A Randomized Phase 2 Trial of 177Lu Radiolabeled Anti-PSMA Monoclonal Antibody J591in Patients with High-Risk Castrate, Biochemically Relapsed Prostate Cancer

DTIC Science & Technology

2012-09-01

micrometastases that may be targeted with radioimmunotherapy. Prostate specific membrane antigen (PSMA) is the single, most well-established, highly restricted...Radiolabeled anti- prostate specific membrane antigen (PSMA) monoclonal antibody J591 (177Lu-J591) for nonmetastatic castration-resistant prostate cancer...rationale for systemic salvage targeted anti- prostate specific membrane antigen radioimmunotherapy. Adv Urol 2012, Article ID 921674, doi:10.1155

Radioimmunotherapy with an antibody to HPV16 E6 oncoprotein is effective in experimental cervical tumor expressing low levels of E6

PubMed Central

Jiang, Zewei; Wang, Xing Guo; Einstein, Mark H; Goldberg, Gary L; Casadevall, Arturo

2010-01-01

Purpose HPV16 is associated with ∼50% of all cervical cancers worldwide. The E6 and E7 genes of oncogenic HPV types, such as HPV16, are necessary for the HPV transforming function and tumorogenesis making them ideal targets for novel treatments. Radioimmunotherapy employs systemically administered radiolabeled monoclonal antibodies (mAbs) that bind to tumor-associated antigens. Previously we demonstrated in mice that radioimmunotherapy targeting viral antigens with mAb to HPV16 E6 suppressed CasKi cervical tumors expressing high levels of E6 (∼600 copies of HPV per cell). However, that study opened the question whether radioimmunotherapy can suppress the growth of cervical tumors with low E6 and E7 expression, such as may be seen in patients. Experimental Design We evaluated the expression of E6 in patients' tumors and in the SiHa cell line expressing low levels of E6 and E7 (1–2 copies of HPV per cell) and found them comparable. We initiated SiHa tumors in nude mice, radiolabeled C1P5 mAb to E6 with a beta-emitter 188-Rhenium (188Re) and treated tumor-bearing mice with: (1) 200 µCi 188Re-C1P5 alone; (2) proteasome inhibitor MG132 alone; (3) MG132 followed by 200 µCi 188Re-C1P5; (4) unlabeled C1P5; (5) 200 µCi 188Re-18B7 (isotype-matching control mAb); (6) no treatment. 188Re-C1P5 alone and in combination with MG-132 significantly retarded tumor growth compared to all control groups. Conclusions Our data demonstrate the possibility to suppress tumor growth by targeting viral antigens even in cervical tumors with low E6 expression and provide additional evidence for the potential usefulness of radioimmunotherapy targeting HPV-related antigens in the clinic. PMID:20861673

Improved radioimmunotherapy of hematologic malignancies. [Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Press, O.W.

This research project proposes to develop novel new approaches of improving the radioimmunodetection and radioimmunotherapy of malignancies by augmenting retention of radioimmunoconjugates by tumor cells. The approaches shown to be effective in these laboratory experiments will subsequently be incorporated into out ongoing clinical trials in patients. Specific project objectives include: to study the rates of endocytosis, intracellular routing, and metabolic degradation of radiolabeled monoclonal antibodies targeting tumor-associated antigens on human leukemia and lymphoma cells; To examine the effects of lysosomotropic amines (e.g. chloroquine, amantadine), carboxylic ionophores (monensin, nigericin), and thioamides (propylthiouracil), on the retention of radiolabeled MoAbs by tumor cells;more » to examine the impact of newer radioiodination techniques (tyramine cellobiose, paraiodobenzoyl) on the metabolic degradation of radioiodinated antibodies; to compare the endocytosis, intracellular routing, and degradation of radioimmunoconjugates prepared with different radionuclides ({sup 131}Iodine, {sup 111}Indium, {sup 90}Yttrium, {sup 99m}Technetium, {sup 186}Rhenium); and to examine the utility of radioimmunoconjugates targeting oncogene products for the radioimmunotherapy and radioimmunoscintigraphy of cancer.« less

Improved radioimmunotherapy of hematologic malignancies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Press, O.W.

This research project proposes to develop novel new approaches of improving the radioimmunodetection and radioimmunotherapy of malignancies by augmenting retention of radioimmunoconjugates by tumor cells. The approaches shown to be effective in these laboratory experiments will subsequently be incorporated into out ongoing clinical trials in patients. Specific project objectives include: to study the rates of endocytosis, intracellular routing, and metabolic degradation of radiolabeled monoclonal antibodies targeting tumor-associated antigens on human leukemia and lymphoma cells; To examine the effects of lysosomotropic amines (e.g. chloroquine, amantadine), carboxylic ionophores (monensin, nigericin), and thioamides (propylthiouracil), on the retention of radiolabeled MoAbs by tumor cells;more » to examine the impact of newer radioiodination techniques (tyramine cellobiose, paraiodobenzoyl) on the metabolic degradation of radioiodinated antibodies; to compare the endocytosis, intracellular routing, and degradation of radioimmunoconjugates prepared with different radionuclides ({sup 131}Iodine, {sup 111}Indium, {sup 90}Yttrium, {sup 99m}Technetium, {sup 186}Rhenium); and to examine the utility of radioimmunoconjugates targeting oncogene products for the radioimmunotherapy and radioimmunoscintigraphy of cancer.« less

Alpha imaging confirmed efficient targeting of CD45-positive cells after astatine-211 (211At)-radioimmunotherapy for hematopoietic cell transplantation

PubMed Central

Frost, Sofia H.L.; Miller, Brian W.; Bäck, Tom A.; Santos, Erlinda B.; Hamlin, Donald K.; Knoblaugh, Sue E.; Frayo, Shani L.; Kenoyer, Aimee L.; Storb, Rainer; Press, Oliver W.; Wilbur, D. Scott; Pagel, John M.; Sandmaier, Brenda M.

2015-01-01

Alpha-radioimmunotherapy targeting CD45 may substitute for total body irradiation in hematopoietic cell transplantation (HCT) preparative regimens for lymphoma. Our goal was to optimize the anti-CD45 monoclonal antibody (MAb; CA12.10C12) protein dose for astatine-211 (211At)-radioimmunotherapy, extending the analysis to include intra-organ 211At activity distribution and α-imaging-based small-scale dosimetry, along with immunohistochemical staining. Methods Eight normal dogs were injected with either 0.75 (n=5) or 1.00 mg/kg (n=3) of 211At-B10-CA12.10C12 (11.5–27.6 MBq/kg). Two were euthanized and necropsied 19–22 hours post injection (p.i.), and six received autologous HCT three days after 211At-radioimmunotherapy, following lymph node and bone marrow biopsies at 2–4 and/or 19 hours p.i. Blood was sampled to study toxicity and clearance; CD45 targeting was evaluated by flow cytometry. 211At localization and small-scale dosimetry were assessed using two α-imaging systems: α-camera and iQID. Results Uptake of 211At was highest in spleen (0.31–0.61 %IA/g), lymph nodes (0.02–0.16 %IA/g), liver (0.11–0.12 %IA/g), and marrow (0.06–0.08 %IA/g). Lymphocytes in blood and marrow were efficiently targeted using either MAb dose. Lymph nodes remained unsaturated, but displayed targeted 211At localization in T lymphocyte-rich areas. Absorbed doses to blood, marrow, and lymph nodes were estimated at 3.1, 2.4, and 3.4 Gy/166 MBq, respectively. All transplanted dogs experienced transient hepatic toxicity. Liver enzyme levels were temporarily elevated in 5 of 6 dogs; 1 treated with 1.00 mg MAb/kg developed ascites and was euthanized 136 days after HCT. Conclusion 211At-anti-CD45 radioimmunotherapy with 0.75 mg MAb/kg efficiently targeted blood and marrow without severe toxicity. Dosimetry calculations and observed radiation-induced effects indicated that sufficient 211At-B10-CA12.10C12 localization was achieved for efficient conditioning for HCT. PMID:26338894

Immune modulatory effects of radiotherapy as basis for well-reasoned radioimmunotherapies.

PubMed

Rückert, Michael; Deloch, Lisa; Fietkau, Rainer; Frey, Benjamin; Hecht, Markus; Gaipl, Udo S

2018-06-01

Radiotherapy (RT) has been known for decades as a local treatment modality for malign and benign disease. In order to efficiently exploit the therapeutic potential of RT, an understanding of the immune modulatory properties of ionizing radiation is mandatory. These should be used for improvement of radioimmunotherapies for cancer in particular. We here summarize the latest research and review articles about immune modulatory properties of RT, with focus on radiation dose and on combination of RT with selected immunotherapies. Based on the knowledge of the manifold immune mechanisms that are triggered by RT, thought-provoking impulse for multimodal radioimmunotherapies is provided. It has become obvious that ionizing radiation induces various forms of cell death and associated processes via DNA damage initiation and triggering of cellular stress responses. Immunogenic cell death (ICD) is of special interest since it activates the immune system via release of danger signals and via direct activation of immune cells. While RT with higher single doses in particular induces ICD, RT with a lower dose is mainly responsible for immune cell recruitment and for attenuation of an existing inflammation. The counteracting immunosuppression emanating from tumor cells can be overcome by combining RT with selected immunotherapies such as immune checkpoint inhibition, TGF-β inhibitors, and boosting of immunity with vaccination. In order to exploit the full power of RT and thereby develop efficient radioimmunotherapies, the dose per fraction used in RT protocols, the fractionation, the quality, and the quantity of certain immunotherapies need to be qualitatively and chronologically well-matched to the individual immune status of the patient.

RadioImmunotherapy for adenoid cystic carcinoma: a single-institution series of combined treatment with cetuximab

PubMed Central

2010-01-01

Background Local control in adjuvant/definitive RT of adenoid cystic carcinoma (ACC) is largely dose-dependent. However, some clinical situations do not allow application of tumouricidal doses (i.e. re-irradiation) hence radiation sensitization by exploitation of high endothelial growth factor receptor (EGFR)-expression in ACC seems beneficial. This is a single-institution experience of combined radioimmunotherapy (RIT) with the EGFR-inhibitor cetuximab. Methods Between 2006 and 2010, 9 pts received RIT for advanced/recurrent ACC, 5/9 pts as re-irradiation. Baseline characteristics as well as treatment parameters were retrieved to evaluate efficacy and toxicity of the combination regimen were evaluated. Control rates (local/distant) and overall survival were calculated using Kaplan-Meier estimation. Results Median dose was 65 Gy, pts received a median of 6 cycles cetuximab. RIT was tolerated well with only one °III mucositis/dysphagia. Overall response/remission rates were high (77,8%); 2-year estimate of local control was 80% hence reaching local control levels comparable to high-dose RT. Progression-free survival (PFS) at 2 years and median overall survival were only 62,5% and 22,2 mo respectively. Conclusion While local control and treatment response in RIT seems promising, PFS and overall survival are still hampered by distant failure. The potential benefit of RIT with cetuximab warrants exploration in a prospective controlled clinical trial. PMID:21047402

131I-tositumomab myeloablative radioimmunotherapy for non-Hodgkin’s lymphoma: radiation dose to the testes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hattori, Naoya; Gopal, Ajay K.; Shields, Andrew T.

Purpose: To investigate radiation doses to the testes delivered by a radiolabeled anti-CD20 antibody and its effects on male sex hormone levels. Materials and methods: Testicular uptake and retention of 131I-tositumomab were measured, and testicular absorbed doses were calculated for 67 male patients (54+/-11 years of age) with non-Hodgkin's lymphoma who had undergone myeloablative radioimmunotherapy (RIT) using 131I-tositumomab. Time-activity curves for the major organs, testes, and whole body were generated from planar imaging studies. In a subset of patients, male sex hormones were measured before and 1 year after the therapy. Results: The absorbed dose to the testes showed considerablemore » variability (range=4.4-70.2 Gy). Pretherapy levels of total testosterone were below the lower limit of the reference range, and post-therapy evaluation demonstrated further reduction [4.6+/-1.8 nmol/l (pre-RIT) vs. 3.8+/-2.9 nmol/l (post-RIT), P<0.05]. Patients receiving higher radiation doses to the testes (>=25 Gy) showed a greater reduction [4.7+/-1.6 nmol/l (pre-RIT) vs. 3.3+/-2.7 nmol/l (post-RIT), P<0.05] compared with patients receiving lower doses (<25 Gy), who showed no significant change in total testosterone levels. Conclusion: The testicular radiation absorbed dose varied highly among individual patients. Finally, patients receiving higher doses to the testes were more likely to show post-RIT suppression of testosterone levels.« less

Modifications in Dynamic Contrast-Enhanced Magnetic Resonance Imaging Parameters After α-Particle-Emitting {sup 227}Th-trastuzumab Therapy of HER2-Expressing Ovarian Cancer Xenografts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heyerdahl, Helen, E-mail: Helen.Heyerdahl@rr-research.no; Røe, Kathrine; Brevik, Ellen Mengshoel

2013-09-01

Purpose: The purpose of this study was to investigate the effect of α-particle-emitting {sup 227}Th-trastuzumab radioimmunotherapy on tumor vasculature to increase the knowledge about the mechanisms of action of {sup 227}Th-trastuzumab. Methods and Materials: Human HER2-expressing SKOV-3 ovarian cancer xenografts were grown bilaterally in athymic nude mice. Mice with tumor volumes 253 ± 36 mm{sup 3} (mean ± SEM) were treated with a single injection of either {sup 227}Th-trastuzumab at a dose of 1000 kBq/kg body weight (treated group, n=14 tumors) or 0.9% NaCl (control group, n=10 tumors). Dynamic T1-weighted contrast-enhanced magnetic resonance imaging (DCEMRI) was used to study themore » effect of {sup 227}Th-trastuzumab on tumor vasculature. DCEMRI was performed before treatment and 1, 2, and 3 weeks after therapy. Tumor contrast-enhancement curves were extracted voxel by voxel and fitted to the Brix pharmacokinetic model. Pharmacokinetic parameters for the tumors that underwent radioimmunotherapy were compared with the corresponding parameters of control tumors. Results: Significant increases of k{sub ep}, the rate constant of diffusion from the extravascular extracellular space to the plasma (P<.05), and k{sub el,} the rate of clearance of contrast agent from the plasma (P<.01), were seen in the radioimmunotherapy group 2 and 3 weeks after injection, compared with the control group. The product of k{sub ep} and the amplitude parameter A, associated with increased vessel permeability and perfusion, was also significantly increased in the radioimmunotherapy group 2 and 3 weeks after injection (P<.01). Conclusions: Pharmacokinetic modeling of MRI contrast-enhancement curves evidenced significant alterations in parameters associated with increased tumor vessel permeability and tumor perfusion after {sup 227}Th-trastuzumab treatment of HER2-expressing ovarian cancer xenografts.« less

Modifications in dynamic contrast-enhanced magnetic resonance imaging parameters after α-particle-emitting ²²⁷Th-trastuzumab therapy of HER2-expressing ovarian cancer xenografts.

PubMed

Heyerdahl, Helen; Røe, Kathrine; Brevik, Ellen Mengshoel; Dahle, Jostein

2013-09-01

The purpose of this study was to investigate the effect of α-particle-emitting (227)Th-trastuzumab radioimmunotherapy on tumor vasculature to increase the knowledge about the mechanisms of action of (227)Th-trastuzumab. Human HER2-expressing SKOV-3 ovarian cancer xenografts were grown bilaterally in athymic nude mice. Mice with tumor volumes 253 ± 36 mm(3) (mean ± SEM) were treated with a single injection of either (227)Th-trastuzumab at a dose of 1000 kBq/kg body weight (treated group, n=14 tumors) or 0.9% NaCl (control group, n=10 tumors). Dynamic T1-weighted contrast-enhanced magnetic resonance imaging (DCEMRI) was used to study the effect of (227)Th-trastuzumab on tumor vasculature. DCEMRI was performed before treatment and 1, 2, and 3 weeks after therapy. Tumor contrast-enhancement curves were extracted voxel by voxel and fitted to the Brix pharmacokinetic model. Pharmacokinetic parameters for the tumors that underwent radioimmunotherapy were compared with the corresponding parameters of control tumors. Significant increases of kep, the rate constant of diffusion from the extravascular extracellular space to the plasma (P<.05), and kel, the rate of clearance of contrast agent from the plasma (P<.01), were seen in the radioimmunotherapy group 2 and 3 weeks after injection, compared with the control group. The product of kep and the amplitude parameter A, associated with increased vessel permeability and perfusion, was also significantly increased in the radioimmunotherapy group 2 and 3 weeks after injection (P<.01). Pharmacokinetic modeling of MRI contrast-enhancement curves evidenced significant alterations in parameters associated with increased tumor vessel permeability and tumor perfusion after (227)Th-trastuzumab treatment of HER2-expressing ovarian cancer xenografts. Copyright © 2013 Elsevier Inc. All rights reserved.

Preclinical evaluation of a diabody-based (177)Lu-radioimmunoconjugate for CD22-directed radioimmunotherapy in a non-Hodgkin lymphoma mouse model.

PubMed

Weber, Tobias; Bötticher, Benedikt; Arndt, Michaela A E; Mier, Walter; Sauter, Max; Exner, Evelyn; Keller, Armin; Krämer, Susanne; Leotta, Karin; Wischnjow, Artjom; Grosse-Hovest, Ludger; Strumberg, Dirk; Jäger, Dirk; Gröne, Hermann-Josef; Haberkorn, Uwe; Brem, Gottfried; Krauss, Jürgen

2016-10-28

Radioimmunotherapy is considered as treatment option in recurrent and/or refractory B-cell non-Hodgkin lymphoma (B-NHL). To overcome the dose limiting bone marrow toxicity of IgG-based radioimmunoconjugates (RICs), we modified a humanized diabody with 5-, 10-, or 20-kDa polyethylene glycol (PEG) for CD22-targeted radioimmunotherapy using the low-energy β-emitter lutetium-177 ((177)Lu). A favorable pharmacokinetic profile was observed for the 10-kDa-PEG-diabody in nude mice being xenografted with subcutaneous human Burkitt lymphoma. Even at high doses of 16 MBq this diabody RIC was well tolerated by NOD Rag1(null) IL2rγ(null) (NRG) mice and did not reveal signs of organ long-term toxicity 80 days post injection. Combination therapy of the diabody RIC with unconjugated anti-CD20 Rituximab demonstrated therapeutic efficacy in established disseminated mantle cell lymphoma xenograft models. When compared with the combination of the IgG formatted (177)Lu anti-CD22 antibody and Rituximab, dual targeted therapy with the diabody RIC achieved an improved reduction of disease burden in the first nine days following treatment. The data indicate that the PEGylated anti-CD22 diabody may have potential for extending the repertoire of radiopharmaceuticals for the treatment of patients with B-NHL. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Radioimmunotherapy for non-Hodgkin's lymphoma: A review for radiation oncologists

DOE Office of Scientific and Technical Information (OSTI.GOV)

Macklis, Roger M.; Pohlman, Brad

Purpose: The aim of this study was to review advances in radioimmunotherapy (RIT) for non-Hodgkin's lymphoma (NHL) and to discuss the role of Radiation oncologist in administering this important new form of biologically targeted radiotherapy. Methods and Materials: A review of articles and abstracts on the clinical efficacy, safety, and radiation safety of yttrium Y 90 ({sup 9}Y) ibritumomab tiuxetan (Zevalin) and iodine I 131 tositumomab (Bexxar) was performed. Results: The clinical efficacy of RIT in NHL has been shown in numerous clinical trials of {sup 9}Y ibritumomab tiuxetan and {sup 131}I tositumomab. Both agents have produced significant responses inmore » patients with low-grade, follicular, or transformed NHL, including patients with disease that had not responded or had responded poorly to previous chemotherapy or immunotherapy. Reversible toxicities such as neutropenia, thrombocytopenia, and anemia are the most common adverse events with both agents. Conclusions: Radioimmunotherapy is safe and effective in many patients with B-cell NHL. {sup 9}Y ibritumomab tiuxetan and {sup 131}I tositumomab can produce clinically meaningful and durable responses even in patients in whom chemotherapy has failed. Treatment with RIT requires a multispecialty approach and close communication between Radiation oncologist and other members of the treatment team. Radiation oncologist plays an important role in treating patients with RIT and monitoring them for responses and adverse events after treatment.« less

Radioimmunotherapy

MedlinePlus

... be involved in RIT. top of page What equipment is used? In addition to equipment needed to ... dimensional images. top of page Who operates the equipment? A radiologist who has specialized training in nuclear ...

A pioneer experience in Malaysia on In-house Radio-labelling of (131)I-rituximab in the treatment of Non-Hodgkin's Lymphoma and a case report of high dose (131)I-rituximab-BEAM conditioning autologous transplant.

PubMed

Kuan, Jew Win; Law, Chiong Soon; Wong, Xiang Qi; Ko, Ching Tiong; Awang, Zool Hilmi; Chew, Lee Ping; Chang, Kian Meng

2016-10-01

Radioimmunotherapy is an established treatment modality in Non-Hodgkin's lymphoma. The only two commercially available radioimmunotherapies - (90)Y-ibritumomab tiuxetan is expensive and (131)I-tositumomab has been discontinued from commercial production. In resource limited environment, self-labelling (131)I-rituximab might be the only viable practical option. We reported our pioneer experience in Malaysia on self-labelling (131)I-rituximab, substituting autologous haematopoietic stem cell transplantation (HSCT) and a patient, the first reported case, received high dose (131)I-rituximab (6000MBq/163mCi) combined with BEAM conditioning for autologous HSCT. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparative efficacy of 177Lu and 90Y for Anti-CD20 Pretargeted Radioimmunotherapy in Murine Lymphoma Xenograft Models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frost, Sofia H. L.; Frayo, Shani L.; Miller, Brian W.

Purpose Pretargeted radioimmunotherapy (PRIT) is a multi-step method of selectively delivering high doses of radiotherapy to tumor cells while minimizing exposure to surrounding tissues. Yttrium-90 ( 90Y) and lutetium-177 ( 177Lu) are two of the most promising beta-particle emitting radionuclides used for radioimmunotherapy, which despite having similar chemistries differ distinctly in terms of radiophysical features. These differences may have important consequences for the absorbed dose to tumors and normal organs. Whereas 90Y has been successfully applied in a number of preclinical and clinical radioimmunotherapy settings, there have been few published pretargeting studies with 177Lu. We therefore compared the therapeutic potentialmore » of targeting either 90Y or 177Lu to human B-cell lymphoma xenografts in mice. Methods Parallel experiments evaluating the biodistribution, imaging, dosimetry, therapeutic efficacy, and toxicity were performed in female athymic nude mice bearing either Ramos (Burkitt lymphoma) or Granta (mantle cell lymphoma) xenografts, utilizing an anti-CD20 antibodystreptavidin conjugate (1F5-SA) and an 90Y- or 177Lu-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-biotin second step reagent. Results The two radionuclides displayed comparable biodistributions in tumors and normal organs; however, the absorbed radiation dose delivered to tumor was more than twice as high for 90Y (1.3 Gy/MBq) as for 177Lu (0.6 Gy/MBq). More importantly, therapy with 90Y-DOTAbiotin was dramatically more effective than with 177Lu-DOTA-biotin, with 100% of Ramos xenograft-bearing mice cured with 37 MBq 90Y, whereas 0% were cured using identical amounts of 177Lu-DOTA-biotin. Similar results were observed in mice bearing Granta xenografts, with 80% of the mice cured with 90Y-PRIT and 0% cured with 177Lu-PRIT. Toxicities were comparable with both isotopes. Conclusion 90Y was therapeutically superior to 177Lu for streptavidin-biotin PRIT approaches in these human lymphoma xenograft models.« less

Comparative efficacy of 177Lu and 90Y for Anti-CD20 Pretargeted Radioimmunotherapy in Murine Lymphoma Xenograft Models

DOE PAGES

Frost, Sofia H. L.; Frayo, Shani L.; Miller, Brian W.; ...

2015-03-18

Purpose Pretargeted radioimmunotherapy (PRIT) is a multi-step method of selectively delivering high doses of radiotherapy to tumor cells while minimizing exposure to surrounding tissues. Yttrium-90 ( 90Y) and lutetium-177 ( 177Lu) are two of the most promising beta-particle emitting radionuclides used for radioimmunotherapy, which despite having similar chemistries differ distinctly in terms of radiophysical features. These differences may have important consequences for the absorbed dose to tumors and normal organs. Whereas 90Y has been successfully applied in a number of preclinical and clinical radioimmunotherapy settings, there have been few published pretargeting studies with 177Lu. We therefore compared the therapeutic potentialmore » of targeting either 90Y or 177Lu to human B-cell lymphoma xenografts in mice. Methods Parallel experiments evaluating the biodistribution, imaging, dosimetry, therapeutic efficacy, and toxicity were performed in female athymic nude mice bearing either Ramos (Burkitt lymphoma) or Granta (mantle cell lymphoma) xenografts, utilizing an anti-CD20 antibodystreptavidin conjugate (1F5-SA) and an 90Y- or 177Lu-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-biotin second step reagent. Results The two radionuclides displayed comparable biodistributions in tumors and normal organs; however, the absorbed radiation dose delivered to tumor was more than twice as high for 90Y (1.3 Gy/MBq) as for 177Lu (0.6 Gy/MBq). More importantly, therapy with 90Y-DOTAbiotin was dramatically more effective than with 177Lu-DOTA-biotin, with 100% of Ramos xenograft-bearing mice cured with 37 MBq 90Y, whereas 0% were cured using identical amounts of 177Lu-DOTA-biotin. Similar results were observed in mice bearing Granta xenografts, with 80% of the mice cured with 90Y-PRIT and 0% cured with 177Lu-PRIT. Toxicities were comparable with both isotopes. Conclusion 90Y was therapeutically superior to 177Lu for streptavidin-biotin PRIT approaches in these human lymphoma xenograft models.« less

Stress-induced molecules MICA as potential target for radioimmunotherapy of cancer

NASA Astrophysics Data System (ADS)

Abakushina, E. V.; Anokhin, Yu N.; Abakushin, D. N.; Kaprin, A. D.

2017-01-01

Improving the treatment of cancer, increasing their effectiveness and safety is the main objective in the medicine. Molecular nuclear medicine plays an important role in the therapy of cancer. Radioimmunotherapy (RIT) involves the use of antibodies conjugated with therapeutic radionuclides. More often for RIT use the radiolabeled monoclonal antibodies against tumor-associated antigens. Encouraging results have been achieved with this technology in the management of hematologic malignancies. On the contrary, solid tumors have been less responsive. Despite these encouraging results, new potential target for radioimmunodetection and RIT should be found. It was found to increase the level of tumor-associated molecules MICA in the serum of cancer patients. Use of anti-MICA monoclonal antibodies capable a specifically attach to cancer cell via NKG2D ligands and destroy it, is a very promising direction, both therapeutic and diagnostic standpoint.

Radioimmunotherapy with monoclonal antibodies. A new horizon in nuclear medicine therapy?

PubMed

Sautter-Bihl, M L; Bihl, H

1994-08-01

Radioimmunotherapy (RIT) with labeled tumor-associated monoclonal antibodies (MAbs) is a promising concept in oncology, which essentially consists of biological targeting of ionising radiation to tumors. Some encouraging clinical results have been achieved with RIT. However, there are severe problems associated with both understanding the mechanisms and predicting the effectiveness of RIT. This paper reviews the results of some major clinical trials, especially in malignant lymphomas and in some solid tumors. Furthermore, problems with RIT are described such as the significance of dose inhomogeneity and dose-rate effects, the appropriate dose calculation method, the toxicity of RIT and the development of HAMAs. It is suggested that newer technologies including chimeric antibodies, multiple-step targeting protocols, bone marrow transplantation, parallel application of external radiation, heat or bioreductive drugs will enable RIT to make an essential contribution to strategies for combating cancer.

BCR-ABL1 molecular remission after 90Y-epratuzumab tetraxetan radioimmunotherapy in CD22+ Ph+ B-ALL: proof of principle.

PubMed

Chevallier, Patrice; Bodet-Milin, Caroline; Robillard, Nelly; Eugene, Thomas; Menard, Audrey; Le Houerou, Claire; Guillaume, Thierry; Delaunay, Jacques; Escoffre-Barbe, Martine; Wegener, William A; Goldenberg, David M; Kraeber-Bodéré, Francoise

2013-12-01

Although targeted therapies are used increasingly in hematologic malignancies, we are unaware of any prior studies of radioimmunotherapy (RAIT) in B-acute lymphoblastic leukemia (ALL), even though this radiosensitive tumor expresses CD22, potentially a good target for this approach. Here, we report a patient with Philadelphia chromosome-positive B-ALL in third relapse who received RAIT with (90) yttrium ((90) Y)-labeled anti-CD22 epratuzumab tetraxetan. Seven weeks after initiating therapy, the patient achieved a BCR-ABL1 molecular remission documented by RT-qPCR, which is now continuing at 6 months while awaiting an allogeneic hematopoietic stem cell transplant. (90) Y-Epratuzumab tetraxetan may be a promising therapeutic option for CD22(+) B-ALL patients. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Monoclonal Antibodies Radiolabeling with Rhenium-188 for Radioimmunotherapy

PubMed Central

Martini, Petra; Pasquali, Micol

2017-01-01

Rhenium-188, obtained from an alumina-based tungsten-188/rhenium-188 generator, is actually considered a useful candidate for labeling biomolecules such as antibodies, antibody fragments, peptides, and DNAs for radiotherapy. There is a widespread interest in the availability of labeling procedures that allow obtaining 188Re-labeled radiopharmaceuticals for various therapeutic applications, in particular for the rhenium attachment to tumor-specific monoclonal antibodies (Mo)Abs for immunotherapy. Different approaches have been developed in order to obtain 188Re-radioimmunoconjugates in high radiochemical purity starting from the generator eluted [188Re]ReO4−. The aim of this paper is to provide a short overview on 188Re-labeled (Mo)Abs, focusing in particular on the radiolabeling methods, quality control of radioimmunoconjugates, and their in vitro stability for radioimmunotherapy (RIT), with particular reference to the most important contributions published in literature in this topic. PMID:28951872

Monoclonal Antibodies Radiolabeling with Rhenium-188 for Radioimmunotherapy.

PubMed

Uccelli, Licia; Martini, Petra; Pasquali, Micol; Boschi, Alessandra

2017-01-01

Rhenium-188, obtained from an alumina-based tungsten-188/rhenium-188 generator, is actually considered a useful candidate for labeling biomolecules such as antibodies, antibody fragments, peptides, and DNAs for radiotherapy. There is a widespread interest in the availability of labeling procedures that allow obtaining 188 Re-labeled radiopharmaceuticals for various therapeutic applications, in particular for the rhenium attachment to tumor-specific monoclonal antibodies (Mo)Abs for immunotherapy. Different approaches have been developed in order to obtain 188 Re-radioimmunoconjugates in high radiochemical purity starting from the generator eluted [ 188 Re]ReO 4 - . The aim of this paper is to provide a short overview on 188 Re-labeled (Mo)Abs, focusing in particular on the radiolabeling methods, quality control of radioimmunoconjugates, and their in vitro stability for radioimmunotherapy (RIT), with particular reference to the most important contributions published in literature in this topic.

177Lu-DOTA-Bevacizumab: Radioimmunotherapy Agent for Melanoma.

PubMed

Camacho, Ximena; Calzada, Victoria; Fernandez, Marcelo; Alonso, Omar; Chammas, Roger; Riva, Eloisa; Gambini, Juan Pablo; Cabral, Pablo

2017-01-01

Vascular endothelial growth factor (VEGF) is one of the classic factors to tumor-induced angiogenesis in several types, including melanoma. Bevacizumab is a humanized monoclonal antibody directed against VEGF. To radiolabel Bevacizumab with 177-Lutetium as a potential radioimmunotherapy agent for melanoma. Bevacizumab was derivatized with DOTA-NHS-ester at 4 ºC for 18 h. DOTABevacizumab was radiolabeled with 177LuCl3 (15 MBq/mg) at 37 ºC for 1 h. The studies were performed in healthy and B16F1 tumor-bearing C57BL/6J mice at 24 and 48 h (n = 5). Scinthigraphic imaging studies were performed at 24 h to determine the radiochemical stability, targeting specificity and pharmacokinetics of the 177Lutetium-labeled antibody. DOTA-Bevacizumab was efficiently labeled with 177LuCl3 at 37 °C. The in-vitro stability of labeled product was optimal over 72 h. In-vivo biodistribution studies showed a high liver and tumor uptake of 177Lu-DOTA-Bevacizumab, with tumor-to-muscle ratios of 11.58 and 6.37 at 24 and 48 h p.i. Scintigraphic imaging of melanoma tumor-bearing C57BL/6J mice showed liver and a high tumor selective uptake of 177Lu-DOTA-Bevacizumab at 24 h. Our results support the potential role of 177Lu-DOTA-Bevacizumab as a novel radioimmunotherapy agent for melanoma. We hope that these novel molecular imaging agents will open the path to new diagnostic and therapeutic strategies for Melanoma disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Targeting Phosphatidylserine for Radioimmunotherapy of Breast Cancer Brain Metastasis

DTIC Science & Technology

2015-12-01

blockade of phosphatidylserine enhances the antitumor effect of sorafenib in hepatocellular carcinoma xenografts . Submitted. * equal contribution...Antiphosphatidylserine antibody combined with irradiation damages blood vessels and induces tumor immunity in a rat model of glioblastoma . Clin. Can. Res. 2009

Preparation and radiolabeling of a lyophilized (kit) formulation of DOTA-rituximab with ⁹⁰Y and ¹¹¹In for domestic radioimmunotherapy and radioscintigraphy of non-Hodgkin's lymphoma.

PubMed

Gholipour, Nazila; Jalilian, Amir Reza; Khalaj, Ali; Johari-Daha, Fariba; Yavari, Kamal; Sabzevari, Omid; Khanchi, Ali Reza; Akhlaghi, Mehdi

2014-07-29

On the basis of results of our previous investigations on 90Y-DTPA-rituximab and in order to fulfil national demands to radioimmunoconjugates for radioscintigraphy and radioimmunotherapy of Non-Hodgkin's Lymphoma (NHL), preparation and radiolabeling of a lyophilized formulation (kit) of DOTA-rituximab with 111In and 90Y was investigated. 111In and 90Y with high radiochemical and radionuclide purity were prepared by 112Cd (p,2n)111In nuclear reaction and a locally developed 90Sr/90Y generator, respectively. DOTA-rituximab immunoconjugates were prepared by the reaction of solutions of p-SCN-Bz-DOTA and rituximab in carbonate buffer (pH = 9.5) and the number of DOTA per molecule of conjugates were determined by transchelation reaction between DOTA and arsenaso yttrium(III) complex. DOTA-rituximab immunoconjugates were labeled with 111In and 90Y and radioimmunoconjugates were checked for radiochemical purity by chromatography methods and for immunoreactivity by cell-binding assay using Raji cell line. The stability of radiolabeled conjugate with the approximate number of 7 DOTA molecules per one rituximab molecule which was prepared in moderate yield and showed moderate immunoreactivity, compared to two other prepared radioimmunoconjugates, was determined at different time intervals and against EDTA and human serum by chromatography methods and reducing SDS-polyacrylamide gel electrophoresis, respectively. The biodistribution of the selected radioimmunoconjugate in rats was determined by measurement of the radioactivity of different organs after sacrificing the animals by ether asphyxiation. The radioimmunoconjugate with approximate DOTA/rituximab molar ratio of 7 showed stability after 24 h at room temperature, after 96 h at 4°C, as the lyophilized formulation after six months storage and against EDTA and human serum. This radioimmunoconjugate had a biodistribution profile similar to that of 90Y-ibritumomab, which is approved by FDA for radioimmunotherapy of NHL, and showed low brain and lung uptakes and low yttrium deposition into bone. Findings of this study suggest that further investigations may result in a lyophilized (kit) formulation of DOTA-rituximab which could be easily radiolabeled with 90Y and 111In in order to be used for radioimmunotherapy and radioscintigraphy of B-cell lymphoma in Iran.

Durable donor engraftment after radioimmunotherapy using α-emitter astatine-211–labeled anti-CD45 antibody for conditioning in allogeneic hematopoietic cell transplantation

PubMed Central

Chen, Yun; Kornblit, Brian; Hamlin, Donald K.; Sale, George E.; Santos, Erlinda B.; Wilbur, D. Scott; Storer, Barry E.; Storb, Rainer

2012-01-01

To reduce toxicity associated with external γ-beam radiation, we investigated radioimmunotherapy with an anti-CD45 mAb labeled with the α-emitter, astatine-211 (211At), as a conditioning regimen in dog leukocyte antigen-identical hematopoietic cell transplantation (HCT). Dose-finding studies in 6 dogs treated with 100 to 618 μCi/kg 211At-labeled anti-CD45 mAb (0.5 mg/kg) without HCT rescue demonstrated dose-dependent myelosuppression with subsequent autologous recovery, and transient liver toxicity in dogs treated with 211At doses less than or equal to 405 μCi/kg. Higher doses of 211At induced clinical liver failure. Subsequently, 8 dogs were conditioned with 155 to 625 μCi/kg 211At-labeled anti-CD45 mAb (0.5 mg/kg) before HCT with dog leukocyte antigen-identical bone marrow followed by a short course of cyclosporine and mycophenolate mofetil immunosuppression. Neutropenia (1-146 cells/μL), lymphopenia (0-270 cells/μL), and thrombocytopenia (1500-6560 platelets/μL) with prompt recovery was observed. Seven dogs had long-term donor mononuclear cell chimerism (19%-58%), whereas 1 dog treated with the lowest 211At dose (155 μCi/kg) had low donor mononuclear cell chimerism (5%). At the end of follow-up (18-53 weeks), only transient liver toxicity and no renal toxicity had been observed. In conclusion, conditioning with 211At-labeled anti-CD45 mAb is safe and efficacious and provides a platform for future clinical trials of nonmyeloablative transplantation with radioimmunotherapy-based conditioning. PMID:22134165

Targeting Phosphatidylserince for Radioimmunotherapy of Breast Cancer Brain Metastasis

DTIC Science & Technology

2014-10-01

remained negative for exposed PS. 15. SUBJECT TERMS Nothing Listed 16. SECURITY CLASSIFICATION OF: unclassified 17. LIMITATION OF ABSTRACT 18...cells of brain metastases. • PS-targeting antibody, PGN635F(ab’)2 has been successfully conjugated with radioisotope , enabling in vivo PET imaging

Anti-CD20 Radioimmunotherapy Before Chemotherapy and Stem Cell Transplant in Treating Patients With High-Risk B-Cell Malignancies

ClinicalTrials.gov

2018-03-13

Burkitt Lymphoma; CD20-Positive Neoplastic Cells Present; Diffuse Large B-Cell Lymphoma; Indolent Non-Hodgkin Lymphoma; Mantle Cell Lymphoma; Recurrent B-Cell Non-Hodgkin Lymphoma; Refractory Mature B-Cell Non-Hodgkin Lymphoma

Feasibility and toxicity of concomitant radio/immunotherapy with MabThera (Rituximab®) for patients with non-Hodkin's Lymphoma: results of a prospective phase I/II study.

PubMed

Haidenberger, Alfred; Fromm-Haidenberger, Sabine; de Vries, Alexander; Popper, Bela-Andre; Steurer, Michael; Skvortsova, Ira; Kantner, Johanna; Gunsilius, Eberhard; Lukas, Peter

2011-05-01

Non-Hodgkin's lymphomas (NHL) have a high radio- and chemosensitivity. Although initially responsive, approximately 50% of low grade B-cell lymphomas relapse after 10-15 years. Besides chemo- and radiotherapy, rituximab, a mouse/human chimeric antibody targeting CD20 antigen on the surface of B-cell lymphoma cells, is another treatment approach. In vitro data showed potentiation of radiation-induced apoptosis by addition of rituximab. The purpose of this study was to evaluate the feasibility and toxicity of radiotherapy with concomitant application of rituximab in NHL patients. A total of 21 patients with B-cell lymphoma (stage I: n = 11; II: n = 5; III: n = 1; IV: n = 4) were included in this study, treated with radiotherapy of 30-40 Gy and weekly application of rituximab (375 mg/m²). Nine patients had R-CHOP chemotherapy previously, 1 patient leuceran chemotherapy, and 2 patients an initial treatment with 6 cycles of rituximab. Mean time of follow-up was 41.7 months. No grade 4 toxicity or treatment-related death was observed. In 1 patient, rituximab application had to be stopped after 3 cycles due to radiation-induced side effects. No late toxicities were reported. All patients were in complete remission after treatment. Progression or relapse was observed in 6 patients (28%); the mean time to progression was 27 months. The mean overall survival (OS) was 53 months. Combined radio/immunotherapy is feasible and safe. Treatment was well tolerated, no late toxicities were observed, and treatment outcome is promising. Randomized trials are necessary to clarify the benefit of this treatment approach and its applicability.

Trial Watch: Radioimmunotherapy for oncological indications.

PubMed

Bloy, Norma; Pol, Jonathan; Manic, Gwenola; Vitale, Ilio; Eggermont, Alexander; Galon, Jérôme; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

2014-10-01

During the past two decades, it has become increasingly clear that the antineoplastic effects of radiation therapy do not simply reflect the ability of X-, β- and γ-rays to damage transformed cells and directly cause their permanent proliferative arrest or demise, but also involve cancer cell-extrinsic mechanisms. Indeed, among other activities, radiotherapy has been shown to favor the establishment of tumor-specific immune responses that operate systemically, underpinning the so-called 'out-of-field' or 'abscopal' effect. Thus, ionizing rays appear to elicit immunogenic cell death, a functionally peculiar variant of apoptosis associated with the emission of a particularly immunostimulatory combination of damage-associated molecular patterns. In line with this notion, radiation therapy fosters, and thus exacerbates, the antineoplastic effects of various treatment modalities, including surgery, chemotherapy and various immunotherapeutic agents. Here, we summarize recent advances in the use of ionizing rays as a means to induce or potentiate therapeutically relevant anticancer immune responses. In addition, we present clinical trials initiated during the past 12 months to test the actual benefit of radioimmunotherapy in cancer patients.

Targeting Phosphatidylserine for Radioimmunotherapy of Breast Cancer Brain Metastasis

DTIC Science & Technology

2013-10-01

be construed as an official Department of the Army position, policy or decision unless so designated by other documentation. 2 REPORT...1:10 10 desalting c f the dye at 7 7 of dye bound t rexisF(ab’) 2 t h ematic represe n l ls. odels al procedure s Medical Ce n , Manassas, V A

Comparing the cost-effectiveness of rituximab maintenance and radioimmunotherapy consolidation versus observation following first-line therapy in patients with follicular lymphoma.

PubMed

Chen, Qiushi; Ayer, Turgay; Nastoupil, Loretta J; Rose, Adam C; Flowers, Christopher R

2015-03-01

Phase 3 randomized trials have shown that maintenance rituximab (MR) therapy or radioimmunotherapy (RIT) consolidation following frontline therapy can improve progression-free survival for patients with follicular lymphoma (FL), but the cost-effectiveness of these approaches with respect to observation has not been examined using a common modeling framework. To evaluate and compare the economic impact of MR and RIT consolidation versus observation, respectively, following the first-line induction therapy for patients with advanced-stage FL. We developed Markov models to estimate patients' lifetime costs, quality-adjusted life-years (QALYs), and life-years (LYs) after MR, RIT, and observation following frontline FL treatment from the US payer's perspective. Progression risks, adverse event probabilities, costs, and utilities were estimated from clinical data of Primary RItuximab and MAintenance (PRIMA) trial, Eastern Cooperative Oncology Group (ECOG) trial (for MR), and First-line Indolent Trial (for RIT) and the published literature. We evaluated the incremental cost-effectiveness ratio for direct comparisons between MR/RIT and observation. Model robustness was addressed by one-way and probabilistic sensitivity analyses. Compared with observation, MR provided an additional 1.089 QALYs (1.099 LYs) and 1.399 QALYs (1.391 LYs) on the basis of the PRIMA trial and the ECOG trial, respectively, and RIT provided an additional 1.026 QALYs (1.034 LYs). The incremental cost per QALY gained was $40,335 (PRIMA) or $37,412 (ECOG) for MR and $40,851 for RIT. MR and RIT had comparable incremental QALYs before first progression, whereas RIT had higher incremental costs of adverse events due to higher incidences of cytopenias. MR and RIT following frontline FL therapy demonstrated favorable and similar cost-effectiveness profiles. The model results should be interpreted within the specific clinical settings of each trial. Selection of MR, RIT, or observation should be based on patient characteristics and expected trade-offs for these alternatives. Copyright © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Donor Peripheral Blood Stem Cell Transplant and Pretargeted Radioimmunotherapy in Treating Patients With High-Risk Advanced Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Myelodysplastic Syndrome

ClinicalTrials.gov

2017-08-28

Chronic Myelomonocytic Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Cytopenia With Multilineage Dysplasia; Refractory Cytopenia With Multilineage Dysplasia and Ringed Sideroblasts; Secondary Acute Myeloid Leukemia

Improved radioimmunotherapy of hematologic malignancies. Progress report, November 1, 1993--October 31, 1994

DOE Office of Scientific and Technical Information (OSTI.GOV)

Press, O.W.

1994-08-04

This report summaries progress made during the time interval between November 1, 1993 and October 31, 1994 and briefly describes studies on the metabolism of antibodies targeting B cell antigens, retention of labeled antibodies by human B cell lymphocytes, and tissue distribution of Chloramine T and tyramine cellobiose labeled antibodies in mice harboring a human erythroleukemia tumor transplant.

Binding Affinity, Specificity and Comparative Biodistribution of the Parental Murine Monoclonal Antibody MX35 (Anti-NaPi2b) and Its Humanized Version Rebmab200

PubMed Central

Lindegren, Sture; Andrade, Luciana N. S.; Bäck, Tom; Machado, Camila Maria L.; Horta, Bruno Brasil; Buchpiguel, Carlos; Moro, Ana Maria; Okamoto, Oswaldo Keith; Jacobsson, Lars; Cederkrantz, Elin; Washiyama, Kohshin; Aneheim, Emma; Palm, Stig; Jensen, Holger; Tuma, Maria Carolina B.; Chammas, Roger; Hultborn, Ragnar; Albertsson, Per

2015-01-01

The aim of this preclinical study was to evaluate the characteristics of the monoclonal antibody Rebmab200, which is a humanized version of the ovarian-specific murine antibody MX35. This investigation contributes to the foundation for future clinical α-radioimmunotherapy of minimal residual ovarian cancer with 211At-Rebmab200. Here, the biodistribution of 211At-Rebmab200 was evaluated, as was the utility of 99mTc-Rebmab200 for bioimaging. Rebmab200 was directly compared with its murine counterpart MX35 in terms of its in-vitro capacity for binding the immobilized NaPi2B epitope and live cells; we also assessed its biodistribution in nude mice carrying subcutaneous OVCAR-3 tumors. Tumor antigen and cell binding were similar between Rebmab200 and murine MX35, as was biodistribution, including normal tissue uptake and in-vivo tumor binding. We also demonstrated that 99mTc-Rebmab200 can be used for single-photon emission computed tomography of subcutaneous ovarian carcinomas in tumor-bearing mice. Taken together, our data support the further development of Rebmab200 for radioimmunotherapy and diagnostics. PMID:25970341

Binding Affinity, Specificity and Comparative Biodistribution of the Parental Murine Monoclonal Antibody MX35 (Anti-NaPi2b) and Its Humanized Version Rebmab200.

PubMed

Lindegren, Sture; Andrade, Luciana N S; Bäck, Tom; Machado, Camila Maria L; Horta, Bruno Brasil; Buchpiguel, Carlos; Moro, Ana Maria; Okamoto, Oswaldo Keith; Jacobsson, Lars; Cederkrantz, Elin; Washiyama, Kohshin; Aneheim, Emma; Palm, Stig; Jensen, Holger; Tuma, Maria Carolina B; Chammas, Roger; Hultborn, Ragnar; Albertsson, Per

2015-01-01

The aim of this preclinical study was to evaluate the characteristics of the monoclonal antibody Rebmab200, which is a humanized version of the ovarian-specific murine antibody MX35. This investigation contributes to the foundation for future clinical α-radioimmunotherapy of minimal residual ovarian cancer with 211At-Rebmab200. Here, the biodistribution of 211At-Rebmab200 was evaluated, as was the utility of 99mTc-Rebmab200 for bioimaging. Rebmab200 was directly compared with its murine counterpart MX35 in terms of its in-vitro capacity for binding the immobilized NaPi2B epitope and live cells; we also assessed its biodistribution in nude mice carrying subcutaneous OVCAR-3 tumors. Tumor antigen and cell binding were similar between Rebmab200 and murine MX35, as was biodistribution, including normal tissue uptake and in-vivo tumor binding. We also demonstrated that 99mTc-Rebmab200 can be used for single-photon emission computed tomography of subcutaneous ovarian carcinomas in tumor-bearing mice. Taken together, our data support the further development of Rebmab200 for radioimmunotherapy and diagnostics.

Targeting Phosphatidylserine for Radioimmunotherapy of Breast Cancer Brain Metastasis

DTIC Science & Technology

2015-12-01

response. e. Correlate imaging findings with histological studies of vascular damage, tumor cell and endothelial cell apoptosis or necrosis and vascular ...phosphatidylserine (PS) is exposed exclusively on tumor vascular endothelium of brain metastases in mouse models. A novel PS-targeting antibody, PGN635... vascular endothelial cells in multi-focal brain metastases throughout the whole mouse brain. Vascular endothelium in normal brain tissues is negative

Improved Therapy by Pretargeted Radioimmunotherapy of Non-Hodgkin Lymphoma with a New Recombinant, Trivalent, Anti-CD20, Bispecific Antibody

PubMed Central

Sharkey, Robert M.; Karacay, Habibe; Litwin, Samuel; Rossi, Edmund A.; McBride, William J.; Chang, Chein-Hsing; Goldenberg, David M.

2008-01-01

We examined whether a pretargeting method using a new, recombinant anti-CD20 bispecific antibody (bsMAb) followed by 90Y-DOTA-peptide could reduce hematological toxicity yet improve therapeutic responses, compared to conventional 90Y-anti-CD20 IgG and a chemically-conjugated bsMAb. TF4, a humanized, tri-Fab, bsMAb with 2 Fabs binding CD20 and 1 Fab binding HSG (histamine-succinyl-glycine), developed by the Dock-and-Lock (DNL) method, was tested in nude mice with Ramos B-cell lymphomas. Optimal pretargeting required a 29-h interval between TF4 and 90Y-DOTA-HSG, and 20-fold more moles of TF4. TF4 cleared more rapidly from the blood than anti-CD20 IgG, with early processing in the liver, spleen and kidneys. At 24 h, TF4 improved tumor uptake of 111In-HSG-peptide 2.6-fold (13% vs 5% injected-dose/g) and enhanced tumor/blood ratios more than 45-fold (770 vs 17), compared to an anti-CD20 Fab x anti-HSG Fab chemical conjugate, and by 1.6-fold (9.0% vs 5.6% injected-dose/g) and 1600-fold (522 vs 0.32), respectively, compared to radiolabeled anti-CD20 IgG. A severe (≥90%) and prolonged reduction of white blood cells was observed at the maximum dose of 90Y-anti-CD20 IgG, whereas pretargeting resulted in a ≤60% transient drop. TF4-pretargeting resulted in highly significant improvement in survival, curing 33-90% of the animals, even at relatively low doses, while most tumors progressed quickly without cures with 90Y-anti-CD20 IgG. These results indicate an improved therapeutic index with pretargeting radioimmunotherapy using a DNL-constructed tri-Fab, bsMAb, as compared to conventional therapy with directly-radiolabeled antibody or with a chemically-conjugated bsMAb. These encouraging results prompt testing of these constructs for pretargeting radioimmunotherapy in patients. PMID:18593929

A phase II study of radioimmunotherapy with intraventricular 131 I-3F8 for medulloblastoma.

PubMed

Kramer, Kim; Pandit-Taskar, Neeta; Humm, John L; Zanzonico, Pat B; Haque, Sofia; Dunkel, Ira J; Wolden, Suzanne L; Donzelli, Maria; Goldman, Debra A; Lewis, Jason S; Lyashchenko, Serge K; Khakoo, Yasmin; Carrasquillo, Jorge A; Souweidane, Mark M; Greenfield, Jeffrey P; Lyden, David; De Braganca, Kevin D; Gilheeney, Stephen W; Larson, Steven M; Cheung, Nai-Kong V

2018-01-01

High-risk and recurrent medulloblastoma (MB) is associated with significant mortality. The murine monoclonal antibody 3F8 targets the cell-surface disialoganglioside GD2 on MB. We tested the efficacy, toxicity, and dosimetry of compartmental radioimmunotherapy (cRIT) with intraventricular 131 I-labeled 3F8 in patients with MB on a phase II clinical trial. Patients with histopathologically confirmed high-risk or recurrent MB were eligible for cRIT. After determining adequate cerebrospinal fluid (CSF) flow, patients received 2 mCi (where Ci is Curie) 124 I-3F8 or 131 I-3F8 with nuclear imaging for dosimetry, followed by up to four therapeutic (10 mCi/dose) 131 I-3F8 injections. Dosimetry estimates were based on serial CSF and blood samplings over 48 hr plus region-of-interest analyses on serial imaging scans. Disease evaluation included pre- and posttherapy brain/spine magnetic resonance imaging approximately every 3 months for the first year after treatment, and every 6-12 months thereafter. Forty-three patients received a total of 167 injections; 42 patients were evaluable for outcome. No treatment-related deaths occurred. Toxicities related to drug administration included acute bradycardia with somnolence, headache, fatigue, and CSF pleocytosis consistent with chemical meningitis and dystonic reaction. Total CSF absorbed dose was 1,453 cGy (where Gy is Gray; 350.0-2,784). Median overall survival from first dose of cRIT was 24.9 months (95% confidence interval [CI]:16.3-55.8). Patients treated in radiographic and cytologic remission were at a lower risk of death compared to patients with radiographically measurable disease (hazard ratio: 0.40, 95% CI: 0.18-0.88, P = 0.024). cRIT with 131 I-3F8 is safe, has favorable dosimetry to CSF, and when added to salvage therapy using conventional modalities, may have clinical utility in maintaining remission in high-risk or recurrent MB. © 2017 Wiley Periodicals, Inc.

Targeting Phosphatidylserine for Radioimmunotherapy of Breast Cancer Brain Metastasis

DTIC Science & Technology

2014-10-01

care for these patients is whole brain radiotherapy ( WBRT ). WBRT , however, is often associated with neurological complications that preclude...models. We further hypothesize that RIT in combination with low dose WBRT will not only achieve effective treatment of brain metastases but also...metastases by pimonidazole staining, indicating other causes than hypoxia may be related to PS exposure. 8 Fig. 4 Enhanced PS exposure after WBRT . Top. T2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carrasquillo, J.A.; Krohn, K.A.; Beaumier, P.

Antibodies which are directed against human tumor-associated antigens can potentially be used as carriers of radioactivity for in vivo diagnosis (radioimmunodetection) or treatment (radioimmunotherapy) of solid tumors, including colon, hepatoma, cholangiocarcinoma, and melanoma. Murine monoclonal antibodies (MOAB), produced by the hybridoma technique of Kohler and Milstein, are replacing conventional heterosera as sources of antibodies, because MOAB can be produced in large quantities as reproducible reagents with homogeneous binding properties. We have studied human melanoma using MOAB IgG and Fab fragments that recognize the human melanoma-associated antigens p97 and ''high-molecular-weight antigen''. Both antigens are found in the membrane of melanomas atmore » much larger concentrations than in normal adult tissues. We have performed radioimmunodetection studies with whole immunoglobulin and have detected 88% of lesions greater than 1.5 cm. We have used Fab fragments for radioimmunotherapy and have found that large doses of radiolabeled antibodies (up to 342 mCi) can be repetitively given to patients without excessive end-organ toxicity. Two of three patients treated with high-dose radiolabeled antimelanoma Fab showed an effect from the treatment. Although both technical and biologic problems remain, the use of radiolabeled antibodies that are directed against tumor-associated antigens holds future promise as a new therapeutic approach to solid tumors that are resistant to conventional therapy.« less

Radioimmunotherapy of nude mice with intraperitoneally growing ovarian cancer xenograft utilizing 211At-labelled monoclonal antibody MOv18.

PubMed

Andersson, H; Lindegren, S; Back, T; Jacobsson, L; Leser, G; Horvath, G

2000-01-01

The aim of this study was to investigate the therapeutic efficacy of 211At-labelled monoclonal antibody given intraperitoneally to nude mice with intraperitoneal growth of a human ovarian cancer cell line. Female nude mice were inoculated intraperitoneally with 1 x 10(7) cells of the human ovarian cancer cell line NIH:OVCAR 3. After about two weeks they were injected with the 211At-labelled specific monoclonal antibody MOv18 intraperitoneally. For comparison, other groups of mice were given the same labelled antibody intravenously, 211At-labelled unspecific antibody C242 intraperitoneally or unalbelled MOv18 intraperitoneally. Six weeks later the animals were sacrificed and the occurrence of tumour and ascites was determined. When the mice were treated with 211At-labelled MOv18 intraperitoneally 9 out of 10 were apparently free of both ascites and tumour compared to none of the mice given unlabelled antibody. 211At-labelled MOv18 given intravenously or 211At-labelled unspecific antibody given intraperitoneally were less effective. Regional radioimmunotherapy with the alpa-emitter 211Astatine seems to be an effective treatment of nude mice with intraperitoneally growing human ovarian cancer. Hopefully this treatment can be given in an adjuvant setting to women with minimal residual ovarian cancer in the future.

Development of a Novel, Non-Invasive Diagnostic Test for Prostate Cancer

DTIC Science & Technology

2006-01-01

Chang JJ, Bhargava V , Shinohara K. The optimal systematic prostate biopsy scheme should include 8 rather than 6 biopsies: results of a prospective...sextant and laterally directed biopsies for the detection of prostate cancer. J Urol, 2001, 165:1554-9. 19. Djavan B, Ravery V , Zlotta A, Dobronski P...Smith-Jones PM, Navarro V , Goldsmith SJ, Bander NH. Radioimmunotherapy of prostate cancer in human xenografts using monoclonal antibodies specific to

Improving cancer treatment with cyclotron produced radionuclides. Progress report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Larson, S.M.; Finn, R.D.

1992-08-04

Our goal is to improve the scientific basis for tumor diagnosis, treatment and treatment follow-up based on the use of cyclotron produced radiotracers in oncology. The grant includes 3 interactive components: Radiochemistry/Cyclotron; Pharmacology; and Immunology. The radiochemistry group seeks to develop innovative cyclotron targetry, radiopharmaceuticals, and radiolabeled antibodies, which are then used to assess important unanswered questions in tumor pharmacology and immunology. Examples include selected positron emitting radionuclides, such as Iodine-124, and Ga-66; I-124, I-123, I-131 labeled iododeoxyuridine, C-11 colchicine, and antimetabolites, like C-11 methotrexate; and radiolabeled antibodies, 3F8, M195, A33, and MRK16 for application in the pharmacology and immunologymore » projects. The pharmacology program studies tumor resistance to chemotherapy, particularly the phenomenon of multidrug resistance and the relationship between tumor uptake and retention and the tumor response for anti-metabolite drugs. The immunology program studies the physiology of antibody localization at the tissue level as the basis for novel approaches to improving tumor localization such as through the use of an artificial lymphatic system which mechanically reduces intratumoral pressures in tumors in vivo. Quantitative imaging approaches based on PET and SPECT in radioimmunotherapy are studied to give greater insight into the physiology of tumor localization and dosimetry.« less

Improving cancer treatment with cyclotron produced radionuclides

DOE Office of Scientific and Technical Information (OSTI.GOV)

Larson, S.M.; Finn, R.D.

