumor heterogeneity was observed for a mutation within an autoinhibitory domain of the mammalian target of rapamycin (mTOR) kinase, correlating with S6...

Efficient spin-current injection in single-molecule magnet junctions

Directory of Open Access Journals (Sweden)

Haiqing Xie

2018-01-01

Full Text Available We study theoretically spin transport through a single-molecule magnet (SMM in the sequential and cotunneling regimes, where the SMM is weakly coupled to one ferromagnetic and one normal-metallic leads. By a master-equation approach, it is found that the spin polarization injected from the ferromagnetic lead is amplified and highly polarized spin-current can be generated, due to the exchange coupling between the transport electron and the anisotropic spin of the SMM. Moreover, the spin-current polarization can be tuned by the gate or bias voltage, and thus an efficient spin injection device based on the SMM is proposed in molecular spintronics.

Efficient spin-current injection in single-molecule magnet junctions

Science.gov (United States)

Xie, Haiqing; Xu, Fuming; Jiao, Hujun; Wang, Qiang; Liang, J.-Q.

2018-01-01

We study theoretically spin transport through a single-molecule magnet (SMM) in the sequential and cotunneling regimes, where the SMM is weakly coupled to one ferromagnetic and one normal-metallic leads. By a master-equation approach, it is found that the spin polarization injected from the ferromagnetic lead is amplified and highly polarized spin-current can be generated, due to the exchange coupling between the transport electron and the anisotropic spin of the SMM. Moreover, the spin-current polarization can be tuned by the gate or bias voltage, and thus an efficient spin injection device based on the SMM is proposed in molecular spintronics.

Quantitative Clinical Imaging Methods for Monitoring Intratumoral Evolution.

Science.gov (United States)

Kim, Joo Yeun; Gatenby, Robert A

2017-01-01

Solid tumors are multiscale, open, complex, dynamic systems: complex because they have many interacting components, dynamic because both the components and their interactions can change with time, and open because the tumor freely communicates with surrounding and even distant host tissue. Thus, it is not surprising that striking intratumoral variations are commonly observed in clinical imaging such as MRI and CT and that several recent studies found striking regional variations in the molecular properties of cancer cells from the same tumor. Interestingly, this spatial heterogeneity in molecular properties of tumor cells is typically ascribed to branching clonal evolution due to accumulating mutations while macroscopic variations observed in, for example, clinical MRI scans are usually viewed as functions of blood flow. The clinical significance of spatial heterogeneity has not been fully determined but there is a general consensus that the varying intratumoral landscape along with patient factors such as age, morbidity and lifestyle, contributes significantly to the often unpredictable response of individual patients within a disease cohort treated with the same standard-of-care therapy.Here we investigate the potential link between macroscopic tumor heterogeneity observed by clinical imaging and spatial variations in the observed molecular properties of cancer cells. We build on techniques developed in landscape ecology to link regional variations in the distribution of species with local environmental conditions that define their habitat. That is, we view each region of the tumor as a local ecosystem consisting of environmental conditions such as access to nutrients, oxygen, and means of waste clearance related to blood flow and the local population of tumor cells that both adapt to these conditions and, to some extent, change them through, for example, production of angiogenic factors. Furthermore, interactions among neighboring habitats can produce broader

Rapid dual-injection single-scan 13N-ammonia PET for quantification of rest and stress myocardial blood flows

International Nuclear Information System (INIS)

Rust, T C; DiBella, E V R; McGann, C J; Christian, P E; Hoffman, J M; Kadrmas, D J

2006-01-01

Quantification of myocardial blood flows at rest and stress using 13 N-ammonia PET is an established method; however, current techniques require a waiting period of about 1 h between scans. The objective of this study was to test a rapid dual-injection single-scan approach, where 13 N-ammonia injections are administered 10 min apart during rest and adenosine stress. Dynamic PET data were acquired in six human subjects using imaging protocols that provided separate single-injection scans as gold standards. Rest and stress data were combined to emulate rapid dual-injection data so that the underlying activity from each injection was known exactly. Regional blood flow estimates were computed from the dual-injection data using two methods: background subtraction and combined modelling. The rapid dual-injection approach provided blood flow estimates very similar to the conventional single-injection standards. Rest blood flow estimates were affected very little by the dual-injection approach, and stress estimates correlated strongly with separate single-injection values (r = 0.998, mean absolute difference = 0.06 ml min -1 g -1 ). An actual rapid dual-injection scan was successfully acquired in one subject and further demonstrates feasibility of the method. This study with a limited dataset demonstrates that blood flow quantification can be obtained in only 20 min by the rapid dual-injection approach with accuracy similar to that of conventional separate rest and stress scans. The rapid dual-injection approach merits further development and additional evaluation for potential clinical use

Tunneling spin injection into single layer graphene.

Science.gov (United States)

Han, Wei; Pi, K; McCreary, K M; Li, Yan; Wong, Jared J I; Swartz, A G; Kawakami, R K

2010-10-15

We achieve tunneling spin injection from Co into single layer graphene (SLG) using TiO₂ seeded MgO barriers. A nonlocal magnetoresistance (ΔR(NL)) of 130  Ω is observed at room temperature, which is the largest value observed in any material. Investigating ΔR(NL) vs SLG conductivity from the transparent to the tunneling contact regimes demonstrates the contrasting behaviors predicted by the drift-diffusion theory of spin transport. Furthermore, tunnel barriers reduce the contact-induced spin relaxation and are therefore important for future investigations of spin relaxation in graphene.

Limited utility of tissue micro-arrays in detecting intra-tumoral heterogeneity in stem cell characteristics and tumor progression markers in breast cancer.

Science.gov (United States)

Kündig, Pascale; Giesen, Charlotte; Jackson, Hartland; Bodenmiller, Bernd; Papassotirolopus, Bärbel; Freiberger, Sandra Nicole; Aquino, Catharine; Opitz, Lennart; Varga, Zsuzsanna

2018-05-08

Intra-tumoral heterogeneity has been recently addressed in different types of cancer, including breast cancer. A concept describing the origin of intra-tumoral heterogeneity is the cancer stem-cell hypothesis, proposing the existence of cancer stem cells that can self-renew limitlessly and therefore lead to tumor progression. Clonal evolution in accumulated single cell genomic alterations is a further possible explanation in carcinogenesis. In this study, we addressed the question whether intra-tumoral heterogeneity can be reliably detected in tissue-micro-arrays in breast cancer by comparing expression levels of conventional predictive/prognostic tumor markers, tumor progression markers and stem cell markers between central and peripheral tumor areas. We analyzed immunohistochemical expression and/or gene amplification status of conventional prognostic tumor markers (ER, PR, HER2, CK5/6), tumor progression markers (PTEN, PIK3CA, p53, Ki-67) and stem cell markers (mTOR, SOX2, SOX9, SOX10, SLUG, CD44, CD24, TWIST) in 372 tissue-micro-array samples from 72 breast cancer patients. Expression levels were compared between central and peripheral tumor tissue areas and were correlated to histopathological grading. 15 selected cases additionally underwent RNA sequencing for transcriptome analysis. No significant difference in any of the analyzed between central and peripheral tumor areas was seen with any of the analyzed methods/or results that showed difference. Except mTOR, PIK3CA and SOX9 (nuclear) protein expression, all markers correlated significantly (p < 0.05) with histopathological grading both in central and peripheral areas. Our results suggest that intra-tumoral heterogeneity of stem-cell and tumor-progression markers cannot be reliably addressed in tissue-micro-array samples in breast cancer. However, most markers correlated strongly with histopathological grading confirming prognostic information as expression profiles were independent on the site of the

Experimental investigations of a single cylinder genset engine with common rail fuel injection system

Directory of Open Access Journals (Sweden)

Gupta Paras

2014-01-01

Full Text Available Performance and emissions characteristics of compression ignition (CI engines are strongly dependent on quality of fuel injection. In an attempt to improve engine combustion, engine performance and reduce the exhaust emissions from a single cylinder constant speed genset engine, a common rail direct injection (CRDI fuel injection system was deployed and its injection timings were optimized. Results showed that 34°CA BTDC start of injection (SOI timings result in lowest brake specific fuel consumption (BSFC and smoke opacity. Advanced injection timings showed higher cylinder peak pressure, pressure rise rate, and heat release rate due to relatively longer ignition delay experienced.

Effects of Stator Shroud Injection on the Aerodynamic Performance of a Single-Stage Transonic Axial Compressor

Energy Technology Data Exchange (ETDEWEB)

Dinh, Cong-Truong; Ma, Sang-Bum; Kim, Kwang Yong [Inha Univ., Incheon (Korea, Republic of)

2017-01-15

In this study, stator shroud injection in a single-stage transonic axial compressor is proposed. A parametric study of the effect of stator shroud injection on aerodynamic performances was conducted using the three-dimensional Reynolds-averaged Navier-Stokes equations. The curvature, length, width, and circumferential angle of the stator shroud injector and the air injection mass flow rate were selected as the test parameters. The results of the parametric study show that the aerodynamic performances of the single-stage transonic axial compressor were improved by stator shroud injection. The aerodynamic performances were the most sensitive to the injection mass flow rate. Further, the total pressure ratio and adiabatic efficiency were the maximum when the ratio of circumferential angle was 10%.

Effects of Stator Shroud Injection on the Aerodynamic Performance of a Single-Stage Transonic Axial Compressor

International Nuclear Information System (INIS)

Dinh, Cong-Truong; Ma, Sang-Bum; Kim, Kwang Yong

2017-01-01

In this study, stator shroud injection in a single-stage transonic axial compressor is proposed. A parametric study of the effect of stator shroud injection on aerodynamic performances was conducted using the three-dimensional Reynolds-averaged Navier-Stokes equations. The curvature, length, width, and circumferential angle of the stator shroud injector and the air injection mass flow rate were selected as the test parameters. The results of the parametric study show that the aerodynamic performances of the single-stage transonic axial compressor were improved by stator shroud injection. The aerodynamic performances were the most sensitive to the injection mass flow rate. Further, the total pressure ratio and adiabatic efficiency were the maximum when the ratio of circumferential angle was 10%.

Performance characterization of pneumatic single pellet injection system

International Nuclear Information System (INIS)

Schuresko, D.D.; Milora, S.L.; Hogan, J.T.; Foster, C.A.; Combs, S.K.

1982-01-01

The Oak Ridge National Laboratory single-shot pellet injector, which has been used in plasma fueling experiments on ISX and PDX, has been upgraded and extensively instrumented in order to study the gas dynamics of pneumatic pellet injection. An improved pellet transport line was developed which utilizes a 0.3-cm-diam by 100-cm-long guide tube. Pellet gun performance was characterized by measurements of breech and muzzle dynamic pressures and by pellet velocity and mass determinations. Velocities up to 1.4 km/s were achieved for intact hydrogen pellets using hydrogen propellant at 5-MPa breech pressure. These data have been compared with new pellet acceleration calculations which include the effects of propellant friction, heat transfer, time-dependent boundary conditions, and finite gun geometry. These results provide a basis for the extrapolation of present-day pneumatic injection system performance to velocities in excess of 2 km/s

Performance characterization of pneumatic single pellet injection system

International Nuclear Information System (INIS)

Schuresko, D.D.; Milora, S.L.; Hogan, J.T.; Foster, C.A.; Combs, S.K.

1983-01-01

The Oak Ridge National Laboratory single-shot pellet injector, which has been used in plasma fueling experiments on ISX and PDX, has been upgraded and extensively instrumented in order to study the gas dyamics of pneumatic pellet injection. An improved pellet transport line was developed which utilizes a 0.3-cm-diam by 100-cm-long guide tube. Pellet gun performance was characterized by measurements of breech and muzzle dynamic pressures and by pellet velocity and mass determinations. Velocities of up to 1.4 km/s were achieved for intact hydrogen pellets using hydrogen propellant at 5-MPa breech pressure. These data have been compared with new pellet acceleration calculations which include the effects of propellant friction, heat transfer, time-dependent boundary conditions, and finite gun geometry. These results provide a basis for the extrapolation of present-day pneumatic injection system performance to velocities in excess of 2 km/s

Influence of intra-tumoral heterogeneity on the evaluation of BCL2, E-cadherin, EGFR, EMMPRIN, and Ki-67 expression in tissue microarrays from breast cancer.

Science.gov (United States)

Tramm, Trine; Kyndi, Marianne; Sørensen, Flemming B; Overgaard, Jens; Alsner, Jan

2018-01-01

The influence of intra-tumoral heterogeneity on the evaluation of immunohistochemical (IHC) biomarker expression may affect the analytical validity of new biomarkers substantially and hence compromise the clinical utility. The aim of this study was to examine the influence of intra-tumoral heterogeneity as well as inter-observer variability on the evaluation of various IHC markers with potential prognostic impact in breast cancer (BCL2, E-cadherin, EGFR, EMMPRIN and Ki-67). From each of 27 breast cancer patients, two tumor-containing paraffin blocks were chosen. Intra-tumoral heterogeneity was evaluated (1) within a single tumor-containing paraffin block ('intra-block agreement') by comparing information from a central, a peripheral tissue microarray (TMA) core and a whole slide section (WS), (2) between two different tumor-containing blocks from the same primary tumor ('inter-block agreement') by comparing information from TMA cores (central/peripheral) and WS. IHC markers on WS and TMA cores were evaluated by two observers independently, and agreements were estimated by Kappa statistics. For BCL2, E-cadherin and EGFR, an almost perfect intra- and inter-block agreement was found. EMMPRIN and Ki-67 showed a more heterogeneous expression with moderate to substantial intra-block agreements. For both stainings, there was a moderate inter-block agreement that improved slightly for EMMPRIN, when using WS instead of TMA cores. Inter-observer agreements were found to be almost perfect for BCL2, E-cadherin and EGFR (WS: κ > 0.82, TMAs: κ > 0.90), substantial for EMMPRIN (κ > 0.63), but only fair to moderate for Ki-67 (WS: κ = 0.54, TMAs: κ = 0.33). BCL2, E-cadherin and EGFR were found to be homogeneously expressed, whereas EMMPRIN and Ki-67 showed a more pronounced degree of intra-tumoral heterogeneity. The results emphasize the importance of securing the analytical validity of new biomarkers by examining the intra-tumoral heterogeneity of

Successful treatment of unicameral bone cyst by single percutaneous injection of alpha-BSM.

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Thawrani, Dinesh; Thai, Chia Che; Welch, Robert D; Copley, Lawson; Johnston, Charles E

2009-01-01

Unicameral bone cyst (UBC) is a benign bone lesion, recognized for its high rate of recurrence and need for repeat procedures to achieve healing. We hypothesized that the osteoconductive material apatitic calcium phosphate (alpha-BSM) could be effective in filling and stimulating resolution of UBC. The purpose of this study was to evaluate clinical and radiographic outcomes of UBC treated by a single injection of alpha-BSM. Thirteen patients (6 male, 7 female) with a mean age of 10.5 years, underwent single percutaneous injection of alpha-BSM for presumed UBC. The aspiration of the cysts was followed by vigorous saline lavage using 2 wide bore needles to disrupt the cyst walls. alpha-BSM "paste" was then injected under fluoroscopic guidance. Radiographs were digitized to measure cystic area (millimeter squares) on 2 orthogonal views. Healing was rated according to a modified Neer outcome grading system. Nine of the 13 patients had had pathologic fractures in the past. Eleven of the 13 patients had had past unsuccessful treatment: multiple steroid injections in 6, curettage and bone grafting in 3, and bone marrow and demineralized bone matrix (Grafton) injection in 2. Five cysts were grade 1 (healed 100%), 6 grade 2 (healed >50%), 2 grade 3 (healed <50% with increased cortical thickness), and none grade 4 (recurrence/enlargement). The average resolution of cystic area in 11/13 cysts was 85.7% at final follow-up of 35.8 months (P=0.0001) with 2.8 mm of average gain in cortical thickness (P=0.0018). None of the 13 lesions required an additional procedure or repeat injection. All patients were clinically asymptomatic at latest follow-up. This is the first study quantifying cyst resolution objectively according to actual decrease in area (millimeter squares). A single injection of alpha-BSM is a safe, minimally invasive and efficacious method to treat UBC in the pediatric population.

Single-use autoinjector for once-weekly intramuscular injection of IFNβ-1a.

Science.gov (United States)

Limmroth, Volker; Gerbershagen, Kathrin

2014-12-01

IFNβ products and glatiramer acetate are established treatment first-line options in long-term disease-modifying therapy of multiple sclerosis (MS). These self-injectable medications are used once weekly to once daily. Injection-related issues are common patient-cited reasons for nonadherence. Autoinjectors have been shown to support long-term adherence to injectable medications. The ability to self-inject in MS patients has been associated with a reduced risk of missed injections and drug discontinuation, and a beneficial effect on patient independence. The recently introduced easy-to-use prefilled once-weekly pen is a safe and effective device for intramuscular (IM) IFNβ-1a application and provides a convenient method for self-injection. We reviewed the available published evidence on the characteristics of this device. The once-weekly pen facilitates self-injection and was preferred over prefilled syringes by patients in a prospective open-label, multicenter Phase IIIb trial in MS patients who had been using IM IFNβ-1a in prefilled syringes. The simple and safe handling, shielded short needle, single-use disposable design and virtually painless injection by the device may contribute to adherence, quality of life and independence in patients using IM IFNβ-1a.

Single intra-articular injection of high molecular weight hyaluronic acid for hip osteoarthritis.

Science.gov (United States)

Rivera, Fabrizio

2016-03-01

Intra-articular (IA) injection of hyaluronic acid (HA) into the hip joint appears to be safe and well tolerated but only a small number of randomized clinical trials in humans has been published. The objective of this prospective study was to evaluate the efficacy and safety of a single IA injection of high-molecular-weight (2800 kDa) HA (Coxarthrum) for hip osteoarthritis. All patients received a single IA administration of 2.5 % sodium hyaluronate (75 mg/3 mL) of high molecular weight. Fluoroscopy requires an iodized contrast medium (iopamidol, 1 ml) which highlights the capsule before administering HA. Patients were evaluated before IA injection (T0), after 3 months, after 6 months and after 1 year from injection. Results were evaluated by the Brief Pain Inventory (BPI II), Harris Hip Score and a visual analog scale of pain (pain VAS). All treated patients were considered for statistical analysis. Two hundred seven patients were included at T0. The mean age was 67 years (range 46-81). Regarding BPI severity score, changes in pain between T0 and the three following visits were statistically highly significant (p injection of Coxarthrum is effective from the third month and that the results are stable or continue to improve up to 1 year. IV.

Locally disordered methylation forms the basis of intratumor methylome variation in chronic lymphocytic leukemia.

Science.gov (United States)

Landau, Dan A; Clement, Kendell; Ziller, Michael J; Boyle, Patrick; Fan, Jean; Gu, Hongcang; Stevenson, Kristen; Sougnez, Carrie; Wang, Lili; Li, Shuqiang; Kotliar, Dylan; Zhang, Wandi; Ghandi, Mahmoud; Garraway, Levi; Fernandes, Stacey M; Livak, Kenneth J; Gabriel, Stacey; Gnirke, Andreas; Lander, Eric S; Brown, Jennifer R; Neuberg, Donna; Kharchenko, Peter V; Hacohen, Nir; Getz, Gad; Meissner, Alexander; Wu, Catherine J

2014-12-08

Intratumoral heterogeneity plays a critical role in tumor evolution. To define the contribution of DNA methylation to heterogeneity within tumors, we performed genome-scale bisulfite sequencing of 104 primary chronic lymphocytic leukemias (CLLs). Compared with 26 normal B cell samples, CLLs consistently displayed higher intrasample variability of DNA methylation patterns across the genome, which appears to arise from stochastically disordered methylation in malignant cells. Transcriptome analysis of bulk and single CLL cells revealed that methylation disorder was linked to low-level expression. Disordered methylation was further associated with adverse clinical outcome. We therefore propose that disordered methylation plays a similar role to that of genetic instability, enhancing the ability of cancer cells to search for superior evolutionary trajectories. Copyright © 2014 Elsevier Inc. All rights reserved.

Intratumoral Delivery of Doxorubicin on Folate-Conjugated Graphene Oxide by In-Situ Forming Thermo-Sensitive Hydrogel for Breast Cancer Therapy

Directory of Open Access Journals (Sweden)

Yi Teng Fong

2017-11-01

Full Text Available By taking advantage of the pH-sensitive drug release property of graphene oxide (GO after intracellular uptake, we prepared folic acid (FA-conjugated GO (GOFA for targeted delivery of the chemotherapeutic drug doxorubicin (DOX. GOFA-DOX was further encapsulated in an injectable in-situ forming thermo-sensitive hyaluronic acid-chitosan-g-poly(N-isopropylacrylamide (HACPN hydrogel for intratumoral delivery of DOX. As the degradation time of HACPN could be extended up to 3 weeks, intratumoral delivery of GOFA-DOX/HACPN could provide controlled and targeted delivery of DOX through slow degradation HACPN and subsequent cellular uptake of released GOFA-DOX by tumor cells through interactions of GOFA with folate receptors on the tumor cell’s surface. GOFA nano-carrier and HACPN hydrogel were first characterized for the physico-chemical properties. The drug loading experiments indicated the best preparation condition of GOFA-DOX was by reacting 0.1 mg GOFA with 2 mg DOX. GOFA-DOX showed pH-responsive drug release with ~5 times more DOX released at pH 5.5 than at pH 7.4 while only limited DOX was released from GOFA-DOX/HACPN at pH 7.4. Intracellular uptake of GOFA by endocytosis and release of DOX from GOFA-DOX in vitro could be confirmed from transmission electron microscopic and confocal laser scanning microscopic analysis with MCF-7 breast cancer cells. The targeting effect of FA was revealed when intracellular uptake of GOFA was blocked by excess FA. This resulted in enhanced in vitro cytotoxicity as revealed from the lower half maximal inhibitory concentration (IC50 value of GOFA-DOX (7.3 μg/mL compared with that of DOX (32.5 μg/mL and GO-DOX (10 μg/mL. The flow cytometry analysis indicated higher apoptosis rates for cells treated with GOFA-DOX (30% compared with DOX (8% and GO-DOX (11%. Animal studies were carried out with subcutaneously implanted MCF-7 cells in BALB/c nude mice and subject to intratumoral administration of drugs. The relative

MO-FG-BRA-01: Development of An Image-Guided Dosimetric Planning System for Injectable Brachytherapy Using ELP Nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Lafata, K [Duke University, Durham, North Carolina (United States); Duke University Medical Center, Durham, NC (United States); Schaal, J; Liu, W [Duke University, Durham, North Carolina (United States); Cai, J [Duke University Medical Center, Durham, NC (United States)

2015-06-15

Purpose: To develop, validate, and evaluate a methodology for determining dosimetry for intratumoral injections of elastin-like-polypeptide (ELP) brachytherapy nanoparticles. These organic-polymer-based nanoparticles are injectable, biodegradable, and genetically tunable. We present a genetically encoded polymer-solution, composed of novel radiolabeled-ELP nanoparticles that are custom-designed to self-assemble into a local source upon intratumoral injection. Our preliminary results of a small animal study demonstrate 100% tumor response, effective radionuclide retention-rates, strong in vivo stability, and no polymer-induced toxicities. While our approach is therefore highly promising for improved brachytherapy, the current workflow lacks a dosimetry framework. Methods: We are developing a robust software framework that provides image-guided dosimetric-planning capabilities for ELP brachytherapy. The user graphically places ELP injection sites within a µCT-planning-image, and independently defines each injection volume, concentration, and radioisotope to be used. The resulting internal dosimetry is then pre-determined by first modeling post-injection ELP advection-diffusion, and then calculating the resulting dose distribution based on a point- dose-kernel-convolution algorithm. We have experimentally measured ELP steady-state concentrations via µSPECT acquisition, and validated our dose calculation algorithm against Monte Carlo simulations of several radioactivity distributions. Finally, we have investigated potential advantages and limitations of various ELP injection parameters. Results: The µSPECT results demonstrated inhomogeneous steady-state distributions of ELP in tissue, and Monte Carlo radioactivity distributions were designed accordingly. Our algorithm yielded a root-mean-square-error of less than 2% for each distribution tested (average root-mean-square-error was 0.73%). Dose-Volume-Histogram analysis of five different plans showed how strategic

Radiation Dosimetry of Intratumoral Injection of Radionuclides into Human Breast Cancer. Revision

Science.gov (United States)

2007-07-01

products will be eliminated by nuclear decay in storage behind lead bricks for at least 4 weeks. The synthesis and testing procedures typically last 80...to be sensitive to T2*. Injection may be preceded with surface or subcutaneous local anesthesia (1cc of 4% lidocaine , if the patient has no...history of allergy or adverse reactions to lidocaine ; otherwise, an alternative local anesthetics will be used) at the needle entrance through the surface

Injection of a single electron from static to moving quantum dots.

Science.gov (United States)

Bertrand, Benoit; Hermelin, Sylvain; Mortemousque, Pierre-André; Takada, Shintaro; Yamamoto, Michihisa; Tarucha, Seigo; Ludwig, Arne; Wieck, Andreas D; Bäuerle, Christopher; Meunier, Tristan

2016-05-27

We study the injection mechanism of a single electron from a static quantum dot into a moving quantum dot. The moving quantum dots are created with surface acoustic waves (SAWs) in a long depleted channel. We demonstrate that the injection process is characterized by an activation law with a threshold that depends on the SAW amplitude and on the dot-channel potential gradient. By sufficiently increasing the SAW modulation amplitude, we can reach a regime where the transfer has unity probability and is potentially adiabatic. This study points to the relevant regime to use moving dots in quantum information protocols.

Use and safety of intratumoral application of European mistletoe (Viscum album L) preparations in Oncology.

Science.gov (United States)

Steele, Megan L; Axtner, Jan; Happe, Antje; Kröz, Matthias; Matthes, Harald; Schad, Friedemann

2015-03-01

Intratumoral (IT) injection of European mistletoe (Viscum album L) preparations might induce local tumor response through combined cytotoxic and immunomodulatory actions of the preparations. Although promising in vitro and in vivo data, along with clinical case studies suggest the need for validation of this hypothesis in prospective trials, the safety of IT mistletoe injections has yet to be thoroughly assessed. The present study summarizes the practice and safety of off-label IT mistletoe therapy within the Network Oncology, a conjoint clinical registry of German hospitals and outpatients specialized in anthroposophic and integrative medicine. Demographic, diagnosis and treatment data of cancer patients who received IT mistletoe applications between 2007 and 2013 were assessed. Suspected adverse drug reactions (ADRs) were analyzed in terms of type, frequency, severity, seriousness and potential risk factors. A total of 123 cancer patients received 862 IT mistletoe injections (preparations from Abnoba, Helixor and Iscucin). The most commonly applied preparations were Abnoba viscum Fraxini (71 patients) and Helixor Mali (54 patients). Of the total patients, 26 patients (21.1%) experienced 74 ADRs. All ADRs were in response to either Abnoba viscum Fraxini (25.4% of exposed patients) or Helixor Mali (18.5% of exposed patients). ADRs were mostly body temperature or immune related and of mild (83.8%) or moderate (14.9%) intensity. Only one possible ADR was described as severe (hypertension) and no serious ADRs occurred. The frequency of ADRs to IT mistletoe injections was 3 times and 5 times higher than has previously been found for subcutaneous and intravenous applications of mistletoe, respectively. IT injection of mistletoe preparations resulted in a relatively high frequency of ADRs. Nearly all ADRs were mild to moderate however, and no serious ADRs occurred. Furthermore, it is possible that immune-related ADRs such as pyrexia and local inflammatory reactions might

Intratumor cholesteryl ester accumulation is associated with human breast cancer proliferation and aggressive potential: a molecular and clinicopathological study

International Nuclear Information System (INIS)

a Claret, 167 08025, Barcelona (Spain))" data-affiliation=" (Cardiovascular Research Center, CSIC-ICCC, IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, Sant Antoni Ma Claret, 167 08025, Barcelona (Spain))" >Gonzalo-Calvo, David de; López-Vilaró, Laura; a Claret, 167 08025, Barcelona (Spain))" data-affiliation=" (Cardiovascular Research Center, CSIC-ICCC, IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, Sant Antoni Ma Claret, 167 08025, Barcelona (Spain))" >Nasarre, Laura; Perez-Olabarria, Maitane; Vázquez, Tania; Escuin, Daniel; a Claret, 167 08025, Barcelona (Spain))" data-affiliation=" (Cardiovascular Research Center, CSIC-ICCC, IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, Sant Antoni Ma Claret, 167 08025, Barcelona (Spain))" >Badimon, Lina; Barnadas, Agusti; Lerma, Enrique; a Claret, 167 08025, Barcelona (Spain))" data-affiliation=" (Cardiovascular Research Center, CSIC-ICCC, IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, Sant Antoni Ma Claret, 167 08025, Barcelona (Spain))" >Llorente-Cortés, Vicenta

2015-01-01

The metabolic effect of intratumor cholesteryl ester (CE) in breast cancer remains poorly understood. The objective was to analyze the relationship between intratumor CE content and clinicopathological variables in human breast carcinomas. We classified 30 breast carcinoma samples into three subgroups: 10 luminal-A tumors (ER+/PR+/Her2-), 10 Her-2 tumors (ER-/PR-/Her2+), and 10 triple negative (TN) tumors (ER-/PR-/Her2-). We analyzed intratumor neutral CE, free cholesterol (FC) and triglyceride (TG) content by thin layer chromatography after lipid extraction. RNA and protein levels of lipid metabolism and invasion mediators were analyzed by real time PCR and Western blot analysis. Group-wise comparisons, linear regression and logistic regression models showed a close association between CE-rich tumors and higher histologic grade, Ki-67 and tumor necrosis. CE-rich tumors displayed higher mRNA and protein levels of low-density lipoprotein receptor (LDLR) and scavenger receptor class B member 1 (SCARB1). An increased expression of acetyl-Coenzyme A acetyltransferase 1 (ACAT1) in CE-rich tumors was also reported. Intratumor CE accumulation is intimately linked to proliferation and aggressive potential of breast cancer tumors. Our data support the link between intratumor CE content and poor clinical outcome and open the door to new antitumor interventions. The online version of this article (doi:10.1186/s12885-015-1469-5) contains supplementary material, which is available to authorized users

High resolution SPECT imaging for visualization of intratumoral heterogeneity using a SPECT/CT scanner dedicated for small animal imaging

International Nuclear Information System (INIS)

Umeda, Izumi O.; Tani, Kotaro; Tsuda, Keisuke

2012-01-01

Tumor interiors are never homogeneous and in vivo visualization of intratumoral heterogeneity would be an innovation that contributes to improved cancer therapy. But, conventional nuclear medicine tests have failed to visualize heterogeneity in vivo because of limited spatial resolution. Recently developed single photon emission computed tomographic (SPECT) scanners dedicated for small animal imaging are of interest due to their excellent spatial resolution of 111 In and simulations of actual small animal imaging. The optimal conditions obtained were validated by in vivo imaging of sarcoma 180-bearing mice. Larger number of counts must be obtained within limited acquisition time to visualize tumor heterogeneity in vivo in animal imaging, compared to cases that simply detect tumors. At an acquisition time of 30 min, better image quality was obtained with pinhole apertures diameter of 1.4 mm than of 1.0 mm. The obtained best spatial resolution was 1.3 mm, it was acceptable for our purpose, though a little worse than the best possible performance of the scanner (1.0 mm). Additionally, the reconstruction parameters, such as noise suppression, voxel size, and iteration/subset number, needed to be optimized under the limited conditions and were different from those found under the ideal condition. The minimal radioactivity concentration for visualization of heterogeneous tumor interiors was estimated to be as high as 0.2-0.5 MBq/mL. Liposomes containing 111 In met this requirement and were administered to tumor-bearing mice. SPECT imaging successfully showed heterogeneous 111 In distribution within the tumors in vivo with good spatial resolution. A threshold of 0.2 MBq/g for clear visualization of tumor heterogeneity was validated. Autoradiograms obtained ex vivo of excised tumors confirmed that the in vivo SPECT images accurately depicted the heterogeneous intratumoral accumulation of liposomes. Intratumoral heterogeneity was successfully visualized under the optimized

Locally disordered methylation forms the basis of intra-tumor methylome variation in chronic lymphocytic leukemia

Science.gov (United States)

Landau, Dan A.; Clement, Kendell; Ziller, Michael J.; Boyle, Patrick; Fan, Jean; Gu, Hongcang; Stevenson, Kristen; Sougnez, Carrie; Wang, Lili; Li, Shuqiang; Kotliar, Dylan; Zhang, Wandi; Ghandi, Mahmoud; Garraway, Levi; Fernandes, Stacey M.; Livak, Kenneth J.; Gabriel, Stacey; Gnirke, Andreas; Lander, Eric S.; Brown, Jennifer R.; Neuberg, Donna; Kharchenko, Peter V.; Hacohen, Nir; Getz, Gad; Meissner, Alexander; Wu, Catherine J.

2014-01-01

SUMMARY Intra-tumoral heterogeneity plays a critical role in tumor evolution. To define the contribution of DNA methylation to heterogeneity within tumors, we performed genome-scale bisulfite sequencing of 104 primary chronic lymphocytic leukemias (CLL). Compared to 26 normal B cell samples, CLLs consistently displayed higher intra-sample variability of DNA methylation patterns across the genome, which appears to arise from stochastically disordered methylation in malignant cells. Transcriptome analysis of bulk and single CLL cells revealed that methylation disorder was linked to low-level expression. Disordered methylation was further associated with adverse clinical outcome. We therefore propose that disordered methylation plays a similar role to genetic instability, enhancing the ability of cancer cells to search for superior evolutionary trajectories. PMID:25490447

Prognostic value of podoplanin expression in intratumoral stroma and neoplastic cells of uterine cervical carcinomas

Science.gov (United States)

Carvalho, Filomena M; Zaganelli, Fabricia L; Almeida, Bernardo G L; Goes, Joao Carlos Sampaio; Baracat, Edmund C; Carvalho, Jesus P

2010-01-01

OBJECTIVE: To investigate the clinicopathological significance of podoplanin expression in the intratumoral stroma and neoplastic cells of early stage uterine cervical cancer. MATERIALS AND METHODS: A total of 143 patients with clinical stage I and IIA uterine cervical carcinomas underwent surgery between 2000 and 2007. Clinicopathological data and slides associated with these cases were retrospectively reviewed. Immunodetection of podoplanin expression in histologic sections of tissue microarray blocks was performed using the monoclonal antibody D2‐40. RESULTS: Expression of podoplanin was detected in neoplastic cells in 31/143 (21.6%) cases, with 29/31 (93.5%) of these cases diagnosed as squamous carcinoma. For all of the cases examined, the strongest signal for podoplanin expression was observed at the proliferating edge of the tumor nests. The rate of positive podoplanin expression for node‐positive cases was lower than that of node‐negative (18.9% vs. 22.6%, respectively). Furthermore, the rate of positive podoplanin expression in fatal cases was 10.5% vs. 21.6%, respectively. In 27/143 (18.8%) cases, podoplanin expression was detected in fibroblasts of the intratumoral stroma, and this expression did not correlate with patient age, clinical stage, tumor size, histologic type, depth of infiltration, or vascular involvement. Moreover, expression of podoplanin in intratumoral stroma fibroblasts was only negatively associated with nodal metastasis. A greater number of fatal cases was observed among negative intratumoral stroma fibroblasts (15.5% vs. 3.7%, respectively), although this difference was not significant. CONCLUSIONS: These preliminary results suggest that podoplanin may have a role in host‐tumor interactions and, as a result, may represent a favorable prognostic factor for squamous cervical carcinomas. PMID:21340215

Prognostic value of podoplanin expression in intratumoral stroma and neoplastic cells of uterine cervical carcinomas

Directory of Open Access Journals (Sweden)

Filomena M Carvalho

2010-01-01

Full Text Available OBJECTIVE: To investigate the clinicopathological significance of podoplanin expression in the intratumoral stroma and neoplastic cells of early stage uterine cervical cancer. MATERIALS AND METHODS: A total of 143 patients with clinical stage I and IIA uterine cervical carcinomas underwent surgery between 2000 and 2007. Clinicopathological data and slides associated with these cases were retrospectively reviewed. Immunodetection of podoplanin expression in histologic sections of tissue microarray blocks was performed using the monoclonal antibody D2-40. RESULTS: Expression of podoplanin was detected in neoplastic cells in 31/143 (21.6% cases, with 29/31 (93.5% of these cases diagnosed as squamous carcinoma. For all of the cases examined, the strongest signal for podoplanin expression was observed at the proliferating edge of the tumor nests. The rate of positive podoplanin expression for node-positive cases was lower than that of node-negative (18.9% vs. 22.6%, respectively. Furthermore, the rate of positive podoplanin expression in fatal cases was 10.5% vs. 21.6%, respectively. In 27/143 (18.8% cases, podoplanin expression was detected in fibroblasts of the intratumoral stroma, and this expression did not correlate with patient age, clinical stage, tumor size, histologic type, depth of infiltration, or vascular involvement. Moreover, expression of podoplanin in intratumoral stroma fibroblasts was only negatively associated with nodal metastasis. A greater number of fatal cases was observed among negative intratumoral stroma fibroblasts (15.5% vs. 3.7%, respectively, although this difference was not significant. CONCLUSIONS: These preliminary results suggest that podoplanin may have a role in host-tumor interactions and, as a result, may represent a favorable prognostic factor for squamous cervical carcinomas.

Intratumoral heterogeneity as a confounding factor in clonogenic assays for tumour radioresponsiveness

International Nuclear Information System (INIS)

Britten, R.A.; Evans, A.J.; Allalunis-Turner, M.J.; Franko, A.J.; Pearcey, R.G.

1996-01-01

The level of intra-tumoral heterogeneity of cellular radiosensitivity within primary cultures of three carcinomas of the cervix has been established. All three cultures contained clones that varied by as much as 3-fold in their clinically relevant radiosensitivity (SF 2 ). The level of intra-tumoral heterogeneity observed in these cervical tumour cultures was sufficient to be a major confounding factor to the use of pre-treatment assessments of radiosensitivity to predict for clinical radioresponsiveness. Mathematical modeling of the relative elimination of the tumour clones during fractionated radiotherapy indicates that, in two of the three biopsy samples, the use of pre-treatment derived SF 2 values from the heterogeneous tumour sample would significantly overestimate radioresponsiveness. We conclude that assays of cellular radiosensitivity that identify the radiosensitivity of the most radioresistant clones and measure their relative abundance could potentially increase the effectiveness of SF 2 values as a predictive marker of radioresponsiveness

Vectorization in an oncolytic vaccinia virus of an antibody, a Fab and a scFv against programmed cell death -1 (PD-1) allows their intratumoral delivery and an improved tumor-growth inhibition.

Science.gov (United States)

Kleinpeter, Patricia; Fend, Laetitia; Thioudellet, Christine; Geist, Michel; Sfrontato, Nathalie; Koerper, Véronique; Fahrner, Catherine; Schmitt, Doris; Gantzer, Murielle; Remy-Ziller, Christelle; Brandely, Renée; Villeval, Dominique; Rittner, Karola; Silvestre, Nathalie; Erbs, Philippe; Zitvogel, Laurence; Quéméneur, Eric; Préville, Xavier; Marchand, Jean-Baptiste

2016-01-01

We report here the successful vectorization of a hamster monoclonal IgG (namely J43) recognizing the murine Programmed cell death-1 (mPD-1) in Western Reserve (WR) oncolytic vaccinia virus. Three forms of mPD-1 binders have been inserted into the virus: whole antibody (mAb), Fragment antigen-binding (Fab) or single-chain variable fragment (scFv). MAb, Fab and scFv were produced and assembled with the expected patterns in supernatants of cells infected by the recombinant viruses. The three purified mPD-1 binders were able to block the binding of mPD-1 ligand to mPD-1 in vitro . Moreover, mAb was detected in tumor and in serum of C57BL/6 mice when the recombinant WR-mAb was injected intratumorally (IT) in B16F10 and MCA 205 tumors. The concentration of circulating mAb detected after IT injection was up to 1,900-fold higher than the level obtained after a subcutaneous (SC) injection (i.e., without tumor) confirming the virus tropism for tumoral cells and/or microenvironment. Moreover, the overall tumoral accumulation of the mAb was higher and lasted longer after IT injection of WR-mAb1, than after IT administration of 10 µg of J43. The IT injection of viruses induced a massive infiltration of immune cells including activated lymphocytes (CD8 + and CD4 + ). Interestingly, in the MCA 205 tumor model, WR-mAb1 and WR-scFv induced a therapeutic control of tumor growth similar to unarmed WR combined to systemically administered J43 and superior to that obtained with an unarmed WR. These results pave the way for next generation of oncolytic vaccinia armed with immunomodulatory therapeutic proteins such as mAbs.

Improved Intratumoral Oxygenation Through Vascular Normalization Increases Glioma Sensitivity to Ionizing Radiation

International Nuclear Information System (INIS)

McGee, Mackenzie C.; Hamner, J. Blair; Williams, Regan F.; Rosati, Shannon F.; Sims, Thomas L.; Ng, Catherine Y.; Gaber, M. Waleed; Calabrese, Christopher; Wu Jianrong; Nathwani, Amit C.; Duntsch, Christopher; Merchant, Thomas E.; Davidoff, Andrew M.

2010-01-01

Purpose: Ionizing radiation, an important component of glioma therapy, is critically dependent on tumor oxygenation. However, gliomas are notable for areas of necrosis and hypoxia, which foster radioresistance. We hypothesized that pharmacologic manipulation of the typically dysfunctional tumor vasculature would improve intratumoral oxygenation and, thus, the antiglioma efficacy of ionizing radiation. Methods and Materials: Orthotopic U87 xenografts were treated with either continuous interferon-β (IFN-β) or bevacizumab, alone, or combined with cranial irradiation (RT). Tumor growth was assessed by quantitative bioluminescence imaging; the tumor vasculature using immunohistochemical staining, and tumor oxygenation using hypoxyprobe staining. Results: Both IFN-β and bevaziumab profoundly affected the tumor vasculature, albeit with different cellular phenotypes. IFN-β caused a doubling in the percentage of area of perivascular cell staining, and bevacizumab caused a rapid decrease in the percentage of area of endothelial cell staining. However, both agents increased intratumoral oxygenation, although with bevacizumab, the effect was transient, being lost by 5 days. Administration of IFN-β or bevacizumab before RT was significantly more effective than any of the three modalities as monotherapy or when RT was administered concomitantly with IFN-β or bevacizumab or 5 days after bevacizumab. Conclusion: Bevacizumab and continuous delivery of IFN-β each induced significant changes in glioma vascular physiology, improving intratumoral oxygenation and enhancing the antitumor activity of ionizing radiation. Additional investigation into the use and timing of these and other agents that modify the vascular phenotype, combined with RT, is warranted to optimize cytotoxic activity.

Numerical simulations of single and multi-staged injection of H2 in a supersonic scramjet combustor

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L. Abu-Farah

2014-12-01

Full Text Available Computational fluid dynamics (CFD simulations of a single staged injection of H2 through a central wedge shaped strut and a multi-staged injection through wall injectors are carried out by using Ansys CFX-12 code. Unstructured tetrahedral grids for narrow channel and quarter geometries of the combustor are generated by using ICEM CFD. Steady three-dimensional (3D Reynolds-averaged Navier-stokes (RANS simulations are carried out in the case of no H2 injection and compared with the simulations of single staged pilot and/or main H2 injections and multistage injection. Shear stress transport (SST based on k-ω turbulent model is adopted. Flow field visualization (complex shock waves interactions and static pressure distribution along the wall of the combustor are predicted and compared with the experimental schlieren images and measured wall static pressures for validation. A good agreement is found between the CFD predicted results and the measured data. The narrow and quarter geometries of the combustor give similar results with very small differences. Multi-staged injections of H2 enhance the turbulent H2/air mixing by forming vortices and additional shock waves (bow shocks.

Safe and Effective Use of the Once Weekly Dulaglutide Single-Dose Pen in Injection-Naïve Patients With Type 2 Diabetes.

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Matfin, Glenn; Van Brunt, Kate; Zimmermann, Alan G; Threlkeld, Rebecca; Ignaut, Debra A

2015-04-21

This 4-week, phase 3b, multicenter, open-label, single-arm, outpatient study demonstrated the safe and effective use of the dulaglutide single-dose pen containing 0.5 mL of placebo for subcutaneous injection in injection-naïve adult patients with type 2 diabetes (T2D), with A1C ≤ 8.5% (69 mmol/mol), BMI ≥ 23 kg/m2 and ≤ 45 kg/m(2). Patients completed a modified self-injecting subscale of the Diabetes Fear of Injecting and Self-Testing Questionnaire (mD-FISQ) and were trained to self-inject with the single-dose pen. Patients completed the initial self-injection at the site, injected at home for 2 subsequent weeks, and returned to the site for the final injection. The initial and final self-injections were evaluated for success; the final (initial) self-injection success rate was the primary (secondary) outcome measure, and the primary (secondary) objective was to demonstrate this success rate as being significantly greater than 80%. Patients recorded their level of pain after each injection. After the final injection, patients completed the mD-FISQ and the Medication Delivery Device Assessment Battery (MDDAB) to assess their perceptions of the single-dose pen, including ease of use and experience with the device. Among 211 patients (mean age: 61 years), the primary objective was met, with a final injection success rate of 99.1% (95% CI: 96.6% to 99.7%). Among 214 patients, the initial injection success rate was 97.2% (95% CI: 94.0% to 98.7%), meeting the key secondary objective. Overall, most patients (>96%) found the device easy to use, were satisfied with the device, and would be willing to continue to use the single-dose pen after the study. There was a significant reduction (P injecting, as measured by the mD-FISQ. The dulaglutide single-dose pen was found to be a safe and effective device for use by patients with T2D who were injection-naïve. A positive injection experience is an important factor for patients and providers when initiating injectable

Viral-Cellular DNA Junctions as Molecular Markers for Assessing Intra-Tumor Heterogeneity in Cervical Cancer and for the Detection of Circulating Tumor DNA

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Katrin Carow

2017-09-01

Full Text Available The development of cervical cancer is frequently accompanied by the integration of human papillomaviruses (HPV DNA into the host genome. Viral-cellular junction sequences, which arise in consequence, are highly tumor specific. By using these fragments as markers for tumor cell origin, we examined cervical cancer clonality in the context of intra-tumor heterogeneity. Moreover, we assessed the potential of these fragments as molecular tumor markers and analyzed their suitability for the detection of circulating tumor DNA in sera of cervical cancer patients. For intra-tumor heterogeneity analyses tumors of 8 patients with up to 5 integration sites per tumor were included. Tumor islands were micro-dissected from cryosections of several tissue blocks representing different regions of the tumor. Each micro-dissected tumor area served as template for a single junction-specific PCR. For the detection of circulating tumor-DNA (ctDNA junction-specific PCR-assays were applied to sera of 21 patients. Samples were collected preoperatively and during the course of disease. In 7 of 8 tumors the integration site(s were shown to be homogenously distributed throughout different tumor regions. Only one tumor displayed intra-tumor heterogeneity. In 5 of 21 analyzed preoperative serum samples we specifically detected junction fragments. Junction-based detection of ctDNA was significantly associated with reduced recurrence-free survival. Our study provides evidence that HPV-DNA integration is as an early step in cervical carcinogenesis. Clonality with respect to HPV integration opens new perspectives for the application of viral-cellular junction sites as molecular biomarkers in a clinical setting such as disease monitoring.

Transcatheter aortic-valve implantation with one single minimal contrast media injection.

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Arrigo, Mattia; Maisano, Francesco; Haueis, Sabine; Binder, Ronald K; Taramasso, Maurizio; Nietlispach, Fabian

2015-06-01

Performing transcatheter aortic valve implantation (TAVI) with the use of minimal contrast in patients at high-risk for acute kidney injury (AKI). Contrast-induced nephropathy (CIN) is a major cause of AKI following TAVI and is associated with increased morbidity and mortality. The amount of contrast media used increases the risk for CIN. Computed tomography was omitted during the screening process. For the procedure transfemoral access was default. The self-expanding CoreValve prosthesis was chosen in all patients to minimize the risk of annular rupture in case of oversizing. Valve sizing was based on echocardiography, aortography, calcification on fluoroscopy, as well as weight and height of the patient. A single contrast injection was performed to confirm correct position of the pigtail catheter at the level of the annulus. The pigtail then served as the marker for the device landing zone. Intraprocedural assessment of the implantation result relied on echocardiography and hemodynamics. Five patients with severe aortic stenosis and at high risk for developing CIN were included. Device success was achieved in all patients and no major complications occurred. The median dose of injected contrast media was 8 ml (4-9). All but one patient had improved renal function after the intervention compared to baseline. Our study shows feasibility of performing TAVI with a single minimal contrast media injection, using a self-expandable valve. This technique has the potential to reduce the incidence of CIN. © 2015 Wiley Periodicals, Inc.

Anti-tumoral effect of recombinant vaccinia virus through US guided injection in a rabbit model of hepatic VX2 carcinoma

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Oh, Jong Young; Park, Byeong Ho; Kang, Myong Jin; Cho, Jin Han; Choi, Jong Cheol; Choi, Sun Seob; Nam, Kyung Jin; Hwang, Tae Ho; Jeong, Jin Sook [College of Medicine, Dong-A University, Busan (Korea, Republic of)

2006-02-15

The purpose of this study was to evaluate the anti-tumoral effect of recombinant vaccinia virus (rVV) (Thymidine kinase (-)/GM-CSF (+)) that was administered as a US guided intratumoral injection in a rabbit model of hepatic VX2 carcinoma. VX2 carcinoma was implanted in the livers of 12 rabbits. US was performed at every week interval to detect hepatic mass after the implantation of VX2 carcinoma. The accurate tumor size and volume was evaluated with CT when the tumor was detected on US. US guided injection of rVV (10{sup 9} pfu/ml) was preformed in three rabbits, intravenous injection of the same dose of rVV was done in two rabbits and another seven rabbits that were without any treatment were selected as a control group. We evaluated the change of the hepatic tumor size and extrahepatic metastasis on serial CT. Tumor specimens were harvested from rabbits that were killed at 8 weeks after VX2 implantation. These tissues were histoimmuopathologically compared to each other (the virus injection group and the control group). The differences between these groups were statistically assessed with student t-tests. Tumor growth was significantly suppressed in the US guided injection group compared with the intravenous injection group or the control group ({rho} < 0.01). The intravenous injection group showed statistically significant tumor suppression compared to the control group ({rho} < 0.01) until 2 weeks after virus injection. Quantification of the pulmonary metastatic nodules was performed in view of both the number and volume. The average number or volume of the pulmonary metastatic nodules in the US injection group was much smaller than these in the control group. Histopathologically, the tumors of the US guided injection group showed less extensive necrosis than those of the control group. Immunohistochemically, the tumor of the US guided injection group showed more prominent infiltration of CD4 (+) and CD8 (+) lymphocytes than did the tumors of the other group

Sentinel node biopsy and concomitant probe-guided tumor excision of nonpalpable breast cancer

NARCIS (Netherlands)

van Rijk, Maartje C.; Tanis, Pieter J.; Nieweg, Omgo E.; Loo, Claudette E.; Valdés Olmos, Renato A.; Oldenburg, Hester S. A.; Rutgers, Emiel J. Th; Hoefnagel, Cornelis A.; Kroon, Bin B. R.

2007-01-01

BACKGROUND: Preliminary data have shown encouraging results of a single intratumoral radiopharmaceutical injection that enables both sentinel node biopsy and probe-guided excision of the primary tumor in patients with nonpalpable breast cancer. The aim of the study was to evaluate this approach in a

The efficacy of multiple versus single hyaluronic acid injections: a systematic review and meta-analysis.

Science.gov (United States)

Concoff, Andrew; Sancheti, Parag; Niazi, Faizan; Shaw, Peter; Rosen, Jeffrey

2017-12-21

Intra-articular hyaluronic acid (IA-HA) is a common therapy used to treat knee pain and suppress knee inflammation in knee osteoarthritis (OA), typically prescribed in regimens ranging from a single injection to 5 weekly injections given once weekly. We conducted a systematic review to determine the efficacy of IA-HA, with subgroup analyses to explore the differences in knee pain and adverse events (AEs) across different dosing regimens. We conducted a systematic search of the literature to identify studies evaluating IA-HA for the management of knee OA compared to IA-saline. Primary outcome measure was the mean knee pain score at 13 Weeks (3 months) or 26 weeks (6 months). Secondary outcome was the number of treatment-related AEs and treatment-related serious adverse events (SAEs). We evaluated differences in levels of pain and AEs/SAEs between dosing regimens compared to IA-Saline. Thirty articles were included. Overall, IA-HA injections were associated with less knee pain compared to IA-Saline injections for all dosing regimens. 2-4 injections of IA-HA vs. IA-Saline produced the largest effect size at both 3-months and 6-months (Standard mean difference [SMD] = -0.76; -0.98 to -0.53, 95% CI, P injection studies yielded a non-significant treatment effect at 3 and 6 months, while ≥5 5 injections demonstrated a significant improvement in pain only at 6 months. Five or more injections of IA-HA were associated with a higher risk of treatment-related AEs compared to IA-Saline (Risk ratio [RR] = 1.67; 1.09 to 2.56 95% CI, p = 0.02), which was a result not seen within the 1 and 2-4 injection subgroups. Overall, 2-4 and ≥5 injection regimens provided pain relief over IA-Saline, while single injection did not. Intra-articular injections of HA used in a 2-4 injection treatment regimen provided the greatest benefit when compared to IA-Saline with respect to pain improvement in patients with knee OA, and was generally deemed safe with few to no

3D-CFD Simulation of Confined Cross-Flow Injection Process Using Single Piston Pump

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M. Elashmawy

2017-12-01

Full Text Available Injection process into a confined cross flow is quite important for many applications including chemical engineering and water desalination technology. The aim of this study is to investigate the performance of the injection process into a confined cross-flow of a round pipe using a single piston injection pump. A computational fluid dynamics (CFD analysis has been carried out to investigate the effect of the locations of the maximum velocity and minimum pressure on the confined cross-flow process. The jet trajectory is analyzed and related to the injection pump shaft angle of rotation during the injection duty cycle by focusing on the maximum instant injection flow of the piston action. Results indicate a low effect of the jet trajectory within the range related to the injection pump operational conditions. Constant cross-flow was used and injection flow is altered to vary the jet to line flow ratio (QR. The maximum jet trajectory exhibits low penetration inside the cross-flow. The results showed three regions of the flow ratio effect zones with different behaviors. Results also showed that getting closer to the injection port causes a significant decrease on the locations of the maximum velocity and minimum pressure.

Spatial intratumoral heterogeneity of proliferation in immunohistochemical images of solid tumors

International Nuclear Information System (INIS)

Valous, Nektarios A.; Lahrmann, Bernd; Halama, Niels; Grabe, Niels; Bergmann, Frank; Jäger, Dirk

2016-01-01

Purpose: The interactions of neoplastic cells with each other and the microenvironment are complex. To understand intratumoral heterogeneity, subtle differences should be quantified. Main factors contributing to heterogeneity include the gradient ischemic level within neoplasms, action of microenvironment, mechanisms of intercellular transfer of genetic information, and differential mechanisms of modifications of genetic material/proteins. This may reflect on the expression of biomarkers in the context of prognosis/stratification. Hence, a rigorous approach for assessing the spatial intratumoral heterogeneity of histological biomarker expression with accuracy and reproducibility is required, since patterns in immunohistochemical images can be challenging to identify and describe. Methods: A quantitative method that is useful for characterizing complex irregular structures is lacunarity; it is a multiscale technique that exhaustively samples the image, while the decay of its index as a function of window size follows characteristic patterns for different spatial arrangements. In histological images, lacunarity provides a useful measure for the spatial organization of a biomarker when a sampling scheme is employed and relevant features are computed. The proposed approach quantifies the segmented proliferative cells and not the textural content of the histological slide, thus providing a more realistic measure of heterogeneity within the sample space of the tumor region. The aim is to investigate in whole sections of primary pancreatic neuroendocrine neoplasms (pNENs), using whole-slide imaging and image analysis, the spatial intratumoral heterogeneity of Ki-67 immunostains. Unsupervised learning is employed to verify that the approach can partition the tissue sections according to distributional heterogeneity. Results: The architectural complexity of histological images has shown that single measurements are often insufficient. Inhomogeneity of distribution depends

Spatial intratumoral heterogeneity of proliferation in immunohistochemical images of solid tumors.

Science.gov (United States)

Valous, Nektarios A; Lahrmann, Bernd; Halama, Niels; Bergmann, Frank; Jäger, Dirk; Grabe, Niels

2016-06-01

The interactions of neoplastic cells with each other and the microenvironment are complex. To understand intratumoral heterogeneity, subtle differences should be quantified. Main factors contributing to heterogeneity include the gradient ischemic level within neoplasms, action of microenvironment, mechanisms of intercellular transfer of genetic information, and differential mechanisms of modifications of genetic material/proteins. This may reflect on the expression of biomarkers in the context of prognosis/stratification. Hence, a rigorous approach for assessing the spatial intratumoral heterogeneity of histological biomarker expression with accuracy and reproducibility is required, since patterns in immunohistochemical images can be challenging to identify and describe. A quantitative method that is useful for characterizing complex irregular structures is lacunarity; it is a multiscale technique that exhaustively samples the image, while the decay of its index as a function of window size follows characteristic patterns for different spatial arrangements. In histological images, lacunarity provides a useful measure for the spatial organization of a biomarker when a sampling scheme is employed and relevant features are computed. The proposed approach quantifies the segmented proliferative cells and not the textural content of the histological slide, thus providing a more realistic measure of heterogeneity within the sample space of the tumor region. The aim is to investigate in whole sections of primary pancreatic neuroendocrine neoplasms (pNENs), using whole-slide imaging and image analysis, the spatial intratumoral heterogeneity of Ki-67 immunostains. Unsupervised learning is employed to verify that the approach can partition the tissue sections according to distributional heterogeneity. The architectural complexity of histological images has shown that single measurements are often insufficient. Inhomogeneity of distribution depends not only on percentage

Spatial intratumoral heterogeneity of proliferation in immunohistochemical images of solid tumors

Energy Technology Data Exchange (ETDEWEB)

Valous, Nektarios A. [Applied Tumor Immunity Clinical Cooperation Unit, National Center for Tumor Diseases, German Cancer Research Center, Heidelberg 69120 (Germany); Lahrmann, Bernd; Halama, Niels; Grabe, Niels [Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg 69120 (Germany); Bergmann, Frank [Institute of Pathology, Heidelberg University Hospital, Heidelberg 69120 (Germany); Jäger, Dirk [Department of Medical Oncology, National Center for Tumor Diseases, German Cancer Research Center, Heidelberg 69120, Germany and National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg 69120 (Germany)

2016-06-15

Purpose: The interactions of neoplastic cells with each other and the microenvironment are complex. To understand intratumoral heterogeneity, subtle differences should be quantified. Main factors contributing to heterogeneity include the gradient ischemic level within neoplasms, action of microenvironment, mechanisms of intercellular transfer of genetic information, and differential mechanisms of modifications of genetic material/proteins. This may reflect on the expression of biomarkers in the context of prognosis/stratification. Hence, a rigorous approach for assessing the spatial intratumoral heterogeneity of histological biomarker expression with accuracy and reproducibility is required, since patterns in immunohistochemical images can be challenging to identify and describe. Methods: A quantitative method that is useful for characterizing complex irregular structures is lacunarity; it is a multiscale technique that exhaustively samples the image, while the decay of its index as a function of window size follows characteristic patterns for different spatial arrangements. In histological images, lacunarity provides a useful measure for the spatial organization of a biomarker when a sampling scheme is employed and relevant features are computed. The proposed approach quantifies the segmented proliferative cells and not the textural content of the histological slide, thus providing a more realistic measure of heterogeneity within the sample space of the tumor region. The aim is to investigate in whole sections of primary pancreatic neuroendocrine neoplasms (pNENs), using whole-slide imaging and image analysis, the spatial intratumoral heterogeneity of Ki-67 immunostains. Unsupervised learning is employed to verify that the approach can partition the tissue sections according to distributional heterogeneity. Results: The architectural complexity of histological images has shown that single measurements are often insufficient. Inhomogeneity of distribution depends

[Comparison of basic carboxypeptidases activity in male rats tissues at a single injection of haloperidol].

Science.gov (United States)

Pravosudova, N A; Bykova, I O

2014-01-01

The influence of a single injection of haloperidol on basic carboxypeptidases (biologically active peptide processing enzymes) activity in rat tissues was studied. Acute exposure to haloperidol increased the activity of carboxypeptidases H (CP H) in hypothalamic-pituitary-adrenal system and cerebellum and reduced such activity in testes. Multidirectional changes of PMSF-inhibited carboxypeptidases activity (PMSF-CP) were observed after a single haloperidol injection in all studied tissues except testes. It is suggested that changes of CP H and PMSF-CP activity might affect levels of regulatory peptides in the brain and blood and thus may be involved in general and side effects of haloperidol on the organism.

Opto-injection into single living cells by femtosecond near-infrared laser

Science.gov (United States)

Peng, Cheng

This dissertation presents a novel technique to deliver membrane impermeable molecules into single living cells with the assistance of femtosecond (fs) near-infrared (NIR) laser pulses. This approach merges ultrafast laser technology with key biological, biomedical, and medical applications, such as gene transfection, gene therapy and drug delivery. This technique promises several major advantages, namely, very high transfection efficiency, high cell survival rate (≈100%) and fully preserved cell viabilities. It is also a promising method to deliver molecules into cells that are difficult or even completely resistant to established physical methods, such as microinjection by glass pipettes, electroporation, and biolistics. In this work, the system for fs NIR opto-injection was designed and built. Successful fs NIR opto-injection has been performed on several cell systems including single mammalian cells (bovine aortic endothelial cells), marine animal eggs (Spisula solidissima oocytes), and human cancer cells (fibrosarcoma HT1080) cultured in a tissue-like environment. The connections between laser parameters and cell responses were explored through further experiments and in-depth analyses, especially the relationship between dye uptake rate and incident laser intensity, and the relationship between pore size created on cell membranes and incident laser intensity. Dye uptake rate of the target cells was observed to depend on incident laser intensity. Pore size was found dependent on incident laser intensity. The conclusion was made that laser-induced breakdown and plasma-induced ablation in cell membrane are the physical principles that govern the process of fs NIR opto-injection.

Efficacy Of A Single-Injection Sodium Hyaluronate Treatment In Lateral Epicondylitis.

Science.gov (United States)

Khan, Inam Ullah; Awan, Abdus Saboor; Khan, Aimal Sattar; Marwat, Imran; Meraj, Muhammad

2018-01-01

Lateral epicondylitis or tennis elbow is a disease of tendons arising from common extensor origin at the lateral epicondyle of elbow and is commonly characterized by pain on supination of forearms as well as extension of fingers and wrists. This descriptive case series aims to determine the efficacy of a single-injection sodium hyaluronate treatment for lateral epicondylitis. The study was conducted at the Department of Orthopaedics. Ayub Teaching Hospital Abbottabad. From February 1 to August 31, 2014. Patients diagnosed with lateral epicondylitis were administered 1 cc of 1% Sodium hyaluronate 1 cm from the lateral epicondyle into the soft tissue. Hyaluronic acid is more effective in patients with moderate pain of lateral epicondylitis (VAS score ≤7 than in patients with severe pain (VAS score >7). Paired sample t-test was used to compared the means of the pre- and post-procedure VAS score and the difference was found to be statistically very significant (p=0.00) with a mean±SD change in VAS of 2.31±1.35 at 4 weeks. A single injection of sodium hyaluronate is effective in management of moderate, but not severe pain of lateral epicondylitis.

Single step production of Cas9 mRNA for zygote injection.

Science.gov (United States)

Redel, Bethany K; Beaton, Benjamin P; Spate, Lee D; Benne, Joshua A; Murphy, Stephanie L; O'Gorman, Chad W; Spate, Anna M; Prather, Randall S; Wells, Kevin D

2018-03-01

Production of Cas9 mRNA in vitro typically requires the addition of a 5´ cap and 3´ polyadenylation. A plasmid was constructed that harbored the T7 promoter followed by the EMCV IRES and a Cas9 coding region. We hypothesized that the use of the metastasis associated lung adenocarcinoma transcript 1 (Malat1) triplex structure downstream of an IRES/Cas9 expression cassette would make polyadenylation of in vitro produced mRNA unnecessary. A sequence from the mMalat1 gene was cloned downstream of the IRES/Cas9 cassette described above. An mRNA concentration curve was constructed with either commercially available Cas9 mRNA or the IRES/ Cas9/triplex, by injection into porcine zygotes. Blastocysts were genotyped to determine if differences existed in the percent of embryos modified. The concentration curve identified differences due to concentration and RNA type injected. Single step production of Cas9 mRNA provides an alternative source of Cas9 for use in zygote injections.

Imaging intratumor heterogeneity: role in therapy response, resistance, and clinical outcome.

Science.gov (United States)

O'Connor, James P B; Rose, Chris J; Waterton, John C; Carano, Richard A D; Parker, Geoff J M; Jackson, Alan

2015-01-15

Tumors exhibit genomic and phenotypic heterogeneity, which has prognostic significance and may influence response to therapy. Imaging can quantify the spatial variation in architecture and function of individual tumors through quantifying basic biophysical parameters such as CT density or MRI signal relaxation rate; through measurements of blood flow, hypoxia, metabolism, cell death, and other phenotypic features; and through mapping the spatial distribution of biochemical pathways and cell signaling networks using PET, MRI, and other emerging molecular imaging techniques. These methods can establish whether one tumor is more or less heterogeneous than another and can identify subregions with differing biology. In this article, we review the image analysis methods currently used to quantify spatial heterogeneity within tumors. We discuss how analysis of intratumor heterogeneity can provide benefit over more simple biomarkers such as tumor size and average function. We consider how imaging methods can be integrated with genomic and pathology data, instead of being developed in isolation. Finally, we identify the challenges that must be overcome before measurements of intratumoral heterogeneity can be used routinely to guide patient care. ©2014 American Association for Cancer Research.

Doxorubicin-loaded QuadraSphere microspheres: plasma pharmacokinetics and intratumoral drug concentration in an animal model of liver cancer.

