Antinociceptive, anti-inflammatory and antiarthritic activities of Bungarus fasciatus venom in experimental animal models.

PubMed

Ghosh, Susmita; Saha, Partha Pratim; Dasgupta, Subir C; Gomes, Antony

2016-09-01

Pain and inflammation are intimately associated with rheumatoid arthritis, a growing bone-joint related problem of the modern society. Though several therapeutic managements are available for arthritis, their side effects not only limit their use, but also advocate the quest for natural therapies. In this study, we explored the antinociceptive, anti-inflammatory and antiarthritic activities of Bungarus fasciatus venom (BFV) in experimental animal models. Rheumatoid arthritis was induced by Freund’s complete adjuvant (FCA) in male Wistar albino rats. Lyophilized BFV was diluted in 0.9% NaCl. Antiarthritic activity showed that BFV significantly reduced the paw and ankle diameters; urinary hydroxyproline, glucosamine levels and serum ACP/ALP/TNF-α/IL-1β/IL-17/Cathepsin-K/MMP-1 levels. These parameters were significantly increased in FCA induced arthritic animals. Joint histopathology study indicated the partial restoration of joint structure. Treatment with BFV significantly reduced the mean latency time of tail flick response, acetic acid induced writhing response and formalin induced licking response in male albino mice. BFV treatment also significantly reduced carrageenan induced paw edema and xylene induced ear edema in male albino mice. The results indicated that BFV possess antinociceptive, anti-inflammatory and antiarthritic properties and further studies are warranted to find the active constituents present in BFV.

A Chinese Herbal Decoction, Shaoyao-Gancao Tang, Exerts Analgesic Effect by Down-Regulating the TRPV1 Channel in a Rat Model of Arthritic Pain.

PubMed

Sui, Feng; Zhou, Hai-Yu; Meng, Jing; Du, Xin-Liang; Sui, Yun-Peng; Zhou, Zhi-Kun; Dong, Cheng; Wang, Zhu-Ju; Wang, Wei-Hao; Dai, Li; Ma, Hai; Huo, Hai-Ru; Jiang, Ting-Liang

2016-01-01

Shaoyao-Gancao Tang (SGT) is one of the most frequently used compound formulas in the treatment of pain-related diseases in the medical practice of traditional Chinese medicine (TCM). To investigate the anti-inflammatory and antinociceptive effects, as well as to uncover the molecular mechanism of SGT, the rat pain model of arthritis was experimentally induced by single unilateral injection of rats' left hind paw with Freund's complete adjuvant (FCA). SGT was orally administered to the rats daily at three doses individually for a period of 16 days post-model induction. Swollen degrees and pain thresholds of the rats in different groups were measured for evaluation of the anti-inflammatory and anti-nociceptive effects of SGT. Furthermore, the mRNA and protein expression levels of transient receptor potential ion channel protein vanilloid receptor 1 (TRPV1) channel as well as its calcium-mediating function in the isolated DRG neurons were further detected to provide indexes for exploration of the molecular mechanisms mediating anti-arthritic activities of SGT. As a result, FCA injection induced significant allodynia, inflammation and edema, accompanied by a significant increase in both expression and calcium-mediating function of the TRPV1 channel. Pharmacologically, oral administration of SGT at a high or middle dose demonstrated a significant relief from the above-mentioned pathological conditions in a dose-dependent manner. Simultaneously the mRNA and protein expressional levels of TRPV1 channel, as well as its calcium-mediating function, were down-regulated greatly. These findings suggest that SGT possesses a significant analgesic and anti-inflammatory effect on arthritis rats; its therapeutic activities might be achieved through reversing the elevated expression and function of TRPV1 channel evoked by FCA.

Effects of ethanol and water extracts of propolis (bee glue) on acute inflammatory animal models.

PubMed

Hu, Fuliang; Hepburn, H R; Li, Yinghua; Chen, M; Radloff, S E; Daya, S

2005-09-14

The anti-inflammatory effects of ethanol (EEP) and water (WSD) extracts in ICR mice and Wistar rats were analyzed. Both WSD and EEP exhibited significant anti-inflammatory effects in animal models with respect to thoracic capillary vessel leakage in mice, carrageenan-induced oedema, carrageenan-induced pleurisy, acute lung damage in rats. The mechanisms for the anti-inflammatory effects probably involve decreasing prostaglandin-E(2) (PGE(2)) and nitric oxide (NO) levels. In rats with Freund's complete adjuvant (FCA) induced arthritis, propolis extracts significantly inhibited the increase of interleukin-6 (IL-6) in inflamed tissues, but had no significant effect on levels of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma). The results are consistent with the interpretation that EEP and WSD may exert these effects by inhibiting the activation and differentiation of mononuclear macrophages.

[Therapeutic effect of nux vomica total alkali gel on adjuvants arthritis rats].

PubMed

Zheng, Yongqiu; Wu, Zhenzhen; Liu, Jianxun; Hu, Jie; Yang, Chi

2012-05-01

To observe the therapeutic effect and mechanism of nux vomica total alkali gel (NVTAG) on adjuvants arthritis (AA) rats. SD rats were randomly divided into nine groups: the normal group, the AA model group, NVTAG high, middle and low-dose (25, 12.5, 6.25 mg x kg(-1)) groups and the Votalin control (diclofenac diethylamine emulgel, 50 mg x kg(-1)) group. Except for the normal group, the remaining groups were transcutaneously administered with 0.1 mL freund's adjuvant complete (FCA) for inflammation in left rear feet and then evenly treated with medicine and packed with oilpapers. The foot volume method was adopted to determine foot swelling degree, with pain scoring and polyarthritis scoring. HE staining was used to observe arthro-pathologic injury. The content of prostaglandin E2 (PGE2), interleukin-1 (IL-1), IL-6, tumor necrosis factor (TNF-alpha) and vascular epidermal growth factor (VEGF) in synovium homogenates were measured by enzyme-linked immuno-absorbent assay (ELISA) respectively. Compared with the model group, NVTAG and control gel can obviously reduce the foot swelling degree, polyarthritis indicators and relieve arthro-pathologic injury in AA rats (17-21 d). The levels of IL-1, PGE2, IL-6, VEGF and TNF-alpha in synovial homogenates of AA rats were also reduced by NVTAG significantly. NVTAG shows an antergic effect on AA progress in rats, which is closely related to inhibition of development of inflammatory mediator.

Distortion Representation of Forecast Errors for Model Skill Assessment and Objective Analysis

NASA Technical Reports Server (NTRS)

Hoffman, Ross N.

2001-01-01

We completed the formulation of the smoothness penalty functional this past quarter. We used a simplified procedure for estimating the statistics of the FCA solution spectral coefficients from the results of the unconstrained, low-truncation FCA (stopping criterion) solutions. During the current reporting period we have completed the calculation of GEOS-2 model-equivalent brightness temperatures for the 6.7 micron and 11 micron window channels used in the GOES imagery for all 10 cases from August 1999. These were simulated using the AER-developed Optimal Spectral Sampling (OSS) model.

Improvement of bioavailability and anti-inflammatory potential of curcumin in combination with emu oil.

PubMed

Jeengar, Manish Kumar; Shrivastava, Shweta; Nair, Kala; Singareddy, Sreenivasa Reddy; Putcha, Uday Kumar; Talluri, M V N Kumar; Naidu, V G M; Sistla, Ramakrishna

2014-12-01

The purpose of the present study is to evaluate the effect of emu oil on bioavailability of curcumin when co-administered and to evaluate the property that enhances the anti-inflammatory potential of curcumin. Oral bioavailability of curcumin in combination with emu oil was determined by measuring the plasma concentration of curcumin by HPLC. The anti-inflammatory potential was evaluated in carrageenan-induced paw edema model (acute model) and in Freund's complete adjuvant (FCA)-induced arthritis model (chronic model) in male SD rats. The anti-inflammatory potential of curcumin in combination with emu oil has been significantly increased in both acute and chronic inflammatory models as evident from inhibition of increase in paw volume, arthritic score, and expression of pro-inflammatory cytokines. The increased anti-inflammatory activity in combination therapy is due to enhanced bioavailability (5.2-fold compared to aqueous suspension) of curcumin by emu oil. Finally, it is concluded that the combination of emu oil with curcumin will be a promising approach for the treatment of arthritis.

Therapeutic effects of lornoxicam-loaded nanomicellar formula in experimental models of rheumatoid arthritis.

PubMed

Helmy, Hebatullah Samy; El-Sahar, Ayman E; Sayed, Rabab H; Shamma, Rehab Nabil; Salama, Alaa Hamed; Elbaz, Eman Maher

2017-01-01

Rheumatoid arthritis (RA) is a chronic inflammatory disease treated by nonsteroidal anti-inflammatory drugs (NSAIDs) including lornoxicam (LX). Nanocarriers have been used to increase the efficacy and reduce the side effects of various drugs. The objective of the present study was to compare the therapeutic efficacy of systemic administration of lornoxicam-loaded nanomicellar formula (LX-NM) with that of free LX. The LX-loaded mixed polymeric nanomicellar formula was prepared by direct equilibrium technique. Two rat models were used in the study: carrageenan-induced acute edema and Freund's complete adjuvant (FCA)-induced chronic arthritis. The inhibitory effect of LX-NM on carrageenan-induced edema was higher than free LX for the same dose (1.3 mg/kg, i.p.). LX-NM (0.325 mg/kg, i.p.) produced effects comparable to that of diclofenac, which served as a standard. In the FCA model, daily treatment with LX-NM (0.325 mg/kg, i.p.) starting on day 14 significantly reduced the percentage of edema and increased weight growth. However, the same dose of LX failed to confer any significant change. Additionally, LX-NM significantly attenuated the rise of tumor necrosis factor-α (TNF-α), interleukin-1β, prostaglandin E2, nuclear factor-κβ, malondialdehyde and nitric oxide serum levels. In contrast, LX failed to show any significant reduction in elevated serum biomarkers except for TNF-α. LX-NM is an alternative delivery system that is simply prepared at low costs. It showed a superior therapeutic efficacy against RA compared to free LX. Thus, LX-NM can be considered as a promising candidate for treatment of RA and similar inflammatory disorders.

Different approaches to valuing the lost productivity of patients with migraine.

PubMed

Lofland, J H; Locklear, J C; Frick, K D

2001-01-01

To calculate and compare the human capital approach (HCA) and friction cost approach (FCA) methods for estimating the cost of lost productivity of migraineurs after the initiation of sumatriptan from a US societal perspective. Secondary, retrospective analysis to a prospective observational study. A mixed-model managed care organisation in western Pennsylvania, USA. Patients with migraine using sumatriptan therapy. Patient-reported questionnaires collected at baseline, 3 and 6 months after initiation of sumatriptan therapy. The cost of lost productivity estimated with the HCA and FCA methods. Of the 178 patients who completed the study, 51% were full-time employees, 13% were part-time, 18% were not working and 17% changed work status. Twenty-four percent reported a clerical or administrative position. From the HCA, the estimated total cost of lost productivity for 6 months following the initiation of sumatriptan was $US117905 (1996 values). From the FCA, the six-month estimated total cost of lost productivity ranged from $US28329 to $US117905 (1996 values). This was the first study to retrospectively estimate lost productivity of patients with migraine using the FCA methodology. Our results demonstrate that depending on the assumptions and illustrations employed, the FCA can yield lost productivity estimates that vary greatly as a percentage of the HCA estimate. Prospective investigations are needed to better determine the components and the nature of the lost productivity for chronic episodic diseases such as migraine headache.

Amelioration of FCA induced arthritis on topical application of curcumin in combination with emu oil.

PubMed

Jeengar, Manish Kumar; Shrivastava, Shweta; Mouli Veeravalli, S Chandra; Naidu, V G M; Sistla, Ramakrishna

2016-09-01

The aim of the present study was to investigate the skin penetration potential of emu oil and the possibility of enhancing the antiarthritic potential of lipophilic bioactive curcumin, which has poor permeability through biological membranes. Solubility and ex vivo skin permeation studies were performed with water, corn oil, and emu oil as a vehicle using curcumin as a model drug. Carrageenan induced inflammation and Freund's complete adjuvant-induced arthritic rat models were used to evaluate enhanced antiinflammatory and antiarthritic effect of curcumin in combination of emu oil via topical route. The skin permeation study resulted in the combination of emu oil with curcumin enhancing the flux 1.84 and 4.25 times through the rat skin compared to corn oil and water, respectively. Results of carrageenan induced rat paw edema model demonstrated that percentage of paw inhibition shown by curcumin-emu oil combination was 1.42-fold more compared to the total effect shown by both groups treated with curcumin aqueous suspension and emu oil per se. In Freund's complete adjuvant-induced arthritic model, the combined treatment was effective in bringing significant changes in the functional, biochemical, histopathologic, and radiologic parameters. Topical application of curcumin-emu oil combination resulted in significant reduced levels of proinflammatory mediators TNF-α, IL-1 β, and IL-6 (P < 0.05, 0.001, and 0.01, respectively) compared to arthritic animals. Topical delivery of curcumin with emu oil holds promise as a noninvasive and efficacious intervention for the treatment of inflammatory arthritis and it assists in further development of a topical formulation of curcumin using emu oil as a vehicle. Copyright © 2016 Elsevier Inc. All rights reserved.

FY is an RNA 3' end-processing factor that interacts with FCA to control the Arabidopsis floral transition.

PubMed

Simpson, Gordon G; Dijkwel, Paul P; Quesada, Victor; Henderson, Ian; Dean, Caroline

2003-06-13

The nuclear RNA binding protein, FCA, promotes Arabidopsis reproductive development. FCA contains a WW protein interaction domain that is essential for FCA function. We have identified FY as a protein partner for this domain. FY belongs to a highly conserved group of eukaryotic proteins represented in Saccharomyces cerevisiae by the RNA 3' end-processing factor, Pfs2p. FY regulates RNA 3' end processing in Arabidopsis as evidenced through its role in FCA regulation. FCA expression is autoregulated through the use of different polyadenylation sites within the FCA pre-mRNA, and the FCA/FY interaction is required for efficient selection of the promoter-proximal polyadenylation site. The FCA/FY interaction is also required for the downregulation of the floral repressor FLC. We propose that FCA controls 3' end formation of specific transcripts and that in higher eukaryotes, proteins homologous to FY may have evolved as sites of association for regulators of RNA 3' end processing.

Fuzzy and rough formal concept analysis: a survey

NASA Astrophysics Data System (ADS)

Poelmans, Jonas; Ignatov, Dmitry I.; Kuznetsov, Sergei O.; Dedene, Guido

2014-02-01

Formal Concept Analysis (FCA) is a mathematical technique that has been extensively applied to Boolean data in knowledge discovery, information retrieval, web mining, etc. applications. During the past years, the research on extending FCA theory to cope with imprecise and incomplete information made significant progress. In this paper, we give a systematic overview of the more than 120 papers published between 2003 and 2011 on FCA with fuzzy attributes and rough FCA. We applied traditional FCA as a text-mining instrument to 1072 papers mentioning FCA in the abstract. These papers were formatted in pdf files and using a thesaurus with terms referring to research topics, we transformed them into concept lattices. These lattices were used to analyze and explore the most prominent research topics within the FCA with fuzzy attributes and rough FCA research communities. FCA turned out to be an ideal metatechnique for representing large volumes of unstructured texts.

Abscisic acid does not disrupt either the Arabidopsis FCA-FY interaction or its rice counterpart in vitro.

PubMed

Jang, Yun Hee; Lee, Jeong Hwan; Kim, Jeong-Kook

2008-12-01

We examined the effect of (+)-ABA on the in vitro interaction of rice FCA and FY homologs, OsFCA and OsFY. From this analysis, we found no disruption of the OsFCA-OsFY complexes by ABA treatment. This result prompted us to examine the effect of ABA on the FCA-FY interaction. In these experiments, we could not reproduce the inhibitory effect of (+)-ABA on the interaction between FCA and FY. Based on these combined results, we believe that the inhibitory effect of (+)-ABA on the FCA-FY interaction should be cautiously reconsidered.

Family Caregiver Alliance

MedlinePlus

... content Search form Search About FCA Mission and Values Programs and Services Overview Board and Staff Grants and Awards FCA Donors FCA History Jobs at FCA Caregiver Education Health Conditions Caregiving Issues and Strategies Fact and ...

Hands-On Skills for Caregivers

MedlinePlus

... content Search form Search About FCA Mission and Values Programs and Services Overview Board and Staff Grants and Awards FCA Donors FCA History Jobs at FCA Calendar Caregiver Education Learning Center Health Conditions Caregiving Issues and Strategies ...

Detection of Felis catus gammaherpesvirus 1 (FcaGHV1) in peripheral blood B- and T-lymphocytes in asymptomatic, naturally-infected domestic cats

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

McLuckie, Alicia J.; Barrs, Vanessa R.

The domestic cat is natural host to both feline immunodeficiency virus and Felis catus gammaherpesvirus 1 (FcaGHV1). Comparative data suggest that these agents might act as synergistic copathogens in feline AIDS-related lymphoma. To identify leucocyte subsets harbouring gammaherpesvirus DNA, whole blood from 5 healthy, FcaGHV1-infected cats was labelled with monoclonal antibodies to feline CD21, CD4, CD8 and CD14 for 4-way fluorescence-activated cell sorting. FcaGHV1gB qPCR was performed on DNA extracted from purified fractions and whole blood longitudinally. FcaGHV1 DNA was detected in CD21+, CD4+, CD8+, but not CD14+ cells. Variation in whole blood load, up to 19,788 copies/10{sup 6}cells, wasmore » detected in individual cats over time. FcaGHV1 DNA was undetectable in one cat on one occasion highlighting that qPCR of whole blood from a single time point will not detect all cases of FcaGHV1 infection. Further investigation of the role of FcaGHV1 in feline lymphoid malignancies is warranted. -- Highlights: •FcaGHV1 DNA detected in circulating B and T lymphocytes in domestic cats. •Peripheral FcaGHV1 load fluctuates widely in healthy, chronically-infected cats. •qPCR of blood taken at a single time-point will fail to detect some FcaGHV-infected cats. •A role for FcaGHV1 in FIV-associated lymphoid malignancies is supported.« less

Felis catus papillomavirus type-2 but not type-1 is detectable and transcriptionally active in the blood of healthy cats.

PubMed

Altamura, G; Jebara, G; Cardeti, G; Borzacchiello, G

2018-04-01

Papillomaviruses (PVs) are small DNA viruses that induce benign and/or malignant epithelial tumours in different species, including the domestic cat (Felis catus). To date, five F. catus papillomavirus genotypes have been identified (FcaPV-1 to FcaPV-5). FcaPV-1 is associated with skin and oral benign lesions, while FcaPV-2 infection is widely associated with feline squamous cell carcinomas. Several human and animal PVs have been found in body fluids such as peripheral blood; however, the presence of FcaPVs in non-epithelial tissues has not previously been investigated. The aim of this study was to assess the presence and gene expression of FcaPV-1 and FcaPV-2 in the blood of healthy cats. We detected FcaPV-2 DNA in 26 of 103 (25%) blood samples. Importantly, FcaPV-2 L1, E2, E6 and E7 genes were found to be expressed in 3 (25%), 11 (92%), 6 (50%) and 5 (42%) of the samples available for mRNA analysis, respectively. FcaPV-1 was not detected in any of the blood samples analysed here. The data obtained in this work suggest active and eventually productive infection of FcaPV-2 in the blood of healthy cats, implying a possible role in intra-individual spreading as well as in vertical and horizontal transmission. © 2017 Blackwell Verlag GmbH.

Molecular Diagnosis of Felis catus Gammaherpesvirus 1 (FcaGHV1) Infection in Cats of Known Retrovirus Status with and without Lymphoma

PubMed Central

McLuckie, Alicia J.; Barrs, Vanessa R.; Lindsay, Scott; Aghazadeh, Mahdis; Sangster, Cheryl

2018-01-01

The pathogenicity of Felis catus gammaherpesvirus 1 (FcaGHV1), a common infection of domestic cats, is unknown. To explore an association between FcaGHV1 detection and feline lymphoma, a retrospective, cross-sectional, disease-association study was conducted. The infection status of all cats for feline immunodeficiency virus and feline leukaemia virus was determined. Neither a molecular diagnosis of FcaGHV1 nor whole-blood FcaGHV1 load was related to outcome in 122 lymphoma cases compared with 71 controls matched for age and sex. Molecular analysis of lymphoma-derived DNA paired with autologous uninvolved tissue did not suggest restriction of FcaGHV1 DNA to tumour tissue. FcaGHV1 DNA detection was associated with significantly shorter survival in lymphoma cases, an observation that could not be adequately explained by treatment differences. In addition, regressive feline leukaemia virus infection was identified as a risk factor for lymphoma. A history of fighting or roaming was identified as a novel epidemiological risk factor for FcaGHV1 detection, lending support to intercat aggression as a potential route of transmission. Studies investigating the cellular location and expression of FcaGHV1 are indicated to assist in ruling out a lymphomagenic role for this virus. Prospective investigation of FcaGHV1 DNA detection as a prognostic marker in feline lymphoma is warranted. PMID:29538321

Transforming properties of Felis catus papillomavirus type 2 E6 and E7 putative oncogenes in vitro and their transcriptional activity in feline squamous cell carcinoma in vivo

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

Altamura, Gennaro, E-mail: gennaro.altamura@unina.it; Corteggio, Annunziata, E-mail: ancorteg@unina.it; Pacini, Laura, E-mail: PaciniL@students.iarc.fr

Felis catus papillomavirus type 2 (FcaPV2) DNA is found in feline cutaneous squamous cell carcinomas (SCCs); however, its biological properties are still uncharacterized. In this study, we successfully expressed FcaPV2 E6 and E7 putative oncogenes in feline epithelial cells and demonstrated that FcaPV2 E6 binds to p53, impairing its protein level. In addition, E6 and E7 inhibited ultraviolet B (UVB)-triggered accumulation of p53, p21 and pro-apoptotic markers such as Cleaved Caspase3, Bax and Bak, suggesting a synergistic action of the virus with UV exposure in tumour pathogenesis. Furthermore, FcaPV2 E7 bound to feline pRb and impaired pRb levels, resulting inmore » upregulation of the downstream pro-proliferative genes Cyclin A and Cdc2. Importantly, we demonstrated mRNA expression of FcaPV2 E2, E6 and E7 in feline SCC samples, strengthening the hypothesis of a causative role in the development of feline SCC. - Highlights: • FcaPV2 E6 binds to and deregulates feline p53 protein. • FcaPV2 E7 binds to and deregulates feline pRb protein. • FcaPV2 oncogenes inhibit UVB-induced apoptosis. • FcaPV2 E6E7 and E7 increase the lifespan of primary cells. • FcaPV2 E2, E6 and E7 are expressed at the mRNA level in feline SCC in vivo.« less

12 CFR 623.2 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... business with the FCA, including but not limited to: (1) The representation of another person at any... or knowledge in connection with any filing with the FCA; (3) A presentation to the FCA or a presiding...

12 CFR 623.2 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... business with the FCA, including but not limited to: (1) The representation of another person at any... or knowledge in connection with any filing with the FCA; (3) A presentation to the FCA or a presiding...

Learn About FCA Violations

EPA Pesticide Factsheets

Learn about EPA's issued notice of violation (NOV) of the Clean Air Act (CAA) to Fiat Chrysler Automobiles N.V. and FCA US LLC. The NOV alleges that FCA installed software that circumvents EPA emissions standards for certain air pollutants.

Chemical Dissolution of Simulant FCA Cladding and Plates

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

Daniel, G.; Pierce, R.; O'Rourke, P.

The Savannah River Site (SRS) has received some fast critical assembly (FCA) fuel from the Japan Atomic Energy Agency (JAEA) for disposition. Among the JAEA FCA fuel are approximately 7090 rectangular Stainless Steel clad fuel elements. Each element has an internal Pu-10.6Al alloy metal wafer. The thickness of each element is either 1/16 inch or 1/32 inch. The dimensions of each element ranges from 2 inches x 1 inch to 2 inches x 4 inches. This report discusses the potential chemical dissolution of the FCA clad material or stainless steel. This technology uses nitric acid-potassium fluoride (HNO 3-KF) flowsheets ofmore » H-Canyon to dissolve the FCA elements from a rack of materials. Historically, dissolution flowsheets have aimed to maximize Pu dissolution rates while minimizing stainless steel dissolution (corrosion) rates. Because the FCA cladding is made of stainless steel, this work sought to accelerate stainless steel dissolution.« less

Advancing Transportation through Vehicle Electrification - PHEV

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

Bazzi, Abdullah; Barnhart, Steven

2014-12-31

FCA US LLC viewed the American Recovery and Reinvestment Act (ARRA) as an historic opportunity to learn about and develop PHEV technologies and create the FCA US LLC engineering center for Electrified Powertrains. The ARRA funding supported FCA US LLC’s light-duty electric drive vehicle and charging infrastructure-testing activities and enabled FCA US LLC to utilize the funding on advancing Plug-in Hybrid Electric Vehicle (PHEV) technologies for production on future programs. FCA US LLC intended to develop the next-generations of electric drive and energy batteries through a properly paced convergence of standards, technology, components and common modules. To support the developmentmore » of a strong, commercially viable supplier base, FCA US LLC also utilized this opportunity to evaluate various designated component and sub-system suppliers. The original proposal of this project was submitted in May 2009 and selected in August 2009. The project ended in December 2014.« less

Survey of rice proteins interacting with OsFCA and OsFY proteins which are homologous to the Arabidopsis flowering time proteins, FCA and FY.

PubMed

Jang, Yun Hee; Park, Hyo-Young; Kim, Soon-Kap; Lee, Jeong Hwan; Suh, Mi Chung; Chung, Young Soo; Paek, Kyung-Hee; Kim, Jeong-Kook

2009-08-01

The FCA protein is involved in controlling flowering time and plays more general roles in RNA-mediated chromatin silencing in Arabidopsis. It contains two RNA-binding domains and a WW domain. The FCA protein interacts with FY, a polyadenylation factor, via its WW domain. We previously characterized a rice gene, OsFCA, which was homologous to FCA. Here, we found that the OsFCA protein could interact through its WW domain with the following proteins: OsFY, a protein containing a CID domain present in RNA-processing factors such as Pcf11 and Nrd1; a protein similar to splicing factor SF1; a protein similar to FUSE splicing factor; and OsMADS8. The FY protein is associated with the 3' end processing machinery in Arabidopsis. Thus, we examined interactions between OsFY and the rice homologs (OsCstF-50, -64 and -77) of the AtCstF-50, -64 and -77 proteins. We found that OsFY could bind OsCstF50, whereas the OsCstF77 protein could bridge the interaction between OsCstF50 and OsCstF64. Taken together, our data suggest that OsFCA could interact with several proteins other than OsFY through its WW domain and may play several roles in rice.

Altered interactions within FY/AtCPSF complexes required for Arabidopsis FCA-mediated chromatin silencing.

PubMed

Manzano, David; Marquardt, Sebastian; Jones, Alexandra M E; Bäurle, Isabel; Liu, Fuquan; Dean, Caroline

2009-05-26

The role of RNA metabolism in chromatin silencing is now widely recognized. We have studied the Arabidopsis RNA-binding protein FCA that down-regulates an endogenous floral repressor gene through a chromatin mechanism involving histone demethylase activity. This mechanism needs FCA to interact with an RNA 3' processing/polyadenylation factor (FY/Pfs2p), but the subsequent events leading to chromatin changes are unknown. Here, we show that this FCA-FY interaction is required for general chromatin silencing roles where hairpin transgenes induce DNA methylation of an endogenous gene. We also show 2 conserved RNA processing factors, AtCPSF100 and AtCPSF160, but not FCA, are stably associated with FY in vivo and form a range of different-sized complexes. A hypomorphic fy allele producing a shorter protein, able to provide some FY functions but unable to interact with FCA, reduces abundance of some of the larger MW complexes. Suppressor mutants, which specifically disrupt the FY motif through which FCA interacts, also lacked these larger complexes. Our data support a model whereby FCA, perhaps after recognition of a specific RNA feature, transiently interacts with FY, an integral component of the canonical RNA 3' processing machinery, changing the interactions of the different RNA processing components. These altered interactions would appear to be a necessary step in this RNA-mediated chromatin silencing.

Transformation Characteristics of Ferrite/Carbide Aggregate in Continuously Cooled, Low Carbon-Manganese Steels

NASA Astrophysics Data System (ADS)

Di Martino, S. F.; Thewlis, G.

2014-02-01

Transformation characteristics and morphological features of ferrite/carbide aggregate (FCA) in low carbon-manganese steels have been investigated. Work shows that FCA has neither the lamellae structure of pearlite nor the lath structure of bainite and martensite. It consists of a fine dispersion of cementite particles in a smooth ferrite matrix. Carbide morphologies range from arrays of globular particles or short fibers to extended, branched, and densely interconnected fibers. Work demonstrates that FCA forms over similar cooling rate ranges to Widmanstätten ferrite. Rapid transformation of both phases occurs at temperatures between 798 K and 973 K (525 °C and 700 °C). FCA reaction is not simultaneous with Widmanstätten ferrite but occurs at temperatures intermediate between Widmanstätten ferrite and bainite. Austenite carbon content calculations verify that cementite precipitation is thermodynamically possible at FCA reaction temperatures without bainite formation. The pattern of precipitation is confirmed to be discontinuous. CCT diagrams have been constructed that incorporate FCA. At low steel manganese content, Widmanstätten ferrite and bainite bay sizes are significantly reduced so that large amounts of FCA are formed over a wide range of cooling rates.

[Genetic diversity of microsatellite loci in captive Amur tigers].

PubMed

Zhang, Yu-Gaung; Li, Di-Qiang; Xiao, Qi-Ming; Rao, Li-Qun; Zhang, Xue-Wen

2004-09-01

The tiger is one of the most threatened wildlife species since the abundance and distribution of tiger have decreased dramatically in the last century. The wild Amur tiger (Panthera tigris altaica) only distributed in northeast China, the far east area of Russia and the north Korea and its size of wild population is about 450 in the world and 20 in China. Several hundred captive populations of Amur tigers are the main source to protect gene library of tiger and the source of recovering the wild populations. The Breeding Center for Felidae at Hengdaohezi and Haoerbin Tiger Park in Heilongjiang Province is the biggest captive breeding base in China. How to make clear the genetic pedigree and establish reasonable breeding system is the urgent issues. So we use the microsatellite DNA markers and non-invasive technology to research on the genetic diversity of captive Amur tiger in this study. Ten microsatellite loci (Fca005, Fca075, Fca094, Fca152, Fca161, Fca294, Pti002, Pti003, Pti007 and Pti010), highly variable nuclear markers, were studied their genetic diversity in 113 captive Amur tigers. The PCR amplified products of microsatellite loci were detected by non-denatured polyacrylamide gel electrophoresis. Allele numbers, allelic frequency, gene heterozygosity(H(e)), polymorphism information content(PIC) and effective number of allele(N(e)) were calculated. 41 alleles were found and their size were ranged from 110bp to 250bp in ten microsatellite loci, Fca152 had 6 alleles, Fca075, Fca094 and Fca294 had 5 alleles, Fca005 and Pti002 had 4 alleles and the others had 3 alleles in all tiger samples, respectively. The allelic frequencies were from 0.009 to 0.767; The He ranged from 0.385 to 0.707, and Fca294 and Pti010 locus had the highest and lowest value; the PIC were from 0.353 to 0.658, Fca294 and Pti010 locus had the highest and lowest value; and N(e) were from 1.626 to 3.409, Fca294 and Pti010 locus had the highest and lowest value, which showed the ten microsatellie loci had high or medium polymorphism in these Amur tigers and had high genetic diversity. At the same time, we only found even bases variability which showed the even bases repeat sequence (CA/GT) maybe the basic unit for length variability of microsatellite in all loci. In this study, the samples were made up of 75 hair specimens, 23 blood specimens and 15 tissue specimens, we obtained the genome DNA from hairs using the non-invasive DNA technology and demonstrated that DNA derived from hair samples is as good as that obtained from blood samples for the analysis of microsatellite polymorphism. These results imply that microsatellite DNA markers and non-invasive DNA technology can help study the genetic diversity of Amur tiger. This method could be used in the captive management of other endangered species.

Four-corner arthrodesis with a radiolucent locking dorsal circular plate: technique and outcomes.

PubMed

Rudnick, Benjamin; Goljan, Peter; Pruzansky, Jason S; Bachoura, Abdo; Jacoby, Sidney M; Rekant, Mark S

2014-09-01

Scaphoid excision and four-corner arthrodesis (FCA) is an acceptable motion sparing procedure used to treat wrist arthritis. Recently, a locking dorsal circular plate composed of polyether-ether-ketone has been introduced (Xpode®; TriMed Inc.). The purpose of this study is to assess the efficacy of this specific plate design with regard to FCA. A retrospective chart review of all patients who underwent FCA with an Xpode® between January 1, 2008 and December 31, 2012 was conducted. Patients were contacted and asked to return to clinic for clinical and radiographic follow-up. Patient demographics, range of motion, grip strength, and complications were collected from medical records. Patients completed a patient-rated wrist evaluation (PRWE). A paired t test was used to compare means, and p values <0.05 were considered statistically significant. Twenty-six procedures (24 patients) were identified. One patient required full wrist fusion following the initial procedure. Of the 25 remaining wrists, arthrodesis was successfully achieved in 20 (80 %). Eleven patients (13 wrists, 52 %) returned to clinic for an average follow-up of 28 months. Mean wrist extension improved from 30 to 47°, and flexion decreased from 33 to 23°. Average grip strength was 77 % of the uninjured side. The mean PRWE scores for pain and function were 19.7 and 17.1, respectively. Five patients underwent additional operations (two hardware removals, two contracture releases, and one distal radial ulnar joint arthroplasty). FCA with the Xpode® yielded reasonable results for pain and function and demonstrated a fusion rate of 80 %.

78 FR 42893 - Statement on Regulatory Burden

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-18

... efficiency reasons, commenters are encouraged to submit comments by email or through FCA's Web site. As... the following methods: Email: Send us an email at [email protected] . FCA Web site: http://www.fca.gov... and addresses, will be publicly available. However, we will attempt to remove email addresses to help...

Suppression of chronic experimental autoimmune neuritis by nasally administered recombinant rat interleukin-6

PubMed Central

DERETZI, G; PELIDOU, S-H; ZOU, L-P; QUIDING, C; MIX, E; LEVI, M; WAHREN, B; ZHU, J

1999-01-01

Experimental autoimmune neuritis (EAN) is a CD4+ T-cell-mediated demyelinating disease of the peripheral nervous system (PNS) and serves as experimental model for human immune-demyelinating neurophathies, especially the Guillain–Barré syndrome. In this study, we examined the effect of recombinant rat interleukin-6 (rrIL-6) on chronic EAN in Lewis rats induced by immunization with P2 peptide 57-81 and Freund’s complete adjuvant (FCA). Nasal administration of rat rIL-6 (1 μg/rat/day) beginning in the initial phase of EAN as a therapeutic agent, decreased the severity and the duration of clinical EAN. Low-grade inflammation and suppression of regional demyelination within the sciatic nerves were seen in rrIL-6-treated rats. Hyporesponsiveness of lymph node T cells, down-regulation of serum tumour necrosis factor-α (TNF-α) and increased levels of P2-specific immunoglobulin G1 (IgG1) antibodies document that nasal administration of rrIL-6 was effective systemically. However, because of the non-specific nature of the treatment and multiple effects of IL-6, more experience and great caution are needed, before nasal administration of IL-6 can be considered as a treatment of human autoimmune demyelinating neurophathies. PMID:10447716

Immunological cross-reactivity between acid extracts of myelin, liver and neoplastic tissues: studies in immunized guinea-pigs.

PubMed Central

Flavell, D. J.; Goepel, J.; Wilson, A. P.; Potter, C. W.

1979-01-01

Groups of 4 guinea-pigs were immunized with acid extracts prepared from bovine myelin (EF), normal human liver tissue and malignant or benign neoplastic tissues in Freund's complete adjuvant (FCA1. The animals were weighed daily and examined for clinical signs of experimental allergic encephalomyelitis (EAE). All the animals immunized with EF developed clinical symptoms of EAE within 21 days of the initial immunization, whilst some of the animals immunized with certain tumour extracts developed symptoms which closely resembled those of EAE. Control animals immunized with FCA only remained asymptomatic. Cellular immunity to the various extracts in immunized animals was assessed 20 days after immunization by i.d. skin testing, and upon killing at Day 21 with the direct peritoneal-exudate macrophage migration inhibition (MMI) test. Brains and spinal cords were removed at killing, fixed in formalin and processed for histological examination. I.d. skin testing was shown to be most consistent in demonstrating positive delayed hypersensitivity, whilst the MMI test frequently gave negative results in the presence of pronounced skin responses to specific extracts. Thus it was shown that 3/4 animals immunized with basic proteins extracted from an adenocarcinoma of the lung or related hepatic metastases, and 1/2 animals immunized with an extract of a carcinoma of the breast, gave intense erythema and induration responses 5 mm in diameter 24 h after i.d. challenge with EF. No such response was obtained in animals immunized with basic proteins extracted from normal human liver, any of the other neoplastic tissues, or in control animals immunized with FCA only. Examination of brains and spinal cords from animals immunized with EF revealed dense infiltration by mononuclear cells in the ependyma and choroid plexus of levels in the spinal cord. Examination of brains and spinal cords from animals immunized with the lung-tumour extract or related hepatic metastases which showed demonstrable immunological cross-reactivity with EF in immunized animals, revealed a number of inflammatory changes characterized by dense infiltrates of mononuclear cells sub-ependymally, and perivascular cuffing in the cortex. However, no significant lesions were seen in the spinal cords of these animals. Polyacrylamide-gel electrophoresis of the 2 tumour extracts exerting this apparent encephalitogenic effect did not reveal proteins within the mol. wt range of EF. Thus the observed pathological effects and cross-reactivity with EF were probably not due to contamination with nervous-tissue components. It is suggested that these tumour extracts may have contained a component or components other than EF, immunologically cross-reactive with EF, and capable of inducing the observed encephalitis. Images Fig. 2 Fig. 3a, b Fig. 3c, d PMID:92328

The prefrontal cortical endocannabinoid system modulates fear-pain interactions in a subregion-specific manner.

PubMed

Rea, Kieran; McGowan, Fiona; Corcoran, Louise; Roche, Michelle; Finn, David P

2018-05-30

The emotional processing and coordination of top-down responses to noxious and conditioned aversive stimuli involves the medial prefrontal cortex (mPFC). Evidence suggests that subregions of the mPFC, (infralimbic (IL), prelimbic (PrL), anterior cingulate (ACC) cortices), differentially alter the expression of contextually-induced fear and nociceptive behaviour. We investigated the role of the endocannabinoid system in the IL, PrL and ACC in formalin-evoked nociceptive behaviour, fear-conditioned analgesia (FCA) and conditioned fear in the presence of nociceptive tone. FCA was modelled in male Lister-hooded rats by assessing formalin-evoked nociceptive behaviour in an arena previously paired with footshock. The effects of intra-mPFC administration of AM251 (CB 1 receptor antagonist/inverse agonist), URB597 (fatty acid amide hydrolase inhibitor) or URB597 + AM251 on FCA and freezing behaviour were assessed. AM251 attenuated FCA when injected into the IL or PrL and reduced contextually induced freezing behaviour when injected intra-IL, but not intra-PrL or intra-ACC. Intra-ACC administration of AM251 alone or in combination with URB597 had no effect on FCA or freezing. URB597 attenuated FCA and freezing behaviour when injected intra-IL, prolonged the expression of FCA when injected intra-PrL and had no effect on these behaviours when injected intra-ACC. These results suggest important and differential roles for FAAH substrates or CB 1 receptors in the PrL, IL and ACC in the expression of FCA and conditioned fear in the presence of nociceptive tone. This article is protected by copyright. All rights reserved.

12 CFR 602.23 - Responses to demands served on FCA employees.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Responses to demands served on FCA employees. 602.23 Section 602.23 Banks and Banking FARM CREDIT ADMINISTRATION ADMINISTRATIVE PROVISIONS RELEASING....23 Responses to demands served on FCA employees. (a) An employee served with a demand or a subpoena...

76 FR 65212 - Caterpillar, Inc., Large Power Systems Division, Including On-Site Leased Workers From Gray...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-20

..., River City, GCA, Lozier, Obrien Bros., HK, FCA and Clifton Gunderson, Mossville, IL; Amended..., Inc., ATS, URS, River City, GCA, Lozier, Obrien Bros., HK, FCA, and Clifton Gunderson were employed on... Interplant Systems, Inc., ATS, URS, River City, GCA, Lozier, Obrien Bros., HK, FCA, and Clifton Gunderson...

Critical Analysis on Open Source LMSs Using FCA

ERIC Educational Resources Information Center

Sumangali, K.; Kumar, Ch. Aswani

2013-01-01

The objective of this paper is to apply Formal Concept Analysis (FCA) to identify the best open source Learning Management System (LMS) for an E-learning environment. FCA is a mathematical framework that represents knowledge derived from a formal context. In constructing the formal context, LMSs are treated as objects and their features as…

Felis catus papillomavirus types 1 and 4 are rarely present in neoplastic and inflammatory oral lesions of cats.

PubMed

Munday, John S; French, Adrienne F

2015-06-01

Oral squamous cell carcinomas (OSCCs) are common feline cancers. Why OSCCs are so common in cats is unknown; however, 25% of human OSCCs are caused by papillomaviruses (PVs). Two feline oral PVs (FcaPV-1 and 4) are recognized. As PVs are highly host and location specific, if PVs do cause feline OSCCs, FcaPV-1 and 4 are the most likely etiological agents. PCR primers specific for FcaPV-1 amplified DNA from 1 of 36 feline OSCCs and 1 of 16 inflammatory oral lesions. No DNA was amplified by primers specific for FcaPV-4. PV DNA was not amplified from any additional sample using consensus primers. No PV cytopathology was visible in the OSCC that contained FcaPV-1 DNA, but viral cytopathology was present in a focus of epithelial hyperplasia in the non-neoplastic sample. This study does not support a PV etiology of feline OSCCs, but shows that FcaPV-1 can asymptomatically infect the mouth of cats. Copyright © 2015 Elsevier Ltd. All rights reserved.

Antihyperalgesic activity of a novel nonpeptide bradykinin B1 receptor antagonist in transgenic mice expressing the human B1 receptor

PubMed Central

Fox, Alyson; Kaur, Satbir; Li, Bifang; Panesar, Moh; Saha, Uma; Davis, Clare; Dragoni, Ilaria; Colley, Sian; Ritchie, Tim; Bevan, Stuart; Burgess, Gillian; McIntyre, Peter

2005-01-01

We describe the properties of a novel nonpeptide kinin B1 receptor antagonist, NVP-SAA164, and demonstrate its in vivo activity in models of inflammatory pain in transgenic mice expressing the human B1 receptor. NVP-SAA164 showed high affinity for the human B1 receptor expressed in HEK293 cells (Ki 8 nM), and inhibited increases in intracellular calcium induced by desArg10kallidin (desArg10KD) (IC50 33 nM). While a similar high affinity was observed in monkey fibroblasts (Ki 7.7 nM), NVP-SAA164 showed no affinity for the rat B1 receptor expressed in Cos-7 cells. In transgenic mice in which the native B1 receptor was deleted and the gene encoding the human B1 receptor was inserted (hB1 knockin, hB1-KI), hB1 receptor mRNA was induced in tissues following LPS treatment. No mRNA encoding the mouse or human B1 receptor was detected in mouse B1 receptor knockout (mB1-KO) mice following LPS treatment. Freund's complete adjuvant-induced mechanical hyperalgesia was similar in wild-type and hB1-KI mice, but was significantly reduced in mB1-KO animals. Mechanical hyperalgesia induced by injection of the B1 agonist desArg10KD into the contralateral paw 24 h following FCA injection was similar in wild-type and hB1-KI mice, but was absent in mB1-KO animals. Oral administration of NVP-SAA164 produced a dose-related reversal of FCA-induced mechanical hyperalgesia and desArg10KD-induced hyperalgesia in hB1-KI mice, but was inactive against inflammatory pain in wild-type mice. These data demonstrate the use of transgenic technology to investigate the in vivo efficacy of species selective agents and show that NVP-SAA164 is a novel orally active B1 receptor antagonist, providing further support for the utility of B1 receptor antagonists in inflammatory pain conditions in man. PMID:15685199

Structural Insights into Membrane Targeting by the Flagellar Calcium-binding Protein (FCaBP) a Myristoylated and Palmitoylated Calcium Sensor in Trypanosoma cruzi

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

J Wingard; J Ladner; M Vanarotti

2011-12-31

The flagellar calcium-binding protein (FCaBP) of the protozoan Trypanosoma cruzi is targeted to the flagellar membrane where it regulates flagellar function and assembly. As a first step toward understanding the Ca{sup 2+}-induced conformational changes important for membrane-targeting, we report here the x-ray crystal structure of FCaBP in the Ca{sup 2+}-free state determined at 2.2{angstrom} resolution. The first 17 residues from the N terminus appear unstructured and solvent-exposed. Residues implicated in membrane targeting (Lys-19, Lys-22, and Lys-25) are flanked by an exposed N-terminal helix (residues 26-37), forming a patch of positive charge on the protein surface that may interact electrostatically withmore » flagellar membrane targets. The four EF-hands in FCaBP each adopt a 'closed conformation' similar to that seen in Ca{sup 2+}-free calmodulin. The overall fold of FCaBP is closest to that of grancalcin and other members of the penta EF-hand superfamily. Unlike the dimeric penta EF-hand proteins, FCaBP lacks a fifth EF-hand and is monomeric. The unstructured N-terminal region of FCaBP suggests that its covalently attached myristoyl group at the N terminus may be solvent-exposed, in contrast to the highly sequestered myristoyl group seen in recoverin and GCAP1. NMR analysis demonstrates that the myristoyl group attached to FCaBP is indeed solvent-exposed in both the Ca{sup 2+}-free and Ca{sup 2+}-bound states, and myristoylation has no effect on protein structure and folding stability. We propose that exposed acyl groups at the N terminus may anchor FCaBP to the flagellar membrane and that Ca{sup 2+}-induced conformational changes may control its binding to membrane-bound protein targets..« less

Altered interactions within FY/AtCPSF complexes required for Arabidopsis FCA-mediated chromatin silencing

PubMed Central

Manzano, David; Marquardt, Sebastian; Jones, Alexandra M. E.; Bäurle, Isabel; Liu, Fuquan; Dean, Caroline

2009-01-01

The role of RNA metabolism in chromatin silencing is now widely recognized. We have studied the Arabidopsis RNA-binding protein FCA that down-regulates an endogenous floral repressor gene through a chromatin mechanism involving histone demethylase activity. This mechanism needs FCA to interact with an RNA 3′ processing/polyadenylation factor (FY/Pfs2p), but the subsequent events leading to chromatin changes are unknown. Here, we show that this FCA–FY interaction is required for general chromatin silencing roles where hairpin transgenes induce DNA methylation of an endogenous gene. We also show 2 conserved RNA processing factors, AtCPSF100 and AtCPSF160, but not FCA, are stably associated with FY in vivo and form a range of different-sized complexes. A hypomorphic fy allele producing a shorter protein, able to provide some FY functions but unable to interact with FCA, reduces abundance of some of the larger MW complexes. Suppressor mutants, which specifically disrupt the FY motif through which FCA interacts, also lacked these larger complexes. Our data support a model whereby FCA, perhaps after recognition of a specific RNA feature, transiently interacts with FY, an integral component of the canonical RNA 3′ processing machinery, changing the interactions of the different RNA processing components. These altered interactions would appear to be a necessary step in this RNA-mediated chromatin silencing. PMID:19439664

Functionalized gold nanorod-based labels for amplified electrochemical immunoassay of E. coli as indicator bacteria relevant to the quality of dairy product.

PubMed

Zhang, Xinai; Zhang, Fan; Zhang, Hongyin; Shen, Jianzhong; Han, En; Dong, Xiaoya

2015-01-01

In this paper, we report an amplified electrochemical immunoassay for Escherichia coli as indicator bacteria relevant to the quality of dairy product using the functionalized gold nanorod-based labels ({dAb-AuNR-FCA}). The {dAb-AuNR-FCA} labels were designed by exploiting silica-functionalized gold nanorods (AuNR@SiO2) as the carriers for immobilization of detection antibody (dAb) and ferrocenecarboxylic acid (FCA), in which dAb was used for recognition of E. coli and FCA tags served as signal-generating molecule. Greatly amplified signal was achieved in the sandwich-type immunoassay when enormous FCA linked to AuNR@SiO2. Compared with the commercially available {dAb-FCA}, the {dAb-AuNR-FCA} labels exhibited a better performance for E. coli assay due to the advantages of AuNR@SiO2 as carriers. Under optimal experimental conditions, it showed a linear relationship between the peak current of FCA and the logarithmic value of E. coli concentration ranging from 1.0×10(2) to 5.0×10(4) cfu mL(-1) with a detection limit of 60 cfu mL(-1) (S/N=3), and the electrochemical detection of E. coli could be achieved in 3h. Moreover, the proposed strategy was used to determine E. coli in dairy product (pure fresh milk, yogurt in shelf-life, and expired yogurt), and the recoveries of standard additions were in the range of 95.1-106%. This proposed strategy exhibited rapid response, high sensitivity and specificity for E. coli assay in dairy product, and could become a promising technique to estimate the quality of dairy product. Copyright © 2014 Elsevier B.V. All rights reserved.

The joint impact of cognitive performance in adolescence and familial cognitive aptitude on risk for major psychiatric disorders: a delineation of four potential pathways to illness.

PubMed

Kendler, K S; Ohlsson, H; Keefe, R S E; Sundquist, K; Sundquist, J

2018-04-01

How do joint measures of premorbid cognitive ability and familial cognitive aptitude (FCA) reflect risk for a diversity of psychiatric and substance use disorders? To address this question, we examined, using Cox models, the predictive effects of school achievement (SA) measured at age 16 and FCA-assessed from SA in siblings and cousins, and educational attainment in parents-on risk for 12 major psychiatric syndromes in 1 140 608 Swedes born 1972-1990. Four developmental patterns emerged. In the first, risk was predicted jointly by low levels of SA and high levels of FCA-that is a level of SA lower than would be predicted from the FCA. This pattern was strongest in autism spectrum disorders and schizophrenia, and weakest in bipolar illness. In these disorders, a pathologic process seems to have caused cognitive functioning to fall substantially short of familial potential. In the second pattern, seen in the internalizing conditions of major depression and anxiety disorders, risk was associated with low SA but was unrelated to FCA. Externalizing disorders-drug abuse and alcohol use disorders-demonstrated the third pattern, in which risk was predicted jointly by low SA and low FCA. The fourth pattern, seen in eating disorders, was directly opposite of that observed in externalizing disorders with risk associated with high SA and high FCA. When measured together, adolescent cognitive ability and FCA identified four developmental patterns leading to diverse psychiatric disorders. The value of cognitive assessments in psychiatric research can be substantially increased by also evaluating familial cognitive potential.

Advancing Plug-In Hybrid Technology and Flex Fuel Application on a Chrysler Minivan

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

Bazzi, Abdullah; Barnhart, Steven

2014-12-31

FCA US LLC viewed this DOE funding as a historic opportunity to begin the process of achieving required economies of scale on technologies for electric vehicles. The funding supported FCA US LLC’s light-duty electric drive vehicle and charging infrastructure-testing activities and enabled FCA US LLC to utilize the funding on advancing Plug-in Hybrid Electric Vehicle (PHEV) technologies to future programs. FCA US LLC intended to develop the next generations of electric drive and energy batteries through a properly paced convergence of standards, technology, components, and common modules, as well as first-responder training and battery recycling. To support the development ofmore » a strong, commercially viable supplier base, FCA US LLC also used this opportunity to evaluate various designated component and sub-system suppliers. The original project proposal was submitted in December 2009 and selected in January 2010. The project ended in December 2014.« less

Information Superiority via Formal Concept Analysis

NASA Astrophysics Data System (ADS)

Koester, Bjoern; Schmidt, Stefan E.

This chapter will show how to get more mileage out of information. To achieve that, we first start with an introduction to the fundamentals of Formal Concept Analysis (FCA). FCA is a highly versatile field of applied lattice theory, which allows hidden relationships to be uncovered in relational data. Moreover, FCA provides a distinguished supporting framework to subsequently find and fill information gaps in a systematic and rigorous way. In addition, we would like to build bridges via a universal approach to other communities which can be related to FCA in order for other research areas to benefit from a theory that has been elaborated for more than twenty years. Last but not least, the essential benefits of FCA will be presented algorithmically as well as theoretically by investigating a real data set from the MIPT Terrorism Knowledge Base and also by demonstrating an application in the field of Web Information Retrieval and Web Intelligence.

12 CFR 602.24 - Responses to demands served on non-FCA employees or entities.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Responses to demands served on non-FCA employees or entities. 602.24 Section 602.24 Banks and Banking FARM CREDIT ADMINISTRATION ADMINISTRATIVE... Not a Named Party § 602.24 Responses to demands served on non-FCA employees or entities. If you are...

Design of Launch Vehicle Flight Control Augmentors and Resulting Flight Stability and Control (Center Director's Discretionary Fund Project 93-05, Part III)

NASA Technical Reports Server (NTRS)

Barret, C.

1997-01-01

This publication presents the control requirements, the details of the designed Flight Control Augmentor's (FCA's), the static stability and dynamic stability wind tunnel test programs, the static stability and control analyses, the dynamic stability characteristics of the experimental Launch Vehicle (LV) with the designed FCA's, and a consideration of the elastic vehicle. Dramatic improvements in flight stability have been realized with all the FCA designs; these ranged from 41 percent to 72 percent achieved by the blunt TE design. The control analysis showed that control increased 110 percent with only 3 degrees of FCA deflection. The dynamic stability results showed improvements with all FCA designs tested at all Mach numbers tested. The blunt TE FCA's had the best overall dynamic stability results. Since the lowest elastic vehicle frequency must be well separated from that of the control system, the significant frequencies and modes of vibration have been identified, and the response spectra compared for the experimental LV in both the conventional and the aft cg configuration. Although the dynamic response was 150 percent greater in the aft cg configuration, the lowest bending mode frequency decreased by only 2.8 percent.

Association between occupation and contact allergy to the fragrance mix: a multifactorial analysis of national surveillance data

PubMed Central

Uter, W; Schnuch, A; Geier, J; Pfahlberg, A; Gefeller, O

2001-01-01

OBJECTIVES—To assess the role of potential (occupational) risk factors for fragrance contact allergy (FCA). Most studies assessing the range of contact sensitisation in various clinical populations found the fragrance mix, a good screening tool for the detection of FCA in general, to be one of the leading allergens. The role of occupational exposure to fragrances is, however, yet unclear.
METHODS—Firstly, crude analyses of the prevalence of FCA in various occupational fields including all 57 779 patients patch tested in the participating centres of the Information Network of Departments of Dermatology (IVDK) between January 1992 and December 1998. Secondly, a multifactorial Poisson regression analysis of these patients, including several potential risk factors.
RESULTS—(a) The proportion of patients with FCA varied greatly between different occupational groups from 2.5% to 17.4%, (b) the highest occupational risk of FCA was associated with work as a masseur or physiotherapist, metal furnace operator, potter or glass maker etc, or geriatric nurse, (c) non-occupational factors that influenced risk of FCA included atopy, female sex, several sites, in particular the axillae, and increasing age.
CONCLUSIONS—Occupations with a high risk of FCA were identified as targets of preventive action—that is, the substitution of scented products with fragrance free materials with which to work (skin disinfectants, cleaning solutions, personal care products) wherever possible.


Keywords: contact allergy; occupational risk factors; fragrances PMID:11351055

76 FR 54637 - Board Policy Statements

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-01

...The Farm Credit Administration (FCA) Board recently undertook its 5-year review of FCA Board policy statements. This review resulted in revisions to 14 policy statements that are mostly technical, grammatical, or syntactical. However, a few of the revisions add clarity to the policy statements and other revisions incorporate changes required either by new laws or by changes in the functional statement of operations for some FCA offices.

Flow cytometry analysis using sysmex UF-1000i classifies uropathogens based on bacterial, leukocyte, and erythrocyte counts in urine specimens among patients with urinary tract infections.

PubMed

Monsen, Tor; Rydén, Patrik

2015-02-01

Urinary tract infections (UTIs) are the second most common bacterial infection. Urine culture is the gold standard for diagnosis, but new techniques, such as flow cytometry analysis (FCA), have been introduced. The aim of the present study was to evaluate FCA characteristics regarding bacteriuria, leukocyturia, and erythrocyturia in relation to cultured uropathogens in specimens from patients with a suspected UTI. We also wanted to evaluate whether the FCA characteristics can identify uropathogens prior to culture. From a prospective study, 1,587 consecutive urine specimens underwent FCA prior to culture during January and February 2012. Outpatients and inpatients (79.6% and 19.4%, respectively) were included, of whom women represented 67.5%. In total, 620 specimens yielded growth, of which Escherichia coli represented 65%, Enterococcus spp. 8%, Klebsiella spp. 7%, and Staphylococcus spp. 5%. For the uropathogens, the outcome of FCA was compared against the results for specimens with E. coli and those with a negative culture. E. coli had high bacterial (median, 17,914/μl), leukocyte (median, 348/μl), and erythrocyte (median, 23/μl) counts. With the exception of Klebsiella spp., the majority of the uropathogens had considerable or significantly lower bacterial counts than that of E. coli. High leukocyte counts were found in specimens with Staphylococcus aureus, Proteus mirabilis, Pseudomonas aeruginosa, and group C streptococci. Elevated erythrocyte counts were found for P. vulgaris, P. aeruginosa, and group C streptococci, as well as for Staphylococcus saprophyticus. In essence, FCA adds new information about the bacterial, leukocyte, and erythrocyte counts in urine specimens for different uropathogens. Based on FCA characteristics, uropathogens can be classified and identified prior to culture. E. coli and Klebsiella spp. have similar FCA characteristics. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

A new concept and a comprehensive evaluation of SYSMEX UF-1000i  flow cytometer to identify culture-negative urine specimens in patients with UTI.

PubMed

Monsen, T; Ryden, P

2017-09-01

Urinary tract infections (UTIs) are among the most common bacterial infections in men and urine culture is gold standard for diagnosis. Considering the high prevalence of culture-negative specimens, any method that identifies such specimens is of interest. The aim was to evaluate a new screening concept for flow cytometry analysis (FCA). The outcomes were evaluated against urine culture, uropathogen species and three conventional screening methods. A prospective, consecutive study examined 1,312 urine specimens, collected during January and February 2012. The specimens were analyzed using the Sysmex UF1000i FCA. Based on the FCA data culture negative specimens were identified in a new model by use of linear discriminant analysis (FCA-LDA). In total 1,312 patients were included. In- and outpatients represented 19.6% and 79.4%, respectively; 68.3% of the specimens originated from women. Of the 610 culture-positive specimens, Escherichia coli represented 64%, enterococci 8% and Klebsiella spp. 7%. Screening with FCA-LDA at 95% sensitivity identified 42% (552/1312) as culture negative specimens when UTI was defined according to European guidelines. The proposed screening method was either superior or similar in comparison to the three conventional screening methods. In conclusion, the proposed/suggested and new FCA-LDA screening method was superior or similar to three conventional screening methods. We recommend the proposed screening method to be used in clinic to exclude culture negative specimens, to reduce workload, costs and the turnaround time. In addition, the FCA data may add information that enhance handling and support diagnosis of patients with suspected UTI pending urine culture [corrected].

Prevalence and risk factors of gammaherpesvirus infection in domestic cats in Central Europe.

PubMed

Ertl, Reinhard; Korb, Melanie; Langbein-Detsch, Ines; Klein, Dieter

2015-09-17

Gammaherpesviruses (GHVs) are a large group of dsDNA viruses that can infect humans and several animal species. The two human GHVs, Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus are known for their oncogenic properties in individuals with immunodeficiency. Recently, the first feline GHV, Felis catus gammaherpesvirus 1 (FcaGHV1) was discovered and frequently found in domestic cats in Australia, Singapore and the USA. FcaGHV1 is more likely to be detected in cats co-infected with the feline immunodeficiency virus (FIV). The prevalence of FcaGHV1 in pet cats from Germany and Austria was 16.2 % (95 % CI = 12.38-20.02). The odds for GHV infection were greater for FIV positive (OR = 4.5), male (OR = 13.32) and older (OR = 2.36) cats. Furthermore, FcaGHV1 viral loads were significantly higher in FIV-infected cats compared to matched controls. GHV infections are common in domestic cats in Central Europe. The worldwide distribution of FcaGHV1 can be assumed. A potential role as a co-factor in FIV-induced pathogeneses is supported.

77 FR 74183 - Farm Credit Administration Board Action To Approve a Plan of Voluntary Liquidation for, and To...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-13

...On August 22, 2012, the Farm Credit Administration (FCA) Board authorized the voluntary liquidation of the Farm Credit Finance Corporation of Puerto Rico (FCFCPR) without the appointment of a receiver, and the cancellation of FCFCPR's charter arising out of the voluntary liquidation of the corporation. The Farm Credit Administration (FCA) Board also granted preliminary and final approval of the proposed Plan of Liquidation for the FCFCPR under 12 CFR 627.2795--Voluntary Liquidation of FCA regulations.

Involvement of oxygen free radicals in the respiratory uncoupling induced by free calcium and ADP-magnesium in isolated cardiac mitochondria: comparing reoxygenation in cultured cardiomyocytes.

PubMed

Meynier, Alexandra; Razik, Hafida; Cordelet, Catherine; Grégoire, Stéphane; Demaison, Luc

2003-01-01

Recently, we have observed that the simultaneous application of free calcium (fCa) and ADP-magnesium (Mg) reduced the ADP:O ratio in isolated cardiac mitochondria. The uncoupling was prevented by cyclosporin A, an inhibitor of the permeability transition pore. The purpose of this study was to know if the generation of oxygen free radicals (OFR) is involved in this phenomenon and if it occurs during reoxygenation (Reox) of cultured cardiomyocytes. Cardiac mitochondria were harvested from male Wistar rats. Respiration was assessed in two media with different fCa concentrations (0 or 0.6 microM) with palmitoylcarnitine and ADP-Mg as respiration substrates. The production of Krebs cycle intermediates (KCI) was determined. Without fCa in the medium, the mitochondria displayed a large production of citrate + isocitrate + alpha-ketoglutarate. fCa drastically reduced these KCI and promoted the accumulation of succinate. To know if OFR are involved in the respiratory uncoupling, the effect of 4OH-TEMPO (250 microM), a hydrosoluble scavenger of OFR, was tested. 4OH-TEMPO completely abolished the fCa- and ADP-Mg-induced uncoupling. Conversely, vitamin E contributed to further decreasing the ADP:O ratio. Since no hydrosoluble electron acceptor was added in our experiment, the oxygen free radical-induced oxidized vitamin E was confined near the mitochondrial membranes, which should reduce the ADP:O ratio by opening the permeability transition pore. The generation of OFR could result from the matrix accumulation of succinate. Taken together, these results indicate that mitochondrial Ca uptake induces a slight increase in membrane permeability. Thereafter, Mg enters the matrix and, in combination with Ca, stimulates the isocitrate and/or alpha-ketoglutarate dehydrogenases. Matrix succinate favors oxygen free radical generation that further increases membrane permeability and allows respiratory uncoupling through proton leakage. To determine whether the phenomenon takes place during Reox, cultured cardiomyocytes were subjected to hypoxia and Reox. 14C-palmitate was added during Reox to determine the KCI profile. Succinate had not increased during Reox. In conclusion, calcium- and ADP-Mg-induced respiratory uncoupling is due to oxygen free radical generation through excess matrix accumulation of succinate. The phenomenon does not occur during reoxygenation because of a total restoration of mitochondrial magnesium and/or ADP concentration.

Hot Weather Tips

MedlinePlus

... Caregiver Stories Connections e-Newsletter Research Registry FCA+(plus) Services Press Media Kit What’s New FCA Blog ... person plenty of water and fruit or vegetable juice even if they say they’re not thirsty. ...

A formal concept analysis approach to consensus clustering of multi-experiment expression data

PubMed Central

2014-01-01

Background Presently, with the increasing number and complexity of available gene expression datasets, the combination of data from multiple microarray studies addressing a similar biological question is gaining importance. The analysis and integration of multiple datasets are expected to yield more reliable and robust results since they are based on a larger number of samples and the effects of the individual study-specific biases are diminished. This is supported by recent studies suggesting that important biological signals are often preserved or enhanced by multiple experiments. An approach to combining data from different experiments is the aggregation of their clusterings into a consensus or representative clustering solution which increases the confidence in the common features of all the datasets and reveals the important differences among them. Results We propose a novel generic consensus clustering technique that applies Formal Concept Analysis (FCA) approach for the consolidation and analysis of clustering solutions derived from several microarray datasets. These datasets are initially divided into groups of related experiments with respect to a predefined criterion. Subsequently, a consensus clustering algorithm is applied to each group resulting in a clustering solution per group. These solutions are pooled together and further analysed by employing FCA which allows extracting valuable insights from the data and generating a gene partition over all the experiments. In order to validate the FCA-enhanced approach two consensus clustering algorithms are adapted to incorporate the FCA analysis. Their performance is evaluated on gene expression data from multi-experiment study examining the global cell-cycle control of fission yeast. The FCA results derived from both methods demonstrate that, although both algorithms optimize different clustering characteristics, FCA is able to overcome and diminish these differences and preserve some relevant biological signals. Conclusions The proposed FCA-enhanced consensus clustering technique is a general approach to the combination of clustering algorithms with FCA for deriving clustering solutions from multiple gene expression matrices. The experimental results presented herein demonstrate that it is a robust data integration technique able to produce good quality clustering solution that is representative for the whole set of expression matrices. PMID:24885407

Measuring Spatial Accessibility of Health Care Providers – Introduction of a Variable Distance Decay Function within the Floating Catchment Area (FCA) Method

PubMed Central

Groneberg, David A.

2016-01-01

We integrated recent improvements within the floating catchment area (FCA) method family into an integrated ‘iFCA`method. Within this method we focused on the distance decay function and its parameter. So far only distance decay functions with constant parameters have been applied. Therefore, we developed a variable distance decay function to be used within the FCA method. We were able to replace the impedance coefficient β by readily available distribution parameter (i.e. median and standard deviation (SD)) within a logistic based distance decay function. Hence, the function is shaped individually for every single population location by the median and SD of all population-to-provider distances within a global catchment size. Theoretical application of the variable distance decay function showed conceptually sound results. Furthermore, the existence of effective variable catchment sizes defined by the asymptotic approach to zero of the distance decay function was revealed, satisfying the need for variable catchment sizes. The application of the iFCA method within an urban case study in Berlin (Germany) confirmed the theoretical fit of the suggested method. In summary, we introduced for the first time, a variable distance decay function within an integrated FCA method. This function accounts for individual travel behaviors determined by the distribution of providers. Additionally, the function inherits effective variable catchment sizes and therefore obviates the need for determining variable catchment sizes separately. PMID:27391649

Matching biomedical ontologies based on formal concept analysis.