1992-08-04

Our goal is to improve the scientific basis for tumor diagnosis, treatment and treatment follow-up based on the use of cyclotron produced radiotracers in oncology. The grant includes 3 interactive components: Radiochemistry/Cyclotron; Pharmacology; and Immunology. The radiochemistry group seeks to develop innovative cyclotron targetry, radiopharmaceuticals, and radiolabeled antibodies, which are then used to assess important unanswered questions in tumor pharmacology and immunology. Examples include selected positron emitting radionuclides, such as Iodine-124, and Ga-66; I-124, I-123, I-131 labeled iododeoxyuridine, C-11 colchicine, and antimetabolites, like C-11 methotrexate; and radiolabeled antibodies, 3F8, M195, A33, and MRK16 for application in the pharmacology and immunologymore » projects. The pharmacology program studies tumor resistance to chemotherapy, particularly the phenomenon of multidrug resistance and the relationship between tumor uptake and retention and the tumor response for anti-metabolite drugs. The immunology program studies the physiology of antibody localization at the tissue level as the basis for novel approaches to improving tumor localization such as through the use of an artificial lymphatic system which mechanically reduces intratumoral pressures in tumors in vivo. Quantitative imaging approaches based on PET and SPECT in radioimmunotherapy are studied to give greater insight into the physiology of tumor localization and dosimetry.« less

Optimising the therapeutic ratio of radioimmunotherapy; an investigation of the roles of chimerisation, fractionation and radiation dosimetry

NASA Astrophysics Data System (ADS)

Violet, John Albert

2007-12-01

Radioimmunotherapy (RIT) is a targeted form of treatment for cancer which uses tumour-associated antibodies to selectively deliver a therapeutic radionuclide to sites of disease. In lymphoma, radioimmunotherapy has proved a remarkably effective agent due to the high radiosensitivity of the tumour and its propensity to undergo apoptosis following irradiation. However, success in the treatment of the more radioresistant common solid tumours has been less successful, and for these patients RIT remains investigative. The effectiveness of RIT is limited by non-specific irradiation of normal tissues whilst antibody remains in the circulation, in particular bone marrow, and also by immunogenicity of antibody which does not allow for repeated therapy. In the first chapter I have hypothesised that lymphomas expressing the interleukin-2 receptor might be effectively treated using a radiolabeled antibody to this receptor. In a phase I/II clinical study, 131I labelled CHT-25, a chimeric antibody against the IL-2Ra chain, has shown encouraging evidence of efficacy in the 9 patients with multiply- relapsed lymphomas treated so far. In addition, use of this antibody has been associated with low immunogenicity allowing for repeated therapies to be given. In the second chapter I have hypothesised that dosimetry led, individual patient therapy, might further optimise 1311 CHT-25 treatment. To investigate this I have used marrow toxicity as a biological assay of absorbed dose and shown that simple, but individual, patient biodistribution indices correlate better with observed toxicity than the population-based dose estimates currently employed. I have proposed that adoption of individual patient dosimetry using tracer studies is worthy of further investigation for the future development of 131I- CHT-25. In the third chapter I have hypothesised that dose fractionation might improve the therapeutic ratio of RIT. This has been investigated in a pre-clinical human colorectal xenograft model in nude mice using 131I-A5B7, a murine antibody against CEA. In this setting fractionation neither reduces normal tissue toxicity nor increases the effectiveness of therapy. This thesis demonstrates, using both pre-clinical and clinical data, how the therapeutic ratio of RIT might be improved through antibody design, leading to reduced immunogenicity, dose fractionation and radiation dosimetry, and proposes how these approaches might be used to optimise the effectiveness of RIT in the clinic.

Improved radioimmunotherapy of hematologic malignancies. Progress report, 1988--1991

DOE Office of Scientific and Technical Information (OSTI.GOV)

Press, O.W.; Barofsky, D.F.

1991-12-31

This progress report describes accomplishments under four headings, namely: The study of the relative rates of metabolic degradation of radiolabeled monoclonal antibodies (MAb) targeting tumor associated antigens; Effects of lysosomotropic amines, carboxylic ionophores, and thioamides on the retention of radiolabeled MAbs by tumor cells; Subcellular site of radioimmunoconjugate degradation and the sizes of fragments generated by intracellular metabolism of radiolabeled antibodies; and Patterns of metabolic degradation of radioimmunoconjugates made with different techniques and with different radionuclides.

Radioimmunotherapy (RIT) Dose-Escalation Studies in Prostate Cancer Using Anti-PSMA Antibody 177Lu-J591: RIT Alone and RIT in Combination with Docetaxel

DTIC Science & Technology

2009-10-01

product consists of DOTA-HuJ591 antibody in 0.3 M ammonium acetate, pH 7.2, in 2 mL thermoplastic vials with gray butyl rubber stoppers and blue flip-off...crimp seal closures . The nominal concentration is 8.0 mg/mL and the nominal fill volume is 1.3 mL. There are no other excipients added. 177Lu

Radioimmunotherapy (RIT) Dose-Escalation Studies in Prostate Cancer Using Anti-PSMA Antibody 177Lu-J591: RIT Alone and RIT in Combination with Docetaxel

DTIC Science & Technology

2007-10-01

drug product consists of DOTA-HuJ591 antibody in 0.3 M ammonium acetate, pH 7.2, in 2 mL thermoplastic vials with gray butyl rubber stoppers and blue...flip-off crimp seal closures . The nominal concentration is 8.0 mg/mL and the nominal fill volume is 1.3 mL. There are no other excipients added

A phase II study of intraperitoneal radioimmunotherapy with iodine-131-labeled monoclonal antibody OC-125 in patients with residual ovarian carcinoma.

PubMed

Mahé, M A; Fumoleau, P; Fabbro, M; Guastalla, J P; Faurous, P; Chauvot, P; Chetanoud, L; Classe, J M; Rouanet, P; Chatal, J F

1999-10-01

Standard treatment of advanced ovarian cancer is a combination of surgery and chemotherapy. Additional therapies using the i.p. route are considered as a potential means of improving the locoregional control rate. This Phase II study evaluated the efficacy of i.p. radioimmunotherapy (RIT) in patients with minimal residual ovarian adenocarcinoma after primary treatment with surgery and chemotherapy. Between February 1995 and March 1996, six patients with residual macroscopic (<5 mm) or microscopic disease as demonstrated by laparotomy and multiple biopsies received i.p. RIT. All had initial stage III epithelial carcinoma and were treated with debulking surgery and one line (four patients) or two lines (two patients) of chemotherapy. RIT was performed with 60 mg of OC 125 F(ab')2 monoclonal antibody labeled with 4.44 GBq (120 mCi) of 131I injected 5-10 days after the surgical procedure. Systematic laparoscopy or laparotomy with multiple biopsies performed 3 months after RIT in five patients (clinical progression was seen in one patient) showed no change in three patients and progression in two patients. Toxicity was mainly hematological, with grade III neutropenia and thrombocytopenia in two patients. Human antimouse antibody production was demonstrated in all six patients. This study showed little therapeutic benefit from i.p. RIT in patients with residual ovarian carcinoma.

Pretargeting CD45 enhances the selective delivery of radiation to hematolymphoid tissues in nonhuman primates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Green, Damian J.; Pagel, John M.; Nemecek, Eneida R.

2009-08-06

Pretargeted radioimmunotherapy (PRIT) is designed to enhance the directed delivery of radionuclides to malignant cells. Through a series of studies in nineteen nonhuman primates (M. fascicularis) the potential therapeutic advantage of anti-CD45 PRIT was evaluated. Anti-CD45 PRIT demonstrated a significant improvement in target-to-normal organ ratios of absorbed radiation when compared to directly radiolabeled bivalent antibody (conventional radioimmunotherapy [RIT]). Radio-DOTA-biotin administered 48 hours after anti-CD45 streptavidin fusion protein (FP) [BC8 (scFv)4SA] produced markedly lower concentrations of radiation in non-target tissues when compared to conventional RIT. PRIT generated superior target:normal organ ratios in the blood, lung and liver (10.3:1, 18.9:1 and 9.9:1more » respectively) when compared to the conventional RIT controls (2.6:1, 6.4:1 and 2.9:1 respectively). The FP demonstrated superior retention in target tissues relative to comparable directly radiolabeled bivalent anti-CD45 RIT. The time-point of administration of the second step radiolabeled ligand (radio-DOTA-biotin) significantly impacted the biodistribution of radioactivity in target tissues. Rapid clearance of the FP from the circulation rendered unnecessary the addition of a synthetic clearing agent in this model. These results support proceeding to anti-CD45 PRIT clinical trials for patients with both leukemia and lymphoma.« less

A Randomized Phase 2 Trial of 177Lu Radiolabeled Anti-PSMA Monoclonal Antibody J591 in Patients With High-Risk Castrate, Biochemically Relapsed Prostate Cancer

DTIC Science & Technology

2017-09-01

MDS Myelodysplastic syndrome and acute myeloid leukemia has been reported in patients previously treated with anti-CD20 based RIT for non-hodgkin’s...RR, Rossi A, Jhaveri K, Feldman EJ, Leonard JP. Therapy-related myelodysplastic syndrome and acute myeloid leukemia following initial treatment with... syndrome and acute myelogenous leukemia in patients treated with ibritumomab tiuxetan radioimmunotherapy. J Clin Oncol. 2007 Sep 20;25(27):4285-92. 119

Radionuclide development at BNL for nuclear medicine therapy.

PubMed

Mausner, L F; Kolsky, K L; Joshi, V; Srivastava, S C

1998-04-01

Radionuclides with medium energy beta emission and a several day half-life have often been viewed as attractive candidates for radioimmunotherapy. Among the most promising in this category are 47Sc, 67Cu, 153Sm, 188Re, and 199Au. The production of 67Cu, 153Sm, 199Au at BNL is summarized and the development of the latest candidate for this application, 47Sc, is described in detail. We also summarize the development of another important therapeutic radionuclide, 117mSn for bone pain palliation.

Breast Tumor Detection and Treatment Using Tarvacin Labeled with Arsenic Radionuclides

DTIC Science & Technology

2009-04-01

IVRT), or radio-immunotherapy (RIT). This radionuclide can be produced from natural germanium in nuclear reactors through the neutron induced nuclear... ra ts. When primary tumors reach 1 cm diameter 74As-SATA-Tarvacin will be adm inistered IV and biodistribution assessed in vivo using PET after 24...changes for the irradiation will be as follows. Production of ± 37 GBq of 74As by natGe(α,x)74As reaction. Estimated beam time 1 hour at 15μΑ on

Radioimmunotherapy (RIT) Dose-Escalation Studies in Prostate Cancer Using Anti-PSMA Antibody 177Lu-J591: RIT Alone and RIT in Combination with Docetaxel

DTIC Science & Technology

2008-10-01

for > 3 platelet transfusion in 30 days • Gr 4 neutropenia • Febrile neutropenia • Attributable Gr > 3 non-hematologic toxicity (excluding infusion...0% No febrile neutropenia (no growth factor use) • Transaminitis (n=12 evaluable) Transient Gr 1 17% (no Gr > 1) Figure-1...therapies and 36% progressed on 1-4 lines of chemotherapy including docetaxel. No DLT’s have been seen. 2 pts experienced reversible Gr 3 neutropenia

A comparative analysis of conventional and pretargeted radioimmunotherapy of B-cell lymphomas by targeting CD20, CD22, and HLA-DR singly and in combinations

PubMed Central

Orgun, Nural; Hamlin, Donald K.; Wilbur, D. Scott; Gooley, Theodore A.; Gopal, Ajay K.; Park, Steven I.; Green, Damian J.; Lin, Yukang; Press, Oliver W.

2009-01-01

Relapsed B-cell lymphomas are currently incurable with conventional chemotherapy and radiation treatments. Radiolabeled antibodies directed against B-cell surface antigens have emerged as effective and safe therapies for relapsed lymphomas. We therefore investigated the potential utility of both directly radiolabeled 1F5 (anti-CD20), HD39 (anti-CD22), and Lym-1 (anti-DR) antibodies (Abs) and of pretargeted radioimmunotherapy (RIT) using Ab-streptavidin (SA) conjugates, followed by an N-acetylgalactosamine dendrimeric clearing agent and radiometal-labeled DOTA-biotin, for treatment of lymphomas in mouse models using Ramos, Raji, and FL-18 human lymphoma xenografts. This study demonstrates the marked superiority of pretargeted RIT for each of the antigenic targets with more complete tumor regressions and longer mouse survival compared with conventional one-step RIT. The Ab-SA conjugate yielding the best tumor regression and progression-free survival after pretargeted RIT varied depending upon the lymphoma cell line used, with 1F5 Ab-SA and Lym-1 Ab-SA conjugates yielding the most promising results overall. Contrary to expectations, the best rates of mouse survival were obtained using optimal single Ab-SA conjugates rather than combinations of conjugates targeting different antigens. We hypothesize that clinical implementation of pretargeted RIT methods will provide a meaningful prolongation of survival for patients with relapsed lymphomas compared with currently available treatment strategies. PMID:19124831

Preparation and biological evaluation of (177)Lu conjugated PR81 for radioimmunotherapy of breast cancer.

PubMed

Salouti, Mojtaba; Babaei, Mohammad Hossein; Rajabi, Hossein; Rasaee, Mohammad javad

2011-08-01

PR81 is a monoclonal antibody that binds with high affinity to MUC1 antigen that is over expressed in 80% of breast cancers. In this study, we developed a method for indirect labeling of PR81 with lutetium-177 and performed all preclinical qualifications in production of a biologic agent for radioimmunotherapy of breast cancer. The radiochemical purity and in vitro stability of (177)Lu labeled PR81 was determined by instant thin layer chromatography. The immunoreactivity and cell toxicity of the complex were tested on MCF7 cell line. The biodistribution and scintigraphy studies were performed in BALB/c mice with breast tumor. The radiochemical purity was 91.2±3.8% after 2 h. The in vitro stabilities in phosphate buffer and human blood serum were 83.1±3.4% and 76.2±3.6% at 96 h, respectively. The immunoreactivity of the complex was 83.4±2.4%. The cell toxicity study showed that the complex inhibited 85.2±3.4% growth of MCF7 cells at a concentration of 2500 ng/ml after 96 h. The biodistribution and scintigraphy studies showed the accumulation of the complex at the site of tumors with high sensitivity and specificity. The results showed that one may consider (177)Lu-DOTA-PR81 as a potential radiopharmaceutical for therapy of human breast cancer, which needs further investigations. Copyright © 2011 Elsevier Inc. All rights reserved.

Addressing challenges of heterogeneous tumor treatment through bispecific protein-mediated pretargeted drug delivery.

PubMed

Yang, Qi; Parker, Christina L; McCallen, Justin D; Lai, Samuel K

2015-12-28

Tumors are frequently characterized by genomically and phenotypically distinct cancer cell subpopulations within the same tumor or between tumor lesions, a phenomenon termed tumor heterogeneity. These diverse cancer cell populations pose a major challenge to targeted delivery of diagnostic and/or therapeutic agents, as the conventional approach of conjugating individual ligands to nanoparticles is often unable to facilitate intracellular delivery to the full spectrum of cancer cells present in a given tumor lesion or patient. As a result, many cancers are only partially suppressed, leading to eventual tumor regrowth and/or the development of drug-resistant tumors. Pretargeting (multistep targeting) approaches involving the administration of 1) a cocktail of bispecific proteins that can collectively bind to the entirety of a mixed tumor population followed by 2) nanoparticles containing therapeutic and/or diagnostic agents that can bind to the bispecific proteins accumulated on the surface of target cells offer the potential to overcome many of the challenges associated with drug delivery to heterogeneous tumors. Despite its considerable success in improving the efficacy of radioimmunotherapy, the pretargeting strategy remains underexplored for a majority of nanoparticle therapeutic applications, especially for targeted delivery to heterogeneous tumors. In this review, we will present concepts in tumor heterogeneity, the shortcomings of conventional targeted systems, lessons learned from pretargeted radioimmunotherapy, and important considerations for harnessing the pretargeting strategy to improve nanoparticle delivery to heterogeneous tumors. Copyright © 2015 Elsevier B.V. All rights reserved.

Radioimmunotherapy (RIT) Dose-Escalation Studies in Prostate Cancer Using Anti-PSMA Antibody 177Lu-J591: RIT Alone and RIT in Combination with Docetaxel

DTIC Science & Technology

2010-10-01

count < 15,000 > 7 days or need for > 3 plt transfusions in 30 days • Gr 4 neutropenia > 7 days • Febrile neutropenia • Attributable Gr > 3...11% No febrile neutropenia (no growth factor use) • Transaminitis Transient Gr 1 AST 29% (1 Gr 2) Need for transfusions 6 pts...No pts had significant bleeding; 2 received plt transfusions (cohort 6) • Neutropenia Gr 0 = 40%; Gr 1-2 = 32%; Gr 3 = 29%; Gr 4

A preclinical model of CD38-pretargeted radioimmunotherapy for plasma cell malignancies.

PubMed

Green, Damian J; Orgun, Nural N; Jones, Jon C; Hylarides, Mark D; Pagel, John M; Hamlin, Donald K; Wilbur, D S; Lin, Yukang; Fisher, Darrell R; Kenoyer, Aimee L; Frayo, Shani L; Gopal, Ajay K; Orozco, Johnnie J; Gooley, Theodore A; Wood, Brent L; Bensinger, William I; Press, Oliver W

2014-02-15

The vast majority of patients with plasma cell neoplasms die of progressive disease despite high response rates to novel agents. Malignant plasma cells are very radiosensitive, but the potential role of radioimmunotherapy (RIT) in the management of plasmacytomas and multiple myeloma has undergone only limited evaluation. Furthermore, CD38 has not been explored as a RIT target despite its uniform high expression on malignant plasma cells. In this report, both conventional RIT (directly radiolabeled antibody) and streptavidin-biotin pretargeted RIT (PRIT) directed against the CD38 antigen were assessed as approaches to deliver radiation doses sufficient for multiple myeloma cell eradication. PRIT demonstrated biodistributions that were markedly superior to conventional RIT. Tumor-to-blood ratios as high as 638:1 were seen 24 hours after PRIT, whereas ratios never exceeded 1:1 with conventional RIT. (90)Yttrium absorbed dose estimates demonstrated excellent target-to-normal organ ratios (6:1 for the kidney, lung, liver; 10:1 for the whole body). Objective remissions were observed within 7 days in 100% of the mice treated with doses ranging from 800 to 1,200 μCi of anti-CD38 pretargeted (90)Y-DOTA-biotin, including 100% complete remissions (no detectable tumor in treated mice compared with tumors that were 2,982% ± 2,834% of initial tumor volume in control animals) by day 23. Furthermore, 100% of animals bearing NCI-H929 multiple myeloma tumor xenografts treated with 800 μCi of anti-CD38 pretargeted (90)Y-DOTA-biotin achieved long-term myeloma-free survival (>70 days) compared with none (0%) of the control animals. ©2013 AACR.

Prediction of Therapy Tumor-Absorbed Dose Estimates in I-131 Radioimmunotherapy Using Tracer Data Via a Mixed-Model Fit to Time Activity

PubMed Central

Koral, Kenneth F.; Avram, Anca M.; Kaminski, Mark S.; Dewaraja, Yuni K.

2012-01-01

Abstract Background For individualized treatment planning in radioimmunotherapy (RIT), correlations must be established between tracer-predicted and therapy-delivered absorbed doses. The focus of this work was to investigate this correlation for tumors. Methods The study analyzed 57 tumors in 19 follicular lymphoma patients treated with I-131 tositumomab and imaged with SPECT/CT multiple times after tracer and therapy administrations. Instead of the typical least-squares fit to a single tumor's measured time-activity data, estimation was accomplished via a biexponential mixed model in which the curves from multiple subjects were jointly estimated. The tumor-absorbed dose estimates were determined by patient-specific Monte Carlo calculation. Results The mixed model gave realistic tumor time-activity fits that showed the expected uptake and clearance phases even with noisy data or missing time points. Correlation between tracer and therapy tumor-residence times (r=0.98; p<0.0001) and correlation between tracer-predicted and therapy-delivered mean tumor-absorbed doses (r=0.86; p<0.0001) were very high. The predicted and delivered absorbed doses were within±25% (or within±75 cGy) for 80% of tumors. Conclusions The mixed-model approach is feasible for fitting tumor time-activity data in RIT treatment planning when individual least-squares fitting is not possible due to inadequate sampling points. The good correlation between predicted and delivered tumor doses demonstrates the potential of using a pretherapy tracer study for tumor dosimetry-based treatment planning in RIT. PMID:22947086

Anti-CD45 Pretargeted Radioimmunotherapy using Bismuth-213: High Rates of Complete Remission and Long-Term Survival in a Mouse Myeloid Leukemia Xenograft Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pagel, John M; Kenoyer, Aimee L; Back, Tom

2011-07-21

Pretargeted radioimmunotherapy (PRIT) using an anti-CD45 antibody (Ab)-streptavidin (SA) conjugate and DOTA-biotin labeled with β-emitting radionuclides has been explored as a strategy to decrease relapse and toxicity. α-emitting radionuclides exhibit high cytotoxicity coupled with a short path-length, potentially increasing the therapeutic index and making them an attractive alternative to β-emitting radionuclides for patients with Acute Myeloid Leukemia (AML). Accordingly, we have used 213Bi in mice with human leukemia xenografts. Results demonstrated excellent localization of 213Bi-DOTA-biotin to tumors with minimal uptake into normal organs. After 10 minutes, 4.5 ± 1.1% of the injected dose of 213Bi was delivered per gram ofmore » tumor. α imaging demonstrated uniform radionuclide distribution within tumor tissue 45 minutes after 213Bi-DOTA-biotin injection. Radiation absorbed doses were similar to those observed using a β-emitting radionuclide (90Y) in the same model. We conducted therapy experiments in a xenograft model using a single-dose of 213Bi-DOTA-biotin given 24 hours after anti-CD45 Ab-SA conjugate. Among mice treated with anti-CD45 Ab-SA conjugate followed by 800 μCi of 213Bi- or 90Y-DOTA-biotin, 80% and 20%, respectively, survived leukemia-free for >100 days with minimal toxicity. These data suggest that anti-CD45 PRIT using an α-emitting radionuclide may be highly effective and minimally toxic for treatment of AML.« less

Radioimmunotherapy of non-Hodgkin's lymphoma: molecular targeting and novel agents.

PubMed

Pauwels, Ernest K J; Erba, Paola

2007-03-01

In recent years monoclonal antibodies have played an important role in cancer therapy. This successful track is grosso modo based upon developments in the production of desired antibody molecules, the identification of suitable tumor antigens and the construction of chimeric and fully humanized antibodies. Especially in hematologic disorders, notably in non-Hodgkin's disease, the monoclonal antibody rituximab has proven to be of value in relapsed or refractory disease. Yet, to overcome the nonoptimal properties of this drug, especially in relation to the time to next therapy, radiolabeled immunoconjugates have been synthesized. For this purpose, the radionuclide yttrium-90 has been linked to the monoclonal antibody ibritumomab via the chelator tiuxetan. The most recent clinical results of this radiolabeled agent versus the nonradioactive drug treatment are reviewed in this paper. Furthermore, attention is paid to the monoclonal antibody tositumomab labeled with iodine-131, of which the first clinical results have become available most recently. This overview also mentions possibilities to increase the therapeutic efficacy of radionuclide immunoconjugates. This can be achieved by enhancing the targeting characteristics of the antibody and the use of alpha radiation-emitting radionuclides.

Yttrium 90 ibritumomab tiuxetan radioimmunotherapy for relapsed or refractory low-grade non-Hodgkin's lymphoma.

PubMed

Gordon, Leo I; Witzig, Thomas E; Wiseman, Greg A; Flinn, Ian W; Spies, Stewart S; Silverman, Daniel H; Emmanuolides, Christos; Cripe, Larry; Saleh, Mansoor; Czuczman, Myron S; Olejnik, Teresa; White, Christine A; Grillo-López, Antonio J

2002-02-01

The treatment of malignant lymphoma has improved over the past 20 years, but the majority of patients are not cured. New modalities using targeted therapy based on new information in molecular biology and immunology hold promise for better outcomes with less toxicity. We review data on the use of radiolabeled monoclonal antibodies directed against the CD20 antigen on malignant B cells. We discuss the major radionuclides available, iodine 131 ( 131 I), tositumomab, and yttrium 90 ( 90 Y) ibritumomab tiuxetan (Zevalin; IDEC Pharmaceuticals, San Diego, CA) and present data on new approaches in labeling antibodies that have facilitated their use. Clinical trial data with the yttrium-labeled antibodies are discussed. The use of dosimetry as a means for predicting toxicity is discussed, and the questions of long-term toxicity (late effects) are addressed. These targeted approaches to the treatment of malignancy, and lymphoma in particular, hold great promise. Semin Oncol 29 (suppl 2):87-92. Copyright © 2002 by W.B. Saunders Company. Copyright © 2002 W.B. Saunders Company. All rights reserved.

Improved survival of mice bearing liver metastases of colon cancer cells treated with a combination of radioimmunotherapy and antiangiogenic therapy.

PubMed

Kinuya, Seigo; Yokoyama, Kunihiko; Koshida, Kiyoshi; Mori, Hirofumi; Shiba, Kazuhiro; Watanabe, Naoto; Shuke, Noriyuki; Bai, Jingming; Michigishi, Takatoshi; Tonami, Norihisa

2004-07-01

We attempted to determine whether the combined regimen of radioimmunotherapy (RIT) and antiangiogenic therapy would favorably affect the survival of animals bearing liver metastases of colon cancer cells. Daily antiangiogenic therapy with 2-methoxyestradiol (2-ME), 75 mg/kg, was initiated at 3 days following intrasplenic cell inoculation of LS180 colon cancer cells. RIT with 7 MBq of (131)I-A7, an IgG1 anti-colorectal monoclonal antibody, or (131)I-HPMS-1, an irrelevant IgG1, was conducted at 7 days. Production of vascular endothelial growth factor (VEGF) by LS180 cells was assessed in vitro. All nontreated mice died by 31 days following cell inoculation ( n=5). Monotherapy comprising 2-ME treatment resulted in slightly better survival of mice ( n=8) ( P<0.05). (131)I-A7 RIT displayed a marked therapeutic effect ( n=8) ( P<0.001); however, all animals eventually died due to metastases by 99 days. The combined regimen of (131)I-A7 RIT and antiangiogenic therapy demonstrated a superior therapeutic effect in comparison to monotherapy consisting of either RIT or antiangiogenic therapy ( n=10) ( P<0.05); three mice survived the entire 160-day observation period. The combination of antiangiogenic therapy and (131)I-HPMS-1 RIT failed to provide an appreciable benefit ( n=5). Treatment with 2-ME decreased VEGF production by LS180 cells in a dose-dependent fashion. In conclusion, a combination regimen comprising RIT and antiangiogenic therapy initiated at the early stage of metastasis would be of great benefit in terms of improvement of the therapeutic efficacy with respect to liver metastases.

Radiometals as payloads for radioimmunotherapy for lymphoma.

PubMed

DeNardo, Gerald L; Kennel, Stephen J; Siegel, Jeffry A; Denardo, Sally J

2004-10-01

Because of their remarkable effectiveness in radioimmunotherapy (RIT), 2 anti-CD20 monoclonal antibody (MAb) drugs, one labeled with indium 111 for imaging or yttrium 90 for therapy, and another labeled with iodine I 131 for imaging and therapy, have been approved for use in patients with non-Hodgkin's lymphoma (NHL). Successful RIT for lymphomas is due in large part to the rapid and efficient binding of the targeted MAb to lymphoma cells. Carcinomas are more difficult to access, necessitating novel strategies matched with radionuclides with specific physical properties. Because there are many radionuclides from which to choose, a systematic approach is required to select those preferred for a specific application. Thus far, radionuclides with g emissions for imaging and particulate emissions for therapy have been investigated. Radionuclides of iodine were the first to be used for RIT. Many conventionally radioiodinated MAbs are degraded after endocytosis by target cells, releasing radioiodinated peptides and amino acids. In contrast, radiometals have been shown to have residualizing properties, advantageous when the MAb is localized in malignant tissue. b-emitting lanthanides like those of 90Y, lutetium 177, etc. have attractive combinations of biologic, physical, radiochemical, production, economic, and radiation safety characteristics. Other radiometals, such as copper-67 and copper-64, are also of interest. a-emitters, including actinium-225 and bismuth-213, have been used for therapy in selected applications. Evidence for the impact of the radionuclide is provided by data from the randomized pivotal phase III trial of 90Y ibritumomab tiuxetan (Zevalin) in patients with NHL; responses were about 2 times greater in the 90Y ibritumomab tiuxetan arm than in the rituximab arm. It is clear that RIT has emerged as a safe and efficient method for treatment of NHL, especially in specific settings.

Mechanisms of Cell Killing Response from Low Linear Energy Transfer (LET) Radiation Originating from 177Lu Radioimmunotherapy Targeting Disseminated Intraperitoneal Tumor Xenografts

PubMed Central

Yong, Kwon Joong; Milenic, Diane E.; Baidoo, Kwamena E.; Brechbiel, Martin W.

2016-01-01

Radiolabeled antibodies (mAbs) provide efficient tools for cancer therapy. The combination of low energy β−-emissions (500 keVmax; 130 keVave) along with a γ-emission for imaging makes 177Lu (T1/2 = 6.7 day) a suitable radionuclide for radioimmunotherapy (RIT) of tumor burdens possibly too large to treat with α-particle radiation. RIT with 177Lu-trastuzumab has proven to be effective for treatment of disseminated HER2 positive peritoneal disease in a pre-clinical model. To elucidate mechanisms originating from this RIT therapy at the molecular level, tumor bearing mice (LS-174T intraperitoneal xenografts) were treated with 177Lu-trastuzumab comparatively to animals treated with a non-specific control, 177Lu-HuIgG, and then to prior published results obtained using 212Pb-trastuzumab, an α-particle RIT agent. 177Lu-trastuzumab induced cell death via DNA double strand breaks (DSB), caspase-3 apoptosis, and interfered with DNA-PK expression, which is associated with the repair of DNA non-homologous end joining damage. This contrasts to prior results, wherein 212Pb-trastuzumab was found to down-regulate RAD51, which is involved with homologous recombination DNA damage repair. 177Lu-trastuzumab therapy was associated with significant chromosomal disruption and up-regulation of genes in the apoptotic process. These results suggest an inhibition of the repair mechanism specific to the type of radiation damage being inflicted by either high or low linear energy transfer radiation. Understanding the mechanisms of action of β−- and α-particle RIT comparatively through an in vivo tumor environment offers real information suitable to enhance combination therapy regimens involving α- and β−-particle RIT for the management of intraperitoneal disease. PMID:27196891

A model for hematopoietic death in man from irradiation of bone marrow during radioimmunotherapy.

PubMed

Scott, B R; Dillehay, L E

1990-11-01

There are numerous institutions worldwide performing clinical trials of radioimmunotherapy (RIT) for cancer. For RIT, an exponentially decaying radionuclide is attached by using a chelating agent to a specific monoclonal or polyclonal tumour antibody (e.g. antiferritin IgG). The major limitation to RIT is toxicity to normal tissue in organs other than the one containing the tumour (e.g. bone marrow). The focus of this manuscript is on modelling the risk (or probability) of hematopoietic death in man for exponentially decaying patterns of high-energy beta irradiation (e.g. 90Y) of bone marrow by radioimmunoglobulin injected into the blood. The analytical solutions presented are only applicable to protocols for which significant uptake of radioactivity by the bone marrow does not occur, and only for high energy beta emitters. However, the generic equation used to obtain the analytical solutions is applicable to any continuous pattern of high energy beta irradiation. A model called the "normalized dose model" was used to generate calculated values for the LD50 as a function of the effective half-time for the radioimmunoglobulin in the blood. A less complicated empirical model was used to describe the calculated values. This model is presumed to be valid for effective half-times in blood of up to about 20 days. For longer effective half-times, the LD50 can be estimated using the normalized-dose model presented. In this manuscript, we also provide a modified Weibull model that allows estimation of the risk of hematopoietic death for single or multiple injections (in one cycle) of radioimmunoglobulin, for patients with normal susceptibility to irradiation and for patients with heightened susceptibility. With the modified Weibull model, the risk of hematopoietic death depends on the level of medical treatment provided to mitigate radiation injuries.

SU-E-J-03: A Comprehensive Comparison Between Alpha and Beta Emitters for Cancer Radioimmunotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, C.Y.; Guatelli, S; Oborn, B

2014-06-01

Purpose: The purpose of this study is to perform a comprehensive comparison of the therapeutic efficacy and cytotoxicity of alpha and beta emitters for Radioimmunotherapy (RIT). For each stage of cancer development, specific models were built for the separate objectives of RIT to be addressed:a) kill isolated cancer cells in transit in the lymphatic and vascular circulation,b) regress avascular cell clusters,c) regress tumor vasculature and tumors. Methods: Because of the nature of short range, high LET alpha and long energy beta radiation and heterogeneous antigen expression among cancer cells, the microdosimetric approach is essential for the RIT assessment. Geant4 basedmore » microdosimetric models are developed for the three different stages of cancer progression: cancer cells, cell clusters and tumors. The energy deposition, specific energy resulted from different source distribution in the three models was calculated separately for 4 alpha emitting radioisotopes ({sup 211}At, {sup 213}Bi, {sup 223}Ra and {sup 225}Ac) and 6 beta emitters ({sup 32}P, {sup 33}P, {sup 67}Cu, {sup 90}Y, {sup 131}I and {sup 177}Lu). The cell survival, therapeutic efficacy and cytotoxicity are determined and compared between alpha and beta emitters. Results: We show that internal targeted alpha radiation has advantages over beta radiation for killing isolated cancer cells, regressing small cell clusters and also solid tumors. Alpha particles have much higher dose specificity and potency than beta particles. They can deposit 3 logs more dose than beta emitters to single cells and solid tumor. Tumor control probability relies on deep penetration of radioisotopes to cancer cell clusters and solid tumors. Conclusion: The results of this study provide a quantitative understanding of the efficacy and cytotoxicity of RIT for each stage of cancer development.« less

Inhibitory effects of Rhenium-188-labeled Herceptin on prostate cancer cell growth: a possible radioimmunotherapy to prostate carcinoma.

PubMed

Wang, Hsin-Yi; Lin, Wan-Yu; Chen, Mei-Chih; Lin, Teh; Chao, Chih-Hao; Hsu, Fu-Ning; Lin, Eugene; Huang, Chih-Yang; Luo, Tsai-Yueh; Lin, Ho

2013-05-01

Herceptin is widely used in treating Her2-overexpressing breast cancer. However, the application of Herceptin in prostate cancer is still controversial. Our previous results have indicated the relevance of Her2 in the transition of the androgen requirement in prostate cancer cells. In this study, the effects of radioimmunotherapy against Her2 in prostate cancer were investigated. DU145, an androgen receptor-negative prostate cancer cell line, was used in vitro and in vivo to evaluate the effects of Herceptin labeled with a beta emitter, Rhenium-188 (Re-188). Its effects on cell growth, extent of apoptosis, the bio-distribution of Re-188 labeled Herceptin (Re-H), and protein levels were determined. Treatments with Re-188 and Re-H reduced the proliferation of DU145 cells in dose- and time-dependent manners compared to the Herceptin-treated group. Growth inhibition and apoptosis were induced after Re-H treatment; growth inhibition was more distinct in cells with high Her2/p-Her2 levels. Our in vivo xenograft studies revealed that Re-H treatment significantly retarded tumor growth and altered the levels of apoptosis-related proteins. The bio-distribution of Re-H in mice demonstrated a tissue-specific pattern. Importantly, the levels of p35 protein, which is related to cancer cell survival and invasion, dramatically decreased after Re-H treatment. Our data demonstrate that Re-188-labeled Herceptin effectively inhibited the growth of DU145 cells compared to the Herceptin- and Re-188-treated cohorts. This implies that targeting Her2 by both radio- and immuno- therapy might be a potential strategy for treating patients with androgen-independent prostate cancer.

Conventional and pretargeted radioimmunotherapy using bismuth-213 to target and treat non-Hodgkin lymphomas expressing CD20: a preclinical model toward optimal consolidation therapy to eradicate minimal residual disease.

PubMed

Park, Steven I; Shenoi, Jaideep; Pagel, John M; Hamlin, Don K; Wilbur, D Scott; Orgun, Nural; Kenoyer, Aimee L; Frayo, Shani; Axtman, Amanda; Bäck, Tom; Lin, Yukang; Fisher, Darrell R; Gopal, Ajay K; Green, Damian J; Press, Oliver W

2010-11-18

Radioimmunotherapy (RIT) with α-emitting radionuclides is an attractive approach for the treatment of minimal residual disease because the short path lengths and high energies of α-particles produce optimal cytotoxicity at small target sites while minimizing damage to surrounding normal tissues. Pretargeted RIT (PRIT) using antibody-streptavidin (Ab-SA) constructs and radiolabeled biotin allows rapid, specific localization of radioactivity at tumor sites, making it an optimal method to target α-emitters with short half-lives, such as bismuth-213 (²¹³Bi). Athymic mice bearing Ramos lymphoma xenografts received anti-CD20 1F5(scFv)(4)SA fusion protein (FP), followed by a dendrimeric clearing agent and [²¹³Bi]DOTA-biotin. After 90 minutes, tumor uptake for 1F5(scFv)₄SA was 16.5% ± 7.0% injected dose per gram compared with 2.3% ± .9% injected dose per gram for the control FP. Mice treated with anti-CD20 PRIT and 600 μ Ci [²¹³Bi]DOTA-biotin exhibited marked tumor growth delays compared with controls (mean tumor volume .01 ± .02 vs. 203.38 ± 83.03 mm³ after 19 days, respectively). The median survival for the 1F5(scFv)₄SA group was 90 days compared with 23 days for the control FP (P < .0001). Treatment was well tolerated, with no treatment-related mortalities. This study demonstrates the favorable biodistribution profile and excellent therapeutic efficacy attainable with ²¹³Bi-labeled anti-CD20 PRIT.

Tetraspanin 8 (TSPAN 8) as a potential target for radio-immunotherapy of colorectal cancer

PubMed Central

Navarro-Teulon, Isabelle; Berthier-Vergnes, Odile; Fois, Giovanna; Zhu, Yingying; Besse, Sophie; Bawa, Olivia; Briat, Arnaud; Quintana, Mercedes; Pichard, Alexandre; Bonnet, Mathilde; Rubinstein, Eric; Pouget, Jean-Pierre; Opolon, Paule; Maigne, Lydia; Miot-Noirault, Elisabeth; Chezal, Jean-Michel

2017-01-01

Tetraspanin 8 (TSPAN8) overexpression is correlated with poor prognosis in human colorectal cancer (CRC). A murine mAb Ts29.2 specific for human TSPAN8 provided significant efficiency for immunotherapy in CRC pre-clinical models. We therefore evaluate the feasability of targeting TSPAN8 in CRC with radiolabeled Ts29.2. Staining of tissue micro-arrays with Ts29.2 revealed that TSPAN8 espression was restricted to a few human healthy tissues. DOTA-Ts29.2 was radiolabeled with 111In or 177Lu with radiochemical purities >95%, specific activity ranging from 300 to 600 MBq/mg, and radioimmunoreactive fractions >80%. The biodistribution of [111In]DOTA-Ts29.2 in nude mice bearing HT29 or SW480 CRC xenografts showed a high specificity of tumor localization with high tumor/blood ratios (HT29: 4.3; SW480-TSPAN8: 3.9 at 72h and 120h post injection respectively). Tumor-specific absorbed dose calculations for [177Lu]DOTA-Ts29.2 was 1.89 Gy/MBq, establishing the feasibility of using radioimmunotherapy of CRC with this radiolabeled antibody. A significant inhibition of tumor growth in HT29 tumor-bearing mice treated with [177Lu]DOTA-Ts29.2 was observed compared to control groups. Ex vivo experiments revealed specific DNA double strand breaks associated with cell apoptosis in [177Lu]DOTA-Ts29.2 treated tumors compared to controls. Overall, we provide a proof-of-concept for the use of [111In/177Lu]DOTA-Ts29.2 that specifically target in vivo aggressive TSPAN8-positive cells in CRC. PMID:28423546

Theranostic pretargeted radioimmunotherapy of colorectal cancer xenografts in mice using picomolar affinity Y-86- or Lu-177-DOTA-Bn binding scFv C825/GPA33 IgG bispecific immunoconjugates

PubMed Central

Cheal, Sarah M.; Xu, Hong; Guo, Hong-fen; Lee, Sang-gyu; Punzalan, Blesida; Chalasani, Sandhya; Fung, Edward K.; Jungbluth, Achim; Zanzonico, Pat B.; Carrasquillo, Jorge A.; O’Donoghue, Joseph; Smith-Jones, Peter M.; Wittrup, K. Dane; Cheung, Nai-Kong V.; Larson, Steven M.

2015-01-01

Purpose GPA33 is a colorectal cancer (CRC) antigen with unique retention properties after huA33-mediated tumor targeting. We tested a pre-targeted radioimmunotherapy (PRIT) approach for CRC using a tetravalent bispecific antibody with dual specificity for GPA33 tumor antigen and DOTA-Bn (radiolanthanide metal) complex. Methods PRIT was optimized in vivo by titrating sequential intravenous doses of huA33-C825, the dextran-based clearing agent (CA), and the C825-haptens 177Lu-or 86Y-DOTA-Bn in mice bearing the SW1222 subcutaneous (s.c.) CRC xenograft model. Results Using optimized PRIT, therapeutic indices (TIs) for tumor radiation absorbed dose of 73 (tumor/blood) and 12 (tumor/kidney) were achieved. Estimated absorbed doses (cGy/MBq) to tumor, blood, liver, spleen, and kidney for single-cycle PRIT were 65.8, 0.9 (TI: 73), 6.3 (TI: 10), 6.6 (TI: 10), and 5.3 (TI: 12), respectively. Two cycles of PRIT treatment (66.6 or 111 MBq 177Lu-DOTA-Bn) were safe and effective, with 9/9 complete responses of established s.c. tumors (100–700 mm3) and 2/9 alive without recurrence >140 d. Tumor log kill in this model was estimated to be 2.1–3.0 based time to 500-mm3 tumor recurrence. In addition, PRIT dosimetry/diagnosis was performed by PET imaging of the positron-emitting DOTA-hapten 86Y-DOTA-Bn. Conclusions We have developed anti-GPA33 PRIT, as a triple-step theranostic strategy for pre-clinical detection, dosimetry and safe targeted radiotherapy of established human colorectal mouse xenografts. PMID:26596724

Development of DOTA-Rituximab to be Labeled with 90Y for Radioimmunotherapy of B-cell Non-Hodgkin Lymphoma

PubMed Central

Johari doha, Fariba; Rahmani, Siyavash; Rikhtechi, Pedram; Rasaneh, Samira; Sheikholislam, Zahra; Shahhosseini, Soraya

2017-01-01

NHL is the most common hematologic cancer in adults. Rituximab is the FDA approved treatment of relapsed or refractory low grade B-cell Non-Hodgkin Lymphoma (NHL). But patients eventually become resistant to rituximab. Since lymphocytes and lymphoma cells are highly radiosensitive, low grade NHL that has relapsed or refractory to standard therapy is treated by RIT in which a beta-emitting radionuclide coupled to anti-CD20 antibody. The association of beta emitter radionuclide to rituximab enhances its therapeutic efficacy. The cells which lack antigen or cells which cannot be reached due to poor vascularization and intratumoral pressure in a bulky tumor would be irradiated and killed by cross fire effect of beta emitter. 90Y, a pure high energy β-emitter with a half-life of 64 h, a maximum energy of 2.28 MeV, and maximum board of 11.3 mm in tissue is radionuclide of choice for radioimmunotherapy of outpatient administration. In this study, rituximab was conjugated to DOTA and radiolabeled with 90YCl3. The stability, affinity, and immunoreactivity of radiolabeled antibody was determined in vitro and the conditions were optimized. Biodistribution studies were done in normal mice. The optimum conditions of conjugation and radiolabeling was 1-2 h at 37 °C and 1 h at 45 °C, respectively. Results showed approximately 4 DOTA molecules conjugated per antibody molecule. The purified antibody was stable and intact over 6 months stored at -20 °C. The result of immunoreactivity (≈70%), affinity (≈3 nM) and biodistribution in normal mice are acceptable. PMID:28979315

Theranostic pretargeted radioimmunotherapy of colorectal cancer xenografts in mice using picomolar affinity ⁸⁶Y- or ¹⁷⁷Lu-DOTA-Bn binding scFv C825/GPA33 IgG bispecific immunoconjugates.

PubMed

Cheal, Sarah M; Xu, Hong; Guo, Hong-Fen; Lee, Sang-Gyu; Punzalan, Blesida; Chalasani, Sandhya; Fung, Edward K; Jungbluth, Achim; Zanzonico, Pat B; Carrasquillo, Jorge A; O'Donoghue, Joseph; Smith-Jones, Peter M; Wittrup, K Dane; Cheung, Nai-Kong V; Larson, Steven M

2016-05-01

GPA33 is a colorectal cancer (CRC) antigen with unique retention properties after huA33-mediated tumor targeting. We tested a pretargeted radioimmunotherapy (PRIT) approach for CRC using a tetravalent bispecific antibody with dual specificity for GPA33 tumor antigen and DOTA-Bn-(radiolanthanide metal) complex. PRIT was optimized in vivo by titrating sequential intravenous doses of huA33-C825, the dextran-based clearing agent, and the C825 haptens (177)Lu-or (86)Y-DOTA-Bn in mice bearing the SW1222 subcutaneous (s.c.) CRC xenograft model. Using optimized PRIT, therapeutic indices (TIs) for tumor radiation-absorbed dose of 73 (tumor/blood) and 12 (tumor/kidney) were achieved. Estimated absorbed doses (cGy/MBq) to tumor, blood, liver, spleen, and kidney for single-cycle PRIT were 65.8, 0.9 (TI 73), 6.3 (TI 10), 6.6 (TI 10), and 5.3 (TI 12), respectively. Two cycles of PRIT (66.6 or 111 MBq (177)Lu-DOTA-Bn) were safe and effective, with a complete response of established s.c. tumors (100 - 700 mm(3)) in nine of nine mice, with two mice alive without recurrence at >140 days. Tumor log kill in this model was estimated to be 2.1 - 3.0 based on time to 500-mm(3) tumor recurrence. In addition, PRIT dosimetry/diagnosis was performed by PET imaging of the positron-emitting DOTA hapten (86)Y-DOTA-Bn. We have developed anti-GPA33 PRIT as a triple-step theranostic strategy for preclinical detection, dosimetry, and safe targeted radiotherapy of established human colorectal mouse xenografts.

A pretargeting system for tumor PET imaging and radioimmunotherapy

PubMed Central

Kraeber-Bodéré, Françoise; Rousseau, Caroline; Bodet-Milin, Caroline; Frampas, Eric; Faivre-Chauvet, Alain; Rauscher, Aurore; Sharkey, Robert M.; Goldenberg, David M.; Chatal, Jean-François; Barbet, Jacques

2015-01-01

Labeled antibodies, as well as their fragments and antibody-derived recombinant constructs, have long been proposed as general vectors to target radionuclides to tumor lesions for imaging and therapy. They have indeed shown promise in both imaging and therapeutic applications, but they have not fulfilled the original expectations of achieving sufficient image contrast for tumor detection or sufficient radiation dose delivered to tumors for therapy. Pretargeting was originally developed for tumor immunoscintigraphy. It was assumed that directly-radiolabled antibodies could be replaced by an unlabeled immunoconjugate capable of binding both a tumor-specific antigen and a small molecular weight molecule. The small molecular weight molecule would carry the radioactive payload and would be injected after the bispecific immunoconjugate. It has been demonstrated that this approach does allow for both antibody-specific recognition and fast clearance of the radioactive molecule, thus resulting in improved tumor-to-normal tissue contrast ratios. It was subsequently shown that pretargeting also held promise for tumor therapy, translating improved tumor-to-normal tissue contrast ratios into more specific delivery of absorbed radiation doses. Many technical approaches have been proposed to implement pretargeting, and two have been extensively documented. One is based on the avidin-biotin system, and the other on bispecific antibodies binding a tumor-specific antigen and a hapten. Both have been studied in preclinical models, as well as in several clinical studies, and have shown improved targeting efficiency. This article reviews the historical and recent preclinical and clinical advances in the use of bispecific-antibody-based pretargeting for radioimmunodetection and radioimmunotherapy of cancer. The results of recent evaluation of pretargeting in PET imaging also are discussed. PMID:25873896

Engineering an antibody with picomolar affinity to DOTA chelates of multiple radionuclides for pretargeted radioimmunotherapy and imaging

PubMed Central

Orcutt, Kelly Davis; Slusarczyk, Adrian L; Cieslewicz, Maryelise; Ruiz-Yi, Benjamin; Bhushan, Kumar R; Frangioni, John V; Wittrup, K Dane

2014-01-01

Introduction In pretargeted radioimmunotherapy (PRIT), a bifunctional antibody is administered and allowed to pre-localize to tumor cells. Subsequently, a chelated radionuclide is administered and captured by cell-bound antibody while unbound hapten clears rapidly from the body. We aim to engineer high-affinity binders to DOTA chelates for use in PRIT applications. Methods We mathematically modeled antibody and hapten pharmacokinetics to analyze hapten tumor retention as a function of hapten binding affinity. Motivated by model predictions, we used directed evolution and yeast surface display to affinity mature the 2D12.5 antibody to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), reformatted as a single chain variable fragment (scFv). Results Modeling predicts that for high antigen density and saturating bsAb dose, a hapten binding affinity of 100 picomolar (pM) is needed for near-maximal hapten retention. We affinity matured 2D12.5 with an initial binding constant of about 10 nanomolar (nM) to DOTA-yttrium chelates. Affinity maturation resulted in a 1000-fold affinity improvement to biotinylated DOTA-yttrium, yielding an 8.2 ± 1.9 picomolar binder. The high-affinity scFv binds DOTA complexes of lutetium and gadolinium with similar picomolar affinity and indium chelates with low nanomolar affinity. When engineered into a bispecific antibody construct targeting carcinoembryonic antigen (CEA), pretargeted high-affinity scFv results in significantly higher tumor retention of a 111In-DOTA hapten compared to pretargeted wild-type scFv in a xenograft mouse model. Conclusions We have engineered a versatile, high-affinity DOTA-chelate-binding scFv. We anticipate it will prove useful in developing pretargeted imaging and therapy protocols to exploit the potential of a variety of radiometals. PMID:21315278

Radiolabeled F(ab')2-cetuximab for theranostic purposes in colorectal and skin tumor-bearing mice models.

PubMed

Bellaye, P-S; Moreau, M; Raguin, O; Oudot, A; Bernhard, C; Vrigneaud, J-M; Dumont, L; Vandroux, D; Denat, F; Cochet, A; Brunotte, F; Collin, B

2018-05-17

This study aimed to investigate theranostic strategies in colorectal and skin cancer based on fragments of cetuximab, an anti-EGFR mAb, labeled with radionuclide with imaging and therapeutic properties, 111 In and 177 Lu, respectively. We designed F(ab') 2 -fragments of cetuximab radiolabeled with 111 In and 177 Lu. 111 In-F(ab') 2 -cetuximab tumor targeting and biodistribution were evaluated by SPECT in BalbC nude mice bearing primary colorectal tumors. The efficacy of 111 In-F(ab') 2 -cetuximab to assess therapy efficacy was performed on BalbC nude mice bearing colorectal tumors receiving 17-DMAG, an HSP90 inhibitor. Therapeutic efficacy of the radioimmunotherapy based on 177 Lu-F(ab') 2 -cetuximab was evaluated in SWISS nude mice bearing A431 tumors. Radiolabeling procedure did not change F(ab') 2 -cetuximab and cetuximab immunoreactivity nor affinity for HER1 in vitro. 111 In-DOTAGA-F(ab') 2 -cetuximab exhibited a peak tumor uptake at 24 h post-injection and showed a high tumor specificity determined by a significant decrease in tumor uptake after the addition of an excess of unlabeled-DOTAGA-F(ab') 2 -cetuximab. SPECT imaging of 111 In-DOTAGA-F(ab') 2 -cetuximab allowed an accurate evaluation of tumor growth and successfully predicted the decrease in tumor growth induced by 17-DMAG. Finally, 177 Lu-DOTAGA-F(ab') 2 -cetuximab radioimmunotherapy showed a significant reduction of tumor growth at 4 and 8 MBq doses. 111 In-DOTAGA-F(ab') 2 -cetuximab is a reliable and stable tool for specific in vivo tumor targeting and is suitable for therapy efficacy assessment. 177 Lu-DOTAGA-F(ab') 2 -cetuximab is an interesting theranostic tool allowing therapy and imaging.

An oncolytic adenovirus regulated by a radiation-inducible promoter selectively mediates hSulf-1 gene expression and mutually reinforces antitumor activity of I131-metuximab in hepatocellular carcinoma.

PubMed

Zhang, Yan; Fang, Lin; Zhang, Quan'an; Zheng, Qin; Tong, Jinlong; Fu, Xiaohui; Jiang, Xiaoqing; Su, Changqing; Zheng, Junnian

2013-06-01

Gene therapy and antibody approaches are crucial auxiliary strategies for hepatocellular carcinoma (HCC) treatment. Previously, we established a survivin promoter-regulated oncolytic adenovirus that has inhibitory effect on HCC growth. The human sulfatase-1 (hSulf-1) gene can suppress the growth factor signaling pathways, then inhibit the proliferation of cancer cells and enhance cellular sensitivity to radiotherapy and chemotherapy. I(131)-metuximab (I(131)-mab) is a monoclonal anti-HCC antibody that conjugated to I(131) and specifically recognizes the HAb18G/CD147 antigen on HCC cells. To integrate the oncolytic adenovirus-based gene therapy and the I(131)-mab-based radioimmunotherapy, this study combined the CArG element of early growth response-l (Egr-l) gene with the survivin promoter to construct a radiation-inducible enhanced promoter, which was used to recombine a radiation-inducible oncolytic adenovirus as hSulf-1 gene vector. When I(131)-mab was incorporated into the treatment regimen, not only could the antibody produce radioimmunotherapeutic effect, but the I(131) radiation was able to further boost adenoviral proliferation. We demonstrated that the CArG-enhanced survivin promoter markedly improved the proliferative activity of the oncolytic adenovirus in HCC cells, thereby augmenting hSulf-1 expression and inducing cancer cell apoptosis. This novel strategy that involved multiple, synergistic mechanisms, including oncolytic therapy, gene therapy and radioimmunotherapy, was demonstrated to exert an excellent anti-cancer outcome, which will be a promising approach in HCC treatment. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Evaluation of 177Lu[Lu]-CHX-A″-DTPA-6A10 Fab as a radioimmunotherapy agent targeting carbonic anhydrase XII.

PubMed

Fiedler, L; Kellner, M; Gosewisch, A; Oos, R; Böning, G; Lindner, S; Albert, N; Bartenstein, P; Reulen, H-J; Zeidler, R; Gildehaus, F J

2018-05-01

Due to their infiltrative growth behavior, gliomas have, even after surgical resection, a high recurrence tendency. The approach of intracavitary radioimmunotherapy (RIT) is aimed at inhibiting tumor re-growth by directly administering drugs into the resection cavity (RC). Direct application of the radioconjugate into the RC has the advantage of bypassing the blood-brain barrier, which allows the administration of higher radiation doses than systemic application. Carbonic anhydrase XII (CA XII) is highly expressed on glioma cells while being absent from normal brain and thus an attractive target molecule for RIT. We evaluated a CA XII-specific 6A10 Fab (fragment antigen binding) labelled with 177 Lu as an agent for RIT. 6A10 Fab fragment was modified and radiolabelled with 177 Lu and characterized by MALDI-TOF, flow cytometry and radio-TLC. In vitro stability was determined under physiological conditions. Biodistribution studies, autoradiography tumor examinations and planar scintigraphy imaging were performed on SCID-mice bearing human glioma xenografts. The in vitro CA XII binding capacity of the modified Fab was confirmed. Radiochemical purity was determined to be >90% after 72 h of incubation under physiological conditions. Autoradiography experiments proved the specific binding of the Fab to CA XII on tumor cells. Biodistribution studies revealed a tumor uptake of 3.0%ID/g after 6 h and no detectable brain uptake. The tumor-to-contralateral ratio of 10/1 was confirmed by quantitative planar scintigraphy. The radiochemical stability in combination with a successful in vivo tumor uptake shows the potential suitability for future RIT applications with the 6A10 Fab. Copyright © 2018 Elsevier Inc. All rights reserved.

Radioimmunotherapy of cancer with high linear energy transfer (LET) radiation delivered by radionuclides emitting α-particles or Auger electrons.

PubMed

Aghevlian, Sadaf; Boyle, Amanda J; Reilly, Raymond M

2017-01-15

Radioimmunotherapy (RIT) aims to selectively deliver radionuclides emitting α-particles, β-particles or Auger electrons to tumors by conjugation to monoclonal antibodies (mAbs) that recognize tumor-associated antigens/receptors. The approach has been most successful for treatment of non-Hodgkin's B-cell lymphoma but challenges have been encountered in extending these promising results to the treatment of solid malignancies. These challenges include the low potency of β-particle emitters such as 131 I, 177 Lu or 90 Y which have been commonly conjugated to the mAbs, due to their low linear energy transfer (LET=0.1-1.0keV/μm). Furthermore, since the β-particles have a 2-10mm range, there has been dose-limiting non-specific toxicity to hematopoietic stem cells in the bone marrow (BM) due to the cross-fire effect. Conjugation of mAbs to α-particle-emitters (e.g. 225 Ac, 213 Bi, 212 Pb or 211 At) or Auger electron-emitters (e.g. 111 In, 67 Ga, 123 I or 125 I) would increase the potency of RIT due to their high LET (50-230keV/μm and 4 to 26keV/μm, respectively). In addition, α-particles have a range in tissues of 28-100μm and Auger electrons are nanometer in range which greatly reduces or eliminates the cross-fire effect compared to β-particles, potentially reducing their non-specific toxicity to the BM. In this review, we describe the results of preclinical and clinical studies of RIT of cancer using radioimmunoconjugates emitting α-particles or Auger electrons, and discuss the potential of these high LET forms of radiation to improve the outcome of cancer patients. Copyright © 2015 Elsevier B.V. All rights reserved.

Patient-specific dosimetry based on quantitative SPECT imaging and 3D-DFT convolution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Akabani, G.; Hawkins, W.G.; Eckblade, M.B.

1999-01-01

The objective of this study was to validate the use of a 3-D discrete Fourier Transform (3D-DFT) convolution method to carry out the dosimetry for I-131 for soft tissues in radioimmunotherapy procedures. To validate this convolution method, mathematical and physical phantoms were used as a basis of comparison with Monte Carlo transport (MCT) calculations which were carried out using the EGS4 system code. The mathematical phantom consisted of a sphere containing uniform and nonuniform activity distributions. The physical phantom consisted of a cylinder containing uniform and nonuniform activity distributions. Quantitative SPECT reconstruction was carried out using the Circular Harmonic Transformmore » (CHT) algorithm.« less

Dosimetric Considerations in Radioimmunotherapy and Systemic Radionuclide Therapies: A Review

PubMed Central

Loke, Kelvin S. H.; Padhy, Ajit K.; Ng, David C. E.; Goh, Anthony S.W.; Divgi, Chaitanya

2011-01-01

Radiopharmaceutical therapy, once touted as the “magic bullet” in radiation oncology, is increasingly being used in the treatment of a variety of malignancies; albeit in later disease stages. With ever-increasing public and medical awareness of radiation effects, radiation dosimetry is becoming more important. Dosimetry allows administration of the maximum tolerated radiation dose to the tumor/organ to be treated but limiting radiation to critical organs. Traditional tumor dosimetry involved acquiring pretherapy planar scans and plasma estimates with a diagnostic dose of intended radiopharmaceuticals. New advancements in single photon emission computed tomography and positron emission tomography systems allow semi-quantitative measurements of radiation dosimetry thus allowing treatments tailored to each individual patient. PMID:22144871

Disease Control and Ototoxicity Using Intensity-Modulated Radiation Therapy Tumor-Bed Boost for Medulloblastoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Polkinghorn, William R.; Dunkel, Ira J.; Souweidane, Mark M.

2011-11-01

Purpose: We previously reported excellent local control for treating medulloblastoma with a limited boost to the tumor bed. In order to decrease ototoxicity, we subsequently implemented a tumor-bed boost using intensity-modulated radiation therapy (IMRT), the clinical results of which we report here. Patients and Methods: A total of 33 patients with newly diagnosed medulloblastoma, 25 with standard risk, and 8 with high risk, were treated on an IMRT tumor-bed boost following craniospinal irradiation (CSI). Six standard-risk patients were treated with an institutional protocol with 18 Gy CSI in conjunction with intrathecal iodine-131-labeled monoclonal antibody. The majority of patients received concurrentmore » vincristine and standard adjuvant chemotherapy. Pure-tone audiograms were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. Results: Median age was 9 years old (range, 4-46 years old). Median follow-up was 63 months. Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS) rates for standard-risk patients who received 23.4 or 36 Gy CSI (not including those who received 18 Gy CSI with radioimmunotherapy) were 81.4% and 88.4%, respectively, at 5 years; 5-year PFS and OS rates for high-risk patients were both 87.5%. There were no isolated posterior fossa failures outside of the boost volume. Posttreatment audiograms were available for 31 patients, of whom 6%, at a median follow-up of 19 months, had developed Grade 3 hearing loss. Conclusion: An IMRT tumor-bed boost results in excellent local control while delivering a low mean dose to the cochlea, resulting in a low rate of ototoxicity.« less

PET imaging of tumor angiogenesis in mice with VEGF-A targeted 86Y-CHX-A″-DTPA-bevacizumab

PubMed Central

Nayak, Tapan K.; Garmestani, Kayhan; Baidoo, Kwamena E.; Milenic, Diane E.; Brechbiel, Martin W.