Science.gov (United States)

Lee, Kwang-Hun; Liapi, Eleni A; Cornell, Curt; Reb, Philippe; Buijs, Manon; Vossen, Josephina A; Ventura, Veronica Prieto; Geschwind, Jean-Francois H

2010-06-01

The purpose of this study was to evaluate, in vitro and in vivo, doxorubicin-loaded poly (vinyl alcohol-sodium acrylate) copolymer microspheres [QuadraSphere microspheres (QSMs)] for transcatheter arterial delivery in an animal model of liver cancer. Doxorubicin loading efficiency and release profile were first tested in vitro. In vivo, 15 rabbits, implanted with a Vx-2 tumor in the liver, were divided into three groups of five rabbits each, based on the time of euthanasia. Twenty-five milligrams of QSMs was diluted in 10 ml of a 10 mg/ml doxorubicin solution and 10 ml of nonionic contrast medium for a total volume of 20 ml. One milliliter of a drug-loaded QSM solution containing 5 mg of doxorubicin was injected into the tumor feeding artery. Plasma doxorubicin and doxorubicinol concentrations, and intratumoral and peritumoral doxorubicin tissue concentrations, were measured. Tumor specimens were pathologically evaluated to record tumor necrosis. As a control, one animal was blandly embolized with plain QSMs in each group. In vitro testing of QSM doxorubicin loadability and release over time showed 82-94% doxorubicin loadability within 2 h and 6% release within the first 6 h after loading, followed by a slow release pattern. In vivo, the doxorubicin plasma concentration declined at 40 min. The peak doxorubicin intratumoral concentration was observed at 3 days and remained detectable till the study's end point (7 days). Mean percentage tumor cell death in the doxorubicin QSM group was 90% at 7 days and 60% in the bland QSM embolization group. In conclusion, QSMs can be efficiently loaded with doxorubicin. Initial experiments with doxorubicin-loaded QSMs show a safe pharmacokinetic profile and effective tumor killing in an animal model of liver cancer.

Doxorubicin-Loaded QuadraSphere Microspheres: Plasma Pharmacokinetics and Intratumoral Drug Concentration in an Animal Model of Liver Cancer

International Nuclear Information System (INIS)

Lee, Kwang-Hun; Liapi, Eleni A.; Cornell, Curt; Reb, Philippe; Buijs, Manon; Vossen, Josephina A.; Ventura, Veronica Prieto; Geschwind, Jean-Francois H.

2010-01-01

The purpose of this study was to evaluate, in vitro and in vivo, doxorubicin-loaded poly (vinyl alcohol-sodium acrylate) copolymer microspheres [QuadraSphere microspheres (QSMs)] for transcatheter arterial delivery in an animal model of liver cancer. Doxorubicin loading efficiency and release profile were first tested in vitro. In vivo, 15 rabbits, implanted with a Vx-2 tumor in the liver, were divided into three groups of five rabbits each, based on the time of euthanasia. Twenty-five milligrams of QSMs was diluted in 10 ml of a 10 mg/ml doxorubicin solution and 10 ml of nonionic contrast medium for a total volume of 20 ml. One milliliter of a drug-loaded QSM solution containing 5 mg of doxorubicin was injected into the tumor feeding artery. Plasma doxorubicin and doxorubicinol concentrations, and intratumoral and peritumoral doxorubicin tissue concentrations, were measured. Tumor specimens were pathologically evaluated to record tumor necrosis. As a control, one animal was blandly embolized with plain QSMs in each group. In vitro testing of QSM doxorubicin loadability and release over time showed 82-94% doxorubicin loadability within 2 h and 6% release within the first 6 h after loading, followed by a slow release pattern. In vivo, the doxorubicin plasma concentration declined at 40 min. The peak doxorubicin intratumoral concentration was observed at 3 days and remained detectable till the study's end point (7 days). Mean percentage tumor cell death in the doxorubicin QSM group was 90% at 7 days and 60% in the bland QSM embolization group. In conclusion, QSMs can be efficiently loaded with doxorubicin. Initial experiments with doxorubicin-loaded QSMs show a safe pharmacokinetic profile and effective tumor killing in an animal model of liver cancer.

FUNCTIONAL SUBCLONE PROFILING FOR PREDICTION OF TREATMENT-INDUCED INTRA-TUMOR POPULATION SHIFTS AND DISCOVERY OF RATIONAL DRUG COMBINATIONS IN HUMAN GLIOBLASTOMA

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Reinartz, Roman; Wang, Shanshan; Kebir, Sied; Silver, Daniel J.; Wieland, Anja; Zheng, Tong; Küpper, Marius; Rauschenbach, Laurèl; Fimmers, Rolf; Shepherd, Timothy M.; Trageser, Daniel; Till, Andreas; Schäfer, Niklas; Glas, Martin; Hillmer, Axel M.; Cichon, Sven; Smith, Amy A.; Pietsch, Torsten; Liu, Ying; Reynolds, Brent A.; Yachnis, Anthony; Pincus, David W.; Simon, Matthias; Brüstle, Oliver; Steindler, Dennis A.; Scheffler, Björn

2016-01-01

Purpose Investigation of clonal heterogeneity may be key to understanding mechanisms of therapeutic failure in human cancer. However, little is known on the consequences of therapeutic intervention on the clonal composition of solid tumors. Experimental Design Here, we used 33 single cell-derived subclones generated from five clinical glioblastoma specimens for exploring intra- and inter-individual spectra of drug resistance profiles in vitro. In a personalized setting, we explored whether differences in pharmacological sensitivity among subclones could be employed to predict drug-dependent changes to the clonal composition of tumors. Results Subclones from individual tumors exhibited a remarkable heterogeneity of drug resistance to a library of potential anti-glioblastoma compounds. A more comprehensive intra-tumoral analysis revealed that stable genetic and phenotypic characteristics of co-existing subclones could be correlated with distinct drug sensitivity profiles. The data obtained from differential drug response analysis could be employed to predict clonal population shifts within the naïve parental tumor in vitro and in orthotopic xenografts. Furthermore, the value of pharmacological profiles could be shown for establishing rational strategies for individualized secondary lines of treatment. Conclusions Our data provide a previously unrecognized strategy for revealing functional consequences of intra-tumor heterogeneity by enabling predictive modeling of treatment-related subclone dynamics in human glioblastoma. PMID:27521447

Symptomatic Spinal Epidural Lipomatosis After a Single Local Epidural Steroid Injection

International Nuclear Information System (INIS)

Tok, Chung Hong; Kaur, Shaleen; Gangi, Afshin

2011-01-01

Spinal epidural lipomatosis is a rare disorder that can manifest with progressive neurological deficits. It is characterized by abnormal accumulation of unencapsulated epidural fat commonly associated with the administration of exogenous steroids associated with a variety of systemic diseases, endocrinopathies, and Cushing syndrome (Fogel et al. Spine J 5:202–211, 2005). Occasionally, spinal epidural lipomatosis may occur in patients not exposed to steroids or in patients with endocrinopathies, primarily in obese individuals (Fogel et al. Spine J 5:202–211, 2005). However, spinal lumbar epidural lipomatosis resulting from local steroid injection has rarely been reported. We report the case of a 45-year-old diabetic man with claudication that was probably due to symptomatic lumbar spinal lipomatosis resulting from a single local epidural steroid injection.

Intratumoral macrophages contribute to epithelial-mesenchymal transition in solid tumors

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Bonde, Anne-Katrine; Tischler, Verena; Kumar, Sushil; Soltermann, Alex; Schwendener, Reto A

2012-01-01

Several stromal cell subtypes including macrophages contribute to tumor progression by inducing epithelial-mesenchymal transition (EMT) at the invasive front, a mechanism also linked to metastasis. Tumor associated macrophages (TAM) reside mainly at the invasive front but they also infiltrate tumors and in this process they mainly assume a tumor promoting phenotype. In this study, we asked if TAMs also regulate EMT intratumorally. We found that TAMs through TGF-β signaling and activation of the β-catenin pathway can induce EMT in intratumoral cancer cells. We depleted macrophages in F9-teratocarcinoma bearing mice using clodronate-liposomes and analyzed the tumors for correlations between gene and protein expression of EMT-associated and macrophage markers. The functional relationship between TAMs and EMT was characterized in vitro in the murine F9 and mammary gland NMuMG cells, using a conditioned medium culture approach. The clinical relevance of our findings was evaluated on a tissue microarray cohort representing 491 patients with non-small cell lung cancer (NSCLC). Gene expression analysis of F9-teratocarcinomas revealed a positive correlation between TAM-densities and mesenchymal marker expression. Moreover, immunohistochemistry showed that TAMs cluster with EMT phenotype cells in the tumors. In vitro, long term exposure of F9-and NMuMG-cells to macrophage-conditioned medium led to decreased expression of the epithelial adhesion protein E-cadherin, activation of the EMT-mediating β-catenin pathway, increased expression of mesenchymal markers and an invasive phenotype. In a candidate based screen, macrophage-derived TGF-β was identified as the main inducer of this EMT-associated phenotype. Lastly, immunohistochemical analysis of NSCLC patient samples identified a positive correlation between intratumoral macrophage densities, EMT markers, intraepithelial TGF-β levels and tumor grade. Data presented here identify a novel role for macrophages in EMT

The data analysis of the single well injection-withdraw tracer experiment using the MACRO II

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Shirakawa, Toshihiko; Kanazawa, Yasuo; Hatanaka, Koichiro

2001-04-01

On understanding the radionuclide transport in natural barrier in radioactive waste isolation research, the macroscopic dispersion in heterogeneous permeability field in the underground rock is regarded as an important process. Therefore, we have conducted lots of tracer experiments by the MACRO II facility with an artificially constructed heterogeneous permeability field. In order to study the scale dependence of dispersion coefficients in case of laboratory experiments, we placed the flow cell horizontally, and conducted injection-withdraw tracer experiment with a single well. We have conducted 15 cases experiments. These cases were prepared by changing a position of single well and the injection-withdraw time. At each position we have conducted 9 cases and 6 cases experiments. In this report, we evaluated the macroscopic dispersion coefficients by the fitting of analytical solution to breakthrough curve measured by the 15 cases pumping tracer experiment. Consequently, we could evaluate the dispersion coefficients for 12 cases of 15 cases. Then, we discussed the relation between a injection-withdraw flow rate and a property of heterogeneous media and dispersion coefficient. The conclusions obtained from the results of the evaluation are summarized as follows, It was found that the macroscopic dispersion coefficients tend to be increased with increase of the average radius of tracer front spread around a single well. We have conducted any experiments with s single well settled at two positions. In case of that there is low permeability around a single well, we found dispersion coefficients are large. In case of that there is high permeability around a single well, we found dispersion coefficients are small. In three cases that we could not evaluate because of incorrect accuracy of fitting, we have found it possible that there is some points that dispersion coefficients were strikingly small in tracer front. (author)

Co-encapsulation of magnetic Fe3O4 nanoparticles and doxorubicin into biodegradable PLGA nanocarriers for intratumoral drug delivery

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Jia Y

2012-03-01

Full Text Available Yanhui Jia1, Mei Yuan1, Huidong Yuan1, Xinglu Huang2, Xiang Sui1, Xuemei Cui1, Fangqiong Tang2, Jiang Peng1, Jiying Chen1, Shibi Lu1, Wenjing Xu1, Li Zhang1, Quanyi Guo11Institute of Orthopedics, General Hospital of the Chinese People's Liberation Army, Beijing, People's Republic of China; 2Laboratory of Controllable Preparation and Application of Nanomaterials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, People's Republic of ChinaAbstract: In this study, the authors constructed a novel PLGA [poly(D,L-lactic-co-glycolic acid]-based polymeric nanocarrier co-encapsulated with doxorubicin (DOX and magnetic Fe3O4 nanoparticles (MNPs using a single emulsion evaporation method. The DOX-MNPs showed high entrapment efficiency, and they supported a sustained and steady release of DOX. Moreover, the drug release was pH sensitive, with a faster release rate in an acidic environment than in a neutral environment. In vitro, the DOX-MNPs were easily internalized into murine Lewis lung carcinoma cells and they induced apoptosis. In vivo, the DOX-MNPs showed higher antitumor activity than free DOX solution. Furthermore, the antitumor activity of the DOX-MNPs was higher with than without an external magnetic field; they were also associated with smaller tumor volume and a lower metastases incidence rate. This work may provide a new modality for developing an effective drug delivery system.Keywords: antitumor activity, external magnetic field, intratumoral injection, apoptosis, Lewis lung carcinoma

Transfer of single dose of intravitreal injection of ranibizumab and bevacizumab into milk of sheep

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Tugba Cakmak Argun

2017-07-01

Full Text Available AIM: To investigate whether single-dose intravitreal injections of bevacizumab and ranibizumab transfer into milk. METHODS: This study included lactating 12 sheep and a single 3-month old suckling lamb of each sheep. Two groups consisting of 6 sheep and their lambs were constituted; the ranibizumab group and the bevacizumab group before the administration of intravitreal injections, blood and milk samples were obtained from all sheep and, following the injections, blood and milk samples of all sheep and blood samples of all lambs were collected at regular time points. Serum and milk concentrations of bevacizumab and ranibizumab were measured using an enzyme-linked immunosorbent assay (ELISA kit. The limit of determination was 0.9 ng/mL for bevacizumab and 0.62 ng/mL for ranibizumab. RESULTS: At 6h after intravitreal injections, bevacizumab concentration was above the limit of determination in the blood of all sheep. At 3wk, when the study was terminated, bevacizumab concentrations were high in 4 sheep. Even though bevacizumab concentrations in milk showed fluctuations, the drug transferred into the milk of all sheep at detectable concentrations. Ranibizumab drug concentrations in the blood and milk of sheep and those in the blood of lambs were below the limit of determination by the ELISA kit. CONCLUSION: This sheep model study demonstrate that intravitreal injection of ranibizumab, which did not transfer into the milk of sheep and suckling lambs, is safer than bevacizumab during lactation period.

The malignant pleural effusion as a model to investigate intratumoral heterogeneity in lung cancer.

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Saroj K Basak

Full Text Available Malignant Pleural Effusions (MPE may be useful as a model to study hierarchical progression of cancer and/or intratumoral heterogeneity. To strengthen the rationale for developing the MPE-model for these purposes, we set out to find evidence for the presence of cancer stem cells (CSC in MPE and demonstrate an ability to sustain intratumoral heterogeneity in MPE-primary cultures. Our studies show that candidate lung CSC-expression signatures (PTEN, OCT4, hTERT, Bmi1, EZH2 and SUZ12 are evident in cell pellets isolated from MPE, and MPE-cytopathology also labels candidate-CSC (CD44, cMET, MDR-1, ALDH subpopulations. Moreover, in primary cultures that use MPE as the source of both tumor cells and the tumor microenvironment (TME, candidate CSC are maintained over time. This allows us to live-sort candidate CSC-fractions from the MPE-tumor mix on the basis of surface markers (CD44, c-MET, uPAR, MDR-1 or differences in xenobiotic metabolism (ALDH. Thus, MPE-primary cultures provide an avenue to extract candidate CSC populations from individual (isogenic MPE-tumors. This will allow us to test whether these cells can be discriminated in functional bioassays. Tumor heterogeneity in MPE-primary cultures is evidenced by variable immunolabeling, differences in colony-morphology, and differences in proliferation rates of cell subpopulations. Collectively, these data justify the ongoing development of the MPE-model for the investigation of intratumoral heterogeneity, tumor-TME interactions, and phenotypic validation of candidate lung CSC, in addition to providing direction for the pre-clinical development of rational therapeutics.

Noninvasive visualization of in vivo release and intratumoral distribution of surrogate MR contrast agent using the dual MR contrast technique.

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Onuki, Yoshinori; Jacobs, Igor; Artemov, Dmitri; Kato, Yoshinori

2010-09-01

A direct evaluation of the in vivo release profile of drugs from carriers is a clinical demand in drug delivery systems, because drug release characterized in vitro correlates poorly with in vivo release. The purpose of this study is to demonstrate the in vivo applicability of the dual MR contrast technique as a useful tool for noninvasive monitoring of the stability and the release profile of drug carriers, by visualizing in vivo release of the encapsulated surrogate MR contrast agent from carriers and its subsequent intratumoral distribution profile. The important aspect of this technique is that it incorporates both positive and negative contrast agents within a single carrier. GdDTPA, superparamagnetic iron oxide nanoparticles, and 5-fluorouracil were encapsulated in nano- and microspheres composed of poly(D,L-lactide-co-glycolide), which was used as a model carrier. In vivo studies were performed with orthotopic xenograft of human breast cancer. The MR-based technique demonstrated here has enabled visualization of the delivery of carriers, and release and intratumoral distribution of the encapsulated positive contrast agent. This study demonstrated proof-of-principle results for the noninvasive monitoring of in vivo release and distribution profiles of MR contrast agents, and thus, this technique will make a great contribution to the field. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Phase I/IIa study of intratumoral/intracerebral or intravenous/intracerebral administration of Parvovirus H-1 (ParvOryx) in patients with progressive primary or recurrent glioblastoma multiforme: ParvOryx01 protocol

International Nuclear Information System (INIS)

Geletneky, Karsten; Hajda, Jacek; Huesing, Johannes; Rommelaere, Jean; Schlehofer, Joerg R; Leuchs, Barbara; Dahm, Michael; Krebs, Ottheinz; Knebel Doeberitz, Magnus von; Huber, Bernard

2012-01-01

The treatment of patients with malignant brain tumors remains a major oncological problem. The median survival of patients with glioblastoma multiforme (GBM), the most malignant type, is only 15 months after initial diagnosis and even less after tumor recurrence. Improvements of standard treatment including surgery and radio-chemotherapy have not lead to major improvements. Therefore, alternative therapeutics such as oncolytic viruses that specifically target and destroy cancer cells are under investigation. Preclinical data of oncolytic parvovirus H-1 (H-1PV) infection of glioma cells demonstrated strong cytotoxic and oncosuppressing effects, leading to a phase I/IIa trial of H-1PV in patients with recurrent GBM (ParvOryx01). ParvOryx01 is the first trial with a replication competent oncolytic virus in Germany. ParvOryx01 is an open, non-controlled, two groups, intra-group dose escalation, single center, phase I/IIa trial. 18 patients with recurrent GBM will be treated in 2 groups of 9 patients each. Treatment group 1 will first receive H-1PV by intratumoral injection and second by administration into the walls of the tumor cavity during tumor resection. In treatment group 2 the virus will initially be injected intravenously and afterwards, identical to group 1, into the surrounding brain tissue during tumor removal. Main eligibility criteria are: age of 18 years, unifocal recurrent GBM, amenable to complete or subtotal resection. Dose escalation will be based on the Continual Reassessment Method. The primary objective of the trial is local and systemic safety and tolerability and to determine the maximum tolerated dose (MTD). Secondary objectives are proof of concept (PoC) and Progression-free Survival (PFS) up to 6 months. This is the first trial with H-1PV in patients with recurrent GBM. The risks for the participants appear well predictable and justified. Furthermore, ParvOryx01 will be the first assessment of combined intratumoral and intravenous application

A Second Radioisotope Injection Enhances Intraoperative Sentinel Node Identification in Breast Cancer Patients without Visualized Nodes on Preoperative Lymphoscintigraphy

International Nuclear Information System (INIS)

Leikola, J.P.; Leppaenen, E.A.; Smitten, K.A.J. von; Leidenius, M.H.K

2006-01-01

Purpose: To evaluate the influence of a second radioisotope injection on the intraoperative success rate in patients with non-visualized axillary sentinel nodes (SN). Material and Methods: Altogether, 534 consecutive breast cancer patients with lymphoscintigraphy (LS) and SN biopsy and were included. An intratumoral injection of 99m Tc-labeled human albumin colloid with a median dose of 93 MBq was applied. Forty-two of the 80 patients without axillary hot spots on LS received a second tracer injection with a median dose of 70 MBq. Results: The visualization rate of axillary SN was 454/534 (85%). The intraoperative SN identification rate was 97% in patients with and 69% in patients without visualized SN in the axilla ( P <0.00005), but the success rate was higher (88%) with a second radioisotope injection than without it (47%; P <0.0002). Conclusion: The failure rate in intraoperative SN identification was minimized using a second radioisotope injection in patients without axillary SN on LS

Single injection of basic fibroblast growth factor to treat severe vocal fold lesions and vocal fold paralysis.

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Kanazawa, Takeharu; Komazawa, Daigo; Indo, Kanako; Akagi, Yusuke; Lee, Yogaku; Nakamura, Kazuhiro; Matsushima, Koji; Kunieda, Chikako; Misawa, Kiyoshi; Nishino, Hiroshi; Watanabe, Yusuke

2015-10-01

Severe vocal fold lesions such as vocal fold sulcus, scars, and atrophy induce a communication disorder due to severe hoarseness, but a treatment has not been established. Basic fibroblast growth factor (bFGF) therapies by either four-time repeated local injections or regenerative surgery for vocal fold scar and sulcus have previously been reported, and favorable outcomes have been observed. In this study, we modified bFGF therapy using a single of bFGF injection, which may potentially be used in office procedures. Retrospective chart review. Five cases of vocal fold sulcus, six cases of scars, seven cases of paralysis, and 17 cases of atrophy were treated by a local injection of bFGF. The injection regimen involved injecting 50 µg of bFGF dissolved in 0.5 mL saline only once into the superficial lamina propria using a 23-gauge injection needle. Two months to 3 months after the injection, phonological outcomes were evaluated. The maximum phonation time (MPT), mean airflow rate, pitch range, speech fundamental frequency, jitter, and voice handicap index improved significantly after the bFGF injection. Furthermore, improvement in the MPT was significantly greater in patients with (in increasing order) vocal fold atrophy, scar, and paralysis. The improvement in the MPT among all patients was significantly correlated with age; the MPT improved more greatly in younger patients. Regenerative treatments by bFGF injection—even a single injection—effectively improve vocal function in vocal fold lesions. 4 © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

Presence of intratumoral platelets is associated with tumor vessel structure and metastasis

International Nuclear Information System (INIS)

Li, Rong; Zhang, Xu; Zhang, Zhuo; Zhang, Xiao; Ran, Bing; Wu, Jianbo; Ren, Meiping; Chen, Ni; Luo, Mao; Deng, Xin; Xia, Jiyi; Yu, Guang; Liu, Jinbo; He, Bing

2014-01-01

Platelets play a fundamental role in maintaining hemostasis and have been shown to participate in hematogenous dissemination of tumor cells. Abundant platelets were detected in the tumor microenvironment outside of the blood vessel, thus, platelet -tumor cell interaction outside of the bloodstream may play a role in regulating primary tumor growth and metastasis initiation. However, it is unclear that platelet depletion affects tumor vessel structure and dynamics. Using thrombocytopenia induction in two different tumor-bearing mouse models, tumor tissues were performed by Westernblotting and immunohistochemical staining. Vascular permeability was evaluated by determination of intratumoral Evans blue and Miles vascular permeability assay. Furthermore, microdialysis was used to examining the intratumoral extracellular angiogenic growth factors (VEGF, TGF-β) by ELISA. Platelet depletion showed no change in tumor growth and reduced lung metastasis. Platelet depletion led to reduced tumor hypoxia and Met receptor activation and was associated with a decreased release of MMP-2, 9, PAI-1, VEGF, and TGF-β. Tumor vessels in platelet-depleted mice showed impaired vessel density and maturation. Our findings demonstrate that platelets within the primary tumor microenvironment play a critical role in the induction of vascular permeability and initiation of tumor metastasis

Effective conversion of irinotecan to SN-38 after intratumoral drug delivery to an intracranial murine glioma model in vivo. Laboratory investigation.

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Wang, Weijun; Ghandi, Alex; Liebes, Leonard; Louie, Stan G; Hofman, Florence M; Schönthal, Axel H; Chen, Thomas C

2011-03-01

Irinotecan (CPT-11), a topoisomerase I inhibitor, is a cytotoxic agent with activity against malignant gliomas and other tumors. After systemic delivery, CPT-11 is converted to its active metabolite, SN-38, which displays significantly higher cytotoxic potency. However, the achievement of therapeutically effective plasma levels of CPT-11 and SN-38 is seriously complicated by variables that affect drug metabolism in the liver. Thus the capacity of CPT-11 to be converted to the active SN38 intratumorally in gliomas was addressed. For in vitro studies, 2 glioma cell lines, U87 and U251, were tested to determine the cytotoxic effects of CPT-11 and SN-38 in a dose-dependent manner. In vivo studies were performed by implanting U87 intracranially into athymic/nude mice. For a period of 2 weeks, SN-38, CPT-11, or vehicle was administered intratumorally by means of an osmotic minipump. One series of experiments measured the presence of SN-38 or CPT-11 in the tumor and surrounding brain tissues after 2 weeks' exposure to the drug. In a second series of experiments, after 2 weeks' exposure to the drug, the animals were maintained, in the absence of drug, until death. The survival curves were then calculated. The results show that the animals that had CPT-11 delivered intratumorally by the minipump expressed SN-38 in vivo. Furthermore, both CPT-11 and SN-38 accumulated at higher levels in tumor tissues compared with uninvolved brain. Intratumoral delivery of CPT-11 or SN-38 extended the average survival time of tumor-bearing animals from 22 days to 46 and 65 days, respectively. These results demonstrate that intratumorally administered CPT-11 can be effectively converted to SN-38 and this method of drug delivery is effective in extending the survival time of animals bearing malignant gliomas.

Single, double or multiple-injection techniques for non-ultrasound guided axillary brachial plexus block in adults undergoing surgery of the lower arm.

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Chin, Ki Jinn; Alakkad, Husni; Cubillos, Javier E

2013-08-08

Regional anaesthesia comprising axillary block of the brachial plexus is a common anaesthetic technique for distal upper limb surgery. This is an update of a review first published in 2006 and updated in 2011. To compare the relative effects (benefits and harms) of three injection techniques (single, double and multiple) of axillary block of the brachial plexus for distal upper extremity surgery. We considered these effects primarily in terms of anaesthetic effectiveness; the complication rate (neurological and vascular); and pain and discomfort caused by performance of the block. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE and reference lists of trials. We contacted trial authors. The date of the last search was March 2013 (updated from March 2011). We included randomized controlled trials that compared double with single-injection techniques, multiple with single-injection techniques, or multiple with double-injection techniques for axillary block in adults undergoing surgery of the distal upper limb. We excluded trials using ultrasound-guided techniques. Independent study selection, risk of bias assessment and data extraction were performed by at least two investigators. We undertook meta-analysis. The 21 included trials involved a total of 2148 participants who received regional anaesthesia for hand, wrist, forearm or elbow surgery. Risk of bias assessment indicated that trial design and conduct were generally adequate; the most common areas of weakness were in blinding and allocation concealment.Eight trials comparing double versus single injections showed a statistically significant decrease in primary anaesthesia failure (risk ratio (RR 0.51), 95% confidence interval (CI) 0.30 to 0.85). Subgroup analysis by method of nerve location showed that the effect size was greater when neurostimulation was used rather than the transarterial technique.Eight trials comparing multiple with single

Impact of charge carrier injection on single-chain photophysics of conjugated polymers

Energy Technology Data Exchange (ETDEWEB)

Hofmann, Felix J.; Vogelsang, Jan, E-mail: jan.vogelsang@physik.uni-regensburg.de; Lupton, John M. [Institut für Experimentelle und Angewandte Physik, Universität Regensburg, Universitätsstrasse 31, 93053 Regensburg (Germany)

2016-06-27

Charges in conjugated polymer materials have a strong impact on the photophysics and their interaction with the primary excited state species has to be taken into account in understanding device properties. Here, we employ single-molecule spectroscopy to unravel the influence of charges on several photoluminescence (PL) observables. The charges are injected either stochastically by a photochemical process or deterministically in a hole-injection sandwich device configuration. We find that upon charge injection, besides a blue-shift of the PL emission and a shortening of the PL lifetime due to quenching and blocking of the lowest-energy chromophores, the non-classical photon arrival time distribution of the multichromophoric chain is modified towards a more classical distribution. Surprisingly, the fidelity of photon antibunching deteriorates upon charging, whereas one would actually expect the opposite: the number of chromophores to be reduced. A qualitative model is presented to explain the observed PL changes. The results are of interest to developing a microscopic understanding of the intrinsic charge-exciton quenching interaction in devices.

Single intravitreal bevacizumab injection effects on contrast sensitivity in macular edema from branch retinal vein occlusion

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Rony Carlos Preti

2012-02-01

Full Text Available PURPOSE: To evaluate the effect of a single intravitreal bevacizumab injection on visual acuity, contrast sensitivity and optical coherence tomography-measured central macular thickness in eyes with macular edema from branch retinal vein occlusion. METHODS: Seventeen eyes of 17 patients with macular edema from unilateral branch retinal vein occlusion were treated with a single bevacizumab injection. Patients were submitted to a complete evaluation including best corrected visual acuity, contrast sensitivity and optical coherence tomography measurements before treatment and one and three months after injection. Visual acuity, contrast sensitivity and optical coherence tomography measurements were compared to baseline values. RESULTS: Mean visual acuity measurement improved from 0.77 logMAR at baseline to 0.613 logMAR one month after injection (P=0.0001 but worsened to 0.75 logMAR after three months. Contrast sensitivity test demonstrated significant improvement at spatial frequencies of 3, 6, 12 and 18 cycles/degree one month after injection and at the spatial frequency of 12 cycles/degree three months after treatment. Mean ± standard deviation baseline central macular thickness (552 ± 150 µm reduced significantly one month (322 ± 127 µm, P=0.0001 and three months (439 ± 179 µm, P=0.01 after treatment. CONCLUSIONS: Bevacizumab injection improves visual acuity and contrast sensitivity and reduces central macular thickness one month after treatment. Visual acuity returns to baseline levels at the 3-month follow-up, but some beneficial effect of the treatment is still present at that time, as evidenced by optical coherence tomography-measured central macular thickness and contrast sensitivity measurements.

Intra-tumor genetic heterogeneity and mortality in head and neck cancer: analysis of data from the Cancer Genome Atlas.

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Mroz, Edmund A; Tward, Aaron D; Tward, Aaron M; Hammon, Rebecca J; Ren, Yin; Rocco, James W

2015-02-01

Although the involvement of intra-tumor genetic heterogeneity in tumor progression, treatment resistance, and metastasis is established, genetic heterogeneity is seldom examined in clinical trials or practice. Many studies of heterogeneity have had prespecified markers for tumor subpopulations, limiting their generalizability, or have involved massive efforts such as separate analysis of hundreds of individual cells, limiting their clinical use. We recently developed a general measure of intra-tumor genetic heterogeneity based on whole-exome sequencing (WES) of bulk tumor DNA, called mutant-allele tumor heterogeneity (MATH). Here, we examine data collected as part of a large, multi-institutional study to validate this measure and determine whether intra-tumor heterogeneity is itself related to mortality. Clinical and WES data were obtained from The Cancer Genome Atlas in October 2013 for 305 patients with head and neck squamous cell carcinoma (HNSCC), from 14 institutions. Initial pathologic diagnoses were between 1992 and 2011 (median, 2008). Median time to death for 131 deceased patients was 14 mo; median follow-up of living patients was 22 mo. Tumor MATH values were calculated from WES results. Despite the multiple head and neck tumor subsites and the variety of treatments, we found in this retrospective analysis a substantial relation of high MATH values to decreased overall survival (Cox proportional hazards analysis: hazard ratio for high/low heterogeneity, 2.2; 95% CI 1.4 to 3.3). This relation of intra-tumor heterogeneity to survival was not due to intra-tumor heterogeneity's associations with other clinical or molecular characteristics, including age, human papillomavirus status, tumor grade and TP53 mutation, and N classification. MATH improved prognostication over that provided by traditional clinical and molecular characteristics, maintained a significant relation to survival in multivariate analyses, and distinguished outcomes among patients having

Intraperitoneal Injection Is Not a Suitable Administration Route for Single-Walled Carbon Nanotubes in Biomedical Applications

OpenAIRE

Liu, Xudong; Guo, Qing; Zhang, Yuchao; Li, Jinquan; Li, Rui; Wu, Yang; Ma, Ping; Yang, Xu

2016-01-01

Given the extensive application of carbon nanotubes (CNTs) in biomedical fields, there is increasing concern regarding unintentional health impacts. Research into safe usage is therefore increasingly necessary. This study investigated the responses of the mouse brain to single-walled CNTs (SWCNTs) delivered via intraperitoneal (IP) injection and compared these results with the previous study where SWCNTs were delivered via intravenous (IV) injection so as to explore which administration route...

Intratumoral estrogen production and actions in luminal A type invasive lobular and ductal carcinomas.

Science.gov (United States)

Takagi, Mayu; Miki, Yasuhiro; Miyashita, Minoru; Hata, Shuko; Yoda, Tomomi; Hirakawa, Hisashi; Sagara, Yasuaki; Rai, Yoshiaki; Ohi, Yasuyo; Tamaki, Kentaro; Ishida, Takanori; Suzuki, Takashi; Ouchi, Noriaki; Sasano, Hironobu

2016-02-01

The great majority of invasive lobular carcinoma (ILC) is estrogen-dependent luminal A type carcinoma but the details of estrogen actions and its intratumoral metabolism have not been well studied compared to invasive ductal carcinoma (IDC). We first immunolocalized estrogen-related enzymes including estrogen sulfotransferase (EST), estrogen sulfatase (STS), 17β-hydroxysteroid dehydrogenase (HSD) 1/2, and aromatase. We then evaluated the tissue concentrations of estrogens in ILC and IDC and subsequently estrogen-responsive gene profiles in these tumors in order to explore the possible differences and/or similarity of intratumoral estrogen environment of these two breast cancer subtypes. The status of STS and 17βHSD1 was significantly lower in ILCs than IDCs (p = 0.022 and p < 0.0001), but that of EST and 17βHSD2 vice versa (p < 0.0001 and p = 0.0106). In ILCs, tissue concentrations of estrone and estradiol were lower than those in IDCs (p = 0.0709 and 0.069). In addition, the great majority of estrogen response genes tended to be lower in ILCs. Among those genes above, FOXP1 was significantly higher in ILCs than in IDCs (p = 0.002). FOXP1 expression was reported to be significantly higher in relapse-free IDC patients treated with tamoxifen. Therefore, tamoxifen may be considered an option of endocrine therapy for luminal A type ILC patients. This is the first study to demonstrate the detailed and comprehensive status of intratumoral production and metabolism of estrogens and the status of estrogen response genes in luminal A-like ILC with comparison to those in luminal A-like IDCs.

CT and clinical study for intratumoral gas formation in post transarterial embolization of hepatoma and renal cell carcinoma

Energy Technology Data Exchange (ETDEWEB)

Katsuragi, M; Matsuo, N; Yoshikawa, K [Nara Medical Univ., Kashihara (Japan)

1982-09-01

Thirty-two patients with hepatocellular carcinoma and six patients with renal cell carcinoma for whom the arterial embolization therapy was performed were studied by CT and clinical follow-up for investigating intratumoral gas detected on CT in post-embolization cases. The intratumoral air was found by CT in seven patients with hepatocellular carcinoma and four patients with renal cell carcinoma. The air was composed of a collection of multiple small round gas bubbles in the embolized tumor except in one case where it formed a serpiginous pattern. There was no hematologic nor clinical evidence of liver abscess in all the cases. It was possible to distinguish gas from abscess or fat by a combination of CT and clinical findings.

Using anti-VEGF monoclonal antibody and magnetic nanoparticles

International Nuclear Information System (INIS)

Chen Jing; Wuhua; Hang Deyan; Xie Changsheng

2004-01-01

Objective: To study the biodistribution of 131 I-anti-vascular endothelial growth factor (VEGF) monoclonal antibody (Sc-7269)-dextran magnetic nanoparticles (DMN) in nude mice bearing human liver cancer where an external magnetic field was focused on, and to evaluate its therapeutic effects and safety. Methods: Eighteen nude mice bearing human liver cancer where an external magnetic field was focused on, were used for the bio-distribution study after intratumoral injection (n=9) or intravenous injection (n=9) of 131 I-Sc-7269-DMN. Another 25 tumor-bearing nude mice were divided into five groups, four groups of them were treated with 74 MBq/ml 131 I-Sc-7269-DMN, 131 I-Sc-7269, 131 I-DMN and 131 I by a single intratumoral injection, respectively. And an external magnetic field was bound to the tumor of the nude mice that were injected 131 I-Sc-7269-DMN or 131 I-DMN. For control study, the remaining one group was injected with physiological saline. Tumor growth delay (TGD) and tumor inhibition rate were observed as antitumor effects. Peripheral white cell counts and the loss of body weight were tested as indicators of systemic toxicity. Results: The retention percentages of radioactivity (%ID/g) in tumors after intratumoral injection were 104.06, 101.58 and 100.96%ID/g at 4, 24 and 48 h, respectively, while in the case of intravenous injection, the %ID/g values were lower (85.33, 89.67 and 90.00%ID/g, respectively, P 131 I-Sc-7269-DMN [ (13.3 ± 3.3) d] was the longest, and tumor inhibition rate (89.0%)was the highest compared with that in other groups (P 131 I-Sc-7269-DMN-treated mice as monitored by the decrease in peripheral white cell counts and the loss of body weight. Conclusions: The radioimmunotherapy with intratumoral injection of 131 I-Sc-7269-DMN may be safe and efficient for the treatment of liver cancer. Furthermore, the radioimmunotherapy using DMN as a carrier system may be a highly potential approach in targeted treatment of other kinds of tumors

Single-mode Brillouin fiber laser passively stabilized at resonance frequency with self-injection locked pump laser

International Nuclear Information System (INIS)

Spirin, V V; Lopez-Mercado, C A; Megret, P; Fotiadi, A A

2012-01-01

We demonstrate a single-mode Brillouin fiber ring laser, which is passively stabilized at pump resonance frequency by using self-injection locking of semiconductor pump laser. Resonance condition for Stokes radiation is achieved by length fitting of Brillouin laser cavity. The laser generate single-frequency Stokes wave with linewidth less than 0.5 kHz using approximately 17-m length cavity

High intratumoral accumulation of stealth liposomal doxorubicin in sarcomas--rationale for combination with radiotherapy

International Nuclear Information System (INIS)

Koukourakis, M.I.; Koukouraki, S.; Giatromanolaki, A.; Kakolyris, S.; Georgoulias, V.; Velidaki, A.; Archimandritis, S.; Karkavitsas, N.N.

2000-01-01

Sarcomas are radioresistant tumors, the only curative therapy being radical surgical resection. Stealth liposomal doxorubicin (Caelyx) is a novel drug formulation that allows prolonged circulation and high intratumoral concentration. This study investigates the concurrent use of radiotherapy with Caelyx in a cohort of 7 patients with locally advanced or recurrent sarcoma. Radiotherapy was given as a standard fractionation regimen to a total dose of 70 Gy. Caelyx was given as a 30-min infusion at a dose of 25 mg/m 2 every 2 weeks. Scintigraphic imaging with Caelyx- 99m Tc-DTPA showed an increased (2.8 +/- 0.9 times higher) intratumoral drug accumulation compared to the surrounding healthy tissue. The regimen was well tolerated without any severe hematological or systemic toxicity. 'In field' radiation toxicity was not increased. Complete response was observed in 4/7 cases. It is concluded that combined chemo-radiotherapy with stealth liposomal doxorubicin for locally advanced sarcomas is feasible and promising, the benefit expected from the unique ability of the stealth liposomes to accumulate selectively in the tumoral tissue

Optimizing CT angiography in patients with Fontan physiology: single-center experience of dual-site power injection

International Nuclear Information System (INIS)

Sandler, K.L.; Markham, L.W.; Mah, M.L.; Byrum, E.P.; Williams, J.R.

2014-01-01

Aim: To identify adult patients with single-ventricle congenital heart disease and Fontan procedure palliation who have been misdiagnosed with or incompletely evaluated for pulmonary embolism. Additionally, this study was designed to demonstrate that simultaneous, dual-injection of contrast medium into an upper and lower extremity vein is superior to single-injection protocols for CT angiography (CTA) of the chest in this population. Materials and methods: Patients included in the study were retrospectively selected from the Adult Congenital Heart Disease (ACHD) database. Search criteria included history of Fontan palliation and available chest CT examination. Patients were evaluated for (1) type of congenital heart disease and prior operations;(2) indication for initial CT evaluation;(3) route of contrast medium administration for the initial CT examination and resulting diagnosis;(4) whether or not anticoagulation therapy was initiated; and (5) final diagnosis and treatment plan. Results: The query of the ACHD database resulted in 28 individuals or patients with Fontan palliation (superior and inferior venae cavae anastomosed to the pulmonary arteries). Of these, 19 patients with Fontan physiology underwent CTA of the pulmonary circulation, and 17 had suboptimal imaging studies. Unfortunately, seven of these 17 patients (41%) were started on anticoagulation therapy due to a diagnosis of pulmonary embolism that was later excluded. Conclusion: Patients with single-ventricle/Fontan physiology are at risk of thromboembolic disease. Therefore, studies evaluating their complex anatomy must be performed with the optimal imaging protocol to ensure diagnostic accuracy, which is best achieved with dual-injection of an upper and lower extremity central vein. - Highlights: • The adult congenital heart disease population is growing. • Many of these patients have single ventricle/Fontan physiology. • Patients with Fontan physiology are at increased risk for

Sustained neuroprotection from a single intravitreal injection of PGJ₂ in a nonhuman primate model of nonarteritic anterior ischemic optic neuropathy.

Science.gov (United States)

Miller, Neil R; Johnson, Mary A; Nolan, Theresa; Guo, Yan; Bernstein, Alexander M; Bernstein, Steven L

2014-10-08

Prostaglandin J₂ (PGJ₂) is neuroprotective in a murine model of nonarteritic anterior ischemic optic neuropathy (NAION). After assessing for potential toxicity, we evaluated the efficacy of a single intravitreal (IVT) injection of PGJ₂ in a nonhuman primate model of NAION (pNAION). We assessed PGJ₂ toxicity by administering it as a single high-dose intravenous (IV) injection, consecutive daily high-dose IV injections, or a single IVT injection in one eye of five adult rhesus monkeys. To assess efficacy, we induced pNAION in one eye of five adult male rhesus monkeys using a laser-activated rose bengal induction method. We then injected the eye with either PGJ₂ or phosphate-buffered saline (PBS) intravitreally immediately or 5 hours post induction. We performed a clinical assessment, optical coherence tomography, electrophysiological testing, fundus photography, and fluorescein angiography in all animals prior to induction and at 1 day, 1 week, 2 weeks, and 4 weeks after induction. Following analysis of the first eye, we induced pNAION in the contralateral eye and then injected either PGJ₂ or PBS. We euthanized all animals 5 weeks after final assessment of the fellow eye and performed both immunohistochemical and light and electron microscopic analyses of the retina and optic nerves. PGJ₂ caused no permanent systemic toxicity regardless of the amount injected or route of delivery, and there was no evidence of any ocular toxicity with the dose of PGJ₂ used in efficacy studies. Transient reduction in the amplitudes of the visual evoked potentials and the N95 component of the pattern electroretinogram (PERG) occurred after both IV and IVT administration of high doses of PGJ₂; however, the amplitudes returned to normal in all animals within 1 week. In all eyes, a single IVT dose of PGJ₂ administered immediately or shortly after induction of pNAION resulted in a significant reduction of clinical, electrophysiological, and histological damage compared

Recovery of rat muscle size but not function more than 1 year after a single botulinum toxin injection.

Science.gov (United States)

Ward, Samuel R; Minamoto, Viviane B; Suzuki, Kentaro P; Hulst, Jonah B; Bremner, Shannon N; Lieber, Richard L

2018-03-01

Neurotoxin injection is used to treat a wide variety of neuromuscular disorders. The purpose of this study was to measure the functional and structural properties of botulinum toxin-injected adult rat skeletal muscle over nearly the entire lifespan. Ten groups of animals were subjected to either neurotoxin injection [Botox, Type A (BT-A); Allergan, Irvine, California] or saline solution injection. Neurotoxin-injected animals (n = 90) were analyzed at different time-points: 1 week; 1 month; 3 months; 6 months; 12 months; or 18 months. In spite of the recovery of structural features, such as muscle mass and fiber area, dorsiflexion torque production remained significantly depressed by 25%, even at 12 months after neurotoxin injection. The data demonstrate that, after a single BT-A injection, although gross muscle morphology recovered over a 12-month time period, loss of contractile function did not recover. Muscle Nerve 57: 435-441, 2018. © 2017 Wiley Periodicals, Inc.

GSK1265744 pharmacokinetics in plasma and tissue after single-dose long-acting injectable administration in healthy subjects.

Science.gov (United States)

Spreen, William; Ford, Susan L; Chen, Shuguang; Wilfret, David; Margolis, David; Gould, Elizabeth; Piscitelli, Stephen

2014-12-15

GSK1265744 (744) is an HIV-1 integrase inhibitor in clinical development as a long-acting (LA) injectable formulation. This study evaluated plasma and tissue pharmacokinetics after single-dose administration of 744 LA administered by intramuscular (IM) or subcutaneous injections. This was a phase I, open-label, 9-cohort, parallel study of 744 in healthy subjects. 744 was administered as a 200 mg/mL nanosuspension at doses of 100-800 mg IM and 100-400 mg subcutaneous. Eight (6 active and 2 placebo) male and female subjects participated in each of the first 7 cohorts. All 8 subjects, 4 males and 4 females, received active 744 LA in cohorts 8 and 9 and underwent rectal and cervicovaginal tissue sampling, respectively. Plasma pharmacokinetic sampling was performed for a minimum of 12 weeks or until 744 concentrations were ≤0.1 μg/mL. Rectal and cervicovaginal tissue biopsies were performed at weeks 2 and 8 (cohort 8) and weeks 4 and 12 (cohort 9). 744 LA was generally safe and well tolerated after single injections. A majority of subjects reported injection site reactions, all graded as mild in intensity. Plasma concentration-time profiles were prolonged with measureable concentrations up to 52 weeks after dosing. 744 LA 800 mg IM achieved mean concentrations above protein adjusted-IC90 for approximately 16 weeks. Rectal and cervicovaginal tissue concentrations ranged from injection has potential application as a monthly or less frequent HIV treatment or prevention agent.

Critical firing and misfiring boundary in a spark ignition methanol engine during cold start based on single cycle fuel injection

International Nuclear Information System (INIS)

Li, Zhaohui; Gong, Changming; Qu, Xiang; Liu, Fenghua; Sun, Jingzhen; Wang, Kang; Li, Yufeng

2015-01-01

The influence of the mass of methanol injected per cycle, ambient temperature, injection and ignition timing, preheating methods, and supplying additional liquefied petroleum gas (LPG) injection into the intake manifold on the critical firing and misfiring boundary of an electronically injection controlled spark ignition (SI) methanol engine during cold start were investigated experimentally based on a single cycle fuel injection with cycle-by-cycle control strategy. The critical firing and misfiring boundary was restricted by all parameters. For ambient temperatures below 16 °C, methanol engines must use auxiliary start-aids during cold start. Optimal control of the methanol injection and ignition timing can realize ideal next cycle firing combustion after injection. Resistance wire and glow plug preheating can provide critical firing down to ambient temperatures of 5 °C and 0 °C, respectively. Using an additional LPG injection into the intake manifold can provide critical firing down to an ambient temperature of −13 °C during cold start. As the ambient temperature decreases, the optimal angle difference between methanol injection timing and LPG injection timing for critical firing of a methanol engine increases rapidly during cold start. - Highlights: • A single cycle fuel injection and cycle-by-cycle control strategy are used to study. • In-cylinder pressure and instantaneous speed were used to determine firing boundary. • For the ambient temperatures below 16 °C, an auxiliary start-aids must be used. • A preheating and additional LPG were used to expand critical firing boundary. • Additional LPG can result in critical firing down to ambient temperature of −13 °C

All-in-polymer injection molded device for single cell capture using multilevel silicon master fabrication

DEFF Research Database (Denmark)

Tanzi, S.; Larsen, S.T.; Matteucci, M.

2012-01-01

This work demonstrates a novel all-in-polymer device for single cell capture applicable for biological recordings. The chip is injection molded and comprises a "cornered" (non planar) aperture. It has been demonstrated how cornered apertures are straightforward to mold in PDMS [1,2]. In this stud...

Pharmacokinetics of enrofloxacin and ciprofloxacin in Atlantic horseshoe crabs (Limulus polyphemus) after single injection.

Science.gov (United States)

Kirby, A; Lewbart, G A; Hancock-Ronemus, A; Papich, M G

2018-04-01

The pharmacokinetics of enrofloxacin and the metabolite ciprofloxacin were studied in horseshoe crabs after a single injection of 5 mg/kg. Twelve Atlantic horseshoe crabs (Limulus polyphemus) of undetermined age were injected with enrofloxacin into the dorsal cardiac sinus. Hemolymph samples were collected by syringe and needle at regular intervals for 120 hr. Samples were analyzed by high-pressure liquid chromatography and compartmental analysis performed on the results. Following injection, the elimination half-life (T½), peak concentration, area under the curve (AUC), and volume of distribution (VD) for enrofloxacin were 27.9 (29.13) hr, 8.98 (18.09) μg/ml, 367.38 (35.41) hr μg/ml, and 0.575 (20.48) L/kg, respectively (mean value, CV%). For ciprofloxacin, the elimination T½, peak concentration, and AUC were 61.36 (34.55) hr, 2.34 (24.11) μg/ml, and 304.46 (24.69) μg hr/ml. In these animals, the ciprofloxacin concentrations comprised an average of 45.8% of the total fluoroquinolone concentrations, which is substantial compared to other marine invertebrates. The total AUC produced (sum of enrofloxacin and ciprofloxacin) was 682.69 ± 180.61 μg hr/ml. Concentrations that were achieved after a single dose of 5 mg/kg horseshoe crabs were sufficient to treat bacteria susceptible to enrofloxacin and ciprofloxacin. © 2017 John Wiley & Sons Ltd.

Multiple PRP injections are more effective than single injections and hyaluronic acid in knees with early osteoarthritis: a randomized, double-blind, placebo-controlled trial.

Science.gov (United States)

Görmeli, Gökay; Görmeli, Cemile Ayşe; Ataoglu, Baybars; Çolak, Cemil; Aslantürk, Okan; Ertem, Kadir

2017-03-01

To compare the effectiveness of intraarticular (IA) multiple and single platelet-rich plasma (PRP) injections as well as hyaluronic acid (HA) injections in different stages of osteoarthritis (OA) of the knee. A total of 162 patients with different stages of knee OA were randomly divided into four groups receiving 3 IA doses of PRP, one dose of PRP, one dose of HA or a saline injection (control). Then, each group was subdivided into two groups: early OA (Kellgren-Lawrence grade 0 with cartilage degeneration or grade I-III) and advanced OA (Kellgren-Lawrence grade IV). The patients were evaluated before the injection and at the 6-month follow-ups using the EuroQol visual analogue scale (EQ-VAS) and International Knee Documentation Committee (IKDC) subjective scores. Adverse events and patient satisfaction were recorded. There was a statistically significant improvement in the IKDC and EQ-VAS scores in all the treatment groups compared with the control group. The knee scores of patients treated with three PRP injections were significantly better than those patients of the other groups. There was no significant difference in the scores of patients injected with one dose of PRP or HA. In the early OA subgroups, significantly better clinical results were achieved in the patients treated with three PRP injections, but there was no significant difference in the clinical results of patients with advanced OA among the treatment groups. The clinical results of this study suggest IA PRP and HA treatment for all stages of knee OA. For patients with early OA, multiple (3) PRP injections are useful in achieving better clinical results. For patients with advanced OA, multiple injections do not significantly improve the results of patients in any group. I.

Single injection thoracic paravertebral block (TPVB for breast surgery in morbidly obese patient

Directory of Open Access Journals (Sweden)

Anita Kulkarni

2017-01-01

Full Text Available Morbidly obese (MO patients with associated restrictive airway disease, obstructive sleep apnea, and coronary artery disease pose challenge to an anesthesiologist. Regional block combined with general anesthesia (GA is the anesthetic technique of choice as it will decrease the requirement of opioids, anesthetics, and postoperative respiratory depression. A MO patient for modified radical mastectomy was successfully managed with single-injection thoracic paravertebral block and conventional GA.

Intratumoral Administration of Holmium-166 Acetylacetonate Microspheres : Antitumor Efficacy and Feasibility of Multimodality Imaging in Renal Cancer

NARCIS (Netherlands)

Bult, Wouter; Kroeze, Stephanie G. C.; Elschot, Mattijs; Seevinck, Peter R.; Beekman, Freek J.; de Jong, Hugo W. A. M.; Uges, Donald R. A.; Kosterink, Jos G. W.; Luijten, Peter R.; Hennink, Wim E.; Schip, Alfred D. van Het; Bosch, J. L. H. Ruud; Nijsen, J. Frank W.; Jans, Judith J. M.

2013-01-01

Purpose: The increasing incidence of small renal tumors in an aging population with comorbidities has stimulated the development of minimally invasive treatments. This study aimed to assess the efficacy and demonstrate feasibility of multimodality imaging of intratumoral administration of

Application of single-cell technology in cancer research.

Science.gov (United States)

Liang, Shao-Bo; Fu, Li-Wu

2017-07-01

In this review, we have outlined the application of single-cell technology in cancer research. Single-cell technology has made encouraging progress in recent years and now provides the means to detect rare cancer cells such as circulating tumor cells and cancer stem cells. We reveal how this technology has advanced the analysis of intratumor heterogeneity and tumor epigenetics, and guided individualized treatment strategies. The future prospects now are to bring single-cell technology into the clinical arena. We believe that the clinical application of single-cell technology will be beneficial in cancer diagnostics and treatment, and ultimately improve survival in cancer patients. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Knee Viscosupplementation: Cost-Effectiveness Analysis between Stabilized Hyaluronic Acid in a Single Injection versus Five Injections of Standard Hyaluronic Acid

Directory of Open Access Journals (Sweden)

Francisco J. Estades-Rubio

2017-03-01

Full Text Available Given the wide difference in price per vial between various presentations of hyaluronic acid, this study seeks to compare the effectiveness and treatment cost of stabilized hyaluronic acid (NASHA in a single injection with standard preparations of hyaluronic acid (HA in five injections in osteoarthritis (OA of the knee. Fifty-four patients with knee osteoarthritis (Kellgren–Lawrence Grade II and III and the Western Ontario and McMaster Universities Arthritis Index (WOMAC pain score greater than 7, with a homogeneous distribution of age, sex, BMI, and duration of disease, were included in this study. Patients were randomized into two groups: Group I was treated with NASHA (Durolane® and Group II with HA (Go-ON®. Patient’s evolution was followed up at the 1st, 2nd, 4th, 8th, 12th, and 26th week after treatment. A statistically significant improvement in WOMAC score was observed for patients treated with NASHA versus those who received HA at Week 26. In addition, the need for analgesia was significantly reduced at Week 26 in the NASHA-treated group. Finally, the economic analysis showed an increased cost of overall treatment with HA injections. Our data support the use of the NASHA class of products in the treatment of knee OA.

Knee Viscosupplementation: Cost-Effectiveness Analysis between Stabilized Hyaluronic Acid in a Single Injection versus Five Injections of Standard Hyaluronic Acid.

Science.gov (United States)

Estades-Rubio, Francisco J; Reyes-Martín, Alvaro; Morales-Marcos, Victor; García-Piriz, Mercedes; García-Vera, Juan J; Perán, Macarena; Marchal, Juan A; Montañez-Heredia, Elvira

2017-03-17

Given the wide difference in price per vial between various presentations of hyaluronic acid, this study seeks to compare the effectiveness and treatment cost of stabilized hyaluronic acid (NASHA) in a single injection with standard preparations of hyaluronic acid (HA) in five injections in osteoarthritis (OA) of the knee. Fifty-four patients with knee osteoarthritis (Kellgren-Lawrence Grade II and III) and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score greater than 7, with a homogeneous distribution of age, sex, BMI, and duration of disease, were included in this study. Patients were randomized into two groups: Group I was treated with NASHA (Durolane ® ) and Group II with HA (Go-ON ® ). Patient's evolution was followed up at the 1st, 2nd, 4th, 8th, 12th, and 26th week after treatment. A statistically significant improvement in WOMAC score was observed for patients treated with NASHA versus those who received HA at Week 26. In addition, the need for analgesia was significantly reduced at Week 26 in the NASHA-treated group. Finally, the economic analysis showed an increased cost of overall treatment with HA injections. Our data support the use of the NASHA class of products in the treatment of knee OA.

Will a single periarticular lidocaine-corticosteroid injection improve the clinical efficacy of intraarticular hyaluronic acid treatment of symptomatic knee osteoarthritis?

Science.gov (United States)

Ertürk, Cemil; Altay, Mehmet Akif; Altay, Nuray; Kalender, Ali Murat; Öztürk, İbrahim Avşin

2016-11-01

A local injection of corticosteroid-lidocaine into the periarticular soft tissue structures is used commonly for rapid pain relief. It is hypothesized that knee pain associated with knee osteoarthritis would be relieved quickly and effectively in patients receiving intraarticular hyaluronic acid combined with a periarticular lidocaine-corticosteroid injection. To test this hypothesis, the clinical effect of the combined treatment with hyaluronic acid injection alone in patients with symptomatic knee osteoarthritis as compared in this prospective single-blinded randomized trial. This study included 70 patients. Group 1 (n = 35) received intraarticular hyaluronic acid injections only, whereas group 2 (n = 35) received intraarticular hyaluronic acid injections combined with a single local injection of corticosteroid-lidocaine. Injections were administered to the most painful areas of the anterior or posterior medial condyle of the femur or tibia. The outcome was measured by independent assessors (blinded to treatment) using a linear VAS pain scale and WOMAC and HSS knee scores. Assessments were performed at baseline and at 1, 3, 6, 12, 26, and 52 weeks. During the first 3 weeks, group 2 patients showed significantly better all scores than did group 1 patients (p hyaluronic acid alone in patients with knee osteoarthritis and can be considered a useful adjunctive treatment modality. This combined method may provide early return to patient's daily activity. Therapeutic study, Level I.

Sustained Neuroprotection From a Single Intravitreal Injection of PGJ2 in a Nonhuman Primate Model of Nonarteritic Anterior Ischemic Optic Neuropathy

Science.gov (United States)

Miller, Neil R.; Johnson, Mary A.; Nolan, Theresa; Guo, Yan; Bernstein, Alexander M.; Bernstein, Steven L.

2014-01-01

Purpose. Prostaglandin J2 (PGJ2) is neuroprotective in a murine model of nonarteritic anterior ischemic optic neuropathy (NAION). After assessing for potential toxicity, we evaluated the efficacy of a single intravitreal (IVT) injection of PGJ2 in a nonhuman primate model of NAION (pNAION). Methods. We assessed PGJ2 toxicity by administering it as a single high-dose intravenous (IV) injection, consecutive daily high-dose IV injections, or a single IVT injection in one eye of five adult rhesus monkeys. To assess efficacy, we induced pNAION in one eye of five adult male rhesus monkeys using a laser-activated rose bengal induction method. We then injected the eye with either PGJ2 or phosphate-buffered saline (PBS) intravitreally immediately or 5 hours post induction. We performed a clinical assessment, optical coherence tomography, electrophysiological testing, fundus photography, and fluorescein angiography in all animals prior to induction and at 1 day, 1 week, 2 weeks, and 4 weeks after induction. Following analysis of the first eye, we induced pNAION in the contralateral eye and then injected either PGJ2 or PBS. We euthanized all animals 5 weeks after final assessment of the fellow eye and performed both immunohistochemical and light and electron microscopic analyses of the retina and optic nerves. Results. Toxicity: PGJ2 caused no permanent systemic toxicity regardless of the amount injected or route of delivery, and there was no evidence of any ocular toxicity with the dose of PGJ2 used in efficacy studies. Transient reduction in the amplitudes of the visual evoked potentials and the N95 component of the pattern electroretinogram (PERG) occurred after both IV and IVT administration of high doses of PGJ2; however, the amplitudes returned to normal in all animals within 1 week. Efficacy: In all eyes, a single IVT dose of PGJ2 administered immediately or shortly after induction of pNAION resulted in a significant reduction of clinical, electrophysiological, and

Intratumoral heterogeneity of 18F-FDG uptake predicts survival in patients with pancreatic ductal adenocarcinoma

International Nuclear Information System (INIS)

Hyun, Seung Hyup; Kim, Ho Seong; Lee, Kyung-Han; Kim, Byung-Tae; Choi, Joon Young; Choi, Seong Ho; Choi, Dong Wook; Lee, Jong Kyun; Lee, Kwang Hyuck; Park, Joon Oh

2016-01-01

To assess whether intratumoral heterogeneity measured by 18 F-FDG PET texture analysis has potential as a prognostic imaging biomarker in patients with pancreatic ductal adenocarcinoma (PDAC). We evaluated a cohort of 137 patients with newly diagnosed PDAC who underwent pretreatment 18 F-FDG PET/CT from January 2008 to December 2010. First-order (histogram indices) and higher-order (grey-level run length, difference, size zone matrices) textural features of primary tumours were extracted by PET texture analysis. Conventional PET parameters including metabolic tumour volume (MTV), total lesion glycolysis (TLG), and standardized uptake value (SUV) were also measured. To assess and compare the predictive performance of imaging biomarkers, time-dependent receiver operating characteristic (ROC) curves for censored survival data and areas under the ROC curve (AUC) at 2 years after diagnosis were used. Associations between imaging biomarkers and overall survival were assessed using Cox proportional hazards regression models. The best imaging biomarker for overall survival prediction was first-order entropy (AUC = 0.720), followed by TLG (AUC = 0.697), MTV (AUC = 0.692), and maximum SUV (AUC = 0.625). After adjusting for age, sex, clinical stage, tumour size and serum CA19-9 level, multivariable Cox analysis demonstrated that higher entropy (hazard ratio, HR, 5.59; P = 0.028) was independently associated with worse survival, whereas TLG (HR 0.98; P = 0.875) was not an independent prognostic factor. Intratumoral heterogeneity of 18 F-FDG uptake measured by PET texture analysis is an independent predictor of survival along with tumour stage and serum CA19-9 level in patients with PDAC. In addition, first-order entropy as a measure of intratumoral metabolic heterogeneity is a better quantitative imaging biomarker of prognosis than conventional PET parameters. (orig.)

Intraperitoneal Injection Is Not a Suitable Administration Route for Single-Walled Carbon Nanotubes in Biomedical Applications.

Science.gov (United States)

Liu, Xudong; Guo, Qing; Zhang, Yuchao; Li, Jinquan; Li, Rui; Wu, Yang; Ma, Ping; Yang, Xu

2016-01-01

Given the extensive application of carbon nanotubes (CNTs) in biomedical fields, there is increasing concern regarding unintentional health impacts. Research into safe usage is therefore increasingly necessary. This study investigated the responses of the mouse brain to single-walled CNTs (SWCNTs) delivered via intraperitoneal (IP) injection and compared these results with the previous study where SWCNTs were delivered via intravenous (IV) injection so as to explore which administration route is potentially better for SWCNTs application. This study suggests SWCNTs delivered via IP injection can have negative effects on the mouse brain through oxidative stress and inflammation at high concentration exposure, but these responses were not consistent and showed no dose-dependent effect. In a previous study, the results showed that IV-delivered SWCNTs induced a more consistent and dose-dependent effect. The comparison of the 2 studies suggested that using SWCNTs at a safe dosage delivered via IV injection may be a better administration route for SWCNTs in biomedical applications.

[Basic Studies on Locoregional Injection of a Newly Designed Chitin Sol].

Science.gov (United States)

Chiba, Takehiro; Sugitachi, Akio; Kume, Kouhei; Segawa, Takenori; Nishinari, Yutaka; Ishida, Kaoru; Noda, Hironobu; Nishizuka, Satoshi; Kimura, Yusuke; Koeda, Keisuke; Sasaki, Akira

2015-11-01

Systemic chemotherapy in advanced cancer cases often provokes serious adverse events. We aimed to examine the fundamental properties and efficacy of a novel chitin sol, an anti-cancer agent with minor side effects designed to avoid the adverse effects of chemotherapy and enhance the QOL and ADL of patients. DAC-70 was used to create the novel agent termed DAC-70 sol. The anti-proliferative activity was assayed by the WST method using different types of cell lines. The anti-cancer efficacy of the novel agent was examined using cancer-bearing mice. DAC-70 sol was easily injectable through a 21-G needle. The sol suppressed proliferation of the cells in vitro. Intra-tumor injection of DAC-70 sol inhibited the rapid growth of solid tumors in the mice. CDDP-loaded DAC-70 sol, CDDP/DAC-70 sol, successfully controlled malignant ascites in the mice (psol and CDDP/DAC-70 sol is clinically useful as novel cancer chemotherapy for advanced cases. This warrants further clinical studies in cancer chemotherapy.

Intra-tumoral Heterogeneity of KRAS and BRAF Mutation Status in Patients with Advanced Colorectal Cancer (aCRC and Cost-Effectiveness of Multiple Sample Testing

Directory of Open Access Journals (Sweden)

Susan D. Richman

2011-01-01

Full Text Available KRAS mutation status is established as a predictive biomarker of benefit from anti-EGFr therapies. Mutations are normally assessed using DNA extracted from one formalin-fixed, paraffin-embedded (FFPE tumor block. We assessed heterogeneity of KRAS and BRAF mutation status intra-tumorally (multiple blocks from the same primary tumor. We also investigated the utility and efficiency of genotyping a ‘DNA cocktail’ prepared from multiple blocks. We studied 68 consenting patients in two randomized clinical trials. DNA was extracted, from ≥2 primary tumor FFPE blocks per patient. DNA was genotyped by pyrosequencing for KRAS codons 12, 13 and 61 and BRAF codon 600. In patients with heterogeneous mutation status, DNA cocktails were prepared and genotyped. Among 69 primary tumors in 68 patients, 7 (10.1% showed intratumoral heterogeneity; 5 (7.2% at KRAS codons 12, 13 and 2 (2.9% at BRAF codon 600. In patients displaying heterogeneity, the relevant KRAS or BRAF mutation was also identified in ‘DNA cocktail’ samples when including DNA from mutant and wild-type blocks. Heterogeneity is uncommon but not insignificant. Testing DNA from a single block will wrongly assign wild-type status to 10% patients. Testing more than one block, or preferably preparation of a ‘DNA cocktail’ from two or more tumor blocks, improves mutation detection at minimal extra cost.

Sustained neuroprotection from a single intravitreal injection of PGJ2 in a rodent model of anterior ischemic optic neuropathy.

Science.gov (United States)

Touitou, Valerie; Johnson, Mary A; Guo, Yan; Miller, Neil R; Bernstein, Steven L

2013-11-11

Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common cause of sudden optic nerve-related vision loss in persons older than 50 in the United States. There currently is no treatment for this disorder. We previously showed that systemic administration of 15-deoxy, delta (12, 14) prostaglandin J2 (PGJ2) is neuroprotective in our rodent model of AION (rAION). In this study, we determined if a single intravitreal (IVT) injection of PGJ2 is neuroprotective after rAION, and if this method of administration is toxic to the retina, optic nerve, or both. TOXICITY was assessed after a single IVT injection of PGJ2 in one eye and PBS in the contralateral eye of normal, adult Long-Evans rats. EFFICACY was assessed by inducing rAION in one eye and injecting either PGJ2 or vehicle immediately following induction, with the fellow eye serving as naïve control. Visual evoked potentials (VEPs) and ERGs were performed before induction and at specific intervals thereafter. Animals were euthanized 30 days after induction, after which immunohistochemistry, transmission electron microscopy, and quantitative stereology of retinal ganglion cell (RGC) numbers were performed. IVT PGJ2 did not alter the VEP or ERG compared with PBS-injected control eyes, and neither IVT PGJ2 nor PBS reduced overall RGC numbers. IVT PGJ2 preserved VEP amplitude, reduced optic nerve edema, and resulted in significant preservation of RGCs and axons in eyes with rAION. A single IVT injection of PGJ2 is nontoxic to the retina and optic nerve and neuroprotective when given immediately after rAION induction.