PubMed

Zhao, Mengyi; Zhang, Songmao; Li, Weizhuo; Chen, Guowei

2018-03-19

The goal of ontology matching is to identify correspondences between entities from different yet overlapping ontologies so as to facilitate semantic integration, reuse and interoperability. As a well developed mathematical model for analyzing individuals and structuring concepts, Formal Concept Analysis (FCA) has been applied to ontology matching (OM) tasks since the beginning of OM research, whereas ontological knowledge exploited in FCA-based methods is limited. This motivates the study in this paper, i.e., to empower FCA with as much as ontological knowledge as possible for identifying mappings across ontologies. We propose a method based on Formal Concept Analysis to identify and validate mappings across ontologies, including one-to-one mappings, complex mappings and correspondences between object properties. Our method, called FCA-Map, incrementally generates a total of five types of formal contexts and extracts mappings from the lattices derived. First, the token-based formal context describes how class names, labels and synonyms share lexical tokens, leading to lexical mappings (anchors) across ontologies. Second, the relation-based formal context describes how classes are in taxonomic, partonomic and disjoint relationships with the anchors, leading to positive and negative structural evidence for validating the lexical matching. Third, the positive relation-based context can be used to discover structural mappings. Afterwards, the property-based formal context describes how object properties are used in axioms to connect anchor classes across ontologies, leading to property mappings. Last, the restriction-based formal context describes co-occurrence of classes across ontologies in anonymous ancestors of anchors, from which extended structural mappings and complex mappings can be identified. Evaluation on the Anatomy, the Large Biomedical Ontologies, and the Disease and Phenotype track of the 2016 Ontology Alignment Evaluation Initiative campaign demonstrates the effectiveness of FCA-Map and its competitiveness with the top-ranked systems. FCA-Map can achieve a better balance between precision and recall for large-scale domain ontologies through constructing multiple FCA structures, whereas it performs unsatisfactorily for smaller-sized ontologies with less lexical and semantic expressions. Compared with other FCA-based OM systems, the study in this paper is more comprehensive as an attempt to push the envelope of the Formal Concept Analysis formalism in ontology matching tasks. Five types of formal contexts are constructed incrementally, and their derived concept lattices are used to cluster the commonalities among classes at lexical and structural level, respectively. Experiments on large, real-world domain ontologies show promising results and reveal the power of FCA.

Viral Vaccine Immunogenicity in Relation to Host Cell-Mediated and Humoral Immune Responses.

DTIC Science & Technology

1976-05-01

adjuvants, particularly complete Freund’s adjuvant or Bordetella pertussis , were donors capable of consistently transferring adoptive immunity...vac- cine combined with adjuvants, particularly complete Freund’s adjuvant or Bordetella pertussis , were donors capable of consistently transferring...Freund’s adjuvant and Bordetella pertussis , are consistently capable of producing early and brisk serum neutralizing antibody responses in adoptively

An allelic series reveals essential roles for FY in plant development in addition to flowering-time control.

PubMed

Henderson, Ian R; Liu, Fuquan; Drea, Sinead; Simpson, Gordon G; Dean, Caroline

2005-08-01

The autonomous pathway functions to promote flowering in Arabidopsis by limiting the accumulation of the floral repressor FLOWERING LOCUS C (FLC). Within this pathway FCA is a plant-specific, nuclear RNA-binding protein, which interacts with FY, a highly conserved eukaryotic polyadenylation factor. FCA and FY function to control polyadenylation site choice during processing of the FCA transcript. Null mutations in the yeast FY homologue Pfs2p are lethal. This raises the question as to whether these essential RNA processing functions are conserved in plants. Characterisation of an allelic series of fy mutations reveals that null alleles are embryo lethal. Furthermore, silencing of FY, but not FCA, is deleterious to growth in Nicotiana. The late-flowering fy alleles are hypomorphic and indicate a requirement for both intact FY WD repeats and the C-terminal domain in repression of FLC. The FY C-terminal domain binds FCA and in vitro assays demonstrate a requirement for both C-terminal FY-PPLPP repeats during this interaction. The expression domain of FY supports its roles in essential and flowering-time functions. Hence, FY may mediate both regulated and constitutive RNA 3'-end processing.

Productivity Losses Associated with Head and Neck Cancer Using the Human Capital and Friction Cost Approaches.

PubMed

Pearce, Alison M; Hanly, Paul; Timmons, Aileen; Walsh, Paul M; O'Neill, Ciaran; O'Sullivan, Eleanor; Gooberman-Hill, Rachael; Thomas, Audrey Alforque; Gallagher, Pamela; Sharp, Linda

2015-08-01

Previous studies suggest that productivity losses associated with head and neck cancer (HNC) are higher than in other cancers. These studies have only assessed a single aspect of productivity loss, such as temporary absenteeism or premature mortality, and have only used the Human Capital Approach (HCA). The Friction Cost Approach (FCA) is increasingly recommended, although has not previously been used to assess lost production from HNC. The aim of this study was to estimate the lost productivity associated with HNC due to different types of absenteeism and premature mortality, using both the HCA and FCA. Survey data on employment status were collected from 251 HNC survivors in Ireland and combined with population-level survival estimates and national wage data. The cost of temporary and permanent time off work, reduced working hours and premature mortality using both the HCA and FCA were calculated. Estimated total productivity losses per employed person of working age were EUR253,800 using HCA and EUR6800 using FCA. The main driver of HCA costs was premature mortality (38% of total) while for FCA it was temporary time off (73% of total). The productivity losses associated with head and neck cancer are substantial, and return to work assistance could form an important part of rehabilitation. Use of both the HCA and FCA approaches allowed different drivers of productivity losses to be identified, due to the different assumptions of the two methods. For future estimates of productivity losses, the use of both approaches may be pragmatic.

Valuing productivity costs in a changing macroeconomic environment: the estimation of colorectal cancer productivity costs using the friction cost approach.

PubMed

Hanly, Paul; Koopmanschap, Marc; Sharp, Linda

2016-06-01

The friction cost approach (FCA) has been proposed as an alternative to the human capital approach for productivity cost valuation. However, FCA estimates are context dependent and influenced by extant macroeconomic conditions. We applied the FCA to estimate colorectal cancer labor productivity costs and assessed the impact of a changing macroeconomic environment on these estimates. Data from colorectal cancer survivors (n = 159) derived from a postal survey undertaken in Ireland March 2010 to January 2011 were combined with national wage data, population-level survival data, and occupation-specific friction periods to calculate temporary and permanent disability, and premature mortality costs using the FCA. The effects of changing labor market conditions between 2006 and 2013 on the friction period were modeled in scenario analyses. Costs were valued in 2008 euros. In the base-case, the total FCA per-person productivity cost for incident colorectal cancer patients of working age at diagnosis was €8543. In scenario 1 (a 2.2 % increase in unemployment), the fall in the friction period caused total productivity costs to decrease by up to 18 % compared to base-case estimates. In scenario 2 (a 9.2 % increase in unemployment), the largest decrease in productivity cost was up to 65 %. Adjusting for the vacancy rate reduced the effect of unemployment on the cost results. The friction period used in calculating labor productivity costs greatly affects the derived estimates; this friction period requires reassessment following changes in labor market conditions. The influence of changes in macroeconomic conditions on FCA-derived cost estimates may be substantial.

Ferrocene tripeptide Gly-Pro-Arg conjugates: synthesis and inhibitory effects on Alzheimer's Aβ(1-42) fibrillogenesis and Aβ-induced cytotoxicity in vitro.

PubMed

Zhou, Binbin; Li, Chun-Lan; Hao, Yuan-Qiang; Johnny, Muya Chabu; Liu, You-Nian; Li, Juan

2013-01-15

Alzheimer's disease (AD) is the most common cause of dementia, and currently there is no clinical treatment to cure it or to halt its progression. Aggregation and fibril formation of β-amyloid peptides (Aβ) are central events in the pathogenesis of AD. Many efforts have been spent on the development of effective inhibitors to prevent Aβ fibrillogenesis and cause disaggregation of preformed Aβ fibrils. In this study, the conjugates of ferrocene and Gly-Pro-Arg (GPR) tripeptide, Boc-Gly-Pro-Arg(NO(2))-Fca-OMe (4, GPR-Fca) and Fc-Gly-Pro-Arg-OMe (7, Fc-GPR) (Fc: ferrocene; Fca: ferrocene amino acid) were synthesized by HOBT/HBTU protocol in solution. These ferrocene GPR conjugates were employed to inhibit Aβ(1-42) fibrillogenesis and to disaggregate preformed Aβ fibrils. The inhibitory properties of ferrocene GPR conjugates on Aβ(1-42) fibrillogenesis were evaluated by thioflavin T (ThT) fluorescence assay, and confirmed by atomic force microscopy (AFM) analysis. The interaction between the ferrocene GPR conjugates and Aβ(1-42) was monitored by electrochemical means. Our results showed that both GPR and GPR-Fca can significantly inhibit the fibril formation of Aβ(1-42), and cause disaggregation of the preformed fibrils. As expected, GPR-Fca shows stronger inhibitory effect on Aβ(1-42) fibrillogenesis than that of its parent peptide GPR. In contrast, Fc-GPR shows no inhibitory effect on fibrillogenesis of Aβ(1-42). Furthermore, GPR-Fca demonstrates significantly protection against Aβ-induced cytotoxicity and exhibits high resistance to proteolysis and good lipophilicity. Copyright © 2012 Elsevier Ltd. All rights reserved.

FCA Group LLC Request for GHG Credit for Variable Crankcase Suction Valve Technology in Denso AC Compressors

EPA Pesticide Factsheets

FCA Group LLC request to the EPA regarding greenhouse (GHG) off-cycle credit for the use of the Denso SAS AC compressor with variable crankcase suction valve technology beginning with the 2019 MY Ram pickup truck.

12 CFR 606.602 - Application.

Code of Federal Regulations, 2010 CFR

2010-01-01

... open meetings of the Farm Credit Board. (2) Making inquiries or filing complaints. (3) Using the FCA library in McLean, Virginia. (4) Seeking employment with FCA. (5) Attending any meeting, conference, seminar, or other program open to the public. This list is illustrative only and failure to include an...

12 CFR 606.602 - Application.

Code of Federal Regulations, 2011 CFR

2011-01-01

... open meetings of the Farm Credit Board. (2) Making inquiries or filing complaints. (3) Using the FCA library in McLean, Virginia. (4) Seeking employment with FCA. (5) Attending any meeting, conference, seminar, or other program open to the public. This list is illustrative only and failure to include an...

12 CFR 602.7 - Confidential business information.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Confidential business information. 602.7... Availability of Records of the Farm Credit Administration § 602.7 Confidential business information. (a) FCA disclosure. FCA may disclose business information from a business submitter only under this section. This...

12 CFR 602.7 - Confidential business information.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 6 2011-01-01 2011-01-01 false Confidential business information. 602.7... Availability of Records of the Farm Credit Administration § 602.7 Confidential business information. (a) FCA disclosure. FCA may disclose business information from a business submitter only under this section. This...

12 CFR 623.4 - Suspension and debarment.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM PRACTICE BEFORE THE FARM CREDIT... the FCA or may deny, temporarily or permanently, the privilege of any person to practice before the..., contemptuous, contumacious or other unethical or improper conduct before FCA; or (4) To have willfully violated...

Data-Linking Requirements in Facilities Condition Audit RFPs.

ERIC Educational Resources Information Center

DeFranco, Randall W.

2002-01-01

Discusses why, when preparing a Request for Proposal (RFP) for Facilities Condition Audit (FCA)--including software-based delivery of findings--facilities managers should avoid complicating the bidding process with nondescript data-linking requirements. Presents ways to get an apples-to-apples comparison of bids for a proposed FCA project and…

75 FR 64728 - Cooperative Operating Philosophy-Serving the Members of Farm Credit System Institutions

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-20

... System (System) institutions are required to operate.\\1\\ The FCA emphasizes cooperative principles by... the management, control, and ownership of their institutions.\\2\\ The FCA also emphasizes cooperative principles in the examination function and Financial Institution Rating System (FIRS) used to categorize the...

12 CFR 608.808 - Right to offer to repay claim.

Code of Federal Regulations, 2010 CFR

2010-01-01

... explanation. The statement shall recite that the written explanation was read and understood before execution... would create a financial hardship, the FCA shall analyze the debtor's financial condition. The FCA may... financial hardship for the debtor. The written agreement shall set forth the amount and frequency of...

Concepts of formal concept analysis

NASA Astrophysics Data System (ADS)

Žáček, Martin; Homola, Dan; Miarka, Rostislav

2017-07-01

The aim of this article is apply of Formal Concept Analysis on concept of world. Formal concept analysis (FCA) as a methodology of data analysis, information management and knowledge representation has potential to be applied to a verity of linguistic problems. FCA is mathematical theory for concepts and concept hierarchies that reflects an understanding of concept. Formal concept analysis explicitly formalizes extension and intension of a concept, their mutual relationships. A distinguishing feature of FCA is an inherent integration of three components of conceptual processing of data and knowledge, namely, the discovery and reasoning with concepts in data, discovery and reasoning with dependencies in data, and visualization of data, concepts, and dependencies with folding/unfolding capabilities.

Recent developments in false claims enforcement: a minefield for health care providers.

PubMed

Whitaker, Glenn V; Walton, Victor A

2007-01-01

Actions under the False Claims Act represent potentially billions of dollars in damages returned to the state and federal governments each year for fraud recovery. Over the past several years, health care providers have been the target of about half of the FCA suits filed and have paid out an even greater percentage of the damages recovered. Because of the enumerable opportunities for fraud, waste, and abuse in the health care industry, it will likely continue to be a prominent target of FCA suits. Key provisions of the Deficit Reduction Act of 2005, effective on January 1, 2007, will only increase the reach of the FCA. Providers beware.

76 FR 7204 - Privacy Act of 1974; Establishment of a New System of Records

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-09

... as of January 31, 2011, the FCA has blocked its own retrieval access to the registration information... will allow a number of Federal agencies, including the FCA, to retrieve the registration information by... retrieve the registration information by identifying particulars only with respect to employees of the...

77 FR 39387 - Loan Policies and Operations; Lending and Leasing Limits and Risk Management; Effective Date

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-03

... FARM CREDIT ADMINISTRATION 12 CFR Part 614 RIN 3052-AC60 Loan Policies and Operations; Lending and Leasing Limits and Risk Management; Effective Date AGENCY: Farm Credit Administration. ACTION: Notice of effective date. SUMMARY: The Farm Credit Administration (FCA or Agency), through the FCA Board (Board...

76 FR 71343 - Ethics, Independence, Arm's-Length Role, Ex Parte Communications and Open Government

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-17

... FARM CREDIT ADMINISTRATION [FCA-PS-81; NV 11-25] Ethics, Independence, Arm's-Length Role, Ex Parte...) and the public. The FCA Board also is committed to the ethics principles and laws governing all Executive Branch employees and to the Agency's strong ethics program. DATES: Effective Date: November 7...

Immunostimulatory Oligodeoxynucleotides Containing the CpG Motif are Effective as Immune Adjuvants in Tumor Antigen Immunization

NASA Astrophysics Data System (ADS)

Weiner, George J.; Liu, Hsin-Ming; Wooldridge, James E.; Dahle, Christopher E.; Krieg, Arthur M.

1997-09-01

Recent advances in our understanding of the immune response are allowing for the logical design of new approaches to cancer immunization. One area of interest is the development of new immune adjuvants. Immunostimulatory oligodeoxynucleotides containing the CpG motif (CpG ODN) can induce production of a wide variety of cytokines and activate B cells, monocytes, dendritic cells, and NK cells. Using the 38C13 B cell lymphoma model, we assessed whether CpG ODN can function as immune adjuvants in tumor antigen immunization. The idiotype served as the tumor antigen. Select CpG ODN were as effective as complete Freund's adjuvant at inducing an antigen-specific antibody response but were associated with less toxicity. These CpG ODN induced a higher titer of antigen-specific IgG2a than did complete Freund's adjuvant, suggesting an enhanced TH1 response. Mice immunized with CpG ODN as an adjuvant were protected from tumor challenge to a degree similar to that seen in mice immunized with complete Freund's adjuvant. We conclude that CpG ODN are effective as immune adjuvants and are attractive as part of a tumor immunization strategy.

Smart protein biogate as a mediator to regulate competitive host-guest interaction for sensitive ratiometric electrochemical assay of prion

NASA Astrophysics Data System (ADS)

Yu, Peng; Zhang, Xiaohua; Zhou, Jiawan; Xiong, Erhu; Li, Xiaoyu; Chen, Jinhua

2015-11-01

A novel competitive host-guest strategy regulated by protein biogate was developed for sensitive and selective analysis of prion protein. The methylene blue (MB)-tagged prion aptamer (MB-Apt) was introduced to the multiwalled carbon nanotubes-β-cyclodextrins (MWCNTs-β-CD) composites-modified glassy carbon (GC) electrode through the host-guest interaction between β-CD and MB. In the absence of prion, MB-Apt could be displaced by ferrocenecarboxylic acid (FCA) due to its stronger binding affinity to β-CD, resulting in a large oxidation peak of FCA. However, in the presence of prion, the specific prion-aptamer interaction drove the formation of protein biogate to seal the cavity of β-CD, which hindered the guest displacement of MB by FCA and resulted in the oxidation peak current of MB (IMB) increased and that of FCA (IFCA) decreased. The developed aptasensor showed good response towards the target (prion protein) with a low detection limit of 160 fM. By changing the specific aptamers, this strategy could be easily extended to detect other proteins, showing promising potential for extensive applications in bioanalysis.

Additional targets of the Arabidopsis autonomous pathway members, FCA and FY.

PubMed

Marquardt, S; Boss, P K; Hadfield, J; Dean, C

2006-01-01

A central player in the Arabidopsis floral transition is the floral repressor FLC, the MADS-box transcriptional regulator that inhibits the activity of genes required to switch the meristem from vegetative to floral development. One of the many pathways that regulate FLC expression is the autonomous promotion pathway composed of FCA, FY, FLD, FPA, FVE, LD, and FLK. Rather than a hierarchical set of activities the autonomous promotion pathway comprises sub-pathways of genes with different biochemical functions that all share FLC as a target. One sub-pathway involves FCA and FY, which interact to regulate RNA processing of FLC. Several of the identified components (FY, FVE, and FLD) are homologous to yeast and mammalian proteins with rather generic roles in gene regulation. So why do mutations in these genes specifically show a late-flowering phenotype in Arabidopsis? One reason, found during the analysis of fy alleles, is that the mutant alleles identified in flowering screens can be hypomorphic, they still have partial function. A broader role for the autonomous promotion pathway is supported by a microarray analysis which has identified genes mis-regulated in fca mutants, and whose expression is also altered in fy mutants.

MSW fly ash stabilized with coal ash for geotechnical application.

PubMed

Kamon, M; Katsumi, T; Sano, Y

2000-09-15

The solidification and stabilization of municipal solid waste (MSW) fly ash for the purpose of minimizing the geo-environmental impact caused by toxic heavy metals as well as ensuring engineering safety (strength and soaking durability) are experimentally evaluated. The mixtures of MSW fly ash stabilized with cement and fluidized bed combustion coal fly ash (FCA) were used for unconfined compressive strength tests, leachate tests, and soaking tests. The behavior of soluble salts contained in the MSW fly ash significantly affects strength development, soaking durability, and the hardening reaction of the stabilized MSW fly ash mixtures. The cement stabilization of the MSW fly ash does not have enough effect on strength development and soaking durability. The addition of cement only contributes to the containment of heavy metals due to the high level of alkalinity. When using FCA as a stabilizing agent for MSW fly ash, the mixture exhibits high strength and durability. However, the Cd leachate cannot be prevented in the early stages of curing. Using a combination of cement and FCA as a MSW fly ash stabilizer can attain high strength, high soaking durability, and the containment of heavy metals. The stabilized MSW fly ash with cement and FCA can be practically applied to embankments.

12 CFR 611.1221 - Submission to FCA of plan of termination and disclosure information; other required submissions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Submission to FCA of plan of termination and disclosure information; other required submissions. 611.1221 Section 611.1221 Banks and Banking FARM CREDIT... mail the equity holder notice under § 611.1210(b). If you send us the plan of termination in electronic...

12 CFR 611.1221 - Submission to FCA of plan of termination and disclosure information; other required submissions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 6 2011-01-01 2011-01-01 false Submission to FCA of plan of termination and disclosure information; other required submissions. 611.1221 Section 611.1221 Banks and Banking FARM CREDIT... mail the equity holder notice under § 611.1210(b). If you send us the plan of termination in electronic...

Tuberculosis-like lesions arising from the use of Freund's complete adjuvant in an owl monkey (Aotus sp)

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

Malaga, Carlos A.; Weller, Richard E.; Broderson, J R.

An apparently normal, non-tuberculin-reacting, splenectomized owl monkey presented tuberculosis-like lesions of the lung at necropsy. Histological and bacteriological examination failed to demonstrate the presence of acid-fast organisms. Retrospective inquiry showed the animal had been inoculated using complete Freund's Adjuvant during a malaria vaccine trial. Lesions observed were compatible with lipid embolism of the adjuvant in the lungs.

Breast and prostate cancer productivity costs: a comparison of the human capital approach and the friction cost approach.

PubMed

Hanly, Paul; Timmons, Aileen; Walsh, Paul M; Sharp, Linda

2012-05-01

Productivity costs constitute a substantial proportion of the total societal costs associated with cancer. We compared the results of applying two different analytical methods--the traditional human capital approach (HCA) and the emerging friction cost approach (FCA)--to estimate breast and prostate cancer productivity costs in Ireland in 2008. Data from a survey of breast and prostate cancer patients were combined with population-level survival estimates and a national wage data set to calculate costs of temporary disability (cancer-related work absence), permanent disability (workforce departure, reduced working hours), and premature mortality. For breast cancer, productivity costs per person using the HCA were € 193,425 and those per person using the FCA were € 8,103; for prostate cancer, the comparable estimates were € 109,154 and € 8,205, respectively. The HCA generated higher costs for younger patients (breast cancer) because of greater lifetime earning potential. In contrast, the FCA resulted in higher productivity costs for older male patients (prostate cancer) commensurate with higher earning capacity over a shorter time period. Reduced working hours postcancer was a key driver of total HCA productivity costs. HCA costs were sensitive to assumptions about discount and growth rates. FCA costs were sensitive to assumptions about the friction period. The magnitude of the estimates obtained in this study illustrates the importance of including productivity costs when considering the economic impact of illness. Vastly different results emerge from the application of the HCA and the FCA, and this finding emphasizes the importance of choosing the study perspective carefully and being explicit about assumptions that underpin the methods. Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Hypomorphic alleles reveal FCA-independent roles for FY in the regulation of FLOWERING LOCUS C.

PubMed

Feng, Wei; Jacob, Yannick; Veley, Kira M; Ding, Lei; Yu, Xuhong; Choe, Goh; Michaels, Scott D

2011-03-01

The autonomous floral promotion pathway plays a key role in the regulation of flowering in rapid-cycling Arabidopsis (Arabidopsis thaliana) by providing constitutive repression of the floral inhibitor FLOWERING LOCUS C (FLC). As a result, autonomous pathway mutants contain elevated levels of FLC and are late flowering. Winter annual Arabidopsis, in contrast, contain functional alleles of FRIGIDA (FRI), which acts epistatically to the autonomous pathway to up-regulate FLC and delay flowering. To further explore the relationship between FRI and the autonomous pathway, we placed autonomous pathway mutants in a FRI-containing background. Unexpectedly, we found that a hypomorphic allele of the autonomous pathway gene fy (fy null alleles are embryo lethal) displayed background-specific effects on FLC expression and flowering time; in a rapid-cycling background fy mutants contained elevated levels of FLC and were late flowering, whereas in a winter annual background fy decreased FLC levels and partially suppressed the late-flowering phenotype conferred by FRI. Because FY has been shown to have homology to polyadenylation factors, we examined polyadenylation site selection in FLC transcripts. In wild type, two polyadenylation sites were detected and used at similar levels. In fy mutant backgrounds, however, the ratio of products was shifted to favor the distally polyadenylated form. FY has previously been shown to physically interact with another member of the autonomous pathway, FCA. Interestingly, we found that fy can partially suppress FLC expression in an fca null background and promote proximal polyadenylation site selection usage in the absence of FCA. Taken together, these results indicate novel and FCA-independent roles for FY in the regulation of FLC.

Hypomorphic Alleles Reveal FCA-Independent Roles for FY in the Regulation of FLOWERING LOCUS C1[C][W][OA

PubMed Central

Feng, Wei; Jacob, Yannick; Veley, Kira M.; Ding, Lei; Yu, Xuhong; Choe, Goh; Michaels, Scott D.

2011-01-01

The autonomous floral promotion pathway plays a key role in the regulation of flowering in rapid-cycling Arabidopsis (Arabidopsis thaliana) by providing constitutive repression of the floral inhibitor FLOWERING LOCUS C (FLC). As a result, autonomous pathway mutants contain elevated levels of FLC and are late flowering. Winter annual Arabidopsis, in contrast, contain functional alleles of FRIGIDA (FRI), which acts epistatically to the autonomous pathway to up-regulate FLC and delay flowering. To further explore the relationship between FRI and the autonomous pathway, we placed autonomous pathway mutants in a FRI-containing background. Unexpectedly, we found that a hypomorphic allele of the autonomous pathway gene fy (fy null alleles are embryo lethal) displayed background-specific effects on FLC expression and flowering time; in a rapid-cycling background fy mutants contained elevated levels of FLC and were late flowering, whereas in a winter annual background fy decreased FLC levels and partially suppressed the late-flowering phenotype conferred by FRI. Because FY has been shown to have homology to polyadenylation factors, we examined polyadenylation site selection in FLC transcripts. In wild type, two polyadenylation sites were detected and used at similar levels. In fy mutant backgrounds, however, the ratio of products was shifted to favor the distally polyadenylated form. FY has previously been shown to physically interact with another member of the autonomous pathway, FCA. Interestingly, we found that fy can partially suppress FLC expression in an fca null background and promote proximal polyadenylation site selection usage in the absence of FCA. Taken together, these results indicate novel and FCA-independent roles for FY in the regulation of FLC. PMID:21209277

High fat diet enriched with saturated, but not monounsaturated fatty acids adversely affects femur, and both diets increase calcium absorption in older female mice.

PubMed

Wang, Yang; Dellatore, Peter; Douard, Veronique; Qin, Ling; Watford, Malcolm; Ferraris, Ronaldo P; Lin, Tiao; Shapses, Sue A

2016-07-01

Diet induced obesity has been shown to reduce bone mineral density (BMD) and Ca absorption. However, previous experiments have not examined the effect of high fat diet (HFD) in the absence of obesity or addressed the type of dietary fatty acids. The primary objective of this study was to determine the effects of different types of high fat feeding, without obesity, on fractional calcium absorption (FCA) and bone health. It was hypothesized that dietary fat would increase FCA and reduce BMD. Mature 8-month-old female C57BL/6J mice were fed one of three diets: a HFD (45% fat) enriched either with monounsaturated fatty acids (MUFAs) or with saturated fatty acids (SFAs), and a normal fat diet (NFD; 10% fat). Food consumption was controlled to achieve a similar body weight gain in all groups. After 8wk, total body bone mineral content and BMD as well as femur total and cortical volumetric BMD were lower in SFA compared with NFD groups (P<.05). In contrast, femoral trabecular bone was not affected by the SFAs, whereas MUFAs increased trabecular volume fraction and thickness. The rise over time in FCA was greater in mice fed HFD than NFD and final FCA was higher with HFD (P<.05). Intestinal calbindin-D9k gene and hepatic cytochrome P450 2r1 protein levels were higher with the MUFA than the NFD diet (P<.05). In conclusion, HFDs elevated FCA overtime; however, an adverse effect of HFD on bone was only observed in the SFA group, while MUFAs show neutral or beneficial effects. Copyright © 2016 Elsevier Inc. All rights reserved.

Civil society and the negotiation of the Framework Convention on Tobacco Control

PubMed Central

MAMUDU, H. M.

2008-01-01

Tobacco control civil society organisations mobilised to influence countries during the negotiation of the World Health Organization (WHO) Framework Convention on Tobacco Control (FCTC) between 1999 and 2003. Tobacco control civil society organisations and coalitions around the world embraced the idea of an international tobacco control treaty and came together as the Framework Convention Alliance (FCA), becoming an important non-state actor within the international system of tobacco control. Archival documents and interviews demonstrate that the FCA successfully used strategies including publication of a newsletter, shaming, symbolism and media advocacy to influence policy positions of countries during the FCTC negotiation. The FCA became influential in the negotiation process by mobilising tobacco control civil society organisations and resources with the help of the Internet and framing the tobacco control discussion around global public health. PMID:19333806

Plaque Burden Influences Accurate Classification of Fibrous Cap Atheroma by In-Vivo Optical Coherence Tomography in a Porcine Model of Advanced Coronary Atherosclerosis.

PubMed

Poulsen, Christian B; Pedrigi, Ryan M; Pareek, Nilesh; Kilic, Ismail D; Holm, Niels Ramsing; Bentzon, Jacob F; Bøtker, Hans Erik; Falk, Erling; Krams, Rob; de Silva, Ranil

2018-04-03

In-vivo validation of coronary optical coherence tomography (OCT) against histology and the effects of plaque burden (PB) on plaque classification remain unreported. We investigated this in a porcine model with human-like coronary atherosclerosis. Five female Yucatan D374Y-PCSK9 transgenic hypercholesterolemic mini-pigs were implanted with a coronary shear-modifying stent to induce advanced atherosclerosis. OCT frames (n=201) were obtained 34 weeks after implantation. Coronary arteries were perfusion-fixed, serially sectioned and co-registered with OCT using a validated algorithm. Lesions were adjudicated using the Virmani classification and PB assessed from histology. OCT had a high sensitivity, but modest specificity (92.9% and 74.6%), for identifying fibrous cap atheroma (FCA). The reduced specificity for OCT was due to misclassification of plaques with histologically defined pathological intimal thickening (PIT) as FCA (46.1% of the frames with histological PIT were misclassified). PIT lesions misclassified as FCA by OCT had a statistically higher PB than in other OCT frames (median 32.0% versus 13.4%; p<0.0001). Misclassification of PIT lesions by OCT occurred when PB exceeded approximately 20%. Compared with histology, in-vivo OCT classification of FCA had high sensitivity but reduced specificity due to misclassification of PITs with high PB.

Genetically divergent strains of feline immunodeficiency virus from the domestic cat (Felis catus) and the African lion (Panthera leo) share usage of CD134 and CXCR4 as entry receptors.

PubMed

McEwan, William A; McMonagle, Elizabeth L; Logan, Nicola; Serra, Rodrigo C; Kat, Pieter; Vandewoude, Sue; Hosie, Margaret J; Willett, Brian J

2008-11-01

The env open reading frames of African lion (Panthera leo) lentivirus (feline immunodeficiency virus [FIV(Ple)]) subtypes B and E from geographically distinct regions of Africa suggest two distinct ancestries, with FIV(Ple)-E sharing a common ancestor with the domestic cat (Felis catus) lentivirus (FIV(Fca)). Here we demonstrate that FIV(Ple)-E and FIV(Fca) share the use of CD134 (OX40) and CXCR4 as a primary receptor and coreceptor, respectively, and that both lion CD134 and CXCR4 are functional receptors for FIV(Ple)-E. The shared usage of CD134 and CXCR4 by FIV(Fca) and FIV(Ple)-E may have implications for in vivo cell tropism and the pathogenicity of the E subtype among free-ranging lion populations.

Full cost accounting in the analysis of separated waste collection efficiency: A methodological proposal.

PubMed

D'Onza, Giuseppe; Greco, Giulio; Allegrini, Marco

2016-02-01

Recycling implies additional costs for separated municipal solid waste (MSW) collection. The aim of the present study is to propose and implement a management tool - the full cost accounting (FCA) method - to calculate the full collection costs of different types of waste. Our analysis aims for a better understanding of the difficulties of putting FCA into practice in the MSW sector. We propose a FCA methodology that uses standard cost and actual quantities to calculate the collection costs of separate and undifferentiated waste. Our methodology allows cost efficiency analysis and benchmarking, overcoming problems related to firm-specific accounting choices, earnings management policies and purchase policies. Our methodology allows benchmarking and variance analysis that can be used to identify the causes of off-standards performance and guide managers to deploy resources more efficiently. Our methodology can be implemented by companies lacking a sophisticated management accounting system. Copyright © 2015 Elsevier Ltd. All rights reserved.

Co-administration of recombinant major envelope proteins (rA27L and rH3L) of buffalopox virus provides enhanced immunogenicity and protective efficacy in animal models.

PubMed

Kumar, Amit; Yogisharadhya, Revanaiah; Venkatesan, Gnanavel; Bhanuprakash, Veerakyathappa; Pandey, Awadh Bihari; Shivachandra, Sathish Bhadravati

2017-05-01

Buffalopox virus (BPXV) and other vaccinia-like viruses (VLVs) are causing an emerging/re-emerging zoonosis affecting buffaloes, cattle and humans in India and other countries. A27L and H3L are immuno-dominant major envelope proteins of intracellular mature virion (IMV) of orthopoxviruses (OPVs) and are highly conserved with an ability to elicit neutralizing antibodies. In the present study, two recombinant proteins namely; rA27L ( 21 S to E 110 ; ∼30 kDa) and rH3L( 1 M to I 280 ; ∼50 kDa) of BPXV-Vij/96 produced from Escherichia coli were used in vaccine formulation. A combined recombinant subunit vaccine comprising rA27L and rH3L antigens (10 μg of each) was used for active immunization of adult mice (20μg/dose/mice) with or without adjuvant (FCA/FIA) by intramuscular route. Immune responses revealed a gradual increase in antigen specific serum IgG as well as neutralizing antibody titers measured by using indirect-ELISA and serum neutralization test (SNT) respectively, which were higher as compared to that elicited by individual antigens. Suckling mice passively administered with combined anti-A27L and anti-H3L sera showed a complete (100%) pre-exposure protection upon challenge with virulent BPXV. Conclusively, this study highlights the potential utility of rA27L and rH3L proteins as safer candidate prophylactic antigens in combined recombinant subunit vaccine for buffalopox as well as passive protective efficacy of combined sera in employing better pre-exposure protection against virulent BPXV. Copyright © 2017 Elsevier B.V. All rights reserved.

Dermal Sensitization Potential of Niclosamide in Guinea Pigs

DTIC Science & Technology

1988-09-01

al--3 sterile water, from the same lot as for DNCB stock solution, were used to prepare the dilutions of FCA. Sodium lauryl sulfate (SLS) was obtained...test agent was non- irritating, the area was pretreated with 10% sodium lauryl sulfate in petrolatum immediately after the clipping and shaving. The SLS...control combination was prepared by adding 0.25 ml of FCA stock to 4.75 ml of propylene glycol. Topical Induction and Challenge: The sodium lauryl

Adjuvant effects of saponins on animal immune responses*

PubMed Central

Rajput, Zahid Iqbal; Hu, Song-hua; Xiao, Chen-wen; Arijo, Abdullah G.

2007-01-01

Vaccines require optimal adjuvants including immunopotentiator and delivery systems to offer long term protection from infectious diseases in animals and man. Initially it was believed that adjuvants are responsible for promoting strong and sustainable antibody responses. Now it has been shown that adjuvants influence the isotype and avidity of antibody and also affect the properties of cell-mediated immunity. Mostly oil emulsions, lipopolysaccharides, polymers, saponins, liposomes, cytokines, ISCOMs (immunostimulating complexes), Freund’s complete adjuvant, Freund’s incomplete adjuvant, alums, bacterial toxins etc., are common adjuvants under investigation. Saponin based adjuvants have the ability to stimulate the cell mediated immune system as well as to enhance antibody production and have the advantage that only a low dose is needed for adjuvant activity. In the present study the importance of adjuvants, their role and the effect of saponin in immune system is reviewed. PMID:17323426

[Role of Pharmacists in Completion of Adjuvant Cisplatin-Vinorelbine Chemotherapy in Japanese Patients with Non-small Cell Lung Cancer].

PubMed

Morimoto, Yoshihito; Takei, Hidefumi; Tachibana, Keisei; Nakazato, Yoko; Tanaka, Ryota; Nagashima, Yasushi; Watanabe, Kazuhiro; Seki, Reisuke; Shinohara, Takao; Kondo, Haruhiko

2018-01-01

　Adjuvant cisplatin-vinorelbine chemotherapy has been shown to be effective in patients with completely resected non-small cell lung cancer (NSCLC) in several Phase III trials, but not yet in the Japanese population. Pharmacists are expected to assist patients with completion of adjuvant chemotherapy. The aim of this retrospective study was to evaluate the compliance with and safety of adjuvant cisplatin-vinorelbine chemotherapy in Japanese patients and to evaluate the contribution of pharmacists to completion of treatment. Thirty-four patients with NSCLC who received adjuvant cisplatin-vinorelbine chemotherapy at Kyorin University Hospital between January 2006 and June 2015 were reviewed. The treatment schedule comprised cisplatin 80 mg/m 2 on day 1 and vinorelbine 25 mg/m 2 on days 1 and 8 every 3 weeks. Four 3-week cycles were planned. A pharmacist provided guidance to all patients and monitored them for adverse effects thereafter. The pharmacist intervened with advice to doctors as necessary. The 4 cycles were administered in 67.6% of cases. There were no treatment-related deaths. The main grade 3 or 4 toxicities were neutropenia (76.5%) and anorexia (38.2%). The most common reason for discontinuation and dose reduction was anorexia. There were 56 instances of pharmacist intervention. In total, 96.4% of the pharmacist interventions were implemented by doctors, which included administration of an antiemetic on 15 occasions and hot fomentation for prevention of vasculitis on 7 occasions. Adjuvant cisplatin-vinorelbine chemotherapy was tolerated by most patients but was discontinued because of adverse events in some. Pharmacist intervention aids completion of planned chemotherapy and management of treatment-related adverse events.

Dual roles for FY in the regulation of FLC

PubMed Central

Feng, Wei

2011-01-01

In Arabidopsis, the flowering decision is determined by multiple pathways that integrate information from both endogenous signals and environmental cues. The genes of the autonomous pathway promote flowering by suppressing the expression of the floral repressor FLOWERING LOCUS C (FLC). Thus, autonomous-pathway mutants have elevated levels of FLC and are late flowering. Previous work has shown that two autonomous pathway proteins, FCA and FY, physically interact and this interaction is important in the repression of FLC. Recent work from our laboratory has shown that a hypomorphic allele of FY (fy-5) can cause earlier or later flowering, depending on the genetic background. These results suggest that FY has the potential to act as both an activator and a repressor of FLC. The FLC-activating activity of FY appears to be FCA-independent, as fy-5 causes earlier flowering in an fca-null background. Here we present a speculative model that reconciles these opposing phenotypes by proposing a dual role for FY in the regulation of flowering time. PMID:21633188

Dual roles for FY in the regulation of FLC.

PubMed

Feng, Wei; Michaels, Scott D

2011-05-01

In Arabidopsis, the flowering decision is determined by multiple pathways that integrate information from both endogenous signals and environmental cues. The genes of the autonomous pathway promote flowering by suppressing the expression of the floral repressor FLOWERING LOCUS C (FLC). Thus, autonomous-pathway mutants have elevated levels of FLC and are late flowering. Previous work has shown that two autonomous pathway proteins, FCA and FY, physically interact and this interaction is important in the repression of FLC. Recent work from our laboratory has shown that a hypomorphic allele of FY (fy-5) can cause earlier or later flowering, depending on the genetic background. These results suggest that FY has the potential to act as both an activator and a repressor of FLC. The FLC-activating activity of FY appears to be FCA-independent, as fy-5 causes earlier flowering in an fca-null background. Here we present a speculative model that reconciles these opposing phenotypes by proposing a dual role for FY in the regulation of flowering time.

Evaluation of NK Cell Function by Flowcytometric Measurement and Impedance Based Assay Using Real-Time Cell Electronic Sensing System

PubMed Central

Park, Ki-Hyun; Park, Hyesun; Kim, Myungshin; Kim, Yonggoo; Han, Kyungja; Oh, Eun-Jee

2013-01-01

Although real-time cell electronic sensing (RT-CES) system-based natural killer (NK) cytotoxicity has been introduced, it has not been evaluated using human blood samples. In present study, we measured flowcytometry based assay (FCA) and RT-CES based NK cytotoxicity and analyzed degranulation activity (CD107a) and cytokine production. In 98 healthy individuals, FCA with peripheral blood mononuclear cells (PBMCs) at effector to target (E/T) ratio of 32 revealed 46.5 ± 2.6% cytolysis of K562 cells, and 23.5 ± 1.1% of NK cells showed increased degranulation. In RT-CES system, adherent NIH3T3 target cells were resistant to basal killing by PBMC or NK cells. NK cell activation by adding IL-2 demonstrated real-time dynamic killing activity, and lymphokine-activated PBMC (E/T ratio of 32) from 15 individuals showed 59.1 ± 6.2% cytotoxicity results after 4 hours incubation in RT-CES system. However, there was no significant correlation between FCA and RT-CES cytotoxicity. After K562 target cell stimulation, PBMC produced profound proinflammatory and immunoregulatory cytokines/chemokines including IL-2, IL-8, IL-10, MIP-1α β, IFN-γ, and TNF-α, and cytokine/chemokine secretion was related to flowcytometry-based NK cytotoxicity. These data suggest that RT-CES and FCA differ in sensitivity, applicability and providing information, and further investigations are necessary in variable clinical conditions. PMID:24236291

Evaluation of NK cell function by flowcytometric measurement and impedance based assay using real-time cell electronic sensing system.

PubMed

Park, Ki-Hyun; Park, Hyesun; Kim, Myungshin; Kim, Yonggoo; Han, Kyungja; Oh, Eun-Jee

2013-01-01

Although real-time cell electronic sensing (RT-CES) system-based natural killer (NK) cytotoxicity has been introduced, it has not been evaluated using human blood samples. In present study, we measured flowcytometry based assay (FCA) and RT-CES based NK cytotoxicity and analyzed degranulation activity (CD107a) and cytokine production. In 98 healthy individuals, FCA with peripheral blood mononuclear cells (PBMCs) at effector to target (E/T) ratio of 32 revealed 46.5 ± 2.6% cytolysis of K562 cells, and 23.5 ± 1.1% of NK cells showed increased degranulation. In RT-CES system, adherent NIH3T3 target cells were resistant to basal killing by PBMC or NK cells. NK cell activation by adding IL-2 demonstrated real-time dynamic killing activity, and lymphokine-activated PBMC (E/T ratio of 32) from 15 individuals showed 59.1 ± 6.2% cytotoxicity results after 4 hours incubation in RT-CES system. However, there was no significant correlation between FCA and RT-CES cytotoxicity. After K562 target cell stimulation, PBMC produced profound proinflammatory and immunoregulatory cytokines/chemokines including IL-2, IL-8, IL-10, MIP-1 α β , IFN- γ , and TNF- α , and cytokine/chemokine secretion was related to flowcytometry-based NK cytotoxicity. These data suggest that RT-CES and FCA differ in sensitivity, applicability and providing information, and further investigations are necessary in variable clinical conditions.

Adjuvant Chemotherapy for Patients with T2N0M0 NSCLC.

PubMed

Morgensztern, Daniel; Du, Lingling; Waqar, Saiama N; Patel, Aalok; Samson, Pamela; Devarakonda, Siddhartha; Gao, Feng; Robinson, Cliff G; Bradley, Jeffrey; Baggstrom, Maria; Masood, Ashiq; Govindan, Ramaswamy; Puri, Varun

2016-10-01

Adjuvant chemotherapy improves survival in patients with completely resected stage II and III NSCLC. However, its role in patients with stage IB NSCLC disease remains unclear. We evaluated the role of adjuvant chemotherapy in a large data set of patients with completely resected T2N0M0 NSCLC. Patients with pathologic stage T2N0M0 NSCLC who underwent complete (R0) resection between 2004 and 2011 were identified from the National Cancer Data Base and classified into four groups based on tumor size: 3.1 to 3.9 cm, 4 to 4.9 cm, 5 to 5.9 cm, and 6 to 7 cm. Patients who died within 1 month after their operation were excluded. Survival curves were estimated by the Kaplan-Meier product-limit method and compared by log-rank test. Among the 25,267 patients who met the inclusion criteria, there were 4996 (19.7%) who received adjuvant chemotherapy. Adjuvant chemotherapy was associated with improved median and 5-year overall survival compared with observation for all tumor size groups. In patients with T2 tumors smaller than 4 cm, adjuvant chemotherapy was associated with improved median and 5-year overall survival in univariate (101.6 versus 68.2 months [67% versus 55%], hazard ratio [HR] = 0.66, 95% confidence interval [CI]: 0.61-0.72, p < 0.0001) and multivariable analysis (HR = 0.77, 95% CI: 0.70-0.83, p < 0.001) as well as propensity-matched score (101.6 versus 78.9 months [68% versus 60%], HR = 0.75, 95% CI: 0.70-0.86; p < 0.0001). In patients with completely resected T2N0M0, adjuvant chemotherapy is associated with improved survival in all tumor size groups. The benefit in patients with tumors smaller than 4 cm strongly suggests a role for chemotherapy in this patient population and counters its current status as an exclusion criteria for adjuvant trials. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Estimating sediment quality thresholds to prevent restrictions on fish consumption: Application to polychlorinated biphenyls and dioxins-furans in the Canadian Great Lakes.

PubMed

Bhavsar, Satyendra P; Gewurtz, Sarah B; Helm, Paul A; Labencki, Tanya L; Marvin, Christopher H; Fletcher, Rachael; Hayton, Alan; Reiner, Eric J; Boyd, Duncan

2010-10-01

Sediment quality thresholds (SQTs) are used by a variety of agencies to assess the potential for adverse impact of sediment-associated contaminants on aquatic biota, typically benthic invertebrates. However, sedimentary contaminants can also result in elevated fish contaminant levels, triggering consumption advisories that are protective of humans. As such, SQTs that would result in fish concentrations below consumption advisory levels should also be considered. To illustrate how this can be addressed, we first calculate biota sediment accumulation factors (BSAFs) for polychlorinated biphenyls (total PCB) and polychlorinated dioxins-furans (PCDD/Fs) in the Canadian Great Lakes using measured lake sediment and fish tissue concentrations in 4 fish species, namely, lake trout, whitefish, rainbow trout, and channel catfish. Using these BSAFs and tissue residue values for fish consumption advisories employed by the Ontario Ministry of the Environment (OMOE, Canada), we derive fish consumption advisory-based SQTs (fca-SQTs) that are likely to result in fish tissue residues that are safe to eat without restriction. The PCDD/Fs fca-SQTs ranged from 6 to 128 pg toxic equivalents (TEQ)/g dry weight (dw) and were above the Canadian Council of the Ministers of the Environment (CCME) threshold effect level (TEL) of 0.85 pg TEQ/g dw. In contrast, the total PCB fca-SQTs ranged from 1 to 60 ng/g dw and were generally below the CCME's TEL of 34.1 ng/g and OMOE's lowest effect level (LEL) of 70 ng/g; however, they were consistent with the OMOE's no effect level (NEL) of 10 ng/g. The fca-SQTs derived using the BSAF as well as food chain multiplier (FCM) approach for a smaller scale system (Hamilton Harbour in Lake Ontario) corresponded well with average lakewide Lake Ontario fca-SQTs. This analysis provides approximate sediment concentrations necessary for reducing fish consumption advisories for each of the Canadian Great Lakes and emphasizes the impacts of historical lake sediment contamination on fish advisories. We believe that this approach merits consideration in sediment guideline development. © 2010 SETAC.

The endocannabinoid system in the rat dorsolateral periaqueductal grey mediates fear-conditioned analgesia and controls fear expression in the presence of nociceptive tone

PubMed Central

Olango, WM; Roche, M; Ford, GK; Harhen, B; Finn, DP

2012-01-01

BACKGROUND AND PURPOSE Endocannabinoids in the midbrain periaqueductal grey (PAG) modulate nociception and unconditioned stress-induced analgesia; however, their role in fear-conditioned analgesia (FCA) has not been examined. The present study examined the role of the endocannabinoid system in the dorsolateral (dl) PAG in formalin-evoked nociceptive behaviour, conditioned fear and FCA in rats. EXPERIMENTAL APPROACH Rats received intra-dlPAG administration of the CB1 receptor antagonist/inverse agonist rimonabant, or vehicle, before re-exposure to a context paired 24 h previously with foot shock. Formalin-evoked nociceptive behaviour and fear-related behaviours (freezing and 22 kHz ultrasonic vocalization) were assessed. In a separate cohort, levels of endocannabinoids [2-arachidonoyl glycerol (2-AG) and N-arachidonoyl ethanolamide (anandamide; AEA)] and the related N-acylethanolamines (NAEs) [N-palmitoyl ethanolamide (PEA) and N-oleoyl ethanolamide (OEA)] were measured in dlPAG tissue following re-exposure to conditioned context in the presence or absence of formalin-evoked nociceptive tone. KEY RESULTS Re-exposure of rats to the context previously associated with foot shock resulted in FCA. Intra-dlPAG administration of rimonabant significantly attenuated FCA and fear-related behaviours expressed in the presence of nociceptive tone. Conditioned fear without formalin-evoked nociceptive tone was associated with increased levels of 2-AG, AEA, PEA and OEA in the dlPAG. FCA was specifically associated with an increase in AEA levels in the dlPAG. CONCLUSIONS AND IMPLICATIONS Conditioned fear to context mobilises endocannabinoids and NAEs in the dlPAG. These data support a role for endocannabinoids in the dlPAG in mediating the potent suppression of pain responding which occurs during exposure to conditioned aversive contexts. LINKED ARTICLES This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue-7 PMID:21564082

A possible relationship between Takotsubo cardiomyopathy and female sex steroid-related modulation of functional cerebral asymmetry.

PubMed

Drača, S

2015-03-01

Takotsubo cardiomyopathy (Tc) is a transient left ventricular apical ballooning syndrome, with symptoms and signs of acute myocardial infarction. Tc syndrome, which occurs predominantly in postmenopausal women, is characterized by increase of sympathetic activity. Studies on the gender-specific differences in sympatho-vagal regulation and functional cerebral asymmetry (FCA) imply that female pattern of dominance is characterized by the left hemisphere, which is believed to have parasympathetic predominance, whereas male pattern indicates dominance of the right hemisphere, which is believed to have sympathetic predominance. Fluctuating levels of female sex steroids are supposed to change FCA, modulating transcallosal inter-hemispheric inhibition across the menstrual cycle. The findings suggest that FCA is enhanced during the low steroid phase (menstrual phase), whereas, during high estrogen and/or progesterone phases (follicular and luteal phase) FCA is reduced. This theory is in line with concept of decreased magnitude of inter-hemispheric cortical lateralization in premenopausal women compared to men and postmenopausal women. Therefore, if postmenopausal women are more lateralized for a variety of cerebral functions, they have less balanced equilibrium between the right-sided sympathetic and left-sided parasympathetic predominance. Decrease of endogenous female sex steroid levels in postmenopausal women leads to reduced influence of estrogens to the left hemisphere, which is believed to have parasympathetic predominance. If both of these mechanisms result in sympatho-vagal imbalance, increasing sympathetic system activity in postmenopausal women, it seems reasonable why postmenopausal women became more susceptible to sympathetically-mediated syndromes such as Takotsubo cardiomyopathy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Fragrance contact allergy in Iran.

PubMed

Firooz, A; Nassiri-Kashani, M; Khatami, A; Gorouhi, F; Babakoohi, S; Montaser-Kouhsari, L; Davari, P; Dowlati, Y

2010-12-01

Fragrances are considered as one of the most common causes of allergic contact dermatitis. About 1-4% of the general population suffer from fragrance contact allergy (FCA). To determine the frequency of FCA and its clinical relevance in a sample of Iranian patients with history of contact and/or atopic dermatitis from January 2004 to December 2008. Standardized patch testing with 28-allergen screening series recommended by the German Contact Dermatitis Research Group and European Standard Series was used at six dermatological clinics in Iran. Fragrance allergens comprised of fragrance mix I (FM I), Myroxylon pereirae (MP; balsam of Peru), Lyral, turpentine and FM II. Fragrance contact allergy was detected in 7.2% of the patients. The frequency of positive reactions to FM I, MP and FM II were 3.7% (41/1105), 2.8% (32/1135) and 1.1% (3/267) respectively. 82.4% of the reactions to fragrance allergens were clinically relevant. The most common involved areas were hands (68.4%) and face (35.4%). Fragrance allergy predominantly affected women aged more than 40 years (P=0.008). Positive reaction to more than two allergens was significantly higher in FCA patients compared with other contact dermatitis patients (P<0.0001), and FM I, nickel and MP were the most frequent allergens in these patients. Despite less frequency of FCA in comparison with some European countries, its clinical relevance in Iranian patients seems to be high. It mostly affects the hands and the face predominantly in women aged more than 40 years. © 2010 The Authors. Journal compilation © 2010 European Academy of Dermatology and Venereology.

[A Case of Advanced Transverse Colon Cancer with Nephrotic Syndrome Treated with Curative Resection and Complete Adjuvant Chemotherapy].

PubMed

Sato, Nobutaka; Fuyuno, Seiya; Hatada, Teppei; Furuhashi, Takashi; Abe, Toshihiko

2017-05-01

A 74-year-old woman was diagnosed as having transverse colon cancer after diagnosis of nephrotic syndrome caused by membranous nephropathy. Although she had hypoproteinemia and hypoalbuminemia, we judged that she had no major nutritional problem. In previous, similar case reports, the use of human serum albumin and fresh-frozen plasma was suggested to be important to avoid complications in the perioperative period. Thus, we used the same in our patient in the perioperative period. In addition, we paid special attention to perioperative nutrition management and used total parenteral nutrition in perioperative period. We performed laparoscopic assisted right hemicolectomy. On the 15th day after the surgical resection, the patient was discharged without any problems. We considered that postoperative adjuvant chemotherapy with XELOX (CapeOX)should be performed because the TNM pathological stage was pStage III b. Regarding adjuvant chemotherapy for gastrointestinal cancer with nephrotic syndrome, no previous reports detailed the indications for postoperative adjuvant chemotherapy. Upon introduction of adjuvant chemotherapy, we determined adaptation in accordance with the general adaptation criteria. While observing the patient's progress with a nephrologist, we safely completed the scheduled 8 courses adjuvant chemotherapy.

Collagen gel droplet-embedded culture drug sensitivity test for adjuvant chemotherapy after complete resection of non-small-cell lung cancer.

PubMed

Inoue, Masayoshi; Maeda, Hajime; Takeuchi, Yukiyasu; Fukuhara, Kenjiro; Shintani, Yasushi; Funakoshi, Yasunobu; Funaki, Soichiro; Nojiri, Takashi; Kusu, Takashi; Kusumoto, Hidenori; Kimura, Toru; Okumura, Meinoshin

2018-04-01

We conducted a prospective clinical study to individualize adjuvant chemotherapy after complete resection of non-small-cell lung cancer (NSCLC), based on the drug sensitivity test. Patients with resectable c-stage IB-IIIA NSCLC were registered between 2005 and 2010. We performed the collagen gel droplet-embedded culture drug sensitivity test (CD-DST) on a fresh surgical specimen to assess in vitro chemosensitivity and evaluated the prognostic outcome after adjuvant chemotherapy with carboplatin/paclitaxel based on the CD-DST. Among 92 registered patients, 87 were eligible for inclusion in the analysis. The success rate of CD-DST was 86% and chemosensitivity to carboplatin and/or paclitaxel was evident in 57 (76%) of the 75 patients. Adjuvant chemotherapy was completed in 22 (73%) of 30 patients. The 5-year overall survival rates were 71, 73, and 75% for all, CD-DST success, and chemosensitive patients, respectively. The 5-year disease-free survival and overall survival rates of the chemosensitive patients who completed adjuvant chemotherapy using carboplatin/paclitaxel were 68 and 82%, respectively. The 5-year disease-free survival and overall survival rates of the patients with stage II-IIIA chemosensitive NSCLC were 58 and 75%, respectively. Comparative analyses of the chemosensitive and non-chemosensitive/CD-DST failure groups showed no significant survival difference. CD-DST can be used to evaluate chemosensitivity after lung cancer surgery; however, its clinical efficacy for assessing individualized treatment remains uncertain.

Bromodomain-containing Protein 4 Activates Voltage-gated Sodium Channel 1.7 Transcription in Dorsal Root Ganglia Neurons to Mediate Thermal Hyperalgesia in Rats.

PubMed

Hsieh, Ming-Chun; Ho, Yu-Cheng; Lai, Cheng-Yuan; Wang, Hsueh-Hsiao; Lee, An-Sheng; Cheng, Jen-Kun; Chau, Yat-Pang; Peng, Hsien-Yu

2017-11-01

Bromodomain-containing protein 4 binds acetylated promoter histones and promotes transcription; however, the role of bromodomain-containing protein 4 in inflammatory hyperalgesia remains unclear. Male Sprague-Dawley rats received hind paw injections of complete Freund's adjuvant to induce hyperalgesia. The dorsal root ganglia were examined to detect changes in bromodomain-containing protein 4 expression and the activation of genes involved in the expression of voltage-gated sodium channel 1.7, which is a key pain-related ion channel. The intraplantar complete Freund's adjuvant injections resulted in thermal hyperalgesia (4.0 ± 1.5 s; n = 7). The immunohistochemistry and immunoblotting results demonstrated an increase in the bromodomain-containing protein 4-expressing dorsal root ganglia neurons (3.78 ± 0.38 fold; n = 7) and bromodomain-containing protein 4 protein levels (2.62 ± 0.39 fold; n = 6). After the complete Freund's adjuvant injection, histone H3 protein acetylation was enhanced in the voltage-gated sodium channel 1.7 promoter, and cyclin-dependent kinase 9 and phosphorylation of RNA polymerase II were recruited to this area. Furthermore, the voltage-gated sodium channel 1.7-mediated currents were enhanced in neurons of the complete Freund's adjuvant rats (55 ± 11 vs. 19 ± 9 pA/pF; n = 4 to 6 neurons). Using bromodomain-containing protein 4-targeted antisense small interfering RNA to the complete Freund's adjuvant-treated rats, the authors demonstrated a reduction in the expression of bromodomain-containing protein 4 (0.68 ± 0.16 fold; n = 7), a reduction in thermal hyperalgesia (7.5 ± 1.5 s; n = 7), and a reduction in the increased voltage-gated sodium channel 1.7 currents (21 ± 4 pA/pF; n = 4 to 6 neurons). Complete Freund's adjuvant triggers enhanced bromodomain-containing protein 4 expression, ultimately leading to the enhanced excitability of nociceptive neurons and thermal hyperalgesia. This effect is likely mediated by the enhanced expression of voltage-gated sodium channel 1.7.

Feline Immunodeficiency Virus Vif N-Terminal Residues Selectively Counteract Feline APOBEC3s.

PubMed

Gu, Qinyong; Zhang, Zeli; Cano Ortiz, Lucía; Franco, Ana Cláudia; Häussinger, Dieter; Münk, Carsten

2016-12-01

Feline immunodeficiency virus (FIV) Vif protein counteracts feline APOBEC3s (FcaA3s) restriction factors by inducing their proteasomal degradation. The functional domains in FIV Vif for interaction with FcaA3s are poorly understood. Here, we have identified several motifs in FIV Vif that are important for selective degradation of different FcaA3s. Cats (Felis catus) express three types of A3s: single-domain A3Z2, single-domain A3Z3, and double-domain A3Z2Z3. We proposed that FIV Vif would selectively interact with the Z2 and the Z3 A3s. Indeed, we identified two N-terminal Vif motifs (12LF13 and 18GG19) that specifically interacted with the FcaA3Z2 protein but not with A3Z3. In contrast, the exclusive degradation of FcaA3Z3 was regulated by a region of three residues (M24, L25, and I27). Only a FIV Vif carrying a combination of mutations from both interaction sites lost the capacity to degrade and counteract FcaA3Z2Z3. However, alterations in the specific A3s interaction sites did not affect the cellular localization of the FIV Vif protein and binding to feline A3s. Pulldown experiments demonstrated that the A3 binding region localized to FIV Vif residues 50 to 80, outside the specific A3 interaction domain. Finally, we found that the Vif sites specific to individual A3s are conserved in several FIV lineages of domestic cat and nondomestic cats, while being absent in the FIV Vif of pumas. Our data support a complex model of multiple Vif-A3 interactions in which the specific region for selective A3 counteraction is discrete from a general A3 binding domain. Both human immunodeficiency virus (HIV) and feline immunodeficiency virus (FIV) Vif proteins counteract their host's APOBEC3 restriction factors. However, these two Vif proteins have limited sequence homology. The molecular interaction between FIV Vif and feline APOBEC3s are not well understood. Here, we identified N-terminal FIV Vif sites that regulate the selective interaction of Vif with either feline APOBEC3Z2 or APOBEC3Z3. These specific Vif sites are conserved in several FIV lineages of domestic cat and nondomestic cats, while being absent in FIV Vif from puma. Our findings provide important insights for future experiments describing the FIV Vif interaction with feline APOBEC3s and also indicate that the conserved feline APOBEC3s interaction sites of FIV Vif allow FIV transmissions in Felidae. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Feline Immunodeficiency Virus Vif N-Terminal Residues Selectively Counteract Feline APOBEC3s

PubMed Central

Gu, Qinyong; Zhang, Zeli; Cano Ortiz, Lucía; Franco, Ana Cláudia; Häussinger, Dieter

2016-01-01

ABSTRACT Feline immunodeficiency virus (FIV) Vif protein counteracts feline APOBEC3s (FcaA3s) restriction factors by inducing their proteasomal degradation. The functional domains in FIV Vif for interaction with FcaA3s are poorly understood. Here, we have identified several motifs in FIV Vif that are important for selective degradation of different FcaA3s. Cats (Felis catus) express three types of A3s: single-domain A3Z2, single-domain A3Z3, and double-domain A3Z2Z3. We proposed that FIV Vif would selectively interact with the Z2 and the Z3 A3s. Indeed, we identified two N-terminal Vif motifs (12LF13 and 18GG19) that specifically interacted with the FcaA3Z2 protein but not with A3Z3. In contrast, the exclusive degradation of FcaA3Z3 was regulated by a region of three residues (M24, L25, and I27). Only a FIV Vif carrying a combination of mutations from both interaction sites lost the capacity to degrade and counteract FcaA3Z2Z3. However, alterations in the specific A3s interaction sites did not affect the cellular localization of the FIV Vif protein and binding to feline A3s. Pulldown experiments demonstrated that the A3 binding region localized to FIV Vif residues 50 to 80, outside the specific A3 interaction domain. Finally, we found that the Vif sites specific to individual A3s are conserved in several FIV lineages of domestic cat and nondomestic cats, while being absent in the FIV Vif of pumas. Our data support a complex model of multiple Vif-A3 interactions in which the specific region for selective A3 counteraction is discrete from a general A3 binding domain. IMPORTANCE Both human immunodeficiency virus (HIV) and feline immunodeficiency virus (FIV) Vif proteins counteract their host's APOBEC3 restriction factors. However, these two Vif proteins have limited sequence homology. The molecular interaction between FIV Vif and feline APOBEC3s are not well understood. Here, we identified N-terminal FIV Vif sites that regulate the selective interaction of Vif with either feline APOBEC3Z2 or APOBEC3Z3. These specific Vif sites are conserved in several FIV lineages of domestic cat and nondomestic cats, while being absent in FIV Vif from puma. Our findings provide important insights for future experiments describing the FIV Vif interaction with feline APOBEC3s and also indicate that the conserved feline APOBEC3s interaction sites of FIV Vif allow FIV transmissions in Felidae. PMID:27630243

Compliance with post-operative adjuvant chemotherapy in non-small cell lung cancer. An analysis of National Cancer Institute of Canada and intergroup trial JBR.10 and a review of the literature.

PubMed

Alam, Naveed; Shepherd, Frances A; Winton, Timothy; Graham, Barbara; Johnson, David; Livingston, Robert; Rigas, James; Whitehead, Marlo; Ding, Keyue; Seymour, Lesley

2005-03-01

Resected non-small cell lung cancer (NSCLC) has 5-years survival rates of 30-70%. The role of adjuvant chemotherapy remains unclear with poor compliance reported in most trials. The compliance with adjuvant chemotherapy (ACT) for stage IB and II NSCLC was analyzed using data from a North American multi-centre phase III study (accrual 1994-2001) that compared adjuvant chemotherapy to observation. Planned chemotherapy consisted of cisplatin (CIS) 50 mg/m2 days 1, 8 and vinorelbine (VIN) 25 mg/m2 days 1, 8, 15, 22 for four cycles; the VIN dose had been reduced from 30 mg/m2 after an initial cohort of patients experienced unacceptable toxicity. Four hundred and twenty-four patients were randomized after the amendment, 215 to the chemotherapy arm. Median age was 60 years, 64% were male and 84% had stage II disease. Thirty-seven patients completed one cycle, 14 completed two, 20 completed three and 108 patients completed all four cycles. Ten patients received no therapy. Multivariate analysis demonstrated statistically significant differences in compliance with extent of surgery, gender and age. Patients randomized in Canada were more likely to fail to complete chemotherapy due to refusal of therapy than their American counterparts. Patients who had pneumonectomies were more likely to discontinue therapy due to toxicity than those who had lesser resections. Extent of surgery may play a role in both the compliance and toxicity of ACT. Differences between nations in the perception of the risks and benefits of adjuvant chemotherapy regimens, both between physicians and patients, should be investigated further.

Adjuvant FOLFOX chemotherapy and splenomegaly in patients with stages II-III colorectal cancer.

PubMed

Angitapalli, Revathi; Litwin, Alan M; Kumar, Prasanna R G; Nasser, Eiad; Lombardo, Jeffrey; Mashtare, Terry; Wilding, Gregory E; Fakih, Marwan G

2009-01-01

The impact of adjuvant chemotherapy on hepatic function and portal hypertension in patients with stages II-III colon cancer has not been previously described. We conducted a retrospective study to assess the effects of adjuvant FOLFOX chemotherapy on the splenic index (SI) as a surrogate marker for portal hypertension. Stage II-III colorectal cancer patients treated with adjuvant FOLFOX or fluorouracil/leucovorin (5-FU/LV) at Roswell Park Cancer Institute between 2002 and 2006 were identified. Computerizedt omography (CT) scans obtained prior to and at completion of chemotherapy, and every 6 months thereafter were reviewed. Splenic size was evaluated using the SI (SI = length x width x height of the spleen). 40 patients were identified in the FOLFOX group and 23 in the 5-FU/LV group. After 6 months of adjuvant chemotherapy, the mean increase in SI was 45.7 and 16.3% in the FOLFOX and 5-FU/LV groups, respectively (p = 0.0069). SI increased by >100% in 6 patients (15%) in the FOLFOX group versus none in the 5-FU/LV group (p = 0.16). The mean SI at completion of adjuvant chemotherapy was significantly higher in the FOLFOX group than in the 5-FU/LV group (p = 0.007). The mean SI decreased steadily over a period of 2 years after discontinuation of FOLFOX, suggesting potential reversibility of oxaliplatin-induced hepatic injury in this setting. Adjuvant FOLFOX significantly increases the SI in patients with resected colorectal cancer in comparison to adjuvant 5-FU/LV. The increase in SI may be a marker of oxaliplatin-induced hepatic injury and should be investigated further in prospective longitudinal studies of oxaliplatin-based adjuvant chemotherapy. Copyright 2009 S. Karger AG, Basel.

Weight gain after adjuvant chemotherapy in patients with early breast cancer in Istanbul Turkey.