2010-01-01

Bevacizumab is a humanized monoclonal antibody that binds to tumor-secreted VEGF-A and inhibits tumor angiogenesis. In 2004, the antibody was approved by the United States FDA for the treatment of metastatic colorectal carcinoma in combination with chemotherapy. This report describes the preclinical evaluation of a radioimmunoconjugate, 86Y-CHX-A″-DTPA-bevacizumab, for potential use in PET imaging of VEGF-A tumor angiogenesis and as a surrogate marker for 90Y based radioimmunotherapy. Bevacizumab was conjugated to CHX-A″-DTPA and radiolabeled with 86Y. In vivo biodistribution and PET imaging studies were performed on mice bearing VEGF-A secreting human colorectal (LS-174T), human ovarian (SKOV-3) and VEGF-A negative human mesothelioma (MSTO-211H) xenografts. Biodistribution and PET imaging studies demonstrated high specific tumor uptake of the radioimmunoconjugate. In mice bearing VEGF-A secreting LS-174T, SKOV-3 and VEGF-A negative MSTO-211H tumors, the tumor uptake at 3 d post-injection (p.i) was 13.6 ± 1.5, 17.4 ± 1.7 and 6.8 ± 0.7 % ID/g, respectively. The corresponding tumor uptake in mice co-injected with 0.05 mg cold bevacizumab were 5.8 ± 1.3, 8.9 ± 1.9 and 7.4 ± 1.0 % ID/g, respectively at the same time point, demonstrating specific blockage of the target in VEGF-A secreting tumors. The LS-174T and SKOV3 tumors were clearly visualized by PET imaging after injecting 1.8–2.0 MBq 86Y-CHX-A″-DTPA-bevacizumab. Organ uptake quantified by PET closely correlated (r2=0.87, p=0.64, n=18) to values determined by biodistribution studies. This preclinical study demonstrates the potential of the radioimmunoconjugate, 86Y-CHX-A″-DTPA-bevacizumab, for non-invasive assessment of the VEGF-A tumor angiogenesis status and as a surrogate marker for 90Y-CHX-A″-DTPA-bevacizumab radioimmunotherapy. PMID:20473899

Successful radioimmunotherapy for micro and occult metastases in a SCID mouse model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yokoyama, K.; Koshida, K.; Kinuya, S.

1996-05-01

It is often addressed that the most appropriate candidate, theoretically, for radioimmunotherapy (RIT) is not bulky tumor burden but for micro or occult metastatic foci, The major obstacles in the verification for veracious efficacy of RIT had been clinically and preclinically the difficulty in obtaining such a model. We have developed the model of testicular tumor (primary site) with visible small metastases to the lymph nodes (LNs) and non-visible (occult) lesions to distant organs in severe combined immunodeficient (SCID) mice. And thus, the suppression of minute tumor depositions after RIT was evaluated. One week after hemilateral intratesticular injection of 2more » million of HELA Hep 2 cells that expressed placental alkaline phosphatase (PLAP), the group of the mice were treated with a single dose of I-131 labeled HPMS-1, anti-PLAP MoAb or with saline control. The I-131 labeled HPMS-1 (5.6 MBq / 150 {mu}g) was intravenously administered and at 2 weeks after, the testis, retroperitoneal and intraperitoneal LNs and other gans were removed. For the control group, the testicular tumor and LNs metastases were found in 100% and 86% of the mice. The metastases in the liver and lung were not observed by histological examination but in all mouse samples, the PCR (polymerase chain reaction) assay could identify the human {beta}-globin gene derived from HeLa cells, indicating the presence of definitive metastases. For the treated group, the average testicular tumor weight was significantly reduced by the factor of 2.4 (132 mg vs 311 mg, p<0.01). The LNs metastases were even more distinctively suppressed by the factor of 45.7 (13 mg vs 599 mg, p,0.05). Remarkably, the PCR products from the occult metastases were almost completely controlled; 97% suppression found for the liver and 81% for the lung. Thus, we conclude that using I-131 as a label, RIT is justified to used for targeting and killing minute tumor foci.« less

Pretargeted Radioimmunotherapy using Genetically Engineered Antibody-Streptavidin Fusion Proteins for Treatment of Non-Hodgkin Lymphoma

PubMed Central

Park, Steven I.; Shenoi, Jaideep; Frayo, Shani M.; Hamlin, Donald K.; Lin, Yukang; Wilbur, D. Scott; Stayton, Patrick S.; Orgun, Nural; Hylarides, Mark; Buchegger, Franz; Kenoyer, Aimee L.; Axtman, Amanda; Gopal, Ajay K.; Green, Damian J.; Pagel, John M.; Press, Oliver W.

2011-01-01

Purpose Pretargeted radioimmunotherapy (PRIT) using streptavidin (SAv)-biotin technology can deliver higher therapeutic doses of radioactivity to tumors than conventional RIT. However, “endogenous” biotin can interfere with the effectiveness of this approach by blocking binding of radiolabeled biotin to SAv. We engineered a series of SAv FPs that down-modulate the affinity of SAv for biotin, while retaining high avidity for divalent DOTA-bis-biotin to circumvent this problem. Experimental Design The single-chain variable region gene of the murine 1F5 anti-CD20 antibody was fused to the wild-type (WT) SAv gene and to mutant SAv genes, Y43A-SAv and S45A-SAv. FPs were expressed, purified and compared in studies using athymic mice bearing Ramos lymphoma xenografts. Results Biodistribution studies demonstrated delivery of more radioactivity to tumors of mice pretargeted with mutant SAv FPs followed by 111In-DOTA-bis-biotin (6.2 ± 1.7 % of the injected dose per gram [%ID/gm] of tumor 24 hours after Y43A-SAv FP and 5.6 ± 2.2 %ID/g with S45A-SAv FP) than in mice on normal diets pretargeted with WT-SAv FP (2.5 ± 1.6 %ID/g; p = 0.01). These superior biodistributions translated into superior anti-tumor efficacy in mice treated with mutant FPs and 90Y-DOTA-bis-biotin (tumor volumes after 11 days: 237 ± 66 mm3 with Y43A-SAv, 543 ± 320 mm3 with S45A-SAv, 1129 ± 322 mm3 with WT-SAv and 1435 ± 212 mm3 with control FP [p < 0.0001]). Conclusions Genetically engineered mutant-SAv FPs and bis-biotin reagents provide an attractive alternative to current SAv-biotin PRIT methods in settings where endogenous biotin levels are high. PMID:21976541

Pretargeted radioimmunotherapy using genetically engineered antibody-streptavidin fusion proteins for treatment of non-hodgkin lymphoma.

PubMed

Park, Steven I; Shenoi, Jaideep; Frayo, Shani M; Hamlin, Donald K; Lin, Yukang; Wilbur, D Scott; Stayton, Patrick S; Orgun, Nural; Hylarides, Mark; Buchegger, Franz; Kenoyer, Aimee L; Axtman, Amanda; Gopal, Ajay K; Green, Damian J; Pagel, John M; Press, Oliver W

2011-12-01

Pretargeted radioimmunotherapy (PRIT) using streptavidin (SAv)-biotin technology can deliver higher therapeutic doses of radioactivity to tumors than conventional RIT. However, "endogenous" biotin can interfere with the effectiveness of this approach by blocking binding of radiolabeled biotin to SAv. We engineered a series of SAv FPs that downmodulate the affinity of SAv for biotin, while retaining high avidity for divalent DOTA-bis-biotin to circumvent this problem. The single-chain variable region gene of the murine 1F5 anti-CD20 antibody was fused to the wild-type (WT) SAv gene and to mutant SAv genes, Y43A-SAv and S45A-SAv. FPs were expressed, purified, and compared in studies using athymic mice bearing Ramos lymphoma xenografts. Biodistribution studies showed delivery of more radioactivity to tumors of mice pretargeted with mutant SAv FPs followed by (111)In-DOTA-bis-biotin [6.2 ± 1.7% of the injected dose per gram (%ID/gm) of tumor 24 hours after Y43A-SAv FP and 5.6 ± 2.2%ID/g with S45A-SAv FP] than in mice on normal diets pretargeted with WT-SAv FP (2.5 ± 1.6%ID/g; P = 0.01). These superior biodistributions translated into superior antitumor efficacy in mice treated with mutant FPs and (90)Y-DOTA-bis-biotin [tumor volumes after 11 days: 237 ± 66 mm(3) with Y43A-SAv, 543 ± 320 mm(3) with S45A-SAv, 1129 ± 322 mm(3) with WT-SAv, and 1435 ± 212 mm(3) with control FP (P < 0.0001)]. Genetically engineered mutant-SAv FPs and bis-biotin reagents provide an attractive alternative to current SAv-biotin PRIT methods in settings where endogenous biotin levels are high. ©2011 AACR.

Pretargeted Radioimmunotherapy Using Anti-CD45 Monoclonal Antibodies to Deliver Radiation to Murine Hematolymphoid Tissues and Human Myeloid Leukemia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pagel, John M.; Matthews, Dana C.; Kenoyer, Aimee L.

2009-01-01

The efficacy of radioimmunotherapy (RIT) for treatment of patients with hematological malignancies frequently fails because of disease recurrence. We therefore conducted pretargeted RIT studies to augment the efficacy in mice of therapy using a pretargeted anti-human (h)CD45 antibody (Ab)-streptavidin (SA) conjugate followed by delivery of a biotinylated clearing agent and radiolabeled-DOTA-biotin. Tumor-to-blood ratios at 24 hours were 20:1 using pretargeted anti-hCD45 RIT and <1:1 with conventional RIT. In vivo imaging studies confirmed that the pretargeted RIT approach provided high-contrast tumor images with minimal blood-pool activity, whereas directly-labeled anti-hCD45 Ab produced distinct tumor images but the blood pool retained a largemore » amount of labeled antibody for a prolonged time. Therapy experiments demonstrated that 90Y-DOTA-biotin significantly prolonged survival of mice treated pretargeted with anti-hCD45 Ab-SA compared to mice treated with conventional RIT using 90Y-labeled anti-hCD45 Ab at the maximally tolerated dose (400 µCi). Since human CD45 antigens are confined to xenograft tumor cells in this model, and all murine tissues are devoid of hCD45 and will not bind anti-hCD45 Ab, we also compared one-step and pretargeted RIT using an anti-murine (m)CD45 Ab (A20 ) in a model where the target antigen is present on normal hematopoietic tissues. After 24 hours, 27.3 ± 2.8% of the injected dose of radionuclide was delivered per gram (% ID/g) of lymph node using 131I-A20-Ab compared with 40.0 ± 5.4% ID/g for pretargeted 111In-DOTA-biotin (p value). These data suggest that multi-step pretargeted methods for delivering RIT are superior to conventional RIT when targeting CD45 for the treatment of leukemia and may allow for the intensification of therapy, while minimizing toxicities.« less

A Prototype {sup 212}Pb Medical Dose Calibrator for Alpha Radioimmunotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mueller, W.F.; Patil, A.; Russ, W.R.

AREVA Med, an AREVA group subsidiary, is developing innovative cancer-fighting therapies involving the use of {sup 212}Pb for alpha radioimmunotherapy. Canberra Industries, the nuclear measurement subsidiary of AREVA, has been working with AREVA Med to develop a prototype measurement system to assay syringes containing a {sup 212}Pb solution following production by an elution system. The relative fraction of emitted radiation from the source associated directly with the {sup 212}Pb remains dynamic for approximately 6 hours after the parent is chemically purified. A significant challenge for this measurement application is that the short half-life of the parent nuclide requires assay priormore » to reaching equilibrium with progeny nuclides. A gross counting detector was developed to minimize system costs and meet the large dynamic range of source activities. Prior to equilibrium, a gross counting system must include the period since the {sup 212}Pb was pure to calculate the count rate attributable to the parent rather than the progeny. The dynamic state is determined by solving the set of differential equations, or Bateman equations, describing the source decay behavior while also applying the component measurement efficiencies for each nuclide. The efficiencies were initially estimated using mathematical modeling (MCNP) but were then benchmarked with source measurements. The goal accuracy of the system was required to be within 5%. Independent measurements of the source using a high resolution spectroscopic detector have shown good agreement with the prototype system results. The prototype design was driven by cost, compactness and simplicity. The detector development costs were minimized by using existing electronics and firmware with a Geiger-Mueller tube derived from Canberra's EcoGamma environmental monitoring product. The acquisition electronics, communications and interface were controlled using Python with the EcoGamma software development kit on a Raspberry Pi Linux computer mounted inside a standard project box. The results of initial calibration measurements are presented. (authors)« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schweitzer, Andrew D.; Howard Hughes Medical Institute-Medical Fellows Program, Chevy Chase, MD; The Mount Sinai School of Medicine, New York, NY

Purpose: Protection of bone marrow against radiotoxicity during radioimmunotherapy and in some cases external beam radiation therapy such as hemi-body irradiation would permit administration of significantly higher doses to tumors, resulting in increased efficacy and safety of treatment. Melanin, a naturally occurring pigment, possesses radioprotective properties. We hypothesized that melanin, which is insoluble, could be delivered to the bone marrow by intravenously administrated melanin-covered nanoparticles (MNs) because of the human body's 'self-sieving' ability, protecting it against ionizing radiation. Methods and Materials: The synthesis of MNs was performed via enzymatic polymerization of 3,4-dihydroxyphenylalanine and/or 5-S-cysteinyl-3,4-dihydroxyphenylalanine on the surface of 20-nm plainmore » silica nanoparticles. The biodistribution of radiolabeled MNs in mice was done at 3 and 24 h. Healthy CD-1 mice (Charles River Laboratories International, Inc., Wilmington, MA) or melanoma tumor-bearing nude mice were given MNs intravenously, 50 mg/kg of body weight, 3 h before either whole-body exposure to 125 cGy or treatment with 1 mCi of {sup 188}Re-labeled 6D2 melanin-binding antibody. Results: Polymerization of melanin precursors on the surface of silica nanoparticles resulted in formation of a 15-nm-thick melanin layer as confirmed by light scattering, transmission electron microscopy, and immunofluorescence. The biodistribution after intravenous administration showed than MN uptake in bone marrow was 0.3% and 0.2% of injected dose per gram at 3 and 24 h, respectively, whereas pre-injection with pluronic acid increased the uptake to 6% and 3% of injected dose per gram, respectively. Systemic MN administration reduced hematologic toxicity in mice treated with external radiation or radioimmunotherapy, whereas no tumor protection by MNs was observed. Conclusions: MNs or similar structures provide a novel approach to protection of bone marrow from ionizing radiation based on prevention of free radical formation by melanin.« less

Melanin-covered nanoparticles for protection of bone marrow during radiation therapy of cancer.

PubMed

Schweitzer, Andrew D; Revskaya, Ekaterina; Chu, Peter; Pazo, Valeria; Friedman, Matthew; Nosanchuk, Joshua D; Cahill, Sean; Frases, Susana; Casadevall, Arturo; Dadachova, Ekaterina

2010-12-01

Protection of bone marrow against radiotoxicity during radioimmunotherapy and in some cases external beam radiation therapy such as hemi-body irradiation would permit administration of significantly higher doses to tumors, resulting in increased efficacy and safety of treatment. Melanin, a naturally occurring pigment, possesses radioprotective properties. We hypothesized that melanin, which is insoluble, could be delivered to the bone marrow by intravenously administrated melanin-covered nanoparticles (MNs) because of the human body's "self-sieving" ability, protecting it against ionizing radiation. The synthesis of MNs was performed via enzymatic polymerization of 3,4-dihydroxyphenylalanine and/or 5-S-cysteinyl-3,4-dihydroxyphenylalanine on the surface of 20-nm plain silica nanoparticles. The biodistribution of radiolabeled MNs in mice was done at 3 and 24 h. Healthy CD-1 mice (Charles River Laboratories International, Inc., Wilmington, MA) or melanoma tumor-bearing nude mice were given MNs intravenously, 50 mg/kg of body weight, 3 h before either whole-body exposure to 125 cGy or treatment with 1 mCi of (188)Re-labeled 6D2 melanin-binding antibody. Polymerization of melanin precursors on the surface of silica nanoparticles resulted in formation of a 15-nm-thick melanin layer as confirmed by light scattering, transmission electron microscopy, and immunofluorescence. The biodistribution after intravenous administration showed than MN uptake in bone marrow was 0.3% and 0.2% of injected dose per gram at 3 and 24 h, respectively, whereas pre-injection with pluronic acid increased the uptake to 6% and 3% of injected dose per gram, respectively. Systemic MN administration reduced hematologic toxicity in mice treated with external radiation or radioimmunotherapy, whereas no tumor protection by MNs was observed. MNs or similar structures provide a novel approach to protection of bone marrow from ionizing radiation based on prevention of free radical formation by melanin. Copyright © 2010 Elsevier Inc. All rights reserved.

Dosimetric model for intraperitoneal targeted liposomal radioimmunotherapy of ovarian cancer micrometastases

NASA Astrophysics Data System (ADS)

Syme, A. M.; McQuarrie, S. A.; Middleton, J. W.; Fallone, B. G.

2003-05-01

A simple model has been developed to investigate the dosimetry of micrometastases in the peritoneal cavity during intraperitoneal targeted liposomal radioimmunotherapy. The model is applied to free-floating tumours with radii between 0.005 cm and 0.1 cm. Tumour dose is assumed to come from two sources: free liposomes in solution in the peritoneal cavity and liposomes bound to the surface of the micrometastases. It is assumed that liposomes do not penetrate beyond the surface of the tumours and that the total amount of surface antigen does not change over the course of treatment. Integrated tumour doses are expressed as a function of biological parameters that describe the rates at which liposomes bind to and unbind from the tumour surface, the rate at which liposomes escape from the peritoneal cavity and the tumour surface antigen density. Integrated doses are translated into time-dependent tumour control probabilities (TCPs). The results of the work are illustrated in the context of a therapy in which liposomes labelled with Re-188 are targeted at ovarian cancer cells that express the surface antigen CA-125. The time required to produce a TCP of 95% is used to investigate the importance of the various parameters. The relative contributions of surface-bound radioactivity and unbound radioactivity are used to assess the conditions required for a targeted approach to provide an improvement over a non-targeted approach during intraperitoneal radiation therapy. Using Re-188 as the radionuclide, the model suggests that, for microscopic tumours, the relative importance of the surface-bound radioactivity increases with tumour size. This is evidenced by the requirement for larger antigen densities on smaller tumours to affect an improvement in the time required to produce a TCP of 95%. This is because for the smallest tumours considered, the unbound radioactivity is often capable of exerting a tumouricidal effect before the targeting agent has time to accumulate significantly on the tumour surface.

MicroSPECT imaging of triple negative breast cancer cell tumor xenografted in athymic mice with radioiodinated anti-ICAM-1 monoclonal antibody.

PubMed

You, Linyi; Wang, Xiangyu; Guo, Zhide; Zhang, Deliang; Zhang, Pu; Li, Jindian; Su, Xinhui; Pan, Weimin; Zhang, Xianzhong

2018-04-04

Intercellular adhesion molecule-1(ICAM-1) is a potential molecular target and biomarker for triple negative breast cancer (TNBC) therapy and diagnosis. In this study, aICAM-1 was radioiodinated with 125 I/ 131 I in high radiochemical yield and the probes for TNBC tumor targeting and radioimmunotherapy were evaluated in tumor-bearing mice. High and specific accumulation of 125 I-aICAM1 in TNBC MDA-MB-231 tumor was observed in SPECT imaging and the tumor grew was inhibited obviously by 131 I-aICAM1. Thus, the radioiodinated aICAM1 could serve as potential agents for TNBC theranostics. Copyright © 2018 Elsevier Ltd. All rights reserved.

Tumor resistance to vascular disrupting agents: mechanisms, imaging, and solutions

PubMed Central

Liang, Wenjie; Ni, Yicheng; Chen, Feng

2016-01-01

The emergence of vascular disrupting agents (VDAs) is a significant advance in the treatment of solid tumors. VDAs induce rapid and selective shutdown of tumor blood flow resulting in massive necrosis. However, a viable marginal tumor rim always remains after VDA treatment and is a major cause of recurrence. In this review, we discuss the mechanisms involved in the resistance of solid tumors to VDAs. Hypoxia, tumor-associated macrophages, and bone marrow-derived circulating endothelial progenitor cells all may contribute to resistance. Resistance can be monitored using magnetic resonance imaging markers. The various solutions proposed to manage tumor resistance to VDAs emphasize combining these agents with other approaches including antiangiogenic agents, chemotherapy, radiotherapy, radioimmunotherapy, and sequential dual-targeting internal radiotherapy. PMID:26812886

Has the time to come leave the “watch-and-wait” strategy in newly diagnosed asymptomatic follicular lymphoma patients?

PubMed Central

2012-01-01

Background Historically, the median overall survival for follicular lymphoma (FL) has been considered to be 9-10 years, and no treatment had ever prolonged this time period. Studies conducted more than 20 years ago demonstrated that treating patients with asymptomatic FL at the onset of the disease did not increase their survival, and that almost 20% of these patients did not need any treatment in the first 10 years of follow-up. Based on these facts, most clinical practice guidelines recommend active surveillance policies for patients with asymptomatic FL. Discussion The introduction of antiCD-20 monoclonal antibodies, over the last 15 years, has significantly increased the median survival rate to above 14 years. This improvement was achieved before the combination of rituximab and chemotherapy regimens became extensively used in patients with symptomatic disease. Therefore, this increase in survival may currently be more significant. At present, several clinical trials have evaluated low-toxicity therapies that prolong progression-free periods, among which rituximab monotherapy, radioimmunotherapy or the combination of rituximab with bendamustine are the most relevant. Unfortunately, these clinical trials have included only patients with symptomatic FL. The results of a recently reported clinical trial show that treatment with single-agent rituximab prolongs progression-free survival rates, time to new treatment and the quality of life of asymptomatic patients, as compared with the active surveillance strategy. Longer follow-up of these results and data regarding overall survival are awaited before this treatment can be recommended as the standard initial therapy. Summary There are different therapeutic possibilities for asymptomatic FL patients, but no data are currently available to indicate which option is the best. Patients need to understand the risks and benefits of observation versus treatment before a final decision can be made. For patients who want active treatment the administration of four weekly rituximab doses should be considered. PMID:22650448

Nanoparticles for Control of Biofilms of Acinetobacter Species

PubMed Central

Singh, Richa; Nadhe, Shradhda; Wadhwani, Sweety; Shedbalkar, Utkarsha; Chopade, Balu Ananda

2016-01-01

Biofilms are the cause of 80% of microbial infections. Acinetobacter species have emerged as multi- and pan-drug-resistant bacteria and pose a great threat to human health. These act as nosocomial pathogens and form excellent biofilms, both on biotic and abiotic surfaces, leading to severe infections and diseases. Various methods have been developed for treatment and control of Acinetobacter biofilm including photodynamic therapy, radioimmunotherapy, prophylactic vaccines and antimicrobial peptides. Nanotechnology, in the present scenario, offers a promising alternative. Nanomaterials possess unique properties, and multiple bactericidal mechanisms render them more effective than conventional drugs. This review intends to provide an overview of Acinetobacter biofilm and the significant role of various nanoparticles as anti-biofouling agents, surface-coating materials and drug-delivery vehicles for biofilm control and treatment of Acinetobacter infections. PMID:28773507

p53-Based Strategy for Protection of Bone Marrow From Y-90 Ibritumomab Tiuxetan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Su, Hang, E-mail: suh3@uthscsa.edu; Ganapathy, Suthakar; Li, Xiaolei

Purpose: The main drawbacks of radioimmunotherapy have been severe hematological toxicity and potential development of myelodysplastic syndrome and secondary leukemia. Activation of p53 follows a major pathway by which normal tissues respond to DNA-damaging agents, such as chemotherapy and radiation therapy, that result in injuries and pathological consequences. This pathway is separate from the tumor suppressor pathway of p53. We have previously reported that use of low-dose arsenic (LDA) temporarily and reversibly suppresses p53 activation, thereby ameliorating normal tissue toxicity from exposure to 5-fluorouracil and X rays. We have also demonstrated that LDA-mediated protection requires functional p53 and thus ismore » selective to normal tissues, as essentially every cancer cell has dysfunctional p53. Here we tested the protective efficacy of LDA for bone marrow tissue against radioimmunotherapy through animal experiments. Methods and Materials: Mice were subjected to LDA pretreatment for 3 days, followed by treatment with Y-90 ibritumomab tiuxetan. Both dose course (10, 25, 50, 100, and 200 μCi) and time course (6, 24, and 72 hours and 1 and 2 weeks) experiments were performed. The response of bone marrow cells to LDA was determined by examining the expression of NFκB, Glut1, and Glut3. Staining with hematoxylin and eosin, γ-H2AX, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was used to examine morphology, DNA damage response, and apoptotic cell populations. Results: Elevated levels of NFκB, Glut1, and Glut3 were observed in bone marrow cells after LDA treatment. Bone marrow damage levels induced by Y-90 ibritumomab tiuxetan were greatly reduced by LDA pretreatment. Consistent with this observation, significantly less DNA damage and fewer apoptotic cells were accumulated after Y-90 ibritumomab tiuxetan treatment in LDA-pretreated mice. Furthermore, in the mouse xenograft model implanted with human Karpas-422 lymphoma cells, LDA pretreatment did not have any detectable effect on either tumor growth or Y-90 ibritumomab tiuxetan (200 μCi)-induced tumor suppression. Conclusions: LDA pretreatment protected bone marrow without compromising tumor control caused by Y-90 ibritumomab tiuxetan.« less

Y-90-DOTA-hLL2: An Agent for Radioimmunotherapy of Non-Hodgkin's Lymphoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Griffiths, Gary L.; Govindan, Serengulam V.; Sharkey, Robert M.

2003-01-01

The goal of this work was to determine an optimal radioimmunotherapy agent for non-Hodgkin's lymphoma. We established the stability profile of yttrium-90-labeled humanized LL2 (hLL2) monoclonal antibody prepared with different chelating agents, and from these data estimated the improvement using the most stable yttrium-90 chelate-hLL2 complex. Methods: The complementary-determining region- (cdr)-grafted (humanized) anti-CD22 mAb, hLL2 (epratuzumab), was conjugated to derivatives of DTPA and 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA). The conjugates were labeled with Y-90 and tested against a 10,000-fold molar excess of free DTPA and against human serum. The conjugates were also labeled with Y-88 and compared for biodistribution in normal andmore » lymphoma xenograft-bearing athymic mice. In vivo data were analyzed for uptake of yttrium in bone and washed bone when either the DOTA or the Mx-DTPA chelates were used, and dosimetry calculations were made for each. Results: Y-90-DOTA -mAb were stable to either DTPA or serum challenge. DTPA complexes of hLL2 lost 3-4% of Y-90 (days 1-4) and 10-15% thereafter. In vivo, stability differences showed lower Y-90 uptake in bone using DOTA. Absorbed doses per 37 MBq (1 mCi) Y-90-mAb were 3555 and 5405 cGy for bone, and 2664 and 4524 cGy for washed-bone for 90Y-DOTA-hLL2 and 90Y-MxDTPA-hLL2, respectively, amounting to 52% and 69.8% increases in absorbed radiation doses for bone and washed-bone when switching from a DOTA to a Mx-DTPA chelate. Conclusion: Y-90-hLL2 prepared with the DOTA chelate represents a preferred agent for RAIT of non-Hodgkin's lymphoma, with an in vivo model demonstrating a large reduction in bone-deposited yttrium, as compared to yttrium-90-hLL2 agents prepared with open-chain DTPA-type chelating agents. Dosimetry suggests that this will result in a substantial toxicological advantage for a DOTA-based hLL2 conjugate.« less

Evaluation of glycodendron and synthetically-modified dextran clearing agents for multi-step targeting of radioisotopes for molecular imaging and radioimmunotherapy

PubMed Central

Cheal, Sarah M.; Yoo, Barney; Boughdad, Sarah; Punzalan, Blesida; Yang, Guangbin; Dilhas, Anna; Torchon, Geralda; Pu, Jun; Axworthy, Don B.; Zanzonico, Pat; Ouerfelli, Ouathek; Larson, Steven M.

2014-01-01

A series of N-acetylgalactosamine-dendrons (NAG-dendrons) and dextrans bearing biotin moieties were compared for their ability to complex with and sequester circulating bispecific anti-tumor antibody (scFv4) streptavidin (SA) fusion protein (scFv4-SA) in vivo, to improve tumor to normal tissue concentration ratios for targeted radioimmunotherapy and diagnosis. Specifically, a total of five NAG-dendrons employing a common synthetic scaffold structure containing 4, 8, 16, or 32 carbohydrate residues and a single biotin moiety were prepared (NAGB), and for comparative purposes, a biotinylated-dextran with average molecular weight (MW) of 500 kD was synthesized from amino-dextran (DEXB). One of the NAGB compounds, CA16, has been investigated in humans; our aim was to determine if other NAGB analogs (e.g. CA8 or CA4) were bioequivalent to CA16 and/or better suited as MST reagents. In vivo studies included dynamic positron-emission tomography (PET) imaging of 124I-labelled-scFv4-SA clearance and dual-label biodistribution studies following multi-step targeting (MST) directed at subcutaneous (s.c.) human colon adenocarcinoma xenografts in mice. The MST protocol consists of three injections: first, a bispecific antibody specific for an anti-tumor associated glycoprotein (TAG-72) single chain genetically-fused with SA (scFv4-SA); second, CA16 or other clearing agent; and third, radiolabeled biotin. We observed using PET imaging of 124I-labelled-scFv4-SA clearance that the spatial arrangement of ligands conjugated to NAG (i.e. biotin) can impact the binding to antibody in circulation and subsequent liver uptake of the NAG-antibody complex. Also, NAGB CA32-LC or CA16-LC can be utilized during MST to achieve comparable tumor- to-blood ratios and absolute tumor uptake seen previously with CA16. Finally, DEXB was equally effective as NAGB CA32-LC at lowering scFv4-SA in circulation, but at the expense of reducing absolute tumor uptake of radiolabeled biotin. PMID:24219178

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adelstein, S.J.; Kassis, A.I.

This report describes many factors that need to be considered if radioimmunotherapy is to become a commonplace reality. For beta-emitting radionuclides, two physical features of importance are half-life and energy, with the latter determining the range. These features must be matched to the pharmacokinetics of the carrier and the distribution of the radionuclide, both macroscopically and microscopically. Alpha-particle emitters could be considered for cells that are readily accessible to the labeled antibody and for populations that uniformly and constantly display the targeted antigen or idiotype, e.g., trafficking cells such as T or B lymphocytes. For cells that concentrate the radioactivemore » label, the use of low-energy electrons should be examined. If the radionuclide is translocated to the nucleus, the Auger effect can be particularly lethal because of the high LET-like biological response. 15 refs., 3 figs., 2 tabs.« less

On the possibility of 'real-time' Monte Carlo calculations for the estimation of absorbed dose in radioimmunotherapy.

PubMed

Johnson, T K; Vessella, R L

1989-07-01

Dosimetry calculations of monoclonal antibodies (MABs) are made difficult because the focus of radioactivity is targeted for a nonstandard volume in a nonstandard geometry, precluding straightforward application of the MIRD formalism. The MABDOS software addresses this shortcoming by interactive placement of a spherical perturbation into the Standard Man geometry for each tumor focus. S tables are calculated by a Monte Carlo simulation of photon transport for each organ system (including tumor) that localizes activity. Performance benchmarks are reported that measure the time required to simulate 60,000 photons for each penetrating radiation in the spectrum of 99mTc and 131I using the kidney as source organ. Results indicate that calculation times are probably prohibitive on current microcomputer platforms. Mini and supercomputers offer a realistic platform for MABDOS patient dosimetry estimates.

Pretargeted Molecular Imaging and Radioimmunotherapy

PubMed Central

Goldenberg, David M.; Chang, Chien-Hsing; Rossi, Edmund A.; J, William; McBride; Sharkey, Robert M.

2012-01-01

Pretargeting is a multi-step process that first has an unlabeled bispecific antibody (bsMAb) localize within a tumor by virtue of its anti-tumor binding site(s) before administering a small, fast-clearing radiolabeled compound that then attaches to the other portion of the bsMAb. The compound's rapid clearance significantly reduces radiation exposure outside of the tumor and its small size permits speedy delivery to the tumor, creating excellent tumor/nontumor ratios in less than 1 hour. Haptens that bind to an anti-hapten antibody, biotin that binds to streptavidin, or an oligonucleotide binding to a complementary oligonucleotide sequence have all been radiolabeled for use by pretargeting. This review will focus on a highly flexible anti-hapten bsMAb platform that has been used to target a variety of radionuclides to image (SPECT and PET) as well as treat tumors. PMID:22737190

(124)I-L19-SIP for immuno-PET imaging of tumour vasculature and guidance of (131)I-L19-SIP radioimmunotherapy.

PubMed

Tijink, Bernard M; Perk, Lars R; Budde, Marianne; Stigter-van Walsum, Marijke; Visser, Gerard W M; Kloet, Reina W; Dinkelborg, Ludger M; Leemans, C René; Neri, Dario; van Dongen, Guus A M S

2009-08-01

The human monoclonal antibody (MAb) fragment L19-SIP is directed against extra domain B (ED-B) of fibronectin, a marker of tumour angiogenesis. A clinical radioimmunotherapy (RIT) trial with (131)I-L19-SIP was recently started. In the present study, after GMP production of (124)I and efficient production of (124)I-L19-SIP, we aimed to demonstrate the suitability of (124)I-L19-SIP immuno-PET for imaging of angiogenesis at early-stage tumour development and as a scouting procedure prior to clinical (131)I-L19-SIP RIT. (124)I was produced in a GMP compliant way via (124)Te(p,n)(124)I reaction and using a TERIMO module for radioiodine separation. L19-SIP was radioiodinated by using a modified version of the IODO-GEN method. The biodistribution of coinjected (124)I- and (131)I-L19-SIP was compared in FaDu xenograft-bearing nude mice, while (124)I PET images were obtained from mice with tumours of <50 to approximately 700 mm(3). (124)I was produced highly pure with an average yield of 15.4 +/- 0.5 MBq/microAh, while separation yield was approximately 90% efficient with <0.5% loss of TeO(2). Overall labelling efficiency, radiochemical purity and immunoreactive fraction were for (124)I-L19-SIP: approximately 80 , 99.9 and >90%, respectively. Tumour uptake was 7.3 +/- 2.1, 10.8 +/- 1.5, 7.8 +/- 1.4, 5.3 +/- 0.6 and 3.1 +/- 0.4%ID/g at 3, 6, 24, 48 and 72 h p.i., resulting in increased tumour to blood ratios ranging from 6.0 at 24 h to 45.9 at 72 h p.i.. Fully concordant labelling and biodistribution results were obtained with (124)I- and (131)I-L19-SIP. Immuno-PET with (124)I-L19-SIP using a high-resolution research tomograph PET scanner revealed clear delineation of the tumours as small as 50 mm(3) and no adverse uptake in other organs. (124)I-MAb conjugates for clinical immuno-PET can be efficiently produced. Immuno-PET with (124)I-L19-SIP appeared qualified for sensitive imaging of tumour neovasculature and for predicting (131)I-L19-SIP biodistribution.

α-Imaging Confirmed Efficient Targeting of CD₄₅-Positive Cells After ²¹¹At-Radioimmunotherapy for Hematopoietic Cell Transplantation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frost, Sophia; Miller, Brian W.; Back, Tom

Alpha-radioimmunotherapy (α-RIT) targeting CD45 may substitute for total body irradiation in hematopoietic cell transplantation (HCT) preparative regimens for lymphoma. Our goal was to optimize the anti-CD45 monoclonal antibody (MAb; CA12.10C12) protein dose for astatine-²¹¹(²¹¹At)-RIT, extending the analysis to include intra-organ ²¹¹At activity distribution and α-imaging-based small-scale dosimetry, along with imunohistochemical staining. Methods: Eight normal dogs were injected with either 0.75 (n=5) or 1.00 mg/kg (n=3) of ²¹¹At-B10-CA12.10C12 (11.5–27.6 MBq/kg). Two were euthanized and necropsied 19–22 hours postinjection (p.i.), and six received autologous HCT three days after ²¹¹At-RIT, following lymph node and bone marrow biopsies at 2–4 and/or 19 hours p.i.more » Blood was sampled to study toxicity and clearance; CD45 targeting was evaluated by flow cytometry. ²¹¹At localization and small scale dosimetry were assessed using two α-imaging : α-camera and iQID. Results: Uptake of ²¹¹At was highest in spleen (0.31–0.61 %IA/g), lymph nodes (0.02–0.16 %IA/g), liver (0.11–0.12 %IA/g), and marrow (0.06–0.08 %IA/g). Lymphocytes in blood and marrow were efficiently targeted using either MAb dose. Lymph nodes remained unsaturated, but displayed targeted ²¹¹At localization in T lymphocyte-rich areas. Absorbed doses to blood, marrow, and lymph nodes were estimated at 3.9, 3.0, and 4.2 Gy/210 MBq, respectively. All transplanted dogs experienced transient hepatic toxicity. Liver enzyme levels were temporarily elevated in 5 of 6 dogs; 1 treated with 1.00 mg MAb/kg developed ascites and was euthanized 136 days after HCT. Conclusion: ²¹¹At-anti-CD45 RIT with 0.75 mg MAb/kg efficiently targeted blood and marrow without severe toxicity. Dosimetry calculations and observed radiation-induced effects indicated that sufficient ²¹¹At-B10-CA12.10C12 localization was achieved for efficient conditioning for HCT.« less

Simulation of metastatic progression using a computer model including chemotherapy and radiation therapy.

PubMed

Bethge, Anja; Schumacher, Udo; Wedemann, Gero

2015-10-01

Despite considerable research efforts, the process of metastasis formation is still a subject of intense discussion, and even established models differ considerably in basic details and in the conclusions drawn from them. Mathematical and computational models add a new perspective to the research as they can quantitatively investigate the processes of metastasis and the effects of treatment. However, existing models look at only one treatment option at a time. We enhanced a previously developed computer model (called CaTSiT) that enables quantitative comparison of different metastasis formation models with clinical and experimental data, to include the effects of chemotherapy, external beam radiation, radioimmunotherapy and radioembolization. CaTSiT is based on a discrete event simulation procedure. The growth of the primary tumor and its metastases is modeled by a piecewise-defined growth function that describes the growth behavior of the primary tumor and metastases during various time intervals. The piecewise-defined growth function is composed of analytical functions describing the growth behavior of the tumor based on characteristics of the tumor, such as dormancy, or the effects of various therapies. The spreading of malignant cells into the blood is modeled by intravasation events, which are generated according to a rate function. Further events in the model describe the behavior of the released malignant cells until the formation of a new metastasis. The model is published under the GNU General Public License version 3. To demonstrate the application of the computer model, a case of a patient with a hepatocellular carcinoma and multiple metastases in the liver was simulated. Besides the untreated case, different treatments were simulated at two time points: one directly after diagnosis of the primary tumor and the other several months later. Except for early applied radioimmunotherapy, no treatment strategy was able to eliminate all metastases. These results emphasize the importance of early diagnosis and of proceeding with treatment even if no clinically detectable metastases are present at the time of diagnosis of the primary tumor. CaTSiT could be a valuable tool for quantitative investigation of the process of tumor growth and metastasis formation, including the effects of various treatment options. Copyright © 2015 Elsevier Inc. All rights reserved.

Tumor and red bone marrow dosimetry: comparison of methods for prospective treatment planning in pretargeted radioimmunotherapy.

PubMed

Woliner-van der Weg, Wietske; Schoffelen, Rafke; Hobbs, Robert F; Gotthardt, Martin; Goldenberg, David M; Sharkey, Robert M; Slump, Cornelis H; van der Graaf, Winette Ta; Oyen, Wim Jg; Boerman, Otto C; Sgouros, George; Visser, Eric P

2015-12-01

Red bone marrow (RBM) toxicity is dose-limiting in (pretargeted) radioimmunotherapy (RIT). Previous blood-based and two-dimensional (2D) image-based methods have failed to show a clear dose-response relationship. We developed a three-dimensional (3D) image-based RBM dosimetry approach using the Monte Carlo-based 3D radiobiological dosimetry (3D-RD) software and determined its additional value for predicting RBM toxicity. RBM doses were calculated for 13 colorectal cancer patients after pretargeted RIT with the two-step administration of an anti-CEA × anti-HSG bispecific monoclonal antibody and a (177)Lu-labeled di-HSG-peptide. 3D-RD RBM dosimetry was based on the lumbar vertebrae, delineated on single photon emission computed tomography (SPECT) scans acquired directly, 3, 24, and 72 h after (177)Lu administration. RBM doses were correlated to hematologic effects, according to NCI-CTC v3 and compared with conventional 2D cranium-based and blood-based dosimetry results. Tumor doses were calculated with 3D-RD, which has not been possible with 2D dosimetry. Tumor-to-RBM dose ratios were calculated and compared for (177)Lu-based pretargeted RIT and simulated pretargeted RIT with (90)Y. 3D-RD RBM doses of all seven patients who developed thrombocytopenia were higher (range 0.43 to 0.97 Gy) than that of the six patients without thrombocytopenia (range 0.12 to 0.39 Gy), except in one patient (0.47 Gy) without thrombocytopenia but with grade 2 leucopenia. Blood and 2D image-based RBM doses for patients with grade 1 to 2 thrombocytopenia were in the same range as in patients without thrombocytopenia (0.14 to 0.29 and 0.11 to 0.26 Gy, respectively). Blood-based RBM doses for two grade 3 to 4 patients were higher (0.66 and 0.51 Gy, respectively) than the others, and the cranium-based dose of only the grade 4 patient was higher (0.34 Gy). Tumor-to-RBM dose ratios would increase by 25% on average when treating with (90)Y instead of (177)Lu. 3D dosimetry identifies patients at risk of developing any grade of RBM toxicity more accurately than blood- or 2D image-based methods. It has the added value to enable calculation of tumor-to-RBM dose ratios.

Imaging, biodistribution, and dosimetry of radionuclide-labeled PD-L1 antibody in an immunocompetent mouse model of breast cancer

PubMed Central

Josefsson, Anders; Nedrow, Jessie R.; Park, Sunju; Banerjee, Sangeeta Ray; Rittenbach, Andrew; Jammes, Fabien; Tsui, Benjamin; Sgouros, George

2015-01-01

The programmed cell death ligand 1 (PD-L1) participates in an immune checkpoint system involved in preventing autoimmunity. PD-L1 is expressed on tumor cells, tumor-associated macrophages, and other cells in the tumor microenvironment. Anti-PD-L1 antibodies are active against a variety of cancers, and combined anti-PD-L1 therapy with external beam radiotherapy has been shown to increase therapeutic efficacy. PD-L1 expression status is an important indicator of prognosis and therapy responsiveness, but methods to precisely capture the dynamics of PD-L1 expression in the tumor microenvironment are still limited. In this study, we developed a murine anti-PD-L1 antibody conjugated to the radioactive isotope Indium-111 (111In) for imaging and biodistribution studies in an immune-intact mouse model of breast cancer. The distribution of 111In-DTPA-anti-PD-L1 in tumors as well as the spleen, liver, thymus, heart, and lungs peaked 72 hours after injection. Co-injection of labeled and 100-fold unlabeled antibody significantly reduced spleen uptake at 24 hours, indicating that an excess of unlabeled antibody effectively blocked PD-L1 sites in the spleen, thus shifting the concentration of 111In-DTPA-anti-PD-L1 into the blood stream and potentially increasing tumor uptake. Clearance of 111In-DTPA-anti-PD-L1 from all organs occurred at 144 hours. Moreover, dosimetry calculations revealed that radionuclide-labeled anti-PD-L1 antibody yielded tolerable projected marrow doses, further supporting its use for radiopharmaceutical therapy. Taken together, these studies demonstrate the feasibility of using anti-PD-L1 antibody for radionuclide imaging and radioimmunotherapy, and highlight a new opportunity to optimize and monitor the efficacy of immune checkpoint inhibition therapy. PMID:26554829

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leichner, P.K.

This report summarizes research in beta-particle dosimetry, quantitative single-photon emission computed tomography (SPECT), the clinical implementation of these two areas of research in radioimmunotherapy (RIT), and postgraduate training provided since the inception of this grant on July 15, 1989. To improve beta-particle dosimetry, a point source function was developed that is valid for a wide range of beta emitters. Analytical solutions for beta-particle dose rates within out outside slabs of finite thickness were validated in experimental tumors and are now being used in clinical RIT. Quantitative SPECT based on the circular harmonic transform (CHT) algorithm was validated in phantom, experimental,more » and clinical studies. This has led to improved macrodosimetry in clinical RIT. In dosimetry at the multi-cellular level studies were made of the HepG2 human hepatoblastoma grown subcutaneously in nude mice. Histologic sections and autoradiographs were prepared to quantitate activity distributions of radiolabeled antibodies. Absorbed-dose calculations are being carried out for {sup 131}I and {sup 90}Y beta particles for these antibody distributions.« less

Enhanced tumor retention of a radiohalogen label for site-specific modification of antibodies.

PubMed

Boswell, C Andrew; Marik, Jan; Elowson, Michael J; Reyes, Noe A; Ulufatu, Sheila; Bumbaca, Daniela; Yip, Victor; Mundo, Eduardo E; Majidy, Nicholas; Van Hoy, Marjie; Goriparthi, Saritha N; Trias, Anthony; Gill, Herman S; Williams, Simon P; Junutula, Jagath R; Fielder, Paul J; Khawli, Leslie A

2013-12-12

A known limitation of iodine radionuclides for labeling and biological tracking of receptor targeted proteins is the tendency of iodotyrosine to rapidly diffuse from cells following endocytosis and lysosomal degradation. In contrast, radiometal-chelate complexes such as indium-111-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (In-111-DOTA) accumulate within target cells due to the residualizing properties of the polar, charged metal-chelate-amino acid adduct. Iodine radionuclides boast a diversity of nuclear properties and chemical means for incorporation, prompting efforts to covalently link radioiodine with residualizing molecules. Herein, we describe the Ugi-assisted synthesis of [I-125]HIP-DOTA, a 4-hydroxy-3-iodophenyl (HIP) derivative of DOTA, and demonstration of its residualizing properties in a murine xenograft model. Overall, this study displays the power of multicomponent synthesis to yield a versatile radioactive probe for antibodies across multiple therapeutic areas with potential applications in both preclinical biodistribution studies and clinical radioimmunotherapies.

Biologic agents in the management of Hodgkin lymphoma.

PubMed

Rashidi, Armin; Bartlett, Nancy L

2015-05-01

The advent of biologic approaches for the treatment of solid tumors and hematologic malignancies has been a major accomplishment in oncology and a rapidly growing field of clinical and translational research in cancer therapeutics. Classical Hodgkin lymphoma (HL) is no exception. Although the investigation of biologic therapies in HL started decades ago, it has only recently flourished, largely because of the development of new monoclonal antibody drug conjugates and checkpoint inhibitors. Biologic therapies represent a potent treatment option that have produced durable remissions even in patients who have had multiple relapses or with refractory disease. This article reviews 8 major classes of biologic approaches that have been investigated in HL: monoclonal antibodies, immunotoxins, antibody-drug conjugates, radioimmunotherapy, adoptive immunotherapy, immunomodulators, chimeric antigen receptor T cells, and checkpoint inhibitors. An armamentarium of biologic therapies for HL that are well tolerated and potentially more effective is expected to be available in the near future. Copyright © 2015 by the National Comprehensive Cancer Network.

Utility of γH2AX as a molecular marker of DNA double-strand breaks in nuclear medicine: applications to radionuclide therapy employing auger electron-emitting isotopes.

PubMed

Mah, Li-Jeen; Orlowski, Christian; Ververis, Katherine; El-Osta, Assam; Karagiannis, Tom C

2011-01-01

There is an intense interest in the development of radiopharmaceuticals for cancer therapy. In particular, radiopharmaceuticals which involve targeting radionuclides specifically to cancer cells with the use of monoclonal antibodies (radioimmunotherapy) or peptides (targeted radiotherapy) are being widely investigated. For example, the ultra-short range Auger electron-emitting isotopes, which are discussed in this review, are being considered in the context of DNAtargeted radiotherapy. The efficient quantitative evaluation of the levels of damage caused by such potential radiopharmaceuticals is required for assessment of therapeutic efficacy and determination of relevant doses for successful treatment. The DNA double-strand break surrogate marker, γH2AX, has emerged as a useful biomonitor of damage and thus effectiveness of treatment, offering a highly specific and sensitive means of assessment. This review will cover the potential applications of γH2AX in nuclear medicine, in particular radionuclide therapy.

Radioimmunotherapy with Tenarad, a 131I-labelled antibody fragment targeting the extra-domain A1 of tenascin-C, in patients with refractory Hodgkin's lymphoma.

PubMed

Aloj, Luigi; D'Ambrosio, Laura; Aurilio, Michela; Morisco, Anna; Frigeri, Ferdinando; Caraco', Corradina; Di Gennaro, Francesca; Capobianco, Gaetana; Giovannoni, Leonardo; Menssen, Hans D; Neri, Dario; Pinto, Antonio; Lastoria, Secondo

2014-05-01

The extra-domain A1 of tenascin-C (TC-A1) is highly expressed in the extracellular matrix of tumours and on newly formed blood vessels and is thus a valuable target for radionuclide therapy. Tenarad is a fully human miniantibody or small immunoprotein (SIP, molecular weight 80 kDa) labelled with (131)I that is derived from a TC-A1-binding antibody. Previous phase I/II studies with a similar compound ((131)I-L19SIP) used for radioimmunotherapy (RIT) have shown preliminary efficacy in a variety of cancer types. In this ongoing phase I/II trial, Tenarad was administered to patients with recurrent Hodgkin's lymphoma (HL) refractory to conventional treatments. Eight patients (four men, four women; age range 19 - 41) were enrolled between April 2010 and March 2011. All patients had received a median of three previous lines of chemotherapy (range three to six) and seven had also undergone autologous stem cell transplantation (ASCT) or bone marrow transplantation. In addition, seven patients received external beam radiation. All patients had nodal disease, constitutional B symptoms and some showed extranodal disease in skeletal bone (four patients), lung (three), liver (two) and spleen (one). Baseline assessments included whole-body FDG PET with contrast-enhanced CT and diagnostic Tenarad planar and SPECT studies. Patients were considered eligible to receive a therapeutic dose of Tenarad (2.05 GBq/m(2)) if tumour uptake was more than four times higher than that of muscle. All patients were eligible and received the therapeutic dose of Tenarad. Only one patient developed grade 4 thrombocytopenia and leucocytopenia, requiring hospitalization and therapeutic intervention. All other patients had haematological toxicity of grade 3 or lower, which resolved spontaneously. At the first response assessment (4 - 6 weeks after therapy), one patient showed a complete response, one showed a partial response (PR) and five had disease stabilization (SD). Five patients were given up to three repeated Tenarad treatments. One patient showed SD which then improved to a PR, three showed clinical benefit while maintaining SD and one patient showed disease progression. Tenarad RIT is effective in chemorefractory HL and resulted in objective responses or clinical benefit in the majority of patients. Toxicity was acceptable despite the high load of prior treatments, previous ASCT and multiple Tenarad administrations. Further studies are planned to define the most effective schedule for this type of RIT in HL patients.

Rhenium‐186‐mercaptoacetyltriglycine‐labeled Monoclonal Antibody for Radioimmunotherapy: In vitro Assessment, in vivo Kinetics and Dosimetry in Tumor‐bearing Nude Mice

PubMed Central

Yokoyama, Kunihiko; Tega, Harunobu; Hiramatsu, Takashi; Konishi, Shota; Yamamoto, Wakako; Shuke, Noriyuki; Aburano, Tamio; Watanabe, Naoto; Takayama, Terahiko; Michigishi, Takatoshi; Tonami, Norihisa

1998-01-01

Stability and immunoreactivity of 186Re‐labeled monoclonal antibody were examined, and its in vivo kinetics was investigated in tumor‐bearing Balb/c nu/nu female mice to assess the feasibility of using it in radioimmunotherapy (RIT). A murine IgG1, A7, against a 45 kD glycoprotein in human colon cancer was radiolabeled with 186Re by using a chelating method with a mercaptoacetyltriglycine (MAG3). 186Re‐MAG3 complex was conjugated to A7 after esterification of 186Re‐MAG3 with tetrafluorophenol (TFP). The efficiency of 186Re‐MAG3‐TFP production and the labeling efficiency of A7 were 51–59% and 57–60%, respectively. Immunoreactivity of purified 186Re‐MAG3‐A7 was 68.2% at infinite antigen excess. In 0.9% NaCl at 4°C, the radioactivity (12.7 MBq/mg, 3.55 MBq/ml) dissociated with time from 186Re‐MAG3‐A7 as a small molecular weight moiety because of autoradiolysis. The addition of ascorbic acid, 5 mg/ml, as a radioprotectant or storage at –80°C could effectively prevent the radiolysis of 186Re‐MAG3‐A7 for 7 days. Immunoreactivity of 186Re‐MAG3‐A7, 6.70 MBq/mg (6.66 MBq/ml), stored in the presence of ascorbic acid was well retained up to 8 days after the preparation. In colon cancer xenografted mice, 31.0% of the injected dose/g of 186Re‐MAG3‐A7 had accumulated in the tumors at 24 h postinjection. Estimated radiation dose to tumors was 14.9 cGy/37 kBq up to 8 days postinjection which was 12‐fold greater than the whole‐body radiation dose. These in vivo characteristics were superior to those of A7 labeled with radioiodine, affording greater therapeutic ratios than 131I‐A7. Because of the better image quality of 186Re‐MAG3‐A7 as well as more favorable dosimetry, 186Re‐MAG3‐A7 would be a better choice for RIT of colon cancer than 131I‐A7. These results indicated the feasibility of RIT with 186Re‐MAG3‐A7, though the prevention of radiolysis of the labeled antibody should be considered. PMID:9765625

Beta emitters rhenium-188 and lutetium-177 are equally effective in radioimmunotherapy of HPV-positive experimental cervical cancer.

PubMed

Phaeton, Rebecca; Jiang, Zewei; Revskaya, Ekaterina; Fisher, Darrell R; Goldberg, Gary L; Dadachova, Ekaterina

2016-01-01

Cervical cancer caused by the infection with the human papillomavirus (HPV) remains the fourth leading killer of women worldwide. Therefore, more efficacious treatments are needed. We are developing radioimmunotherapy (RIT) of HPV-positive cervical cancers by targeting E6 and E7 viral oncoproteins expressed by the cancer cells with the radiolabeled monoclonal antibodies (mAbs). To investigate the influence of different radionuclides on the RIT efficacy-we performed RIT of experimental cervical cancer with Rhenium-188 ((188) Re) and Lutetium-177 ((177) Lu)-labeled mAb C1P5 to E6. The biodistribution of (188) Re- and (177) Lu-labeled C1P5 was performed in nude female mice bearing CasKi cervical cancer xenografts and the radiation dosimetry calculations for the tumors and organs were carried out. For RIT the mice were treated with 7.4 MBq of either (188) Re-C1P5 or (177) Lu-C1P5 or left untreated, and observed for their tumor size for 28 days. The levels of (188) Re- and (177) Lu-C1P5 mAbs-induced double-strand breaks in CasKi tumors were compared on days 5 and 10 post treatment by staining with anti-gamma H2AX antibody. The radiation doses to the heart and lungs were similar for both (177) Lu-C1P5 and (188) Re-C1P5. The dose to the liver was five times higher for (177) Lu-C1P5. The doses to the tumor were 259 and 181 cGy for (177) Lu-C1P5 and (188) Re-C1P5, respectively. RIT with either (177) Lu-C1P5 or (188) Re-C1P5 was equally effective in inhibiting tumor growth when each was compared to the untreated controls (P = 0.001). On day 5 there was a pronounced staining for gamma H2AX foci in (177) Lu-C1P5 group only and on day 10 it was observed in both (177) Lu-C1P5 and (188) Re-C1P5 groups. (188) Re- and (177) Lu-labeled mAbs were equally effective in arresting the growth of CasKi cervical tumors. Thus, both of these radionuclides are candidates for the clinical trials of this approach in patients with advanced, recurrent or metastatic cervical cancer. © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

A comparative analysis of prognostic factor models for follicular lymphoma based on a phase III trial of CHOP-rituximab versus CHOP + 131iodine--tositumomab.

PubMed

Press, Oliver W; Unger, Joseph M; Rimsza, Lisa M; Friedberg, Jonathan W; LeBlanc, Michael; Czuczman, Myron S; Kaminski, Mark; Braziel, Rita M; Spier, Catherine; Gopal, Ajay K; Maloney, David G; Cheson, Bruce D; Dakhil, Shaker R; Miller, Thomas P; Fisher, Richard I

2013-12-01

There is currently no consensus on optimal frontline therapy for patients with follicular lymphoma. We analyzed a phase III randomized intergroup trial comparing six cycles of CHOP-R (cyclophosphamide-Adriamycin-vincristine-prednisone (Oncovin)-rituximab) with six cycles of CHOP followed by iodine-131 tositumomab radioimmunotherapy (RIT) to assess whether any subsets benefited more from one treatment or the other, and to compare three prognostic models. We conducted univariate and multivariate Cox regression analyses of 532 patients enrolled on this trial and compared the prognostic value of the FLIPI (follicular lymphoma international prognostic index), FLIPI2, and LDH + β2M (lactate dehydrogenase + β2-microglobulin) models. Outcomes were excellent, but not statistically different between the two study arms [5-year progression-free survival (PFS) of 60% with CHOP-R and 66% with CHOP-RIT (P = 0.11); 5-year overall survival (OS) of 92% with CHOP-R and 86% with CHOP-RIT (P = 0.08); overall response rate of 84% for both arms]. The only factor found to potentially predict the impact of treatment was serum β2M; among patients with normal β2M, CHOP-RIT patients had better PFS compared with CHOP-R patients, whereas among patients with high serum β2M, PFS by arm was similar (interaction P value = 0.02). All three prognostic models (FLIPI, FLIPI2, and LDH + β2M) predicted both PFS and OS well, though the LDH + β2M model is easiest to apply and identified an especially poor risk subset. In an exploratory analysis using the latter model, there was a statistically significant trend suggesting that low-risk patients had superior observed PFS if treated with CHOP-RIT, whereas high-risk patients had a better PFS with CHOP-R. ©2013 AACR.

Phase III Randomized Study of Rituximab/Carmustine, Etoposide, Cytarabine, and Melphalan (BEAM) Compared With Iodine-131 Tositumomab/BEAM With Autologous Hematopoietic Cell Transplantation for Relapsed Diffuse Large B-Cell Lymphoma: Results From the BMT CTN 0401 Trial

PubMed Central

Vose, Julie M.; Carter, Shelly; Burns, Linda J.; Ayala, Ernesto; Press, Oliver W.; Moskowitz, Craig H.; Stadtmauer, Edward A.; Mineshi, Shin; Ambinder, Richard; Fenske, Timothy; Horowitz, Mary; Fisher, Richard; Tomblyn, Marcie

2013-01-01

Purpose This clinical trial evaluated standard-dose radioimmunotherapy with a chemotherapy-based transplantation regimen followed by autologous hematopoietic cell transplantation versus rituximab with the same regimen in patients with relapsed diffuse large B-cell lymphoma (DLBCL). Patients and Methods Patients with chemotherapy-sensitive persistent or relapsed DLBCL were randomly assigned to receive iodine-131 tositumomab (dosimetric dose of 5 mCi on day −19 and therapeutic dose of 0.75 Gy on day −12), carmustine 300 mg/m2 (day −6), etoposide 100 mg/m2 twice daily (days −5 to −2), cytarabine 100 mg/m2 twice daily (days −5 to −2), and melphalan 140 mg/m2 (day −1; B-BEAM) or rituximab 375 mg/m2 on days −19 and −12 and the same chemotherapy regimen (R-BEAM). Results Two hundred twenty-four patients were enrolled, with 113 patients randomly assigned to R-BEAM and 111 patients assigned to B-BEAM. Two-year progression-free survival (PFS) rates, the primary end point, were 48.6% (95% CI, 38.6% to 57.8%) for R-BEAM and 47.9% (95% CI, 38.2% to 57%; P = .94) for B-BEAM, and the 2-year overall survival (OS) rates were 65.6% (95% CI, 55.3% to 74.1%) for R-BEAM and 61% (95% CI, 50.9% to 69.9%; P = .38) for B-BEAM. The 100-day treatment-related mortality rates were 4.1% (95% CI, 0.2% to 8.0%) for R-BEAM and 4.9% (95% CI, 0.8% to 9.0%; P = .97) for B-BEAM. The maximum mucositis score was higher in the B-BEAM arm (0.72) compared with the R-BEAM arm (0.31; P < .001). Conclusion The B-BEAM and R-BEAM regimens produced similar 2-year PFS and OS rates for patients with chemotherapy-sensitive relapsed DLBCL. No differences in toxicities other than mucositis were noted. PMID:23478060

The curative and palliative potential of the monoclonal antibody MOv18 labelled with 211At in nude mice with intraperitoneally growing ovarian cancer xenografts--a long-term study.