Robust Intratumor Partitioning to Identify High-Risk Subregions in Lung Cancer: A Pilot Study

International Nuclear Information System (INIS)

Wu, Jia; Gensheimer, Michael F.; Dong, Xinzhe; Rubin, Daniel L.; Napel, Sandy; Diehn, Maximilian; Loo, Billy W.; Li, Ruijiang

2016-01-01

Purpose: To develop an intratumor partitioning framework for identifying high-risk subregions from "1"8F-fluorodeoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT) imaging and to test whether tumor burden associated with the high-risk subregions is prognostic of outcomes in lung cancer. Methods and Materials: In this institutional review board–approved retrospective study, we analyzed the pretreatment FDG-PET and CT scans of 44 lung cancer patients treated with radiation therapy. A novel, intratumor partitioning method was developed, based on a 2-stage clustering process: first at the patient level, each tumor was over-segmented into many superpixels by k-means clustering of integrated PET and CT images; next, tumor subregions were identified by merging previously defined superpixels via population-level hierarchical clustering. The volume associated with each of the subregions was evaluated using Kaplan-Meier analysis regarding its prognostic capability in predicting overall survival (OS) and out-of-field progression (OFP). Results: Three spatially distinct subregions were identified within each tumor that were highly robust to uncertainty in PET/CT co-registration. Among these, the volume of the most metabolically active and metabolically heterogeneous solid component of the tumor was predictive of OS and OFP on the entire cohort, with a concordance index or CI of 0.66-0.67. When restricting the analysis to patients with stage III disease (n=32), the same subregion achieved an even higher CI of 0.75 (hazard ratio 3.93, log-rank P=.002) for predicting OS, and a CI of 0.76 (hazard ratio 4.84, log-rank P=.002) for predicting OFP. In comparison, conventional imaging markers, including tumor volume, maximum standardized uptake value, and metabolic tumor volume using threshold of 50% standardized uptake value maximum, were not predictive of OS or OFP, with CI mostly below 0.60 (log-rank P>.05). Conclusion: We propose a robust intratumor

Robust Intratumor Partitioning to Identify High-Risk Subregions in Lung Cancer: A Pilot Study

Energy Technology Data Exchange (ETDEWEB)

Wu, Jia; Gensheimer, Michael F.; Dong, Xinzhe [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Rubin, Daniel L. [Department of Radiology, Stanford University School of Medicine, Stanford, California (United States); Department of Medicine (Biomedical Informatics Research), Stanford University School of Medicine, Stanford, California (United States); Napel, Sandy [Department of Radiology, Stanford University School of Medicine, Stanford, California (United States); Diehn, Maximilian [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California (United States); Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California (United States); Loo, Billy W. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California (United States); Li, Ruijiang, E-mail: rli2@stanford.edu [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California (United States)

2016-08-01

Purpose: To develop an intratumor partitioning framework for identifying high-risk subregions from {sup 18}F-fluorodeoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT) imaging and to test whether tumor burden associated with the high-risk subregions is prognostic of outcomes in lung cancer. Methods and Materials: In this institutional review board–approved retrospective study, we analyzed the pretreatment FDG-PET and CT scans of 44 lung cancer patients treated with radiation therapy. A novel, intratumor partitioning method was developed, based on a 2-stage clustering process: first at the patient level, each tumor was over-segmented into many superpixels by k-means clustering of integrated PET and CT images; next, tumor subregions were identified by merging previously defined superpixels via population-level hierarchical clustering. The volume associated with each of the subregions was evaluated using Kaplan-Meier analysis regarding its prognostic capability in predicting overall survival (OS) and out-of-field progression (OFP). Results: Three spatially distinct subregions were identified within each tumor that were highly robust to uncertainty in PET/CT co-registration. Among these, the volume of the most metabolically active and metabolically heterogeneous solid component of the tumor was predictive of OS and OFP on the entire cohort, with a concordance index or CI of 0.66-0.67. When restricting the analysis to patients with stage III disease (n=32), the same subregion achieved an even higher CI of 0.75 (hazard ratio 3.93, log-rank P=.002) for predicting OS, and a CI of 0.76 (hazard ratio 4.84, log-rank P=.002) for predicting OFP. In comparison, conventional imaging markers, including tumor volume, maximum standardized uptake value, and metabolic tumor volume using threshold of 50% standardized uptake value maximum, were not predictive of OS or OFP, with CI mostly below 0.60 (log-rank P>.05). Conclusion: We propose a robust

Investigating intra-tumor heterogeneity and expression gradients of miR-21, miR-92a and miR-200c and their potential of predicting lymph node metastases in early colorectal cancer

DEFF Research Database (Denmark)

Jepsen, Rikke Karlin; Novotny, Guy Wayne; Klarskov, Louise Laurberg

2016-01-01

Introduction miR-21, miR-92a and miR-200c are regulators of pathways involved in migration, intravasation and metastasis, and their tumor expression levels have been proposed as potential prognostic markers in colorectal cancer (CRC). In two parallel cohorts we examine intra-tumor expression levels...... in early stage CRC tissue in order to determine intra-tumor heterogeneity, potential systematic intra-tumor expression gradients of the miRNAs and to investigate the association to metastatic disease in early stage CRC. Material and methods Two parallel studies on archived formalin-fixed paraffin......-embedded (FFPE) CRC tissue. Intra-tumor and inter-patient variances were analyzed in 9 early metastatic CRCs by measuring expression levels by qRT-PCR on isolated tissue samples from luminal, central and invasive border zones. Associations between miRNA expression levels and early metastasizing tumors...

Performance of single cylinder, direct injection Diesel engine using water fuel emulsions

International Nuclear Information System (INIS)

Abu-Zaid, M.

2004-01-01

A single cylinder Diesel engine study of water-in-Diesel emulsions was conducted to investigate the effect of water emulsification on the engine performance and gases exhaust temperature. Emulsified Diesel fuels of 0, 5, 10, 15 and 20 water/Diesel ratios by volume, were used in a single cylinder, direct injection Diesel engine, operating at 1200-3300 rpm. The results indicate that the addition of water in the form of emulsion improves combustion efficiency. The engine torque, power and brake thermal efficiency increase as the water percentage in the emulsion increases. The average increase in the brake thermal efficiency for 20% water emulsion is approximately 3.5% over the use of Diesel for the engine speed range studied. The proper brake specific fuel consumption and gases exhaust temperature decrease as the percentage of water in the emulsion increases

Distribution of 14C-lindane in the rat after a single dose intraperitoneal and intravenous injection

International Nuclear Information System (INIS)

Lievremont, Maurice; Le Flohic, J.-F.; Pascaud, Marc

1981-01-01

14 C-Lindane retentions in rat tissues were studied until 24 hrs after a single dose pesticide administration. Each organ shows particular kinetics. Adipose tissue is the most active in pesticide fixation but the lungs retain momentarily a large fraction of Lindane after intravenous injection [fr

Review: study of single-pellet injection experiments and development of pellet injector in JFT-2M

International Nuclear Information System (INIS)

Kasai, Satoshi; Miura, Yukitoshi; Hasegawa, Kouichi; Sengoku, Seio

1987-10-01

The single pellet injector developed for JFT-2M and the improvement of plasma characteristics in the auxiliary-heated discharges by single-pellet injection are reviewed for the period 1982 - 1986. The pellet injector is a pneumatic type and the designed pellet size is 1.65 mmD x 1.65 mmL and 1 mmD x 1 mmL. The hydrogen, deuterium and mixed (H 2 + D 2 ) pellets can be produced with good reproducibility. Maximum pellet velocity is about 970 m/s (pellet is deuterium and propellant gas is hydrogen). In the pellet injection experiments into auxiliary-heated (NB, ICRF) divertor or limiter discharges, the plasma confinement time is improved by a factor of 1.4 - 1.7 compared with the confinement time in the Ohmic discharges. The achieved confinement time is longer than that on the high confinement mode (H-mode) in gas fueled discharges, although the phenomena are transient. (author)

Intratumoral metabolic heterogeneity predicts invasive components in breast ductal carcinoma in situ

Energy Technology Data Exchange (ETDEWEB)

Yoon, Hai-Jeon [Ewha Womans University School of Medicine, Department of Nuclear Medicine, Yangchun-Ku, Seoul (Korea, Republic of); Kim, Yemi [Ewha Womans University, Clinical Research Institute, Seoul (Korea, Republic of); Kim, Bom Sahn [Ewha Womans University School of Medicine, Department of Nuclear Medicine, Yangchun-Ku, Seoul (Korea, Republic of); Ewha Womans University, Clinical Research Institute, Seoul (Korea, Republic of)

2015-12-15

This study investigated whether texture-based imaging parameters could identify invasive components of ductal carcinoma in situ (DCIS). We enrolled 65 biopsy-confirmed DCIS patients (62 unilateral, 3 bilateral) who underwent {sup 18}F-FDG PET, diffusion-weighted imaging (DWI), or breast-specific gamma imaging (BSGI). We measured SUV{sub max} and intratumoral metabolic heterogeneity by the area under the curve (AUC) of cumulative SUV histograms (CSH) on PET, tumour-to-normal ratio (TNR) and coefficient of variation (COV) as an index of heterogeneity on BSGI, minimum ADC (ADC{sub min}) and ADC difference (ADC{sub diff}) as an index of heterogeneity on DWI. After surgery, final pathology was categorized as pure-DCIS (DCIS-P), DCIS with microinvasion (DCIS-MI), or invasive ductal carcinoma (IDC). Clinicopathologic features of DCIS were correlated with final classification. Final pathology confirmed 44 DCIS-P, 14 DCIS-MI, and 10 IDC. The invasive component of DCIS was significantly correlated with higher SUV{sub max} (p = 0.017) and lower AUC-CSH (p < 0.001) on PET, higher TNR (p = 0.008) and COV (p = 0.035) on BSGI, lower ADC{sub min} (p = 0.016) and higher ADC{sub diff} (p = 0.009) on DWI, and larger pathologic size (p = 0.018). On multiple regression analysis, AUC-CSH was the only significant predictor of invasive components (p = 0.044). The intratumoral metabolic heterogeneity of {sup 18}F-FDG PET was the most important predictor of invasive components of DCIS. (orig.)

Intratumoral metabolic heterogeneity predicts invasive components in breast ductal carcinoma in situ

International Nuclear Information System (INIS)

Yoon, Hai-Jeon; Kim, Yemi; Kim, Bom Sahn

2015-01-01

This study investigated whether texture-based imaging parameters could identify invasive components of ductal carcinoma in situ (DCIS). We enrolled 65 biopsy-confirmed DCIS patients (62 unilateral, 3 bilateral) who underwent 18 F-FDG PET, diffusion-weighted imaging (DWI), or breast-specific gamma imaging (BSGI). We measured SUV max and intratumoral metabolic heterogeneity by the area under the curve (AUC) of cumulative SUV histograms (CSH) on PET, tumour-to-normal ratio (TNR) and coefficient of variation (COV) as an index of heterogeneity on BSGI, minimum ADC (ADC min ) and ADC difference (ADC diff ) as an index of heterogeneity on DWI. After surgery, final pathology was categorized as pure-DCIS (DCIS-P), DCIS with microinvasion (DCIS-MI), or invasive ductal carcinoma (IDC). Clinicopathologic features of DCIS were correlated with final classification. Final pathology confirmed 44 DCIS-P, 14 DCIS-MI, and 10 IDC. The invasive component of DCIS was significantly correlated with higher SUV max (p = 0.017) and lower AUC-CSH (p < 0.001) on PET, higher TNR (p = 0.008) and COV (p = 0.035) on BSGI, lower ADC min (p = 0.016) and higher ADC diff (p = 0.009) on DWI, and larger pathologic size (p = 0.018). On multiple regression analysis, AUC-CSH was the only significant predictor of invasive components (p = 0.044). The intratumoral metabolic heterogeneity of 18 F-FDG PET was the most important predictor of invasive components of DCIS. (orig.)

Assessment of the efficacy and safety of single platelet-rich plasma injection on different types and grades of facial wrinkles.

Science.gov (United States)

Elnehrawy, Naema Y; Ibrahim, Zeinab A; Eltoukhy, Azza M; Nagy, Hala M

2017-03-01

Platelet-rich plasma (PRP) is considered as a growing modality for tissue regeneration and a developing research area for clinicians and researchers. PRP injection treatment provides supraphysiological concentrations of growth factors that may help in accelerated tissue remodeling and regeneration. To evaluate the efficacy and safety of single autologous PRP intradermal injection for treatment of facial wrinkles and for facial rejuvenation. A total of 20 subjects with different types of facial wrinkles were included in this study. All subjects received single PRP intradermal injection and were clinically assessed before and after treatment for a period of 8 weeks using Wrinkle Severity Rating Scale (WSRS), Skin Homogeneity and Texture (SHnT) Scale, Physician Assessment Scale, and Subject Satisfaction Scale. The mean value of WSRS reduced from 2.90 ± 0.91 before treatment to 2.10 ± 0.79 after 8 weeks of treatment. The most significant results were with younger subjects that have mild and moderate wrinkles of the nasolabial folds (NLFs). Fourteen of seventeen subjects with NLFs showed more than 25% improvement in their appearance. Side effects of PRP treatment were minimal to mild and with excellent tolerability. Single PRP intradermal injection is well tolerated and capable of rejuvenating the face and producing a significant correction of wrinkles especially the NLFs. © 2016 Wiley Periodicals, Inc.

Synthesis of Poly[APMA]-DOTA-64Cu Conjugates for Interventional Radionuclide Therapy of Prostate Cancer: Assessment of Intratumoral Retention by Micro–Positron Emission Tomography

Directory of Open Access Journals (Sweden)

Jianchao Yuan

2007-01-01

Full Text Available To develop new radiopharmaceuticals for interventional radionuclide therapy of locally recurrent prostate cancer, poly[N-(3-aminopropylmethacrylamide] [poly(APMA] polymers were synthesized by free radical precipitation polymerization in acetonedimethylsulfoxide using N,N‘-azobis(isobutyronitrile as the initiator. The polymers were characterized with nuclear magnetic resonance, size exclusion chromatography, and dynamic light scattering (Mn 5 2.40 × 104, Mw/Mn = 1.87. Subsequently, poly[APMA] was coupled with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA using 1-(3-dimethylaminopropyl-3-ethylcarbodiimide hydrochloride as an activator, followed by conjugation with 64Cu radionuclide. Prolonged retention of poly[APMA]-DOTA-64Cu conjugates within the tumor tissues was demonstrated by micro–positron emission tomography at 24 hours following intra-tumoral injection of the conjugates to human prostate xenografts in mice. The data suggest that the poly[APMA]-DOTA-64Cu conjugates might be useful for interventional radionuclide therapy of locally recurrent prostate cancer in humans.

Enhanced intratumoral uptake of quantum dots concealed within hydrogel nanoparticles

International Nuclear Information System (INIS)

Nair, Ashwin; Shen Jinhui; Thevenot, Paul; Zou Ling; Tang Liping; Cai Tong; Hu Zhibing

2008-01-01

Effective nanomedical devices for tumor imaging and drug delivery are not yet available. In an attempt to construct a more functional device for tumor imaging, we have embedded quantum dots (which have poor circulatory behavior) within hydrogel nanoparticles made of poly-N-isopropylacrylamide. We found that the hydrogel encapsulated quantum dots are more readily taken up by cultured tumor cells. Furthermore, in a melanoma model, hydrogel encapsulated quantum dots also preferentially accumulate in the tumor tissue compared with normal tissue and have ∼16-fold greater intratumoral uptake compared to non-derivatized quantum dots. Our results suggest that these derivatized quantum dots, which have greatly improved tumor localization, may enhance cancer monitoring and chemotherapy.

Diffuse chorioretinal atrophy after a single standard low- dose intravitreal melphalan injection in a child with retinoblastoma: a case report.

Science.gov (United States)

Chao, An- Ning; Kao, Ling-Yuh; Liu, Laura; Wang, Nan-Kai

2016-03-15

Controlling retinoblastoma with seeding is challenging despite advances in treatment modalities. Intravitreal melphalan is an alternative to external beam radiation or enucleation for recurrent or refractory vitreous seeds. Significant ocular side effects following intravitreal melphalan injections are uncommon. Complications have been reported in eyes receiving higher concentrations of melphalan and repetitive injections. We report a case in which diffuse chorioretinal atrophy was developed at the injection site after a single, standard low-dose intravitreal melphalan injection. A 12-month-old female child without a family history of retinoblastoma presented with unilateral group C retinoblastoma in her right eye. A solitary tumour with retinal breaks on the tumour surface, and vitreous seeds overlying the tumour were observed at the 8 o'clock position of the retina. After two cycles of intra-arterial chemotherapy with melphalan, the main tumour displayed significant regression, but the vitreous seeds overlying the main tumour were still active. Because of the persistence of vitreous seeds and the inadequate response to intra-arterial melphalan treatment, intravitreal melphalan (8 μg in 0.05 mL) was injected using a 32-gauge needle 2.5 mm from the 5 o'clock position of the limbus, the meridian opposite to the vitreous seeds. After 1 month, the retina around the injection site demonstrated diffuse retinal pigment epithelium alterations with dense hard exudates. Although the main retinal mass, and vitreous seeds resolved, the hard exudates persisted for more than 2 years after the single low-dose melphalan injection. Intravitreal melphalan injections should be cautiously used for eyes with refractory seeds, particularly when multiple injections are required to control retinoblastoma seeds. Dose- related retinal toxicity could occur in pre-treated eyes even when a relatively low standard dose is used. Such patients should be followed up closely to monitor the

UV-visible digital imaging of split injection in a Gasoline Direct Injection engine

Directory of Open Access Journals (Sweden)

Merola Simona Silvia

2015-01-01

Full Text Available Ever tighter limits on pollutant emissions and the need to improve energy conversion efficiency have made the application of gasoline direct injection (GDI feasible for a much wider scale of spark ignition engines. Changing the way fuel is delivered to the engine has thus provided increased flexibility but also challenges, such as higher particulate emissions. Therefore, alternative injection control strategies need to be investigated in order to obtain optimum performance and reduced environmental impact. In this study, experiments were carried out on a single-cylinder GDI optical engine fuelled with commercial gasoline in lean-burn conditions. The single-cylinder was equipped with the head of a commercial turbocharged engine with similar geometrical specifications (bore, stroke, compression ratio and wall guided fuel injection. Optical accessibility was ensured through a conventional elongated hollow Bowditch piston and an optical crown, accommodating a fused-silica window. Experimental tests were performed at fixed engine speed and injection pressure, whereas the injection timing and the number of injections were adjusted to investigate their influence on combustion and emissions. UV-visible digital imaging was applied in order to follow the combustion process, from ignition to the late combustion phase. All the optical data were correlated with thermodynamic analysis and measurements of exhaust emissions. Split injection strategies (i.e. two injections per cycle with respect to single injection increased combustion efficiency and stability thanks to an improvement of fuel air mixing. As a consequence, significant reduction in soot formation and exhaust emission with acceptable penalty in terms of HC and NOx were measured.

High-power actively Q-switched single-mode 1342 nm Nd:YVO4 ring laser, injection-locked by a cw single-frequency microchip laser.

Science.gov (United States)

Koch, Peter; Bartschke, Juergen; L'huillier, Johannes A

2015-11-30

In this paper we report on the realization of a single-mode Q-switched Nd:YVO4 ring laser at 1342 nm. Unidirectional and single-mode operation of the ring laser is achieved by injection-locking with a continuous wave Nd:YVO4 microchip laser, emitting a single-frequency power of up to 40 mW. The ring laser provides a single-mode power of 13.9 W at 10 kHz pulse repetition frequency with a pulse duration of 18.2 ns and an excellent beam quality (M2 laser, a power of 8.7 W at 671 nm with a pulse duration of 14.8 ns and a beam propagation factor of M2 < 1.1 is obtained. The 671 nm radiation features a long-term spectral width of 75 MHz.

Fat injection to correct contour deformities of the reconstructed breast: a single surgeon experience

Directory of Open Access Journals (Sweden)

Youssef Tahiri

2015-06-01

Full Text Available Aim: Autologous fat grafting has gained acceptance as a technique to improve aesthetic outcomes in breast reconstruction. The purpose of this study was to share our clinical experience using autologous fat injection to correct contour deformities during breast reconstruction. Methods: A single surgeon, prospectively maintained database of patients who underwent autologous fat injection during breast reconstruction from January 2008 to November 2013 at McGill University Health Center was reviewed. Patient characteristics, breast history, type of breast reconstruction, volume of fat injected, and complications were analyzed. Results: One hundred and twenty-four patients benefited from autologous fat injection from January 2008 to November 2013, for a total of 187 treated breasts. The patients were on average 49.3 years old (΁ 8.9 years. Fat was harvested from the medial thighs (20.5%, flanks (39.1%, medial thighs and flanks (2.9%, trochanters (13.3%, medial knees (2.7%, and abdomen (21.9%. An average of 49.25 mL of fat was injected into each reconstructed breast. A total of 187 breasts in 124 patients were lipo-infiltrated during the second stage of breast reconstruction. Thirteen breasts (in 12 separate patients were injected several years after having undergone lumpectomy and radiotherapy. Of the 187 treated breasts, 118 were reconstructed with expanders to implants, 45 with deep inferior epigastric perforator flaps, 9 with latissimus dorsi flaps with implants, 4 with transverse rectus abdominis myocutaneous flaps, and 13 had previously undergone lumpectomy and radiotherapy. Six complications were noted in the entire series, for a rate of 3.2%. All were in previously radiated breasts. Average follow-up time was 12 months (range: 2-36 months. Conclusion: Fat injection continues to grow in popularity as an adjunct to breast reconstruction. Our experience demonstrates a low complication rate as compared to most surgical interventions of the breast

Enhancement of anticancer activity in antineovascular therapy is based on the intratumoral distribution of the active targeting carrier for anticancer drugs

International Nuclear Information System (INIS)

Maeda, Noriyuki; Miyazawa, Souichiro; Shimizu, Kosuke; Asai, Tomohiro; Yonezawa, Sei; Oku, Naoto; Kitazawa, Sadaya; Namba, Yukihiro; Tsukada, Hideo

2006-01-01

We previously observed the enhanced anticancer efficacy of anticancer drugs encapsulated in Ala-Pro-Arg-Pro-Gly-polyethyleneglycol-modified liposome (APRPG-PEG-Lip) in tumor-bearing mice, since APRPG peptide was used as an active targeting tool to angiogenic endothelium. This modality, antineovascular therapy (ANET), aims to eradicate tumor cells indirectly through damaging angiogenic vessels. In the present study, we examined the in vivo trafficking of APRPG-PEG-Lip labeled with [2- 18 F]2-fluoro-2-deoxy- D -glucose ([2- 18 F]FDG) by use of positron emission tomography (PET), and observed that the trafficking of this liposome was quite similar to that of non-targeted long-circulating liposome (PEG-Lip). Then, histochemical analysis of intratumoral distribution of both liposomes was performed by use of fluorescence-labeled liposomes. In contrast to in vivo trafficking, intratumoral distribution of both types of liposomes was quite different: APRPG-PEG-Lip was colocalized with angiogenic endothelial cells that were immunohistochemically stained for CD31, although PEG-Lip was localized around the angiogenic vessels. These results strongly suggest that intratumoral distribution of drug carrier is much more important for therapeutic efficacy than the total accumulation of the anticancer drug in the tumor, and that active delivery of anticancer drugs to angiogenic vessels is useful for cancer treatment. (author)

Salivary gland tumors of the parotid gland: CT and MR imaging findings with emphasis on intratumoral cystic components

Energy Technology Data Exchange (ETDEWEB)

Kato, Hiroki; Watanabe, Haruo [Gifu University School of Medicine, Department of Radiology, Gifu (Japan); Kanematsu, Masayuki [Gifu University School of Medicine, Department of Radiology, Gifu (Japan); Gifu University Hospital, High-Level Imaging Diagnosis Center, Gifu (Japan); Mizuta, Keisuke; Aoki, Mitsuhiro [Gifu University School of Medicine, Department of Otolaryngology, Gifu (Japan)

2014-09-15

The purpose of this study was to assess computed tomography (CT) and magnetic resonance (MR) imaging findings of salivary gland tumors of the parotid gland with emphasis on intratumoral cystic components. Seventy-two histopathologically confirmed salivary gland tumors of the parotid gland (44 benign and 28 malignant), which underwent both CT and MR imaging including contrast-enhanced study, were included in this study. We retrospectively reviewed images for the presence, number, occupying rate, margin characteristics, distribution, and predominant MR signal intensity of intratumoral cystic components. The prevalence of cystic components was greater in malignant than benign tumors (79 vs. 50 %, p < 0.05). The number and occupying rate were similar between benign and malignant tumors. The irregular margins were more frequent in malignant than benign tumors (73 vs. 27 %, p < 0.01). The frequency of eccentric location was greater in benign than malignant tumors (91 vs. 55 %, p < 0.01), whereas the frequency of centric location was greater in malignant than benign tumors (32 vs. 0 %, p < 0.01). On T1-weighted images, the frequency of hyperintensity was greater in benign than malignant tumors (50 vs. 9 %, p < 0.01), whereas that of isointensity was greater in malignant than benign tumors (50 vs. 0 %, p < 0.01). Multiple logistic regression analysis showed that the absence of irregular margins of cystic components only was significantly correlated with the presence of benign salivary gland tumors (p < 0.01). Imaging features of intratumoral cystic components may help to differentiate benign from malignant tumors of the parotid salivary gland. (orig.)

Single-shot measurements of low emittance beams from laser-plasma accelerators comparing two triggered injection methods

Science.gov (United States)

van Tilborg, Jeroen

2017-10-01

The success of laser plasma accelerator (LPA) based applications, such as a compact x-ray free electron laser (FEL), relies on the ability to produce electron beams with excellent 6D brightness, where brightness is defined as the ratio of charge to the product of the three normalized emittances. As such, parametric studies of the emittance of LPA generated electron beams are essential. Profiting from a stable and tunable LPA setup, combined with a carefully designed single-shot energy-dispersed emittance diagnostic, we present a direct comparison of charge dependent emittance measurements of electron beams generated by two different injection mechanisms: ionization injection and shock-induced density down-ramp injection. Both injection mechanisms have gained in popularity in recent years due to their demonstrated stable LPA performance. For the down-ramp injection configuration, normalized emittances a factor of two lower were recorded: less than 1 micron at spectral charge densities up to 2 pC/MeV. For both injection mechanisms, a contributing correlation of space charge to the emittance was identified. This measurement technique in general, and these results specifically, are critical to the evaluation of LPA injection methods and development of high-quality LPA beam lines worldwide. This work is supported by the U.S. DOE under Contract No. DE-AC02-05CH11231, by the U.S. DOE NNSA, DNN R&D (NA22), by the National Science Foundation under Grant No. PHY-1415596, and by the Gordon and Betty Moore Foundation under Grant ID GBMF4898.

The comparison of knee osteoarthritis treatment with single-dose bone marrow-derived mononuclear cells vs. hyaluronic acid injections.

Science.gov (United States)

Goncars, Valdis; Jakobsons, Eriks; Blums, Kristaps; Briede, Ieva; Patetko, Liene; Erglis, Kristaps; Erglis, Martins; Kalnberzs, Konstantins; Muiznieks, Indrikis; Erglis, Andrejs

2017-01-01

The aim of this study was to compare treatment methods of the knee joint degenerative osteoarthritis, using autologous bone marrow-derived mononuclear cells and hyaluronic acid injections and observe prevalence of adverse effects in both groups. A prospective randomized controlled clinical trial was carried out. The analysis of pain and changes in osteoarthritis symptoms after a single intra-articular bone marrow-derived mononuclear cell injection into the knee joint in the Kellgren-Lawrence stage II-III osteoarthritis during the 12-month period were performed. The results were compared with the control group treated routinely by hyaluronic acid injections therapy. A therapy group of patients (n=28) received single bone marrow-derived mononuclear cell intra-articular injections. A control group of patients (n=28) was treated with a total of three sodium hyaluronate intra-articular injections each one performed a week apart. The clinical results were obtained using the Knee Osteoarthritis Outcome Score (KOOS) and the Knee Society Score (KSS) before and 3, 6, and 12 months after injection. A statistically significant improvement was observed in the mononuclear cell group over the starting point in all scores. At the endpoint at month 12, the KOOS score improved significantly (Phyaluronic acid versus the bone marrow-derived mononuclear cells group at time points 6 and 12 months demonstrated a statistically significant (Phyaluronic acid group. In both groups serious adverse effects were not observed. The intra-articular injection of bone marrow-derived mononuclear cells is a safe manipulation with no side effects during the 12-month period. This treatment provides statistically significant clinical improvement between the starting point and 1, 3, 6, and 12 months after. When compared to hyaluronic acid treatment, better pain relief in the long-term period of mononuclear cell group was observed. Copyright © 2017 The Lithuanian University of Health Sciences. Production

Single injection 51Cr EDTA plasma clearance determination in children using capillary blood samples

International Nuclear Information System (INIS)

Broechner-Mortensen, J.; Christoffersen, J.

1977-01-01

The reliability of a determination of the total 51 Cr EDTA plasma clearance (e) (and with it the glomerular filtration rate), by a simplified single injection method (injected dose: 4.5 μCi per kg b.w.) using capillary blood samples (0.2 ml), was investigated in twenty children. Clearance values determined from capillary blood samples did not differ significantly from those measured simultaneously from venous blood samples, the mean ratio+-SD being 1.02+-0.06(n = 10). The reproducibility (total day-to-day variation) of E determined from capillary blood samples was 6.7% in children with decreased renal function (n = 3) and 6.9% in children with normal renal function (n = 7). The present data indicate that the use of capillary blood samples is an accurate and very precise approach for determination of E in children. (Auth.)

A Single Intravitreal Injection of Ranibizumab Provides No Neuroprotection in a Nonhuman Primate Model of Moderate-to-Severe Nonarteritic Anterior Ischemic Optic Neuropathy.

Science.gov (United States)

Miller, Neil R; Johnson, Mary A; Nolan, Theresa; Guo, Yan; Bernstein, Steven L

2015-12-01

Ranibizumab, a vascular endothelial growth factor-antagonist, is said to be neuroprotective when injected intravitreally in patients with nonarteritic anterior ischemic optic neuropathy (NAION). We evaluated the efficacy of a single intravitreal (IVT) injection of ranibizumab in a nonhuman primate model of NAION (pNAION). We induced pNAION in one eye of four adult male rhesus monkeys using a laser-activated rose Bengal induction method. We then immediately injected the eye with either ranibizumab or normal saline (NS) intravitreally. We performed a clinical assessment, optical coherence tomography, electrophysiological testing, fundus photography, and fluorescein angiography in three of the animals (one animal developed significant retinal hemorrhages and, therefore, could not be analyzed completely) prior to induction, 1 day and 1, 2, and 4 weeks thereafter. Following the 4-week analysis of the first eye, we induced pNAION in the contralateral eye and then injected either ranibizumab or NS, whichever substance had not been injected in the first eye. We euthanized all animals 5 to 12 weeks after the final assessment of the second eye and performed both immunohistochemical and light and electron microscopic analyses of the retina and optic nerves of both eyes. A single IVT dose of ranibizumab administered immediately after induction of pNAION resulted in no significant reduction of clinical, electrophysiological, or histologic damage compared with vehicle-injected eyes. A single IVT dose of ranibizumab is not neuroprotective when administered immediately after induction of pNAION.

Comparative Investigation on 0.4 inch SBLOCA Scenario with Single and Dual Train Passive Safety Injection Systems using SMART-ITL

Energy Technology Data Exchange (ETDEWEB)

Park, Hyun-Sik; Bae, Hwang; Ryu, Sung-Uk; Jeon, Byong-Guk; Yang, Jin-Hwa; Yun, Eun-Koo; Choi, Nam-Hyun; Min, Kyoung-Ho; Shin, Yong-Cheol; Bang, Yoon-Gon; Kim, Myoung-Jun; Seo, Chan-Jong; Yi, Sung-Jae [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2016-10-15

The Standard Design Approval (SDA) for SMART was certificated in 2012 at the Korea Atomic Energy Research Institute (KAERI). In December 2015, Saudi Arabia and Korea started conducting a three-year project of Pre-Project Engineering (PPE) to prepare a Preliminary Safety Analysis Report (PSAR) and to review the feasibility of constructing SMART reactors in Saudi Arabia. In addition, an Integral Test Loop for the SMART design (SMART-ITL, or FESTA) has been constructed and it finished its commissioning tests in 2012. Consequently, a set of Design Base Accident (DBA) scenarios have been simulated using SMART-ITL. In this paper, a comparative investigation was performed on 0.4 inch SBLOCA scenario with single and dual train passive safety injection systems using SMART-ITL. In this paper, the effect of the train number of PSIS on a SBLOCA scenario is investigated for a break size of 0.4 inch. The single and dual train tests show a similar trend in general but the injected water migrates slightly differently in the RV and is discharged through the break nozzle. The parameters of the RV pressure, RV water level, accumulated break mass, and injection flowrates from the CMT and SIT were compared. Compared with the single train test, the increased injection rates from the two trains of the PSIS during the dual train test raised the RV water level, ensuring the safety of the reactor core.

Direct Endoscopic Intratumoral Injection of Onyx for the Preoperative Embolization of a Recurrent Juvenile Nasal Angiofibroma

Science.gov (United States)

Hira, A.; Chao, K.

2011-01-01

Summary Percutaneous injection of embolization material within head and neck tumors is being described as an alternative or adjunct to transarterial embolization. Access in these reports is by computed tomography (CT) guidance, which is cumbersome given the need to transport the patient from the CT scanner to angiography suite. We describe a case of direct percutaneous onyx embolization of juvenile nasal angiofibroma following endoscopic access in the angiography suite including self-sustained onyx combustion during surgical electrocautery. PMID:22192553

Efficacy and safety of single injection of cross-linked sodium hyaluronate vs. three injections of high molecular weight sodium hyaluronate for osteoarthritis of the knee: a double-blind, randomized, multi-center, non-inferiority study.

Science.gov (United States)

Ha, Chul-Won; Park, Yong-Beom; Choi, Chong-Hyuk; Kyung, Hee-Soo; Lee, Ju-Hong; Yoo, Jae Doo; Yoo, Ju-Hyung; Choi, Choong-Hyeok; Kim, Chang-Wan; Kim, Hee-Chun; Oh, Kwang-Jun; Bin, Seong-Il; Lee, Myung Chul

2017-05-26

This randomized, double-blind, multi-center, non-inferiority trial was conducted to assess the efficacy and safety of a cross-linked hyaluronate (XLHA, single injection form) compared with a linear high molecular hyaluronate (HMWHA, thrice injection form) in patients with symptomatic knee osteoarthritis. Two hundred eighty seven patients with osteoarthritis (Kellgren-Lawrence grade I to III) were randomized to each group. Three weekly injections were given in both groups but two times of saline injections preceded XLHA injection to maintain double-blindness. Primary endpoint was the change of weight-bearing pain (WBP) at 12 weeks after the last injection. Secondary endpoints included Western Ontario and McMaster Universities Osteoarthritis index; patient's and investigator's global assessment; pain at rest, at night, or in motion; OMERACT-OARSI responder rate; proportion of patients achieving at least 20 mm or 40% decrease in WBP; and rate of rescue medicine use and its total consumption. Mean changes of WBP at 12 weeks after the last injection were -33.3 mm with XLHA and -29.2 mm with HMWHA, proving non-inferiority of XLHA to HMWHA as the lower bound of 95% CI (-1.9 mm, 10.1 mm) was well above the predefined margin (-10 mm). There were no significant between-group differences in all secondary endpoints. Injection site pain was the most common adverse event and no remarkable safety issue was identified. This study demonstrated that a single injection of XLHA was non-inferior to three weekly injections of HMWHA in terms of WBP reduction, and supports XLHA as an effective and safe treatment for knee osteoarthritis. ClinicalTrials.gov ( NCT01510535 ). This trial was registered on January 6, 2012.

Stability of methadone hydrochloride in 0.9% sodium chloride injection in single-dose plastic containers.

Science.gov (United States)

Denson, D D; Crews, J C; Grummich, K W; Stirm, E J; Sue, C A

1991-03-01

The stability of methadone hydrochloride in 0.9% sodium chloride injection in flexible polyvinyl chloride containers was studied. Commercially available methadone hydrochloride 20 mg/mL and 25-mL single-dose bags of 0.9% sodium chloride injection were used. Six samples each were prepared at methadone hydrochloride concentrations of 1, 2, and 5 mg/mL. The solutions were stored at room temperature and were not protected from light. Immediately after preparation and after two, three, and four weeks of storage, each of the 18 samples was divided into three aliquots, each of which was analyzed in duplicate for methadone hydrochloride concentration by gas chromatography. There was less than 10% change in methadone hydrochloride concentration in any sample throughout the four-week study period. Methadone hydrochloride at concentrations of 1, 2, and 5 mg/mL prepared in commercially available flexible polyvinyl chloride containers of 0.9% sodium chloride injection and stored at room temperature without deliberate protection from light is stable for at least four weeks.

Robust Intratumor Partitioning to Identify High-Risk Subregions in Lung Cancer: A Pilot Study.

Science.gov (United States)

Wu, Jia; Gensheimer, Michael F; Dong, Xinzhe; Rubin, Daniel L; Napel, Sandy; Diehn, Maximilian; Loo, Billy W; Li, Ruijiang

2016-08-01

To develop an intratumor partitioning framework for identifying high-risk subregions from (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT) imaging and to test whether tumor burden associated with the high-risk subregions is prognostic of outcomes in lung cancer. In this institutional review board-approved retrospective study, we analyzed the pretreatment FDG-PET and CT scans of 44 lung cancer patients treated with radiation therapy. A novel, intratumor partitioning method was developed, based on a 2-stage clustering process: first at the patient level, each tumor was over-segmented into many superpixels by k-means clustering of integrated PET and CT images; next, tumor subregions were identified by merging previously defined superpixels via population-level hierarchical clustering. The volume associated with each of the subregions was evaluated using Kaplan-Meier analysis regarding its prognostic capability in predicting overall survival (OS) and out-of-field progression (OFP). Three spatially distinct subregions were identified within each tumor that were highly robust to uncertainty in PET/CT co-registration. Among these, the volume of the most metabolically active and metabolically heterogeneous solid component of the tumor was predictive of OS and OFP on the entire cohort, with a concordance index or CI of 0.66-0.67. When restricting the analysis to patients with stage III disease (n=32), the same subregion achieved an even higher CI of 0.75 (hazard ratio 3.93, log-rank P=.002) for predicting OS, and a CI of 0.76 (hazard ratio 4.84, log-rank P=.002) for predicting OFP. In comparison, conventional imaging markers, including tumor volume, maximum standardized uptake value, and metabolic tumor volume using threshold of 50% standardized uptake value maximum, were not predictive of OS or OFP, with CI mostly below 0.60 (log-rank P>.05). We propose a robust intratumor partitioning method to identify clinically relevant, high

Observing Exoplanets with High-dispersion Coronagraphy. II. Demonstration of an Active Single-mode Fiber Injection Unit

Energy Technology Data Exchange (ETDEWEB)

Mawet, D.; Ruane, G.; Xuan, W.; Echeverri, D.; Klimovich, N.; Randolph, M.; Fucik, J.; Wang, J.; Dekany, R.; Delorme, J.-R. [Department of Astronomy, California Institute of Technology, 1200 East California Boulevard, MC 249-17, Pasadena, CA 91125 (United States); Wallace, J. K.; Vasisht, G.; Mennesson, B.; Choquet, E.; Serabyn, E., E-mail: dmawet@astro.caltech.edu [Jet Propulsion Laboratory, California Institute of Technology, 4800 Oak Grove Drive, Pasadena, CA 91109 (United States)

2017-04-01

High-dispersion coronagraphy (HDC) optimally combines high-contrast imaging techniques such as adaptive optics/wavefront control plus coronagraphy to high spectral resolution spectroscopy. HDC is a critical pathway toward fully characterizing exoplanet atmospheres across a broad range of masses from giant gaseous planets down to Earth-like planets. In addition to determining the molecular composition of exoplanet atmospheres, HDC also enables Doppler mapping of atmosphere inhomogeneities (temperature, clouds, wind), as well as precise measurements of exoplanet rotational velocities. Here, we demonstrate an innovative concept for injecting the directly imaged planet light into a single-mode fiber, linking a high-contrast adaptively corrected coronagraph to a high-resolution spectrograph (diffraction-limited or not). Our laboratory demonstration includes three key milestones: close-to-theoretical injection efficiency, accurate pointing and tracking, and on-fiber coherent modulation and speckle nulling of spurious starlight signal coupling into the fiber. Using the extreme modal selectivity of single-mode fibers, we also demonstrated speckle suppression gains that outperform conventional image-based speckle nulling by at least two orders of magnitude.

Impact of physical properties of biodiesel on the injection process in a common-rail direct injection system

International Nuclear Information System (INIS)

Boudy, Frederic; Seers, Patrice

2009-01-01

This paper presents the influence of biodiesel fuel properties on the injection mass flow rate of a diesel common-rail injection system. Simulations are first performed with ISO 4113 diesel fuel on a four-cylinder common-rail system to evaluate a single and triple injection strategies. For each injection strategy, the impact of modifying a single fuel property at a time is evaluated so as to quantify its influence on the injection process. The results show that fuel density is the main property that affects the injection process, such as total mass injected and pressure wave in the common-rail system. The fuel's viscosity and bulk modulus also influence, but to a lessen degree, the mass flow rate of the injector notably during multiple injection strategies as individual properties change the fuel's dampening property and friction coefficient.

Single-dose Intramuscular-injection Toxicology Test of Water-soluble Carthami-flos and Cervi cornu parvum Pharmacopuncture in a Rat Model

Directory of Open Access Journals (Sweden)

Sunju Park

2015-09-01

Full Text Available Objectives: The aim of the study is to investigate both the single-dose intramuscular injection toxicity and the approximate lethal dose of water-soluble Carthami-flos and Cervi cornu parvum pharmacopuncture (WCFC in male and female Sprague-Dawley (SD rats. Methods: The study was conducted at Biotoxtech Co. according to the Good Laboratory Practice (GLP regulation and the toxicity test guidelines of the Ministry of Food and Drug Safety (MFDS after approval of the Institutional Animal Care and Use Committee. Dosages for the control, high dose, middle dose and low dose groups were 0.5 mL/animal of saline and 0.5, 0.25 and 0.125 mL/animal of WCFC, respectively. WCFC was injected into the muscle of the left femoral region by using a disposable syringe (1 mL, 26 gauge. The general symptoms and mortality were observed 30 minutes, 1, 2, 4, and 6 hours after the first injection and then daily for 14 days after the injection. The body weights of the SD rats were measured on the day of the injection (before injection and on the third, seventh, and fourteenth days after the injection. Serum biochemical and hematologic tests, necropsy examinations, and histopathologic examinations at the injection site were performed after the observation period. Results: No deaths, abnormal clinical symptoms, or significant weight changes were observed in either male or female SD rats in the control or the test (0.125, 0.25, and 0.5 mL/animal groups during the observation period. No significant differences in hematology and serum biochemistry and no macroscopic abnormalities at necropsy were found. No abnormal reactions at injection sites were noted on the topical tolerance tests. Conclusion: The results of this single-dose toxicity study show that WCFC is safe, its lethal doses in male and female SD rats being estimated to be higher than 0.5 mL/animal.

Temporal analysis of intratumoral metabolic heterogeneity characterized by textural features in cervical cancer.

Science.gov (United States)

Yang, Fei; Thomas, Maria A; Dehdashti, Farrokh; Grigsby, Perry W

2013-05-01

The aim of this pilot study was to explore heterogeneity in the temporal behavior of intratumoral [(18)F]fluorodeoxyglucose (FDG) accumulation at a regional scale in patients with cervical cancer undergoing chemoradiotherapy. Included in the study were 20 patients with FIGO stages IB1 to IVA cervical cancer treated with combined chemoradiotherapy. Patients underwent FDG PET/CT before treatment, during weeks 2 and 4 of treatment, and 12 weeks after completion of therapy. Patients were classified based on response to therapy as showing a complete metabolic response (CMR), a partial metabolic response (PMR), or residual disease and the development of new disease (NEW). Based on the presence of residual primary tumor following therapy, patients were divided into two groups, CMR and PMR/NEW. Temporal profiles of intratumoral FDG heterogeneity as characterized by textural features at a regional scale were assessed and compared with those of the standardized uptake value (SUV) indices (SUVmax and SUVmean) within the context of differentiating response groups. Textural features at a regional scale with emphasis on characterizing contiguous regions of high uptake in tumors decreased significantly with time (P features describing contiguous regions of low uptake along with those measuring the nonuniformity of contiguous isointense regions in tumors exhibited significant temporal changes in the PMR/NEW group (P textural features may provide an adjunctive or alternative option for understanding tumor response to chemoradiotherapy and interpreting FDG accumulation dynamics in patients with malignant cervical tumors during the course of the disease.

Intra-tumor heterogeneity of microRNA-92a, microRNA-375 and microRNA-424 in colorectal cancer

DEFF Research Database (Denmark)

Jepsen, Rikke Karlin; Novotny, Guy Wayne; Klarskov, Louise Laurberg

2016-01-01

Various microRNAs (miRNAs) have been investigated in order to improve diagnostics and risk assessment in colorectal cancer (CRC). To clarify the potential of miRNA profiling in CRC, knowledge of intra-tumor heterogeneity in expression levels is crucial. The study aim was to estimate the intra...

Transcriptional profiling of dividing tumor cells detects intratumor heterogeneity linked to cell proliferation in a brain tumor model

Czech Academy of Sciences Publication Activity Database

Endaya, B.; Lam, P.Y.P.; Meedeniya, A.C.B.; Neužil, Jiří

2016-01-01

Roč. 10, č. 1 (2016), s. 126-137 ISSN 1574-7891 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 Keywords : Intratumor heterogeneity * Click chemistry * Proliferation * Gene profiling Subject RIV: FD - Oncology ; Hematology Impact factor: 5.314, year: 2016

Effect of single and repeated injections of selective D2-antagonist clebopride on maternal behavior of albino rats.

Science.gov (United States)

Tanaeva, K K; Dobryakova, Yu V; Dubynin, V A; Kamensky, A A

2012-06-01

This study examined the effect of clebopride at low concentration that did not modify the motor activity on the parental care in female albino rats. Single injection of the drug attenuated the parental care reactions on postinjection minute 20, but not one day thereafter. The daily injection of the drug during the post partum period (1-6 days) resulted in significantly more pronounced and stable effects. The data obtained substantiated the views on the major contribution of D(2)-receptors in the development of behavioral manifestations of puerperal depression.

Interleukin-33/ST2 axis promotes breast cancer growth and metastases by facilitating intratumoral accumulation of immunosuppressive and innate lymphoid cells.

Science.gov (United States)

Jovanovic, Ivan P; Pejnovic, Nada N; Radosavljevic, Gordana D; Pantic, Jelena M; Milovanovic, Marija Z; Arsenijevic, Nebojsa N; Lukic, Miodrag L

2014-04-01

The role of IL-33/ST2 pathway in antitumor immunity is unclear. Using 4T1 breast cancer model we demonstrate time-dependent increase of endogenous IL-33 at both the mRNA and protein levels in primary tumors and metastatic lungs during cancer progression. Administration of IL-33 accelerated tumor growth and development of lung and liver metastases, which was associated with increased intratumoral accumulation of CD11b(+) Gr-1(+) TGF-β1(+) myeloid-derived suppressor cells (MDSCs) that expressed IL-13α1R, IL-13-producing Lin(-) Sca-1(+) ST2(+) innate lymphoid cells (ILCs) and CD4(+) Foxp3(+) ST2(+) IL-10(+) Tregs compared to untreated mice. Higher incidence of monocytic vs. granulocytic MDSCs and plasmocytoid vs. conventional dendritic cells (DCs) was present in mammary tumors of IL-33-treated mice. Intratumoral NKp46(+) NKG2D(+) and NKp46(+) FasL(+) cells were markedly reduced after IL-33 treatment, while phosphate-buffered saline-treated ST2-deficient mice had increased frequencies of these tumoricidal natural killer (NK) cells compared to untreated wild-type mice. IL-33 promoted intratumoral cell proliferation and neovascularization, which was attenuated in the absence of ST2. Tumor-bearing mice given IL-33 had increased percentages of splenic MDSCs, Lin(-) Sca-1(+) ILCs, IL-10-expressing CD11c(+) DCs and alternatively activated M2 macrophages and higher circulating levels of IL-10 and IL-13. A significantly reduced NK cell, but not CD8(+) T-cell cytotoxicity in IL-33-treated mice was observed and the mammary tumor progression was not affected when CD8(+) T cells were in vivo depleted. We show a previously unrecognized role for IL-33 in promoting breast cancer progression through increased intratumoral accumulation of immunosuppressive cells and by diminishing innate antitumor immunity. Therefore, IL-33 may be considered as an important mediator in the regulation of breast cancer progression. © 2013 UICC.

Prediction of microvascular invasion of hepatocellular carcinomas with gadoxetic acid-enhanced MR imaging: Impact of intra-tumoral fat detected on chemical-shift images

Energy Technology Data Exchange (ETDEWEB)

Min, Ji Hye [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, Young Kon, E-mail: jmyr@dreamwiz.com [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Lim, Sanghyeok [Department of Radiology, Guri Hospital, Hanyang University College of Medicine, Guri (Korea, Republic of); Jeong, Woo Kyoung; Choi, Dongil; Lee, Won Jae [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

2015-06-15

Highlights: • Intra-tumoral fat detected with MR imaging may suggest lower risk for MVI of HCC. • Alfa-fetoprotein, tumor size, and fat component were associated with MVI of HCC. • Chemical shift MRI should be considered for the evaluation of HCC. - Abstract: Purpose: To investigate the impact of intra-tumoral fat detected by chemical-shift MR imaging in predicting the MVI of HCC. Materials and methods: Gadoxetic acid-enhanced MR imaging of 365 surgically proven HCCs from 365 patients (306 men, 59 women; mean age, 55.6 years) were evaluated. HCCs were classified into two groups, fat-containing and non-fat-containing, based on the presence of fat on chemical-shift images. Fat-containing HCCs were subdivided into diffuse or focal fatty change groups. Logistic regression analyses were used to identify clinical and MR findings associated with MVI. Results: Based on MR imaging, 66 tumors were classified as fat-containing HCCs and 299 as non-fat-containing HCCs. Among the 66 fat-containing HCCs, 38 (57.6%) showed diffuse fatty changes and 28 (42.4%) showed focal fatty changes. MVI was present in 18 (27.3%) fat-containing HCCs and in 117 (39.1%) non-fat-containing HCCs (P = 0.07). Univariate analysis revealed that serum alpha-fetoprotein (AFP) and tumor size were significantly associated with MVI (P < 0.001). A multiple logistic regression analysis showed that log AFP (odds ratio 1.178, P = 0.0016), tumor size (odds ratio 1.809, P < 0.001), and intra-tumoral fat (odds ratio 0.515, P = 0.0387) were independent variables associated with MVI. Conclusion: Intra-tumoral fat detected with MR imaging may suggest lower risk for MVI of HCC and, therefore, a possibly more favorable prognosis, but the clinical value of this finding is uncertain.

Prediction of microvascular invasion of hepatocellular carcinomas with gadoxetic acid-enhanced MR imaging: Impact of intra-tumoral fat detected on chemical-shift images

International Nuclear Information System (INIS)

Min, Ji Hye; Kim, Young Kon; Lim, Sanghyeok; Jeong, Woo Kyoung; Choi, Dongil; Lee, Won Jae

2015-01-01

Highlights: • Intra-tumoral fat detected with MR imaging may suggest lower risk for MVI of HCC. • Alfa-fetoprotein, tumor size, and fat component were associated with MVI of HCC. • Chemical shift MRI should be considered for the evaluation of HCC. - Abstract: Purpose: To investigate the impact of intra-tumoral fat detected by chemical-shift MR imaging in predicting the MVI of HCC. Materials and methods: Gadoxetic acid-enhanced MR imaging of 365 surgically proven HCCs from 365 patients (306 men, 59 women; mean age, 55.6 years) were evaluated. HCCs were classified into two groups, fat-containing and non-fat-containing, based on the presence of fat on chemical-shift images. Fat-containing HCCs were subdivided into diffuse or focal fatty change groups. Logistic regression analyses were used to identify clinical and MR findings associated with MVI. Results: Based on MR imaging, 66 tumors were classified as fat-containing HCCs and 299 as non-fat-containing HCCs. Among the 66 fat-containing HCCs, 38 (57.6%) showed diffuse fatty changes and 28 (42.4%) showed focal fatty changes. MVI was present in 18 (27.3%) fat-containing HCCs and in 117 (39.1%) non-fat-containing HCCs (P = 0.07). Univariate analysis revealed that serum alpha-fetoprotein (AFP) and tumor size were significantly associated with MVI (P < 0.001). A multiple logistic regression analysis showed that log AFP (odds ratio 1.178, P = 0.0016), tumor size (odds ratio 1.809, P < 0.001), and intra-tumoral fat (odds ratio 0.515, P = 0.0387) were independent variables associated with MVI. Conclusion: Intra-tumoral fat detected with MR imaging may suggest lower risk for MVI of HCC and, therefore, a possibly more favorable prognosis, but the clinical value of this finding is uncertain

Numerical Simulations of Two-Phase Reacting Flow in a Single-Element Lean Direct Injection (LDI) Combustor Using NCC

Science.gov (United States)

Liu, Nan-Suey; Shih, Tsan-Hsing; Wey, C. Thomas

2011-01-01

A series of numerical simulations of Jet-A spray reacting flow in a single-element lean direct injection (LDI) combustor have been conducted by using the National Combustion Code (NCC). The simulations have been carried out using the time filtered Navier-Stokes (TFNS) approach ranging from the steady Reynolds-averaged Navier-Stokes (RANS), unsteady RANS (URANS), to the dynamic flow structure simulation (DFS). The sub-grid model employed for turbulent mixing and combustion includes the well-mixed model, the linear eddy mixing (LEM) model, and the filtered mass density function (FDF/PDF) model. The starting condition of the injected liquid spray is specified via empirical droplet size correlation, and a five-species single-step global reduced mechanism is employed for fuel chemistry. All the calculations use the same grid whose resolution is of the RANS type. Comparisons of results from various models are presented.

Understanding intratumor heterogeneity by combining genome analysis and mathematical modeling.

Science.gov (United States)

Niida, Atsushi; Nagayama, Satoshi; Miyano, Satoru; Mimori, Koshi

2018-04-01

Cancer is composed of multiple cell populations with different genomes. This phenomenon called intratumor heterogeneity (ITH) is supposed to be a fundamental cause of therapeutic failure. Therefore, its principle-level understanding is a clinically important issue. To achieve this goal, an interdisciplinary approach combining genome analysis and mathematical modeling is essential. For example, we have recently performed multiregion sequencing to unveil extensive ITH in colorectal cancer. Moreover, by employing mathematical modeling of cancer evolution, we demonstrated that it is possible that this ITH is generated by neutral evolution. In this review, we introduce recent advances in a research field related to ITH and also discuss strategies for exploiting novel findings on ITH in a clinical setting. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Effects of hypertonic dextrose injections in the rabbit carpal tunnel.

Science.gov (United States)

Yoshii, Yuichi; Zhao, Chunfeng; Schmelzer, James D; Low, Phillip A; An, Kai-Nan; Amadio, Peter C

2011-07-01

This study investigated the effects of different doses of hypertonic dextrose injection on the carpal tunnel subsynovial connective tissue (SSCT) and median nerve in a rabbit model. Thirty-eight New Zealand white rabbits weighing 4.0-4.5 kg were used. One forepaw carpal tunnel was randomly injected with one of five different treatments: saline-single injection; saline-two injections 1 week apart; 10% dextrose-single injection; 20% dextrose-single injection; or 10% dextrose-two injections 1 week apart. Animals were sacrificed at 12 weeks after the initial injection and were evaluated by electrophysiology (EP), SSCT mechanical testing and histology. There were significant increases in the energy absorption of the SSCT in the 10% dextrose-double injection group compared to the saline injection groups. SSCT stiffness was also significantly increased in the 10% dextrose-double injection group compared to the other groups. There was a significant increase in the thickness of the SSCT in the 10% dextrose-double injection group compared to the saline-single injection group and a significant decrease in the nerve short-long diameter ratio in the 10% dextrose-double injection group compared to the saline-single injection group. There were no changes in EP among the groups. SSCT fibrosis is present for up to 12 weeks after dextrose injection; multiple injections have bigger effects, including what appears to be a secondary change in nerve flattening. This model may be useful to study the effects of external fibrosis on nerve morphology and physiology, such as occurs clinically in carpal tunnel syndrome. Copyright © 2011 Orthopaedic Research Society.

Diesel Combustion and Emission Using High Boost and High Injection Pressure in a Single Cylinder Engine

Science.gov (United States)

Aoyagi, Yuzo; Kunishima, Eiji; Asaumi, Yasuo; Aihara, Yoshiaki; Odaka, Matsuo; Goto, Yuichi

Heavy-duty diesel engines have adopted numerous technologies for clean emissions and low fuel consumption. Some are direct fuel injection combined with high injection pressure and adequate in-cylinder air motion, turbo-intercooler systems, and strong steel pistons. Using these technologies, diesel engines have achieved an extremely low CO2 emission as a prime mover. However, heavy-duty diesel engines with even lower NOx and PM emission levels are anticipated. This study achieved high-boost and lean diesel combustion using a single cylinder engine that provides good engine performance and clean exhaust emission. The experiment was done under conditions of intake air quantity up to five times that of a naturally aspirated (NA) engine and 200MPa injection pressure. The adopted pressure booster is an external supercharger that can control intake air temperature. In this engine, the maximum cylinder pressure was increased and new technologies were adopted, including a monotherm piston for endurance of Pmax =30MPa. Moreover, every engine part is newly designed. As the boost pressure increases, the rate of heat release resembles the injection rate and becomes sharper. The combustion and brake thermal efficiency are improved. This high boost and lean diesel combustion creates little smoke; ISCO and ISTHC without the ISNOx increase. It also yields good thermal efficiency.

Intratumoral and peritumoral radiomics for the pretreatment prediction of pathological complete response to neoadjuvant chemotherapy based on breast DCE-MRI.

Science.gov (United States)

Braman, Nathaniel M; Etesami, Maryam; Prasanna, Prateek; Dubchuk, Christina; Gilmore, Hannah; Tiwari, Pallavi; Plecha, Donna; Madabhushi, Anant

2017-05-18

In this study, we evaluated the ability of radiomic textural analysis of intratumoral and peritumoral regions on pretreatment breast cancer dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to predict pathological complete response (pCR) to neoadjuvant chemotherapy (NAC). A total of 117 patients who had received NAC were retrospectively analyzed. Within the intratumoral and peritumoral regions of T1-weighted contrast-enhanced MRI scans, a total of 99 radiomic textural features were computed at multiple phases. Feature selection was used to identify a set of top pCR-associated features from within a training set (n = 78), which were then used to train multiple machine learning classifiers to predict the likelihood of pCR for a given patient. Classifiers were then independently tested on 39 patients. Experiments were repeated separately among hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR + , HER2 - ) and triple-negative or HER2 + (TN/HER2 + ) tumors via threefold cross-validation to determine whether receptor status-specific analysis could improve classification performance. Among all patients, a combined intratumoral and peritumoral radiomic feature set yielded a maximum AUC of 0.78 ± 0.030 within the training set and 0.74 within the independent testing set using a diagonal linear discriminant analysis (DLDA) classifier. Receptor status-specific feature discovery and classification enabled improved prediction of pCR, yielding maximum AUCs of 0.83 ± 0.025 within the HR + , HER2 - group using DLDA and 0.93 ± 0.018 within the TN/HER2 + group using a naive Bayes classifier. In HR + , HER2 - breast cancers, non-pCR was characterized by elevated peritumoral heterogeneity during initial contrast enhancement. However, TN/HER2 + tumors were best characterized by a speckled enhancement pattern within the peritumoral region of nonresponders. Radiomic features were found to strongly predict pCR independent of

The 15N-leucine single-injection method allows for determining endogenous losses and true digestibility of amino acids in cecectomized roosters.

Directory of Open Access Journals (Sweden)

Rujiu Hu

Full Text Available This study was conducted to assess the influence of dietary protein content in poultry when using the 15N-leucine single-injection method to determine endogenous amino acid losses (EAALs in poultry. Forty-eight cecectomized roosters (2.39 ± 0.23 kg were randomly allocated to eight dietary treatments containing protein levels of 0, 3%, 6%, 9%, 12%, 15%, 18% and 21%. Each bird was precisely fed an experimental diet of 25 g/kg of body weight. After feeding, all roosters were subcutaneously injected with a 15N-leucine solution at a dose of 20 mg/kg of body weight. Blood was sampled 23 h after the injection, and excreta samples were continuously collected during the course of the 48-h experiment. The ratio of 15N-enrichment of leucine in crude mucin to free leucine in plasma ranged from 0.664 to 0.763 and remained relatively consistent (P > 0.05 across all treatments. The amino acid (AA profiles of total endogenous AAs, except isoleucine, alanine, aspartic acid, cysteine, proline and serine, were not influenced (P > 0.05 by dietary protein contents. The predominant endogenous AAs in the excreta were glutamic acid, aspartic acid, threonine, serine and proline. The order of the relative proportions of these predominant AAs also remained relatively constant (P > 0.05. The endogenous losses of total AAs determined with the 15N-leucine single-injection method increased curvilinearly with the dietary protein contents. The true digestibility of most AAs and total AAs was independent of their respective dietary protein levels. Collectively, the 15N-leucine single-injection method is appropriate for determining EAALs and the true digestibility of AAs in poultry fed varying levels of protein-containing ingredients.

The Assessment of Estrogen Receptor Status and Its Intratumoral Heterogeneity in Patients With Breast Cancer by Using 18F-Fluoroestradiol PET/CT.

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Yang, Zhongyi; Sun, Yifei; Xu, Xiaoping; Zhang, Yongping; Zhang, Jianping; Xue, Jing; Wang, Mingwei; Yuan, Huiyu; Hu, Silong; Shi, Wei; Zhu, Beiling; Zhang, Yingjian

2017-06-01

The aim of this study was to investigate the clinical value of F-fluoroestradiol (F-FES) PET/CT in the assessment of the estrogen receptor (ER) and its intratumoral heterogeneity in breast cancer patients. Forty-six female patients (50 lesions) with histologically confirmed invasive breast cancer who underwent both F-FES and F-FDG PET/CT in our center were retrospectively included. All the patients enrolled were scheduled to undergo biopsy. The F-FES and FDG uptakes were compared with pathological features (tumor size, ER, progesterone receptor, human epidermal growth factor receptor 2, and Ki67%). The optimal threshold to discriminate ER-positive and ER-negative lesions was determined by receiver operating characteristic curve analysis. Furthermore, we observed the intratumoral heterogeneity by a heterogeneity index (SUVmax/SUVmean) and compared the results with the Chang-Gung Image Texture Analysis. There was good agreement between F-FES uptake and ER, progesterone receptor, and human epidermal growth factor receptor 2 expression (P heterogeneity index-FES can easily observe ER heterogeneity. In addition, our results suggested that recurrent/metastatic patients and lesions located other than breast might have greater heterogeneity. F-FES PET/CT is a feasible, noninvasive method for assessing ER expression in breast cancer patients. Because intratumoral heterogeneity exists, F-FES PET/CT might better reflect the ER expression, especially in metastatic patients after treatment, thus assisting in making individualized treatment decisions.

Sentinel node biopsy and concomitant probe-guided tumor excision of nonpalpable breast cancer.

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van Rijk, Maartje C; Tanis, Pieter J; Nieweg, Omgo E; Loo, Claudette E; Olmos, Renato A Valdés; Oldenburg, Hester S A; Rutgers, Emiel J Th; Hoefnagel, Cornelis A; Kroon, Bin B R

2007-02-01

Preliminary data have shown encouraging results of a single intratumoral radiopharmaceutical injection that enables both sentinel node biopsy and probe-guided excision of the primary tumor in patients with nonpalpable breast cancer. The aim of the study was to evaluate this approach in a large group of patients. Lymphoscintigraphy was performed in 368 patients with nonpalpable breast cancer after intratumoral injection of (99m)Tc-nanocolloid (.2 mL, 123 MBq, 3.3 mCi) guided by ultrasound or stereotaxis. The sentinel node was pursued with the aid of vital blue dye (1.0 mL, intratumoral) and a gamma ray detection probe. In case of breast-conserving surgery, the probe was used to guide the excision. At least one sentinel node could be identified intraoperatively in 357 patients (97%), of whom 69 had involved nodes (19%). Age over 60 years was associated with less frequent nonaxillary lymphatic drainage and absence of internal mammary chain dissemination. Tumor-free margins were obtained in 262 (89%) of the 293 patients who underwent segmental excision. Re-excision of the primary tumor bed was performed in six patients (2%). During a median follow-up of 22 months, one breast recurrence and one axillary recurrence were observed. Lymphatic mapping and probe-guided tumor excision of nonpalpable breast cancer by intralesional administration of a single dose of (99m)Tc-nanocolloid and blue dye resulted in 97% identification of the sentinel node and in tumor-free margins in 89% of the patients who underwent breast-conserving surgery. Longer follow-up is needed to substantiate the accuracy and safety of this technique.

Intratumoral heterogeneity: Role of differentiation in a potentially lethal phenotype of testicular cancer.

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Tu, Shi-Ming; Bilen, Mehmet Asim; Hess, Kenneth R; Broaddus, Russell R; Kopetz, Scott; Wei, Chongjuan; Pagliaro, Lance C; Karam, Jose A; Ward, John F; Wood, Christopher G; Rao, Priya; Tu, Zachary H; General, Rosale; Chen, Adrienne H; Nieto, Yago L; Yeung, Sai-Ching J; Lin, Sue-Hwa; Logothetis, Christopher J; Pisters, Louis L

2016-06-15

Intratumoral heterogeneity presents a major obstacle to the widespread implementation of precision medicine. The authors assessed the origin of intratumoral heterogeneity in nonseminomatous germ cell tumor of the testis (NSGCT) and identified distinct tumor subtypes and a potentially lethal phenotype. In this retrospective study, all consecutive patients who had been diagnosed with an NSGCT between January 2000 and December 2010 were evaluated. The histologic makeup of primary tumors and the clinical course of disease were determined for each patient. A Fine and Gray proportional hazards regression analysis was used to determine the prognostic risk factors, and the Gray test was used to detect differences in the cumulative incidence of cancer death. In a separate prospective study, next-generation sequencing was performed on tumor samples from 9 patients to identify any actionable mutations. Six hundred fifteen patients were included in this study. Multivariate analysis revealed that the presence of yolk sac tumor in the primary tumor (P = .0003) was associated with an unfavorable prognosis. NSGCT could be divided into 5 subgroups. Patients in the yolk sac-seminoma subgroup had the poorest clinical outcome (P = .0015). These tumors tended to undergo somatic transformation (P Cancer 2016;122:1836-43. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. © 2016 American Cancer Society.