PubMed

Basaran, Gul; Turhal, Nazım Serdar; Cabuk, Devrim; Yurt, Nevin; Yurtseven, Gul; Gumus, Mahmut; Teomete, Mehmet; Dane, Faysal; Yumuk, Perran Fulden

2011-06-01

Weight gain is a well-known and unwanted complication of adjuvant chemotherapy in breast cancer. We observed that the female Turkish cancer patients frequently gain weight with adjuvant treatment of breast cancer and planned to examine the magnitude of this problem in early breast cancer patients treated at our hospital. A total of 176 early breast cancer patients who received their adjuvant systemic therapy in Marmara University Hospital between 2003 and 2007 are included in the study. We recorded their weight before and after chemotherapy and also a year after chemotherapy to find out whether the change with weight is transitory. We have also recorded demographic information, including the educational level, menopausal status, the type of chemotherapy or hormonal treatment administered stage of disease, marital status, occupation and the underlying diseases to analyze the relationship between change in weight and these parameters. Median age of patients was 53 and 72% of patients were postmenopausal. Educational level was equally distributed for primary education (27%), high school (40%), and university (33%). The majority of the patients (76%) was married, had two children (69%) and was housewife (60%). Family history of any cancer was high (32%). Most of the patients had stage II cancer (56%), received anthracyclines+/- taxane based chemotherapy (98%) and had no underlying disease (68%). The majority also did not smoke (73%) or drink alcohol (93%). A total of 67% and 72% patients gained weight upon completion and one year after completion of chemotherapy. Mean weight before the chemotherapy, upon completion of chemotherapy and one year after completion of chemotherapy were 68.9 kg, 70.6 kg (P = 0.000) and 71.9 kg (P = 0.000) respectively. Mean body mass index was 27.1 at baseline, 27.8 upon completion of chemotherapy (P = 0.000) and 28.3 one year after completion of chemotherapy (P = 0.000). Age, menopausal status, multiparity and presence of comorbid diseases had statistically significant impact on weight gain following adjuvant therapy in breast cancer patients (P = 0.000, P = 0.008, P = 0.015 and P = 0.017 respectively). This study shows that Turkish women with early breast cancer gain weight after adjuvant systemic therapy, in line with European and American counterparts. This increase in weight is maintained at least one year after adjuvant therapy. Given the adverse consequences of weight gain in terms of both breast cancer prognosis and general health, it is necessary to inform patients about this change and to develop strategies for weight maintenance during and after systemic therapy.

Association Between Adjuvant Chemotherapy and Overall Survival in Patients With Rectal Cancer and Pathological Complete Response After Neoadjuvant Chemotherapy and Resection.

PubMed

Dossa, Fahima; Acuna, Sergio A; Rickles, Aaron S; Berho, Mariana; Wexner, Steven D; Quereshy, Fayez A; Baxter, Nancy N; Chadi, Sami A

2018-04-19

Although American guidelines recommend use of adjuvant chemotherapy in patients with locally advanced rectal cancer, individuals who achieve a pathological complete response (pCR) following neoadjuvant chemoradiotherapy are less likely to receive adjuvant treatment than incomplete responders. The association and resection of adjuvant chemotherapy with survival in patients with pCR is unclear. To determine whether patients with locally advanced rectal cancer who achieve pCR after neoadjuvant chemoradiation therapy and resection benefit from the administration of adjuvant chemotherapy. This retrospective propensity score-matched cohort study identified patients with locally advanced rectal cancer from the National Cancer Database from 2006 through 2012. We selected patients with nonmetastatic invasive rectal cancer who achieved pCR after neoadjuvant chemoradiation therapy and resection. We matched patients who received adjuvant chemotherapy to patients who did not receive adjuvant treatment in a 1:1 ratio. We separately matched subgroups of patients with node-positive disease before treatment and node-negative disease before treatment to investigate for effect modification by pretreatment nodal status. We compared overall survival between groups using Kaplan-Meier survival methods and Cox proportional hazards models. We identified 2455 patients (mean age, 59.5 years; 59.8% men) with rectal cancer with pCR after neoadjuvant chemoradiation therapy and resection. We matched 667 patients with pCR who received adjuvant chemotherapy and at least 8 weeks of follow-up after surgery to patients with pCR who did not receive adjuvant treatment. Over a median follow-up of 3.1 years (interquartile range, 1.94-4.40 years), patients treated with adjuvant chemotherapy demonstrated better overall survival than those who did not receive adjuvant treatment (hazard ratio, 0.44; 95% CI, 0.28-0.70). When stratified by pretreatment nodal status, only those patients with pretreatment node-positive disease exhibited improved overall survival with administration of adjuvant chemotherapy (hazard ratio, 0.24; 95% CI, 0.10-0.58). The administration of adjuvant chemotherapy in patients with rectal cancer with pCR is associated with improved overall survival, particularly in patients with pretreatment node-positive disease. Although this study suggests a beneficial effect of adjuvant treatment on survival in patients with pCR, these results are limited by the presence of potential unmeasured confounding in this nonrandomized study.

Nyctanthes arbor-tristis Ameliorated FCA-Induced Experimental Arthritis: A Comparative Study among Different Extracts

PubMed Central

Uroos, Maliha; Sattar, Shumaila; Umer, Nigarish; Sharif, Ahsan

2017-01-01

Nyctanthes arbor-tristis (NAT) is commonly used traditionally for the treatment of rheumatism and inflammatory diseases. Current study evaluates the antiarthritic potential of NAT using Freund's adjuvant-induced arthritic rat model. Treatments with methanolic, ethyl acetate, and n-hexane extracts were continued for consecutive 20 days. Macroscopic arthritic scoring and water displacement plethysmometry were used to evaluate arthritic development. Hematological and biochemical parameters were investigated and ankle joints were processed for histopathological evaluation. Qualitative phytochemical analysis and GC-MS analysis were conducted for identification of constituents. NAT extracts suppressed arthritic scoring, paw edema, infiltration of inflammatory cells, pannus formation, and bone erosion. The plant extracts ameliorated total leukocytes and platelet counts and nearly normalized red blood cells (RBC) counts and hemoglobin (Hb) content. The extracts were found safe in terms of hepatotoxicity and nephrotoxicity as determined by aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, and urea levels. Comparative analysis showed that ethyl acetate extract produced the highest inhibition of paw edema. The major constituents found in ethyl acetate extract can be classified into three major classes, that is, terpenes, terpenoids, fatty acids, and iridoid glycosides. Current study showed that Nyctanthes arbor-tristis ameliorated experimental rheumatoid arthritis and ethyl acetate extract possessed the highest inhibitory activity. PMID:28676830

75 FR 18725 - Organization; Eligibility and Scope of Financing; Funding and Fiscal Affairs, Loan Policies and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-12

...The Farm Credit Administration (FCA or we) issues this final rule on Farm Credit System (System) bank and association director elections and other voting procedures. The final rule clarifies director election processes and updates FCA regulations to incorporate interpretations made through bookletters to System institutions. It also consolidates general election procedures, clarifies the role of nominating committees, enhances eligibility and disclosure requirements for director candidates, and improves annual meeting information statement instructions. The final rule also adds new regulations on floor nominations and meetings of stockholders. We expect this final rule will increase stockholder participation, enhance impartiality, and strengthen disclosures in director elections.

Assessing the Allocation of Special Elderly Nursing Homes in Tokyo, Japan

PubMed Central

You, Ninglong; Shen, Zhenjiang; Nishino, Tatsuya

2017-01-01

Social welfare and public health departments require reliable assessments to enhance the rationality of phased construction of special elderly nursing homes (SENHs). This paper aims to assess the allocation of SENHs based on a beds-needed index for SENHs (BNIS). This may help departments determine the priority for approving locations of SENHs more accurately with a limited budget. Traditional assessments in Tokyo use the sphere of welfare, ward, and sphere of daily life as spatial units for estimating beds-to-elderly population ratios. We calculate the BNIS by introducing a parameter-improved floating catchment area method (PI-FCA) at a smaller spatial unit, the Chome. In the PI-FCA, the catchment area is generated according to the standard of average population served by SENHs and capacity, the population demand is the population of the elderly requiring care levels 3–5 and is further modified by a coefficient of potential demand via building a multivariate linear model. Improved results were obtained using the PI-FCA. Finally, this study maps the distribution of the degree of BNIS, to provide a basis for the allocation assessment of SENHs. This caters to the needs of departments and is easily applicable in other public healthcare facilities. PMID:28937659

Antimalarial activity of Ajuga remota Benth (Labiatae) and Caesalpinia volkensii Harms (Caesalpiniaceae): in vitro confirmation of ethnopharmacological use.

PubMed

Kuria, K A; De Coster, S; Muriuki, G; Masengo, W; Kibwage, I; Hoogmartens, J; Laekeman, G M

2001-02-01

Field trips to herbalists' practices in an area about 200 miles around Nairobi (Kenya) enabled us to make a list of medicinal plant species preferentially used to treat malaria. Ajuga remota and Caesalpinia volkensii were further investigated as being the most frequently used species. Aqueous decoctions, ethanol macerates, and petroleum ether, methanol and water Soxhlet extracts of these plants were further tested for their in vitro antimalarial properties in a chloroquine sensitive (FCA/20GHA) and resistant (W2) strain of Plasmodium falciparum. The activity was assessed by the parasite lactate dehydrogenase (pLDH) assay method. There was a concentration-dependent inhibition by the vegetal extracts of both plants. The IC(50) of the most active A. remota extract (ethanol macerate) was 55 and 57 microg/ml against FCA/20GHA and W2, respectively. For C. volkensii, it was the Soxhlet-water extract which was most active against FCA/20GHA with an IC(50) of 404 microg/ml while the petroleum ether extract exhibited the most activity against W2 with an IC(50) of 250 microg/ml. Further phytochemical work is being done in order to identify the active principles.

Firearm and nonfirearm homicide in 5 South African cities: a retrospective population-based study.

PubMed

Matzopoulos, Richard G; Thompson, Mary Lou; Myers, Jonathan E

2014-03-01

We assessed the effectiveness of South Africa's Firearm Control Act (FCA), passed in 2000, on firearm homicide rates compared with rates of nonfirearm homicide across 5 South African cities from 2001 to 2005. We conducted a retrospective population-based study of 37 067 firearm and nonfirearm homicide cases. Generalized linear models helped estimate and compare time trends of firearm and nonfirearm homicides, adjusting for age, sex, race, day of week, city, year of death, and population size. There was a statistically significant decreasing trend regarding firearm homicides from 2001, with an adjusted year-on-year homicide rate ratio of 0.864 (95% confidence interval [CI] = 0.848, 0.880), representing a decrease of 13.6% per annum. The year-on-year decrease in nonfirearm homicide rates was also significant, but considerably lower at 0.976 (95% CI = 0.954, 0.997). Results suggest that 4585 (95% CI = 4427, 4723) lives were saved across 5 cities from 2001 to 2005 because of the FCA. Strength, timing and consistent decline suggest stricter gun control mediated by the FCA accounted for a significant decrease in homicide overall, and firearm homicide in particular, during the study period.

Letrozole: a review of its use in the treatment of postmenopausal women with hormone-responsive early breast cancer.

PubMed

Keating, Gillian M

2009-08-20

Letrozole (Femara) is a third-generation, nonsteroidal aromatase inhibitor. Adjuvant therapy with letrozole is more effective than tamoxifen in postmenopausal women with hormone-responsive early breast cancer, and extended adjuvant therapy with letrozole after the completion of adjuvant tamoxifen therapy is more effective than placebo in this patient population; letrozole is generally well tolerated. Ongoing trials will help answer outstanding questions regarding the optimal duration of letrozole therapy in early breast cancer and its efficacy compared with other third-generation aromatase inhibitors such as anastrozole. In the meantime, letrozole should be considered a valuable option in the treatment of postmenopausal women with hormone-responsive early breast cancer, both as adjuvant and extended adjuvant therapy.

Tubastatin, a selective histone deacetylase 6 inhibitor shows anti-inflammatory and anti-rheumatic effects.

PubMed

Vishwakarma, Santosh; Iyer, Lakshmi R; Muley, Milind; Singh, Pankaj Kumar; Shastry, Arun; Saxena, Ambrish; Kulathingal, Jayanarayan; Vijaykanth, G; Raghul, J; Rajesh, Navin; Rathinasamy, Suresh; Kachhadia, Virendra; Kilambi, Narasimhan; Rajgopal, Sridharan; Balasubramanian, Gopalan; Narayanan, Shridhar

2013-05-01

Epigenetic modifications represent a promising new approach to modulate cell functions as observed in autoimmune diseases. Emerging evidence suggests the utility of HDAC inhibitors in the treatment of chronic immune and inflammatory disorders. However, class and isoform selective inhibition of HDAC is currently favored as it limits the toxicity that has been observed with pan-HDAC inhibitors. HDAC6, a member of the HDAC family, whose major substrate is α-tubulin, is being increasingly implicated in the pathogenesis of inflammatory disorders. The present study was carried out to study the potential anti-inflammatory and anti-rheumatic effects of HDAC6 selective inhibitor Tubastatin. Tubastatin, a potent human HDAC6 inhibitor with an IC50 of 11 nM showed significant inhibition of TNF-α and IL-6 in LPS stimulated human THP-1 macrophages with an IC50 of 272 nM and 712 nM respectively. Additionally, Tubastatin inhibited nitric oxide (NO) secretion in murine Raw 264.7 macrophages dose dependently with an IC50 of 4.2 μM and induced α-tubulin hyperacetylation corresponding to HDAC6 inhibition in THP-1 cells without affecting the cell viability. Tubastatin showed significant inhibition of paw volume at 30 mg/kg i.p. in a Freund's complete adjuvant (FCA) induced animal model of inflammation. The disease modifying activity of Tubastatin was also evident in collagen induced arthritis DBA1 mouse model at 30 mg/kg i.p. The significant attenuation of clinical scores (~70%) by Tubastatin was confirmed histopathologically and was found comparable to dexamethasone (~90% inhibition of clinical scores). Tubastatin showed significant inhibition of IL-6 in paw tissues of arthritic mice. The present work has demonstrated anti-inflammatory and antirheumatic effects of a selective HDAC6 inhibitor Tubastatin. Copyright © 2013 Elsevier B.V. All rights reserved.

Oral administration of the amino acids cystine and theanine attenuates the adverse events of S-1 adjuvant chemotherapy in gastrointestinal cancer patients.

PubMed

Tsuchiya, Takashi; Honda, Hiroshi; Oikawa, Masaya; Kakita, Tetsuya; Oyama, Atsushi; Oishi, Hidekazu; Tochikubo, Katsuyuki; Hashimoto, Takanao; Kurihara, Shigekazu; Shibakusa, Tetsuro; Kayahara, Takashi

2016-12-01

Nutritional therapy is used to reduce the adverse events (AEs) of anticancer drugs. Here, we determined whether the amino acids cystine and theanine, which provide substrates for glutathione, attenuated the AEs of S-1 adjuvant chemotherapy. Patients scheduled to receive S-1 adjuvant chemotherapy were randomized to the C/T or the control groups. The C/T group received 700 mg cystine and 280 mg theanine orally 1 week before the administration of S-1, which then continued for 5 weeks. Each group received S-1 for 4 weeks. Blood sampling was performed and AEs were evaluated (CTCAE ver. 4.0) before and after the administration of S-1. S-1 was discontinued when AEs ≥ grade 2 occurred. The incidences of AEs of any grade and those over grade 2 were lower in the C/T group than in the controls. The incidence of diarrhea (G ≥ 2) was significantly less (p < 0.05) in the C/T group (3.1 %) than in the controls (25.8 %). The duration and completion rate of the S-1 adjuvant chemotherapy were significantly longer (p < 0.01) and higher (p < 0.01), respectively, in the C/T group (complete ratio: 75.0 %, duration: 24.8 ± 5.8 days) than in the controls (complete ratio: 35.5 %, duration: 20.0 ± 7.7 days). The oral administration of cystine and theanine attenuated the AEs of S-1 adjuvant chemotherapy and increased the S-1 completion rate, suggesting that cystine and theanine is a useful supportive care for chemotherapy.

Adjuvant therapy sparing in rectal cancer achieving complete response after chemoradiation

PubMed Central

García-Albéniz, Xabier; Gallego, Rosa; Hofheinz, Ralf Dieter; Fernández-Esparrach, Gloria; Ayuso-Colella, Juan Ramón; Bombí, Josep Antoni; Conill, Carles; Cuatrecasas, Miriam; Delgado, Salvadora; Ginés, Angels; Miquel, Rosa; Pagés, Mario; Pineda, Estela; Pereira, Verónica; Sosa, Aarón; Reig, Oscar; Victoria, Iván; Feliz, Luis; María de Lacy, Antonio; Castells, Antoni; Burkholder, Iris; Hochhaus, Andreas; Maurel, Joan

2014-01-01

AIM: To evaluate the long-term results of conventional chemoradiotherapy and laparoscopic mesorectal excision in rectal adenocarcinoma patients without adjuvant therapy. METHODS: Patients with biopsy-proven adenocarcinoma of the rectum staged cT3-T4 by endoscopic ultrasound or magnetic resonance imaging received neoadjuvant continuous infusion of 5-fluorouracil for five weeks and concomitant radiotherapy. Laparoscopic surgery was planned after 5-8 wk. Patients diagnosed with ypT0N0 stage cancer were not treated with adjuvant therapy according to the protocol. Patients with ypT1-2N0 or ypT3-4 or N+ were offered 5-fluorouracil-based adjuvant treatment on an individual basis. An external cohort was used as a reference for the findings. RESULTS: One hundred and seventy six patients were treated with induction chemoradiotherapy and 170 underwent total mesorectal excision. Cancer staging of ypT0N0 was achieved in 26/170 (15.3%) patients. After a median follow-up of 58.3 mo, patients with ypT0N0 had five-year disease-free and overall survival rates of 96% (95%CI: 77-99) and 100%, respectively. We provide evidence about the natural history of patients with localized rectal cancer achieving a complete response after preoperative chemoradiation. The inherent good prognosis of these patients will have implications for clinical trial design and care of patients. CONCLUSION: Withholding adjuvant chemotherapy after complete response following standard neoadjuvant chemoradiotherapy and laparoscopic mesorectal excision might be safe within an experienced multidisciplinary team. PMID:25400468

Adjuvant Bidirectional Chemotherapy Using an Intraperitoneal Port

PubMed Central

Sugarbaker, Paul H.; Bijelic, Lana

2012-01-01

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been established as treatment options for patients with peritoneal metastases or peritoneal mesothelioma. However, this novel treatment strategy remains associated with a large percentage of local-regional treatment failures. These treatment failures are attributed to the inadequacy of HIPEC to maintain a surgical complete response. Management strategies to supplement CRS and HIPEC are indicated. A simplified approach to the intraoperative placement of an intraperitoneal port for adjuvant bidirectional chemotherapy (ABC) was devised. Four different chemotherapy treatment plans were utilized depending upon the primary site of the malignancy. Thirty-one consecutive patients with an intraoperative placement of the intraperitoneal port were available for study. The incidence of adverse events that caused an early discontinuation of the bidirectional chemotherapy occurred in 75% of the 8 patients who had an incomplete cytoreduction and in 0% of patients who had a complete cytoreduction. All of the patients who had complete cytoreduction completed at least 5 of the scheduled 6 bidirectional chemotherapy treatments. Adjuvant bidirectional chemotherapy is possible following a major cytoreductive surgical procedure using a simplified method of intraoperative intraperitoneal port placement. PMID:22888340

Familial pancreatic cancer: the case for prophylactic pancreatectomy in lieu of serial screening and shared decision making.

PubMed

Iskandar, Mazen E; Wayne, Michael G; Steele, Justin G; Cooperman, Avram M

2014-01-01

At-risk family members with familial pancreatic cancer (FCaP) face uncertainty regarding the individual risk of developing pancreatic cancer (CaP) and whether to choose serial screening or prophylactic pancreatectomy to avoid CaP. We treated 2 at-risk siblings with a history of FCaP, congenital hepatic fibrosis (CHF), and jaundice secondary to a bile duct stricture. In one, a pancreaticoduodenal resection was done and in the second a total pancreatectomy. Malignancy was not present, but extensive pancreatic intraepithelial neoplasia (PanIn) 2 was present throughout both pancreata. The clinical course and literature review are presented along with the previously unreported association of CHF and CaP.

Cooperative Friedel-Crafts catalysis in heterobimetallic regime: alkylation of aromatics by pi-activated alcohols.

PubMed

Choudhury, Joyanta; Podder, Susmita; Roy, Sujit

2005-05-04

The highly active Friedel-Crafts alkylation (FCA) catalyst, [Ir(COD)Cl(SnCl3)(SnCl4)(arene)]+Cl- (1-SnCl4), is easily generated in one-pot from [Ir(COD)Cl]2 or [Ir(COD)(mu-Cl)Cl(SnCl3)]2 (1) and SnCl4. The reaction of arenes, heteroarenes with benzyl, and allyl alcohols is promoted by 1-SnCl4 (1 mol %) with high turnover frequency. Kinetic evidence is presented to establish FCA pattern. From dual-catalyst combination studies varying the transition metal and main group metal partner, the efficiency of the present catalysts is attributed to the electrophilic "IrIII-SnIV" core.

Feasibility of adjuvant chemotherapy with S-1 plus carboplatin followed by single-agent maintenance therapy with S-1 for completely resected non-small-cell lung cancer: results of the Setouchi Lung Cancer Group Study 1001.

PubMed

Okumura, Norihito; Sonobe, Makoto; Okabe, Kazunori; Nakamura, Hiroshige; Kataoka, Masafumi; Yamashita, Motohiro; Nakata, Masao; Kataoka, Kazuhiko; Yamashita, Yoshinori; Soh, Junichi; Yoshioka, Hiroshige; Hotta, Katsuyuki; Matsuo, Keitaro; Sakamoto, Junichi; Toyooka, Shinichi; Date, Hiroshi

2017-04-01

This multicenter study evaluated the feasibility of novel adjuvant chemotherapy with S-1 plus carboplatin followed by single-agent, long-term maintenance with S-1 in patients with completely resected stage II-IIIA non-small-cell lung cancer (NSCLC). Patients received four cycles of S-1 (80 mg/m 2 /day for 2 weeks, followed by 2 weeks rest) plus carboplatin (area under the curve 5, day 1) followed by S-1 (80 mg/m 2 /day for 2 weeks, followed by a 1-week rest). Patients unable to continue S-1 plus carboplatin because of severe toxicity converted to single-agent S-1 maintenance. The duration of adjuvant chemotherapy was 10 months in both situations. The primary endpoint was feasibility, defined as the proportion of patients who completed four cycles of S-1 plus carboplatin and single-agent S-1 maintenance for 10 months. The treatment completion rate was determined; treatment was considered feasible if the lower 90% confidence interval (CI) was ≥50%. Eighty-nine patients were enrolled, of whom 87 were eligible and assessable. Seventy-eight patients (89.7%) completed four cycles of S-1 plus carboplatin and 55 (63.2%) completed the following S-1 maintenance therapy for a total of 10 months. The treatment completion rate was 63.2% (90% CI, 54.4-71.2%), indicating feasibility. There were no treatment-related deaths. Grade 3/4 toxicities included neutropenia (13.8%), thrombocytopenia (11.5%), and anorexia (4.6%). The 2-year relapse-free survival rate was 59.8%. We concluded that adjuvant chemotherapy with S-1 plus carboplatin followed by single-agent maintenance therapy with S-1 is feasible and tolerable in patients with completely resected NSCLC. UMIN000005041.

Health care and lost productivity costs of overweight and obesity in New Zealand.

PubMed

Lal, Anita; Moodie, Marj; Ashton, Toni; Siahpush, Mohammad; Swinburn, Boyd

2012-12-01

To estimate the costs of health care and lost productivity attributable to overweight and obesity in New Zealand (NZ) in 2006. A prevalence-based approach to costing was used in which costs were calculated for all cases of disease in the year 2006. Population attributable fractions (PAFs) were calculated based on the relative risks obtained from large cohort studies and the prevalence of overweight and obesity. For each disease, the PAF was multiplied by the total health care cost. The costs of lost productivity associated with premature mortality were estimated using both the Human Capital approach (HCA) and Friction Cost approach (FCA). Health care costs attributable to overweight and obesity were estimated to be NZ$686m or 4.5% of New Zealand's total health care expenditure in 2006. The costs of lost productivity using the FCA were estimated to be NZ$98m and NZ$225m using the HCA. The combined costs of health care and lost productivity using the FCA were $784m and $911m using the HCA. The cost burden of overweight and obesity in NZ is considerable. Policies and interventions are urgently needed to reduce the prevalence of obesity thereby decreasing these substantial costs. © 2012 The Authors. ANZJPH © 2012 Public Health Association of Australia.

Analyzing coastal environments by means of functional data analysis

NASA Astrophysics Data System (ADS)

Sierra, Carlos; Flor-Blanco, Germán; Ordoñez, Celestino; Flor, Germán; Gallego, José R.

2017-07-01

Here we used Functional Data Analysis (FDA) to examine particle-size distributions (PSDs) in a beach/shallow marine sedimentary environment in Gijón Bay (NW Spain). The work involved both Functional Principal Components Analysis (FPCA) and Functional Cluster Analysis (FCA). The grainsize of the sand samples was characterized by means of laser dispersion spectroscopy. Within this framework, FPCA was used as a dimension reduction technique to explore and uncover patterns in grain-size frequency curves. This procedure proved useful to describe variability in the structure of the data set. Moreover, an alternative approach, FCA, was applied to identify clusters and to interpret their spatial distribution. Results obtained with this latter technique were compared with those obtained by means of two vector approaches that combine PCA with CA (Cluster Analysis). The first method, the point density function (PDF), was employed after adapting a log-normal distribution to each PSD and resuming each of the density functions by its mean, sorting, skewness and kurtosis. The second applied a centered-log-ratio (clr) to the original data. PCA was then applied to the transformed data, and finally CA to the retained principal component scores. The study revealed functional data analysis, specifically FPCA and FCA, as a suitable alternative with considerable advantages over traditional vector analysis techniques in sedimentary geology studies.

Firearm and Nonfirearm Homicide in 5 South African Cities: A Retrospective Population-Based Study

PubMed Central

Thompson, Mary Lou; Myers, Jonathan E.

2014-01-01

Objective. We assessed the effectiveness of South Africa’s Firearm Control Act (FCA), passed in 2000, on firearm homicide rates compared with rates of nonfirearm homicide across 5 South African cities from 2001 to 2005. Methods. We conducted a retrospective population-based study of 37 067 firearm and nonfirearm homicide cases. Generalized linear models helped estimate and compare time trends of firearm and nonfirearm homicides, adjusting for age, sex, race, day of week, city, year of death, and population size. Results. There was a statistically significant decreasing trend regarding firearm homicides from 2001, with an adjusted year-on-year homicide rate ratio of 0.864 (95% confidence interval [CI] = 0.848, 0.880), representing a decrease of 13.6% per annum. The year-on-year decrease in nonfirearm homicide rates was also significant, but considerably lower at 0.976 (95% CI = 0.954, 0.997). Results suggest that 4585 (95% CI = 4427, 4723) lives were saved across 5 cities from 2001 to 2005 because of the FCA. Conclusions. Strength, timing and consistent decline suggest stricter gun control mediated by the FCA accounted for a significant decrease in homicide overall, and firearm homicide in particular, during the study period. PMID:24432917

Influence of adjuvant detached mindfulness and stress management training compared to pharmacologic treatment in primiparae with postpartum depression.

PubMed

Ahmadpanah, Mohammad; Nazaribadie, Marzieh; Aghaei, Elham; Ghaleiha, Ali; Bakhtiari, Azade; Haghighi, Mohammad; Bahmani, Dena Sadeghi; Akhondi, Amineh; Bajoghli, Hafez; Jahangard, Leila; Holsboer-Trachsler, Edith; Brand, Serge

2018-02-01

Ten to 15% of mothers experience postpartum depression (PPD). If untreated, PPD may negatively affect mothers' and infants' mental health in the long term. Accordingly, effective treatments are required. In the present study, we investigated the effect of detached mindfulness (DM) and stress management training (SMT) as adjuvants, compared to pharmacologic treatment only, on symptoms of depression in women with PPD. Forty-five primiparae (mean age: M = 24.5 years) with diagnosed PPD and treated with an SSRI (citalopram; CIT) took part in the study. At baseline, they completed questionnaires covering socio-demographic data and symptoms of depression. Experts rated also symptoms of depression. Next, participants were randomly assigned to one of the following study conditions: adjuvant detached mindfulness (CIT+DM); adjuvant stress management training (CIT+SMT); control condition (CIT). Self- and experts' ratings were completed at the end of the study 8 weeks later, and again at 8 weeks follow-up. Symptoms of depression decreased significantly over time, but more so in the CIT+DM and CIT+SMT group, compared to the control condition. The pattern of results remained stable at follow-up. In primiparae with PPD and treated with a standard SSRI, adjuvant psychotherapeutic interventions led to significant and longer-lasting improvements.

Induction of the 'ASIA' syndrome in NZB/NZWF1 mice after injection of complete Freund's adjuvant (CFA).

PubMed

Bassi, N; Luisetto, R; Del Prete, D; Ghirardello, A; Ceol, M; Rizzo, S; Iaccarino, L; Gatto, M; Valente, M L; Punzi, L; Doria, A

2012-02-01

Adjuvants, commonly used in vaccines, may be responsible for inducing autoimmunity and autoimmune diseases, both in humans and mice. The so-called 'ASIA' (Autoimmune/inflammatory Syndrome Induced by Adjuvants) syndrome has been recently described, which is caused by the exposure to a component reproducing the effect of adjuvants. The aim of our study was to evaluate the effect of injection of complete Freund's adjuvant (CFA) in NZB/NZWF1 mice, a lupus-prone murine model. We injected 10 NZB/NZWF1 mice with CFA/PBS and 10 with PBS, three times, 3 weeks apart, and followed-up until natural death. CFA-injected mice developed both anti-double-stranded DNA and proteinuria earlier and at higher levels than the control group. Proteinuria-free survival rate and survival rate were significantly lower in CFA-treated mice than in the control mice (p = 0.002 and p = 0.001, respectively). Histological analyses showed a more severe glomerulonephritis in CFA-injected mice compared with the control mice. In addition, lymphoid hyperplasia in spleen and lungs, myocarditis, and vasculitis were observed in the former, but not in the latter group. In conclusion, the injection of CFA in NZB/NZWF1 mice accelerated autoimmune manifestations resembling 'ASIA' syndrome in humans.

Feasibility of oral administration of S-1 as adjuvant chemotherapy in gastric cancer: 4-week S-1 administration followed by 2-week rest vs. 2-week administration followed by 1-week rest

PubMed Central

YAMATSUJI, TOMOKI; FUJIWARA, YASUHIRO; MATSUMOTO, HIDEO; HATO, SHINJI; NAMIKAWA, TSUTOMU; HANAZAKI, KAZUHIRO; TAKAOKA, MUNENORI; HAYASHI, JIRO; SHIGEMITSU, KAORI; YOSHIDA, KAZUHIRO; URAKAMI, ATSUSHI; UNO, FUTOSHI; NISHIZAKI, MASAHIKO; KAGAWA, SHUNSUKE; NINOMIYA, MOTOKI; FUJIWARA, TOSHIYOSHI; HIRAI, TOSHIHIRO; NAKAMURA, MASAFUMI; HAISA, MINORU; NAOMOTO, YOSHIO

2015-01-01

In 2006, the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer (ACTS-GC) demonstrated that S-1 is an effective adjuvant therapy for gastric cancer. Following that study, S-1 has been used as the standard adjuvant therapy for gastric cancer in Japan. However, the 1-year completion rate was only 65.8% in the ACTS-GC study and feasibility remains a critical issue. We conducted a study to evaluate the feasibility of 2 weekly administration regimens of S-1 as adjuvant chemotherapy in gastric cancer. The criteria for eligibility included histologically proven stage II (excluding T1), IIIA or IIIB gastric cancer with D2 lymph-node dissection. The patients were randomly assigned to either arm A (S-1 administration for 4 weeks followed by 2 weeks of rest) or arm B (S-1 administration for 2 weeks followed by 1 week of rest). In each arm, treatment was continued for 12 months unless recurrence or severe adverse events were observed. The primary endpoint was feasibility (protocol treatment completion rate). The secondary endpoints were safety, relapse-free survival and overall survival. A total of 47 patients were assigned to arms A or B between May, 2008 and February, 2010. During the first interim analysis, the protocol treatment completion rates in arms A and B were 83 and 100%, respectively at 6 months and 49 and 89%, respectively, at 12 months (P=0.0046). Therefore, S-1 administration for 2 weeks followed by 1 week rest was more feasible as adjuvant chemotherapy in gastric cancer. Grade 3 adverse events in arm A included fatigue (8.0%), anorexia (8.0%), nausea (4.0%), vomiting (4.0%) and hand-foot syndrome (4.0%), whereas none were observed in arm B. There were no reported grade 4 adverse events in either arm. In conclusion, the 2-week S-1 administration followed by 1-week rest regimen appears to be a more feasible oral administration regimen for S-1 as adjuvant chemotherapy in gastric cancer. PMID:26137261

Efficacy and safety of azathioprine and dapsone as an adjuvant in the treatment of bullous pemphigoid.

PubMed

Tirado-Sánchez, A; Díaz-Molina, V; Ponce-Olivera, R M

2012-01-01

Bullous pemphigoid is a chronic, blistering and autoimmune disease, common in old age. The treatment usually includes systemic steroids, however, these cause high morbidity rates, and then different products that function as adjuvants have been tried. At present, there are no studies to determine which adjuvant offers a better efficacy and safety profile. We performed a retrospective study which included the records of patients with bullous pemphigoid, treated either with azathioprine or dapsone. We evaluated the time to achieve complete remission, the time to inhibit disease progression, and the control of pruritus. Fifteen records of patients were selected, eight (53%) treated with azathioprine and seven (47%) with dapsone. Complete remission was achieved at week six in both groups. We found no difference in the inhibition of disease progression (p=0.083). Pruritus was controlled at four weeks of treatment in both treatments. Both products are effective as adjuvant in the treatment of bullous pemphigoid, with an acceptable safety profile. Copyright © 2010 SEICAP. Published by Elsevier Espana. All rights reserved.

Integrated optimisation technique based on computer-aided capacity and safety evaluation for managing downstream lane-drop merging area of signalised junctions

NASA Astrophysics Data System (ADS)

Chen, CHAI; Yiik Diew, WONG

2017-02-01

This study provides an integrated strategy, encompassing microscopic simulation, safety assessment, and multi-attribute decision-making, to optimize traffic performance at downstream merging area of signalized intersections. A Fuzzy Cellular Automata (FCA) model is developed to replicate microscopic movement and merging behavior. Based on simulation experiment, the proposed FCA approach is able to provide capacity and safety evaluation of different traffic scenarios. The results are then evaluated through data envelopment analysis (DEA) and analytic hierarchy process (AHP). Optimized geometric layout and control strategies are then suggested for various traffic conditions. An optimal lane-drop distance that is dependent on traffic volume and speed limit can thus be established at the downstream merging area.

Deep first formal concept search.

PubMed

Zhang, Tao; Li, Hui; Hong, Wenxue; Yuan, Xiamei; Wei, Xinyu

2014-01-01

The calculation of formal concepts is a very important part in the theory of formal concept analysis (FCA); however, within the framework of FCA, computing all formal concepts is the main challenge because of its exponential complexity and difficulty in visualizing the calculating process. With the basic idea of Depth First Search, this paper presents a visualization algorithm by the attribute topology of formal context. Limited by the constraints and calculation rules, all concepts are achieved by the visualization global formal concepts searching, based on the topology degenerated with the fixed start and end points, without repetition and omission. This method makes the calculation of formal concepts precise and easy to operate and reflects the integrity of the algorithm, which enables it to be suitable for visualization analysis.

Familial Pancreatic Cancer: The Case for Prophylactic Pancreatectomy in Lieu of Serial Screening and Shared Decision Making

PubMed Central

Iskandar, Mazen E.; Wayne, Michael G.; Steele, Justin G.; Cooperman, Avram M.

2014-01-01

At-risk family members with familial pancreatic cancer (FCaP) face uncertainty regarding the individual risk of developing pancreatic cancer (CaP) and whether to choose serial screening or prophylactic pancreatectomy to avoid CaP. We treated 2 at-risk siblings with a history of FCaP, congenital hepatic fibrosis (CHF), and jaundice secondary to a bile duct stricture. In one, a pancreaticoduodenal resection was done and in the second a total pancreatectomy. Malignancy was not present, but extensive pancreatic intraepithelial neoplasia (PanIn) 2 was present throughout both pancreata. The clinical course and literature review are presented along with the previously unreported association of CHF and CaP. PMID:25506012

Advax-Adjuvanted Recombinant Protective Antigen Provides Protection against Inhalational Anthrax That Is Further Enhanced by Addition of Murabutide Adjuvant

PubMed Central

Feinen, Brandon; Petrovsky, Nikolai; Verma, Anita

2014-01-01

Subunit vaccines against anthrax based on recombinant protective antigen (PA) potentially offer more consistent and less reactogenic anthrax vaccines but require adjuvants to achieve optimal immunogenicity. This study sought to determine in a murine model of pulmonary anthrax infection whether the polysaccharide adjuvant Advax or the innate immune adjuvant murabutide alone or together could enhance PA immunogenicity by comparison to an alum adjuvant. A single immunization with PA plus Advax adjuvant afforded significantly greater protection against aerosolized Bacillus anthracis Sterne strain 7702 than three immunizations with PA alone. Murabutide had a weaker adjuvant effect than Advax when used alone, but when murabutide was formulated together with Advax, an additive effect on immunogenicity and protection was observed, with complete protection after just two doses. The combined adjuvant formulation stimulated a robust, long-lasting B-cell memory response that protected mice against an aerosol challenge 18 months postimmunization with acceleration of the kinetics of the anamnestic IgG response to B. anthracis as reflected by ∼4-fold-higher anti-PA IgG titers by day 2 postchallenge versus mice that received PA with Alhydrogel. In addition, the combination of Advax plus murabutide induced approximately 3-fold-less inflammation than Alhydrogel as measured by in vivo imaging of cathepsin cleavage resulting from injection of ProSense 750. Thus, the combination of Advax and murabutide provided enhanced protection against inhalational anthrax with reduced localized inflammation, making this a promising next-generation anthrax vaccine adjuvanting strategy. PMID:24554695

Advax-adjuvanted recombinant protective antigen provides protection against inhalational anthrax that is further enhanced by addition of murabutide adjuvant.

PubMed

Feinen, Brandon; Petrovsky, Nikolai; Verma, Anita; Merkel, Tod J

2014-04-01

Subunit vaccines against anthrax based on recombinant protective antigen (PA) potentially offer more consistent and less reactogenic anthrax vaccines but require adjuvants to achieve optimal immunogenicity. This study sought to determine in a murine model of pulmonary anthrax infection whether the polysaccharide adjuvant Advax or the innate immune adjuvant murabutide alone or together could enhance PA immunogenicity by comparison to an alum adjuvant. A single immunization with PA plus Advax adjuvant afforded significantly greater protection against aerosolized Bacillus anthracis Sterne strain 7702 than three immunizations with PA alone. Murabutide had a weaker adjuvant effect than Advax when used alone, but when murabutide was formulated together with Advax, an additive effect on immunogenicity and protection was observed, with complete protection after just two doses. The combined adjuvant formulation stimulated a robust, long-lasting B-cell memory response that protected mice against an aerosol challenge 18 months postimmunization with acceleration of the kinetics of the anamnestic IgG response to B. anthracis as reflected by ∼4-fold-higher anti-PA IgG titers by day 2 postchallenge versus mice that received PA with Alhydrogel. In addition, the combination of Advax plus murabutide induced approximately 3-fold-less inflammation than Alhydrogel as measured by in vivo imaging of cathepsin cleavage resulting from injection of ProSense 750. Thus, the combination of Advax and murabutide provided enhanced protection against inhalational anthrax with reduced localized inflammation, making this a promising next-generation anthrax vaccine adjuvanting strategy.

GLA-AF, an emulsion-free vaccine adjuvant for pandemic influenza.

PubMed

Clegg, Christopher H; Roque, Richard; Perrone, Lucy A; Rininger, Joseph A; Bowen, Richard; Reed, Steven G

2014-01-01

The ongoing threat from Influenza necessitates the development of new vaccine and adjuvant technologies that can maximize vaccine immunogenicity, shorten production cycles, and increase global vaccine supply. Currently, the most successful adjuvants for Influenza vaccines are squalene-based oil-in-water emulsions. These adjuvants enhance seroprotective antibody titers to homologous and heterologous strains of virus, and augment a significant dose sparing activity that could improve vaccine manufacturing capacity. As an alternative to an emulsion, we tested a simple lipid-based aqueous formulation containing a synthetic TLR4 ligand (GLA-AF) for its ability to enhance protection against H5N1 infection. GLA-AF was very effective in adjuvanting recombinant H5 hemagglutinin antigen (rH5) in mice and was as potent as the stable emulsion, SE. Both adjuvants induced similar antibody titers using a sub-microgram dose of rH5, and both conferred complete protection against a highly pathogenic H5N1 challenge. However, GLA-AF was the superior adjuvant in ferrets. GLA-AF stimulated a broader antibody response than SE after both the prime and boost immunization with rH5, and ferrets were better protected against homologous and heterologous strains of H5N1 virus. Thus, GLA-AF is a potent emulsion-free adjuvant that warrants consideration for pandemic influenza vaccine development.

Metastatic Spinal Cord Compression from Non-Small-Cell Lung Cancer Treated with Surgery and Adjuvant Therapies: A Retrospective Analysis of Outcomes and Prognostic Factors in 116 Patients.

PubMed

Tang, Yu; Qu, Jintao; Wu, Juan; Li, Song; Zhou, Yue; Xiao, Jianru

2015-09-02

Metastatic spinal cord compression is a disastrous consequence of non-small-cell lung cancer (NSCLC). There have been few studies of the outcomes or prognostic factors in patients with metastatic spinal cord compression from NSCLC treated with surgery and adjuvant therapies. From 2002 to 2013, 116 patients with metastatic spinal cord compression from NSCLC treated with surgery and adjuvant therapies were enrolled in this retrospective analysis. Kaplan-Meier methods and Cox regression analysis were used to estimate overall survival and identify prognostic factors for survival. Multivariate analysis suggested that the Eastern Cooperative Oncology Group performance status (ECOG-PS), preoperative and postoperative Frankel scores, postoperative adjuvant radiation therapy, and target therapy were independent prognostic factors. Ninety patients died at a median of twelve months (range, three to forty-seven months) postoperatively, and twenty-six patients were still alive at the time of final follow-up (at a median of fifteen months [range, five to fifty-four months]). The complete disappearance of deficits in spinal cord function after surgery was the most robust predictor of survival. Adjuvant radiation therapy and target therapy were also associated with a better prognosis. Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence. Copyright © 2015 by The Journal of Bone and Joint Surgery, Incorporated.

Adjuvant therapy in renal cell carcinoma: does higher risk for recurrence improve the chance for success?

PubMed

Figlin, R A; Leibovich, B C; Stewart, G D; Negrier, S

2018-02-01

The success of targeted therapies, including inhibitors of the vascular endothelial growth factor pathway or the mammalian target of rapamycin, in the treatment of metastatic renal cell carcinoma led to interest in testing their efficacy in the adjuvant setting. Results from the first trials are now available, with other studies due to report imminently. This review provides an overview of adjuvant targeted therapy in renal cell carcinoma, including interpretation of currently available conflicting data and future direction of research. We discuss the key differences between the completed targeted therapy adjuvant trials, and highlight the importance of accurately identifying patients who are likely to benefit from adjuvant treatment. We also consider reasons why blinded independent radiology review and treatment dose may prove critical for adjuvant treatment success. The implications of using disease-free survival as a surrogate end point for overall survival from the patient perspective and measurement of health benefit have recently been brought into focus and are discussed. Finally, we discuss how the ongoing adjuvant trials with targeted therapies and checkpoint inhibitors may improve our understanding and ability to prevent tumor recurrence after nephrectomy in the future.

41 CFR 101-26.501-4 - Submission of orders.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Interdepartmental Purchase Request (MIPR), to the General Services Administration, Automotive Commodity Center (FCA... deviations from such standards are required, unless already waived by the Director, Automotive Commodity...

Histopathological lesions and DNA adducts in the liver of European flounder (Platichthys flesus) collected in the Seine estuary versus two reference estuarine systems on the French Atlantic coast.

PubMed

Cachot, Jérôme; Cherel, Yan; Larcher, Thibaut; Pfohl-Leszkowicz, Annie; Laroche, Jean; Quiniou, Louis; Morin, Jocelyne; Schmitz, Julien; Burgeot, Thierry; Pottier, Didier

2013-02-01

An epidemiological survey was conducted in the Seine estuary and in two smaller and relatively preserved estuaries on the French Atlantic coast in order to estimate the occurrence of liver lesions in European flounder, Platichthys flesus, and also to seek putative risk factors for the recorded pathologies. Four hundred and seventy-eight fish of both sexes and of different size ranges were sampled in the three studied areas, 338 of which in the Seine estuary. All fish were examined for histopathological liver lesions, while DNA adducts and otoliths were analyzed on a subsample. Five categories of hepatic lesions were recorded with the following prevalence for the Seine estuary: 36.7 % inflammations, 8 % parasites (mainly encysted nematodes), 6.5 % foci of cellular alteration (FCA), 5.3 % foci of necrosis or regeneration (FNR), and 1.5 % tumors. Inflammation occurrence increased according to age, contrary to parasitic infestations and FCA which were more prevalent in young fish, notably those of <1 year old (group 0). Tumors were only observed in females of more than two winters. Females exhibited a higher prevalence of tumors (3.0 %) and FCA (6.5 %) than males (0 and 2.6 %, respectively). Parasitic and infectious lesions and FNR were equally distributed in males and females. The prevalence of FNR was also shown to vary according to sampling season, with significantly more occurrences of liver necrosis in the fish collected in summer than in spring. Spatial differences were observed with a higher occurrence of encysted parasites in flounders from the upper Seine estuary, while inflammations predominated in flounders living downstream. Temporal trends were also noted, with an increased prevalence of parasitic infestations, inflammations, and FCA in the 2002-2003 period in comparison to the 1996-1997 one. The three flounder populations from the Seine estuary (Normandy), Ster estuary (Brittany), and Bay of Veys (Normandy) showed different spectra of hepatic lesions. Flounders from the Bay of Veys had relatively few liver lesions as compared to flounders from the two other estuaries. Flounders from the Ster estuary exhibited the highest prevalence of parasites (37.2 %) and inflammations (51.1 %). Finally, FCA and liver tumors occurred at very similar levels in both flounder populations from the Seine and the Ster estuaries. Group 0 flounders inhabiting the upper Seine estuary were more prone to parasitic and pre-neoplastic hepatic lesions and had higher levels of liver DNA adducts than the older ones living downstream. It was postulated that group 0 European flounders may serve as valuable bioindicators for assessing the quality of estuarine waters and the health status of euryhaline fish populations.

COS/FUV Mapping of Stray PtNe Lamp Light Through FCA

NASA Astrophysics Data System (ADS)

Oliveira, Cristina

2010-09-01

This program determines which cross-dispersion locations lead to wavecal lamp {PtNe} light leaking through the flat-field calibration aperture {FCA}. This unexpected effect, observed initially in program 12096, led to a shut down of the COS/FUV detector due to a global count rate violation in Segment A of the G140L/1230 setting. Detector? threshold ?is ?600,000 ?FEC ?counts ?in? 10 seconds ?on each ?segment. ?If ?this ?level? is ?exceeded, ?the? detector? shuts ?down? the ?HV.In program 12096, for the G140L/1230 setting, at +6" from the nominal position in the cross-dispersion direction, 180,000 cts/sec were observed through the FCA in Segment A, and 49,000 cts/sec in Segment B {PtNe/FCA}. The corresponding wavecal count rate {PtNe/WCA} is 685 cts/sec in Segment A, implying that there is a scale factor of 263 between the FCA and WCA count rates. This scale factor could not be verified for Segment B, given that the PtNe lamp does not produce counts at the short wavelengths seen by G140L/1230/FUVB. However, this scaling factor is expected to be the same for both segments.The scaling factor derived from program 12096 is then used to predict the FCA count rates seen with all the gratings, in off-nominal positions where light might leak through the FCA in the current program.There is no light leak between the nominal position and positions up to and including +3" {at least not in Mar 2010 when program 12096 executed}, but somewhere above +3" and certainly at +6" the PtNe light starts leaking through the FCA.Light is not predicted to leak at negative POS-TARG positions from the nominal, and the purpose of this program is to verify that as well.Visits 1N to 6N take data at positions from +1.0" to +6.0", while visits 1S to 6S take data at positions from -1.0" to -6.0". Visits 10 through 13 take data at the nominal position, 0.0".At each position in the detector data is taken with the following settings:G130M/1055/1291/1327, G160M/1577/1623, and G140L/1280/1105, in this order.LAMP2 with CURRENT=LOW is used in all of these visits. In addition, at each position, one exposure with LAMP1 CURRENT=MED is also taken with the G130M/1055 setting, which leads to total counts in 10 sec more than a factor of 10 below the 600,000 limit. This exposure is used so that the ratio of LAMP1/MED to LAMP2/LOW can be calculated for the FCA at each position {in conjunction with the data obtained in visits 11, 12, and 13; see below}. In addition, the G130M/1055 exposures with LAMP1/MED and LAMP2/LOW will be used to determine if the lamp spot size is changing at each position.Depending on the total counts estimated for each setting, either a typical wave exposure is taken or special flash commands are used. Details are given in each visit.Exposures obtained with LAMP1/CURRENT=LOW are expected to have a 20% smaller count rate than exposures obtained with LAMP1/CURRENT=MED. Exposures obtained with LAMP2/CURRENT=MED are expected to have count rates similar to those obtained with LAMP1/CURRENT=MED, and exposures obtained with LAMP2/CURRENT=LOW are expected to have a count rate which is 1/7 of that obtainedwith LAMP2/CURRENT=MED.VISIT 10 OBTAINS LAMP1/CURRENT=MED+ LOW SPECTRA AT ALL THE M SETTINGS USED IN THIS PROGRAM, AT THE NOMINAL POSITION {0.0"}.VISIT 11 OBTAINS LAMP2/CURRENT=MED SPECTRA AT ALL THE M SETTINGS USED IN THIS PROGRAM, AT THE NOMINAL POSITION {0.0"}.VISIT 12 OBTAINS LAMP2/CURRENT=LOW SPECTRA AT ALL THE M SETTINGS USED IN THIS PROGRAM, AT THE NOMINAL POSITION {0.0"}.VISIT 13 OBTAINS LAMP1/CURRENT=MED, LOW AND LAMP2/CURRENT=MED, LOW SPECTRA AT ALL OF THE L SETTINGS USED IN THIS PROGRAM, AT THE NOMINAL POSITION {0.0"}.THE GOAL OF THESE VISITS IS TO DETERMINE THE RATIOS OF THE DIFFERENT LAMP SETTINGS AT DIFFERENT WAVELENGTHS, TO HELP IN ANALYZING THE DATA OBTAINED IN VISITS WHERE ONLY LAMP2/LOW IS USED.ALSO, THESE DATA WILL BE USED TO PREDICT WHAT THE COUNTS WOULD BE WITH G140L/1280/LAMP1/MED AT THE +6.0" POSITION {VIS6N, WHERE LAMP2/LOW IS USED}. THESE COUNTS WILL BE COMPARED WITH THE COUNTS OBTAINED IN PROGRAM 12096 WITH G140L/1230/LAMP1/MED, MORE THAN ONE YEAR AGO, TO LOOK FOR VARIABILITY, POSSIBLY INDICATING CHANGES TO THE LAMP SPOT SIZE.Visits 10 through 13, all executed at the nominal position, pose no safety concerns.CONSTRAINTS:- Visits 1N, 2N, 3N can be executed back to back as no light is expected to leak through the FCA. Visit 1N should execute before visit 2N, which should execute before visit 3N.- Visits 1S, 2S, and 3S can be executed back to back and do not have constraints relative to the other visits. Visit 1S should execute before visit 2S, which should execute before visit 3S- Visits 10, 11, 12, and 13 {data obtained at nominal position}, can also be executed back to back and have no constraints relative to other visits. However, these visits should be scheduled as soon as possible, because results of data anaysis will be used to inform execution of program 12678.- There should be an interval of at least two days between any of the visits mentioned above and the other visits in this program {4N, 5N, 6N, 4S, 5S, 6S} which could see light leaking through the FCA.- Visits 4S and 4N can be scheduled in the same week, but they don't need to be.- Visits 5S and 5N can be scheduled in the same week, but they don't need to be.- There should be an interval of at least 3 weeks between visit 4N and visit 5N.- Visits 6S and 6N can be scheduled in the same week, but they don't need to be.- There should be an interval of at least 3 weeks between visit 5N and visit 6N.- Visits 1S through 5S should be scheduled as soon as possible, the same is true for visits 1N to 4N.

Adjuvant Chemotherapy Improves the Probability of Freedom From Recurrence in Patients With Resected Stage IB Lung Adenocarcinoma.

PubMed

Hung, Jung-Jyh; Wu, Yu-Chung; Chou, Teh-Ying; Jeng, Wen-Juei; Yeh, Yi-Chen; Hsu, Wen-Hu

2016-04-01

The benefit of adjuvant chemotherapy remains controversial for patients with stage IB non-small-cell lung cancer (NSCLC). This study investigated the effect of adjuvant chemotherapy and the predictors of benefit from adjuvant chemotherapy in patients with stage IB lung adenocarcinoma. A total of 243 patients with completely resected pathologic stage IB lung adenocarcinoma were included in the study. Predictors of the benefits of improved overall survival (OS) or probability of freedom from recurrence (FFR) from platinum-based adjuvant chemotherapy in patients with resected stage IB lung adenocarcinoma were investigated. Among the 243 patients, 70 (28.8%) had received platinum-based doublet adjuvant chemotherapy. A micropapillary/solid-predominant pattern (versus an acinar/papillary-predominant pattern) was a significantly worse prognostic factor for probability of FFR (p = 0.033). Although adjuvant chemotherapy (versus surgical intervention alone) was not a significant prognostic factor for OS (p = 0.303), it was a significant prognostic factor for a better probability of FFR (p = 0.029) on multivariate analysis. In propensity-score-matched pairs, there was no significant difference in OS between patients who received adjuvant chemotherapy and those who did not (p = 0.386). Patients who received adjuvant chemotherapy had a significantly better probability of FFR than those who did not (p = 0.043). For patients with a predominantly micropapillary/solid pattern, adjuvant chemotherapy (p = 0.033) was a significant prognostic factor for a better probability of FFR on multivariate analysis. Adjuvant chemotherapy is a favorable prognostic factor for the probability of FFR in patients with stage IB lung adenocarcinoma, particularly in those with a micropapillary/solid-predominant pattern. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Selection of Optimal Adjuvant Chemotherapy and Targeted Therapy for Early Breast Cancer: ASCO Clinical Practice Guideline Focused Update.

PubMed

Denduluri, Neelima; Chavez-MacGregor, Mariana; Telli, Melinda L; Eisen, Andrea; Graff, Stephanie L; Hassett, Michael J; Holloway, Jamie N; Hurria, Arti; King, Tari A; Lyman, Gary H; Partridge, Ann H; Somerfield, Mark R; Trudeau, Maureen E; Wolff, Antonio C; Giordano, Sharon H

2018-05-22

Purpose To update key recommendations of the ASCO guideline adaptation of the Cancer Care Ontario guideline on the selection of optimal adjuvant chemotherapy regimens for early breast cancer and adjuvant targeted therapy for breast cancer. Methods An Expert Panel conducted targeted systematic literature reviews guided by a signals approach to identify new, potentially practice-changing data that might translate to revised practice recommendations. Results The Expert Panel reviewed phase III trials that evaluated adjuvant capecitabine after completion of standard preoperative anthracycline- and taxane-based combination chemotherapy by patients with early-stage breast cancer HER2-negative breast cancer with residual invasive disease at surgery; the addition of 1 year of adjuvant pertuzumab to combination chemotherapy and trastuzumab for patients with early-stage, HER2-positive breast cancer; and the use of neratinib as extended adjuvant therapy for patients after combination chemotherapy and trastuzumab-based adjuvant therapy with early-stage, HER2-positive breast cancer. Recommendations Patients with early-stage HER2-negative breast cancer with pathologic, invasive residual disease at surgery following standard anthracycline- and taxane-based preoperative therapy may be offered up to six to eight cycles of adjuvant capecitabine. Clinicians may add 1 year of adjuvant pertuzumab to trastuzumab-based combination chemotherapy in patients with high-risk, early-stage, HER2-positive breast cancer. Clinicians may use extended adjuvant therapy with neratinib to follow trastuzumab in patients with early-stage, HER2-positive breast cancer. Neratinib causes substantial diarrhea, and diarrhea prophylaxis must be used. Additional information can be found at www.asco.org/breast-cancer-guidelines .

CpG Oligodeoxynucleotide and Montanide ISA 51 Adjuvant Combination Enhanced the Protective Efficacy of a Subunit Malaria Vaccine

PubMed Central

Kumar, Sanjai; Jones, Trevor R.; Oakley, Miranda S.; Zheng, Hong; Kuppusamy, Shanmuga P.; Taye, Alem; Krieg, Arthur M.; Stowers, Anthony W.; Kaslow, David C.; Hoffman, Stephen L.

2004-01-01

Unmethylated CpG dinucleotide motifs present in bacterial genomes or synthetic oligodeoxynucleotides (ODNs) serve as strong immunostimulatory agents in mice, monkeys and humans. We determined the adjuvant effect of murine CpG ODN 1826 on the immunogenicity and protective efficacy of the Saccharomyces cerevisiae-expressed 19-kDa C-terminal region of merozoite surface protein 1 (yMSP119) of the murine malaria parasite Plasmodium yoelii. We found that in C57BL/6 mice, following sporozoite challenge, the degree of protective immunity against malaria induced by yMSP119 in a formulation of Montanide ISA 51 (ISA) plus CpG ODN 1826 was similar or superior to that conferred by yMSP119 emulsified in complete Freund's adjuvant (CFA/incomplete Freund's adjuvant). In total, among mice immunized with yMSP119, 22 of 32 (68.7%) with ISA plus CpG 1826, 0 of 4 (0%) with CFA/incomplete Freund’s adjuvant, 0 of 4 (0%) with CpG 1826 mixed with ISA (no yMSP119), and 0 of 11 (0%) with CpG 1826 alone were completely protected against development of erythrocytic stage infection after sporozoite challenge. The adjuvant effect of CpG ODN 1826 was manifested as both significantly improved complete protection from malaria (defined as the absence of detectable erythrocytic form parasites) (P = 0.007, chi square) and reduced parasite burden in infected mice. In vivo depletions of interleukin-12 and gamma interferon cytokines and CD4+ and CD8+ T cells in vaccinated mice had no significant effect on immunity. On the other hand, immunoglobulin G (IgG) isotype levels appeared to correlate with protection. Inclusion of CpG ODN 1826 in the yMSP119 plus ISA vaccine contributed towards the induction of higher levels of IgG2a and IgG2b (Th1 type) antibodies, suggesting that CpG ODN 1826 caused a shift towards a Th1 type of immune response that could be responsible for the higher degree of protective immunity. Our results indicate that this potent adjuvant formulation should be further evaluated for use in clinical trials of recombinant malarial vaccine candidates. PMID:14742540

Aluminium based adjuvants and their effects on mitochondria and lysosomes of phagocytosing cells.

PubMed

Ohlsson, Lars; Exley, Christopher; Darabi, Anna; Sandén, Emma; Siesjö, Peter; Eriksson, Håkan

2013-11-01

Aluminium oxyhydroxide, Al(OH)3 is one of few compounds approved as an adjuvant in human vaccines. However, the mechanism behind its immune stimulating properties is still poorly understood. In vitro co-culture of an aluminium adjuvant and the human monocytic cell line THP-1 resulted in reduced cell proliferation. Inhibition occurred at concentrations of adjuvant several times lower than would be found at the injection site using a vaccine formulation containing an aluminium adjuvant. Based on evaluation of the mitochondrial membrane potential, THP-1 cells showed no mitochondrial rupture after co-culture with the aluminium adjuvant, instead an increase in mitochondrial activity was seen. The THP-1 cells are phagocytosing cells and after co-culture with the aluminium adjuvant the phagosomal pathway was obstructed. Primary or early phagosomes mature into phagolysosomes with an internal pH of 4.5 - 5 and carry a wide variety of hydrolysing enzymes. Co-culture with the aluminium adjuvant yielded a reduced level of acidic vesicles and cathepsin L activity, a proteolytic enzyme of the phagolysosomes, was almost completely inhibited. THP-1 cells are an appropriate in vitro model in order to investigate the mechanism behind the induction of a phagocytosing antigen presenting cell into an inflammatory cell by aluminium adjuvants. Much information will be gained by investigating the phagosomal pathway and what occurs inside the phagosomes and to elucidate the ultimate fate of phagocytosed aluminium particles. © 2013.

Immunogenicity and Protective Efficacy in Mice and Hamsters of a β-Propiolactone Inactivated Whole Virus SARS-CoV Vaccine

PubMed Central

Roberts, Anjeanette; Lamirande, Elaine W.; Vogel, Leatrice; Baras, Benoît; Goossens, Geneviève; Knott, Isabelle; Chen, Jun; Ward, Jerrold M.; Vassilev, Ventzislav

2010-01-01

Abstract The immunogenicity and efficacy of β-propiolactone (BPL) inactivated whole virion SARS-CoV (WI-SARS) vaccine was evaluated in BALB/c mice and golden Syrian hamsters. The vaccine preparation was tested with or without adjuvants. Adjuvant Systems AS01B and AS03A were selected and tested for their capacity to elicit high humoral and cellular immune responses to WI-SARS vaccine. We evaluated the effect of vaccine dose and each adjuvant on immunogenicity and efficacy in mice, and the effect of vaccine dose with or without the AS01B adjuvant on the immunogenicity and efficacy in hamsters. Efficacy was evaluated by challenge with wild-type virus at early and late time points (4 and 18 wk post-vaccination). A single dose of vaccine with or without adjuvant was poorly immunogenic in mice; a second dose resulted in a significant boost in antibody levels, even in the absence of adjuvant. The use of adjuvants resulted in higher antibody titers, with the AS01B-adjuvanted vaccine being slightly more immunogenic than the AS03A-adjuvanted vaccine. Two doses of WI-SARS with and without Adjuvant Systems were highly efficacious in mice. In hamsters, two doses of WI-SARS with and without AS01B were immunogenic, and two doses of 2 μg of WI-SARS with and without the adjuvant provided complete protection from early challenge. Although antibody titers had declined in all groups of vaccinated hamsters 18 wk after the second dose, the vaccinated hamsters were still partially protected from wild-type virus challenge. Vaccine with adjuvant provided better protection than non-adjuvanted WI-SARS vaccine at this later time point. Enhanced disease was not observed in the lungs or liver of hamsters following SARS-CoV challenge, regardless of the level of serum neutralizing antibodies. PMID:20883165

Phenotypic characterization of circulating tumor cells in triple negative breast cancer patients.

PubMed

Agelaki, Sofia; Dragolia, Melina; Markonanolaki, Harris; Alkahtani, Saad; Stournaras, Christos; Georgoulias, Vassilis; Kallergi, Galatea

2017-01-17

Patients with triple negative breast cancer (TNBC), are considered as a poor prognosis group for whom no targeted therapies are currently available. The aim of the present study was to phenotypically characterize their CTCs in order to explore potential therapeutic targets. PBMC's cytospins were prepared from 45 early (before and after adjuvant chemotherapy), 10 metastatic TNBC and 21 hormone receptor (HR) -positive patients. The expression of Cytokeratins (CK), ER, PR, EGFR and HER2 on CTCs was assessed using immunofluoresence staining and ARIOL analysis. In early stage TNBC, ER, PR, HER2 and EGFR expressing-CTCs were detected in 24.4%, 24.4%, 20% and 40% of patients before the initiation of adjuvant chemotherapy, and in 17.8%, 13.3% 6.7% and 51.1% respectively after the completion of adjuvant treatment. Triple staining experiments revealed distinct subpopulations of CTC expressed HR, and ErbB family receptors. In patients with metastatic disease, the frequency of HER2+ CTCs was significantly increased compared to adjuvant setting (60% vs 20%, p=0.014). The presence of CK+PR- CTCs, before adjuvant treatment was associated with reduced OS (p=0.032) and DFI (p=0.04). Furthermore, the frequency of ER-, PR- and HER2+ CTCs was higher in HR(+) than in TNBC tumors (57.1%, p=0.006; 52.4%, p=0.021 and 52.38%, p=0.009, respectively). The CTCs in patients with early TNBC are phenotypically heterogeneous based on the expression of HR, EGFR and HER2 both before and after the completion of adjuvant chemotherapy whereas the presence of HER2+ CTCs prevails during disease evolution. These findings could be of clinical relevance in terms of CTC targeting.

Biodegradable and biocompatible poly(DL-lactide-co-glycolide) microspheres as an adjuvant for staphylococcal enterotoxin B toxoid which enhances the level of toxin-neutralizing antibodies.

PubMed Central

Eldridge, J H; Staas, J K; Meulbroek, J A; Tice, T R; Gilley, R M

1991-01-01

Microspheres composed of biocompatible, biodegradable poly(DL-lactide-co-glycolide) (DL-PLG) and staphylococcal enterotoxin B (SEB) toxoid were evaluated as a vaccine delivery system when subcutaneously injected into mice. As measured by circulating immunoglobulin G (IgG) antitoxin titers, the delivery of SEB toxoid via DL-PLG microspheres, 1 to 10 microns in diameter, induced an immune response which was approximately 500 times that seen with nonencapsulated toxoid. The kinetics, magnitude, and duration of the antitoxin response induced with microencapsulated toxoid were similar to those obtained when an equal toxoid dose was administered as an emulsion with complete Freund adjuvant. However, the microspheres did not induce the inflammation and granulomata formation seen with complete Freund adjuvant. The adjuvant activity of the microspheres was not dependent on the superantigenicity of SEB toxin and was equally effective at potentiating circulating IgG antitrinitrophenyl levels in response to microencapsulated trinitrophenyl-keyhole limpet hemocyanin. Empty DL-PLG microspheres were not mitogenic, and SEB toxoid injected as a mixture with empty DL-PLG microspheres was no more effective as an immunogen than toxoid alone. Antigen-containing microspheres 1 to 10 microns in diameter exhibited stronger adjuvant activity than those greater than 10 microns, which correlated with the delivery of the 1- to 10-microns, but not the greater than 10-microns, microspheres into the draining lymph nodes within macrophages. The antibody response induced through immunization with microencapsulated SEB toxoid was protective against the weight loss and splenic V beta 8+ T-cell expansion induced by intravenous toxin administration. These results show that DL-PLG microsphere vaccine delivery systems, which are composed of pharmaceutically acceptable components, possess a strong adjuvant activity for their encapsulated antigens. PMID:1879922

Adjuvant treatment or primary topical monotherapy for ocular surface squamous neoplasia: a systematic review.