PubMed

Andersson, H; Lindegren, S; Bäck, T; Jacobsson, L; Leser, G; Horvath, G

2000-01-01

The purpose of the present study was to investigate the therapeutic efficacy of 211At-labelled specific monoclonal antibody MOv18 in nude mice with intraperitoneal growth of the human ovarian cancer cell line OVCAR3. In the first part of the study the antibody was injected intraperitoneally when the cancer growth was microscopic. The injected activity was 485-555 kBq. The median survival for treated mice was 213 days compared to 138 days for untreated mice (p < 0.014, log-rank test). No obvious toxicity was seen. Thirty-three percent of the mice were apparently free of cancer after 7 months and were probably cured. In the second part of the study mice with macroscopic cancer and signs of ascites were injected intraperitoneally with the same 211At-labelled antibody (377-389 kBq). This treatment possibly delayed the production of ascites. Hopefully radioimmunotherapy with regionally administered 211At-labelled antibody will be of value in women with ovarian cancer as well.

Electron microscopy and computed microtomography studies of in vivo implanted mini-TL dosimeters.

PubMed

Strand, S E; Strandh, M; Spanne, P

1993-01-01

The need for direct methods of measuring the absorbed dose in vivo increases for systemic radiation therapy, and in more sophisticated methodologies developed for radioimmunotherapy. One method suggested is the use of mini-thermoluminescent dosimeters (TLD). Recent reports indicate a marked loss of signal when the dosimeters are used in vivo. We investigated the exterior surface of the dosimeters with scanning electron microscopy and the interior dosimeter volume with computed microtomography. The results show that the dosimeters initially have crystals uniformly embedded in the teflon matrix, with some of them directly exposed to the environment. After incubation in gel, holes appear in the dosimeter matrix where the crystals should have been. The computed microtomographic images show that crystals remain in the interior of the matrix, producing the remaining signal. We conclude that these dosimeters should be very carefully handled, and for practical use of mini-TLDs in vivo the dosimeters should be calibrated in equivalent milieus. An alternative solution to the problem of decreased TL efficiency, would be to coat the dosimeters with a thin layer, of Teflon, or other suitable material.

Production and characterization of monoclonal antibodies specific for canine CD138 (syndecan-1) for nuclear medicine preclinical trials on spontaneous tumours.

PubMed

Diab, M; Nguyen, F; Berthaud, M; Maurel, C; Gaschet, J; Verger, E; Ibisch, C; Rousseau, C; Chérel, M; Abadie, J; Davodeau, F

2017-09-01

We isolated 11 antibodies specific for canine CD138 (cCD138) to validate the interest of CD138 antigen targeting in dogs with spontaneous mammary carcinoma. The affinity of the monoclonal antibodies in the nanomolar range is suitable for immunohistochemistry and nuclear medicine applications. Four distinct epitopes were recognized on cCD138 by this panel of antibodies. CD138 expression in canine healthy tissues is comparable to that reported in humans. CD138 is frequently expressed in canine mammary carcinomas corresponding to the human triple negative breast cancer subtype, with cytoplasmic and membranous expression. In canine diffuse large B-cell lymphoma, CD138 expression is associated with the 'non-germinal center' phenotype corresponding to the most aggressive subtype in humans. This homology of CD138 expression between dogs and humans confirms the relevance of tumour-bearing dogs as spontaneous models for nuclear medicine applications, especially for the evaluation of new tumour targeting strategies for diagnosis by phenotypic imaging and radio-immunotherapy. © 2016 John Wiley & Sons Ltd.

Improving external beam radiotherapy by combination with internal irradiation.

PubMed

Dietrich, A; Koi, L; Zöphel, K; Sihver, W; Kotzerke, J; Baumann, M; Krause, M

2015-07-01

The efficacy of external beam radiotherapy (EBRT) is dose dependent, but the dose that can be applied to solid tumour lesions is limited by the sensitivity of the surrounding tissue. The combination of EBRT with systemically applied radioimmunotherapy (RIT) is a promising approach to increase efficacy of radiotherapy. Toxicities of both treatment modalities of this combination of internal and external radiotherapy (CIERT) are not additive, as different organs at risk are in target. However, advantages of both single treatments are combined, for example, precise high dose delivery to the bulk tumour via standard EBRT, which can be increased by addition of RIT, and potential targeting of micrometastases by RIT. Eventually, theragnostic radionuclide pairs can be used to predict uptake of the radiotherapeutic drug prior to and during therapy and find individual patients who may benefit from this treatment. This review aims to highlight the outcome of pre-clinical studies on CIERT and resultant questions for translation into the clinic. Few clinical data are available until now and reasons as well as challenges for clinical implementation are discussed.

TU-F-12A-01: Quantitative Non-Linear Compartment Modeling of 89Zr- and 124I- Labeled J591 Monoclonal Antibody Kinetics Using Serial Non-Invasive Positron Emission Tomography Imaging in a Pre-Clinical Human Prostate Cancer Mouse Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fung, EK; Cheal, SM; Chalasani, S

2014-06-15

Purpose: To examine the binding kinetics of human IgG monoclonal antibody J591 which targets prostate-specific membrane antigen (PSMA) in a pre-clinical mouse cancer model using quantitative PET compartmental analysis of two radiolabeled variants. Methods: PSMA is expressed in normal human prostate, and becomes highly upregulated in prostate cancer, making it a promising therapeutic target. Two forms of J591, radiolabeled with either {sup 89}Zr or {sup 124}I, were prepared. {sup 89}Zr is a radiometal that becomes trapped in the cell upon internalization by the antigen-antibody complex, while radioiodine leaves the cell. Mice with prostate cancer xenografts underwent non-invasive serial imaging onmore » a Focus 120 microPET up to 144 hours post-injection of J591. A non-linear compartmental model describing the binding and internalization of antibody in tumor xenograft was developed and applied to the PET-derived time-activity curves. The antibody-antigen association rate constant (ka), total amount of antigen per gram tumor (Ag-total), internalization rate of antibody-antigen complex, and efflux rate of radioisotope from tumor were fitted using the model. The surface-bound and the internalized activity were also estimated. Results: Values for ka, Ag-total, and internalization rate were found to be similar regardless of radiolabel payload used. The efflux rate, however, was ∼ 9-fold higher for {sup 124}I-J591 than for {sup 89}Zr-J591. Time-dependent surface-bound and internalized radiotracer activity were similar for both radiolabels at early times post-injection, but clearly differed beyond 24 hours. Conclusion: Binding and internalization of J591 to PSMA-expressing tumor xenografts were similar when radiolabeled with either {sup 89}Zr or {sup 124}I payload. The difference in efflux of radioactivity from tumor may be attributable to differential biological fate intracellularly of the radioisotopes. This has great significance for radioimmunotherapy and antibody-drug conjugates. Further exploration using the model will examine binding and radioisotope residence as antibody dose is increased to antigen saturation. The Center for Targeted Radioimmunotherapy and Theranostics, Ludwig Center for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center (MSK), NIH (R25-CA096945). Technical services provided by the MSK Small-Animal Imaging Core Facility were supported by the NIH (R24-CA83084, P30-CA08748, and P50-CA92629; Zanzonico). NCI, Center to Reduce Cancer Health Disparity (R21 CA153177-03; Osborne)« less

Evaluation of Efficacy of Radioimmunotherapy with 90Y-Labeled Fully Human Anti-Transferrin Receptor Monoclonal Antibody in Pancreatic Cancer Mouse Models

PubMed Central

Sugyo, Aya; Tsuji, Atsushi B.; Sudo, Hitomi; Okada, Maki; Koizumi, Mitsuru; Satoh, Hirokazu; Kurosawa, Gene; Kurosawa, Yoshikazu; Saga, Tsuneo

2015-01-01

Objective Pancreatic cancer is an aggressive tumor and the prognosis remains poor. Therefore, development of more effective therapy is needed. We previously reported that 89Zr-labeled TSP-A01, an antibody against transferrin receptor (TfR), is highly accumulated in a pancreatic cancer xenograft, but not in major normal organs. In the present study, we evaluated the efficacy of radioimmunotherapy (RIT) with 90Y-TSP-A01 in pancreatic cancer mouse models. Methods TfR expression in pancreatic cancer cell lines (AsPC-1, BxPC-3, MIAPaCa-2) was evaluated by immunofluorescence staining. 111In-labeled anti-TfR antibodies (TSP-A01, TSP-A02) were evaluated in vitro by cell binding assay with the three cell lines and by competitive inhibition assay with MIAPaCa-2. In vivo biodistribution was evaluated in mice bearing BxPC-3 and MIAPaCa-2 xenografts. Tumor volumes of BxPC-3 and MIAPaCa-2 were sequentially measured after 90Y-TSP-A01 injection and histological analysis of tumors was conducted. Results MIAPaCa-2 cells showed the highest TfR expression, followed by AsPC-1 and BxPC-3 cells. 111In-TSP-A01 and 111In-TSP-A02 bound specifically to the three cell lines according to TfR expression. The dissociation constants for TSP-A01, DOTA-TSP-A01, TSP-A02, and DOTA-TSP-A02 were 0.22, 0.28, 0.17, and 0.22 nM, respectively. 111In-TSP-A01 was highly accumulated in tumors, especially in MIAPaCa-2, but this was not true of 111In-TSP-A02. The absorbed dose for 90Y-TSP-A01 was estimated to be 8.3 Gy/MBq to BxPC-3 and 12.4 Gy/MBq to MIAPaCa-2. MIAPaCa-2 tumors treated with 3.7 MBq of 90Y-TSP-A01 had almost completely disappeared around 3 weeks after injection and regrowth was not observed. Growth of BxPC-3 tumors was inhibited by 3.7 MBq of 90Y-TSP-A01, but the tumor size was not reduced. Conclusion 90Y-TSP-A01 treatment achieved an almost complete response in MIAPaCa-2 tumors, whereas it merely inhibited the growth of BxPC-3 tumors. 90Y-TSP-A01 is a promising RIT agent for pancreatic cancer, although further investigation is necessary to improve the efficacy for the radioresistant types like BxPC-3. PMID:25893775

New Production Routes for Medical Isotopes 64Cu and 67Cu Using Accelerator Neutrons

NASA Astrophysics Data System (ADS)

Kin, Tadahiro; Nagai, Yasuki; Iwamoto, Nobuyuki; Minato, Futoshi; Iwamoto, Osamu; Hatsukawa, Yuichi; Segawa, Mariko; Harada, Hideo; Konno, Chikara; Ochiai, Kentaro; Takakura, Kosuke

2013-03-01

We have measured the activation cross sections producing 64Cu and 67Cu, promising medical radioisotopes for molecular imaging and radioimmunotherapy, by bombarding a natural zinc sample with 14 MeV neutrons. We estimated the production yields of 64Cu and 67Cu by fast neutrons from \\text{natC(d,n) with 40 MeV 5 mA deuterons. We used the present result together with the evaluated cross section of Zn isotopes. The calculated 64Cu yield is 1.8 TBq (175 g 64Zn) for 12 h of irradiation; the yields of 67Cu by 67Zn(n,p)67Cu and 68Zn(n,x)67Cu were 249 GBq (184 g 67Zn) and 287 GBq (186 g 68Zn) at the end of 2 days of irradiation, respectively. From the results, we proposed a new route to produce 67Cu with very little radionuclide impurity via the 68Zn(n,x)67Cu reaction, and showed the 64Zn(n,p)64Cu reaction to be a promising route to produce 64Cu. Both 67Cu and 64Cu are noted to be produced using fast neutrons.

Re-188 Enhances the Inhibitory Effect of Bevacizumab in Non-Small-Cell Lung Cancer.

PubMed

Xiao, Jie; Xu, Xiaobo; Li, Xiao; Li, Yanli; Liu, Guobing; Tan, Hui; Shen, Hua; Shi, Hongcheng; Cheng, Dengfeng

2016-09-30

The malignant behaviors of solid tumors such as growth, infiltration and metastasis are mainly nourished by tumor neovascularization. Thus, anti-angiogenic therapy is key to controlling tumor progression. Bevacizumab, a humanized anti-vascular endothelial growth factor (VEGF) antibody, plus chemotherapy or biological therapy can prolong survival for cancer patients, but treatment-related mortality is a concern. To improve inhibitory effect and decrease side-effects on non-small-cell lung cancer (NSCLC), we used Re-188, which is a β emitting radionuclide, directly labeled with bevacizumab for radioimmunotherapy in a human A549 tumor model. Cytotoxic assay data showed that, after 188 ReO₄ - or 188 Re-bevacizumab at different concentration for 4 and 24 h, a time- and radioactivity does-dependent reduction in cell viability occurred. Also, an apoptosis assay conformed great apoptosis in the 188 Re-bevacizumab group compared with controls and other treatment groups. In vivo, tumor volumes in the 188 Re-bevacizumab (11.1 MBq/mice) group were not reduced but growth was delayed compared with other groups. Thus, 188 Re-bevacizumab enhanced the therapeutic effect of bevacizumab, suggesting a potential therapeutic strategy for NSCLC treatment.

A mechanistic compartmental model for total antibody uptake in tumors.

PubMed

Thurber, Greg M; Dane Wittrup, K

2012-12-07

Antibodies are under development to treat a variety of cancers, such as lymphomas, colon, and breast cancer. A major limitation to greater efficacy for this class of drugs is poor distribution in vivo. Localization of antibodies occurs slowly, often in insufficient therapeutic amounts, and distributes heterogeneously throughout the tumor. While the microdistribution around individual vessels is important for many therapies, the total amount of antibody localized in the tumor is paramount for many applications such as imaging, determining the therapeutic index with antibody drug conjugates, and dosing in radioimmunotherapy. With imaging and pretargeted therapeutic strategies, the time course of uptake is critical in determining when to take an image or deliver a secondary reagent. We present here a simple mechanistic model of antibody uptake and retention that captures the major rates that determine the time course of antibody concentration within a tumor including dose, affinity, plasma clearance, target expression, internalization, permeability, and vascularization. Since many of the parameters are known or can be estimated in vitro, this model can approximate the time course of antibody concentration in tumors to aid in experimental design, data interpretation, and strategies to improve localization. Copyright © 2012 Elsevier Ltd. All rights reserved.

A mechanistic compartmental model for total antibody uptake in tumors

PubMed Central

Thurber, Greg M.; Dane Wittrup, K.

2012-01-01

Antibodies are under development to treat a variety of cancers, such as lymphomas, colon, and breast cancer. A major limitation to greater efficacy for this class of drugs is poor distribution in vivo. Localization of antibodies occurs slowly, often in insufficient therapeutic amounts, and distributes heterogeneously throughout the tumor. While the microdistribution around individual vessels is important for many therapies, the total amount of antibody localized in the tumor is paramount for many applications such as imaging, determining the therapeutic index with antibody drug conjugates, and dosing in radioimmunotherapy. With imaging and pretargeted therapeutic strategies, the time course of uptake is critical in determining when to take an image or deliver a secondary reagent. We present here a simple mechanistic model of antibody uptake and retention that captures the major rates that determine the time course of antibody concentration within a tumor including dose, affinity, plasma clearance, target expression, internalization, permeability, and vascularization. Since many of the parameters are known or can be estimated in vitro, this model can approximate the time course of antibody concentration in tumors to aid in experimental design, data interpretation, and strategies to improve localization. PMID:22974563

Approaches to Manufacturing Alpha Emitters For Radioimmunotherapeutic Drugs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gaylord King, A.; Givens, Kenneth R.; Miller, William H.

Several alpha emitting isotopes have been proposed for radioimmunotherapy. To produce these nuclides reliably and in quantities needed, unique manufacturing approaches will be required. This paper describes the approaches that are being developed for the manufacture of 225Actinium (225 Ac) that decays to 213Bismuth (213 Bi) and the commercial manufacturing approaches. Oak Ridge National Laboratory (ORNL) currently supplies the actinium used for research and medical use. Today the ORNL 233U stockpiles only provide sufficient material for research quantities of 213 Bi. At the Institute for Transuranium Elements (ITU), in Karlsruhe, researchers have also developed a method of irradiating radium-226 withmore » protons in a cyclotron to produce actinium- 225 through the reaction 226Ra (p, 2n) 225Ac. Researchers from the Missouri University (MU), the Missouri University Research Reactor (MURR), MedActinium, Inc. and Los Alamos National Laboratory (LANL) are working on a collaborative effort to benchmark and optimize the production of 213Bi via neutron bombardment of 226Ra. MedActinium, Inc., in collaboration with commercial and institutional investigators at PG Research Foundation (PGRF) and Memorial Sloan Kettering Cancer Center (MSKCC), is developing commercial approaches to manufacturing these unique radioimmunotherapeutic drugs.« less

Dosimetric analysis of 177Lu-DOTA-rituximab in patients with relapsed/refractory non-Hodgkin's lymphoma.

PubMed

Yadav, Madhav P; Singla, Suhas; Thakral, Parul; Ballal, Sanjana; Bal, Chandrasekhar

2016-07-01

Radioimmunotherapy targeting CD20 receptors in lymphoma using radiolabeled chimeric antibodies may lead to better therapeutic responses than cold anti-CD20 antibodies. This study aimed to assess the biodistribution and present reasonable estimates of normal organ doses, including red marrow using Lu-DOTA-rituximab. Patients with relapsed/refractory CD20+ B-cell non-Hodgkin's lymphoma were recruited into this prospective study. In-house labeling of Lu-DOTA-rituximab was performed and administered after quality assurance. Rituximab (375 mg/m), followed by 50 mCi (1850 MBq) of Lu-DOTA-rituximab was administered as a slow intravenous infusion and emission images were acquired. Regions of interest were drawn for kidney, liver, heart, bladder, spleen, and tumor lesions on both anterior and posterior images. Internal dose estimation was performed using OLINDA v1.0 software. The mean age of the 10 patients (eight men and two women) was 52±13 years. The uptake of radiolabeled antibody was visualized within 30 min of administration in the liver, kidneys, heart, spleen, and bladder. The coefficient of determination (R) was greater than 0.95 for organs and the whole body in all patients. The effective half-life of radioimmunoconjugate was 100±28 h (42-126 h). The critical organ in our study was the red marrow. The average total body dose, effective dose, and effective dose equivalent calculated in all 10 patients were 0.13±0.02, 0.15±0.03, and 0.22±0.04 mGy/MBq, respectively. There may be considerable interindividual differences in absorbed doses of organs and generalization or extrapolation of doses in the clinical setting at present is not feasible with Lu-DOTA-rituximab in non-Hodgkin's lymphoma patients. Patient-specific dosimetry is thus recommended to eliminate the variations and reduce the possibility of dose-limiting toxicity.

Aligning physics and physiology: Engineering antibodies for radionuclide delivery.

PubMed

Tsai, Wen-Ting K; Wu, Anna M

2018-03-14

The exquisite specificity of antibodies and antibody fragments renders them excellent agents for targeted delivery of radionuclides. Radiolabeled antibodies and fragments have been successfully used for molecular imaging and radioimmunotherapy (RIT) of cell surface targets in oncology and immunology. Protein engineering has been used for antibody humanization essential for clinical applications, as well as optimization of important characteristics including pharmacokinetics, biodistribution, and clearance. Although intact antibodies have high potential as imaging and therapeutic agents, challenges include long circulation time in blood, which leads to later imaging time points post-injection and higher blood absorbed dose that may be disadvantageous for RIT. Using engineered fragments may address these challenges, as size reduction and removal of Fc function decreases serum half-life. Radiolabeled fragments and pretargeting strategies can result in high contrast images within hours to days, and a reduction of RIT toxicity in normal tissues. Additionally, fragments can be engineered to direct hepatic or renal clearance, which may be chosen based on the application and disease setting. This review discusses aligning the physical properties of radionuclides (positron, gamma, beta, alpha, and Auger emitters) with antibodies and fragments and highlights recent advances of engineered antibodies and fragments in preclinical and clinical development for imaging and therapy. Copyright © 2018 John Wiley & Sons, Ltd.

Intraperitoneal radioimmunotherapy for ovarian cancer: pharmacokinetics, toxicity, and efficacy of I-131 labeled monoclonal antibodies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stewart, J.S.; Hird, V.; Snook, D.

Thirty-six patients with ovarian cancer were treated with intraperitoneal I-131 labeled monoclonal antibodies to tumor associated antigens. The activity of I-131 administered was increased from 20 mCi to 158 mCi and the pharmacokinetics and toxicity evaluated. Five patients who had developed HAMA (Human Antimouse Antibodies) were retreated, and the pharmacokinetics and toxicity of the first and second treatment compared. Patients receiving their first therapy (HAMA negative), had a maximum of 25% (range 19.8-39.8%) of the injected activity in their circulation. This was accompanied by severe marrow suppression at I-131 activities over 120 mCi. The 5 HAMA positive patients had onlymore » 5% injected activity in the systemic circulation (range 3.8-6%), with rapid urinary excretion and neglible marrow suppression. In 31 patients with assessable disease there were no responses in 8 patients with gross disease (nodules greater than 2 cms), partial responses in 2 out of 15 patients with nodules less than 2 cms, and complete responses in 3 out of 6 patients with microscopic disease. The non specific radiation dose to the peritoneal cavity was estimated to be less than 500 cGy by lithium fluoride TLD, and could not be expected to account for the responses seen.« less

Comparison of non-invasive approaches to red marrow dosimetry for radiolabelled monoclonal antibodies.

PubMed

Plaizier, M A; Roos, J C; Teule, G J; van Dieren, E B; den Hollander, W; Haisma, H J; DeJager, R L; van Lingen, A

1994-03-01

Red marrow is usually the dose-limiting organ during radioimmunotherapy. Several non-invasive approaches to calculate the red marrow dose have been proposed. We compared four approaches to analyse the differences in calculated red marrow doses. The data were obtained from immunoscintigraphy of two antibodies with different red marrow kinetics [iodine-131-16.88 IgM and indium-111-OV-TL-3 F(ab')2]. The approaches are based on, respectively, homogeneously distributed activity in the body, a red marrow-blood activity concentration ratio of 0.3, scintigraphic quantification, and a combination of the second and third approaches. This fourth approach may be more adequate because of its independence from the chosen antibody. In addition, the influence of activity accumulation in liver, kidneys or cancellous bone on red marrow dose was studied. The calculated red marrow dose varied between 0.14 and 0.42 mGy/MBq for 111In-OV-TL-3 and between 0.13 and 0.68 mGy/MBq for 131I-16.88. If the radiopharmaceutical shows high affinity for cancellous bone or another organ situated near the red marrow, the activity in these organs must be included in dose calculations. This study shows a large variation in calculated red marrow dose and selection of the definitive non-invasive approach awaits validation.

In vivo generator for radioimmunotherapy

DOEpatents

Mausner, Leonard F.; Srivastava, Suresh G.; Straub, Rita F.

1988-01-01

The present invention involves labeling monoclonal antibodies with intermediate half-life radionuclides which decay to much shorter half-life daughters with desirable high energy beta emissions. Since the daughter will be in equilibrium with the parent, it can exert an in-situ tumoricidal effect over a prolonged period in a localized fashion, essentially as an "in-vivo generator". This approach circumvents the inverse relationship between half-life and beta decay energy. Compartmental modeling was used to determine the relative distribution of dose from both parent and daughter nuclei in target and non-target tissues. Actual antibody biodistribution data have been used to fit realistic rate constants for a model containing tumor, blood, and non-tumor compartments. These rate constants were then used in a variety of simulations for two generator systems, Ba-128/Cs-128 (t.sub.1/2 =2.4d/3.6m) and Pd-112/Ag-112 (t.sub.1/2 =0.9d/192m). The results show that higher tumor/background dose ratios may be achievable by virtue of the rapid excretion of a chemically different daughter during the uptake and clearance phases. This modeling also quantitatively demonstrates the favorable impact on activity distribution of a faster monoclonal antibody tumor uptake, especially when the antibody is labeled with a radionuclide with a comparable half-life.

In vivo generator for radioimmunotherapy

DOEpatents

Mausner, Leonard F.; Srivastava, Suresh G.; Straub, Rita F.

1988-11-01

The present invention involves labeling monoclonal antibodies with intermediate half-life radionuclides which decay to much shorter half-life daughters with desirable high energy beta emissions. Since the daughter will be in equilibrium with the parent, it can exert an in-situ tumoricidal effect over a prolonged period in a localized fashion, essentially as an "in-vivo generator". This approach circumvents the inverse relationship between half-life and beta decay energy. Compartmental modeling was used to determine the relative distribution of dose from both parent and daughter nuclei in target and non-target tissues. Actual antibody biodistribution data have been used to fit realistic rate constants for a model containing tumor, blood, and non-tumor compartments. These rate constants were then used in a variety of simulations for two generator systems, Ba-128/Cs-128 (t.sub.1/2 =2.4d/3.6m) and Pd-112/Ag-112 (t.sub.1/2 =0.9d/192m). The results show that higher tumor/background dose ratios may be achievable by virtue of the rapid excretion of a chemically different daughter during the uptake and clearance phases. This modeling also quantitatively demonstrates the favorable impact on activity distribution of a faster monoclonal antibody tumor uptake, especially when the antibody is labeled with a radionuclide with a comparable half-life.

Radiation safety considerations with therapeutic 90Y Zevalin.

PubMed

Zhu, Xiaowei

2003-08-01

ABSTRACT Radioimmunotherapy with the 90Y-labeled Zevalin radioimmunoconjugate is a new and promising modality in cancer treatment that combines the targeting power of monoclonal antibodies with the cytotoxicity of localized radiation. 90Y is a pure beta emitter, with different physical characteristics than traditional therapeutic radionuclides such as 131I. It is important that radiation safety professionals understand the characteristics of this radionuclide so that effective radiation safety procedures can be implemented with the Zevalin regimen. Because 90Y is a pure beta emitter, the Zevalin regimen is routinely administered as an outpatient procedure and is administered by using plastic shielding. Once the radioimmunoconjugate has been administered, the risk of radiation exposure to healthcare workers and family members is minimal. The primary route of biologic elimination of 90Y Zevalin is through the urinary system, with approximately 7% of the total activity administered eliminated over the course of 1 wk. Standard universal precautions, which should already be in place in healthcare facilities, should be sufficient to prevent radiation exposure to personnel working with patients who have been treated with Zevalin. Written radiation safety instructions for patients are not required, but basic instructions to the patient and his or her family may help further minimize the risk of radiation exposure and help alleviate patient and family concerns.

Management of fear of radiation exposure in carers of outpatients treated with iodine-131.

PubMed

Calais, Phillipe J; Page, Andrew C; Turner, J Harvey

2012-07-01

To characterise potential fear of radiation exposure in a normal population of individuals who have volunteered to care for a radioactive family member or friend after outpatient radioimmunotherapy (RIT) treatment for cancer, and obtain their knowing and willing acceptance of the risk. Over 750 carers of 300 patients confined to their homes for 1 week following outpatient iodine-131 rituximab RIT of lymphoma were interviewed by a nuclear medicine physicist according to a multi-visit integrated protocol designed to minimise radiation exposure, define risk and gain informed consent. Median radiation exposure of carers was 0.49 mSv (range 0.01-3.7 mSv) which is below the Western Australian regulatory limit of 5 mSv for consenting adult carers of radioactive patients. After signing a declaration of consent, only 2 carers of 750 abrogated their responsibility and none of those who carried out their duties expressed residual concerns at the end of the exit interview with respect to their radiation exposure. Fear of radiation exposure in a normal population may be characterised as a normal emotional response. In the special case of carers of radioactive patients, this fear may be successfully managed by rational, authoritative and empathic explanation to define the risk and gain willing acceptance within the context of domiciliary patient care.

[Are Two-Year Vocational Retraining Programs Really Better than One-Year Programs? Findings of a Propensity Score Matched Analysis].

PubMed

Bethge, M; Streibelt, M

2015-12-01

To analyze if one- and 2-year vocational retraining programs achieve similar effects on employment. Analyses were performed with longitudinal administrative data. We included persons aged 18-59 years, who started their retraining between January and June 2005. One- and 2-year program participants were matched by propensity scores. The matched groups were balanced regarding all baseline scores (one-year program: n=514; 2-year program: n=514). 4 and 5 years after start of the vocational retraining program, annual income, the duration of welfare benefits and the risk of a disability pension were comparable in both groups. However, the accumulative income between 2005 and 2009 was 9 294 Euro higher (95% CI: 3 656-14 932 Euro) in one-year retraining participants. Moreover, participants of one-year programs received less welfare benefits. The development of a vocational rehabilitation strategy needs to consider the accumulative advantage of one-year programs. © Georg Thieme Verlag KG Stuttgart · New York.

Geriatric medicine fellowship programs: a national study from the Association of Directors of Geriatric Academic Programs' Longitudinal Study of Training and Practice in Geriatric Medicine.

PubMed

Warshaw, Gregg A; Bragg, Elizabeth J; Shaull, Ruth W; Goldenhar, Linda M; Lindsell, Christopher J

2003-07-01

This report documents the development and growth of geriatric medicine fellowship training in the United States through 2002. A cross-sectional survey of geriatric medicine fellowship programs was conducted in the fall 2001. All allopathic (119) and osteopathic (7) accredited geriatric medicine fellowship-training programs in the United States were involved. Data were collected using self-administered mailed and Web-based survey instruments. Longitudinal data from the American Medical Association (AMA) and the Association of American Medical Colleges' (AAMC) National Graduate Medical Education (GME) Census, the Accreditation Council for Graduate Medical Education (ACGME), and the American Osteopathic Association (AOA) were also analyzed. The survey instrument was designed to gather data about faculty, fellows, program curricula, and program directors (PDs). In addition, annual AMA/AAMC data from 1991 to the present was compiled to examine trends in the number of fellowship programs and the number of fellows. The overall survey response rate was 76% (96 of 126 PDs). Most (54%) of the PDs had been in their current position 4 or more years (range: <1-20 years), and 59% of PDs reported that they had completed formal geriatric medicine fellowship training. The number of fellowship programs and the number of fellows entering programs has slowly increased over the past decade. During 2001-02, 338 fellows were training in allopathic programs and seven in osteopathic programs (all years of training). Forty-six percent (n = 44) of responding programs offered only 1-year fellowship-training experiences. PDs reported that application rates for fellowship positions were stable during the academic years (AYs) 1999-2002, with the median number of applications per first year position available in AY 2000-01 being 10 (range: 1-77). In 2001-02, data from the AMA/AAMC National GME Census indicated a fill rate for first-year geriatric medicine fellowship positions of 69% (259 first-year fellows for 373 positions). During 2001-02, more than half of programs (53%) reported having two or fewer first-year fellows, whereas 31% had three or four first-year fellows. Thirty-three programs (36%) reported having no U.S. medical school graduate first-year fellows, and another 25 (28%) reported having only one. Of the 51 programs offering second-year fellowship training, PDs reported 61 post-first-year fellows (median 1, range: 0-7). During the past 10 years, 27 new allopathic geriatric medicine fellowship programs opened; there are now 119 programs. There are also seven osteopathic programs. The recruitment of high-quality U.S. medical school graduates into these programs remains a challenge for the discipline. Furthermore, the retention of first-year fellows for additional years of academic training has been difficult. Incentives will be needed to attract the best graduates of U.S. family practice and internal medicine training programs into academic careers in geriatric medicine.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jaggi, Jaspreet Singh; Seshan, Surya V.; McDevitt, Michael R.

Purpose: Internal irradiation of kidneys as a consequence of radioimmunotherapy, radiation accidents, or nuclear terrorism can result in radiation nephropathy. We attempted to modify pharmacologically, the functional and morphologic changes in mouse kidneys after injection with the actinium ({sup 225}Ac) nanogenerator, an in vivo generator of {alpha}- and {beta}-particle emitting elements. Methods and Materials: The animals were injected with 0.35 {mu}Ci of the {sup 225}Ac nanogenerator, which delivers a dose of 27.6 Gy to the kidneys. Then, they were randomized to receive captopril (angiotensin-converting enzyme inhibitor), L-158,809 (angiotensin II receptor-1 blocker), spironolactone (aldosterone receptor antagonist), or a placebo. Results: Fortymore » weeks after the {sup 225}Ac injection, the placebo-control mice showed a significant increase in blood urea nitrogen (BUN) (87.6 {+-} 6.9 mg/dL), dilated Bowman spaces, and tubulolysis with basement membrane thickening. Captopril treatment accentuated the functional (BUN 119.0 {+-} 4.0 mg/dL; p <0.01 vs. placebo controls) and histopathologic damage. In contrast, L-158,809 offered moderate protection (BUN 66.6 {+-} 3.9 mg/dL; p = 0.02 vs. placebo controls). Spironolactone treatment, however, significantly prevented the development of histopathologic and functional changes (BUN 31.2 {+-} 2.5 mg/dL; p <0.001 vs. placebo controls). Conclusions: Low-dose spironolactone and, to a lesser extent, angiotensin receptor-1 blockade can offer renal protection in a mouse model of internal {alpha}-particle irradiation.« less

Radioimmunotherapy of human hepatocellular carcinoma xenografts with 131I-labelled antiferritin antibody.

PubMed Central

Saiful Alam, A. F.

1991-01-01

The effects of 131-labelled antiferritin polyclonal antibody for the treatment of established hepatocellular carcinoma (HC-04) in athymic nude mice were evaluated. 131I-labelled antiferritin antibody localised specifically to a subcutaneous tumour with a mean of 8.1% of the infused dose per gram of tumour at 24 h after infusion when the experiment was started 15 days after inoculation and with a mean of about 6.5% of the infused dose per gram of tumour when the experiment was started 30 days after tumour transplantation. The concentrations of 131I-antiferritin antibody in tumour delivered a mean of 1994 cGy to tumour following infusion of 500 microCi of radiolabelled antiferritin antibody in the early group and a mean of 1600 cGy in the late group. Treatment with 500 microCi led to regression of the tumour in 55% of animals in the early group and 44% in the late group. In contrast, unlabelled antiferritin and 131I-labelled IgG failed to exert any significant effect on tumour growth. The transplanted tumours in the early groups of animals had relatively higher concentration of ferritin than those in the late group. There was accelerated inhibition of tumour growth and prolonged survival in animals in the early group compared with those in the late group. PMID:2021533

Dosimetry of radium-223 and progeny

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fisher, D.R.; Sgouros, G.

Radium-223 is a short-lived (11.4 d) alpha emitter with potential applications in radioimmunotherapy of cancer. Radium-223 can be complexed and linked to protein delivery molecules for specific tumor-cell targeting. It decays through a cascade of short-lived alpha- and beta-emitting daughters with emission of about 28 MeV of energy through complete decay. The first three alpha particles are essentially instantaneous. Photons associated with Ra-223 and progeny provide the means for tumor and normal-organ imaging and dosimetry. Two beta particles provide additional therapeutic value. Radium-223 may be produced economically and in sufficient amounts for widescale application. Many aspects of the chemistry ofmore » carrier-free isotope preparation, complexation, and linkage to the antibody have been developed and are being tested. The radiation dosimetry of a Ra-223-labeled antibody shows favorable tumor to normal tissue dose ratios for therapy. The 11.4-d half-life of Ra-223 allows sufficient time for immunoconjugate preparation, administration, and tumor localization by carrier antibodies before significant radiological decay takes place. If 0.01 percent of a 37 MBq (1 mCi) injection deposits in a one gram tumor mass, and if the activity is retained with a typical effective half-time (75 h), the absorbed dose will be 163 mGy MBq{sup {minus}1} (600 rad mCi{sup {minus}1}) administered. 49 refs., 5 figs., 2 tabs.« less

Synthesis and preliminary biological evaluations of fluorescent or 149Promethium labeled Trastuzumab-polyethylenimine

DOE PAGES

Fitzsimmons, Jonathan; Nayak, Tapan; Cutler, Cathy; ...

2015-12-30

Radioimmunotherapy utilize a targeting antibody coupled to a therapeutic isotope to target and treat a tumor or disease. In this study we examine the synthesis and cell binding of a polymer scaffold containing a radiotherapeutic isotope and a targeting antibody. Methods: The multistep synthesis of a fluorescent or 149Promethium-labeled Trastuzumab-polyethyleneimine (PEI), Trastuzumab, or PEI is described. In vitro uptake, internalization and/or the binding affinity to the Her2/neu expressing human breast adenocarcinoma SKBr3 cells was investigated with the labeled compounds. Fluorescent-labeled Trastuzumab-PEI was internalized more into cells at 2 and 18 h than fluorescent-labeled Trastuzumab or PEI. The fluorescent-labeled Trastuzumab wasmore » concentrated on the cell surface at 2 and 18 h and the labeled PEI had minimal uptake. DOTA-PEI was prepared and contained an average of 16 chelates per PEI; the compound was radio-labeled with 149Promethium and conjugated to Trastuzumab. The purified 149Pm-DOTA-PEI-Trastuzumab had a radiochemical purity of 96.7% and a specific activity of 0.118 TBq/g. The compound demonstrated a dissociation constant for the Her2/neu receptor of 20.30 ± 6.91 nM. In conclusion, the results indicate the DOTA-PEI-Trastuzumab compound has potential as a targeted therapeutic carrier, and future in vivo studies should be performed.« less

Production of 64Cu and 67Cu radiopharmaceuticals using zinc target irradiated with accelerator neutrons

NASA Astrophysics Data System (ADS)

Kawabata, Masako; Hashimoto, Kazuyuki; Saeki, Hideya; Sato, Nozomi; Motoishi, Shoji; Nagai, Yasuki

2014-09-01

Copper radioisotopes have gained a lot of attention in radiopharmaceuticals owing to their unique decay characteristics. The longest half-life β emitter, 67Cu, is thought to be suitable for targeted radio-immunotherapy. Adequate production of 67Cu to meet the demands of clinical studies has not been fully established. Another attractive copper isotope, 64Cu has possible applications as a diagnostic imaging tracer combined with a therapeutic effect. This work proposes a production method using accelerator neutrons in which two copper radioisotopes can be produced: 1) 68Zn(n,x)67Cu and 2) 64Zn(n,p)64Cu using ~14 MeV neutrons generated by natC(d, n) reaction, both from natural or enriched zinc oxides. The generated 64,67Cu were separated from the target zinc oxide using a chelating and an anion exchange columns and were labelled with two widely studied chelators where the labelling efficiency was found to be acceptably good. The major advantage of this method is that a significant amount of 64,67Cu with a very few impurity radionuclides are produced which also makes the separation procedure simple. Provided an accelerator supplying an Ed = ~ 40 MeV, a wide application of 64,67Cu based drugs in nuclear medicine is feasible in the near future. We will present the characteristics of this production method using accelerator neutrons including the chemical separation processes.

25 CFR 39.1100 - Interim fiscal year 1980 and fiscal year 1981 funding for pre-kindergarten programs previously...

Code of Federal Regulations, 2014 CFR

2014-04-01

... 25 Indians 1 2014-04-01 2014-04-01 false Interim fiscal year 1980 and fiscal year 1981 funding for pre-kindergarten programs previously funded by the Bureau. 39.1100 Section 39.1100 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR EDUCATION THE INDIAN SCHOOL EQUALIZATION PROGRAM Pre-kindergarten Programs § 39.1100 Interim fiscal year...

25 CFR 39.1100 - Interim fiscal year 1980 and fiscal year 1981 funding for pre-kindergarten programs previously...

Code of Federal Regulations, 2012 CFR

2012-04-01

... 25 Indians 1 2012-04-01 2011-04-01 true Interim fiscal year 1980 and fiscal year 1981 funding for pre-kindergarten programs previously funded by the Bureau. 39.1100 Section 39.1100 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR EDUCATION THE INDIAN SCHOOL EQUALIZATION PROGRAM Pre-kindergarten Programs § 39.1100 Interim fiscal year...

25 CFR 39.1100 - Interim fiscal year 1980 and fiscal year 1981 funding for pre-kindergarten programs previously...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Interim fiscal year 1980 and fiscal year 1981 funding for pre-kindergarten programs previously funded by the Bureau. 39.1100 Section 39.1100 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR EDUCATION THE INDIAN SCHOOL EQUALIZATION PROGRAM Pre-kindergarten Programs § 39.1100 Interim fiscal year...

25 CFR 39.1100 - Interim fiscal year 1980 and fiscal year 1981 funding for pre-kindergarten programs previously...

Code of Federal Regulations, 2013 CFR

2013-04-01

... 25 Indians 1 2013-04-01 2013-04-01 false Interim fiscal year 1980 and fiscal year 1981 funding for pre-kindergarten programs previously funded by the Bureau. 39.1100 Section 39.1100 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR EDUCATION THE INDIAN SCHOOL EQUALIZATION PROGRAM Pre-kindergarten Programs § 39.1100 Interim fiscal year...

25 CFR 39.1100 - Interim fiscal year 1980 and fiscal year 1981 funding for pre-kindergarten programs previously...

Code of Federal Regulations, 2011 CFR

2011-04-01

... 25 Indians 1 2011-04-01 2011-04-01 false Interim fiscal year 1980 and fiscal year 1981 funding for pre-kindergarten programs previously funded by the Bureau. 39.1100 Section 39.1100 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR EDUCATION THE INDIAN SCHOOL EQUALIZATION PROGRAM Pre-kindergarten Programs § 39.1100 Interim fiscal year...

A vascular disease educational program in the preclinical years of medical school increases student interest in vascular disease.

PubMed

Godshall, Christopher J; Moore, Phillip S; Fleming, Shawn H; Andrews, Jeanette S; Hansen, Kimberley J; Hoyle, John R; Edwards, Matthew S

2010-09-01

New training paradigms in vascular surgery necessitate medical student interest in vascular disease. We examined the effects of incorporation of a vascular disease educational program during the second year of the medical school curriculum on student acquisition of knowledge and interest in the treatment of vascular disease. We developed and administered a new educational program on vascular disease and delivered the program to all second-year medical students. The new program encompassed 9 didactic hours, including 7 traditional lecture hours and 2 hours of problem-based learning. After completing the program, students were surveyed regarding vascular disease-specific knowledge, interest in treating vascular disease, and career choices. Third-year students who were not exposed to the program were surveyed as a control group. We recorded the voluntary student enrollment in the vascular and endovascular surgery rotation during the following academic year. Voluntary enrollment of the students exposed to the vascular disease education program was compared with enrollment for the previous 8 years. Before the introduction of the new educational program, 946 total lecture hours were delivered to first- and second-year medical students, comprising 490 hours (52%) given by nonsurgeon physicians, 445 (47%) by nonphysicians, and 11 (1%) by surgeons. Survey response rate was 93% (112 of 121) for second-year students and 95% (39 of 41) for third-year students. After the vascular disease program, second-year students answered 7.1 +/- 1.4 of 9 vascular disease questions correctly, whereas unexposed third-year students answered 7.2 +/- 1.7 questions correctly (P = .96). Most second-year medical students described a "somewhat" or "much greater" interest in the medical (63%), procedural (59%), and overall (63%) management of vascular disease after exposure to the program. Most also had a "somewhat" or "much greater" interest in a vascular medicine (64%) or vascular and endovascular surgery (60%) rotation. Enrollment in the vascular surgery third-year clerkship increased significantly to a mean of 3.0 students/month from 1.16 students/month in the prior year (P = .0032, postintervention year vs 8 prior years). A vascular disease educational program administered to second-year medical students increases interest in vascular disease and interest in further training. The increased interest translates to greater student enrollment in the vascular surgery clerkship in the subsequent academic year.

Learning Communities, First Year Programs and Their Effectiveness: The Role of the IR Office. AIR 2002 Forum Paper.

ERIC Educational Resources Information Center

Knight, William E.

Several learning communities and first-year programs have been developed at Bowling Green State University, a public doctoral-research intensive university in the midwest, over the last few years. Such programs include the Bowling Green Effect Mentoring Program, the Literacy Serve and Learn program, the Honors Program, the Center for Multicultural…

Trends in Environmental Health Engineering

ERIC Educational Resources Information Center

Rowe, D. R.

1972-01-01

Reviews the trends in environmental health engineering and describes programs in environmental engineering technology and the associated environmental engineering courses at Western Kentucky University (four-year program), Wytheville Community College (two-year program), and Rensselaer Polytechnic Institute (four-year program). (PR)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Larsen, Barbara L.

The annual program report provides detailed information about all aspects of the SNL/CA Environmental Planning and Ecology Program for a given calendar year. It functions as supporting documentation to the SNL/CA Environmental Management System Program Manual. The 2005 program report describes the activities undertaken during the past year, and activities planned in future years to implement the Planning and Ecology Program, one of six programs that supports environmental management at SNL/CA.

Smoking Prevention for Students: Findings From a Three-Year Program of Integrated Harm Minimization School Drug Education.

PubMed

Midford, Richard; Cahill, Helen; Lester, Leanne; Foxcroft, David R; Ramsden, Robyn; Venning, Lynne

2016-01-01

This study investigated the impact of the Drug Education in Victorian Schools (DEVS) program on tobacco smoking. The program taught about licit and illicit drugs in an integrated manner over 2 years, with follow up in the third year. It focused on minimizing harm, rather than achieving abstinence, and employed participatory, critical-thinking and skill-based teaching methods. A cluster-randomized, controlled trial of the program was conducted with a student cohort during years 8 (13 years), 9 (14 years), and 10 (15 years). Twenty-one schools were randomly allocated to the DEVS program (14 schools, n = 1163), or their usual drug education program (7 schools, n = 589). One intervention school withdrew in year two. There was a greater increase in the intervention students' knowledge about drugs, including tobacco, in all 3 years. Intervention students talked more with their parents about smoking at the end of the 3-year program. They recalled receiving more education on smoking in all 3 years. Their consumption of cigarettes had not increased to the same extent as controls at the end of the program. Their change in smoking harms, relative to controls, was positive in all 3 years. There was no difference between groups in the proportionate increase of smokers, or in attitudes towards smoking, at any time. These findings indicate that a school program that teaches about all drugs in an integrated fashion, and focuses on minimizing harm, does not increase initiation into smoking, while providing strategies for reducing consumption and harm to those who choose to smoke.

78 FR 58291 - TRICARE; Fiscal Year 2014 Continued Health Care Benefit Program Premium Update

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-23

... DEPARTMENT OF DEFENSE Office of the Secretary TRICARE; Fiscal Year 2014 Continued Health Care... Health Care Benefit Program Premiums for Fiscal Year 2014. SUMMARY: This notice provides the updated Continued Health Care Benefit Program Premiums for Fiscal Year 2014. DATES: The Fiscal Year 2014 rates...

Mercer County Community College Remedial Program Assessment, August 1988. Two Year Follow-Up of the Fall 1986 Cohort.

ERIC Educational Resources Information Center

Porter, Al

This assessment of New Jersey's Mercer County Community College's (MCCC's) remedial program provides a program overview, results of a two-year follow-up of fall 1986 remedial students, and comparative data from previous years. The program overview examines policies and procedures concerning placement criteria, exit standards, program acceptance,…

Course Outlines in Business of the Rumson-Fair Haven Senior Elective Program.

ERIC Educational Resources Information Center

1976

The Rumson-Fair Haven Senior Elective Program was developed and implemented by students, faculty, and administrators over the three-year period from 1971 to 1974. The program offers high school students who complete graduation requirements in the first three years of the four-year program a combination of the following options for the senior year:…

Parents and Children through the School Years: The Effects of the Home Instruction Program for Preschool Youngsters.

ERIC Educational Resources Information Center

Baker, Amy J. L.; Piotrkowski, Chaya S.

The Home Instruction Program for Preschool Youngsters (HIPPY) is a free 2-year family oriented early childhood education and parent involvement program for parents with limited formal education to help them provide educational enrichment for their 4-year-old and 5-year-old children. As of 1996, HIPPY programs serve over 15,000 economically…

Course Outlines in Science of the Rumson-Fair Haven Senior Elective Program.

ERIC Educational Resources Information Center

1976

The Rumson-Fair Haven Senior Elective Program was developed and implemented by students, faculty, and administrators over the three-year period from 1971 to 1974. The program offers high school students who complete graduation requirements in the first three years of the four-year program a combination of the following options for the senior year:…

Governor's Educator Excellence Grant (GEEG) Program: Year One Evaluation Report. Policy Evaluation Report

ERIC Educational Resources Information Center

Springer, Matthew G.; Podgursky, Michael J.; Lewis, Jessica L.; Ehlert, Mark W.; Gardner, Catherine G.; Ghoshdastidar, Bonnie; Lopez, Omar S.; Patterson, Christine H.; Taylor, Lori L.

2007-01-01

This report presents findings stemming from the first-year evaluation of the Governor's Educator Excellence Grant (GEEG) program, one of several statewide performance incentive programs in Texas. In the fall of 2006, the GEEG program made available non-competitive, three-year grants to 99 schools ranging from $60,000 to $220,000 per year. Grants…

DOE Office of Scientific and Technical Information (OSTI.GOV)

Larsen, Barbara L.

The annual program report provides detailed information about all aspects of the Sandia National Laboratories, California (SNL/CA) Environmental Planning and Ecology Program for a given calendar year. It functions as supporting documentation to the SNL/CA Environmental Management System Program Manual. The 2006 program report describes the activities undertaken during the past year, and activities planned in future years to implement the Planning and Ecology Program, one of six programs that supports environmental management at SNL/CA.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Larsen, Barbara L.

The annual program report provides detailed information about all aspects of the Sandia National Laboratories, California (SNL/CA) Environmental Planning and Ecology Program for a given calendar year. It functions as supporting documentation to the SNL/CA Environmental Management System Program Manual. The program report describes the activities undertaken during the past year, and activities planned in future years to implement the Planning and Ecology Program, one of six programs that supports environmental management at SNL/CA.

Comparison of traditional six-year and new four-year dental curricula in South Korea.

PubMed

Komabayashi, Takashi; Ahn, Chul; Kim, Kang-Ju; Oh, Hyo-Won

2012-01-01

This study aimed to compare the dental curriculum of the traditional six-year system with that of the new four-year (graduate-entry) system in South Korea. There are 11 dental schools in South Korea: six are public and five are private. Eight offer the new four-year program and the other three offer the traditional six-year program. Descriptive analyses were conducted using bibliographic data and local information along with statistical analyses such as chi-square tests. In the six-year programs, clinical dentistry subjects were taught almost equally in practical and didactic courses, while the basic science courses were taught more often as practical courses (P < 0.0001). In the four-year programs, both the basic science and clinical dentistry subjects were taught didactically more often; while more dentistry subjects were taught than basic sciences (P = 0.004). The four-year program model in South Korea is more focused on dentistry than on basic science, while both basic and clinical dentistry subjects were equally taught in the six-year program.

Headwaters: The Next Stage in High School Integrated Programming

ERIC Educational Resources Information Center

Elrick, Michael

2007-01-01

For 12 years, Centennial High School in Guelph has run an integrated program called the Community Environmental Leadership Program (CELP). In 1995 the program was offered at the grade 11 level. The program ran successfully in the second semester for seven years. In 2001, with the high school system being modified to fit into a four-year model, and…

Evaluation of the School Breakfast Program Pilot Project: Findings from the First Year of Implementation. Nutrition Assistance Program Report Series.

ERIC Educational Resources Information Center

McLaughlin, Joan E.; Bernstein, Lawrence S.; Crepinsek, May Kay; Daft, Lynn M.; Murphy, J. Michael

In 1998, Congress authorized implementation of a 3-year pilot breakfast program involving 4,300 students in elementary schools in 6 school districts representing a range of economic and demographic characteristics. The program began in the 2000-01 school year. This lengthy report presents the findings from the pilot's first year. The study had two…

The AAS Visiting Professor Programs: Three Anniversaries

NASA Astrophysics Data System (ADS)

Philip, A. G. Davis

2003-05-01

The AAS Program of Visiting Professors was started in 1958 with three astronomers as lecturers. They were Paul Merrill (Mt. Wilson and Palomar Observatories), Seth Nicholson (Mt. Wilson and Palomar Observatories) and Harlow Shapley (Harvard College Observatory). The program was run by a Committee on Visiting Professors from 1958 through 1963. The program was funded by grants from the National Science Foundation. The Executive Officer of the AAS, Paul Routley headed the program from the 1963 - 64 academic year through the 1968 - 69 academic year. Larry Fredrick headed the program for 1969 - 70 and then Hank Gurin headed it through 1973 -74, the last year of the program. At the end of this summer meeting, the combined Visiting Professors Program and the Shapley Program will be starting their 47th year. The Shapley Visiting Lectureships in Astronomy Program was started in the 1974 - 75 academic year under the leadership of Hank Gurin. The original funding came from the Perkin Fund and a three year grant from the Research Corporation. In 1975 the Shapley Endowment fund was set up to help pay the expenses of the program. In 1976 there was support from the Slipher fund which lasted through the 1978 - 79 academic year. From 1979 to the present the program is financed by the Shapley Endowment Fund and by the contributions made by institutions which host the visits. In the fall of 1998 the fee that Institutions pay to the AAS in support of their Shapley visits was reduced from 300 to 250 to make it easier for them to apply for visits. Members of the AAS have made contributions to the program over the years and we are very appreciative of this support. In 1974 there were 42 lecturers in the program, of whom four are still active giving lectures (George Carruthers, Larry Fredrick, Arlo Landolt and Davis Philip). After the summer meeting, the Shapley Program will be embarking on its 30th year. Now there are 82 astronomers in the program and we get from 40 to 60 requests a year. Shapley visits have been made to Canadian institutions since 1976 and to Mexican institutions since 1998. After the summer meeting it will be the start of the 10th year of my directing the program. On May 26 there will be a Shapley Dinner at Dyer Observatory in Nashville for the Shapley lecturers who are attending the AAS meeting and we will celebrate these three anniversaries.

Establishment of an appropriate fall prevention program: A community-based study.

PubMed

Otaka, Yohei; Morita, Mitsuo; Mimura, Toshio; Uzawa, Mitsuyoshi; Liu, Meigen

2017-07-01

To identify an appropriate community-based fall prevention program METHODS: We introduced two programs to 24 senior centers, "community salons," in a Japanese city, and carried out a prospective controlled trial between 2004 and 2005. Eight salons (185 participants aged 72.0 ± 7.1 years) received a single-visit program consisting of one multidisciplinary team visit that included fall risk assessment with feedback and a fall prevention lecture. A total of 16 salons (418 participants aged 73.6 ± 7.4 years) received a year-round comprehensive program, with visits carried out every 3 months. We compared the fall rates for 1 year between the two programs. Based on the results, we implemented a modified program until 2014 and examined the long-term consequences. In the prospective controlled trial, fall rates did not differ significantly between programs (P = 0.449). Instead, fall rates for both programs decreased significantly by 0.89 (95% CI 0.84-0.94) times each month. Therefore, we implemented a modified version of the single-visit program. By March 2014, the programs had been delivered to 1863 individuals, and the total number of attendees was 6622. The average attendance frequency per participant was 0.62 times per year. The majority (85.3%) of salons requested the program every year. Overall, the risk of falling (fall rates in the preceding year) decreased significantly as the number of program attendances increased (incident rate ratio = 0.89, 95% CI 0.85-0.92) irrespective of initial program types. The programs including fall risk assessment with feedback and a fall prevention lecture reduced falls when embedded into the community, and they were accepted well over the course of 10 years. Geriatr Gerontol Int 2017; 17: 1081-1089. © 2016 The Authors. Geriatrics & Gerontology International published by John Wiley & Sons Australia, Ltd on behalf of Japan Geriatrics Society.

Six year improvement program : fiscal years 1996-97 thru 2001-2002 (Vol. 2)

DOT National Transportation Integrated Search

1997-01-01

This program is the Commonwealth Transportation Board's plan for the use of funds anticipated to be available for ports, airports, public transit, and highway construction in the 1996-97 fiscal year. The Board also uses this Six-Year Program to distr...

Six Year Improvement Program: Fiscal Years 1996-97 thru 2001-2002 (Vol. 1)

DOT National Transportation Integrated Search

1997-01-01

This program is the Commonwealth Transportation Board's plan for the use of funds anticipated to be available for ports, airports, public transit, and highway construction in the 1996-97 fiscal year. The Board also uses this Six-Year Program to distr...

Effects of a Full-Day Preschool Program on 4-Year-Old Children

ERIC Educational Resources Information Center

Herry, Yves; Maltais, Claire; Thompson, Katherine

2007-01-01

This study explored the effects of a full-day preschool program on 4-year-old children. The study compared the development of a group of children (N = 403) who attended the preschool program on a half-day basis during the 1999-2000 school year (the last year the half-day program was in place) with the development of a group of children (N = 418)…

Urban Rail Supporting Technology Program Fiscal Year 1975 - Year End Summary

DOT National Transportation Integrated Search

1975-12-01

The Urban Rail Supporting Technology Program is described for the 1975 fiscal year period. Important areas include program management, technical support and applications engineering, facilities development, test and evaluation, and technology develop...

Clinical Track Program Expansion Increases Rotation Capacity for Experiential Program.

PubMed

Tofade, Toyin S; Brueckl, Mark; Ross, Patricia A

2017-10-01

Objective. To evaluate the rotation capacity at the University of Maryland School of Pharmacy and see if the implementation of clinical track programs across the state correlates to an increase in rotation capacity for the school. Methods. The following information was collected: number of preceptors over the years in the school's experiential learning program, number of clinical track programs from 2012 to 2015, rotation type, availability submissions per rotation type per year, and availability submissions per hospital participant in the clinical track program per year. The rotation capacity and rotation types from 2012 to 2015 academic years were assessed and compared to see if there was any impact on the clinical track programs implemented. Results. There was no statistically significant difference in the frequency distribution of rotation types among all sites from 2012 through 2015 academic years. However, there was a statistically significant difference in the total number/capacity of rotations from 2012 to 2015 academic years. There were also statistically significant differences in the rotation capacity in all sites except for three sites. Conclusion. Adding clinical track programs can help increase the capacity of a school's clinical rotations.

A three-year reflective writing program as part of introductory pharmacy practice experiences.

PubMed

Nuffer, Wesley; Vaughn, Jessica; Kerr, Kevin; Zielenski, Christopher; Toppel, Brianna; Johnson, Lauren; McCauley, Patrina; Turner, Christopher J

2013-06-12

To implement and evaluate a 3-year reflective writing program incorporated into introductory pharmacy practice experiences (IPPEs) in the first- through third-year of a doctor of pharmacy (PharmD) program. Reflective writing was integrated into 6 IPPE courses to develop students' lifelong learning skills. In their writing, students were required to self-assess their performance in patient care activities, identify and describe how they would incorporate learning opportunities, and then evaluate their progress. Practitioners, faculty members, and fourth-year PharmD students served as writing preceptors. The success of the writing program was assessed by reviewing class performance and surveying writing preceptor's opinions regarding the student's achievement of program objectives. Class pass rates averaged greater than 99% over the 8 years of the program and the large majority of the writing preceptors reported that student learning objectives were met. A support pool of 99 writing preceptors was created. A 3-year reflective writing program improved pharmacy students' reflection and reflective writing skills.

Required and Elective Experiences During the 4th Year: An Analysis of ACGME Accredited Psychiatry Residency Program Websites.

PubMed

Vestal, Heather S; Belitsky, Richard; Bernstein, Carol A; Chaukos, Deanna; Cohen, Mitchell B; Dickstein, Leah J; Hilty, Donald M; Hutner, Lucy; Sakman, Ferda; Scheiber, Stephen C; Wrzosek, Marika I; Silberman, Edward K

2016-10-01

The objective of this study was to assess and describe required and elective components of the 4th post-graduate year (PGY4) in psychiatry residency programs. We reviewed the websites of all 193 2014-2015 ACGME accredited psychiatry residency programs for content describing the specific components of the PGY4 year. Nearly all residency programs (99 %) had some form of required experiences during the PGY4 year. Ninety-four percent had clinical requirements for PGY4 residents, with longitudinal outpatient clinic being the most common (77 %). All programs offered some elective time during PGY4, but the amount of time ranged from 2 months to 100 %. Virtually all residency programs include some requirements in the 4th year (most commonly didactics and outpatient clinic) in addition to a broad array of elective experiences. Although 3 years may suffice for residents to complete ACGME requirements, a variety of factors may motivate programs to include required 4th year curricula. Future studies should explore the rationales for and possible benefits of programmatic requirements throughout 4 versus only 3 years of psychiatric training.

Enhancing positive attitudes towards disability: evaluation of an integrated physiotherapy program.