Basal cardiomyopathy develops in rabbits with ventricular tachyarrhythmias induced by a single injection of adrenaline.

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Ashida, Terunao; Takato, Tetsuya; Matsuzaki, Gen; Seko, Yoshinori; Fujii, Jun; Kawai, Sachio

2014-01-01

We have recently demonstrated that basal cardiomyopathy develops in rabbits with ventricular tachyarrhythmias that have been induced by electrical stimulation of the cervical vagus. This study investigated whether similar basal cardiomyopathy would develop in rabbits with ventricular tachyarrhythmias induced by a single injection of adrenaline. Adrenaline was intravenously infused for 10-360 seconds in anesthetized rabbits. Colloidal carbon was injected after adrenaline infusion. Wall movement velocity of the left ventricular base was assessed by tissue Doppler echocardiography. Animals were killed either 1 week or 3-4 weeks later. Pathological lesions were identified by deposits of carbon particles. Animals were divided into two groups according to the infused dose of adrenaline. The small-dose group (group S, n = 15) received 1-10 μg and the large-dose group (group L, n = 23) received 15-60 μg of adrenaline. Adrenaline infusion induced premature ventricular contractions followed by monomorphic ventricular tachycardias in 22 of 23 animals in group L, but in only 1 of 15 animals in group S. Wall movement velocity of the left ventricular base decreased just after adrenaline infusion, remained low after 1 week, and recovered to near-baseline levels after 3-4 weeks in group L. Unique cardiac lesions identified by deposits of carbon particles were frequently observed on the left ventricular basal portion, almost always associated with the mitral valve and papillary muscles, but were never observed in the apical area. Lesions involving all areas of the left ventricular basal portion were observed in 22 of 23 animals in group L, but in only 2 of 15 animals in group S. Basal cardiomyopathy developed in rabbits with ventricular tachycardias induced by a single injection of adrenaline.

Rapid induction of dopamine sensitization in the nucleus accumbens shell induced by a single injection of cocaine.

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Singer, Bryan F; Bryan, Myranda A; Popov, Pavlo; Robinson, Terry E; Aragona, Brandon J

2017-05-01

Repeated intermittent exposure to cocaine results in the neurochemical sensitization of dopamine (DA) transmission within the nucleus accumbens (NAc). Indeed, the excitability of DA neurons in the ventral tegmental area (VTA) is enhanced within hours of initial psychostimulant exposure. However, it is not known if this is accompanied by a comparably rapid change in the ability of cocaine to increase extracellular DA concentrations in the ventral striatum. To address this question we used fast-scan cyclic voltammetry (FSCV) in awake-behaving rats to measure DA responses in the NAc shell following an initial intravenous cocaine injection, and then again 2-h later. Both injections quickly elevated DA levels in the NAc shell, but the second cocaine infusion produced a greater effect than the first, indicating sensitization. This suggests that a single injection of cocaine induces sensitization-related plasticity very rapidly within the mesolimbic DA system. Copyright © 2017 Elsevier B.V. All rights reserved.

3D pulmonary perfusion MRI and MR angiography of pulmonary embolism in pigs after a single injection of a blood pool MR contrast agent

International Nuclear Information System (INIS)

Fink, Christian; Ley, Sebastian; Puderbach, Michael; Plathow, Christian; Kauczor, Hans-Ulrich; Bock, Michael

2004-01-01

The purpose of this study was to assess the feasibility of contrast-enhanced 3D perfusion MRI and MR angiography (MRA) of pulmonary embolism (PE) in pigs using a single injection of the blood pool contrast Gadomer. PE was induced in five domestic pigs by injection of autologous blood thrombi. Contrast-enhanced first-pass 3D perfusion MRI (TE/TR/FA: 1.0 ms/2.2 ms/40 ; voxel size: 1.3 x 2.5 x 4.0 mm 3 ; TA: 1.8 s per data set) and high-resolution 3D MRA (TE/TR/FA: 1.4 ms/3.4 ms/40 ; voxel size: 0.8 x 1.0 x 1.6 mm 3 ) was performed during and after a single injection of 0.1 mmol/kg body weight of Gadomer. Image data were compared to pre-embolism Gd-DTPA-enhanced MRI and post-embolism thin-section multislice CT (n=2). SNR measurements were performed in the pulmonary arteries and lung. One animal died after induction of PE. In all other animals, perfusion MRI and MRA could be acquired after a single injection of Gadomer. At perfusion MRI, PE could be detected by typical wedge-shaped perfusion defects. While the visualization of central PE at MRA correlated well with the CT, peripheral PE were only visualized by CT. Gadomer achieved a higher peak SNR of the lungs compared to Gd-DTPA (21±8 vs. 13±3). Contrast-enhanced 3D perfusion MRI and MRA of PE can be combined using a single injection of the blood pool contrast agent Gadomer. (orig.)

An experimental study of fuel injection strategies in CAI gasoline engine

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Hunicz, J.; Kordos, P. [Department of Combustion Engines and Transport, Lublin University of Technology, Nadbystrzycka 36, 20-618 Lublin (Poland)

2011-01-15

Combustion of gasoline in a direct injection controlled auto-ignition (CAI) single-cylinder research engine was studied. CAI operation was achieved with the use of the negative valve overlap (NVO) technique and internal exhaust gas re-circulation (EGR). Experiments were performed at single injection and split injection, where some amount of fuel was injected close to top dead centre (TDC) during NVO interval, and the second injection was applied with variable timing. Additionally, combustion at variable fuel-rail pressure was examined. Investigation showed that at fuel injection into recompressed exhaust fuel reforming took place. This process was identified via an analysis of the exhaust-fuel mixture composition after NVO interval. It was found that at single fuel injection in NVO phase, its advance determined the heat release rate and auto-ignition timing, and had a strong influence on NO{sub X} emission. However, a delay of single injection to intake stroke resulted in deterioration of cycle-to-cycle variability. Application of split injection showed benefits of this strategy versus single injection. Examinations of different fuel mass split ratios and variable second injection timing resulted in further optimisation of mixture formation. At equal share of the fuel mass injected in the first injection during NVO and in the second injection at the beginning of compression, the lowest emission level and cyclic variability improvement were observed. (author)

Effect of injection pressure on performance, emission, and combustion characteristics of diesel-acetylene-fuelled single cylinder stationary CI engine.

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Srivastava, Anmesh Kumar; Soni, Shyam Lal; Sharma, Dilip; Jain, Narayan Lal

2018-03-01

In this paper, the effect of injection pressure on the performance, emission, and combustion characteristics of a diesel-acetylene fuelled single cylinder, four-stroke, direct injection (DI) diesel engine with a rated power of 3.5 kW at a rated speed of 1500 rpm was studied. Experiments were performed in dual-fuel mode at four different injection pressures of 180, 190, 200, and 210 bar with a flow rate of 120 LPH of acetylene and results were compared with that of baseline diesel operation. Experimental results showed that highest brake thermal efficiency of 27.57% was achieved at injection pressure of 200 bar for diesel-acetylene dual-fuel mode which was much higher than 23.32% obtained for baseline diesel. Carbon monoxide, hydrocarbon, and smoke emissions were also measured and found to be lower, while the NO x emissions were higher at 200 bar in dual fuel mode as compared to those in other injection pressures in dual fuel mode and also for baseline diesel mode. Peak cylinder pressure, net heat release rate, and rate of pressure rise were also calculated and were higher at 200 bar injection pressure in dual fuel mode.

Limited Role for Biliary Stent as Surrogate Fiducial Marker in Pancreatic Cancer: Stent and Intratumoral Fiducials Compared

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Horst, Astrid van der, E-mail: a.vanderhorst@amc.uva.nl [Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Lens, Eelco; Wognum, Silvia; Jong, Rianne de [Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Hooft, Jeanin E. van [Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Tienhoven, Geertjan van; Bel, Arjan [Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands)

2014-07-01

Purpose: Because of low soft-tissue contrast of cone beam computed tomography (CBCT), fiducial markers are often used for radiation therapy patient setup verification. For pancreatic cancer patients, biliary stents have been suggested as surrogate fiducials. Using intratumoral fiducials as standard for tumor position, this study aims to quantify the suitability of biliary stents for measuring interfractional and respiratory-induced position variations of pancreatic tumors. Methods and Materials: Eleven pancreatic cancer patients with intratumoral fiducials and a biliary stent were included in this study. Daily CBCT scans (243 in total) were registered with a reference CT scan, based on bony anatomy, on fiducial markers, and on the biliary stent, respectively. We analyzed the differences in tumor position (ie, markers center-of-mass position) among these 3 registrations. In addition, we measured for 9 patients the magnitude of respiratory-induced motion (MM) of the markers and of the stent on 4-dimensional CT (4DCT) and determined the difference between these 2 magnitudes (ΔMM). Results: The stent indicated tumor position better than bony anatomy in 67% of fractions; the absolute difference between the markers and stent registration was >5 mm in 46% of fractions and >10 mm in 20% of fractions. Large PTV margins (superior-inferior direction, >19 mm) would be needed to account for this interfractional position variability. On 4DCT, we found in superior-inferior direction a mean ΔMM of 0.5 mm (range, –2.6 to 4.2 mm). Conclusions: For respiratory-induced motion, the mean ΔMM is small, but for individual patients the absolute difference can be >4 mm. For interfractional position variations, a stent is, on average, a better surrogate fiducial than bony anatomy, but large PTV margins would still be required. Therefore, intratumoral fiducials are recommended for online setup verification for all pancreatic patients scheduled for radiation therapy, including

Single injection techniques in determining age-related changes in porcine renal function

International Nuclear Information System (INIS)

Robbins, M.E.C.

1984-01-01

Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were determined in 32 anaesthetised female Large White pigs, aged 4-24 months, from the plasma disappearance curves of [sup(99m)Tc]DTPA and [ 131 I]hippuran respectively. Clearance was also monitored by external counting over the heart. GFR and ERPF increased markedly with age in pigs up to 12 months old, reaching mean values of 242.06 +- 5.89 and 919.39 +- 79.01 mL/min. In pigs aged 12-24 months ERPF increased slightly but renal function remained essentially unchanged after 1 yr of age. These results for renal function were similar to previous estimates, using continuous infusion techniques inferring that GFR and ERPF could be accurately monitored using single injection procedures. (author)

Electrically injected GaAsBi/GaAs single quantum well laser diodes

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Juanjuan Liu

2017-11-01

Full Text Available We present electrically injected GaAs/GaAsBi single quantum well laser diodes (LDs emitting at a record long wavelength of 1141 nm at room temperature grown by molecular beam epitaxy. The LDs have excellent device performances with internal quantum efficiency of 86%, internal loss of 10 cm-1 and transparency current density of 196 A/cm2. The LDs can operate under continuous-wave mode up to 273 K. The characteristic temperature are extracted to be 125 K in the temperature range of 77∼150 K, and reduced to 90 K in the range of 150∼273 K. The temperature coefficient of 0.3 nm/K is extracted in the temperature range of 77∼273 K.

Safety and effectiveness of a single and repeat intramuscular injection of a GnRH vaccine (GonaCon™) in adult female domestic cats.

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Vansandt, L M; Kutzler, M A; Fischer, A E; Morris, K N; Swanson, W F

2017-04-01

Sterilization is a key strategy to reduce the number of domestic cats entering and killed in shelters each year. However, surgical sterilization is expensive and labour-intensive and cannot fully address the 70 million free-roaming cats estimated to exist in the United States. GonaCon™ is a gonadotropin-releasing hormone vaccine originally developed for use as a wildlife immunocontraceptive. An earlier formulation was tested in domestic cats and found to be safe and effective for long-term contraception. However, the current Environmental Protection Agency (EPA)-registered formulation consists of a different antigen-carrier protein and increased antigen concentration and has never been tested in cats. A pilot study was undertaken to evaluate the short-term safety of a single GonaCon immunization, assess the consequences of vaccinated cats receiving an accidental second GonaCon injection and determine the humoral immune response to immunization. During Phase 1, cats in Group A (n = 3) received a single intramuscular injection of GonaCon and Group B (n = 3) received a single intramuscular injection of saline. During Phase 2, Group A received a second GonaCon injection and Group B received their initial GonaCon injection. All cats developed GnRH antibodies within 30 days of vaccine administration. The endpoint titre (1:1,024,000) was similar among all cats, and levels remained high throughout the duration of the study. Four cats developed a sterile, painless, self-limiting mass at the site of injection. The mean number of days to mass development was 110.3 (range, 18-249 days). In conclusion, this preliminary study suggests that the EPA-registered GonaCon formulation is safe for continued testing in domestic cats, an accidental revaccination should not increase the risk of a vaccine reaction and the EPA-registered formulation effectively elicits a strong humoral immune response. © 2016 Blackwell Verlag GmbH.

Endoscopic treatment of vesicoureteral reflux in children with subureteral dextranomer/hyaluronic acid injection: a single-centre, 7-year experience

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Biočíc, Mihovil; Todoríc, Jakov; Budimir, Dražen; Roíc, Andrea Cvitkovíc; Pogorelíc, Zenon; Juríc, Ivo; Šušnjar, Tomislav

2012-01-01

Background The goals of medical intervention in patients with vesicoureteral reflux are to allow normal renal growth, prevent infections and pyelonephritis, and prevent renal failure. We present our experience with endoscopic treatment of vesicoureteral reflux in children by subureteral dextranomer/hyaluronic acid copolymer injection. Methods Under cystoscopic guidance, dextranomer/hyaluronic acid copolymer underneath the intravesical portion of the ureter in a subureteral or submucosal location was injected in patients undergoing endoscopic correction of vesicoureteral reflux. Results A total of 282 patients (120 boys and 162 girls) underwent the procedure. There were 396 refluxed ureters altogether. The mean age of patients was 4.9 years. The mean overall follow-up period was 44 months. Among the 396 ureters treated, 76% were cured with a single injection. A second and third injection raised the cure rate to 93% and 94%, respectively. Twenty-two (6%) ureters failed all 3 injections, and were converted to open surgery. Conclusion Endoscopic treatment of vesicoureteral reflux can be recommended as a first-line therapy for most cases of vesicoureteral reflux, because of the short hospital stay, absence of complications and the high success rate. PMID:22854114

Development and validation of double and single Wiebe function for multi-injection mode Diesel engine combustion modelling for hardware-in-the-loop applications

International Nuclear Information System (INIS)

Maroteaux, Fadila; Saad, Charbel; Aubertin, Fabrice

2015-01-01

Highlights: • Modelling of Diesel engine combustion with multi-injection mode was conducted. • Double and single Wiebe correlations for pilot, main and post combustion processes were calibrated. • Ignition delay time correlations have been developed and calibrated using experimental data for each injection. • The complete in-cylinder model has been applied successfully to real time simulations on HiL test bed. - Abstract: The improvement of Diesel engine performances in terms of fuel consumption and pollutant emissions has a huge impact on management system and diagnostic procedure. Validation and testing of engine performances can benefit from the use of theoretical models, for the reduction of development time and costs. Hardware in the Loop (HiL) test bench is a suitable way to achieve these objectives. However, the increasing complexity of management systems rises challenges for the development of very reduced physical models able to run in real time applications. This paper presents an extension of a previously developed phenomenological Diesel combustion model suitable for real time applications on a HiL test bench. In the earlier study, the modelling efforts have been targeted at high engine speeds with a very short computational time window, and where the engine operates with single injection. In the present work, a modelling of in-cylinder processes at low and medium engine speeds with multi-injection is performed. In order to reach an adequate computational time, the combustion progress during the pilot and main injection periods has been treated through a double Wiebe function, while the post combustion period has required a single Wiebe function. This paper describes the basic system models and their calibration and validation against experimental data. The use of the developed correlations of Wiebe coefficients and ignition delay times for each combustion phase, included in the in-cylinder crank angle global model, is applied for the prediction

Intratumor heterogeneity of DCE-MRI reveals Ki-67 proliferation status in breast cancer

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Cheng, Hu; Fan, Ming; Zhang, Peng; Liu, Bin; Shao, Guoliang; Li, Lihua

2018-03-01

Breast cancer is a highly heterogeneous disease both biologically and clinically, and certain pathologic parameters, i.e., Ki67 expression, are useful in predicting the prognosis of patients. The aim of the study is to identify intratumor heterogeneity of breast cancer for predicting Ki-67 proliferation status in estrogen receptor (ER)-positive breast cancer patients. A dataset of 77 patients was collected who underwent dynamic contrast enhancement magnetic resonance imaging (DCE-MRI) examination. Of these patients, 51 were high-Ki-67 expression and 26 were low-Ki-67 expression. We partitioned the breast tumor into subregions using two methods based on the values of time to peak (TTP) and peak enhancement rate (PER). Within each tumor subregion, image features were extracted including statistical and morphological features from DCE-MRI. The classification models were applied on each region separately to assess whether the classifiers based on features extracted from various subregions features could have different performance for prediction. An area under a receiver operating characteristic curve (AUC) was computed using leave-one-out cross-validation (LOOCV) method. The classifier using features related with moderate time to peak achieved best performance with AUC of 0.826 than that based on the other regions. While using multi-classifier fusion method, the AUC value was significantly (P=0.03) increased to 0.858+/-0.032 compare to classifier with AUC of 0.778 using features from the entire tumor. The results demonstrated that features reflect heterogeneity in intratumoral subregions can improve the classifier performance to predict the Ki-67 proliferation status than the classifier using features from entire tumor alone.

Well-differentiated adenocarcinoma of the gallbladder with intratumoral cystic components due to abundant mucin production: a mimicker of adenomyomatosis

International Nuclear Information System (INIS)

Yoshimitsu, Kengo; Irie, Hiroyuki; Aibe, Hitoshi; Tajima, Tsuyoshi; Nishie, Akihiro; Asayama, Yoshiki; Matake, Kunishige; Honda, Hiroshi; Yamaguchi, Kouji; Matsuura, Shuji

2005-01-01

The prevalence and etiology of the cystic components within gallbladder carcinomas as seen on MR images were evaluated. A retrospective review of MR images was performed for 35 proven gallbladder carcinomas in search of radiologically detectable intratumoral cystic components. The pathologic specimens were meticulously reviewed to determine the etiology. MR images of 31 adenomyomatoses were also reviewed for comparison to clarify the difference in MR features between these two entities. Three cases out of 35 proven gallbladder carcinomas were found to have intratumoral cystic components. They were all well-differentiated adenocarcinomas, and the cystic components consisted of dilated neoplastic glands filled with abundant mucin pool. Adenomyomatosis tended to have more and rounded cystic components (Rokitansky-Aschoff sinuses) lined in a linear fashion and were flat-elevated in shape, smaller in size and had a regular surface, as compared to the three carcinomas. Although rare, radiologists need to be aware that well-differentiated gallbladder carcinoma with mucin production can have cystic components, which may mimic adenomyomatosis. Careful interpretation of MR images may provide useful information in the differentiation of these two entities. (orig.)

Modelling of profile control with LH wave injection in the HL-2A single-null divertor plasma

International Nuclear Information System (INIS)

Gao Qingdi; Yuan Baoshan; Li Fangzhu; Wang, Aike; Budny, R.V.

2005-01-01

In the HL-2A tokamak a single-null divertor configuration has been established. The separatrix of the single-null diverted plasma was identified with a filament model, and the determined striking area on the target plate is in agreement with the measurements of electric probe array. Higher power LH wave (1.5MW) is injected to the diverted plasma with a nearly symmetric spectrum. Dominant electron heating and current profile control are investigated with numerical simulation. Plasma heating by electron Landau interaction results in operation scenarios of preferentially dominant electron heating. Due to the off-axis driven current, an optimized q-profile is formed, and an enhanced confinement regime with steep electron temperature gradient is produced. The clear decrease of the electron thermal conductivity in the LH power deposition region shows that an electron-ITB is developed. When higher LH power injects into the target plasma that is heated by NBI (0.5MW), the ion temperature has a large increment in addition to the high increase of electron temperature. The temperature profiles indicate that an enhanced core confinement is established with both ion-ITB and electron-ITB developed. (author)

Quantitative image analysis of intra-tumoral bFGF level as a molecular marker of paclitaxel resistance

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Wientjes M Guillaume

2008-01-01

Full Text Available Abstract Background The role of basic fibroblast growth factor (bFGF in chemoresistance is controversial; some studies showed a relationship between higher bFGF level and chemoresistance while other studies showed the opposite finding. The goal of the present study was to quantify bFGF levels in archived tumor tissues, and to determine its relationship with chemosensitivity. Methods We established an image analysis-based method to quantify and convert the immunostaining intensity of intra-tumor bFGF to concentrations; this was accomplished by generating standard curves using human xenograft tumors as the renewable tissue source for simultaneous image analysis and ELISA. The relationships between bFGF concentrations and tumor chemosensitivity of patient tumors (n = 87 to paclitaxel were evaluated using linear regression analysis. Results The image analysis results were compared to our previous results obtained using a conventional, semi-quantitative visual scoring method. While both analyses indicated an inverse relationship between bFGF level and tumor sensitivity to paclitaxel, the image analysis method, by providing bFGF levels in individual tumors and therefore more data points (87 numerical values as opposed to four groups of staining intensities, further enabled the quantitative analysis of the relationship in subgroups of tumors with different pathobiological properties. The results show significant correlation between bFGF level and tumor sensitivity to the antiproliferation effect, but not the apoptotic effect, of paclitaxel. We further found stronger correlations of bFGF level and paclitaxel sensitivity in four tumor subgroups (high stage, positive p53 staining, negative aFGF staining, containing higher-than-median bFGF level, compared to all other groups. These findings suggest that the relationship between intra-tumoral bFGF level and paclitaxel sensitivity was context-dependent, which may explain the previous contradictory findings

Forecast of thermal-hydrological conditions and air injection test results of the single heater test at Yucca Mountain

International Nuclear Information System (INIS)

Birkholzer, J.T.; Tsang, Y.W.

1996-12-01

The heater in the Single Heater Test (SHT) in alcove 5 of the Exploratory Studies Facility (ESF) was turned on August 26, 1996. A large number of sensors are installed in the various instrumented boreholes to monitor the coupled thermal-hydrological-mechanical-chemical responses of the rock mass to the heat generated in the single heater. In this report the authors present the results of the modeling of both the heating and cooling phases of the Single Heater Test (SHT), with focus on the thermal-hydrological aspect of the coupled processes. Also in this report, the authors present simulations of air injection tests will be performed at different stages of the heating and cooling phase of the SHT

Anesthetic efficacy of a repeated intraosseous injection following a primary intraosseous injection.

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Jensen, Joanne; Nusstein, John; Drum, Melissa; Reader, Al; Beck, Mike

2008-02-01

The purpose of this prospective, randomized, single-blinded study was to determine the anesthetic efficacy of a repeated intraosseous injection given 30 minutes after a primary intraosseous injection. Using a crossover design, 55 subjects randomly received a primary X-tip intraosseous injection (Dentsply Inc, York, PA) of 1.4 mL of 2% lidocaine with epinephrine (using the Wand; Milestone Scientific, Deerfield, IL) and a repeated intraosseous or mock injection at 30 minutes in two appointments. The first molar and adjacent teeth were pulp tested every 2 minutes for a total of 120 minutes. Success was defined as obtaining two consecutive 80 readings with the electric pulp tester. Success of the initial intraosseous injection was 100% for the first molar. The repeated intraosseous injection mimicked the initial intraosseous injection in terms of pulpal anesthesia and statistically provided another 15 minutes of pulpal anesthesia. In conclusion, using the methodology presented, repeating the intraosseous injection 30 minutes after an initial intraosseous injection will provide an additional 15 minutes of pulpal anesthesia.

Long-term Dose Stability of OnabotulinumtoxinA Injection for Adductor Spasmodic Dysphonia: A 19-Year Single Institution Experience

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Paul Paddle

2017-11-01

Full Text Available ObjectivesAdductor spasmodic dysphonia (AdSD is a focal dystonia predominantly involving the laryngeal adductor muscles. AdSD is reported to be a largely non-progressive neurological disorder, though fluctuations in symptom severity do occur. Repeated laryngeal onabotulinumtoxinA (BTX-A injections are the primary management for AdSD. A number of studies have demonstrated long-term dose stability as evidence of this long-term disease stability.MethodsA retrospective review was performed on all patients undergoing BTX-A injections for AdSD from April 1994 to September 2013 by a single laryngologist at a tertiary referral laryngology center. Patient demographics, injection doses, use of diazepam and/or lidocaine, and self-reported vocal function were recorded. Multiple linear regression analyses were performed.Results83 patients underwent a total of 1,168 injections over 19 years. The mean starting dose was 2.35 MU (0.79 SD. The mean long-term dose was 2.36 MU (0.79 SD. After adjusting for confounders, the change in the relative dose of BTX-A, with every year elapsed since initial dose was 0.13% (95% confidence interval −0.31 to 0.57%, p = 0.568.ConclusionBTX-A dose is stable over time in our large cohort of patients treated with bilateral thyroarytenoid injections for AdSD.

Multisite tumor sampling enhances the detection of intratumor heterogeneity at all different temporal stages of tumor evolution.

Science.gov (United States)

Erramuzpe, Asier; Cortés, Jesús M; López, José I

2018-02-01

Intratumor heterogeneity (ITH) is an inherent process of tumor development that has received much attention in previous years, as it has become a major obstacle for the success of targeted therapies. ITH is also temporally unpredictable across tumor evolution, which makes its precise characterization even more problematic since detection success depends on the precise temporal snapshot at which ITH is analyzed. New and more efficient strategies for tumor sampling are needed to overcome these difficulties which currently rely entirely on the pathologist's interpretation. Recently, we showed that a new strategy, the multisite tumor sampling, works better than the routine sampling protocol for the ITH detection when the tumor time evolution was not taken into consideration. Here, we extend this work and compare the ITH detections of multisite tumor sampling and routine sampling protocols across tumor time evolution, and in particular, we provide in silico analyses of both strategies at early and late temporal stages for four different models of tumor evolution (linear, branched, neutral, and punctuated). Our results indicate that multisite tumor sampling outperforms routine protocols in detecting ITH at all different temporal stages of tumor evolution. We conclude that multisite tumor sampling is more advantageous than routine protocols in detecting intratumor heterogeneity.

Interface inductive currents and carrier injection in hybrid perovskite single crystals

Science.gov (United States)

Kovalenko, Alexander; Pospisil, Jan; Krajcovic, Jozef; Weiter, Martin; Guerrero, Antonio; Garcia-Belmonte, Germà

2017-10-01

Interfaces between the absorbing perovskite and transporting layers are gaining attention as the key locus that governs solar cell operation and long term performance. The interplay of ionic and electronic processes, along with the asymmetrical architecture of any solar cell, makes the interpretation of electrical measurements always inconclusive. A strategy to progress in relating electric responses, operating mechanisms, and device architecture relies upon simplifying the probing structure. Macroscopic CH3NH3PbBr3 single crystals with symmetrical contacts are tested by means of long-time current transient and impedance spectroscopy. It is observed that interfaces govern carrier injection to (and extraction from) perovskite layers through an inductive (negative capacitance) mechanism with a response time in the range of ˜ 1 - 100 s under dark conditions and inert atmosphere. Current transient exhibits a slow recovering after the occurrence of an undershoot, signaling a complex carrier dynamics which involves changes in surface state occupancy.

Dramatic changes in muscle contractile and structural properties after 2 botulinum toxin injections.

Science.gov (United States)

Minamoto, Viviane B; Suzuki, Kentaro P; Bremner, Shannon N; Lieber, Richard L; Ward, Samuel R

2015-10-01

Botulinum toxin is frequently administered serially to maintain therapeutic muscle paralysis, but the effect of repeated doses on muscle function are largely unknown. This study characterized the muscle response to 2 onabotulinum toxin (BoNT) injections separated by 3 months. Animal subjects received a single toxin injection (n = 8), 2 BoNT injections separated by 3 months (n = 14), or 1 BoNT and 1 saline injection separated by 3 months (n = 8). The functional effect of 2 serial injections was exponentially greater than the effect of a single injection. While both groups treated with a single BoNT injection had decreased torque in the injected leg by approximately 50% relative to contralateral legs, the double BoNT injected group had decreased torque by over 95% relative to the preinjection level. Both single and double BoNT injections produced clear signs of fiber-type grouping. These experiments demonstrate a disproportionately greater effect of repeated BoNT injections. © 2015 Wiley Periodicals, Inc.

Intratumoral and peritumoral lymphovascular invasion detected by D2-40 immunohistochemistry correlates with metastasis in primary cutaneous Merkel cell carcinoma.

Science.gov (United States)

Al-Rohil, Rami N; Milton, Denái R; Nagarajan, Priyadharsini; Curry, Jonathan L; Feldmeyer, Laurence; Torres-Cabala, Carlos A; Ivan, Doina; Prieto, Victor G; Tetzlaff, Michael T; Aung, Phyu P

2018-07-01

Primary cutaneous Merkel cell carcinoma (MCC) is an aggressive neuroendocrine malignancy in which lymphovascular invasion (LVI) correlates with more aggressive phenotype. The prognostic significance of LVI detected by D2-40 immunohistochemistry (IHC) in MCC remains controversial. We aimed to determine how LVI detected by D2-40 IHC compares with LVI detected by hematoxylin and eosin (H&E) staining in predicting MCC metastasis. Clinical and histopathologic features of MCCs diagnosed and treated in 2002 to 2015 were assembled and included 58 MCC tumors from 58 patients. H&E-stained tissue sections and D2-40 IHC studies were reviewed. When LVI was present, the location (peritumoral or intratumoral) and the size of the largest invaded vessel were recorded. LVI findings by H&E staining and D2-40 IHC were compared with each other and with histologic features and clinical outcomes. H&E staining showed LVI in 37 of 58 cases; D2-40 IHC confirmed LVI in 30 of these cases but failed to confirm LVI in 7. D2-40 IHC also detected 14 cases of LVI not identified on H&E staining. Histologically, D2-40-detected LVI was associated with infiltrative growth pattern and nonbrisk lymphoid infiltrate (P = .005 and P = .055, respectively). There was a statistically significant difference between the frequency of detection of peritumoral LVI by H&E in comparison to D2-40 IHC (P = .0009). MCCs in which D2-40 IHC-detected both intratumoral and peritumoral LVI were typically larger than MCCs without (mean, 24.5 mm versus 17.3 mm; P = .03) and more frequently metastasized (87% versus 51%; P = .03). D2-40 IHC detection of both intratumoral and peritumoral LVI is associated with metastasis. Copyright © 2018 Elsevier Inc. All rights reserved.

The Impact of Optimal Respiratory Gating and Image Noise on Evaluation of Intratumor Heterogeneity on 18F-FDG PET Imaging of Lung Cancer

NARCIS (Netherlands)

Grootjans, W.; Tixier, F.; van der Vos, Charlotte Sophie; Vriens, D.; Le Rest, C.C.; Bussink, J.; Oyen, W.J.; de Geus-Oei, Lioe-Fee; Visvikis, D.; Visser, E.P.

2016-01-01

Accurate measurement of intratumor heterogeneity using parameters of texture on PET images is essential for precise characterization of cancer lesions. In this study, we investigated the influence of respiratory motion and varying noise levels on quantification of textural parameters in patients

Reactive Power Injection Strategies for Single-Phase Photovoltaic Systems Considering Grid Requirements

DEFF Research Database (Denmark)

Yang, Yongheng; Wang, Huai; Blaabjerg, Frede

2014-01-01

.g. Germany and Italy. Those advanced features can be provided by next generation PV systems, and will be enhanced in the future to ensure an even efficient and reliable utilization of PV systems. In light of this, Reactive Power Injection (RPI) strategies for single-phase PV systems are explored...... in this paper. The RPI possibilities are: a) constant average active power control, b) constant active current control, c) constant peak current control and d) thermal optimized control strategy. All those strategies comply with the currently active grid codes, but are with different objectives. The proposed...... RPI strategies are demonstrated firstly by simulations and also tested experimentally on a 1 kW singe-phase grid-connected system in LVRT operation mode. Those results show the effectiveness and feasibilities of the proposed strategies with reactive power control during LVRT operation. The design...

Watt-level widely tunable single-mode emission by injection-locking of a multimode Fabry-Perot quantum cascade laser

Science.gov (United States)

Chevalier, Paul; Piccardo, Marco; Anand, Sajant; Mejia, Enrique A.; Wang, Yongrui; Mansuripur, Tobias S.; Xie, Feng; Lascola, Kevin; Belyanin, Alexey; Capasso, Federico

2018-02-01

Free-running Fabry-Perot lasers normally operate in a single-mode regime until the pumping current is increased beyond the single-mode instability threshold, above which they evolve into a multimode state. As a result of this instability, the single-mode operation of these lasers is typically constrained to few percents of their output power range, this being an undesired limitation in spectroscopy applications. In order to expand the span of single-mode operation, we use an optical injection seed generated by an external-cavity single-mode laser source to force the Fabry-Perot quantum cascade laser into a single-mode state in the high current range, where it would otherwise operate in a multimode regime. Utilizing this approach, we achieve single-mode emission at room temperature with a tuning range of 36 cm-1 and stable continuous-wave output power exceeding 1 W at 4.5 μm. Far-field measurements show that a single transverse mode is emitted up to the highest optical power, indicating that the beam properties of the seeded Fabry-Perot laser remain unchanged as compared to free-running operation.

[Incidence rate of adverse reaction/event by Qingkailing injection: a Meta-analysis of single rate].

Science.gov (United States)

Ai, Chun-ling; Xie, Yan-ming; Li, Ming-quan; Wang, Lian-xin; Liao, Xing

2015-12-01

To systematically review the incidence rate of adverse drug reaction/event by Qingkailing injection. Such databases as the PubMed, EMbase, the Cochrane library, CNKI, VIP WanFang data and CBM were searched by computer from foundation to July 30, 2015. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data and cross check data. Then, Meta-analysis was performed by using the R 3.2.0 software, subgroup sensitivity analysis was performed based on age, mode of medicine, observation time and research quality. Sixty-three studies involving 9,793 patients with Qingkailing injection were included, 367 cases of adverse reactions/events were reported in total. The incidence rate of adverse reaction in skin and mucosa group was 2% [95% CI (0.02; 0.03)]; the digestive system adverse reaction was 6% [95% CI(0.05; 0.07); the injection site adverse reaction was 4% [95% CI (0.02; 0.07)]. In the digestive system as the main types of adverse reactions/events, incidence of children and adults were 4.6% [0.021 1; 0.097 7] and 6.9% [0.053 5; 0.089 8], respectively. Adverse reactions to skin and mucous membrane damage as the main performance/event type, the observation time > 7 days and ≤ 7 days incidence of 3% [0.012 9; 0.068 3] and 1.9% [0.007 8; 0.046 1], respectively. Subgroup analysis showed that different types of adverse reactions, combination in the incidence of adverse reactions/events were higher than that of single drug, the difference was statistically significant (P reactions occur, and clinical rational drug use, such as combination, age and other fators, and the influence factors vary in different populations. Therefore, clinical doctors for children and the elderly use special care was required for a clear and open spirit injection, the implementation of individualized medication.

Induction of generalized Shwartzman reaction (GSR) in irradiated rabbits by a single injection of endotoxin

International Nuclear Information System (INIS)

Wronowski, T.; Uchanska-Dudzinska, B.; Teisseyre, E.; Kopec, M.

1976-01-01

Rabbits were prepared to GSR by either a single dose 30 μg/kg of Salmonella enteritidis endotoxin or by a single whole-body exposure to 850 R of x ray. After 24 hrs provocative dose of endotoxin 50 μg/kg was injected. Histological examinations of kidneys revealed that GSR occurred with equal frequency in both groups of rabbits but was more severe in the animals prepared by irradiation. Protamine gelation test detected soluble fibrin complexes in plasma in about 50% of rabbits 24 hrs after either of the preparatory procedures and virtually in 100% after the provocative endotoxin dose. During the preparatory phase of GSR the irradiation induced a profound decrease in blood lymphocyte count and in the weight of thymus and spleen. It is postulated that early postexposure lysis of lymphatic cells participates in mechanisms leading to thrombotic phenomena after irradiation

High intratumoral macrophage content is an adverse prognostic feature in anaplastic large cell lymphoma

DEFF Research Database (Denmark)

Pedersen, Martin Bjerregård; Hamilton-Dutoit, Stephen Jacques; Bendix, Knud

2014-01-01

AIMS: Macrophage infiltration has been associated with prognosis in several cancers, including lymphoma, but has not been assessed systematically in anaplastic large cell lymphoma (ALCL). The aim of the study was to correlate expression of the macrophage-associated antigens CD68 and CD163 with pre......-therapeutic parameters and outcome in a cohort of treatment-naive ALCL patients. METHODS AND RESULTS: Pre-therapeutic tumour specimens from 52 patients with ALCL were included in a tissue microarray. The intratumoral macrophage content was assessed by immunohistochemical staining for CD68 and CD163, and quantified using......-free survival in ALK-negative patients (P macrophages correlates with an adverse outcome in ALK-negative ALCL....

Tertiary Intratumor Lymphoid Tissue in Colo-Rectal Cancer

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Federica Marchesi

2011-12-01

Full Text Available Ectopic (or tertiary lymphoid tissue develops at sites of inflammation or infection in non lymphoid organs and is associated with chronic inflammation. In colon mucosa, small lymphoid aggregates are already present in homeostatic conditions, as part of the gut-associated lymphoid tissue and play an essential role in the immune response to perturbations of the mucosal microenvironment. Despite the recognized role of inflammation in tumor progression, the presence and biological function of lymphoid tissue in cancer has been poorly investigated. We identified aggregates of lymphocytes resembling tertiary lymphoid tissue in human colorectal cancer specimens; intratumor accumulations of lymphocytes display a high degree of compartmentalization, with B and T cells, mature dendritic cells and a network of CD21+ follicular dendritic cells (FDC. We analyzed the adaptation of colon lymphoid tissue in a murine model of colitis-associated cancer (AOM/DSS. B cell follicle formation increases in the context of the chronic inflammation associated to intestinal neoplasia, in this model. A network of lymphatic and haematic vessels surrounding B cell follicles is present and includes high endothelial venules (HEV. Future task is to determine whether lymphoid tissue contributes to the persistence of the tumor-associated inflammatory reaction, rather than represent a functional immune compartment, potentially participating to the anti tumor response.

Tertiary Intratumor Lymphoid Tissue in Colo-Rectal Cancer

Energy Technology Data Exchange (ETDEWEB)

Bergomas, Francesca [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Grizzi, Fabio [Laboratory of Molecular Gastroenterology, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Doni, Andrea; Pesce, Samantha [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Laghi, Luigi [Laboratory of Molecular Gastroenterology, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Department of Gastroenterology, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Allavena, Paola [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Mantovani, Alberto [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Department of Translational Medicine, University of Milan, Milan 20089 (Italy); Marchesi, Federica, E-mail: federica.marchesi@humanitasresearch.it [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy)

2011-12-28

Ectopic (or tertiary) lymphoid tissue develops at sites of inflammation or infection in non lymphoid organs and is associated with chronic inflammation. In colon mucosa, small lymphoid aggregates are already present in homeostatic conditions, as part of the gut-associated lymphoid tissue and play an essential role in the immune response to perturbations of the mucosal microenvironment. Despite the recognized role of inflammation in tumor progression, the presence and biological function of lymphoid tissue in cancer has been poorly investigated. We identified aggregates of lymphocytes resembling tertiary lymphoid tissue in human colorectal cancer specimens; intratumor accumulations of lymphocytes display a high degree of compartmentalization, with B and T cells, mature dendritic cells and a network of CD21{sup +} follicular dendritic cells (FDC). We analyzed the adaptation of colon lymphoid tissue in a murine model of colitis-associated cancer (AOM/DSS). B cell follicle formation increases in the context of the chronic inflammation associated to intestinal neoplasia, in this model. A network of lymphatic and haematic vessels surrounding B cell follicles is present and includes high endothelial venules (HEV). Future task is to determine whether lymphoid tissue contributes to the persistence of the tumor-associated inflammatory reaction, rather than represent a functional immune compartment, potentially participating to the anti tumor response.

Tertiary Intratumor Lymphoid Tissue in Colo-Rectal Cancer

International Nuclear Information System (INIS)

Bergomas, Francesca; Grizzi, Fabio; Doni, Andrea; Pesce, Samantha; Laghi, Luigi; Allavena, Paola; Mantovani, Alberto; Marchesi, Federica

2011-01-01

Ectopic (or tertiary) lymphoid tissue develops at sites of inflammation or infection in non lymphoid organs and is associated with chronic inflammation. In colon mucosa, small lymphoid aggregates are already present in homeostatic conditions, as part of the gut-associated lymphoid tissue and play an essential role in the immune response to perturbations of the mucosal microenvironment. Despite the recognized role of inflammation in tumor progression, the presence and biological function of lymphoid tissue in cancer has been poorly investigated. We identified aggregates of lymphocytes resembling tertiary lymphoid tissue in human colorectal cancer specimens; intratumor accumulations of lymphocytes display a high degree of compartmentalization, with B and T cells, mature dendritic cells and a network of CD21 + follicular dendritic cells (FDC). We analyzed the adaptation of colon lymphoid tissue in a murine model of colitis-associated cancer (AOM/DSS). B cell follicle formation increases in the context of the chronic inflammation associated to intestinal neoplasia, in this model. A network of lymphatic and haematic vessels surrounding B cell follicles is present and includes high endothelial venules (HEV). Future task is to determine whether lymphoid tissue contributes to the persistence of the tumor-associated inflammatory reaction, rather than represent a functional immune compartment, potentially participating to the anti tumor response

Conversion from non-orthogonally to orthogonally polarized optical single-sideband modulation using optically injected semiconductor lasers.

Science.gov (United States)

Hung, Yu-Han; Tseng, Chin-Hao; Hwang, Sheng-Kwang

2018-06-01

This Letter investigates an optically injected semiconductor laser for conversion from non-orthogonally to orthogonally polarized optical single-sideband modulation. The underlying mechanism relies solely on nonlinear laser characteristics and, thus, only a typical semiconductor laser is required as the key conversion unit. This conversion can be achieved for a broadly tunable frequency range up to at least 65 GHz. After conversion, the microwave phase quality, including linewidth and phase noise, is mostly preserved, and simultaneous microwave amplification up to 23 dB is feasible.

Symposium on single cell analysis and genomic approaches, Experimental Biology 2017 Chicago, Illinois, April 23, 2017.

Science.gov (United States)

Coller, Hilary A

2017-09-01

Emerging technologies for the analysis of genome-wide information in single cells have the potential to transform many fields of biology, including our understanding of cell states, the response of cells to external stimuli, mosaicism, and intratumor heterogeneity. At Experimental Biology 2017 in Chicago, Physiological Genomics hosted a symposium in which five leaders in the field of single cell genomics presented their recent research. The speakers discussed emerging methodologies in single cell analysis and critical issues for the analysis of single cell data. Also discussed were applications of single cell genomics to understanding the different types of cells within an organism or tissue and the basis for cell-to-cell variability in response to stimuli. Copyright © 2017 the American Physiological Society.

The mechanism of the transient depression of the erythropoietic rate induced in the rat by a single injection of uranyl nitrate

International Nuclear Information System (INIS)

Giglio, M.J.; Brandan, N.; Leal, T.L.; Bozzini, C.E.

1989-01-01

With the purpose of assessing the effect of uranyl nitrate (UN) on the rate of erythropoiesis, 1 mg/kg of the compound was injected iv to adult female Wistar rats. The dosing vehicle was injected into control animals. A single injection of UN induced a transient depression of the rate of red cell volume 59 Fe uptake, which reached its lowest value (68% depression) by the seventh postinjection day. By 14 days, 59 Fe incorporation had returned to normal. The amount of iron going to erythroid tissue per hour, reticulocyte count, and immunoreactive erythropoietin concentration in both plasma and kidney extracts were also significantly depressed in UN-treated rats in relation to these values in vehicle-injected rats by the seventh postinjection day. Dose-response curves for exogenous erythropoietin (Epo) performed in polycythemic intact and UN-treated rats 7 days after drug injection revealed a significant depression of the response in UN-injected animals. Moreover, bone marrow cells obtained from rats pretreated with UN formed a reduced number of erythroid colonies in vitro in response to Epo. Therefore, possible mechanisms for the observed transient depression in the rate of erythropoiesis associated with acute UN treatment include decreased Epo production and direct or indirect damage of erythroid progenitor cells

SU-D-207B-05: Robust Intra-Tumor Partitioning to Identify High-Risk Subregions for Prognosis in Lung Cancer

Energy Technology Data Exchange (ETDEWEB)

Wu, J; Gensheimer, M; Dong, X; Rubin, D; Napel, S; Diehn, M; Loo, B; Li, R [Stanford University, Palo Alto, CA (United States)

2016-06-15

Purpose: To develop an intra-tumor partitioning framework for identifying high-risk subregions from 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and CT imaging, and to test whether tumor burden associated with the high-risk subregions is prognostic of outcomes in lung cancer. Methods: In this institutional review board-approved retrospective study, we analyzed the pre-treatment FDG-PET and CT scans of 44 lung cancer patients treated with radiotherapy. A novel, intra-tumor partitioning method was developed based on a two-stage clustering process: first at patient-level, each tumor was over-segmented into many superpixels by k-means clustering of integrated PET and CT images; next, tumor subregions were identified by merging previously defined superpixels via population-level hierarchical clustering. The volume associated with each of the subregions was evaluated using Kaplan-Meier analysis regarding its prognostic capability in predicting overall survival (OS) and out-of-field progression (OFP). Results: Three spatially distinct subregions were identified within each tumor, which were highly robust to uncertainty in PET/CT co-registration. Among these, the volume of the most metabolically active and metabolically heterogeneous solid component of the tumor was predictive of OS and OFP on the entire cohort, with a concordance index or CI = 0.66–0.67. When restricting the analysis to patients with stage III disease (n = 32), the same subregion achieved an even higher CI = 0.75 (HR = 3.93, logrank p = 0.002) for predicting OS, and a CI = 0.76 (HR = 4.84, logrank p = 0.002) for predicting OFP. In comparison, conventional imaging markers including tumor volume, SUVmax and MTV50 were not predictive of OS or OFP, with CI mostly below 0.60 (p < 0.001). Conclusion: We propose a robust intra-tumor partitioning method to identify clinically relevant, high-risk subregions in lung cancer. We envision that this approach will be applicable to identifying useful

Advanced diesel electronic fuel injection and turbocharging

Science.gov (United States)

Beck, N. J.; Barkhimer, R. L.; Steinmeyer, D. C.; Kelly, J. E.

1993-12-01

The program investigated advanced diesel air charging and fuel injection systems to improve specific power, fuel economy, noise, exhaust emissions, and cold startability. The techniques explored included variable fuel injection rate shaping, variable injection timing, full-authority electronic engine control, turbo-compound cooling, regenerative air circulation as a cold start aid, and variable geometry turbocharging. A Servojet electronic fuel injection system was designed and manufactured for the Cummins VTA-903 engine. A special Servojet twin turbocharger exhaust system was also installed. A series of high speed combustion flame photos was taken using the single cylinder optical engine at Michigan Technological University. Various fuel injection rate shapes and nozzle configurations were evaluated. Single-cylinder bench tests were performed to evaluate regenerative inlet air heating techniques as an aid to cold starting. An exhaust-driven axial cooling air fan was manufactured and tested on the VTA-903 engine.

Differential diagnosis of pituitary adenomas and Rathke's cleft cysts by diffusion-weighted MRI using single-shot fast spin echo technique

International Nuclear Information System (INIS)

Abe, Takumi; Izumiyama, Hitoshi; Fukuda, Ataru; Tanioka, Daisuke; Kunii, Norihiko; Komatsu, Daisuke; Fujita, Shogo; Ukisu, Ryutaro; Moritani, Toshio

2002-01-01

The purpose of the present study was to prospectively evaluate the diagnostic ability of diffusion-weighted magnetic resonance imaging (DWI) using single-shot fast spin echo (SSFSE) technique to discriminate pituitary adenomas from Rathke's cleft cysts. DWIs were obtained from 40 patients with pathologically proven pituitary macroadenomas and 15 patients with proven Rathke's cleft cysts. Pituitary adenomas were divided into 27 cases with solid components alone, five with non-hemorrhagic large cysts, and eight with intratumoral hemorrhage. On SSFSE DWI, solid components of pituitary adenomas revealed iso or slightly increased intensity and intratumoral hemorrhage showed higher intensity than normal brain parenchyma, whereas Rathke's cleft cysts and intratumoral cysts demonstrated very low intensity. SSFSE DWI did not display the susceptibility artifacts that are seen close to the skull base and sinonasal cavities on echo planar diffusion imaging. On the basis of our preliminary findings, DWI may enable us to differentiate pituitary adenomas with only solid components and hemorrhagic pituitary adenomas appearing hyperintense on T1-weighted images from Rathke's cleft cysts without administration of gadolinium-DTPA. SSFSE DWI appears to be a useful technique for characterizing pituitary diseases without the susceptibility artifacts. Our study is the first report to demonstrate the identification of pituitary disorders on SSFSE DWI. (author)

Magnetic resonance imaging of single co-labeled mesenchymal stromal cells after intracardial injection in mice

International Nuclear Information System (INIS)

Salamon, J.; Adam, G.; Peldschus, K.; Wicklein, D.; Schumacher, U.; Didie, M.; Lange, C.

2014-01-01

Purpose: The aim of this study was to establish co-labeling of mesenchymal stromal cells (MSC) for the detection of single MSC in-vivo by MRI and histological validation. Materials and Methods: Mouse MSC were co-labeled with fluorescent iron oxide micro-particles and carboxyfluorescein succinimidyl ester (CFSE). The cellular iron content was determined by atomic absorption spectrometry. Cell proliferation and expression of characteristic surface markers were determined by flow cytometry. The chondrogenic differentiation capacity was assessed. Different amounts of cells (n1 = 5000, n2 = 15 000, n3 = 50 000) were injected into the left heart ventricle of 12 mice. The animals underwent sequential MRI on a clinical 3.0T scanner (Intera, Philips Medical Systems, Best, The Netherlands). For histological validation cryosections were examined by fluorescent microscopy. Results: Magnetic and fluorescent labeling of MSC was established (mean cellular iron content 23.6 ± 3 pg). Flow cytometry showed similar cell proliferation and receptor expression of labeled and unlabeled MSC. Chondrogenic differentiation of labeled MSC was verified. After cell injection MRI revealed multiple signal voids in the brain and fewer signal voids in the kidneys. In the brain, an average of 4.6 ± 1.2 (n1), 9.0 ± 3.6 (n2) and 25.0 ± 1.0 (n3) signal voids were detected per MRI slice. An average of 8.7 ± 3.1 (n1), 22.0 ± 6.1 (n2) and 89.8 ± 6.5 (n3) labeled cells per corresponding stack of adjacent cryosections could be detected in the brain. Statistical correlation of the numbers of MRI signal voids in the brain and single MSC found by histology revealed a correlation coefficient of r = 0.91. Conclusion: The study demonstrates efficient magnetic and fluorescent co-labeling of MSC and their detection on a single cell level in mice by in-vivo MRI and histology. The described techniques may broaden the methods for in-vivo tracking of MSC. (orig.)

Intratumoral delivery of CpG-conjugated anti-MUC1 antibody enhances NK cell anti-tumor activity.

Science.gov (United States)

Schettini, Jorge; Kidiyoor, Amritha; Besmer, Dahlia M; Tinder, Teresa L; Roy, Lopamudra Das; Lustgarten, Joseph; Gendler, Sandra J; Mukherjee, Pinku

2012-11-01

Monoclonal antibodies (mAbs) against tumor-associated antigens are useful anticancer agents. Antibody-dependent cellular cytotoxicity (ADCC) is one of the major mechanisms responsible for initiating natural killer cell (NK)-mediated killing of tumors. However, the regulation of ADCC via NK cells is poorly understood. We have investigated the cytolytic activity of NK cells against pancreatic cancer cells that were coated with an antibody directed against the human tumor antigen, Mucin-1 designated HMFG-2, either alone or conjugated to CpG oligodeoxynucleotide (CpG ODN). Conjugated antibodies were tested for their ability to elicit ADCC in vitro and in vivo against pancreatic cancer cells. NK cells cultured in the presence of immobilized CpG ODN, HMFG-2 Ab, or CpG ODN-conjugated HMFG-2 Ab were able to up-regulate perforin similarly. Interestingly, a significant higher ADCC was observed when CpG ODN-conjugated HMFG-2-coated tumor cells were co-cultured with NK cells compared to unconjugated HMFG-2 Ab or CpG ODN alone. Moreover, MyD88-deficient NK cells can perform ADCC in vitro. Furthermore, intratumoral injections of CpG ODN-conjugated HMFG-2 induced a significant reduction in tumor burden in vivo in an established model of pancreatic tumor in nude mice compared to CpG ODN or the HMFG-2 alone. Depletion of macrophages or NK cells before treatment confirmed that both cells were required for the anti-tumor response in vivo. Results also suggest that CpG ODN and HMFG-2 Ab could be sensed by NK cells on the mAb-coated tumor cells triggering enhanced ADCC in vitro and in vivo.

Long-term correction of obesity and diabetes in genetically obese mice by a single intramuscular injection of recombinant adeno-associated virus encoding mouse leptin

Science.gov (United States)

Murphy, John E.; Zhou, Shangzhen; Giese, Klaus; Williams, Lewis T.; Escobedo, Jaime A.; Dwarki, Varavani J.

1997-01-01

The ob/ob mouse is genetically deficient in leptin and exhibits a phenotype that includes obesity and non-insulin-dependent diabetes melitus. This phenotype closely resembles the morbid obesity seen in humans. In this study, we demonstrate that a single intramuscular injection of a recombinant adeno-associated virus (AAV) vector encoding mouse leptin (rAAV-leptin) in ob/ob mice leads to prevention of obesity and diabetes. The treated animals show normalization of metabolic abnormalities including hyperglycemia, insulin resistance, impaired glucose tolerance, and lethargy. The effects of a single injection have lasted through the 6-month course of the study. At all time points measured the circulating levels of leptin in the serum were similar to age-matched control C57 mice. These results demonstrate that maintenance of normal levels of leptin (2–5 ng/ml) in the circulation can prevent both the onset of obesity and associated non-insulin-dependent diabetes. Thus a single injection of a rAAV vector expressing a therapeutic gene can lead to complete and long-term correction of a genetic disorder. Our study demonstrates the long-term correction of a disease caused by a genetic defect and proves the feasibility of using rAAV-based vectors for the treatment of chronic disorders like obesity. PMID:9391128

Baseline performance and emissions data for a single-cylinder, direct-injected diesel engine

Science.gov (United States)

Dezelick, R. A.; Mcfadden, J. J.; Ream, L. W.; Barrows, R. F.

1983-01-01

Comprehensive fuel consumption, mean effective cylinder pressure, and emission test results for a supercharged, single-cylinder, direct-injected, four-stroke-cycle, diesel test engine are documented. Inlet air-to-exhaust pressure ratios were varied from 1.25 to 3.35 in order to establish the potential effects of turbocharging techniques on engine performance. Inlet air temperatures and pressures were adjusted from 34 to 107 C and from 193 to 414 kPa to determine the effects on engine performance and emissions. Engine output ranged from 300 to 2100 kPa (brake mean effective pressure) in the speed range of 1000 to 3000 rpm. Gaseous and particulate emission rates were measured. Real-time values of engine friction and pumping loop losses were measured independently and compared with motored engine values.

Improved Tumor Penetration and Single-Cell Targeting of Antibody-Drug Conjugates Increases Anticancer Efficacy and Host Survival.

Science.gov (United States)

Cilliers, Cornelius; Menezes, Bruna; Nessler, Ian; Linderman, Jennifer; Thurber, Greg M

2018-02-01

Current antibody-drug conjugates (ADC) have made advances in engineering the antibody, linker, conjugation site, small-molecule payload, and drug-to-antibody ratio (DAR). However, the relationship between heterogeneous intratumoral distribution and efficacy of ADCs is poorly understood. Here, we compared trastuzumab and ado-trastuzumab emtansine (T-DM1) to study the impact of ADC tumor distribution on efficacy. In a mouse xenograft model insensitive to trastuzumab, coadministration of trastuzumab with a fixed dose of T-DM1 at 3:1 and 8:1 ratios dramatically improved ADC tumor penetration and resulted in twice the improvement in median survival compared with T-DM1 alone. In this setting, the effective DAR was lowered, decreasing the amount of payload delivered to each targeted cell but increasing the number of cells that received payload. This result is counterintuitive because trastuzumab acts as an antagonist in vitro and has no single-agent efficacy in vivo , yet improves the effectiveness of T-DM1 in vivo Novel dual-channel fluorescence ratios quantified single-cell ADC uptake and metabolism and confirmed that the in vivo cellular dose of T-DM1 alone exceeded the minimum required for efficacy in this model. In addition, this technique characterized cellular pharmacokinetics with heterogeneous delivery after 1 day, degradation and payload release by 2 days, and in vitro cell killing and in vivo tumor shrinkage 2 to 3 days later. This work demonstrates that the intratumoral distribution of ADC, independent of payload dose or plasma clearance, plays a major role in ADC efficacy. Significance: This study shows how lowering the drug-to-antibody ratio during treatment can improve the intratumoral distribution of a antibody-drug conjugate, with implications for improving the efficacy of this class of cancer drugs. Cancer Res; 78(3); 758-68. ©2017 AACR . ©2017 American Association for Cancer Research.

Direct current injection and thermocapillary flow for purification of aligned arrays of single-walled carbon nanotubes

Energy Technology Data Exchange (ETDEWEB)

Xie, Xu; Islam, Ahmad E.; Seabron, Eric; Dunham, Simon N.; Du, Frank; Lin, Jonathan; Wilson, William L.; Rogers, John A., E-mail: jrogers@illinois.edu [Department of Materials Science and Engineering, Frederick Seitz Materials Research Laboratory, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801 (United States); Wahab, Muhammad A.; Alam, Muhammad A. [School of Electrical and Computer Engineering, Purdue University, West Lafayette, Indiana 47907 (United States); Li, Yuhang [Institute of Solid Mechanics, Beihang University, Beijing 100191 (China); Tomic, Bojan [Department of Electrical Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801 (United States); Huang, Jiyuan [Department of Physics, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801 (United States); Burns, Branden [Department of Physics, Purdue University, West Lafayette, Indiana 47907 (United States); Song, Jizhou [Department of Engineering Mechanics and Soft Matter Research Center, Zhejiang University, Hangzhou 310027 (China); Huang, Yonggang [Department of Civil and Environmental Engineering, Department of Mechanical Engineering, Center for Engineering and Health, and Skin Disease Research Center, Northwestern University, Evanston, Illinois 60208 (United States)

2015-04-07

Aligned arrays of semiconducting single-walled carbon nanotubes (s-SWNTs) represent ideal configurations for use of this class of material in high performance electronics. Development of means for removing the metallic SWNTs (m-SWNTs) in as-grown arrays represents an essential challenge. Here, we introduce a simple scheme that achieves this type of purification using direct, selective current injection through interdigitated electrodes into the m-SWNTs, to allow their complete removal using processes of thermocapillarity and dry etching. Experiments and numerical simulations establish the fundamental aspects that lead to selectivity in this process, thereby setting design rules for optimization. Single-step purification of arrays that include thousands of SWNTs demonstrates the effectiveness and simplicity of the procedures. The result is a practical route to large-area aligned arrays of purely s-SWNTs with low-cost experimental setups.

Direct current injection and thermocapillary flow for purification of aligned arrays of single-walled carbon nanotubes

International Nuclear Information System (INIS)

Xie, Xu; Islam, Ahmad E.; Seabron, Eric; Dunham, Simon N.; Du, Frank; Lin, Jonathan; Wilson, William L.; Rogers, John A.; Wahab, Muhammad A.; Alam, Muhammad A.; Li, Yuhang; Tomic, Bojan; Huang, Jiyuan; Burns, Branden; Song, Jizhou; Huang, Yonggang

2015-01-01

Aligned arrays of semiconducting single-walled carbon nanotubes (s-SWNTs) represent ideal configurations for use of this class of material in high performance electronics. Development of means for removing the metallic SWNTs (m-SWNTs) in as-grown arrays represents an essential challenge. Here, we introduce a simple scheme that achieves this type of purification using direct, selective current injection through interdigitated electrodes into the m-SWNTs, to allow their complete removal using processes of thermocapillarity and dry etching. Experiments and numerical simulations establish the fundamental aspects that lead to selectivity in this process, thereby setting design rules for optimization. Single-step purification of arrays that include thousands of SWNTs demonstrates the effectiveness and simplicity of the procedures. The result is a practical route to large-area aligned arrays of purely s-SWNTs with low-cost experimental setups

Analysis of pulsed injection for microgravity receiver tank chilldown

Science.gov (United States)

Honkonen, Scott C.; Pietrzyk, Joe R.; Schuster, John R.

The dominant heat transfer mechanism during the hold phase of a tank chilldown cycle in a low-gravity environment is due to fluid motion persistence following the charge. As compared to the single-charge per vent cycle case, pulsed injection maintains fluid motion and the associated high wall heat transfer coefficients during the hold phase. As a result, the pulsed injection procedure appears to be an attractive method for reducing the time and liquid mass required to chill a tank. However, for the representative conditions considered, no significant benefit can be realized by using pulsed injection as compared to the single-charge case. A numerical model of the charge/hold/vent process was used to evaluate the pulsed injection procedure for tank chilldown in microgravity. Pulsed injection results in higher average wall heat transfer coefficients during the hold, as compared to the single-charge case. However, these high levels were not coincident with the maximum wall-to-fluid temperature differences, as in the single-charge case. For representative conditions investigated, the charge/hold/vent process is very efficient. A slightly shorter chilldown time was realized by increasing the number of pulses.

Prevalence and correlates of neck injection among people who inject drugs in Tijuana, Mexico.

Science.gov (United States)

Rafful, Claudia; Wagner, Karla D; Werb, Dan; González-Zúñiga, Patricia E; Verdugo, Silvia; Rangel, Gudelia; Strathdee, Steffanie A

2015-11-01

Injecting drugs in the neck has been related to adverse health conditions such as jugular vein thrombosis, deep neck infections, aneurysm, haematomas, airway obstruction, vocal cord paralysis and wound botulism, among others. We identified prevalence and correlates of neck injection among people who inject drugs (PWID) in Tijuana, Mexico. Beginning in 2011, PWID aged ≥18 years who injected drugs within the last month were recruited into a prospective cohort. At baseline and semi-annually, PWID completed interviewer-administered surveys soliciting data on drug-injecting practices. Logistic regression was used to identify predictors of injecting in the neck as the most frequent injection site at a single visit. Of 380 PWID, 35.3% injected in the neck at least once in the past 6 months, among whom 71.6% reported it as their most common injection site, the most common injecting site after the arms (47%). Controlling for age, years injecting and injecting frequency, injecting heroin and methamphetamine two or more times per day and having sought injection assistance were associated with injecting in the neck [adjusted odds ratios (AOR): 2.12; 95% confidence intervals (CI): 1.27-3.53 and AOR: 2.65; 95% CI: 1.52-4.53 respectively]. Injecting in the neck was very common among PWID in Tijuana and was associated with polydrug use and seeking injection assistance. Tailoring harm reduction education interventions for individuals who provide injection assistance ('hit doctors') may allow for the dissemination of safe injecting knowledge to reduce injection-related morbidity and mortality. © 2015 Australasian Professional Society on Alcohol and other Drugs.

Intra-articular injection of hyaluronic acid is not superior to saline solution injection for ankle arthritis: a randomized, double-blind, placebo-controlled study.

Science.gov (United States)

DeGroot, Henry; Uzunishvili, Sofia; Weir, Robert; Al-omari, Ali; Gomes, Bruna

2012-01-04

Intra-articular injections of hyaluronic acid are potentially useful to treat ankle osteoarthritis, yet their effectiveness has not been proven. Both single and multiple-dose treatments for ankle arthritis with use of various hyaluronic acid products have been recommended, but few high-quality studies have been published. The aim of this study was to compare the effectiveness of a single intra-articular injection of hyaluronic acid with a single intra-articular injection of normal saline solution (placebo) for osteoarthritis of the ankle. Sixty-four patients with ankle osteoarthritis who met all study criteria were randomly assigned to a single intra-articular injection of 2.5 mL of low-molecular-weight, non-cross-linked hyaluronic acid or a single intra-articular injection of 2.5 mL of normal saline solution. The primary outcome measure was the change from baseline in the American Orthopaedic Foot & Ankle Society (AOFAS) clinical rating score at the six-week and twelve-week follow-up examination. Secondary outcome measures included the Ankle Osteoarthritis Scale score and patient-reported pain with use of a visual analog pain scale. Of the sixty-four patients randomized and treated, eight patients withdrew, leaving fifty-six patients who completed the entire study. There was one mild adverse event (1.6%) among the sixty-four patients. At six weeks and twelve weeks, the mean AOFAS scores in the hyaluronic acid group had improved from baseline by 4.9 and 4.9 points, respectively, whereas the mean AOFAS scores in the placebo group initially worsened by 0.4 point at six weeks and then improved by 5.4 points at twelve weeks. While the change at twelve weeks from baseline was substantial for both groups, the between-group differences were not significant. We found that a single intra-articular injection of low-molecular-weight, non-cross-linked hyaluronic acid is not demonstrably superior to a single intra-articular injection of saline solution for the treatment of

Radial oil injection applied to main engine bearings: evaluation of injection control rules

DEFF Research Database (Denmark)

Estupiñan, EA; Santos, Ilmar

2012-01-01

, the dynamic behaviour of the main bearing of a medium-size engine is theoretically analysed when the engine operates with controllable radial oil injection and four different injection control rules. The theoretical investigation is based on a single-cylinder combustion engine model. The performance......The performance of main bearings in a combustion engine affects key functions such as durability, noise and vibration. Thus, with the aim of reducing friction losses and vibrations between the crankshaft and the bearings, the work reported here evaluates different strategies for applying...... controllable radial oil injection to main crankshaft journal bearings. In an actively lubricated bearing, conventional hydrodynamic lubrication is combined with controllable hydrostatic lubrication, where the oil injection pressures can be modified depending on the operational conditions. In this study...

Pointwise mutual information quantifies intratumor heterogeneity in tissue sections labeled with multiple fluorescent biomarkers

Directory of Open Access Journals (Sweden)

Daniel M Spagnolo

2016-01-01

Full Text Available Background: Measures of spatial intratumor heterogeneity are potentially important diagnostic biomarkers for cancer progression, proliferation, and response to therapy. Spatial relationships among cells including cancer and stromal cells in the tumor microenvironment (TME are key contributors to heterogeneity. Methods: We demonstrate how to quantify spatial heterogeneity from immunofluorescence pathology samples, using a set of 3 basic breast cancer biomarkers as a test case. We learn a set of dominant biomarker intensity patterns and map the spatial distribution of the biomarker patterns with a network. We then describe the pairwise association statistics for each pattern within the network using pointwise mutual information (PMI and visually represent heterogeneity with a two-dimensional map. Results: We found a salient set of 8 biomarker patterns to describe cellular phenotypes from a tissue microarray cohort containing 4 different breast cancer subtypes. After computing PMI for each pair of biomarker patterns in each patient and tumor replicate, we visualize the interactions that contribute to the resulting association statistics. Then, we demonstrate the potential for using PMI as a diagnostic biomarker, by comparing PMI maps and heterogeneity scores from patients across the 4 different cancer subtypes. Estrogen receptor positive invasive lobular carcinoma patient, AL13-6, exhibited the highest heterogeneity score among those tested, while estrogen receptor negative invasive ductal carcinoma patient, AL13-14, exhibited the lowest heterogeneity score. Conclusions: This paper presents an approach for describing intratumor heterogeneity, in a quantitative fashion (via PMI, which departs from the purely qualitative approaches currently used in the clinic. PMI is generalizable to highly multiplexed/hyperplexed immunofluorescence images, as well as spatial data from complementary in situ methods including FISSEQ and CyTOF, sampling many different

Pharmacokinetics of cefquinome in red-eared slider turtles (Trachemys scripta elegans) after single intravenous and intramuscular injections.