PubMed

Viani, Gustavo Arruda; Fendi, Ligia Issa de

2017-01-01

In this systematic review, we evaluated studies involving adjuvant and primary topical treatment for ocular surface squamous neoplasia (OSSN). The findings were: (i) adjuvant 5-fluorouracil (5-FU) reduces the risk of relapse after surgical excision with mild side effects [level Ib, grade of recommendation (GR) A]. (ii) Primary topical mitomycin (MMC) produces a high rate of complete response, low recurrence rate, and mild side effects (level Ib, GR A). (iii) Primary chemotherapy versus adjuvant chemotherapy produce similar rates of recurrence, with no significant difference (level IIb, GR B). (iv) Adjuvant 5-FU versus MMC showed no significant differences, with mild side effects in both groups and a better toxicity profile for MMC (level III, GR C). (v) Primary topical 5-FU versus MMC versus interferon (IFN) showed similar rates of tumor recurrence, mild side effects for all drugs, and more severe side effects in the 5-FU arm, followed successively by MMC and IFN (level III, GR C).

Critical decision-making in radiotherapy for early stage breast cancer in a neo-adjuvant treatment era.

PubMed

De Felice, Francesca; Osti, Mattia Falchetto; De Sanctis, Vitaliana; Musio, Daniela; Tombolini, Vincenzo

2017-05-01

In breast cancer management, the role of adjuvant radiation therapy (RT) has been the subject of intense controversy over the past several years, due to the improvement in neoadjuvant chemotherapy (NACT) prescription. One of the most controversial questions regarding indication for adjuvant RT is whether or not RT is essential in patients with early stage disease at diagnosis. The value of adjuvant RT remains highly debatable in those patients with clinically negative nodes at the completion of NACT. Areas covered: This review is focused on this gray area and is intended to assist with clinical decision-making. We provide a comprehensive review using PubMed and meeting proceedings of San Antonio Breast Cancer Symposium, European Society for Radiotherapy & Oncology, European Society of Medical Oncology and American Society of Clinical Oncology. Expert commentary: The identification of potential prognostic factors may lead to novel adjuvant RT indications. Phase III clinical trials are underway and their results will help guide treatment decisions.

Melatonin and Fertoprotective Adjuvants: Prevention against Premature Ovarian Failure during Chemotherapy

PubMed Central

Jang, Hoon; Hong, Kwonho; Choi, Youngsok

2017-01-01

Premature ovarian failure is one of the side effects of chemotherapy in pre-menopausal cancer patients. Preservation of fertility has become increasingly important in improving the quality of life of completely recovered cancer patients. Among the possible strategies for preserving fertility such as ovarian tissue cryopreservation, co-treatment with a pharmacological adjuvant is highly effective and poses less of a burden on the human body. Melatonin is generally produced in various tissues and acts as a universally acting antioxidant in cells. Melatonin is now more widely used in various biological processes including treating insomnia and an adjuvant during chemotherapy. In this review, we summarize the information indicating that melatonin may be useful for reducing and preventing premature ovarian failure in chemotherapy-treated female patients. We also mention that many adjuvants other than melatonin are developed and used to inhibit chemotherapy-induced infertility. This information will give us novel insights on the clinical use of melatonin and other agents as fertoprotective adjuvants for female cancer patients. PMID:28590419

77 FR 1066 - Farm Credit Administration Board; Sunshine Act; Regular Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-09

... B. New Business System Audit Committee--Proposed Rule C. Reports Auditor's Report on FCA FY 2011...). Executive Meeting with Auditors Dated: January 5, 2012. Dale L. Aultman, Secretary, Farm Credit...

78 FR 940 - Sunshine Act Meetings; Farm Credit Administration Board

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-07

... the meeting are: Open Session Approval of Minutes December 13, 2012 Reports Auditor's Report on FCA FY...). Executive Meeting with Auditors Dated: January 2, 2013. Dale L. Aultman, Secretary, Farm Credit...

12 CFR 625.29 - Payment of award.

Code of Federal Regulations, 2010 CFR

2010-01-01

... FCA will pay the amount awarded to the applicant within 60 days of receipt of the applicant's... EXPENSES UNDER THE EQUAL ACCESS TO JUSTICE ACT Procedures for Considering Applications § 625.29 Payment of...

Environmental Enterprise Risk Management Benefits for a Government Contractor

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

Linda Guinn

An often overlooked advantage that an Environmental Enterprise Risk Management System (ERMS) has to organizations is the added protection from the Civil False Claims Act (FCA) for activities under a government contract.

12 CFR 602.16 - Combining requests.

Code of Federal Regulations, 2013 CFR

2013-01-01

....16 Combining requests. You may not avoid paying fees by filing multiple requests at the same time. When FCA reasonably believes that you, alone or with others, are breaking down a request into a series...

12 CFR 602.16 - Combining requests.

Code of Federal Regulations, 2011 CFR

2011-01-01

....16 Combining requests. You may not avoid paying fees by filing multiple requests at the same time. When FCA reasonably believes that you, alone or with others, are breaking down a request into a series...

12 CFR 602.16 - Combining requests.

Code of Federal Regulations, 2012 CFR

2012-01-01

....16 Combining requests. You may not avoid paying fees by filing multiple requests at the same time. When FCA reasonably believes that you, alone or with others, are breaking down a request into a series...

Basic research for development of the beam profile monitor based on a Faraday cup array system

NASA Astrophysics Data System (ADS)

Park, Mook-Kwang

2015-10-01

The basic design used to develop a beam profile monitor based on a Faraday cup array (FCA), which has the advantages of high robustness, reliability, and long-term stability, along with the ability to measure the ion current over a wide dynamic range, was developed. The total system is divided into three parts: i.e., a faraday cup, measuring electronics, and a display program part. The FCA was considered to consist of a collimator, suppressor, insulator frame, and 64 (8 × 8 array) tiny Faraday cups (FC). An electronic circuit using a multiplexer was applied to effectively address many signal lines and the printed circuit board (PCB) was designed to be divided into three parts, i.e., an electrode PCB (ELEC PCB), capacitance PCB (CAP PCB), and control PCB (CON PCB).

Usefulness and limitations of various guinea-pig test methods in detecting human skin sensitizers-validation of guinea-pig tests for skin hypersensitivity.

PubMed

Marzulli, F; Maguire, H C

1982-02-01

Several guinea-pig predictive test methods were evaluated by comparison of results with those obtained with human predictive tests, using ten compounds that have been used in cosmetics. The method involves the statistical analysis of the frequency with which guinea-pig tests agree with the findings of tests in humans. In addition, the frequencies of false positive and false negative predictive findings are considered and statistically analysed. The results clearly demonstrate the superiority of adjuvant tests (complete Freund's adjuvant) in determining skin sensitizers and the overall superiority of the guinea-pig maximization test in providing results similar to those obtained by human testing. A procedure is suggested for utilizing adjuvant and non-adjuvant test methods for characterizing compounds as of weak, moderate or strong sensitizing potential.

Adjuvants for Vaccines to Drugs of Abuse and Addiction

PubMed Central

Alving, Carl R.; Matyas, Gary R.; Torres, Oscar; Jalah, Rashmi; Beck, Zoltan

2015-01-01

Immunotherapeutic vaccines to drugs of abuse, including nicotine, cocaine, heroin, oxycodone, methamphetamine, and others are being developed. The theoretical basis of such vaccines is to induce antibodies that sequester the drug in the blood in the form of antibody-bound drug that cannot cross the blood brain barrier, thereby preventing psychoactive effects. Because the drugs are haptens a successful vaccine relies on development of appropriate hapten-protein carrier conjugates. However, because induction of high and prolonged levels of antibodies is required for an effective vaccine, and because injection of T-independent haptenic drugs of abuse does not induce memory recall responses, the role of adjuvants during immunization plays a critical role. As reviewed herein, preclinical studies often use strong adjuvants such as complete and incomplete Freund's adjuvant and others that cannot be, or in the case of many newer adjuvants, have never been, employed in humans. Balanced against this, the only adjuvant that has been included in candidate vaccines in human clinical trials to nicotine and cocaine has been aluminum hydroxide gel. While aluminum salts have been widely utilized worldwide in numerous licensed vaccines, the experience with human responses to aluminum salt-adjuvanted vaccines to haptenic drugs of abuse has suggested that the immune responses are too weak to allow development of a successful vaccine. What is needed is an adjuvant or combination of adjuvants that are safe, potent, widely available, easily manufactured, and cost-effective. Based on our review of the field we recommend the following adjuvant combinations either for research or for product development for human use: aluminum salt with adsorbed monophosphoryl lipid A (MPLA); liposomes containing MPLA [L(MPLA)]; L(MPLA) adsorbed to aluminum salt; oil-in-water emulsion; or oil-in-water emulsion containing MPLA. PMID:25111169

Subjective cognitive complaints one year after ceasing adjuvant endocrine treatment for early-stage breast cancer.

PubMed

Ribi, K; Aldridge, J; Phillips, K-A; Thompson, A; Harvey, V; Thürlimann, B; Cardoso, F; Pagani, O; Coates, A S; Goldhirsch, A; Price, K N; Gelber, R D; Bernhard, J

2012-05-08

In the BIG 1-98 trial objective cognitive function improved in postmenopausal women 1 year after cessation of adjuvant endocrine therapy for breast cancer. This report evaluates changes in subjective cognitive function (SCF). One hundred postmenopausal women, randomised to receive 5 years of adjuvant tamoxifen, letrozole, or a sequence of the two, completed self-reported measures on SCF, psychological distress, fatigue, and quality of life during the fifth year of trial treatment (year 5) and 1 year after treatment completion (year 6). Changes between years 5 and 6 were evaluated using the Wilcoxon signed-rank test. Subjective cognitive function and its correlates were explored. Subjective cognitive function and the other patient-reported outcomes did not change significantly after cessation of endocrine therapy with the exception of improvement for hot flushes (P=0.0005). No difference in changes was found between women taking tamoxifen or letrozole. Subjective cognitive function was the only psychosocial outcome with a substantial correlation between year 5 and 6 (Spearman's R=0.80). Correlations between SCF and the other patient-reported outcomes were generally low. Improved objective cognitive function but not SCF occur following cessation of adjuvant endocrine therapy in the BIG 1-98 trial. The substantial correlation of SCF scores over time may represent a stable attribute.

Febrile neutropaenia and chemotherapy discontinuation in women aged 70 years or older receiving adjuvant chemotherapy for early breast cancer.

PubMed

Adjogatse, D; Thanopoulou, E; Okines, A; Thillai, K; Tasker, F; Johnston, S R D; Harper-Wynne, C; Torrisi, E; Ring, A

2014-11-01

Low rates of adjuvant chemotherapy use are frequently reported in older women with early breast cancer. One of the reasons for this may be the risk of febrile neutropaenia or the perception that older patients will probably not complete the chemotherapy course prescribed. There are no data regarding these adverse outcomes in routine clinical practice. We identified 128 patients aged 70 years or over who received neoadjuvant or adjuvant chemotherapy for early breast cancer in seven UK cancer centres between 2006 and 2012. Data were collected regarding standard clinical and pathological variables and treatment toxicity and outcomes. Twenty-four patients (19%) had an episode of febrile neutropaenia. Overall, 27 patients (21%) did not complete their planned therapy. Chemotherapy discontinuation was more common in those patients with an episode of febrile neutropaenia (46% versus 16%, P = 0.004). Thirty patients (23%) were admitted with chemotherapy-related complications. There were no treatment-related deaths. The rates of febrile neutropaenia and treatment discontinuation are high in women aged 70 years or over receiving adjuvant chemotherapy for breast cancer. Close attention should be paid to the choice or regimen and the use of supportive therapies in this patient population. Copyright © 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

48 CFR 23.1005 - Contract clause.

Code of Federal Regulations, 2010 CFR

2010-10-01

... within the FCA or an environmental management system audit. ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Contract clause. 23.1005 Section 23.1005 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION SOCIOECONOMIC...

Adjuvant chemotherapy in lymph node positive bladder cancer.

PubMed

Gofrit, Ofer N; Stadler, Walter M; Zorn, Kevin C; Lin, Shang; Silvestre, Josephine; Shalhav, Arieh L; Zagaja, Gregory P; Steinberg, Gary D

2009-01-01

Lymph node-positive bladder cancer is a systemic disease in the majority of patients. Adjuvant chemotherapy given shortly after surgery, when tumor burden is low, seems reasonable, yet there is no proof that it improves survival. In this retrospective study, we compare the outcomes of patients with microscopic lymph node positive bladder cancer (pN1 or pN2) treated with radical cystectomy followed by adjuvant chemotherapy and those who declined chemotherapy. Sixty-seven patients with lymph node positive bladder cancer (26 pN1 and 41 pN2) who underwent radical cystectomy between April 1995 and April 2005 were reviewed. Combined adjuvant chemotherapy (gemcitabine and cisplatin in most patients) was given to 35 patients (52%), but declined by 32 (48%). The two groups were similar in performance status, postoperative complication rate, and N stage but deferring patients were on average 5 years older and had a more advanced T stage. Study primary endpoint was overall survival (OS). Adjuvant chemotherapy was well tolerated and 28/35 patients (80%) completed all 4 cycles. Median OS of patients given adjuvant chemotherapy was 48 months compared with 8 months for declining patients (hazard ratio 0.13, 95% CI 0.04-0.4, P < 0.0001). Multivariate age adjusted analysis showed that adjuvant chemotherapy was an independent factor affecting OS (hazard ratio 0.2, P < 0.0001). This study supports the use of adjuvant chemotherapy after radical cystectomy in patients with node positive bladder cancer. Study design and patient imbalances make it impossible to draw definitive conclusions.

Silica Nanoparticles as the Adjuvant for the Immunisation of Mice Using Hepatitis B Core Virus-Like Particles

PubMed Central

Skrastina, Dace; Petrovskis, Ivars; Lieknina, Ilva; Bogans, Janis; Renhofa, Regina; Ose, Velta; Dishlers, Andris; Dekhtyar, Yuri; Pumpens, Paul

2014-01-01

Advances in nanotechnology and nanomaterials have facilitated the development of silicon dioxide, or Silica, particles as a promising immunological adjuvant for the generation of novel prophylactic and therapeutic vaccines. In the present study, we have compared the adjuvanting potential of commercially available Silica nanoparticles (initial particles size of 10–20 nm) with that of aluminium hydroxide, or Alum, as well as that of complete and incomplete Freund's adjuvants for the immunisation of BALB/c mice with virus-like particles (VLPs) formed by recombinant full-length Hepatitis B virus core (HBc) protein. The induction of B-cell and T-cell responses was studied after immunisation. Silica nanoparticles were able to adsorb maximally 40% of the added HBc, whereas the adsorption capacity of Alum exceeded 90% at the same VLPs/adjuvant ratio. Both Silica and Alum formed large complexes with HBc VLPs that sedimented rapidly after formulation, as detected by dynamic light scattering, spectrophotometry, and electron microscopy. Both Silica and Alum augmented the humoral response against HBc VLPs to the high anti-HBc level in the case of intraperitoneal immunisation, whereas in subcutaneous immunisation, the Silica-adjuvanted anti-HBc level even exceeded the level adjuvanted by Alum. The adjuvanting of HBc VLPs by Silica resulted in the same typical IgG2a/IgG1 ratios as in the case of the adjuvanting by Alum. The combination of Silica with monophosphoryl lipid A (MPL) led to the same enhancement of the HBc-specific T-cell induction as in the case of the Alum and MPL combination. These findings demonstrate that Silica is not a weaker putative adjuvant than Alum for induction of B-cell and T-cell responses against recombinant HBc VLPs. This finding may have an essential impact on the development of the set of Silica-adjuvanted vaccines based on a long list of HBc-derived virus-like particles as the biological component. PMID:25436773

Role of radiation therapy in patients with resectable pancreatic cancer.

PubMed

Palta, Manisha; Willett, Christopher; Czito, Brian

2011-07-01

The 5-year overall survival of patients with pancreatic cancer is approximately 5%, with potentially resectable disease representing the curable minority. Although surgical resection remains the cornerstone of treatment, local and distant failure rates are high after complete resection, and debate continues as to the appropriate adjuvant therapy. Many oncologists advocate for adjuvant chemotherapy alone, given that high rates of systemic metastases are the primary cause of patient mortality. Others, however, view locoregional failure as a significant contributor to morbidity and mortality, thereby justifying the use of adjuvant chemoradiation. As in other gastrointestinal malignancies, neoadjuvant chemoradiotherapy offers potential advantages in resectable patients, and clinical investigation of this approach has shown promising results; however, phase III data are lacking. Further therapeutic advances and prospective trials are needed to better define the optimal role of adjuvant and neoadjuvant treatment in patients with resectable pancreatic cancer.

Use of adjuvants to minimize leaching of herbicides in soil

NASA Astrophysics Data System (ADS)

Alva, Ashok K.; Singh, Megh

1991-03-01

Excessive leaching of herbicides affects their efficacy against target weeds and results in contamination of groundwater. Use of adjuvants that can weakly bind herbicides and in turn release them slowly is a valuable technique to prolong the efficacy of herbicides and to minimize their leaching into groundwater. Effects of activated charcoal, three humic substances (Enersol SP 85%, Enersol 12%, and Agroliz), or a synthetic polymer (Hydrosorb) on the leaching of bromacil, dicamba, and simazine were investigated in leaching columns using a Candler fine sand (Typic Quartzipsamment). The addition of adjuvants had no harmful effects on physical properties of the soil as evident from lack of its affects on water percolation. When no adjuvants were used, 69%, 37%, and 4% of applied dicamba, bromacil, and simazine, respectively, were leached in the first pore volume of leachate (⋍3.2 cm rainfall). With five pore volumes of leachate (⋍16 cm rainfall), bromacil and dicamba were leached completely and only 80% of simazine was leached. Using Enersol 12% adjuvant resulted in a 13%-18% reduction in leaching of dicamba and bromacil in five pore volumes of leachate. The leaching of simazine was significantly decreased when any of the five adjuvants mentioned above were used. However, the decrease in leaching was significantly greater when using Enersol SP 85% or Enersol 12% (24%-28%) than when using the other adjuvants (12%-16%).

Adjuvant therapy in early-stage non-small cell lung cancer.

PubMed

Serke, Monika

2010-01-01

Evidence clearly supports adjuvant chemotherapy following resection in patients with stage II or III non-small cell lung cancer (NSCLC). Based on 3 landmark studies, adjuvant chemotherapy has become standard in completely resected NSCLC stage II and IIIA. Survival benefit from adjuvant chemotherapy is estimated to be between 3% and 15%, depending on stage. Treatment should include 4 cycles of platinum-based combination chemotherapy. There is uncertainty about chemotherapy prescription in those patients with resected stage IB NSCLC, as the risk of recurrence is lower in early NSCLC and the magnitude of benefit of adjuvant therapy is proportional to the risk of relapse according to stage. Postoperative radiotherapy (PORT) should not be used for stage I or II NSCLC, and remains controversial in resected stage IIIA (N2) disease. All positive adjuvant trials have utilized a cisplatin-based regimen, usually in combination with vinorelbine, and this should be considered the standard approach. Prognostic factors to select patients who will benefit from adjuvant therapy in general or from platinum-based chemotherapy are under discussion, but not yet established. In future we hope to optimize treatment convenience for the patients by using other combinations with the hope of better efficacy results. Work is currently under way to identify prognostic factors which in future may help to identify patients who are most likely to benefit from chemotherapy. Copyright 2010 S. Karger AG, Basel.

Gemcitabine-Based Combination Chemotherapy Followed by Radiation With Capecitabine as Adjuvant Therapy for Resected Pancreas Cancer

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

Desai, Sameer; Ben-Josef, Edgar; Griffith, Kent A.

2009-12-01

Purpose: To report outcomes for patients with resected pancreas cancer treated with an adjuvant regimen consisting of gemcitabine-based combination chemotherapy followed by capecitabine and radiation. Patients and Methods: We performed a retrospective review of a series of patients treated at a single institution with a common postoperative adjuvant program. Between January 2002 and August 2006, 43 resected pancreas cancer patients were offered treatment consisting of 4, 21-day cycles of gemcitabine 1 g/m{sup 2} intravenously over 30 min on Days 1 and 8, with either cisplatin 35 mg/m{sup 2} intravenously on Days 1 and 8 or capecitabine 1500 mg/m{sup 2} orallymore » in divided doses on Days 1-14. After completion of combination chemotherapy, patients received a course of radiotherapy (54 Gy) with concurrent capecitabine (1330 mg/m{sup 2} orally in divided doses) day 1 to treatment completion. Results: Forty-one patients were treated. Median progression-free survival for the entire group was 21.7 months (95% confidence interval 13.9-34.5 months), and median overall survival was 45.9 months. In multivariate analysis a postoperative CA 19-9 level of >=180 U/mL predicted relapse and death. Toxicity was mild, with only two hospitalizations during adjuvant therapy. Conclusions: A postoperative adjuvant program using combination chemotherapy with gemcitabine and either cisplatin or capecitabine followed by radiotherapy with capecitabine is tolerable and efficacious and should be considered for Phase III testing in this group of patients.« less

75 FR 64727 - Joint and Several Liability Reallocation Agreement

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-20

... more capital at the bank level. After giving the public notice with the opportunity to comment and... any grounds or basis for challenging the FCA's or the FCSIC's actions with respect to the creation or...

The effect of the size of the system, aspect ratio and impurities concentration on the dynamic of emergent magnetic monopoles in artificial spin ice systems

NASA Astrophysics Data System (ADS)

León, Alejandro

2013-08-01

In this work we study the dynamical properties of a finite array of nanomagnets in artificial kagome spin ice at room temperature. The dynamic response of the array of nanomagnets is studied by implementing a "frustrated celular autómata" (FCA), based in the charge model and dipolar model. The FCA simulations allow us to study in real-time and deterministic way, the dynamic of the system, with minimal computational resource. The update function is defined according to the coordination number of vertices in the system. Our results show that for a set geometric parameters of the array of nanomagnets, the system exhibits high density of Dirac strings and high density emergent magnetic monopoles. A study of the effect of disorder in the arrangement of nanomagnets is incorporated in this work.

Psychosocial and Physical Effects of Adjuvant Chemotherapy

PubMed Central

Hislop, Thomas Gregory; Elwood, J. Mark; Waxler-Morrison, Nancy; Ragaz, Joseph; Skippen, Diane Hazel; Turner, I.D.

1991-01-01

Breast cancer patients younger than 55 completed a questionnaire on psychosocial factors and physical side effects shortly after diagnosis and 9 to 15 months after diagnosis. Those who had used adjuvant chemotherapy were more likely than those who had not to report physical side effects; there was little difference in psychosocial factors. Recent users were more likely than ex-users to report physical side effects, difficulties with domestic chores, and improvement in psychosocial factors. PMID:21229020

Safety and efficacy of adjuvant therapy with oxaliplatin, leucovorin and 5-fluorouracil after mesorectal excision with lateral pelvic lymph node dissection for stage iii lower rectal cancer.

PubMed

Iwasa, Satoru; Souda, Hiroaki; Yamazaki, Kentaro; Takahari, Daisuke; Miyamoto, Yuji; Takii, Yasumasa; Ikeda, Satoshi; Hamaguchi, Tetsuya; Kanemitsu, Yukihide; Shimada, Yasuhiro

2015-03-01

Preoperative chemoradiotherapy followed by total mesorectal excision (TME) is the standard treatment for stage III lower rectal cancer worldwide. However, in Japan, the standard treatment is TME with lateral pelvic lymph node dissection (LPLD) followed by adjuvant chemotherapy. We examined the safety and efficacy of adjuvant therapy with oxaliplatin, leucovorin, and 5-fluorouracil (modified FOLFOX6) after TME with LPLD. This retrospective study included 33 patients who received modified FOLFOX6 after TME with LPLD for stage III lower rectal cancer. The overall completion rate of 12 cycles of adjuvant modified FOLFOX6 was 76%. Grade 3 or 4 neutropenia was observed in eight patients (24%). Sensory neuropathy was observed in 32 patients (97%) with 4 (12%) having a grade 3 event. The disease-free survival (DFS) rate was 45% at 3 years. Adjuvant modified FOLFOX6 was feasible in patients with stage III lower rectal cancer after TME with LPLD. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Localized malignant pleural mesothelioma: report of two cases.

PubMed

Tanzi, Silvia; Tiseo, Marcello; Internullo, Eveline; Cacciani, Giancarlo; Capra, Roberto; Carbognani, Paolo; Rusca, Michele; Rindi, Guido; Ardizzoni, Andrea

2009-08-01

Localized malignant pleural mesothelioma is very rare tumor disease. There are sporadic reports in the literature showing that this entity has a different biologic behavior compared with diffuse pleural mesothelioma. We report two cases of radically resected localized pleural malignant mesothelioma, with a previous history of asbestos exposure. Both cases showed a microscopic and immunohistochemical findings of malignant mesothelioma, biphasic and sarcomatoid lympho-histiocitoid variant type, respectively, without evidence of diffuse pleural spread. The first is very peculiar case of bilateral localized malignant pleural mesothelioma with complete response to chemotherapy and localized late recurrence, radically resected and treated with adjuvant radiotherapy. The second case revealed as a solitary localized mass, underwent a complete en bloc resection and adjuvant radiotherapy. Both cases demonstrate that the localized malignant mesothelioma should be distinguished from diffuse form and that complete resection is associated with good prognosis.

Metronomic adjuvant chemotherapy improves treatment outcome in nasopharyngeal carcinoma patients with postradiation persistently detectable plasma Epstein-Barr virus deoxyribonucleic acid.

PubMed

Twu, Chih-Wen; Wang, Wen-Yi; Chen, Chien-Chih; Liang, Kai-Li; Jiang, Rong-San; Wu, Ching-Te; Shih, Yi-Ting; Lin, Po-Ju; Liu, Yi-Chun; Lin, Jin-Ching

2014-05-01

To investigate the effects of adjuvant chemotherapy in nasopharyngeal carcinoma (NPC) patients with persistently detectable plasma Epstein-Barr virus DNA (pEBV DNA) after curative radiation therapy plus induction/concurrent chemotherapy. The study population consisted of 625 NPC patients with available pEBV DNA levels before and after treatment. Eighty-five patients with persistently detectable pEBV DNA after 1 week of completing radiation therapy were eligible for this retrospective study. Of the 85 patients, 33 were administered adjuvant chemotherapy consisting of oral tegafur-uracil (2 capsules twice daily) for 12 months with (n=4) or without (n=29) preceding intravenous chemotherapy of mitomycin-C, epirubicin, and cisplatin. The remaining 52 patients who did not receive adjuvant chemotherapy served as the control group. Baseline patient characteristics at diagnosis (age, sex, pathologic type, performance status, T classification, N classification, and overall stage), as well as previous treatment modality, were comparable in both arms. After a median follow-up of 70 months for surviving patients, 45.5% (15 of 33 patients) with adjuvant chemotherapy and 71.2% (37 of 52 patients) without adjuvant chemotherapy experienced tumor relapses (P=.0323). There were a significant reduction in distant failure (P=.0034) but not in local or regional recurrence. The 5-year overall survival rate was 71.6% for patients with adjuvant chemotherapy and 28.7% for patients without adjuvant chemotherapy (hazard ratio 0.27; 95% confidence interval 0.17-0.55; P<.0001). Our retrospective data showed that adjuvant chemotherapy can reduce distant failure and improve overall survival in NPC patients with persistently detectable pEBV DNA after curative radiation therapy plus induction/concurrent chemotherapy. Copyright © 2014 Elsevier Inc. All rights reserved.

Metronomic Adjuvant Chemotherapy Improves Treatment Outcome in Nasopharyngeal Carcinoma Patients With Postradiation Persistently Detectable Plasma Epstein-Barr Virus Deoxyribonucleic Acid

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

Twu, Chih-Wen; Department of Otorhinolaryngology, Taichung Veterans General Hospital, Taichung, Taiwan; Wang, Wen-Yi

Purpose: To investigate the effects of adjuvant chemotherapy in nasopharyngeal carcinoma (NPC) patients with persistently detectable plasma Epstein-Barr virus DNA (pEBV DNA) after curative radiation therapy plus induction/concurrent chemotherapy. Methods and Materials: The study population consisted of 625 NPC patients with available pEBV DNA levels before and after treatment. Eighty-five patients with persistently detectable pEBV DNA after 1 week of completing radiation therapy were eligible for this retrospective study. Of the 85 patients, 33 were administered adjuvant chemotherapy consisting of oral tegafur-uracil (2 capsules twice daily) for 12 months with (n=4) or without (n=29) preceding intravenous chemotherapy of mitomycin-C, epirubicin, and cisplatin.more » The remaining 52 patients who did not receive adjuvant chemotherapy served as the control group. Results: Baseline patient characteristics at diagnosis (age, sex, pathologic type, performance status, T classification, N classification, and overall stage), as well as previous treatment modality, were comparable in both arms. After a median follow-up of 70 months for surviving patients, 45.5% (15 of 33 patients) with adjuvant chemotherapy and 71.2% (37 of 52 patients) without adjuvant chemotherapy experienced tumor relapses (P=.0323). There were a significant reduction in distant failure (P=.0034) but not in local or regional recurrence. The 5-year overall survival rate was 71.6% for patients with adjuvant chemotherapy and 28.7% for patients without adjuvant chemotherapy (hazard ratio 0.27; 95% confidence interval 0.17-0.55; P<.0001). Conclusions: Our retrospective data showed that adjuvant chemotherapy can reduce distant failure and improve overall survival in NPC patients with persistently detectable pEBV DNA after curative radiation therapy plus induction/concurrent chemotherapy.« less

Hospital variation and the impact of postoperative complications on the use of perioperative chemo(radio)therapy in resectable gastric cancer. Results from the Dutch Upper GI Cancer Audit.

PubMed

Schouwenburg, M G; Busweiler, L A D; Beck, N; Henneman, D; Amodio, S; van Berge Henegouwen, M I; Cats, A; van Hillegersberg, R; van Sandick, J W; Wijnhoven, B P L; Wouters, M W J; Nieuwenhuijzen, G A P

2018-04-01

Dutch national guidelines on the diagnosis and treatment of gastric cancer recommend the use of perioperative chemotherapy in patients with resectable gastric cancer. However, adjuvant chemotherapy is often not administered. The aim of this study was to evaluate hospital variation on the probability to receive adjuvant chemotherapy and to identify associated factors with special attention to postoperative complications. All patients who received neoadjuvant chemotherapy and underwent an elective surgical resection for stage IB-IVa (M0) gastric adenocarcinoma between 2011 and 2015 were identified from a national database (Dutch Upper GI Cancer Audit). A multivariable linear mixed model was used to evaluate case-mix adjusted hospital variation and to identify factors associated with adjuvant therapy. Of all surgically treated gastric cancer patients who received neoadjuvant chemotherapy (n = 882), 68% received adjuvant chemo(radio)therapy. After adjusting for case-mix and random variation, a large hospital variation in the administration rates for adjuvant was observed (OR range 0.31-7.1). In multivariable analysis, weight loss, a poor health status and failure of neoadjuvant chemotherapy completion were strongly associated with an increased likelihood of adjuvant therapy omission. Patients with severe postoperative complications had a threefold increased likelihood of adjuvant therapy omission (OR 3.07 95% CI 2.04-4.65). Despite national guidelines, considerable hospital variation was observed in the probability of receiving adjuvant chemo(radio)therapy. Postoperative complications were strongly associated with adjuvant chemo(radio)therapy omission, underlining the need to further reduce perioperative morbidity in gastric cancer surgery. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

32 CFR 536.115 - Claims procedures for claims arising overseas under international agreements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... otherwise allowed under the FCA or MCA. For example, receiving state claims offices in Germany require that....S. involvement. If the filing period is about to expire for claims arising in Germany, have the...

32 CFR 536.115 - Claims procedures for claims arising overseas under international agreements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... otherwise allowed under the FCA or MCA. For example, receiving state claims offices in Germany require that....S. involvement. If the filing period is about to expire for claims arising in Germany, have the...

32 CFR 536.115 - Claims procedures for claims arising overseas under international agreements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... otherwise allowed under the FCA or MCA. For example, receiving state claims offices in Germany require that....S. involvement. If the filing period is about to expire for claims arising in Germany, have the...

32 CFR 536.115 - Claims procedures for claims arising overseas under international agreements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... otherwise allowed under the FCA or MCA. For example, receiving state claims offices in Germany require that....S. involvement. If the filing period is about to expire for claims arising in Germany, have the...

32 CFR 536.115 - Claims procedures for claims arising overseas under international agreements.

Code of Federal Regulations, 2014 CFR

2014-07-01

... otherwise allowed under the FCA or MCA. For example, receiving state claims offices in Germany require that....S. involvement. If the filing period is about to expire for claims arising in Germany, have the...

12 CFR 652.30 - Temporary regulatory waivers or modifications for extraordinary situations.

Code of Federal Regulations, 2010 CFR

2010-01-01

... modification, the FCA may, in its sole discretion: (a) Modify or waive the minimum liquidity reserve requirement in § 652.20 of this subpart; and/or (b) Modify the amount, qualities, and types of eligible...

A clinically applicable adjuvant for an atherosclerosis vaccine in mice.

PubMed

Kobiyama, Kouji; Vassallo, Melanie; Mitzi, Jessica; Winkels, Holger; Pei, Hong; Kimura, Takayuki; Miller, Jacqueline; Wolf, Dennis; Ley, Klaus

2018-06-22

Vaccination with MHC-II-restricted peptides from Apolipoprotein B (ApoB) with complete and incomplete Freund's adjuvant (CFA/IFA) is known to protect mice from atherosclerosis. This vaccination induces antigen-specific IgG1 and IgG2c antibody responses and a robust CD4 T cell response in lymph nodes. However, CFA/IFA cannot be used in humans. To find a clinically applicable adjuvant, we tested the effect of vaccinating Apoe-deficient mice with ApoB peptide P6 (TGAYSNASSTESASY). In a broad screening experiment, Addavax, a squalene oil similar to MF59, was the only adjuvant that showed similar efficacy as CFA/IFA. This was confirmed in a confirmation experiment for both the aortic arch and whole aorta analyzed by en face analysis after atherosclerotic lesion staining. Mechanistically, restimulated peritoneal cells from mice immunized with P6 in Addavax released significant amounts of IL-10. Unlike P6 in CFA/IFA, vaccination with P6 in Addavax did not induce any detectable IgG1 or IgG2c antibodies to P6. These data suggest that squalene-based adjuvants such as MF59 are good candidate adjuvants for developing a clinically effective atherosclerosis vaccine. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

A Case of Therapy-Related Acute Myeloid Leukemia Associated with Adjuvant Temozolomide Chemotherapy for Anaplastic Astrocytoma.

PubMed

Kosugi, Kenzo; Saito, Katsuya; Takahashi, Wataru; Tokuda, Yukina; Tomita, Hideyuki

2017-05-01

Temozolomide (TMZ) is now standard adjuvant therapy in combination with radiotherapy for patients with newly diagnosed malignant glioma. Treatment-related myelodysplastic syndrome and acute treatment-related leukemia (t-AML) associated with TMZ chemotherapy for patients with glioma is quite a rare complication. A 43-year-old man with an anaplastic astrocytoma received radiation therapy synchronized with ranimustine and adjuvant TMZ chemotherapy for 15 cycles. Close follow-up magnetic resonance imaging of the head during TMZ chemotherapy showed no evidence of tumor progression. One year after the completion of TMZ chemotherapy, a bone-marrow aspiration was performed because the patient's white blood cell count decreased. He was diagnosed with t-AML based on the bone marrow examination, and then he was referred to the cancer center for the treatment of t-AML. In this case study, we continued adjuvant TMZ therapy beyond the recommended 6 cycles. Currently, there is no consensus as to how long the adjuvant TMZ therapy should be continued for the treatment of residual tumor showing no apparent interval change. A new decision-making tool to assess the clinical benefits against the side effects for long-term adjuvant TMZ therapy is needed. Copyright © 2017 Elsevier Inc. All rights reserved.

Adjuvant chemotherapy for gastric cancer: Current evidence and future challenges

PubMed Central

Miceli, Rosalba; Tomasello, Gianluca; Bregni, Giacomo; Di Bartolomeo, Maria; Pietrantonio, Filippo

2014-01-01

Gastric cancer still represents one of the major causes of cancer mortality worldwide. Patients survival is mainly related to stage, with a high proportion of patients with metastatic disease at presentation. Thus, the cure rate largely depend upon surgical resection. Despite the additional, albeit small, benefit of adjuvant chemotherapy has been clearly demonstrated, no general consensus has been reached on the best treatment option. Moreover, the narrow therapeutic index of adjuvant chemotherapy (i.e., limited survival benefit with considerable toxicity) requires a careful assessment of expected risks and benefits for individual patients. Treatment choices vary widely based on the different geographic areas, with chemotherapy alone more often preferred in Europe or Asia and chemoradiotherapy in the United States. In the present review we discuss the current evidence and future challenges regarding adjuvant chemotherapy in curatively resected gastric cancer with particular emphasis on the recently completed landmark studies and meta-analyses. The most recent patient-level meta-analysis demonstrated the benefit of adjuvant chemotherapy over curative surgery; the same Authors also showed that disease-free survival may be used as a surrogate end-point for overall survival. We finally discuss future research issues such as the need of economic evaluations, development of prognostic or predictive biomarkers, and the unmet clinical need of trials comparing perioperative chemotherapy with adjuvant treatment. PMID:24782604

Prognosis after surgical treatment for pancreatic cancer in patients aged 80 years or older: a multicenter study.

PubMed

Sho, Masayuki; Murakami, Yoshiaki; Kawai, Manabu; Motoi, Fuyuhiko; Satoi, Sohei; Matsumoto, Ippei; Honda, Goro; Uemura, Kenichiro; Yanagimoto, Hiroaki; Kurata, Masanao; Akahori, Takahiro; Kinoshita, Shoichi; Nagai, Minako; Nishiwada, Satoshi; Fukumoto, Takumi; Unno, Michiaki; Yamaue, Hiroki; Nakajima, Yoshiyuki

2016-03-01

The optimal therapeutic strategy for very elderly pancreatic cancer patients remains to be determined. The aim of this study was to clarify the role of pancreatic resection in patients 80 years of age or older. A retrospective multicenter analysis of 1401 patients who had undergone pancreatic resection for pancreatic cancer was performed. The patients aged ≥ 80 years (n = 99) were compared with a control group <80 years of age (n = 1302). There were no significant differences in the postoperative complications and mortality between the two groups. However, the prognosis of octogenarians was poorer than that of younger patients for both resectable and borderline resectable tumors. Importantly, there were few long-term survivors in the elderly group, especially among those with borderline resectable pancreatic cancer. A multivariate analysis of the prognostic factors in the very elderly patients indicated that the completion of adjuvant chemotherapy was the only significant factor. In addition, preoperative albumin level was the only independent risk factor for a failure to complete adjuvant chemotherapy. This study demonstrates that the postoperative prognosis in octogenarian patients was not good as that in younger patients possibly due to less frequent completion of adjuvant chemotherapy. © 2016 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Early Migration Predicts Aseptic Loosening of Cementless Femoral Stems: A Long-term Study.

PubMed

Streit, Marcus R; Haeussler, Daniel; Bruckner, Thomas; Proctor, Tanja; Innmann, Moritz M; Merle, Christian; Gotterbarm, Tobias; Weiss, Stefan

2016-07-01

Excessive early migration of cemented stems and cups after THA has been associated with poor long-term survival and allows predictable evaluation of implant performance. However, there are few data regarding the relationship between early migration and aseptic loosening of cementless femoral components, and whether early migration might predict late failure has not been evaluated, to our knowledge. Einzel-Bild-Röntgen-Analyse-femoral component analysis (EBRA-FCA) is a validated technique to accurately measure axial femoral stem migration without the need for tantalum markers, can be performed retrospectively, and may be a suitable tool to identify poor performing implants before their widespread use. We asked: (1) Is axial migration within the first 24 months as assessed by EBRA-FCA greater among cementless stems that develop aseptic loosening than those that remain well fixed through the second decade; (2) what is the diagnostic performance of implant migration at 24 months postoperatively to predict later aseptic loosening of these components; and (3) how does long-term stem survivorship compare between groups with high and low early migration? We evaluated early axial stem migration in 158 cementless THAs using EBRA-FCA. The EBRA-FCA measurements were performed during the first week postoperatively (baseline measurement) and at regular followups of 3, 6, and 12 months postoperatively and annually thereafter. The mean duration of followup was 21 years (range, 18-24 years). The stems studied represented 45% (158 of 354) of the cementless THAs performed during that time, and cementless THAs represented 34% (354 of 1038) of the THA practice during that period. No patient enrolled in this study was lost to followup. Multivariate survivorship analysis using Cox's regression model was performed with an endpoint of aseptic loosening of the femoral component. Loosening was defined according to the criteria described by Engh et al. and assessed by two independent observers. Patients with a diagnosis of prosthetic joint infection were excluded. Receiver operating characteristic (ROC) curve analysis was used to evaluate diagnostic performance of axial stem migration 1, 2, 3, and 4 years postoperatively as a predictor of aseptic loosening. Survivorship of hips with high (≥ 2.7 mm) and low (< 2.7 mm) migration was compared using a competing-events analysis. Femoral components that had aseptic loosening develop showed greater mean distal migration at 24 months postoperatively than did components that remained well fixed throughout the surveillance period (4.2 mm ± 3.1 mm vs 0.8 mm ± 0.9 mm; mean difference, 3.4 mm, 95% CI, 2.5-4.4; p ≤ 0.001). Distal migration at 24 months postoperatively was a strong risk factor for aseptic loosening (hazard ratio, 1.98; 95% CI, 1.51-2.57; p < 0.001). The associated overall diagnostic performance of 2-year distal migration for predicting aseptic loosening was good (area under the ROC curve, 0.86; 95% CI, 0.72-1.00; p < 0.001). Sensitivity of early migration measurement was high for the prediction of aseptic loosening during the first decade after surgery but decreased markedly thereafter. Stems with large amounts of early migration (≥ 2.7 mm) had lower 18-year survivorship than did stems with little early migration (29% [95% CI, 0%-62%] versus 95% [95% CI, 90%-100%] p < 0.001). Early migration, as measured by EBRA-FCA at 2 years postoperatively, has good diagnostic capabilities for detection of uncemented femoral components at risk for aseptic loosening during the first and early second decades after surgery. However, there was no relationship between early migration patterns and aseptic loosening during the late second and third decades. EBRA-FCA can be used as a research tool to evaluate new cementless stems or in clinical practice to evaluate migration patterns in patients with painful femoral components. Level III, diagnostic study.

Evaluation of health status of horses immunized with snake venom and montanide adjuvants, IMS 3012 (nanoparticle), ISA 206 and ISA 35 (emulsion based) during polyvalent snake antivenom production: hematological and biochemical assessment.

PubMed

Waghmare, A B; Salvi, N C; Deopurkar, R L; Shenoy, P A; Sonpetkar, J M

2014-05-01

Several biochemical and hematological changes in horses are observed during production of snake antivenom. Although conventional adjuvants like Freund's (Complete and Incomplete) are good immunopotentiators, they produce considerable local reactions in animals. Variety of commercial adjuvants, like montanide adjuvants, having high immunopotentiation and showing lesser side effects are available. The prime objective during antivenom production is to strike a balance between safety of immunized horses and efficacy of the product. In our earlier work, efficacy of montanide group of adjuvants in antivenom production has already been established. The aim of the present work was to assess the safety parameters in horses, viz.: biochemical and hematological, during production of snake antivenom. In the present study, 33 new horses were randomly divided into four groups and hyperimmunized using mixture of snake venoms, viz.: Cobra venom, Russell's viper venom, Krait venom and Echis venom along with montanide adjuvants, IMS 3012, ISA 206, ISA 35 and Incomplete Freund's adjuvant as a control adjuvant; through subcutaneous route at intervals of two weeks. During the immunization period, biochemical and hematological parameters were monitored at 0th, 14th, 21st, 30th and 42nd weeks. The mean hemoglobin values dropped slightly during initial immunization but subsequently regained to normal levels. The mean serum total protein values and globulin levels showed an increment in all the four groups, compared to day zero, vice-versa a slight drop was observed in albumin levels. No significant changes were observed in serum creatinine, bilirubin, alkaline phosphatase and blood urea nitrogen values. Finally, we conclude that montanide adjuvants could be a safer alternative to the conventional adjuvants for primary phase of immunization in antivenom production. Copyright © 2014 Elsevier Ltd. All rights reserved.

Letrozole in the extended adjuvant setting: MA.17

PubMed Central

2007-01-01

Relapse after completing adjuvant tamoxifen therapy is a persistent threat for women with hormone-responsive breast cancer. Third-generation aromatase inhibitors, such as letrozole, provide a new option for extended adjuvant hormonal therapy after 5 years of tamoxifen. MA.17 was conducted to determine whether letrozole improves outcome after discontinuation of tamoxifen. Postmenopausal women with hormone receptor-positive breast cancer (N = 5,187) were randomized to letrozole 2.5 mg or placebo once daily for 5 years. At a median follow-up of 30 months, letrozole significantly improved disease-free survival (DFS; P < 0.001), the primary end point, compared with placebo (hazard ratio [HR] for recurrence or contralateral breast cancer 0.58; 95% confidence interval [CI] 0.45, 0.76] P < 0.001). Furthermore, letrozole significantly improved distant DFS (HR = 0.60; 95% CI 0.43, 0.84; P = 0.002) and, in women with node-positive tumors, overall survival (HR = 0.61; 95% CI 0.38, 0.98; P = 0.04). Clinical benefits, including an overall survival advantage, were also seen in women who crossed over from placebo to letrozole after unblinding, indicating that tumors remain sensitive to hormone therapy despite a prolonged period since discontinuation of tamoxifen. The efficacy and safety of letrozole therapy beyond 5 years is being assessed in a re-randomization study, following the emergence of new data suggesting that clinical benefit correlates with the duration of letrozole. MA.17 showed that letrozole is extremely well-tolerated relative to placebo. Letrozole should be considered for all women completing tamoxifen; new results from the post-unblinding analysis suggest that letrozole treatment should also be considered for all disease-free women for periods up to 5 years following completion of adjuvant tamoxifen. PMID:17912635

Gait Analysis in Rats with Single Joint Inflammation: Influence of Experimental Factors

PubMed Central

Ängeby Möller, Kristina; Kinert, Susanne; Størkson, Rolf; Berge, Odd-Geir

2012-01-01

Disability and movement-related pain are major symptoms of joint disease, motivating the development of methods to quantify motor behaviour in rodent joint pain models. We used observational scoring and automated methods to compare weight bearing during locomotion and during standing after single joint inflammation induced by Freund's complete adjuvant (0.12–8.0 mg/mL) or carrageenan (0.47–30 mg/mL). Automated gait analysis was based on video capture of prints generated by light projected into the long edge of the floor of a walkway, producing an illuminated image of the contact area of each paw with light intensity reflecting the contact pressure. Weight bearing was calculated as an area-integrated paw pressure, that is, the light intensity of all pixels activated during the contact phase of a paw placement. Automated static weight bearing was measured with the Incapacitance tester. Pharmacological sensitivity of weight-bearing during locomotion was tested in carrageenan-induced monoarthritis by administration of the commonly used analgesics diclofenac, ibuprofen, and naproxen, as well as oxycodone and paracetamol. Observational scoring and automated quantification yielded similar results. We found that the window between control rats and monoarthritic rats was greater during locomotion. The response was more pronounced for inflammation in the ankle as compared to the knee, suggesting a methodological advantage of using this injection site. The effects of both Freund's complete adjuvant and carrageenan were concentration related, but Freund's incomplete adjuvant was found to be as effective as lower, commonly used concentrations of the complete adjuvant. The results show that gait analysis can be an effective method to quantify behavioural effects of single joint inflammation in the rat, sensitive to analgesic treatment. PMID:23071540

Phase 2 trial of neoadjuvant chemotherapy and transoral endoscopic surgery with risk-adapted adjuvant therapy for squamous cell carcinoma of the head and neck.

PubMed

Weiss, Jared M; Grilley-Olson, Juneko E; Deal, Allison Mary; Zevallos, Jose P; Chera, Bhishamjit S; Paul, Jennifer; Knowles, Mary Fleming; Usenko, Dmitriy; Weissler, Mark C; Patel, Samip; Hayes, David N; Hackman, Trevor

2018-05-09

The objective of this study was to demonstrate the feasibility and efficacy of induction chemotherapy, surgery, and pathology-guided adjuvant therapy to treat transorally resectable squamous head and neck cancer. Patients had squamous head and neck cancer that was resectable by the transoral route and advanced-stage disease (American Joint Committee on Cancer stage III-IV, T3-T4 tumors, and/or positive lymph nodes). They received treatment with weekly carboplatin at an area under the curve of 2, plus paclitaxel 135 mg/m 2 , and daily lapatinib 1000mg for 6 weeks followed by surgical resection. Pathology that revealed margins <5 mm, extracapsular extension, N2a of N2b lymph node status, perineural invasion, or lymphovascular space invasion resulted in adjuvant radiotherapy concurrent with weekly cisplatin. Pathology with N2c/N3 lymph node status or positive margins resulted in radiation with bolus cisplatin. The primary endpoint was the clinical response rate to induction chemotherapy, and a key secondary endpoint was feasibility. Toxicity was modest, and 37 of 40 patients completed study procedures as planned. The clinical response rate was 93%, the pathologic complete response rate was 36%, and the clinical response did not predict for a pathologic complete response. No patient on study follow-up has recurred or died. Twenty-nine of 39 patients who underwent surgery avoided radiation. Speech and swallowing function were well preserved. The study met both its primary efficacy endpoint and the secondary feasibility endpoint. Neoadjuvant, systemic therapy and surgical resection followed by risk-adapted adjuvant therapy resulted in high response rates and excellent long-term outcomes and should be further studied. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

Adjuvant chemotherapy and whole abdominal irradiation for gastric carcinoma.

PubMed

Kundel, Yulia; Levitt, Mark L; Oberman, Bernice; Sadezki, Siegal; Tichler, Thomas; Symon, Zvi; Catane, Raphael; Pfeffer, Raphael; Brenner, Baruch

2008-01-01

To analyze the efficacy and toxicity of adjuvant chemotherapy followed by whole abdominal irradiation in the treatment of resectable gastric cancer with positive lymph nodes. Between 1996 and 1999, 10 patients with node-positive gastric cancer underwent complete gross resection and were treated by postoperative chemoradiotherapy. The chemotherapy regimen consisted of 5-fluorouracil, 1000 mg/m2/day as a 96-hr continuous infusion on day 1, and cisplatin, 100 mg/m2 on day 2, every 21 days. Six courses were planned. Radiotherapy was administered 3 weeks after completion of the chemotherapy protocol as a single-fraction dose of 600 cGy in a two-field (anterior and posterior) configuration. Treatment was generally well tolerated, with no treatment-related deaths. However, 9 of the 10 patients died of recurrent disease, with a median survival of 20 months (range, 7-84). Adjuvant chemotherapy with whole abdominal irradiation for gastric cancer is safe and tolerable but has no apparent effect on patient outcome. Studies in larger series are needed to evaluate the role of the approach in this disease.

Improved immunogenicity of tetanus toxoid by Brucella abortus S19 LPS adjuvant.

PubMed

Mohammadi, Mohsen; Kianmehr, Zahra; Kaboudanian Ardestani, Sussan; Gharegozlou, Behnaz

2014-09-01

Adjuvants are used to increase the immunogenicity of new generation vaccines, especially those based on recombinant proteins. Despite immunostimulatory properties, the use of bacterial lipopolysaccharide (LPS) as an adjuvant has been hampered due to its toxicity and pyrogenicity. Brucella abortus LPS is less toxic and has no pyrogenic properties compared to LPS from other gram negative bacteria. To evaluate the adjuvant effect of B. abortus (vaccine strain, S19) LPS for tetanus toxoid antigen (TT) and to investigate the protective effect of different tetanus vaccine preparations. LPS was extracted and purified from B. abortus S19 and KDO, glycan, phosphate content, and protein contamination were measured. Adipic acid dihydrazide (ADH) was used as a linker for conjugation of TT to LPS. Different amounts of B. abortus LPS, TT, TT conjugated with LPS, and TT mixed with LPS or complete Freund's adjuvant (CFA) were injected into mice and antibody production against TT was measured. The protective effect of induced antibodies was determined by LD50. Immunization of mice with TT+LPS produced the highest anti-TT antibody titer in comparison to the group immunized with TT without any adjuvant or the groups immunized with TT-LPS or TT+CFA. Tetanus toxid-S19 LPS also produced a 100% protective effect against TT in immunized mice. These data indicate that B. abortus LPS enhances the immune responses to TT and suggest the possible use of B. abortus LPS as an adjuvant in vaccine preparations.

78 FR 42457 - Hazardous Materials: Revision to Fireworks Regulations (RRR)

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-16

... the current level of transportation safety of Division 1.4G consumer fireworks. A. Notice of Proposed... and whether the FCA certification process provides an equivalent level of oversight as the current... level of safety while allowing [[Page 42459

12 CFR 652.1 - Purpose.

Code of Federal Regulations, 2010 CFR

2010-01-01

... FISCAL AFFAIRS Investment Management § 652.1 Purpose. This subpart contains the Farm Credit Administration's (FCA) rules for governing liquidity and non-program investments held by the Federal Agricultural... of directors to adopt policies covering such areas as investment management, interest rate risk, and...

77 FR 65098 - Board Policy Statements

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-25

... Disability in Agency Programs and Activities FCA-PS-68 FCS Building Association Management Operations... staff for deciding and taking action in these critical areas. Importance Unquestionably, the employees... programs, activities, and services will be treated fairly. The Chairman and Chief Executive Officer (CEO...

Evaluation of the concomitant use of methotrexate and curcumin on Freund's complete adjuvant-induced arthritis and hematological indices in rats.

PubMed

Banji, David; Pinnapureddy, Jyothi; Banji, Otilia J F; Kumar, A Ranjith; Reddy, K Narsi

2011-09-01

To evaluate the concomitant administration of methotrexate and curcumin for antiarthiritic activity in rats. Arthritis was induced in rats following a single subplantar injection of Freund's complete adjuvant (0.1 ml). Rats were divided into six groups of six animals each. Group I and II were control injected with saline and Freund's complete adjuvant (0.1 ml), respectively. Group III arthritic rats were treated with curcumin (100 mg/kg, i.p.) on alternate days. Group IV received methotrexate (MTX) (2 mg/kg, i.p.) once in a week. Group-V and VI were treated with MTX (1 mg/kg, i.p.) once in a week and after 30 min received curcumin (30 mg/kg and 100 mg/kg, thrice a week, i.p.) from 10(th) to 45(th) days, respectively. Body weight and the paw volume was measured on 9(th), 16(th), 23(rd), 30(th), 37(th), and 45(th) days. Determination of complete blood cell counts, hemoglobin concentration, hematocrit, mean corpuscular volume, and mean corpuscular hemoglobin concentration was determined on the 46(th) day. An improvement in body weight and a significant (P < 0.05) reduction in arthritis was observed with the combination treatment as compared to the positive control. A significant improvement in the hematological profile was also observed in rats treated with curcumin and methotrexate. The study showed a significant anti-arthritic action and protection from hematological toxicity with the combination treatment of methotrexate and curcumin.

Phase II, randomized study of concomitant chemoradiotherapy followed by surgery and adjuvant capecitabine plus oxaliplatin (CAPOX) compared with induction CAPOX followed by concomitant chemoradiotherapy and surgery in magnetic resonance imaging-defined, locally advanced rectal cancer: Grupo cancer de recto 3 study.

PubMed

Fernández-Martos, Carlos; Pericay, Carles; Aparicio, Jorge; Salud, Antonieta; Safont, Mariajose; Massuti, Bertomeu; Vera, Ruth; Escudero, Pilar; Maurel, Joan; Marcuello, Eugenio; Mengual, Jose Luis; Saigi, Eugenio; Estevan, Rafael; Mira, Moises; Polo, Sonia; Hernandez, Ana; Gallen, Manuel; Arias, Fernando; Serra, Javier; Alonso, Vicente

2010-02-10

PURPOSE The optimal therapeutic sequence of the adjuvant chemotherapy component of preoperative chemoradiotherapy (CRT) for patients with locally advanced rectal cancer is controversial. Induction chemotherapy before preoperative CRT may be associated with better efficacy and compliance. PATIENTS AND METHODS A total of 108 patients with locally advanced rectal cancer were randomly assigned to arm A-preoperative CRT with capecitabine, oxaliplatin, and concurrent radiation followed by surgery and four cycles of postoperative adjuvant capecitabine and oxaliplatin (CAPOX)-or arm B-induction CAPOX followed by CRT and surgery. The primary end point was pathologic complete response rate (pCR). Results On an intention-to-treat basis, the pCR for arms A and B were 13.5% (95% CI, 5.6% to 25.8%) and 14.3% (95% CI, 6.4% to 26.2%), respectively. There were no statistically significant differences in other end points, including downstaging, tumor regression, and R0 resection. Overall, chemotherapy treatment exposure was higher in arm B than in arm A for both oxaliplatin (P < .0001) and capecitabine (P < .0001). During CRT, grades 3 to 4 adverse events were similar in both arms but were significantly higher in arm A during postoperative adjuvant CT than with induction CT in arm B. There were three deaths in each arm during the treatment period. CONCLUSION Compared with postoperative adjuvant CAPOX, induction CAPOX before CRT had similar pCR and complete resection rates. It did achieve more favorable compliance and toxicity profiles. On the basis of these findings, a phase III study to definitively test the induction strategy is warranted.

Prospective study of the impact of the Prosigna assay on adjuvant clinical decision-making in unselected patients with estrogen receptor positive, human epidermal growth factor receptor negative, node negative early-stage breast cancer.

PubMed

Martín, Miguel; González-Rivera, Milagros; Morales, Serafín; de la Haba-Rodriguez, Juan; González-Cortijo, Lucía; Manso, Luis; Albanell, Joan; González-Martín, Antonio; González, Sónia; Arcusa, Angels; de la Cruz-Merino, Luis; Rojo, Federico; Vidal, María; Galván, Patricia; Aguirre, Elena; Morales, Cristina; Ferree, Sean; Pompilio, Kristen; Casas, Maribel; Caballero, Rosalía; Goicoechea, Uxue; Carrasco, Eva; Michalopoulos, Steven; Hornberger, John; Prat, Aleix

2015-06-01

Improved understanding of risk of recurrence (ROR) is needed to reduce cases of recurrence and more effectively treat breast cancer patients. The purpose of this study was to examine how a gene-expression profile (GEP), identified by Prosigna, influences physician adjuvant treatment selection for early breast cancer (EBC) and the effects of this influence on optimizing adjuvant treatment recommendations in clinical practice. A prospective, observational, multicenter study was carried out in 15 hospitals across Spain. Participating medical oncologists completed pre-assessment, post-assessment, and follow-up questionnaires recording their treatment recommendations and confidence in these recommendations, before and after knowing the patient's ROR. Patients completed questionnaires on decision-making, anxiety, and health status. Between June 2013 and January 2014, 217 patients enrolled and a final 200 were included in the study. Patients were postmenopausal, estrogen receptor positive, human epidermal growth hormone factor negative, and node negative with either stage 1 or stage 2 tumors. After receiving the GEP results, treatment recommendations were changed for 40 patients (20%). The confidence of medical oncologists in their treatment recommendations increased in 41.6% and decreased in 6.5% of total cases. Patients reported lower anxiety after physicians made treatment recommendations based on the GEP results (p < 0.05). Though this study does not include evaluation of the impact of GEP on long-term outcomes, it was found that GEP results influenced the treatment decisions of medical oncologists and their confidence in adjuvant therapy selection. Patients' anxiety about the selected adjuvant therapy decreased with use of the GEP.

Postoperative Radiotherapy for Pathologic N2 Non–Small-Cell Lung Cancer Treated With Adjuvant Chemotherapy: A Review of the National Cancer Data Base

PubMed Central

Robinson, Cliff G.; Patel, Aalok P.; Bradley, Jeffrey D.; DeWees, Todd; Waqar, Saiama N.; Morgensztern, Daniel; Baggstrom, Maria Q.; Govindan, Ramaswamy; Bell, Jennifer M.; Guthrie, Tracey J.; Colditz, Graham A.; Crabtree, Traves D.; Kreisel, Daniel; Krupnick, Alexander S.; Patterson, G. Alexander; Meyers, Bryan F.; Puri, Varun

2015-01-01

Purpose To investigate the impact of modern postoperative radiotherapy (PORT) on overall survival (OS) for patients with N2 non–small-cell lung cancer (NSCLC) treated nationally with surgery and adjuvant chemotherapy. Patients and Methods Patients with pathologic N2 NSCLC who underwent complete resection and adjuvant chemotherapy from 2006 to 2010 were identified from the National Cancer Data Base and stratified by use of PORT (≥ 45 Gy). A total of 4,483 patients were identified (PORT, n = 1,850; no PORT, n = 2,633). The impact of patient and treatment variables on OS was explored using Cox regression. Results Median follow-up time was 22 months. On univariable analysis, improved OS correlated with younger age, treatment at an academic facility, female sex, urban population, higher income, lower Charlson comorbidity score, smaller tumor size, multiagent chemotherapy, resection with at least a lobectomy, and PORT. On multivariable analysis, improved OS remained independently predicted by younger age, female sex, urban population, lower Charlson score, smaller tumor size, multiagent chemotherapy, resection with at least a lobectomy, and PORT (hazard ratio, 0.886; 95% CI, 0.798 to 0.988). Use of PORT was associated with an increase in median and 5-year OS compared with no PORT (median OS, 45.2 v 40.7 months, respectively; 5-year OS, 39.3% [95% CI, 35.4% to 43.5%] v 34.8% [95% CI, 31.6% to 38.3%], respectively; P = .014). Conclusion For patients with N2 NSCLC after complete resection and adjuvant chemotherapy, modern PORT seems to confer an additional OS advantage beyond that achieved with adjuvant chemotherapy alone. PMID:25667283

Vaccination of heifers with anaflatoxin improves the reduction of aflatoxin b1 carry over in milk of lactating dairy cows.

PubMed

Giovati, Laura; Gallo, Antonio; Masoero, Francesco; Cerioli, Carla; Ciociola, Tecla; Conti, Stefania; Magliani, Walter; Polonelli, Luciano

2014-01-01

It was previously reported that injection of anaflatoxin B1 (AnAFB1) conjugated to keyhole limpet hemocyanin (KLH), together with Freund's adjuvant, was effective in inducing in cows a long lasting titer of anti-aflatoxin B1 (AFB1) antibodies (Abs), cross-reacting with other aflatoxins, which were able to hinder, proportionally to their titer, the secretion of aflatoxin M1 (AFM1) into the milk of cows continuously fed with AFB1. According to anti-AFB1 Ab titer, 50% of the vaccinated cows were recognized as high responder animals. In an attempt to prepare a more effective formulation for vaccination of cows, it was compared the immunogenicity, in Holstein Friesian heifers, of AnAFB1 covalently conjugated to KLH or to recombinant diphtheria toxin (CRM197) molecules, and injected together with various adjuvants. This study demonstrated that injection of AnAFB1 conjugated to KLH and mixed with complete (priming) and incomplete Freund's adjuvant (boosters), as in the previous schedule of immunization, was the most effective regimen for inducing Ab responses against AFB1, although pre-calving administration could increase the effectiveness of vaccination, resulting in 100% high responder animals. After one booster dose at the beginning of the milk production cycle, anti-AFB1 Ab titers were comparable to those recorded at the end of the immunization schedule, and proved to be effective in reducing significantly AFB1 carry over, as AFM1, from feed to milk. Pre-calving vaccination of dairy heifers with conjugated AnAFB1, adjuvated with complete and incomplete Freund's adjuvant, may represent the most effective tool for preventing the public health hazard constituted by milk and cheese contaminated with aflatoxins.

The effect of adjuvant radiation on survival in early stage clear cell ovarian carcinoma.

PubMed

Hogen, Liat; Thomas, Gillian; Bernardini, Marcus; Bassiouny, Dina; Brar, Harinder; Gien, Lilian T; Rosen, Barry; Le, Lisa; Vicus, Danielle

2016-11-01

To assess the impact of adjuvant radiotherapy (RT) on survival in patients with stage I and II ovarian clear cell carcinoma (OCCC). Data collection and analysis of stage I and II OCCC patients treated at two tertiary centers in Toronto, between 1995 and 2014, was performed. Descriptive statistics and Kaplan-Meier survival probability estimates were completed. The log-rank test was used to compare survival curves. 163 patients were eligible. 44 (27%) patients were treated with adjuvant RT: 37 of them received adjuvant chemotherapy (CT), and 7 had RT only. In the no-RT group, there were 119 patients: 83 patients received adjuvant CT and 36 had no adjuvant treatment. The 10year progression free survival (PFS) was 65% for patients treated with RT, and 59% no-RT patients. There were a total of 41 (25%) recurrences in the cohort: 12 (27.2%) patients in RT group and 29 (24.3%) in the no-RT group. On multivariable analysis, adjuvant RT was not significantly associated with an increased PFS (0.85 (0.44-1.63) p=0.63) or overall survival (OS) (0.84 (0.39-1.82) p=0.66). In the subset of 59 patients defined as high-risk: stage IC with positive cytology and/or surface involvement and stage II: RT was not found to be associated with a better PFS (HR 1.18 (95% CI: 0.55-2.54) or O S(HR 1.04 (95% CI: 0.40-2.69)). Adjuvant RT was not found to be associated with a survival benefit in patients with stage I and II ovarian clear cell carcinoma or in a high risk subset of patients including stage IC cytology positive/surface involvement and stage II patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Stage III Melanoma in the Axilla: Patterns of Regional Recurrence After Surgery With and Without Adjuvant Radiation Therapy

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

Pinkham, Mark B., E-mail: mark.pinkham@health.qld.gov.au; University of Queensland, Brisbane; Foote, Matthew C.

Purpose: To describe the anatomic distribution of regionally recurrent disease in patients with stage III melanoma in the axilla after curative-intent surgery with and without adjuvant radiation therapy. Methods and Materials: A single-institution, retrospective analysis of a prospective database of 277 patients undergoing curative-intent treatment for stage III melanoma in the axilla between 1992 and 2012 was completed. For patients who received radiation therapy and those who did not, patterns of regional recurrence were analyzed, and univariate analyses were performed to assess for potential factors associated with location of recurrence. Results: There were 121 patients who received adjuvant radiation therapymore » because their clinicopathologic features conferred a greater risk of regional recurrence. There were 156 patients who received no radiation therapy. The overall axillary control rate was 87%. There were 37 patients with regional recurrence; 17 patients had received adjuvant radiation therapy (14%), and 20 patients (13%) had not. The likelihood of in-field nodal recurrence was significantly less in the adjuvant radiation therapy group (P=.01) and significantly greater in sites adjacent to the axilla (P=.02). Patients with high-risk clinicopathologic features who did not receive adjuvant radiation therapy also tended to experience in-field failure rather than adjacent-field failure. Conclusions: Patients who received adjuvant radiation therapy were more likely to experience recurrence in the adjacent-field regions rather than in the in-field regions. This may not simply reflect higher-risk pathology. Using this data, it may be possible to improve outcomes by reducing the number of adjacent-field recurrences after adjuvant radiation therapy.« less

End points for adjuvant therapy trials: has the time come to accept disease-free survival as a surrogate end point for overall survival?