PubMed

Morgan, Prue Elizabeth; Lo, Kristin

2013-02-01

This study explored whether attitudes towards disability in second year undergraduate physiotherapy students could be enhanced by an on-campus integrated curriculum program. A pre-post design was used. Year 2 (pre-clinical) students participated in a 12-week program focused on optimising attitudes towards people with acquired or developmental neurological disability. The Discomfort subscale of the Interaction with Disabled Persons scale, rated on a six-point Likert scale, was applied prior to and at completion of the 12-week program, and compared to year 4 students, just prior to graduation. Qualitative data from year 2 reflective narratives was also gathered. Forty-seven second year and 45 fourth year physiotherapy students participated. The difference in Discomfort subscale scores between weeks 1 and 12 of year 2 was statistically significant (p = 0.0016). The difference in Discomfort subscale scores between year 2 week 1 and year 4 students was also statistically significant (p = 0.040). There was no significant difference in attitudes between students at the end of year 2 and the end of year 4 (p = 0.703). Qualitative data supported the development of more positive attitudes towards neurological disability across the 12 week year 2 pre-clinical program. Student attitudes towards people with acquired and/or developmental neurological disabilities can be enhanced through an on campus integrated curriculum program.

Peer Mentoring to Develop Psychological Literacy in First-Year and Graduating Students

ERIC Educational Resources Information Center

Burton, Lorelle J.; Chester, Andrea; Xenos, Sophie; Elgar, Karen

2013-01-01

First- and final-year undergraduate students have unique transition issues. To support both the transition of first-year students into the program, and the transition of third-year students out of the program and into the workforce or further study, a face-to-face peer mentoring program was embedded into the first-year psychology curricula at RMIT…

"2+2" Articulated Health Occupations Project. Nursing Program. Second Year Final Report.

ERIC Educational Resources Information Center

Paris Independent School District, TX.

A project was conducted to develop a 2 + 2 articulated training program in health careers to link the last 2 years of secondary and the first 2 years of postsecondary training. During the second year of the secondary project, the first year of training was implemented and the model program was further developed and refined. Project tasks included…

Urban Rail Supporting Technology Program - Fiscal Year 1973 - Year-End Summary

DOT National Transportation Integrated Search

1974-01-01

The Urban Rail Supporting Technology Program, being conducted for the Department of Transportation Urban Mass Transportation Administration (UMTA) is described for the 1973 Fiscal Year period. Major areas covered include program management, technical...

Graduated driver licensing programs and fatal crashes of 16-year-old drivers: a national evaluation.

PubMed

Chen, Li-Hui; Baker, Susan P; Li, Guohua

2006-07-01

Implementation of graduated driver licensing programs is associated with reductions in crash rates of young drivers, but graduated driver licensing programs vary in their components. The impact of programs with different components is unknown. The purpose of this work was to determine which graduated driver licensing programs are associated with the greatest reductions in fatal motor vehicle crashes involving 16-year-old drivers. We conducted a retrospective study of all 16-year-old drivers involved in fatal crashes in the United States from 1994 through 2004 using data from the Fatality Analysis Reporting System and the US Census Bureau. We measured incidence rate ratios of fatal motor vehicle crashes involving 16-year-old drivers according to graduated driver licensing programs, adjusted for state and year. Compared with state quarters with no graduated driver licensing program components, reductions of 16% to 21% in fatal crash involvement rates of 16-year-old drivers occurred with programs that included > or = 3-month mandatory waiting period, nighttime driving restriction, and either > or = 30 hours of supervised driving or passenger restriction. Reductions of 18% to 21% occurred in state quarters with programs that included > or = 5 of the 7 components examined. Drivers aged 20 to 24 or 25 to 29 years did not experience significant reductions. Comprehensive graduated driver licensing programs are associated with reductions of approximately 20% in 16-year-old drivers' fatal crash involvement rates. The greatest benefit seems to be associated with programs that include age requirements and > or = 3 months of waiting before the intermediate stage, nighttime driving restriction, and either > or = 30 hours of supervised driving or passenger restriction.

NATIONAL EVALUATION OF THE WEATHERIZATION ASSISTANCE PROGRAM DURING THE ARRA PERIOD: PROGRAM YEARS 2009-2011

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tonn, Bruce Edward; Rose, Erin M; Schmoyer, Richard L

This report describes the third major evaluation of the Program, encompassing program years 2009 to 2011. In this report, this period of time is referred to as the ARRA Period. This is a special period of time for the Program because the American Recovery and Reinvestment Act (ARRA) of 2009 has allocated $5 billion of funding for the Program. In normal program years, WAP s annual appropriation is in the range of $200-250 million, supporting the weatherization of approximately 100,000 homes. With the addition of ARRA funding during these program years, the expectation is that weatherization activity will exceed 300,000more » homes per year. In addition to saving energy and reducing low-income energy bills, expanded WAP funding is expected to stimulate the economy by providing new jobs in the weatherization field and allowing low-income households to spend more money on goods and services by spending less on energy.« less

NSF Programs That Support Research in the Two-Year College Classroom

NASA Astrophysics Data System (ADS)

Carter, V.; Ryan, J. G.; Singer, J.

2011-12-01

The National Science Foundation recognizes the significant role provided by two-year institutions in providing high quality STEM courses to large numbers of students. For some students the STEM courses completed while attending a two-year institution represent the only STEM courses a student may take; for others the courses serve as the foundation to continue on into a STEM major at a four-year institution; and some students complete STEM courses that lead directly into the workforce. Several programs in the Division of Undergraduate Research, including the Advanced Technological Education (ATE) program, STEM Talent Expansion Program (STEP), and the Transforming Undergraduate Education in STEM (TUES) program, support the inclusion of student research experiences at two-year institutions. Information about these programs and examples of successful funded projects will be provided. Resources for faculty considering applying for support will be shared with special attention to a faculty development program designed to help faculty learn about funding opportunities and prepare proposals for submission to the TUES and ATE programs.

2012-2013 Federal Pell Grant Program End-of-Year Report

ERIC Educational Resources Information Center

Office of Postsecondary Education, US Department of Education, 2013

2013-01-01

The Federal Pell Grant End-of-Year Report presents primary aspects of Federal Pell Grant Program activity for the 2012-2013 award year. This presentation is a compilation of quantitative program data assembled to offer insights into the changes to the Title IV applicant universe and the Federal Pell Grant Program. The Federal Pell Grant…

2011-2012 Federal Pell Grant Program End-of-Year Report

ERIC Educational Resources Information Center

Office of Postsecondary Education, US Department of Education, 2012

2012-01-01

The Federal Pell Grant End-of-Year Report presents primary aspects of Federal Pell Grant Program activity for the 2011-2012 award year. This presentation is a compilation of quantitative program data assembled to offer insights into the changes to the Title IV applicant universe and the Federal Pell Grant Program. The Federal Pell Grant…

Measuring the Success of a Summer Reading Program: A Five-Year Study

ERIC Educational Resources Information Center

Liljequist, Laura; Stone, Staci

2009-01-01

Students were surveyed about a first-year summer reading program (SRP) at Murray State University, a regional, comprehensive university, for five consecutive years. Data are presented on how well the program met five stated goals: (a) providing a common academic experience for incoming first-year students, (b) introducing students to intellectual…

Social marketing program sales.

PubMed

1987-01-01

This table presents data on social marketing program sales for projects that provide more than 5000 couple-years of protection. Cited are social marketing programs in Bangladesh, Costa Rica, Egypt, El Salvador, Guatemala, Honduras, India, Indonesia, Jamaica, Nepal, Pakistan, Peru, and Sri Lanka. Included in the table are data on program funding, product sales (generally condoms, pills, and foaming tablets), and couple-years of protection provided. Among the social marketing programs reporting particularly high couple-years of protection levels are the Bangladesh Family Planning Social Marketing Program (1,165,100), the Egyptian Family Planning Association's Family for the Future Program (732,200), India's Nirodh Marketing Program (2,225,000), and Pakistan's Social Marketing Contraceptive Program (280,000).

NASA Multidisciplinary Design and Analysis Fellowship Program

NASA Technical Reports Server (NTRS)

1995-01-01

This report is a Year 1 interim report of the progress on the NASA multidisciplinary Design and Analysis Fellowship Program covering the period, January 1, 1995 through September 30, 1995. It summarizes progress in establishing the MDA Fellowship Program at Georgia Tech during the initial year. Progress in the advertisement of the program, recruiting results for the 1995-96 academic year, placement of the Fellows in industry during Summer 1995, program development at the M.S. and Ph.D. levels, and collaboration and dissemination of results are summarized in this report. Further details of the first year's progress will be included in the report from the Year 1 Workshop to be held at NASA Langley on December 7-8, 1995.

Cost-Effectiveness of a Program to Eliminate Disparities in Pneumococcal Vaccination Rates in Elderly Minority Populations: An Exploratory Analysis

PubMed Central

Michaelidis, Constantinos I.; Zimmerman, Richard K.; Nowalk, Mary Patricia; Smith, Kenneth J.

2013-01-01

Objective Invasive pneumococcal disease is a major cause of preventable morbidity and mortality in the United States, particularly among the elderly (>65 years). There are large racial disparities in pneumococcal vaccination rates in this population. Here, we estimate the cost-effectiveness of a hypothetical national vaccination intervention program designed to eliminate racial disparities in pneumococcal vaccination in the elderly. Methods In an exploratory analysis, a Markov decision-analysis model was developed, taking a societal perspective and assuming a 1-year cycle length, 10-year vaccination program duration, and lifetime time horizon. In the base-case analysis, it was conservatively assumed that vaccination program promotion costs were $10 per targeted minority elder per year, regardless of prior vaccination status and resulted in the elderly African American and Hispanic pneumococcal vaccination rate matching the elderly Caucasian vaccination rate (65%) in year 10 of the program. Results The incremental cost-effectiveness of the vaccination program relative to no program was $45,161 per quality-adjusted life-year gained in the base-case analysis. In probabilistic sensitivity analyses, the likelihood of the vaccination program being cost-effective at willingness-to-pay thresholds of $50,000 and $100,000 per quality-adjusted life-year gained was 64% and 100%, respectively. Conclusions In a conservative analysis biased against the vaccination program, a national vaccination intervention program to ameliorate racial disparities in pneumococcal vaccination would be cost-effective. PMID:23538183

The effect of a comprehensive injury audit program on injury incidence in ballet: a 3-year prospective study.

PubMed

Allen, Nick; Nevill, Alan M; Brooks, John H M; Koutedakis, Yiannis; Wyon, Matthew A

2013-09-01

The aim of this study was to determine whether an intervention with individualized conditioning program based on injury history and functional movement screening would be effective in reducing ballet injury incidence. Prospective 3-year epidemiological study. Professional ballet company and its in-house medical facility. Dancers from a professional ballet company over the 3-year study period. Participant numbers ranged from 52 to 58 (year 1: 52; year 2: 58; year 3: 53). The intervention consisted of individual conditioning programs developed using injury history and functional movement screening. Analysis was undertaken of the all dancers who were present in the company during the study period. The significance of change in injuries over a 3-year period was determined using a Poisson distribution model. To determine whether individual conditioning programs resulted in a decrease in injury incidence over the study period. The injury count reduced significantly in years 2 and 3 (P < 0.001). Injury incidence for male dancers declined from year 1 (in year/1000 h) (4.76/1000 h) to year 2 (2.40/1000 h) and year 3 (2.22/1000 h). For women, a reduction in the injury incidence was observed from year 1 (4.14/1000 h) to year 2 (1.71/1000 h) and year 3 (1.81/1000 h). Through prospective injury surveillance, we were able to demonstrate the benefit of individualized conditioning programs based on injury history and functional movement screening in reducing injuries in ballet. The implementation of well-structured injury surveillance programs can impact on injury incidence through its influence on intervention programs.

Year-End Clinic Handoffs: A National Survey of Academic Internal Medicine Programs.

PubMed

Phillips, Erica; Harris, Christina; Lee, Wei Wei; Pincavage, Amber T; Ouchida, Karin; Miller, Rachel K; Chaudhry, Saima; Arora, Vineet M

2017-06-01

While there has been increasing emphasis and innovation nationwide in training residents in inpatient handoffs, very little is known about the practice and preparation for year-end clinic handoffs of residency outpatient continuity practices. Thus, the latter remains an identified, yet nationally unaddressed, patient safety concern. The 2014 annual Association of Program Directors in Internal Medicine (APDIM) survey included seven items for assessing the current year-end clinic handoff practices of internal medicine residency programs throughout the country. Nationwide survey. All internal medicine program directors registered with APDIM. Descriptive statistics of programs and tools used to formulate a year-end handoff in the ambulatory setting, methods for evaluating the process, patient safety and quality measures incorporated within the process, and barriers to conducting year-end handoffs. Of the 361 APDIM member programs, 214 (59%) completed the Transitions of Care Year-End Clinic Handoffs section of the survey. Only 34% of respondent programs reported having a year-end ambulatory handoff system, and 4% reported assessing residents for competency in this area. The top three barriers to developing a year-end handoff system were insufficient overlap between graduating and incoming residents, inability to schedule patients with new residents in advance, and time constraints for residents, attendings, and support staff. Most internal medicine programs do not have a year-end clinic handoff system in place. Greater attention to clinic handoffs and resident assessment of this care transition is needed.

30 years of ergonomics at 3M: a case study.

PubMed

Larson, N; Wick, H

2012-01-01

The added value of the Ergonomics Program at 3M was found to be improved employee safety, compliance with regulations and reduction of work-related illness, increases in productivity, and quality and operating efficiency. This paper describes the thirty years of existence of this program. For the first twenty years, the program objectives were to: respond to requests for assistance related to work-related musculoskeletal disorder (WMSD) concerns, raise employee awareness of MSDs and ergonomics; educate engineers in ergonomics design; and develop ergonomics teams at manufacturing locations. Since the year 2000, 3M's Ergonomics Program has been in transition from a US-centric and corporate-based technical-expertled program to a global program applying participatory ergonomics strategies within a macroergonomics framework. During that transition, the existing program requirements were revised, new methods and program tools were created, and expectations for implementation at the manufacturing locations clarified. This paper focuses on the company's manufacturing ergonomics program activities during the past ten years and includes specifics of the program's objectives, risk assessment reduction process, and ergonomics technical expertise development. The main benefit achieved throughout the company is reducing employee injury while also increasing productivity and operating efficiency.

Developing and Implementing an REU Program Philosophy

NASA Astrophysics Data System (ADS)

LaDue, D. S.

2013-12-01

Each individual REU and REU-like program takes place in different fields, in unique contexts, with unique individuals, some of whom are different each year. Because of this, copying program elements from one year to another, or from another program, may not recreate outcomes. Having an underlying program philosophy, or approach to the program, creates the conditions for innovation and creativity to provide new spark to a program each year. As a former REU participant in a nuclear physics REU, and now an adult learning scientist, the director of the National Weather Center REU Program focuses on clarifying goals and outcomes of the program to the participants, and adapting the program each year to best help each participant learn research skills, reflect upon their experiences with research, and find leads to careers that would suit them well. How decisions are made regarding what types of activities to do every year will be contrasted with how other activities are created or adapted according to the needs of the unique individual students. Consideration is also given toward trends in the field, such as exposing participants to whatever current lively discussions are taking place locally or in the broader field.

Safer Choice Partner of the Year Awards Application Form

EPA Pesticide Factsheets

EPA's Design for the Environment program developed the Safer Product Labeling Program Partner of the Year Award program to recognize DfE stakeholders that have furthered the safer chemistry goals of the program

76 FR 13351 - Notice of Funds Availability (NOFA) Inviting Applications for the Biorefinery Assistance Program

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-11

.... Applications must be received by May 10, 2011 to compete for Fiscal Year 2011 program funds. The Notice... 10, 2011, to compete for Fiscal Year 2011 program funds. Any application received after 4:30 p.m... on May 10, 2011, in order to be considered for Fiscal Year 2011 program funds. Any application...

Effects Five Years Later: The Michigan School Readiness Program Evaluation through Age 10.

ERIC Educational Resources Information Center

Xiang, Zongping; Schweinhart, Lawrence J.

This follow-up study examined the outcomes of children who had participated in the Michigan School Readiness Program (MSRP), a preschool program for 4-year-olds identified as being at risk for school failure, up to 5 years following their participation in the program. For the evaluation, 338 children who had participated in the state-funded…

Medical cost savings for participants and nonparticipants in health risk assessments, lifestyle management, disease management, depression management, and nurseline in a large financial services corporation.

PubMed

Serxner, Seth; Alberti, Angela; Weinberger, Sarah

2012-01-01

To compare changes in medical costs between participants and nonparticipants in five different health and productivity management (HPM) programs. Quasi-experimental pre/post intervention study. A large financial services corporation. A cohort population of employees enrolled in medical plans (n  =  49,723) [corrected]. A comprehensive HPM program, which addressed health risks, acute and chronic conditions, and psychosocial disorders from 2005 to 2007. Incentives were used to encourage health risk assessment participation in years 2 and 3. Program participation and medical claims data were collected for members at the end of each program year to assess the change in total costs from the baseline period. Analysis . Multivariate analyses for participation categories were conducted comparing baseline versus program year cost differences, controlling for demographics. All participation categories yielded a lower cost increase compared to nonparticipation and a positive return on investment (ROI) for years 2 and 3, resulting in a 2.45∶1 ROI for the combined program years. Medical cost savings exceeded program costs in a wide variety of health and productivity management programs by the second year.

The Longitudinal Elderly Person Shadowing Program: Outcomes from an Interprofessional Senior Partner Mentoring Program

ERIC Educational Resources Information Center

Basran, Jenny F. S.; Dal Bello-Haas, Vanina; Walker, Doreen; MacLeod, Peggy; Allen, Bev; D'Eon, Marcel; McKague, Meredith; Chopin, Nicola S.; Trinder, Krista

2012-01-01

The University of Saskatchewan's Longitudinal Elderly Person Shadowing (LEPS) is an interprofessional senior mentors program (SMP) where teams of undergraduate students in their first year of medicine, pharmacy, and physiotherapy; 2nd year of nutrition; 3rd year nursing; and 4th year social work partner with community-dwelling older adults.…

Residence Life Programs and the First-Year Experience. The Freshman Year Experience. Monograph Series No. 5.

ERIC Educational Resources Information Center

Zeller, William, Ed.; And Others

This monograph contains papers which suggest means of implementing residential programs, services, and facilities that will help to meet the needs of first-year college students. Fourteen papers are presented and are as follows: "Reflections on the First Year Residential Experience" (John N. Gardner); "The Role of Residential Programs in the…

Addressing the academic gap between 4- and 6-year pharmacy programs in South Korea.

PubMed

Yoo, Sujin; Song, Seungyeon; Lee, Sangmi; Kwon, Kwangil; Kim, Eunyoung

2014-10-15

To address the academic gap (or lack of adequate training and programs) between 4- and 6-year pharmacy programs and suggest methods for reducing this gap and to evaluate pharmacists' perceptions of preceptorship. We surveyed a convenience sample of 200 community pharmacists who graduated from a 4-year program who were participating in a continuing education program for clinical pharmacy as organized by the Daejeon branch of the Korea Pharmaceutical Association in 2011. Twenty-one questions were asked about the academic gap, needs for an education program, preceptorship, and medication therapy management services. International precedents were examined through a literature review to glean ideas of how to bridge the academic gap between the 4- and 6-year programs. In total, 132 pharmacists answered the survey (return rate=66.0%). The survey findings included problems caused by the academic gap, high need for an adequate education program, low acceptability of preceptorship, and the possibility of medication therapy management services. US-based, non-traditional PharmD programs and new curriculum-support training in Japan provided examples of how the academic gap has been successfully bridged. Nationwide efforts and government support are urgently required to close the academic gap, and experiential education should be included in transitional programs for 4-year pharmacy program pharmacists.

A Three-Year Reflective Writing Program as Part of Introductory Pharmacy Practice Experiences

PubMed Central

Vaughn, Jessica; Kerr, Kevin; Zielenski, Christopher; Toppel, Brianna; Johnson, Lauren; McCauley, Patrina; Turner, Christopher J.

2013-01-01

Objectives. To implement and evaluate a 3-year reflective writing program incorporated into introductory pharmacy practice experiences (IPPEs) in the first- through third-year of a doctor of pharmacy (PharmD) program. Design. Reflective writing was integrated into 6 IPPE courses to develop students’ lifelong learning skills. In their writing, students were required to self-assess their performance in patient care activities, identify and describe how they would incorporate learning opportunities, and then evaluate their progress. Practitioners, faculty members, and fourth-year PharmD students served as writing preceptors. Assessment. The success of the writing program was assessed by reviewing class performance and surveying writing preceptor’s opinions regarding the student’s achievement of program objectives. Class pass rates averaged greater than 99% over the 8 years of the program and the large majority of the writing preceptors reported that student learning objectives were met. A support pool of 99 writing preceptors was created. Conclusions. A 3-year reflective writing program improved pharmacy students’ reflection and reflective writing skills. PMID:23788811

Economic Evaluation of a School-based Combined Program with a Targeted Pit and Fissure Sealant and Fluoride Mouth Rinse in Japan.

PubMed

Sakuma, Shihoko; Yoshihara, Akihiro; Miyazaki, Hideo; Kobayashi, Seigo

2010-01-01

In Niigata prefecture, Japan, a system has been developed based on a school-based fluoride mouth rinse program as follows; students with caries susceptible teeth are screened in a school dental examination, and encouraged to receive sealant placement in local dental clinics. However, the cost-effectiveness of sealant application in the public health has been questioned. The aim of this study was to estimate of the cost-effectiveness and cost-benefit ratio for a school-based combined program with fluoride mouth rinse and targeted fissure sealant in children residing in non-fluoridated areas in Japan. The analysis was based on comparing an intervention group with two cohorts in the 8-year-old (n=66) and 11-year-old (n=58) participating in the combined program for four and seven years, respectively, with a control group of the same grades (n=43 and n=54 respectively). The study measured mean differences in number of decayed and filled teeth (DFT) between the study groups and a combined program cost per child during study periods. The cost-effectiveness ratio was expressed as an individual annual program cost per DFT averted. In the cost-benefit ratio the mean difference in treatment cost between groups (program benefit) was compared to program cost. The mean reduced DFT differences between groups were 1.44 in 8-year-old and 3.17 in 11-year-old children. The cost-effectiveness ratio was ¥ 493 in the 8-year-old and ¥ 202 in the 11-year-old, respectively. The cost-benefit ratio was 1.84 in 8-year-old children and 2.42 in 11-year-old. This combined program indicated acceptable cost-effectiveness and cost -benefit ratio.

Immuno-SPET/CT and immuno-PET/CT: a step ahead to translational imaging.

PubMed

Pecking, Alain P; Bellet, Dominique; Alberini, Jean Louis

2012-10-01

Malignant tumours have the remarkable property to express cell surface antigens. Pressman was first reporting that radiolabeled antibodies were capable of organ localization. It was a promising challenge but the expected success and the development of this imaging method was limited by a poor imaging resolution despite a rather good specificity of the antibodies used. Identification of key cell surface markers is opening a new era as potential molecular imaging biomarkers in oncologic applications. Antibodies production has been promoted by the development of engineered fragments with preserved immunological properties and pharmacokinetics optimized for molecular imaging. A good compromise has to be obtained between the biological properties of the antibody and the physical half-life of the radionuclide. Several positron emission tomography (PET) radionuclides such as iodine-124, copper-64, yttrium-86 or zirconium-89 have been the focus of recent immuno-PET studies with interesting informative images in preclinical and clinical studies. Thanks to the development of more sensitive new detectors and specific software, molecular imaging methods, particularly PET imaging, allow nowadays the detection of lesions smaller than 5 mm in human. Immuno-PET can potentially be used for tumour detection and identification at diagnosis, staging and restaging, for treatment selection and monitoring, and during follow-up. Moreover the availability of matched imaging or therapeutic radionuclide pairs, such as (124)I/(131)I, (64)Cu/(67)Cu and (86)Y/(90)Y, make easier the quantification of tissue uptake and dosimetry calculation for radioimmunotherapy.

Comparison of normal tissue pharmacokinetics with {sup 111}In/{sup 9}Y monoclonal antibody m170 for breast and prostate cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lehmann, Joerg; Department of Radiodiagnosis and Therapy, Division of Hematology/Oncology, University of California Davis School of Medicine, Sacramento, CA; DeNardo, Gerald L.

Purpose: Radioactivity deposition in normal tissues limits the dose deliverable by radiopharmaceuticals (RP) in radioimmunotherapy (RIT). This study investigated the absorbed radiation dose in normal tissues for prostate cancer patients in comparison to breast cancer patients for 2 RPs using the monoclonal antibody (MAb) m170. Methods and Materials: {sup 111}In-DOTA-glycylglycylglycyl-L-p-isothiocyanatophenylalanine amide (GGGF)-m170 and {sup 111}In-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA) 2-iminothiolane (2IT)-m170, representing the same MAb and chelate with and without a cleavable linkage, were studied in 13 breast cancer and 26 prostate cancer patients. Dosimetry for {sup 9}Y was calculated using {sup 111}In MAb pharmacokinetics from the initial imaging study for eachmore » patient, using reference man- and patient-specific masses. Results: The reference man-specific radiation doses (cGy/MBq) were not significantly different for the breast and the prostate cancer patients for both RPs in all but one tissue-RP combination (liver, DOTA-2IT). The patient-specific doses had differences between the groups most of which can be related to weight differences. Conclusions: Similar normal tissue doses were calculated for two groups of patients having different cancers and genders. This similarity combined with continued careful analysis of the imaging data might allow the use of higher starting doses in early phase RIT studies.« less

Immunotherapy of Cryptococcus infections.

PubMed

Antachopoulos, C; Walsh, T J

2012-02-01

Despite appropriate antifungal treatment, the management of cryptococcal disease remains challenging, especially in immunocompromised patients, such as human immunodeficiency virus-infected individuals and solid organ transplant recipients. During the past two decades, our knowledge of host immune responses against Cryptococcus spp. has been greatly advanced, and the role of immunomodulation in augmenting the response to infection has been investigated. In particular, the role of 'protective' Th1 (tumour necrosis factor-α, interferon (IFN)-γ, interleukin (IL)-12, and IL-18) and Th17 (IL-23 and IL-17) and 'non-protective' Th2 (IL-4, IL-10, and IL-13) cytokines has been extensively studied in vitro and in animal models of cryptococcal infection. Immunomodulation with monoclonal antibodies against the capsular polysaccharide glucuronoxylomannan, glucosylceramides, melanin and β-glucan and, lately, with radioimmunotherapy has also yielded promising results in animal models. As a balance between sufficiently protective Th1 responses and excessive inflammation is important for optimal outcome, the effect of immunotherapy may range from beneficial to deleterious, depending on factors related to the host, the infecting organism, and the immunomodulatory regimen. Clinical evidence supporting immunomodulation in patients with cryptococcal infection remains too limited to allow firm recommendations. Limited human data suggest a role for IFN-γ. Identification of surrogate markers characterizing patients' immunological status could possibly suggest candidate patients for immunotherapy and the type of immunomodulation to be administered. © 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.

Distribution of OV-TL 3 and MOv18 in normal and malignant ovarian tissue.

PubMed

Buist, M R; Molthoff, C F; Kenemans, P; Meijer, C J

1995-07-01

To analyse the distribution of OV-TL 3 and MOv18 in normal ovarian tissue to determine which antibody is most suitable for (radio)immunotherapy of ovarian carcinoma. The distribution of OV-TL 3 and MOv18 was determined using immunohistochemistry and flow cytometry. Epithelial and other cells in many tissues, and leucocytes in peripheral blood, bone marrow and spleen stained positively with OV-TL 3. The staining pattern of MOv18 in normal tissues was more restricted and was confined to epithelial cells in the lung, kidney, pancreas, salivary gland, ovary, Fallopian tubes, and cervix. Reactivity was also observed with pneumocytes in the lung, tubuli in the kidney, acinar cells in the salivary gland and pancreas, in the placenta, and with Kupffer cells in the liver. The staining pattern of chimeric MOv18 was identical with the murine form. OV-TL 3 and MOv18 reacted with 100% and 98% (45/46) of the 46 tested epithelial ovarian cancers, respectively. In ovarian carcinoma tissue homogeneous staining of epithelial cells was observed with OV-TL 3 and more heterogeneous staining with MOv18. In 12 and nine patients, respectively, a difference in staining intensity for OV-TL 3 and MOv18 was observed between various tumour samples from the same patient. MOv18 has greater therapeutic potential because of its restricted reactivity with normal tissues and especially, in contrast to OV-TL 3, its lack of reactivity with haematopoietic cells.

Astatine-211 conjugated to an anti-CD20 monoclonal antibody eradicates disseminated B-cell lymphoma in a mouse model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Green, Damian J.; Shadman, Mazyar; Jones, Jon C.

Alpha emitting radionuclides release a large amount of energy within a few cell diameters and may be particularly effective for radioimmunotherapy targeting minimal residual disease (MRD) conditions in which micrometastatic disease satellites are broadly distributed. To evaluate this hypothesis, 211At conjugated 1F5 mAb (anti-CD20) was studied in both bulky lymphoma tumor xenograft and MRD animal models. Superior treatment responses to 211At conjugated 1F5 mAb were evident in the MRD setting. Lymphoma xenograft tumor bearing animals treated with doses of up to 48µCi of anti-CD20 211At-decaborate [211At-B10-1F5] experienced modest responses (0% cures but 2-3-fold prolongation of survival compared to negative controls).more » In contrast, 70% of animals in the MRD lymphoma model demonstrated complete eradication of disease when treated with 211At-B10-1F5 at a radiation dose that was less than one-third (15 µCi) of the highest dose given to xenograft animals. Tumor progression among untreated control animals in both models was uniformly lethal. After 130 days, no significant renal or hepatic toxicity is observed in the cured animals receiving 15 µCi of 211At-B10-1F5. These findings suggest that in a MRD lymphoma model, where isolated cells and tumor microclusters prevail, α-emitters may be uniquely efficacious.« less

National Aeronautics and Space Administration Budget Estimates, Fiscal Year 2011

NASA Technical Reports Server (NTRS)

2010-01-01

The Budget includes three new robust exploration programs: (1) Technology demonstration program, $7.8 five years. Funds the development and demonstration of technologies that reduce the cost and expand the capabilities of future exploration activities, including in-orbit refueling and storage. (2) Heavy-Lift and Propulsion R&D, $3.1 billion over five years. Funds R&D for new launch systems, propellants, materials, and combustion processes. (3) Robotic precursor missions, $3.0 billion over five years. Funds cost-effective means to scout exploration targets and identify hazards and resources for human visitation and habitation. In addition, the Budget enhances the current Human Research Program by 42%; and supports the Participatory Exploration Program at 5 million per year for activities across many NASA programs.

A Study of Year-Round Schools. Volume III: Handbook for Conducting Cost Analysis of Year-Round School Programs.

ERIC Educational Resources Information Center

Burnett, Robert W.

This manual is intended for use by district officials undertaking analysis of the costs of year-round school (YRS) programs. To analyze the budgetary impact of YRS, it is necessary to determine the actual costs incurred with the YRS program and to compare these costs to expenses that would be incurred without the YRS program. A simulated…

Linking College and Work: Exemplary Policies and Practices of Two-Year College Work-Based Learning Programs.

ERIC Educational Resources Information Center

Bragg, Debra D.; Hamm, Russell E.

Based on an initial phase of a study conducted in 1993 that surveyed 1,200 two-year colleges to describe the scope and character of work-based learning programs already in existence, phase 2 sought a more in-depth understanding of selected exemplary work-based learning programs. Ten programs in eight two-year colleges were identified for further…

Student Retention and First-Year Programs: A Comparison of Students in Liberal Arts Colleges in the Mountain South

ERIC Educational Resources Information Center

Howard, Jeff S.

2013-01-01

The purpose of this study was to examine the association between the retention rate and 9 first-year student programs at Liberal Arts Colleges in the Mountain South, a region in the southern Appalachian Mountains of the United States. Nine first-year programs were studied: Summer Bridge Programs, Preterm Orientation, Outdoor Adventure Orientation,…

Listening to Students: Modification of a Reading Program Based on the Sources of Foreign Language Reading Anxiety

ERIC Educational Resources Information Center

Aydin, Belgin; Kuru Gonen, Ipek

2012-01-01

This paper is concerned with the modifications implemented in a second year foreign language (FL) reading program with respect to the problems students experience while reading in FL. This research draws on the sources of FL reading anxiety identified in the first year reading program with a motivation to re-design the second year program to help…

Environmental Hazards Assessment Program annual report, [June 1992--June 1993

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1993-10-01

This report, the Environment Hazards Assessment Program (EHAP) Annual Report, is the second of three reports that document activities under the EHAP grant and details progress made during the first year of the grant. The first year was devoted to the development of a working program implementation plan. During the developmental process some key objectives were achieved such as developing a Doctor of Philosophy degree program in Environmental Studies at MUSC (Medical University of South Carolina) and conducting the first Crossroads of Humanity series Round Table Forum. The PIP (Program Implementation Program) details the objectives, management and budgetary basis formore » the overall management and control of the grant over the next four years, the yearly program plans provide the monthly and day-to-day programmatic and budgetary control by which the PIP was developed.« less

Military Construction and Family Housing Program. Fiscal Year (FY) 2001 Budget Estimates

DTIC Science & Technology

2000-02-01

Department of the Air Force Military Construction and Family Housing Program Fiscal Year (FY) 2001 Budget Estimates Justification Data...Department of the Air Force Military Construction and Military Family Housing Program Summary Fiscal Year 2001 Appropriation Authorization Request... FISCAL YEAR 2001 (DOLLARS IN THOUSANDS) STATE/COUNTRY INSTALLATION TITLE APPROP REQUEST AUTH REQUEST PAGE INSIDE THE U.S. ALABAMA

A Directory of Public Service Internships: Opportunities for the Graduate, Post-Graduate and Mid-Career Professional, 1974-75.

ERIC Educational Resources Information Center

National Center for Public Service Internship Programs, Washington, DC.

Listed alphabetically by program title, the information for each public service internship program includes: address and phone number, program director, administering agency, year commenced, interns/fellows per year, objectives of program, program design, scope of placement, sponsors/mentors, scope of recruitment, recruitment strategies, screening…

National Program for e-Learning in Taiwan

ERIC Educational Resources Information Center

Chang, Maiga; Wang, Chin-Yeh; Chen, Gwo-Dong

2009-01-01

Taiwan government has initiated a five-year program since 2002: the National Science and Technology Program for e-Learning. The national program started from 2003 and was completed at the end of year 2007, involving thirteen government agencies. This paper describes the results that the national program has accomplished at its first phase, 2003 to…

Characteristics, Similarities, and Differences among Four-Year Cooperative Engineering Programs in the United States

ERIC Educational Resources Information Center

Egbert, Robert I.; Stone, Lorene H.; Adams, David L.

2011-01-01

Four-year cooperative engineering programs are becoming more common in the United States. Cooperative engineering programs typically involve a "parent" institution with an established engineering program and one or more "satellite" institutions which typically have few or no engineering programs and are located in an area where…

76 FR 52006 - Announcement of Funding Awards for the Assisted Living Conversion Program; Fiscal Year 2009

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-19

... Awards for the Assisted Living Conversion Program; Fiscal Year 2009 AGENCY: Office of the Assistant... funding under the Notice of Funding Availability (NOFA) for the Assisted Living Conversion Program (ALCP... for this program is 14.314. The Assisted Living Conversion Program is designed to provide funds to...

78 FR 28606 - Announcement of Funding Awards for the Assisted Living Conversion Program Fiscal Year 2012

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-15

... Awards for the Assisted Living Conversion Program Fiscal Year 2012 AGENCY: Office of the Assistant... funding under the Notice of Funding Availability (NOFA) for the Assisted Living Conversion Program (ALCP... for this program is 14.314. The Assisted Living Conversion Program is designed to provide funds to...

Coordination Problems in Graduate Programs for Two-Year College English Teachers.

ERIC Educational Resources Information Center

Sparrow, W. Keats

Six problems in coordinating a graduate program for two-year college English teachers are discussed in this paper. The problems are: how to implement national guidelines for such programs, how to staff the programs, how to accommodate traditional university personnel guidelines and regulations to the nontraditional staff for the programs, how to…

Bringing the Incredible Years® Programs to Scale

ERIC Educational Resources Information Center

Webster-Stratton, Carolyn; McCoy, Kathleen P.

2015-01-01

The Incredible Years® (IY) program series is a set of interlocking and comprehensive training programs for parents, teachers, and children. This article briefly reviews the theoretical foundations, goals, and research underlying these programs. The main purpose of the paper is to describe how the IY programs have been scaled up slowly and…

Characteristics of Emergency Medicine Residency Programs in Colombia

PubMed Central

Patiño, Andrés; Alcalde, Victor; Gutierrez, Camilo; Romero, Mauricio Garcia; Carrillo, Atilio Moreno; Vargas, Luis E.; Vallejo, Carlos E.; Zarama, Virginia; Mora Rodriguez, José L.; Bustos, Yury; Granada, Juliana; Aguiar, Leonar G.; Menéndez, Salvador; Cohen, Jorge I.; Saavedra, Miguel A.; Rodriguez, Juan M.; Roldan, Tatiana; Arbelaez, Christian

2017-01-01

Introduction Emergency medicine (EM) is in different stages of development around the world. Colombia has made significant strides in EM development in the last two decades and recognized it as a medical specialty in 2005. The country now has seven EM residency programs: three in the capital city of Bogotá, two in Medellin, one in Manizales, and one in Cali. The seven residency programs are in different stages of maturity, with the oldest founded 20 years ago and two founded in the last two years. The objective of this study was to characterize these seven residency programs. Methods We conducted semi-structured interviews with faculty and residents from all the existing programs in 2013–2016. Topics included program characteristics and curricula. Results Colombian EM residencies are three-year programs, with the exception of one four-year program. Programs accept 3–10 applicants yearly. Only one program has free tuition and the rest charge tuition. The number of EM faculty ranges from 2–15. EM rotation requirements range from 11–33% of total clinical time. One program does not have a pediatric rotation. The other programs require 1–2 months of pediatrics or pediatric EM. Critical care requirements range from 4–7 months. Other common rotations include anesthesia, general surgery, internal medicine, obstetrics, gynecology, orthopedics, ophthalmology, radiology, toxicology, psychiatry, neurology, cardiology, pulmonology, and trauma. All programs offer 4–6 hours of protected didactic time each week. Some programs require Advanced Cardiac Life Support, Pediatric Advanced Life Support and Advanced Trauma Life Support, with some programs providing these trainings in-house or subsidizing the cost. Most programs require one research project for graduation. Resident evaluations consist of written tests and oral exams several times per year. Point-of-care ultrasound training is provided in four of the seven programs. Conclusion As emergency medicine continues to develop in Colombia, more residency programs are expected to emerge. Faculty development and sustainability of academic pursuits will be critically important. In the long term, the specialty will need to move toward certifying board exams and professional development through a national EM organization to promote standardization across programs. PMID:29085546

Characteristics of Emergency Medicine Residency Programs in Colombia.

PubMed

Patiño, Andrés; Alcalde, Victor; Gutierrez, Camilo; Romero, Mauricio Garcia; Carrillo, Atilio Moreno; Vargas, Luis E; Vallejo, Carlos E; Zarama, Virginia; Mora Rodriguez, José L; Bustos, Yury; Granada, Juliana; Aguiar, Leonar G; Menéndez, Salvador; Cohen, Jorge I; Saavedra, Miguel A; Rodriguez, Juan M; Roldan, Tatiana; Arbelaez, Christian

2017-10-01

Emergency medicine (EM) is in different stages of development around the world. Colombia has made significant strides in EM development in the last two decades and recognized it as a medical specialty in 2005. The country now has seven EM residency programs: three in the capital city of Bogotá, two in Medellin, one in Manizales, and one in Cali. The seven residency programs are in different stages of maturity, with the oldest founded 20 years ago and two founded in the last two years. The objective of this study was to characterize these seven residency programs. We conducted semi-structured interviews with faculty and residents from all the existing programs in 2013-2016. Topics included program characteristics and curricula. Colombian EM residencies are three-year programs, with the exception of one four-year program. Programs accept 3-10 applicants yearly. Only one program has free tuition and the rest charge tuition. The number of EM faculty ranges from 2-15. EM rotation requirements range from 11-33% of total clinical time. One program does not have a pediatric rotation. The other programs require 1-2 months of pediatrics or pediatric EM. Critical care requirements range from 4-7 months. Other common rotations include anesthesia, general surgery, internal medicine, obstetrics, gynecology, orthopedics, ophthalmology, radiology, toxicology, psychiatry, neurology, cardiology, pulmonology, and trauma. All programs offer 4-6 hours of protected didactic time each week. Some programs require Advanced Cardiac Life Support, Pediatric Advanced Life Support and Advanced Trauma Life Support, with some programs providing these trainings in-house or subsidizing the cost. Most programs require one research project for graduation. Resident evaluations consist of written tests and oral exams several times per year. Point-of-care ultrasound training is provided in four of the seven programs. As emergency medicine continues to develop in Colombia, more residency programs are expected to emerge. Faculty development and sustainability of academic pursuits will be critically important. In the long term, the specialty will need to move toward certifying board exams and professional development through a national EM organization to promote standardization across programs.

Development and implementation of a writing program to improve resident authorship rates.

PubMed

Clemmons, Amber Bradley; Hoge, Stephanie C; Cribb, Ashley; Manasco, Kalen B

2015-09-01

The development, implementation, and evaluation of a writing program with a formalized writing project as a component of postgraduate year 1 (PGY1) and postgraduate year 2 (PGY2) pharmacy residencies are described. The writing program at Georgia Regents Medical Center/University of Georgia College of Pharmacy, a collaborative and jointly funded program, was initiated in the 2010-11 residency year. The goals of the program are to teach residents to communicate effectively, apply leadership skills, employ project management skills, and provide medication- and practice- related education and training. The program combines both writing experiences and mentorship. At the beginning of the residency year, trainees are presented with opportunities to participate in both research projects and writing projects. Specifically, opportunities within the writing program include involvement in review articles, case reports, drug information rounds, book chapters, letters to the editor, and high-quality medication-use evaluations for potential publication. The writing project is highly encouraged, and completion of a manuscript to be submitted for publication is expected by graduation. Nine papers were published by 8 of 18 PGY1 and PGY2 residents in the four years before program implementation. A total of 23 publications were published by 18 (72%) of the 25 PGY1 and PGY2 residents in the four years after implementation of the writing program. Implementation of a formal writing program increased the overall publication rate of residents. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

The Integrated Sequence: An Innovative Component of Four Courses in the General Education Program at Davis & Elkins College. A Digest of Program Elements, Developmental Background, and Faculty Dynamics.

ERIC Educational Resources Information Center

Gartmann, Will

The Integrated Sequence Program at Davis & Elkins College, which consists of four team-taught, interdisciplinary courses, is described, along with the origins and philosophy of the program. The courses are as follows: Human Freedom and the Counterforces (freshman year); World Culture (sophomore year); Comparative Ideas (junior year); and The…

7 CFR 760.108 - Payment limitation.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 2008 program year under TAP. (b) For 2009 and subsequent program years, no person or legal entity... SURE combined; or (2) $100,000 per program year under TAP. (c) The Deputy Administrator may take such..., LIP, SURE, and TAP if the individual's or entity's average adjusted gross income (AGI) exceeds $2.5...

The 1985 long-range program plan

NASA Technical Reports Server (NTRS)

1984-01-01

That continual evolution of NASA's research and development, is reflected in the missions, goals, and objectives planned for FY1985 and later years, in accordance with the responsibilities by the National Aeronautics and Space Act of 1958, as amended. New starts for the next ten years and space program activities to year 2000 are highlighted including space science and applications, space flight, space station, space tracking and data systems, and space research and technology. Space programs for the early 21st century and aeronautics programs up to and beyond the year 2000 are also covered.

77 FR 67439 - Fiscal Year 2013 Public Transportation on Indian Reservations Program

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-09

... Year 2013 Public Transportation on Indian Reservations Program AGENCY: Federal Transit Administration... changes in the Public Transportation on Indian Reservations program (Tribal Transit Program) in accordance... Public Meeting: FTA will provide outreach in conjunction with the National Tribal Transportation...

75 FR 33573 - Rural Housing Service

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-14

... Housing Program (GRRHP) Demonstration Program for Fiscal Year 2010; Correction AGENCY: Rural Housing... in the Federal Register of May 10, 2010, announcing the implementation of a demonstration program under the section 538 Guaranteed Rural Rental Housing Program (GRHHP) for Fiscal Year 2010. A correction...

SUPERFUND INNOVATIVE TECHNOLOGY EVALUATION PROGRAM: PROGRESS AND ACCOMPLISHMENTS - FISCAL YEAR 1991

EPA Science Inventory

The Superfund Innovative Technology Evaluation (SITE) program was the first major program for demonstrating and evaluating full-scale innovative treatment technologies at hazardous waste sites. Having concluded its fifth year, the SITE program is recognized as a leading advocate ...

The Market for School Choice in Indiana. AEI Education Policy Working Paper 2012-1

ERIC Educational Resources Information Center

McShane, Michael Q.

2012-01-01

The Indiana Choice Scholarship Program has the potential to be the largest school voucher program in the country. Though the authorizing legislation capped enrollment in the program at 7,500 for its first year (the 2011-12 school year), that cap was increased to 15,000 for this year, and will be removed for all subsequent years. With careful…

Children's Readiness Gains in Publically Funded, Community-Based Pre-Kindergarten Programs for 4 Year Olds and Preschool for 3 Year Olds

ERIC Educational Resources Information Center

Goldstein, Peggy; Warde, Beverly; Peluso, Paul

2013-01-01

Background: Many states provide public funding to facilitate school readiness for community-based pre-K and preschool programs for 4 year old children and "at risk" 3 year old children. Little research exists on the school readiness gains of children participating in these "garden variety" community-based programs. Objective:…

Environmental hazards assessment program. Annual report, July 1, 1994--June 30, 1995

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1995-07-31

This report describes activities and reports on progress for the third year of the DOE grant to support the Environmental Hazards Assessment Program (EHAP). It reports progress against grant objectives and the Program Implementation Plan published at the end of the first year of the grant. As the program has evolved, more projects have been funded and many existing projects have become more complex. Thus, to accomplish better the objectives over the years and retain a solid focus on the total mission, we have reorganized the grant effort from three to five majoe elements: Public and professional outreach; Clinical programs;more » Science programs; Information systems; and, Program management.« less

Pilot Programs in Vocational Agriculture. Agribusiness Programs for People; Final Report of Wisconsin's 5 Years of Pilot Programs in Agriculture.

ERIC Educational Resources Information Center

Thompson, John F.

The committee for Vocational Agriculture Pilot Programs in Wisconsin was appointed in 1967; this report analyzes the impact of five years of pilot programs on Wisconsin's vocational agriculture as a whole. During this period, the committee granted funding to 34 vocational agriculture departments in the State. A wide variety of programs were…

Sandia National Laboratories California Waste Management Program Annual Report February 2008.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brynildson, Mark E.

The annual program report provides detailed information about all aspects of the Sandia National Laboratories, California (SNL/CA) Waste Management Program. It functions as supporting documentation to the SNL/CA Environmental Management System Program Manual. This annual program report describes the activities undertaken during the past year, and activities planned in future years to implement the Waste Management (WM) Program, one of six programs that supports environmental management at SNL/CA.

Economic comparison of natural service and timed artificial insemination breeding programs in dairy cattle.

PubMed

Lima, F S; De Vries, A; Risco, C A; Santos, J E P; Thatcher, W W

2010-09-01

The objective was to compare the costs of natural service (NS) and timed artificial insemination (TAI) as breeding programs for dairy cows. Both programs were directly compared in a field study from November 2006 to March 2008. Reproductive results in that study were similar and served as inputs for this study. A herd budget accounting for all costs and revenues was created. Net cost during the field study for the NS program was $100.49/cow per year and for the TAI program was $67.80/cow per year, unadjusted for differences in voluntary waiting period for first insemination (VWP) and pregnancy rates (PR). After inclusion of the differences in VWP and PR, the economic advantage of the TAI program was $9.73/cow per year. Costs per day a cow was eligible for insemination were estimated at $1.45 for the NS program and $1.06 for the TAI program. Sensitivity analysis revealed that if the marginal feed cost increased to $5/hundredweight (cwt; 1 cwt=45.36kg), the advantage of TAI increased to $48.32/cow per year. In addition, higher milk prices and greater genetic progress increased the advantage of TAI. When semen price increased from $6 to $22, the NS program had an economic advantage of $33.29/cow per year. If each NS bull was replaced by an additional cow, the advantage of the TAI program was $60.81/cow per year. Setting the PR for both programs at 18% and the VWP at 80 d resulted in an advantage of $37.87/cow per year for the TAI program. In conclusion, any advantage of TAI depended greatly on cost to feed bulls, semen price, and genetic merit of semen. Copyright (c) 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

[Development of a New Scholastic Program for Medication Counseling Practice in Preclinical Training, Constructed for Junior Students by Senior Students Based on Their Experiences of On-site Practice].

PubMed

Suzuki, Sayo; Aono, Izumi; Imai, Natsumi; Kuwabara, Aki; Kenda, Yuki; Matsumoto, Minako; Yoshida, Aya; Watanabe, Asuka; Takagi, Akinori; Kobayashi, Noriko; Saeki, Haruko; Ohtani, Hisakazu; Nakamura, Tomonori; Kizu, Junko

2017-01-01

 Long-term practical on-site training, based on the Model Core Curriculum for Pharmaceutical Education, is a core program of the 6-year course of pharmaceutical education, introduced in Japan in 2010. In particular, medication counseling in practical training in 5th-year provides valuable opportunities for communication with real patients rather than simulated patients (SPs). However, it can also cause anxiety in 4th-year students before practical training. To address such concerns, upperclassmen (5th- and 6th-year students), who have already completed practical training, constructed and conducted a new educational program for medication counseling practice in preclinical training based on their experiences. They also developed case scenarios and played the role of patients themselves to create more realistic clinical settings. Advice from professional SPs was also provided. The 5-step program is composed of 1st counseling, 1st small group discussion (SGD) for improving counseling, 2nd revised counseling based on the 1st SGD, 2nd SGD, and development of a counseling plan and presentation. Educational effects of the program were evaluated by questionnaire survey after preclinical training in 4th-year students and after their practical training in 5th-year students. This new program, the Advanced Medication Counseling Practice, was found to be useful to reduce anxiety about communication with patients among 4th-year students (about 90%). Even after their practical training in 5th-year, they still appreciated usefulness of this program (about 80%). This program is still valued 4 years after its development. We developed the Advanced Medication Counseling Practice in preclinical training for junior students by senior students.

A 5-Year Update on the Uneven Distribution of Women in Orthopaedic Surgery Residency Training Programs in the United States.

PubMed

Van Heest, Ann E; Fishman, Felicity; Agel, Julie

2016-08-03

This study was undertaken to update our report from academic years 2004-2005 through 2008-2009, to include 5 additional years of the Association of American Medical Colleges GME Track data. This study will test the hypothesis that, when compared with the data from 2004-2005 through 2008-2009, there were no substantial changes from 2009-2010 through 2013-2014 in the distribution of orthopaedic surgery residency programs that train female residents and have been accredited by the Accreditation Council for Graduate Medical Education (ACGME). Data for all ACGME-accredited orthopaedic surgery residency training programs in the United States were analyzed for 2009-2010 through 2013-2014, in the same manner as our previous report analyzed data for 2004-2005 through 2008-2009. Programs were classified as having 0, 1, 2, or >2 women in training (i.e., for postgraduate year [PGY]-1 through PGY-5) for each of the 5 academic years. Programs were also analyzed for the percentage of female residents in training and were classified as being above the national average (>20%), similar to the national average (between 10% and 20%), or below the national average (<10%) for each of the 5 academic years. During the time period of 2004 to 2009, the mean percentage of female trainees in U.S. orthopaedic surgery residency programs was 11.6%, and during the time period of 2009 to 2014, this mean percentage increased to 12.6%. Residency programs in the United States do not train women at an equal rate. In the 5 years examined (2009 to 2014), 30 programs had no female trainees and 49 programs had >20% women enrolled in at least 1 of the 5 years, 8 programs had no female trainees enrolled in any of the 5 years, and 9 programs had >20% women enrolled in each of the 5 years. Female medical students continue to pursue orthopaedic surgery as a career at rates lagging behind all other surgical specialties. Not all residency programs train women at equal rates. The period of 2009-2010 through 2013-2014 showed a greater percentage of programs (68%) training ≥2 women than the period of 2004-2005 through 2008-2009 (61%). Obstacles to attracting women to orthopaedic surgery should continue to be identified and to be addressed. Copyright © 2016 by The Journal of Bone and Joint Surgery, Incorporated.

Outcomes of an antimicrobial control program in a teaching hospital.

PubMed

Gentry, C A; Greenfield, R A; Slater, L N; Wack, M; Huycke, M M

2000-02-01

The clinical outcomes and cost-effectiveness of an antimicrobial control program (ACP) were studied. The impact of an ACP in a teaching hospital was analyzed by comparing clinical outcomes and intravenous antimicrobial costs over two two-year periods, the two years before the program and the first two years after the program's inception. Admission baseline data, length of stay, mortality, and readmission rates were gathered for each patient. Patients were identified by using the International Classification of Diseases. Multivariate logistic regression models were constructed for mortality and for lengths of stay of 12 or more days. The acquisition costs of intravenous antimicrobial agents for the second baseline year and the entire program period were tabulated and compared. The average daily inpatient census was determined. The ACP was associated with a 2.4-day decrease in length of stay and a reduction in mortality from 8.28% to 6.61%. Rates of readmission for infection within 30 days of discharge remained about the same. Inpatient pharmacy costs other than intravenous antimicrobials decreased an average of only 5.7% over the two program years, but the acquisition cost of intravenous antimicrobials for both program years yielded a total cost saving of $291,885, a reduction of 30.8%. The institution's average daily census fell 19% between the second baseline year and the second program year. An ACP directed by a clinical pharmacist trained in infectious diseases was associated with improvements in inpatient length of stay and mortality. The ACP decreased intravenous antimicrobial costs and facilitated the approval process for restricted and nonformulary antimicrobial agents.

After-School Program Engagement: Links to Child Competence and Program Quality and Content

ERIC Educational Resources Information Center

Mahoney, Joseph L; Parente, Maria E.; Lord, Heather

2007-01-01

This 2-year study assessed program-level differences in after-school program (ASP) engagement in relation to child competencies (effectance motivation, social competence, school grades) and program quality and content. Participants were 141 children (M age = 8.4 years) who attended 9 ASPs in an urban, disadvantaged city in the United States.…

76 FR 49458 - TRICARE, Formerly Known as the Civilian Health and Medical Program of the Uniformed Services...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-10

... Medical Program of the Uniformed Services (CHAMPUS); Fiscal Year 2012 Continued Health Care Benefit... Health Care Benefit Program premiums for Fiscal Year 2012. CHCBP is a premium-based health care program...) set forth rules to implement the Continued Health Care Benefit Program (CHCBP) required by 10 United...

Foreign Currency Requirements Automated Data System,

DTIC Science & Technology

1984-12-07

undated (Contract Number MDA903-84-C-0117, Item Nos. 0002AD and 0002AJ). dd. "Tape Submissions Requirements for Fiscal Year 󈨚 Budget Exhibits," OSD...fuel each fiscal year within each appropriation. OP-30 0030 Categories of Units/Costs (Financed and Maintenance Unfinanced) OP-32 0032 Line Codes...Program Cost/Foreign Currency- Adjustments/Price Growth/Program Growth/Program Cost next Fiscal year PB-18 0018 Country Code Program Cost/Exhange Rate PB

75 FR 81138 - Medicare Program; Home Health Prospective Payment System Rate Update for Calendar Year 2011...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-27

... [CMS-1510-CN2] RIN 0938-AP88 Medicare Program; Home Health Prospective Payment System Rate Update for Calendar Year 2011; Changes in Certification Requirements for Home Health Agencies and Hospices AGENCY... ``Medicare Program; Home Health Prospective Payment System Rate Update for Calendar Year 2011; Changes in...

Health economic evaluation of an infection prevention and control program: are quality and patient safety programs worth the investment?

PubMed

Raschka, Stefanie; Dempster, Linda; Bryce, Elizabeth

2013-09-01

The effect of regional consolidation of an infection prevention and control (IPC) program on reduction of selected health care-acquired infections (HAIs), the economic burden of these illnesses, and where the potential for greatest financial benefit in reducing infection rates lies was assessed. Cost-benefit analysis (in Canadian $) was used to evaluate the effectiveness of a regional IPC program in preventing incident cases of HAIs. The costs of managing these infections, as well as the operational costs of the IPC program were compared against reductions in HAI rates over a 4-year period. Benefits were calculated as cost avoided by reducing HAI cases year over year. The Health Authority spent more than $66.3 million managing 24,937 HAI cases over the 4-year evaluation period. Urinary tract infections, methicillin-resistant Staphylococcus aureus, and bacteremias incurred the greatest costs. A reduction of 4,739 HAI cases led to avoided costs of $9.1 million in 4 years; the IPC program budget was $6.7 million during this period. Regionalization of the IPC program with standardized policies, procedures, and initiatives led to a 19% reduction in selected HAIs over 4 years and a cost avoidance of at least $9 million. This was particularly evident in years 3 and 4 of the program when $7.2 million (79% of the total) savings were realized. Copyright © 2013 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

Enhancing youth outcomes following parental divorce: a longitudinal study of the effects of the new beginnings program on educational and occupational goals.

PubMed

Sigal, Amanda B; Wolchik, Sharlene A; Tein, Jenn-Yun; Sandler, Irwin N

2012-01-01

This study examined whether the New Beginnings Program for divorced families led to improvements in youth's educational goals and job aspirations 6 years following participation and tested whether several parenting and youth variables mediated the program effects. Participants were 240 youth aged 9 to 12 years at the initial assessment, and data were part of a randomized, experimental trial of a parenting skills preventive intervention targeting children's postdivorce adjustment. The results revealed positive effects of the program on youth's educational goals and job aspirations 6 years after participation for those who were at high risk for developing later problems at program entry. Further, intervention-induced changes in mother-child relationship quality and youth externalizing problems, internalizing problems, self-esteem, and academic competence at the 6-year follow-up mediated the effects of the program on the educational expectations of high-risk youth. Intervention-induced changes in youth externalizing problems and academic competence at the 6-year follow-up mediated the effects of the program on the job aspirations of high-risk youth.

ASBO's Certificate of Excellence in Financial Reporting by School Systems.

ERIC Educational Resources Information Center

Gatti, Bernard F.

1989-01-01

The Certificate of Excellence in Financial Reporting by Schools Program reached a high of 180 submissions for program year 1989. Describes technical developments, including a 90-minute videotape about the program, highlights of the previous year, and a summary of certain program specifics. (MLF)

Putting It All Together: A Minority Transition Program.

ERIC Educational Resources Information Center

Sacramento City Coll., CA.

Sacramento City College (SCC) created a transfer opportunity program to implement joint activities with four-year colleges and high schools, establish an academic skills program for potential minority transfers, improve telecommunications with local four-year institutions, expand its existing junior high school program. and continue its formalized…

A pilot demonstration project of technology application from the aerospace industry to city management (four cities program)

NASA Technical Reports Server (NTRS)

Ervin, G. F.; Blomeyer, L. S.

1972-01-01

The Four Cities Program has completed the first year of the planned two-year program. At the beginning of the first year, a variety of program initiation activities were accomplished. Contracts were negotiated; science and technology advisors were interviewed, selected and assigned; general indoctrination and integration of the advisors into city affairs occurred; technical needs were identified and related projects pursued; pilot projects for the second year were identified; inter-city coordination on technical problems began to emerge; and the general soundness of the four cities program seems to have been established. Above all, the inter-personal relationships between the advisors and their interfaces in city government appear to be functioning smoothly. The establishment of such mutual respect, trusts, and confidences are believed essential to the success of the program.

45 CFR 2521.60 - To what extent must my share of program costs increase over time?

Code of Federal Regulations, 2010 CFR

2010-10-01

...(percent) Year 7(percent) Year 8(percent) Year 9(percent) Year 10(percent) Minimum member support 15 15 15...(percent) Year 6(percent) Year 7(percent) Year 8(percent) Year 9(percent) Year 10(percent) Minimum member... 45 Public Welfare 4 2010-10-01 2010-10-01 false To what extent must my share of program costs...

45 CFR 2521.60 - To what extent must my share of program costs increase over time?

Code of Federal Regulations, 2011 CFR

2011-10-01

...(percent) Year 7(percent) Year 8(percent) Year 9(percent) Year 10(percent) Minimum member support 15 15 15...(percent) Year 6(percent) Year 7(percent) Year 8(percent) Year 9(percent) Year 10(percent) Minimum member... 45 Public Welfare 4 2011-10-01 2011-10-01 false To what extent must my share of program costs...

76 FR 7881 - Discount Rates for Cost-Effectiveness Analysis of Federal Programs

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-11

... and Bonds of Specified Maturities (in percent) 3-Year 5-Year 7-Year 10-Year 20-Year 30-Year 1.4 1.9 2...-Year 5-Year 7-Year 10-Year 20-Year 30-Year 0.0 0.4 0.8 1.3 2.1 2.3 Analyses of programs with terms... longer than 30 years may use the 30-year interest rate. [FR Doc. 2011-3044 Filed 2-10-11; 8:45 am...