Science.gov (United States)

Uney, K; Altan, F; Cetin, G; Aboubakr, M; Dik, B; Sayın, Z; Er, A; Elmas, M

2018-02-01

The purpose of this study was to evaluate the pharmacokinetics of cefquinome (CFQ) following single intravenous (IV) or intramuscular (IM) injections of 2 mg/kg body weight in red-eared slider turtles. Plasma concentrations of CFQ were determined by high-performance liquid chromatography and analyzed using noncompartmental methods. The pharmacokinetic parameters following IV injection were as follows: elimination half-life (t 1/2λz ) 21.73 ± 4.95 hr, volume of distribution at steady-state (V dss ) 0.37 ± 0.11 L/kg, area under the plasma concentration-time curve (AUC 0-∞ ) 163 ± 32 μg hr -1  ml -1 , and total body clearance (Cl T ) 12.66 ± 2.51 ml hr -1  kg -1 . The pharmacokinetic parameters after IM injection were as follows: peak plasma concentration (C max ) 3.94 ± 0.84 μg/ml, time to peak concentration (T max ) 3 hr, t 1/2λz 26.90 ± 4.33 hr, and AUC 0-∞ 145 ± 48 μg hr -1  ml -1 . The bioavailability after IM injection was 88%. Data suggest that CFQ has a favorable pharmacokinetic profile with a long half-life and a high bioavailability in red-eared slider turtles. Further studies are needed to establish a multiple dosage regimen and evaluate clinical efficacy. © 2017 John Wiley & Sons Ltd.

Effect of injection timing and injection pressure on the performance ...

African Journals Online (AJOL)

DR OKE

This paper discusses the feasibility study on the utilization of biodiesel ester of Honge oil (EHO) in common rail direct injection. (CRDI) engine. Biodiesel of EHO has been obtained by transesterification process and characterization has been done. Existing single cylinder diesel engine fitted with conventional mechanical ...

Therapeutic evaluation of sorafenib for hepatocellular carcinoma using contrast-enhanced ultrasonography: Preliminary result.

Science.gov (United States)

Shiozawa, Kazue; Watanabe, Manabu; Ikehara, Takashi; Kogame, Michio; Kikuchi, Yoshinori; Igarashi, Yoshinori; Sumino, Yasukiyo

2016-07-01

The present study aimed to determine the usefulness of contrast-enhanced ultrasonography (CEUS) with Sonazoid in evaluating the therapeutic response to sorafenib for hepatocellular carcinoma (HCC). In total, 26 patients with advanced HCC who received sorafenib and were followed up by CEUS were enrolled in the present study. CEUS was performed prior to and within 2-4 weeks of treatment, and the images of the target lesion in the post-vascular phase with a re-injection method were analyzed. The presence (+) or absence (-) of intratumoral necrosis and the intratumoral vascular architecture on micro-flow imaging (MFI) were compared prior to and subsequent to treatment. Target lesions that exhibited non-enhancement after re-injection were considered to indicate intratumoral necrosis. The intratumoral vascular architecture was classified into three groups, as follows: Vd, the intratumoral vessels visually narrowed or decreased; Vnc, the vessels remained unchanged; and Vi, the vessels were thickened or increased. Survival curves were estimated using the Kaplan-Meier method and compared using the log rank test between the intratumoral necrosis (+) and (-) groups, and among the Vd, Vnc and Vi groups. PVnc group and 5 patients in the Vi group. The MSTs in the Vd, Vnc and Vi groups were 15.6 months (95% CI, 5.0-23.3), 11.0 months (95% CI, 3.5-17.6) and 3.6 months (95% CI: 1.2-6.0), respectively. The P-value for the differences between the Vd and Vnc groups, Vd and Vi groups, and Vnc and Vi groups were 0.78, 0.016 and 0.047, respectively, which indicated that the survival time decreased significantly in the Vi group. Evaluation of intratumoral vascular architecture using MFI demonstrates promise for assessing the therapeutic response to sorafenib in patients with HCC.

Electroluminescence from single nanowires by tunnel injection: an experimental study

International Nuclear Information System (INIS)

Zimmler, Mariano A; Bao Jiming; Shalish, Ilan; Yi, Wei; Yoon, Joonah; Narayanamurti, Venkatesh; Capasso, Federico

2007-01-01

We present a hybrid light-emitting diode structure composed of an n-type gallium nitride nanowire on a p-type silicon substrate in which current is injected along the length of the nanowire. The device emits ultraviolet light under both bias polarities. Tunnel injection of holes from the p-type substrate (under forward bias) and from the metal (under reverse bias) through thin native oxide barriers consistently explains the observed electroluminescence behaviour. This work shows that the standard p-n junction model is generally not applicable to this kind of device structure

Single-injection method for evaluation of renal function with 14C-inulin and 3H-tetraethylammonium bromide in dogs and cats

International Nuclear Information System (INIS)

Fettman, M.J.; Allen, T.A.; Wilke, W.L.; Radin, M.J.; Eubank, M.C.

1985-01-01

A double-isotope single-injection method without urine collection for the estimation of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) in dogs and cats was evaluated. The GFR was determined, using 14 C-inulin and ERPF was determined, using [ 3 H]tetraethylammonium bromide. Using a modified single exponential, 1-compartment mathematical model, the renal clearance of these solutes was estimated with a plasma radioactivity disappearance curve constructed from samples collected over a 150-minute time period. In 25 dogs, GFR, ERPF, and filtration fraction were 3.55 +/- 0.14 ml/kg/min, 10.51 +/- 0.72 ml/kg/min, and 0.34 +/- 0.02, respectively. In 25 cats, GFR, ERPF, and filtration fraction were 3.24 +/- 0.14 ml/kg/min, 8.14 +/- 0.53 ml/kg/min, and 0.39 +/- 0.02, respectively. This time-efficient and reliable method, using beta-emitting isotopes, yielded renal functional values well within the normal ranges reported by a variety of other isotopic and nonisotopic procedures. The advantages of the present procedure over previous double-isotope single-injection methods include the use of less costly, lower energy-using, and less penetrating beta emittors, as well as a shortened blood sampling schedule

The intratumoral distribution of radiolabeled 177Lu-BR96 monoclonal antibodies changes in relation to tumor histology over time in a syngeneic rat colon carcinoma model.

Science.gov (United States)

Örbom, Anders; Eriksson, Sophie E; Elgström, Erika; Ohlsson, Tomas; Nilsson, Rune; Tennvall, Jan; Strand, Sven-Erik

2013-08-01

The therapeutic effect of radioimmunotherapy depends on the distribution of the absorbed dose in relation to viable cancer cells within the tumor, which in turn is a function of the activity distribution. The aim of this study was to investigate the distribution of (177)Lu-DOTA-BR96 monoclonal antibodies targeting the Lewis Y antigen over 7 d using a syngeneic rat model of colon carcinoma. Thirty-eight tumor-bearing rats were intravenously given 25 or 50 MBq of (177)Lu-DOTA-BR96 per kilogram of body weight and were sacrificed 2, 8, 24, 48, 72, 96, 120, or 168 h after injection, with activity measured in blood and tumor samples. Adjacent cryosections of each tumor were analyzed in 3 ways: imaging using a silicon-strip detector for digital autoradiography, staining for histologic characterization, or staining to determine the distribution of the antigen, vasculature, and proliferating cells using immunohistochemistry. Absorbed-dose rate distribution images at the moment of sacrifice were calculated using the activity distribution and a point-dose kernel. The correlations between antigen expression and both activity uptake and absorbed-dose rate were calculated for several regions of interest in each tumor. Nine additional animals with tumors were given unlabeled antibody to evaluate possible immunologic effects. At 2-8 h after injection, activity was found in the tumor margins; at 24 h, in viable antigen-expressing areas within the tumor; and at 48 h and later, increasingly in antigen-negative areas of granulation tissue. The correlation between antigen expression and both the mean activity and the absorbed-dose rate in regions of interest changed from positive to negative after 24 h after injection. Antigen-negative areas also increased over time in animals injected with unlabeled BR96, compared with untreated tumors. The results indicate that viable Lewis Y-expressing tumor cells are most efficiently treated during the initial uptake period. The activity then seems

The impact of optimal respiratory gating and image noise on evaluation of intra-tumor heterogeneity in 18F-FDG positron emission tomography imaging of lung cancer

NARCIS (Netherlands)

Grootjans, W.; Tixier, F.; Vos, C.S. van der; Vriens, D.; Rest, C.C. Le; Bussink, J.; Oyen, W.J.G.; Geus-Oei, L.F. de; Visvikis, D.; Visser, E.P.

2016-01-01

Assessment of measurement accuracy of intra-tumor heterogeneity using texture features in positron emission tomography (PET) images is essential to characterize cancer lesions with high precision. In this study, we investigated the influence of respiratory motion and varying noise levels on

Study of the post-equilibrium slope approximation in the calculation of glomerular filtration rate using the 51Cr-EDTA single injection technique

International Nuclear Information System (INIS)

Nimmon, C.C.; McAlister, J.M.; Hickson, B.; Cattell, W.R.

1975-01-01

A comparison of methods for calculating the renal clearance of EDTA from the plasma disappearance curve, after a single injection, has been made. Measurements were made on 38 patients, using external monitoring and venous blood sampling techniques, over a period of 24 h after an injection of 100 μCi of 51 Cr-EDTA. The results indicate that the period 3 - 6 h after injection is suitable for sampling the post-equilibrium part of the plasma disappearance curve for values of the glomerular filtration rate (GFR) in the range 0 - 140 ml/min. It was also found that, to within the individual measurement errors, the values of the clearance calculated by using the post-equilibrium period only (PES clearance) can be considered to show a constant proportionality to the values calculated by using the entire plasma disappearance curve (total clearance). (author)

Injection-locked single-mode VCSEL for orthogonal multiplexing and amplitude noise suppression

DEFF Research Database (Denmark)

Chipouline, Arkadi; Lyubopytov, Vladimir S.; Malekizandi, Mohammadreza

2017-01-01

It has been shown earlier, that the injection locked semiconductor lasers enable effective amplitude noise suppression [1] and makes possible an extra level of signal multiplexing-orthogonal modulation [2], where DPSK and ASK NRZ channels propagate at the same wavelength [3]. In our work we use...... an injection-locked 1550 nm VCSEL as a slave laser providing separation of amplitude and phase modulations, carrying independent information flows. To validate the possibility of phase modulation extraction by an injection-locked VCSEL, an experimental setup shown in Fig. 1 has been built....

Comparison of intratumoral FDG and Cu-ATSM distributions in cancer tissue originated spheroid (CTOS) xenografts, a tumor model retaining the original tumor properties

International Nuclear Information System (INIS)

Furukawa, Takako; Yuan, Qinghua; Jin, Zhao-Hui; Aung, Winn; Yoshii, Yukie; Hasegawa, Sumitaka; Endo, Hiroko; Inoue, Masahiro; Zhang, Ming-Rong; Fujibayashi, Yasuhisa; Saga, Tsuneo

2014-01-01

Introduction: The intratumoral distributions of [ 18 F]FDG and [ 64 Cu]Cu-ATSM have been reported to be similar in adenocarcinomas but different in squamous cell carcinoma (SCC) in clinical studies. In the present study, we compared the intratumoral distributions of these two tracers in cancer tissue originated spheroid (CTOS) xenografts derived from adenocarcinoma and SCC, which retain the histological characteristics of the original tumors, and in cancer cell line xenografts of corresponding origin, to investigate the underlying mechanism of the distinct FDG and Cu-ATSM distribution patterns in adenocarcinoma and SCC. Methods: CTOSs derived from colon adenocarcinoma and lung SCC and cell lines established from colon adenocarcinoma and lung SCC, which were used for comparison, were subcutaneously transplanted into immunodeficient mice. One hour after administering [ 14 C]FDG and [ 64 Cu]Cu-ATSM, the intratumoral distributions were compared in the xenografts by using dual-tracer autoradiography. Adjacent sections were evaluated for necrosis, vasculature anatomy, Ki-67 antigen, and pimonidazole adducts using hematoxylin and eosin and immunohistochemical staining. Results: There was a higher regional overlap of high FDG and Cu-ATSM accumulations in the adenocarcinoma CTOS xenografts than in the SCC CTOS xenografts, while the overlap in the adenocarcinoma cell line xenograft was lower than that observed in the SCC cell line. High FDG accumulation occurred primarily in proximity to necrotic or pimonidazole adduct positive regions, while high Cu-ATSM accumulation occurred primarily in live cell regions separate from the necrotic regions. The adenocarcinoma CTOS xenograft had the stereotypical glandular structure, resulting in more intricately mixed regions of live and necrotic cells compared to those observed in the SCC CTOS or the cell line xenografts. Conclusion: Tumor morphological characteristics, specifically the spatial distribution of live and necrotic cell

Anti-tumor effect of 131I labeled 17-allylamino-17-demethoxygeldanamycin on human non-small cell lung cancer in xenograft-bearing nude mice

International Nuclear Information System (INIS)

Sun Jin; Liu Lu; Zhu Xiaoli; Chen Daozhen; Gao Wen; Jiang Xinyu; Huang Ying

2008-01-01

Objective: 17-allylamino-17-demethoxygeldanamycin (17-AAG) has been developed as a novel heat shock protein 90 (HSP90) inhibitor being used in clinical trials. HSP90 is known as a molecular target for tumor therapy. The goal of this study was to investigate the inhibitive effects of 131 I labeled 17-AAG on human non-small cell lung cancer in xenograft-bearing nude mice. Methods: 17-AAG was labeled with 131 I. Twenty-eight BALB/c nude mice bearing H460 human non-small cell lung carcinoma tumor xenograft were randomly divided into seven groups, one control group and six treatment groups according to the route of administration (via tail vein injection or intratumoral injection) and the doses of injected radio-activity (5.5 MBq x 2 with 8 d interval, 11.0 MBq and 5.5 MBq). Two additional mice were treated with intratumoral injection of Na 131 I solution that was served as seintigraphic imaging controls. In each group two mice underwent scintigraphy at 2 h, 6 h, 24 h, 2 d, 3 d, 7 d, 10 d and 16 d. After 16 d the tumor inhibition rate was calculated. Then all of the mice were sacrificed and the tumor tissues were obtained for histological examination and immunohistochemical assay. Results: Persistent accumulation of 131 I-17-AAG in the tumors was seen on seintigraphic images. Tumor inhibiting effect was demonstrated in all treatment groups with varying degrees. The highest tumor inhibition rate (86.77 ± 4.57)% was shown in the group with interval intratumoral injection (5.5 MBq x 2). There was no significant difference of tumor inhibition rates between 5.5 MBq x 2 group (via tail vein injection) and 11.0 MBq group( via tail vein injection, q=1.67, P>0.05). While among the other treatment groups, there was significant difference in tumor inhibition rates( q=3.16-24.34, all P 131 I-17-AAG may effectively inhibit the tumor growth and expression of HSP90α antigen expression in non-small cell lung cancer bearing nude mice. The more prominent anti-tumor effect may be

Single-cell analysis of targeted transcriptome predicts drug sensitivity of single cells within human myeloma tumors.

Science.gov (United States)

Mitra, A K; Mukherjee, U K; Harding, T; Jang, J S; Stessman, H; Li, Y; Abyzov, A; Jen, J; Kumar, S; Rajkumar, V; Van Ness, B

2016-05-01

Multiple myeloma (MM) is characterized by significant genetic diversity at subclonal levels that have a defining role in the heterogeneity of tumor progression, clinical aggressiveness and drug sensitivity. Although genome profiling studies have demonstrated heterogeneity in subclonal architecture that may ultimately lead to relapse, a gene expression-based prediction program that can identify, distinguish and quantify drug response in sub-populations within a bulk population of myeloma cells is lacking. In this study, we performed targeted transcriptome analysis on 528 pre-treatment single cells from 11 myeloma cell lines and 418 single cells from 8 drug-naïve MM patients, followed by intensive bioinformatics and statistical analysis for prediction of proteasome inhibitor sensitivity in individual cells. Using our previously reported drug response gene expression profile signature at the single-cell level, we developed an R Statistical analysis package available at https://github.com/bvnlabSCATTome, SCATTome (single-cell analysis of targeted transcriptome), that restructures the data obtained from Fluidigm single-cell quantitative real-time-PCR analysis run, filters missing data, performs scaling of filtered data, builds classification models and predicts drug response of individual cells based on targeted transcriptome using an assortment of machine learning methods. Application of SCATT should contribute to clinically relevant analysis of intratumor heterogeneity, and better inform drug choices based on subclonal cellular responses.

Charge Injection and Transport in Organic Nanofibers

DEFF Research Database (Denmark)

Kjelstrup-Hansen, Jakob; Bøggild, Peter; Rubahn, H. G.

2007-01-01

the injection barrier height equal to the difference between the metal electrode work function and the HOMO energy level of the organic semiconductor. Semiquantitative modeling suggests that the weak temperature dependence is due to injection into a distribution of states rather than into a single energy level...

Intratumoral Macroscopic Fat and Hemorrhage Combination Useful in the Differentiation of Benign and Malignant Solid Renal Masses.

Science.gov (United States)

Sun, Jun; Xing, Zhaoyu; Xing, Wei; Zheng, Linfeng; Chen, Jie; Fan, Min; Chen, Tongbing; Zhang, Zhuoli

2016-03-01

To evaluate the value of combining the detection of intratumoral macroscopic fat and hemorrhage in the differentiation of the benign from malignant solid renal masses.Conventional magnetic resonance imaging (MRI), chemical shift (CS)-MRI, and susceptibility-weighted imaging were performed in 152 patients with 152 solid renal masses, including 48 benign and 104 malignant masses all pathologically confirmed. The presence of macroscopic fat detected by CS-MRI and hemorrhage detected by susceptibility-weighted imaging were evaluated in all masses. The rates of macroscopic fat and hemorrhage observed between benign and malignant masses were compared by a χ test. All masses found to contain macroscopic fat with or without hemorrhage were considered to be benign. The remaining masses (without macroscopic fat) found not to contain hemorrhage were considered to be benign. Only those found to contain hemorrhage alone were considered to be malignant. The evaluation indexes for differentiating and forecasting the benign and malignant masses were calculated.Significant differences in the rate of macroscopic fat (observed in 85.42% of benign masses vs. 0% of malignant masses) and hemorrhage (observed in 4.17% of benign masses vs. 95.19% of malignant masses) were measured in the benign and malignant groups (P benign and malignant masses were 96.05%, 95.19%, and 97.92%, respectively, and the accuracy and error rate of forecasting the benign and malignant masses were 95.39% and 4.61%, respectively.Combining the detection intratumoral macroscopic fat and hemorrhage can be used to differentiate the benign from malignant solid renal masses.

Single well injection withdrawal tests (SWIW) in fractured rock. Some aspects on interpretation

International Nuclear Information System (INIS)

Neretnieks, Ivars

2007-08-01

Single-Well-Injection-Withdrawal, SWIW, tests are used to try to extract information on fracture apertures, sorption and diffusion properties and dispersion information in individual fractures. It is done by injecting a given amount of traced water into an isolated fracture. After a waiting period water is withdrawn from the fracture and the tracer concentration is measured. The concentration time curve is fitted to a model and the parameter values quantifying the different interaction mechanisms are determined. A number of different mechanisms influence the recovery of the tracer. One or more of the following mechanisms are considered. They include: dispersion due to velocity differences, sorption on fracture surface and on infill, diffusion in rock fragments in the fracture, diffusion between 'streamlines', diffusion into rock matrix and other stagnant water volumes, sorption kinetics and slow drift of the plume caused by the natural gradient. Many of the interaction mechanisms can influence the recovery curve in a similar way. For example, diffusion into rock matrix water and into stagnant water in the fracture adjacent to the flowing channels cannot be distinguished if only one tracer is used. Tracers with different properties can in principle be used but they will encounter different parts of the fracture, the sorbing tracer will move out less from the injection point than a nonsorbing tracer will. Diffusion and sorption in small particles in the flowpath can influence the recovery curve in a similar way as rock matrix diffusion does. Dispersion caused by diffusion between 'streamlines', Taylor dispersion, can give very different results in channels of different shapes. Such dispersion effects can be difficult to distinguish from matrix diffusion effects. Dispersion coefficients obtained in a SWIW test may have little relation to dispersion of a tracer moving from A to B. This is partly due to the different mechanisms and partly due to different time scales

Single well injection withdrawal tests (SWIW) in fractured rock. Some aspects on interpretation

Energy Technology Data Exchange (ETDEWEB)

Neretnieks, Ivars [Dept. of Chemical Engineering and Technology, Royal Inst. of Technology, Stockholm (Sweden)

2007-08-15

Single-Well-Injection-Withdrawal, SWIW, tests are used to try to extract information on fracture apertures, sorption and diffusion properties and dispersion information in individual fractures. It is done by injecting a given amount of traced water into an isolated fracture. After a waiting period water is withdrawn from the fracture and the tracer concentration is measured. The concentration time curve is fitted to a model and the parameter values quantifying the different interaction mechanisms are determined. A number of different mechanisms influence the recovery of the tracer. One or more of the following mechanisms are considered. They include: dispersion due to velocity differences, sorption on fracture surface and on infill, diffusion in rock fragments in the fracture, diffusion between 'streamlines', diffusion into rock matrix and other stagnant water volumes, sorption kinetics and slow drift of the plume caused by the natural gradient. Many of the interaction mechanisms can influence the recovery curve in a similar way. For example, diffusion into rock matrix water and into stagnant water in the fracture adjacent to the flowing channels cannot be distinguished if only one tracer is used. Tracers with different properties can in principle be used but they will encounter different parts of the fracture, the sorbing tracer will move out less from the injection point than a nonsorbing tracer will. Diffusion and sorption in small particles in the flowpath can influence the recovery curve in a similar way as rock matrix diffusion does. Dispersion caused by diffusion between 'streamlines', Taylor dispersion, can give very different results in channels of different shapes. Such dispersion effects can be difficult to distinguish from matrix diffusion effects. Dispersion coefficients obtained in a SWIW test may have little relation to dispersion of a tracer moving from A to B. This is partly due to the different mechanisms and partly due to

Alters Intratumoral Drug Distribution and Affects Therapeutic Synergy of Antiangiogenic Organoselenium Compound

Directory of Open Access Journals (Sweden)

Youcef M. Rustum

2010-01-01

Full Text Available Tumor differentiation enhances morphologic and microvascular heterogeneity fostering hypoxia that retards intratumoral drug delivery, distribution, and compromise therapeutic efficacy. In this study, the influence of tumor biologic heterogeneity on the interaction between cytotoxic chemotherapy and selenium was examined using a panel of human tumor xenografts representing cancers of the head and neck and lung along with tissue microarray analysis of human surgical samples. Tumor differentiation status, microvessel density, interstitial fluid pressure, vascular phenotype, and drug delivery were correlated with the degree of enhancement of chemotherapeutic efficacy by selenium. Marked potentiation of antitumor activity was observed in H69 tumors that exhibited a well-vascularized, poorly differentiated phenotype. In comparison, modulation of chemotherapeutic efficacy by antiangiogenic selenium was generally lower or absent in well-differentiated tumors with multiple avascular hypoxic, differentiated regions. Tumor histomorphologic heterogeneity was found prevalent in the clinical samples studied and represents a primary and critical physiological barrier to chemotherapy.

Metaplastic thymoma with myasthenia gravis presumably caused by an accumulation of intratumoral immature T cells: a case report.

Science.gov (United States)

Tajima, Shogo; Yanagiya, Masahiro; Sato, Masaaki; Nakajima, Jun; Fukayama, Masashi

2015-01-01

Among human neoplasms, thymomas are well known for their association with paraneoplastic autoimmune diseases such as myasthenia gravis. However, regarding rare metaplastic thymoma, only one case of an association with myasthenia gravis has been reported. Here, we present the second case of a 44-year-old woman with metaplastic thymoma associated with myasthenia gravis. In metaplastic thymoma, intratumoral terminal deoxynucleotidyl transferase-positive T-cells (immature T-cells) are generally scarce, while they were abundant in the present case. We believe that these immature T-cells could be related to the occurrence of myasthenia gravis.

Non-invasive assessment of intratumoral vascularity using arterial spin labeling: A comparison to susceptibility-weighted imaging for the differentiation of primary cerebral lymphoma and glioblastoma

International Nuclear Information System (INIS)

Furtner, J.; Schöpf, V.; Preusser, M.; Asenbaum, U.; Woitek, R.; Wöhrer, A.; Hainfellner, J.A.; Wolfsberger, S.; Prayer, D.

2014-01-01

Using conventional MRI methods, the differentiation of primary cerebral lymphomas (PCNSL) and other primary brain tumors, such as glioblastomas, is difficult due to overlapping imaging characteristics. This study was designed to discriminate tumor entities using normalized vascular intratumoral signal intensity values (nVITS) obtained from pulsed arterial spin labeling (PASL), combined with intratumoral susceptibility signals (ITSS) from susceptibility-weighted imaging (SWI). Thirty consecutive patients with glioblastoma (n = 22) and PCNSL (n = 8), histologically classified according to the WHO brain tumor classification, were included. MRIs were acquired on a 3 T scanner, and included PASL and SWI sequences. nVITS was defined by the signal intensity ratio between the tumor and the contralateral normal brain tissue, as obtained by PASL images. ITSS was determined as intratumoral low signal intensity structures detected on SWI sequences and were divided into four different grades. Potential differences in the nVITS and ITSS between glioblastomas and PCNSLs were revealed using statistical testing. To determine sensitivity, specificity, and diagnostic accuracy, as well as an optimum cut-off value for the differentiation of PCNSL and glioblastoma, a receiver operating characteristic analysis was used. We found that nVITS (p = 0.011) and ITSS (p = 0.001) values were significantly higher in glioblastoma than in PCNSL. The optimal cut-off value for nVITS was 1.41 and 1.5 for ITSS, with a sensitivity, specificity, and accuracy of more than 95%. These findings indicate that nVITS values have a comparable diagnostic accuracy to ITSS values in differentiating glioblastoma and PCNSL, offering a completely non-invasive and fast assessment of tumoral vascularity in a clinical setting

Non-invasive assessment of intratumoral vascularity using arterial spin labeling: A comparison to susceptibility-weighted imaging for the differentiation of primary cerebral lymphoma and glioblastoma.

Science.gov (United States)

Furtner, J; Schöpf, V; Preusser, M; Asenbaum, U; Woitek, R; Wöhrer, A; Hainfellner, J A; Wolfsberger, S; Prayer, D

2014-05-01

Using conventional MRI methods, the differentiation of primary cerebral lymphomas (PCNSL) and other primary brain tumors, such as glioblastomas, is difficult due to overlapping imaging characteristics. This study was designed to discriminate tumor entities using normalized vascular intratumoral signal intensity values (nVITS) obtained from pulsed arterial spin labeling (PASL), combined with intratumoral susceptibility signals (ITSS) from susceptibility-weighted imaging (SWI). Thirty consecutive patients with glioblastoma (n=22) and PCNSL (n=8), histologically classified according to the WHO brain tumor classification, were included. MRIs were acquired on a 3T scanner, and included PASL and SWI sequences. nVITS was defined by the signal intensity ratio between the tumor and the contralateral normal brain tissue, as obtained by PASL images. ITSS was determined as intratumoral low signal intensity structures detected on SWI sequences and were divided into four different grades. Potential differences in the nVITS and ITSS between glioblastomas and PCNSLs were revealed using statistical testing. To determine sensitivity, specificity, and diagnostic accuracy, as well as an optimum cut-off value for the differentiation of PCNSL and glioblastoma, a receiver operating characteristic analysis was used. We found that nVITS (p=0.011) and ITSS (p=0.001) values were significantly higher in glioblastoma than in PCNSL. The optimal cut-off value for nVITS was 1.41 and 1.5 for ITSS, with a sensitivity, specificity, and accuracy of more than 95%. These findings indicate that nVITS values have a comparable diagnostic accuracy to ITSS values in differentiating glioblastoma and PCNSL, offering a completely non-invasive and fast assessment of tumoral vascularity in a clinical setting. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Non-invasive assessment of intratumoral vascularity using arterial spin labeling: A comparison to susceptibility-weighted imaging for the differentiation of primary cerebral lymphoma and glioblastoma

Energy Technology Data Exchange (ETDEWEB)

Furtner, J., E-mail: julia.furtner@meduniwien.ac.at [Department of Biomedical Imaging und Image-guided Therapy, Medical University of Vienna (Austria); Comprehensive Cancer Center-Central Nervous System Tumors Unit (CCC-CNS), Medical University of Vienna (Austria); Schöpf, V., E-mail: veronika.schoepf@meduniwien.ac.at [Department of Biomedical Imaging und Image-guided Therapy, Medical University of Vienna (Austria); Preusser, M., E-mail: matthias.preusser@meduniwien.ac.at [Department of Medicine I, Division of Oncology, Medical University of Vienna (Austria); Comprehensive Cancer Center-Central Nervous System Tumors Unit (CCC-CNS), Medical University of Vienna (Austria); Asenbaum, U., E-mail: ulrika.asenbaum@meduniwien.ac.at [Department of Biomedical Imaging und Image-guided Therapy, Medical University of Vienna (Austria); Woitek, R., E-mail: ramona.woitek@meduniwien.ac.at [Department of Biomedical Imaging und Image-guided Therapy, Medical University of Vienna (Austria); Wöhrer, A., E-mail: adelheid.woehrer@meduniwien.ac.at [Institute of Neurology, Medical University of Vienna (Austria); Comprehensive Cancer Center-Central Nervous System Tumors Unit (CCC-CNS), Medical University of Vienna (Austria); Hainfellner, J.A., E-mail: johannes.hainfellner@meduniwien.ac.at [Institute of Neurology, Medical University of Vienna (Austria); Comprehensive Cancer Center-Central Nervous System Tumors Unit (CCC-CNS), Medical University of Vienna (Austria); Wolfsberger, S., E-mail: stefan.wolfsberger@meduniwien.ac.at [Department of Neurosurgery, Medical University of Vienna (Austria); Comprehensive Cancer Center-Central Nervous System Tumors Unit (CCC-CNS), Medical University of Vienna (Austria); Prayer, D., E-mail: daniela.prayer@meduniwien.ac.at [Department of Biomedical Imaging und Image-guided Therapy, Medical University of Vienna (Austria); Comprehensive Cancer Center-Central Nervous System Tumors Unit (CCC-CNS), Medical University of Vienna (Austria)

2014-05-15

Using conventional MRI methods, the differentiation of primary cerebral lymphomas (PCNSL) and other primary brain tumors, such as glioblastomas, is difficult due to overlapping imaging characteristics. This study was designed to discriminate tumor entities using normalized vascular intratumoral signal intensity values (nVITS) obtained from pulsed arterial spin labeling (PASL), combined with intratumoral susceptibility signals (ITSS) from susceptibility-weighted imaging (SWI). Thirty consecutive patients with glioblastoma (n = 22) and PCNSL (n = 8), histologically classified according to the WHO brain tumor classification, were included. MRIs were acquired on a 3 T scanner, and included PASL and SWI sequences. nVITS was defined by the signal intensity ratio between the tumor and the contralateral normal brain tissue, as obtained by PASL images. ITSS was determined as intratumoral low signal intensity structures detected on SWI sequences and were divided into four different grades. Potential differences in the nVITS and ITSS between glioblastomas and PCNSLs were revealed using statistical testing. To determine sensitivity, specificity, and diagnostic accuracy, as well as an optimum cut-off value for the differentiation of PCNSL and glioblastoma, a receiver operating characteristic analysis was used. We found that nVITS (p = 0.011) and ITSS (p = 0.001) values were significantly higher in glioblastoma than in PCNSL. The optimal cut-off value for nVITS was 1.41 and 1.5 for ITSS, with a sensitivity, specificity, and accuracy of more than 95%. These findings indicate that nVITS values have a comparable diagnostic accuracy to ITSS values in differentiating glioblastoma and PCNSL, offering a completely non-invasive and fast assessment of tumoral vascularity in a clinical setting.

Summary of air permeability data from single-hole injection tests in unsaturated fractured tuffs at the Apache Leap Research Site: Results of steady-state test interpretation

International Nuclear Information System (INIS)

Guzman, A.G.; Geddis, A.M.; Henrich, M.J.; Lohrstorfer, C.F.; Neuman, S.P.

1996-03-01

This document summarizes air permeability estimates obtained from single hole pneumatic injection tests in unsaturated fractured tuffs at the Covered Borehole Site (CBS) within the larger apache Leap Research Site (ALRS). Only permeability estimates obtained from a steady state interpretation of relatively stable pressure and flow rate data are included. Tests were conducted in five boreholes inclined at 45 degree to the horizontal, and one vertical borehole. Over 180 borehole segments were tested by setting the packers 1 m apart. Additional tests were conducted in segments of lengths 0.5, 2.0, and 3.0 m in one borehole, and 2.0 m in another borehole, bringing the total number of tests to over 270. Tests were conducted by maintaining a constant injection rate until air pressure became relatively stable and remained so for some time. The injection rate was then incremented by a constant value and the procedure repeated. The air injection rate, pressure, temperature, and relative humidity were recorded. For each relatively stable period of injection rate and pressure, air permeability was estimated by treating the rock around each test interval as a uniform, isotropic porous medium within which air flows as a single phase under steady state, in a pressure field exhibiting prolate spheroidal symmetry. For each permeability estimate the authors list the corresponding injection rate, pressure, temperature and relative humidity. They also present selected graphs which show how the latter quantities vary with time; logarithmic plots of pressure versus time which demonstrate the importance of borehole storage effects during the early transient portion of each incremental test period; and semilogarithmic plots of pressure versus recovery time at the end of each test sequence

[Utility and advantages of single tracer subareolar injection in sentinel lymph node biopsy in breast cancer].

Science.gov (United States)

Armas, Fayna; Hernández, María Jesús; Vega, Víctor; Gutiérrez, Isabel; Jiménez, Concepción; Pavcovich, Marta; Báez, Beatriz; Pérez-Correa, Pedro; Núñez, Valentín

2005-10-01

Sentinel lymph node (SLN) biopsy is a reliable technique for determining axillary status in patients with early breast cancer. This technique is a minimally invasive procedure that can avoid the use of lymphadenectomy in patients without axillary involvement. We present a validation study of SLN biopsy with subareolar injection of 99mTc-nanocolloids. We studied 100 patients with early breast cancer (T1 and T2) over a 2-year period. All patients underwent deep subareolar-injection of 99mTc-nanocoloid for localization of the sentinel node. Images were obtained and when the sentinel node was seen, it was marked on the skin. All patients underwent tumor excision and radioguided SLN biopsy followed by complete lymphadenectomy. Histopathological analysis of sentinel nodes was performed by hematoxylin-eosin and immunohistochemistry with cytokeratins. The sentinel node was identified in all patients, and a mean of 1.95 sentinel nodes per patient were found. Lymphatic metastases in the sentinel node were found in 44 patients and in 15 of these tumoral spread was also found in the remaining axillary nodes. In the 56 remaining patients the sentinel node was free of metastasis, but in two of them a non-sentinel node was found to be positive (4.5% false negative rate). Sensitivity was 95.7% (44/46), specificity was 100% (54/54), the positive predictive value was 100% and the negative predictive value was 96.4% (54/56). SLN biopsy is an accurate alternative to complete axillary lymph node dissection in patients with early-stage breast cancer. This technique improves the staging of these patients and decreases the morbidity associated with lymphadenectomy. The advantages of subareolar injection are that a single injection site is required, the tumor does not have to be located by other techniques, it allows rapid visualization of the sentinel node and avoids the "shine through phenomenon" when the tumor is located near the axilla.

Differential diagnosis of pituitary adenomas and Rathke's cleft cysts by diffusion-weighted MRI using single-shot fast spin echo technique

Energy Technology Data Exchange (ETDEWEB)

Abe, Takumi; Izumiyama, Hitoshi; Fukuda, Ataru; Tanioka, Daisuke; Kunii, Norihiko; Komatsu, Daisuke; Fujita, Shogo; Ukisu, Ryutaro; Moritani, Toshio [Showa Univ., Tokyo (Japan). School of Medicine

2002-09-01

The purpose of the present study was to prospectively evaluate the diagnostic ability of diffusion-weighted magnetic resonance imaging (DWI) using single-shot fast spin echo (SSFSE) technique to discriminate pituitary adenomas from Rathke's cleft cysts. DWIs were obtained from 40 patients with pathologically proven pituitary macroadenomas and 15 patients with proven Rathke's cleft cysts. Pituitary adenomas were divided into 27 cases with solid components alone, five with non-hemorrhagic large cysts, and eight with intratumoral hemorrhage. On SSFSE DWI, solid components of pituitary adenomas revealed iso or slightly increased intensity and intratumoral hemorrhage showed higher intensity than normal brain parenchyma, whereas Rathke's cleft cysts and intratumoral cysts demonstrated very low intensity. SSFSE DWI did not display the susceptibility artifacts that are seen close to the skull base and sinonasal cavities on echo planar diffusion imaging. On the basis of our preliminary findings, DWI may enable us to differentiate pituitary adenomas with only solid components and hemorrhagic pituitary adenomas appearing hyperintense on T1-weighted images from Rathke's cleft cysts without administration of gadolinium-DTPA. SSFSE DWI appears to be a useful technique for characterizing pituitary diseases without the susceptibility artifacts. Our study is the first report to demonstrate the identification of pituitary disorders on SSFSE DWI. (author)

Phase I Trial of Intratumoral Administration of NIS-Expressing Strain of Measles Virus in Unresectable or Recurrent Malignant Peripheral Nerve Sheath Tumor

Science.gov (United States)

2017-10-01

AWARD NUMBER: W81XWH-15-1-0115 TITLE: Phase I Trial of Intratumoral Administration of NIS-Expressing Strain of Measles Virus in Unresectable or...Fort Detrick, Maryland 21702-5012 DISTRIBUTION STATEMENT: Approved for Public Release; Distribution Unlimited REPORT DOCUMENTATION PAGE Form...Approved OMB No. 0704-0188 Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time

AA injection kicker in its tank

CERN Multimedia

CERN PhotoLab

1980-01-01

For single-turn injection of the antiprotons, a septum at the end of the injection line made the beam parallel to the injection orbit, and a quarter of a betatron-wavelength downstream a fast kicker corrected the angle. Kicker type: lumped delay line. PFN voltage 56 kV. Bending angle 7.5 mrad; kick-strength 0.9 Tm; fall-time 95%-5% in 150 ns. The injection orbit is to the left, the stack orbit to the far right. A fast shutter near the central orbit had to be closed before the kicker fired, so as to protect the stack core from being shaken by the kicker's fringe field. The shutter is shown in closed position.

Methodological study on determining endogenous amino acid excretion of broiler chickens by single intravenous injection of 3H-leucine

International Nuclear Information System (INIS)

Yao Junhu; Wang Kangning; Yang Feng; Zhou Anguo; Cai Xuelin; Duanmu Dao

1999-01-01

Forty broiler chickens (1.5 kg of body weight, BW) were randomly divided into 20 groups. Every fifth group was force-fed a nitrogen-free diet (NFD) or a NFd + 3.20% enzyme hydrolysed casein (EHC) diet or diets with 5% and 20% crude protein (CP) in which soybean meal (sol.) was the sole nitrogen source. 30μCi 3 H-leucine/kg BW was intravenously injected into all birds just after the force-feeding. Venous blood samples were taken at 5 min, 4h, 24h, 36h and 48h after the injection, and the amount of excreta for the whole period of 48h was collected. The amino acids excreted after force-feeding NFD + 3.20% EHC of CP5% diet were theoretically endogenous. The ratios of specific radioactivity (SR) in excreta and the value of definite integral in free plasma from 0 to 48 h after injection of labelled leucine were not different (P > 0.05) when NFD, NFD + 3.20% EHC or CP5% diet was fed. From these results and theoretical analysis, it was suggested that for the birds with CP20% diet, the ratio of SR in endogenous leucine and value of definite integral in free plasma from 0 to 48 h after injection of labelled leucine would be the same as that of the birds with NFD diet, and thus endogenous losses of leucine and other amino acids, by the endogenous amino acid pattern measured with NFD diet, could be estimated for CP20% diet. The endogenous amino acid losses measured by this new technique was 120.50% of those measured by NFD method. It was suggested that single intravenous injection of 3 H-leucine first proposed would be more valuable for determining endogenous amino acid losses, especially when practical nitrogen-containing diet was fed

Volume of high-risk intratumoral subregions at multi-parametric MR imaging predicts overall survival and complements molecular analysis of glioblastoma

Energy Technology Data Exchange (ETDEWEB)

Cui, Yi; Li, Ruijiang [Stanford University, Department of Radiation Oncology, Palo Alto, CA (United States); Hokkaido University, Global Station for Quantum Medical Science and Engineering, Global Institution for Collaborative Research and Education, Hokkaido (Japan); Ren, Shangjie [Tianjin University, School of Electrical Engineering and Automation, Tianjin Shi (China); Tha, Khin Khin; Shirato, Hiroki [Hokkaido University, Global Station for Quantum Medical Science and Engineering, Global Institution for Collaborative Research and Education, Hokkaido (Japan); Hokkaido University, Department of Radiology and Nuclear Medicine, Hokkaido (Japan); Wu, Jia [Stanford University, Department of Radiation Oncology, Palo Alto, CA (United States)

2017-09-15

To develop and validate a volume-based, quantitative imaging marker by integrating multi-parametric MR images for predicting glioblastoma survival, and to investigate its relationship and synergy with molecular characteristics. We retrospectively analysed 108 patients with primary glioblastoma. The discovery cohort consisted of 62 patients from the cancer genome atlas (TCGA). Another 46 patients comprising 30 from TCGA and 16 internally were used for independent validation. Based on integrated analyses of T1-weighted contrast-enhanced (T1-c) and diffusion-weighted MR images, we identified an intratumoral subregion with both high T1-c and low ADC, and accordingly defined a high-risk volume (HRV). We evaluated its prognostic value and biological significance with genomic data. On both discovery and validation cohorts, HRV predicted overall survival (OS) (concordance index: 0.642 and 0.653, P < 0.001 and P = 0.038, respectively). HRV stratified patients within the proneural molecular subtype (log-rank P = 0.040, hazard ratio = 2.787). We observed different OS among patients depending on their MGMT methylation status and HRV (log-rank P = 0.011). Patients with unmethylated MGMT and high HRV had significantly shorter survival (median survival: 9.3 vs. 18.4 months, log-rank P = 0.002). Volume of the high-risk intratumoral subregion identified on multi-parametric MRI predicts glioblastoma survival, and may provide complementary value to genomic information. (orig.)

Sonographically guided deep plantar fascia injections: where does the injectate go?

Science.gov (United States)

Maida, Eugene; Presley, James C; Murthy, Naveen; Pawlina, Wojciech; Smith, Jay

2013-08-01

To determine the distribution of sonographically guided deep plantar fascia injections in an unembalmed cadaveric model. A single experienced operator completed 10 sonographically guided deep plantar fascia injections in 10 unembalmed cadaveric specimens (5 right and 5 left) obtained from 6 donors (2 male and 4 female) aged 49 to 95 years (mean, 77.5 years) with a mean body mass index of 23.2 kg/m(2) (range, 18.4-26.3 kg/m(2)). A 12-3-MHz linear array transducer was used to direct a 22-gauge, 38-mm stainless steel needle deep to the plantar fascia at the anterior aspect of the calcaneus using an in-plane, medial-to-lateral approach. In each case, 1.5 mL of 50% diluted colored latex was injected deep to the plantar fascia. After a minimum of 72 hours, study coinvestigators dissected each specimen to assess injectate placement. All 10 injections accurately placed latex adjacent to the deep side of the plantar fascia at the anterior calcaneus. However, the flexor digitorum brevis (FDB) origin from the plantar fascia variably limited direct latex contact with the plantar fascia, and small amounts of latex interdigitated with the FDB origin in 90% (9 of 10). In all 10 specimens, latex also covered the traversing first branch of the lateral plantar nerve (FBLPN, ie, Baxter nerve) between the FDB and quadratus plantae muscles. No latex was found in the plantar fat pad or plantar fascia in any specimen. Sonographically guided deep plantar fascia injections reliably deliver latex deep to the plantar fascia while avoiding intrafascial injection. However, the extent of direct plantar fascia contact is variable due to the intervening FDB. On the contrary, the traversing FBLPN is reliably covered by the injection. Deep plantar fascia injections may have a role in the management of refractory plantar fasciitis, particularly following failed superficial perifascial or intrafascial injections, in cases of preferential deep plantar fascia involvement, or when entrapment

Linking transcriptional and genetic tumor heterogeneity through allele analysis of single-cell RNA-seq data.

Science.gov (United States)

Fan, Jean; Lee, Hae-Ock; Lee, Soohyun; Ryu, Da-Eun; Lee, Semin; Xue, Catherine; Kim, Seok Jin; Kim, Kihyun; Barkas, Nikolas; Park, Peter J; Park, Woong-Yang; Kharchenko, Peter V

2018-06-13

Characterization of intratumoral heterogeneity is critical to cancer therapy, as presence of phenotypically diverse cell populations commonly fuels relapse and resistance to treatment. Although genetic variation is a well-studied source of intratumoral heterogeneity, the functional impact of most genetic alterations remains unclear. Even less understood is the relative importance of other factors influencing heterogeneity, such as epigenetic state or tumor microenvironment. To investigate the relationship between genetic and transcriptional heterogeneity in a context of cancer progression, we devised a computational approach called HoneyBADGER to identify copy number variation and loss-of-heterozygosity in individual cells from single-cell RNA-sequencing data. By integrating allele and normalized expression information, HoneyBADGER is able to identify and infer the presence of subclone-specific alterations in individual cells and reconstruct underlying subclonal architecture. Examining several tumor types, we show that HoneyBADGER is effective at identifying deletion, amplifications, and copy-neutral loss-of-heterozygosity events, and is capable of robustly identifying subclonal focal alterations as small as 10 megabases. We further apply HoneyBADGER to analyze single cells from a progressive multiple myeloma patient to identify major genetic subclones that exhibit distinct transcriptional signatures relevant to cancer progression. Surprisingly, other prominent transcriptional subpopulations within these tumors did not line up with the genetic subclonal structure, and were likely driven by alternative, non-clonal mechanisms. These results highlight the need for integrative analysis to understand the molecular and phenotypic heterogeneity in cancer. Published by Cold Spring Harbor Laboratory Press.

Tumor treatment by sustained intratumoral release of cisplatin: effects of drug alone and combined with radiation

International Nuclear Information System (INIS)

Yapp, Donald T.T.; Lloyd, David K.; Zhu, Julian; Lehnert, Shirley M.

1997-01-01

Purpose: The effect of intratumoral delivery of cisplatin to a mouse tumor model (RIF-1) by means of a biodegradable polymer implant with and without radiation was studied. Methods and Materials: The polymer bis(p-carboxyphenoxy)propane-sebacic acid (CPP:SA; 80:20) and its degradation products have been characterized. Polymer rods (8 x 0.5 mm) containing 17% cisplatin by weight were prepared by extrusion, and the in vitro degradation rate measured. The implants were placed into mouse tumors and their effect (with and without radiation) on tumor growth delay studied. The levels of Pt in the mouse kidney, tumor, and blood plasma at selected intervals after implant were also determined. These results were compared with those obtained when cisplatin was delivered systematically. Results: When cisplatin was delivered by the polymer implants, higher levels were present in the tumor for longer time periods (cf. systemic delivery of the drug). For both nonirradiated and irradiated tumors, those treated with the polymer implants had significantly longer tumor growth delays compared to nonimplanted controls and to systematically treated tumors. Conclusions: The results show that intratumoral delivery of cisplatin is more efficient than systemic delivery. Using the biodegradable polymer implant, higher doses of cisplatin can be tolerated by the animal as the drug is localized within the tumor, and the high levels of the drug in the tumor can be maintained for an extended period of time. When radiation is given in conjunction with cisplatin, the tumor response is supraadditive for all modes of cisplatin administration but is potentiated to a greater extent when cisplatin is delivered through the polymer implant. The greatest effect is seen for treatment with cisplatin delivered by polymer implant combined with fractionated radiation

External and Intraparticle Diffusion of Coumarin 102 with Surfactant in the ODS-silica Gel/water System by Single Microparticle Injection and Confocal Fluorescence Microspectroscopy

OpenAIRE

NAKATANI, Kiyoharu; MATSUTA, Emi

2015-01-01

The release mechanism of coumarin 102 from a single ODS-silica gel microparticle into the water phase in the presence of Triton X-100 was investigated by confocal fluorescence microspectroscopy combined with the single microparticle injection technique. The release rate significantly depended on the Triton X-100 concentration in the water phase and was not limited by diffusion in the pores of the microparticle. The release rate constant was inversely proportional to the microparticle radius s...

Factors Controlling the Pharmacokinetics, Biodistribution and Intratumoral Penetration of Nanoparticles

Science.gov (United States)

Ernsting, Mark J.; Murakami, Mami; Roy, Aniruddha; Li, Shyh-Dar

2014-01-01

Nanoparticle drug delivery to the tumor is impacted by multiple factors: nanoparticles must evade clearance by renal filtration and the reticuloendothelial system, extravasate through the enlarged endothelial gaps in tumors, penetrate through dense stroma in the tumor microenvironment to reach the tumor cells, remain in the tumor tissue for a prolonged period of time, and finally release the active agent to induce pharmacological effect. The physicochemical properties of nanoparticles such as size, shape, surface charge, surface chemistry (PEGylation, ligand conjugation) and composition affect the pharmacokinetics, biodistribution, intratumoral penetration and tumor bioavailability. On the other hand, tumor biology (blood flow, perfusion, permeability, interstitial fluid pressure and stroma content) and patient characteristics (age, gender, tumor type, tumor location, body composition and prior treatments) also have impact on drug delivery by nanoparticles. It is now believed that both nanoparticles and the tumor microenvironment have to be optimized or adjusted for optimal delivery. This review provides a comprehensive summary of how these nanoparticle and biological factors impact nanoparticle delivery to tumors, with discussion on how the tumor microenvironment can be adjusted and how patients can be stratified by imaging methods to receive the maximal benefit of nanomedicine. Perspectives and future directions are also provided. PMID:24075927

C-stop production by micro injection moulding

DEFF Research Database (Denmark)

Islam, Aminul

of engineering micro product which integrate many features like beam snapfit, annular snapfit, hinge connection, filter grid, house, lid etc in a single product. All the features are in micro dimensional scale and manufactured by single step of injection moulding. This presentation will cover industrial...

The biological effects of radium-224 injected into dogs

International Nuclear Information System (INIS)

Muggenburg, B.A.; Hahn, F.F.; Boecker, B.B.

1996-01-01

A life-span study was conducted in 128 beagle dogs to determine the biological effects of intravenously injected 224 Ra chloride. The 224 Ra chloride was prepared by the same method used for intravenous injections in humans who were treated for ankylosing spondylitis and tuberculosis. Thus the results obtained from dogs can be compared directly to the population of treated humans, both for the elucidation of the effect of exposure rate and for comparison with other radionuclides for which data for humans are unavailable. Using equal numbers of males and females, the dogs were injected with one of four levels of 224 Ra resulting in initial body burdens of approximately 13, 40, 120 or 350 kBq of 224 Ra kg -1 body mass. A control group of dogs was injected with diluent only. All dogs were divided further into three groups for which the amount of injected 224 Ra (half-life of 3.62 days) or diluent was given in a single injection or divided equally into 10 or 50 weekly injections. As a result of these three injection schedules, the accumulation of dose from the injected 224 Ra was distributed over approximately 1, 3 or 12 months. Each injection schedule included four different injection levels resulting in average absorbed α-particle doses to bone of 0.1, 0.3, 1 and 3 Gy, respectively. The primary early effect observed was a hematological dyscrasia in the dogs receiving either of the two highest injection levels. The effect was most severe in the dogs receiving a single injection of 224 Ra and resulted in the death of three dogs injected at the highest level. The late-occurring biological effects were tumors. Bone tumors were the most common followed by tumors in the nasal mucosa. 52 refs., 8 figs., 8 tabs

Selective injection locking of a multi-mode semiconductor laser to a multi-frequency reference beam

Science.gov (United States)

Pramod, Mysore Srinivas; Yang, Tao; Pandey, Kanhaiya; Giudici, Massimo; Wilkowski, David

2014-07-01

Injection locking is a well known and commonly used method for coherent light amplification. Usually injection locking is obtained on a single-mode laser injected by a single-frequency seeding beam. In this work we show that selective injection locking of a single-frequency may also be achieved on a multi-mode semiconductor laser injected by a multi-frequency seeding beam, if the slave laser provides sufficient frequency filtering. This selective injection locking condition depends critically on the frequency detuning between the free-running slave emission frequency and each injected frequency component. Stable selective injection locking to a set of three seeding components separated by 1.2 GHz is obtained. This system provides an amplification up to 37 dB of each component. This result suggests that, using distinct slave lasers for each frequency line, a set of mutually coherent high-power radiation modes can be tuned in the GHz frequency domain.

Quantitative image variables reflect the intratumoral pathologic heterogeneity of lung adenocarcinoma.

Science.gov (United States)

Choi, E-Ryung; Lee, Ho Yun; Jeong, Ji Yun; Choi, Yoon-La; Kim, Jhingook; Bae, Jungmin; Lee, Kyung Soo; Shim, Young Mog

2016-10-11

We aimed to compare quantitative radiomic parameters from dual-energy computed tomography (DECT) of lung adenocarcinoma and pathologic complexity.A total 89 tumors with clinical stage I/II lung adenocarcinoma were prospectively included. Fifty one radiomic features were assessed both from iodine images and non-contrast images of DECT datasets. Comprehensive histologic subtyping was evaluated with all surgically resected tumors. The degree of pathologic heterogeneity was assessed using pathologic index and the number of mixture histologic subtypes in a tumor. Radiomic parameters were correlated with pathologic index. Tumors were classified as three groups according to the number of mixture histologic subtypes and radiomic parameters were compared between the three groups.Tumor density and 50th through 97.5th percentile Hounsfield units (HU) of histogram on non-contrast images showed strong correlation with the pathologic heterogeneity. Radiomic parameters including 75th and 97.5th percentile HU of histogram, entropy, and inertia on 1-, 2- and 3 voxel distance on non-contrast images showed incremental changes while homogeneity showed detrimental change according to the number of mixture histologic subtypes (all Ps heterogeneity, which may help in the prediction of intratumoral heterogeneity of the whole tumor.

Numerical Simulation of Single-anode and Double-anode Magnetron Injection Guns for 127.5 GHz 1 MW Gyrotron

Science.gov (United States)

Singh, Udaybir; Kumar, Nitin; Kumar, Anil; Purohit, Laxmi Prasad; Sinha, Ashok Kumar

2011-07-01

This paper presents the design of two types of magnetron injection guns (MIG's) for 1 MW, 127.5 GHz gyrotron. TE24,8 mode has been chosen as the operating mode. In-house developed code MIGSYN has been used to estimate the initial gun parameters. The electron trajectory tracing program EGUN and in-house developed code MIGANS have been used to optimize the single-anode and the double-anode design for 80 kV, 40 A MIG. The parametric analysis of MIG has also been presented. The advantages and the disadvantages of each kind of configuration have been critically examined.

Platform for Quantitative Evaluation of Spatial Intratumoral Heterogeneity in Multiplexed Fluorescence Images.

Science.gov (United States)

Spagnolo, Daniel M; Al-Kofahi, Yousef; Zhu, Peihong; Lezon, Timothy R; Gough, Albert; Stern, Andrew M; Lee, Adrian V; Ginty, Fiona; Sarachan, Brion; Taylor, D Lansing; Chennubhotla, S Chakra

2017-11-01

We introduce THRIVE (Tumor Heterogeneity Research Interactive Visualization Environment), an open-source tool developed to assist cancer researchers in interactive hypothesis testing. The focus of this tool is to quantify spatial intratumoral heterogeneity (ITH), and the interactions between different cell phenotypes and noncellular constituents. Specifically, we foresee applications in phenotyping cells within tumor microenvironments, recognizing tumor boundaries, identifying degrees of immune infiltration and epithelial/stromal separation, and identification of heterotypic signaling networks underlying microdomains. The THRIVE platform provides an integrated workflow for analyzing whole-slide immunofluorescence images and tissue microarrays, including algorithms for segmentation, quantification, and heterogeneity analysis. THRIVE promotes flexible deployment, a maintainable code base using open-source libraries, and an extensible framework for customizing algorithms with ease. THRIVE was designed with highly multiplexed immunofluorescence images in mind, and, by providing a platform to efficiently analyze high-dimensional immunofluorescence signals, we hope to advance these data toward mainstream adoption in cancer research. Cancer Res; 77(21); e71-74. ©2017 AACR . ©2017 American Association for Cancer Research.

Complete Resolution of a Giant Pigment Epithelial Detachment Secondary to Exudative Age-Related Macular Degeneration after a Single Intravitreal Ranibizumab (Lucentis Injection: Results Documented by Optical Coherence Tomography

Directory of Open Access Journals (Sweden)

Eleni Loukianou

2010-12-01

Full Text Available Aim:To describe a patient with a giant pigment epithelial detachment (PED secondary to exudative age-related macular degeneration (ARMD successfully treated with a single intravitreal ranibizumab (Lucentis injection (0.5 mg/0.05 ml.Methods:An 89-year-old woman presented with a six-day history of reduced vision and distortion in the left eye. Best-corrected visual acuity in that eye was 6/15. Fundoscopy revealed a giant PED and exudates temporally to the fovea. Optical coherence tomography showed a PED associated with subretinal and intraretinal fluid. Fluorescein angiography confirmed the diagnosis of an occult choroidal neovascularization. Treatment with intravitreal injections of ranibizumab (Lucentis was recommended, although the increased risk of retinal pigment epithelium (RPE rip was mentioned. Results:Four weeks after the first intravitreal Lucentis injection, the visual acuity in the left eye improved to 6/7.5, with a significant improvement of the distortion and a complete anatomical resolution of the PED confirmed by optical coherence tomography. Conclusion:Giant PED secondary to exudative ARMD can be successfully treated with intravitreal ranibizumab, despite the increased risk of RPE rip. To our knowledge, this is the first case presenting with complete resolution of PED after a single ranibizumab injection.

EXPERIMENTAL TARGET INJECTION AND TRACKING SYSTEM CONSTRUCTION AND SINGLE SHOT TESTING

International Nuclear Information System (INIS)

PETZOLDT, R.W.; ALEXANDER, N.B.; DRAKE, T.J.; GOODIN, D.T; JONESTRACK, K; VERMILLION, B.A

2003-01-01

Targets must be injected into an IFE power plant at a rate of approximately 5 to 10 Hz. Targets must be tracked very accurately to allow driver beams to be aligned with defined points on the targets with accuracy ± 150 (micro)m for indirect drive and ± 20 (micro)m for direct drive. An experimental target injection and tracking system has been constructed at General Atomics. The injector system will be used as a tool for testing the survivability of various target designs and provide feedback to the target designers. Helium gas propels the targets down an 8 m gun barrel up to 400 m/s. Direct-drive targets are protected in the barrel by sabots that are spring loaded to separate into two halves after acceleration. A sabot deflector directs the sabot halves away from the target injection path. Targets will be optically tracked with laser beams and line-scan cameras. Target position and arrival time will be predicted in real time based on early target position measurements. The system installation will be described. System testing to overcome excessive projectile wear and debris in the gun barrel is presented

Single beam pass migmacell method and apparatus

International Nuclear Information System (INIS)

Maglich, B.C.; Nering, J.E.; Mazarakis, M.G.; Miller, R.A.

1976-01-01

The invention provides improvements in migmacell apparatus and method by dispensing with the need for metastable confinement of injected molecular ions for multiple precession periods. Injected molecular ions undergo a 'single pass' through the reaction volume. By preconditioning the injected beam such that it contains a population distribution of molecules in higher vibrational states than in the case of a normal distribution, injected molecules in the single pass exper-ience collisionless dissociation in the migmacell under magnetic influence, i.e., so-called Lorentz dissociation. Dissociationions then form atomic migma

Pseudorandom binary injection of levitons for electron quantum optics

Science.gov (United States)

Glattli, D. C.; Roulleau, P.

2018-03-01

The recent realization of single-electron sources lets us envision performing electron quantum optics experiments, where electrons can be viewed as flying qubits propagating in a ballistic conductor. To date, all electron sources operate in a periodic electron injection mode, leading to energy spectrum singularities in various physical observables which sometimes hide the bare nature of physical effects. To go beyond this, we propose a spread-spectrum approach where electron flying qubits are injected in a nonperiodic manner following a pseudorandom binary bit pattern. Extending the Floquet scattering theory approach from periodic to spread-spectrum drive, the shot noise of pseudorandom binary sequences of single-electron injection can be calculated for leviton and nonleviton sources. Our new approach allows us to disentangle the physics of the manipulated excitations from that of the injection protocol. In particular, the spread-spectrum approach is shown to provide better knowledge of electronic Hong-Ou-Mandel correlations and to clarify the nature of the pulse train coherence and the role of the dynamical orthogonality catastrophe for noninteger charge injection.

40 CFR 146.5 - Classification of injection wells.

Science.gov (United States)

2010-07-01

... establishment septic tank. The UIC requirements do not apply to single family residential septic system wells, nor to non-residential septic system wells which are used solely for the disposal of sanitary waste... whether what is injected is a radioactive waste or not. (9) Septic system wells used to inject the waste...

Do not rush to return to sports after trigger finger injection.

Science.gov (United States)

Oh, Jeehae; Jo, Leechan; Lee, Jong In

2015-04-01

Trigger finger, or digital stenosing tenosynovitis, is a common hand problem. A widely accepted treatment is steroid injection into the flexor tendon sheath. This can cause rupture of the flexor tendon. However, to the best of our knowledge, there is no report on tendon rupture after a single corticosteroid injection. Moreover, there are no guidelines for patients with tendinopathy who want to return to sports after corticosteroid injection. Clinicians who perform local steroid injections for tendinopathy treatment should be aware of the possible dangers of tendon rupture and should confirm that steroids are not administrated into the tendon. Patients should also be warned about returning to sports prematurely and should be encouraged to gradually resume sports after the injection to prevent further damage. Herein, we report an unusual case of flexor digitorum profundus rupture after a single corticosteroid injection in a 57-yr-old male golfer and we also present a review of the literature.

A PIV Study of Slotted Air Injection for Jet Noise Reduction

Science.gov (United States)

Henderson, Brenda S.; Wernet, Mark P.

2012-01-01

Results from acoustic and Particle Image Velocimetry (PIV) measurements are presented for single and dual-stream jets with fluidic injection on the core stream. The fluidic injection nozzles delivered air to the jet through slots on the interior of the nozzle at the nozzle trailing edge. The investigations include subsonic and supersonic jet conditions. Reductions in broadband shock noise and low frequency mixing noise were obtained with the introduction of fluidic injection on single stream jets. Fluidic injection was found to eliminate shock cells, increase jet mixing, and reduce turbulent kinetic energy levels near the end of the potential core. For dual-stream subsonic jets, the introduction of fluidic injection reduced low frequency noise in the peak jet noise direction and enhanced jet mixing. For dual-stream jets with supersonic fan streams and subsonic core streams, the introduction of fluidic injection in the core stream impacted the jet shock cell structure but had little effect on mixing between the core and fan streams.

Identification of Hürthle cell tumor by single-injection, double-phase scintigraphy with technetium-99m-sestamibi.

Science.gov (United States)

Vattimo, A; Bertelli, P; Cintorino, M; Burroni, L; Volterrani, D; Vella, A

1995-05-01

Early and late (double-phase) scintigraphy with 99mTc-MIBI was used in a comparative study of the scintigraphic aspects of Hürthle cell tumors and other thyroid tumors. Single-injection, dual-phase (15-30 min and 3-4 hr) thyroid scintigraphy with 99mTc-sestamibi (MIBI) was performed on 41 patients who displayed a cold nodule on previous 99mTc scintigraphy. Visual scoring of nodular uptake was done to compare thyroidal and background tracer uptake. In addition, the nodular-to-thyroid (N/T) uptake ratio in the early and late images and the washout rate from the nodule (WON) and thyroidal tissue (WOT) were measured. Cytologic results were obtained for all patients; histopathologic results were obtained for the 20 patients who had surgery. In eight patients (Group A), the nodule displayed intense and persistent uptake of MIBI (N/T = 1.77 +/- 0.46 and 3.20 +/- 1.37; WON = 17.2% +/- 6.3%; WOT = 24.6% +/- 7.5%); histopathology revealed Hürthle cell tumors (two carcinomas and three adenomas) in five surgical patients. In 15 patients (Group B), the nodule displayed intense uptake in the early image with fading activity in the late image (N/T = 1.45 +/- 0.54 and 0.84 +/- 0.30; WON = 30.0% +/- 7.3%; WOT = 24.5% +/- 6.8%); histopathology revealed a colloid nodule (n = 1), papillary carcinoma (n = 4) and follicular carcinoma (n = 5) in 10 surgical patients. In the remaining 18 patients (Group C), the nodule was cold and late images were not acquired. Histopathology revealed colloid nodules (n = 2) and follicular adenoma (n = 3) in five surgical patients. Single-injection, dual-phase MIBI scintigraphy of the thyroid can identify Hürthle cell tumors because these tumors have intense, persistent tracer uptake in contrast to other thyroid tumors.

An injection seeded single frequency Nd:YAG Q-switched laser with precisely controllable laser pulse firing time

Science.gov (United States)

Wu, Frank F.; Khizhnyak, Anatoliy; Markov, Vladimir

2010-02-01

We have realized a single frequency Q-switched Nd:YAG laser with precisely controllable lasing time and thus enabled synchronization of multi-laser systems. The use of injection seeding to the slave ring oscillator results in unidirectional Q-switched laser oscillation with suppression of bidirectional Q-switched oscillation that otherwise would be initiated from spontaneous emission if the seeding laser is not present. Under normal condition, the cavity is high in loss during the pumping period; then a Pockels cell opens the cavity to form the pulse build up, with a second Pockels cell to perform cavity dumping, generating the Q-switched pulse output with optimized characteristics. The two Pockels cells can be replaced by a single unit if an adjustable gated electrical pulse is applied to the Pockels cell in which the pulse front is used to open the cavity and the falling edge to dump the laser pulse. Proper selection of the pump parameters and Pockels-cell gating enables operation of the system in a mode in which the Q-switched pulse can be formed only under the seeding condition. The advantage of the realized regime is in stable laser operation with no need in adjustment of the seeded light wavelength and the mode of the cavity. It is found that the frequency of the Q-switched laser radiation matches well to the injected seeded laser mode. By using two-stage amplifiers, an output energy better than 300 mJ has been achieved in MOPA configuration without active control of the cavity length and with pulse width adjustability from several nanoseconds to 20 ns. The Q-switched oscillator operates not only at precisely controlled firing time but also can be tuned over wide range. This will enable multi-laser systems synchronization and frequency locking down each other if necessary.