PubMed

Gill, Sharlene; Sargent, Daniel

2006-06-01

The intent of adjuvant therapy is to eradicate micro-metastatic residual disease following curative resection with the goal of preventing or delaying recurrence. The time-honored standard for demonstrating efficacy of new adjuvant therapies is an improvement in overall survival (OS). This typically requires phase III trials of large sample size with lengthy follow-up. With the intent of reducing the cost and time of completing such trials, there is considerable interest in developing alternative or surrogate end points. A surrogate end point may be employed as a substitute to directly assess the effects of an intervention on an already accepted clinical end point such as mortality. When used judiciously, surrogate end points can accelerate the evaluation of new therapies, resulting in the more timely dissemination of effective therapies to patients. The current review provides a perspective on the suitability and validity of disease-free survival (DFS) as an alternative end point for OS. Criteria for establishing surrogacy and the advantages and limitations associated with the use of DFS as a primary end point in adjuvant clinical trials and as the basis for approval of new adjuvant therapies are discussed.

Polyphenolics isolated from virgin coconut oil inhibits adjuvant induced arthritis in rats through antioxidant and anti-inflammatory action.

PubMed

Vysakh, A; Ratheesh, M; Rajmohanan, T P; Pramod, C; Premlal, S; Girish kumar, B; Sibi, P I

2014-05-01

We evaluated the protective efficacy of the polyphenolic fraction from virgin coconut oil (PV) against adjuvant induced arthritic rats. Arthritis was induced by intradermal injection of complete Freund's adjuvant. The activities of inflammatory, antioxidant enzymes and lipid peroxidation were estimated. PV showed high percentage of edema inhibition at a dose of 80mg/kg on 21st day of adjuvant arthritis and is non toxic. The expression of inflammatory genes such as COX-2, iNOS, TNF-α and IL-6 and the concentration of thiobarbituric acid reactive substance were decreased by treatment with PV. Antioxidant enzymes were increased and on treatment with PV. The increased level of total WBC count and C-reactive protein in the arthritic animals was reduced in PV treated rats. Synovial cytology showed that inflammatory cells and reactive mesothelial cells were suppressed by PV. Histopathology of paw tissue showed less edema formation and cellular infiltration on supplementation with PV. Thus the results demonstrated the potential beneficiary effect of PV on adjuvant induced arthritis in rats and the mechanism behind this action is due to its antioxidant and anti-inflammatory effects. Copyright © 2014 Elsevier B.V. All rights reserved.

Adjuvant effects and antiserum action potentiation by a (herbal) compound 2-hydroxy-4-methoxy benzoic acid isolated from the root extract of the Indian medicinal plant 'sarsaparilla' (Hemidesmus indicus R. Br.).

PubMed

Alam, M I; Gomes, A

1998-10-01

The adjuvant effect and antiserum potentiation of a compound 2-hydroxy-4-methoxy benzoic acid were explored in the present investigation. This compound, isolated and purified from the Indian medicinal plant Hemidesmus indicus R. Br, possessed antisnake venom activity. Rabbits immunized with Vipera russellii venom in the presence and absence of the compound along with Freund's complete adjuvant, produced a precipitating band in immunogel diffusion and immunogel electrophoresis. The venom neutralizing capacity of this antiserum showed positive adjuvant effects as evident by the higher neutralization capacity (lethal and hemorrhage) when compared with the antiserum raised with venom alone. The pure compound potentiated the lethal action neutralization of venom by commercial equine polyvalent snake venom antiserum in experimental models. These observations raised the possibility of the use of chemical antagonists (from herbs) against snake bite, which may provide a better protection in presence of antiserum, especially in the rural parts of India.

Intradermal Vaccination With Adjuvanted Ebola Virus Soluble Glycoprotein Subunit Vaccine by Microneedle Patches Protects Mice Against Lethal Ebola Virus Challenge.

PubMed

Liu, Ying; Ye, Ling; Lin, Fang; Gomaa, Yasmine; Flyer, David; Carrion, Ricardo; Patterson, Jean L; Prausnitz, Mark R; Smith, Gale; Glenn, Gregory; Wu, Hua; Compans, Richard W; Yang, Chinglai

2018-06-08

In this study, we investigated immune responses induced by purified Ebola virus (EBOV) soluble glycoprotein (sGP) subunit vaccines via intradermal immunization with microneedle (MN) patches in comparison with intramuscular (IM) injection in mice. Our results showed that MN delivery of EBOV sGP was superior to IM injection in eliciting higher levels and longer lasting antibody responses against EBOV sGP and GP antigens. Moreover, sGP-specific immune responses induced by MN or IM immunizations were effectively augmented by formulating sGP with a saponin-based adjuvant, and they were shown to confer complete protection of mice against lethal mouse-adapted EBOV (MA-EBOV) challenge. In comparison, mice that received sGP without adjuvant by MN or IM immunizations succumbed to lethal MA-EBOV challenge. These results show that immunization with EBOV sGP subunit vaccines with adjuvant by MN patches, which have been shown to provide improved safety and thermal stability, is a promising approach to protect against EBOV infection.

Fourth International Conference: Modern Vaccines/Adjuvants Formulation--Impact on Future Development: May 15-17 2013, CHUV, Lausanne, Switzerland.

PubMed

Tupin, Emmanuel

2013-09-01

On the 15-17th of May 2013, about 120 scientists, postdoctoral fellows and professors representing renowned academic institutes and senior scientists and executives from small biotechs, contract research organizations (CROs) and Big Pharma companies, gathered at the Centre Hospitalier Universitaire Vaudois (CHUV) in Lausanne, Switzerland for the 4th international conference on Modern Vaccines and Adjuvants Formulation. Despite this relative small number, the speakers and attendees covered together a very broad field of expertise. Indeed, experts in microbiology, immunology, biochemistry, formulation, virus and nanoparticle characterization, vaccine production, quality control as well as regulatory professionals attended the conference and were able to present their works and discuss new developments within the field of vaccine and adjuvant development, characterization and approval process. This broad diversity was a highpoint of the conference and allowed for a stimulating environment and underlined the complexity of the challenges that the field currently faces in order to develop better or completely new vaccines and adjuvants.

78 FR 63380 - Farm Credit Administration Board Policy Statements

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-24

... FARM CREDIT ADMINISTRATION 12 CFR Chapter VI Farm Credit Administration Board Policy Statements AGENCY: Farm Credit Administration. ACTION: Notice of policy statements and index. SUMMARY: The Farm Credit Administration (FCA), as part of its annual public notification process, is publishing for notice...

Improving the thermal stability of cellobiohydrolase Cel7A from Hypocrea jecorina by directed evolution.

PubMed

Goedegebuur, Frits; Dankmeyer, Lydia; Gualfetti, Peter; Karkehabadi, Saeid; Hansson, Henrik; Jana, Suvamay; Huynh, Vicky; Kelemen, Bradley R; Kruithof, Paulien; Larenas, Edmund A; Teunissen, Pauline J M; Ståhlberg, Jerry; Payne, Christina M; Mitchinson, Colin; Sandgren, Mats

2017-10-20

Secreted mixtures of Hypocrea jecorina cellulases are able to efficiently degrade cellulosic biomass to fermentable sugars at large, commercially relevant scales. H. jecorina Cel7A, cellobiohydrolase I, from glycoside hydrolase family 7, is the workhorse enzyme of the process. However, the thermal stability of Cel7A limits its use to processes where temperatures are no higher than 50 °C. Enhanced thermal stability is desirable to enable the use of higher processing temperatures and to improve the economic feasibility of industrial biomass conversion. Here, we enhanced the thermal stability of Cel7A through directed evolution. Sites with increased thermal stability properties were combined, and a Cel7A variant (FCA398) was obtained, which exhibited a 10.4 °C increase in T m and a 44-fold greater half-life compared with the wild-type enzyme. This Cel7A variant contains 18 mutated sites and is active under application conditions up to at least 75 °C. The X-ray crystal structure of the catalytic domain was determined at 2.1 Å resolution and showed that the effects of the mutations are local and do not introduce major backbone conformational changes. Molecular dynamics simulations revealed that the catalytic domain of wild-type Cel7A and the FCA398 variant exhibit similar behavior at 300 K, whereas at elevated temperature (475 and 525 K), the FCA398 variant fluctuates less and maintains more native contacts over time. Combining the structural and dynamic investigations, rationales were developed for the stabilizing effect at many of the mutated sites. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Influence of complete administration of adjuvant chemotherapy cycles on overall and disease-free survival in locally advanced rectal cancer: post hoc analysis of a randomized, multicenter, non-inferiority, phase 3 trial.

PubMed

Sandra-Petrescu, Flavius; Herrle, Florian; Burkholder, Iris; Kienle, Peter; Hofheinz, Ralf-Dieter

2018-04-03

A randomized trial demonstrated that capecitabine is at least as effective as fluorouracil in the adjuvant treatment of patients with locally advanced rectal cancer. However, not all patients receive all planned cycles of chemotherapy. Therefore it is of interest how complete or partial administration of chemotherapy influences oncological outcome. A post hoc analysis of a trial with 401 randomized patients, nine being excluded because of missing data, was performed. 392 patients (197 - capecitabine, 195 - fluorouracil) could be analyzed regarding the number of administered adjuvant chemotherapy cycles. In the subgroup of 361 patients with an overall survival of at least six months, five-year overall and disease-free survival were analyzed in respect to completion (complete vs. incomplete) of chemotherapy cycles. Survival rates and curves were calculated and compared using the log-rank test. The effect of completion of chemotherapy was adjusted for relevant confounding factors. Two hundred fifty-one (64.0%) of analyzed patients received all postoperative scheduled cycles. Five-year overall survival was significantly better in these patients compared to the incomplete group (76.0 vs. 60.6%, p < 0.0001). Of 361 patients with an overall survival of at least six months, 251(69.5%) patients received all cycles. Five-year overall survival was also significantly better than in the incomplete group (76.0 vs. 66.4%, p = 0.0073). Five-year disease free survival was numerically better (64.9 vs. 58.7%, p = 0.0646; HR [not all cycles vs. all cycles] = 1.42 95% CI: [0.98, 2.07]). Cox regression models show a non-significant better OS (p = 0.061) and DFS (p = 0.083), if chemotherapy cycles were administered completely. Complete administration of chemotherapy cycles was associated with improved five-year overall and disease-free survival in patients with locally advanced rectal cancer.

Effect of a Shortened Duration of FOLFOX Chemotherapy on the Survival Rate of Patients with Stage II and III Colon Cancer.

PubMed

Ji, Woong Bae; Hong, Kwang Dae; Kim, Jung-Sik; Joung, Sung-Yup; Um, Jun Won; Min, Byung-Wook

2018-01-01

FOLFOX chemotherapy is widely used as an adjuvant treatment for advanced colon cancer. The duration of adjuvant chemotherapy is usually set to 6 months, which is based on a former study of 5-fluorouracil/leucovorin chemotherapy. However, the FOLFOX regimen is known to have complications, such as peripheral neuropathy. The aim of this study was to compare the survival rates and complications experienced by patients receiving either 4 or 6 months of FOLFOX chemotherapy. Retrospective data analysis was performed for stage II and III patients who underwent radical resection of colon cancer. We compared the 5-year survival rates and the occurrence of complications in patients who completed only 8 cycles of FOLFOX chemotherapy with patients who completed 12 cycles of chemotherapy. Among 188 patients who underwent adjuvant FOLFOX chemotherapy for stage II or III colon cancer, 83 (44.1%) completed 6 months of FOLFOX chemotherapy and 64 (34.0%) patients discontinued after 4 months of chemotherapy. The 5-year overall survival and disease-free survival rates did not show a significant difference. Patients in the 6-month group had peripheral neuropathy more frequently (p = 0.028). Five-year overall and disease-free survival were not significantly different between the 2 groups. Large-scale prospective studies are necessary for the analysis of complications and survival rates. © 2017 S. Karger AG, Basel.

12 CFR 602.1 - Purpose and scope.

Code of Federal Regulations, 2010 CFR

2010-01-01

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12 CFR 615.5201 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

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Exploring patient experiences of neo-adjuvant chemotherapy for breast cancer.

PubMed

Beaver, Kinta; Williamson, Susan; Briggs, Jean

2016-02-01

Neo-adjuvant chemotherapy is recommended for 'inoperable' locally advanced and inflammatory breast cancers. For operable breast cancers, trials indicate no survival differences between chemotherapy given pre or post-surgery. Communicating evidence based information to patients is complex and studies examining patient experiences of neo-adjuvant chemotherapy are lacking. This study aims to explore the experiences of women who received neo-adjuvant chemotherapy for breast cancer. A qualitative approach using in-depth interviews with 20 women who had completed neo-adjuvant chemotherapy for breast cancer. Interview data were analysed using thematic analysis. The sample included a relatively young group of women, with caring responsibilities. Five main themes emerged: coping with the rapid transition from 'well' to 'ill', information needs and decision making, needing support and empathy, impact on family, and creating a new 'normal'. More support was needed towards the end of chemotherapy, when side effects were at their most toxic, and decisions about forthcoming surgery were being made. Some women were referred to psychological services, but usually when a crisis point had been reached. Information and support would have been beneficial at key time points. This information is vital in developing services and interventions to meet the complex needs of these patients and potentially prevent late referral to psychological services. Specialist oncology nurses are able to develop empathetic relationships with patients and have the experience, knowledge and skills to inform and support women experiencing neo-adjuvant chemotherapy. Targeting key time points and maintaining relationship throughout neo-adjuvant chemotherapy would be highly beneficial. Copyright © 2015 Elsevier Ltd. All rights reserved.

Impact on disease-free survival of adjuvant erlotinib or gefitinib in patients with resected lung adenocarcinomas that harbor epidermal growth factor receptor (EGFR) mutations

PubMed Central

Janjigian, Yelena Y.; Park, Bernard J.; Zakowski, Maureen F.; Ladanyi, Marc; Pao, William; D’Angelo, Sandra P.; Kris, Mark G.; Shen, Ronglai; Zheng, Junting; Azzoli, Christopher G.

2013-01-01

Background Patients with stage IV lung adenocarcinoma and EGFR mutation derive clinical benefit from treatment with EGFR tyrosine kinase inhibitors (TKI). Whether treatment with TKI improves outcomes in patients with resected lung adenocarcinoma and EGFR mutation is unknown. Methods Data were analyzed from a surgical database of patients with resected lung adenocarcinoma harboring EGFR exon 19 or 21 mutations. In a multivariate analysis, we evaluated the impact of treatment with adjuvant TKI. Results The cohort consists of 167 patients with completely resected stage I–III lung adenocarcinoma. 93 patients (56%) had exon 19 del, 74 patients (44%) had exon 21 mutations, 56 patients (33%) received perioperative TKI. In a multivariate analysis controlling for sex, stage, type of surgery and adjuvant platinum chemotherapy, the 2-year DFS was 89% for patients treated with adjuvant TKI compared with 72% in control group (hazard ratio [HR] = 0.53; 95% confidence interval [CI] 0.28 to 1.03; p = 0.06). The 2-year OS was 96% with adjuvant EGFR TKI and 90% in the group that did not receive TKI (HR 0.62; 95% CI 0.26 to 1.51; p = 0.296). Conclusions Compared to patients who did not receive adjuvant TKI, we observed a trend toward improvement in disease free survival among individuals with resected stages I–III lung adenocarcinomas harboring mutations in EGFR exons 19 or 21 who received these agents as adjuvant therapy. Based on these data, 320 patients are needed for a randomized trial to prospectively validate this DFS benefit. PMID:21150674

Large-scale, Exhaustive Lattice-based Structural Auditing of SNOMED CT.

PubMed

Zhang, Guo-Qiang; Bodenreider, Olivier

2010-11-13

One criterion for the well-formedness of ontologies is that their hierarchical structure forms a lattice. Formal Concept Analysis (FCA) has been used as a technique for assessing the quality of ontologies, but is not scalable to large ontologies such as SNOMED CT (> 300k concepts). We developed a methodology called Lattice-based Structural Auditing (LaSA), for auditing biomedical ontologies, implemented through automated SPARQL queries, in order to exhaustively identify all non-lattice pairs in SNOMED CT. The percentage of non-lattice pairs ranges from 0 to 1.66 among the 19 SNOMED CT hierarchies. Preliminary manual inspection of a limited portion of the over 544k non-lattice pairs, among over 356 million candidate pairs, revealed inconsistent use of precoordination in SNOMED CT, but also a number of false positives. Our results are consistent with those based on FCA, with the advantage that the LaSA pipeline is scalable and applicable to ontological systems consisting mostly of taxonomic links.

Study of system-size effects on the emergent magnetic monopoles and Dirac strings in artificial kagome spin ice

NASA Astrophysics Data System (ADS)

Leon, Alejandro

2012-02-01

In this work we study the dynamical properties of a finite array of nanomagnets in artificial kagome spin ice at room temperature. The dynamic response of the array of nanomagnets is studied by implementing a ``frustrated celular aut'omata'' (FCA), based in the charge model. In this model, each dipole is replaced by a dumbbell of two opposite charges, which are situated at the neighbouring vertices of the honeycomb lattice. The FCA simulations, allow us to study in real-time and deterministic way, the dynamic of the system, with minimal computational resource. The update function is defined according to the coordination number of vertices in the system. Our results show that for a set geometric parameters of the array of nanomagnets, the system exhibits high density of Dirac strings and high density emergent magnetic monopoles. A study of the effect of disorder in the arrangement of nanomagnets is incorporated in this work.

Large-scale, Exhaustive Lattice-based Structural Auditing of SNOMED CT

PubMed Central

Zhang, Guo-Qiang; Bodenreider, Olivier

2010-01-01

One criterion for the well-formedness of ontologies is that their hierarchical structure forms a lattice. Formal Concept Analysis (FCA) has been used as a technique for assessing the quality of ontologies, but is not scalable to large ontologies such as SNOMED CT (> 300k concepts). We developed a methodology called Lattice-based Structural Auditing (LaSA), for auditing biomedical ontologies, implemented through automated SPARQL queries, in order to exhaustively identify all non-lattice pairs in SNOMED CT. The percentage of non-lattice pairs ranges from 0 to 1.66 among the 19 SNOMED CT hierarchies. Preliminary manual inspection of a limited portion of the over 544k non-lattice pairs, among over 356 million candidate pairs, revealed inconsistent use of precoordination in SNOMED CT, but also a number of false positives. Our results are consistent with those based on FCA, with the advantage that the LaSA pipeline is scalable and applicable to ontological systems consisting mostly of taxonomic links. PMID:21347113

Serum IGF-1, IGFBP-3 levels and circulating tumor cells (CTCs) in early breast cancer patients.

PubMed

Papadakis, Georgios Z; Mavroudis, Dimitrios; Georgoulias, Vasilios; Souglakos, John; Alegakis, Athanasios K; Samonis, George; Bagci, Ulas; Makrigiannakis, Antonis; Zoras, Odysseas

2017-04-01

Insulin-like growth factor (IGF)-axis is involved in human oncogenesis and metastasis development for various solid tumors including breast cancer. Aim of this study was to assess the association between IGF-1, IGF-binding protein-3 (IGFBP-3) serum levels and the presence of circulating tumor cells (CTCs) in the peripheral blood of women diagnosed with early breast cancer (EBC), before and after adjuvant chemotherapy. 171 patients with early-stage breast adenocarcinomas were retrospectively evaluated. Immunoradiometric (IRMA) assays were employed for the in-vitro determination of IGF-1 and IGFBP-3 serum levels in blood samples collected after surgical treatment and before initiation of adjuvant chemotherapy. CTCs' presence was assessed through detection of cytokeratin-19 (CK-19) mRNA transcripts using quantitative real time reverse transcription polymerase chain reaction (RT-PCR). IGF-1, IGFBP-3 serum levels were correlated with CTCs' presence before and after adjuvant chemotherapy as well as with tumor characteristics including tumor size, axillary lymph node status, oestrogen (ER)/progestorene (PR) and human epidermural growth factor receptor 2 (HER2) receptor status. Log-rank test was applied to investigate possible association between IGF-1, IGFBP-3 serum levels and disease-free interval (DFI) and overall survival (OS). Before initiation of adjuvant therapy IGF-1, IGFBP-3 serum levels were moderately associated (Spearman's rho=0.361, p<0.001) with each other, while presenting significant differences across age groups (all p values<0.05). IGF-1 serum levels did not correlate with the presence of CTCs before initiation (p=0.558) or after completion (p=0.474) of adjuvant chemotherapy. Similarly, IGFBP-3 serum levels did not show significant association with detectable CTCs either before (p=0.487) or after (p=0.134) completion of adjuvant chemotherapy. There was no statistically significant association between the clinical outcome of patients in terms of DFI, OS and IGF-1(DFI: p=0.499; OS: p=0.220) or IGFBP-3 (DFI: p=0.900; OS: p=0.406) serum levels. IGF-1 and IGFBP-3 serum levels before initiation of adjuvant chemotherapy are not indicative of CTCs' presence in the blood and do not correlate with clinical outcome of women with early-stage breast cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Models of Inflammation: Carrageenan- or Complete Freund's Adjuvant (CFA)-Induced Edema and Hypersensitivity in the Rat.

PubMed

McCarson, Kenneth E

2015-09-01

Animal models of inflammation are used to assess the production of inflammatory mediators at sites of inflammation, the processing of pain sensation at CNS sites, the anti-inflammatory properties of agents such as nonsteroidal anti-inflammatory drugs (NSAIDs), and the efficacy of putative analgesic compounds in reversing cutaneous hypersensitivity. Detailed in this unit are methods to elicit and measure carrageenan- and complete Freund's adjuvant (CFA)-induced cutaneous inflammation. Due to possible differences between the dorsal root sensory system and the trigeminal sensory system, injections into either the footpad or vibrissal pad are described. In this manner, cutaneous inflammation can be assessed in tissue innervated by the lumbar dorsal root ganglion neurons (footpad) or by the trigeminal ganglion neurons (vibrissal pad). Copyright © 2015 John Wiley & Sons, Inc.

Fiat Chrysler Application for Alternative Methodology for Off-Cycle Technology Credits: High Efficiency Alternators

EPA Pesticide Factsheets

FCA Group LLC request to the EPA regarding greenhouse gas, off-cycle CO2 credits for High Efficiency Alternators used on 2009 and subsequent model year vehicles and off-cycle fuel consumption credits for 2017 and subsequent model year vehicles.

12 CFR 609.930 - Policies and procedures.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Boards and Management § 609.930 Policies and procedures. The FCA supports E-commerce and wants to facilitate it and other new technologies and innovations to enhance the efficient conduct of business and the... management; (h) Liability insurance; and (i) Prompt reporting of known or suspected criminal violations...

12 CFR 608.804 - Delegation of authority.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 6 2011-01-01 2011-01-01 false Delegation of authority. 608.804 Section 608.804 Banks and Banking FARM CREDIT ADMINISTRATION ADMINISTRATIVE PROVISIONS COLLECTION OF CLAIMS OWED THE UNITED STATES Administrative Collection of Claims § 608.804 Delegation of authority. The FCA...

12 CFR 602.11 - Fees by type of requester.

Code of Federal Regulations, 2013 CFR

2013-01-01

... noncommercial scientific institution and that you seek the records for scholarly or scientific research, not for..., the FCA may charge you the direct costs of searching for responsive records, reviewing the records...) Educational institutions and noncommercial scientific institutions. We charge fees for reproduction costs only...

12 CFR 602.11 - Fees by type of requester.

Code of Federal Regulations, 2014 CFR

2014-01-01

... noncommercial scientific institution and that you seek the records for scholarly or scientific research, not for..., the FCA may charge you the direct costs of searching for responsive records, reviewing the records...) Educational institutions and noncommercial scientific institutions. We charge fees for reproduction costs only...

12 CFR 602.11 - Fees by type of requester.

Code of Federal Regulations, 2012 CFR

2012-01-01

... noncommercial scientific institution and that you seek the records for scholarly or scientific research, not for..., the FCA may charge you the direct costs of searching for responsive records, reviewing the records...) Educational institutions and noncommercial scientific institutions. We charge fees for reproduction costs only...

Fiat Chrysler Application for Alternative Methodology for Off-Cycle Technology Credits: Engine and Transmission Warmup

EPA Pesticide Factsheets

FCA Group LLC request to the EPA regarding greenhouse gas, off-cycle CO2 credits for Active Engine Warm Up used in 2011-2013 model year vehicles and Active Transmission Warm Up Technologies used in 2013 model year vehicles.

12 CFR 609.930 - Policies and procedures.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Boards and Management § 609.930 Policies and procedures. The FCA supports E-commerce and wants to... delivery of safe and sound credit and closely related services. Through E-commerce, System institutions can... time, E-commerce presents challenges and risks that your board must carefully consider in advance...

12 CFR 609.930 - Policies and procedures.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Boards and Management § 609.930 Policies and procedures. The FCA supports E-commerce and wants to... delivery of safe and sound credit and closely related services. Through E-commerce, System institutions can... time, E-commerce presents challenges and risks that your board must carefully consider in advance...

12 CFR 609.930 - Policies and procedures.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Boards and Management § 609.930 Policies and procedures. The FCA supports E-commerce and wants to... delivery of safe and sound credit and closely related services. Through E-commerce, System institutions can... time, E-commerce presents challenges and risks that your board must carefully consider in advance...

12 CFR 609.930 - Policies and procedures.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Boards and Management § 609.930 Policies and procedures. The FCA supports E-commerce and wants to... delivery of safe and sound credit and closely related services. Through E-commerce, System institutions can... time, E-commerce presents challenges and risks that your board must carefully consider in advance...

PCBs, liver lesions, and biomarker responses in adult walleye (Stizostedium vitreum vitreum) collected from Green Bay, Wisconsin

USGS Publications Warehouse

Barron, Mace G.; Anderson, Michael J.; Cacela, Dave; Lipton, Joshua; Teh, Swee J.; Hinton, David E.; Zelikoff, Judith T.; Dikkeboom, Audrey L.; Tillitt, Donald E.; Holey, Mark; Denslow, Nancy

2000-01-01

Adult walleye were collected from several locations in the Lower Fox River and Green Bay, Wisconsin (the assessment area) and two relatively uncontaminated reference locations (Lake Winnebago and Patten Lake, Wisconsin) between July and October in 1996 and 1997. Whole body and liver samples collected in 1996 were analyzed for total PCBs, PCB congeners, and liver histological lesions. Follow-up sampling in 1997 included examination of liver histopathology, PCBs in liver samples, measurement of ethoxyresorufin-O-deethylase (EROD) activity, immunological evaluation of kidney and blood samples, measurement of plasma vitellogenin, and examination of tissues for parasites as well as bacterial and viral infections. Mean PCB concentrations in whole body and liver samples were elevated in assessment area walleye (4.6 to 8.6 and 3.6 to 6.4 mg/kg wet weight, respectively) compared to PCB concentrations in reference areas (0.04 mg/kg in walleye fillets from Lake Winnebago). A significant (p < 0.01) elevation was observed in the prevalence (26%) of hepatic preneoplastic foci of cellular alteration (FCA) and neoplasms in 5 to 8 year old walleye collected from the assessment area, compared to reference area fish (6% prevalence). Walleye from the assessment area also contained multiple FCA and hepatic tumors per liver sample, whereas no tumors and a reduced prevalence of FCA were observed in reference area walleye. Both tumors and FCA were more prevalent in female fish than in male fish within the 5 to 8 year age classes. There were no remarkable effects on immunological parameters in assessment area walleye, although hematocrit was elevated and blood monocyte counts were 40% lower than those of reference area fish. The data did not show any clear distinctions in the prevalence of disease between reference and assessment area walleye. EROD activity was similar in assessment area and reference area walleye. Plasma vitellogenin was elevated in female walleye from eastern Green Bay, but was not detected in male fish from this location. The results of this investigation demonstrate significant elevation in hepatic preneoplastic lesions and hepatocellular adenomas and carcinomas in assessment area walleye exposed to elevated concentrations of PCBs. These histopathological lesions are consistent with long-term exposure to tumor promoters such as PCBs, although quantitative association between tumors and PCBs was not observed at the level of the individual fish. Additional research would be needed to elucidate the causal mechanisms underlying tumorigenesis.

Adjuvant Everolimus for Resected Kidney Cancer

Cancer.gov

In this clinical trial, patients with renal cell cancer who have undergone partial or complete nephrectomy will be randomly assigned to take everolimus tablets or matching placebo tablets daily for 54 weeks.

T Helper 1–Inducing Adjuvant Protects against Experimental Paracoccidioidomycosis

PubMed Central

de Oliveira, Leandro Licursi; Coltri, Kely Cristine; Cardoso, Cristina Ribeiro Barros; Roque-Barreira, Maria-Cristina; Panunto-Castelo, Ademilson

2008-01-01

Immunostimulatory therapy is a promising approach to improving the treatment of systemic fungal infections such as paracoccidioidomycosis (PCM), whose drug therapy is usually prolonged and associated with toxic side effects and relapses. The current study was undertaken to determine if the injection of a T helper (Th) 1–stimulating adjuvant in P. brasiliensis–infected mice could have a beneficial effect on the course of experimental PCM. For this purpose, mice were infected and treated with complete Freund's adjuvant (CFA), a well-established Th1 experimental inductor, or incomplete Freund's adjuvant (IFA - control group) on day 20 postinfection. Four weeks after treatment, the CFA-treated mice presented a mild infection in the lungs characterized by absence of epithelioid cell granulomas and yeast cells, whereas the control mice presented multiple sites of focal epithelioid granulomas with lymphomonocytic halos circumscribing a high number of viable and nonviable yeast cells. In addition, CFA administration induced a 2.4 log reduction (>99%) in the fungal burden when compared to the control group, and led to an improvement of immune response, reversing the immunosuppression observed in the control group. The immunotherapy with Th1-inducing adjuvant, approved to be used in humans, might be a valuable tool in the treatment of PCM and potentially useful to improve the clinical cure rate in humans. PMID:18335066

Feasibility of sequential adjuvant chemotherapy with a 3-month oxaliplatin-based regimen followed by 3 months of capecitabine in patients with stage III and high-risk stage II colorectal cancer: JSWOG-C2 study

PubMed Central

Tsuruta, Atsushi; Yamashita, Kazuki; Tanioka, Hiroaki; Tsuji, Akihito; Inukai, Michio; Yamakawa, Toshiki; Yamatsuji, Tomoki; Yoshimitsu, Masanori; Toyota, Kazuhiro; Yamano, Taketoshi; Nagasaka, Takeshi; Okajima, Masazumi

2016-01-01

Background Six months of oxaliplatin-based chemotherapy is the standard adjuvant chemotherapy for completely resected stage III colorectal cancer (CRC). Also, patients with stage II CRC who are considered to be at high risk of disease recurrence often receive the same adjuvant chemotherapy treatment. We prospectively investigated the extent and degree of neuropathy suffered by stage III and high-risk stage II resectable CRC patients who underwent sequential approach involving 3 months of an oxaliplatin-based regimen followed by 3 months of capecitabine. Patients and methods Patients with completely resected stage III and high-risk stage II CRC aged ≥20 years were eligible. Patients were treated with folinic acid, fluorouracil, and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (CAPOX) for 3 months followed by capecitabine (2,500 mg/m2 on days 1–14 every 3 weeks) for 3 months. Primary end points were frequency and the grade of oxaliplatin-induced neurotoxicity as evaluated using the physician-based Common Terminology Criteria for Adverse Events version 4.0 (CTCAE) grading and the patient-based scale, self-reported Patient Neurotoxicity Questionnaire. Results Ninety-one patients were enrolled and 86 patients assessed. Eighty-four percent of patients completed the planned oxaliplatin-based therapy for 3 months, and 63% of patients completed all treatments for the full 6 months. Overall incidences of grade 3 or 4 peripheral sensory or motor neuropathy according to the CTCAE were 3.5% and 1.2%, respectively. Regarding the peripheral sensory neuropathy, the proportion of Patient Neurotoxicity Questionnaire (grade C–E) and CTCAE (grade 2–4) at months 1.5/3/6 were 11.3/22.1/29.4% and 5.3/4.4/11.3%, respectively (Spearman correlation coefficient: 0.47). Conclusion A sequential approach to adjuvant chemotherapy with 3 months of an oxaliplatin-based regimen followed by 3 months of capecitabine was tolerated by patients and associated with a low incidence of neuropathy. PMID:27920498

Feasibility of sequential adjuvant chemotherapy with a 3-month oxaliplatin-based regimen followed by 3 months of capecitabine in patients with stage III and high-risk stage II colorectal cancer: JSWOG-C2 study.

PubMed

Tsuruta, Atsushi; Yamashita, Kazuki; Tanioka, Hiroaki; Tsuji, Akihito; Inukai, Michio; Yamakawa, Toshiki; Yamatsuji, Tomoki; Yoshimitsu, Masanori; Toyota, Kazuhiro; Yamano, Taketoshi; Nagasaka, Takeshi; Okajima, Masazumi

2016-01-01

Six months of oxaliplatin-based chemotherapy is the standard adjuvant chemotherapy for completely resected stage III colorectal cancer (CRC). Also, patients with stage II CRC who are considered to be at high risk of disease recurrence often receive the same adjuvant chemotherapy treatment. We prospectively investigated the extent and degree of neuropathy suffered by stage III and high-risk stage II resectable CRC patients who underwent sequential approach involving 3 months of an oxaliplatin-based regimen followed by 3 months of capecitabine. Patients with completely resected stage III and high-risk stage II CRC aged ≥20 years were eligible. Patients were treated with folinic acid, fluorouracil, and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (CAPOX) for 3 months followed by capecitabine (2,500 mg/m 2 on days 1-14 every 3 weeks) for 3 months. Primary end points were frequency and the grade of oxaliplatin-induced neurotoxicity as evaluated using the physician-based Common Terminology Criteria for Adverse Events version 4.0 (CTCAE) grading and the patient-based scale, self-reported Patient Neurotoxicity Questionnaire. Ninety-one patients were enrolled and 86 patients assessed. Eighty-four percent of patients completed the planned oxaliplatin-based therapy for 3 months, and 63% of patients completed all treatments for the full 6 months. Overall incidences of grade 3 or 4 peripheral sensory or motor neuropathy according to the CTCAE were 3.5% and 1.2%, respectively. Regarding the peripheral sensory neuropathy, the proportion of Patient Neurotoxicity Questionnaire (grade C-E) and CTCAE (grade 2-4) at months 1.5/3/6 were 11.3/22.1/29.4% and 5.3/4.4/11.3%, respectively (Spearman correlation coefficient: 0.47). A sequential approach to adjuvant chemotherapy with 3 months of an oxaliplatin-based regimen followed by 3 months of capecitabine was tolerated by patients and associated with a low incidence of neuropathy.

The Carbomer-Lecithin Adjuvant Adjuplex Has Potent Immunoactivating Properties and Elicits Protective Adaptive Immunity against Influenza Virus Challenge in Mice

PubMed Central

Wegmann, Frank; Moghaddam, Amin E.; Schiffner, Torben; Gartlan, Kate H.; Powell, Timothy J.; Russell, Rebecca A.; Baart, Matthijs; Carrow, Emily W.

2015-01-01

The continued discovery and development of adjuvants for vaccine formulation are important to safely increase potency and/or reduce the antigen doses of existing vaccines and tailor the adaptive immune response to newly developed vaccines. Adjuplex is a novel adjuvant platform based on a purified lecithin and carbomer homopolymer. Here, we analyzed the adjuvant activity of Adjuplex in mice for the soluble hemagglutinin (HA) glycoprotein of influenza A virus. The titration of Adjuplex revealed an optimal dose of 1% for immunogenicity, eliciting high titers of HA-specific IgG but inducing no significant weight loss. At this dose, Adjuplex completely protected mice from an otherwise lethal influenza virus challenge and was at least as effective as the adjuvants monophosphoryl lipid A (MPL) and alum in preventing disease. Adjuplex elicited balanced Th1-/Th2-type immune responses with accompanying cytokines and triggered antigen-specific CD8+ T-cell proliferation. The use of the peritoneal inflammation model revealed that Adjuplex recruited dendritic cells (DCs), monocytes, and neutrophils in the context of innate cytokine and chemokine secretion. Adjuplex neither triggered classical maturation of DCs nor activated a pathogen recognition receptor (PRR)-expressing NF-κB reporter cell line, suggesting a mechanism of action different from that reported for classical pathogen-associated molecular pattern (PAMP)-activated innate immunity. Taken together, these data reveal Adjuplex to be a potent and well-tolerated adjuvant with application for subunit vaccines. PMID:26135973

Phase II Trial of Adjuvant Pelvic Radiation “Sandwiched” Between Combination Paclitaxel and Carboplatin in Women with Uterine Papillary Serous Carcinoma

PubMed Central

Einstein, Mark H.; Frimer, Marina; Kuo, Dennis Y-S; Reimers, Laura L.; Mehta, Keyur; Mutyala, Subhakar; Huang, Gloria S.; Hou, June Y.; Goldberg, Gary L.

2013-01-01

Objective To evaluate the safety and survival in women treated with adjuvant pelvic radiation “sandwiched” between six cycles of paclitaxel and carboplatin chemotherapy with completely resected UPSC. Methods Surgically staged women with UPSC (FIGO stage 1-4) and no visible residual disease were enrolled. Treatment involved paclitaxel (175 mg/m2) and carboplatin (AUC=6.0-7.5) every 21 days for 3 doses, followed by radiation therapy (RT), followed by an additional 3 cycles of paclitaxel and carboplatin (AUC=5-6). Survival analysis, using Kaplan-Meier methods, was performed on patients who completed at least 3 cycles of chemotherapy and RT. Results A total of 81 patients were enrolled, of which 72 patients completed the first 3 cycles of chemotherapy followed by prescribed RT. Median age was 67 years (range: 43–82 years). 59/72 (82%) had disease confined to the uterus and 13/72 (18%) had completely resected extra-uterine disease (stage 3&4). 65 (83%) completed the protocol. Overall PFS and OS for combined stage 1&2 patients was 65.5±3.6 months and 76.5±4.3 months, respectively. PFS and OS for combined stage 3&4 patients was 25.8±3.0 and 35.9±5.3 months, respectively. Three-year % survival probability for stage 1&2 patients was 84% and for stage 3&4 patients was 50%. Of the 435 chemotherapy cycles administered, there were 11(2.5%) G3/G4 non-hematologic toxicities. 26(6.0%) cycles had dose reductions and 37(8.5%) had dose delays. Conclusions Compared to prior studies of single modality adjuvant therapy, RT “sandwiched” between paclitaxel and carboplatin chemotherapy is well-tolerated and highly efficacious in women with completely resected UPSC. PMID:22035806

76 FR 44933 - Statement of Organization, Functions, and Delegations of Authority

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-27

...) Office of Equal Opportunity and Civil Rights (FCA) Office of Legislation (FCC) Office of the Actuary (FCE... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Medicare & Medicaid Services Statement of... Delegations of Authority for the Department of Health and Human Services, Centers for Medicare & Medicaid...

12 CFR 602.12 - Fees.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Fees. 602.12 Section 602.12 Banks and Banking FARM CREDIT ADMINISTRATION ADMINISTRATIVE PROVISIONS RELEASING INFORMATION FOIA Fees § 602.12 Fees. (a) FCA may charge: (1) For manual searches for records and for review, the pro rated cost of the salary...

12 CFR 607.6 - Payment of assessment.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 6 2011-01-01 2011-01-01 false Payment of assessment. 607.6 Section 607.6 Banks and Banking FARM CREDIT ADMINISTRATION ADMINISTRATIVE PROVISIONS ASSESSMENT AND APPORTIONMENT OF... scheduled in the FCA Notice of Assessment. Payment shall be made by electronic funds transfer (EFT) for...

12 CFR 607.6 - Payment of assessment.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Payment of assessment. 607.6 Section 607.6 Banks and Banking FARM CREDIT ADMINISTRATION ADMINISTRATIVE PROVISIONS ASSESSMENT AND APPORTIONMENT OF... scheduled in the FCA Notice of Assessment. Payment shall be made by electronic funds transfer (EFT) for...

77 FR 31438 - Agency Information Collection Activities: Proposed Information Collection; Submission for OMB Review

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-25

... institution regulated by the FCA (Agency-regulated institutions) who engages in the business of a residential... easily accessible information at no charge regarding the employment history of, and the publicly... (2) personal history and experience, including authorization for the Registry to obtain information...

33 CFR 209.345 - Water resource policies and authorities.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 3 2014-07-01 2014-07-01 false Water resource policies and... ARMY, DEPARTMENT OF DEFENSE ADMINISTRATIVE PROCEDURE § 209.345 Water resource policies and authorities... other Non-Federal Entities on Authorized Water Resources Projects.” (3) Section 221, FCA of 1970 (Pub. L...

Decades-Scale Degradation of Commercial, Side-Chain, Fluorotelomer-Based Polymers in Soils and Water

EPA Science Inventory

Fluorotelomer-based polymers (FTPs) are a primary product of the jluorotelomer industry, yet the role of commercial FTPs in degrading to form perjluorocarboxylic acids (P FCAs), including perjluorooctanoic acid, and P FCA precursors, remains ill-defined. Here we report on a 376-d...

Designing a definitive trial for adjuvant targeted therapy in genotype defined lung cancer: the ALCHEMIST trials.

PubMed

Alden, Ryan S; Mandrekar, Sumithra J; Oxnard, Geoffrey R

2015-09-01

Genotype-directed targeted therapies have revolutionized the treatment of metastatic non-small cell lung cancer (NSCLC) but they have not yet been comprehensively studied in the adjuvant setting. Previous trials of adjuvant targeted therapy in unselected early stage NSCLC patients showed no benefit versus placebo, however retrospective data suggests improved disease free survival (DFS) with epidermal growth factor receptor (EGFR) inhibitors in patients with appropriate molecular alterations. A definitive prospective, randomized, placebo-controlled trial of targeted therapies for NSCLC is needed to determine the efficacy of targeted therapy following surgical resection and standard adjuvant therapy. The principal challenges facing such a trial are (I) identification of actionable alterations in early stage patients; and (II) realization of sufficient enrollment to power definitive analyses. The ALCHEMIST trial (Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial) was designed to overcome these challenges. Using the national clinical trials network (NCTN) of the National Cancer Institute (NCI), several thousand patients with operable NSCLC will undergo tumor genotyping for EGFR mutations or rearrangement of anaplastic lymphoma kinase (ALK). Following resection and completion of standard adjuvant therapy, patients with EGFR-mutant NSCLC will be randomized to erlotinib versus placebo (1:1), those with ALK-rearranged NSCLC will be randomized to crizotinib versus placebo (1:1), while those not enrolled onto the adjuvant trials will continue to be followed on the screening trial. ALCHEMIST also provides for the collection of tissue at baseline and at recurrence (if available) to characterize mechanisms of recurrence and of resistance to targeted therapy. Thus, ALCHEMIST is a platform for validation of targeted therapy as part of curative care in NSCLC and creates an opportunity to advance our understanding of disease biology.

Review of Adjuvant Radiochemotherapy for Resected Pancreatic Cancer and Results From Mayo Clinic for the 5th JUCTS Symposium

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

Miller, Robert C.; Iott, Matthew J.; Corsini, Michele M.

2009-10-01

Purpose: To present an overview of Phase III trials in adjuvant therapy for pancreatic cancer and review outcomes at the Mayo Clinic after adjuvant radiochemotherapy (RT/CT) for resected pancreatic cancer. Methods and Materials: A literature review and a retrospective review of 472 patients who underwent an R0 resection for T1-3N0-1M0 invasive carcinoma of the pancreas from 1975 to 2005 at the Mayo Clinic, Rochester, MN. Patients with metastatic or unresectable disease at the time of surgery, positive surgical margins, or indolent tumors and those treated with intraoperative radiotherapy were excluded from the analysis. Median radiotherapy dose was 50.4Gy in 28more » fractions, with 98% of patients receiving concurrent 5-fluorouracil- based chemotherapy. Results: Median follow-up was 2.7 years. Median overall survival (OS) was 1.8 years. Median OS after adjuvant RT/CT was 2.1 vs. 1.6 years for surgery alone (p = 0.001). The 2-y OS was 50% vs. 39%, and 5-y was 28% vs. 17% for patients receiving RT/CT vs. surgery alone. Univariate and multivariate analysis revealed that adverse prognostic factors were positive lymph nodes (risk ratio [RR] 1.3, p < 0.001) and high histologic grade (RR 1.2, p < 0.001). T3 tumor status was found significant on univariate analysis only (RR 1.1, p = 0.07). Conclusions: Results from recent clinical trials support the use of adjuvant chemotherapy in resected pancreatic cancer. The role of radiochemotherapy in adjuvant treatment of pancreatic cancer remains a topic of debate. Results from the Mayo Clinic suggest improved outcomes after the administration of adjuvant radiochemotherapy after a complete resection of invasive pancreatic malignancies.« less

Th1 immune response to Plasmodium falciparum recombinant thrombospondin-related adhesive protein (TRAP) antigen is enhanced by TLR3-specific adjuvant, poly(I:C) in BALB/c mice.

PubMed

Mehrizi, A A; Ameri Torzani, M; Zakeri, S; Jafary Zadeh, A; Babaeekhou, L

2018-07-01

Sporozoite-based malaria vaccines have provided a gold standard for malaria vaccine development, and thrombospondin-related adhesive protein (TRAP) serves as the main vaccine candidate antigen on sporozoites. As recombinant malaria vaccine candidate antigens are poorly immunogenic, additional appropriate immunostimulants, such as an efficient adjuvant, are highly essential to modulate Th1-cell predominance and also to induce a protective and long-lived immune response. In this study, polyinosinic:polycytidylic acid [poly(I:C)], the ligand of TLR3, was considered as the potential adjuvant for vaccines targeting stronger Th1-based immune responses. For this purpose, BALB/c mice were immunized with rPfTRAP delivered in putative poly(I:C) adjuvant, and humoural and cellular immune responses were determined in different immunized mouse groups. Delivery of rPfTRAP with poly(I:C) induced high levels and titres of persisted and also high-avidity anti-rPfTRAP IgG antibodies comparable to complete Freund's adjuvant (CFA)/incomplete Freund's adjuvant (IFA) adjuvant after the second boost. In addition, rPfTRAP formulated with poly(I:C) elicited a higher ratio of IFN-γ/IL-5, IgG2a/IgG1, and IgG2b/IgG1 than with CFA/IFA, indicating that poly(I:C) supports the induction of a stronger Th1-based immune response. This is a first time study which reveals the potential of rPfTRAP delivery in poly(I:C) to increase the level, avidity and durability of both anti-PfTRAP cytophilic antibodies and Th1 cytokines. © 2018 John Wiley & Sons Ltd.

Long term effects of extended adjuvant endocrine therapy on quality of life in breast cancer patients.

PubMed

Kool, M; Fontein, D B Y; Meershoek-Klein Kranenbarg, E; Nortier, J W R; Rutgers, E J T; Marang-van de Mheen, P J; van de Velde, C J H

2015-06-01

The standard treatment for hormone-receptor positive, postmenopausal early breast cancer patients is 5 years of adjuvant endocrine therapy. Previous studies demonstrate that prolonging adjuvant endocrine therapy may improve disease-free survival. However, endocrine therapy is known for its adverse events, which may negatively affect Quality of Life (QoL). The aim of this study is to assess the impact of extended adjuvant endocrine therapy on long-term QoL outcomes. 471 patients selected from the IDEAL trial were invited to complete a questionnaire 1-1.5 years after starting with extended therapy. The questionnaire consisted of the EORTC QLQ-C30 and QLQ-BR23 questionnaires. Mean QoL outcomes were compared with EORTC reference values for stage I and II breast cancer patients and the general population. Furthermore, QoL outcomes were compared between different treatment regimens. A difference of eight points was considered clinically relevant. IDEAL patients receiving extended adjuvant endocrine therapy have significantly and clinically relevant better global QoL compared with reference values for stage I and II breast cancer patients (79.6 versus 64.6; p < 0.01) and the general population (79.6 versus 71.2; p < 0.01). Similar results were found for emotional function, pain, appetite loss, diarrhea and financial problems. Between treatment regimens prior to extended adjuvant endocrine therapy, differences were only found on specific QoL domains (e.g. arm symptoms). Breast cancer patients on extended adjuvant endocrine therapy have significantly and clinically relevant better global QoL compared with other stage I-II breast cancer patients and the general population, 6-8.5 years after diagnosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Randomized feasibility study of S-1 for adjuvant chemotherapy in completely resected Stage IA non-small-cell lung cancer: results of the Setouchi Lung Cancer Group Study 0701.

PubMed

Soh, Junichi; Okumura, Norihito; Nakata, Masao; Nakamura, Hiroshige; Fukuda, Minoru; Kataoka, Masafumi; Kajiwara, Shinsuke; Sano, Yoshifumi; Aoe, Motoi; Kataoka, Kazuhiko; Hotta, Katsuyuki; Matsuo, Keitaro; Toyooka, Shinichi; Date, Hiroshi

2016-08-01

The aim of this multicenter study was to determine the appropriate administration schedule for S-1, an oral fluoropyrimidine, for adjuvant chemotherapy in patients with completely resected pathological-Stage IA (tumor diameter, 2-3 cm) non-small-cell lung cancer. Patients were randomly assigned to receive adjuvant chemotherapy consisting of either the 4-week oral administration of S-1 (80-120 mg/body/day) followed by a 2-week rest (Group A), or the 2-week oral administration of S-1 (80-120 mg/body/day) followed by a 1-week rest (Group B). The duration of adjuvant chemotherapy was 1 year in both arms. The primary endpoint was compliance, namely drug discontinuation-free survival, which was calculated using the Kaplan-Meier method with log-rank test. Eighty patients were enrolled in this study, and 76 patients actually received S-1 treatment. The drug discontinuation-free survival rates at 1 year were 49.1% in Group A and 52.7% in Group B (P = 0.373). The means of the relative dose intensities were 55.3% in Group A and 64.6% in Group B (P = 0.237). There were no treatment-related deaths. Patients with grade 3/4 toxicities were significantly more frequent in Group A (40.5%) than in Group B (15.4%, P = 0.021). The 2-year relapse-free survival rates were 97.5% in Group A and 92.5% in Group B, and the 2-year overall survival rates were 100% in both groups. The feasibility showed no significant difference between the two groups among patients with completely resected Stage IA (tumor diameter, 2-3 cm) non-small-cell lung cancer. © The Author 2016. Published by Oxford University Press.

The 2017 complete overhaul of adjuvant therapies for high-risk melanoma and its consequences for staging and management of melanoma patients.

PubMed

Eggermont, Alexander M M; Dummer, Reinhard

2017-11-01

The spectacular outcomes of the phase III trials regarding nivolumab versus ipilimumab in fully resected stage IIIB/C-IV and of the combination of dabrafenib (D) plus trametinib (T) in BRAF-mutant stage III patients demonstrate that effective treatments in advanced melanoma are also highly effective in the adjuvant setting. In 2016, an overall survival benefit with adjuvant high-dose ipilimumab was demonstrated, and the European Organisation for Research and Treatment of Cancer trial 1325 comparing pembrolizumab versus placebo will complete the picture in the early 2018. Toxicity profiles are in line with the experience in advanced melanoma, i.e. favourable for the anti-PD1 agents and for D + T and problematic for ipilimumab. The 2017 outcomes are practice changing and put an end to the use of interferon (IFN) and ipilimumab. In countries with only access to IFN, its use can be restricted to patients with ulcerated melanoma, based on the individual patient data meta-analysis recently published. Because of the results of the Melanoma Sentinel Lymph node Trial-2 (MSLT-2) trial, completion lymph node dissection (CLND) will decrease sharply, leading to a lack of optimal prognostic information. Prognosis in sentinel node-positive stage IIIA/B patients is extremely heterogeneous with 5-year survival rates varying from 90% to 40% and depends mostly on the number of positive nodes identified by CLND. This information is crucial for clinical decision-making. How to guarantee optimal staging information needs to be discussed urgently. Further improvements of adjuvant therapies will have to address all these questions as well as the exploration of neoadjuvant use of active drugs and combination approaches. Important paradigm shifts in the management of high-risk melanoma patients are upon us. Copyright © 2017 Elsevier Ltd. All rights reserved.

Recirculant hyperthermic IntraVEsical chemotherapy (HIVEC) in intermediate-high-risk non-muscle-invasive bladder cancer.

PubMed

Sousa, Alejandro; Piñeiro, Idelfonso; Rodríguez, Silvia; Aparici, Vicente; Monserrat, Victor; Neira, Pilar; Carro, Enrique; Murias, Cármen; Uribarri, Carlos

2016-06-01

Purpose To examine the effectiveness of hyperthermic intravesical chemotherapy (HIVEC™) with mitomycin-C (MMC) for patients with intermediate-high-risk non-muscle invasive bladder cancer (NMIBC). Materials and methods From November 2010 to April 2015, 40 patients with intermediate-high-risk NMIBC received HIVEC™ treatment with a Combat BRS system. Of these patients, 24 received neoadjuvant HIVEC™ treatment (eight weekly instillations) before a transurethral resection of the bladder (TURBT) and 16 received adjuvant HIVEC™ treatment post-TURBT (four instillations weekly + six monthly). The pathological response of each tumour was evaluated after the neoadjuvant treatment. Recurrence rates and adverse effects were evaluated in both groups. Results A total of 40 patients completed the induction therapy: 24 patients received the Neoadjuvant HIVEC™ treatment. Of these patients, 15 (62.5%) showed a complete response. Eight patients (33.3%) showed a partial response, and one patient (4.1%) showed no response at all. The 4-year cumulative incidence of recurrence was 20.8%. The adjuvant HIVEC™ treatment was given to 16 patients. The 2-year cumulative incidence of recurrence was 12.5% for this group. The incidence and severity of side effects were slightly lower in the adjuvant group than in the neoadjuvant group. However, the difference was not statistically significant (p < 0.3). Most of the side effects were low grade and had virtually no effect on the treatment plan, and 97% of patients completed all of the HIVEC™ instillations scheduled. Conclusions The recirculation of hyperthermic MMC using Combat's HIVEC™ treatment is safe and effective and is capable of achieving good success rates in both neoadjuvant and adjuvant settings. This treatment seems to be appropriate for NMIBC intermediate-high-risk patients who cannot tolerate or have contraindications for standard BCG therapy or in cases in which there are supply issues or shortages of BCG.

Adjuvant Radiation Therapy Treatment Time Impacts Overall Survival in Gastric Cancer

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

McMillan, Matthew T.; Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; Ojerholm, Eric

Purpose: Prolonged radiation therapy treatment time (RTT) is associated with worse survival in several tumor types. This study investigated whether delays during adjuvant radiation therapy impact overall survival (OS) in gastric cancer. Methods and Materials: The National Cancer Data Base was queried for patients with resected gastric cancer who received adjuvant radiation therapy with National Comprehensive Cancer Network–recommended doses (45 or 50.4 Gy) between 1998 and 2006. RTT was classified as standard (45 Gy: 33-36 days, 50.4 Gy: 38-41 days) or prolonged (45 Gy: >36 days, 50.4 Gy: >41 days). Cox proportional hazards models evaluated the association between the following factors and OS: RTT, interval from surgery to radiationmore » therapy initiation, interval from surgery to radiation therapy completion, radiation therapy dose, demographic/pathologic and operative factors, and other elements of adjuvant multimodality therapy. Results: Of 1591 patients, RTT was delayed in 732 (46%). Factors associated with prolonged RTT were non-private health insurance (OR 1.3, P=.005) and treatment at non-academic facilities (OR 1.2, P=.045). Median OS and 5-year actuarial survival were significantly worse in patients with prolonged RTT compared with standard RTT (36 vs 51 months, P=.001; 39 vs 47%, P=.005); OS worsened with each cumulative week of delay (P<.0004). On multivariable analysis, prolonged RTT was associated with inferior OS (hazard ratio 1.2, P=.002); the intervals from surgery to radiation therapy initiation or completion were not. Prolonged RTT was particularly detrimental in patients with node positivity, inadequate nodal staging (<15 nodes examined), and those undergoing a cycle of chemotherapy before chemoradiation therapy. Conclusions: Delays during adjuvant radiation therapy appear to negatively impact survival in gastric cancer. Efforts to minimize cumulative interruptions to <7 days should be considered.« less

Intranasal and sublingual delivery of inactivated polio vaccine.

PubMed

Kraan, Heleen; Soema, Peter; Amorij, Jean-Pierre; Kersten, Gideon

2017-05-09

Polio is on the brink of eradication. Improved inactivated polio vaccines (IPV) are needed towards complete eradication and for the use in the period thereafter. Vaccination via mucosal surfaces has important potential advantages over intramuscular injection using conventional needle and syringe, the currently used delivery method for IPV. One of them is the ability to induce both serum and mucosal immune responses: the latter may provide protection at the port of virus entry. The current study evaluated the possibilities of polio vaccination via mucosal surfaces using IPV based on attenuated Sabin strains. Mice received three immunizations with trivalent sIPV via intramuscular injection, or via the intranasal or sublingual route. The need of an adjuvant for the mucosal routes was investigated as well, by testing sIPV in combination with the mucosal adjuvant cholera toxin. Both intranasal and sublingual sIPV immunization induced systemic polio-specific serum IgG in mice that were functional as measured by poliovirus neutralization. Intranasal administration of sIPV plus adjuvant induced significant higher systemic poliovirus type 3 neutralizing antibody titers than sIPV delivered via the intramuscular route. Moreover, mucosal sIPV delivery elicited polio-specific IgA titers at different mucosal sites (IgA in saliva, fecal extracts and intestinal tissue) and IgA-producing B-cells in the spleen, where conventional intramuscular vaccination was unable to do so. However, it is likely that a mucosal adjuvant is required for sublingual vaccination. Further research on polio vaccination via sublingual mucosal route should include the search for safe and effective adjuvants, and the development of novel oral dosage forms that improve antigen uptake by oral mucosa, thereby increasing vaccine immunogenicity. This study indicates that both the intranasal and sublingual routes might be valuable approaches for use in routine vaccination or outbreak control in the period after complete OPV cessation and post-polio eradication. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Circulating ESR1 mutations at the end of aromatase inhibitor adjuvant treatment and after relapse in breast cancer patients.

PubMed

Allouchery, Violette; Beaussire, Ludivine; Perdrix, Anne; Sefrioui, David; Augusto, Laetitia; Guillemet, Cécile; Sarafan-Vasseur, Nasrin; Di Fiore, Frédéric; Clatot, Florian

2018-05-16

Detection of circulating ESR1 mutations is associated with acquired resistance to aromatase inhibitor (AI) in metastatic breast cancer. Until now, the presence of circulating ESR1 mutations at the end of adjuvant treatment by AI in early breast cancer had never been clearly established. In this context, the aim of the present study was to evaluate the circulating ESR1 mutation frequency at the end of adjuvant treatment and after relapse. This monocentric retrospective study was based on available stored plasmas and included all early breast cancer patients who completed at least 2 years of AI adjuvant treatment and experienced a documented relapse after the end of their treatment. Circulating ESR1 mutations (D538G, Y537S/N/C) were assessed by droplet digital PCR in plasma samples taken at the end of adjuvant treatment, at time of relapse and at time of progression under first line metastatic treatment. A total of 42 patients were included, with a median adjuvant AI exposure of 60 months (range 41-85). No circulating ESR1 mutation was detectable at the end of AI adjuvant therapy. At first relapse, 5.3% of the patients (2/38) had a detectable circulating ESR1 mutation. At time of progression on first-line metastatic treatment, 33% of the patients (7/21) under AI had a detectable circulating ESR1 mutation compared to none of the patients under chemotherapy (0/10). The two patients with a detectable ESR1 mutation at relapse were treated by AI and had an increase of their variant allele fraction at time of progression on first-line metastatic treatment. Circulating ESR1 mutation detection at the end of AI-based adjuvant treatment is not clinically useful. Circulating ESR1 mutation could be assessed as soon as first relapse to guide interventional studies.

An Eimeria vaccine candidate based on Eimeria tenella immune mapped protein 1 and the TLR-5 agonist Salmonella typhimurium FliC flagellin

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

Yin, Guangwen; Qin, Mei; Liu, Xianyong

Highlights: •We found a new protective protein – (IMPI) in Eimeria tenella. •EtIMP1-flagellin fusion protein is an effective immunogen against Eimeria infection. •Flagellin can be as an apicomplexan parasite vaccine adjuvant in chickens. -- Abstract: Immune mapped protein-1 (IMP1) is a new protective protein in apicomplexan parasites, and exits in Eimeria tenella. But its structure and immunogenicity in E. tenella are still unknown. In this study, IMPI in E. tenella was predicted to be a membrane protein. To evaluate immunogenicity of IMPI in E. tenella, a chimeric subunit vaccine consisting of E. tenella IMP1 (EtIMP1) and a molecular adjuvant (amore » truncated flagellin, FliC) was constructed and over-expressed in Escherichia coli and its efficacy against E. tenella infection was evaluated. Three-week-old AA broiler chickens were vaccinated with the recombinant EtIMP1-truncated FliC without adjuvant or EtIMP1 with Freund’s Complete Adjuvant. Immunization of chickens with the recombinant EtIMP1-truncated FliC fusion protein resulted in stronger cellular immune responses than immunization with only recombinant EtIMP1 with adjuvant. The clinical effect of the EtIMP1-truncated FliC without adjuvant was also greater than that of the EtIMP1 with adjuvant, which was evidenced by the differences between the two groups in body weight gain, oocyst output and caecal lesions of E. tenella-challenged chickens. The results suggested that the EtIMP1-flagellin fusion protein can be used as an effective immunogen in the development of subunit vaccines against Eimeria infection. This is the first demonstration of antigen-specific protective immunity against avian coccidiosis using a recombinant flagellin as an apicomplexan parasite vaccine adjuvant in chickens.« less

The recombinant gut-associated M17 leucine aminopeptidase in combination with different adjuvants confers a high level of protection against Fasciola hepatica infection in sheep.

PubMed

Maggioli, Gabriela; Acosta, Daniel; Silveira, Fernando; Rossi, Silvina; Giacaman, Sheila; Basika, Tatiana; Gayo, Valeria; Rosadilla, Diego; Roche, Leda; Tort, José; Carmona, Carlos

2011-11-08

Fasciola hepatica M17 leucine aminopeptidase (FhLAP) is thought to play a role in catabolizing peptides generated by the concerted activity of gut-associated endopeptidases on host polypeptides, thus releasing amino acids to be used in protein anabolism. In this study, a recombinant functional form of this homo hexameric metallopeptidase produced in Escherichia coli was used in combination with adjuvants of different types in a vaccination trial in Corriedale sheep against experimental challenge with F. hepatica metacercariae. The experimental assay consisted of 6 groups of 10 animals; 5 of the groups (1-5) were subcutaneously inoculated at weeks 0 and 4 with 100 μg of rFhLAP mixed with Freund's complete plus incomplete adjuvant (group 1), Alum (group 2), Adyuvac 50 (group 3), DEAE-D (group 4) and Ribi (group 5); the adjuvant control group (group 6) received Freund's adjuvant. Two weeks after the booster, the sheep were orally challenged with 200 metacercariae. Immunization with rFhLAP induced significant reduction in fluke burdens in all vaccinated groups: 83.8% in the Freund's group, 86.7% in the Alum group, 74.4% in the Adyuvac 50 group, 49.8% in the Ribi group and 49.5% in the DEAE-D group compared to the adjuvant control group. Morphometric analysis of recovered liver flukes showed no significant size modifications in the different vaccination groups. All vaccine preparations elicited specific IgG, IgG1 and IgG2 responses. This study shows that a liver fluke vaccine based on rFhLAP combined with different adjuvants significantly reduced worm burden in a ruminant species that was high in animals that received the enzyme along with the commercially approved adjuvants Alum and Adyuvac 50. Copyright © 2011 Elsevier Ltd. All rights reserved.

Adjuvant Lapatinib and Trastuzumab for Early Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: Results From the Randomized Phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Trial

PubMed Central

Holmes, Eileen; Baselga, José; de Azambuja, Evandro; Dueck, Amylou C.; Viale, Giuseppe; Zujewski, Jo Anne; Goldhirsch, Aron; Armour, Alison; Pritchard, Kathleen I.; McCullough, Ann E.; Dolci, Stella; McFadden, Eleanor; Holmes, Andrew P.; Tonghua, Liu; Eidtmann, Holger; Dinh, Phuong; Di Cosimo, Serena; Harbeck, Nadia; Tjulandin, Sergei; Im, Young-Hyuck; Huang, Chiun-Sheng; Diéras, Véronique; Hillman, David W.; Wolff, Antonio C.; Jackisch, Christian; Lang, Istvan; Untch, Michael; Smith, Ian; Boyle, Frances; Xu, Binghe; Gomez, Henry; Suter, Thomas; Gelber, Richard D.; Perez, Edith A.

2016-01-01

Background Lapatinib (L) plus trastuzumab (T) improves outcomes for metastatic human epidermal growth factor 2–positive breast cancer and increases the pathologic complete response in the neoadjuvant setting, but their role as adjuvant therapy remains uncertain. Methods In the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial, patients with centrally confirmed human epidermal growth factor 2–positive early breast cancer were randomly assigned to 1 year of adjuvant therapy with T, L, their sequence (T→L), or their combination (L+T). The primary end point was disease-free survival (DFS), with 850 events required for 80% power to detect a hazard ratio (HR) of 0.8 for L+T versus T. Results Between June 2007 and July 2011, 8,381 patients were enrolled. In 2011, due to futility to demonstrate noninferiority of L versus T, the L arm was closed, and patients free of disease were offered adjuvant T. A protocol modification required P ≤ .025 for the two remaining pairwise comparisons. At a protocol-specified analysis with a median follow-up of 4.5 years, a 16% reduction in the DFS hazard rate was observed with L+T compared with T (555 DFS events; HR, 0.84; 97.5% CI, 0.70 to 1.02; P = .048), and a 4% reduction was observed with T→L compared with T (HR, 0.96; 97.5% CI, 0.80 to 1.15; P = .61). L-treated patients experienced more diarrhea, cutaneous rash, and hepatic toxicity compared with T-treated patients. The incidence of cardiac toxicity was low in all treatment arms. Conclusion Adjuvant treatment that includes L did not significantly improve DFS compared with T alone and added toxicity. One year of adjuvant T remains standard of care. PMID:26598744

Comparison of capecitabine and oxaliplatin with S-1 as adjuvant chemotherapy in stage III gastric cancer after D2 gastrectomy.

PubMed

Cho, Jang Ho; Lim, Jae Yun; Cho, Jae Yong

2017-01-01

To compare capecitabine and oxaliplatin (XELOX) with S-1 as adjuvant chemotherapy in stage III gastric cancer after D2 gastrectomy. Clinical data from 206 patients who received XELOX or S-1 regimens as adjuvant chemotherapy in stage III gastric cancer were collected. Patients were divided into 2 groups according to regimen; the groups were XELOX (n = 114) and S-1 monotherapy (n = 92). 3-year disease-free survival (DFS) was higher in the S-1 group than in the XELOX group (66.6% vs 59.1%; p = 0.636). 3-year overall survival (OS) was 75.6% in the S-1 group and 69.6% in the XELOX group (p = 0.495). But, the difference was not statistically significant. Especially, for patients with stage IIIC disease, 3-year overall survival was 55.2% in the XELOX group and 39.0% in the S-1 group (hazard ratio, HR 0.50, 95% confidence interval, CI 0.23-1.10; p = 0.075). In multivariate analysis, N stage (HR, 5.639; 95% CI, 1.297-24.522; p = 0.021) and cycle completion as planned (HR, 5.734; 95% CI, 3.007-10.936; p<0.001) were independent predictors of overall survival. Adjuvant XELOX and S-1 regimen did not prove anything superior for stage III gastric cancer in this study. But, XELOX had a tendency to be superior to S-1 in stage IIIC gastric cancer after D2 gastrectomy although the difference was not statistically significant. N stage and cycle completion as planned were prognostic factors.