The Effects of the Home Instruction Program for Preschool Youngsters (HIPPY) on Children's School Performance at the End of the Program and One Year Later.

ERIC Educational Resources Information Center

Baker, Amy J. L.; Piotrkowski, Chaya S.; Brooks-Gunn, Jeanne

1998-01-01

Evaluated whether participation in HIPPY (Home Instruction Program for Preschool Youngsters) has a positive impact on young children's performance in school. Assessed 182 children at baseline, the program's end, and one year later. Interpreted findings as mixed support for the effectiveness of the HIPPY program. (JS)

Mental Health Associate Program T-056: A Program Review, Spring 1991.

ERIC Educational Resources Information Center

Lenoir Community Coll., Kinston, NC.

At Lenoir Community College (LCC) in Kinston, North Carolina, 20% of established programs and 33% of the non-academic support services are reviewed each year in an annual cycle, with all programs reviewed within a 5-year period. To evaluate the Mental Health Associate (MHA) Program at LCC, assessment surveys were sent to 44 graduates from the…

YRE Program Guide.

ERIC Educational Resources Information Center

California State Dept. of Education, Sacramento. Div. of School Facilities Planning.

This report examines single- and multi-track educational programs as found in California's public school system, explores the pros and cons of using year-round education (YRE) programs, and how to implement these programs. Each year-round tracking system is detailed using each of their calendars in a side-by-side comparison along with the…

The State of Enrollment Management in Journalism and Mass Communication Programs.

ERIC Educational Resources Information Center

Rawlins, Brad L.; Soenksen, Roger; Jensen, Matt

Some programs in journalism and mass communication have been forced to incorporate limited enrollment strategies, as undergraduate interest in these programs continues to grow. After 4 years of moderate growth, undergraduate enrollments in journalism and mass communication programs increased dramatically in the year 2000. Some of the limited…

78 FR 7387 - Continuation of Farm Service Agency 2008 Farm Bill Programs

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-01

..., Conservation, and Energy Act of 2008 (the 2008 Farm Bill) through the 2013 crop year, fiscal year (FY), or... conservation programs administered by the Farm Service Agency (FSA). This notice provides information about... eligibility requirements, commodity programs, and conservation programs previously authorized or amended in...

Students Talking about Assessment: Insights on Program Learning Outcomes

ERIC Educational Resources Information Center

Donohue, William J.

2017-01-01

This study examines the student writer perspective of a first-year composition program's student learning outcomes. Student descriptions of learning are a valuable, yet often overlooked data source. The student voice broadens a first-year composition program's outcomes-based, student learning assessment process as program assessment data is often…

THE SUPERFUND INNOVATIVE TECHNOLOGY EVALUATION PROGRAM: PROGRESS AND ACCOMPLISHMENTS - FISCAL YEAR 1990 A FOURTH REPORT TO CONGRESS

EPA Science Inventory

The SITE Program was the first major program for demonstrating and evaluating fullscale innovative treatment technologies at hazardous waste sites. Having concluded its fourth year, the SITE Program is recognized as a leading advocate of innovative technology development and comm...

School-Home-Community Services for 3-5 Year Old Hearing Impaired Children.

ERIC Educational Resources Information Center

Texarkana School District 7, AR.

The final report discusses achievements of a 3 year program for hearing impaired preschoolers. The following topics are addressed in the report: program objectives (involving the community, improving student skills, and training parents); program variables (personnel, process of conducting program activities, and student behavioral changes); the…

NIDRR Program Directory, Fiscal Year 1998.

ERIC Educational Resources Information Center

National Inst. on Disability and Rehabilitation Research (ED/OSERS), Washington, DC.

This directory lists all projects funded by the National Institute of Disability and Rehabilitation Research (NIDRR) during the 1998 fiscal year. It includes summaries, funding data, and contact information for a broad range of programs. An introduction discusses the mission of NIDRR and provides an overview of its research program. Programs are…

Four-Year Results of a Youth Smoking Prevention Program Using Assertiveness Training.

ERIC Educational Resources Information Center

Del Greco, Linda; And Others

1986-01-01

Seventh graders (N=161) participated in health education classes consisting of either an innovative smoking education program, the program plus assertiveness training, or a traditional smoking education program. Data collected four years later revealed no significant differences in smoking behavior, changes in assertion, or sex differences among…

77 FR 57074 - Indirect Cost Rates for the Damage Assessment, Remediation, and Restoration Program for Fiscal...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-17

... Damage Assessment, Remediation, and Restoration Program for Fiscal Year 2011 AGENCY: National Oceanic and..., Remediation, and Restoration Program for Fiscal Year 2011. SUMMARY: The National Oceanic and Atmospheric Administration's (NOAA's) Damage Assessment, Remediation, and Restoration Program (DARRP) is announcing new...

Significant Reduction in the Incidence of Genital Warts in Young Men 5 Years into the Danish Human Papillomavirus Vaccination Program for Girls and Women.

PubMed

Bollerup, Signe; Baldur-Felskov, Birgitte; Blomberg, Maria; Baandrup, Louise; Dehlendorff, Christian; Kjaer, Susanne K

2016-04-01

Denmark introduced the quadrivalent human papillomavirus vaccine into the vaccination program for 12- to 15-year-old girls in 2008 to 2009. In 2012, the program was supplemented with a catch-up program for women aged up to 27 years. We evaluated the effectiveness of the Danish vaccination program on the nationwide incidence of genital warts (GWs), after the second catch-up by including information on both hospital treatments and on self-administered treatment with podophyllotoxin. Genital wart incidence was investigated in both sexes; however, the main focus was on potential herd protection of men. Incident cases of GWs were identified from the Danish National Patient Register and through redemptions of prescription for podophyllotoxin in the Danish National Prescription Registry in 2006 to 2013. Age-specific incidence rates (IRs) were assessed, and estimated annual percentage change (EAPC) was calculated by Poisson regression. Genital wart incidence was either stable or increased in both sexes in 2006 to 2008. After introduction of the vaccination program, GW incidence decreased significantly in women aged 12 to 35 years and men aged 12 to 29 years, with rapid decrease among 16- to 17-year-olds (IRwomen, from 1071 to 58 per 100,000 person-years [EAPC, -55.1%; 95% confidence interval, -58.7 to-51.2]; IRmen, from 365 to 77 per 100,000 person-years [EAPC, -36.6%; 95% confidence interval, -40.5 to -32.5] in 2008-2013). We found a significantly decreasing incidence of GWs in women up to 35 years of age after the start of the human papillomavirus vaccination program. A similar pattern was observed for men aged 12 to 29 years, indicating substantial herd protection.

NASA Celebrates the World Year of Physics

NASA Technical Reports Server (NTRS)

Adams, M. L.

2005-01-01

Celebrating the World Year of Physics presents NASA with an opportunity to inform educators of the importance of physics in our everyday lives. indeed, almost all NASA programs fake advantage of physical concepts in some fashion. Special programs throughout the year, affiliated with the World Year of Physics, are identifed to inform and inspire educators, students, and the general public. We will discuss these programs in detail and outline how educators may become more involved.

76 FR 9786 - NIOSH Dose Reconstruction Program Ten-Year Review-Phase I Report on Customer Service; Request for...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-22

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention NIOSH Dose Reconstruction Program Ten-Year Review--Phase I Report on Customer Service; Request for Public Review and Comment... requests public review and comment on the draft publication, ``NIOSH Dose Reconstruction Program Ten-Year...

Child Nutrition Program Operations Study: First Year Report Executive Summary.

ERIC Educational Resources Information Center

St. Pierre, Robert; And Others

Summarizing the first year report of a multi-year study of the Food and Nutrition Service's (Department of Agriculture) Child Nutrition Programs, this report describes the programs and methods of the study. Data were collected through telephone interviews with states and School Food Authorities (SFAs) between 1987 and 1992. Findings from 1987-1988…

Navigating Uncharted Waters: Study Abroad Predeparture Activities and the 2-Year-College Student

ERIC Educational Resources Information Center

Woods, Angie L.; Sipple, Susan M.; Otten, Mark R. M.; Roos, Michael E.

2017-01-01

Study abroad programs typically reveal issues that are not commonly found in classes on the home campus. At University of Cincinnati Blue Ash College (UCBA), a 2-year regional campus of University of Cincinnati, we offer three short-term summer study abroad programs each year. Students in these programs have traditionally participated in social…

34 CFR 691.16 - Rigorous secondary school program of study.

Code of Federal Regulations, 2011 CFR

2011-07-01

...: biology, chemistry, and physics. (iv) Three years of social studies. (v) One year of a language other than... 34 Education 4 2011-07-01 2011-07-01 false Rigorous secondary school program of study. 691.16... Procedures § 691.16 Rigorous secondary school program of study. (a)(1) For each award year commencing with...

34 CFR 691.16 - Rigorous secondary school program of study.

Code of Federal Regulations, 2013 CFR

2013-07-01

...: biology, chemistry, and physics. (iv) Three years of social studies. (v) One year of a language other than... 34 Education 4 2013-07-01 2013-07-01 false Rigorous secondary school program of study. 691.16... Procedures § 691.16 Rigorous secondary school program of study. (a)(1) For each award year commencing with...

34 CFR 691.16 - Rigorous secondary school program of study.

Code of Federal Regulations, 2014 CFR

2014-07-01

...: biology, chemistry, and physics. (iv) Three years of social studies. (v) One year of a language other than... 34 Education 4 2014-07-01 2014-07-01 false Rigorous secondary school program of study. 691.16... Procedures § 691.16 Rigorous secondary school program of study. (a)(1) For each award year commencing with...

34 CFR 691.16 - Rigorous secondary school program of study.

Code of Federal Regulations, 2012 CFR

2012-07-01

...: biology, chemistry, and physics. (iv) Three years of social studies. (v) One year of a language other than... 34 Education 4 2012-07-01 2012-07-01 false Rigorous secondary school program of study. 691.16... Procedures § 691.16 Rigorous secondary school program of study. (a)(1) For each award year commencing with...

Prospects and Problems of the Year-Round School in Contemporary American Education: A Sociological Examination.

ERIC Educational Resources Information Center

Ibsen, C. A.

A number of school divisions have entered year-round education without fully realizing the effects of such a program on the family and the community. Family vacations, child care, and routine living are disrupted by year-round educational programs. Community recreational facilities, church activities, public service programs, police work, and…

Effects of an Affective-Social Education Program Over Two Years.

ERIC Educational Resources Information Center

Stilwell, William E.; Barclay, James R.

This report describes the effects of a 2-year affective-social education program offered by the elementary guidance services of the Stuttgart School District in Arkansas. Four groups of children (a total of 105 boys and 116 girls) were identified for this evaluation: Group I, involved in the program for two full years; Group II, participating one…

Impact of California's Transitional Kindergarten Program, 2013-14

ERIC Educational Resources Information Center

Manship, Karen; Quick, Heather; Holod, Aleksandra; Mills, Nicholas; Ogut, Burhan; Chernoff, Jodi Jacobson; Blum, Jarah; Hauser, Alison; Anthony, Jennifer; González, Raquel

2015-01-01

Transitional kindergarten--the first year of a two-year kindergarten program for California children born between September 2 and December 2--is intended to better prepare young five-year-olds for kindergarten and ensure a strong start to their educational career. The goal of this study was to measure the success of the program by determining the…

Great Careers in Two Years: The Associate Degree Option. High Skill and High Wage Jobs Available through Two-Year Programs.

ERIC Educational Resources Information Center

Phifer, Paul

This book explores high-skill and high-wage jobs available through two-year programs. It identifies 100 high-need occupational areas, and discusses "hot" programs and starting salaries for graduates of dental hygiene, manufacturing, process technology, telecommunications, physical therapy assisting, and registered nursing. Each career article…

Accelerating Literacy Program: The First Year 1993-94.

ERIC Educational Resources Information Center

Smith, Ralph J.

The 1993-94 school year was the first year of the Accelerating Literacy Program (ALP) of the Austin (Texas) Independent School District. The ALP used a grant from the Texas Education Agency to train elementary educators in the methods of a short-term reading intervention program based on the Reading Recovery/Whole Language theory. A group of 367…

Michigan Extended School Year Programs 1992-1995. An Evaluation of a State Grant Initiative.

ERIC Educational Resources Information Center

Axelrad-Lentz, Susan F.

Michigan lawmakers funded a competitive grant program for school districts to plan and implement extended school year (ESY) programs of 200 days. The primary purpose was to raise academic achievement. In the spring of 1992, 16 diverse school districts were awarded ESY planning grants. Continuation grants funded 2 ESY implementation years, for…

FTA multi-year research program plan (FY 2009 - FY 2013).

DOT National Transportation Integrated Search

2008-09-01

The Multi-Year Research Program Plan (Program Plan), prepared by the Federal Transit Administrations (FTA) Office of : Research, Demonstration, and Innovation (TRI), is part of FTAs strategic planning process. It provides descriptive : summarie...

World weather program: Plan for fiscal year 1972

NASA Technical Reports Server (NTRS)

1971-01-01

The World Weather Program which is composed of the World Weather Watch, the Global Atmospheric Research Program, and the Systems Design and Technological Development Program is presented. The U.S. effort for improving the national weather services through advances in science, technology and expanded international cooperation during FY 72 are described. The activities of the global Atmospheric Research Program for last year are highlighted and fiscal summary of U.S. programs is included.

Development and evaluation of the evidence-based medicine program in surgery: a spiral approach

PubMed Central

Elçin, Melih; Turan, Sevgi; Odabaşı, Orhan; Sayek, İskender

2014-01-01

Background Evidence-based medicine (EBM) aims to provide skills that help physicians answer clinically important questions, determine new evidence, and incorporate the acquired knowledge in practice. EBM skills are necessary for the practice of modern medicine, since physicians should use up-to-date knowledge and information to justify their medical decisions. Purpose We aimed to evaluate the EBM program implemented at Hacettepe University School of Medicine. Methods In 2004, a spiral program for the teaching and practice of EBM was developed for the first 3 years of medical school. Following this program, a practice of EBM was included in the fourth year during the surgery clerkship, after an introductory lecture. The students worked within collaborative teams of 3–5 and practiced EBM with actual cases seen in the surgical service in which they were involved. Each student was asked to complete a questionnaire that evaluated the more theoretical program from the first 3 years and the practical application in the fourth year. Results Nearly half of the students stated that the preclinical years of the EBM program were ‘adequate’, but only 30% of the students indicated that the program was practical. They stated that ‘more practical approaches were used in the fourth year, whereas more theory-based approaches were used during the preclinical years’. More than 75% of the students declared that the practice of EBM in the fourth year was useful and appropriate for team-based learning. Conclusions The EBM program was evaluated as ‘adequate’. EBM courses should be included in the entire curriculum in an integrated manner. The students understand the main philosophy of EBM in the clinical year when involved in its practical application with actual patients. PMID:24767706

Evaluating the implementation of a multicomponent asthma education program for Head Start staff.

PubMed

Ruvalcaba, Elizabeth; Chung, Shang-En; Rand, Cynthia; Riekert, Kristin A; Eakin, Michelle

2018-03-15

Asthma disproportionately affects minority groups, low income populations, and young children under 5. Head Start (HS) programs predominantly serve this high-risk population, yet staff are not trained on asthma management. The objective of this study was to assess a 5-year, multicomponent HS staff asthma education program in Baltimore City HS programs. All HS programs were offered annual staff asthma education by a medical research team that included didactic lectures and hands-on training. Attendees received continuing education credits. HS staff were anonymously surveyed on asthma knowledge and skills and asthma medication management practices in Year 1 (preimplementation) and Year 5. There was an estimated response rate of 94% for Year 1 and 82% for Year 5. Compared to staff in Year 1, Year 5 staff were significantly more likely to report they had very good knowledge and skills related to asthma [odds ratio (OR) 1.63; p < 0.05] and were engaged in asthma care activities (OR 2.02; p < 0.05). Self-reported presence of asthma action plans for all children with asthma was 82% at Year 1 and increased to 89% in Year 5 (p = 0.064). Year 5 HS staff reported higher self-assessed knowledge and skills, self-reports of asthma medication management practices, and self-reports of asthma activities compared to Year 1 staff. HS serves high-risk children with asthma, and a multicomponent program can adequately prepare staff to manage asthma in the child care setting. Our results indicate the feasibility of providing efficacious health skill education into child care provider training to reduce asthma knowledge gaps.

A Two-Year Multidisciplinary Training Program for the Frontline Workforce in Community Treatment of Severe Mental Illness.

PubMed

Ruud, Torleif; Flage, Karin Blix; Kolbjørnsrud, Ole-Bjørn; Haugen, Gunnar Brox; Sørlie, Tore

2016-01-01

Since 1999, a national two-year multidisciplinary onsite training program has been in operation in Norway. The program trains frontline workforce personnel who provide community treatment to people with severe mental illness. A national network of mental health workers, consumers, caregivers, and others providing or supporting psychosocial treatment and rehabilitation for people with severe mental illness has organized local onsite part-time training programs in collaboration with community mental health centers (CMHCs), municipalities, and primary care providers. CMHC and primary care staff are trained together to increase collaboration. Nationwide dissemination has continued, with new local programs established every year. Evaluations have shown that the program is successful.

The International Heliophysical Year

NASA Technical Reports Server (NTRS)

Thompson, Barbara J.

2007-01-01

In 1957 a program of international research, inspired by the International Polar Years of 1882 and 1932, was organized as the International Geophysical Year (IGY) to study global phenomena of the Earth and geospace. Fifty years later, the world s space science community will again come together for international programs of scientific collaboration: the International Heliophysical Year (IHY), the Electronic Geophysical Year (eGY), and the International Polar Year (IPY) 2007. This time, research will extend out into the Heliosphere to focus on solar-terrestrial-planetary interactions. The ambitious plans for the IHY, eGY and IPY incorporate the activities of scientists in 191 nations, as well as the IGY Gold Historical Preservation initiative, plus a series of coordinated campaigns involving more than 100 instruments and models, education and public outreach programs, a developing nations instrument development program, and opportunities for supported research worldwide. The presentation will focus on the efforts and operations which will make these activities possible.

A Summer Math and Physics Program for High School Students: Student Performance and Lessons Learned in the Second Year

NASA Astrophysics Data System (ADS)

Timme, Nicholas; Baird, Michael; Bennett, Jake; Fry, Jason; Garrison, Lance; Maltese, Adam

2013-05-01

For the past two years, the Foundations in Physics and Mathematics (FPM) summer program has been held at Indiana University in order to fulfill two goals: provide additional physics and mathematics instruction at the high school level, and provide physics graduate students with experience and autonomy in designing curricula and teaching courses. In this paper we will detail changes made to the program for its second year and the motivation for these changes, as well as implications for future iterations of the program. We gauge the impact of the changes on student performance using pre-/post-test scores, student evaluations, and anecdotal evidence. These data show that the program has a positive impact on student knowledge and this impact was greater in magnitude in the second year of the program. We attribute this improvement primarily to the inclusion of more inquiry-driven activities. All activities, worksheets, and lesson plans used in the program are available online.

Development of an Applied Fisheries Science Program for Native Alaskans at Sheldon Jackson College. Sixth Progress Report.

ERIC Educational Resources Information Center

Seifert, Mel

The sixth semi-annual report of the Sheldon Jackson College Aquaculture Program covers the period January 1 through June 30, 1977, and summarizes the last half of the second year of operation of the educational program and the entire year for the hatchery. The educational component of the program is described in terms of the academic program,…

40 CFR 35.688 - Award limitations.

Code of Federal Regulations, 2010 CFR

2010-07-01

... protection program or agrees to establish an approvable program within four years of the initial award. (b... within the four-year period after initial award. After the four-year period expires, the Regional...

Library Programs. Library Programs for the Handicapped. Fiscal Year 1987.

ERIC Educational Resources Information Center

Neff, Evaline B.

One in a series of published reports on selected Library Services and Construction Act (LSCA) program areas, this report presents the record of accomplishments in library services to the disabled during fiscal year 1987 nationwide, including programs in Guam, the Virgin Islands, and Puerto Rico. The typical services reported include the recordings…

Louisiana Standards for Programs Serving Four-Year-Old Children: Bulletin.

ERIC Educational Resources Information Center

Picard, Cecil J.

As part of Louisiana's efforts to expand and improve the quality of its early childhood programs, a committee of educators from across the state collaborated to develop standards for programs serving 4-year-olds. This guide presents program standards to assist the ongoing development, evaluation, and improvement of early childhood center-based…

34 CFR 645.6 - What definitions apply to the Upward Bound Program?

Code of Federal Regulations, 2012 CFR

2012-07-01

..., chemistry, and physics. (iv) Three years of social studies. (v) One year of a language other than English... by the individual's State. Rigorous secondary school program of study means a program of study that... recognized as a rigorous secondary school program of study by the Secretary through the process described in...

34 CFR 645.6 - What definitions apply to the Upward Bound Program?

Code of Federal Regulations, 2014 CFR

2014-07-01

..., chemistry, and physics. (iv) Three years of social studies. (v) One year of a language other than English... by the individual's State. Rigorous secondary school program of study means a program of study that... recognized as a rigorous secondary school program of study by the Secretary through the process described in...

34 CFR 645.6 - What definitions apply to the Upward Bound Program?

Code of Federal Regulations, 2013 CFR

2013-07-01

..., chemistry, and physics. (iv) Three years of social studies. (v) One year of a language other than English... by the individual's State. Rigorous secondary school program of study means a program of study that... recognized as a rigorous secondary school program of study by the Secretary through the process described in...

34 CFR 645.6 - What definitions apply to the Upward Bound Program?

Code of Federal Regulations, 2011 CFR

2011-07-01

..., chemistry, and physics. (iv) Three years of social studies. (v) One year of a language other than English... by the individual's State. Rigorous secondary school program of study means a program of study that... recognized as a rigorous secondary school program of study by the Secretary through the process described in...

Program-Wide Positive Behavioral Interventions and Supports in Rural Preschools

ERIC Educational Resources Information Center

Steed, Elizabeth A.; Pomerleau, Tina; Muscott, Howard; Rohde, Leigh

2013-01-01

This article describes the quantitative findings from an evaluation of program-wide positive behavioral interventions and supports (PBIS) in three rural preschool programs. Each rural preschool program included children 3 through 5 years of age with and without disabilities. Following 3 years of on-site training, technical assistance, and coaching…

Memphis State University's New Five-year Program For the Initial Preparation of Teachers.

ERIC Educational Resources Information Center

Saunders, Robert L.

A description is presented of a new extended teacher education program at Memphis State University. Instituted in 1985, the program has four objectives: (1) to develop and implement an extended (five-year) program covering all areas of teacher preparation, with institutional recommendation for certification coming only after completion of the…

77 FR 3788 - Announcement of Funding Awards for the Assisted Living Conversion Program; Fiscal Year 2010

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-25

... Awards for the Assisted Living Conversion Program; Fiscal Year 2010 AGENCY: Office of the Assistant... competition for funding under the Notice of Funding Availability (NOFA) for the Assisted Living Conversion... Assistance number for this program is 14.314. The Assisted Living Conversion Program is designed to provide...

The Induction Program--Teachers' Experience after Five Years of Practice

ERIC Educational Resources Information Center

Eisenschmidt, Eve; Oder, Tuuli; Reiska, Epp

2013-01-01

The induction program to provide support for novice teachers was introduced into teacher education in Estonia in 2004. The teachers who participated in the first program have now been working for several years. To evaluate the effectiveness of induction activities, we explored how mentoring and an induction program influence teachers' opinions…

77 FR 58359 - TRICARE, Formerly Known as the Civilian Health and Medical Program of the Uniformed Services...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-20

... Medical Program of the Uniformed Services; Calendar Year 2013 TRICARE Young Adult Program Premium Update... Young Adult Premiums for Calendar Year 2013. SUMMARY: This notice provides the updated TRICARE Young... to implement the TRICARE Young Adult (TYA) program as required by Title 10, United States Code...

77 FR 56631 - TRICARE, Formerly Known as the Civilian Health and Medical Program of the Uniformed Services...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-13

... Medical Program of the Uniformed Services; Fiscal Year 2013 Continued Health Care Benefit Program Premium Update AGENCY: Office of the Secretary, DoD. ACTION: Notice of updated continued health care benefit program premiums for fiscal year 2013. SUMMARY: This notice provides the updated Continued Health Care...

Evaluation of Progress, Bilingual Mini-Head Start, November 1973.

ERIC Educational Resources Information Center

McConnell, Beverly

A 5-year experimental project, the Bilingual Mini Head Start program is an early education program for children of migrant farm workers. The program has 2 components: the mobile and the stationary components. In the stationary program, 2 year-round centers are operated in Connell and Moses Lake (Washington). These centers' purpose is to…

University Reaches Out--Programs Bring Education to Communities.

ERIC Educational Resources Information Center

Grant, Agnes

Brandon University's teacher education programs address the need to train Native people to teach in Indian schools. A mature entry policy allows students to enter the university without a high school diploma, provided they are at least 21 years old. Several programs lead to four-year Bachelor of Education degrees. Through the Program for Educating…

34 CFR 403.30 - What documents must a State submit to receive a grant?

Code of Federal Regulations, 2010 CFR

2010-07-01

...) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION STATE VOCATIONAL AND APPLIED TECHNOLOGY... Technology Education Program on the basis of program years that coincide with program years under section 104... Technology Education Program. (Approved by the Office of Management and Budget under Control No. 1830-0029...

A 5-year evaluation of a smoking cessation incentive program for chemical employees.

PubMed

Olsen, G W; Lacy, S E; Sprafka, J M; Arceneaux, T G; Potts, T A; Kravat, B A; Gondek, M R; Bond, G G

1991-11-01

This 5-year study of the Dow Chemical Texas Operations 1984-1985 Smoking Cessation Incentive Program (SCIP) evaluated the smoking habits of 1,097 participants and 1,174 nonparticipants. We observed, via questionnaire and saliva cotinine data, that participants were 2.3 times more likely to be long-term (greater than or equal to 5 years) nonusers of tobacco than nonparticipants (10.2% vs 4.4%, P less than or equal to 0.01). However, smoking cessation rates for 3-4 years, 1-2 years, and less than 1 year were similar for participants who remained smokers at the conclusion of SCIP and nonparticipants. Age and the interaction between the management job category and having quit smoking for at least 30 days sometime prior to the worksite program were important predictors of smoking cessation among participants. Thirty-six percent of the participants who were considered exsmokers of 6 months duration at the conclusion of the program in 1985 remained long-term quitters 5 years later. Stress and enjoyment of smoking were the two most important reasons provided by participants for recidivism. The results of this 5-year evaluation demonstrate the heterogeneity of employee participation and success with a worksite smoking cessation program.

Differences of Cutaneous Two-Point Discrimination Thresholds Among Students in Different Years of a Chiropractic Program.

PubMed

Dane, Andrew B; Teh, Elaine; Reckelhoff, Kenneth E; Ying, Pee Kui

2017-09-01

The aim of this study was to investigate if there were differences in the two-point discrimination (2-PD) of fingers among students at different stages of a chiropractic program. This study measured 2-PD thresholds for the dominant and nondominant index finger and dominant and nondominant forearm in groups of students in a 4-year chiropractic program at the International Medical University in Kuala Lumpur, Malaysia. Measurements were made using digital calipers mounted on a modified weighing scale. Group comparisons were made among students for each year of the program (years 1, 2, 3, and 4). Analysis of the 2-PD threshold for differences among the year groups was performed with analysis of variance. The mean 2-PD threshold of the index finger was higher in the students who were in the higher year groups. Dominant-hand mean values for year 1 were 2.93 ± 0.04 mm and 1.69 ± 0.02 mm in year 4. There were significant differences at finger sites (P < .05) among all year groups compared with year 1. There were no significant differences measured at the dominant forearm between any year groups (P = .08). The nondominant fingers of the year groups 1, 2, and 4 showed better 2-PD compared with the dominant finger. There was a significant difference (P = .005) between the nondominant (1.93 ± 1.15) and dominant (2.27 ± 1.14) fingers when all groups were combined (n = 104). The results of this study demonstrated that the finger 2-PD of the chiropractic students later in the program was more precise than that of students in the earlier program. Copyright © 2017. Published by Elsevier Inc.

Prevalence-Based Targets Underestimate Home Dialysis Program Activity and Requirements for Growth.

PubMed

Bevilacqua, Micheli U; Er, Lee; Copland, Michael A; Singh, R Suneet; Jamal, Abeed; Dunne, Órla Marie; Brumby, Catherine; Levin, Adeera

2018-01-01

Many renal programs have targets to increase home dialysis prevalence. Data from a large Canadian home dialysis program were analyzed to determine if home dialysis prevalence accurately reflects program activity and whether prevalence-based assessments adequately reflect the work required for program growth. Data from home dialysis programs in British Columbia, Canada, were analyzed from 2005 to 2015. Prevalence data were compared to dialysis activity data including intakes and exits to describe program turnover. Using current attrition rates, recruitment rates needed to increase home dialysis prevalence proportions were identified. We analyzed 7,746 patient-years of peritoneal dialysis (PD) and 1,362 patient-years of home hemodialysis (HHD). The proportion of patients on home dialysis increased by 3.34% over the ten years examined, while the number of prevalent home dialysis patients increased 2.65% per year and the number of patients receiving home dialysis at any time in the year increased 4.04% per year. For every 1 patient net home dialysis growth, 13.6 new patients were recruited. Patient turnover included higher rates of transplantation in home dialysis than facility-based HD. Overall, the proportion dialyzing at home increased from 29.3 to 32.6%. There is high patient turnover in home dialysis such that program prevalence is an incomplete marker of total program activity. This turnover includes high rates of transplantation, which is a desirable interaction that affects home dialysis prevalence. The shortcomings of this commonly used metric are important for renal programs to consider, and better understanding of the activities that support home dialysis and the complex trajectories that home dialysis patients follow is needed. Copyright © 2018 International Society for Peritoneal Dialysis.

Effects of the Family Bereavement Program on Academic Outcomes, Educational Expectations and Job Aspirations 6 Years Later: The Mediating Role of Parenting and Youth Mental Health Problems

PubMed Central

Schoenfelder, Erin N.; Tein, Jenn-Yun; Wolchik, Sharlene; Sandler, Irwin N.

2014-01-01

Experiencing the death of a parent during childhood is associated with a variety of difficulties, including lower academic achievement, that have implications for functioning in childhood and adulthood. This study examines effects of the Family Bereavement Program (FBP), a preventive intervention for parentally-bereaved youth and their caregivers, on grade point averages (GPA), educational expectations and job aspirations of youths 6 years after the intervention. A total of 244 bereaved youths ages 8-16 and their caregivers were randomized to either the FBP or a comparison group that received books about bereavement. Assessments occurred at pretest, post-test, and 11-month and 6-year follow-ups. Direct program effects on educational outcomes and job aspirations 6 years later were non-significant, although the program improved educational expectations for children with fewer behavior problems at program entry, and GPA for younger children. Mediational pathways for program effects on educational outcomes were also tested. Program-induced improvements in effective parenting at 11-month follow-up were associated with higher GPAs at 6-year follow-up for youth who were younger or for whom more time had passed since the loss. Program-induced improvements in parenting and teacher-rated youth mental health problems at the 6-year follow-up mediated program effects on youths’ educational expectations for those with fewer behavior problems at program entry. The implications of these findings for understanding processes related to academic and educational outcomes following the death of a parent and for prevention efforts to help bereaved and other high-risk children succeed in school are discussed. PMID:25052624

In China, Thinking like an American Lawyer

ERIC Educational Resources Information Center

Blumenstyk, Goldie

2009-01-01

Temple University's program with Tsinghua University, now in its 10th year, is the oldest of its kind in China. It may take years to understand how a program that trains a few dozen legal professionals a year may affect the legal rights of 1.3 billion Chinese. But there is no question about the benefits that this program has produced for Temple's…

A Research Preparatory Program for First-Year College Students: Student Selection and Preparation Lead to Persistence in Research

ERIC Educational Resources Information Center

Baiduc, Rachael R.; Drane, Denise; Beitel, Greg J.; Flores, Luke C.

2017-01-01

Undergraduate research experiences may increase persistence in STEM majors. We describe a research program that targets first-year students selected for their curiosity and attitudes towards science. We explain the implementation of the program over 3 years and present evaluation data using a group of matched controls. Participants and controls…

Implementing a Year-Long Reading While Listening Program for Japanese University EFL Students

ERIC Educational Resources Information Center

Gobel, Peter; Kano, Makimi

2014-01-01

This paper describes the implementation and evaluation of a year-long reading while listening (RWL) program run for university first-year students at a private university in Japan. The program was developed to give students practice in listening to a large volume of spoken English--a practice that the majority of Japanese students lack. The…

Participation during the First Four Years of Tennessee's Voluntary Prekindergarten Program. Issues & Answers. REL 2011-No. 107

ERIC Educational Resources Information Center

Grehan, Anna; Cavalluzzo, Linda; Gnuschke, John; Hanson, Ryan; Oliver, Simon; Vosters, Kelly

2011-01-01

This study examines the first four years of Tennessee's Voluntary Prekindergarten program, directed to four-year-olds eligible for free or reduced-price lunch. It reviews participation levels and trends for the program as a whole, for collaborative partner classrooms, and for student and district subgroups and discusses the geographic distribution…

Undergraduate Certificate Programs of Less than Two Years: 1991-92. Research Briefs, Volume 6, Number 1, 1995.

ERIC Educational Resources Information Center

Henderson, Cathy

Many higher education institutions serve students enrolled in specialized training courses who receive undergraduate certificates rather than degrees. In academic year 1991-92, almost 65,000 postsecondary students earned certificates for programs of less than 1 year, and nearly 117,000 completed requirements for programs lasting between 1 and 2…

The Prevention of Depression in 8- to 9-Year-Old Children: A Pilot Study

ERIC Educational Resources Information Center

Rooney, Rosanna; Roberts, Clare; Kane, Robert; Pike, Lisbeth; Winsor, Amber; White, Julia; Brown, Annette

2006-01-01

The outcomes of a new universal program aimed at preventing depressive symptoms and disorders in 8- to 9-year-old children are presented. The Positive Thinking Program is a mental health promotion program based on cognitive and behavioural strategies. It is designed to meet the developmental needs of children in the middle primary school Years 4…

An Investigation of the Effectiveness of Four-Year Industrial Technology Programs In Preparing Industrial Electronic Technicians to Meet the Requirements of Industry.

ERIC Educational Resources Information Center

Prewitt, Roger W.

To determine the effectiveness of the 4-year industrial technology programs in preparing industrial electronic technicians for employment in industry, data were obtained through an opinionnaire, which was sent to the higher education institutions offering a 4-year electronic technician program and to selected industrial representatives located in…

Peer Mentor Program for the General Chemistry Laboratory Designed to Improve Undergraduate STEM Retention

ERIC Educational Resources Information Center

Damkaci, Fehmi; Braun, Timothy F.; Gublo, Kristin

2017-01-01

We describe the design and implementation of an undergraduate peer mentor program that can overlay an existing general chemistry laboratory and is designed to improve STEM student retention. For the first four freshman cohorts going through the program, year-to-year retention improved by a four-year average of 20% for students in peer-mentored…

A Review of the Status and Projections for the Dade County Quinmester Extended School Year Program.

ERIC Educational Resources Information Center

Dade County Public Schools, Miami, FL.

This document summarizes the background of the Dade County Quinmester Extended School Year Program involving five high schools in a pilot project. The program resulted from a study of alternative plant utilization plans for the most efficient use of school facilities to reduce the need for capital expenditure during the next five years. Discussed…

Job Corps Annual Report: Program Year July 1, 2005 - June 30, 2006

ERIC Educational Resources Information Center

Job Corps, 2006

2006-01-01

For more than 40 years, Job Corps has led America as one of the most successful job training programs nationwide, meeting the needs of high school graduates and those without a diploma who have the desire to embark on a successful career path. In Program Year 2005, Job Corps implemented a new initiative called STARS (Speakers, Tutors, Achievement,…

Determining the Impact of a Summer Bridge Program on Academic Success for First-Year College Students

ERIC Educational Resources Information Center

Medina, Mary Christine

2016-01-01

The purpose of this study was to determine the impact of a summer bridge program geared toward first-year students at a large public university located in the Southeastern United States. The research question guiding this study was, "Does participation in a summer bridge program increase academic success for first-year college students?"…

Texas Educator Excellence Grant (TEEG) Program: Year Three Evaluation Report. Policy Evaluation Report

ERIC Educational Resources Information Center

Springer, Matthew G.; Lewis, Jessica L.; Podgursky, Michael J.; Ehlert, Mark W.; Gronberg, Timothy J.; Hamilton, Laura S.; Jansen, Dennis W.; Stecher, Brian M.; Taylor, Lori L.; Lopez, Omar S.; Peng, Art

2009-01-01

The Texas Educator Excellence Grant (TEEG) program was state-funded and provided annual grants to schools to design and implement performance pay plans during the 2006-07 to 2009-10 school year. This report builds on the previous TEEG evaluation reports, presenting findings from three years of the TEEG program. Overall, the report discusses the…

Decreasing Heavy Drinking in First-Year Students: Evaluation of a Web-Based Personalized Feedback Program Administered during Orientation

ERIC Educational Resources Information Center

Doumas, Diana M.; Kane, Christina M.; Navarro, Tabitha B.; Roman, Jennifer

2011-01-01

This study evaluated the effectiveness of a web-based personalized normative feedback program, electronic Check-Up to Go (e-CHUG), in decreasing heavy drinking among 1st-year university students. Results indicated high-risk students receiving the e-CHUG program during 1st-year orientation activities reported significantly greater reductions in…

78 FR 65705 - Request for Comments on the Annual Progress Report on the Outer Continental Shelf (OCS) Oil and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-01

... (Five Year Program). The Annual Progress Report is available for review at: www.boem.gov/Five-Year-Program-Annual-Progress-Report/ . Information on the Five Year Program is available online at http://www... final on August 27, 2012, after the required 60-day congressional review period. Section 18(e) of the...

Handbook 2006-2007: Federal Student Aid. Volume 3--Calculating Awards & Packaging

ERIC Educational Resources Information Center

US Department of Education, 2006

2006-01-01

Every eligible program, including graduate programs, must have a defined academic year. Award limits are generally connected to a period of time. For instance, all of the programs except Federal Work-Study have a maximum amount that can be awarded for an academic year or award year. This handbook is a resource for learning about Federal Student…

A Survey of College Reading Programs in New York State: Diagnosis, Placement and Program Components.

ERIC Educational Resources Information Center

Malinowski, Patricia A.

In February 1988, a survey was conducted to examine placement procedures and developmental reading programs at two- and four-year colleges in New York State. Surveys were mailed to 30 two-year colleges and 28 four-year colleges, requesting information on the placement tests and cut-off scores used; types of additional diagnostic testing; course…

Implementation of the thinking skills for work program in a psychosocial clubhouse.

PubMed

McGurk, Susan R; Schiano, Diane; Mueser, Kim T; Wolfe, Rosemarie

2010-01-01

Cognitive remediation programs aimed at improving role functioning have been implemented in a variety of different mental health treatment settings, but not in psychosocial clubhouses. This study sought to determine the feasibility and preliminary outcomes of providing a cognitive remediation program (the Thinking Skills for Work program), developed and previously implemented in supported employment programs at mental health agencies, in a psychosocial club-house. Twenty-three members with a history of difficulties getting or keeping jobs, who were participating in a supported employment program at a psychosocial clubhouse, were enrolled in the Thinking Skills for Work program. A neurocognitive battery was administered at baseline and 3 months later after completion of the computer cognitive training component of the program. Hours of competitive work were tracked for the 2 years before enrollment and 2 years following enrollment. Other work-related activities (school, volunteer) were also tracked for 2 years following enrollment. Twenty-one members (91%) completed 6 or more computer cognitive training sessions. Participants demonstrated significant improvements on neurocognitive measures of processing speed, verbal learning and memory, and executive functions. Sixty percent of the members obtained a competitive job during the 2-year follow-up, and 74% were involved in some type of work-related activity. Participants worked significantly more competitive hours over the 2 years after joining the Thinking Skills for Work program than before. The findings support the feasibility and promise of implementing the Thinking Skills for Work program in the context of supported employment provided at psychosocial clubhouses.

The uneven distribution of women in orthopaedic surgery resident training programs in the United States.

PubMed

Van Heest, Ann E; Agel, Julie

2012-01-18

Although women represented 58% of undergraduate students and 48% of medical students in the U.S. in the 2008-2009 academic year, only 13% of orthopaedic residents and only 4% of American Academy of Orthopaedic Surgeons (AAOS) Fellows in 2009 were women. Are all orthopaedic surgery programs in the U.S. equal in their ability to attract female medical students and train female orthopaedic surgeons? This study was undertaken to test the hypothesis that all Accreditation Council for Graduate Medical Education (ACGME)-accredited orthopaedic surgery residency programs in the U.S. train a similar number of female residents. Data for all ACGME-accredited orthopaedic surgery residency training programs in the U.S. for five academic years (2004-2005 through 2008-2009) were collected with use of the Graduate Medical Education (GME) Track database. Orthopaedic residency programs in the U.S. do not train women at an equal frequency. In the academic years from 2004-2005 through 2008-2009, forty-five programs had no female residents during at least one of the five academic years reviewed, and nine programs had no female residents during any of the years. More than fifty orthopaedic residency programs in the U.S. had an average of <10% female trainees over the five-year period, and more than ten programs had an average of >20%. There was no significant change in the distribution among these categories over the five years examined (p = 0.234). Significant differences in the representation of women exist among orthopaedic residency training programs in the U.S. Further examination of the characteristics of orthopaedic residency programs that are successful in attracting female residents, particularly the composition of their faculty as role models, will be important in furthering our understanding of how orthopaedic surgery can continue to attract the best and the brightest individuals. Changes in the cultural experiences in programs that have not trained female orthopaedic surgeons, such as an increased number of female faculty, and policies that emphasize diversity may provide a greater opportunity for our orthopaedic profession to attract female medical students.

Peer to peer mentoring: Outcomes of third-year midwifery students mentoring first-year students.

PubMed

Hogan, Rosemarie; Fox, Deborah; Barratt-See, Georgina

2017-06-01

Undergraduate midwifery students commonly experience anxiety in relation to their first clinical placement. A peer mentoring program for midwifery students was implemented in an urban Australian university. The participants were first-year mentee and third-year mentor students studying a three-year Bachelor degree in midwifery. The program offered peer support to first-year midwifery students who had little or no previous exposure to hospital clinical settings. Mentors received the opportunity to develop mentoring and leadership skills. The aim was to explore the benefits, if any, of a peer mentoring program for midwifery students. The peer mentoring program was implemented in 2012. Sixty-three peer mentors and 170 mentees participated over three academic years. Surveys were distributed at the end of each academic year. Quantitative survey data were analysed descriptively and qualitative survey data were analysed thematically using NVivo 10 software. Over 80% of mentors and mentees felt that the program helped mentees adjust to their midwifery clinical placement. At least 75% of mentors benefited, in developing their communication, mentoring and leadership skills. Three themes emerged from the qualitative data, including 'Receiving start-up advice'; 'Knowing she was there' and 'Wanting more face to face time'. There is a paucity of literature on midwifery student peer mentoring. The findings of this program demonstrate the value of peer support for mentees and adds knowledge about the mentor experience for undergraduate midwifery students. The peer mentor program was of benefit to the majority of midwifery students. Copyright © 2017 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

Participation in modified sports programs: a longitudinal study of children's transition to club sport competition.

PubMed

Eime, Rochelle M; Casey, Meghan M; Harvey, Jack T; Charity, Melanie J; Young, Janet A; Payne, Warren R

2015-07-14

Many children are not physically active enough for a health benefit. One avenue of physical activity is modified sport programs, designed as an introduction to sport for young children. This longitudinal study identified trends in participation among children aged 4-12 years. Outcomes included continuation in the modified sports program, withdrawal from the program or transition to club sport competition. De-identified data on participant membership registrations in three popular sports in the Australian state of Victoria were obtained from each sport's state governing body over a 4-year period (2009-2012 for Sport A and 2010-2013 for Sports B and C). From the membership registrations, those who were enrolled in a modified sports program in the first year were tracked over the subsequent three years and classified as one of: transition (member transitioned from a modified sport program to a club competition); continue (member continued participation in a modified sport program; or withdraw (member discontinued a modified program and did not transition to club competition). Many modified sports participants were very young, especially males aged 4-6 years. More children withdrew from their modified sport program rather than transitioning. There were age differences between when boys and girls started, withdrew and transitioned from the modified sports programs. If we can retain children in sport it is likely to be beneficial for their health. This study highlights considerations for the development and implementation of sport policies and programming to ensure lifelong participation is encouraged for both males and females.

76 FR 8811 - FTA Fiscal Year 2011 Apportionments, Allocations and Program Information: Corrections

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-15

... Apportionments) and Table 10 (Prior Year Unobligated Section 5309 Bus and Bus Related Equipment and Facilities... DEPARTMENT OF TRANSPORTATION Federal Transit Administration FTA Fiscal Year 2011 Apportionments... titled ``FTA Fiscal Year 2011 Apportionments, Allocations and Program Information.'' FOR FURTHER...

A quality improvement program to improve nutritional status of children with Cystic Fibrosis aged 2-12 years old over a 3 year period at CF center Roscoff, Brittany.

PubMed

Revert, Krista; Audran, Laurence; Pengam, Jocelyne; Lesne, Pascal; Pougheon Bertrand, Dominique

2018-02-08

The Cystic Fibrosis (CF) center in Roscoff (Brittany) has been involved in therapeutic education programs (TEP) since 2006 and took part in the pilot phase of the French quality improvement program (QIP) since 2011. The aim was to improve the nutritional status of children with cystic fibrosis aged 2-12 years old in order to optimize their health status as they enter adolescence. A multidisciplinary quality team was created in order to select and address a specific health problem among our pediatric population. Following analysis of yearly indicators for our CF center, our team chose to improve quality of care concerning nutritional status of children aged 2-12 years old. Factors influencing efficacy were studied, tools were developed to implement a new nutritional program, results were analyzed on a real-time basis. Over the 3 year period, all patients from 2 years of age, were monitored with the new follow-up program (2012: N = 34; 2014: N = 44). Each patient was followed up at every clinic visit, their BMI z-score was calculated to decide their nutritional risk and personalize their follow-up program consequently. Between 1/1/2012 and 31/12/2014, the mean BMI z-score of the open cohort improved from -0.49 to -0.22. Since 2014, focus on nutrition using the newly-adapted program has become routine practice at each follow-up visit. Patients and parents expressed a high level of satisfaction (75% very satisfied). The follow-up program aimed at improving nutritional status for children aged 2-12 years old was successfully implemented and integrated into routine practice; it was therefore extended to all children with CF (1 month - 18 years) in our center. The relationship among professional and patients and parents was strengthened.

Could a federal program to promote influenza vaccination among elders be cost-effective?

PubMed

Patel, Mitesh S; Davis, Matthew M

2006-03-01

Influenza-related mortality predominately and disproportionately impacts the elderly. Rates of annual influenza vaccination among the elderly are approximately 65%, far below the Healthy People 2010 target of 90%. We estimated the cost-effectiveness of a 10-year federal program to promote influenza vaccine, intended to increase vaccination rates among persons > or = 65 years old. Published estimates regarding influenza-associated mortality rates and vaccine efficacy among the US elderly were used to calculate the number needed to vaccinate (NNV) to prevent one all-cause death due to influenza, as well as the mortality reduction expected from increased vaccination rates. The costs per life-year saved were estimated for a hypothetical federal promotional campaign, patterned after a direct-to-consumer (DTC) advertising program (2006-2015). The base case scenario presumed a 25-percentage-point increase in vaccination rates to 90%; in sensitivity analyses, we examined programs that increased rates by 10-20 points. The base case NNV was 1116 (95% CI: 993-1348). Over the 10-year DTC-style influenza vaccine promotion program, 6516 (5576-7435) elderly lives would be saved. The incremental cost-effectiveness (C/E) of the program was dollar 16,300 (dollar 11,347-dollar 25,174) per life-year saved in 2006 and increased to dollar 199,906 (dollar 138,613-dollar 307,423) per life-year saved by 2015. Overall, the C/E for the 10-year program was dollar 37,621 (dollar 32,644-dollar 43,939) per life-year saved. Programs that yielded a 15-percentage-point increase or less in vaccination rates would have C/E values exceeding dollar 50,000 per life-year saved and save fewer than 4000 total lives. DTC-style promotional campaigns for influenza vaccine among elders may represent a cost-effective strategy for the federal government to pursue as a means of increasing elders' vaccination rates and reducing influenza-related mortality.

The Development of a Stress Management Program for the Adult Degree Completion Program Admissions Team at a Four-Year Private Liberal Arts College.

ERIC Educational Resources Information Center

Satterlee, Brian

A stress management program was developed for the adult degree completion program admissions team at Warner Southern College, a four-year private liberal arts college. A relatively recent stress-inducing change was caused by an administrative decision to expand the program offerings from five sites to seven, using current staff. Derived from the…

Targeted human papillomavirus vaccination for young men who have sex with men in Australia yields significant population benefits and is cost-effective.

PubMed

Zhang, Lei; Regan, David G; Ong, Jason J; Gambhir, Manoj; Chow, Eric P F; Zou, Huachun; Law, Matthew; Hocking, Jane; Fairley, Christopher K

2017-09-05

We investigated the effectiveness and cost-effectiveness of a targeted human papillomavirus (HPV) vaccination program for young (15-26) men who have sex with men (MSM). We developed a compartmental model to project HPV epidemic trajectories in MSM for three vaccination scenarios: a boys program, a targeted program for young MSM only and the combination of the two over 2017-2036. We assessed the gain in quality-adjusted-life-years (QALY) in 190,000 Australian MSM. A targeted program for young MSM only that achieved 20% coverage per year, without a boys program, will prevent 49,283 (31,253-71,500) cases of anogenital warts, 191 (88-319) person-years living with anal cancer through 2017-2036 but will only stablise anal cancer incidence. In contrast, a boys program will prevent 82,056 (52,100-117,164) cases of anogenital warts, 447 (204-725) person-years living with anal cancers through 2017-2036 and see major declines in anal cancer. This can reduce 90% low- and high-risk HPV in young MSM by 2024 and 2032, respectively, but will require vaccinating ≥84% of boys. Adding a targeted program for young MSM to an existing boys program would prevent an additional 14,912 (8479-21,803) anogenital wart and 91 (42-152) person-years living with anal cancer. In combination with a boys' program, a catch-up program for young MSM will cost an additional $AUD 6788 ($4628-11,989) per QALY gained, but delaying its implementation reduced its cost-effectiveness. A boys program that achieved coverage of about 84% will result in a 90% reduction in HPV. A targeted program for young MSM is cost-effective if timely implemented. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cost-effectiveness of a patient navigation program to improve cervical cancer screening.

PubMed

Li, Yan; Carlson, Erin; Villarreal, Roberto; Meraz, Leah; Pagán, José A

2017-07-01

To assess the cost-effectiveness of a community-based patient navigation program to improve cervical cancer screening among Hispanic women 18 or older in San Antonio, Texas. We used a microsimulation model of cervical cancer to project the long-term cost-effectiveness of a community-based patient navigation program compared with current practice. We used program data from 2012 to 2015 and published data from the existing literature as model input. Taking a societal perspective, we estimated the lifetime costs, life expectancy, and quality-adjusted life-years and conducted 2-way sensitivity analyses to account for parameter uncertainty. The patient navigation program resulted in a per-capita gain of 0.2 years of life expectancy. The program was highly cost-effective relative to no intervention (incremental cost-effectiveness ratio of $748). The program costs would have to increase up to 10 times from $311 for it not to be cost-effective. The 3-year community-based patient navigation program effectively increased cervical cancer screening uptake and adherence and improved the cost-effectiveness of the screening program for Hispanic women 18 years or older in San Antonio, Texas. Future research is needed to translate and disseminate the patient navigation program to other socioeconomic and demographic groups to test its robustness and design.

Association of school performance indicators with implementation of the Healthy Kids, Smart Kids program: case study

PubMed Central

Nansel, Tonja R.; Huang, Terry T.K.; Rovner, Alisha J.; Sanders-Butler, Yvonne

2009-01-01

Objective: The purpose of this analysis was to examine secular trends in school performance indicators in relationship to the implementation of a program targeting the school food and physical activity environment. Design: Data on available school performance indicators were obtained; retrospective analyses were conducted to assess trends in indicators in association with program implementation; each outcome was regressed on year, beginning with the year prior to program implementation. Setting: The Healthy Kids, Smart Kids program was a grass-roots effort to enhance the school food and physical activity environment in the Browns Mill Elementary School in Georgia. Subjects: Data included publicly available school records from the years 1995 to 2006. Results: The number of nurse, counseling, and disciplinary referrals per 100 students demonstrated a downward trend, while standardized test scores demonstrated an upward trend beginning the year of program implementation. School year was a significant predictor of all indicators. Conclusions: Promoting nutrition and physical activity within the school environment may be a promising approach for enhancing both student health and educational outcomes. PMID:19454125

NASA Year 2000 (Y2K) Program Plan

NASA Technical Reports Server (NTRS)

1998-01-01

NASA initiated the Year 2000 (Y2K) program in August 1996 to address the challenges imposed on Agency software, hardware, and firmware systems by the new millennium. The Agency program is centrally managed by the NASA Chief Information Officer, with decentralized execution of program requirements at each of the nine NASA Centers, Headquarters and the Jet Propulsion Laboratory. The purpose of this Program Plan is to establish Program objectives and performance goals; identify Program requirements; describe the management structure; and detail Program resources, schedules, and controls. Project plans are established for each NASA Center, Headquarters, and the Jet Propulsion Laboratory.

Impact of 2 employer-sponsored population health management programs on medical care cost and utilization.

PubMed

Mattke, Soeren; Serxner, Seth A; Zakowski, Sarah L; Jain, Arvind K; Gold, Daniel B

2009-02-01

Integrated health management programs combining disease prevention and disease management services, although popular with employers, have been insufficiently researched with respect to their effect on costs. To estimate the overall impact of a population health management program and its components on cost and utilization. STUDY DESIGN, SETTING, AND PARTICIPANTS: Observational study of 2 employer-sponsored health management programs involving more than 200,000 health plan members. We used claims data for the first program year and the 2 preceding years to calculate cost and utilization metrics, and program activity data to determine program uptake. Using an intent-to-treat approach and regression-based risk adjustment, we estimated whether the program was associated with changes in cost and utilization. Data on program fees were unavailable. Overall, the program was associated with a nonsignificant cost increase of $13.75 per member per month (PMPM). The wellness component alone was associated with a significant increase of $20.14 PMPM. Case and disease management were associated with a significant decrease in hospital admissions of 4 and 1 per 1000 patient-years, respectively. Our results suggest that the programs did not reduce medical cost in their first year, despite a beneficial effect on hospital admissions. If we had been able to include program fees, it is likely that the overall cost would have increased significantly. Although this study had important limitations, the results suggest that a belief that these programs will save money may be too optimistic and better evaluation is needed.

Trained simulated ultrasound patients: medical students as models, learners, and teachers.

PubMed

Blickendorf, J Matthew; Adkins, Eric J; Boulger, Creagh; Bahner, David P

2014-01-01

Medical educators must develop ultrasound education programs to ensure that future physicians are prepared to face the changing demands of clinical practice. It can be challenging to find human models for hands-on scanning sessions. This article outlines an educational model from a large university medical center that uses medical students to fulfill the need for human models. During the 2011-2012 academic year, medical students from The Ohio State University College of Medicine served as trained simulated ultrasound patients (TSUP) for hands-on scanning sessions held by the college and many residency programs. The extracurricular program is voluntary and coordinated by medical students with faculty supervision. Students receive a longitudinal didactic and hands-on ultrasound education program as an incentive for serving as a TSUP. The College of Medicine and 7 residency programs used the program, which included 47 second-year and 7 first-year student volunteers. Participation has increased annually because of the program's ease, reliability, and cost savings in providing normal anatomic models for ultrasound education programs. A key success of this program is its inherent reproducibility, as a new class of eager students constitutes the volunteer pool each year. The TSUP program is a feasible and sustainable method of fulfilling the need for normal anatomic ultrasound models while serving as a valuable extracurricular ultrasound education program for medical students. The program facilitates the coordination of ultrasound education programs by educators at the undergraduate and graduate levels.

Art Enrichment: Evaluating a Collaboration between Head Start and a Graduate Art Therapy Program

ERIC Educational Resources Information Center

Klorer, P. Gussie; Robb, Megan

2012-01-01

Head Start, a U.S. federally funded program, prepares children for school through early childhood intervention in social-emotional and cognitive arenas. This article describes program evaluation survey results from the past 5 years of an 18-year collaboration between a university graduate art therapy program and 8 Head Start centers. Graduate art…

Transitional Class Program, 1979-80. OEE Evaluation Report.

ERIC Educational Resources Information Center

Opperman, Prudence Ward; And Others

This evaluation report describes the implementation and results of the 1979-80 Transitional Class Program. Although the program no longer exists as a centrally-coordinated effort, it serves as a final summary of the program's two years of operation by comparing the results from one year (1978-1979) to the next (1979-1980), and provides guidance to…

Using a Geriatric Mentoring Narrative Program to Improve Medical Student Attitudes towards the Elderly

ERIC Educational Resources Information Center

Duke, Pamela; Cohen, Diane; Novack, Dennis

2009-01-01

This study examined first-year medical student attitudes concerning the elderly before and after instituting a geriatric mentoring program. The program began and ended with a survey designed to assess students' attitudes toward the elderly. During the mentoring program, students visited the same senior for four visits throughout the academic year.…

Flash Memory Reliability: Read, Program, and Erase Latency Versus Endurance Cycling

NASA Technical Reports Server (NTRS)

Heidecker, Jason

2010-01-01

This report documents the efforts and results of the fiscal year (FY) 2010 NASA Electronic Parts and Packaging Program (NEPP) task for nonvolatile memory (NVM) reliability. This year's focus was to measure latency (read, program, and erase) of NAND Flash memories and determine how these parameters drift with erase/program/read endurance cycling.

Texas Nutrition Education and Training Program. Final Evaluation Report for Federal Fiscal Year 1994.

ERIC Educational Resources Information Center

Ahmad, Mahassen

This report presents federally mandated evaluations and needs assessments conducted by the Texas Nutrition Education and Training (NET) program during Federal Fiscal Year 1994. General program performance of NET reflected an increase in the number of children in Texas and expansion in NET program activities. Needs assessment data collected from…

Evaluation of Selected New York City Umbrella Programs, 1974-1975 School Year.

ERIC Educational Resources Information Center

Fordham Univ., Bronx, NY. Inst. for Research and Evaluation.

An evaluation of twelve different New York City Umbrella Programs coordinated in New York City public schools during the 1974-1975 school year is contained in this document. This report presents a description and evaluation of these programs, together with the major findings. The programs were implemented in the following areas: (1) tutoring in…

Breaking down Barriers: A Bridge Program Helps First-Year Biology Students Connect with Faculty

ERIC Educational Resources Information Center

Cooper, Katelyn M.; Ashley, Michael; Brownell, Sara E.

2018-01-01

Summer bridge programs often aim to build social connections for first-year students to ease their transition into college, yet few studies have reported on bridge programs successfully leading to these outcomes. We backward designed a summer bridge program for incoming biology majors to increase the comfort and connections among students and…

Evaluation of the first year of the Washington nighttime seat belt enforcement program.

DOT National Transportation Integrated Search

2010-12-01

The Washington Traffic Safety Commission (WTSC) received funding from the National Highway Traffic Safety Administration to conduct a high-visibility nighttime seat belt enforcement (NTSBE) program in Washington State. The two-year program is followi...

7 CFR 1400.210 - Deceased and incapacitated persons.

Code of Federal Regulations, 2010 CFR

2010-01-01

... CORPORATION, DEPARTMENT OF AGRICULTURE GENERAL REGULATIONS AND POLICIES PAYMENT LIMITATION AND PAYMENT ELIGIBILITY FOR 2009 AND SUBSEQUENT CROP, PROGRAM, OR FISCAL YEARS Payment Eligibility § 1400.210 Deceased and... determination to be in effect for that program year or fiscal year, as applicable. However, the following year...

George Washington High School Bilingual Academic and Career Orientation Program, 1982-1983. O.E.E. Evaluation Report.