A single exposure to cocaine during development elicits regionally-selective changes in basal basic Fibroblast Growth Factor (FGF-2) gene expression and alters the trophic response to a second injection.

Science.gov (United States)

Giannotti, Giuseppe; Caffino, Lucia; Malpighi, Chiara; Melfi, Simona; Racagni, Giorgio; Fumagalli, Fabio

2015-02-01

During adolescence, the brain is maturing and more sensitive to drugs of abuse that can influence its developmental trajectory. Recently, attention has been focused on basic fibroblast growth factor (FGF-2) given that its administration early in life enhances the acquisition of cocaine self-administration and sensitization at adulthood (Turner et al. (Pharmacol Biochem Behav 92:100-4, 2009), Clinton et al. (Pharmacol Biochem Behav103:6-17, 2012)). Additionally, we found that abstinence from adolescent cocaine exposure long lastingly dysregulates FGF-2 transcription (Giannotti et al. (Psychopharmacology (Berl) 225:553-60, 2013 ). The objectives of the study are to evaluate if (1) a single injection of cocaine (20 mg/kg) at postnatal day 35 alters FGF-2 messenger RNA (mRNA) levels and (2) the first injection influences the trophic response to a second injection (10 mg/kg) provided 24 h or 7 days later. We found regional differences in the FGF-2 expression pattern as either the first or the second injection of cocaine by themselves upregulated FGF-2 mRNA in the medial prefrontal cortex and nucleus accumbens while downregulating it in the hippocampus. The first injection influences the trophic response of the second. Of note, 24 h after the first injection, accumbal and hippocampal FGF-2 changes produced by cocaine in saline-pretreated rats were prevented in cocaine-pretreated rats. Conversely, in the medial prefrontal cortex and hippocampus 7 days after the first injection, the cocaine-induced FGF-2 changes were modified by the subsequent exposure to the psychostimulant. These findings show that a single cocaine injection is sufficient to produce enduring changes in the adolescent brain and indicate that early cocaine priming alters the mechanisms regulating the trophic response in a brain region-specific fashion.

Myocardial blood flow rate and capillary permeability for 99mTc-DTPA in patients with angiographically normal coronary arteries. Evaluation of the single-injection, residue detection method with intracoronary indicator bolus injection and the use of a mobile gamma camera

DEFF Research Database (Denmark)

Svendsen, Jesper Hastrup; Kelbaek, H; Efsen, F

1994-01-01

The aims of the present study were to quantitate myocardial perfusion and capillary permeability in the human heart by means of the single-injection, residue detection method using a mobile gamma camera. With this method, the intravascular mean transit time and the capillary extraction fraction (E...

Direct injection of high pressure gas : scaling properties of pulsed turbulent jets

NARCIS (Netherlands)

Baert, R.S.G.; Klaassen, A.; Doosje, E.

2010-01-01

Existing gasoline DI injection equipment has been modified to generate single hole pulsed gas jets. Injection experiments have been performed at combinations of 3 different pressure ratios (2 of which supercritical) respectively 3 different hole geometries (i.e. length to diameter ratios). Injection

External and Intraparticle Diffusion of Coumarin 102 with Surfactant in the ODS-silica Gel/water System by Single Microparticle Injection and Confocal Fluorescence Microspectroscopy.

Science.gov (United States)

Nakatani, Kiyoharu; Matsuta, Emi

2015-01-01

The release mechanism of coumarin 102 from a single ODS-silica gel microparticle into the water phase in the presence of Triton X-100 was investigated by confocal fluorescence microspectroscopy combined with the single microparticle injection technique. The release rate significantly depended on the Triton X-100 concentration in the water phase and was not limited by diffusion in the pores of the microparticle. The release rate constant was inversely proportional to the microparticle radius squared, indicating that the rate-determining step is the external diffusion between the microparticle and the water phase.

External and intraparticle diffusion of coumarin 102 with surfactant in the ODS-silica gel/water system by single microparticle injection and confocal fluorescence microspectroscopy

International Nuclear Information System (INIS)

Nakatani, Kiyoharu; Matsuta, Emi

2015-01-01

The release mechanism of coumarin 102 from a single ODS-silica gel microparticle into the water phase in the presence of Triton X-100 was investigated by confocal fluorescence microspectroscopy combined with the single microparticle injection technique. The release rate significantly depended on the Triton X-100 concentration in the water phase and was not limited by diffusion in the pores of the microparticle. The release rate constant was inversely proportional to the microparticle radius squared, indicating that the rate-determining step is the external diffusion between the microparticle and the water phase. (author)

Adaptation of a load-inject valve for a flow injection chemiluminescence system enabling dual-reagent injection enhances understanding of environmental Fenton chemistry

International Nuclear Information System (INIS)

Jones, Matthew R.; Nightingale, Philp D.; Turner, Suzanne M.; Liss, Peter S.

2013-01-01

Graphical abstract: -- Highlights: •Measurement of multiple components of Fenton chemistry; Fe(II) and H 2 O 2 . •Rapid, quasi-simultaneous analysis enables calculation of environmental kinetics. •Low, nano to pico-molar detection limits with dual analyte analysis. •Able to measure complex matrix samples – organically enriched seawater. •Low cost system with appreciable sensitivity compared to single analyte analysis. -- Abstract: Environmental Fenton chemistry has been poorly constrained within the marine environment at a multi-component level. A simple, unique, reconfiguration of a flow-injection analytical system combined with luminol chemiluminescence allows quasi-simultaneously the measurement, using a single load-inject valve and a single photon multiplier tube, of reduced iron, Fe(II), and hydrogen peroxide. The system enables rapid, every 22 s, measurements with good accuracy at environmentally relevant concentrations, less than 5% relative standard deviations on both a 5 nM Fe(II) standard and a 60 nM hydrogen peroxide standard. Limits of detection were as low as 40 pM Fe(II) and 100 pM hydrogen peroxide. The system showed excellent capability by measuring from within an organic rich seawater the photochemically induced production of Fe(II) and hydrogen peroxide and their subsequent cycling and Fenton like interactions

Improved healing of transected rabbit Achilles tendon after a single injection of cartilage-derived morphogenetic protein-2.

Science.gov (United States)

Forslund, Carina; Aspenberg, Per

2003-01-01

Achilles tendon ruptures in humans might be treated more efficiently with the help of a growth factor. Cartilage-derived morphogenetic protein-2 has been shown to induce formation of tendon-like tissue. Cartilage-derived morphogenetic protein-2 has a positive effect on mechanical parameters for tendon healing in a rabbit model with Achilles tendon transection. Controlled laboratory study. The right Achilles tendon of 40 rabbits was transected without tendon suture. Cartilage-derived morphogenetic protein-2 (10 micro g) or vehicle control (acetate buffer) was injected locally 2 hours postoperatively. All tendons were tested biomechanically at 8 and 14 days, and treated tendons were histologically and radiographically evaluated at 56 days. At 14 days, both failure load and stiffness of treated tendons were increased by 35%. The treated tendons had significantly larger callus size at 8 and 14 days. Histologic and radiographic examination showed no signs of ossification in the treated tendons after 56 days. A single injection of cartilage-derived morphogenetic protein-2 led to a stronger and stiffer tendon callus than that in the controls without inducing bone formation. Similar results from a larger animal model would suggest a possible future use of cartilage-derived morphogenetic protein-2 in the treatment of human Achilles tendon ruptures.

Internal dosimetry of radiopharmaceuticals derived of antitumor polypeptide isolated from venoms: Crotalus durissus terrifucus and Scorpaena plumieri

International Nuclear Information System (INIS)

Andrade, Henrique Martins de

2009-01-01

MBq for both intravenous injection and for the intratumoral injection. In tumor, the value was 3.28 mGy/370MBq for intravenous injection and 107.18 mGy/370MBq for intratumoral injection. For the administration of 131 I-SPGP values for the bone marrow were 1.34 mGy/370MBq for intravenous injection and 0.12 mGy/370MBq for intratumoral injection. In tumor, 256.29 mGy/370MBq for intravenous injection and 895.69 mGy/370MBq for intratumoral injection. The results suggest good radiation safety for both radiopharmaceuticals considering the values found for the bone marrow by both intratumoral and intravenous routes, in view of the importance of this body to generate blood cells. The results for the tumor intravenously indicate diagnostic applicability for both molecules. Through intratumoral, the values suggest the feasibility for use of 131 I-Crtx and of 131 I-SPGP as a therapeutic agent, given the persistence of radioactivity in the tumor site. Although 131 I-Crtx has proved to be more secure for applications in diagnosis, its potential for application in internal radiotherapy is lower than that of 131 I-SPGp. Both 131 I-Crtx and 131 I-SPGP, proved to be good prototypes for the development of radiopharmaceuticals. This study indicates that is necessary the synthesis of analogues with lower uptake in healthy organs and a higher tumor uptake, as well as pharmaceutical formulations, using nano technology, such as liposomes, nano-materials for controlled release of drugs. (author)

Internal dosimetry of radiopharmaceuticals derived of antitumor polypeptide isolated from venoms: Crotalus durissus terrifucus and Scorpaena plumieri;Dosimetria interna de radiofarmacos derivados de polipeptideos antitumorais isolados dos venenos de: Crotalus durissus terrificus e Scorpaena plumieri

Energy Technology Data Exchange (ETDEWEB)

Andrade, Henrique Martins de

2009-07-01

administration of {sup 131} I-Crtx was 0.01 mGy/370MBq for both intravenous injection and for the intratumoral injection. In tumor, the value was 3.28 mGy/370MBq for intravenous injection and 107.18 mGy/370MBq for intratumoral injection. For the administration of {sup 131}I-SPGP values for the bone marrow were 1.34 mGy/370MBq for intravenous injection and 0.12 mGy/370MBq for intratumoral injection. In tumor, 256.29 mGy/370MBq for intravenous injection and 895.69 mGy/370MBq for intratumoral injection. The results suggest good radiation safety for both radiopharmaceuticals considering the values found for the bone marrow by both intratumoral and intravenous routes, in view of the importance of this body to generate blood cells. The results for the tumor intravenously indicate diagnostic applicability for both molecules. Through intratumoral, the values suggest the feasibility for use of {sup 131}I-Crtx and of {sup 131}I-SPGP as a therapeutic agent, given the persistence of radioactivity in the tumor site. Although {sup 131}I-Crtx has proved to be more secure for applications in diagnosis, its potential for application in internal radiotherapy is lower than that of {sup 131}I-SPGp. Both {sup 131}I-Crtx and {sup 131}I-SPGP, proved to be good prototypes for the development of radiopharmaceuticals. This study indicates that is necessary the synthesis of analogues with lower uptake in healthy organs and a higher tumor uptake, as well as pharmaceutical formulations, using nano technology, such as liposomes, nano-materials for controlled release of drugs. (author)

Modelling the effect of injection pressure on heat release parameters and nitrogen oxides in direct injection diesel engines

Directory of Open Access Journals (Sweden)

Yüksek Levent

2014-01-01

Full Text Available Investigation and modelling the effect of injection pressure on heat release parameters and engine-out nitrogen oxides are the main aim of this study. A zero-dimensional and multi-zone cylinder model was developed for estimation of the effect of injection pressure rise on performance parameters of diesel engine. Double-Wiebe rate of heat release global model was used to describe fuel combustion. extended Zeldovich mechanism and partial equilibrium approach were used for modelling the formation of nitrogen oxides. Single cylinder, high pressure direct injection, electronically controlled, research engine bench was used for model calibration. 1000 and 1200 bars of fuel injection pressure were investigated while injection advance, injected fuel quantity and engine speed kept constant. The ignition delay of injected fuel reduced 0.4 crank angle with 1200 bars of injection pressure and similar effect observed in premixed combustion phase duration which reduced 0.2 crank angle. Rate of heat release of premixed combustion phase increased 1.75 % with 1200 bar injection pressure. Multi-zone cylinder model showed good agreement with experimental in-cylinder pressure data. Also it was seen that the NOx formation model greatly predicted the engine-out NOx emissions for both of the operation modes.

Systematic assessment of microneedle injection into the mouse cornea.

Science.gov (United States)

Matthaei, Mario; Meng, Huan; Bhutto, Imran; Xu, Qingguo; Boelke, Edwin; Hanes, Justin; Jun, Albert S

2012-06-20

Corneal intrastromal injection is an important mode of gene-vector application to subepithelial layers. In a mouse model, this procedure is substantially complicated by the reduced corneal dimensions. Furthermore, it may be difficult to estimate the corneal area reached by the volume of a single injection. This study aimed to investigate intrastromal injections into the mouse cornea using different microneedles and to quantify the effect of injecting varying volumes. A reproducible injection technique is described. Forty eyes of 20 129 Sv/J mice were tested. India ink was intrastromally injected using 30° beveled 33 G needles, tri-surface 25° beveled 35 G needles, or hand-pulled and 25° beveled glass needles. Each eye received a single injection of a volume of 1 or 2 μL. Corneoscleral buttons were fixed and flat mounted for computer-assisted quantification of the affected corneal area. Histological assessment was performed to investigate the intrastromal location of the injected dye. A mean corneal area of 5.0 ± 1.4 mm(2) (mean ± SD) and 7.7 ± 1.4 mm(2) was covered by intrastromal injections of 1 and 2 μL, respectively. The mean percentage of total corneal area reached ranged from 39% to 53% for 1 μL injections, and from 65% to 81% for 2 μL injections. Injections using the 33 G needles tended to provide the highest distribution area. Perforation rates were 8% for 30° beveled 33 G needles and 44% for tri-surface beveled 35 G needles. No perforation was observed with glass needle; however, intrastromal breakage of needle tips was noted in 25% of these cases. Intracorneal injection using a 30° beveled 33 G needle was safe and effective. The use of tri-surface beveled 35 G needles substantially increased the number of corneal perforations. Glass needles may break inside the corneal stroma. Injections of 1 μL and 2 μL resulted in an overall mean of 49% and 73% respectively of total corneal area involved.

Influence of heat exchange of reservoir with rocks on hot gas injection via a single well

Science.gov (United States)

Nikolaev, Vladimir E.; Ivanov, Gavril I.

2017-11-01

In the computational experiment the influence of heat exchange through top and bottom of the gas-bearing reservoir on the dynamics of temperature and pressure fields during hot gas injection via a single well is investigated. The experiment was carried out within the framework of modified mathematical model of non-isothermal real gas filtration, obtained from the energy and mass conservation laws and the Darcy law. The physical and caloric equations of state together with the Newton-Riemann law of heat exchange of gas reservoir with surrounding rocks, are used as closing relations. It is shown that the influence of the heat exchange with environment on temperature field of the gas-bearing reservoir is localized in a narrow zone near its top and bottom, though the size of this zone is increased with time.

Spin-injection into epitaxial graphene on silicon carbide

Science.gov (United States)

Konishi, Keita; Cui, Zhixin; Hiraki, Takahiro; Yoh, Kanji

2013-09-01

We have studied the spin-injection properties in epitaxial graphene on SiC. The ferromagnetic metal (FM) electrodes were composed of a tunnel barrier layer AlOx (14 Å) and a ferromagnetic Co (600 Å) layer. We have successfully observed the clear resistance peaks indicating spin-injection both in the "local" and "non-local" spin measurement set-ups at low temperatures. We estimate spin-injection rate of 1% based on "non-local" measurement and 1.6% based on local measurements. Spin-injection rate of multilayer graphene by mechanical exfoliation method was twice as high as single layer graphene on SiC based on "local" measurement.

Predictive Factors of Patients' and Their Partners' Sexual Function Improvement After Collagenase Clostridium Histolyticum Injection for Peyronie's Disease: Results From a Multi-Center Single-Arm Study.

Science.gov (United States)

Cocci, Andrea; Russo, Giorgio Ivan; Salonia, Andrea; Cito, Gianmartin; Regis, Federica; Polloni, Gaia; Giubilei, Gianluca; Cacciamani, Giovanni; Capece, Marco; Falcone, Marco; Greco, Isabella; Timpano, Massimiliano; Minervini, Andrea; Gacci, Mauro; Cai, Tommaso; Garaffa, Giulio; Giammusso, Bruno; Arcaniolo, Davide; Mirone, Vincenzo; Mondaini, Nicola

2018-05-01

Collagenase Clostridium histolyticum (CCH; Xiapex) injections represent the only licensed medical treatment for Peyronie's disease (PD). To evaluate the efficacy and safety of CCH injections in men with stable PD, using a modified treatment protocol and to assess partners' bother improvement in a large cohort of White-European sexually active heterosexual men treated in a single tertiary-referral center. All the 135 patients enrolled underwent a thorough assessment, which included history taking, physical examination, and pharmacologically induced artificial erection test (intra-cavernous injection) to assess the degree of penile curvature (PC) at baseline and after the completion of the treatment. Patients with calcified plaque and/or ventral curvature were excluded. All patients underwent a modified treatment protocol, which consisted of 3 intra-lesional injections of 0.9 mg of CCH performed at 4-week intervals at the point of maximum curvature. After each injection, patients were instructed to follow a strict routine involving daily penile stretching in the intervals between injections. International Index of Erectile Function (IIEF)-15, Global Assessment of PD, PD questionnaires (PDQ), and Female Sexual Function Index (FSFI) questionnaire were performed at baseline and at the end of treatment. Overall, 135 patients completed the study protocol. Before treatment, 18 (13.33%) partners showed a degree of sexual dysfunction. Baseline median IIEF-15, FSFI, and PDQ scores were, respectively, 59.0, 35.0, and 23.0. Overall, both IIEF-total and all domains significantly improved after treatment (all P < .01). A PC mean change of 19.07 (P = .00) was measured. At the univariate linear regression analysis, IIEF-15, IIEF-erectile function, IIEF-sexual desire, and IIEF-intercourse satisfaction were positively associated with FSFI (all P ≤ .03); conversely, PDQ-penile pain, PDQ-symptom bother, and post-treament penile curvature (P ≤ .04) were associated with a decreased

Multidose Botulinum Toxin A for Intralaryngeal Injection: A Cost Analysis.

Science.gov (United States)

Gilbert, Mark R; Young, VyVy N; Smith, Libby J; Rosen, Clark A

2018-01-04

Botulinum toxin A (BtxA) injection is the mainstay treatment for laryngeal dystonias. BtxA product labeling states that reconstituted toxin should be used within 4 hours on a single patient despite several studies that have demonstrated multidose BtxA to be safe and effective. Many insurance carriers mandate the use of an outside pharmacy which necessitates a single-use approach. This study compares the cost savings of multidose BtxA for laryngeal dystonia compared to single-use. This is a retrospective review and projected cost savings analysis. Records and billing information were reviewed for patients receiving BtxA for intralaryngeal injection at a single laryngology division in 2015. Inclusion criteria included CPT 64617 or J0585; exclusion criteria included CPT 64616. The price of BtxA 100 unit vial for calculation was $670. A total of 142 patients were seen for intralaryngeal BtxA injection resulting in 337 visits over 1 year. The average BtxA dose per visit was 2.86 units with an average of 3.06 procedure visits per year. The calculated cost of BtxA treatment using a single vial approach was found to be $2,050 per patient per year. If billed instead for $7/unit with 5 units wastage charge per visit, the yearly per patient charge is $168. Single vial-use of BtxA injection thus represents a 1,118% price increase versus multidose use. When estimated for yearly prevalence of spasmodic dysphonia, multidose BtxA use would save almost $100 million annually. Multidose botulinum toxin A application utilizing per unit billing is significantly less expensive than per single-use vial billing and would save the health-care system significant amount of money without any sacrifice in safety or effectiveness. Copyright © 2018. Published by Elsevier Inc.

76 FR 22610 - Implantation or Injectable Dosage Form New Animal Drugs; Enrofloxacin

Science.gov (United States)

2011-04-22

.... FDA-2011-N-0003] Implantation or Injectable Dosage Form New Animal Drugs; Enrofloxacin AGENCY: Food... the indications for use of enrofloxacin solution in cattle, as a single injection, for the treatment... supplement to NADA 141-068 for BAYTRIL 100 (enrofloxacin), an injectable solution. The supplemental NADA...

Pellet injection in WVIIA

International Nuclear Information System (INIS)

Renner, H.; Wuersohing, E.; Weller, A.; Jaeckel, H.; Hartfuss, H.; Hacker, H.; Ringler, H.; Buechl, K.

1986-01-01

The results of pellet injection experiments in the Wendelstein VII A stellarator are presented. The injector was a single shot pneumatic gun using deuterium pellets. Experiments were carried out in both ECRH and NI plasmas. Data is shown for plasma density, energy confinement, penetration depth and pellet ablation. Results are compared to a neutral gas shielding model

Embolic stroke associated with injection of buprenorphine tablets.

Science.gov (United States)

Lim, C C Tchoyoson; Lee, Sze Haur; Wong, Yee-Choon; Hui, Francis

2009-09-15

Drug users who crush, dissolve, and inject buprenorphine tablets parenterally may be at risk of severe thromboembolic complications or death. We describe patients with neurologic complications after injecting buprenorphine tablets. Brain MRI including diffusion-weighted imaging (DWI) in patients admitted to the neurologic department after injecting buprenorphine tablets were reviewed. Seven men had neurologic complications after buprenorphine tablet injection. In 5 patients, multiple small scattered hyperintense lesions were detected on DWI in the cortex, white matter, and basal ganglia of the cerebral hemisphere; one patient had a single small lesion. The side of MRI abnormality corresponded to the side of needle marks on the neck except in one patient who had bilateral injections. One patient, who denied injecting into the neck, had DWI abnormalities in the middle cerebral artery territory on one side and occlusion of the ipsilateral internal carotid artery. Buprenorphine tablets can be intentionally or inadvertently injected into the carotid artery, causing a characteristic appearance on diffusion-weighted imaging, consistent with embolic cerebral infarction.

Curcumin protects dopaminergic neurons against inflammation-mediated damage and improves motor dysfunction induced by single intranigral lipopolysaccharide injection.

Science.gov (United States)

Sharma, Neha; Sharma, Sheetal; Nehru, Bimla

2017-06-01

Various studies have indicated a lower incidence and prevalence of neurological conditions in people consuming curcumin. The ability of curcumin to target multiple cascades, simultaneously, could be held responsible for its neuroprotective effects. The present study was designed to investigate the potential of curcumin in minimizing microglia-mediated damage in lipopolysaccharide (LPS) induced model of PD. Altered microglial functions and increased inflammatory profile of the CNS have severe behavioral consequences. In the current investigation, a single injection of LPS (5 ug/5 µl PBS) was injected into the substantia nigra (SN) of rats, and curcumin [40 mg/kg b.wt (i.p.)] was administered daily for a period of 21 days. LPS triggered an inflammatory response characterized by glial activation [Iba-1 and glial fibrillary acidic protein (GFAP)] and pro-inflammatory cytokine production (TNF-α and IL-1β) leading to extensive dopaminergic loss and behavioral abnormality in rats. The behavioral observations, biochemical markers, quantification of dopamine and its metabolites (DOPAC and HVA) using HPLC followed by IHC of tyrosine hydroxylase (TH) were evaluated after 21 days of LPS injection. Curcumin supplementation prevented dopaminergic degeneration in LPS-treated animals by normalizing the altered levels of biomarkers. Also, a significant improvement in TH levels as well as behavioral parameters (actophotometer, rotarod, beam walking and grid walking tests) were seen in LPS injected rats. Curcumin shielded the dopaminergic neurons against LPS-induced inflammatory response, which was associated with suppression of glial activation (microglia and astrocytes) and transcription factor NF-κB as depicted from RT-PCR and EMSA assay. Curcumin also suppressed microglial NADPH oxidase activation as observed from NADPH oxidase activity. The results suggested that one of the important mechanisms by which curcumin mediates its protective effects in the LPS-induced PD

Intratumoral conversion of adrenal androgen precursors drives androgen receptor-activated cell growth in prostate cancer more potently than de novo steroidogenesis.

Science.gov (United States)

Kumagai, Jinpei; Hofland, Johannes; Erkens-Schulze, Sigrun; Dits, Natasja F J; Steenbergen, Jacobie; Jenster, Guido; Homma, Yukio; de Jong, Frank H; van Weerden, Wytske M

2013-11-01

Despite an initial response to hormonal therapy, patients with advanced prostate cancer (PC) almost always progress to castration-resistant disease (CRPC). Although serum testosterone (T) is reduced by androgen deprivation therapy, intratumoral T levels in CRPC are comparable to those in prostate tissue of eugonadal men. These levels could originate from intratumoral conversion of adrenal androgens and/or from de novo steroid synthesis. However, the relative contribution of de novo steroidogenesis to AR-driven cell growth is unknown. The relative contribution of androgen biosynthetic pathways to activate androgen receptor (AR)-regulated cell growth and expression of PSA, FKBP5, and TMPRSS2 was studied at physiologically relevant levels of adrenal androgen precursors and intermediates of de novo androgen biosynthesis in human prostate cancer cell lines, PC346C, VCaP, and LNCaP. In PC346C and VCaP, responses to pregnenolone and progesterone were absent or minimal, while large effects of adrenal androgen precursors were found. VCaP CRPC clones overexpressing CYP17A1 did not acquire an increased ability to use pregnenolone or progesterone to activate AR. In contrast, all precursors stimulated growth and gene expression in LNCaP cells, presumably resulting from the mutated AR in these cells. Our data indicate that at physiological levels of T precursors PC cells can generally convert adrenal androgens, while de novo steroidogenesis is not generally possible in PC cells and is not able to support AR transactivation and PC growth. © 2013 Wiley Periodicals, Inc.

Safety and efficacy of multiuse botulinum toxin vials for intralaryngeal injection.

Science.gov (United States)

Barrow, Emily M; Rosen, Clark A; Hapner, Edie R; Smith, Sarah; Hatcher, Jeanne L; Simpson, Blake; Johns, Michael M

2015-05-01

Centers for Disease Control and Prevention guidelines maintain that single-use vials cannot be used for multiple patients. Botox product labeling states that the reconstituted toxin should be used within 4 hours on a single patient based on concerns of reduced potency, contamination, and consequent infections. The purpose of this study was to determine the safety and efficacy of using single-use vials in a multidose fashion. Prospective study and cohort chart review. A multi-institutional three-part study was performed between May 2013 and October 2013: 1) a summation of subjects' recall of their past experiences (symptoms/response) with previous multidose Botox injections, 2) a prospective study of intralaryngeal injections, and 3) a chart review of injection responses in a subset of the cohort. Seven hundred forty-three subjects receiving 6,216 injections demonstrated zero infection-related complications on retrospective chart review. One hundred seventy-nine subjects recalled 24.0% overall adverse events, 10.6% redness, 7.3% pain and swelling at the injection site, and 0% fever. One hundred seventy-four subjects prospectively reported 12.6% overall adverse events. The self-reported efficacy rate of Botox injection was 96.6%. The low rates of adverse events following the use of Botox in a multipatient fashion are consistent with other percutaneous injections. No evidence of infection was found with multidose Botox use. Given the low incidence of side effects and high success rate, Botox can be used both safely and effectively in a multipatient fashion. 4 © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Identification and weighting factors influencing the establishment of a single minute exchange of dies in plastic injection industry using VIKOR and Shannon Entropy

Directory of Open Access Journals (Sweden)

Gholam Reza Hashemzadeh

2014-05-01

Full Text Available Single minute exchange of dies (SMED is one of the most important tools to achieve lean production system. The main idea of this system is to provide methods and to use creative and innovative solutions for continuous improvement. Due to the importance of this issue and its effect on reducing waste during the production process, this study presents a method to identify and to weight factors in the establishment of a single minute exchange of dies in 14 plastic injection factories. In this study, fourteen factories in injection industry were chosen and the factors influencing the implementation of single minute exchange of dies were identified. Following data collection, decision matrix was formed and the weight of each factor was determined by using Shannon Entropy. Then, in order to determine the readiness of factories, VIKOR method was used to rank companies. The results indicate priorities of the following factors in establishing SMED that include: Senior management support, technical capabilities, technical knowledge of staff and consultants, knowledge of mold design, manufacturing infrastructure, team work, combination of the project team work, benchmarking, training, clear understanding of project objectives, rewards and motivation, proper management expectation, project management, teamwork and organizational culture. Practical implications: Due to the factors, Top manager can make the best decision for implementing of SMED technique. This study develops factors influencing on SMED implementation based on Shannon and VIKOR methods for ranking parameters and plants.

Recombinant heat shock protein 70 in combination with radiotherapy as a source of tumor antigens to improve dendritic cell immunotherapy

Energy Technology Data Exchange (ETDEWEB)

Wang, Yu-Shan [Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan (China); Department of Animal Science, National Ilan University, Ilan, Taiwan (China); Liu, Shih-Jen [Vaccine Research and Development Center, National Health Research Institutes, Miaoli, Taiwan (China); Huang, Su-Chen; Chang, Chao-Chun; Huang, Yi-Chun; Fong, Weng-Lam; Chi, Mau-Shin [Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan (China); Chi, Kwan-Hwa, E-mail: m006565@ms.skh.org.tw [Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan (China); School of Medicine and Institute of Radiation Science and Image Research, National Yang-Ming Medical University, Taipei, Taiwan (China)

2012-10-29

Local radiotherapy (RT) plus intratumoral dendritic cell (DC) injection can mediate immunological response. We hypothesized that co-injection of exogenous recombinant heat shock protein 70 (rHsp70) in combination with RT-DC could be as effective as co-injection of HSP-peptide for evoking specific immune response. rHsp70-prostate-specific antigen (rHSP70C′-PSA) and α-fetoprotein (rHSP70C′-AFP) were used to compare specific response. Growth inhibition of the tumor and the systemic anti-tumor immune response were measured on CT26/PSA and CT26/AFP mice model. Intratumoral co-injection of rHsp70 and DC into the irradiated tumor site induced a more potent anti-tumor immune response than injection of DC alone. rHsp70 was as effective as rHsp70C′-PSA or rHsp70C′-AFP in inducing a tumor-specific cytotoxic T lymphocyte response or tumor growth delay. These results demonstrate that co-administration with rHsp70 and RT could be a simple and effective source of tumor antigens to achieve RT-DC immunotherapy protocol and easy to apply in clinical use.

Recombinant heat shock protein 70 in combination with radiotherapy as a source of tumor antigens to improve dendritic cell immunotherapy

International Nuclear Information System (INIS)

Wang, Yu-Shan; Liu, Shih-Jen; Huang, Su-Chen; Chang, Chao-Chun; Huang, Yi-Chun; Fong, Weng-Lam; Chi, Mau-Shin; Chi, Kwan-Hwa

2012-01-01

Local radiotherapy (RT) plus intratumoral dendritic cell (DC) injection can mediate immunological response. We hypothesized that co-injection of exogenous recombinant heat shock protein 70 (rHsp70) in combination with RT-DC could be as effective as co-injection of HSP-peptide for evoking specific immune response. rHsp70-prostate-specific antigen (rHSP70C′-PSA) and α-fetoprotein (rHSP70C′-AFP) were used to compare specific response. Growth inhibition of the tumor and the systemic anti-tumor immune response were measured on CT26/PSA and CT26/AFP mice model. Intratumoral co-injection of rHsp70 and DC into the irradiated tumor site induced a more potent anti-tumor immune response than injection of DC alone. rHsp70 was as effective as rHsp70C′-PSA or rHsp70C′-AFP in inducing a tumor-specific cytotoxic T lymphocyte response or tumor growth delay. These results demonstrate that co-administration with rHsp70 and RT could be a simple and effective source of tumor antigens to achieve RT-DC immunotherapy protocol and easy to apply in clinical use.

The Impact of Optimal Respiratory Gating and Image Noise on Evaluation of Intratumor Heterogeneity on 18F-FDG PET Imaging of Lung Cancer.

Science.gov (United States)

Grootjans, Willem; Tixier, Florent; van der Vos, Charlotte S; Vriens, Dennis; Le Rest, Catherine C; Bussink, Johan; Oyen, Wim J G; de Geus-Oei, Lioe-Fee; Visvikis, Dimitris; Visser, Eric P

2016-11-01

Accurate measurement of intratumor heterogeneity using parameters of texture on PET images is essential for precise characterization of cancer lesions. In this study, we investigated the influence of respiratory motion and varying noise levels on quantification of textural parameters in patients with lung cancer. We used an optimal-respiratory-gating algorithm on the list-mode data of 60 lung cancer patients who underwent 18 F-FDG PET. The images were reconstructed using a duty cycle of 35% (percentage of the total acquired PET data). In addition, nongated images of varying statistical quality (using 35% and 100% of the PET data) were reconstructed to investigate the effects of image noise. Several global image-derived indices and textural parameters (entropy, high-intensity emphasis, zone percentage, and dissimilarity) that have been associated with patient outcome were calculated. The clinical impact of optimal respiratory gating and image noise on assessment of intratumor heterogeneity was evaluated using Cox regression models, with overall survival as the outcome measure. The threshold for statistical significance was adjusted for multiple comparisons using Bonferroni correction. In the lower lung lobes, respiratory motion significantly affected quantification of intratumor heterogeneity for all textural parameters (P 0.007). The mean increase in entropy, dissimilarity, zone percentage, and high-intensity emphasis was 1.3% ± 1.5% (P = 0.02), 11.6% ± 11.8% (P = 0.006), 2.3% ± 2.2% (P = 0.002), and 16.8% ± 17.2% (P = 0.006), respectively. No significant differences were observed for lesions in the upper lung lobes (P > 0.007). Differences in the statistical quality of the PET images affected the textural parameters less than respiratory motion, with no significant difference observed. The median follow-up time was 35 mo (range, 7-39 mo). In multivariate analysis for overall survival, total lesion glycolysis and high-intensity emphasis were the two most

AN EXPERIMENTAL NOX REDUCTION POTENTIAL INVESTIGATION OF THE PARTIAL HCCI APPLICATION, ON A HIGH PRESSURE FUEL INJECTION EQUIPPED DIESEL ENGINE BY IMPLEMENTING FUMIGATION OF GASOLINE PORT INJECTION

OpenAIRE

ERGENÇ, Alp Tekin; YÜKSEK, Levent; ÖZENER, Orkun; IŞIN, Övün

2016-01-01

This work investigates the effects of partial HCCI (Homogeneous charge compression ignition) application on today's modern diesel engine tail pipe NOx emissions. Gasoline fumigation is supplied via a port fuel injection system located in the intake port of DI(Direct injection) diesel engine to maintain partial HCCI conditions and also diesel fuel injected directly into the combustion chamber before TDC(Top dead center). A single cylinder direct injection diesel research engine equipped w...

A single intracoronary injection of midkine reduces ischemia/reperfusion injury in swine hearts: a novel therapeutic approach for acute coronary syndrome

Directory of Open Access Journals (Sweden)

Hisaaki eIshiguro

2011-06-01

Full Text Available Several growth factors are effective for salvaging myocardium and limiting infarct size in experimental studies with small animals. Their benefit in large animals and feasibility in clinical practice remains to be elucidated. We investigate the cardioprotective effect of midkine (MK in swine subjected to ischemia/reperfusion (I/R. I/R was created in swine by left anterior descending coronary artery occlusion for 45 min using a percutaneous over-the-wire balloon catheter. MK protein was injected as a bolus through the catheter at the initiation of reperfusion (midkine injected group; MKT. Saline was injected in controls (CONT. Survival rate 24h after I/R was significantly higher in MKT than in CONT, whereas infarct size/area at risk was almost 5 times smaller. Echocardiography in MKT revealed a significantly higher percent wall thickening of the interventricular septum, a higher % fractional shortening and a lower E/e’ compared with CONT. LV catheterization in MKT showed a lower LVEDP, and a higher dP/dtmax compared with CONT. TUNEL-positive myocytes and CD45-positive cell infiltration in the peri-infarct area were significantly less in MKT than in CONT. Here, we showed that a single intracoronary injection of MK protein in swine hearts at the onset of reperfusion dramatically reduces infarct size and mortality and ameliorates systolic/diastolic LV function. This beneficial effect is associated with a reduction of apoptotic and inflammatory reactions. MK application during percutaneous coronary intervention may become a promising adjunctive therapy in acute coronary syndromes.

Single-well injection-withdrawal tests (SWIW). Investigation of evaluation aspects under heterogeneous crystalline bedrock conditions

International Nuclear Information System (INIS)

Nordqvist, Rune; Gustafsson, Erik

2004-08-01

Single-well injection-withdrawal (SWIW) tracer tests have been identified by SKB as an investigation method for solute transport properties in the forthcoming site investigations. A previous report presents a literature study as well as scoping calculations for SWIW tests in homogeneous crystalline bedrock environments. The present report comprises further scoping calculations under assumptions of heterogeneous bedrock conditions. Simple but plausible homogeneous evaluation models are tested on simulated SWIW tests in hypothetical heterogeneous two-dimensional fractures. The results from this study indicate that heterogeneity may cause effects of flow irreversibility when background hydraulic gradients are significant and the tested section is located in a dominating flow path. This implies that such conditions make it more difficult to interpret results from SWIW tests of longer duration with sorbing and/or diffusing tracers. Sorption and diffusion processes may be best studied when SWIW tests are conducted in borehole sections with low natural flow rates

Bolus injections of measured amounts of radioactivity

International Nuclear Information System (INIS)

Wesolowski, C.A.; Hogendoorn, P.; Vandierendonck, R.; Driedger, A.A.

1988-01-01

Many time-based radionuclide techniques, such as glomerular filtration rate measurement (GFR), require prompt intravenous delivery of and accurately measured tracer bolus with minimal residual tracer retention at the injection site. The quality assurance aspects of two antecubital vein, quantitative injection techniques were investigated. A flush bolus technique using a tuberculin syringe piggybacked onto a 10-ml saline flush was compared to a single blood pressure cuff injection technique. Scintillation camera data for each technique were compared for bolus duration in the abdominal aorta and for residual activity at the injection site at 5 min. Bolus times were measured as the FWHM of the gamma variate fit to the abdominal aortic regional time-activity curves. Relatively little focal activity was seen in the antecubital injection site following the flush bolus: marked residual activity was seen following the blood pressure cuff injections. The injection site/arm background ratios averaged 1.3 for the flush bolus and 30.1 for the cuff technique. Although both methods allowed accurate in vitro determination of administered radioactivity, only the tuberculin syringe flush bolus technique was acceptable for time-based quantitation because of its superior in vivo characteristics

Effects of curcumin-loaded PLGA nanoparticles on the RG2 rat glioma model.

Science.gov (United States)

Orunoğlu, Merdan; Kaffashi, Abbas; Pehlivan, Sibel Bozdağ; Şahin, Selma; Söylemezoğlu, Figen; Oğuz, Kader Karli; Mut, Melike

2017-09-01

Curcumin, the active ingredient of turmeric, has a remarkable antitumor activity against various cancers, including glioblastoma. However, it has poor absorption and low bioavailability; thus, to cross the blood-brain barrier and reach tumor tissue, it needs to be transferred to tumor site by special drug delivery systems, such as nanoparticles. We aimed to evaluate the antitumor activity of curcumin on glioblastoma tissue in the rat glioma-2 (RG2) tumor model when it is loaded on poly(lactic-co-glycolic acid)-1,2-distearoyl-glycerol-3-phospho-ethanolamine-N-[methoxy (polyethylene glycol)-2000] ammonium salt (PLGA-DSPE-PEG) hybrid nanoparticles. Glioblastoma was induced in 42 adult female Wistar rats (250-300g) by RG2 tumor model. The curcumin-loaded nanoparticles were injected by intravenous (n=6) or intratumoral route (n=6). There were five control groups, each containing six rats. First control group was not applied any treatment. The remaining four control groups were given empty nanoparticles or curcumin alone by intravenous or intratumoral route, respectively. The change in tumor volume was assessed by magnetic resonance imaging and histopathology before and 5days after drug injections. Tumor size decreased significantly after 5days of intratumoral injection of curcumin-loaded nanoparticle (from 66.6±44.6 to 34.9±21.7mm 3 , p=0.028), whereas it significantly increased in nontreated control group (from 33.9±21.3 to 123.7±41.1mm 3 , p=0.036) and did not significantly change in other groups (p>0.05 for all). In this in vivo experimental model, intratumoral administration of curcumin-loaded PLGA-DSPE-PEG hybrid nanoparticles was effective against glioblastoma. Curcumine-loaded nanoparticles may have potential application in chemotherapy of glioblastoma. Copyright © 2017 Elsevier B.V. All rights reserved.

Systematic assessment of microneedle injection into the mouse cornea

Directory of Open Access Journals (Sweden)

Matthaei Mario

2012-06-01

Full Text Available Abstract Background Corneal intrastromal injection is an important mode of gene-vector application to subepithelial layers. In a mouse model, this procedure is substantially complicated by the reduced corneal dimensions. Furthermore, it may be difficult to estimate the corneal area reached by the volume of a single injection. This study aimed to investigate intrastromal injections into the mouse cornea using different microneedles and to quantify the effect of injecting varying volumes. A reproducible injection technique is described. Methods Forty eyes of 20 129 Sv/J mice were tested. India ink was intrastromally injected using 30° beveled 33 G needles, tri-surface 25° beveled 35 G needles, or hand-pulled and 25° beveled glass needles. Each eye received a single injection of a volume of 1 or 2 μL. Corneoscleral buttons were fixed and flat mounted for computer-assisted quantification of the affected corneal area. Histological assessment was performed to investigate the intrastromal location of the injected dye. Results A mean corneal area of 5.0 ±1.4 mm2 (mean ± SD and 7.7 ±1.4 mm2 was covered by intrastromal injections of 1 and 2 μL, respectively. The mean percentage of total corneal area reached ranged from 39% to 53% for 1 μL injections, and from 65% to 81% for 2 μL injections. Injections using the 33 G needles tended to provide the highest distribution area. Perforation rates were 8% for 30° beveled 33 G needles and 44% for tri-surface beveled 35 G needles. No perforation was observed with glass needle; however, intrastromal breakage of needle tips was noted in 25% of these cases. Conclusions Intracorneal injection using a 30° beveled 33 G needle was safe and effective. The use of tri-surface beveled 35 G needles substantially increased the number of corneal perforations. Glass needles may break inside the corneal stroma. Injections of 1 μL and 2 μL resulted in an overall mean of 49% and 73% respectively

Spin Injection in Indium Arsenide

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Mark eJohnson

2015-08-01

Full Text Available In a two dimensional electron system (2DES, coherent spin precession of a ballistic spin polarized current, controlled by the Rashba spin orbit interaction, is a remarkable phenomenon that’s been observed only recently. Datta and Das predicted this precession would manifest as an oscillation in the source-drain conductance of the channel in a spin-injected field effect transistor (Spin FET. The indium arsenide single quantum well materials system has proven to be ideal for experimental confirmation. The 2DES carriers have high mobility, low sheet resistance, and high spin orbit interaction. Techniques for electrical injection and detection of spin polarized carriers were developed over the last two decades. Adapting the proposed Spin FET to the Johnson-Silsbee nonlocal geometry was a key to the first experimental demonstration of gate voltage controlled coherent spin precession. More recently, a new technique measured the oscillation as a function of channel length. This article gives an overview of the experimental phenomenology of the spin injection technique. We then review details of the application of the technique to InAs single quantum well (SQW devices. The effective magnetic field associated with Rashba spin-orbit coupling is described, and a heuristic model of coherent spin precession is presented. The two successful empirical demonstrations of the Datta Das conductance oscillation are then described and discussed.

Current Harmonics from Single-Phase Grid-Connected Inverters

DEFF Research Database (Denmark)

Yang, Yongheng; Zhou, Keliang; Blaabjerg, Frede

2016-01-01

Environmental conditions and operational modes may significantly impact the distortion level of the injected current from single-phase grid-connected inverter systems, such as photovoltaic (PV) inverters, which may operate in cloudy days with a maximum power point tracking, in a non-unity power...... factor, or in the low voltage ride through mode with reactive current injection. In this paper, the mechanism of the harmonic current injection from grid-connected single-phase inverter systems is thus explored, and the analysis is conducted on single-phase PV systems. In particular, the analysis...... is focused on the impacts of the power factor and the feed-in grid current level on the quality of the feed-in grid current from single-phase inverters. As a consequence, an internal model principle based high performance current control solution is tailor-made and developed for single-phase grid-connected...

5.7  W cw single-frequency laser at 671  nm by single-pass second harmonic generation of a 17.2  W injection-locked 1342  nm Nd : YVO4 ring laser using periodically poled MgO : LiNbO3.

Science.gov (United States)

Koch, Peter; Ruebel, Felix; Bartschke, Juergen; L'huillier, Johannes A

2015-11-20

We demonstrate a continuous wave single-frequency laser at 671.1 nm based on a high-power 888 nm pumped Nd:YVO4 ring laser at 1342.2 nm. Unidirectional operation of the fundamental ring laser is achieved with the injection-locking technique. A Nd:YVO4 microchip laser serves as the injecting seed source, providing a tunable single-frequency power of up to 40 mW. The ring laser emits a single-frequency power of 17.2 W with a Gaussian beam profile and a beam propagation factor of M2beam profile and a beam propagation factor of M2lasers. This work opens possibilities in cold atoms experiments with lithium, allowing the use of larger ensembles in magneto-optical traps or higher diffraction orders in atomic beam interferometers.

Reduction of waveform distortion in grid-injection current from single-phase utility interactive PV-inverter

International Nuclear Information System (INIS)

Hamid, Muhammad Imran; Jusoh, Awang

2014-01-01

Highlights: • A reduction scheme for harmonics from utility interactive PV-inverter is proposed. • Single-phase conditioner with 3-phase expandability structure is used. • The single-phase conditioner in 3-phase structure work independently. • The scheme works effectively within overall operation range of the PV-inverter. • Conditioner in the scheme also improves the PV-inverter and plant’s utility factor. - Abstract: As the natural behavior of energy source and design characteristic, the current generated by a grid-interactive PV-inverter may contain harmonics. This distortion component will be carried on from the PV-inverter during injection power into the grid. Excessive harmonics in a grid will lead to a variety of power quality problems. This paper presents a distortion reduction scheme, utilizing a fed forward single-phase, generation-side power conditioner with a structure that can be expanded for use in a three-phase system and can work independently under imbalanced condition. Conditioner is placed in parallel with the photovoltaic plant and it functions to compensate the plant’s output current distortion, so that the total current flow to the grid is sinusoidal. This method also includes the implementation of a simpler control system for the conditioner, which consists of a combination of distortion current extraction, synchronization and a current control system, and realized through a TMS320F28335: a 150 MHz floating point DSP controller. Testing of the conditioner prototype, which was conducted on a real operation of a PV plant, showed that the scheme worked effectively within the overall operation range of the PV plant. This paper also discusses the potential of utility factor improvement of the PV-inverter and plant due to implementation of conditioner in the scheme

Performance and combustion analysis of Mahua biodiesel on a single cylinder compression ignition engine using electronic fuel injection system

Directory of Open Access Journals (Sweden)

Gunasekaran Anandkumar

2016-01-01

Full Text Available In this investigation, experiment is carried out on a 1500 rpm constant speed single cylinder Diesel engine. The test is carried out with Neat diesel, neat biodiesel, and blend B20. The engine considered was run with electronic fuel injection system supported by common rail direct injection to obtain high atomization and effective air utilization inside the combustion chamber. The performance of the engine in terms of break thermal efficiency and brake specific energy consumption was found and compared. The B20 blend shows 1.11% decrease in break thermal efficiency and 3.35% increase in brake specific energy consumption than diesel. The combustion characteristics found are in-cylinder pressure, rate of pressure rise, and heat release rate and compared for peak pressure load to understand the nature of combustion process. For each fuel test run, the maximum peak pressure is observed at part load condition. The rate of change of pressure and heat release rate of diesel is high compared to pure biodiesel and B20 blend. The diffusion combustion is observed to be predominant in case of B100 than B20 and Neat diesel.

Dual fuel injection piggyback controller system

Science.gov (United States)

Muji, Siti Zarina Mohd.; Hassanal, Muhammad Amirul Hafeez; Lee, Chua King; Fawzi, Mas; Zulkifli, Fathul Hakim

2017-09-01

Dual-fuel injection is an effort to reduce the dependency on diesel and gasoline fuel. Generally, there are two approaches to implement the dual-fuel injection in car system. The first approach is changing the whole injector of the car engine, the consequence is excessive high cost. Alternatively, it also can be achieved by manipulating the system's control signal especially the Electronic Control Unit (ECU) signal. Hence, the study focuses to develop a dual injection timing controller system that likely adopted to control injection time and quantity of compressed natural gas (CNG) and diesel fuel. In this system, Raspberry Pi 3 reacts as main controller unit to receive ECU signal, analyze it and then manipulate its duty cycle to be fed into the Electronic Driver Unit (EDU). The manipulation has changed the duty cycle to two pulses instead of single pulse. A particular pulse mainly used to control injection of diesel fuel and another pulse controls injection of Compressed Natural Gas (CNG). The test indicated promising results that the system can be implemented in the car as piggyback system. This article, which was originally published online on 14 September 2017, contained an error in the acknowledgment section. The corrected acknowledgment appears in the Corrigendum attached to the pdf.

Injection of demineralized bone matrix with bone marrow concentrate improves healing in unicameral bone cyst.

Science.gov (United States)

Di Bella, Claudia; Dozza, Barbara; Frisoni, Tommaso; Cevolani, Luca; Donati, Davide

2010-11-01

Unicameral bone cysts are benign lesions that usually spontaneously regress with skeletal maturity; however, the high risk of pathologic fractures often justifies treatment that could reinforce a weakened bone cortex. Various treatments have been proposed but there is no consensus regarding the best procedure. We compared the healing rates and failures of two methods of cure based on multiple injections of corticosteroid or a single injection of demineralized bone matrix (DBM) in association with bone marrow concentrate (BMC). We retrospectively reviewed 184 patients who had one of the two treatments for unicameral bone cysts with cortical erosion. Clinical records were reviewed for treatment failures and radiographs for healing in all patients. The minimum followup was 12 months for the Steroids Group (mean, 48 months; range, 12-120 months) and 12 months for the DBM + BMC Group (mean, 20 months; range, 12-28 months). After one treatment we observed a lower healing rate of cysts treated with multiple injections of steroids compared with the healing after the first injection of DBM + BMC (21% versus 58%, respectively). At last followup, 38% healed with steroids and 71% with DBM + BMC. The rate of failure after one steroid injection was higher than after a single injection of BDM + BMC (63% versus 24%, respectively). We observed no difference in fracture rates after treatment between the two groups. A single injection of DBM added with autologous bone marrow concentrate appears to provide a higher healing rate with a lower number of failures compared with a single injection of steroids.

Peripheral Leukocytosis Is Inversely Correlated with Intratumoral CD8+ T-Cell Infiltration and Associated with Worse Outcome after Chemoradiotherapy in Anal Cancer

Directory of Open Access Journals (Sweden)

Daniel Martin

2017-09-01

Full Text Available Peripheral blood leukocytosis has been implicated in promoting tumor progression leading to worse survival, but the mechanisms behind this phenomenon remain unexplored. Here, we examined the prognostic role of pretreatment white blood cell (WBC count and clinicopathologic parameters in the context of CD8+ tumor-infiltrating lymphocytes (TIL and myeloperoxidase+ tumor-associated neutrophils (TANs in patients with anal squamous cell carcinoma (ASCC treated with definitive chemoradiotherapy (CRT. After a median follow-up of 26 months, leukocytosis correlated with advanced T-stage (p < 0.001 and N-stage (p < 0.001, and predicted for worse distant-metastasis-free survival (p = 0.006, disease-free-survival (DFS, p = 0.029, and overall survival (p = 0.013. Importantly, leukocytosis was associated with a lower intraepithelial CD8+ TIL density (p = 0.014, whereas low CD8+ TIL expression in the intraepithelial compartment was associated with worse DFS (p = 0.028. Additionally, high TAN expression in the peritumoral compartment was associated with a significantly lower density of CD8+ TIL (p = 0.039, albeit, TAN expression lacked prognostic value. In conclusion, leukocytosis constitutes an important prognostic marker in ASCC patients treated with CRT. In conjunction with intratumoral TIL and TAN, these data provide for the first time important insight on the correlation of peripheral blood leukocytosis with the intratumoral immune contexture and could be relevant for future patient stratification using immunotherapies in ASCC.

Effect of radiation combined with p53 gene therapy and endostatin on mouse prostate cancer

International Nuclear Information System (INIS)

Zhang Min; Ren Jun; Xu Bo; Gao Xianshu; He Zhisong; He Xiaoming; Zhang Ming; Liu Chaoxing; He Xinyong; Cao Guangming; Zhang Shaolong

2009-01-01

Objective: To test the hypothesis that p53 gene therapy combined with endostatin can enhance tumor response to radiation therapy of RM-1 mouse xenograft prostate cancer and to investigate its mechanism. Methods: A mouse prostate cancer model was established. Then mice with xenograft tumor were randomly divided into group A (control), B (radiation), C (radiation and rAdp53), D (radiation and rh-endostatin) and E (radiation and rAdp53 and rhendostatin). On day 1, rAdp53 was injected intra-tumorously with 1 x 10 10 vp per animal to group C and E. From day 1 to 14, rh-endostatin was given 15 mg/kg intraperitoneally daily to group D and E. On day 4 single fraction of 15 Gy was given to tumors in groups B, C, D and E. Normal saline was injected intra-tumorously or intraperitoneaUy accordingly as control. No treatment was done to group A. Tumor volume was measured daily. Samples were collected on Days 5, 10 and 15. Ki67, CD31, p53 and VEGF were detected by means of immunohistochemistry. Results: (1) Radiation alone, radiation combined with intra-tumorous injection of Adp53 and/or intraperitoneal injection of rhendostatin resulted in tumor growth arrest of RM-1 cells in vivo (P = 0.000). Radiation combined with both rAdp53 and rhendostatin was the most effective treatment (P < 0.05). (2) All the four treatment groups had a decreased expression of mutant type P53 (P = 0.000). The expression of Ki67 in groups B and C were equal (P 0.05) and increasing (P = 0.000), respectively. Group D had a up-down-up curve (P < 0.05), but group E had a up-down one. On day 5 the expresion of VEGF in group E was the lowest (P < 0.05). An increased expression of MVD compared with the control was shown, and MVD in groups C, D and E were always higher than that in the control (P < 0.05). Conclusions: The limitation of radiotherapy could be overcome by combination with beth p53 gene therapy and endostatin on the growth of mouse prostate cancer cell. Radiation, rAdp53 and endostatin have their

Tritium retention in the femoral bone marrow and spleens of mice receiving single intravenous injections of tritiated water and tritiated thymidine

International Nuclear Information System (INIS)

Joshima, Hisamasa; Matsushita, Satoru; Fukutsu, Kumiko; Kashima, Masatoshi

1987-01-01

To derive parameters necessary for evaluating the possible hazards of tritium, retention of tritium in total and TCA-insoluble fractions of the femoral marrow and spleen of mice were observed after single intravenous injections of tritiated water and tritiated thymidine. Retention curves of tritium in TCA-insoluble fractions of the femoral marrow and spleen were resolved fairly well into two exponential components. After injecting tritiated thymidine, most of the activity was detected in the TCA-insoluble fraction. Tritium in this fraction decreased with half-times of 2.2 days in the femoral marrow and 3.6 days in the spleen as the first component, and 23.9 days and 30.5 days, respectively, as the second component. After tritiated water injections, the tritium incorporated into the TCA-insoluble fraction was quite small. Most of the activity was considered to be in the TCA-soluble fraction. Tritium in this fraction was estimated to decrease with half-times of 2.6 days in the femoral marrow and 2.3 days in the spleen as the first component, and 8.0 days and 8.2 days, respectively, as the second component. It is concluded that the retention curves of tritium in the bone marrow are similar to those in the spleen for tritiated water, but not for tritiated thymidine. (author)

Diagnosing the PEP-II Injection System

Energy Technology Data Exchange (ETDEWEB)

Decker, F.-J.; Donald, M.H.; Iverson, R.H.; Kulikov, A.; Pappas, G.C.; Weaver, M.; /SLAC

2005-05-09

The injection of beam into the PEP-II B-Factory, especially into the High Energy Ring (HER) has some challenges. A high background level in the BaBar detector has for a while inhibited us from trickling charge into the HER similar to the Low Energy Ring (LER). Analyzing the injection system has revealed many issues which could be improved. The injection bump between two kickers was not closed, mainly because the phase advance wasn't exactly 180{sup o} and the two kicker strengths were not balanced. Additionally we found reflections which kick the stored beam after the main kick and cause the average luminosity to drop about 3% for a 10 Hz injection rate. The strength of the overall kick is nearly twice as high as the design, indicating a much bigger effective septum thickness. Compared with single beam the background is worse when the HER beam is colliding with the LER beam. This hints that the beam-beam force and the observed vertical blow-up in the HER pushes the beam and especially the injected beam further out to the edge of the dynamic aperture or beyond.

Diagnosing the PEP-II Injection System

International Nuclear Information System (INIS)

Decker, F.-J.; Donald, M.H.; Iverson, R.H.; Kulikov, A.; Pappas, G.C.; Weaver, M.; SLAC

2005-01-01

The injection of beam into the PEP-II B-Factory, especially into the High Energy Ring (HER) has some challenges. A high background level in the BaBar detector has for a while inhibited us from trickling charge into the HER similar to the Low Energy Ring (LER). Analyzing the injection system has revealed many issues which could be improved. The injection bump between two kickers was not closed, mainly because the phase advance wasn't exactly 180 o and the two kicker strengths were not balanced. Additionally we found reflections which kick the stored beam after the main kick and cause the average luminosity to drop about 3% for a 10 Hz injection rate. The strength of the overall kick is nearly twice as high as the design, indicating a much bigger effective septum thickness. Compared with single beam the background is worse when the HER beam is colliding with the LER beam. This hints that the beam-beam force and the observed vertical blow-up in the HER pushes the beam and especially the injected beam further out to the edge of the dynamic aperture or beyond

Contrast-enhanced Harmonic power Doppler ultrasonography: Improved depiction of vascularity and characterization of flow pattern in hepatocellular carcinoma

International Nuclear Information System (INIS)

Baek, Hyung Chul; Yoon, Kwon Ha; Kim, Chang Guhn; Park, Ki Han; Won, Jong Jin

2000-01-01

To evaluate the value of contrast-enhanced harmonic power Doppler ultrasonography (PDUS) in depiction and characterization of tumoral vascularity in hepatocellular carcinoma (HCC). Thirty-three patients with HCC were prospectively evaluated with harmonic PDUS before and after injection of the contrast agent SH U 508A (2.5g, 300 mg/ml ). Unenhanced and serial dynamic scans at 15, 30, 45, 60, 90, 120, 150, 180, 240, 300 seconds after injection of contrast agents were obtained using a tissue harmonic technique with power Doppler imaging. The tumoral vascularity was expressed as percentage of power Doppler area, which was measured quantitatively by a computerized program (Ultrasonic Imaging Tool; Soongsil University, Seoul, Korea). The grade (0, no signal; 1, less than 5%; 2, 5-25%; 3, more than 25%) and flow pattern (intratumoral, detour, basket, and mixed) of tumoral vascularity were analyzed. Peak time of contrast-enhancement was measured on each tumor. After injection of contrast agent, tumoral flow signals increased in all lesions (100%). At unenhanced harmonic PDUS, flow signals were detected in 17 HCCs (52%); 15 tumors (46%) demonstrated grade 1 vascularity; and two (6%), grade 2. At contrast-enhanced harmonic PDUS, all tumors were detected vascularity; five (15%) were grade 1; eight (24%), grade 2; and 20 (61%), grade 3. Flow patterns were demonstated as follows at unenhanced harmonic PDUS; intratumoral pattern in 13 tumors (76%), detour in 2 (12%), and basket in 2 (12%). After injection of contrast agent, intratumoral pattern in 7 tumors (21%), detour 0 (0%), basket in 3 (9%) and mixed in 23 (70%) were demonstrated. Peak time of enhancement after injection of contrast agent was 30- 90 seconds in majority of the patients. Contrast-enhanced harmonic PDUS would be valuable in depiction of vascularity and characterization of flow pattern in HCC.

Contrast-enhanced Harmonic power Doppler ultrasonography: Improved depiction of vascularity and characterization of flow pattern in hepatocellular carcinoma

Energy Technology Data Exchange (ETDEWEB)

Baek, Hyung Chul; Yoon, Kwon Ha; Kim, Chang Guhn; Park, Ki Han; Won, Jong Jin [Wonkwang University School of Medicine, Iksa (Korea, Republic of)

2000-12-15

To evaluate the value of contrast-enhanced harmonic power Doppler ultrasonography (PDUS) in depiction and characterization of tumoral vascularity in hepatocellular carcinoma (HCC). Thirty-three patients with HCC were prospectively evaluated with harmonic PDUS before and after injection of the contrast agent SH U 508A (2.5g, 300 mg/ml ). Unenhanced and serial dynamic scans at 15, 30, 45, 60, 90, 120, 150, 180, 240, 300 seconds after injection of contrast agents were obtained using a tissue harmonic technique with power Doppler imaging. The tumoral vascularity was expressed as percentage of power Doppler area, which was measured quantitatively by a computerized program (Ultrasonic Imaging Tool; Soongsil University, Seoul, Korea). The grade (0, no signal; 1, less than 5%; 2, 5-25%; 3, more than 25%) and flow pattern (intratumoral, detour, basket, and mixed) of tumoral vascularity were analyzed. Peak time of contrast-enhancement was measured on each tumor. After injection of contrast agent, tumoral flow signals increased in all lesions (100%). At unenhanced harmonic PDUS, flow signals were detected in 17 HCCs (52%); 15 tumors (46%) demonstrated grade 1 vascularity; and two (6%), grade 2. At contrast-enhanced harmonic PDUS, all tumors were detected vascularity; five (15%) were grade 1; eight (24%), grade 2; and 20 (61%), grade 3. Flow patterns were demonstated as follows at unenhanced harmonic PDUS; intratumoral pattern in 13 tumors (76%), detour in 2 (12%), and basket in 2 (12%). After injection of contrast agent, intratumoral pattern in 7 tumors (21%), detour 0 (0%), basket in 3 (9%) and mixed in 23 (70%) were demonstrated. Peak time of enhancement after injection of contrast agent was 30- 90 seconds in majority of the patients. Contrast-enhanced harmonic PDUS would be valuable in depiction of vascularity and characterization of flow pattern in HCC.

Single-cell quantitative HER2 measurement identifies heterogeneity and distinct subgroups within traditionally defined HER2-positive patients.

Science.gov (United States)

Onsum, Matthew D; Geretti, Elena; Paragas, Violette; Kudla, Arthur J; Moulis, Sharon P; Luus, Lia; Wickham, Thomas J; McDonagh, Charlotte F; MacBeath, Gavin; Hendriks, Bart S

2013-11-01

Human epidermal growth factor receptor 2 (HER2) is an important biomarker for breast and gastric cancer prognosis and patient treatment decisions. HER2 positivity, as defined by IHC or fluorescent in situ hybridization testing, remains an imprecise predictor of patient response to HER2-targeted therapies. Challenges to correct HER2 assessment and patient stratification include intratumoral heterogeneity, lack of quantitative and/or objective assays, and differences between measuring HER2 amplification at the protein versus gene level. We developed a novel immunofluorescence method for quantitation of HER2 protein expression at the single-cell level on FFPE patient samples. Our assay uses automated image analysis to identify and classify tumor versus non-tumor cells, as well as quantitate the HER2 staining for each tumor cell. The HER2 staining level is converted to HER2 protein expression using a standard cell pellet array stained in parallel with the tissue sample. This approach allows assessment of HER2 expression and heterogeneity within a tissue section at the single-cell level. By using this assay, we identified distinct subgroups of HER2 heterogeneity within traditional definitions of HER2 positivity in both breast and gastric cancers. Quantitative assessment of intratumoral HER2 heterogeneity may offer an opportunity to improve the identification of patients likely to respond to HER2-targeted therapies. The broad applicability of the assay was demonstrated by measuring HER2 expression profiles on multiple tumor types, and on normal and diseased heart tissues. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Monoclonal origin of peritoneal implants and lymph node deposits in serous borderline ovarian tumors (s-BOT) with high intratumoral homogeneity.

Science.gov (United States)

Horn, Lars-Christian; Höhn, Anne K; Einenkel, Jens; Siebolts, Udo

2014-11-01

Molecular studies have shown that the most prevalent mutations in serous ovarian borderline tumors (s-BOT) are BRAF and/or KRAS alterations. About one third of s-BOT represent peritoneal implants and/or lymph node involvement. These extraovarian deposits may be monoclonal or polyclonal in origin. To test both the hypotheses, mutational analyses using pyrosequencing for BRAF codon 600 and KRAS codon 12/13 and 61 of microdissected tissue was performed in 15 s-BOT and their invasive and noninvasive peritoneal implants. Two to 6 implants from different peritoneal sites were examined in 13 cases. Lymph node deposits were available for the analysis in 3 cases. Six s-BOT showed mutation in exon 2 codon 12 of the KRAS proto-oncogen. Five additional cases showed BRAF p.V600E mutation representing an overall mutation rate of 73.3%. Multiple (2-6) peritoneal implants were analyzed after microdissection in 13 of 15 cases. All showed identical mutational results when compared with the ovarian site of the disease. All lymph node deposits, including those with multiple deposits in different nodes, showed identical results, suggesting high intratumoral mutational homogeneity. The evidence presented in this study and the majority of data reported in the literature support the hypothesis that s-BOT with their peritoneal implants and lymph node deposits show identical mutational status of BRAF and KRAS suggesting a monoclonal rather than a polyclonal disease regarding these both tested genetic loci. In addition, a high intratumoral genetic homogeneity can be suggested. In conclusion, the results of the present study support the monoclonal origin of s-BOT and their peritoneal implants and lymph node deposits.