Preoperative chemotherapy for operable breast cancer is associated with better compliance with adjuvant therapy in matched stage II and IIIA patients.

PubMed

Komenaka, Ian K; Hsu, Chiu-Hsieh; Martinez, Maria Elena; Bouton, Marcia E; Low, Boo Ghee; Salganick, Jason A; Nodora, Jesse; Hibbard, Michael L; Jha, Chandra

2011-01-01

Preoperative chemotherapy (PC) for operable breast cancer has shown significant benefits in prospective trials. Many patients are treated in the community setting and some may question the applicability of PC outside the university setting. Retrospective review was performed of stage II and IIIA breast cancer patients treated from January 2002 to July 2009. Fifty-three of 57 patients who underwent PC were matched based on age, tumor size, and hormone receptor status with 53 patients who did not undergo PC. Differences in patient compliance with physician recommendations for all types of adjuvant therapy were evaluated. Crude odds ratios and adjusted odds ratios derived from conditional logistic regression models were calculated. There were 106 patients included. Patient compliance with chemotherapy was better in the PC group than in the adjuvant chemotherapy (AC) group (100% versus 70%; p = .0001). Similarly, more patients in the PC group completed radiation therapy (96% versus 65%; p = .0003) and initiated hormonal therapy (100% versus 62%; p = .0001). Conditional logistic regression revealed that higher pathologic stage and current cigarette smoking were associated with poorer compliance with chemotherapy. For radiation therapy, the univariate model revealed that compliance with chemotherapy and being employed were associated with completion of radiation, whereas current cigarette smoking and larger pathologic size were associated with poorer compliance with radiation. For hormonal therapy, current cigarette smokers were more likely to be noncompliant with initiation of hormonal therapy. PC for operable breast cancer can improve patient compliance with chemotherapy. Current cigarette smokers were more likely to be noncompliant with all types of adjuvant therapy.

[Neoadjuvant Radiochemotherapy Followed by Curative Resection in Patients with Advanced Non-Small Cell Lung Cancer in Stage IIIA/IIIB: Prognostic Factors and Results].

PubMed

Schreiner, W; Dudek, W; Lettmaier, S; Gavrychenkova, S; Rieker, R; Fietkau, R; Sirbu, H

2016-06-01

The role of surgical lung resection following neo-adjuvant radio-chemotherapy (RCT) in patients with locally advanced non-small cell lung cancer (NSCLC) is yet not clearly defined. The aim of our study was to analyze the postoperative survival and to identify relevant prognostic factors. 46 patients underwent curative resections after neo-adjuvant RCT for locally advanced NSCLC (IIIA/IIIB) between February 2008 and February 2015. A retrospective data analysis regarding preoperative regression status, perioperative mortality, postoperative survival, patho-histological remission, relapse pattern and other prognostic factors was performed. A neo-adjuvant RCT with a median radiation dose of 50.4 [range, 45-60] Gy was performed in 44 (96 %) patients. Partial and/or complete regression was observed in 32 (70 %) patients. R0-resection was achieved in 44 (96 %) patients. The 30-day mortality was 4 % and the perioperative morbidity was 37 %. The overall and progression free 5-year survival rate was 47 % and respectively 45 % [in median 58 months]. The 5-year survival rate of 64 % in the "responder"-group was significantly better when compared with 24 % in the "non-responder"-group (p = 0.038). The tri-modality therapy improved the prognosis in patients with locally advanced NSCLC (stage IIIA/IIIB). The complete patho-histological remission is an important prognostic factor for better long term survival. Dividing the patients in "responder" and "non-responder" after neo-adjuvant RCT may have large therapeutically consequences in the future. Georg Thieme Verlag KG Stuttgart · New York.

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

Douillard, Jean-Yves; Rosell, Rafael; De Lena, Mario

Purpose: To study the impact of postoperative radiation therapy (PORT) on survival in the Adjuvant Navelbine International Trialist Association (ANITA) randomized study of adjuvant chemotherapy. Methods and Materials: ANITA is a randomized trial of adjuvant cisplatin and vinorelbine chemotherapy vs. observation in completely resected non-small-cell lung carcinoma (NSCLC) Stages IB to IIIA. Use of PORT was recommended for pN+ disease but was not randomized or mandatory. Each center decided whether to use PORT before initiation of the study. We describe here the survival of patients with and without PORT within each treatment group of ANITA. No statistical comparison of survivalmore » was performed because this was an unplanned subgroup analysis. Results: Overall, 232 of 840 patients received PORT (33.3% in the observation arm and 21.6% in the chemotherapy arm). In univariate analysis, PORT had a deleterious effect on the overall population survival. Patients with pN1 disease had an improved survival from PORT in the observation arm (median survival [MS] 25.9 vs. 50.2 months), whereas PORT had a detrimental effect in the chemotherapy group (MS 93.6 months and 46.6 months). In contrast, survival was improved in patients with pN2 disease who received PORT, both in the chemotherapy (MS 23.8 vs. 47.4 months) and observation arm (median 12.7 vs. 22.7 months). Conclusion: This retrospective evaluation suggests a positive effect of PORT in pN2 disease and a negative effect on pN1 disease when patients received adjuvant chemotherapy. The results support further evaluation of PORT in prospectively randomized studies in completely resected pN2 NSCLC.« less

Pilot study of postoperative adjuvant chemoradiation for advanced gastric cancer: Adjuvant 5-FU/cisplatin and chemoradiation with capecitabine

PubMed Central

Lee, Hyung-Sik; Choi, Youngmin; Hur, Won-Joo; Kim, Hyo-Jin; Kwon, Hyuk-Chan; Kim, Sung-Hyun; Kim, Jae-Seok; Lee, Jong-Hoon; Jung, Ghap-Joong; Kim, Min-Chan

2006-01-01

AIM: To evaluate the efficacy and toxicity of postoperative chemoradiation using FP chemotherapy and oral capecitabine during radiation for advanced gastric cancer following curative resection. METHODS: Thirty-one patients who had underwent a potentially curative resection for Stage III and IV (M0) gastric cancer were enrolled. Therapy consists of one cycle of FP (continuous infusion of 5-FU 1000 mg/m2 on d 1 to 5 and cisplatin 60 mg/m2 on d 1) followed by 4500 cGy (180 cGy/d) with capecitabine (1650 mg/m2 daily throughout radiotherapy). Four wk after completion of the radiotherapy, patients received three additional cycles of FP every three wk. The median follow-up duration was 22.2 mo. RESULTS: The 3-year disease free and overall survival in this study were 82.7% and 83.4%, respectively. Four patients (12.9%) showed relapse during follow-up. Eight patients did not complete all planned adjuvant therapy. Grade 3/4 toxicities included neutropenia in 50.2%, anemia in 12.9%, thrombocytopenia in 3.2% and nausea/vomiting in 3.2%. Neither grade 3/4 hand foot syndrome nor treatment related febrile neutropenia or death were observed. CONCLUSION: These preliminary results suggest that this postoperative adjuvant chemoradiation regimen of FP before and after capecitabine and concurrent radiotherapy appears well tolerated and offers a comparable toxicity profile to the chemoradiation regimen utilized in INT-0116. This treatment modality allowed successful loco-regional control rate and 3-year overall survival. PMID:16489675

Phase III trial comparing 3-6 months of adjuvant FOLFOX4/XELOX in stage II-III colon cancer: safety and compliance in the TOSCA trial.

PubMed

Lonardi, S; Sobrero, A; Rosati, G; Di Bartolomeo, M; Ronzoni, M; Aprile, G; Massida, B; Scartozzi, M; Banzi, M; Zampino, M G; Pasini, F; Marchetti, P; Cantore, M; Zaniboni, A; Rimassa, L; Ciuffreda, L; Ferrari, D; Barni, S; Zagonel, V; Maiello, E; Rulli, E; Labianca, R

2016-11-01

Six months of oxaliplatin-based adjuvant chemotherapy is standard of care for radically resected stage III colon cancer and an accepted option for high-risk stage II. A shorter duration of therapy, if equally efficacious, would be advantageous for patients and Health-Care Systems. TOSCA ['Randomized trial investigating the role of FOLFOX-4 or XELOX (3 versus 6 months) regimen duration and bevacizumab as adjuvant therapy for patients with stage II/III colon cancer] is an open-label, phase III, multicenter, noninferiority trial randomizing patients with high-risk stage II or stage III radically resected colon cancer to receive 3 months (arm 3 m) versus 6 months (arm 6 m) of FOLFOX4/XELOX. Primary end-point was relapse-free survival. We present here safety and compliance data. From June 2007 to March 2013, 3759 patients were accrued from 130 Italian sites, 64% receiving FOLFOX4 and 36% XELOX in either arm. Treatment completion rate without any modification was 35% versus 12% and with delays or dose reduction 52% versus 44% in arm 3 and 6 m. Treatment was permanently discontinued in 8% (arm 3 m) and 33% (arm 6 m). In arm 6 m, 50% of patients discontinuing treatment did so after completing 80% of planned program. Grade 3+ toxicities were higher in arm 6 m than that in 3 m. Grade 2+ neuropathy was 31.2% versus 8.8% (P < 0.0001) while grade 3+ was 8.4 versus 1.3 (P < 0.0001), in arm 3 and 6 m. Seven deaths within 30 days from last treatment administration in arm 6 m and three deaths in arm 3 m were observed (0.3% versus 0.1%, P = 0.34). TOSCA is the first trial comparing 3 versus 6 months of adjuvant chemotherapy completing accrual within the international initiative of treatment duration evaluation (International Duration Evaluation of Adjuvant, IDEA). High compliance to treatment in control arm will allow a correct assessment of potential differences between the two treatment durations. NCT00646607. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Systemic targeted therapy for her2-positive early female breast cancer: a systematic review of the evidence for the 2014 Cancer Care Ontario systemic therapy guideline.

PubMed

Mates, M; Fletcher, G G; Freedman, O C; Eisen, A; Gandhi, S; Trudeau, M E; Dent, S F

2015-03-01

This systematic review addresses the question "What is the optimal targeted therapy for female patients with early-stage human epidermal growth factor receptor 2 (her2)-positive breast cancer?" The medline and embase databases were searched for the period January 2008 to May 2014. The Standards and Guidelines Evidence directory of cancer guidelines and the Web sites of major guideline organizations were also searched. Sixty publications relevant to the targeted therapy portion of the systematic review were identified. In four major trials (hera, National Surgical Adjuvant Breast and Bowel Project B-31, North Central Cancer Treatment Group N9831, and Breast Cancer International Research Group 006), adjuvant trastuzumab for 1 year was superior in disease-free survival (dfs) and overall survival (os) to no trastuzumab; trastuzumab showed no benefit in one trial (pacs 04). A shorter duration of trastuzumab (less than 1 year compared with 1 year) was evaluated, with mixed results for dfs: one trial showed superiority (finher), one trial could not demonstrate noninferiority (phare), another trial showed equivalent results (E 2198), and one trial is still ongoing (persephone). Longer trastuzumab duration (hera: 2 years vs. 1 year) showed no improvement in dfs or os and a higher rate of cardiac events. Newer her2-targeted agents (lapatinib, pertuzumab, T-DM1, neratinib) have been or are still being evaluated in both adjuvant and neoadjuvant trials, either by direct comparison with trastuzumab alone or combined with trastuzumab. In the neoadjuvant setting (neoaltto, GeparQuinto, Neosphere), trastuzumab alone or in combination with another anti-her2 agent (lapatinib, pertuzumab) was compared with either lapatinib or pertuzumab alone and showed superior or equivalent rates of pathologic complete response. In the adjuvant setting, lapatinib alone or in combination with trastuzumab, compared with trastuzumab alone (altto) or with placebo (teach), was not superior in dfs. The results of the completed aphinity trial, evaluating the role of dual her2 blockade with trastuzumab and pertuzumab, are highly anticipated. Ongoing trials are evaluating trastuzumab as a single agent without adjuvant chemotherapy (respect) and in patients with low her2 expression (National Surgical Adjuvant Breast and Bowel Project B-47). Taking into consideration disease characteristics and patient preference, 1 year of trastuzumab should be offered to all patients with her2-positive breast cancer who are receiving adjuvant chemotherapy. Cardiac function should be regularly assessed in this patient population.

Systemic targeted therapy for her2-positive early female breast cancer: a systematic review of the evidence for the 2014 Cancer Care Ontario systemic therapy guideline

PubMed Central

Mates, M.; Fletcher, G.G.; Freedman, O.C.; Eisen, A.; Gandhi, S.; Trudeau, M.E.; Dent, S.F.

2015-01-01

Background This systematic review addresses the question “What is the optimal targeted therapy for female patients with early-stage human epidermal growth factor receptor 2 (her2)–positive breast cancer?” Methods The medline and embase databases were searched for the period January 2008 to May 2014. The Standards and Guidelines Evidence directory of cancer guidelines and the Web sites of major guideline organizations were also searched. Results Sixty publications relevant to the targeted therapy portion of the systematic review were identified. In four major trials (hera, National Surgical Adjuvant Breast and Bowel Project B-31, North Central Cancer Treatment Group N9831, and Breast Cancer International Research Group 006), adjuvant trastuzumab for 1 year was superior in disease-free survival (dfs) and overall survival (os) to no trastuzumab; trastuzumab showed no benefit in one trial (pacs 04). A shorter duration of trastuzumab (less than 1 year compared with 1 year) was evaluated, with mixed results for dfs: one trial showed superiority (finher), one trial could not demonstrate noninferiority (phare), another trial showed equivalent results (E 2198), and one trial is still ongoing (persephone). Longer trastuzumab duration (hera: 2 years vs. 1 year) showed no improvement in dfs or os and a higher rate of cardiac events. Newer her2-targeted agents (lapatinib, pertuzumab, T-DM1, neratinib) have been or are still being evaluated in both adjuvant and neoadjuvant trials, either by direct comparison with trastuzumab alone or combined with trastuzumab. In the neoadjuvant setting (neoaltto, GeparQuinto, Neosphere), trastuzumab alone or in combination with another anti-her2 agent (lapatinib, pertuzumab) was compared with either lapatinib or pertuzumab alone and showed superior or equivalent rates of pathologic complete response. In the adjuvant setting, lapatinib alone or in combination with trastuzumab, compared with trastuzumab alone (altto) or with placebo (teach), was not superior in dfs. The results of the completed aphinity trial, evaluating the role of dual her2 blockade with trastuzumab and pertuzumab, are highly anticipated. Ongoing trials are evaluating trastuzumab as a single agent without adjuvant chemotherapy (respect) and in patients with low her2 expression (National Surgical Adjuvant Breast and Bowel Project B-47). Conclusions Taking into consideration disease characteristics and patient preference, 1 year of trastuzumab should be offered to all patients with her2-positive breast cancer who are receiving adjuvant chemotherapy. Cardiac function should be regularly assessed in this patient population. PMID:25848335

Factors Predictive of Receiving Adjuvant Radiotherapy in High-Intermediate-Risk Stage I Endometrial Cancer.

PubMed

McGunigal, Mary; Pollock, Ariel; Doucette, John T; Liu, Jerry; Chadha, Manjeet; Kalir, Tamara; Gupta, Vishal

2018-06-01

Randomized trials have shown a local control benefit with adjuvant radiotherapy (RT) in high-intermediate-risk endometrial cancer patients, although not all such patients receive RT. We reviewed the National Cancer Data Base to investigate which patient/tumor-related factors are associated with delivery of adjuvant RT. The National Cancer Data Base was queried for patients diagnosed with International Federation of Gynecology and Obstetrics 2009 stage I endometrioid adenocarcinoma from 1998 to 2012 who underwent surgery +/- adjuvant RT. Exclusion criteria were unknown stage/grade, nonsurgical primary therapy, less than 30 days' follow-up, RT of more than 6 months after surgery, or palliative treatment. High-intermediate risk was defined based on Post Operative Radiation Therapy in Endometrial Carcinoma 2 criteria: older than 60 years with stage IA grade 3 or stage IB grade 1-2. Seventeen thousand five hundred twenty-four met inclusion criteria, and the 13,651 patients with complete data were subjected to a multiple logistic regression analysis; 7814 (57.2%) received surgery alone, and 5837 (42.8%) received surgery + RT. Receipt of adjuvant RT was more likely among black women and women with higher income, Northeastern residence, diagnosis after 2010, greater than 50% myometrial invasion, and receipt of adjuvant chemotherapy (P < 0.05). Patients older than 80 years or those undergoing lymph node dissection were less likely to receive adjuvant RT (P < 0.05). Of those treated with RT, 44.0% received external beam therapy, 54.8% received vaginal cuff brachytherapy, and 0.6% received both. Among irradiated women, patients older than 80 years and those with Northeastern residence, treatment at academic facilities, diagnosis after 2004, and lymph node dissection were more likely to undergo brachytherapy over external beam radiation therapy (P < 0.05). Overall use of adjuvant RT was 28.8% between 1998 and 2004, 42.0% between 2005 and 2010, and 43.4% between 2011 and 2012; the difference between 1998-2004 and 2005-2010 was not statistically significant. Fewer than half of patients with high-intermediate-risk endometrial cancer by Post Operative Radiation Therapy in Endometrial Carcinoma 2 criteria received adjuvant RT despite evidence demonstrating improved local control. Both patient- and tumor-related factors are associated with delivery of adjuvant RT and the modality selected.

Hemangiopericytoma of the spleen.

PubMed

Illuminati, Giulio; Pizzardi, Giulia; Calio, Francesco; Pacilè, Maria A; Carboni, Fabio; Palumbo, Piergaspare; Vietri, Francesco

2015-03-01

Hemangiopericytoma of the spleen is a very rare tumor, with 14 isolated reports. It was our aim to review our experience and compare it with all the reported cases in an attempt to standardize surgical treatment, adjuvant treatment and follow-up protocol of this infrequent condition. A consecutive case series study, with a mean follow-up of 44 months. Five patients (mean age, 49 years) underwent simple splenectomy for hemangiopericytoma limited to the spleen followed by adriamycin-based chemotherapy in one patient. All the patients are alive and free from disease. For tumors confined to the spleen, simple splenectomy can be considered curative, without any need for further adjuvant treatment. On review of the medical literature, cure can still be achieved with complete resection of recurrences, when feasible, with adjuvant chemotherapy being also indicated. The slow-growing pattern of the tumor suggests a 10-year follow-up. Copyright © 2015 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

12 CFR 625.20 - Settlement.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Settlement. 625.20 Section 625.20 Banks and... UNDER THE EQUAL ACCESS TO JUSTICE ACT Procedures for Considering Applications § 625.20 Settlement. A prevailing party and the FCA through its counsel may agree on a proposed settlement of an award at any time...

12 CFR 608.814 - Reporting of credit information.

Code of Federal Regulations, 2010 CFR

2010-01-01

... all of the rights and protection afforded to the debtor under 31 U.S.C. 3711(f) have been fulfilled. The FCA shall notify each consumer reporting agency, to which a claim was disclosed, when the debt has... information. The Chairman, or designee of the Chairman, may disclose to a consumer reporting agency...

78 FR 65107 - Loans in Areas Having Special Flood Hazards

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-30

...) 898-3991, Division of Depositor and Consumer Protection. FCA: Paul K. Gibbs, Senior Accountant, Office..., 2012, was not required by Federal or State law to escrow taxes or insurance for the term of the loan and did not have a policy to require escrow of taxes and insurance. The Agencies are proposing to...

77 FR 48520 - Privacy Act of 1974; Revocation of a System of Records

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-14

... Bureau (Bureau). DATES: Effective Date: July 23, 2012. FOR FURTHER INFORMATION CONTACT: Jeffrey Pienta... (703) 883-4020. SUPPLEMENTARY INFORMATION: The Secure and Fair Enforcement for Mortgage Licensing Act... retrieval access to any part of the NMLSR until after FCA's SORN had become effective on March 15, 2011...

75 FR 27660 - Loan Policies and Operations; Loan Purchases From FDIC

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-18

... business. \\2\\ While a System institution could not qualify as a franchise purchaser, it could possibly pair with a non-System lender where that lender could buy the deposits and other loans leaving the System institution to buy the agricultural loans. FCA regulations currently provide that a System institution may not...

12 CFR 602.25 - General.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false General. 602.25 Section 602.25 Banks and... Public Rulemaking Files § 602.25 General. FCA has a public rulemaking file for each regulation. You may get copies of documents in the public rulemaking file by sending a written request to the Director...

12 CFR 602.2 - Disclosing reports of examination.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 12 Banks and Banking 7 2013-01-01 2013-01-01 false Disclosing reports of examination. 602.2... Information and Records Generally § 602.2 Disclosing reports of examination. (a) Disclosure by FCA. Reports of.... We do not give reports of examination to the public. Except as provided in this section, only the...

12 CFR 602.2 - Disclosing reports of examination.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 6 2011-01-01 2011-01-01 false Disclosing reports of examination. 602.2... Information and Records Generally § 602.2 Disclosing reports of examination. (a) Disclosure by FCA. Reports of.... We do not give reports of examination to the public. Except as provided in this section, only the...

12 CFR 602.2 - Disclosing reports of examination.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Disclosing reports of examination. 602.2... Information and Records Generally § 602.2 Disclosing reports of examination. (a) Disclosure by FCA. Reports of.... We do not give reports of examination to the public. Except as provided in this section, only the...

12 CFR 602.2 - Disclosing reports of examination.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 12 Banks and Banking 7 2012-01-01 2012-01-01 false Disclosing reports of examination. 602.2... Information and Records Generally § 602.2 Disclosing reports of examination. (a) Disclosure by FCA. Reports of.... We do not give reports of examination to the public. Except as provided in this section, only the...

Usage Intention Framework Model: A Fuzzy Logic Interpretation of the Classical Utaut Model

ERIC Educational Resources Information Center

Sandaire, Johnny

2009-01-01

A fuzzy conjoint analysis (FCA: Turksen, 1992) model for enhancing management decision in the technology adoption domain was implemented as an extension to the UTAUT model (Venkatesh, Morris, Davis, & Davis, 2003). Additionally, a UTAUT-based Usage Intention Framework Model (UIFM) introduced a closed-loop feedback system. The empirical evidence…

The Theory about CD-CAT Based on FCA and Its Application

ERIC Educational Resources Information Center

Shuqun, Yang; Shuliang, Ding; Zhiqiang, Yao

2009-01-01

Cognitive diagnosis (CD) plays an important role in intelligent tutoring system. Computerized adaptive testing (CAT) is adaptive, fair, and efficient, which is suitable to large-scale examination. Traditional cognitive diagnostic test needs quite large number of items, the efficient and tailored CAT could be a remedy for it, so the CAT with…

Nasal delivery of Protollin-adjuvanted H5N1 vaccine induces enhanced systemic as well as mucosal immunity in mice.

PubMed

Cao, Weiping; Kim, Jin Hyang; Reber, Adrian J; Hoelscher, Mary; Belser, Jessica A; Lu, Xiuhua; Katz, Jacqueline M; Gangappa, Shivaprakash; Plante, Martin; Burt, David S; Sambhara, Suryaprakash

2017-06-05

Sporadic, yet frequent human infections with avian H5N1 influenza A viruses continue to pose a potential pandemic threat. Poor immunogenicity of unadjuvanted H5N1 vaccines warrants developing novel adjuvants and formulations as well as alternate delivery systems to improve their immunogenicity and efficacy. Here, we show that Protollin, a nasal adjuvant composed of Neisseria meningitides outer membrane proteins non-covalently linked to Shigella flexneri 2a lipopolysaccharide, is a potent nasal adjuvant for an inactivated split virion H5N1 clade 1 A/Viet Nam1203/2004 (A/VN/1203/04) vaccine in a mouse model. Protollin-adjuvanted vaccines elicited enhanced serum protective hemagglutination inhibition titers, mucosal IgA responses, and H5N1-specific cell-mediated immunity that resulted in complete protection against a lethal challenge with a homologous virus as well as a heterologous clade 2 virus A/Indonesia/05/2005 (A/IN/05/05). Detailed analysis of adaptive immunity revealed that Protollin increased the frequency of lymphoid- as well as local tissue-resident antibody-secreting cells, local germinal center reaction of B cells, broad-spectrum of CD4 T cell response. Our findings suggest that nasal delivery of H5N1 vaccine with Protollin adjuvant can overcome the poor immunogenicity of H5N1 vaccines, induce both cellular and humoral immune responses, enhance protection against challenge with clade 1 and clade 2 H5N1 viruses and achieve significant antigen dose-sparing. Copyright © 2017. Published by Elsevier Ltd.

Safety evaluation of driver cognitive failures and driving errors on right-turn filtering movement at signalized road intersections based on Fuzzy Cellular Automata (FCA) model.

PubMed

Chai, Chen; Wong, Yiik Diew; Wang, Xuesong

2017-07-01

This paper proposes a simulation-based approach to estimate safety impact of driver cognitive failures and driving errors. Fuzzy Logic, which involves linguistic terms and uncertainty, is incorporated with Cellular Automata model to simulate decision-making process of right-turn filtering movement at signalized intersections. Simulation experiments are conducted to estimate the relationships between cognitive failures and driving errors with safety performance. Simulation results show Different types of cognitive failures are found to have varied relationship with driving errors and safety performance. For right-turn filtering movement, cognitive failures are more likely to result in driving errors with denser conflicting traffic stream. Moreover, different driving errors are found to have different safety impacts. The study serves to provide a novel approach to linguistically assess cognitions and replicate decision-making procedures of the individual driver. Compare to crash analysis, the proposed FCA model allows quantitative estimation of particular cognitive failures, and the impact of cognitions on driving errors and safety performance. Copyright © 2017 Elsevier Ltd. All rights reserved.

Large-Scale, Exhaustive Lattice-Based Structural Auditing of SNOMED CT

NASA Astrophysics Data System (ADS)

Zhang, Guo-Qiang

One criterion for the well-formedness of ontologies is that their hierarchical structure form a lattice. Formal Concept Analysis (FCA) has been used as a technique for assessing the quality of ontologies, but is not scalable to large ontologies such as SNOMED CT. We developed a methodology called Lattice-based Structural Auditing (LaSA), for auditing biomedical ontologies, implemented through automated SPARQL queries, in order to exhaustively identify all non-lattice pairs in SNOMED CT. The percentage of non-lattice pairs ranges from 0 to 1.66 among the 19 SNOMED CT hierarchies. Preliminary manual inspection of a limited portion of the 518K non-lattice pairs, among over 34 million candidate pairs, revealed inconsistent use of precoordination in SNOMED CT, but also a number of false positives. Our results are consistent with those based on FCA, with the advantage that the LaSA computational pipeline is scalable and applicable to ontological systems consisting mostly of taxonomic links. This work is based on collaboration with Olivier Bodenreider from the National Library of Medicine, Bethesda, USA.

Perspectives on Tobacco Product Waste: A Survey of Framework Convention Alliance Members' Knowledge, Attitudes, and Beliefs.

PubMed

Javadian, Sanas; Stigler-Granados, Paula; Curtis, Clifton; Thompson, Francis; Huber, Laurent; Novotny, Thomas E

2015-08-18

Cigarette butts (tobacco product waste (TPW)) are the single most collected item in environmental trash cleanups worldwide. This brief descriptive study used an online survey tool (Survey Monkey) to assess knowledge, attitudes, and beliefs among individuals representing the Framework Convention Alliance (FCA) about this issue. The FCA has about 350 members, including mainly non-governmental tobacco control advocacy groups that support implementation of the World Health Organization's (WHO) Framework Convention on Tobacco Control (FCTC). Although the response rate (28%) was low, respondents represented countries from all six WHO regions. The majority (62%) have heard the term TPW, and nearly all (99%) considered TPW as an environmental harm. Most (77%) indicated that the tobacco industry should be responsible for TPW mitigation, and 72% felt that smokers should also be held responsible. This baseline information may inform future international discussions by the FCTC Conference of the Parties (COP) regarding environmental policies that may be addressed within FCTC obligations. Additional research is planned regarding the entire lifecycle of tobacco's impact on the environment.

Antioxidant and Angiostatic Effect of Spirulina platensis Suspension in Complete Freund’s Adjuvant-Induced Arthritis in Rats

PubMed Central

Ali, Eman A. I.; Barakat, Bassant M.; Hassan, Ranya

2015-01-01

Background Currently, natural products have built a well-recognized role in the management of many degenerative diseases, mainly rheumatoid arthritis. Recent studies suggest that Spirulina, a unicellular blue-green alga, may have a variety of health benefits and curative properties and is also competent of acting as an anti-inflammatory, antioxidant and recently anti-angiogenic agent. In the present study, the antioxidant and the immunomodulatory effect of Spirulina platensis as well as its anti-angiogenic effect against complete Freund's adjuvant-induced arthritis (AIA) in rat model were tested. Results We found that the development of arthritis was concealed; moreover it successfully inhibited the development of macroscopic as well as microscopic and histopathological lesions in AIA rats when compared to control. Spirulina treated group showed a higher survival rate and moreover, it reduced the clinical score of RA in a dose dependent manner. Furthermore, Spirulina decreased serum levels of COX-2, TNF-α, IL-6, TBARS, VEGF and increased serum levels of GSH compared to the RA non-treated group. Conclusions The present study concluded that Spirulina is able to restrain the changes produced through adjuvant-induced arthritis. The suppressing effect of Spirulina could be attributed, at least in part, to anti-inflammatory, antioxidant and anti-angiogenic properties. PMID:25853428

Antioxidant and angiostatic effect of Spirulina platensis suspension in complete Freund's adjuvant-induced arthritis in rats.

PubMed

Ali, Eman A I; Barakat, Bassant M; Hassan, Ranya

2015-01-01

Currently, natural products have built a well-recognized role in the management of many degenerative diseases, mainly rheumatoid arthritis. Recent studies suggest that Spirulina, a unicellular blue-green alga, may have a variety of health benefits and curative properties and is also competent of acting as an anti-inflammatory, antioxidant and recently anti-angiogenic agent. In the present study, the antioxidant and the immunomodulatory effect of Spirulina platensis as well as its anti-angiogenic effect against complete Freund's adjuvant-induced arthritis (AIA) in rat model were tested. We found that the development of arthritis was concealed; moreover it successfully inhibited the development of macroscopic as well as microscopic and histopathological lesions in AIA rats when compared to control. Spirulina treated group showed a higher survival rate and moreover, it reduced the clinical score of RA in a dose dependent manner. Furthermore, Spirulina decreased serum levels of COX-2, TNF-α, IL-6, TBARS, VEGF and increased serum levels of GSH compared to the RA non-treated group. The present study concluded that Spirulina is able to restrain the changes produced through adjuvant-induced arthritis. The suppressing effect of Spirulina could be attributed, at least in part, to anti-inflammatory, antioxidant and anti-angiogenic properties.

Droplet evaporation and spread on waxy and hairy leaves associated with type and concentration of adjuvants.

PubMed

Xu, Linyun; Zhu, Heping; Ozkan, H Erdal; Bagley, William E; Krause, Charles R

2011-07-01

Adjuvants can improve pesticide application efficiency and effectiveness. However, quantifications of the adjuvant-amended pesticide droplet actions on foliage, which could affect application efficiencies, are largely unknown. Droplet evaporation rates and spread on waxy or hairy leaves varied greatly with the adjuvant types tested. On waxy leaves, the wetted areas of droplets containing crop oil concentrate (COC) were significantly smaller than those containing modified seed oil (MSO), non-ionic surfactant (NIS) or oil surfactant blend (OSB), whereas the evaporation rates of COC-amended droplets were significantly higher. On hairy leaves, COC-amended droplets remained on top of the hairs without wetting the epidermis. When the relative concentration was 1.50, the wetted area of droplets with NIS was 9.2 times lower than that with MSO and 6.1 times lower than that with OSB. The wetted area increased as the adjuvant concentration increased. MSO- or OSB-amended droplets spread extensively on the hairy leaf surface until they were completely dried. These results demonstrated that the proper concentration of MSO, NIS or OSB in spray mixtures improved the homogeneity of spray coverage on both waxy and hairy leaf surfaces and could reduce pesticide use. This article is a US Government work and is in the public domain in the USA. Published 2011 by John Wiley & Sons, Ltd.

Sex hormonal modulation of interhemispheric transfer time.

PubMed

Hausmann, M; Hamm, J P; Waldie, K E; Kirk, I J

2013-08-01

It is still a matter of debate whether functional cerebral asymmetries (FCA) of many cognitive processes are more pronounced in men than in women. Some evidence suggests that the apparent reduction in women's FCA is a result of the fluctuating levels of gonadal steroid hormones over the course of the menstrual cycle, making their FCA less static than for men. The degree of lateralization has been suggested to depend on interhemispheric communication that may be modulated by gonadal steroid hormones. Here, we employed visual-evoked EEG potentials to obtain a direct measure of interhemispheric communication during different phases of the menstrual cycle. The interhemispheric transfer time (IHTT) was estimated from the interhemispheric latency difference of the N170 component of the visual-evoked potential from either left or right visual field presentation. Nineteen right-handed women with regular menstrual cycles were tested twice, once during the menstrual phase, when progesterone and estradiol levels are low, and once during the luteal phase when progesterone and estradiol levels are high. Plasma steroid levels were determined by blood-based immunoassay at each session. It was found that IHTT, in particular from right-to-left, was generally longer during the luteal phase relative to the menstrual phase. This effect occurred as a consequence of a slowed absolute N170 latency of the indirect pathway (i.e. left hemispheric response after LVF stimulation) and, in particular, a shortened latency of the direct pathway (i.e. right hemispheric response after LVF stimulation) during the luteal phase. These results show that cycle-related effects are not restricted to modulation of processes between hemispheres but also apply to cortical interactions, especially within the right hemisphere. The findings support the view that plastic changes in the female brain occur during relatively short-term periods across the menstrual cycle. Copyright © 2013 Elsevier Ltd. All rights reserved.

Examining the neural correlates of depressive and motor symptoms in Parkinson's disease using Frequency Component Analysis (FCA)

NASA Astrophysics Data System (ADS)

Song, Xiaopeng; Hu, Xiao; Zhou, Shuqin; Liu, Weiguo; Liu, Yijun; Zhu, Huaiqiu; Gao, Jia-Hong

2016-03-01

Depression is prevalent among patients with Parkinson's disease (PD); however the pathophysiology of depression in PD is not well understood. In order to investigate how depression and motor impairments differentially and interactively affect specific brain regions in Parkinson's disease, we introduced a new data driven approach, namely Frequency Component Analysis (FCA), to decompose the resting-state functional magnetic resonance imaging data of 59 subjects with Parkinson's disease into different frequency bands. We then evaluated the main effects of motor severity and depression, and their interactive effects on the BOLD-fMRI signal oscillation energy in these specific frequency components. Our results show that the severity of motor symptoms is more negatively correlated with energy in the frequency band of 0.10-0.25Hz in the bilateral thalamus (THA), but more positively correlated with energy in the frequency band of 0.01-0.027Hz in the bilateral postcentral gyrus (PoCG). In contrast, the severity of depressive symptoms is more associated with the higher energy of the high frequency oscillations (>0.1Hz) but lower energy of 0.01-0.027Hz in the bilateral subgenual gyrus (SGC). Importantly, the interaction between motor and depressive symptoms is negatively correlated with the energy of high frequency oscillations (>0.1Hz) in the substantia nigra/ventral tegmental area (SN/VTA), left hippocampus (HIPP), left inferior orbital frontal cortex (OFC), and left temporoparietal junction (TPJ), but positively correlated with the energy of 0.02-0.05Hz in the left inferior OFC, left TPJ, left inferior temporal gyrus (ITG), and bilateral cerebellum. These results demonstrated that FCA was a promising method in interrogating the neurophysiological implications of different brain rhythms. Our findings further revealed the neural bases underlying the interactions as well the dissociations between motor and depressive symptoms in Parkinson's disease.

Long-term Assessment of Carbon Budget of Terrestrial Ecosystems of Russia

NASA Astrophysics Data System (ADS)

Maksyutov, S. S.; Shvidenko, A.; Shchepashchenko, D.; Kraxner, F.

2016-12-01

We present a reanalysis of Terrestrial Ecosystems Full Verified Carbon Account (FCA) for Russia for the period of 2000-2012 based on understanding that FCA is an underspecified (fuzzy) system. The methodology used is based on integration of major approaches of carbon cycling assessment with following harmonizing and mutual constraints of the results received by independent methods. The landscape-ecosystem approach (LEA) was used for a systemic design of the account and empirical assessment of the LEA based on a relevant combination of pool-based and flux-based methods. The information background of the LEA is presented in a form of an Integrated Land Information System which include the hybrid landcover (HLC) at resolution of 150 m2 and relevant attributive databases. HLC was developed based on remote sensing multi-sensor concept (using 12 different satellite products), geographic weighted regression and Geo-wiki validation (Schepaschenko et al. 2015). Carbon fluxes which are based on long-term measurements were corrected based on seasonal climatic indicators of individual years. Uncertainties of intermediate and final results within LEA are calculated by sequential algorithms. Results of the LEA were compared with those obtained by eddy covariance, process-based models of different types, inverse modeling and GOSAT Level 4 Products. Uncertainty of the final results was calculated based on the Bayesian approach. It has been shown that terrestrial vegetation of Russia served as a net carbon sink at range of 480-650 Tg C yr-1 during the studied period, mostly at the expense of forests, with interannual variation of around 10-20% at the country's scale. The regional variation was significantly higher that depends on specifics of seasonal weather and accompanying regimes of natural disturbances. The overall uncertainty of the FCA is estimated at 22-25% at the annual basis and 7-9% for the period's average.

Photodynamic therapy and the treatment of malignancies of the head and neck

NASA Astrophysics Data System (ADS)

Biel, Merrill A.

1995-05-01

Sixty-five patients with neoplastic diseases of the larynx, oral cavity, pharynx, and skin have been treated with PDT with followup to 56 months. Patients with carcinoma in situ and T1 carcinomas obtained a complete response after one PDT treatment. All but two have remained free of disease. Eight patients with T2 and T3 carcinomas treated with PDT obtained a complete response, but they all recurred locally. This is due to the inability to adequately deliver laser light to the depths of the tumor bed. five patients with massive neck recurrences of squamous cell carcinomas were treated with intraoperative adjuvant PDT following tumor resection. Only one developed recurrence with 24- month followup. PDT is highly effective for the curative treatment of early carcinomas (CIS, T1) of the head and neck. Also, intraoperative adjuvant PDT may increase cure rates of large infiltrating carcinomas of the head and neck.

Carbon Budget and its Dynamics over Northern Eurasia Forest Ecosystems

NASA Astrophysics Data System (ADS)

Shvidenko, Anatoly; Schepaschenko, Dmitry; Kraxner, Florian; Maksyutov, Shamil

2016-04-01

The presentation contains an overview of recent findings and results of assessment of carbon cycling of forest ecosystems of Northern Eurasia. From a methodological point of view, there is a clear tendency in understanding a need of a Full and Verified Carbon Account (FCA), i.e. in reliable assessment of uncertainties for all modules and all stages of FCA. FCA is considered as a fuzzy (underspecified) system that supposes a system integration of major methods of carbon cycling study (land-ecosystem approach, LEA; process-based models; eddy covariance; and inverse modelling). Landscape-ecosystem approach 1) serves for accumulation of all relevant knowledge of landscape and ecosystems; 2) for strict systems designing the account, 3) contains all relevant spatially distributed empirical and semi-empirical data and models, and 4) is presented in form of an Integrated Land Information System (ILIS). The ILIS includes a hybrid land cover in a spatially and temporarily explicit way and corresponding attributive databases. The forest mask is provided by utilizing multi-sensor remote sensing data, geographically weighed regression and validation within GEO-wiki platform. By-pixel parametrization of forest cover is based on a special optimization algorithms using all available knowledge and information sources (data of forest inventory and different surveys, observations in situ, official statistics of forest management etc.). Major carbon fluxes within the LEA (NPP, HR, disturbances etc.) are estimated based on fusion of empirical data and aggregations with process-based elements by sets of regionally distributed models. Uncertainties within LEA are assessed for each module and at each step of the account. Within method results of LEA and corresponding uncertainties are harmonized and mutually constrained with independent outputs received by other methods based on the Bayesian approach. The above methodology have been applied to carbon account of Russian forests for 2000-2012. It has been shown that the Net Ecosystem Carbon Budget (NECB) of Russian forests for this period was in range of 0.5-0.7 Pg C yr-1 with a slight negative trend during the period due to acceleration of disturbance regimes and negative impacts of weather extremes (heat waves etc.). Uncertainties of the FCA for individual years were estimated at about 25% (CI 0.9). It has been shown that some models (e.g. majority of DGVMs) do not describe some processes on permafrost satisfactory while results of applications of ensembles of inverse models on average are closed to empirical assessments. A most important conclusion from this experience is that future improvements of knowledge of carbon cycling of Northern Eurasia forests requires development of an integrated observing system as a unified information background, as well as systems methodological improvements of all methods of cognition of carbon cycling.

Inhibitory effects of Cynodon dactylon L. on inflammation and oxidative stress in adjuvant treated rats.

PubMed

Sindhu, G; Ratheesh, M; Shyni, G L; Helen, A

2009-01-01

Cynodon dactylon is one of the 10 auspicious herbs that constitute the group Dasapushpam in Ayurveda. Traditionally Cynodon dactylon L. is used against many chronic inflammatory diseases in India. The present study was carried out to evaluate the protective effect of Cynodon dactylon against rats with adjuvant- induced arthritis. Arthritis was induced by intradermal injection of complete Freund's adjuvant into the right hind paw produce inflammation of the joint. A significant increase in the levels of inflammatory mediators, myeloperoxidase, nitrite, C-reactive protein, ceruloplasmin was observed. This was associated with oxidative stress with a marked reduction in the activity of catalase, superoxide dismutase, glutathione peroxidase and the levels of glutathione, vitamins C and E and an increase in the lipid peroxidation as indicated by the higher levels of thiobarbituric acid reactive substances. Cynodon dactylon (20mg/kg/b.wt) was orally administered to arthritic rats after adjuvant injection produced a significant attenuation in the inflammatory response, oxidative stress and ameliorated the arthritic changes to near normal conditions. Hence, the results of this study clearly indicate that Cynodon dactylon extract has a promising protective role against arthritis.

Antigenic Competition Between and Endotoxic Adjuvant and a Protein Antigen

PubMed Central

Leong, Daniel L. Y.; Rudbach, Jon A.

1971-01-01

Antigenic competition between bovine gamma globulin (BGG) and endotoxin from a smooth strain (S-ET) and a rough (R-ET) heptoseless mutant strain of Salmonella minnesota was studied in mice. Both endotoxins acted as adjuvants for enhancing the antibody response to BGG. However, other work showed that the R-ET had minimal antigenicity, and it was used as a control for the competition studies. Antigenic competition between BGG and endotoxin as expressed by a suppression of the antibody response to BGG could not be demonstrated when varying adjuvant doses of S-ET or R-ET were injected simultaneously with a small constant dose of BGG into normal mice. However, mice presensitized with S-ET several weeks before immunization with the S-ET and BGG combination produced anti-BGG levels which were four to eightfold lower than in normal mice. Nearly complete suppression of the anti-BGG response could be obtained in presensitized mice by reducing the BGG dose 10-fold or by increasing the adjuvant dose of endotoxin. Mice pretreated with R-ET and challenged with BGG plus S-ET or R-ET showed no depression of the anti-BGG response. These and other experiments confirmed the immunological basis of the competitive effect. PMID:16557970

Strategies to alleviate original antigenic sin responses to influenza viruses.

PubMed

Kim, Jin Hyang; Davis, William G; Sambhara, Suryaprakash; Jacob, Joshy

2012-08-21

Original antigenic sin is a phenomenon wherein sequential exposure to closely related influenza virus variants reduces antibody (Ab) response to novel antigenic determinants in the second strain and, consequently, impairs the development of immune memory. This could pose a risk to the development of immune memory in persons previously infected with or vaccinated against influenza. Here, we explored strategies to overcome original antigenic sin responses in mice sequentially exposed to two closely related hemagglutinin 1 neuraminidase 1 (H1N1) influenza strains A/PR/8/34 and A/FM/1/47. We found that dendritic cell-activating adjuvants [Bordetella pertussis toxin (PT) or CpG ODN or a squalene-based oil-in-water nanoemulsion (NE)], upon administration during the second viral exposure, completely protected mice from a lethal challenge and enhanced neutralizing-Ab titers against the second virus. Interestingly, PT and NE adjuvants when administered during the first immunization even prevented original antigenic sin in subsequent immunization without any adjuvants. As an alternative to using adjuvants, we also found that repeated immunization with the second viral strain relieved the effects of original antigenic sin. Taken together, our studies provide at least three ways of overcoming original antigenic sin.

Radiotherapy concurrently with weekly cisplatin, followed by adjuvant chemotherapy, for N2–3 nasopharyngeal cancer: a multicenter trial of the Forum for Nuclear Cooperation in Asia

PubMed Central

Ohno, Tatsuya; Thinh, Dang Huy Quoc; Kato, Shingo; Devi, C.R. Beena; Tung, Ngo Thanh; Thephamongkhol, Kullathorn; Calaguas, Miriam Joy C.; Zhou, Juying; Chansilpa, Yaowalak; Supriana, Nana; Erawati, Dyah; Banu, Parvin Akhter; Koo, Cho Chul; Kobayashi, Kunihiko; Nakano, Takashi; Tsujii, Hirohiko

2013-01-01

The purpose of this study was to evaluate the efficacy and toxicity of radiotherapy concurrently with weekly cisplatin, followed by adjuvant chemotherapy, for the treatment of N2–3 nasopharyngeal cancer (NPC) in Asian countries, especially regions of South and Southeast Asian countries where NPC is endemic. Between 2005 and 2009, 121 patients with NPC (T1–4 N2–3 M0) were registered from Vietnam, Malaysia, Indonesia, Thailand, The Philippines, China and Bangladesh. Patients were treated with 2D radiotherapy concurrently with weekly cisplatin (30 mg/m 2), followed by adjuvant chemotherapy, consisting of cisplatin (80 mg/m2 on Day 1) and fluorouracil (800 mg/m2 on Days 1–5) for 3 cycles. Of the 121 patients, 56 patients (46%) required interruption of RT. The reasons for interruption of RT were acute non-hematological toxicities such as mucositis, pain and dermatitis in 35 patients, hematological toxicities in 11 patients, machine break-down in 3 patients, poor general condition in 2 patients, and others in 8 patients. Of the patients, 93% completed at least 4 cycles of weekly cisplatin during radiotherapy, and 82% completed at least 2 cycles of adjuvant chemotherapy. With a median follow-up time of 46 months for the surviving 77 patients, the 3-year locoregional control, distant metastasis-free survival and overall survival rates were 89%, 74% and 66%, respectively. No treatment-related deaths occurred. Grade 3–4 toxicities of mucositis, nausea/vomiting and leukopenia were observed in 34%, 4% and 4% of the patients, respectively. In conclusion, further improvement in survival and locoregional control is necessary, although our regimen showed acceptable toxicities. PMID:23192700

Suppression of complete Freund's adjuvant-induced adjuvant arthritis by cobratoxin.

PubMed

Liu, Yan-Li; Lin, Hai-Ming; Zou, Rong; Wu, Jun-Chao; Han, Rong; Raymond, Laurence N; Reid, Paul F; Qin, Zheng-Hong

2009-02-01

Cobratoxin (CTX), the long-chain alpha-neurotoxin from Thailand cobra venom, has been demonstrated to have analgesic action in rodent pain models. The present study evaluated the anti-inflammatory and anti-nociceptive effects of CTX on adjuvant arthritis (AA) in rats. Arthritis was induced by injection of complete Freund's adjuvant (CFA) in rats. Paw swelling and hyperalgesia of AA rats were measured at various times after CFA administration. Tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-2 (IL-2) and interleukin-10 (IL-10) levels in serum were determined with ELISA. Histopathological changes in synoviocytes were examined under a microscope. Involvement of the cholinergic system in the effects of CTX was examined by pretreatment of animals with the alpha(7) nicotinic receptor (alpha(7)-nAChR) antagonist methyllycaconitine (MLA). CFA induced marked paw swelling and reduced thresholds of mechanical and cold-induced paw withdrawal. The levels of TNF-alpha, IL-1 and IL-2 in the serum of AA rats were increased, whereas the level of IL-10 was decreased. Histopathological examination of synoviocytes showed pronounced inflammation and accumulation of collagen. The administration of CTX (17.0 microg/kg, ip) significantly reduced paw swelling and mechanical and thermal hyperalgesia. CTX also reduced the production of TNF-alpha, IL-1, and IL-2 but increased the production of IL-10 and altered pathohistological changes. The analgesic and anti-inflammatory efficacy of CTX was significantly reduced by MLA (3 mg/kg, sc). These results indicate that CTX has a beneficial effect on CFA-induced arthritis by modulating the production of inflammatory cytokines. alpha(7)-nAChR appears to mediate the anti-nociceptive and anti-inflammatory actions of CTX.

Preoperative Chemotherapy for Operable Breast Cancer Is Associated with Better Compliance with Adjuvant Therapy in Matched Stage II and IIIA Patients

PubMed Central

Hsu, Chiu-Hsieh; Martinez, Maria Elena; Bouton, Marcia E.; Low, Boo Ghee; Salganick, Jason A.; Nodora, Jesse; Hibbard, Michael L.; Jha, Chandra

2011-01-01

Introduction. Preoperative chemotherapy (PC) for operable breast cancer has shown significant benefits in prospective trials. Many patients are treated in the community setting and some may question the applicability of PC outside the university setting. Methods. Retrospective review was performed of stage II and IIIA breast cancer patients treated from January 2002 to July 2009. Fifty-three of 57 patients who underwent PC were matched based on age, tumor size, and hormone receptor status with 53 patients who did not undergo PC. Differences in patient compliance with physician recommendations for all types of adjuvant therapy were evaluated. Crude odds ratios and adjusted odds ratios derived from conditional logistic regression models were calculated. Results. There were 106 patients included. Patient compliance with chemotherapy was better in the PC group than in the adjuvant chemotherapy (AC) group (100% versus 70%; p = .0001). Similarly, more patients in the PC group completed radiation therapy (96% versus 65%; p = .0003) and initiated hormonal therapy (100% versus 62%; p = .0001). Conditional logistic regression revealed that higher pathologic stage and current cigarette smoking were associated with poorer compliance with chemotherapy. For radiation therapy, the univariate model revealed that compliance with chemotherapy and being employed were associated with completion of radiation, whereas current cigarette smoking and larger pathologic size were associated with poorer compliance with radiation. For hormonal therapy, current cigarette smokers were more likely to be noncompliant with initiation of hormonal therapy. Conclusions. PC for operable breast cancer can improve patient compliance with chemotherapy. Current cigarette smokers were more likely to be noncompliant with all types of adjuvant therapy. PMID:21558134

Recruitment to and pilot results of the PACES randomized trial of physical exercise during adjuvant chemotherapy for colon cancer.

PubMed

van Waart, Hanna; Stuiver, Martijn M; van Harten, Wim H; Geleijn, Edwin; de Maaker-Berkhof, Marianne; Schrama, Jolanda; Geenen, Maud M; Meerum Terwogt, Jetske M; van den Heiligenberg, Simone M; Hellendoorn-van Vreeswijk, Jeannette A J H; Sonke, Gabe S; Aaronson, Neil K

2018-01-01

We report the recruitment rate, reasons for and factors influencing non-participation, and descriptive results of a randomized controlled trial of two different exercise programs for patients with colon cancer undergoing adjuvant chemotherapy. Participants were randomized to a low-intensity, home-based program (Onco-Move), a moderate- to high-intensity, combined supervised resistance and aerobic exercise program (OnTrack), or Usual Care. Non-participants provided reasons for non-participation and were asked to complete a questionnaire assessing behavioral and attitudinal variables. Trial participants completed performance-based and self-reported outcome measures prior to randomization, at the end of chemotherapy, and at the 6-month follow-up. Twenty-three of 63 referred patients agreed to participate in the trial. All 40 non-participants provided reasons for non-participation. Forty-five percent of the non-participants completed the questionnaire. Those who did not want to exercise had higher fatigue scores at baseline and a more negative attitude toward exercise. Compliance to both programs was high and no adverse events occurred. On average, the colon cancer participants were able to maintain or improve their physical fitness levels and maintain or decrease their fatigue levels during chemotherapy and follow-up. Recruitment of patients with colon cancer to a physical exercise trial during adjuvant chemotherapy proved to be difficult, underscoring the need to develop more effective strategies to increase participation rates. Both home-based and supervised programs are safe and feasible in patients with colon cancer undergoing chemotherapy. Effectiveness needs to be established in a larger trial. Netherlands Trial Register - NTR2159.

Synergistic activity of curcumin with methotrexate in ameliorating Freund's Complete Adjuvant induced arthritis with reduced hepatotoxicity in experimental animals.

PubMed

Banji, David; Pinnapureddy, Jyothi; Banji, Otilia J F; Saidulu, A; Hayath, Md Sikinder

2011-10-01

Methotrexate is employed in low doses for the treatment of rheumatoid arthritis. One of the major drawbacks with methotrexate is hepatotoxicity resulting in poor compliance of therapy. Curcumin is an extensively used spice possessing both anti-arthritic and hepatoprotective potential. The present study was aimed at investigating the effect of curcumin (30 and 100 mg/kg) in combination with subtherapeutic dose of methotrexate (1 mg/kg) is salvaging hepatotoxicity, oxidative stress and producing synergistic anti-arthritic action with methotrexate. Wistar albino rats were induced with arthritis by subplantar injection of Freund's Complete Adjuvant and pronounced arthritis was seen after 9 days of injection. Groups of animals were treated with subtherapeutic dose of methotrexate followed half an hour later with 30 and 100mg/kg of curcumin from day 9 up to days 45 by intraperitoneal route. Methotrexate treatment in Freund's Complete Adjuvant induced arthritic animals produced elevation in the levels of aminotransferases, alkaline phosphatase, total and direct bilirubin. Enhanced oxidative stress in terms of measured lipid peroxides was observed in the methotrexate treated group. Curcumin significantly circumvented hepatotoxicity induced by methotrexate as evidenced by a change in biochemical markers possibly due to its strong anti-oxidant action. Hepatoprotective potential of curcumin was also confirmed from histological evaluation. Sub-therapeutic dose of methotrexate elicited substantial anti-arthritic action when used in combination with curcumin implying that the latter potentiated its action. Concomitant administration of curcumin with methotrexate was also found to minimize liver damage. Copyright © 2011 Elsevier B.V. All rights reserved.

76 FR 35138 - Federal Agricultural Mortgage Corporation Funding and Fiscal Affairs; Farmer Mac Risk-Based...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-16

... Funding and Fiscal Affairs; Farmer Mac Risk-Based Capital Stress Test, Version 5.0 AGENCY: Farm Credit... credit rating agency) in regulations addressing the Risk-Based Capital Stress Test (RBCST or stress test... Act required FCA to establish a risk- based capital stress test for Farmer Mac's portfolio.\\3\\ This...

12 CFR 602.9 - Current FOIA index.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Current FOIA index. 602.9 Section 602.9 Banks... Records of the Farm Credit Administration § 602.9 Current FOIA index. FCA will make a current index available for public inspection and copying, as required by the FOIA. We will give you an index for the cost...

Space and Missile Systems Center Standard: Test Requirements for Ground Systems

DTIC Science & Technology

2013-09-30

Human Exposure to Radio Frequency Electromagnetic Fields , 3kHz to...5] Federal Code of Regulations FCC Part 15 Federal Code of Regulations, Title 47: Telecommunication, Part 15– Radio Frequency Devices 2.3 Non...DT&E Development test and evaluation EMC Electromagnetic compatibility FAT Factory acceptance test FCA Functional configuration audit FCC

Use of adjuvant chemotherapy (CT) and radiotherapy (RT) in incompletely resected (R1) early stage Non-Small Cell Lung Cancer (NSCLC): a European survey conducted by the European Society for Medical Oncology (ESMO) young oncologists committee.

PubMed

Califano, R; Karamouzis, M V; Banerjee, S; de Azambuja, E; Guarneri, V; Hutka, M; Jordan, K; Kamposioras, K; Martinelli, E; Corral, J; Postel-Vinay, S; Preusser, M; Porcu, L; Torri, V

2014-07-01

Early stage Non-Small Cell Lung Cancer (NSCLC) is potentially curable with surgery. ESMO guidelines recommend cisplatin-based adjuvant chemotherapy (CT) for completely resected stage II-III NSCLC. There is limited evidence for the use of adjuvant CT and/or radiotherapy (RT) in incompletely resected (R1) early stage NSCLC. A European survey of thoracic oncologists was conducted to evaluate use of adjuvant CT and RT for R1-resected NSCLC and to identify factors influencing treatment decisions. Demographics and information on clinical stage, regimens, cycles planned, radiotherapy sites, multidisciplinary management and discussion about inconclusive evidence with the patient were collected. Univariate and multivariate analyses were performed. 768 surveys were collected from 41 European countries. 82.9% of participants were medical oncologists; 49.3% ESMO members; 37.1% based in University Hospitals; 32.6% practicing oncology for over 15 years and 81.4% active in research. 91.4% of participants prescribed adjuvant CT and mostly cisplatin/vinorelbine (81.2%) or cisplatin/gemcitabine (42.9%). 85% discussed limited clinical evidence with the patient. In the univariate analysis, a statistically significant association with CT prescription was found for medical oncology specialty (p<0.001), ESMO membership (p<0.001), activity in clinical research (p=0.002) and increased frequency of ESMO guidelines consultation (p for trend <0.001). 48.3% of participants prescribed adjuvant RT and its prescription were associated with radiation oncology specialty (p<0.001), not being an ESMO member (p<0.001), years practicing specialty (p for trend=0.001), workload of lung cancer patients (p for trend=0.027) and decreased frequency in consulting ESMO guidelines (p<0.001). In the multivariate analysis, medical oncology and radiation oncology were the best discriminator for prescription of adjuvant CT and RT, respectively. This survey demonstrates that adjuvant CT and RT are commonly used in clinical practice for R1-resected NSCLC despite limited evidence. Prospective trials are necessary to clarify optimal management in this setting. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Adjuvant electrochemotherapy for incompletely excised anal sac carcinoma in a dog.

PubMed

Spugnini, Enrico P; Dotsinsky, Ivan; Mudrov, Nikolay; Bufalini, Massimiliano; Giannini, Giovanni; Citro, Gennaro; Feroce, Florinda; Baldi, Alfonso

2008-01-01

Canine anal sac gland carcinoma (ASGC) is a frequently described neoplasm that is highly aggressive and can frequently lead to metastatic spread. In this paper, we describe the successful treatment of an incompletely excised ASGC by using cisplatin selectively driven within the tumor cells by trains of biphasic pulses. The dog received two courses of electrochemotherapy 14 days apart. Neither systemic nor local toxicities were detected during the whole course of therapy. The dog is still in complete remission after 18 months. Electrochemotherapy is a safe and efficacious adjuvant therapy for ASGC and warrants further investigation in order to standardize its protocols.

Nanolipoprotein Particles (NLPs) as Versatile Vaccine Platforms for Co-delivery of Multiple Adjuvants with Subunit Antigens from Burkholderia spp. and F. tularensis - Technical Report

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

Fischer, N. O.

The goal of this proposal is to demonstrate that colocalization of protein subunit antigens and adjuvants on nanolipoprotein particles (NLPs) can increase the protective efficacy of subunit antigens from Burkholderia spp. and Francisella tularensis against an aerosol challenge. In the second quarter of the third year, LLNL finalized all immunological assessments of NLP vaccine formulations in the F344 model. Battelle has immunized rats with three unique NLP formulations by either intramuscular or intranasal administration. All inoculations have been completed, and protective efficacy against an aerosolized challenge will begin at the end of October, 2014.

Protection of mice against Giardia muris infection.

PubMed Central

Roberts-Thomson, I C; Mitchell, G F

1979-01-01

Strains of mice showing relatively rapid (BALB/c) and defective (C3H/He) spontaneous elimination of Giardia muris displayed marked differences in the degree of resistance to infection induced by prior injection of trophozoites in Freund complete adjuvant. PMID:468385

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

Hristov, Boris; Reddy, Sushanth; Lin, Steven H.

Purpose: Surgery followed by chemotherapy and radiation (CRT) offers patients with pancreatic adenocarcinoma a chance for extended survival. In some patients, however, resection is difficult because of vascular involvement by the carcinoma, necessitating resection and grafting of the mesenterico-portal vessels. The purpose of this study was to compare outcomes between pancreaticoduodenectomy (PD) with and without mesenterico-portal vein resection (VR) in patients receiving adjuvant CRT for pancreatic adenocarcinoma. Methods and Materials: Between 1993 and 2005, 160 patients underwent PD with 5-FU-based adjuvant CRT followed by maintenance chemotherapy at the Johns Hopkins Hospital; 20 (12.5%) of the 160 underwent VR. Clinical outcomes,more » including median survival, overall survival, and complication rates were assessed for both groups. Results: Patients who underwent VR had significantly longer operative times (p = 0.009), greater intraoperative blood loss (p = 0.01), and longer postoperative lengths of stay (p = 0.03). However, postoperative morbidity, median survival, and overall survival rates were similar between the two groups. Most patients (70%) from both groups were able to complete CRT, and a subgroup analysis demonstrated no appreciable differences in terms of complications. None of the VR patients who received adjuvant CRT developed veno-occlusive disease or graft failure/leakage. Conclusion: In a cohort of patients treated with adjuvant 5-FU-based CRT at the Johns Hopkins Hospital, having a VR at the time of PD resulted in similar complication rates and survival. These data support the feasibility and safety of adjuvant CRT in patients undergoing VR at the time of PD.« less

Effectiveness of Brucella abortus lipopolysaccharide as an adjuvant for tuberculin PPD.

PubMed

Jamalan, Mostafa; Ardestani, Susan Kaboudanian; Zeinali, Majid; Mosaveri, Nader; Mohammad Taheri, Mohammad

2011-01-01

Bacterial lipopolysaccharide (LPS) has T-helper 1 (Th1) immunostimulatory activities but because of toxicity and pyrogenicity cannot be used as an adjuvant. Brucella abortus LPS has less toxicity and no pyrogenic properties in comparison to other bacterial LPS. In the current study, the immunostimulatory properties of B. abortus LPS were evaluated for its adjuvant activity. Tuberculin purified protein derivative (PPD) from Mycobacterium tuberculosis was extracted and after anion-exchange chromatography on Q-sepharose column, two fractions (17 and 23), which dominantly contained 30- and 70-kDa antigens, were collected for immunological studies. BALB/c mice were immunized with four different antigen preparations (BCG, PPD, 17th and 23rd PPD fractions) along with complete Freund's adjuvant or B. abortus LPS. The T-cell immune response of mice was assessed by measurement of Th1-type cytokine (IFN-γ) and Th2-type cytokines (IL-5 and IL-10) levels. Also, the humoral immunity was evaluated by measuring the specific IgG levels. Our results showed that immunization of mice with 17th PPD fraction along with B. abortus LPS can induce a Th1-type cytokine response characterized with a high IFN-γ/IL-5 ratio, while immunization with PPD or 23rd PPD fraction along with the same adjuvant resulted to a mixed Th1/Th2-type cytokine response. Copyright © 2010 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved.

Retrospective study of adjuvant icotinib in postoperative lung cancer patients harboring epidermal growth factor receptor mutations

PubMed Central

Yao, Shuyang; Zhi, Xiuyi; Wang, Ruotian; Qian, Kun; Hu, Mu

2016-01-01

Background Epidermal growth factor receptor (EGFR) mutations occur in about 50% of Asian patients with non‐small cell lung cancer (NSCLC). Patients with advanced NSCLC and EGFR mutations derive clinical benefit from treatment with EGFR‐tyrosine kinase inhibitors (TKIs). This study assessed the efficacy and safety of adjuvant icotinib without chemotherapy in EGFR‐mutated NSCLC patients undergoing resection of stage IB–IIIA. Methods Our retrospective study enrolled 20 patients treated with icotinib as adjuvant therapy. Survival factors were evaluated by univariate and Cox regression analysis. Results The median follow‐up time was 30 months (range 24–41). At the data cut‐off, five patients (25%) had recurrence or metastasis and one patient had died of the disease. The two‐year disease‐free survival (DFS) rate was 85%. No recurrence occurred in the high‐risk stage IB subgroup during the follow‐up period. In univariate analysis, the micropapillary pattern had a statistically significant effect on DFS (P = 0.040). Multivariate logistic regression analysis showed that there was no independent predictor. Drug related adverse events (AEs) occurred in nine patients (45.0%). The most common AEs were skin‐related events and diarrhea, but were relatively mild. No grade 3 AEs or occurrences of intolerable toxicity were observed. Conclusions Icotinib as adjuvant therapy is effective in patients harboring EGFR mutations after complete resection, with an acceptable AE profile. Further trials with larger sample sizes might confirm the efficiency of adjuvant TKI in selected patients. PMID:27766784

Inactivated HSV-2 in MPL/alum adjuvant provides nearly complete protection against genital infection and shedding following long term challenge and rechallenge.

PubMed

Morello, Christopher S; Kraynyak, Kimberly A; Levinson, Michael S; Chen, Zhijiang; Lee, Kuo-Fen; Spector, Deborah H

2012-10-12

Herpes Simplex Virus Type 2 (HSV-2) infection can result in life-long recurrent genital disease, asymptomatic virus shedding, and transmission. No vaccine to date has shown significant protection clinically. Here, we used a mouse model of genital HSV-2 infection to test the efficacy of a vaccine consisting of whole, formalin-inactivated HSV-2 (FI-HSV2) formulated with monophosphoryl lipid A (MPL) and alum adjuvants. Vaccine components were administered alone or as a prime-boost immunization together with DNA vaccines encoding a truncated glycoprotein D2 (gD2t) and two conserved HSV-2 genes necessary for virus replication, UL5 (DNA helicase) and UL30 (DNA polymerase). Our results show: (1) compared with mock immunized controls, mice immunized with FI-HSV2 plus MPL/alum consistently showed protection against disease burden and total viral shedding while the mice immunized with gD2t protein with MPL/alum did not; (2) protection against genital disease and viral replication correlated with the type of boost in a prime-boost immunization with little advantage afforded by a DNA prime; (3) intramuscular (i.m.) immunization with FI-HSV2 in MPL/Alhydrogel adjuvant provided nearly complete protection against vaginal HSV-2 shedding after a lethal intravaginal (i.vag.) short-term challenge and long-term rechallenge; (4) single formulation immunization with DNA vaccines, FI-HSV2, and MPL in an aluminum phosphate (Adju-Phos) adjuvant did not increase protection relative to FI-HSV2/MPL/Adju-Phos alone; and (5) addition of MPL/alum to the FI-HSV2 was required for optimal protection against disease, viral replication, and latent virus load in the dorsal root ganglia (DRG). Most notably, an optimized vaccine formulation of FI-HSV2 MPL/Alhydrogel given i.m. completely protected against detectable vaginal HSV-2 shedding in the majority of animals and HSV-2 latent DNA in the DRG of all animals. Copyright © 2012 Elsevier Ltd. All rights reserved.