ERIC Educational Resources Information Center

Cotayo, Armando; Collins, Carla

This program, in its final year of a two-year funding cycle, offered bilingual instruction and supportive services with a career orientation focus to 250 Hispanic students in grades 9-12. The major program goal was to expedite the acquisition of the English language skills necessary for full mainstreaming within an average period of three years.…

The Evaluation of Enhanced Academic Instruction in After-School Programs: Findings After the First Year of Implementation. NCEE 2008-4021

ERIC Educational Resources Information Center

Black, Alison Rebeck; Doolittle, Fred; Zhu, Pei; Unterman, Rebecca; Grossman, Jean Baldwin

2008-01-01

This report presents findings, after one year of program implementation, from the Evaluation of Enhanced Academic Instruction in After-School Programs--a two-year intervention and random assignment evaluation of adapted models of regular-school-day math and reading instruction in after-school settings for students in grades 2 through 5. This…

"I Can Feel It Making My Brain Bigger": Thinking Science Australia

ERIC Educational Resources Information Center

Dullard, Heath; Oliver, Mary

2012-01-01

"I can feel it making my brain bigger": from a Year 8 student at Pinjarra Senior High School (SHS) halfway through the two-year Thinking Science Program. Pinjarra was a pilot school for the program in 2009/10 and a growing number of schools in Western Australia (WA) are implementing this program in Years Seven to Nine as part of the…

Bonus Awards for Teachers in Texas' Performance Pay Program: Findings from the First Round of TEEG Schools. Research Brief

ERIC Educational Resources Information Center

National Center on Performance Incentives, 2009

2009-01-01

A recent report published by the National Center on Performance Incentives (NCPI) presents findings from the second-year of a multi-year evaluation of the Texas Educator Excellence Grant (TEEG) program, a statewide educator incentive program that operated in Texas. As part of this evaluation report, researchers examined how first-year TEEG schools…

District Awards for Teacher Excellence (D.A.T.E.) Program: Year One Evaluation Report. Policy Evaluation Report. [Executive Summary

ERIC Educational Resources Information Center

Springer, Matthew G.; Lewis, Jessica L.; Podgursky, Michael J.; Ehlert, Mark W.; Taylor, Lori L.; Lopez, Omar S.; Ghoshdastidar, Bonnie; Peng, Art

2010-01-01

The District Awards for Teacher Excellence's (D.A.T.E.'s) first year of implementation in 2008-09 occurred at a time when Texas was operating several state-funded performance pay programs. The three-year Governor's Educator Excellence Grant (G.E.E.G.) program was coming to its expected completion, while the Texas Educator Excellence Grant…

Targeting CD22 in B-cell malignancies: current status and clinical outlook.

PubMed

Sullivan-Chang, Loretta; O'Donnell, Robert T; Tuscano, Joseph M

2013-08-01

CD22 is a B-cell-specific transmembrane glycoprotein found on the surface of most B cells; it modulates B-cell function, survival and apoptosis. CD22 has emerged as an ideal target for monoclonal antibody (mAb)-based therapy of B-cell malignancies including most lymphomas and many leukemias. Epratuzumab, an anti-CD22 mAb, has been developed in various forms, including as an unlabeled (naked) mAb, as a radioimmunotherapeutic, as an antibody drug conjugate (ADC), and as a vehicle for CD22-targeted nanoparticles. While clinical trials with unlabeled epratuzumab have demonstrated modest results, its combination with rituximab in phase II studies has been more encouraging. Based on the potential for CD22 to become internalized, CD22-targeted constructs carrying radioisotopes or toxins have generated promising results. Radioimmunotherapy, utilizing ⁹⁰Y-labeled epratuzumab, was shown to be highly effective in patients with follicular lymphoma, generating a complete response (CR) rate of 92 % and progression-free survival of more than 2 years. ADC therapy is a promising therapeutic approach to B-cell malignancies which includes the direct conjugation of mAbs with cytotoxic agents. Phase II studies of inotuzumab ozogamicin, an ADC which combines anti-CD22 mAb with calicheamicin, an enediyne antibiotic which mediates apoptosis, in patients with acute lymphoblastic leukemia have produced an overall response rate (ORR) of greater than 50 % in treatment-refractory patients. Phase I trials of moxetumomab pasudotox, an ADC which combines anti-CD22 with PE38, a fragment of Pseudomonas exotoxin A, have been completed in hairy cell leukemia with a ORR of 86 %. Finally, a review of CD22-targeted nanoparticles, that include a doxorubicin-containing lipid complex that uses synthetic high-affinity CD22 ligand mimetics as well as anti-CD22 mAb-coated pegylated liposomas doxorubin (PLD), has demonstrated promising results in pre-clinical models of human lymphoma. Moreover, novel anti-CD22 mAb that block CD22 ligand binding as well as second generation ADC that utilize biodegradable linkers and more potent toxins hold great hope for the future of CD22-targeted therapeutics that may translate into better outcomes for patients with CD22-positive malignancies.

Department of Energy - Office of Science Early Career Research Program

NASA Astrophysics Data System (ADS)

Horwitz, James

The Department of Energy (DOE) Office of Science Early Career Program began in FY 2010. The program objectives are to support the development of individual research programs of outstanding scientists early in their careers and to stimulate research careers in the disciplines supported by the DOE Office of Science. Both university and DOE national laboratory early career scientists are eligible. Applicants must be within 10 years of receiving their PhD. For universities, the PI must be an untenured Assistant Professor or Associate Professor on the tenure track. DOE laboratory applicants must be full time, non-postdoctoral employee. University awards are at least 150,000 per year for 5 years for summer salary and expenses. DOE laboratory awards are at least 500,000 per year for 5 years for full annual salary and expenses. The Program is managed by the Office of the Deputy Director for Science Programs and supports research in the following Offices: Advanced Scientific and Computing Research, Biological and Environmental Research, Basic Energy Sciences, Fusion Energy Sciences, High Energy Physics, and Nuclear Physics. A new Funding Opportunity Announcement is issued each year with detailed description on the topical areas encouraged for early career proposals. Preproposals are required. This talk will introduce the DOE Office of Science Early Career Research program and describe opportunities for research relevant to the condensed matter physics community. http://science.energy.gov/early-career/

DTRA's Nuclear Explosion Monitoring Research and Development Program

NASA Astrophysics Data System (ADS)

Nichols, J.; Dainty, A.; Phillips, J.

2001-05-01

The Defense Threat Reduction Agency (DTRA) has a Program in Basic Research and Development for Nuclear Explosion Technology within the Nuclear Treaties Branch of the Arms Control Technology Division. While the funding justification is Arms Control Treaties (i.e., Comprehensive Nuclear-Test-Ban Treaty, CTBT), the results are made available for any user. Funding for the Program has averaged around \\10m per year recently. By Congressional mandate, the program has disbursed money through competitive, peer-reviewed, Program Research and Development Announcements (PRDAs); there is usually (but not always) a PRDA each year. Typical awards have been for about three years at ~\\100,000 per year, currently there are over 60 contracts in place. In addition to the "typical" awards, there was an initiative 2000 to fund seismic location calibration of the International Monitoring System (IMS) of the CTBT; there are three three-year contracts of ~\\$1,000,000 per year to perform such calibration for Eurasia, and North Africa and the Middle East. Scientifically, four technological areas have been funded, corresponding to the four technologies in the IMS: seismic, infrasound, hydroacoustic, and radionuclide, with the lion's share of the funding going to the seismic area. The scientific focus of the Program for all four technologies is detection of signals, locating their origin, and trying to determine of they are unambiguously natural in origin ("event screening"). Location has been a particular and continuing focus within the Program.

The Shapley Program 1985 - 1990: The Virginia Years

NASA Astrophysics Data System (ADS)

Tolbert, C. R.

1998-05-01

The Shapley Program moved to the University of Virginia from the University of Delaware in the summer of 1985. Prior to moving to Charlottesville the program had been run by Harry Shipman. 1985 - 1986 was the year of Comet Halley, and it was also the year that the program reached its peak of visits made by the astronomical community. We scheduled 135 visits that year. Luckily, I was new on the job and didn't realize the effort that would be involved in coordinating that many visiting astronomers. One way or the other we got through the "big" year and, after consultation with the Council, established a maximum number of visits to be scheduled per year at 80. We maintained that number every year through the Virginia period. It was during this time that the office purchased its first computer and computerized the mailing list. We sent brochures to some 2,000 plus colleges and junior colleges throughout the US, Canada and Mexico. (regrettably, we never received a request form a Mexican school.) The fee charged to the school for each visit was \\75 per visit in the beginning and rose to \\200 per school by the end of the period. The rest of the costs of the program were borne by the Shapley Endowment Fund and the AAS Education Office. We waived the fee from a number of schools on request. In addition to being a Shapley Lecturer myself, I had the great pleasure during this period of receiving the many compliments about the program. There is no question that the Shapley Visiting Lectureships Program provides an excellent service to small colleges in both the US and Canada. Based on the reports of our success, the American Physical Society re-instituted their lecture program as did the American Optical Society.

DITTY - a computer program for calculating population dose integrated over ten thousand years

DOE Office of Scientific and Technical Information (OSTI.GOV)

Napier, B.A.; Peloquin, R.A.; Strenge, D.L.

The computer program DITTY (Dose Integrated Over Ten Thousand Years) was developed to determine the collective dose from long term nuclear waste disposal sites resulting from the ground-water pathways. DITTY estimates the time integral of collective dose over a ten-thousand-year period for time-variant radionuclide releases to surface waters, wells, or the atmosphere. This document includes the following information on DITTY: a description of the mathematical models, program designs, data file requirements, input preparation, output interpretations, sample problems, and program-generated diagnostic messages.

Exploring the Evidence: Initiatives in the First College Year. The First-Year Experience Monograph Series No. 49

ERIC Educational Resources Information Center

Troxel, Wendy G., Ed.; Cutright, Marc, Ed.

2008-01-01

For more than 25 years, educators have developed and institutionalized efforts to help first-year students succeed. This monograph collects case studies from 22 institutions that have created programs and initiatives to support their first-year students. The programs range from encouraging civic engagement and academic achievements to…

Long-term impact of a chronic disease management program on hospital utilization and cost in an Australian population with heart disease or diabetes.

PubMed

Hamar, G Brent; Rula, Elizabeth Y; Coberley, Carter; Pope, James E; Larkin, Shaun

2015-04-22

To evaluate the longitudinal value of a chronic disease management program, My Health Guardian (MHG), in reducing hospital utilization and costs over 4 years. The MHG program provides individualized support via telephonic nurse outreach and online tools for self-management, behavior change and well-being. In follow up to an initial 18-month analysis of MHG, the current study evaluated program impact over 4 years. A matched-cohort analysis retrospectively compared MHG participants with heart disease or diabetes (treatment, N = 4,948) to non-participants (comparison, N = 28,520) on utilization rates (hospital admission, readmission, total bed days) and hospital claims cost savings. Outcomes were evaluated using regression analyses, controlling for remaining demographic, disease, and pre-program admissions or cost differences between the study groups. Over the 4 year period, program participation resulted in significant reductions in hospital admissions (-11.4%, P < 0.0001), readmissions (-36.7%, P < 0.0001), and bed days (-17.2%, P < 0.0001). The effect size increased over time for admissions and bed days. The relative odds of any admission and readmission over the 4 years were 27% and 45% lower, respectively, in the treatment group. Cumulative program savings from reduced hospital claims was $3,549 over 4-years; savings values for each program year were significant and increased with time (P = 0.003 to P < 0.0001). Savings calculations did not adjust for pooled costs (and savings) in Australia's risk equalization system for private insurers. Results confirm and extend prior program outcomes and support the longitudinal value of the MHG program in reducing hospital utilization and costs for individuals with heart disease or diabetes and demonstrate the increasing program effect with continued participation over time.

Needed Research in Year-Round Education.

ERIC Educational Resources Information Center

Parks, David J.; Leffel, Linda G.

The current literature on year-round education is replete with feasibility studies; reports on operational programs; and thoughtful consideration of the potential effects of year-round education on the community, school, family, and child. Lay boards of education are frequently asked to make decisions on whether to implement year-round programs on…

78 FR 58290 - TRICARE; Calendar Year 2014 TRICARE Young Adult Program Premium Update

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-23

... DEPARTMENT OF DEFENSE Office of the Secretary TRICARE; Calendar Year 2014 TRICARE Young Adult... Young Adult Premiums for Calendar Year 2014. SUMMARY: This notice provides the updated TRICARE Young Adult program premiums for Calendar Year (CY) 2014. DATES: The CY 2014 rates contained in this notice...

Increasing family planning in Myanmar: the role of the private sector and social franchise programs.

PubMed

Aung, Tin; Hom, Nang Mo; Sudhinaraset, May

2017-07-01

This study examines the influence of clinical social franchise program on modern contraceptive use. This was a cross-sectional survey of contraceptive use among 2390 currently married women across 25 townships in Myanmar in 2014. Social franchise program measures were from programmatic records. Multivariable models show that women who lived in communities with at least 1-5 years of a clinical social franchise intrauterine device (IUD) program had 4.770 higher odds of using a modern contraceptive method compared to women living in communities with no IUD program [CI: 3.739-6.084]. Townships where the reproductive health program had existed for at least 10 years had 1.428 higher odds of reporting modern method use compared to women living in townships where the programs had existed for less than 10 years [CI: 1.016-2.008]. This study found consistent and robust evidence for an increase in family planning methods over program duration as well as intensity of social franchise programs.

ENVIRONMENTAL MONITORING AND ASSESSMENT PROGRAM: AGROECOSYSTEM 1992 PILOT PLAN

EPA Science Inventory

The Agroecosystem Resource Group (ARG) of the Environmental Protection Monitoring and Assessment Program (EMAP) has developed a five year program strategy for implementation of a suite of indicators for monitoring agroecosystem status and trends. he five-year period (1991-1995) i...

Evaluation of the buckle up in your truck programs.

DOT National Transportation Integrated Search

2009-06-01

In 2006 and 2007, all four States in NHTSAs Region 7 (Iowa, Kansas, Missouri, and Nebraska) participated in a : two-year Buckle Up in Your Truck (BUIYT) program. Each year, this program consisted of a two-week, highvisibility, : seat belt enforcem...

7 CFR 246.15 - Program income other than grants.

Code of Federal Regulations, 2010 CFR

2010-01-01

....15 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS SPECIAL SUPPLEMENTAL NUTRITION PROGRAM FOR WOMEN, INFANTS... years or subsequent fiscal years. Provided that the costs supported by the income further the broad...

Triple Therapy of HER2+ Cancer Using Radiolabeled Multifunctional Iron Oxide Nanoparticles and Alternating Magnetic Field.

PubMed

Zolata, Hamidreza; Afarideh, Hossein; Davani, Fereydoun Abbasi

2016-11-01

By using radio-labeled multifunctional superparamagnetic iron oxide nanoparticles (SPIONs) and an alternating magnetic field (AMF), we carried out targeted hyperthermia, drug delivery, radio-immunotherapy (RIT), and controlled chemotherapy of cancer tumors. We synthesized and characterized Indium-111-labeled, Trastuzumab and Doxorubicin (DOX)-conjugated APTES-PEG-coated SPIONs in our previous work. Then, we evaluated their capability in SPECT/MRI (single photon emission computed tomography/magnetic resonance imaging) dual modal molecular imaging, targeting, and controlled release. In this research, AMF was introduced to evaluate therapeutic effects of magnetic hyperthermia on radionuclide-chemo therapy of HER2 + cells and tumor (HER2 + )-bearing mice. In vitro and in vivo experiments using synthesized complex were repeated under an AMF (f: 100 KHz, H: 280 Gs). Instead of an intra-tumor injection in most hyperthermia experiments, SPIONs were injected to the tail vein, based on our delivery strategies. For magnetic delivery, we held a permanent Nd-B-Fe magnet near the tumor region. The results showed that simultaneous magnetic hyperthermia enhanced SKBR3 cancer cells, killing by 24%, 28%, 33%, and 80% at 48 hours post-treatment for treated cells with (1) bare SPIONs; (2) antibody-conjugated, DOX-free, surface-modified SPIONs; (3) 111 In-labeled, antibody-conjugated surface-modified SPIONs; and (4) 111 In-labeled, antibody- and DOX-conjugated surface-modified SPIONs, respectively. Moreover, tumor volume inhibitory rate was 85% after a 28 day period of treatment. By using this method, multimodal imaging-guided, targeted hyperthermia, RIT, and controlled chemotherapy could be achievable in the near future.

Pre-Clinical Assessment of Lu-Labeled Trastuzumab Targeting HER2 for Treatment and Management of Cancer Patients with Disseminated Intraperitoneal Disease.

PubMed

Ray, Geoffrey L; Baidoo, Kwamena E; Keller, Lanea M M; Albert, Paul S; Brechbiel, Martin W; Milenic, Diane E

2011-12-22

Studies from this laboratory have demonstrated the potential of targeting HER2 for therapeutic and imaging applications with medically relevant radionuclides. To expand the repertoire of trastuzumab as a radioimmunoconjugate (RIC) vector, use of (177)Lu was investigated. The combination of a 6.7 d half-life, lower energy β(-)-emissions (500 keV max; 130 keV ave), and an imagable γ-emission make (177)Lu an attractive candidate for radioimmunotherapy (RIT) regimens for treatment of larger tumor burdens not possible with α-zparticle radiation. Radiolabeling trastuzumab-CHX-A"-DTPA with (177)Lu was efficient with a specific binding of 60.8 ± 6.8% with HER2 positive SKOV-3 cells. Direct quantitation of tumor targeting and normal tissue uptake was performed with athymic mice bearing subcutaneous and intraperitoneal LS-174T xenografts; a peak tumor %ID/g of 24.70 ± 10.29 (96 h) and 31.70 ± 16.20 (72 h), respectively, was obtained. Normal tissue uptake of the RIC was minimal. Tumor targeting was also demonstrated by γ-scintigraphy. A therapy study administering escalating doses of (177)Lu-trastuzumab to mice bearing three day LS-174T i.p. xenografts established the effective therapeutic dose of i.p. administered (177)Lu-trastuzumab at 375 μCi with a median survival of 124.5 d while a median survival of 10 d was noted for the control (untreated) group. In conclusion, trastuzumab radiolabeled with (177)Lu has potential for treatment of disseminated, HER2 positive, peritoneal disease.

Galactosylated streptavidin for improved clearance of biotinylated intact and F(ab')2 fragments of an anti-tumour antibody.

PubMed

Marshall, D; Pedley, R B; Melton, R G; Boden, J A; Boden, R; Begent, R H

1995-01-01

Persistence of high levels of radiolabelled antibody in the circulation is a major limitation of radioimmunotherapy. Biotinylation of the radiolabelled anti-tumour antibody followed by administration of streptavidin is known to give much improved tumour to blood ratios as the radioantibody is complexed and subsequently cleared via the reticuloendothelial system, although prolonged splenic uptake is a problem. We have investigated the effect on the clearance pattern and tumour localisation of a 125I-labelled biotinylated anti-CEA antibody (A5B7) after administration of a galactosylated form of streptavidin (gal-streptavidin) in nude mice bearing a human colon carcinoma xenograft. Fifteen minutes to 1 h after gal-streptavidin administration the complexes were cleared via the liver alone (as opposed to liver and spleen after native streptavidin). Twenty-four hours after administration of gal-streptavidin, the tumour to blood ratio for biotinylated A5B7 IgG increased from 2.9 to 13.2 and for biotinylated F(ab')2 fragments an increase from 4.9 to 33.2 was achieved. The reduction in tumour accumulation of F(ab')2 24 h after injection of the clearing agent was less than that seen with intact antibody. Injection of asialofetuin inhibited clearance, confirming that removal of the gal-streptavidin-biotinylated antibody complexes from the blood was via the asialoglycoprotein receptor on liver hepatocytes. Therefore, galactosylation of the streptavidin clearing agent allows rapid removal of radiolabelled biotinylated antibodies via the liver asialoglycoprotein receptor, as opposed to the reticuloendothelial system.

Enhancement of tumor-to-nontumor localization ratios by hepatocyte-directed blood clearance of antibodies labeled with certain residualizing radiolabels.

PubMed

Patel, S; Stein, R; Ong, G L; Goldenberg, D M; Mattes, M J

1999-08-01

To increase tumor-to-nontumor localization ratios of injected radiolabeled antibodies (Abs), several interrelated methods were used. The model systems used were two human carcinoma xenografts grown in nude mice, targeted by antibodies RS11 (antiepithelial glycoprotein-2) or MN-14 (anticarcinoembryonic antigen). The Abs were conjugated with biotin and 111In-benzyl diethylenetriamine pentaacetic acid, and, at various times after injection, were cleared by intraperitoneal injection of galactosylated streptavidin, which delivers the complexes to hepatocytes. The radiolabel used was selected because it is retained within tumors after catabolism of the Ab by the tumor cell but is quite rapidly excreted from hepatocytes into bile. With blood clearance induced at 24 h, and dissection 5 h later, high tumor-to-nontumor ratios were attained. Depending on the model used, tumor-to-blood ratios were 16:1 to 31:1, and tumor-to-nontumor ratios for the kidney, lungs and bone were also high and greatly increased by the clearance regimen. Despite clearance into the liver, tumor-to-liver ratios remained >1, due to fairly rapid biliary excretion of the label. The absolute antibody uptake by the tumors was also high, because 24 h was allowed for the Ab to penetrate and bind to cells within the subcutaneous tumors. The method described produced high tumor-to-nontumor ratios at 1 d after injection and may be advantageous for tumor imaging with antibodies. Radiation dosimetry calculations indicate that there is only a slight advantage with this approach for radioimmunotherapy.

Cancer Cell Radiobiological Studies Using In-House-Developed α-Particle Irradiator.

PubMed

Nilsson, Jenny; Bauden, Monika Posaric; Nilsson, Jonas M; Strand, Sven-Erik; Elgqvist, Jörgen

2015-11-01

An α-particle irradiator, enabling high-precision irradiation of cells for in vitro studies, has been constructed. The irradiation source was a (241)Am source, on which well inserts containing cancer cells growing in monolayer were placed. The total radioactivity, uniformity, and α-particle spectrum were determined by use of HPGe detector, Gafchromic dosimetry film, and PIPS detector measurements, respectively. Monte Carlo simulations were used for dosimetry. Three prostate cancer (LNCaP, DU145, PC3) and three pancreatic cancer (Capan-1, Panc-1, BxPC-3) cell lines were irradiated by α-particles to the absorbed doses 0, 0.5, 1, and 2 Gy. For reference, cells were irradiated using (137)Cs to the absorbed doses 0, 1, 2, 4, 6, 8, and 10 Gy. Radiation sensitivity was estimated using a tetrazolium salt-based colorimetric assay with absorbance measurements at 450 nm. The relative biological effectiveness for α-particles relative to γ-irradiation at 37% cell survival for the LNCaP, DU145, PC3, Capan-1, Panc-1, and BxPC-3 cells was 7.9 ± 1.7, 8.0 ± 0.8, 7.0 ± 1.1, 12.5 ± 1.6, 9.4 ± 0.9, and 6.2 ± 0.7, respectively. The results show the feasibility of constructing a desktop α-particle irradiator as well as indicate that both prostate and pancreatic cancers are good candidates for further studies of α-particle radioimmunotherapy.

A comparative evaluation of the chelators H4octapa and CHX-A″-DTPA with the therapeutic radiometal (90)Y.

PubMed

Price, Eric W; Edwards, Kimberly J; Carnazza, Kathryn E; Carlin, Sean D; Zeglis, Brian M; Adam, Michael J; Orvig, Chris; Lewis, Jason S

2016-09-01

To compare the radiolabeling performance, stability, and practical efficacy of the chelators CHX-A″-DTPA and H4octapa with the therapeutic radiometal (90)Y. The bifunctional chelators p-SCN-Bn-H4octapa and p-SCN-Bn-CHX-A″-DTPA were conjugated to the HER2-targeting antibody trastuzumab. The resulting immunoconjugates were radiolabeled with (90)Y to compare radiolabeling efficiency, in vitro and in vivo stability, and in vivo performance in a murine model of ovarian cancer. High radiochemical yields (>95%) were obtained with (90)Y-CHX-A″-DTPA-trastuzumab and (90)Y-octapa-trastuzumab after 15min at room temperature. Both (90)Y-CHX-A″-DTPA-trastuzumab and (90)Y-octapa-trastuzumab exhibited excellent in vitro and in vivo stability. Furthermore, the radioimmunoconjugates displayed high tumoral uptake values (42.3±4.0%ID/g for (90)Y-CHX-A″-DTPA-trastuzumab and 30.1±7.4%ID/g for (90)Y-octapa-trastuzumab at 72h post-injection) in mice bearing HER2-expressing SKOV3 ovarian cancer xenografts. Finally, (90)Y radioimmunotherapy studies performed in tumor-bearing mice demonstrated that (90)Y-CHX-A″-DTPA-trastuzumab and (90)Y-octapa-trastuzumab are equally effective therapeutic agents, as treatment with both radioimmunoconjugates yielded substantially decreased tumor growth compared to controls. Ultimately, this work demonstrates that the acyclic chelators CHX-A″-DTPA and H4octapa have comparable radiolabeling, stability, and in vivo performance, making them both suitable choices for applications requiring (90)Y. Copyright © 2016 Elsevier Inc. All rights reserved.

Dosimetry applications in GATE Monte Carlo toolkit.

PubMed

Papadimitroulas, Panagiotis

2017-09-01

Monte Carlo (MC) simulations are a well-established method for studying physical processes in medical physics. The purpose of this review is to present GATE dosimetry applications on diagnostic and therapeutic simulated protocols. There is a significant need for accurate quantification of the absorbed dose in several specific applications such as preclinical and pediatric studies. GATE is an open-source MC toolkit for simulating imaging, radiotherapy (RT) and dosimetry applications in a user-friendly environment, which is well validated and widely accepted by the scientific community. In RT applications, during treatment planning, it is essential to accurately assess the deposited energy and the absorbed dose per tissue/organ of interest, as well as the local statistical uncertainty. Several types of realistic dosimetric applications are described including: molecular imaging, radio-immunotherapy, radiotherapy and brachytherapy. GATE has been efficiently used in several applications, such as Dose Point Kernels, S-values, Brachytherapy parameters, and has been compared against various MC codes which are considered as standard tools for decades. Furthermore, the presented studies show reliable modeling of particle beams when comparing experimental with simulated data. Examples of different dosimetric protocols are reported for individualized dosimetry and simulations combining imaging and therapy dose monitoring, with the use of modern computational phantoms. Personalization of medical protocols can be achieved by combining GATE MC simulations with anthropomorphic computational models and clinical anatomical data. This is a review study, covering several dosimetric applications of GATE, and the different tools used for modeling realistic clinical acquisitions with accurate dose assessment. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Targeting radioimmunotherapy of hepatocellular carcinoma with iodine ({sup 131}I) metuximab injection: Clinical Phase I/II trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen Zhinan; Mi Li; Xu Jing

2006-06-01

Purpose: HAb18G/CD147 is a hepatocellular carcinoma (HCC)-associated antigen. We developed iodine ({sup 131}I) metuximab injection (Licartin), a novel {sup 131}I-labeled HAb18G/CD147-specific monoclonal antibody F(ab'){sub 2} fragment, and evaluated its safety, pharmacokinetics, and clinical efficacy on HCC in Phase I/II trials. Methods and Materials: In a Phase I trial, 28 patients were randomly assigned to receive the injection in 9.25-, 18.5-, 27.75-, or 37-MBq/kg doses by hepatic artery infusion. In a multicenter Phase II trial, 106 patients received the injection (27.75 MBq/kg) on Day 1 of a 28-day cycle. Response rate and survival rate were the endpoints. Results: No life-threatening toxicmore » effects were found. The safe dosage was 27.75 MBq/kg. The blood clearance fitted a biphasic model, and its half-life was 90.56-63.93 h. In the Phase II trial, the injection was found to be targeted and concentrated to tumor tissues. Of the 73 patients completing two cycles, 6 (8.22%) had a partial response, 14 (19.18%) minor response, and 43 (58.90%) stable disease. The 21-month survival rate was 44.54%. The survival rate of progression-free patients was significantly higher than that of patients with progressive disease after either one or two cycles (p < 0.0001 or p 0.0019). Conclusion: Iodine ({sup 131}I) metuximab injection is safe and active for HCC patients.« less

Comparative quantitative analysis of cluster of differentiation 45 antigen expression on lymphocyte subsets.

PubMed

Im, Mijeong; Chae, Hyojin; Kim, Taehoon; Park, Hun-Hee; Lim, Jihyang; Oh, Eun-Jee; Kim, Yonggoo; Park, Yeon-Joon; Han, Kyungja

2011-07-01

Since the recent introduction of radioimmunotherapy (RIT) using antibodies against cluster of differentiation (CD) 45 for the treatment of lymphoma, the clinical significance of the CD45 antigen has been increasing steadily. Here, we analyzed CD45 expression on lymphocyte subsets using flow cytometry in order to predict the susceptibility of normal lymphocytes to RIT. Peripheral blood specimens were collected from 14 healthy individuals aged 25-54 yr. The mean fluorescence intensity (MFI) of the cell surface antigens was measured using a FACSCanto II system (Becton Dickinson Bioscience, USA). MFI values were converted into antibody binding capacity values using a Quantum Simply Cellular microbead kit (Bangs Laboratories, Inc., USA). Among the lymphocyte subsets, the expression of CD45 was the highest (725,368±42,763) on natural killer T (NKT) cells, 674,030±48,187 on cytotoxic/suppressor T cells, 588,750±48,090 on natural killer (NK) cells, 580,211±29,168 on helper T (Th) cells, and 499,436±21,737 on B cells. The Th cells and NK cells expressed a similar level of CD45 (P=0.502). Forward scatter was the highest in NKT cells (P<0.05), whereas side scatter differed significantly between each of the lymphocyte subsets (P<0.05). CD3 expression was highest in the Th and NKT cells. NKT cells express the highest levels of CD45 antigen. Therefore, this lymphocyte subset would be most profoundly affected by RIT or pretargeted RIT. The monitoring of this lymphocyte subset during and after RIT should prove helpful.

Report of the Evaluation of the Race/Human Relations Program. Student and Staff Program and Long Range Goals. Baseline Year 1982-83. Evaluation Services Department Report No. 348.

ERIC Educational Resources Information Center

Tomblin, Elizabeth A.; And Others

In response to a 1982 Superior Court order, a centrally developed, sequential program for improving race/human relations in the San Diego City Schools was developed and field tested or implemented during the 1982-83 school year. This systematic evaluation reports on the student program, "Conflict"; the staff program; and baseline data…

Welfare policies and very young children: experimental data on stage-environment fit.

PubMed

Hill, Heather D; Morris, Pamela

2008-11-01

The authors examined the effects of welfare programs that increased maternal employment and family income on the development of very young children using data from 5 random-assignment experiments. The children were 6 months to 3 years old when their mothers entered the programs; cognitive and behavioral outcomes were measured 2-5 years later. While there were no overall program impacts, positive or negative, on the development of children in this age group, there was a pair of domain- and age-specific effects: The programs decreased positive social behavior among 1-year-olds and increased school achievement among 2-year-olds. After exploring several explanations for these results, the authors suggest that the contextual changes engendered by the programs, including children's exposure to center-based child care, interacted differentially with specific developmental transitions.

North American veterinary pathology residency training programs: an overview of where they are today and where they were five years ago, with an analysis of trends.

PubMed

Fitzgerald, Scott D; Reed, Willie M; Kaneene, John B

2007-01-01

An e-mail/telephone survey of all active North American residency training programs in veterinary pathology was conducted in September 2005. The purpose of this survey was to determine current numbers of trainees, their program length and type, and salaries; to compare current numbers to five years earlier; and, finally, to gauge interest in expanding current programs. All 41 training institutions contacted responded to the survey. Briefly, the survey found that there are currently 235 veterinary pathology residents, for a mean of 5.7 residents per training program. The number of residents currently in training programs and the number of applicants for these programs has increased compared to five years earlier. There is widespread interest in further expanding capacity in these programs, and the coalition of the American College of Veterinary Pathologists and the Society of Toxicologic Pathology is a well-known source of possible funding for additional residents. This survey report further documents the numbers of combined residency/PhD programs, average starting salaries for new residents, outside sponsorship effects on pathology training programs, and some of the common concerns regarding veterinary pathology training programs voiced by the respondents. While residency training capacity has expanded in the last five years, and there is widespread desire to further expand these training programs, a shortage of veterinary pathologists for future market needs will need to be addressed by increased funding from as yet unspecified sources.

Evaluating an employee wellness program.

PubMed

Mukhopadhyay, Sankar; Wendel, Jeanne

2013-12-01

What criteria should be used to evaluate the impact of a new employee wellness program when the initial vendor contract expires? Published academic literature focuses on return-on-investment as the gold standard for wellness program evaluation, and a recent meta-analysis concludes that wellness programs can generate net savings after one or two years. In contrast, surveys indicate that fewer than half of these programs report net savings, and actuarial analysts argue that return-on-investment is an unrealistic metric for evaluating new programs. These analysts argue that evaluation of new programs should focus on contract management issues, such as the vendor's ability to: (i) recruit employees to participate and (ii) induce behavior change. We compute difference-in-difference propensity score matching estimates of the impact of a wellness program implemented by a mid-sized employer. The analysis includes one year of pre-implementation data and three years of post-implementation data. We find that the program successfully recruited a broad spectrum of employees to participate, and it successfully induced short-term behavior change, as manifested by increased preventive screening. However, the effects on health care expenditures are positive (but insignificant). If it is unrealistic to expect new programs to significantly reduce healthcare costs in a few years, then focusing on return-on-investment as the gold standard metric may lead to early termination of potentially useful wellness programs. Focusing short-term analysis of new programs on short-term measures may provide a more realistic evaluation strategy.

Malaria burden and treatment targets in Kachin Special Region II, Myanmar from 2008 to 2016: A retrospective analysis

PubMed Central

Bi, Yaw

2018-01-01

Although drug-based treatment is the primary intervention for malaria control and elimination, optimal use of targeted treatments remains unclear. From 2008 to 2016, three targeted programs on treatment were undertaken in Kachin Special Region II (KR2), Myanmar. Program I (2008–2011) treated all confirmed, clinical and suspected cases; program II (2012–2013) treated confirmed and clinical cases; and program III (2014–2016) targeted confirmed cases only. This study aims to evaluate the impacts of the three programs on malaria burden individually based on the annual parasite incidence (API), slide positivity rate (SPR) and their relative values. The API is calculated from original collected data and the incidence rate ratio (IRR) for each year is calculated by using the first-year API as a reference in each program phase across the KR2. Same method is applied to calculate SPR and risk ratio (RR) at the sentinel hospital too. During program I (2008–2011), malaria burden was reduced by 61% (95%CI: 58%-74%) and the actual API decreased from 9.8 (95%CI: 9.6–10.1) per 100 person-years in 2008 to 3.8 (3.6–4.1) per 100 person-years in 2011. Amid program II (2012–2013), the malaria burden increased by 33% (95%CI: 22%-46%) and the actual API increased from 2.1(95%CI: 2.0–2.3) per 100 person-years in 2012 to 2.8 (95%CI: 2.7–2.9) per 100 person-years in 2013. During program III (2014–2016) the malaria burden increased furtherly by 60% (95%CI: 51% - 69%) and the actual API increased from 3.2(95%CI: 3.0–3.3) per 100 person-years in 2014 to 5.1 (95%CI: 4.9–5.2) per 100 person-years in 2016. Results of the slide positivity of the sentinel hospital also confirm these results. Resurgence of malaria was mainly due to Plasmodium vivax during program II and III. This study indicates that strategy adopted in program I (2008–2011) should be more appropriate for the KR2. Quality-assured treatment of all confirmed, clinical and suspected malaria cases may be helpful for the reduction of malaria burden. PMID:29614088

Cost-benefit analysis of a preventive intervention for divorced families: reduction in mental health and justice system service use costs 15 years later.

PubMed

Herman, Patricia M; Mahrer, Nicole E; Wolchik, Sharlene A; Porter, Michele M; Jones, Sarah; Sandler, Irwin N

2015-05-01

This cost-benefit analysis compared the costs of implementing the New Beginnings Program (NBP), a preventive intervention for divorced families to monetary benefits saved in mental healthcare service use and criminal justice system costs. NBP was delivered when the offspring were 9-12 years old. Benefits were assessed 15 years later when the offspring were young adults (ages 24-27). This study estimated the costs of delivering two versions of NBP, a single-component parenting-after-divorce program (Mother Program, MP) and a two-component parenting-after-divorce and child-coping program (Mother-Plus-Child Program, MPCP), to costs of a literature control (LC). Long-term monetary benefits were determined from actual expenditures from past-year mental healthcare service use for mothers and their young adult (YA) offspring and criminal justice system involvement for YAs. Data were gathered from 202 YAs and 194 mothers (75.4 % of families randomly assigned to condition). The benefits, as assessed in the 15th year after program completion, were $1630/family (discounted benefits $1077/family). These 1-year benefits, based on conservative assumptions, more than paid for the cost of MP and covered the majority of the cost of MPCP. Because the effects of MP versus MPCP on mental health and substance use problems have not been significantly different at short-term or long-term follow-up assessments, program managers would likely choose the lower-cost option. Given that this evaluation only calculated economic benefit at year 15 and not the previous 14 (nor future years), these findings suggest that, from a societal perspective, NBP more than pays for itself in future benefits.

Long-term Effects of the Family Bereavement Program (FBP) on Spousally-Bereaved Parents: Grief, Mental Health, Alcohol Problems, and Coping Efficacy

PubMed Central

Sandler, Irwin; Tein, Jenn-Yun; Cham, Heining; Wolchik, Sharlene; Ayers, Tim

2016-01-01

Objective Reports on the finding from a six-year follow-up of a randomized trial of the Family Bereavement Program (FBP) on outcomes for spousally-bereaved parents. Method Spousally-bereaved parents (N=131) participated in the trial in which they were randomly assigned to receive the FBP (N = 72) or literature control (LC, N = 59). Parents were assessed at four time points, pre-test, post-test, 11-months, and six-year follow-up. Parents reported on mental health problems, grief and parenting at all four time periods. At the six-year follow-up parents reported on additional measures of persistent complex bereavement disorder, alcohol abuse problems, and coping efficacy. Results Bereaved parents in the FBP as compared to those in the LC had lower levels of symptoms of depression, general psychiatric distress, prolonged grief, alcohol problems, and higher coping efficacy at the six-year follow-up. Multiple characteristics of the parent (e.g., gender, age, baseline mental health problems) and of the spousal death (e.g., cause of death) were tested as moderators of program effects on each outcome. Latent-growth modeling found that the effects of the FBP on depression, psychiatric distress and grief occurred immediately following program participation and were maintained over six-years. Mediation analysis found that improvement in positive parenting partially mediated program effects to reduce depression and psychiatric distress, but had an indirect effect to higher levels of grief at the six years follow-up. Mediation analysis also found that improved parenting at the six year follow-up was partially mediated by program effects to reduce depression and that program effects to increase coping efficacy at the six-year follow-up was partially mediated through reduced depression and grief and improved parenting. Conclusions FBP reduced mental health problems, prolonged grief and alcohol abuse and increased coping efficacy of spousally-bereaved parents six years later. Mediation pathways for program effects differed across outcomes at the six-year follow-up. PMID:27427807

Two-Year Findings from a National Effectiveness Trial: Effectiveness of Behavioral and Non-Behavioral Parenting Programs.

PubMed

Högström, Jens; Olofsson, Viveca; Özdemir, Metin; Enebrink, Pia; Stattin, Håkan

2017-04-01

Long-term follow-up studies of selective parent training (PT) programs are scarce, particularly in the case of effectiveness trials conducted within regular care settings. This study evaluated the 2-year effects of 4 programs: Comet, Incredible Years, Cope, and Connect and differences in the rate of change among programs were investigated using Latent Growth Modeling (LGM). Participants were parents who had sought help at 30 local service sector units (e.g., child psychiatric clinics and social services centers) for major problems in managing their children's externalizing behavior. Parents of 749 children (63 % boys) with moderate levels of externalizing behavior, aged 3-12, were randomized to one of the 4 PT programs. Assessments included parent-reported measures of child externalizing, hyperactivity and inattention, as well as parenting practices, sense of competence, and parents' stress and depressive symptoms. At 2-year follow-up, there were no differences in any of the child outcomes among the programs. All programs had reduced externalizing behaviors with large effect sizes (d = 1.21 to d = 1.32), and negative parenting practices with moderate to large effect sizes (d = 0.49 to d = 0.83). LGM analyses showed that the 2 behavioral programs, Comet and Incredible Years, produced more rapid reductions in externalizing behavior during the course of the intervention than the non-behavioral program, Connect. Connect, however, was the only program where children continued to improve after the intervention. Overall, the results indicate that the 4 programs were equally effective in a clinical setting, despite differences in their theoretical origin.

Energy Education Program Development in Two-Year Postsecondary Institutions: A Look at National Surveys.

ERIC Educational Resources Information Center

Mahoney, James R.

This report examines energy-related vocational programs at two-year colleges and discusses the factors to be considered in the future development of these programs. The report first presents the major findings of five surveys conducted between 1975 and 1979 to determine the number of degree and certificate programs offered in energy-related areas.…

First-Year Male Students' Perceptions of a Rape Prevention Program 7 Months after Their Participation: Attitude and Behavior Changes

ERIC Educational Resources Information Center

Foubert, John D.; Tatum, Jerry L.; Godin, Eric E.

2010-01-01

Seven months after seeing The Men's Program, a commonly used rape prevention program, 248 first-year college men responded to four open-ended questions concerning whether or not the program impacted their attitudes or behavior, particularly regarding alcohol related sexual assault. Two thirds of participants reported either attitude or behavior…

Fast Break to Learning School Breakfast Program: A Report of the Second Year Results, 2000-2001.

ERIC Educational Resources Information Center

Peterson, Kristin; Davison, Mark; Wahlstrom, Kyla; Himes, John; Irish, Margaret L.

This report provides Year 2 data comparing two types of school breakfast programs in Minnesota to schools that did not serve breakfast at all (No Breakfast schools): Fast Break to Learning, a universal free breakfast program (Fastbreak schools), and programs with a sliding fee scale (control schools). Data were collected from 30 Fastbreak, 195…

Energy-Related Technology Programs in Community and Junior Colleges: An Analysis of Existing and Planned Programs.

ERIC Educational Resources Information Center

Doggette, John R.

This study was conducted to provide a basis for planning for needed energy-related occupational technology programs in two-year educational institutions. A questionnaire was sent to 1,152 junior, community, and technical colleges in fall 1975; 774 (67%) responded. The survey identified 62 existing one- and two-year energy-related programs and 132…

California Update: Student Progress in State and Federally Funded Adult Education Programs during the 1997-98 Instructional Year.

ERIC Educational Resources Information Center

Comprehensive Adult Student Assessment System, San Diego, CA.

This document outlines student progress within each of California's Adult Education programs for the 1997-1998 academic year. During this time period, California's Adult Education programs served 1,435,341 learners. Among those enrolled, 161,364 students were served by Adult Basic Education (ABE) programs, and an additional 1,220,594 students were…

77 FR 54615 - Strategic Management Program; Fiscal Year 2013-2016 Strategic Plan

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-05

... Manager, Strategic Management Program; National Transportation Safety Board, 490 L'Enfant Plaza SW., MD-1... NATIONAL TRANSPORTATION SAFETY BOARD Strategic Management Program; Fiscal Year 2013-2016 Strategic Plan AGENCY: National Transportation Safety Board. ACTION: Notice: Request for comments. SUMMARY: This...

Enhancing youth outcomes following parental divorce: A longitudinal study of the effects of the New Beginnings Program on educational and occupational goals

PubMed Central

Sigal, Amanda B.; Wolchik, Sharlene A.; Tein, Jenn-Yun; Sandler, Irwin N.

2011-01-01

This study examined whether the New Beginnings Program for divorced families led to improvements in youth’s educational goals and job aspirations six years following participation and tested whether several parenting and youth variables mediated the program effects. Participants were 240 youth aged 9–12 years at the initial assessment, and data were part of a randomized, experimental trial of a parenting skills preventive intervention targeting children’s post-divorce adjustment. The results revealed positive effects of the program on youth’s educational goals and job aspirations six years after participation for those who were at high risk for developing later problems at program entry. Further, intervention-induced changes in mother-child relationship quality and youth externalizing problems, internalizing problems, self-esteem, and academic competence at the six-year follow-up mediated the effects of the program on the educational expectations of high-risk youth. Intervention-induced changes in youth externalizing problems and academic competence at the six-year follow-up mediated the effects of the program on the job aspirations of high-risk youth. Implications of the present findings for research with youth from divorced families and for the public health burden of divorce are discussed. PMID:22417189

The effects of workplace health promotion on absenteeism and employment costs in a large industrial population.

PubMed Central

Bertera, R L

1990-01-01

We evaluated the impact of a comprehensive workplace health promotion program on absences among full-time employees in a large, multi-location, diversified industrial company. A pretest-posttest control group design was used to study 41 intervention sites and 19 control sites with 29,315 and 14,573 hourly employees, respectively. Blue-collar employees at intervention sites experienced an 14.0 percent decline in disability days over two years versus a 5.8 percent decline at control sites. This resulted in a net difference of 11,726 fewer disability days over two years at program sites compared with non-program sites. Savings due to lower disability costs at intervention sites offset program costs in the first year, and provided a return of $2.05 for every dollar invested in the program by the end of the second year. These results suggest that comprehensive workplace health promotion programs can reduce disability days among blue collar employees and provide a good return on investment. PMID:2382748

The accelerated residency program: the Marshall University family practice 9-year experience.

PubMed

Petrany, Stephen M; Crespo, Richard

2002-10-01

In 1989, the American Board of Family Practice (ABFP) approved the first of 12 accelerated residency programs in family practice. These experimental programs provide a 1-year experience for select medical students that combines the requirements of the fourth year of medical school with those of the first year of residency, reducing the total training time by 1 year. This paper reports on the achievements and limitations of the Marshall University accelerated residency program over a 9-year period that began in 1992. Several parameters have been monitored since the inception of the accelerated program and provide the basis for comparison of accelerated and traditional residents. These include initial resident characteristics, performance outcomes, and practice choices. A total of 16 students were accepted into the accelerated track from 1992 through 1998. During the same time period, 44 residents entered the traditional residency program. Accelerated resident tended to be older and had more career experience than their traditional counterparts. As a group, the accelerated residents scored an average of 30 points higher on the final in-training exams provided by the ABFP. All residents in both groups remained at Marshall to complete the full residency training experience, and all those who have taken the ABFP certifying exam have passed. Accelerated residents were more likely to practice in West Virginia, consistent with one of the initial goals for the program. In addition, accelerated residents were more likely to be elected chief resident and choose an academic career than those in the traditional group. Both groups opted for small town or rural practice equally. The Marshall University family practice 9-year experience with the accelerated residency track demonstrates that for carefully selected candidates, the program can provide an overall shortened path to board certification and attract students who excel academically and have high leadership potential. Reports from other accelerated programs are needed to fully assess the outcomes of this experiment in postgraduate medical education.

Practice patterns of graduates of 2- and 3-year family medicine programs: in Ontario, 1996 to 2004.

PubMed

Green, Michael; Birtwhistle, Richard; Macdonald, Ken; Kane, John; Schmelzle, Jason

2009-09-01

To compare patterns of practice between graduates of core 2-year family medicine (FM) training programs and those completing an additional postgraduate year (PGY3) of training. Retrospective cohort study using administrative data from the Ontario Health Insurance Plan. Ontario. Graduates of Ontario FM residency programs from 1996 to 2002 who provided insured services in Ontario for 1 or more fiscal years between 1996 and 2004. Proportion of physician years of service in which a minimum number of services were provided in each of the following categories: anesthesia, emergency medicine (EM), home visits, hospital visits, nursing home visits, intrapartum obstetrics, palliative care, office-only practice, and rural locations, as well as deciles for proportion of billings for emergency department work and "quasi-specialty" designations based on billing patterns. Results are stratified by type of training and years in practice. Graduates of PGY3 programs are significantly more likely to practise in a range of nonoffice settings than their counterparts who completed core 2-year FM training programs. Differences were the most marked in areas in which additional training had been undertaken, but also extended to other categories. There was no effect on the proportion practising in rural locations, unless the training was undertaken in a rural setting or in anesthesia. Physicians including EM in their practices were more likely to practise mostly or almost all EM if they had undertaken either EM programs or self-directed programs at non-northern training sites. Very few graduates of any type were classified as belonging to a quasi-specialty group, other than those who completed care of the elderly or palliative care (hospitalist) and anesthesia programs. Completion of a PGY3 program is strongly associated with increased participation in practice outside the office, particularly in the area of the training provided.

The pediatric resident training on tobacco project: interim findings.

PubMed

Hymowitz, Norman; Schwab, Joseph; Haddock, Christopher Keith; Pyle, Sara; Meshberg, Sarah

2006-02-01

The Pediatric Residency Training on Tobacco Project is a four-year randomized prospective study of the efficacy of training pediatric residents to intervene on tobacco. At the start of the study (baseline), the pediatric residents uniformly agreed that environmental tobacco smoke (ETS) and tobacco use pose serious threats to the health of young people, and pediatricians should play a leadership role in the antismoking arena. However, very few went beyond advising patients and parents to modify their behavior by providing actual assistance, and many of them lacked necessary tobacco intervention skills and knowledge. We hypothesized that both standard training and special training programs would yield positive changes in intervention skills and activities, although the changes would be greater in residents exposed to the special training condition. In the present report, we present two-year outcome data from the resident tobacco surveys and objective structured clinical examinations (OSCEs) administered to independent waves of third-year residents in each experimental condition at baseline and year 2. Fifteen pediatric residency training programs in the New York/New Jersey metropolitan area were assigned randomly to special and standard training conditions (eight to special and seven to standard training). Resident tobacco surveys and OSCEs were administered to third-year residents at the start of the training programs (baseline) and at years 1 and 2 of the study. Comparisons between sequential waves of third-year residents with no (baseline) or two-year exposure to the training programs permitted assessment of changes in resident beliefs, intervention activities and intervention skills within each experimental condition. By year 2, the residents associated with each training condition benefited from the training program, but the annual surveys and OSCEs revealed more significant positive changes for waves of residents in the special training condition. Most important, third-year residents exposed to the special training condition for two years were more likely than comparable residents in the standard training condition to reveal significant increases in the degree to which they provided active assistance for modifying smoking and ETS. The two-year findings from the pediatric tobacco project are encouraging and suggest that the special training program is efficacious, although aspects of the program in need of improvement were identified.

A TWO-YEAR POST-HIGH SCHOOL DISTRIBUTIVE EDUCATION PROGRAM IN THE WHOLESALING FIELD, REPORT OF THE OHIO WHOLESALE MANAGEMENT DEVELOPMENT PROGRAM. MANUAL 2, CURRICULUM FOR A PROGRAM.

ERIC Educational Resources Information Center

LOGAN, WILLIAM B.; AND OTHERS

THE PURPOSE OF THIS MANUAL IS TO SERVE AS A CURRICULUM GUIDE FOR PLANNING COURSES FOR A 2-YEAR POST-HIGH SCHOOL DISTRIBUTIVE EDUCATION PROGRAM IN THE FIELD OF WHOLESALING. THE CONTENT WAS DEVELOPED BY A RESEARCH GROUP AND INCORPORATED SUGGESTIONS THE INSTRUCTORS IN AN EXPERIMENTAL PROGRAM CONDUCTED ON THE CAMPUS OF THE OHIO STATE UNIVERSITY FOR 4…

Processes and Procedures of the Higher Education Programs at Marshall Space Flight Center

NASA Technical Reports Server (NTRS)

Heard, Pamala D.

2002-01-01

The purpose of my research was to investigate the policies, processes, procedures and timelines for the higher education programs at Marshall Space Flight Center. The three higher education programs that comprised this research included: the Graduate Student Researchers Program (GSRP), the National Research Council/Resident Research Associateships Program (NRC/RRA) and the Summer Faculty Fellowship Program (SFFP). The GSRP award fellowships each year to promising U.S. graduate students whose research interest coincides with NASA's mission. Fellowships are awarded for one year and are renewable for up to three years to competitively selected students. Each year, the award provides students the opportunity to spend a period in residence at a NASA center using that installation's unique facilities. This program is renewable for three years, students must reapply. The National Research Council conducts the Resident Research Associateships Program (NRC/RRA), a national competition to identify outstanding recent postdoctoral scientists and engineers and experience senior scientists and engineers, for tenure as guest researchers at NASA centers. The Resident Research Associateship Program provides an opportunity for recipients of doctoral degrees to concentrate their research in association with NASA personnel, often as a culmination to formal career preparation. The program also affords established scientists and engineers an opportunity for research without any interruptions and distracting assignments generated from permanent career positions. All opportunities for research at NASA Centers are open to citizens of the U.S. and to legal permanent residents. The Summer Faculty Fellowship Program (SFFP) is conducted each summer. NASA awards research fellowships to university faculty through the NASA/American Society for Engineering Education. The program is designed to promote an exchange of ideas between university faculties, NASA scientists and engineers. Selected participants in fields of science, engineering, math, and other disciplines spend approximately 10 weeks working with their professional peers on research projects at NASA facilities. Workshops and seminars further enrich the experience. This program is only for U.S. citizens.

The status of PhD education in economic, social, and administrative sciences between 2005 and 2008.

PubMed

Farley, Joel F; Wang, Chi-Chuan; Blalock, Susan J

2010-09-10

To describe the funding, education, enrollment, and graduation patterns from economic, social, and administrative sciences PhD programs in colleges and schools of pharmacy in the United States. Economic, social, and administrative sciences PhD programs were identified from the American Association of Colleges of Pharmacy (AACP) Web site. A 41-item online survey instrument was sent to the director of graduate studies of each identified program. Only programs offering a PhD degree were included in the study. Of the 26 programs surveyed, 20 (77%) provided useable responses to the survey instrument. Approximately 91% of PhD programs guarantee funding to incoming students with an average commitment of 2.9 years. On average, students were paid a stipend of $18,000 per year for commitments to research and teaching assistantships, each averaging approximately 2 years in length. Programs admitted an average of 3.5 students per year and graduated approximately 85% of entering students. The majority of students are non-US citizens and accept positions in either academic or industrial positions after graduation. Most economic, social, and administrative sciences PhD programs guarantee funding to incoming PhD candidates. Programs offering funding packages significantly below the average may be at a competitive disadvantage. It is unclear whether the number of students graduating from PhD programs is adequate to fulfill academic and industrial needs.

Undergraduate design projects to aid persons with disabilities: reflections.

PubMed

Barret, Steven F; Morton, Scott A; Root-Elledge, Sandy

2007-01-01

In Spring 2002 the University of Wyoming, College of Engineering, received a five year grant from the National Science Foundation to link senior capstone design projects with the custom requirements of the assistive technology (AT) community. This serendipitous collaboration has been highly beneficial to our senior design students as well as individuals with a disability requiring one-of-a-kind AT devices. Now that the program is coming to a close on its five year term, we believe there are lessons we have learned that would be valuable to others considering participation in such a program. We will briefly review program development and organization, highlight lessons learned, and discuss program benefits and pitfalls. Paper emphasis will be on the practical implementation and management of this valuable program. Due to the rich benefits received from participating in the program, we plan on applying for a second five year program funding increment.

Women in science & engineering scholarships and summer camp outreach programs : year 7.

DOT National Transportation Integrated Search

2014-08-01

Since the UTC Scholarship program began in the spring of 2005 and continues today on the S&T campus, numerous female students : have benefitted tremendously from this source of financial aid. The program began in the first few years with 15-30 awards...

Academic Year Abroad. 1988-89.

ERIC Educational Resources Information Center

Howard, Edrice Marguerite, Ed.

This directory of study-abroad programs provides information on over 1,500 postsecondary study programs that take place in countries other than the United States during the academic year. An introductory section describes the organization of the listings (which provide program sponsor and name, location, dates, subjects, credit, eligibility,…

24 CFR 91.10 - Consolidated program year.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Consolidated program year. 91.10 Section 91.10 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development CONSOLIDATED SUBMISSIONS FOR COMMUNITY PLANNING AND DEVELOPMENT PROGRAMS General § 91.10...

44 CFR 360.2 - Description of program.

Code of Federal Regulations, 2013 CFR

2013-10-01

... application, to be accompanied by a Training and Education (T&E) plan for a total of three years, only the... three year comprehensive Training and Education Program planning can proceed in a timely and logical... HOMELAND SECURITY PREPAREDNESS STATE ASSISTANCE PROGRAMS FOR TRAINING AND EDUCATION IN COMPREHENSIVE...

44 CFR 360.2 - Description of program.

Code of Federal Regulations, 2012 CFR

2012-10-01

... application, to be accompanied by a Training and Education (T&E) plan for a total of three years, only the... three year comprehensive Training and Education Program planning can proceed in a timely and logical... HOMELAND SECURITY PREPAREDNESS STATE ASSISTANCE PROGRAMS FOR TRAINING AND EDUCATION IN COMPREHENSIVE...

44 CFR 360.2 - Description of program.

Code of Federal Regulations, 2010 CFR

2010-10-01

... application, to be accompanied by a Training and Education (T&E) plan for a total of three years, only the... three year comprehensive Training and Education Program planning can proceed in a timely and logical... HOMELAND SECURITY PREPAREDNESS STATE ASSISTANCE PROGRAMS FOR TRAINING AND EDUCATION IN COMPREHENSIVE...

44 CFR 360.2 - Description of program.

Code of Federal Regulations, 2011 CFR

2011-10-01

... application, to be accompanied by a Training and Education (T&E) plan for a total of three years, only the... three year comprehensive Training and Education Program planning can proceed in a timely and logical... HOMELAND SECURITY PREPAREDNESS STATE ASSISTANCE PROGRAMS FOR TRAINING AND EDUCATION IN COMPREHENSIVE...

44 CFR 360.2 - Description of program.

Code of Federal Regulations, 2014 CFR

2014-10-01

... application, to be accompanied by a Training and Education (T&E) plan for a total of three years, only the... three year comprehensive Training and Education Program planning can proceed in a timely and logical... HOMELAND SECURITY PREPAREDNESS STATE ASSISTANCE PROGRAMS FOR TRAINING AND EDUCATION IN COMPREHENSIVE...

NIDRR Program Directory, Fiscal Year 1997.

ERIC Educational Resources Information Center

KRA Corp., Silver Spring, MD.

This directory lists all projects funded by the National Institute of Disability and Rehabilitation Research (NIDRR) during the 1997 fiscal year. It includes summaries, funding data, and contact information for a broad range of programs. Programs are grouped into the following categories: (1) research and demonstration projects; (2) rehabilitation…

77 FR 74185 - Notice of Debarment

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-13

... from the schools and libraries universal service support mechanism (or ``E-Rate Program'') for a period of three years. The Bureau takes this action to protect the E-Rate Program from waste, fraud and... and libraries universal service support mechanism (E-Rate program) for three years from either the...

76 FR 61089 - Indirect Cost Rates for the Damage Assessment, Remediation, and Restoration Program for Fiscal...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-03

... Damage Assessment, Remediation, and Restoration Program for Fiscal Years 2009 and 2010 AGENCY: National... Damage Assessment, Remediation, and Restoration Program for Fiscal Years 2009 and 2010. SUMMARY: The National Oceanic and Atmospheric Administration's (NOAA's) Damage Assessment, Remediation, and Restoration...

Association of General Surgery Resident Remediation and Program Director Attitudes With Resident Attrition.

PubMed

Schwed, Alexander C; Lee, Steven L; Salcedo, Edgardo S; Reeves, Mark E; Inaba, Kenji; Sidwell, Richard A; Amersi, Farin; Are, Chandrakanth; Arnell, Tracey D; Damewood, Richard B; Dent, Daniel L; Donahue, Timothy; Gauvin, Jeffrey; Hartranft, Thomas; Jacobsen, Garth R; Jarman, Benjamin T; Melcher, Marc L; Mellinger, John D; Morris, Jon B; Nehler, Mark; Smith, Brian R; Wolfe, Mary; Kaji, Amy H; de Virgilio, Christian

2017-12-01

Previous studies of resident attrition have variably included preliminary residents and likely overestimated categorical resident attrition. Whether program director attitudes affect attrition has been unclear. To determine whether program director attitudes are associated with resident attrition and to measure the categorical resident attrition rate. This multicenter study surveyed 21 US program directors in general surgery about their opinions regarding resident education and attrition. Data on total resident complement, demographic information, and annual attrition were collected from the program directors for the study period of July 1, 2010, to June 30, 2015. The general surgery programs were chosen on the basis of their geographic location, previous collaboration with some coauthors, prior work in surgical education and research, or a program director willing to participate. Only categorical surgical residents were included in the study; thus, program directors were specifically instructed to exclude any preliminary residents in their responses. Five-year attrition rates (2010-2011 to 2014-2015 academic years) as well as first-time pass rates on the General Surgery Qualifying Examination and General Surgery Certifying Examination of the American Board of Surgery (ABS) were collected. High- and low-attrition programs were compared. The 21 programs represented different geographic locations and 12 university-based, 3 university-affiliated, and 6 independent program types. Programs had a median (interquartile range [IQR]) number of 30 (20-48) categorical residents, and few of those residents were women (median [IQR], 12 [5-17]). Overall, 85 of 966 residents (8.8%) left training during the study period: 15 (17.6%) left after postgraduate year 1, 34 (40.0%) after postgraduate year 2, and 36 (42.4%) after postgraduate year 3 or later. Forty-four residents (51.8%) left general surgery for another surgical discipline, 21 (24.7%) transferred to a different surgery program, and 18 (21.2%) exited graduate medical education altogether. Each program had an annual attrition rate ranging from 0.73% to 6.0% (median [IQR], 2.5% [1.5%-3.4%]). Low-attrition programs were more likely than high-attrition programs to use resident remediation (21.0% vs 6.8%; P < .001). Median (IQR) Qualifying Examination pass rates (93% [90%-98%] vs 92% [86%-100%]; P = .92) and Certifying Examination pass rates (83% [68%-84%] vs 81% [71%-86%]; P = .47) were similar. Program directors at high-attrition programs were more likely than their counterparts at low-attrition programs to agree with this statement: "I feel that it is my responsibility as a program director to redirect residents who should not be surgeons." The overall 5-year attrition rate of 8.8% was significantly lower than previously reported. Program directors at low-attrition programs were more likely to use resident remediation. Variations in attrition may be explained by program director attitudes, although larger studies are needed to further define program factors affecting attrition.