Effect of the Ethanol Injection Moment During Compression Stroke on the Combustion of Ethanol - Diesel Dual Direct Injection Engine

Science.gov (United States)

Liang, Yu; Zhou, Liying; Huang, Haomin; Xu, Mingfei; Guo, Mei; Chen, Xin

2018-01-01

A set of GDI system is installed on a F188 single-cylinder, air-cooled and direct injection diesel engine, which is used for ethanol injection, with the injection time controlled by the crank angle signal collected by AVL angle encoder. The injection of ethanol amounts to half of the thermal equivalent of an original diesel fuel. A 3D combustion model is established for the ethanol - diesel dual direct injection engine. Diesel was injected from the original fuel injection system, with a fuel supply advance angle of 20°CA. The ethanol was injected into the cylinder during compression process. Diesel injection began after the completion of ethanol injection. Ethanol injection starting point of 240°CA, 260°CA, 280°CA, 300°CA and 319.4°CA were simulated and analyzed. Due to the different timing of ethanol injection, the ignition of the ethanol mixture when diesel fires, results in non-uniform ignition distribution and flame propagation rate, since the distribution and concentration gradients of the ethanol mixture in the cylinder are different, thus affecting the combustion process. The results show that, when ethanol is injected at 319.4°CA, the combustion heat release rate and the pressure rise rate during the initial stage are the highest. Also, the maximum combustion pressure, with a relatively advance phase, is the highest. In case of later initial ethanol injection, the average temperature in the cylinder during the initial combustion period will have a faster rise. In case of initial injection at 319.4°CA, the average temperature in the cylinder is the highest, followed by 240°CA ethanol injection. In the post-combustion stage, the earlier ethanol injection will result in higher average temperature in the cylinder and more complete fuel combustion. The injection of ethanol at 319.4°CA produces earlier and highest NOX emissions.

Cylinder Pressure-based Combustion Control with Multi-pulse Fuel Injection

NARCIS (Netherlands)

Luo, X.; Wang, S.; Jager, B. de; Willems, F.P.T.

2015-01-01

With an increased number of fuel injection pulses, the control problem in diesel engines becomes complex. Consisting of multiple single-input single-output (SISO) controllers, the conventional control strategy shows unsatisfactory dynamic performance in tracking combustion load and phase reference

Correlation of intra-tumor 18F-FDG uptake heterogeneity indices with perfusion CT derived parameters in colorectal cancer.

Science.gov (United States)

Tixier, Florent; Groves, Ashley M; Goh, Vicky; Hatt, Mathieu; Ingrand, Pierre; Le Rest, Catherine Cheze; Visvikis, Dimitris

2014-01-01

Thirty patients with proven colorectal cancer prospectively underwent integrated 18F-FDG PET/DCE-CT to assess the metabolic-flow phenotype. Both CT blood flow parametric maps and PET images were analyzed. Correlations between PET heterogeneity and perfusion CT were assessed by Spearman's rank correlation analysis. Blood flow visualization provided by DCE-CT images was significantly correlated with 18F-FDG PET metabolically active tumor volume as well as with uptake heterogeneity for patients with stage III/IV tumors (|ρ|:0.66 to 0.78; p-valueheterogeneity of 18F-FDG PET accumulation reflects to some extent tracer distribution and consequently indicates that 18F-FDG PET intra-tumor heterogeneity may be associated with physiological processes such as tumor vascularization.

Enhanced therapeutic effect of multiple injections of HSV-TK + GCV gene therapy in combination with ionizing radiation in a mouse mammary tumor model

International Nuclear Information System (INIS)

Vlachaki, Maria T.; Chhikara, Madhu; Aguilar, Laura; Zhu Xiaohong; Chiu, Kam J.; Woo, Shiao; Teh, Bin S.; Thompson, Timothy C.; Butler, E. Brian; Aguilar-Cordova, Estuardo

2001-01-01

Purpose: Standard therapies for breast cancer lack tumor specificity and have significant risk for recurrence and toxicities. Herpes simplex virus-thymidine kinase (HSV-tk) gene therapy combined with radiation therapy (XRT) may be effective because of complementary mechanisms and distinct toxicity profiles. HSV-tk gene therapy followed by systemic administration of ganciclovir (GCV) enhances radiation-induced DNA damage by generating high local concentrations of phosphorylated nucleotide analogs that increase radiation-induced DNA breaks and interfere with DNA repair mechanisms. In addition, radiation-induced membrane damage enhances the 'bystander effect' by facilitating transfer of nucleotide analogs to neighboring nontransduced cells and by promoting local and systemic immune responses. This study assesses the effect of single and multiple courses of HSV-tk gene therapy in combination with ionizing radiation in a mouse mammary cancer model. Methods and Materials: Mouse mammary TM40D tumors transplanted s.c. in syngeneic immunocompetent BALB-c mice were treated with either adenoviral-mediated HSV-tk gene therapy or local radiation or the combination of gene and radiation therapy. A vector consisting of a replication-deficient (E1-deleted) adenovirus type 5 was injected intratumorally to administer the HSV-tk gene, and GCV was initiated 24 h later for a total of 6 days. Radiation was given as a single dose of 5 Gy 48 h after the HSV-tk injection. A metastatic model was developed by tail vein injection of TM40D cells on the same day that the s.c. tumors were established. Systemic antitumor effect was evaluated by counting the number of lung nodules after treating only the primary tumors with gene therapy, radiation, or the combination of gene and radiation therapy. To assess the therapeutic efficacy of multiple courses of this combinatorial approach, one, two, and three courses of HSV-tk + GCV gene therapy, in combination with radiation, were compared to HSV-tk or

ROLE OF THE MORPHOMETRIC PARAMETERS OF INTRATUMORAL MICROVESSELS AND THE PROLIFERATIVE ACTIVITY OF TUMOR CELLS IN RENAL CELL CARCINOMA

Directory of Open Access Journals (Sweden)

N. A. Gorban

2014-08-01

Full Text Available Tumor cell proliferation and angiogenesis are essential factors for tumor growth, progression, and metastasis.Objective: to assess the relationship between the values of proliferative activity and the morphometric parameters of intratumoral microvessels in metastatic and localized carcinomas of the kidney.Materials and methods. Surgical specimens taken from 54 patients (32 men and 22 women aged 26 to 69 years (mean age 55 ± 1.5 years with the verified diagnosis of clear-cell renal cell carcinoma (RCC were studied.Conclusion. Proliferative activity and angioarchitectonics are an important biological characteristic of a tumor of unequal clinical value in RCC. Metastatic carcinoma has a higher proliferative activity and a low tumor vascularization than those of localized carcinoma.

The biological effects of 224Ra injected into dogs

International Nuclear Information System (INIS)

Muggenburg, B.A.; Lloyd, R.D.; Hahn, F.F.; Griffith, W.C.; Boecker, B.B.

1994-01-01

The purpose of this study was to investigate the toxicity of injected 224 Ra in the dog. Radium-224 is a short-lived isotope of radium with a half-life of 3.62 d. When administered parenterally, it deposits on bone surfaces; because of its short half-life, most of its energy is deposited on bone surfaces, in a manner similar to plutonium. The experimental design included a comparison to the exposed human population. Instead of using a single injection of 224 Ra, groups were included in which dogs were injected once, 10 times, or 50 times. This design provided groups that could be compared to the multiple injections often used in people for the treatment of ankylosing spondylitis

Experimental optimization of a direct injection homogeneous charge compression ignition gasoline engine using split injections with fully automated microgenetic algorithms

Energy Technology Data Exchange (ETDEWEB)

Canakci, M. [Kocaeli Univ., Izmit (Turkey); Reitz, R.D. [Wisconsin Univ., Dept. of Mechanical Engineering, Madison, WI (United States)

2003-03-01

Homogeneous charge compression ignition (HCCI) is receiving attention as a new low-emission engine concept. Little is known about the optimal operating conditions for this engine operation mode. Combustion under homogeneous, low equivalence ratio conditions results in modest temperature combustion products, containing very low concentrations of NO{sub x} and particulate matter (PM) as well as providing high thermal efficiency. However, this combustion mode can produce higher HC and CO emissions than those of conventional engines. An electronically controlled Caterpillar single-cylinder oil test engine (SCOTE), originally designed for heavy-duty diesel applications, was converted to an HCCI direct injection (DI) gasoline engine. The engine features an electronically controlled low-pressure direct injection gasoline (DI-G) injector with a 60 deg spray angle that is capable of multiple injections. The use of double injection was explored for emission control and the engine was optimized using fully automated experiments and a microgenetic algorithm optimization code. The variables changed during the optimization include the intake air temperature, start of injection timing and the split injection parameters (per cent mass of fuel in each injection, dwell between the pulses). The engine performance and emissions were determined at 700 r/min with a constant fuel flowrate at 10 MPa fuel injection pressure. The results show that significant emissions reductions are possible with the use of optimal injection strategies. (Author)

Intra-Articular, Single-Shot Hylan G-F 20 Hyaluronic Acid Injection Compared with Corticosteroid in Knee Osteoarthritis: A Double-Blind, Randomized Controlled Trial.

Science.gov (United States)

Tammachote, Nattapol; Kanitnate, Supakit; Yakumpor, Thanasak; Panichkul, Phonthakorn

2016-06-01

The treatment of knee osteoarthritis with hyaluronic acid or corticosteroid injection has been widely used. The purpose of this study was to compare the efficacy of hyaluronic acid (hylan G-F 20) with triamcinolone acetonide as a single intra-articular injection for knee osteoarthritis. This study was a prospective, randomized, double-blind clinical trial. Participants with symptomatic knee osteoarthritis were recruited. They were randomized to receive a single-shot, intra-articular injection of either 6 mL of hylan G-F 20 or 6 mL of a solution comprising 1 mL of 40-mg triamcinolone acetonide and 5 mL of 1% lidocaine with epinephrine. The primary outcomes were knee pain severity, knee function, and range of motion at 6 months. Ninety-nine patients were assessed before injection and underwent a 6-month follow-up. Patients and evaluators were blinded. Multilevel regression models were used to estimate differences between the groups. At the 6-month follow-up, compared with patients who took hylan G-F 20, patients who took triamcinolone acetonide had similar improvement in knee pain, knee function, and range of motion. The difference in mean outcome scores between groups was, with regard to knee pain, a visual analog scale (VAS) score of 3 points (95% confidence interval [95% CI], -6 to 11 points); with regard to knee function, a modified Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score of 0 points (95% CI, -8 to 6 points); and, with regard to range of motion, flexion of -1° (95% CI, -5° to 2°) and extension of 0° (95% CI, -0.5° to 0.5°). However, patients who took triamcinolone acetonide had better pain improvement from 24 hours until 1 week after injection; the mean difference between groups with regard to the VAS score was 12 points (95% CI, 5 to 20 points; p = 0.002) at 24 hours and 9 points (95% CI, 1 to 15 points; p = 0.018) at 1 week. At 2 weeks after injection, patients who took triamcinolone acetonide also had better knee

Intravitreal injection of perfluoropropane for the treatment of vitreomacular traction

Directory of Open Access Journals (Sweden)

Xiao-Ping Wan

2013-07-01

Full Text Available AIM: To study the efficacy of a single intravitreal injection of perfluoropropane(C3F8in releasing vitreomacular traction. METHODS: Twelve eyes of 12 consecutive patients with vitreomacular traction received a single intravitreal injection of 0.3mL 100%(C3F8were retrospectively analyzed. The best corrected vision acuity and the neural epithelium thickness of central macular were observed. RESULTS: One month following treatment, vitreomacular traction was released in 5 eyes(42%, mean final visual acuity(VAimproved 0.04 and mean central foveal thickness decreased by 69μm. The vision acuity before and after treatment were 0.20±0.07, 0.25±0.04 respectively.CONCLUSION: Intravitreal C3F8 injection could offer a minimally invasive alternative to pars plana vitrectomy in patients with vitreomacular traction.

Spin injection into a two-dimensional electron gas using inter-digital-ferromagnetic contacts

DEFF Research Database (Denmark)

Hu, C.M.; Nitta, J.; Jensen, Ane

2002-01-01

We present a model that describes the spin injection across a single interface with two electrodes. The spin-injection rate across a typical hybrid junction made of ferromagnet (FM) and a two-dimensional electron gas (2DEG) is found at the percentage level. We perforin spin-injection-detection ex......-injection-detection experiment on devices with two ferromagnetic contacts on a 2DEG confined in an InAs quantum well. A spin-injection rate of 4.5% is estimated from the measured magnetoresistance....

Delivery of viral vectors to tumor cells: extracellular transport, systemic distribution, and strategies for improvement.

Science.gov (United States)

Wang, Yong; Yuan, Fan

2006-01-01

It is a challenge to deliver therapeutic genes to tumor cells using viral vectors because (i) the size of these vectors are close to or larger than the space between fibers in extracellular matrix and (ii) viral proteins are potentially toxic in normal tissues. In general, gene delivery is hindered by various physiological barriers to virus transport from the site of injection to the nucleus of tumor cells and is limited by normal tissue tolerance of toxicity determined by local concentrations of transgene products and viral proteins. To illustrate the obstacles encountered in the delivery and yet limit the scope of discussion, this review focuses only on extracellular transport in solid tumors and distribution of viral vectors in normal organs after they are injected intravenously or intratumorally. This review also discusses current strategies for improving intratumoral transport and specificity of viral vectors.

Quantitative analysis of fragrance in selectable one dimensional or two dimensional gas chromatography-mass spectrometry with simultaneous detection of multiple detectors in single injection.

Science.gov (United States)

Tan, Hui Peng; Wan, Tow Shi; Min, Christina Liew Shu; Osborne, Murray; Ng, Khim Hui

2014-03-14

A selectable one-dimensional ((1)D) or two-dimensional ((2)D) gas chromatography-mass spectrometry (GC-MS) system coupled with flame ionization detector (FID) and olfactory detection port (ODP) was employed in this study to analyze perfume oil and fragrance in shower gel. A split/splitless (SSL) injector and a programmable temperature vaporization (PTV) injector are connected via a 2-way splitter of capillary flow technology (CFT) in this selectable (1)D/(2)D GC-MS/FID/ODP system to facilitate liquid sample injections and thermal desorption (TD) for stir bar sorptive extraction (SBSE) technique, respectively. The dual-linked injectors set-up enable the use of two different injector ports (one at a time) in single sequence run without having to relocate the (1)D capillary column from one inlet to another. Target analytes were separated in (1)D GC-MS/FID/ODP and followed by further separation of co-elution mixture from (1)D in (2)D GC-MS/FID/ODP in single injection without any instrumental reconfiguration. A (1)D/(2)D quantitative analysis method was developed and validated for its repeatability - tR; calculated linear retention indices (LRI); response ratio in both MS and FID signal, limit of detection (LOD), limit of quantitation (LOQ), as well as linearity over a concentration range. The method was successfully applied in quantitative analysis of perfume solution at different concentration level (RSD≤0.01%, n=5) and shower gel spiked with perfume at different dosages (RSD≤0.04%, n=5) with good recovery (96-103% for SSL injection; 94-107% for stir bar sorptive extraction-thermal desorption (SBSE-TD). Copyright © 2014 Elsevier B.V. All rights reserved.

Calculation of injection and extraction orbits for the IPCR SSC

International Nuclear Information System (INIS)

Goto, A.; Yano, Y.; Kishida, N.; Nakanishi, N.; Wada, T.

1982-01-01

Calculations of beam trajectories in the injection and extraction systems for the IPCR SSC were done and the characteristics of those elements were determined. Beam centering for single turn extraction by use of first harmonic fields were also studied. The rather simple conditions at the injection point for a well-centered acceleration orbit are also discussed

Synchronization of skin ablation and microjet injection for an effective transdermal drug delivery

Science.gov (United States)

Jang, Hun-jae; Yeo, Seonggu; Yoh, Jack J.

2016-04-01

An Er:YAG laser with 2940-nm wavelength and 150-µs pulse duration was built for the purpose of combined ablation and microjet injection. A shorter pulse duration compared to common erbium lasers in dentistry is desirable for a synchronization of skin ablation and subsequent microjet injection into target skin for transdermal injection of liquid dose. A single laser beam is split into two for an optimal energy of pre-ablation of skin and the residual energy allocated to a microjet ejection. A newly designed injector consists of an L-shaped chamber and a parabolic mirror in a single unit, and the handheld laser is a part of an integrated system requiring no optical fiber. Through various injection tests using the porcine skin, the effectiveness of the new delivery system is herein evaluated.

An Optical Method for Measuring Injection Timing in Diesel Engines, Using a Single Port

Science.gov (United States)

2014-09-01

injection, naturally aspirated marine diesel engine with mechanical unit injectors and showed satisfactory results with blends ranging from 25% HRD/75... injector technology, they further concluded that the mechanical unit injectors found throughout the naval fleet and on the Detroit Diesel 3–53 in the...injection timing in a pump-line- nozzle system of blending Fischer- Tropsch derived diesel fuel with low sulfur, ultra-low sulfur and biodiesel fuels. The

Injection system of compact SR light source 'AURORA'

International Nuclear Information System (INIS)

Takayama, Takeshi; Yano, Takashi; Sasaki, Yasushi; Yasumitsu, Naoki

1991-01-01

A half-integer-resonance injection method is introduced for a superconducting SR-ring of 1 m orbit diameter, which is made of a weak focussing single-body magnet. The present method makes it possible to inject an electron beam of an energy of as high as 150 MeV into the ring of a magnetic field strength of 1 T. Several new injection devices are introduced in order to guide the beam under the strong magnetic fringing field, and to excite the half-integer-resonance. The field index of 0.73 is selected for the half-integer-resonance injection. The field index of 0.35 at the maximum magnetic field strength of 4.3 T is to get a sufficiently long quantum lifetime. A new device named resonance jumper is used to pass quickly several resonances of betatron motion without beam loss. The resonances occur when the magnetic field is ramped up and the field index decreases from 0.73 to 0.35. The injection devices except the inflector are air-core magnets in order to work in the strong magnetic field. In November of 1989, the beam was successfully injected and stored. The injection devices and the half-integer-resonance injection method were established. (author)

Dimensional accuracy of Acrylonitrile Butadiene Styrene injection molded parts produced in a pilot produc

DEFF Research Database (Denmark)

Mischkot, Michael; Davoudinejad, Ali; Charalambis, Alessandro

of a geometry including micro-features have been injection-molded in Acrylonitrile Butadiene Styrene (ABS) with a single 20x20x2.5 mm^3 injection molding insert manufactured in a photopolymer composite material. This research investigates the dimensional accuracy of the injection molded parts as a function...

Essentials in clinical application of p53 for tumors intervention-example of liver cancer

International Nuclear Information System (INIS)

Guan Yongsong; He Qing

2008-01-01

Recombinant human adenovirus p53 (Ad-p53)injection has been used for treating tumors in combination with several local therapeutic methods. Taking liver cancer as an example, this article introduces the combination of Ad-p53 in procedures of interventional therapy. Mechanisms of their effects are emphasized to pursue an optimal synergism in killing tumors. Intratumoral injection is suggested as the first choice of Ad- p53 administration with the least recommended dosage for a single tumor. The optimal time for intervention of liver cancer is supposed to be 2 to 5 days after the administration of Ad-p53. There are several theories on the therapeutic method taking p53 as a target, some of them are contradictional; therefore one has to select either activating or inhibiting the p53 pathway beforehand. For advanced malignancies, the selection should be cautious for appropriater cases from the proper candidates. (authors)

Evaluation of acute toxicity and the effect of single injected doses of ...

African Journals Online (AJOL)

USER

2010-07-12

Jul 12, 2010 ... significant in therapeutic applications against diseases of diverse origins .... The rats were killed under ether anesthesia; one hour after injection and blood ..... that zerumbone could be safe for use in one dose treatment.

Clinical and instrumental evaluation of a cross-linked hyaluronic acid filler dermal injection: effects on nasolabial folds skin biophysical parameters and augmentation from a single-dose, monocentric, open-label trial.

Science.gov (United States)

Cameli, Norma; Mariano, Maria; Serio, Mirko; Berardesca, Enzo

2016-10-01

When a hyaluronic acid dermal device to fill soft tissues is chosen, efficacy, safety and durability are key concerns. This is an open-label prospective study to instrumentally evaluate the effects of HA filler dermal injection on nasolabial folds skin biophysical parameters and augmentation. A single Italian site treated female subjects aged 40-55, for nasolabial folds, with a single standardized injection. The outcome was evaluated with objective quantitative measurements after 90 (T1) and 180 days (T2) from the injection comparing to baseline (T0) by means of Corneometer (skin hydration measurement), Cutometer (skin elasticity measurement), and Visioface devices for digital and UV computerized image analysis. Secondary endpoints were safety assessment, subject investigator satisfaction with the intervention. Assessment of aesthetic results included photographic documentation. The computerized image analysis confirmed the clinical assessment showing statistically significant reduction in nasolabial folds both at T1 and T2. Visioface® indexes showed a marked and statistical significant response. An excellent profile of satisfaction of the product at T2 from investigators and patients was recorded. Skin hydration and elasticity did not show significant changes. In our study, a standardized HA filler dermal injection on nasolabial folds did not influence skin biophysical parameters such as skin hydration and elasticity. Nasolabial folds showed a persistent and significative response at T2 confirmed by instrumental evaluation. The tolerability and safety profile of the product was excellent.

Effect of Pilot Injection Timings on the Combustion Temperature Distribution in a Single-Cylinder CI Engine Fueled with DME and ULSD

Directory of Open Access Journals (Sweden)

Jeon Joonho

2016-01-01

Full Text Available Many studies of DiMethyl Ether (DME as an alternative fuel in Compression-Ignition (CI engines have been performed. Although diverse DME engine research has been conducted, the investigation of combustion behavior and temperature distribution in the combustion engine has not progressed due to the fact that there is no sooting flame in DME combustion. In order to investigate the combustion characteristics in this study, the KIVA-3 V code was implemented to research various pilot injection strategies on a single-cylinder CI engines with DME and Ultra-Low-Sulfur Diesel (ULSD fuels. The combustion distribution results obtained from the numerical investigation were validated when compared with the measurement of flame temperature behaviors in the experimental approach. This study showed that long intervals between two injection timings enhanced pilot combustion by increasing the ambient pressure and temperature before the start of the main combustion. Different atomization properties between DME and ULSD fuels contributed to the formation of a fuel-air mixture at the nozzle tip and piston lip regions, separately, which strongly affected the temperature distribution of the two fuels. In addition, the pilot injection timing played a vital role in regard to ignition delay and peak combustion temperatures. Exhaust emissions, such as NOx and soot, are related to the local equivalence ratio and temperature in the combustion chamber, also illustrated by the contrary result on a Φ (equivalence ratio – T (temperature map.

Expression of inhibitory receptors on intratumoral T cells modulates the activity of a T cell-bispecific antibody targeting folate receptor

Science.gov (United States)

Schreiner, Jens; Thommen, Daniela S.; Herzig, Petra; Bacac, Marina; Klein, Christian; Roller, Andreas; Belousov, Anton; Levitsky, Victor; Savic, Spasenija; Moersig, Wolfgang; Uhlenbrock, Franziska; Heinzelmann-Schwarz, Viola A.; Umana, Pablo; Pisa, Pavel; von Bergwelt-Baildon, M.; Lardinois, Didier; Müller, Philipp; Karanikas, Vaios; Zippelius, Alfred

2016-01-01

ABSTRACT T-cell bispecific antibodies (TCBs) are a novel therapeutic tool designed to selectively recruit T-cells to tumor cells and simultaneously activate them. However, it is currently unknown whether the dysfunctional state of T-cells, embedded into the tumor microenvironment, imprints on the therapeutic activity of TCBs. We performed a comprehensive analysis of activation and effector functions of tumor-infiltrating T-cells (TILs) in different tumor types, upon stimulation by a TCB targeting folate receptor 1 and CD3 (FolR1-TCB). We observed a considerable heterogeneity in T-cell activation, cytokine production and tumor cell killing upon exposure to FolR1-TCB among different FolR1-expressing tumors. Of note, tumors presenting with a high frequency of PD-1hi TILs displayed significantly impaired tumor cell killing and T-cell function. Further characterization of additional T-cell inhibitory receptors revealed that PD-1hi TILs defined a T-cell subset with particularly high levels of multiple inhibitory receptors compared with PD-1int and PD-1neg T-cells. PD-1 blockade could restore cytokine secretion but not cytotoxicity of TILs in a subset of patients with scarce PD-1hi expressing cells; in contrast, patients with abundance of PD-1hi expressing T-cells did not benefit from PD-1 blockade. Our data highlight that FolR1-TCB is a promising novel immunotherapeutic treatment option which is capable of activating intratumoral T-cells in different carcinomas. However, its therapeutic efficacy may be substantially hampered by a pre-existing dysfunctional state of T-cells, reflected by abundance of intratumoral PD-1hi T-cells. These findings present a rationale for combinatorial approaches of TCBs with other therapeutic strategies targeting T-cell dysfunction. PMID:27057429

Electrically Injected UV-Visible Nanowire Lasers

Energy Technology Data Exchange (ETDEWEB)

Wang, George T.; Li, Changyi; Li, Qiming; Liu, Sheng; Wright, Jeremy Benjamin; Brener, Igal; Luk, Ting -Shan; Chow, Weng W.; Leung, Benjamin; Figiel, Jeffrey J.; Koleske, Daniel D.; Lu, Tzu-Ming

2015-09-01

There is strong interest in minimizing the volume of lasers to enable ultracompact, low-power, coherent light sources. Nanowires represent an ideal candidate for such nanolasers as stand-alone optical cavities and gain media, and optically pumped nanowire lasing has been demonstrated in several semiconductor systems. Electrically injected nanowire lasers are needed to realize actual working devices but have been elusive due to limitations of current methods to address the requirement for nanowire device heterostructures with high material quality, controlled doping and geometry, low optical loss, and efficient carrier injection. In this project we proposed to demonstrate electrically injected single nanowire lasers emitting in the important UV to visible wavelengths. Our approach to simultaneously address these challenges is based on high quality III-nitride nanowire device heterostructures with precisely controlled geometries and strong gain and mode confinement to minimize lasing thresholds, enabled by a unique top-down nanowire fabrication technique.

Low energy, high power injection in JT-60 NBI

International Nuclear Information System (INIS)

Mizuno, Makoto; Dairaku, Masayuki; Horiike, Hiroshi

1988-05-01

JT-60 neutral beam injector (JT-60 NBI) is designed to inject 20 MW neutral hydrogen beam at energies of 70 ∼ 100 keV and the injection power decreases significantly at low energies (∼40 keV). For the extention of operation region aiming at the low density plasma heating and achieving H-mode by plasma periphery heating, increment of the injection power at low beam energies was required. The single-stage acceleration system was investigated in advance at the Prototype Injector Unit. From this result, the total injection power of 17 MW at 40 keV, 48 A per source was expected at the JT-60 NBI. This system was adopted in the JT-60 NBI from June, 1987 to July, 1987 and 17.6 MW neutral beam injection power was achieved. In the NB heating experiment, the H-mode transition phenomena was observed in JT-60 plasma. (author)

Alteration of sensitivity of intratumor quiescent and total cells to γ-rays following thermal neutron irradiation with or without 10B-compound

International Nuclear Information System (INIS)

Masunaga, Shin-ichiro; Ono, Koji; Suzuki, Minoru; Sakurai, Yoshinori; Kobayashi, Tooru; Takagaki, Masao; Kinashi, Yuko; Akaboshi, Mitsuhiko

2000-01-01

Purpose: Changes in the sensitivity of intratumor quiescent (Q) and total cells to γ-rays following thermal neutron irradiation with or without 10 B-compound were examined. Methods and Materials: 5-Bromo-2'-deoxyuridine (BrdU) was injected to SCC VII tumor-bearing mice intraperitoneally 10 times to label all the proliferating (P) tumor cells. As priming irradiation, thermal neutrons alone or thermal neutrons with 10 B-labeled sodium borocaptate (BSH) or dl-p-boronophenylalanine (BPA) were administered. The tumor-bearing mice then received a series of γ-ray radiation doses, 0 through 24 h after the priming irradiation. During this period, no BrdU was administered. Immediately after the second irradiation, the tumors were excised, minced, and trypsinized. Following incubation of tumor cells with cytokinesis blocker, the micronucleus (MN) frequency in cells without BrdU labeling (= Q cells at the time of priming irradiation) was determined using immunofluorescence staining for BrdU. The MN frequency in the total (P + Q) tumor cells was determined from the tumors that were not pretreated with BrdU before the priming irradiation. To determine the BrdU-labeled cell ratios in the tumors at the time of the second irradiation, each group also included mice that were continuously administered BrdU until just before the second irradiation using mini-osmotic pumps which had been implanted subcutaneously 5 days before the priming irradiation. Results: In total cells, during the interval between the two irradiations, the tumor sensitivity to γ-rays relative to that immediately after priming irradiation decreased with the priming irradiation ranking in the following order: thermal neutrons only > thermal neutrons with BSH > thermal neutrons with BPA. In contrast, in Q cells, during that time the sensitivity increased in the following order: thermal neutrons only 10 B-compound, especially BPA, in thermal neutron irradiation causes the recruitment from the Q to P population

Mycobacterium massiliense outbreak after intramuscular injection, South Korea.

Science.gov (United States)

Kim, H J; Cho, Y; Lee, S; Kook, Y; Lee, D; Lee, J; Park, B J

2012-10-01

SUMMARY We conducted an epidemic investigation to discover the route of transmission and the host factors of an outbreak of post-injection abscesses. Of the 2984 patients who visited a single clinic, 77 cases were identified and 208 age- and sex-matched controls were selected for analysis. Injected medications per se were not found to be responsible, and a deviation from safe injection practice suggested the likelihood of diluent contamination. Therefore the injected medications were classified according to whether there was a need for a diluent, and two medications showed a statistically significant association, i.e. injection with pheniramine [adjusted odds ratios (aOR) 5·93, 95% confidence interval (CI) 2·97-11·87] and ribostamycin (aOR 47·95, 95% CI 11·08-207·53). However, when considered concurrently, pheniramine lost statistical significance (aOR 8·71, 95% CI 0·44-171·61) suggesting that normal saline was the causative agent of this outbreak. Epidemiological evidence strongly suggested that this post-injection outbreak was caused by saline contaminated with Mycobacterium massiliense without direct microbiological evidence.

Design and development of the helicity injection system in Versatile Experiment Spherical Torus

International Nuclear Information System (INIS)

Park, JongYoon; An, Younghwa; Jung, Bongki; Lee, Jeongwon; Lee, HyunYoung; Chung, Kyoung-Jae; Na, Yong-Su; Hwang, Y.S.

2015-01-01

Graphical abstract: - Highlights: • A high current electron gun with single pulse power for both arc and extraction is developed. • The optimal gun operation is confirmed by impedance matching between the PFN and plasma. • The gun injected currents of 0.95 kA with the voltage of ∼410 V for 5 ms with a 1.2 kV PFN. • The helicity injection system using the gun has been developed and tested successfully in VEST. • Toroidal currents of up to 3.8 kA confirm possible relaxation into tokamak-like plasma. - Abstract: A helicity injection system for the Versatile Experiment Spherical Torus (VEST) has been successfully developed and commissioned. A high current electron gun utilizing hollow cathode and washer stacks has been designed and constructed with a single pulse power system that can provide voltages for both arc discharge and extraction sequentially. Tests for electron gun operation with the single pulse power system have been conducted under various toroidal and poloidal field strengths. The estimated plasma impedance, depending on the injection magnetic field structure, can be utilized for the optimal gun operation by impedance matching between the pulse power system and plasma. With the charging voltage of 1.2 kV, injection current of 0.95 kA has been obtained with the injection voltage of 410 V for about 5 ms. Initial helicity injection experiments have been conducted under various toroidal and poloidal field strengths and a toroidal plasma current of up to 3.8 kA is observed with the current multiplication larger than the geometric stacking ratio, confirming the possibility of relaxation into tokamak-like plasma with closed flux formation.

Design and development of the helicity injection system in Versatile Experiment Spherical Torus

Energy Technology Data Exchange (ETDEWEB)

Park, JongYoon; An, Younghwa; Jung, Bongki; Lee, Jeongwon; Lee, HyunYoung; Chung, Kyoung-Jae; Na, Yong-Su; Hwang, Y.S., E-mail: yhwang@snu.ac.kr

2015-10-15

Graphical abstract: - Highlights: • A high current electron gun with single pulse power for both arc and extraction is developed. • The optimal gun operation is confirmed by impedance matching between the PFN and plasma. • The gun injected currents of 0.95 kA with the voltage of ∼410 V for 5 ms with a 1.2 kV PFN. • The helicity injection system using the gun has been developed and tested successfully in VEST. • Toroidal currents of up to 3.8 kA confirm possible relaxation into tokamak-like plasma. - Abstract: A helicity injection system for the Versatile Experiment Spherical Torus (VEST) has been successfully developed and commissioned. A high current electron gun utilizing hollow cathode and washer stacks has been designed and constructed with a single pulse power system that can provide voltages for both arc discharge and extraction sequentially. Tests for electron gun operation with the single pulse power system have been conducted under various toroidal and poloidal field strengths. The estimated plasma impedance, depending on the injection magnetic field structure, can be utilized for the optimal gun operation by impedance matching between the pulse power system and plasma. With the charging voltage of 1.2 kV, injection current of 0.95 kA has been obtained with the injection voltage of 410 V for about 5 ms. Initial helicity injection experiments have been conducted under various toroidal and poloidal field strengths and a toroidal plasma current of up to 3.8 kA is observed with the current multiplication larger than the geometric stacking ratio, confirming the possibility of relaxation into tokamak-like plasma with closed flux formation.

Clinical effectiveness of multiple-drug injection treatment in unruptured ectopic pregnancies: a retrospective study.

Science.gov (United States)

Dai, Quan; Wang, Lu-Lu; Shao, Xiao-Hui; Wang, Si-Ming; Dong, Xiao-Qiu

2012-10-01

To study the effect of local interventional treatment of unruptured ectopic pregnancies with multiple-drug injection guided by color Doppler sonography. In this retrospective analysis, 49 patients with an unruptured ectopic pregnancy were treated with two different local injection methods administered under sonographic guidance. The patients were divided into single-drug (n = 23) and multiple-drug (n = 26) injection groups, and they received a locally administered injection of methotrexate alone or a combination including methotrexate, hemocoagulase, antibiotics, and anti-inflammatory drugs, respectively. Overall, local injection treatment was successful in 44 patients. The 5 patients with failed treatment underwent laparotomy about 1 week after single-drug injection. Serum β-human chorionic gonadotropin (β-hCG ) levels, ectopic pregnancy mass sizes, blood flow at various points after treatment, the incidence of pelvic bleeding, and the time for serum β-hCG levels to return to normal and the mass to resolve were analyzed in the remaining 44 patients. Single-drug treatment was successful in 18 patients; 10 of 23 had low to moderate pelvic bleeding after treatment, and 5 were referred for surgery. All 26 patients were successfully treated by multiple-drug injection. Only 2 patients had a small amount of pelvic bleeding. Differences between groups were statistically significant (P injection under color Doppler guidance is a new, safe, and effective method for treating unruptured ectopic pregnancies. It accelerates the serum β-hCG decline and facilitates mass resolution. This regimen is associated with a very low rate of pelvic bleeding, improves the success rate of conservative treatment, and, therefore, has value as an important clinical application.

Microspheres with Ultrahigh Holmium Content for Radioablation of Malignancies

NARCIS (Netherlands)

Bult, W.; Seevinck, P.R.; Krijger, G.C.; Visser, T.; Kroon-Batenburg, L.M.J.; Bakker, C.J.G.; Hennink, W.E.; van het Schip, A.D.; Nijsen, J.F.W.

2009-01-01

The aim of this study was to develop microspheres with an ultra high holmium content which can be neutron activated for radioablation of malignancies. These microspheres are proposed to be delivered selectively through either intratumoral injections into solid tumors or administered via an

Rapid colorimetric assay for gentamicin injection.

Science.gov (United States)

Tarbutton, P

1987-01-01

A rapid colorimetric method for determining gentamicin concentration in commercial preparations of gentamicin sulfate injection was developed. Methods currently available for measuring gentamicin concentration via its colored complex with cupric ions in alkaline solution were modified to reduce the time required for a single analysis. The alkaline copper tartrate (ACT) reagent solution was prepared such that each milliliter contained 100 mumol cupric sulfate, 210 mumol potassium sodium tartrate, and 1.25 mmol sodium hydroxide. The assay involves mixing 0.3 mL gentamicin sulfate injection 40 mg/mL (of gentamicin), 1.0 mL ACT reagent, and 0.7 mL water; the absorbance of the resulting solution at 560 nm was used to calculate the gentamicin concentration in the sample. For injections containing 10 mg/mL of gentamicin, the amount of the injection was increased to 0.5 mL and water decreased to 0.5 mL. The concentration of gentamicin in samples representing 11 lots of gentamicin sulfate injection 40 mg/mL and 8 lots of gentamicin sulfate injection 10 mg/mL was determined. The specificity, reproducibility, and accuracy of the assay were assessed. The colored complex was stable for at least two hours. Gentamicin concentration ranged from 93.7 to 108% and from 95 to 109% of the stated label value of the 40 mg/mL and the 10 mg/mL injections, respectively. No components of the preservative system present in the injections interfered with the assay. Since other aminoglycosides produced a colored complex, the assay is not specific for gentamicin. The assay was accurate and reproducible over the range of 4-20 mg of gentamicin. This rapid and accurate assay can be easily applied in the hospital pharmacy setting.

Safe injection procedures, injection practices, and needlestick ...

African Journals Online (AJOL)

Results: Safe injection procedures regarding final waste disposal were sufficiently adopted, while measures regarding disposable injection equipment, waste containers, hand hygiene, as well as injection practices were inadequately carried out. Lack of job aid posters that promote safe injection and safe disposal of ...

Multi-region and single-cell sequencing reveal variable genomic heterogeneity in rectal cancer.

Science.gov (United States)

Liu, Mingshan; Liu, Yang; Di, Jiabo; Su, Zhe; Yang, Hong; Jiang, Beihai; Wang, Zaozao; Zhuang, Meng; Bai, Fan; Su, Xiangqian

2017-11-23

Colorectal cancer is a heterogeneous group of malignancies with complex molecular subtypes. While colon cancer has been widely investigated, studies on rectal cancer are very limited. Here, we performed multi-region whole-exome sequencing and single-cell whole-genome sequencing to examine the genomic intratumor heterogeneity (ITH) of rectal tumors. We sequenced nine tumor regions and 88 single cells from two rectal cancer patients with tumors of the same molecular classification and characterized their mutation profiles and somatic copy number alterations (SCNAs) at the multi-region and the single-cell levels. A variable extent of genomic heterogeneity was observed between the two patients, and the degree of ITH increased when analyzed on the single-cell level. We found that major SCNAs were early events in cancer development and inherited steadily. Single-cell sequencing revealed mutations and SCNAs which were hidden in bulk sequencing. In summary, we studied the ITH of rectal cancer at regional and single-cell resolution and demonstrated that variable heterogeneity existed in two patients. The mutational scenarios and SCNA profiles of two patients with treatment naïve from the same molecular subtype are quite different. Our results suggest each tumor possesses its own architecture, which may result in different diagnosis, prognosis, and drug responses. Remarkable ITH exists in the two patients we have studied, providing a preliminary impression of ITH in rectal cancer.

Intra-Tumor Genetic Heterogeneity in Wilms Tumor: Clonal Evolution and Clinical Implications

Directory of Open Access Journals (Sweden)

George D. Cresswell

2016-07-01

Full Text Available The evolution of pediatric solid tumors is poorly understood. There is conflicting evidence of intra-tumor genetic homogeneity vs. heterogeneity (ITGH in a small number of studies in pediatric solid tumors. A number of copy number aberrations (CNA are proposed as prognostic biomarkers to stratify patients, for example 1q+ in Wilms tumor (WT; current clinical trials use only one sample per tumor to profile this genetic biomarker. We multisampled 20 WT cases and assessed genome-wide allele-specific CNA and loss of heterozygosity, and inferred tumor evolution, using Illumina CytoSNP12v2.1 arrays, a custom analysis pipeline, and the MEDICC algorithm. We found remarkable diversity of ITGH and evolutionary trajectories in WT. 1q+ is heterogeneous in the majority of tumors with this change, with variable evolutionary timing. We estimate that at least three samples per tumor are needed to detect >95% of cases with 1q+. In contrast, somatic 11p15 LOH is uniformly an early event in WT development. We find evidence of two separate tumor origins in unilateral disease with divergent histology, and in bilateral WT. We also show subclonal changes related to differential response to chemotherapy. Rational trial design to include biomarkers in risk stratification requires tumor multisampling and reliable delineation of ITGH and tumor evolution.

Autologous blood versus corticosteroid local injection for treatment of Lateral Epicondylosis: A Randomized Clinical Trial

Directory of Open Access Journals (Sweden)

Ajit Singh,

2013-08-01

Full Text Available Objective: The objective of the present single blinded prospective randomized control trial was assessment of efficacy of autologous blood injection versus local steroid injection in treatment of lateral epicondylosis of elbow. Methodology: Using a pre-post experimental design, a total of sixty patients of previously untreated lateral epicondylosis were selected; Group 1 (n=30 was administered single injection of autologous blood and Group 2 (n=30 single local corticosteroid injection. Assessment was done at baseline, 2 weeks, 6 weeks and 12 weeks using PRTEE (Patient Rated Tennis Elbow Evaluation score. Results: Pre injection parameters showed no difference between groups (chi square test, p > 0.005. Analysis between groups showed significant decrease in steroid group at very short term - 2 weeks (unpaired t test, p < 0.005.There was no difference between groups at 6 weeks. There was a significant improvement in blood group at medium term -12 weeks (unpaired t test, p < 0.05. Conclusion: Both the interventions were effective in reducing pain and improving functional status of patients in short term, but autologous blood was more effective in longer run.

Platelet-rich plasma for chronic lateral epicondylitis: is one injection sufficient?

Science.gov (United States)

Glanzmann, Michael C; Audigé, Laurent

2015-12-01

Chronic lateral epicondylitis is generally treated using nonsurgical methods including physiotherapy and infiltrations of cortisone or platelet-rich plasma (PRP). The latter is known for its simple application as well as associated low risk of adverse events, which lend to its widespread use in treating various musculoskeletal conditions. There is limited evidence on the effectiveness of PRP injections to optimally treat chronic lateral epicondylitis. This study explored the effectiveness of single or repeated injections for patients with symptoms that spanned 6 months or more and were unresponsive to alternate conservative measures. Patients with chronic lateral epicondylitis received PRP injections in 4-week intervals that were complemented with standardized physical therapy. Patient-reported outcomes based on the patient-rated elbow evaluation (PREE), quick disabilities of the arm, shoulder and hand (qDASH), and EuroQol (five dimensions) 3-level version (EQ5D3L) questionnaires were documented at each visit including 6 months after the first injection. These outcomes were compared between patients receiving 1 vs. 2 or 3 PRP injections. Sixty-two patients received one (n = 36) or more (n = 26) PRP injections. The mean baseline to 6-month follow-up scores of the PREE and qDASH questionnaires improved significantly from 54.0 to 23.0 and 50.3 to 20.7, respectively. The mean baseline EQ5D3L-visual analogue scale score improved from 62.5 to 82.9 by 6 months post-injection. These outcomes did not significantly differ between the patients who received varying numbers of injections. Patients with chronic lateral epicondylitis reported significant pain relief and gain in function as well as quality of life 6 months after localized PRP treatment. A single PRP injection may be sufficient.

Single-cell transcriptomics uncovers distinct molecular signatures of stem cells in chronic myeloid leukemia.

Science.gov (United States)

Giustacchini, Alice; Thongjuea, Supat; Barkas, Nikolaos; Woll, Petter S; Povinelli, Benjamin J; Booth, Christopher A G; Sopp, Paul; Norfo, Ruggiero; Rodriguez-Meira, Alba; Ashley, Neil; Jamieson, Lauren; Vyas, Paresh; Anderson, Kristina; Segerstolpe, Åsa; Qian, Hong; Olsson-Strömberg, Ulla; Mustjoki, Satu; Sandberg, Rickard; Jacobsen, Sten Eirik W; Mead, Adam J

2017-06-01

Recent advances in single-cell transcriptomics are ideally placed to unravel intratumoral heterogeneity and selective resistance of cancer stem cell (SC) subpopulations to molecularly targeted cancer therapies. However, current single-cell RNA-sequencing approaches lack the sensitivity required to reliably detect somatic mutations. We developed a method that combines high-sensitivity mutation detection with whole-transcriptome analysis of the same single cell. We applied this technique to analyze more than 2,000 SCs from patients with chronic myeloid leukemia (CML) throughout the disease course, revealing heterogeneity of CML-SCs, including the identification of a subgroup of CML-SCs with a distinct molecular signature that selectively persisted during prolonged therapy. Analysis of nonleukemic SCs from patients with CML also provided new insights into cell-extrinsic disruption of hematopoiesis in CML associated with clinical outcome. Furthermore, we used this single-cell approach to identify a blast-crisis-specific SC population, which was also present in a subclone of CML-SCs during the chronic phase in a patient who subsequently developed blast crisis. This approach, which might be broadly applied to any malignancy, illustrates how single-cell analysis can identify subpopulations of therapy-resistant SCs that are not apparent through cell-population analysis.

Optical trapping and binding of particles in an optofluidic stable Fabry-Pérot resonator with single-sided injection.

Science.gov (United States)

Gaber, Noha; Malak, Maurine; Marty, Frédéric; Angelescu, Dan E; Richalot, Elodie; Bourouina, Tarik

2014-07-07

In this article, microparticles are manipulated inside an optofluidic Fabry-Pérot cylindrical cavity embedding a fluidic capillary tube, taking advantage of field enhancement and multiple reflections within the optically-resonant cavity. This enables trapping of suspended particles with single-side injection of light and with low optical power. A Hermite-Gaussian standing wave is developed inside the cavity, forming trapping spots at the locations of the electromagnetic field maxima with a strong intensity gradient. The particles get arranged in a pattern related to the mechanism affecting them: either optical trapping or optical binding. This is proven to eventually translate into either an axial one dimensional (1D) particle array or a cluster of particles. Numerical simulations are performed to model the field distributions inside the cavity allowing a behavioral understanding of the phenomena involved in each case.

Effects on mitochondrial metabolism in livers of guinea pigs after a single or repeated injection of As sub 2 O sub 3

Energy Technology Data Exchange (ETDEWEB)

Reichl, F.X.; Kreppel, H.; Forth, W. (Muenchen Univ. (Germany, F.R.). Walter-Straub-Institut fuer Pharmakologie und Toxikologie); Szinicz, L. (Akademie des Sanitaets- und Gesundheitswesens der Bundeswehr, Muenchen (Germany, F.R.). Inst. fuer Pharmakologie und Toxikologie)

1989-09-01

Differences in the metabolite pattern were observed in previous experiments in guinea pig livers after a single injection or prolonged (5 days) treatment with AS{sub 2}O{sub 3} (Reichl et al. 1988). To elucidate the underlying mechanism the effect of As{sub 2}O{sub 3} on liver metabolism was therefore investigated. Male guinea pigs received either a single dose (s.d.) of As{sub 2}O{sub 3} 10 mgxkg{sup -1} s.c. or repeated doses (r.d.) of 2.5 mgxkg{sup -1} b.i.d. on 5 consecutive days. One hour after the s.d. or 1 h and 16 h after the last injection in the r.d. groups the animals were sacrificed in anaesthesia. The livers were removed by freeze clamping for the determination of various metabolites. In the s.d. group a significant decrease in hydroxybutyrate, acetylCoA, adenosinemonophosphate and in the ratio of hydroxybutyrate/acetoacetate and an increase in pyruvate, citrate, malate, and adenosinetriphosphate were observed. A significant decrease in glycogen, pyruvate, {alpha}-ketoglutarate, acetylCoA, and acetoacetate and a significant increase in malate and in the ratios of lactate/pyruvate and hydroxybutyrate/acetoacetate were observed in the r.d.1-h group. In the r.d.16-h group a significant decrease in glycogen, pyruvate, lactate, and adenosinemonophosphate was found, but the values tended towards control values. The data are consistent with mechanisms of As{sub 2}O toxicity in other species as PDH inhibition with consecutive citric acid cycle and gluconeogenesis inhibition and excessive carbohydrate depletion. (orig.).

MRI mediated, non-invasive tracking of intratumoral distribution of nanocarriers in rat glioma

Energy Technology Data Exchange (ETDEWEB)

Karathanasis, Efstathios; Park, Jaekeun; Agarwal, Abhiruchi; Patel, Vijal; Zhao Fuqiang; Hu Xiaoping; Bellamkonda, Ravi V [Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 313 Ferst Drive, Atlanta, GA 30332 (United States); Annapragada, Ananth V [School of Health Information Sciences, University of Texas Health Science Center, 7000 Fannin Street, Houston, TX 77030 (United States)], E-mail: ravi@gatech.edu

2008-08-06

Nanocarrier mediated therapy of gliomas has shown promise. The success of systemic nanocarrier-based chemotherapy is critically dependent on the so-called leaky vasculature to permit drug extravasation across the blood-brain barrier. Yet, the extent of vascular permeability in individual tumors varies widely, resulting in a correspondingly wide range of responses to the therapy. However, there exist no tools currently for rationally determining whether tumor blood vessels are amenable to nanocarrier mediated therapy in an individualized, patient specific manner today. To address this need for brain tumor therapy, we have developed a multifunctional 100 nm scale liposomal agent encapsulating a gadolinium-based contrast agent for contrast-enhanced magnetic resonance imaging with prolonged blood circulation. Using a 9.4 T MRI system, we were able to track the intratumoral distribution of the gadolinium-loaded nanocarrier in a rat glioma model for a period of three days due to improved magnetic properties of the contrast agent being packaged in a nanocarrier. Such a nanocarrier provides a tool for non-invasively assessing the suitability of tumors for nanocarrier mediated therapy and then optimizing the treatment protocol for each individual tumor. Additionally, the ability to image the tumor in high resolution can potentially constitute a surgical planning tool for tumor resection.

Single-pass BPM system of the Photon Factory storage ring.

Science.gov (United States)

Honda, T; Katoh, M; Mitsuhashi, T; Ueda, A; Tadano, M; Kobayashi, Y

1998-05-01

At the 2.5 GeV ring of the Photon Factory, a single-pass beam-position monitor (BPM) system is being prepared for the storage ring and the beam transport line. In the storage ring, the injected beam position during the first several turns can be measured with a single injection pulse. The BPM system has an adequate performance, useful for the commissioning of the new low-emittance lattice. Several stripline BPMs are being installed in the beam transport line. The continuous monitoring of the orbit in the beam transport line will be useful for the stabilization of the injection energy as well as the injection beam orbit.

Intratumoral injection of radioactive holmium-166 microspheres in recurrent head and neck squamous cell carcinoma : preliminary results of first use

NARCIS (Netherlands)

Bakker, Robbert C; van Es, Robert J J; Rosenberg, Antoine J W P; van Nimwegen, Sebastiaan A; Bastiaannet, Remco; de Jong, Hugo W A M; Nijsen, Johannes F W; Lam, Marnix G E H

BACKGROUND: Limited treatment options exist for patients with locoregional recurrences of head and neck squamous cell carcinoma (HNSCC). In the palliative setting, a single session, minimally invasive, and relatively safe therapy is desirable. This case series illustrates the feasibility of a direct

Injection molded polymer chip for electrochemical and electrophysiological recordings from single cells

DEFF Research Database (Denmark)

Tanzi, Simone; Larsen, Simon Tylsgaard; Taboryski, Rafael J.

We present a novel method to fabricate an all in polymer injection molded chip for electrochemical cell recordings and lateral cell trapping. The complete device is molded in thermoplastic polymer and it results from assembling two halves. We tested spin-coated conductive polymer poly(3,4-ethylen...

A laser-induced-fluorescence visualization study of transverse, sonic fuel injection in a nonreacting supersonic combustor

Science.gov (United States)

Mcdaniel, J. C.; Graves, J., Jr.

1986-01-01

The present paper reports work which has been conducted in the first phase of a research program which is to provide a data base of spatially-resolved measurements in nonreacting supersonic combustors. In the measurements, a nonintrusive diagnostic technique based on the utilization of laser-induced fluorescence (LIF) is employed. The reported work had the objective to conduct LIF visualization studies of the injection of a simulated fuel into a Mach 2.07 airstream for comparison with corresponding numerical calculations. Attention is given to injection from a single orifice into a constant-area duct, injection from a single orifice behind a rearward-facing step, and injection from staged orifices behind a rearward-facing step.

Local Control of Lung Derived Tumors by Diffusing Alpha-Emitting Atoms Released From Intratumoral Wires Loaded With Radium-224

International Nuclear Information System (INIS)

Cooks, Tomer; Schmidt, Michael; Bittan, Hadas; Lazarov, Elinor; Arazi, Lior; Kelson, Itzhak; Keisari, Yona

2009-01-01

Purpose: Diffusing alpha-emitters radiation therapy (DART) is a new form of brachytherapy enabling the treatment of solid tumors with alpha radiation. The present study examines the antitumoral effects resulting from the release of alpha emitting radioisotopes into solid lung carcinoma (LL2, A427, and NCI-H520). Methods and Materials: An in vitro setup tested the dose-dependent killing of tumor cells exposed to alpha particles. In in vivo studies, radioactive wires (0.3 mm diameter, 5 mm long) with 224 Ra activities in the range of 21-38 kBq were inserted into LL/2 tumors in C57BL/6 mice and into human-derived A427 or NCI-H520 tumors in athymic mice. The efficacy of the short-lived daughters of 224 Ra to produce tumor growth retardation and prolong life was assessed, and the spread of radioisotopes inside tumors was measured using autoradiography. Results: The insertion of a single DART wire into the center of 6- to 7-mm tumors had a pronounced retardation effect on tumor growth, leading to a significant inhibition of 49% (LL2) and 93% (A427) in tumor development and prolongations of 48% (LL2) in life expectancy. In the human model, more than 80% of the treated tumors disappeared or shrunk. Autoradiographic analysis of the treated sectioned tissue revealed the intratumoral distribution of the radioisotopes, and histological analysis showed corresponding areas of necrosis. In vitro experiments demonstrated a dose-dependent killing of tumors cells exposed to alpha particles. Conclusions: Short-lived diffusing alpha-emitters produced tumor growth retardation and increased survival in mice bearing lung tumor implants. These results justify further investigations with improved dose distributions.

Estadios precoces de cancer oral: pronóstico en relación con gradación histológica, linfagiogénesis intratumoral y expresión de factor de crecimiento endotelial vascular Tipo-C (VEGF-C Early stage oral cancer: prognosis with regard to histological grading, intratumoral lymphangiogenesis, and the expression of vascular endothelial growth factor-C (VEGF-C

Directory of Open Access Journals (Sweden)

M.F. Muñoz-Guerra

2006-02-01

Full Text Available Objetivos. Los sistemas de gradación histológica se han usado clásicamente como factor pronóstico y marcadores de comportamiento clínico en el carcinoma epidermoide intra-oral (CEI. Sin embargo, su utilidad pronóstica permanece controvertida. Nuestro objetivo ha sido evaluar la presencia de linfangiogénesis intratumoral (LI, un nuevo hallazgo morfológico, en un análisis retrospectivo de muestras de tejido en parafina dentro de un grupo de estadios precoces de CEI, relacionándolo con clásicos sistemas de gradación histológica y teniendo en cuenta su importancia pronóstica. Asimismo, pretendemos determinar si la expresión del factor de crecimiento endotelial vascular -C (VEGF-C se correlaciona con la evolución de la enfermedad. Diseño. Realizamos un estudio retrospectivo basado en 96 casos de CEI. Todos los pacientes presentaban tumores intraorales T1-T2 y fueron tratados primariamente mediante resección local asociada con disección cervical electiva, la cual mostró ausencia de afectación ganglionar regional. En el grupo de 96 muestras analizamos la LI utilizando el marcador específico del endotelio linfático PA2.26. Adicionalmente, estudiamos la expresión del VEGF-C. Todos los casos fueron clasificados de acuerdo con los sistemas de gradación histológica descritos por Broders, Anneroth y Bryne. El estudio estadístico se fundamentó en el análisis univariante de supervivencia causa-específica y supervivencia libre de recidiva según el método de Kaplan-Meier. Resultados. El grupo de pacientes con ausencia de LI mostró mejor pronóstico en cuanto a supervivencia y periodo libre de enfermedad, aunque la diferencia no mostró valores estadísticamente significativos. El estudio no mostró una relación entre la expresión de VEGF-C y la presencia de LI. Sin embargo, no observamos recidivas entre el grupo con ausencia de expresión de VEGF-C. El análisis comparativo de los sistemas de gradación histológica mostró una

Effect of main injection timing for controlling the combustion phasing of a homogeneous charge compression ignition engine using a new dual injection strategy

International Nuclear Information System (INIS)

Das, Pranab; Subbarao, P.M.V.; Subrahmanyam, J.P.

2015-01-01

Highlights: • A new dual injection concept is developed by minimum geometry modification. • The occurrence of combustion parameters strongly depend on main injection timing. • At higher load, premixed equivalence ratio dominates over main injection timing. • Retarded of main injection timing tends to retard combustion phasing. • Slightly retarded main injection timing is recommended to avoid intense knocking. - Abstract: Homogeneous charge compression ignition combustion of diesel fuel is implemented using a novel dual injection strategy. A new experimental technique is developed to modify a single cylinder direct injection diesel engine to run on homogeneous combustion mode. Effect of main injection timing is investigated covering a range from 26 to 8 crank angle degrees before top dead center with an interval of 3°. Retarded main injection timing is identified as a control strategy for delaying combustion phasing and a means of controlled combustion phasing of direct injection homogeneous charge compression ignition combustion. Two load conditions were investigated and it was observed that at higher load, start of combustion depends more on fuel air equivalence ratio than main injection timing, whereas at low load, it significantly varies with varying main injection timing. Significant improvements in smoke and oxides of nitrogen emissions are observed when compared with the baseline conventional combustion. By studying different combustion parameters, it is observed that there is an improvement in performance and emissions with marginal loss in thermal efficiency when the main injection timing is 20° before top dead center. This is identified as the optimum main injection timing for such homogeneous combustion under the same operating condition

Cirugía radioguiada para la resección del cáncer no palpable de la mama

NARCIS (Netherlands)

Gallegos-Hernández, J. Francisco; Tanis, Pieter J.; Nieweg, Omgo E.; Duerloo, E.; Valdés-Olmos, Renato; Rutgers, Emeil J. Th; Kroon, Bin B.

2003-01-01

INTRODUCTION: Intratumoral injection of nanocolloid for lymphatic mapping enables therapeutic excision of clinically occult breast cancer with the aid of a gamma ray detection probe. OBJECTIVE: The aim of this study was to determine the success rate of radioguided tumor excision in addition to a

Microspheres with ultrahigh holmium content for radioablation of malignancies

NARCIS (Netherlands)

Bult, W; Seevinck, P R; Krijger, G C; Visser, T; Kroon-Batenburg, L M J; Bakker, C J G; Hennink, W E; van het Schip, A D; Nijsen, J F W

PURPOSE: The aim of this study was to develop microspheres with an ultra high holmium content which can be neutron activated for radioablation of malignancies. These microspheres are proposed to be delivered selectively through either intratumoral injections into solid tumors or administered via an

Microspheres with Ultrahigh Holmium Content for Radioablation of Malignancies

NARCIS (Netherlands)

Bult, W.; Seevinck, P.R.; Krijger, G.C.; Visser, T.; Kroon-Batenburg, L.M.J.; Bakker, C.J.G.; Hennink, W.E.; Van het Schip, A.D.; Nijsen, J.F.W.

Purpose The aim of this study was to develop microspheres with an ultra high holmium content which can be neutron activated for radioablation of malignancies. These microspheres are proposed to be delivered selectively through either intratumoral injections into solid tumors or administered via an

Sustainment of spherical tokamak by means of repetitive injection of compact torus plasma

International Nuclear Information System (INIS)

Shimamura, Shin; Matsura, Ken; Takahashi, Tsutomu; Nogi, Yasuyuki

2000-01-01

Sustainment of spherical tokamak (S.T.) has been studied. A compact torus (C.T.) plasma was injected into confinement region by magnetized coaxial gun. For start-up and sustainment of large main spherical tokamak, single pulsed injection of small C.T. is not sufficient in many cases. C.T.plasma injection of high repetition rate is required. For this purpose magnetized coaxial gun was driven with high repetition rate current. The first injected C.T. plasma could start-up S.T. without other help. The repetitive C.T. injection grew and sustained the S.T. plasma. A CCD camera with fast gated image intensifier took a cross sectional view of S.T. during the repetitive C.T. injection. (author)

Effect of fuel injection pressure and injection timing of Karanja biodiesel blends on fuel spray, engine performance, emissions and combustion characteristics

International Nuclear Information System (INIS)

Agarwal, Avinash Kumar; Dhar, Atul; Gupta, Jai Gopal; Kim, Woong Il; Choi, Kibong; Lee, Chang Sik; Park, Sungwook

2015-01-01

Highlights: • Effect of FIP on microscopic spray characteristics. • Effect of FIP and SOI timing on CRDI engine performance, emissions and combustion. • Fuel injection duration shortened, peak injection rate increased with increasing FIP. • SMD (D 32 ) and AMD (D 10 ) of fuel droplets decreased for lower biodiesel blends. • Increase in biodiesel blend ratio and FIP, fuel injection duration decreased. - Abstract: In this investigation, effect of 10%, 20% and 50% Karanja biodiesel blends on injection rate, atomization, engine performance, emissions and combustion characteristics of common rail direct injection (CRDI) type fuel injection system were evaluated in a single cylinder research engine at 300, 500, 750 and 1000 bar fuel injection pressures at different start of injection timings and constant engine speed of 1500 rpm. The duration of fuel injection slightly decreased with increasing blend ratio of biodiesel (Karanja Oil Methyl Ester: KOME) and significantly decreased with increasing fuel injection pressure. The injection rate profile and Sauter mean diameter (D 32 ) of the fuel droplets are influenced by the injection pressure. Increasing fuel injection pressure generally improves the thermal efficiency of the test fuels. Sauter mean diameter (D 32 ) and arithmetic mean diameter (D 10 ) decreased with decreasing Karanja biodiesel content in the blend and significantly increased for higher blends due to relatively higher fuel density and viscosity. Maximum thermal efficiency was observed at the same injection timing for biodiesel blends and mineral diesel. Lower Karanja biodiesel blends (up to 20%) showed lower brake specific hydrocarbon (BSHC) and carbon monoxide (BSCO) emissions in comparison to mineral diesel. For lower Karanja biodiesel blends, combustion duration was shorter than mineral diesel however at higher fuel injection pressures, combustion duration of 50% blend was longer than mineral diesel. Up to 10% Karanja biodiesel blends in a CRDI

Electrostatic injection kicker for the KEK digital accelerator

Directory of Open Access Journals (Sweden)

Toshikazu Adachi

2013-05-01

Full Text Available An electrostatic injection kicker (ES-Kicker has been developed and installed in the KEK digital accelerator, which is a synchrotron aimed at accelerating all ion species. The ES-Kicker kicks an injected ion beam horizontally into the ring orbit and consists of two main electrodes for electric field generation and three intermediate electrodes to correct field homogeneity. In our single-turn injection scheme, the circulating beam and the injected beam both pass through the electrode aperture of the kicker, so the kicker field must be turned off before arrival of the first circulating beam. The ES-Kicker is therefore operated in a pulse mode. This means that the excitation circuit for the ES-Kicker must be carefully designed, since the falling edge of the electric field is strongly affected by parasitic capacitance of this circuit, and any remaining field may disturb the circulating beam. This paper describes performance of the ES-Kicker on the basis of simulations and measurement results.

Low pressure powder injection moulding of stainless steel powders

Energy Technology Data Exchange (ETDEWEB)

Zampieron, J.V.; Soares, J.P.; Mathias, F.; Rossi, J.L. [Powder Processing Center CCP, Inst. de Pesquisas Energeticas e Nucleares, Sao Paulo, SP (Brazil); Filho, F.A. [IPEN, Inst. de Pesquisas Energeticas e Nucleares, Cidade Univ., Sao Paulo, SP (Brazil)

2001-07-01

Low-pressure powder injection moulding was used to obtain AISI 316L stainless steel parts. A rheological study was undertaken using gas-atomised powders and binders. The binders used were based on carnauba wax, paraffin, low density polyethylene and microcrystalline wax. The metal powders were characterised in terms of morphology, particle size distribution and specific surface area. These results were correlated to the rheological behaviour. The mixture was injected in the shape of square bar specimens to evaluate the performance of the injection process in the green state, and after sintering. The parameters such as injection pressure, viscosity and temperature were analysed for process optimisation. The binders were thermally removed in low vacuum with the assistance of alumina powders. Debinding and sintering were performed in a single step. This procedure shortened considerably the debinding and sintering time. (orig.)

Relative Bioavailability of a Single 4-mg Dose of Somatropin Administered by Subcutaneous Injection or by Needle-free Device and Coadministered With the Growth Hormone Inhibitor Octreotide Acetate in Healthy Adult Subjects.

Science.gov (United States)

Brimhall, Darin B; Petri, Niclas; D'Angelo, Pina

2018-05-01

Somatropin, used to treat growth hormone deficiency, has been traditionally administered by subcutaneous (SC) injection with needle and syringe. Needle-free devices offer ease of administration and may improve adherence and outcomes. This study evaluated the relative bioavailability of somatropin delivered with a needle-free device compared with traditional SC injection. In this randomized, single-dose, crossover study, healthy adults aged 18 to 35 years received single 4-mg doses of somatropin via a needle-free device or SC injection, along with octreotide to suppress endogenous growth hormone production. Blood samples were analyzed for serum somatropin and insulin-like growth factor-1 (IGF-1) concentrations over 24 hours after somatropin dosing. Pharmacokinetic and pharmacodynamic parameters were evaluated by using noncompartmental methods, and bioequivalence was determined based on ln transformation of the AUC 0-24 , AUC 0-∞ , C max , area under the effect-time curve from time 0 to 24 hours (AUEC 0-24 ), and maximum effect concentration (E max ). Bioequivalence was concluded if the 90% CIs of the needle-free device compared with the SC injection, constructed by using the two 1-sided hypotheses at the α = 0.05 level, for these pharmacokinetic/pharmacodynamic parameters fell within the 80.00% to125.00% regulatory acceptance range. A total of 57 subjects completed both study periods and were included in the pharmacokinetic analyses. Point estimates (90% CIs) of the geometric mean ratio (needle-free device/SC injection) based on serum somatropin were 1.013 (0.987-1.040) for AUC 0-24 , 1.012 (0.986-1.038) for AUC 0-∞ , and 1.200 (1.137-1.267) for C max . For IGF-1, baseline-corrected point estimates (90% CIs) were 0.901 (0.818-0.993) for AUEC 0-24 and 0.867 (0.795-0.946) for E max . Non-baseline-corrected values were 0.978 (0.953-1.004) for AUEC 0-24 and 0.953 (0.923-0.984) for E max . Both treatments were well tolerated; blood glucose levels increased in nearly

Polymeric microchip for the simultaneous determination of anions and cations by hydrodynamic injection using a dual-channel sequential injection microchip electrophoresis system.