NKT Cells as an Ideal Anti-Tumor Immunotherapeutic

PubMed Central

Fujii, Shin-ichiro; Shimizu, Kanako; Okamoto, Yoshitaka; Kunii, Naoki; Nakayama, Toshinori; Motohashi, Shinichiro; Taniguchi, Masaru

2013-01-01

Human natural killer T (NKT) cells are characterized by their expression of an invariant T cell antigen receptor α chain variable region encoded by a Vα24Jα18 rearrangement. These NKT cells recognize α-galactosylceramide (α-GalCer) in conjunction with the MHC class I-like CD1d molecule and bridge the innate and acquired immune systems to mediate efficient and augmented immune responses. A prime example of one such function is adjuvant activity: NKT cells augment anti-tumor responses because they can rapidly produce large amounts of IFN-γ, which acts on NK cells to eliminate MHC negative tumors and also on CD8 cytotoxic T cells to kill MHC positive tumors. Thus, upon administration of α-GalCer-pulsed DCs, both MHC negative and positive tumor cells can be effectively eliminated, resulting in complete tumor eradication without tumor recurrence. Clinical trials have been completed in a cohort of 17 patients with advanced non-small cell lung cancers and 10 cases of head and neck tumors. Sixty percent of advanced lung cancer patients with high IFN-γ production had significantly prolonged median survival times of 29.3 months with only the primary treatment. In the case of head and neck tumors, 10 patients who completed the trial all had stable disease or partial responses 5 weeks after the combination therapy of α-GalCer-DCs and activated NKT cells. We now focus on two potential powerful treatment options for the future. One is to establish artificial adjuvant vector cells containing tumor mRNA and α-GalCer/CD1d. This stimulates host NKT cells followed by DC maturation and NK cell activation but also induces tumor-specific long-term memory CD8 killer T cell responses, suppressing tumor metastasis even 1 year after the initial single injection. The other approach is to establish induced pluripotent stem (iPS) cells that can generate unlimited numbers of NKT cells with adjuvant activity. Such iPS-derived NKT cells produce IFN-γ in vitro and in vivo upon stimulation with α-GalCer/DCs, and mediated adjuvant effects, suppressing tumor growth in vivo. PMID:24348476

Adoption of Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer.

PubMed

Cercek, Andrea; Roxburgh, Campbell S D; Strombom, Paul; Smith, J Joshua; Temple, Larissa K F; Nash, Garrett M; Guillem, Jose G; Paty, Philip B; Yaeger, Rona; Stadler, Zsofia K; Seier, Kenneth; Gonen, Mithat; Segal, Neil H; Reidy, Diane L; Varghese, Anna; Shia, Jinru; Vakiani, Efsevia; Wu, Abraham J; Crane, Christopher H; Gollub, Marc J; Garcia-Aguilar, Julio; Saltz, Leonard B; Weiser, Martin R

2018-03-22

Treatment of locally advanced rectal (LARC) cancer involves chemoradiation, surgery, and chemotherapy. The concept of total neoadjuvant therapy (TNT), in which chemoradiation and chemotherapy are administered prior to surgery, has been developed to optimize delivery of effective systemic therapy aimed at micrometastases. To compare the traditional approach of preoperative chemoradiation (chemoRT) followed by postoperative adjuvant chemotherapy with the more recent TNT approach for LARC. A retrospective cohort analysis using Memorial Sloan Kettering Cancer Center (MSK) records from 2009 to 2015 was carried out. A total of 811 patients who presented with LARC (T3/4 or node-positive) were identified. Of the 811 patients, 320 received chemoRT with planned adjuvant chemotherapy and 308 received TNT (induction fluorouracil- and oxaliplatin-based chemotherapy followed by chemoRT). Treatment and outcome data for the 2 cohorts were compared. Dosing and completion of prescribed chemotherapy were assessed on the subset of patients who received all therapy at MSK. Of the 628 patients overall, 373 (59%) were men and 255 (41%) were women, with a mean (SD) age of 56.7 (12.9) years. Of the 308 patients in the TNT cohort, 181 (49%) were men and 127 (49%) were women. Of the 320 patients in the chemoRT with planned adjuvant chemotherapy cohort, 192 (60%) were men and 128 (40%) were women. Patients in the TNT cohort received greater percentages of the planned oxaliplatin and fluorouracil prescribed dose than those in the chemoRT with planned adjuvant chemotherapy cohort. The complete response (CR) rate, including both pathologic CR (pCR) in those who underwent surgery and sustained clinical CR (cCR) for at least 12 months posttreatment in those who did not undergo surgery, was 36% in the TNT cohort compared with 21% in the chemoRT with planned adjuvant chemotherapy cohort. Our findings provide additional support for the National Comprehensive Cancer Network (NCCN) guidelines that categorize TNT as a viable treatment strategy for rectal cancer. Our data suggest that TNT facilitates delivery of planned systemic therapy. Long-term follow-up will determine if this finding translates into improved survival. In addition, given its high CR rate, TNT may facilitate nonoperative treatment strategies aimed at organ preservation.

A pilot randomized controlled trial of D-cycloserine and distributed practice as adjuvants to constraint-induced movement therapy after stroke.

PubMed

Nadeau, Stephen E; Davis, Sandra E; Wu, Samuel S; Dai, Yunfeng; Richards, Lorie G

2014-01-01

Background. Phase III trials of rehabilitation of paresis after stroke have proven the effectiveness of intensive and extended task practice, but they have also shown that many patients do not qualify, because of severity of impairment, and that many of those who are treated are left with clinically significant deficits. Objective. To test the value of 2 potential adjuvants to normal learning processes engaged in constraint-induced movement therapy (CIMT): greater distribution of treatment over time and the coadministration of d-cycloserine, a competitive agonist at the glycine site of the N-methyl-D-aspartate glutamate receptor. Methods. A prospective randomized single-blind parallel-group trial of more versus less condensed therapy (2 vs 10 weeks) and d-cycloserine (50 mg) each treatment day versus placebo (in a 2 × 2 design), as potential adjuvants to 60 hours of CIMT. Results. Twenty-four participants entered the study, and 22 completed it and were assessed at the completion of treatment and 3 months later. Neither greater distribution of treatment nor treatment with d-cycloserine significantly augmented retention of gains achieved with CIMT. Conclusions. Greater distribution of practice and treatment with d-cycloserine do not appear to augment retention of gains achieved with CIMT. However, concentration of CIMT over 2 weeks ("massed practice") appears to confer no advantage either. © The Author(s) 2014.

Multivariate analysis of prognostic factors for idiopathic sudden sensorineural hearing loss treated with adjuvant hyperbaric oxygen therapy.

PubMed

Xie, Shaobing; Qiang, Qingfen; Mei, Lingyun; He, Chufeng; Feng, Yong; Sun, Hong; Wu, Xuewen

2018-01-01

The objective of this study is to evaluate possible prognostic factors of idiopathic sudden sensorineural hearing loss (ISSNHL) treated with adjuvant hyperbaric oxygen therapy (HBOT) using univariate and multivariate analyses. From January 2008 to October 2016, records of 178 ISSNHL patients treated with auxiliary hyperbaric oxygen therapy were reviewed to assess hearing recovery and evaluate associated prognostic factors (gender, age, localization, initial hearing threshold, presence of tinnitus, vertigo, ear fullness, hypertension, diabetes, onset of HBOT, number of HBOT, and audiogram), by using univariate and multivariate analyses. The overall recovery rate was 37.1%, including complete recovery (19.7%) and partial recovery (17.4%). According to multivariate analysis, later onset of HBOT and higher initial hearing threshold were associated with a poor prognosis in ISSNHL patients treated with HBOT. HBOT is a safe and beneficial adjuvant therapy for ISSNHL patients. 20 sessions of HBOT is possibly enough to show its therapeutic effect. Earlier HBOT onset and lower initial hearing threshold is associated with favorable hearing recovery.

Rural trustees brave the health care funding crisis. Interview by Matthew D. Pavelich.

PubMed

Ramstead, O

1992-01-01

Ole Ramstead, FCA, this issue's interview subject, is board chair at Parkland Regional Care Centre in Melfort, Saskatchewan. He is also a chartered accountant and income tax specialist. Mr. Ramstead discusses potential changes in Canadian health care directions--such as the amalgamation of hospital governing boards and administrations--and their special impact on rural facilities.

RAPID-L Highly Automated Fast Reactor Concept Without Any Control Rods (2) Critical experiment of lithium-6 used in LEM and LIM

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

Tsunoda, Hirokazu; Sato, Osamu; Okajima, Shigeaki

2002-07-01

In order to achieve fully automated reactor operation of RAPID-L reactor, innovative reactivity control systems LEM, LIM, and LRM are equipped with lithium-6 as a liquid poison. Because lithium-6 has not been used as a neutron absorbing material of conventional fast reactors, measurements of the reactivity worth of Lithium-6 were performed at the Fast Critical Assembly (FCA) of Japan Atomic Energy Research Institute (JAERI). The FCA core was composed of highly enriched uranium and stainless steel samples so as to simulate the core spectrum of RAPID-L. The samples of 95% enriched lithium-6 were inserted into the core parallel to themore » core axis for the measurement of the reactivity worth at each position. It was found that the measured reactivity worth in the core region well agreed with calculated value by the method for the core designs of RAPID-L. Bias factors for the core design method were obtained by comparing between experimental and calculated results. The factors were used to determine the number of LEM and LIM equipped in the core to achieve fully automated operation of RAPID-L. (authors)« less

Socioeconomic Disparities in Breast Cancer Treatment Among Older Women

PubMed Central

Richardson, Lisa C.; Krontiras, Helen; Pisu, Maria

2014-01-01

Abstract Background: Racial disparities in breast cancer treatment among Medicare beneficiaries have been documented. This study aimed to determine whether racial disparities exist among white and black female Medicare beneficiaries in Alabama, an economically disadvantaged U.S. state. Methods: From a linked dataset of breast cancer cases from the Alabama Statewide Cancer Registry and fee-for-service claims from Medicare, we identified 2,097 white and black females, aged 66 years and older, who were diagnosed with stages 1–3 breast cancer from January 1, 2000, to December 31, 2002. Generalized estimating equation (GEE) models were used to determine whether there were racial differences in initiating and completing National Comprehensive Cancer Network Clinical Practice guideline-specific treatment. Results: Sixty-two percent of whites and 64.7% of blacks had mastectomy (p=0.27); 34.6% of whites and 30.2% of blacks had breast conserving surgery (BCS) (p=0.12). Among those who had BCS, 76.8% of whites and 83.3% of blacks started adjuvant radiation therapy (p=0.33) and they equally completed adjuvant radiation therapy (p=0.29). For women with tumors over 1 centimeter, whites and blacks were equally likely to start (16.1% of whites and 18.3% of black; p=0.34) and complete (50.6% of whites and 46.3% of black; p=0.87) adjuvant chemotherapy. There were still no differences after adjusting for confounders using GEE. However, differences were observed by area-level socioeconomic status (SES), with lower SES residents more likely to receive a mastectomy (odds ratio [OR]=1.26; 95% confidence interval [CI]: 1.01–1.57) and initiate radiation after BCS (OR=2.24; 95% CI: 1.28–3.93). Conclusions: No racial differences were found in guideline-specific breast cancer treatment or treatment completion, but there were differences by SES. Future studies should explore reasons for SES differences and whether similar results hold in other economically disadvantaged U.S. states. PMID:24350590

Therapeutic effect of melittin on a rat model of chronic prostatitis induced by Complete Freund's Adjuvant.

PubMed

Lin, Li; Zhu, Bao-Ping; Cai, Liang

2017-06-01

The present study was aimed to establish a model of chronic prostatitis in rat with the use of intraprostatic injection of Complete Freund's Adjuvant, and to examine the anti-inflammatory and analgesic effects of melittin on the newly-developed chronic prostatic pain model. Adult male Sprague-Dawley rats were injected with Complete Freund's Adjuvant (CFA) into the prostate. Twelve days after model rats of the treatment group were injected melittin into the prostate, while those of the control group received sterile saline injection. The nociceptive effects of CFA were evaluated by using a behavior approach (i.e. mechanical pain threshold measurement) on the day of CFA injection and 6, 12, and 18days after CFA injection. After the in-live study was done, the prostate was collected for histological examination of inflammatory cell infiltration. Levels of cyclooxygenase (COX)-2 in prostate and glial fibrillary acidic protein (GFAP) in spinal cord were determined using immunohistochemistry. Rats of the sham control group received intraprostatic injection of sterile saline and were studied using the same methods RESULTS: Intraprostatic CFA injection induced local allodynia that lasted over at least 2 weeks. The pain behavior of rat was associated with increases in inflammatory cell infiltration into the prostate. Levels of COX-2 in prostate and GFAP in spinal cord were also elevated. Treatment with melittin significantly raised pain threshold, decreased inflammatory infiltrates, and suppressed COX-2 and GFAP expression. Intraprostatic injection of CFA induced neurogenic prostatitis and prostatic pain. The established model will be useful to the study of CP/CPPS pathogenesis. Melittin demonstrated profound anti-inflammatory and analgesic effects on the chronic prostatic pain model, suggesting melittin may hold promise as a novel therapeutic for treatment of CP/CPPS. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Inter-Clade Protection Offered by Mw-Adjuvanted Recombinant HA, NP Proteins, and M2e Peptide Combination Vaccine in Mice Correlates with Cellular Immune Response.

PubMed

Ingle, Nilesh B; Virkar, Rashmi G; Arankalle, Vidya A

2016-01-01

We documented earlier that Mw (heat-killed suspension of Mycobacterium indicus pranii ) adjuvant when used with conserved antigens, nucleoprotein (NP), and ectodomain of matrix (M2) protein (M2e) provided complete protection against homologous (clade 2.2) virus challenge in mice. The present study extends these observations to inter-clade challenge (clade 2.3.2.1) H5N1 virus and attempts to understand preliminary immunologic basis for the observed protection. Female BALB/c mice immunized with a single or two doses of vaccine formulations (clade 2.2 antigens) were challenged with 100LD50 homologous or heterologous (clade 2.3.2.1) virus. To understand the preliminary immunologic mechanism, we studied proportions of selected immune cell types, immune response gene expression, and Th1/Th2 cytokines induced by antigen-stimulated splenocytes from immunized mice, at different time points. Complete protection was conferred by Mw-HA, Mw-HA + NP, and Mw-HA + NP + M2e against homologous challenge. The protection correlated with IgG2a antibody titers indicating important role of Th1 response. Despite high inter-cladal antigenic differences, complete protection against the heterologous strain was achieved with Mw-HA + NP + M2e. Of note, a single dose with higher antigen concentrations (50 µg HA + 50 μg NP + 50 μg M2e) led to 80% protection against clade 2.3.2.1 strain. The protection conferred by Mw-HNM correlated with induction of IFN-γ, CD8 + T cytotoxic cells, and CD4 + T helper cells. Mw-adjuvanted HA + NP + M2e combination represents a promising vaccine candidate deserving further evaluation.

Adjuvant Ciprofloxacin for Persistent BK Polyomavirus Infection in Kidney Transplant Recipients

PubMed Central

Chandran, Sindhu; Vagefi, Parsia A.

2014-01-01

Background. BK virus (BKV) infection is a common complication following kidney transplantation. Immunosuppression reduction is the cornerstone of treatment while adjuvant drugs have been tried in small uncontrolled studies. We sought to examine our center's experience with the use of ciprofloxacin in patients with persistent BKV infection. Methods. Retrospective evaluation of the effect of a 30-day ciprofloxacin course (250 mg twice daily) on BKV infection in kidney transplant recipients who had been diagnosed with BK viruria ≥106 copies/mL and viremia ≥500 copies/mL and in whom the infection did not resolve after immunosuppression reduction and/or treatment with other adjuvant agents. BKV in plasma and urine was evaluated after 3 months following treatment with ciprofloxacin. Results. Nine kidney transplant recipients received ciprofloxacin at a median of 130 days following the initial reduction in immunosuppression. Three patients showed complete viral clearance and another 3 had a ≥50% decrease in plasma viral load. No serious adverse events secondary to ciprofloxacin were reported and no grafts were lost due to BKV up to 1 year after treatment. Conclusion. Ciprofloxacin may be a useful therapy for persistent BKV infection despite conventional treatment. Randomized trials are required to evaluate the potential benefit of this adjuvant therapy. PMID:25349720

Three-year duration of immunity in cats vaccinated with a canarypox-vectored recombinant rabies virus vaccine.

PubMed

Jas, D; Coupier, C; Toulemonde, C Edlund; Guigal, P-M; Poulet, H

2012-11-19

Despite the availability of efficacious vaccines for animals and humans, rabies is still a major zoonosis. Prevention of rabies in dogs and cats is key for reducing the risk of transmission of this deadly disease to humans. Most veterinary vaccines are adjuvanted inactivated vaccines and have been shown to provide one to four-year duration of immunity. In response to debates about the safety of adjuvanted vaccines in cats, a non-adjuvanted feline rabies vaccine with one-year duration of immunity claim was specifically developed using the canarypoxvirus vector technology. The objective of this study was to validate a vaccination program based on primary vaccination, revaccination one year later and boosters every three years. Seronegative cats were vaccinated at 12 weeks of age and received a booster vaccination one year later. This vaccination regimen induced a strong and sustained antibody response, and all vaccinated animals were protected against virulent rabies challenge carried out 3 years after vaccination. These results validated 3-year duration of immunity after a complete basic vaccination program consisting in primary vaccination from 12 weeks of age followed by revaccination one year later with a non-adjuvanted canarypox-vectored vaccine. Copyright © 2012 Elsevier Ltd. All rights reserved.

Role of phyto-stabilised silver nanoparticles in suppressing adjuvant induced arthritis in rats.

PubMed

Mani, Aparna; Vasanthi, C; Gopal, V; Chellathai, Darling

2016-12-01

The present study was aimed to evaluate the anti-arthritic effects of silver nanoparticles synthesised using Piper nigrum extract and to further establish its mechanism of action in a rat model of adjuvant induced arthritis (AA). Adjuvant arthritis was induced by injecting complete Freund's adjuvant (0.1mL) into the left hind paw of 36 albino Wistar rats (n=6). Silver nanoparticles stabilised with Piper nigrum extract (25 and 50mg/kg). Commercial silver nanoparticles (50mg/kg) and methotrexate (0.1mg/kg) were administered by intraperitoneal route from day 11 to day 22 on alternate days. It was found that treatment with silver nanoparticles stabilised with Piper nigrum (S-AgNPs) significantly reduced the paw edema and alleviated the histopathological changes of cell infiltration, synovial hyperplasia, bone and cartilage destruction. Furthermore, the phytostabilised silver nanoparticles (S-AgNPs) inhibited the protein expression of NF-kβ p65 and TNF-α as evidenced by immunohistochemistry analysis. Our current findings suggest that silver nanoparticles stabilised with Piper nigrum extract (S-AgNPs) have potent anti-arthritic activity which is mediated by inhibition of TNF-α and suppression of pro-inflammatory cytokines that are secreted in response to activated transcription factors of NF-kβ. Copyright © 2016 Elsevier B.V. All rights reserved.

External-beam radiotherapy for differentiated thyroid cancer locoregional control: A statement of the American Head and Neck Society

PubMed Central

Kiess, Ana P.; Agrawal, Nishant; Brierley, James D.; Duvvuri, Umamaheswar; Ferris, Robert L.; Genden, Eric; Wong, Richard J.; Tuttle, R. Michael; Lee, Nancy Y.; Randolph, Gregory W.

2016-01-01

The use of external-beam radiotherapy (EBRT) in differentiated thyroid cancer (DTC) is debated because of a lack of prospective clinical data, but recent retrospective studies have reported benefits in selected patients. The Endocrine Surgery Committee of the American Head and Neck Society provides 4 recommendations regarding EBRT for locoregional control in DTC, based on review of literature and expert opinion of the authors. (1) EBRT is recommended for patients with gross residual or unresectable locoregional disease, except for patients <45 years old with limited gross disease that is radioactive iodine (RAI)-avid. (2) EBRT should not be routinely used as adjuvant therapy after complete resection of gross disease. (3) After complete resection, EBRT may be considered in select patients >45 years old with high likelihood of microscopic residual disease and low likelihood of responding to RAI. (4) Cervical lymph node involvement alone should not be an indication for adjuvant EBRT. PMID:26716601

Prospective, multicenter French study evaluating the clinical impact of the Breast Cancer Intrinsic Subtype-Prosigna® Test in the management of early-stage breast cancers.

PubMed

Hequet, Delphine; Callens, Céline; Gentien, David; Albaud, Benoit; Mouret-Reynier, Marie-Ange; Dubot, Coraline; Cottu, Paul; Huchon, Cyrille; Zilberman, Sonia; Berseneff, Helene; Foa, Cyril; Salmon, Rémy; Roulot, Aurélie; Lerebours, Florence; Salomon, Anne; Ghali, Nadeem; Morel, Pascale; Li, Qianyi; Cayre, Anne; Guinebretière, Jean-Marc; Hornberger, John; Penault-Llorca, Frédérique; Rouzier, Roman

2017-01-01

The Prosigna® breast cancer prognostic gene signature assay identifies a gene-expression profile that permits the classification of tumors into subtypes and gives a score for the risk of recurrence (ROR) at 10 years. The primary objective of this multicenter study was to evaluate the impact of Prosigna's assay information on physicians' adjuvant treatment decisions in patients with early-stage breast cancer. Secondary objectives were to assess confidence of practitioners in their therapeutic recommendations before and after the added information provided by the Prosigna assay; and to evaluate the emotional state of patients before and after the Prosigna test results. Consecutive patients with invasive early-stage breast cancer were enrolled in a prospective, observational, multicenter study carried out in 8 hospitals in France. The Prosigna test was carried out on surgical specimens using the nCounter® Analysis System located at the Institut Curie. Both before and after receiving the Prosigna test results, physicians completed treatment confidence questionnaires and patients completed questionnaires concerning their state of anxiety, the difficulties felt in face of the therapy and quality of life. Information was also collected at 6 months regarding the physicians' opinion on the test results and the patients' degree of anxiety, difficulties with therapy and quality of life. Between March 2015 and January 2016, 8 study centers in France consecutively enrolled 210 postmenopausal women with estrogen receptor (ER) positive, human epidermal growth hormone-2 (HER-2) negative, and node negative tumors, either stage 1 or stage 2. Intrinsic tumor subtypes as assessed by the Prosigna test were 114 (58.2%) Luminal A, 79 (40.3%) Luminal B, 1 (0.5%) HER-2 enriched (HER-2E), and 2 (1.0%) basal-like. Before receiving the Prosigna test results, physicians categorized tumor subtypes based on immunohistochemistry (IHC) as Luminal A in 126 (64%) patients and Luminal B in 70 (36%) patients, an overall discordance rate of 25%. The availability of Prosigna assay results was significantly associated with the likelihood of change in treatment recommendations, with 34 patients (18%) having their treatment plan changed from Adjuvant Chemotherapy to No Adjuvant Chemotherapy or vice versa (p<0.001, Fisher's exact test). Prosigna test results also decreased patients' anxiety about the chosen adjuvant therapy, and improved emotional well-being and measures of personal perceptions of uncertainty. The results of this prospective decision impact study are consistent with 2 previous, identically designed studies carried out in Spain and Germany. The availability of Prosigna test results increased the confidence of treating physicians in their adjuvant treatment decisions, and led to an 18% change in chemotherapy treatment plan (from Adjuvant Chemotherapy to No Adjuvant Chemotherapy or vice versa). Prosigna testing decreased anxiety and improved measures of health-related quality of life in patients facing adjuvant therapy. The 25% discordance between Prosigna test and IHC subtyping underlines the importance of molecular testing for optimal systemic therapy indications in early breast cancer.

Prospective, multicenter French study evaluating the clinical impact of the Breast Cancer Intrinsic Subtype-Prosigna® Test in the management of early-stage breast cancers

PubMed Central

Callens, Céline; Gentien, David; Albaud, Benoit; Mouret-Reynier, Marie-Ange; Dubot, Coraline; Cottu, Paul; Huchon, Cyrille; Zilberman, Sonia; Berseneff, Helene; Foa, Cyril; Salmon, Rémy; Roulot, Aurélie; Lerebours, Florence; Salomon, Anne; Ghali, Nadeem; Morel, Pascale; Li, Qianyi; Cayre, Anne; Guinebretière, Jean-Marc; Hornberger, John; Penault-Llorca, Frédérique; Rouzier, Roman

2017-01-01

Purpose The Prosigna® breast cancer prognostic gene signature assay identifies a gene-expression profile that permits the classification of tumors into subtypes and gives a score for the risk of recurrence (ROR) at 10 years. The primary objective of this multicenter study was to evaluate the impact of Prosigna’s assay information on physicians’ adjuvant treatment decisions in patients with early-stage breast cancer. Secondary objectives were to assess confidence of practitioners in their therapeutic recommendations before and after the added information provided by the Prosigna assay; and to evaluate the emotional state of patients before and after the Prosigna test results. Methods Consecutive patients with invasive early-stage breast cancer were enrolled in a prospective, observational, multicenter study carried out in 8 hospitals in France. The Prosigna test was carried out on surgical specimens using the nCounter® Analysis System located at the Institut Curie. Both before and after receiving the Prosigna test results, physicians completed treatment confidence questionnaires and patients completed questionnaires concerning their state of anxiety, the difficulties felt in face of the therapy and quality of life. Information was also collected at 6 months regarding the physicians’ opinion on the test results and the patients’ degree of anxiety, difficulties with therapy and quality of life. Results Between March 2015 and January 2016, 8 study centers in France consecutively enrolled 210 postmenopausal women with estrogen receptor (ER) positive, human epidermal growth hormone-2 (HER-2) negative, and node negative tumors, either stage 1 or stage 2. Intrinsic tumor subtypes as assessed by the Prosigna test were 114 (58.2%) Luminal A, 79 (40.3%) Luminal B, 1 (0.5%) HER-2 enriched (HER-2E), and 2 (1.0%) basal-like. Before receiving the Prosigna test results, physicians categorized tumor subtypes based on immunohistochemistry (IHC) as Luminal A in 126 (64%) patients and Luminal B in 70 (36%) patients, an overall discordance rate of 25%. The availability of Prosigna assay results was significantly associated with the likelihood of change in treatment recommendations, with 34 patients (18%) having their treatment plan changed from Adjuvant Chemotherapy to No Adjuvant Chemotherapy or vice versa (p<0.001, Fisher’s exact test). Prosigna test results also decreased patients’ anxiety about the chosen adjuvant therapy, and improved emotional well-being and measures of personal perceptions of uncertainty. Conclusions The results of this prospective decision impact study are consistent with 2 previous, identically designed studies carried out in Spain and Germany. The availability of Prosigna test results increased the confidence of treating physicians in their adjuvant treatment decisions, and led to an 18% change in chemotherapy treatment plan (from Adjuvant Chemotherapy to No Adjuvant Chemotherapy or vice versa). Prosigna testing decreased anxiety and improved measures of health-related quality of life in patients facing adjuvant therapy. The 25% discordance between Prosigna test and IHC subtyping underlines the importance of molecular testing for optimal systemic therapy indications in early breast cancer. PMID:29045452

[Synchronous bilateral breast cancer in a male].

PubMed

García-Mejido, José Antonio; Delgado-Jiménez, Carmen; Gutiérrez-Palomino, Laura; Sánchez-Sevilla, Miguel; Iglesias-Bravo, Eva; Caballero-Fernández, Virginia

2013-01-01

male breast cancer is a disease with low incidence, which is further reduced when it comes to bilateral synchronous presentation. There are few published cases in recent years. The aim is to establish guidelines for the management of this disorder that is so rare. a 75-year-old with tumors in both breasts, which were completely resected with removal of palpable nodes. The histopathological study reported ductal carcinoma. The indicated treatment was adjuvant tamoxifen and radiotherapy. The patient is currently in a disease-free period. this is a rare disease, whose main treatment is surgery, hence the importance of early diagnosis. Most cases require adjuvant chemotherapy and radiotherapy because they are usually diagnosed at an advanced stage.

Retrospective study of adjuvant icotinib in postoperative lung cancer patients harboring epidermal growth factor receptor mutations.

PubMed

Yao, Shuyang; Zhi, Xiuyi; Wang, Ruotian; Qian, Kun; Hu, Mu; Zhang, Yi

2016-09-01

Epidermal growth factor receptor (EGFR) mutations occur in about 50% of Asian patients with non-small cell lung cancer (NSCLC). Patients with advanced NSCLC and EGFR mutations derive clinical benefit from treatment with EGFR-tyrosine kinase inhibitors (TKIs). This study assessed the efficacy and safety of adjuvant icotinib without chemotherapy in EGFR-mutated NSCLC patients undergoing resection of stage IB-IIIA. Our retrospective study enrolled 20 patients treated with icotinib as adjuvant therapy. Survival factors were evaluated by univariate and Cox regression analysis. The median follow-up time was 30 months (range 24-41). At the data cut-off, five patients (25%) had recurrence or metastasis and one patient had died of the disease. The two-year disease-free survival (DFS) rate was 85%. No recurrence occurred in the high-risk stage IB subgroup during the follow-up period. In univariate analysis, the micropapillary pattern had a statistically significant effect on DFS ( P = 0.040). Multivariate logistic regression analysis showed that there was no independent predictor. Drug related adverse events (AEs) occurred in nine patients (45.0%). The most common AEs were skin-related events and diarrhea, but were relatively mild. No grade 3 AEs or occurrences of intolerable toxicity were observed. Icotinib as adjuvant therapy is effective in patients harboring EGFR mutations after complete resection, with an acceptable AE profile. Further trials with larger sample sizes might confirm the efficiency of adjuvant TKI in selected patients. © 2016 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Risk of treatment related death and febrile neutropaenia with taxane-based adjuvant chemotherapy for breast cancer in a middle income country outside a clinical trial setting.

PubMed

Phua, Chee Ee; Bustam, Anita Zarina; Yusof, Mastura Md; Saad, Marniza; Yip, Cheng-Har; Taib, Nor Aishah; Ng, Char Hong; Teh, Yew Ching

2012-01-01

The risk of treatment-related death (TRD) and febrile neutropaenia (FN) with adjuvant taxane- based chemotherapy for early breast cancer is unknown in Malaysia despite its widespread usage in recent years. This study aims to determine these rates in patients treated in University Malaya Medical Centre (UMMC). Patients who were treated with adjuvant taxane-based chemotherapy for early breast cancer stages I, II or III from 2007-2011 in UMMC were identified from our UMMC Breast Cancer Registry. The TRD and FN rates were then determined retrospectively from medical records. TRD was defined as death occurring during or within 30 days of completing chemotherapy as a consequence of the chemotherapy treatment. FN was defined as an oral temperature >38.5°C or two consecutive readings of >38.0°C for 2 hours and an absolute neutrophil count <0.5x109/L, or expected to fall below 0.5x109/L. A total of 622 patients received adjuvant chemotherapy during this period. Of these patients 209 (33.6%) received taxane-based chemotherapy. 4 taxane-based regimens were used namely the FEC-D, TC, TAC and AC-PCX regimens. The commonest regimen employed was the FEC-D regimen accounting for 79.9% of the patients. The FN rate was 10% and there was no TRD. Adjuvant taxane-based chemotherapy in UMMC for early breast cancer has a FN rate of 10%. Primary prophylactic G-CSF should be considered for patients with any additional risk factor for FN.

Treatment Patterns and Health Resource Utilization Among Patients Diagnosed With Early Stage Resected Non-Small Cell Lung Cancer at US Community Oncology Practices.

PubMed

Buck, Philip O; Saverno, Kimberly R; Miller, Paul J E; Arondekar, Bhakti; Walker, Mark S

2015-11-01

Data on adjuvant therapy in resected non-small cell lung cancer (NSCLC) in routine practice are lacking in the United States. This retrospective observational database study included 609 community oncology patients with resected stage IB to IIIA NSCLC. Use of adjuvant therapy was 39.1% at disease stage IB and 64.9% to 68.2% at stage II to IIIA. The most common regimen at all stages was carboplatin and paclitaxel. Platin-based adjuvant chemotherapy has extended survival in clinical trials in patients with completely resected non-small cell lung cancer (NSCLC). There are few data on the use of adjuvant therapy in community-based clinical practice in the United States. This was a retrospective observational study using electronic medical record and billing data collected during routine care at US community oncology sites in the Vector Oncology Data Warehouse between January 2007 and January 2014. Patients aged ≥ 18 years with a primary diagnosis of stage IB to IIIA NSCLC were eligible if they had undergone surgical resection. Treatment patterns, health care resource use, and cost were recorded, stratified by stage at diagnosis. The study included 609 patients (mean age, 64.8 years, 52.9% male), of whom 215 had stage IB disease, 130 stage IIA/II, 110 stage IIB, and 154 stage IIIA. Adjuvant systemic therapy after resection was provided to 345 (56.7%) of 609 patients, with lower use in patients with stage IB disease (39.1%) than stage II to IIIA disease (64.9-68.2%) (P < .0001). The most common adjuvant regimen at all stages was the combination of carboplatin and paclitaxel. There were no statistically significant differences in office visits or incidence of hospitalization by disease stage. During adjuvant treatment, the total monthly median cost per patient was $17,389.75 (interquartile range, $8,815.61 to $23,360.85). Adjuvant systemic therapy was used in some patients with stage IB NSCLC and in the majority of patients with stage IIA to IIIA disease. There were few differences in regimen or health care resource use by disease stage. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Immunopotentiation by SGP and Quil A. II. Identification of responding cell populations.

PubMed

Flebbe, L M; Braley-Mullen, H

1986-04-15

The adjuvants SGP (a starch-acrylamide polymer) and Quil A (purified saponin) were shown to markedly augment antibody responses to T-independent (TI) antigens, suggesting that their adjuvant effects may be at least partially mediated through B cells. The ability of both adjuvants to augment primary responses to trinitrophenyl (TNP)-Ficoll (TI-2 antigen) in athymic nude mice further suggested these adjuvants affect B cells. SGP, however, did not induce a response to the T-dependent (TD) antigen dinitrophenyl-keyhole limpet hemocyanin (DNP-KLH) in athymic nude mice, indicating it was unable to replace the requirement for T-helper cells for responses to TD antigens. Responses to TNP-lipopolysaccharide (LPS) were augmented by SGP in CBA/N X Balb/c immune defective (xid) mice. However, SGP was unable to induce a response to TNP-Ficoll in xid mice. The SGP and Quil A augmented responses to TNP-Ficoll were completely inhibited by the mitotic inhibitor, Velban, indicating that SGP and Quil A increased the plaque-forming cell (PFC) response primarily by stimulating cell proliferation, and not by recruitment of antigen-reactive cells. The effects of the adjuvants on secondary responses were investigated using adoptive transfer experiments. SGP and A1(OH)3 both increased the induction of hapten-specific memory B cells in mice primed with DNP-KLH. SGP, Quil A, and A1(OH)3 also increased priming of carrier specific T cells. Priming of memory B cells with DNP-KLH and either A1(OH)3 or SGP was prevented when T cells were depleted with anti-lymphocyte serum (ALS) at the time of antigen priming, indicating that the augmentation of memory B-cell priming by SGP and A1(OH)3 was dependent on the presence of functional T cells. SGP and Quil A were both unable to augment memory cell induction to the TI antigen, TNP-Ficoll, even though both adjuvants markedly augmented primary IgM and IgG responses to this antigen. Based on these results, it is suggested that SGP and Quil A can mediate their adjuvant effects primarily by a direct or indirect effect on B cells although the adjuvants may also affect T cells to some extent.

Fuzzy cluster analysis of high-field functional MRI data.

PubMed

Windischberger, Christian; Barth, Markus; Lamm, Claus; Schroeder, Lee; Bauer, Herbert; Gur, Ruben C; Moser, Ewald

2003-11-01

Functional magnetic resonance imaging (fMRI) based on blood-oxygen level dependent (BOLD) contrast today is an established brain research method and quickly gains acceptance for complementary clinical diagnosis. However, neither the basic mechanisms like coupling between neuronal activation and haemodynamic response are known exactly, nor can the various artifacts be predicted or controlled. Thus, modeling functional signal changes is non-trivial and exploratory data analysis (EDA) may be rather useful. In particular, identification and separation of artifacts as well as quantification of expected, i.e. stimulus correlated, and novel information on brain activity is important for both, new insights in neuroscience and future developments in functional MRI of the human brain. After an introduction on fuzzy clustering and very high-field fMRI we present several examples where fuzzy cluster analysis (FCA) of fMRI time series helps to identify and locally separate various artifacts. We also present and discuss applications and limitations of fuzzy cluster analysis in very high-field functional MRI: differentiate temporal patterns in MRI using (a) a test object with static and dynamic parts, (b) artifacts due to gross head motion artifacts. Using a synthetic fMRI data set we quantitatively examine the influences of relevant FCA parameters on clustering results in terms of receiver-operator characteristics (ROC) and compare them with a commonly used model-based correlation analysis (CA) approach. The application of FCA in analyzing in vivo fMRI data is shown for (a) a motor paradigm, (b) data from multi-echo imaging, and (c) a fMRI study using mental rotation of three-dimensional cubes. We found that differentiation of true "neural" from false "vascular" activation is possible based on echo time dependence and specific activation levels, as well as based on their signal time-course. Exploratory data analysis methods in general and fuzzy cluster analysis in particular may help to identify artifacts and add novel and unexpected information valuable for interpretation, classification and characterization of functional MRI data which can be used to design new data acquisition schemes, stimulus presentations, neuro(physio)logical paradigms, as well as to improve quantitative biophysical models.

Adjuvant chemotherapy for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision: a Dutch Colorectal Cancer Group (DCCG) randomized phase III trial.

PubMed

Breugom, A J; van Gijn, W; Muller, E W; Berglund, Å; van den Broek, C B M; Fokstuen, T; Gelderblom, H; Kapiteijn, E; Leer, J W H; Marijnen, C A M; Martijn, H; Meershoek-Klein Kranenbarg, E; Nagtegaal, I D; Påhlman, L; Punt, C J A; Putter, H; Roodvoets, A G H; Rutten, H J T; Steup, W H; Glimelius, B; van de Velde, C J H

2015-04-01

The discussion on the role of adjuvant chemotherapy for rectal cancer patients treated according to current guidelines is still ongoing. A multicentre, randomized phase III trial, PROCTOR-SCRIPT, was conducted to compare adjuvant chemotherapy with observation for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision (TME). The PROCTOR-SCRIPT trial recruited patients from 52 hospitals. Patients with histologically proven stage II or III rectal adenocarcinoma were randomly assigned (1:1) to observation or adjuvant chemotherapy after preoperative (chemo)radiotherapy and TME. Radiotherapy consisted of 5 × 5 Gy. Chemoradiotherapy consisted of 25 × 1.8-2 Gy combined with 5-FU-based chemotherapy. Adjuvant chemotherapy consisted of 5-FU/LV (PROCTOR) or eight courses capecitabine (SCRIPT). Randomization was based on permuted blocks of six, stratified according to centre, residual tumour, time between last irradiation and surgery, and preoperative treatment. The primary end point was overall survival. Of 470 enrolled patients, 437 were eligible. The trial closed prematurely because of slow patient accrual. Patients were randomly assigned to observation (n = 221) or adjuvant chemotherapy (n = 216). After a median follow-up of 5.0 years, 5-year overall survival was 79.2% in the observation group and 80.4% in the chemotherapy group [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.62-1.39; P = 0.73]. The HR for disease-free survival was 0.80 (95% CI 0.60-1.07; P = 0.13). Five-year cumulative incidence for locoregional recurrences was 7.8% in both groups. Five-year cumulative incidence for distant recurrences was 38.5% and 34.7%, respectively (P = 0.39). The PROCTOR-SCRIPT trial could not demonstrate a significant benefit of adjuvant chemotherapy with fluoropyrimidine monotherapy after preoperative (chemo)radiotherapy and TME on overall survival, disease-free survival, and recurrence rate. However, this trial did not complete planned accrual. Dutch Colorectal Cancer group, CKTO 2003-16, ISRCTN36266738. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

A prospective, multicenter pilot study to investigate the feasibility and safety of a 1-year controlled exercise training after adjuvant chemotherapy in colorectal cancer patients.

PubMed

Piringer, Gudrun; Fridrik, Michael; Fridrik, Alfred; Leiherer, Andreas; Zabernigg, August; Greil, Richard; Eisterer, Wolfgang; Tschmelitsch, Jörg; Lang, Alois; Frantal, Sophie; Burgstaller, Sonja; Gnant, Michael; Thaler, Josef

2018-04-01

Despite advances in adjuvant chemotherapy, 20-30% of patients in stages II-III colorectal cancer will eventually relapse. Observational studies showed a reduction in relapse rate, colon cancer-specific mortality, and overall mortality by physical activity. Results from prospective randomized interventional studies to confirm these observational data are lacking. The aims of this prospective single-arm multicenter pilot study are to evaluate feasibility and safety of exercise training after adjuvant chemotherapy in colorectal cancer patients. The training was performed three times per week for 1 year and was increased gradually in three phases until reaching 18 metabolic equivalent task hours per week. Overall, 30 patients were included. The planned training intensity could be achieved in all three phases. Patients experienced a performance increase of median 35.5 watt, a weight-loss of a median of 3.0 kg, and a reduction in body fat content of median 1.0% during this exercise training. The analysis showed early study termination due to non-compliance in 10/30 patients (33.3%), disease progression in 4 patients (13.3%), and serious adverse events in 2 patients (6.7%). About half of patients (46.7%) completed the pilot study as planned. Biomarker analysis from 20 patients showed a non-significant reduction in insulin-like growth factor 1 (IGF-1), insulin-like growth factor 2 (IGF-2) and insulin-like growth factor binding protein 3 (IGF-BP3) levels, significant increases in adiponectin and leptin levels, and a non-significant increase in C-peptide levels. Exercise training is feasible in patients with colorectal cancer after completion of adjuvant chemotherapy. The main problem encountered during the study was compliance. To improve compliance of exercise training, several measures were adapted for the upcoming prospective randomized ABCSG C08 Exercise II study.

Enhanced expressions of mRNA for neuropeptide Y and interleukin 1 beta in hypothalamic arcuate nuclei during adjuvant arthritis-induced anorexia in Lewis rats.

PubMed

Stofkova, Andrea; Haluzik, Martin; Zelezna, Blanka; Kiss, Alexander; Skurlova, Martina; Lacinova, Zdenka; Jurcovicova, Jana

2009-01-01

Food intake is activated by hypothalamic orexigenic neuropeptide Y (NPY), which is mainly under the dual control of leptin and ghrelin. Rat adjuvant arthritis (AA), similarly as human rheumatoid arthritis, is associated with cachexia caused by yet unknown mechanisms. The aim of our study was to evaluate NPY expression in hypothalamic arcuate nuclei (nARC) under the conditions of AA-induced changes in leptin, ghrelin and adiponectin. Since IL-1beta is involved in the central induction of anorexia, we studied its expression in the nARC as well. AA was induced to Lewis rats using complete Freund's adjuvant. On days 12, 15 and 18 after complete Freund's adjuvant injection, the levels of leptin, adiponectin, ghrelin and IL-1beta were determined by RIA or ELISA. The mRNA expressions for NPY, leptin receptor (OB-R), ghrelin receptor (Ghsr) and IL-1beta were determined by TaqMan RT-PCR from isolated nARC. In AA rats, decreased appetite, body mass and epididymal fat stores positively correlated with reduced circulating and epididymal fat leptin and adiponectin. Ghrelin plasma levels were increased. In nARC, mRNA for OB-R, Ghsr and NPY were overexpressed in AA rats. AA rats showed overexpression of mRNA for IL-1beta in nARC while circulating, and spleen IL-1beta was unaltered. During AA, overexpression of orexigenic NPY mRNA in nARC along with enhanced plasma ghrelin and lowered leptin levels occur. Decreased food intake indicates a predominant effect of the anorexigenic pathway. Activated expression of IL-1beta in nARC suggests its role in keeping AA-induced anorexia in progress. The reduction in adiponectin may also contribute to AA-induced anorexia. Copyright 2009 S. Karger AG, Basel.

Use of a computerised decision aid (DA) to inform the decision process on adjuvant chemotherapy in patients with stage II colorectal cancer: development and preliminary evaluation.

PubMed

Miles, A; Chronakis, I; Fox, J; Mayer, A

2017-03-24

To develop a computerised decision aid (DA) to inform the decision process on adjuvant chemotherapy in patients with stage II colorectal cancer, and examine perceived usefulness, acceptability and areas for improvement of the DA. Mixed methods. Single outpatient oncology department in central London. Consecutive recruitment of 13 patients with stage II colorectal cancer, 12 of whom completed the study. Inclusion criteria were: age >18 years; complete resection for stage II adenocarcinoma of the colon or rectum; patients within 14-56 days after surgery; no contraindication to adjuvant chemotherapy; able to give written informed consent. Exclusion criterion: previous chemotherapy. Patient perceived usefulness (assessed by the PrepDM questionnaire) and acceptability of the DA. PrepDM scores, measuring the perceived usefulness of the DA in preparing the patient to communicate with their doctor and make a health decision, were above those reported in other patient groups. Patient acceptability scores were also high; however, interviews showed that there was evidence of a lack of understanding of key information among some patients, in particular their baseline risk of recurrence, the net benefit of combination chemotherapy and the rationale for having chemotherapy when cancer had apparently gone. Patients found the DA acceptable and useful in supporting their decision about whether or not to have adjuvant chemotherapy. Suggested improvements for the DA include: sequential presentation of treatment options (eg, no treatment vs 1 drug, 1 drug vs 2 drugs) to enhance patient understanding of the difference between combination and single therapy, diagrams to help patients understand the rationale for chemotherapy to prevent a recurrence and inbuilt checks on patient understanding of baseline risk of recurrence and net benefit of chemotherapy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Therapeutic efficacy of PD-L1 blockade in a breast cancer model is enhanced by cellular vaccines expressing B7-1 and glycolipid-anchored IL-12.

PubMed

Bozeman, Erica N; He, Sara; Shafizadeh, Yalda; Selvaraj, Periasamy

2016-01-01

Immunotherapeutic approaches have emerged as promising strategies to treat various cancers, including breast cancer. A single approach, however, is unlikely to effectively combat the complex, immune evasive strategies found within the tumor microenvironment, thus novel, effective combination treatments must be explored. In this study, we investigated the efficacy of a combination therapy consisting of PD-L1 immune checkpoint blockade and whole cell vaccination in a HER-2 positive mouse model of breast cancer. We demonstrate that tumorigenicity is completely abrogated when adjuvanted with immune stimulatory molecules (ISMs) B7-1 and a cell-surface anchored (GPI) form of IL-12 or GM-CSF. Irradiated cellular vaccines expressing the combination of adjuvants B7-1 and GPI-IL-12 completely inhibited tumor formation which was correlative with robust HER-2 specific CTL activity. However, in a therapeutic setting, both cellular vaccination and PD-L1 blockade induced only 10-20% tumor regression when administered alone but resulted in 50% tumor regression as a combination therapy. This protection was significantly hindered following CD4 or CD8 depletion indicating the essential role played by cellular immunity. Collectively, these pre-clinical studies provide a strong rationale for further investigation into the efficacy of combination therapy with tumor cell vaccines adjuvanted with membrane-anchored ISMs along with PD-L1 blockade for the treatment of breast cancer.

Therapeutic efficacy of PD-L1 blockade in a breast cancer model is enhanced by cellular vaccines expressing B7-1 and glycolipid-anchored IL-12

PubMed Central

Bozeman, Erica N; He, Sara; Shafizadeh, Yalda; Selvaraj, Periasamy

2016-01-01

Immunotherapeutic approaches have emerged as promising strategies to treat various cancers, including breast cancer. A single approach, however, is unlikely to effectively combat the complex, immune evasive strategies found within the tumor microenvironment, thus novel, effective combination treatments must be explored. In this study, we investigated the efficacy of a combination therapy consisting of PD-L1 immune checkpoint blockade and whole cell vaccination in a HER-2 positive mouse model of breast cancer. We demonstrate that tumorigenicity is completely abrogated when adjuvanted with immune stimulatory molecules (ISMs) B7-1 and a cell-surface anchored (GPI) form of IL-12 or GM-CSF. Irradiated cellular vaccines expressing the combination of adjuvants B7-1 and GPI-IL-12 completely inhibited tumor formation which was correlative with robust HER-2 specific CTL activity. However, in a therapeutic setting, both cellular vaccination and PD-L1 blockade induced only 10–20% tumor regression when administered alone but resulted in 50% tumor regression as a combination therapy. This protection was significantly hindered following CD4 or CD8 depletion indicating the essential role played by cellular immunity. Collectively, these pre-clinical studies provide a strong rationale for further investigation into the efficacy of combination therapy with tumor cell vaccines adjuvanted with membrane-anchored ISMs along with PD-L1 blockade for the treatment of breast cancer. PMID:26308597

Gastrointestinal stromal tumors: A multidisciplinary challenge

PubMed Central

Sanchez-Hidalgo, Juan Manuel; Duran-Martinez, Manuel; Molero-Payan, Rafael; Rufian-Peña, Sebastian; Arjona-Sanchez, Alvaro; Casado-Adam, Angela; Cosano-Alvarez, Antonio; Briceño-Delgado, Javier

2018-01-01

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors located in the alimentary tract. Its usual manifestation is gastrointestinal bleeding. However, small asymptomatic lesions are frequently detected as incidental finding. Characteristically, most GISTs (> 95%) are positive for the KIT protein (CD117) by IHC staining and approximately 80%-90% of GISTs carry a mutation in the c-KIT or PDGFRA genes. Mutational analysis should be performed when planning adjuvant and neoadjuvant therapy, due to its possible resistance to conventional treatment. The arise of tyrosine kinase inhibitor has supposed a revolution in GISTs treatment being useful as adjuvant, neoadjuvant or recurrence disease treatment. That is why a multidisciplinary approach to this disease is required. The correct characterization of the tumor at diagnosis (the diagnosis of recurrences and the evaluation of the response to treatment with tyrosine kinase inhibitors) is fundamental for facing these tumors and requires specialized Endoscopist, Radiologists and Nuclear Medicine Physician. Surgery is the only potentially curative treatment for suspected resectable GIST. In the case of high risk GISTs, surgery plus adjuvant Imatinib-Mesylate for 3 years is the standard treatment. Neoadjuvant imatinib-mesylate should be considered to shrink the tumor in case of locally advanced primary or recurrence disease, unresectable or potentially resectable metastasic tumors, and potentially resectable disease in complex anatomic locations to decrease the related morbidity. In the case of Metastatic GIST under Neoadjuvant treatment, when there are complete response, stable disease or limited disease progression, complete cytoreductive surgery could be a therapeutic option if feasible. PMID:29760538

Multimodality therapy for medulloblastoma. [Efficacy and complications

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

Thomas, P.R.M.; Duffner, P.K.; Cohen, M.E.

1980-02-15

Eight patients with recurrent medulloblastoma were treated with a chemotherapy regimen consisting of vincristine, BCNU, dexamethasone and intrathecal and intermediate dose intravenous methotrexate (500 mg/m/sup 2/). Five also received local low dose radiotherapy (RT). All 8 patients responded to treatment; 6 completely and 2 partially. These latter 2 were in their second and third recurrences. Three remain in remission. The median duration of response was 18.8 months, and median time from start of chemotherapy to death was 32 months using the Kaplan-Meier technique. In addition, 9 other patients with newly diagnosed medulloblastoma were treated with craniospinal radiation and the samemore » adjuvant chemotherapy as above. The first 5 patients also received intraventricular methotrexate and/or intravenous BCNU during radiotherapy. The toxicity in the 5 patients was very severe. There were three toxic deaths, one death from cancer; one patient survives disease-free, but he is demented. With the discontinuance of intraventricular methotrexate and the postponement of myelosuppressive chemotherapy until after the completion of radiotherapy, the regimen has been well tolerated. All 4 patients treated this way remain alive, well, and disease-free at intervals up to 36 months. We conclude that recurrent medulloblastomas are sensitive to multiagent chemotherapy and that prolonged remissions may occur. With primary adjuvant chemotherapy, extreme caution with myelosuppressive drugs must be exercised during the period of craniospinal radiotherapy. We also do not recommend the use of intraventricular methotrexate. When these two criteria were followed, the preliminary results with adjuvant chemotherapy appear encouraging.« less

Efficacy of an AS03A-adjuvanted split H5N1 influenza vaccine against an antigenically distinct low pathogenic H5N1 virus in pigs.

PubMed

De Vleeschauwer, Annebel R; Baras, Benoît; Kyriakis, Constantinos S; Jacob, Valérie; Planty, Camille; Giannini, Sandra L; Mossman, Sally; Van Reeth, Kristien

2012-08-10

We used the pig model of influenza to examine the efficacy of an AS03(A)-adjuvanted split H5N1 (A/Indonesia/05/2005) vaccine against challenge with a low pathogenic (LP) H5N1 avian influenza (AI) virus (duck/Minnesota/1525/1981) with only 85% amino acid homology in its HA1. Influenza seronegative pigs were vaccinated twice intramuscularly with adjuvanted vaccine at 3 antigen doses, unadjuvanted vaccine or placebo. All pigs were challenged 4 weeks after the second vaccination and euthanized 2 days later. After 2 vaccinations, all pigs in the adjuvanted vaccine groups had high hemagglutination inhibiting (HI) antibody titers to the vaccine strain (160-640), and lower antibody titers to the A/Vietnam/1194/04 H5N1 strain and to 2 LP H5 viruses with 90-91% amino acid homology to the vaccine strain (20-160). Eight out of 12 pigs had HI titers (10-20) to the challenge virus immediately before challenge. Neuraminidase inhibiting antibodies to the challenge virus were detected in most pigs (7/12) and virus neutralizing antibodies in all pigs. There was no antigen-dose dependent effect on the antibody response among the pigs immunized with adjuvanted H5N1 vaccines. After challenge, these pigs showed a complete clinical protection, reduced lung lesions and a significant protection against virus replication in the respiratory tract. Though the challenge virus showed only moderate replication efficiency in pigs, our study suggests that AS03(A)-adjuvanted H5N1 vaccine may confer a broader protection than generally assumed. The pros and cons of the pig as an H5N1 challenge model are also discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

Randomized trial of adjuvant ovarian suppression in 926 premenopausal patients with early breast cancer treated with adjuvant chemotherapy.

PubMed

Arriagada, R; Lê, M G; Spielmann, M; Mauriac, L; Bonneterre, J; Namer, M; Delozier, T; Hill, C; Tursz, T

2005-03-01

The aim of this multicenter trial was to evaluate the role of ovarian suppression in patients with early breast cancer previously treated with local surgery and adjuvant chemotherapy. Nine hundred and twenty-six premenopausal patients with completely resected breast cancer and either axillary node involvement or histological grade 2 or 3 tumors were randomized after surgery to adjuvant chemotherapy alone (control arm) or adjuvant chemotherapy plus ovarian suppression (ovarian suppression arm). Ovarian suppression was obtained by either radiation-induced ovarian ablation or triptorelin for 3 years. The analyses were performed with Cox models stratified by center. Median follow-up was 9.5 years. Mean age was 43 years. Ninety per cent of patients had histologically proven positive axillary nodes, 63% positive hormonal receptors and 77% had received an anthracycline-based chemotherapy regimen. Ovarian suppression was by radiation-induced ovarian ablation (45% of patients) or with triptorelin (48%). At the time of randomization, all patients had regular menses or their follicle-stimulating hormone and estradiol levels indicated a premenopausal status. The 10-year disease-free survival rates were 49% [95% confidence interval (CI) 44% to 54%] in both arms (P = 0.51). The 10-year overall survival rates were 66% (95% CI 61% to 70%) for the ovarian suppression arm and 68% (95% CI 63% to 73%) for the control arm (P = 0.19). There were no variations in the treatment effect according to age, hormonal receptor status or ovarian suppression modality. However, in patients <40 years of age and with estrogen receptor-positive tumors, ovarian suppression significantly decreased the risk of recurrence (P = 0.01). The results of this trial, after at least 10 years of follow-up, do not favor the use of ovarian suppression after adjuvant chemotherapy. The potential beneficial effect in younger women with hormono-dependent tumors should be further assessed.

Oil from the fruits of Pterodon emarginatus Vog.: A traditional anti-inflammatory. Study combining in vivo and in silico.

PubMed

Dos Santos, Cleydson Breno Rodrigues; da Silva Ramos, Ryan; Ortiz, Brenda Lorena Sánchez; da Silva, Gabriel Monteiro; Giuliatti, Silvana; Balderas-Lopez, José Luis; Navarrete, Andrés; Carvalho, José Carlos Tavares

2018-08-10

The oil obtained from the fruits of Pterodon emarginatus Vog. (OPe) is used orally and topically, in traditional medicine for some purposes, such as acute and chronic inflammatory states as rheumatoid arthritis. In this work, the anti-inflammatory activity of the OPe was demonstrated based on several animal models and presented an in silico study based on the 6α,7β-dihydroxy-vouacapan-17β-oic acid (DHVA) majority compound of the OPe to evaluate the interaction this compound, with cyclooxygenase-2 (COX-2) in 4COX (Mus musculus) and 5KIR (Homo sapiens) and molecular dynamics simulation. The OPe (498 mg/kg, p.o) significantly inhibited (p < 0.05, Student t-test) the primary and secondary reactions of arthritis by Freund's Complete Adjuvant (FCA) and in dermatitis induced by croton oil in mice, OPe inhibited peak of edema. In vascular permeability test in rats, the treatment with OPe was able to block the response to PGE 2 , serotonin, and bradykinin (p < 0.05, Student t-test). In the writhing test in mice, the OPe at doses of 498 and 980 mg/kg (p.o) produced inhibition of 73% and 92%, respectively, and was not significantly effective in the hot plate test. In the evaluation of the potency in relation to gastric injury (gastric ulcer induced by stress) and combined assay in the assessment of anti-inflammatory potency and gastric damage, it was observed that indomethacin (10 mg/kg, p.o.) inhibited carrageenan edema by 51% and produced a higher number of gastric lesions when compared to the group treated with OPe, where only areas of hyperemia were observed, without the occurrence of ulcerative lesion, and which inhibited the edema by 47%. In the in silico study, it was found that the DHVA is capable of binding to two organisms (4COX - Mus musculus and 5KIR - Homo sapiens), however, with higher binding affinity to the organism Homo sapiens. As expected, all tested ligands were capable of forming hydrogen interactions with residues at their respective binding sites, but the DHVA ligand was capable of creating slightly more hydrogen bonds when docked to either 4COX or 5KIR than the other tested ligands, thus demonstrating the participation of this compound in the anti-inflammatory and antialgic responses observed in the in vivo assays as a COX-2 inhibitor. Therefore, the results obtained support the traditional use of OPe for inflammatory and gastric problems. Copyright © 2018 Elsevier B.V. All rights reserved.

Impact of liposomal doxorubicin-based adjuvant chemotherapy on autonomy in women over 70 with hormone-receptor-negative breast carcinoma: A French Geriatric Oncology Group (GERICO) phase II multicentre trial.

PubMed

Brain, Etienne G C; Mertens, Cécile; Girre, Véronique; Rousseau, Frédérique; Blot, Emmanuel; Abadie, Sophie; Uwer, Lionel; Bourbouloux, Emmanuelle; Van Praagh-Doreau, Isabelle; Mourey, Loic; Kirscher, Sylvie; Laguerre, Brigitte; Fourme, Emmanuelle; Luneau, Sylvia; Genève, Jean; Debled, Marc

2011-10-01

Breast cancer is a disease of ageing. Functional independence in elderly patients, measured with the Katz activities of daily living (ADL) scale, predicts overall survival and the need for welfare support. Few prospective studies have examined the feasibility of adjuvant chemotherapy and its impact on autonomy in women over 70 years of age with high-risk breast cancer. This multicentre phase II trial was designed to assess the impact of adjuvant anthracycline-based chemotherapy on these patients' autonomy. In a two-stage Fleming design, women aged ≥70 years with histologically proven hormone-receptor-negative early breast cancer and a significant risk of recurrence (pN+ or "high risk" pN0) received 4 cycles of nonpegylated liposomal doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) every 3 weeks postoperatively, on an outpatient basis. The primary endpoint was the change in the ADL score during chemotherapy. Secondary endpoints include comprehensive geriatric, quality-of-life and acceptability assessments, tolerability, and long-term outcome. The results for the primary endpoint and other scales at completion of adjuvant chemotherapy are reported here, while long-term follow-up is not yet complete. Forty patients (median age 75 [70-82]) were enrolled between February 2006 and November 2007. Chemotherapy had no deleterious impact on ADL, cognition, mental status, or the frequency of comorbidities. In contrast, the number of patients at risk of malnutrition, based on the Mini Nutritional Assessment, more than doubled between baseline and the end of chemotherapy, rising from 15% to 38%. Quality-of-life deteriorated in terms of social and role functioning, likely owing to fatigue, loss of appetite, nausea and vomiting. Treatment acceptability was good. The main adverse effect was neutropenia, 15% of the patients experiencing febrile neutropenia. No cardiac toxicity or toxic deaths occurred. This study demonstrates the feasibility of an adjuvant chemotherapy regimen combining nonpegylated liposomal doxorubicin and cyclophosphamide in fit elderly women <85 years with breast cancer. Although chemotherapy had an impact on social and role functioning, autonomy was not impaired and toxicity was acceptable. Special attention should be paid to nutritional status before and after treatment. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

[Evaluation of breast cancer treatment at a tertiary-level institution with Popular Health Insurance in Mexico].

PubMed

Arce-Salinas, Claudia; Lara-Medina, Fernando Ulises; Alvarado-Miranda, Alberto; Castañeda-Soto, Noel; Bargalló-Rocha, Enrique; Ramírez-Ugalde, María Teresa; Pérez-Sánchez, Víctor; Rivera, Lesbia; Gambo-Vignole, Carlos; Santamaría-Galicia, Julieta; Nieves-Casas, Rosa Isela; Morán-Muñoz, Héctor; Mohar-Betancourt, Alejandro

2012-01-01

In our country breast cancer represents a major health problem. Only 45% of all population has access to health services, the consequence is delay in diagnosis and treatment. In Mexico, 66% of all new cases of breast cancer are diagnosed in locally advanced stages. From May 2007 the Health System Protection Against Catastrophic Expenses, called Seguro Popular (SP), breast cancer was included in covering the treatment of this neoplasm in any patient without access to social security. To evaluate the results and impact of SP in the adjuvant and neoadjuvant treatment of a group of patients diagnosed with breast cancer at an institution of national reference. We analyzed a group of 259 patients in stages (I-IIIC). The clinical stages I and II (55 patients) were treated with adjuvant chemotherapy FAC -T (fluorouracil 500 mg/m2, adriamycin 50 mg/m2 and cyclophosphamide 500 mg/m2 (FAC) followed by 12 weeks of paclitaxel 80 mg/m2 +/- trastuzumab loading dose of 4 mg/kg followed by 2 mg/kg); 204 patients in locally advanced stages (IIB-IIIC) received FAC-T +/- trastuzumab followed by surgery. Adjuvant treatment consisted of endocrine therapy for hormone-sensitive patients and radiotherapy 50 cGy according to international standards. The age at diagnosis was 47 years (range 23-68). 80% of them were locally advanced stages (IIB-IIIC) and were treated in a neoadjuvant setting, 20% was in early stages, treated with surgery and adjuvant chemotherapy The disease-free survival and overall survival at 30 months was 85.7 and 90% respectively. Overall pathologic complete response was obtained in 15% of cases. In the subgroup analysis showed that 41% of patients HER2 (+), 29% of triple-negative patients and 9% of hormone-sensitive tumors achieved complete pathological response (p = 0.0001). This is the first analysis of efficacy of adjuvant and neoadjuvant treatment in breast cancer since the introduction of popular secure non-entitled population. It is clear that treatment efficacy is similar to that reported in the literature, with 15% of pRC and survival to 30 months in 94-80%. The coverage of health expenditures treats a larger number of patients optimally. Along with this, efforts should be made to reduce the high frequency of diagnosis at advanced stage.

Health-related quality of life during adjuvant treatment for breast cancer among postmenopausal women.

PubMed

Browall, Maria; Ahlberg, Karin; Karlsson, Per; Danielson, Ella; Persson, Lars-Olof; Gaston-Johansson, Fannie

2008-07-01

The purpose of the present study was twofold: first, to describe changes of Health-Related Quality of Life (HRQoL) during the adjuvant treatment among postmenopausal women with breast cancer; second, in the same population to identify the best predictors of Overall Quality of Life (QoL) after treatment, from perceived functioning, symptoms, emotional distress and clinical/demographic variables measured at baseline. The study group was 150 women (> or = 55 years of age) scheduled for adjuvant chemotherapy (CT, n=75) or radiotherapy (RT, n=75). They were examined before (baseline), during and after completing the treatment. Data about QoL, perceived functioning, symptoms and emotional distress were collected with the European Organisation for Research and Treatment of Cancer (EORTC)-QLQ-C30, BR23 and Hospital Anxiety and Depression Scale (HADS) questionnaires. The general finding was that the adjuvant treatments were associated with decrease in overall QoL, physical and role functioning, anxiety and body image, as well as with increase in fatigue, dyspnoea, pain, nausea/vomiting, constipation and systemic therapy side effects measured over time. For women receiving CT, better emotional functioning and less pain at baseline predicted better overall QoL at the end of the treatment. For women receiving RT, better physical and emotional functioning, less breast symptoms and lower tumour stage at baseline predicted better overall QoL at the end of the treatment.

Efficacy and safety of platinum combination chemotherapy re-challenge for relapsed patients with non-small-cell lung cancer after postoperative adjuvant chemotherapy of cisplatin plus vinorelbine.

PubMed

Imai, Hisao; Shukuya, Takehito; Yoshino, Reiko; Muraki, Keiko; Mori, Keita; Ono, Akira; Akamatsu, Hiroaki; Taira, Tetsuhiko; Kenmotsu, Hirotsugu; Naito, Tateaki; Murakami, Haruyasu; Tomizawa, Yoshio; Takahashi, Toshiaki; Takahashi, Kazuhisa; Saito, Ryusei; Yamamoto, Nobuyuki

2013-01-01

There is no standard therapy for relapsed patients who have received postoperative platinum-based adjuvant chemotherapy for resected non-small-cell lung cancer (NSCLC). We investigated the efficacy and safety of platinum combination chemotherapy re-challenge for such patients. Medical records from 3 institutes from April 2005 to July 2012 were retrospectively reviewed. Patients who underwent complete surgical resection were eligible if they received postoperative adjuvant chemotherapy consisting of cisplatin plus vinorelbine once and then re-challenge with platinum combination chemotherapy. Sixteen patients were enrolled in this study. After re-challenge with platinum combination chemotherapy, we observed an overall response rate of 31.2% (5/16) and a disease control rate of 81.2% (13/16). Median progression-free survival and overall survival from the start of the re-administration of platinum combination chemotherapy were 6.5 and 28.0 months, respectively. Frequently observed severe adverse events (≥grade 3) included neutropenia (31.2%), thrombocytopenia (31.2%), leukopenia (12.5%) and hyponatremia (12.5%). Frequently observed non-hematological toxicities (≥grade 2) were anorexia (37.5%) and nausea (37.5%). Re-challenge with platinum combination chemotherapy was effective and safe; therefore, this therapy should be considered as a treatment option for relapsed patients after postoperative cisplatin-based adjuvant chemotherapy for resected NSCLC. © 2014 S. Karger AG, Basel.

Complete Freund's adjuvant induces experimental autoimmune myocarditis by enhancing IL-6 production during initiation of the immune response.