Nine-year follow-up of a home-visitation program: a randomized trial.

PubMed

Fergusson, David M; Boden, Joseph M; Horwood, L John

2013-02-01

To evaluate the extent to which a home-visitation program (Early Start) had benefits for child abuse, child behavior, and parental- and family-level benefits to the 9-year follow-up. A randomized controlled trial in which 220 families receiving Early Start were contrasted with a control series of 223 families not receiving the program. Families were enrolled in the program for up to 5 years. Outcomes were assessed at 6 months, annually from 1 year to 6 years, and at 9 years after trial entry. Comparisons between the Early Start and control series showed that families in the Early Start program showed significant (P < .05) benefits in reduced risk of hospital attendance for unintentional injury, lower risk of parent-reported harsh punishment, lower levels of physical punishment, higher parenting competence scores, and more positive child behavioral adjustment scores. Effect sizes (Cohen's "d") ranged from 0.13 to 0.29 (median = 0.25). There were no significant differences (all P values > .05) between the Early Start and control series on a range of measures of parental behavior and family outcomes, including maternal depression, parental substance use, intimate partner violence, adverse economic outcomes, and life stress. The Early Start program was associated with small to moderate benefits in a range of areas relating to child abuse, physical punishment, child behavior, and parenting competence. There was little evidence to suggest that the Early Start program had benefits that extended to the level of parents or family overall.

Peer-Mediated Multimodal Intervention Program for the Treatment of Children with ADHD in India: One-Year Followup

PubMed Central

Mehta, Sagar; Shah, Devesh; Shah, Kushal; Mehta, Sanjiv; Mehta, Neelam; Mehta, Vivek; Mehta, Vijay; Mehta, Vaishali; Motiwala, Smita; Mehta, Naina; Mehta, Devendra

2012-01-01

The objective was to assess the efficacy of a one-year, peer-mediated interventional program consisting of yoga, meditation and play therapy maintained by student volunteers in a school in India. The population consisted of 69 students between the ages of 6 and 11 years, previously identified as having attention deficit hyperactivity disorder (ADHD). A program, known as Climb-Up, was initially embedded in the school twice weekly. Local high school student volunteers were then trained to continue to implement the program weekly over the period of one year. Improvements in ADHD symptoms and academic performance were assessed using Vanderbilt questionnaires completed by both parents and teachers. The performance impairment scores for ADHD students assessed by teachers improved by 6 weeks and were sustained through 12 months in 46 (85%) of the enrolled students. The improvements in their Vanderbilt scores assessed by parents were also seen in 92% (P < 0.0001, Wilcoxon). The Climb-Up program resulted in remarkable improvements in the students' school performances that were sustained throughout the year. These results show promise for a cost-effective program that could easily be implemented in any school. PMID:23316384

The Measurable Benefits of a Workplace Wellness Program in Canada: Results After One Year.

PubMed

Lowensteyn, Ilka; Berberian, Violette; Belisle, Patrick; DaCosta, Deborah; Joseph, Lawrence; Grover, Steven A

2018-03-01

The aim of this study was to evaluate the impact of an employee wellness program in Canada. A comprehensive program including web-based lifestyle challenges was evaluated with annual health screenings. Among 730 eligible employees, 688 (94%) registered for the program, 571 (78%) completed a health screening at baseline, and 314 (43%) at 1 year. Most (66%) employees tracked their activity for more than 6 weeks. At 1-year follow-up, there were significant clinical improvements in systolic blood pressure -3.4 mm Hg, and reductions in poor sleep quality (33% to 28%), high emotional stress (21% to 15%), and fatigue (11% to 6%). A positive dose-response was noted where the greatest improvements were observed among those who participated the most. The program had high employee engagement. After 1 year, the benefits included clinically important improvements in physical and mental health.

Los Alamos National Laboratory Science Education Program. Annual progress report, October 1, 1995--September 30, 1996

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gill, D.H.

1997-01-01

The National Teacher Enhancement program (NTEP) is a three-year, multi-laboratory effort funded by the National Science Foundation and the Department of Energy to improve elementary school science programs. The Los Alamos National Laboratory targets teachers in northern New Mexico. FY96, the third year of the program, involved 11 teams of elementary school teachers (grades 4-6) in a three-week summer session, four two-day workshops during the school year and an on-going planning and implementation process. The teams included twenty-one teachers from 11 schools. Participants earned a possible six semester hours of graduate credit for the summer institute and two hours formore » the academic year workshops from the University of New Mexico. The Laboratory expertise in the earth and environmental science provided the tie between the Laboratory initiatives and program content, and allowed for the design of real world problems.« less

Program objectives for the National Water Data Exchange (NAWDEX) for fiscal year 1979

USGS Publications Warehouse

Edwards, Melvin D.

1978-01-01

This report describes the program objectives of the National Water Data Exchange (NAWDEX) for Fiscal Year 1979. These objectives include NAWDEX membership, program administration, management, and coordination, NAWDEX services, identification of sources of water data, indexing of water data, programs and systems documentation, recommended methods for the handling and exchange of water data, training, and technical assistance to NAWDEX members. (Woodard-USGS)

Alternative Basic Comprehensive Program (Project A.B.C.) Special Alternative Instructional Program. Final Evaluation Report 1992-93. OREA Report.

ERIC Educational Resources Information Center

Augustin, Marc A.

The Alternative Basic Comprehension Program (Project A.B.C.) for bilingual high school students was a special alternative instructional program funded by Title VII for the third year at two high schools in the Bronx. In the year under review, Project A.B.C. served 260 students of limited English proficiency (LEP). Participating students received…

EXPLORATORY STUDY AND PLANNING FOR A FOURTH-YEAR, PAID INTERNSHIP TEACHER EDUCATION PROGRAM FOR BOTH ELEMENTARY AND SECONDARY TEACHERS. FINAL REPORT.

ERIC Educational Resources Information Center

RYERSON, NORMAN E.

THROUGH THE DEVELOPMENT OF A COOPERATIVE COLLEGE-UNIVERSITY GRADUATE STUDY PROGRAM, THE AUGMENTATION OF A PAID FOURTH-YEAR INTERNSHIP APPROACH IN A TEACHER TRAINING PROGRAM WAS EXPLORED. STEPS INCLUDED--(1) INVOLVEMENT OF THE FACULTY IN AN EVALUATION OF THE TEACHER EDUCATION PROGRAM AND THE COLLEGE CURRICULUM, (2) CHANGING WEEKLY SCHEDULES AND THE…

Description of a Compensatory College Education Program for the Disadvantaged and Its Associated Research and Evaluation Program.

ERIC Educational Resources Information Center

Spuck, Dennis W.; And Others

This paper reports on a large-scale project of research and evaluation of a program for disadvantaged minority group students conducted by the Center for Educational Opportunity at the Claremont Colleges. The Program of Special Directed Studies for Transition to College (PSDS), a five-year experimental project, is aimed at providing a four-year,…

The Continental Project: A Model Program for School to Work Transition for Students with Disabilities.

ERIC Educational Resources Information Center

Peterson, Patricia; Ellsworth, J'Anne; Penny, Dave

The Continental Project is a school-to-work transition program for students with disabilities. The 6-year old program, which is located at a country club and golf course, serves more than 20 students per year and has successfully transitioned 45 young adults with moderate to severe handicaps into the workforce. The program is a cooperative effort…

A Computer Based Education (CBE) Program for Middle School Mathematics Intervention

ERIC Educational Resources Information Center

Gulley, Bill

2009-01-01

A Computer Based Education (CBE) program for intervention mathematics was developed, used, and modified over a period of three years in a computer lab at an Arizona Title I middle school. The program is described along with a rationale for the need, design, and use of such a program. Data was collected in the third year and results of the program…

Elder Abuse Demonstration Project. Third Interim Report to the Illinois General Assembly on Public Acts 83-1259 and 83-1432.

ERIC Educational Resources Information Center

Illinois State Dept. on Aging, Springfield.

This document contains the third annual interim report of the Illinois Elder Abuse Demonstration Program. It discusses the overall intent of the demonstration program, trends and changes in the third year of the demonstration program compared with the results from the first two years of the program, and achievements and recommendations for a…

The After-School Program for School-Age Children. A Descriptive Report. Report No. 13, Vol. 25.

ERIC Educational Resources Information Center

Popwell, Emma P.

This report describes the administrative structure and program design for an after-school program for school age children (aged between 5 and 13 years) in the 1990-91 school year in the Atlanta (Georgia) Public Schools (APS). The program took policy and regulations from the pertinent Board of Education policy and guidelines and was administered by…

40 years of Landsat images: What we learned about science and politics

NASA Astrophysics Data System (ADS)

Dozier, Jeff

2014-03-01

The first Landsat (then called ERTS - Earth Resources Technology Satellite) launched in 1972. Landsat 8 launched in February 2013. The 40 + years of images have yielded a remarkable history of changes in Earth's land surface, and the program has accomplished significant technological achievements. However, the sustained long-term record owes more to luck than careful program planning, and especially benefitted from the remarkable 27-year life of Landsat 5. Recommendations for the future center mainly on making the program a real Program with a commitment to sustaining it, as well as some ideas to reduce cost and improve effectiveness.

U.S. Geological Survey toxic Waste-Groundwater Contamination Program, fiscal year 1985

NASA Astrophysics Data System (ADS)

Ragone, Stephen E.

1986-09-01

In fiscal year 1982, the U S Geological Survey began an interdisciplinary research thrust entitled Toxic Waste-Groundwater Contamination Program The objective of the thrust was to provide earth sciences information necessary to evaluate and mitigate existing groundwater contamination problems resulting from the planned or inadvertant disposal of wastes and from certain land-use practices, and to improve future waste disposal and land-use practices The program supports process-oriented and interdisciplinary field research, and regional groundwater quality studies This article provides an overview of the current (Fiscal Year 1985) activities of the Toxic Waste Program

The US Air Force suicide prevention program: implications for public health policy.

PubMed

Knox, Kerry L; Pflanz, Steven; Talcott, Gerald W; Campise, Rick L; Lavigne, Jill E; Bajorska, Alina; Tu, Xin; Caine, Eric D

2010-12-01

We evaluated the effectiveness of the US Air Force Suicide Prevention Program (AFSPP) in reducing suicide, and we measured the extent to which air force installations implemented the program. We determined the AFSPP's impact on suicide rates in the air force by applying an intervention regression model to data from 1981 through 2008, providing 16 years of data before the program's 1997 launch and 11 years of data after launch. Also, we measured implementation of program components at 2 points in time: during a 2004 increase in suicide rates, and 2 years afterward. Suicide rates in the air force were significantly lower after the AFSPP was launched than before, except during 2004. We also determined that the program was being implemented less rigorously in 2004. The AFSPP effectively prevented suicides in the US Air Force. The long-term effectiveness of this program depends upon extensive implementation and effective monitoring of implementation. Suicides can be reduced through a multilayered, overlapping approach that encompasses key prevention domains and tracks implementation of program activities.

Report of the Defense Science Board Task Force on National Aero-Space Plane (NASP) Program

NASA Technical Reports Server (NTRS)

1992-01-01

Six years ago, the Defense Science Board (DSB) initiated a review of the concept, technical basis, program content, and missions of the National Aerospace Plane (NASP) program. The report was completed in Sep. 1988, and the recommendations contributed to strengthening the technical efforts in the NASP program. Since then, substantial technological progress has been made in the technology development phase (Phase 2) of the program. Phase 2 of the program is currently scheduled to end in late Fiscal Year 1993, with a decision whether to proceed to the experimental flight vehicle phase (Phase 3) to be made at that time. This decision will be a very significant one for the Department of Defense (DoD) and the National Aeronautics and Space Administration (NASA). In February of this year, the DSB was chartered to revisit the NASP program to assess the degree to which the many technical challenges of the program have been resolved, or are likely to be resolved by the end of Phase 2.

Tank waste remediation system multi-year work plan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

The Tank Waste Remediation System (TWRS) Multi-Year Work Plan (MYWP) documents the detailed total Program baseline and was constructed to guide Program execution. The TWRS MYWP is one of two elements that comprise the TWRS Program Management Plan. The TWRS MYWP fulfills the Hanford Site Management System requirement for a Multi-Year Program Plan and a Fiscal-Year Work Plan. The MYWP addresses program vision, mission, objectives, strategy, functions and requirements, risks, decisions, assumptions, constraints, structure, logic, schedule, resource requirements, and waste generation and disposition. Sections 1 through 6, Section 8, and the appendixes provide program-wide information. Section 7 includes a subsectionmore » for each of the nine program elements that comprise the TWRS Program. The foundation of any program baseline is base planning data (e.g., defendable product definition, logic, schedules, cost estimates, and bases of estimates). The TWRS Program continues to improve base data. As data improve, so will program element planning, integration between program elements, integration outside of the TWRS Program, and the overall quality of the TWRS MYWP. The MYWP establishes the TWRS baseline objectives to store, treat, and immobilize highly radioactive Hanford waste in an environmentally sound, safe, and cost-effective manner. The TWRS Program will complete the baseline mission in 2040 and will incur costs totalling approximately 40 billion dollars. The summary strategy is to meet the above objectives by using a robust systems engineering effort, placing the highest possible priority on safety and environmental protection; encouraging {open_quotes}out sourcing{close_quotes} of the work to the extent practical; and managing significant but limited resources to move toward final disposition of tank wastes, while openly communicating with all interested stakeholders.« less

Tank waste remediation system multi-year work plan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1994-09-01

The Tank Waste Remediation System (TWRS) Multi-Year Work Plan (MYWP) documents the detailed total Program baseline and was constructed to guide Program execution. The TWRS MYWP is one of two elements that comprise the TWRS Program Management Plan. The TWRS MYWP fulfills the Hanford Site Management System requirement for a Multi-Year Program Plan and a Fiscal-Year Work Plan. The MYWP addresses program vision, mission, objectives, strategy, functions and requirements, risks, decisions, assumptions, constraints, structure, logic, schedule, resource requirements, and waste generation and disposition. Sections 1 through 6, Section 8, and the appendixes provide program-wide information. Section 7 includes a subsectionmore » for each of the nine program elements that comprise the TWRS Program. The foundation of any program baseline is base planning data (e.g., defendable product definition, logic, schedules, cost estimates, and bases of estimates). The TWRS Program continues to improve base data. As data improve, so will program element planning, integration between program elements, integration outside of the TWRS Program, and the overall quality of the TWRS MYWP. The MYWP establishes the TWRS baseline objectives to store, treat, and immobilize highly radioactive Hanford waste in an environmentally sound, safe, and cost-effective manner. The TWRS Program will complete the baseline mission in 2040 and will incur costs totalling approximately 40 billion dollars. The summary strategy is to meet the above objectives by using a robust systems engineering effort, placing the highest possible priority on safety and environmental protection; encouraging {open_quotes}out sourcing{close_quotes} of the work to the extent practical; and managing significant but limited resources to move toward final disposition of tank wastes, while openly communicating with all interested stakeholders.« less

Prevention of Weight Gain Following a Worksite Nutrition and Exercise Program

PubMed Central

Thorndike, Anne N.; Sonnenberg, Lillian; Healey, Erica; Myint-U, Khinlei; Kvedar, Joseph C.; Regan, Susan

2012-01-01

Background Many employers are now providing wellness programs to help employees make changes in diet and exercise behaviors. Improving health outcomes and reducing costs will depend on whether employees sustain lifestyle changes and maintain a healthy weight over time. Purpose To determine if a 9-month maintenance intervention immediately following a 10-week worksite exercise and nutrition program would prevent regain of the weight lost during the program. Design RCT. Setting/participants In 2008, a total of 330 employees from 24 teams completed a 10-week exercise and nutrition program at a large hospital worksite and were randomized by team to maintenance or control (usual care) for 9 months. Intervention Internet support with a website for goal-setting and self-monitoring of weight and exercise plus minimal personal support. Main outcome measures Weight loss, percentage weight loss, time spent in physical activity, and frequency of consumption of fruits/vegetables, fatty foods, and sugary foods at 1 year compared to baseline. One-year follow-up was completed in 2010, and data were analyzed in 2011. Results At 1 year, 238 subjects (72%) completed follow-up assessments. Mean baseline BMI was 27.6 and did not differ between intervention and control. Compared to baseline, both groups lost weight during the 10-week program and maintained 65% of weight loss at 1 year (p<0.001). There was no difference in weight loss between groups at end of the 10-week program (4.8 lbs vs 4.3 lbs, p=0.53 for group×time interaction) or end of maintenance at 1 year (3.4 lbs vs 2.5 lbs, p=0.40 for group×time interaction). All subjects had improvements in physical activity and nutrition (increased fruits/vegetables and decreased fat and sugar intake) at 1 year but did not differ by group. Conclusions An intensive 10-week team-based worksite exercise and nutrition program resulted in moderate weight loss and improvements in diet and exercise behaviors at 1 year, but an Internet-based maintenance program immediately following the 10-week program did not improve these outcomes. PMID:22704742

Bioenergy Technologies Office Multi-Year Program Plan: November 2014 Update

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

2014-11-01

This is the November 2014 Update to the Multi-Year Program Plan, which sets forth the goals and structure of the Bioenergy Technologies Office. It identifies the RDD&D activities the Office will focus on over the next four years.

Bioenergy Technologies Office Multi-Year Program Plan: March 2015 Update

DOE Office of Scientific and Technical Information (OSTI.GOV)

none,

2015-03-01

This is the March 2015 Update to the Multi-Year Program Plan, which sets forth the goals and structure of the Bioenergy Technologies Office. It identifies the RDD&D activities the Office will focus on over the next four years.

An economic evaluation: Simulation of the cost-effectiveness and cost-utility of universal prevention strategies against osteoporosis-related fractures

PubMed Central

Nshimyumukiza, Léon; Durand, Audrey; Gagnon, Mathieu; Douville, Xavier; Morin, Suzanne; Lindsay, Carmen; Duplantie, Julie; Gagné, Christian; Jean, Sonia; Giguère, Yves; Dodin, Sylvie; Rousseau, François; Reinharz, Daniel

2013-01-01

A patient-level Markov decision model was used to simulate a virtual cohort of 500,000 women 40 years old and over, in relation to osteoporosis-related hip, clinical vertebral, and wrist bone fractures events. Sixteen different screening options of three main scenario groups were compared: (1) the status quo (no specific national prevention program); (2) a universal primary prevention program; and (3) a universal screening and treatment program based on the 10-year absolute risk of fracture. The outcomes measured were total directs costs from the perspective of the public health care system, number of fractures, and quality-adjusted life-years (QALYs). Results show that an option consisting of a program promoting physical activity and treatment if a fracture occurs is the most cost-effective (CE) (cost/fracture averted) alternative and also the only cost saving one, especially for women 40 to 64 years old. In women who are 65 years and over, bone mineral density (BMD)-based screening and treatment based on the 10-year absolute fracture risk calculated using a Canadian Association of Radiologists and Osteoporosis Canada (CAROC) tool is the best next alternative. In terms of cost-utility (CU), results were similar. For women less than 65 years old, a program promoting physical activity emerged as cost-saving but BMD-based screening with pharmacological treatment also emerged as an interesting alternative. In conclusion, a program promoting physical activity is the most CE and CU option for women 40 to 64 years old. BMD screening and pharmacological treatment might be considered a reasonable alternative for women 65 years old and over because at a healthcare capacity of $50,000 Canadian dollars ($CAD) for each additional fracture averted or for one QALY gained its probabilities of cost-effectiveness compared to the program promoting physical activity are 63% and 75%, respectively, which could be considered socially acceptable. Consideration of the indirect costs could change these findings. PMID:22991210

77 FR 10599 - Surface Transportation Project Delivery Pilot Program; Caltrans Audit Report

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-22

...] Surface Transportation Project Delivery Pilot Program; Caltrans Audit Report AGENCY: Federal Highway... participating in the Pilot Program, 23 U.S.C. 327(g) mandates semiannual audits during each of the first 2 years of State participation and annual audits during each subsequent year of State participation. This...

Microcomputer Software Technician Curriculum.

ERIC Educational Resources Information Center

EASTCONN Regional Educational Services Center, North Windham, CT.

This curriculum guide, developed for high schools in Connecticut, outlines a 4-year program for training microcomputer software technicians. Following a list of nine general objectives of the program, the guide provides a list of competencies that students are expected to develop in each of the courses of the 4-year program. The guide then…

Gifted/Talented: 1985-86 Final Technical Report.

ERIC Educational Resources Information Center

Wilkinson, David; Luna, Natalia

The document contains the annual report (1985/86) of the Austin (Texas) Independent School District's gifted and talented program. Major achievements of the year include the following: continuing implementation of the 5-year plan for reorganizing the gifted education programs; piloting of the AIM High Mathematics Program in 32 elementary schools;…

Dual Certification Program and Course Development in Two-Year Postsecondary Vocational Education Institutions in China

ERIC Educational Resources Information Center

Gong, Wen; Rojewski, Jay W.

2015-01-01

A model describing the development of curriculum and coursework for dual certification programs in two-year postsecondary vocational education institutions throughout China is described. Dual certification programs allow students to obtain an academic diploma and a national vocational qualification certificate concurrently. Chinese educators and…

77 FR 40628 - HUD's Fiscal Year (FY) 2012 Transformation Initiative: Natural Experiments Research Grant Program...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-10

... DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT [Docket No. FR-5600-N-18-C-1] HUD's Fiscal Year (FY) 2012 Transformation Initiative: Natural Experiments Research Grant Program, Cancellation AGENCY: Office... Availability (NOFA) ``Transformation Initiative: Natural Experiments Grant Program'' on Grants.gov . The close...

A Year-Round Professional Development Model for World Language Educators

ERIC Educational Resources Information Center

Steele, Tracy M.; Peterson, Margaret D.; Silva, Duarte M.; Padilla, Amado M.

2009-01-01

The Bay Area Foreign Language Program (BAFLP), one of nine regional sites of the California Foreign Language Project, offers ongoing, year-round professional development programs for world language educators. In addition, its leadership program prepares selected educators to assume leadership positions at their school sites, building capacity for…

Programming Contest Strategy

ERIC Educational Resources Information Center

Trotman, Andrew; Handley, Chris

2008-01-01

Each year the ACM hosts a truly international programming contest--the International Collegiate Programming Contest (ICPC). Dating back to a contest held by Texas A&M University in 1970, this annual event, along with the associated regional contests, has grown to 5606 teams from 1733 universities in 84 countries (in the year 2006). Despite the…

Federal Categorical Aid Programs, 78 Fiscal Year.

ERIC Educational Resources Information Center

National Council for Resource Development, Washington, DC.

The extent to which the nation's community and junior colleges received awards in selected federal categorical aid programs for fiscal year 1978 is outlined. For each aid program the following information is provided: dollars authorized, dollars awarded, dollars obtained by community colleges, total number of proposals submitted, total number of…

The Program of Special Directed Studies: A Five Year Summary.

ERIC Educational Resources Information Center

Mornell, Eugene S.

The report described one relatively small but extensively researched special admission and compensatory education program at The Claremont Colleges, California. The Program of Special Directed Studies for Transition to College (PSDS) was administered by the Claremont University Center. PSDS was a 5-year experimental project primarily funded by the…

Portraits of Human Greatness.

ERIC Educational Resources Information Center

Saint Anselm's Coll., Manchester, NH.

Examined is the Humanities Program at St. Anselm College, a two-year program of readings and lectures ordered chronologically from ancient to contemporary times--from the age of Classical Greek thought and the Old Testament to the twentieth century. The first year of the Humanities Program is organized in eight units on general modes of…

Ornamental Horticulture Technology; Suggested 2-Year Post High School Curriculums.

ERIC Educational Resources Information Center

Bureau of Adult, Vocational, and Technical Education (DHEW/OE), Washington, DC. Div. of Vocational and Technical Education.

Developed by a technical education specialist, this guide is designed to aid school administrators in planning and developing 2-year post-high school programs or evaluating existing programs in ornamental horticulture technology. In addition to general information on the program, contents include course outlines with examples of tests and…

Student Assistance Program in Pennsylvania. Evaluation Final Report.

ERIC Educational Resources Information Center

Fertman, Carl I.; Schlesinger, Jo; Fichter, Cele; Tarasevich, Susan; Zhang, Xiaoyan; Wald, Holly

This report contains the second year evaluation of the Student Assistance Program (SAP) in Pennsylvania. These school-based and school-linked programs address barriers to learning for youth at risk for social and emotional problems, drug and alcohol use and abuse, and depression. Second year evaluation focused on identifying essential components…

Norco College's Summer Advantage Program: Leading Change to Increase College Readiness

ERIC Educational Resources Information Center

Ring, April

2016-01-01

Norco College, in Riverside County, California, developed the Summer Advantage program in 2012. This program is designed to reduce the number of students placed into precollegiate-level courses and increase first-year retention through participation in academic workshops, intrusive advisement, and college orientation. After four years, the Summer…

Report to Congress fourteenth annual report of accomplishments under the Airport Improvement Program : fiscal year 1995

DOT National Transportation Integrated Search

1996-12-01

This annual report of the Airport Improvement Program (AIP) for the fiscal year (FY) ending September 30, 1995, is the 14th report of activity required by Section 47131 of Title 49, United States Code. The current grant program, known as the Airport ...

SAN JUAN BAY ESTUARY PROGRAM COMPREHENSIVE CONSERVATION AND MANAGEMENT PLAN IMPLEMENTATION TRACKING REPORT, 2004

EPA Science Inventory

Four years after the approval of its Comprehensive Conservation and Management Plan (CCMP), the San Juan Bay Estuary Program (SJBEP) is working towards the implementation stage of its 49 actions. During the last three years the program has focused its efforts in developing a coll...

Kindergarten Program for Four-Year-OIds: An Early intervention Strategy.

ERIC Educational Resources Information Center

Klentschy, Michael P.; Hoge, Suzi

The Pasadena Unified School District, in northwest Los Angeles County, recognized that an early intervention program for economically disadvantaged children should be part of its comprehensive district revitalizing and restructuring plan. Consequently, staff developed the Kindergarten Program for Four-Year-Olds, which was designed to provide: (1)…

The Incredible Years. What Works Clearinghouse Intervention Report

ERIC Educational Resources Information Center

What Works Clearinghouse, 2012

2012-01-01

"The Incredible Years" is an intervention composed of training programs for children, parents, and teachers that is intended to reduce children's aggression and improve their social skills. The three programs (child, parent, and teacher) can be used independently or in combination. The child program focuses on building social and…

Upward Bound. Program Objectives, Summer 1971.

ERIC Educational Resources Information Center

Wesleyan Univ., Middletown, CT.

The primary program objectives were as follows: (1) The students will achieve passing grade in the college preparation program; (2) The students will achieve one year academic growth each year as measured by the SCAT and other standardized measurements; (3) The students will achieve the minimum PSAT percentile rank as anticipated for college…

Ten years of Developing International Volcanology Graduate Study Programs

NASA Astrophysics Data System (ADS)

Rose, W. I.

2010-12-01

In 2000 I reported at this symposium about multi-institutional graduate field trips to IAVCEI events, such as the Bali meeting and its importance in building international collegiality and awareness among the volcanology doctoral students. NSF was an enthusiastic supporter of these field sessions and this support has continued through the highly successful Pucon and Reykjavik sessions. International volcanology graduate program development began with several exchange programs. EHaz was a highly successful program (McGill, Simon Fraser, Michigan Tech, Buffalo, UNAM and Universidad de Colima) funded by the Department of Education (FIPSE) that moved students across North America where dozens of graduate students spent semesters of their study abroad and shared annual field trips and online student led graduate seminar classes. Michigan Tech’s volcanology graduate program started a Masters International program that combined Peace Corps service with hazards mitigation graduate study and students were placed by Peace Corps in countries with prominent natural hazards. The new program funded 2 year residences in foreign environments, principally in Pacific Latin America. NSF strongly supported this program from its inception, and eventually it gained NSF PIRE support. Dozens of students have initiated the 3 year program (15 completed) to date. A similar PIRE developed at UAF with a link to volcanology in the Russian Far East. One gain is the development of many socially-conscious research selections. Beginning this year transatlantic dual degree masters programs in volcanology are being offered by a consortium of US and European volcanology programs (Michigan Tech, Buffalo, Clermont Ferrand and University of Milan Bicocca), again aided by FIPSE funding. Students have dual advisors on both sides of the Atlantic and spend about half of their two year programs in Europe and half in US. Faculty also travel in the program and the four campuses are increasingly linked by coursework and research networks. Because the international developments of volcanology programs address the need for more robust coursework and research choices for students than are possible on one campus, and because they lead to a diverse network of professional contacts , we think the next decade will bring many more multi-university volcanology programs linked to field sites all over the world.

Economic evaluation of a comprehensive teenage pregnancy prevention program: pilot program.

PubMed

Rosenthal, Marjorie S; Ross, Joseph S; Bilodeau, Roseanne; Richter, Rosemary S; Palley, Jane E; Bradley, Elizabeth H

2009-12-01

Previous research has suggested that comprehensive teenage pregnancy prevention programs that address sexual education and life skills development and provide academic support are effective in reducing births among enrolled teenagers. However, there have been limited data on the costs and cost effectiveness of such programs. The study used a community-based participatory research approach to develop estimates of the cost-benefit of the Pathways/Senderos Center, a comprehensive neighborhood-based program to prevent unintended pregnancies and promote positive development for adolescents. Using data from 1997-2003, an in-time intervention analysis was conducted to determine program cost-benefit while teenagers were enrolled; an extrapolation analysis was then used to estimate accrued economic benefits and cost-benefit up to age 30 years. The program operating costs totaled $3,228,152.59 and reduced the teenage childbearing rate from 94.10 to 40.00 per 1000 teenage girls, averting $52,297.84 in total societal costs, with an economic benefit to society from program participation of $2,673,153.11. Therefore, total costs to society exceeded economic benefits by $559,677.05, or $1599.08 per adolescent per year. In an extrapolation analysis, benefits to society exceed costs by $10,474.77 per adolescent per year by age 30 years on average, with social benefits outweighing total social costs by age 20.1 years. This comprehensive teenage pregnancy prevention program is estimated to provide societal economic benefits once participants are young adults, suggesting the need to expand beyond pilot demonstrations and evaluate the long-range cost effectiveness of similarly comprehensive programs when they are implemented more widely in high-risk neighborhoods.

Associations between quality indicators of internal medicine residency training programs

PubMed Central

2011-01-01

Background Several residency program characteristics have been suggested as measures of program quality, but associations between these measures are unknown. We set out to determine associations between these potential measures of program quality. Methods Survey of internal medicine residency programs that shared an online ambulatory curriculum on hospital type, faculty size, number of trainees, proportion of international medical graduate (IMG) trainees, Internal Medicine In-Training Examination (IM-ITE) scores, three-year American Board of Internal Medicine Certifying Examination (ABIM-CE) first-try pass rates, Residency Review Committee-Internal Medicine (RRC-IM) certification length, program director clinical duties, and use of pharmaceutical funding to support education. Associations assessed using Chi-square, Spearman rank correlation, univariate and multivariable linear regression. Results Fifty one of 67 programs responded (response rate 76.1%), including 29 (56.9%) community teaching and 17 (33.3%) university hospitals, with a mean of 68 trainees and 101 faculty. Forty four percent of trainees were IMGs. The average post-graduate year (PGY)-2 IM-ITE raw score was 63.1, which was 66.8 for PGY3s. Average 3-year ABIM-CE pass rate was 95.8%; average RRC-IM certification was 4.3 years. ABIM-CE results, IM-ITE results, and length of RRC-IM certification were strongly associated with each other (p < 0.05). PGY3 IM-ITE scores were higher in programs with more IMGs and in programs that accepted pharmaceutical support (p < 0.05). RRC-IM certification was shorter in programs with higher numbers of IMGs. In multivariable analysis, a higher proportion of IMGs was associated with 1.17 years shorter RRC accreditation. Conclusions Associations between quality indicators are complex, but suggest that the presence of IMGs is associated with better performance on standardized tests but decreased duration of RRC-IM certification. PMID:21651768

The value of internship in graduate medical education: survey of emergency medicine residents and program directors.

PubMed

Ray, Adam M

2007-01-01

To assess the opinions of emergency medicine (EM) residents and program directors about the value of completing a nonrequired 1-year internship before entering an EM residency program accredited by the Accreditation Council for Graduate Medical Education (ACGME). An eight-question, self-administered online survey was e-mailed to EM residents who had completed a nonrequired internship before entering ACGME-accredited residency programs. A separate, six-question survey was e-mailed to program directors of ACGME-accredited programs that do not require an internship who had ever had a resident who had completed a nonrequired internship. Forty-six (27 [59%] osteopathic, 19 [41%] allopathic) of 113 residents and 40 of 124 program directors responded to the survey questions. Less than 4% of residents completed a separate nonrequired 1-year internship. The most common reason for completing a nonrequired internship was to obtain licensure by the American Osteopathic Association (19 [41%]). Most residents believed that they were more proficient with history-taking and physical examinations (38 [83%]) and procedures (34 [74%]) during the first year of residency than their colleagues who did not complete an internship, but this percentage decreased over time. The program directors had similar opinions. Most osteopathic residents who completed the internship for osteopathic licensure would not have done so if it were not required. Most (39 of 40) program directors would not recommend taking a nonrequired internship. Completing a 1-year internship before entering an EM residency program may better prepare physicians for their first year of residency in terms of basic clinical competancy, but further study is needed in this area.

Creating Authentic Geoscience Research Experiences for Underrepresented Students in Two-Year Undergraduate Programs

NASA Astrophysics Data System (ADS)

Liou-Mark, J.; Blake, R.

2014-12-01

With community college and two-year program students playing pivotal roles in advancing the nation's STEM agenda now and throughout the remainder of this young millennia, it is incumbent on educators to devise innovative and sustainable STEM initiatives to attract, retain, graduate, and elevate these students to four-year programs and beyond. Involving these students in comprehensive, holistic research experiences is one approach that has paid tremendous dividends. The New York City College of Technology (City Tech) was recently awarded a National Science Foundation Research Experiences for Undergraduates (REU) supplemental grant to integrate a community college/two-year program component into its existing REU program. The program created an inviting and supportive community of scholars for these students, nurtured them through strong, dynamic mentoring, provided them with the support structures needed for successful scholarship, and challenged them to attain the same research prominence as their Bachelor degree program companions. Along with their colleagues, the community college/two-year program students were given an opportunity to conduct intensive satellite and ground-based remote sensing research at the National Oceanic and Atmospheric Administration Cooperative Remote Sensing Science and Technology Center (NOAA-CREST) at City College and its CREST Institute Center for Remote Sensing and Earth System Science (ReSESS) at City Tech. This presentation highlights the challenges, the rewards, and the lessons learned from this necessary and timely experiment. Preliminary results indicate that this paradigm for geoscience inclusion and high expectation has been remarkably successful. (The program is supported by NSF REU grant #1062934.)

Two Kinds of Kindergarten After Four Types of Head Start.

ERIC Educational Resources Information Center

Miller, Louise B.; Dyer, Jean L.

Results are reported at the end of the second year of a 3-year comparison of four prekindergarten programs: Bereiter-Engelmann, DARCEE, Montessori and Traditional. A number of classes in each program style were used with 246 four-year-olds in Head Start. Children were tested early in the year, at the end of the year, and at the end of kindergarten…

Capitation of public mental health services in Colorado: a five-year follow-up of system-level effects.

PubMed

Bloom, Joan R; Wang, Huihui; Kang, Soo Hyang; Wallace, Neal T; Hyun, Jenny K; Hu, Teh-wei

2011-02-01

Capitated Medicaid mental health programs have reduced costs over the short term by lowering the utilization of high-cost inpatient services. This study examined the five-year effects of capitated financing in community mental health centers (CMHCs) by comparing not-for-profit with for-profit programs. Data were from the Medicaid billing system in Colorado for the precapitation year (1994) and a shadow billing system for the postcapitation years (1995-1999). In a panel design, a random-effect approach estimated the impact of two financing systems on service utilization and cost while adjusting for all the covariates. Consistent with predictions, in both the for-profit and the not-for-profit CMHCs, relative to the precapitation year, there were significant reductions in each postcapitation year in high-cost treatments (inpatient treatment) for all but one comparison (not-for-profit CMHCs in 1999). Also consistent with predictions, the for-profit programs realized significant reductions in cost per user for both outpatient services and total services. In the not-for-profit programs, there were no significant changes in cost per user for total services; a significant reduction in cost per user for outpatient services was found only in the first two years, 1995 and 1996). The evidence suggests that different strategies were used by the not-for-profit and for-profit programs to control expenditures and utilization and that the for-profit programs were more successful in reducing cost per user.

Assessment of the technology required to develop photovoltaic power system for large scale national energy applications

NASA Technical Reports Server (NTRS)

Lutwack, R.

1974-01-01

A technical assessment of a program to develop photovoltaic power system technology for large-scale national energy applications was made by analyzing and judging the alternative candidate photovoltaic systems and development tasks. A program plan was constructed based on achieving the 10 year objective of a program to establish the practicability of large-scale terrestrial power installations using photovoltaic conversion arrays costing less than $0.50/peak W. Guidelines for the tasks of a 5 year program were derived from a set of 5 year objectives deduced from the 10 year objective. This report indicates the need for an early emphasis on the development of the single-crystal Si photovoltaic system for commercial utilization; a production goal of 5 x 10 to the 8th power peak W/year of $0.50 cells was projected for the year 1985. The developments of other photovoltaic conversion systems were assigned to longer range development roles. The status of the technology developments and the applicability of solar arrays in particular power installations, ranging from houses to central power plants, was scheduled to be verified in a series of demonstration projects. The budget recommended for the first 5 year phase of the program is $268.5M.

SHARP {Summer High School Apprenticeship Research Program}

NASA Technical Reports Server (NTRS)

Glasco, Deborah (Technical Monitor)

2002-01-01

The Year 2002 was another successful year for SHARP. Even after 22 years of SHARP, the Program continues to grow. There were 12 NASA Field Installations with a total of 210 apprentices who participated in the summer 2002 Program supported by 215 mentors in the fields of science and engineering. The apprentices were chosen from a pool of 1,379 applicants. This was a record year for applications exceeding the previous year by over 60%. For the second consecutive year, the number of female participants exceeded the number of males with 53% female and 47% male participants in the program. The main thrust of our recruiting efforts is still focused on underrepresented populations; especially African American, Hispanic, and Native American. At the conclusion of the summer program, most SHARP Apprentices indicated on the EDCATS that they would be interested in pursuing careers in Aerospace (56.2%) while the second largest career choice was a job at NASA (45.7%). The smallest number (11.9%) were interested in careers in the government. The table of responses is listed in the Appendix. Once again this year we were fortunate in that the SHARP COTR, Ms. Deborah Glasco, gained the support of MURED funding sources at NASA to fully fund additional apprentices and boost the number of apprentices to 210.

Hispanic Parenting Women in Women-Only versus Mixed-Gender Drug Treatment: A 10-Year Prospective Study

PubMed Central

Hser, Yih-Ing; Hunt, Samantha A.; Evans, Elizabeth; Chang, Yen-Jung; Messina, Nena P.

2012-01-01

The present study examined Hispanic substance-using parenting women treated in women-only (WO; n=126) versus mixed-gender (MG; n=853) programs and associated outcomes assessed 10 years after admission. Relative to other races/ethnicities of women admitted to the set of 40 California treatment programs in 2000–2002, Hispanic women were underrepresented in WO programs. Compared to those in MG programs, Hispanic women in WO programs demonstrated more severe treatment needs, indicated by their greater severity in drug and alcohol use, health and mental health problems, and criminal justice involvement at admission. They also had fewer economic resources (15% WO vs. 23% MG were employed, p<.05; 48% vs. 37% on public assistance, p<.05). Data based on administrative records covering 3 years pre-admission and 8 years post-admission showed that Hispanic women treated in WO programs had higher mental health service utilization over 8 years post-treatment admission, though no differences were found in trajectories of arrests and incarceration. In sum, long-term outcomes (in terms of criminal justice involvement) among Hispanic women in WO treatment were comparable to those in the MG treatment, despite greater service needs at admission. WO programs were able to engage more Hispanic women in use of mental health services. Future research should focus on factors limiting Hispanic women’s participation in WO programs, which could suggest ways for improvement so as to benefit all Hispanic women in need of these special services. PMID:22398357

Montessori Public School Pre-K Programs and the School Readiness of Low-Income Black and Latino Children.

PubMed

Ansari, Arya; Winsler, Adam

2014-11-01

Within the United States, there are a variety of early education models and curricula aimed at promoting young children's pre-academic, social, and behavioral skills. This study, using data from the Miami School Readiness Project (MSRP; Winsler et al., 2008, 2012), examined the school readiness gains of low-income Latino ( n = 7,045) and Black children ( n = 6,700) enrolled in two different types of Title-1 public school pre-K programs: those in programs using the Montessori curricula and those in more conventional programs using the High/Scope curricula with a literacy supplement. Parents and teachers reported on children's socio-emotional and behavioral skills with the Devereux Early Childhood Assessment (DECA), while children's pre-academic skills (cognitive, motor, and language) were assessed directly with the Learning Accomplishment Profile Diagnostic (LAP-D) at the beginning and end of their four-year-old pre-K year. All children, regardless of curricula, demonstrated gains across pre-academic, socio-emotional, and behavioral skills throughout the pre-K year; however, all children did not benefit equally from Montessori programs. Latino children in Montessori programs began the year at most risk in pre-academic and behavioral skills, yet exhibited the greatest gains across these domains and ended the year scoring above national averages. Conversely, Black children exhibited healthy gains in Montessori, but demonstrated slightly greater gains when attending more conventional pre-K programs. Findings have implications for tailoring early childhood education programs for Latino and Black children from low-income communities.

Adding A Spending Metric To Medicare's Value-Based Purchasing Program Rewarded Low-Quality Hospitals.

PubMed

Das, Anup; Norton, Edward C; Miller, David C; Ryan, Andrew M; Birkmeyer, John D; Chen, Lena M

2016-05-01

In fiscal year 2015 the Centers for Medicare and Medicaid Services expanded its Hospital Value-Based Purchasing program by rewarding or penalizing hospitals for their performance on both spending and quality. This represented a sharp departure from the program's original efforts to incentivize hospitals for quality alone. How this change redistributed hospital bonuses and penalties was unknown. Using data from 2,679 US hospitals that participated in the program in fiscal years 2014 and 2015, we found that the new emphasis on spending rewarded not only low-spending hospitals but some low-quality hospitals as well. Thirty-eight percent of low-spending hospitals received bonuses in fiscal year 2014, compared to 100 percent in fiscal year 2015. However, low-quality hospitals also began to receive bonuses (0 percent in fiscal year 2014 compared to 17 percent in 2015). All high-quality hospitals received bonuses in both years. The Centers for Medicare and Medicaid Services should consider incorporating a minimum quality threshold into the Hospital Value-Based Purchasing program to avoid rewarding low-quality, low-spending hospitals. Project HOPE—The People-to-People Health Foundation, Inc.

An Analysis of the Navy’s Selective Reenlistment Bonus (SRB) Management System and ROGER Model

DTIC Science & Technology

2008-03-01

SRBMS Selective Reenlistment Bonus Management System STAR Selective Training and Reenlistment Program YOS Years of Service 4YO 4-Year Obligor 5YO...it includes 4-year obligors ( 4YO ) sailors who will reach the end of active obligated service (EAOS) during the fiscal year of the SRB program, as

Appalachian Regional Commission: 1982 Annual Report.

ERIC Educational Resources Information Center

Appalachian Regional Commission, Washington, DC.

Fiscal year 1982 was transitional for the Appalachian Regional Commission (ARC), as it was the last year of the broad economic development program and a year of reduced funding and new limits on programs. In 1981, Congress had requested that ARC prepare a plan for completion of the Appalachian highway system and for a 3 to 5 year ARC finish-up…

Exploring Characteristics of Retained First-Year Students Enrolled in Non-Proximal Distance Learning Programs

ERIC Educational Resources Information Center

Hillstock, Laurie G.; Havice, Pamela A.

2014-01-01

This study explored pre- and post-admission characteristics of retained first-year students enrolled in non-proximal distance learning programs within public, 2-year colleges. Five pre-admission and six post-admission characteristics were explored. The sample for this study consisted of 197 first-year students enrolled in non-proximal distance…

First Year Experience: How We Can Better Assist First-Year International Students in Higher Education

ERIC Educational Resources Information Center

Yan, Zi; Sendall, Patricia

2016-01-01

While many American colleges and universities are providing a First Year Experience (FYE) course or program for their first year students, those programs are not often customized to take into account international students' (IS) unique challenges. Using quantitative and qualitative methods, this study evaluated a FYE course that was customized for…

29 CFR 99.520 - Major program determination.

Code of Federal Regulations, 2014 CFR

2014-07-01

... the two-year period. (c) Step 2. (1) The auditor shall identify Type A programs which are low-risk... $100 million in total Federal awards expended. (ii) $300,000 (or $500,000 for fiscal years ending after... in paragraphs (c), (d), and (e) of this section. (1) A first-year audit is the first year the entity...

29 CFR 99.520 - Major program determination.

Code of Federal Regulations, 2012 CFR

2012-07-01

... the two-year period. (c) Step 2. (1) The auditor shall identify Type A programs which are low-risk... $100 million in total Federal awards expended. (ii) $300,000 (or $500,000 for fiscal years ending after... in paragraphs (c), (d), and (e) of this section. (1) A first-year audit is the first year the entity...

"2 + 2" Articulated Health Occupations Project. Nursing Program. First Year Report.

ERIC Educational Resources Information Center

Paris Independent School District, TX.

This report describes the procedures and accomplishments of the first year of a multiyear project to develop a "2 + 2" articulated training program in health careers that links the last 2 years of secondary and the first 2 years of postsecondary training to prepare students for employment in one or more occupations. A related goal for…

Quantitative Evaluation of a First Year Seminar Program: Relationships to Persistence and Academic Success

ERIC Educational Resources Information Center

Jenkins-Guarnieri, Michael A.; Horne, Melissa M.; Wallis, Aaron L.; Rings, Jeffrey A.; Vaughan, Angela L.

2015-01-01

In the present study, we conducted a quantitative evaluation of a novel First Year Seminar (FYS) program with a coordinated curriculum implemented at a public, four-year university to assess its potential role in undergraduate student persistence decisions and academic success. Participants were 2,188 first-year students, 342 of whom completed the…

Comprehensive care program for elderly patients over 65 years with hip fracture.

PubMed

Fernández-Moyano, A; Fernández-Ojeda, R; Ruiz-Romero, V; García-Benítez, B; Palmero-Palmero, C; Aparicio-Santos, R

2014-01-01

To report the health outcomes of a multidisciplinary care program for patients over 65 years with hip fracture. We have developed a care coordination model for the comprehensive care of hip fracture patients. It establishes what, who, when, how and where orthopedists, internists, family physicians, emergency, intensive care, physiotherapists, anesthetists, nurses and workers social intervene. All elderly patients over 65 years admitted with the diagnosis of hip fracture (years 2006 to 2010) were retrospectively evaluated. One thousand episodes of hip fracture, corresponding to 956 patients, were included. Mean age was 82 years and mean stay 6.7 days. This was reduced by 1.14 days during the 5 years of the program. A total of 85.1% were operated on before 72 yours, and 91.2% during the program. Incidence of surgical site infection was 1.5%. In-hospital mortality was 4.5%, (24.2% at 12 months). Readmissions at one years was 14.9%. Independence for basic activity of daily living was achieved by 40% of the patients. This multidisciplinary care program for hip fracture patients is associated with positive health outcomes, with a high percentage of patients treated early (more than 90%), reduced mean stay (less than 7 days), incidence of surgical site infections, readmissions and inpatient mortality and at one year, as well as adequate functional recovery. Copyright © 2012 Elsevier España, S.L. All rights reserved.

National Weatherization Assistance Program Characterization Describing the Recovery Act Period

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tonn, Bruce Edward; Rose, Erin M.; Hawkins, Beth A.

This report characterizes the U.S. Department of Energy s Weatherization Assistance Program (WAP) during the American Recovery and Reinvestment Act of 2009 (Recovery Act) period. This research was one component of the Recovery Act evaluation of WAP. The report presents the results of surveys administered to Grantees (i.e., state weatherization offices) and Subgrantees (i.e., local weatherization agencies). The report also documents the ramp up and ramp down of weatherization production and direct employment during the Recovery Act period and other challenges faced by the Grantees and Subgrantees during this period. Program operations during the Recovery Act (Program Year 2010) aremore » compared to operations during the year previous to the Recovery Act (Program Year 2008).« less

A Retraining Program for Inactive Physicians

PubMed Central

Brown, Margaret; Sakai, F. Joan; Selzer, Arthur

1969-01-01

During the past two years a pilot project was conducted in which 19 inactive physicians were retrained in preparation for resumption of active practice. The initial program consisted of a flexible training program of six months to one year patterned after conventional internship-residency concepts. During the second year the program was modified by providing an initial condensed indoctrination period of two months' duration especially designed for this purpose, followed by a preceptorship type of training. The project was considered successful in permitting trainees to enter some form of active medical work, or to enroll in formal specialty training. The observations made by the faculty of the program and its accomplishments are discussed in the light of the effort expended and the cost of the project. PMID:5348045

A retraining program for inactive physicians.

PubMed

Brown, M; Sakai, F J; Selzer, A

1969-11-01

During the past two years a pilot project was conducted in which 19 inactive physicians were retrained in preparation for resumption of active practice. The initial program consisted of a flexible training program of six months to one year patterned after conventional internship-residency concepts. During the second year the program was modified by providing an initial condensed indoctrination period of two months' duration especially designed for this purpose, followed by a preceptorship type of training. The project was considered successful in permitting trainees to enter some form of active medical work, or to enroll in formal specialty training. The observations made by the faculty of the program and its accomplishments are discussed in the light of the effort expended and the cost of the project.

What does a Performance Measurement System Tell Us about the National Comprehensive Cancer Control Program?

PubMed Central

Townsend, Julie S.; Moore, Angela R.; Mulder, Tiffani N.; Boyd, Mary

2015-01-01

Context The National Comprehensive Cancer Control Program (NCCCP) performance measurement system seeks to understand both the processes that funded programs undertake with their respective coalitions to implement the objectives of their cancer plans and outcomes of those efforts. Objective To identify areas of achievement and technical assistance needs of NCCCP awardees. Design Program performance was assessed through surveys completed by program directors on performance indicators in 2009 and 2010 and queries from a web-based management information system in 2011 and 2012. Setting Programs funded by CDC’s NCCCP. Participants 69 programs. Main Outcome Measure(s) The key performance measures assessed were: inclusion of diverse partners and key sectors in cancer coalitions; partners’ involvement in activities; receiving in-kind resources from partners; using evidence-based interventions and data for setting priorities; conducting program evaluation; using community- or organization-level strategies to address cancer control efforts; and demonstrating progress toward achieving health outcomes. Results Most programs reported having active coalitions that represent diverse organizational sectors. Nearly all programs routinely assess the burden of cancer. In-kind resources to implement activities peaked at $64,716 in the second year of a five year funding cycle, and declined in subsequent project years. By year 3, over 70% of programs reported having an evaluation plan. While programs reported that nearly two-thirds of their interventions were evidence-based, some programs implemented non-evidence-based interventions. A majority of programs successfully used at least one community- or organization-level change strategy. However, many programs did not incorporate objectives linked to health outcomes as they reported progress in implementing interventions. Conclusions: While NCCCP programs were strong at building and maintaining infrastructure, some programs may need additional technical assistance to increase the adoption of evidence-based interventions, develop solid and responsive evaluation plans, and better link efforts to population-based measures that demonstrate impact toward reducing the burden of cancer. PMID:25136936

Adaptation of an asthma management program to a small clinic.

PubMed

Kwong, Kenny Yat-Choi; Redjal, Nasser; Scott, Lyne; Li, Marilyn; Thobani, Salima; Yang, Brian

2017-07-01

Asthma management programs, such as the Breathmobile program, have been extremely effective in reducing asthma morbidity and increasing disease control; however, their high start-up costs may preclude their implementation in smaller health systems. In this study, we extended validated asthma disease management principles from the Breathmobile program to a smaller clinic system utilizing existing resources and compared clinical outcomes. Cox-regression analyses were conducted to determine the cumulative probability that a new patient entering the program would achieve improved clinical control of asthma with each subsequent visit to the program. A weekly asthma disease management clinic was initiated in an existing multi-specialty pediatric clinic in collaboration with the Breathmobile program. Existing nursing staff was utilized in conjunction with an asthma specialist provider. Patients were referred from a regional healthcare maintenance organization and patients were evaluated and treated every 2 months. Reduction in emergency department (ED) visits and hospitalizations, and improvements in asthma control were assessed at the end of 1 year. A total of 116 patients were enrolled over a period of 1 year. Mean patient age was 6.4 years at the time of their first visit. Patient ethnicity was self-described predominantly as Hispanic or African American. Initial asthma severity for most patients, classified in accordance with national guidelines, was "moderate persistent." After 1 year of enrollment, there was a 69% and 92% reduction in ED/urgent care visits and hospitalizations, respectively, compared with the year before enrollment. Up to 70% of patients achieved asthma control by the third visit. Thirty-six different patients were seen during 1 year for a total of $15,938.70 in contracted reimbursements. A large-scale successful asthma management program can be adapted to a stationary clinic system and achieve comparable results.

1999 Research Reports: NASA/ASEE Summer Faculty Fellowship Program

NASA Technical Reports Server (NTRS)

Hosler, E. Ramon (Editor); Buckingham, Gregg (Editor)

2000-01-01

This document is a collection of technical reports on research conducted by the participants in the 1999 NASA/ASEE Summer Faculty Fellowship Program at the Kennedy Space Center (KSC). This was the 15th year that a NASA/ASEE program has been conducted at KSC. The 1999 program was administered by the University of Central Florida in cooperation with KSC. The program was operated under the auspices of the American Society for Engineering Education (ASEE and the Education Division, NASA Headquarters, Washington, DC, and KSC. The KSC Program was one of nine such Aeronautics and Space Research Programs funded by NASA Headquarters in 1999. The NASA/ASEE Program is intended to be a two-year program to allow in-depth research by the university faculty member.

San Diego transit five year plan update : FY 1982-1986

DOT National Transportation Integrated Search

1981-07-01

The Five Year Plan Update constitutes the annual revision to the operating plan and capital program for the following five year planning period, presents its adopted budget and a specific operating plan and capital program for FY 1982 as well as less...

National Water Program End of the Year Performance Reports and Best Practices

EPA Pesticide Factsheets

Each year, EPA's Office of Water conducts an assessment of the end of the year results for all performance measures of the National Water Program to determine progress in meeting the goals outlined in the Agency's Strategic Plan and NWPG.

State Fiscal Years 1997-2000 Transportation Improvement Program for Green, Miami and Montgomery Counties, Ohio - June 1996

DOT National Transportation Integrated Search

1996-06-01

The Transportation Improvement Program, often referred to as the TIP, is a four-year implementation schedule for transportation projects within the Greene, Miami and Montgomery County Region. The locally developed State Fiscal Year 1997 through Fisca...

Ecological Monitoring and Compliance Program Fiscal/Calendar Year 2004 Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bechtel Nevada

2005-03-01

The Ecological Monitoring and Compliance program, funded through the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office, monitors the ecosystem of the Nevada Test Site and ensures compliance with laws and regulations pertaining to Nevada Test Site biota. This report summarizes the program's activities conducted by Bechtel Nevada during the Fiscal Year 2004 and the additional months of October, November, and December 2004, reflecting a change in the monitoring period to a calendar year rather than a fiscal year as reported in the past. This change in the monitoring period was made to better accommodate information requiredmore » for the Nevada Test Site Environmental Report, which reports on a calendar year rather than a fiscal year. Program activities included: (1) biological surveys at proposed construction sites, (2) desert tortoise compliance, (3) ecosystem mapping and data management, (4) sensitive species and unique habitat monitoring, (5) habitat restoration monitoring, and (6) biological monitoring at the Hazardous Materials Spill Center.« less

Connected Classroom: A Program Evaluation of the Professional Development Program of a One-to-One Educational Technology Initiative in South Carolina

ERIC Educational Resources Information Center

Grant, Kelly J.

2016-01-01

The purpose of this study was to evaluate the impact of the first year of a multi-year, district-wide professional development program for teachers that accompanied a one-to-one Apple device rollout for all students. A mixed-method research design was used to perform a logic model of program evaluation. Teacher self-reported proficiency in basic…

Evaluation of the Second Year (1968-1969) of the Sustained Primary Program for Bilingual Students in the Las Cruces, New Mexico Public School System.

ERIC Educational Resources Information Center

Cordova, Ignacio R.; And Others

Evaluating the 2nd-year K-3 bilingual program in 4 elementary schools, this document assessed (1) the increase in achievement level of Spanish-speaking pupils through use of a sustained K-3 program; (2) the student achievement level between bilingual and monolingual programs; (3) the involvement of Spanish-speaking parents as advisors and…

Beating the Odds (BTO) Program: A Comprehensive Support System for Teachers and Families of At-Risk Students.

ERIC Educational Resources Information Center

Opuni, Kwame A.; And Others

This paper evaluates the effectiveness of the Beating the Odds (BTO) program of the Houston (Texas) schools in the 1990-91 school year, the third and final year of Phase I of the program. The BTO program provided training workshops for teachers of at-risk students and direct counseling and social service support for at-risk students in a selected…

The Impact of a Year-Long, Same School Social Skills Instruction Program on Students' with Verified Behavioral Disorders, Autism Spectrum Disorders, and Attention Deficit Hyperactivity Disorders Perceptions of Program Effectiveness

ERIC Educational Resources Information Center

Gaden, Gregory G.

2012-01-01

The purpose of this study was to determine the impact of a year-long, same school classroom social skills instruction program on students' with verified Emotional Behavior Disorders, Autism Spectrum Disorders, and Attention Deficit Hyperactivity Disorders perceptions of program effectiveness. This study indicated that youth can demonstrate…

Children's Growth and Classroom Experiences in Georgia's Pre-K Program: Findings from the 2011-2012 Evaluation Study

ERIC Educational Resources Information Center

Peisner-Feinberg, Ellen; Schaaf, Jennifer; LaForett, Dore

2013-01-01

Georgia has one of the few state-funded universal pre-kindergarten programs in the United States, with the aim of providing pre-k services to all 4-year-olds whose families want their children to participate in the program, regardless of family income level. In the 2011-2012 school year, Georgia's Pre-K Program served a total of over 94,000…

A System for Analyzing the Cost of Operating Vocational Education Programs at the Secondary Level in Ohio. A Study of School Year 1973-1974.

ERIC Educational Resources Information Center

Ohio State Dept. of Education, Columbus.

As a part of Ohio's program review and evaluation of vocational education, the report is concerned with a study of the costs of operating vocational education programs throughout the State. A cost analysis system for secondary level vocational education instructional programs was developed in 1970 and has been restudied each succeeding year. The…

Evaluation of the School Breakfast Program Pilot Project: Final Report. Special Nutrition Programs. Report Number CN-04-SBP. Nutrition Assistance Program Report Series

ERIC Educational Resources Information Center

Bernstein, Lawrence S.; McLaughlin, Joan E.; Crepinsek, Mary Kay; Daft, Lynn M.

2004-01-01

In 1998, Congress authorized the School Breakfast Program Pilot Project (SBPP) to study the implementation and effects of providing universal free school breakfast in six school districts across the United States. For three years, from School Year (SY) 2000-2001 through SY 2002-2003, these six school districts received federal funds to offer…