Science.gov (United States)

Gaudry, Adam J; Nai, Yi Heng; Guijt, Rosanne M; Breadmore, Michael C

2014-04-01

A dual-channel sequential injection microchip capillary electrophoresis system with pressure-driven injection is demonstrated for simultaneous separations of anions and cations from a single sample. The poly(methyl methacrylate) (PMMA) microchips feature integral in-plane contactless conductivity detection electrodes. A novel, hydrodynamic "split-injection" method utilizes background electrolyte (BGE) sheathing to gate the sample flows, while control over the injection volume is achieved by balancing hydrodynamic resistances using external hydrodynamic resistors. Injection is realized by a unique flow-through interface, allowing for automated, continuous sampling for sequential injection analysis by microchip electrophoresis. The developed system was very robust, with individual microchips used for up to 2000 analyses with lifetimes limited by irreversible blockages of the microchannels. The unique dual-channel geometry was demonstrated by the simultaneous separation of three cations and three anions in individual microchannels in under 40 s with limits of detection (LODs) ranging from 1.5 to 24 μM. From a series of 100 sequential injections the %RSDs were determined for every fifth run, resulting in %RSDs for migration times that ranged from 0.3 to 0.7 (n = 20) and 2.3 to 4.5 for peak area (n = 20). This system offers low LODs and a high degree of reproducibility and robustness while the hydrodynamic injection eliminates electrokinetic bias during injection, making it attractive for a wide range of rapid, sensitive, and quantitative online analytical applications.

Co-Injection Resin Transfer Molding for Optimization of Integral Armor

National Research Council Canada - National Science Library

Fink, B

1998-01-01

... enhancement over existing defense industry practices. CIRTM was invented and developed for single-step manufacturing of integral armor by enabling simultaneous injection of multiple resins into multi-layer preform...

An experimental study on the effects of high-pressure and multiple injection strategies on DI diesel engine emissions

KAUST Repository

Yang, Seung Yeon; Chung, Suk-Ho

2013-01-01

An experimental study on effects of high-pressure injections in conjunction with split fuel injections were conducted on an AVL single cylinder DI diesel engine. Various injection schemes were studied through the use of an electronically controlled

Failure of botulinum toxin injection for neurogenic detrusor overactivity: Switch of toxin versus second injection of the same toxin.

Science.gov (United States)

Peyronnet, Benoit; Castel-Lacanal, Evelyne; Manunta, Andréa; Roumiguié, Mathieu; Marque, Philippe; Rischmann, Pascal; Gamé, Xavier

2015-12-01

To evaluate the efficacy of a second injection of the same toxin versus switching to a different botulinum toxin A after failure of a first detrusor injection in patients with neurogenic detrusor overactivity. The charts of all patients who underwent detrusor injections of botulinum toxin A (either abobotulinumtoxinA or onabotulinumtoxinA) for the management of neurogenic detrusor overactivity at a single institution were retrospectively reviewed. Patients in whom a first detrusor injection had failed were included in the present study. They were managed by a second injection of the same toxin at the same dosage or by a new detrusor injection using a different botulinum toxin A. Success was defined as a resolution of urgency, urinary incontinence and detrusor overactivity in a patient self-catheterizing seven times or less per 24 h. A total of 58 patients were included for analysis. A toxin switch was carried out in 29 patients, whereas the other 29 patients received a reinjection of the same toxin at the same dose. The success rate was higher in patients who received a toxin switch (51.7% vs. 24.1%, P = 0.03). Patients treated with a switch from abobotulinumtoxinA to onabotulinumtoxinA and those treated with a switch from onabotulinumtoxinA to abobotulinumtoxinA had similar success rates (52.9% vs. 50%, P = 0.88). After failure of a first detrusor injection of botulinum toxin for neurogenic detrusor overactivity, a switch to a different toxin seems to be more effective than a second injection of the same toxin. The replacement of onabotulinumtoxin by abobotulinumtoxin or the reverse provides similar results. © 2015 The Japanese Urological Association.

Animal experiments and clinical trials of 166Ho-Chitosan for various cancers

International Nuclear Information System (INIS)

Lim, S.M.; Choi, C.W.; Park, S.Y.; Lee, S.H.; Lee, B.H.; Park, K.B.

1998-01-01

166 Ho-Chitosan is a complex of 166 Ho and N-glucosamine with 400 to 500 kD MW, which chelates metal ions and degrades slowly in vivo. In mice, 166 H-Chitosan administered intraperitoneally was uniformly bound to the peritoneal wall (94%), and the surface dose calculated by Monte Carlo simulation (EGS 4 code) was 81 Gy/uCi/cm 2 . 166 Ho-Chitosan was administered intraperitoneally as an adjunct in the treatment of ovarian cancer with diffuse spread of malignant cells in the peritoneal surfaces including the diaphragm. 97-99% of 166 Ho-Chitosan was localized within the peritoneal cavity, and more than 90% of 166 Ho-Chitosan was attached to the peritoneal wall. Partial response were observed in 4 among 5 patients with ovarian cancer without severe toxicity. Intracavitary radiation therapy with 166 Ho-Chitosan in the cystic brain tumor, 5 or 8 cysts were shrunken in size with thinning of the wall, 2 out of 8 showed growth retardation. For large or multiple primary liver cancers, which were inoperable and resistent to chemotherapy. 166 Ho-Chitosan was used for intraarterial injection, because this solution became gel with neutral pH. In the primary liver cancer, radioactivity was distributed in the territory of selected hepatic arterial branch, and partial responses were observed in 2 cases. For the large solitary liver tumor, which was not operable due to its location, direct intratumoral injection of the radioisotope had a limited response. 18 FDG PET was a useful tool to follow up those radionuclide therapy, and guide to plan the next therapy. In one case of the large single metastatic stomach cancer in the liver, 18 FDG PET was done two weeks after intratumoral injection of 166 Ho-Chitosan, which showed cold defects matched with distribution of 166 Ho-Chitosan, and second injection was guided by PET image. Various methods of the administration of 166 Ho-Chitosan could be used for the treatment of the cancers. (author)

Compact toroid injection fueling in a large field-reversed configuration

Science.gov (United States)

Asai, T.; Matsumoto, T.; Roche, T.; Allfrey, I.; Gota, H.; Sekiguchi, J.; Edo, T.; Garate, E.; Takahashi, Ts.; Binderbauer, M.; Tajima, T.

2017-07-01

A repetitively driven compact toroid (CT) injector has been developed for the large field-reversed configuration (FRC) facility of the C-2/C-2U, primarily for particle refueling. A CT is formed and injected by a magnetized coaxial plasma gun (MCPG) exclusively developed for the C-2/C-2U FRC. To refuel the particles of long-lived FRCs, multiple CT injections are required. Thus, a multi-stage discharge circuit was developed for a multi-pulsed CT injection. The drive frequency of this system can be adjusted up to 1 kHz and the number of CT shots per injector is two; the system can be further upgraded for a larger number of injection pulses. The developed MCPG can achieve a supersonic ejection velocity in the range of ~100 km s-1. The key plasma parameters of electron density, electron temperature and the number of particles are ~5  ×  1021 m-3, ~30 eV and 0.5-1.0  ×  1019, respectively. In this project, single- and double-pulsed counter CT injection fueling were conducted on the C-2/C-2U facility by two CT injectors. The CT injectors were mounted 1 m apart in the vicinity of the mid-plane. To avoid disruptive perturbation on the FRC, the CT injectors were operated at the lower limit of the particle inventory. The experiments demonstrated successful refueling with a significant density build-up of 20-30% of the FRC particle inventory per single CT injection without any deleterious effects on the C-2/C-2U FRC.

Effects of a single glucocorticoid injection on propylene glycol-treated cows with clinical ketosis.

Science.gov (United States)

van der Drift, Saskia G A; Houweling, Martin; Bouman, Marina; Koets, Ad P; Tielens, Aloysius G M; Nielen, Mirjam; Jorritsma, Ruurd

2015-05-01

This study investigated the metabolic effects of glucocorticoids when administered to propylene glycol-treated cows with clinical ketosis. Clinical ketosis was defined by depressed feed intake and milk production, and a maximal score for acetoacetate in urine. All cows received 250 mL oral propylene glycol twice daily for 3 days and were randomly assigned to a single intramuscular injection with sterile isotonic saline solution (n = 14) or dexamethasone-21-isonicotinate (n = 17). Metabolic blood variables were monitored for 6 days and adipose tissue variables for 3 days. β-Hydroxybutyrate (BHBA) concentrations in blood decreased in all cows during treatment, but were lower in glucocorticoid-treated cows. Cows treated with glucocorticoids had higher plasma glucose and insulin concentrations, whereas concentrations of non-esterified fatty acids, 3-methylhistidine and growth hormone were unaffected. mRNA expression of hormone-sensitive lipase, BHBA receptor and peroxisome proliferator-activated receptor type γ in adipose tissue was not affected. This shows that lipolytic effects do not appear to be important in ketotic cows when glucocorticoids are combined with PG. Plasma 3-methyl histidine concentrations were similar in both groups, suggesting that glucocorticoids did not increase muscle breakdown and that the greater rise in plasma glucose in glucocorticoid-treated cows may not be due to increased supply of glucogenic amino acids from muscle. Copyright © 2015 Elsevier Ltd. All rights reserved.

Investigations of needle-free jet injections.

Science.gov (United States)

Schramm-Baxter, J R; Mitragotri, S

2004-01-01

Jet injection is a needle-free drug delivery method in which a high-speed stream of fluid impacts the skin and delivers drugs. Although a number of jet injectors are commercially available, especially for insulin delivery, they have a low market share compared to needles possibly due to occasional pain associated with jet injection. Jets employed by the traditional jet injectors penetrate deep into the dermal and sub-dermal regions where the nerve endings are abundantly located. To eliminate the pain associated with jet injections, we propose to utilize microjets that penetrate only into the superficial region of the skin. However, the choice of appropriate jet parameters for this purpose is challenging owing to the multiplicity of factors that determine the penetration depth. Here, we describe the dependence of jet injections into human skin on the power of the jet. Dermal delivery of liquid jets was quantified using two measurements, penetration of a radiolabeled solute, mannitol, into skin and the shape of jet dispersion in the skin which was visualized using sulforhodamine B. The dependence of the amount of liquid delivered in the skin and the geometric measurements of jet dispersion on nozzle diameter and jet velocity was captured by a single parameter, jet power.

MgO by injection CVD

International Nuclear Information System (INIS)

Abrutis, A.; Kubilius, V.; Teiserkis, A.; Bigelyte, V.; Vengalis, B.; Jukna, A.; Butkute, R.

1997-01-01

Epitaxial YBa 2 Cu 3 O 7 layers with 45 in-plane orientation have been grown by injection CVD on MgO substrates polished off-axis to within 1.4-1.9 of the [100] direction. This new single-source CVD process is based on computer-controlled injection of precise microdoses of a metal-organic precursor solution into a CVD reactor. A wide range of solution compositions was tested to investigate compositional effects on phase purity, surface morphology, texturing and superconducting properties of the prepared films. The highest quality films with pure 45 texture had a smooth surface, zero resistance T c (R=0) of 88-89 K, and critical current density J c (77 K) above 10 6 A/cm 2 . (orig.) and critical current density J c (77 K) above 10 6 A/cm 2 . (orig.)

A new rat model of portal hypertension induced by intraportal injection of microspheres

Science.gov (United States)

Li, Xiang-Nong; Benjamin, IS; Alexander, B

1998-01-01

AIM: To produce a new rat model of portal hypertension by intraportal injection of microspheres. METHODS: Measured aliquots of single or different-sized microspheres (15, 40, 80μm) were injected into the portal vein to block intrahepatic portal radicals. The resultant changes in arterial,portal,hepatic venous and splenic pulp pressures were monitored. The liver and lungs were excised for histological examination. RESULTS: Portal venous pressure was elevated from basal value of 0.89-1.02 kPa to a steady-state of 1.98-3.19 kPa following the sequential injections of single- or different-sized microspheres, with a markedly lowered mean arterial pressure. However, a small-dose injection of 80 μm microspheres (1.8 × 105) produced a steady-state portal venous pressure of 2.53 × 0.17 kPa, and all rats showed normal arterial pressures. In addition, numerous microspheres were found in the lungs in all experimental groups. CONCLUSION: Portal hypertension can be reproduced in rats by intraportal injection of microspheres at a small dose of 80 μm (1.8 × 105). Intrahepatic portal-systemic shunts probably exist in the normal rat liver. PMID:11819236

Histopathological Alterations after Single Epidural Injection of Ropivacaine, Methylprednizolone Acetate, or Contrast Material in Swine

International Nuclear Information System (INIS)

Kitsou, Maria-Chrysanthi; Kostopanagiotou, Georgia; Kalimeris, Konstantinos; Vlachodimitropoulos, Demetrios; Soultanis, Konstantinos; Batistaki, Chrysanthi; Kelekis, Alexis

2011-01-01

Purpose: The consequences from the injection of different types of drugs in the epidural space remains unknown. Increasing evidence suggests that localized inflammation, fibrosis, and arachnoiditis can complicate sequential epidural blockades, or even epidural contrast injection. We investigate the in vivo effect of epidural injections in the epidural space in an animal model. Materials and Methods: A group of ten male adult pigs, five punctures to each at distinct vertebral interspaces under general anesthesia, were examined, testing different drugs, used regularly in the epidural space (iopamidol, methylprednisolone acetate, ropivacaine). Each site was marked with a percutaneous hook wire marker. Histological analysis of the epidural space, the meninges, and the underlying spinal cord of the punctured sites along with staining for caspase-3 followed 20 days later. Results: The epidural space did not manifest adhesions or any other pathology, and the outer surface of the dura was not impaired in any specimen. The group that had the contrast media injection showed a higher inflammation response compared to the other groups (P = 0.001). Positive staining for caspase-3 was limited to <5% of neurons with all substances used. Conclusion: No proof of arachnoiditis and/or fibrosis was noted in the epidural space with the use of the above-described drugs. A higher inflammation rate was noted with the use of contrast media.

Initial assessment of a model relating intratumoral genetic heterogeneity to radiological morphology

Science.gov (United States)

Noterdaeme, O; Kelly, M; Friend, P; Soonowalla, Z; Steers, G; Brady, M

2010-01-01

Tumour heterogeneity has major implications for tumour development and response to therapy. Tumour heterogeneity results from mutations in the genes responsible for mismatch repair or maintenance of chromosomal stability. Cells with different genetic properties may grow at different rates and exhibit different resistance to therapeutic interventions. To date, there exists no approach to non-invasively assess tumour heterogeneity. Here we present a biologically inspired model of tumour growth, which relates intratumoral genetic heterogeneity to gross morphology visible on radiological images. The model represents the development of a tumour as a set of expanding spheres, each sphere representing a distinct clonal centre, with the sprouting of new spheres corresponding to new clonal centres. Each clonal centre may possess different characteristics relating to genetic composition, growth rate and response to treatment. We present a clinical example for which the model accurately tracks tumour growth and shows the correspondence to genetic variation (as determined by array comparative genomic hybridisation). One clinical implication of our work is that the assessment of heterogeneous tumours using Response Evaluation Criteria In Solid Tumours (RECIST) or volume measurements may not accurately reflect tumour growth, stability or the response to treatment. We believe that this is the first model linking the macro-scale appearance of tumours to their genetic composition. We anticipate that our model will provide a more informative way to assess the response of heterogeneous tumours to treatment, which is of increasing importance with the development of novel targeted anti-cancer treatments. PMID:19690073

On-line grid impedance estimation based on harmonic injection for grid-connected PV inverter

DEFF Research Database (Denmark)

Ciobotaru, Mihai; Teodorescu, Remus; Blaabjerg, Frede

2007-01-01

two different signal processing algorithms. The DFT technique is used for the single harmonic injection and the statistic technique is used for the double harmonic injection. The grid impedance estimation is used for compliance with the anti-islanding requirements of the German standard (VDE0126...

Determination of the optional time for taking blood samples by single intravenous injection of 3H-leucine

International Nuclear Information System (INIS)

Meng Delian; Yao Junhu; Lu Jinyin; Wu Xiaobin; Liu Jun

2003-01-01

Twenty four young hens (1.5 kg of body weight, BW) were randomly divided into 4 groups. Every group was diet free (FAS) or force-fed a nitrogen-free diet (NFD) or the diet with 20% crude protein in which soybean meal or cotton seed meal was the sole nitrogen source (30 g DM/kg BW). 30 μCi 3 H-Leu/kg BW was intravenously injected into all birds just after force-fed or on fasting. Venous blood samples were taken at 5, 30 min, 4,24,36 and 48h after injection. The excreta during the whole period of 48h after injection was collected. Special radioactivities of nonprotein plasma at every time point and excreta were measured. The optional time of taking blood samples was 20-24 hours after injected 3 H-Leu

Immersed single-drop microextraction interfaced with sequential injection analysis for determination of Cr(VI) in natural waters by electrothermal-atomic absorption spectrometry

International Nuclear Information System (INIS)

Pena, Francisco; Lavilla, Isela; Bendicho, Carlos

2008-01-01

Single-drop microextraction (SDME) and sequential injection analysis have been hyphenated for ultratrace metal determination by Electrothermal-Atomic Absorption Spectrometry (ETAAS). The novel method was targeted on extraction of the Cr(VI)-APDC chelate and encompasses the potential of SDME as a miniaturized and virtually solvent-free preconcentration technique, the ability of sequential injection analysis to handle samples and the versatility of furnace autosamplers for introducing microliter samples in ETAAS. The variables influencing the microextraction of Cr(VI) onto an organic solvent drop, i.e., type of organic solvent, microextraction time, stirring rate of the sample solution, drop volume, immersion depth of the drop, salting-out effect, temperature of the sample, concentration of the complexing agent and pH of the sample solution were fully investigated. For a 5 and 20 min microextraction time, the preconcentration factors were 20 and 70, respectively. The detection limit was 0.02 μg/L of Cr(VI) and the repeatability expressed as relative standard deviation was 7%. The SDME-SIA-ETAAS technique was validated against BCR CRM 544 (lyophilized solution) and applied to ultrasensitive determination of Cr(VI) in natural waters

Immersed single-drop microextraction interfaced with sequential injection analysis for determination of Cr(VI) in natural waters by electrothermal-atomic absorption spectrometry

Energy Technology Data Exchange (ETDEWEB)

Pena, Francisco; Lavilla, Isela [Departamento de Quimica Analitica y Alimentaria, Area de Quimica Analitica, Facultad de Quimica, Universidad de Vigo, Campus As Lagoas-Marcosende, s/n, 36310 Vigo (Spain); Bendicho, Carlos [Departamento de Quimica Analitica y Alimentaria, Area de Quimica Analitica, Facultad de Quimica, Universidad de Vigo, Campus As Lagoas-Marcosende, s/n, 36310 Vigo (Spain)], E-mail: bendicho@uvigo.es

2008-04-15

Single-drop microextraction (SDME) and sequential injection analysis have been hyphenated for ultratrace metal determination by Electrothermal-Atomic Absorption Spectrometry (ETAAS). The novel method was targeted on extraction of the Cr(VI)-APDC chelate and encompasses the potential of SDME as a miniaturized and virtually solvent-free preconcentration technique, the ability of sequential injection analysis to handle samples and the versatility of furnace autosamplers for introducing microliter samples in ETAAS. The variables influencing the microextraction of Cr(VI) onto an organic solvent drop, i.e., type of organic solvent, microextraction time, stirring rate of the sample solution, drop volume, immersion depth of the drop, salting-out effect, temperature of the sample, concentration of the complexing agent and pH of the sample solution were fully investigated. For a 5 and 20 min microextraction time, the preconcentration factors were 20 and 70, respectively. The detection limit was 0.02 {mu}g/L of Cr(VI) and the repeatability expressed as relative standard deviation was 7%. The SDME-SIA-ETAAS technique was validated against BCR CRM 544 (lyophilized solution) and applied to ultrasensitive determination of Cr(VI) in natural waters.

Performance Analysis of Multi Stage Safety Injection Tank

International Nuclear Information System (INIS)

Shin, Soo Jai; Kim, Young In; Bae, Youngmin; Kang, Han-Ok; Kim, Keung Koo

2015-01-01

In general the integral reactor has such characteristics, the integral reactor requires a high flow rate of coolant safety injection at the initial stage of the accident in which the core level is relatively fast decreased, A medium flow rate of coolant safety injection at the early and middle stages of the accident in which the coolant discharge flow rate is relatively large due to a high internal pressure of the reactor vessel, and a low flow rate of coolant safety injection is required at the middle and late stages of the accident in which the coolant discharge flow rate is greatly reduced due to a decreased pressure of the reactor vessel. It is noted that a high flow rate of the integral reactor is quite smaller compared to a flow rate required in the commercial loop type reactor. However, a nitrogen pressurized safety injection tank has been typically designed to quickly inject a high flow rate of coolant when the internal pressure of the reactor vessel is rapidly decreased, and a core makeup tank has been designed to safely inject at a single mode flow rate due to a gravitational head of water subsequent to making a pressure balance between the reactor vessel and core makeup tank. As a result, in order to compensate such a disadvantage, various type systems are used in a complicated manner in a reactor according to the required characteristic of safety injection during an accident. In the present study, we have investigated numerically the performance of the multi stage safety injection tank. A parameter study has performed to understand the characteristics of the multi stage safety injection tank. The performance of the multi stage safety injection tank has been investigated numerically. When an accident occurs, the coolant in the multi stage safety injection tank is injected into a reactor vessel by a gravitational head of water subsequent to making a pressure balance between the reactor and tank. At the early stages of the accident, the high flow rate of

Performance Analysis of Multi Stage Safety Injection Tank

Energy Technology Data Exchange (ETDEWEB)

Shin, Soo Jai; Kim, Young In; Bae, Youngmin; Kang, Han-Ok; Kim, Keung Koo [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2015-10-15

In general the integral reactor has such characteristics, the integral reactor requires a high flow rate of coolant safety injection at the initial stage of the accident in which the core level is relatively fast decreased, A medium flow rate of coolant safety injection at the early and middle stages of the accident in which the coolant discharge flow rate is relatively large due to a high internal pressure of the reactor vessel, and a low flow rate of coolant safety injection is required at the middle and late stages of the accident in which the coolant discharge flow rate is greatly reduced due to a decreased pressure of the reactor vessel. It is noted that a high flow rate of the integral reactor is quite smaller compared to a flow rate required in the commercial loop type reactor. However, a nitrogen pressurized safety injection tank has been typically designed to quickly inject a high flow rate of coolant when the internal pressure of the reactor vessel is rapidly decreased, and a core makeup tank has been designed to safely inject at a single mode flow rate due to a gravitational head of water subsequent to making a pressure balance between the reactor vessel and core makeup tank. As a result, in order to compensate such a disadvantage, various type systems are used in a complicated manner in a reactor according to the required characteristic of safety injection during an accident. In the present study, we have investigated numerically the performance of the multi stage safety injection tank. A parameter study has performed to understand the characteristics of the multi stage safety injection tank. The performance of the multi stage safety injection tank has been investigated numerically. When an accident occurs, the coolant in the multi stage safety injection tank is injected into a reactor vessel by a gravitational head of water subsequent to making a pressure balance between the reactor and tank. At the early stages of the accident, the high flow rate of

Are needle-free injections a useful alternative for growth hormone therapy in children? Safety and pharmacokinetics of growth hormone delivered by a new needle-free injection device compared to a fine gauge needle.

NARCIS (Netherlands)

Dorr, H.G.; Zabransky, S.; Keller, E.; Otten, B.J.; Partsch, C.J.; Nyman, L.; Gillespie, B.K.; Lester, N.R.; Wilson, A.M.; Hyren, C.; Kuijck, M.A. van; Schuld, P.; Schoenfeld, S.L.

2003-01-01

The clinical safety, use and pharmacokinetics of a new needle-free device for delivery of growth hormone (GH) were compared with those of conventional needle injection devices. In an open-label, randomized, 4-period crossover study, 18 healthy adults received single subcutaneous injections of

Hydrogen pellet injection into Alcator C

International Nuclear Information System (INIS)

Greenwald, M.

1983-09-01

A four-shot pneumatic pellet injector, based on an ORNL design, has been built and operated on the Alcator C tokamak at MIT. The injector fires four independently-timed frozen hydrogen pellets with velocities in the range 8 x 10 4 - 1 x 10 5 cm/sec. Each contains 6 x 10 19 particles which corresponds to = 2 x 10 14 /cm 3 . The objectives of this experiment are to study pellet fueling and penetration, particle confinement, dependence of energy confinement on density profile and fueling mode, and edge physics and recycling as a function of fueling mode. Typical pre-injection plasmas have had anti n/sub e/ = 2 - 3 x 10 14 , Bt = 80 - 100 kG, Ip = 400 - 500 kA, T/sub e/(0) = 1200 - 1500 ev. A single pellet injected into this plasma will roughly double the electron density. Record plasma densities have been obtained by multiple injections. Line average densities in excess of 8 x 10 14 have been achieved, with highly peaked profiles. Central densities of 1.5 - 2 x 10 15 have been measured

Liposomal bupivacaine as a single-injection peripheral nerve block: a dose-response study.

Science.gov (United States)

Ilfeld, Brian M; Malhotra, Nisha; Furnish, Timothy J; Donohue, Michael C; Madison, Sarah J

2013-11-01

Currently available local anesthetics approved for single-injection peripheral nerve blocks have a maximum duration of fashion. The end points included the maximum voluntary isometric contraction (MVIC) of the quadriceps femoris muscle and tolerance to cutaneous electrical current in the femoral nerve distribution. Measurements were performed from baseline until quadriceps MVIC returned to 80% of baseline bilaterally. There were statistically significant dose responses in MVIC (0.09%/mg, SE = 0.03, 95% confidence interval [CI], 0.04-0.14, P = 0.002) and tolerance to cutaneous current (-0.03 mA/mg, SE = 0.01, 95% CI, -0.04 to -0.02, P 40 mg, tolerance to cutaneous current did not return to within 20% above baseline until after 24 hours in 100% of subjects (95% CI, 56%-100%). MVIC did not consistently return to within 20% of baseline until after 24 hours in 90% of subjects (95% CI, 54%-100%). Motor block duration was not correlated with bupivacaine dose (0.06 hour/mg, SE = 0.14, 95% CI, -0.27 to 0.39, P = 0.707). The results of this investigation suggest that deposition of a liposomal bupivacaine formulation adjacent to the femoral nerve results in a partial sensory and motor block of >24 hours for the highest doses examined. However, the high variability of block magnitude among subjects and inverse relationship of dose and response magnitude attests to the need for a phase 3 study with a far larger sample size, and that these results should be viewed as suggestive, requiring confirmation in a future trial.

CFD analysis of poison injection in AHWR calandria

International Nuclear Information System (INIS)

Kansal, A.K.; Kamble, M.T.; Maheshwari, N.K.; Vijayan, P.K.

2014-01-01

The present work intends to give details of design and performance validation of SDS-2. The performance is evaluated on the basis of dispersion of poison in calandria in a given period of time. Location of injection tube and injection holes, size of jet hole and number of holes are some of the design parameters which greatly affect dispersion of poison in calandria. A Computational Fluid Dynamic (CFD) study for axial and radial injection of poison was carried out using open source CFD code OpenFOAM. CFD benchmarking was done using experiments performed by Johari (Johari et al. 1997) to identify suitable turbulence model for this problem. An experimental facility simulating poison injection in moderator in presence of calandria tubes was used to further validate the CFD model is shown in the paper. CFD analysis was carried out for axial as well as radial injection for AHWR geometry. CFD analysis using OpenFOAM has been carried out to study high pressure poison injection for single jet of Shut Down System - 2 (SDS- 2) of Advanced Heavy Water Reactor (AHWR) for various design options. CFD model used in analysis have been validated with experimental data available in literature as well as experiments performed for AHWR specific geometry. Various turbulence models are tested and their adequacy for such flow problems has been established. The CFD model is then used to simulate poison injection for two design options for AHWR and their performance is compared. (author)

Safe injection practices for administration of propofol.

Science.gov (United States)

King, Cecil A; Ogg, Mary

2012-03-01

Sepsis and postoperative infection can occur as a result of unsafe practices in the administration of propofol and other injectable medications. Investigations of infection outbreaks have revealed the causes to be related to bacterial growth in or contamination of propofol and unsafe medication practices, including reuse of syringes on multiple patients, use of single-use medication vials for multiple patients, and failure to practice aseptic technique and adhere to infection control practices. Surveys conducted by AORN and other researchers have provided additional information on perioperative practices related to injectable medications. In 2009, the US Food and Drug Administration and the Centers for Disease Control and Prevention convened a group of clinicians to gain a better understanding of the issues related to infection outbreaks and injectable medications. The meeting participants proposed collecting data to persuade clinicians to adopt new practices, developing guiding principles for propofol use, and describing propofol-specific, site-specific, and practitioner-specific injection techniques. AORN provides resources to help perioperative nurses reduce the incidence of postoperative infection related to medication administration. Copyright © 2012 AORN, Inc. Published by Elsevier Inc. All rights reserved.

SIMULATIONS OF BOOSTER INJECTION EFFICIENCY FOR THE APS-UPGRADE

Energy Technology Data Exchange (ETDEWEB)

Calvey, J.; Borland, M.; Harkay, K.; Lindberg, R.; Yao, C.-Y.

2017-06-25

The APS-Upgrade will require the injector chain to provide high single bunch charge for swap-out injection. One possible limiting factor to achieving this is an observed reduction of injection efficiency into the booster synchrotron at high charge. We have simulated booster injection using the particle tracking code elegant, including a model for the booster impedance and beam loading in the RF cavities. The simulations point to two possible causes for reduced efficiency: energy oscillations leading to losses at high dispersion locations, and a vertical beam size blowup caused by ions in the Particle Accumulator Ring. We also show that the efficiency is much higher in an alternate booster lattice with smaller vertical beta function and zero dispersion in the straight sections.

Multiturn Injection into Accumulators for Heavy Ion Inertial Fusion

CERN Document Server

Prior, C R

1996-01-01

The injection of heavy ions into high current rings is complicated because it is impossible to use charge exchange in material foils to produce the singly charged heavy ions needed to keep space charge manageable on the one hand, and because losses need to be rigorously restricted to < 1 % on the other. With these constraints, the number of turns that may be injected by conventional multiturn injection is limited. This paper describes how the number may be increased by a two-dimensional technique of painting Lissajous-like patterns in x-y space, using an inclined or a corner septum. Simulation examples are presented showing the nature of the beam created in the accumulator and the likely effects of space charge forces.

Devascularization of Head and Neck Paragangliomas by Direct Percutaneous Embolization

International Nuclear Information System (INIS)

Ozyer, Umut; Harman, Ali; Yildirim, Erkan; Aytekin, Cuneyt; Akay, Tankut Hakki; Boyvat, Fatih

2010-01-01

Preoperative transarterial embolization of head and neck paragangliomas using particulate agents has proven beneficial for decreasing intraoperative blood loss. However, the procedure is often incomplete owing to extensive vascular structure and arteriovenous shunts. We report our experience with embolization of these lesions by means of direct puncture and intratumoral injection of n-butyl cyanoacrylate (NBCA) or Onyx. Ten patients aged 32-82 years who were referred for preoperative embolization of seven carotid body tumors and three jugular paragangliomas were retrospectively analyzed. Intratumoral injections were primarily performed in four cases with multiple small-caliber arterial feeders and adjunctive to transarterial embolization in six cases with incomplete devascularization. Punctures were performed under ultrasound and injections were performed under roadmap fluoroscopic guidance. Detailed angiographies were performed before and after embolization procedures. Control angiograms showed complete or near-complete devascularization in all tumors. Three tumors with multiple small-caliber arterial feeders were treated with primary NBCA injections. One tumor necessitated transarterial embolization after primary injection of Onyx. Six tumors showed regional vascularization from the vasa vasorum or small-caliber branches of the external carotid artery following the transarterial approach. These regions were embolized with NBCA injections. No technical or clinical complications related to embolization procedures occurred. All except one of the tumors were surgically removed following embolization. In conclusion, preoperative devascularization with percutaneous direct injection of NBCA or Onyx is feasible, safe, and effective in head and neck paragangliomas with multiple small-caliber arterial feeders and in cases of incomplete devascularization following transarterial embolization.

Lymphoscintigraphy and SPECT/CT in multicentric and multifocal breast cancer: does each tumour have a separate drainage pattern? Results of a Dutch multicentre study (MULTISENT)

Energy Technology Data Exchange (ETDEWEB)

Brouwer, O.R. [Antoni van Leeuwenhoek Hospital, Department of Nuclear Medicine, Netherlands Cancer Institute, Amsterdam (Netherlands); Antoni van Leeuwenhoekhospital, Amsterdam (Netherlands); Vermeeren, L.; Valdes Olmos, R.A. [Antoni van Leeuwenhoek Hospital, Department of Nuclear Medicine, Netherlands Cancer Institute, Amsterdam (Netherlands); Ploeg, I.M.C. van der; Rutgers, E.J.T.; Oldenburg, H.S.A. [Antoni van Leeuwenhoek Hospital, Department of Surgery, Netherlands Cancer Institute, Amsterdam (Netherlands); Loo, C.E. [Antoni van Leeuwenhoek Hospital, Department of Radiology, Netherlands Cancer Institute, Amsterdam (Netherlands); Pereira-Bouda, L.M.; Smit, F. [Rijnland Hospital, Department of Nuclear Medicine, Leiderdorp (Netherlands); Neijenhuis, P. [Rijnland Hospital, Department of Surgery, Leiderdorp (Netherlands); Vrouenraets, B.C. [Sint Lucas Andreas Hospital, Department of Surgery, Amsterdam (Netherlands); Sivro-Prndelj, F. [Sint Lucas Andreas Hospital, Department of Nuclear Medicine, Amsterdam (Netherlands); Jap-a-Joe, S.M.; Borgstein, P.J. [Onze Lieve Vrouwe Gasthuis, Department of Nuclear Medicine, Amsterdam (Netherlands)

2012-07-15

To investigate whether lymphoscintigraphy and SPECT/CT after intralesional injection of radiopharmaceutical into each tumour separately in patients with multiple malignancies in one breast yields additional sentinel nodes compared to intralesional injection of the largest tumour only. Patients were included prospectively at four centres in The Netherlands. Lymphatic flow was studied using planar lymphoscintigraphy and SPECT/CT until 4 h after administration of {sup 99m}Tc-nanocolloid in the largest tumour. Subsequently, the smaller tumour(s) was injected intratumorally followed by the same imaging sequence. Sentinel nodes were intraoperatively localized using a gamma ray detection probe and vital blue dye. Included in the study were 50 patients. Additional lymphatic drainage was depicted after the second and/or third injection in 32 patients (64 %). Comparison of planar images and SPECT/CT images after consecutive injections enabled visualization of the number and location of additional sentinel nodes (32 axillary, 11 internal mammary chain, 2 intramammary, and 1 interpectoral. A sentinel node contained metastases in 17 patients (34 %)). In five patients with a tumour-positive node in the axilla that was visualized after the first injection, an additional involved axillary node was found after the second injection. In two patients, isolated tumour cells were found in sentinel nodes that were only visualized after the second injection, whilst the sentinel nodes identified after the first injection were tumour-negative. Lymphoscintigraphy and SPECT/CT after consecutive intratumoral injections of tracer enable lymphatic mapping of each tumour separately in patients with multiple malignancies within one breast. The high incidence of additional sentinel nodes draining from tumours other than the largest one suggests that separate tumour-related tracer injections may be a more accurate approach to mapping and sampling of sentinel nodes in patients with multicentric or

Lymphoscintigraphy and SPECT/CT in multicentric and multifocal breast cancer: does each tumour have a separate drainage pattern? Results of a Dutch multicentre study (MULTISENT).

Science.gov (United States)

Brouwer, O R; Vermeeren, L; van der Ploeg, I M C; Valdés Olmos, R A; Loo, C E; Pereira-Bouda, L M; Smit, F; Neijenhuis, P; Vrouenraets, B C; Sivro-Prndelj, F; Jap-a-Joe, S M; Borgstein, P J; Rutgers, E J Th; Oldenburg, H S A

2012-07-01

To investigate whether lymphoscintigraphy and SPECT/CT after intralesional injection of radiopharmaceutical into each tumour separately in patients with multiple malignancies in one breast yields additional sentinel nodes compared to intralesional injection of the largest tumour only. Patients were included prospectively at four centres in The Netherlands. Lymphatic flow was studied using planar lymphoscintigraphy and SPECT/CT until 4 h after administration of (99m)Tc-nanocolloid in the largest tumour. Subsequently, the smaller tumour(s) was injected intratumorally followed by the same imaging sequence. Sentinel nodes were intraoperatively localized using a gamma ray detection probe and vital blue dye. Included in the study were 50 patients. Additional lymphatic drainage was depicted after the second and/or third injection in 32 patients (64%). Comparison of planar images and SPECT/CT images after consecutive injections enabled visualization of the number and location of additional sentinel nodes (32 axillary, 11 internal mammary chain, 2 intramammary, and 1 interpectoral. A sentinel node contained metastases in 17 patients (34%). In five patients with a tumour-positive node in the axilla that was visualized after the first injection, an additional involved axillary node was found after the second injection. In two patients, isolated tumour cells were found in sentinel nodes that were only visualized after the second injection, whilst the sentinel nodes identified after the first injection were tumour-negative. Lymphoscintigraphy and SPECT/CT after consecutive intratumoral injections of tracer enable lymphatic mapping of each tumour separately in patients with multiple malignancies within one breast. The high incidence of additional sentinel nodes draining from tumours other than the largest one suggests that separate tumour-related tracer injections may be a more accurate approach to mapping and sampling of sentinel nodes in patients with multicentric or

A new electrode design for ambipolar injection in organic semiconductors.

Science.gov (United States)

Kanagasekaran, Thangavel; Shimotani, Hidekazu; Shimizu, Ryota; Hitosugi, Taro; Tanigaki, Katsumi

2017-10-17

Organic semiconductors have attracted much attention for low-cost, flexible and human-friendly optoelectronics. However, achieving high electron-injection efficiency is difficult from air-stable electrodes and cannot be equivalent to that of holes. Here, we present a novel concept of electrode composed of a bilayer of tetratetracontane (TTC) and polycrystalline organic semiconductors (pc-OSC) covered by a metal layer. Field-effect transistors of single-crystal organic semiconductors with the new electrodes of M/pc-OSC/TTC (M: Ca or Au) show both highly efficient electron and hole injection. Contact resistance for electron injection from Au/pc-OSC/TTC and hole injection from Ca/pc-OSC/TTC are comparable to those for electron injection from Ca and hole injection from Au, respectively. Furthermore, the highest field-effect mobilities of holes (22 cm 2  V -1  s -1 ) and electrons (5.0 cm 2  V -1  s -1 ) are observed in rubrene among field-effect transistors with electrodes so far proposed by employing Ca/pc-OSC/TTC and Au/pc-OSC/TTC electrodes for electron and hole injection, respectively.One of technological challenges building organic electronics is efficient injection of electrons at metal-semiconductor interfaces compared to that of holes. The authors show an air-stable electrode design with induced gap states, which support Fermi level pinning and thus ambipolar carrier injection.

Multiple collagenase injections are safe for treatment of Dupuytren's contractures.

Science.gov (United States)

Gajendran, Varun K; Hentz, Vincent; Kenney, Deborah; Curtin, Catherine M

2014-07-01

The authors report the case of a 65-year-old, right-hand-dominant man who had severe Dupuytren's disease with multiple cords and flexion contractures of the metacarpophalangeal and proximal interphalangeal joints of both hands and underwent repeated collagenase injections for treatment. Collagenase has been shown to be safe and effective in the treatment of Dupuytren's contractures when administered as a single dose, but the results of multiple injections over a prolonged period are unknown. Antibodies to collagenase develop in all patients after several treatments, raising concerns about safety and efficacy as a result of sensitization from repeated exposures. The antibodies generated as a result of repeated exposure to collagenase could theoretically render it less effective with time and could also lead to immune reactions as severe as anaphylaxis. The authors present the case of a single patient who experienced continued correction of his contractures with only minor and self-limited adverse reactions after administration of 12 collagenase doses through 15 injections during a 4-year period. Over time, the injections continued to be effective at correcting metacarpophalangeal joint contractures, but less effective at correcting proximal interphalangeal joint contractures. The patient did eventually require a fasciectomy, but the safety and modest success of the repeated collagenase injections shows promise for a less invasive treatment with a better risk profile than open fasciectomy. Although further studies are needed, repeated administration of collagenase appears to be safe and modestly effective for severe Dupuytren's contractures, although a fasciectomy may ultimately be required in the most severe cases. Copyright 2014, SLACK Incorporated.

Single well surfactant test to evaluate surfactant floods using multi tracer method

Science.gov (United States)

Sheely, Clyde Q.

1979-01-01

Data useful for evaluating the effectiveness of or designing an enhanced recovery process said process involving mobilizing and moving hydrocarbons through a hydrocarbon bearing subterranean formation from an injection well to a production well by injecting a mobilizing fluid into the injection well, comprising (a) determining hydrocarbon saturation in a volume in the formation near a well bore penetrating formation, (b) injecting sufficient mobilizing fluid to mobilize and move hydrocarbons from a volume in the formation near the well bore, and (c) determining the hydrocarbon saturation in a volume including at least a part of the volume of (b) by an improved single well surfactant method comprising injecting 2 or more slugs of water containing the primary tracer separated by water slugs containing no primary tracer. Alternatively, the plurality of ester tracers can be injected in a single slug said tracers penetrating varying distances into the formation wherein the esters have different partition coefficients and essentially equal reaction times. The single well tracer method employed is disclosed in U.S. Pat. No. 3,623,842. This method designated the single well surfactant test (SWST) is useful for evaluating the effect of surfactant floods, polymer floods, carbon dioxide floods, micellar floods, caustic floods and the like in subterranean formations in much less time and at much reduced cost compared to conventional multiwell pilot tests.

Prognostic value of preoperative intratumoral FDG uptake heterogeneity in patients with epithelial ovarian cancer

Energy Technology Data Exchange (ETDEWEB)

Lee, Maria; Kim, Hee Seung; Chung, Hyun Hoon; Kim, Jae-Weon; Park, Noh-Hyun; Song, Yong Sang [Seoul National University College of Medicine, Department of Obstetrics and Gynecology, Cancer Research Institute, Seoul (Korea, Republic of); Lee, Hyunjong; Cheon, Gi Jeong [Seoul National University College of Medicine, Department of Nuclear Medicine, Cancer Research Institute, Seoul (Korea, Republic of)

2017-01-15

To investigate the prognostic value of intratumoral FDG uptake heterogeneity (IFH) derived from PET/CT in patients with epithelial ovarian cancer (EOC). We retrospectively reviewed patients with pathologically proven epithelial ovarian cancer who underwent preoperative {sup 18}F-FDG PET/CT scans. PET/CT parameters such as maximum and average standardized uptake values (SUV{sub max} and SUV{sub avg}), sum of all metabolic tumour volume (MTV), cumulative total lesion glycolysis (TLG) and IFH were assessed. Regression analyses were used to identify clinicopathological and imaging variables associated with disease-free survival (DFS). Clinicopathological data were reviewed for 61 eligible patients. The median duration of DFS was 13 months (range, 6-26 months), and 18 (29.5 %) patients experienced recurrence. High IFH values were associated with tumour recurrence (P = 0.005, hazard ratio 4.504, 95 % CI 1.572-12.902). The Kaplan-Meier survival graphs showed that DFS significantly differed in groups categorized based on IFH (P = 0.002, log-rank test). Moreover, there were significant differences in DFS (P = 0.009) and IFH (P = 0.040) between patients with and without recurrence. Preoperative IFH measured by {sup 18}F-FDG PET/CT was significantly associated with EOC recurrence. FDG-based heterogeneity could be a useful and potential predicator of EOC recurrence before treatment. (orig.)

Distribution and excretion of mercury compounds in rats over a long period after a single injection

Energy Technology Data Exchange (ETDEWEB)

Swensson, A; Ulfvarson, U

1968-01-01

Rats were given single subcutaneous injections of methyl mercuric hydroxide, mercury (II) nitrate and phenyl mercuric hydroxide. The elimination of the compounds and the concentration in the organs at different times were followed by means of isotope techniques, for almost 6 months. The rate of excretion changes during the observation period. A calculated biological half-life therefore will be different from time to time. If the elimination during the first 9 days is considered the half-life is 5 days for mercury (II) nitrate and phenyl mercuric hydroxide and 16 days for methyl mercuric hydroxide. After this the excretion rate becomes slower and slower. The distribution in the organs varies during the first part of the period. The blood concentration decreases rapidly for all compounds, while the concentrations in the kidneys increases and reaches a maximum after some days. The same holds true for the brain and testis when mercury (II) nitrate and methyl mercuric hydroxide are considered. The elimination from the kidneys, the brain and the testes is slower than from other organs for all compounds. The concentrations in different parts of the brain are rather similar, though somewhat higher concentration in lobus olfactorius is indicated.

MHC Intratumoral Heterogeneity May Predict Cancer Progression and Response to Immunotherapy

Directory of Open Access Journals (Sweden)

Irene Romero

2018-01-01

Full Text Available An individual tumor can present intratumoral phenotypic heterogeneity, containing tumor cells with different phenotypes that do not present irreversible genetic alterations. We have developed a mouse cancer model, named GR9, derived from a methylcholanthrene-induced fibrosarcoma that was adapted to tissue culture and cloned into different tumor cell lines. The clones showed diverse MHC-I phenotypes, ranging from highly positive to weakly positive MHC-I expression. These MHC-I alterations are due to reversible molecular mechanisms, because surface MHC-I could be recovered by IFN-γ treatment. Cell clones with high MHC-I expression demonstrated low local oncogenicity and high spontaneous metastatic capacity, whereas MHC-I-low clones showed high local oncogenicity and no spontaneous metastatic capacity. Although MHC-I-low clones did not metastasize, they produced MHC-I-positive dormant micrometastases controlled by the host immune system, i.e., in a state of immunodormancy. The metastatic capacity of each clone was directly correlated with the host T-cell subpopulations; thus, a strong decrease in cytotoxic and helper T lymphocytes was observed in mice with numerous metastases derived from MHC-I positive tumor clones but a strong increase was observed in those with dormant micrometastases. Immunotherapy was administered to the hosts after excision of the primary tumor, producing a recovery in their immune status and leading to the complete eradication of overt spontaneous metastases or their decrease. According to these findings, the combination of MHC-I surface expression in primary tumor and metastases with host T-cell subsets may be a decisive indicator of the clinical outcome and response to immunotherapy in metastatic disease, allowing the identification of responders to this approach.

Spray combustion of biomass-based renewable diesel fuel using multiple injection strategy in a constant volume combustion chamber

KAUST Repository

Jing, Wei

2016-05-26

Effect of a two-injection strategy associated with a pilot injection on the spray combustion process was investigated under conventional diesel combustion conditions (1000 K and 21% O2 concentration) for a biomass-based renewable diesel fuel, i.e., biomass to liquid (BTL), and a regular No. 2 diesel in a constant volume combustion chamber using multiband flame measurement and two-color pyrometry. The spray combustion flame structure was visualized by using multiband flame measurement to show features of soot formation, high temperature and low temperature reactions, which can be characterized by the narrow-band emissions of radicals or intermediate species such as OH, HCHO, and CH. The objective of this study was to identify the details of multiple injection combustion, including a pilot and a main injection, and to provide further insights on how the two injections interact. For comparison, three injection strategies were considered for both fuels including a two-injection strategy (Case TI), single injection strategy A (Case SA), and single injection strategy B (Case SB). Multiband flame results show a strong interaction, indicated by OH emissions between the pilot injection and the main injection for Case TI while very weak connection is found for the narrow-band emissions acquired through filters with centerlines of 430 nm and 470 nm. A faster flame development is found for the main injection of Case TI compared to Cases SA and SB, which could be due to the high temperature environment and large air entrainment from the pilot injection. A lower soot level is observed for the BTL flame compared to the diesel flame for all three injection types. Case TI has a lower soot level compared to Cases SA and SB for the BTL fuel, while the diesel fuel maintains a similar soot level among all three injection strategies. Soot temperature of Case TI is lower for both fuels, especially for diesel. Based on these results, it is expected that the two-injection strategy could be

New injection scheme using a pulsed quadrupole magnet in electron storage rings

Directory of Open Access Journals (Sweden)

Kentaro Harada

2007-12-01

Full Text Available We demonstrated a new injection scheme using a single pulsed quadrupole magnet (PQM with no pulsed local bump at the Photon Factory Advanced Ring (PF-AR in High Energy Accelerator Research Organization (KEK. The scheme employs the basic property of a quadrupole magnet, that the field at the center is zero, and nonzero elsewhere. The amplitude of coherent betatron oscillation of the injected beam is effectively reduced by the PQM; then, the injected beam is captured into the ring without largely affecting the already stored beam. In order to investigate the performance of the scheme with a real beam, we built the PQM providing a higher field gradient over 3  T/m and a shorter pulse width of 2.4  μs, which is twice the revolution period of the PF-AR. After the field measurements confirmed the PQM specifications, we installed it into the ring. Then, we conducted the experiment using a real beam and consequently succeeded in storing the beam current of more than 60 mA at the PF-AR. This is the first successful beam injection using a single PQM in electron storage rings.

A Pressure Injection System for Investigating the Neuropharmacology of Information Processing in Awake Behaving Macaque Monkey Cortex.

Science.gov (United States)

Veith, Vera K; Quigley, Cliodhna; Treue, Stefan

2016-03-14

The top-down modulation of feed-forward cortical information processing is functionally important for many cognitive processes, including the modulation of sensory information processing by attention. However, little is known about which neurotransmitter systems are involved in such modulations. A practical way to address this question is to combine single-cell recording with local and temporary neuropharmacological manipulation in a suitable animal model. Here we demonstrate a technique combining acute single-cell recordings with the injection of neuropharmacological agents in the direct vicinity of the recording electrode. The video shows the preparation of the pressure injection/recording system, including preparation of the substance to be injected. We show a rhesus monkey performing a visual attention task and the procedure of single-unit recording with block-wise pharmacological manipulations.

Development of a 100 W, single frequency, CW Nd:YAG Laser

International Nuclear Information System (INIS)

Veitch, P.J.; Mudge, D.; Munch, J.; Hamilton, M.W.; Ostermeyer, M.; Hosken, D.; Brooks, A.

2002-01-01

Full text: High power, diode-laser-pumped, continuous wave (cw) solid-state lasers with excellent beam quality, efficiency and reliability are required for demanding applications, including gravitational wave interferometry, where current additional requirements include single frequency, low noise and Nd:YAG. Our approach is a chain of injection locked laser oscillators, theoretically capable of achieving the lowest noise possible. We use a single-frequency (100 mW) master laser to injection lock a medium-power (10 W) laser that in turn injection locks a 100 W laser. Injection locking requires an optimized, single mode, power slave laser at each stage. We shall describe the nearly completed 10 W brass-board laser, which will also be deployed at the ACIGA Test Facility at Gingin. We shall also describe our 100 W laser using a scalable diode pumping scheme, an active control of thermal lensing and a stable-unstable resonator. Initial tests showed mode control to be limited by thermal focusing and thermally induced birefringence in the Nd:YAG medium at 70 W output. Recent efforts have identified the source of the thermal lens and significantly reduced its magnitude, leading to a modified design. We shall present our latest results from the experiments to demonstrate single mode, single frequency laser at 100 W

A Single-blind, Split-face, Randomized, Pilot Study Comparing the Effects of Intradermal and Intramuscular Injection of Two Commercially Available Botulinum Toxin A Formulas to Reduce Signs of Facial Aging

Science.gov (United States)

Sapra, Priya; Sapra, Sheetal; Khanna, Julie; Mraud, Kelli; Bonadonna, Jennifer

2017-01-01

Objective: To examine the effectiveness of intradermal botulinum toxin type A injection in improving skin texture and midface lift while reducing pore size and sebum production, as well as investigate the differences in effectiveness between onabotulinumtoxinA and abobotulinumtoxinA using intradermal and intramuscular injection methods. Design: A 16-week, single-blind, split-face, randomized study. Each patient served as their own control, receiving onabotulinumtoxinA and abobotulinumtoxinA randomized to either the left or right side of the face. Patients received intradermal botulinum toxin type A injections at Week 0 and intramuscular botulinum toxin type A injections at Week 2. Participants: Ten women aged 35 to 65 years who exhibited static rhytids in the glabellar and periorbital area. Measurements: The primary endpoint was efficacy of split-face treatment of intradermal and intramuscular onabotulinumtoxinA and abobotulinumtoxinA as assessed by a blinded evaluator using baseline and post-treatment photographs. The secondary endpoints included safety as assessed by adverse events and patient satisfaction measured by questionnaires completed at baseline and post-treatment. Results: Intradermal injection of botulinum toxin type A led to a statistically significant improvement in skin texture (p=0.004) while also resulting in mild midface lift (p=0.024), but did not provide a significant reduction of pore size and sebum production. There was no statistically significant difference between onabotulinumtoxinA and abobotulinumtoxinA when injected intradermally or intramuscularly. Conclusion: Intradermal injection of botulinum toxin type A appears to be a safe and effective therapy that provides an improvement in facial skin texture and midface lift. Registry: clinicaltrials.gov (ID#: NCT02907268). PMID:28367260

Injectable loop recorder implantation in an ambulatory setting by advanced practice providers: Analysis of outcomes.

Science.gov (United States)

Kipp, Ryan; Young, Natasha; Barnett, Anne; Kopp, Douglas; Leal, Miguel A; Eckhardt, Lee L; Teelin, Thomas; Hoffmayer, Kurt S; Wright, Jennifer; Field, Michael

2017-09-01

Implantable loop recorder (ILR) insertion has historically been performed in a surgical environment such as the electrophysiology (EP) lab. The newest generation loop recorder (Medtronic Reveal LINQ™, Minneapolis, MN, USA) is injectable with potential for implantation in a non-EP lab setting by advanced practice providers (APPs) facilitating improved workflow and resource utilization. We report the safety and efficacy of injectable ILR placement in the ambulatory care setting by APPs. A retrospective review was performed including all patients referred for injectable ILR placement from March 2014 to November 2015. All device placement procedures were performed in an ambulatory care setting using the standard manufacturer deployment kit with sterile technique and local anesthetic following a single dose of intravenous antibiotics. Acute procedural success and complication rates following injectable ILR placement in the ambulatory setting were reviewed. During the study period, 125 injectable ILRs were implanted. Acute procedural success with adequate sensing (R-waves ≥ 0.2 mV) occurred in 100% of patients. There were no acute procedural complications. Subacute complications occurred in two patients (1.6% of implantations), including one possible infection treated with oral antibiotics and one device removal due to pain at the implant site. In this retrospective single-center study, implantation of injectable ILR in an ambulatory care setting by APPs following a single dose of intravenous antibiotics and standard manufacturer technique yielded a low complication rate with high acute procedural success. Use of this implantation strategy may improve EP lab workflow while providing a safe and effective technique for device placement. © 2017 Wiley Periodicals, Inc.

Bladder base/trigone injection is safe and as effective as bladder body injection of onabotulinumtoxinA for idiopathic detrusor overactivity refractory to antimuscarinics.

Science.gov (United States)

Kuo, Hann-Chorng

2011-09-01

The purpose of this study was to evaluate the efficacy and safety of onabotulinumtoxinA injections at bladder base/trigone and compare with injections at bladder body or bladder body/trigone for the treatment of idiopathic detrusor overactivity (IDO) refractory to antimuscarinics. A single blind, randomized, paralleled, actively controlled trial was performed in patients with urodynamically proven IDO who failed antimuscarinic therapy. Patients were randomly assigned to receive intravesical injections of 100 U of onabotulinumtoxinA into three different bladder sites. All treatments were evaluated by voiding diary variables, urgency severity score, urodynamic studies, and patient perception of bladder condition. Long-term success rates over 12 months were also determined. Among the patients, 37 were randomized to injections in the bladder body, 35 into the bladder body/trigone, and 33 into the bladder base/trigone. Successful results were reported in 76 (72%) patients at 3 months: 26 (70%) in the bladder body group, 26 (74%) in the bladder body/trigone group, and 24 (73%) in the bladder base/trigone group. There were no significant differences in success rates, changes in urgency and urgency incontinence episodes, urodynamic variables, or long-term success rates among the three subgroups. The incidence of adverse events was similar among three groups. No vesicoureteral reflux was noted in all patients with or without involving trigone injection. Intravesical onabotulinumtoxinA injection is an effective treatment for IDO regardless of the bladder injection site. Bladder base/trigone injection is as safe and effective as bladder body injections with or without trigone involvement. Copyright © 2011 Wiley-Liss, Inc.

Pellet injection experiments on tokamaks in ASIPP, China

International Nuclear Information System (INIS)

Yang, Y.; Bao, Y.; Li, J.; Gu, X.; He, Y.

1999-01-01

Pellet Injection has been proven to be an effective method for deep fuelling of fusion devices. Improvements of both the particle confinement and the energy confinement were observed in many experiments. In HT-6M and HT-7 tokamaks, single and multi-pellet experiments are tried, and attractive results are obtained

Computational simulation of multi-strut central lobed injection of hydrogen in a scramjet combustor

Directory of Open Access Journals (Sweden)

Gautam Choubey

2016-09-01

Full Text Available Multi-strut injection is an approach to increase the overall performance of Scramjet while reducing the risk of thermal choking in a supersonic combustor. Hence computational simulation of Scramjet combustor at Mach 2.5 through multiple central lobed struts (three struts have been presented and discussed in the present research article. The geometry and model used here is slight modification of the DLR (German Aerospace Center scramjet model. Present results show that the presence of three struts injector improves the performance of scramjet combustor as compared to single strut injector. The combustion efficiency is also found to be highest in case of three strut fuel injection system. In order to validate the results, the numerical data for single strut injection is compared with experimental result which is taken from the literature.

Pharmacokinetics and tissue distribution of enrofloxacin after single intramuscular injection in Pacific white shrimp.

Science.gov (United States)

Fang, X; Zhou, J; Liu, X

2018-02-01

The pharmacokinetic properties and tissue distribution of enrofloxacin (EF) were investigated after single intramuscular (i.m.) dose of 10 mg/kg body weight (b.w.) in Pacific white shrimp at 22 to 25°C. EF and its metabolite ciprofloxacin (CF) were determined by high-performance liquid chromatography. After i.m. administration, EF was absorbed quickly, and the peak of EF concentration (C max ) reached at first time point in hemolymph. The volume of distribution V d(area) of EF was 3.84 L/kg, indicating that the distribution of EF was good. The area under the concentration-time curve (AUC) of EF was 90.1 and 274.2 μg hr/ml in muscle and hepatopancreas, respectively, which was higher than 75.8 μg hr/ml in hemolymph. The EF elimination was slow in muscle and hepatopancreas with the half-life (T 1/2β ) of 52.3 and 75.8 hr, respectively. CF, the mainly metabolite of EF, was detected in hemolymph, muscle and hepatopancreas. The C max was 0.030, 0.013 and 0.218 μg/ml, respectively. Based on a minimum inhibitory concentration (MIC) of 0.006-0.032 μg/ml for susceptible strains, EF i.m. injected at a dose 10 mg/kg could be efficacious against common pathogenic bacteria of Pacific white shrimp. © 2017 John Wiley & Sons Ltd.

Long acting injectable hormonal contraceptives.

Science.gov (United States)

Fraser, I S

1982-03-01

Injectable hormonal preparations can be highly effective and satisfactory contraceptives. The two main preparations available today are depot medroxy progesterone acetate (DMPA) and norethisterone oenanthate (NET-OEN), but several other approaches are currently under clinical trial. Injectable contraceptives have some unique advantages which give them justifiably wide appeal amongst many groups of women. However, they do have a number of disadvantages including invariable menstrual disturbance and a delay in the return of fertility. One formulation of DMPA, Depo-Provera, is probably the most extensively investigated single hormonal contraceptive ever made. These studies indicate that it is remarkably safe and does not face any more unresolved issues than the combined pill, intrauterine device or tubal sterilization. However, for a number of disparate emotional and political reasons it has attracted the attention of several consumer and feminist groups, who have waged a prolonged and quite unjustified campaign against it. It is to be hoped that future debate will be conducted on a more informed, rational and less emotional basis. Injectable contraceptives should have an important place in the family planning armamentarium of all countries, and current developments should lead to a decrease in concerns about presently available agents. This should further increase the widespread acceptability of this approach to contraception.

Non-Liouvillean ion injection via resonantly enhanced two-photon ionization

Directory of Open Access Journals (Sweden)

B. A. Knyazev

2004-03-01

Full Text Available The charge-exchange method is now one of the main techniques for ion injection into accelerators and storage rings. The disadvantages of conventional methods, based on the atom or ion stripping in a material target, are emittance growth, energy straggling, and production of ions in many charge states. Recently suggested stripping methods based on direct photoionization require employment of hard-UV lasers, which still do not exist and must obviously be very bulky and expensive. An alternative method, suggested for injection of proton beams, employs excitation of the atom to 3p intermediate state with subsequent Lorentz ionization in a magnetic field gradient. This technique applies rigid requirements to laser characteristic and is not free of growing of the beam divergence. In this paper a variant of the stripping technique based on the resonantly enhanced two-photon ionization (RETPI is considered. The technique allows ionization of singly charged ions of the elements from helium to bismuth. A variant of the technique can be used for proton injection. RETPI can be applied for both ion injection and stacking, as well as for diagnostics of ion beam characteristics on the orbit. Stripping efficiency can be about 100% for the singly charged ions having the singlet ground state and decreases for the other ions. Special methods for “cleaning” unwanted atomic states in such ions, that can provide high stripping efficiency, are discussed. Excimer lasers with very moderate parameters can be employed for implementation of this technique for almost all elements. Numerical examples show that for most of the singly charged ions and for hydrogen atom necessary laser-beam energy density is merely 0.5–8  J/cm^{2} for a 1 m interaction region, and is 10 times higher for several light ions.

Three-Dimensional Changes in the Midface Following Malar Calcium Hydroxyapatite Injection in a Cadaver Model.

Science.gov (United States)

Gatherwright, James R; Brown, Matthew S; Katira, Kristopher M; Rowe, David J

2015-08-01

Three-dimensional (3D) changes in the midface following malar calcium hydroxyapatite (CaHa) injection have not been systematically analyzed. The authors analyzed 3D volume changes in midface and naso-labial fold (NLF) volume, as well as lateral movement in the NLF/naso-labial crease (NLC) junction following malar injection of CaHa in a cadaver model. A single surgeon injected CaHa in the supraperiosteal plane. Sequential images were obtained with the VECTRA 3D system pre- and post-1.5- and 3-cc CaHa injections. All measurements were performed by a single examiner. Injection location was verified anatomically. Injections were performed in 16 fresh cadaver hemi-faces. Maximal increases in projection were centered on the malar injection site, with associated decreases in projection and volume in the infero-medial locations. Relative mean increases in volume of 3.16 cc and 4.94 cc were observed following the 1.5-cc and 3-cc injections, respectively. There was a relative decrease in the volume of the NLF of -0.3 cc and -0.4 cc following the 1.5- and 3-cc injections, respectively. Injection of CaHa was associated with lateral movements of the NLF-NLC junction at the level of the nasal sill, philtral columns, and oral commissure, measuring 2.7, 2.5, and 1.9 mm and 2.8, 2.9, and 2.4 mm following the 1.5- and 3-cc injections, respectively. Anatomical dissection verified the location in the supraperiosteal space and within the middle malar fat pad. Following malar CaHa injection, 3D photographic analysis showed a measureable lifting effect with recruitment of ptotic tissue and lateral movement of the NLF-NLC junction in a cadaver model. © 2015 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

The efficacy of preventive parasternal single injection of bupivacaine on intubation time, blood gas parameters, narcotic requirement, and pain relief after open heart surgery: A randomized clinical trial study

Directory of Open Access Journals (Sweden)

Mahmoud Saeidi

2011-01-01

Full Text Available Background: Postsurgical pain usually results in some complications in the patients. This study has tried to investigate the effects of parasternal single injection of bupivacaine on postoperative pulmonary and pain consequences in patients after open heart surgery. Methods: : In a prospective double blind clinical study, 100 consenting patients undergoing elective open heart surgery were randomized into two groups. In case group, bupivacaine was injected at both sides of sternum, immediately before sternal closure. In the control group, no intervention was performed. Then, the patients were investigated regarding intubation period, length of ICU stay, arterial blood gas (ABG parameters, morphine requirement, and their severity of postoperative pain using a visual analogue scale (VAS device. Results: No differences were found between the two groups regarding to age, sex, pump time, operation time, and body mass index and preoperative cardiac ejection fraction. Mean intubation length in case group was much shorter than that in control group. Mean PaO 2 in case group was lower in different checking times in postoperative period. The patients in the case group needed less morphine compared to those in the control group during the 24-hour observation period in the ICU. Finally, mean VAS scores of pain in case group were significantly lower than those in control group at 6, 12, and 24 hours postoperatively. Conclusions: Patients′ pain relief by parasternal single injection of bupivacaine in early postoperative period can facilitate earlier ventilator weaning and tracheal extubation after open heart surgery as well as achieving lower pain scores and narcotic requirements.

An Exploratory Study Into the Role of Dynamic Contrast-Enhanced Magnetic Resonance Imaging or Perfusion Computed Tomography for Detection of Intratumoral Hypoxia in Head-and-Neck Cancer

Energy Technology Data Exchange (ETDEWEB)

Newbold, Kate [Royal Marsden Hospital, Sutton (United Kingdom); Castellano, Isabel [Institute of Cancer Research, London (United Kingdom); Charles-Edwards, Elizabeth [Institute of Cancer Research, Sutton, Surrey (United Kingdom); Mears, Dorothy; Sohaib, Aslam [Royal Marsden Hospital, Sutton (United Kingdom); Leach, Martin [Institute of Cancer Research, Sutton, Surrey (United Kingdom); Rhys-Evans, Peter; Clarke, Peter; Fisher, Cyril [Royal Marsden Hospital, London (United Kingdom); Harrington, Kevin [Institute of Cancer Research, London (United Kingdom); Royal Marsden Hospital, London (United Kingdom); Nutting, Christopher [Royal Marsden Hospital, London (United Kingdom)

2009-05-01

Purpose: Hypoxia in patients with head-and-neck cancer (HNC) is well established and known to cause radiation resistance and treatment failure in the management of HNC. This study examines the role of parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and perfusion computed tomography (CT) as surrogate markers of intratumoral hypoxia, defined by using the exogenous marker of hypoxia pimonidazole and the endogenous marker carbonic anhydrase 9 (CA9). Methods and Materials: Patients with HNC underwent preoperative DCE-MRI, perfusion CT, and pimonidazole infusion. Imaging parameters were correlated with pimonidazole and CA9 staining. The strength of correlations was tested by using a two-tailed Spearman's rank correlation coefficient. Results: Twenty-three regions of interest were analyzed from the 7 patients who completed the DCE-MRI studies. A number of statistically significant correlations were seen between DCE-MRI parameters (volume transfer between blood plasma and extracellular extravascular space [EES], volume of EES, rate constant between EES and blood plasma, time at arrival of contrast inflow, time to peak, average gradient, and time to onset) and areas with a pimonidazole score of 4. In the case of CA9 staining, only a weak correlation was shown with wash-in rate. There were no significant correlations between perfusion CT parameters and pimonidazole staining or CA9 expression. Conclusion: Intratumoral hypoxia in patients with HNC may be predicted by using DCE-MRI; however, perfusion CT requires further investigation.

Improved estimation of receptor density and binding rate constants using a single tracer injection and displacement

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