PubMed

Fontes, Jillian A; Barin, Jobert G; Talor, Monica V; Stickel, Natalie; Schaub, Julie; Rose, Noel R; Čiháková, Daniela

2017-06-01

Complete Freund's Adjuvant (CFA) emulsified with an antigen is a widely used method to induce autoimmune disease in animal models, yet the contribution of CFA to the immune response is not well understood. We compared the effectiveness of CFA with Incomplete Freund's Adjuvant (IFA) or TiterMax Gold Adjuvant (TMax) in experimental autoimmune myocarditis (EAM) in male mice. EAM was induced in A/J, BALB/c, and IL6KO BALB/c male mice by injection of the myocarditogenic peptide in CFA, IFA, or TMax on days 0 and 7. EAM severity was analyzed by histology on day 21. In addition, specific flow cytometry outcomes were evaluated on day 21. Only mice immunized with CFA and myocarditogenic peptide on both days 0 and 7 developed substantial myocarditis as measured by histology. We observed a significantly increased level of IL6 in the spleen 3 days after CFA immunization. In the spleen and heart on day 21, there was an expansion of myeloid cells in CFA-immunized mice, as compared to IFA or TMax-immunized animals. Recombinant IL-6 at the time of IFA immunization partially restored susceptibility of the mice to EAM. We also treated EAM-resistant IL-6 knockout mice with recombinant IL-6 around the time of the first immunization, on days -1 to 2, completely restoring disease susceptibility, showing that the requirement for IL-6 coincides with primary immunization. Examining APC populations in the lymph node draining the immunization site evidenced the contribution of IL-6 to the CFA-dependence of EAM was through controlling local dendritic cell (DC) trafficking. CFA used with myocarditogenic peptide twice is required to induce EAM in both A/J and Balb/c mice. Although IFA and TiterMax induce antibody responses, only CFA preferentially induced autoantigen-specific responses. CFA expands monocytes in the heart and in the spleen. IL-6 signaling is required during short window around primary immunization to induce EAM. In addition, IL-6 deficient mice resistance to EAM could be reversed by injecting IL-6 around first immunization. IL-6 expands dendritic cell and monocytic populations and ultimately leads to a robust T-cell driven immune response in CFA immunized mice. © 2017 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd.

ASIA syndrome, calcinosis cutis and chronic kidney disease following silicone injections. A case-based review.

PubMed

Barilaro, Giuseppe; Spaziani Testa, Claudia; Cacciani, Antonella; Donato, Giuseppe; Dimko, Mira; Mariotti, Amalia

2016-12-01

An immunologic adjuvant is a substance that enhances the antigen-specific immune response preferably without triggering one on its own. Silicone, a synthetic polymer used for reconstructive and cosmetic purposes, can cause, once injected, local and/or systemic reactions and trigger manifestations of autoimmunity, occasionally leading to an overt autoimmune disease. Siliconosis, calcinosis cutis with hypercalcemia and chronic kidney disease have all been reported in association with silicone injection. Here, we describe a case of autoimmune/auto-inflammatory syndrome induced by adjuvants, calcinosis cutis and chronic kidney disease after liquid silicone multiple injections in a young man who underwent a sex reassignment surgery, followed by a review of the literature. To our knowledge, this is the first report describing the concomitance of the three clinical conditions in the same patients. The link between silicone and the immune system is not completely understood yet and requires further reports and investigations with long-term data, in order to identify the main individual and genetical risk factors predisposing to the wide spectrum of the adjuvant-induced responses.

Dose dense cyclophosphamide, methotrexate, fluorouracil is feasible at 14-day intervals: a pilot study of every-14-day dosing as adjuvant therapy for breast cancer.

PubMed

Drullinsky, Pamela; Sugarman, Steven M; Fornier, Monica N; D'Andrea, Gabriella; Gilewski, Teresa; Lake, Diana; Traina, Tiffany; Wasserheit-Lieblich, Carolyn; Sklarin, Nancy; Atieh-Graham, Deena; Mills, Nancy; Troso-Sandoval, Tiffany; Seidman, Andrew D; Yuan, Jeffrey; Patel, Hamangi; Patil, Sujata; Norton, Larry; Hudis, Clifford

2010-12-01

Cyclophosphamide/methotrexate/fluorouracil (CMF) is a proven adjuvant option for patients with early-stage breast cancer. Randomized trials with other regimens demonstrate that dose-dense (DD) scheduling can offer greater efficacy. We investigated the feasibility of administering CMF using a DD schedule. Thirty-eight patients with early-stage breast cancer were accrued from March 2008 through June 2008. They were treated every 14 days with C 600, M 40, F 600 (all mg/m2) with PEG-filgrastim (Neulasta®) support on day 2 of each cycle. The primary endpoint was tolerability using a Simon's 2-stage optimal design. The design would effectively discriminate between true tolerability (as protocol-defined) rates of ≤ 60% and ≥ 80%. The median age was 52-years-old (range, 38-78 years of age). Twenty-nine of the 38 patients completed 8 cycles of CMF at 14-day intervals. Dose-dense adjuvant CMF is tolerable and feasible at 14-day intervals with PEG-filgrastim support.

Anti-arthritic activity of cell wall content of Lactobacillus plantarum in freund's adjuvant-induced arthritic rats: involvement of cellular inflammatory mediators and other biomarkers.

PubMed

Gohil, Priyanshee; Patel, Vimal; Deshpande, Shrikalp; Chorawala, Mehul; Shah, Gaurang

2018-02-01

Alteration of microbiota is related with rheumatoid arthritis (RA) and administration of certain probiotics showed an improvement in RA. The present study was designed to find out the anti-arthritic activity of cell wall content of Lactobacillus plantarum in complete Freund's adjuvant (CFA)-induced arthritis in rats. Freund's adjuvant was injected into the left footpad in female rats on day 0 and dexamethasone (1 mg kg -1 , s.c.) & cell wall content of L. plantarum (10 5 , 10 7 , and 10 9  cfu/animal, s.c.) treatment were given from day 7 to 21. The change in body weight, paw volume and arthritic index, joint stiffness, gait test, mobility test, erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP) level, serum rheumatoid factor (RF), and serum TNF-α was measured on day 21. Cell wall content of L. plantarum treated animals showed improvement in all the parameters as compared to that in CFA-treated animals and exert anti-arthritic activity.

[Modified Cheng's Juanbi Decoction downregulates expression of prostaglandin E receptor 4 in synovial tissue in rats with adjuvant arthritis].

PubMed

Xu, Xia; Cheng, Hui; Cao, Jian; DU, Huan; Meng, Qingwei; Guo, Mengyuan

2017-06-01

Objective To investigate the effect of modified Cheng's Juanbi Decoction on the expression of prostaglandin E receptor 4 (PTGER4), the T cell receptor in the synovial tissues, in rats with adjuvant arthritis (AA). Methods A rat model of AA was established by subcutaneous injection of Freund's complete adjuvant at the vola pedis combined with ice-water bath and blowing. The degree of joint swelling and arthritis index were determined in each group. The quantitative real-time PCR was performed to assess the effect of modified Cheng's Juanbi Decoction on the mRNA expression of PTGER4in the synovial tissue. Results Cheng's Juanbi Decoction significantly alleviated the damage in the joints and synovial tissues in the AA rats. High-dose (the content of crude drug: 4 g/mL) Cheng's Juanbi Decoction significantly reduced the mRNA expression of PTGER4 in the synovial tissues. Conclusion Cheng's Juanbi Decoction can reduce the level of PTGER4 mRNA in the synovial tissue in AA rats.

DELAYED HYPERSENSITIVITY

PubMed Central

Uhr, Jonathan W.; Salvin, S. B.; Pappenheimer, A. M.

1957-01-01

A general method for induction of the delayed hypersensitive state directed against single protein antigens is described. The method consists of intradermal injection of minute amounts of washed immune precipitates containing the antigen in question. Provided the specific precipitates are formed in the region of antibody excess, maximal sensitivity develops at least 2 to 3 weeks before detectable circulating antibody is formed in guinea pigs against the sensitizing antigen. Neither adjuvant nor killed acid-fast bacteria are required for induction of the delayed hypersensitive state although the degree of sensitization is considerably increased when the sensitizing material is incorporated in Freund's complete adjuvant. Characteristics of the "delayed" as opposed to the "immediate" hypersensitive states in the guinea pig are described and implications of the findings are discussed. PMID:13385403

Model Uncertainty and Test of a Segmented Mirror Telescope

DTIC Science & Technology

2014-03-01

Optical Telescope project EOM: equation of motion FCA: fine control actuator FCD: Face-Centered Cubic Design FEA: finite element analysis FEM: finite...housed in a dark tent to isolate the telescope from stray light, air currents, or dust and other debris. However, the closed volume is prone to...is composed of six hexagonal segments that each have six coarse control actuators (CCA) for segment phasing control, three fine control actuators

Mid-term migration analysis of a femoral short-stem prosthesis: a five-year EBRA-FCA-study.

PubMed

Freitag, Tobias; Fuchs, Michael; Woelfle-Roos, Julia V; Reichel, Heiko; Bieger, Ralf

2018-05-01

The objective of this study was to evaluate the mid-term migration pattern of a femoral short stem. Implant migration of 73 femoral short-stems was assessed by Ein-Bild-Roentgen-Analysis Femoral-Component-Analysis (EBRA-FCA) 5 years after surgery. Migration pattern of the whole group was analysed and compared to the migration pattern of implants "at risk" with a subsidence of more than 1.5 mm 2 years postoperative. Mean axial subsidence was 1.1 mm (-5.0 mm to 1.5 mm) after 60 months. There was a statistical significant axial migration until 2 years postoperative with settling thereafter. 2 years after surgery 18 of 73 Implants were classified "at risk." Nevertheless, all stems showed secondary stabilisation in the following period with no implant failure neither in the group of implants with early stabilisation nor the group with extensive early onset migration. In summary, even in the group of stems with more pronounced early subsidence, delayed settling occurred in all cases. The determination of a threshold of critical early femoral short stem subsidence is necessary because of the differing migration pattern described in this study with delayed settling of the Fitmore stem 2 years postoperatively compared to early settling within the first postoperative year described for conventional stems.

Increased calcium absorption from synthetic stable amorphous calcium carbonate: double-blind randomized crossover clinical trial in postmenopausal women.

PubMed

Vaisman, Nachum; Shaltiel, Galit; Daniely, Michal; Meiron, Oren E; Shechter, Assaf; Abrams, Steven A; Niv, Eva; Shapira, Yami; Sagi, Amir

2014-10-01

Calcium supplementation is a widely recognized strategy for achieving adequate calcium intake. We designed this blinded, randomized, crossover interventional trial to compare the bioavailability of a new stable synthetic amorphous calcium carbonate (ACC) with that of crystalline calcium carbonate (CCC) using the dual stable isotope technique. The study was conducted in the Unit of Clinical Nutrition, Tel Aviv Sourasky Medical Center, Israel. The study population included 15 early postmenopausal women aged 54.9 ± 2.8 (mean ± SD) years with no history of major medical illness or metabolic bone disorder, excess calcium intake, or vitamin D deficiency. Standardized breakfast was followed by randomly provided CCC or ACC capsules containing 192 mg elemental calcium labeled with 44Ca at intervals of at least 3 weeks. After swallowing the capsules, intravenous CaCl2 labeled with 42Ca on was administered on each occasion. Fractional calcium absorption (FCA) of ACC and CCC was calculated from the 24-hour urine collection following calcium administration. The results indicated that FCA of ACC was doubled (± 0.96 SD) on average compared to that of CCC (p < 0.02). The higher absorption of the synthetic stable ACC may serve as a more efficacious way of calcium supplementation. © 2014 American Society for Bone and Mineral Research.

Seafloor monitoring west of Helgoland (German Bight, North Sea) using the acoustic ground discrimination system RoxAnn

NASA Astrophysics Data System (ADS)

Hass, H. Christian; Mielck, Finn; Fiorentino, Dario; Papenmeier, Svenja; Holler, Peter; Bartholomä, Alexander

2017-04-01

Marine habitats of shelf seas are in constant dynamic change and therefore need regular assessment particularly in areas of special interest. In this study, the single-beam acoustic ground discrimination system RoxAnn served to assess seafloor hardness and roughness, and combine these parameters into one variable expressed as RGB (red green blue) color code followed by k-means fuzzy cluster analysis (FCA). The data were collected at a monitoring site west of the island of Helgoland (German Bight, SE North Sea) in the course of four surveys between September 2011 and November 2014. The study area has complex characteristics varying from outcropping bedrock to sandy and muddy sectors with mostly gradual transitions. RoxAnn data enabled to discriminate all seafloor types that were suggested by ground-truth information (seafloor samples, video). The area appears to be quite stable overall; sediment import (including fluid mud) was detected only from the NW. Although hard substrates (boulders, bedrock) are clearly identified, the signal can be modified by inclination and biocover. Manually, six RoxAnn zones were identified; for the FCA, only three classes are suggested. The latter classification based on `hard' boundaries would suffice for stakeholder issues, but the former classification based on `soft' boundaries is preferred to meet state-of-the-art scientific objectives.

All-optical control of light on a graphene-on-silicon nitride chip using thermo-optic effect.

PubMed

Qiu, Ciyuan; Yang, Yuxing; Li, Chao; Wang, Yifang; Wu, Kan; Chen, Jianping

2017-12-06

All-optical signal processing avoids the conversion between optical signals and electronic signals and thus has the potential to achieve a power efficient photonic system. Micro-scale all-optical devices for light manipulation are the key components in the all-optical signal processing and have been built on the semiconductor platforms (e.g., silicon and III-V semiconductors). However, the two-photon absorption (TPA) effect and the free-carrier absorption (FCA) effect in these platforms deteriorate the power handling and limit the capability to realize complex functions. Instead, silicon nitride (Si 3 N 4 ) provides a possibility to realize all-optical large-scale integrated circuits due to its insulator nature without TPA and FCA. In this work, we investigate the physical dynamics of all-optical control on a graphene-on-Si 3 N 4 chip based on thermo-optic effect. In the experimental demonstration, a switching response time constant of 253.0 ns at a switching energy of ~50 nJ is obtained with a device dimension of 60 μm × 60 μm, corresponding to a figure of merit (FOM) of 3.0 nJ mm. Detailed coupled-mode theory based analysis on the thermo-optic effect of the device has been performed.

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

Shassere, Benjamin; Yamamoto, Yukinori; Poplawsky, Jonathan

We have develooped a new Fe-Cr-Al (FCA) alloy system with good oxidation resistance and creep strength at high temperature. The alloy system is a candidate for use in future fossil-fueled power plants. The creep strength of these alloys at 973 K (700 °C) was found to be comparable with traditional 9 pct Cr ferritic–martensitic steels. A few FCA alloys with general composition of Fe-30Cr-3Al-.2Si-xNb (x = 0, 1, or 2) with a ferrite matrix and Fe 2Nb-type Laves precipitates were prepared. The detailed microstructural characterization of samples, before and after creep rupture testing, indicated precipitation of the Laves phase withinmore » the matrix, Laves phase at the grain boundaries, and a 0.5 to 1.5 μm wide precipitate-free zone (PFZ) parallel to all the grain boundaries. In these alloys, the areal fraction of grain boundary Laves phase and the width of the PFZ controlled the cavitation nucleation and eventual grain boundary ductile failure. Finally, we used a phenomenological model to compare the creep strain rates controlled by the effects of the particles on the dislocations within the grain and at grain boundaries. (The research sponsored by US-DOE, Office of Fossil Energy, the Crosscutting Research Program).« less

Self-directed physical activity intervention in older adults undergoing adjuvant chemotherapy for colorectal cancer: Design of a randomized controlled trial.

PubMed

Williams, Grant R; Nyrop, Kirsten A; Deal, Allison M; Muss, Hyman B; Sanoff, Hanna K

2015-05-01

Colorectal cancer (CRC) diagnosis and treatment can have substantial detrimental impacts on health related quality of life (HRQOL) and physical function. This is especially true for older CRC patients and is of paramount concern in chemotherapy treatment decision making; yet, few studies to date have focused on understanding and managing fatigue in older CRC patients. We present the design of a study to evaluate the feasibility and impact of a home-based, self-directed physical activity intervention on fatigue in older CRC patients receiving adjuvant chemotherapy treatment. Secondary aims pertain to intervention impact on HRQOL, physical function, and self-efficacy for managing fatigue. Multi-site, randomized controlled trial of physical activity intervention compared to usual care in a sample of older adults undergoing adjuvant chemotherapy for CRC. Forty CRC patients will be recruited and study questionnaires/assessments will be performed at baseline, 3 months, and after completion of adjuvant chemotherapy. The primary outcome is a comparison of the change in fatigue from baseline to 3 months between Intervention and Control arms. We will also compare changes in engagement in physical activity, HRQOL, physical function, and self-efficacy. Exploratory analyses will compare Intervention and Control arms with regard to changes in muscle mass and a biomarker aging that is known to increase during chemotherapy (p16(INK4a)). If positive, findings from this pilot study would suggest the potential for improving the care of older persons with CRC undergoing adjuvant chemotherapy through a home-based physical activity intervention to manage fatigue, HRQOL, and physical function. NCT02191969. Copyright © 2015 Elsevier Inc. All rights reserved.

The effect of localized injection of adjuvant material on the draining lymph node

PubMed Central

Taub, R. N.; Krantz, Adrienne R.; Dresser, D. W.

1970-01-01

The histological accompaniments of adjuvant activity were studied in popliteal nodes of CBA mice at various intervals after footpad injection. Substances tested possessed either extrinsic adjuvanticity but little or no antigenicity (alum, vitamin A alcohol), antigenicity but no extrinsic adjuvanticity (bovine γA-like globulin), both (Freund's complete adjuvant, killed B. pertussis organisms, alum-precipitated BGG), or neither (paraffin oil BP). Substances possessing extrinsic adjuvanticity produced marked persistent enlargement of the draining lymph node, with prominent expansion, hypercellularity and blast transformation in the paracortical areas by the 4th day after injection. This was followed by germinal centre formation and medullary plasmacytosis occurring between the 4th and 10th day. Substances possessing little or no antigenicity produced a feeble germinal centre response and minimal medullary expansion. Bovine γA-like globulin, which lacks extrinsic adjuvanticity, produced a prominent germinal centre and medullary response but a minimal paracortical response. Only mild, transient lymph node enlargement, lasting 1–2 days, was seen after paraffin oil BP. Passive immunization of CBA mice with CBA anti-pertussis hyperimmune serum inhibited the adjuvant action of pertussis, and diminished and delayed the histological changes in the draining lymph node. These data suggested that paracortical expansion and hyperplasia were characteristic histological accompaniments to the injection of substances with extrinsic adjuvanticity. Because paracortical hypercellularity was observed in some instances to precede blast cell transformation, it is suggested that paracortical expansion induced by adjuvants is partly due to an augmented cellular traffic, with a net flux of recirculating lymphocytes into these areas. ImagesFIG. 1FIG. 2FIG. 5FIG. 6FIG. 8FIG. 10FIG. 11 PMID:4190416

Is febrile neutropenia prophylaxis with granulocyte-colony stimulating factors economically justified for adjuvant TC chemotherapy in breast cancer?

PubMed

Skedgel, Chris; Rayson, Daniel; Younis, Tallal

2016-01-01

Febrile neutropenia (FN) during adjuvant chemotherapy is associated with morbidity, mortality risk, and substantial cost, and subsequent chemotherapy dose reductions may result in poorer outcomes. Patients at high risk of, or who develop FN, often receive prophylaxis with granulocyte colony-stimulating factors (G-CSF). We investigated whether different prophylaxis strategies with G-CSF offered favorable value-for-money. We developed a decision model to estimate the short- and long-term costs and outcomes of a hypothetical cohort of women with breast cancer receiving adjuvant taxotere + cyclophosphamide (TC) chemotherapy. The short-term phase estimated upfront costs and FN risks with adjuvant TC chemotherapy without G-CSF prophylaxis (i.e., chemotherapy dose reductions) as well as with secondary and primary G-CSF prophylaxis strategies. The long-term phase estimated the expected costs and quality-adjusted life years (QALYs) for patients who completed adjuvant TC chemotherapy with or without one or more episodes of FN. Secondary G-CSF was associated with lower costs and greater QALY gains than a no G-CSF strategy. Primary G-CSF appears likely to be cost-effective relative to secondary G-CSF at FN rates greater than 28%, assuming some loss of chemotherapy efficacy at lower dose intensities. The cost-effectiveness of primary vs. secondary G-CSF was sensitive to FN risk and mortality, and loss of chemotherapy efficacy following FN. Secondary G-CSF is more effective and less costly than a no G-CSF strategy. Primary G-CSF may be justified at higher willingness-to-pay thresholds and/or higher FN risks, but this threshold FN risk appears to be higher than the 20% rate recommended by current clinical guidelines.

Feasibility and safety of extended adjuvant temozolomide beyond six cycles for patients with glioblastoma.

PubMed

Hsieh, S Yp; Chan, D Tm; Kam, M Km; Loong, H Hf; Tsang, W K; Poon, D Mc; Ng, S Cp; Poon, W S

2017-12-01

Temozolomide is the first chemotherapeutic agent proven effective for patients with newly diagnosed glioblastoma. The drug is well tolerated for its low toxicity. The current standard practice is concomitant chemoradiotherapy for 6 weeks followed by 6 cycles of adjuvant temozolomide. Some Caucasian studies have suggested that patients might benefit from extended adjuvant cycles of temozolomide (>6 cycles) to lengthen both progression-free survival and overall survival. In the present study, we compared differences in survival and toxicity profile between patients who received conventional 6-cycle temozolomide and those who received more than 6 cycles of temozolomide. Patients with newly diagnosed glioblastoma without progressive disease and completed concomitant chemoradiotherapy during a 4-year period were studied. Progression-free survival was compared using Kaplan-Meier survival curves. t Test, U test, and correlation were chosen accordingly to examine the impact of age, extent of resection, MGMT promoter methylation status and adjuvant cycles on progression-free survival. For factors with a P value of <0.05 in univariate analyses, Cox regression hazard model was adopted to determine the strongest factors related to progression-free survival. The median progression-free survival was 17.0 months for patients who received 6 cycles of temozolomide (n=7) and 43.4 months for those who received more than 6 cycles (n=7) [P=0.007, log-rank test]. Two patients in the former group and one in the latter group encountered grade 1 toxicity and recovered following dose adjustment. Cycles of adjuvant temozolomide were correlated with progression-free survival (P=0.016, hazard ratio=0.68). Extended cycles of temozolomide are safe and feasible for Chinese patients with disease responsive to temozolomide.

Antihyperalgesic and antiallodynic effect of sirolimus in rat model of adjuvant arthritis.

PubMed

Orhan, Cahide Elif; Önal, Aytül; Uyanıkgil, Yiğit; Ülker, Sibel

2013-04-05

Sirolimus is an immunosupressive drug that specifically inhibit the activation of T-lymphocytes. This study was undertaken to investigate whether treatment with sirolimus exert analgesic effect in rat adjuvant-induced arthritis, an animal model of rheumatoid arthritis. Arthritis was induced by a single subcutaneous injection of Freund's complete adjuvant to male Wistar rats that were divided into four groups; control (saline), vehicle (ethanol), sirolimus 0.75 and sirolimus 1.5. Sirolimus (0.75 and 1.5mg/kg/day) was administered intraperitoneally using Monday-Wednesday-Friday dosing schedule for 29 days, this dosing regimen revealed acceptable trough blood concentrations in arthritic rats. Adjuvant inoculation resulted in paw inflammation, hyperalgesia and allodynia as assessed by pletismometer, analgesymeter and dynamic plantar aesthesiometer respectively. Light microscopic evaluation of the arthritic metacarpophalangeal joints revealed synovial hypertrophy with inflammatory cellular infiltration, cartilage destruction and partial subchondral bone resorption. ELISA tests of serum TNF-α, IL-1β or IL-6 did not show any change in arthritic rats, while Western blotting analysis revealed a significant increase in TNF-α (P<0.001), but not IL-1β or IL-6, protein expression in the lumbar spinal cord of arthritic rats. Treatment with sirolimus significantly decreased the arthritic lesions (P<0.001) and paw swelling (P<0.05), alleviated the histological features in the metacarpophalangeal joint, resulted in antihyperalgesic and antiallodynic effects without affecting the locomotor activity and prevented the increased spinal cord TNF-α level (P<0.05). It seems that prevention of the increased TNF-α expression in the spinal cord may partially contribute to the antihyperalgesic effect of sirolimus in adjuvant arthritic rats and sirolimus could be a promising immunosupressive agent in the treatment of arthritic pain. Copyright © 2013 Elsevier B.V. All rights reserved.

A CpG-Ficoll Nanoparticle Adjuvant for Anthrax Protective Antigen Enhances Immunogenicity and Provides Single-Immunization Protection against Inhaled Anthrax in Monkeys.

PubMed

Kachura, Melissa A; Hickle, Colin; Kell, Sariah A; Sathe, Atul; Calacsan, Carlo; Kiwan, Radwan; Hall, Brian; Milley, Robert; Ott, Gary; Coffman, Robert L; Kanzler, Holger; Campbell, John D

2016-01-01

Nanoparticulate delivery systems for vaccine adjuvants, designed to enhance targeting of secondary lymphoid organs and activation of APCs, have shown substantial promise for enhanced immunopotentiation. We investigated the adjuvant activity of synthetic oligonucleotides containing CpG-rich motifs linked to the sucrose polymer Ficoll, forming soluble 50-nm particles (DV230-Ficoll), each containing >100 molecules of the TLR9 ligand, DV230. DV230-Ficoll was evaluated as an adjuvant for a candidate vaccine for anthrax using recombinant protective Ag (rPA) from Bacillus anthracis. A single immunization with rPA plus DV230-Ficoll induced 10-fold higher titers of toxin-neutralizing Abs in cynomolgus monkeys at 2 wk compared with animals immunized with equivalent amounts of monomeric DV230. Monkeys immunized either once or twice with rPA plus DV230-Ficoll were completely protected from challenge with 200 LD50 aerosolized anthrax spores. In mice, DV230-Ficoll was more potent than DV230 for the induction of innate immune responses at the injection site and draining lymph nodes. DV230-Ficoll was preferentially colocalized with rPA in key APC populations and induced greater maturation marker expression (CD69 and CD86) on these cells and stronger germinal center B and T cell responses, relative to DV230. DV230-Ficoll was also preferentially retained at the injection site and draining lymph nodes and produced fewer systemic inflammatory responses. These findings support the development of DV230-Ficoll as an adjuvant platform, particularly for vaccines such as for anthrax, for which rapid induction of protective immunity and memory with a single injection is very important. Copyright © 2015 by The American Association of Immunologists, Inc.

A MultiAir®/MultiFuel Approach to Enhancing Engine System Efficiency

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

Reese, Ronald

2015-05-20

FCA US LLC (formally known as Chrysler Group LLC, and hereinafter “Chrysler”) was awarded an American Recovery and Reinvestment Act (ARRA) funded project by the Department of Energy (DOE) titled “A MultiAir®/MultiFuel Approach to Enhancing Engine System Efficiency” (hereinafter “project”). This award was issued after Chrysler submitted a proposal for Funding Opportunity Announcement DE-FOA- 0000079, “Systems Level Technology Development, Integration, and Demonstration for Efficient Class 8 Trucks (SuperTruck) and Advanced Technology Powertrains for Light-Duty Vehicles (ATP-LD).” Chrysler started work on this project on June 01, 2010 and completed testing activities on August 30, 2014. Overall objectives of this project were;more » Demonstrate a 25% improvement in combined Federal Test Procedure (FTP) City and Highway fuel economy over a 2009 Chrysler minivan; Accelerate the development of highly efficient engine and powertrain systems for light-duty vehicles, while meeting future emissions standards; and Create and retain jobs in accordance with the American Recovery and Reinvestment Act of 2009« less

Randomized Phase II Trial of Adjuvant WT-1 Analog Peptide Vaccine in Patients with Malignant Pleural Mesothelioma after Completion of Multimodality Therapy

DTIC Science & Technology

2017-11-01

journal of cancer research : Gann 1999; 90(2): 194-204. 6. Rosenfeld C, Cheever MA, Gaiger A. WT1 in acute leukemia, chronic myelogenous leukemia...and myelodysplastic syndrome : therapeutic potential of WT1 targeted therapies. Leukemia 2003; 17(7): 1301-12. 7. Cheever MA, Allison JP, Ferris AS...Vaccination with synthetic analog peptides derived from WT1 oncoprotein induces T-cell responses in patients with complete remission from acute myeloid

Concurrent thermochemoradiotherapy for brain high-grade glioma

NASA Astrophysics Data System (ADS)

Ryabova, A. I.; Novikov, V. A.; Choinzonov, E. L.; Gribova, O. V.; Startseva, Zh. A.; Bober, E. E.; Frolova, I. G.; Baranova, A. V.

2016-08-01

Despite the achievements in the current strategies for treatment, the prognosis in malignant glioma patients remains unsatisfactory. Hyperthermia is currently considered to be the most effective and universal modifier of radiotherapy and chemotherapy. Preliminary treatment outcomes for 28 patients with newly diagnosed (23) and recurrent (5) high-grade gliomas were presented. All the patients received multimodality treatment including surgery, thermoche-moradiotherapy followed by 4 cycles of adjuvant chemotherapy. All the patients endured thermochemoradiotherapy well. A complication, limited skin burn (II stage), was diagnosed in two cases and treated conservatively without treatment interruption. A month after thermochemoradiotherapy the results were as follows: complete regression was achieved in 4 cases, partial regression in 4 cases, stable disease in 14 cases and disease progression in 6 cases (one of them is pseudo-progression). After completing the adjuvant chemotherapy 2 more patients demonstrated complete response and 1 patient had disease progression. Introduction of local hyperthermia in multimodal therapy of malignant glioma does not impair the combined modality treatment tolerability of patients with malignant gliomas. A small number of studied patients and short follow-up time do not allow making reliable conclusions about the impact of local hyperthermia on the treatment outcomes; however, there is a tendency towards the increase in disease-free survival in the patients with newly diagnosed malignant gliomas.

Randomized Phase II Trial of Adjuvant WT -1 Analog Peptide Vaccine in Patients with Malignant Pleural Mesothelioma after Completion of Multimodality Therapy

DTIC Science & Technology

2016-09-01

Interest Group 2016 Meeting Poster discussion at the American Society of Clinical Oncology Annual Meeting 2016 CONCLUSION: The clinical trial is now...Clinical Oncology 2016 Annual Meeting, Chicago, IL, Poster Discussion Presentation, June 4, 2016. APPENDICES: None SUPPORTING DATA: None

Discovery of NKT cells and development of NKT cell-targeted anti-tumor immunotherapy

PubMed Central

TANIGUCHI, Masaru; HARADA, Michishige; DASHTSOODOL, Nyambayar; KOJO, Satoshi

2015-01-01

Natural Killer T (NKT) cells are unique lymphocytes characterized by their expression of a single invariant antigen receptor encoded by Vα14Jα18 in mice and Vα24Jα18 in humans, which recognizes glycolipid antigens in association with the monomorphic CD1d molecule. NKT cells mediate adjuvant activity to activate both CD8T cells to kill MHC-positive tumor cells and NK cells to eliminate MHC-negative tumor at the same time in patients, resulting in the complete eradication of tumors without relapse. Therefore, the NKT cell-targeted therapy can be applied to any type of tumor and also to anyone individual, regardless of HLA type. Phase IIa clinical trials on advanced lung cancers and head and neck tumors have been completed and showed significantly prolonged median survival times with only the primary treatment. Another potential treatment option for the future is to use induced pluripotent stem cell (iPS)-derived NKT cells, which induced adjuvant effects on anti-tumor responses, inhibiting in vivo tumor growth in a mouse model. PMID:26194854

How do I deal with the axilla in patients with a positive sentinel lymph node?

PubMed

Falkson, Conrad B

2011-12-01

Optimal management of the axilla in a patient with a positive sentinel node biopsy is not yet defined.These patients usually have Breast Conserving Surgery and receive adjuvant systemic therapy and whole breast radiation.Treatment options for the axilla include: no further surgery with or without radiation completion axillary nodal dissection with or without radiation Radiation options in addition to whole breast radiation include axillary and supraclavicular nodal irradiation regional nodal irradiationincludes supraclavicular and internal mammary nodes Completion axillary dissection has been standard practice in patients with positive sentinel nodes. the number of involved nodes provides prognostic information. theoretically improves local control, but may be obviated by systemic chemotherapy. but avoidance of dissection may not adversely affect locoregional control or survival. dissection has significant morbidity so safe avoidance is desirable. There is little worldwide concordance on the use of radiation: whole breast radiation (commonly used after breast conserving surgery) may radiate the lower axilla supraclavicular radiation is most commonly recommended for patients with four or more nodes but may confer a survival benefit on patients with lower risk disease. adding nodal irradiation reduces local recurrence with only modest toxicity. Adjuvant systemic therapy provides a survival benefit for patients with nodal disease. Most will receive cytostatic chemotherapy containing an anthracycline and a taxane. Hormone therapy is appropriate for estrogen receptor positive disease. The extent to which systemic therapy controls microscopic nodal disease is unknown. Node positive patients should generally receive adjuvant chemotherapy.A small group of patients benefit from specific nodal therapy. Further studies are needed to better identify these patients.

An Observational Study to Examine Changes in Metabolic Syndrome Components in Breast Cancer Patients Receiving Neoadjuvant or Adjuvant Chemotherapy

PubMed Central

Dieli-Conwright, Christina M.; Wong, Louise; Waliany, Sarah; Bernstein, Leslie; Salehian, Behrouz; Mortimer, Joanne E.

2016-01-01

BACKGROUND We sought to determine the effect of chemotherapy on the development of metabolic syndrome (MetS) in premenopausal and postmenopausal women undergoing (neo) adjuvant therapy for early stage breast cancer. METHODS Eighty-six women with early stage (I-III) breast cancer who were free from clinically diagnosed MetS (defined as three out of five components of MetS) were prospectively tested for presence of the five components of MetS within one week before initiating and after completing (neo) adjuvant chemotherapy. The five components of MetS measured were waist circumference, blood pressure, and fasting levels of blood glucose, triglycerides, and high-density lipoprotein cholesterol. Anthropometrics (body weight, percent body fat, fat mass), lipid profile (total cholesterol, low-density lipoprotein cholesterol), glucose metabolism (insulin, homeostatic model assessment-insulin resistance, glycated hemoglobin), and inflammation (C-reactive protein) were also examined before initiating and after completing treatment. RESULTS The study included 46 premenopausal and 40 postmenopausal women. All individual MetS components and overall MetS score were statistically significantly increased (p<0.01) after chemotherapy. Body weight, percent body fat, fat mass, lipids, glucose metabolism, and inflammation were also statistically significantly increased (p<0.01). CONCLUSION A 12–18 week course of chemotherapy statistically significantly increases MetS and related anthropometrics, biomarkers of glucose metabolism, and inflammation in early stage breast cancer patients with no pre-existing MetS. Lifestyle interventions such as diet and exercise may be preventive approaches to employ during chemotherapy to reduce the onset of MetS in breast cancer patients. PMID:27219902

Treatment outcome and prognostic factors of adult glioblastoma multiforme.

PubMed

Ahmadloo, Niloofar; Kani, Amir-Abbas; Mohammadianpanah, Mohammad; Nasrolahi, Hamid; Omidvari, Shapour; Mosalaei, Ahmad; Ansari, Mansour

2013-03-01

This study aimed to report the characteristics, prognostic factors and treatment outcome of 223 patients with glioblastoma multiforme (GBM). This retrospective study was carried out by reviewing the medical records of 223 adult patients diagnosed at a tertiary academic hospital between 1990 and 2008. Patients' follow up ranged from 1 to 69 months (median 11 months). Surgery was attempted in all patients in whom complete resection in 15 patients (7%), subtotal resection in 77 patients (34%), partial resection in 73 patients (33%) and biopsy alone in 58 patients (26%) were done. In addition, we performed a literature review of PubMed to find out and analyze major related series. In all, we collected and analyzed the data of 33 major series including more than 11,000 patients with GBM. There were 141 men and 82 women. The median progression free- and overall survival were 6 (95% CI=5.711-8.289) and 11 (95% CI=9.304-12.696) months respectively. In univariate analysis for overall survival, age (P=0.003), tumor size (P<0.013), performance status (P<0.001), the extent of surgical resection (P=0.009), dose of radiation (P<0.001), and adjuvant chemotherapy (P<0.001) were prognostic factors. However, in multivariate analysis, only radiation dose, extent of surgical resection, and adjuvant chemotherapy were independent prognostic factors for overall survival. The prognosis of adult patients with GBM remains poor; however, complete surgical resection and adjuvant treatments improve progression-free and overall survival. Copyright © 2012. Production and hosting by Elsevier B.V.

Vaxjo: a web-based vaccine adjuvant database and its application for analysis of vaccine adjuvants and their uses in vaccine development.

PubMed

Sayers, Samantha; Ulysse, Guerlain; Xiang, Zuoshuang; He, Yongqun

2012-01-01

Vaccine adjuvants are compounds that enhance host immune responses to co-administered antigens in vaccines. Vaxjo is a web-based central database and analysis system that curates, stores, and analyzes vaccine adjuvants and their usages in vaccine development. Basic information of a vaccine adjuvant stored in Vaxjo includes adjuvant name, components, structure, appearance, storage, preparation, function, safety, and vaccines that use this adjuvant. Reliable references are curated and cited. Bioinformatics scripts are developed and used to link vaccine adjuvants to different adjuvanted vaccines stored in the general VIOLIN vaccine database. Presently, 103 vaccine adjuvants have been curated in Vaxjo. Among these adjuvants, 98 have been used in 384 vaccines stored in VIOLIN against over 81 pathogens, cancers, or allergies. All these vaccine adjuvants are categorized and analyzed based on adjuvant types, pathogens used, and vaccine types. As a use case study of vaccine adjuvants in infectious disease vaccines, the adjuvants used in Brucella vaccines are specifically analyzed. A user-friendly web query and visualization interface is developed for interactive vaccine adjuvant search. To support data exchange, the information of vaccine adjuvants is stored in the Vaccine Ontology (VO) in the Web Ontology Language (OWL) format.

Vaxjo: A Web-Based Vaccine Adjuvant Database and Its Application for Analysis of Vaccine Adjuvants and Their Uses in Vaccine Development

PubMed Central

Sayers, Samantha; Ulysse, Guerlain; Xiang, Zuoshuang; He, Yongqun

2012-01-01

Vaccine adjuvants are compounds that enhance host immune responses to co-administered antigens in vaccines. Vaxjo is a web-based central database and analysis system that curates, stores, and analyzes vaccine adjuvants and their usages in vaccine development. Basic information of a vaccine adjuvant stored in Vaxjo includes adjuvant name, components, structure, appearance, storage, preparation, function, safety, and vaccines that use this adjuvant. Reliable references are curated and cited. Bioinformatics scripts are developed and used to link vaccine adjuvants to different adjuvanted vaccines stored in the general VIOLIN vaccine database. Presently, 103 vaccine adjuvants have been curated in Vaxjo. Among these adjuvants, 98 have been used in 384 vaccines stored in VIOLIN against over 81 pathogens, cancers, or allergies. All these vaccine adjuvants are categorized and analyzed based on adjuvant types, pathogens used, and vaccine types. As a use case study of vaccine adjuvants in infectious disease vaccines, the adjuvants used in Brucella vaccines are specifically analyzed. A user-friendly web query and visualization interface is developed for interactive vaccine adjuvant search. To support data exchange, the information of vaccine adjuvants is stored in the Vaccine Ontology (VO) in the Web Ontology Language (OWL) format. PMID:22505817

Amistad Power Plant.

DTIC Science & Technology

1983-10-01

Worh District AMISTAD POWEI PLANT DEL RIO, TEXAS DTICS LECTE DEC 2 11983 OCTOBER 1063 88 11 281 DISTRIBUTION STATEMENT A Approved fca public relea...A I I I 1 1 ... CORPS OF ENGINEERS FORT WORTH DISTRICT, TEXAS FINAL FOUNDATION REPORT AMISTAD POWER PLANT NTIS G- xi DTI’. T" Jus! if - Distr ’. Avai...Wayne E. McIntosh. Colonel Donald Palladino and Colonel Theodore Stroup served as District Engineers during construction of the Amistad Power Plant

A novel recombinant virus-like particle vaccine for prevention of porcine parvovirus-induced reproductive failure.

PubMed

Antonis, Adriaan F G; Bruschke, Christianne J M; Rueda, Paloma; Maranga, Luis; Casal, J Ignacio; Vela, Carmen; Hilgers, Luuk A Th; Belt, Peter B G M; Weerdmeester, Klaas; Carrondo, Manuel J T; Langeveld, Jan P M

2006-06-29

A novel vaccine against porcine parvovirus (PPV), composed of recombinant virus-like particles (PPV-VLPs) produced with the baculovirus expression vector system (BEVS) at industrial scale, was tested for its immunogenicity and protective potency. A formulation of submicrogram amounts of PPV-VLPs in a water-in-mineral oil adjuvant evoked high serum antibody titres in both guinea pigs, used as reference model, and target species, pigs. A single immunisation with 0.7microg of this antigen yielded complete foetal protection against PPV infection after challenge with a virulent strain of this virus. Furthermore, also in the presence of mild adjuvants the protective action of these PPV-VLPs is excellent. This recombinant subunit vaccine overcomes some of the drawbacks of classical PPV vaccines.

STUDIES ON THE SENSITIZATION OF ANIMALS WITH SIMPLE CHEMICAL COMPOUNDS

PubMed Central

Maguire, Henry C.; Chase, Merrill W.

1972-01-01

A method of establishing regular and intense sensitivity to picric acid is described, based upon an initial sensitization by a "split-adjuvant" technique in which the intradermal injection of mycobacteria in paraffin oil precedes or follows the administration of allergen to the same sites. When subsequent contact applications of picric acid are later made, the degree of sensitivity rises in steps such that reactivity occurs in tests made with low concentrations of picric acid, in the range of 0.06–0.006% but varying somewhat from one experiment to another. This heightening of picric acid reactivity represents an anamnestic response in the area of delayed hypersensitivity. The characteristics of contact reactions to the weak allergen, picric acid, differ from those encountered with covalently binding haptens, PCI and DNCB. A slow evolution from an initial micropapular reaction to full reaction requires about 3 days, leading often to a micaceous scale, with histological evidence of vesiculation even while the reaction is still feeble, and to an infiltrate containing a significant number of polymorphonuclear leukocytes. Substitution of an emulsion of picric acid in complete Freund's adjuvant as a priming experience proved to be much less efficient. The split-adjuvant technique offers a general plan for sensitizing with weak allergens. Indeed, technically, sensitization can be acquired even when, for priming, the allergen is applied topically over intradermal depots of mycobacteria in paraffin oil. Compatibility between sensitizer and adjuvant is not required. PMID:5060294

Speech-language therapy program for mouth opening in patients with oral and oropharyngeal cancer undergoing adjuvant radiotherapy: a pilot study.

PubMed

Marrafon, Caroline Somera; Matos, Leandro Luongo; Simões-Zenari, Marcia; Cernea, Claudio Roberto; Nemr, Katia

2018-01-01

Purpose Assess the effectiveness of an orofacial myofunctional therapeutic program in patients with oral or oropharyngeal cancer submitted to adjuvant radiotherapy through pre- and post-program comparison of maximum mandibular opening. Methods Prospective study involving five adult patients and five elderly patients postoperatively to oral cavity/oropharynx surgery who were awaiting the beginning of radiotherapy or had undergone fewer than five treatment sessions. The study participants had their maximum jaw opening measured using a sliding caliper at the beginning and end of the program. Two mobility exercises and three mandibular traction exercises were selected and weekly monitored presentially for 10 weeks. Descriptive data and pre- and post-therapy comparative measures were statistically analyzed using the Wilcoxon test. Results Ten patients (two women and eight men) with mean age of 58.4 years, median of 57.0 years, completed the therapeutic program. They presented mean maximum mandibular opening of 31.6 ± 11.7 and 36.4 ± 8.0 mm pre- and post-therapy, respectively (p =0.021). Conclusion The proposed orofacial myofunctional therapeutic program increased the maximum jaw opening of patients referred to adjuvant radiotherapy for oral cavity or oropharynx cancer treatment.

Antioxidant effects of Genkwa flos flavonoids on Freund׳s adjuvant-induced rheumatoid arthritis in rats.

PubMed

Zhang, Chun-Feng; Zhang, Su-Li; He, Xin; Yang, Xiao-Lin; Wu, Hai-Tao; Lin, Bao-Qin; Jiang, Cui-Ping; Wang, Jun; Yu, Chun-Hao; Yang, Zhong-Lin; Wang, Chong-Zhi; Li, Ping; Yuan, Chun-Su

2014-05-14

Genkwa flos (Daphne genkwa Sieb. et Zucc.), a Chinese herbal medicine, has been traditionally used for over two thousand years in China for inflammation related symptoms, including joint pain. To evaluate the antioxidative effects of flavonoid aglycones (FA) isolated from Genkwa flos on adjuvant arthritis in rats and to identify the relationship between antioxidant potential and whole blood viscosity (WBV). FA compounds were identified using LC-MS and the content was assayed by HPLC. Arthritis was induced by an intradermal injection of Freund׳s complete adjuvant in the footpad. The effects of FA on paw volumes, secondary arthritis scores, histopathology of joints, and body and organ weights were measured. The antioxidant effects of FA and WBV were determined. LC-MS analysis showed that the FA contained four major compounds: luteolin, apigenin, hydroxygenkwanin and genkwanin. FA significantly decreased paw edema, arthritis scores, and weight loss. These observations were consistent with the reduction of oxidative stress and the improvement of the WBV. FA significantly decreased arthritis in a rat model through antioxidant and hemorheological modulatory mechanisms. The Genkwa flos flavonoids may have clinical potential for the treatment of rheumatoid arthritis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Macrophage-directed immunotherapy as adjuvant to photodynamic therapy of cancer.

PubMed

Korbelik, M; Naraparaju, V R; Yamamoto, N

1997-01-01

The effect of Photofrin-based photodynamic therapy (PDT) and adjuvant treatment with serum vitamin D3-binding protein-derived macrophage-activating factor (DBPMAF) was examined using a mouse SCCVII tumour model (squamous cell carcinoma). The results show that DBPMAF can markedly enhance the curative effect of PDT. The most effective DBPMAF therapy consisted of a combination of intraperitoneal and peritumoral injections (50 and 0.5 ng kg-1 respectively) administered on days 0, 4, 8 and 12 after PDT. Used with a PDT treatment curative to 25% of the treated tumours, this DBPMAF regimen boosted the cures to 100%. The DBPMAF therapy alone showed no notable effect on the growth of SCCVII tumour. The PDT-induced immunosuppression, assessed by the evaluation of delayed-type contact hypersensitivity response in treated mice, was greatly reduced with the combined DBPMAF treatment. These observations suggest that the activation of macrophages in PDT-treated mice by adjuvant immunotherapy has a synergistic effect on tumour cures. As PDT not only reduces tumour burden but also induces inflammation, it is proposed that recruitment of the activated macrophages to the inflamed tumour lesions is the major factor for the complete eradication of tumours.

Macrophage-directed immunotherapy as adjuvant to photodynamic therapy of cancer.

PubMed Central

Korbelik, M.; Naraparaju, V. R.; Yamamoto, N.

1997-01-01

The effect of Photofrin-based photodynamic therapy (PDT) and adjuvant treatment with serum vitamin D3-binding protein-derived macrophage-activating factor (DBPMAF) was examined using a mouse SCCVII tumour model (squamous cell carcinoma). The results show that DBPMAF can markedly enhance the curative effect of PDT. The most effective DBPMAF therapy consisted of a combination of intraperitoneal and peritumoral injections (50 and 0.5 ng kg-1 respectively) administered on days 0, 4, 8 and 12 after PDT. Used with a PDT treatment curative to 25% of the treated tumours, this DBPMAF regimen boosted the cures to 100%. The DBPMAF therapy alone showed no notable effect on the growth of SCCVII tumour. The PDT-induced immunosuppression, assessed by the evaluation of delayed-type contact hypersensitivity response in treated mice, was greatly reduced with the combined DBPMAF treatment. These observations suggest that the activation of macrophages in PDT-treated mice by adjuvant immunotherapy has a synergistic effect on tumour cures. As PDT not only reduces tumour burden but also induces inflammation, it is proposed that recruitment of the activated macrophages to the inflamed tumour lesions is the major factor for the complete eradication of tumours. PMID:9010027

Rechallenge and maintenance therapy using cetuximab and chemotherapy administered to a patient with metastatic colorectal cancer.

PubMed

Ma, Jian; Yang, Quan-Liang; Ling, Yang

2017-02-14

Cetuximab combined with chemotherapy is one of the first-line treatments of metastatic colorectal cancer. Although disease progression inevitably occurs, rechallenge and maintenance therapies using cetuximab-based regimens may be beneficial, particularly for patients with wild-type (WT) KRAS. A 47-year-old female patient who underwent right hemicolectomy presented with an ulcerative adenocarcinoma (grade 2) revealed by histopathological analysis. The patient received three cycles of adjuvant chemotherapy, but disease recurred 15 months later. Cetuximab and a FOLFOX-4 regimen were administered, followed by surgery and adjuvant chemotherapy that was administered for approximately one year. Three years after completing adjuvant therapy, her serum carcinoembryonic antigen levels rapidly increased, and enhanced computed tomography showed widespread metastases. Rechallenge with cetuximab and the FOLFIRI regimen was then initiated, and after 12 cycles, lesions in the lung and liver shrank significantly, and serum CEA levels dramatically declined. Maintenance therapy with cetuximab and capecitabine was then administered for 10 months until the metastatic lesions in the lung and liver enlarged. Rechallenge and maintenance therapy with cetuximab-based chemotherapy were relatively effective for managing a female patient with WT KRAS. Optimization of this strategy requires further in-depth investigations of more patients.

Multicenter study of pars plana vitrectomy for optic disc pit maculopathy: MACPIT study.

PubMed

Avci, R; Kapran, Z; Ozdek, Ş; Teke, M Y; Oz, O; Guven, D; Yilmaz, S; Kaderli, B; Durukan, A H; Sobaci, G; Unver, Y B; Akduman, L; Kaynak, S; Dogan, I; Inan, U U

2017-09-01

PurposeTo evaluate surgical intervention with pars plana vitrectomy (PPV) for correction of optic disc pit maculopathy (ODP-M).Patients and methodsRetrospective chart review from 13 centres of 51 eyes of 50 patients with ODP-M who underwent PPV between 2002-2014. Anatomic and final best-corrected visual acuity (BCVA) outcomes were evaluated for all cases with different adjuvant techniques.ResultsThere were 23 males and 27 females with median age 25.5 (6-68) years. Preoperative median foveal thickness was 694.5 (331-1384) μm and improved to 252.5 (153-1405) μm. Median BCVA improved from 20/200 (20/20000 to 20/40) to 20/40 (20/2000 to 20/20) with 20/40 or better in 31 eyes. Complete retinal reattachment was achieved in 44 eyes (86.3%) at 7.1 (5.9) months. The good surgical outcomes were achieved in different adjuvant groups. Median follow-up was 24 (6 to 120) months.ConclusionsThese results confirm the long-term effectiveness of PPV for ODP-M. Prospective studies are needed to determine the effectiveness of any adjuvant technique in improving the success of PPV for ODP-M.

Impact of implant composition of twin-screw extruded lipid implants on the release behavior.

PubMed

Even, Marie-Paule; Bobbala, Sharan; Kooi, Kok Liang; Hook, Sarah; Winter, Gerhard; Engert, Julia

2015-09-30

The development of vaccine delivery systems that will remove or reduce the need for repeated dosing has led to the investigation of sustained release systems. In this context, the duration of antigen release is of great importance as is the requirement for concomitant adjuvant release. In this work, lipid implants consisting of cholesterol (CHOL), soybean lecithin, Dynasan 114 (D114), the model antigen ovalbumin (OVA) and the adjuvant Quil-A (QA) were produced by twin-screw extrusion. The release of antigen and adjuvant was investigated in vitro and we observed complete OVA release over a period of 7 days while QA was released in a linear fashion over a period of up to 12 days. In order to extend OVA release, lipid implants were subjected to post-extrusion curing at 45-55°C. The OVA release could be extended to up to 14 days. Furthermore the influence of the implant composition on the release of the model antigen was investigated. It was shown that the percentage of cholesterol in particular plays an important role in modulating release. Copyright © 2015 Elsevier B.V. All rights reserved.

Optimal management for surgically Stage 1 serous cancer of the uterus.

PubMed

Elit, L; Kwon, J; Bentley, J; Trim, K; Ackerman, I; Carey, M

2004-01-01

To describe the outcomes of patients who have undergone well-conducted surgery and found to have Stage 1 serous uterine cancer. This retrospective cohort study includes women who have been treated for Stage 1 serous cancer of the uterus from 1985 to 2001. Cases were included from the regional cancer centers in Hamilton, London, Sunnybrook Toronto and Cancer Care Manitoba. Forty-three women met the inclusion criteria: Complete surgical staging (n = 27), surgery followed by pelvic radiation therapy (n = 4), surgery followed by whole abdominal radiation therapy (n = 6), surgery followed by adjuvant chemotherapy (n = 6). Patient age or depth of invasion did not influence survival. Progression free interval was 22 months (SD = 14.29). Recurrence rate was highest for adjuvant chemotherapy (66%). Survival was assessed by treatment modality and a statistically significant poorer survival was seen in the adjuvant chemotherapy group (OR 17.5; 95% CI 1.3-227.6). No comment can be made on a superior treatment regimen given the small numbers in each treatment strata. This study supports the findings of others in the literature. In a group of patients where surgical staging shows limited disease (i.e., surgically Stage 1 disease), then surgery alone appears to be adequate treatment.

Screening vaccine formulations for biological activity using fresh human whole blood

PubMed Central

Brookes, Roger H; Hakimi, Jalil; Ha, Yukyung; Aboutorabian, Sepideh; Ausar, Salvador F; Hasija, Manvi; Smith, Steven G; Todryk, Stephen M; Dockrell, Hazel M; Rahman, Nausheen

2014-01-01

Understanding the relevant biological activity of any pharmaceutical formulation destined for human use is crucial. For vaccine-based formulations, activity must reflect the expected immune response, while for non-vaccine therapeutic agents, such as monoclonal antibodies, a lack of immune response to the formulation is desired. During early formulation development, various biochemical and biophysical characteristics can be monitored in a high-throughput screening (HTS) format. However, it remains impractical and arguably unethical to screen samples in this way for immunological functionality in animal models. Furthermore, data for immunological functionality lag formulation design by months, making it cumbersome to relate back to formulations in real-time. It is also likely that animal testing may not accurately reflect the response in humans. For a more effective formulation screen, a human whole blood (hWB) approach can be used to assess immunological functionality. The functional activity relates directly to the human immune response to a complete formulation (adjuvant/antigen) and includes adjuvant response, antigen response, adjuvant-modulated antigen response, stability, and potentially safety. The following commentary discusses the hWB approach as a valuable new tool to de-risk manufacture, formulation design, and clinical progression. PMID:24401565

Screening vaccine formulations for biological activity using fresh human whole blood.

PubMed

Brookes, Roger H; Hakimi, Jalil; Ha, Yukyung; Aboutorabian, Sepideh; Ausar, Salvador F; Hasija, Manvi; Smith, Steven G; Todryk, Stephen M; Dockrell, Hazel M; Rahman, Nausheen

2014-01-01

Understanding the relevant biological activity of any pharmaceutical formulation destined for human use is crucial. For vaccine-based formulations, activity must reflect the expected immune response, while for non-vaccine therapeutic agents, such as monoclonal antibodies, a lack of immune response to the formulation is desired. During early formulation development, various biochemical and biophysical characteristics can be monitored in a high-throughput screening (HTS) format. However, it remains impractical and arguably unethical to screen samples in this way for immunological functionality in animal models. Furthermore, data for immunological functionality lag formulation design by months, making it cumbersome to relate back to formulations in real-time. It is also likely that animal testing may not accurately reflect the response in humans. For a more effective formulation screen, a human whole blood (hWB) approach can be used to assess immunological functionality. The functional activity relates directly to the human immune response to a complete formulation (adjuvant/antigen) and includes adjuvant response, antigen response, adjuvant-modulated antigen response, stability, and potentially safety. The following commentary discusses the hWB approach as a valuable new tool to de-risk manufacture, formulation design, and clinical progression.

An update on safety and immunogenicity of vaccines containing emulsion-based adjuvants.

PubMed

Fox, Christopher B; Haensler, Jean

2013-07-01

With the exception of alum, emulsion-based vaccine adjuvants have been administered to far more people than any other adjuvant, especially since the 2009 H1N1 influenza pandemic. The number of clinical safety and immunogenicity evaluations of vaccines containing emulsion adjuvants has correspondingly mushroomed. In this review, the authors introduce emulsion adjuvant composition and history before detailing the most recent findings from clinical and postmarketing data regarding the effects of emulsion adjuvants on vaccine immunogenicity and safety, with emphasis on the most widely distributed emulsion adjuvants, MF59® and AS03. The authors also present a summary of other emulsion adjuvants in clinical development and indicate promising avenues for future emulsion-based adjuvant development. Overall, emulsion adjuvants have demonstrated potent adjuvant activity across a number of disease indications along with acceptable safety profiles.

Role of Adjuvant Radiation Therapy After Surgery for Abdominal Desmoplastic Small Round Cell Tumors

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

Atallah, Vincent; Honore, Charles; Orbach, Daniel

Purpose: To identify the prognostic role of adjuvant abdominal radiation therapy (RT) on oncologic outcomes as a part of multimodal treatment in the management of desmoplastic small round cell tumor (DSRCT) and to determine its impact according to the quality of surgical resection. Methods and Materials: All patients treated for primary abdominal DSRCT in 8 French centers from 1991 to 2014 were included. Patients were retrospectively staged into 3 groups: group A treated with adjuvant RT after cytoreductive surgery, group B without RT after cytoreductive surgery, and group C by exclusive chemotherapy. Peritoneal progression-free survival (PPFS), progression-free survival (PFS), andmore » overall survival (OS) were evaluated. We also performed a direct comparison between groups A and B to evaluate RT after cytoreductive surgery. Radiation therapy was also evaluated according to completeness of surgery: complete cytoreductive surgery (CCS) or incomplete cytoreductive surgery (ICS). Results: Thirty-seven (35.9%), thirty-six (34.9%), and thirty (28.0%) patients were included in groups A, B, and C, respectively. Three-year OS was 61.2% (range, 41.0%-76.0%), 37.6% (22.0%-53.1%), and 17.3% (6.3%-32.8%) for groups A, B, and C, respectively. Overall survival, PPFS, and PFS differed significantly among the 3 groups (P<.001, P<.001, and P<.001, respectively). Overall survival and PPFS were higher in group A (RT group) compared with group B (no RT group) (P=.045 and P=.006, respectively). Three-year PPFS was 23.8% (10.3%-40.4%) for group A and 12.51% (4.0%-26.2%) for group B. After CCS, RT improved PPFS (P=.024), but differences in OS and PFS were not significant (P=.40 and P=.30, respectively). After ICS, RT improved OS (P=.044). A trend of PPFS and PFS increase was observed, but the difference was not statistically significant (P=.073 and P=.076). Conclusions: Adjuvant RT as part of multimodal treatment seems to confer oncologic benefits for patients treated for abdominal DSRCT after cytoreductive surgery and perioperative chemotherapy.« less

The interplay between QSAR/QSPR studies and partial order ranking and formal concept analyses.

PubMed

Carlsen, Lars

2009-04-17

The often observed scarcity of physical-chemical and well as toxicological data hampers the assessment of potentially hazardous chemicals released to the environment. In such cases Quantitative Structure-Activity Relationships/Quantitative Structure-Property Relationships (QSAR/QSPR) constitute an obvious alternative for rapidly, effectively and inexpensively generatng missing experimental values. However, typically further treatment of the data appears necessary, e.g., to elucidate the possible relations between the single compounds as well as implications and associations between the various parameters used for the combined characterization of the compounds under investigation. In the present paper the application of QSAR/QSPR in combination with Partial Order Ranking (POR) methodologies will be reviewed and new aspects using Formal Concept Analysis (FCA) will be introduced. Where POR constitutes an attractive method for, e.g., prioritizing a series of chemical substances based on a simultaneous inclusion of a range of parameters, FCA gives important information on the implications associations between the parameters. The combined approach thus constitutes an attractive method to a preliminary assessment of the impact on environmental and human health by primary pollutants or possibly by a primary pollutant well as a possible suite of transformation subsequent products that may be both persistent in and bioaccumulating and toxic. The present review focus on the environmental - and human health impact by residuals of the rocket fuel 1,1-dimethylhydrazine (heptyl) and its transformation products as an illustrative example.

Heterogeneous Creep Deformations and Correlation to Microstructures in Fe-30Cr-3Al Alloys Strengthened by an Fe 2Nb Laves Phase

DOE PAGES

Shassere, Benjamin; Yamamoto, Yukinori; Poplawsky, Jonathan; ...

2017-08-07

We have develooped a new Fe-Cr-Al (FCA) alloy system with good oxidation resistance and creep strength at high temperature. The alloy system is a candidate for use in future fossil-fueled power plants. The creep strength of these alloys at 973 K (700 °C) was found to be comparable with traditional 9 pct Cr ferritic–martensitic steels. A few FCA alloys with general composition of Fe-30Cr-3Al-.2Si-xNb (x = 0, 1, or 2) with a ferrite matrix and Fe 2Nb-type Laves precipitates were prepared. The detailed microstructural characterization of samples, before and after creep rupture testing, indicated precipitation of the Laves phase withinmore » the matrix, Laves phase at the grain boundaries, and a 0.5 to 1.5 μm wide precipitate-free zone (PFZ) parallel to all the grain boundaries. In these alloys, the areal fraction of grain boundary Laves phase and the width of the PFZ controlled the cavitation nucleation and eventual grain boundary ductile failure. Finally, we used a phenomenological model to compare the creep strain rates controlled by the effects of the particles on the dislocations within the grain and at grain boundaries. (The research sponsored by US-DOE, Office of Fossil Energy, the Crosscutting Research Program).« less

A novel strategy for dual-channel detection of metallothioneins and mercury based on the conformational switching of functional chimera aptamer.

PubMed

Tang, Xian; Wang, Yong-Sheng; Xue, Jin-Hua; Zhou, Bin; Cao, Jin-Xiu; Chen, Si-Han; Li, Ming-Hui; Wang, Xiao-Feng; Zhu, Yu-Feng; Huang, Yan-Qin

2015-03-25

A novel strategy for dual-channel detection of metallothioneins (MTs) and Hg(2+) has been proposed. In the absence of Hg(2+), the functional chimera aptamer (FCA) designed can form an intact G-quadruplex with flexibility, which was demonstrated to have peroxidase-like activities upon hemin binding. In the presence of Hg(2+), the formation of T-Hg(2+)-T complex results in the conformational switching of FCA, which lost the peroxidase-like activities and cannot catalyze the oxidation of ABTS by H2O2. Upon addition of MTs in this solution, MTs could interact with Hg(2+) to form a MTs-Hg(2+) complex, leading to the recovery of the G-quadruplex DNAzyme. The color and absorbance of the sensing system were also changed accordingly. In the optimizing condition, ΔA was directly proportional to the concentration ranging from 8.84 nM to 1.0 μM for Hg(2+), and 7.82 nM to 0.462 μM for MTs with the detection limits of 2.65 nM and 2.34 nM, respectively. The proposed dual-channel method avoids the label steps in common methods, and allows direct analysis of the samples without costly instruments, and is reliable, inexpensive and sensitive. Copyright © 2015 Elsevier B.V. All rights reserved.

Constitutive apical membrane recycling in Aplysia enterocytes.

PubMed

Keeton, Robert Aaron; Runge, Steven William; Moran, William Michael

2004-11-01

In Aplysia californica enterocytes, alanine-stimulated Na+ absorption increases both apical membrane exocytosis and fractional capacitance (fCa; a measure of relative apical membrane surface area). These increases are thought to reduce membrane tension during periods of nutrient absorption that cause the enterocytes to swell osmotically. In the absence of alanine, exocytosis and fCa are constant. These findings imply equal rates of constitutive endocytosis and exocytosis and constitutive recycling of the apical plasma membrane. Thus, the purpose of this study was to confirm and determine the relative extent of constitutive apical membrane recycling in Aplysia enterocytes. Biotinylated lectins are commonly used to label plasma membranes and to investigate plasma membrane recycling. Of fourteen biotinylated lectins tested, biotinylated wheat germ agglutinin (bWGA) bound preferentially to the enterocytes apical surface. Therefore, we used bWGA, avidin D (which binds tightly to biotin), and the UV fluorophore 7-amino-4-methylcoumarin-3-acetic acid (AMCA)-conjugated avidin D to assess the extent of constitutive apical membrane recycling. A temperature-dependent (20 vs. 4 degrees C) experimental protocol employed the use of two tissues from each of five snails and resulted in a approximately 60% difference in apical surface fluorescence intensity. Because the extent of membrane recycling is proportional to the difference in surface fluorescence intensity, this difference reveals a relatively high rate of constitutive apical membrane recycling in Aplysia enterocytes.

Assessment of air quality in Haora River basin using fuzzy multiple-attribute decision making techniques.

PubMed

Singh, Ajit Pratap; Chakrabarti, Sumanta; Kumar, Sumit; Singh, Anjaney

2017-08-01

This paper deals with assessment of air quality in Haora River basin using two techniques. Initially, air quality indices were evaluated using a modified EPA method. The indices were also evaluated using a fuzzy comprehensive assessment (FCA) method. The results obtained from the fuzzy comprehensive assessment method were compared to that obtained from the modified EPA method. To illustrate the applicability of the methodology proposed herein, a case study has been presented. Air samples have been collected at 10 sampling sites located along Haora River. Six important air pollutants, namely, carbon monoxide, sulfur dioxide, nitrogen dioxide, suspended particulate matter (SPM), PM 10 , and lead, were monitored continuously, and air quality maps were generated on the GIS platform. Comparison of the methodologies has clearly highlighted superiority and robustness of the fuzzy comprehensive assessment method in determining air quality indices under study. It has effectively addressed the inherent uncertainties involved in the evaluation, modeling, and interpretation of sampling data, which was beyond the scope of the traditional weighted approaches employed otherwise. The FCA method is robust and prepares a credible platform of air quality evaluation and identification, in face of the uncertainties that remain eclipsed in the traditional approaches like the modified EPA method. The insights gained through the present study are believed to be of pivotal significance in guiding the development and implementation of effective environmental remedial action plans in the study area.

Anti-arthritic Effects of Total Flavonoids from Juniperus sabina on Complete Freund's Adjuvant Induced Arthritis in Rats

PubMed Central

Zhao, Jun; Liu, Tao; Xu, Fang; You, Shuping; Xu, Fang; Li, Chenyang; Gu, Zhengyi

2016-01-01

Context: Twigs and leaves of Juniperus sabina L. have been traditionally used as the medicinal herb in China for the treatment of many ailments including rheumatoid arthritis (RA). Aims: To confirm the therapeutic effect of total flavonoids from J. sabina (JSTF) on RA-induced by Complete Freund's Adjuvant (CFA) in rats. Settings and Design: Wistar rats (200 ± 20 g) were immunized by intradermal injection of 0.1 mL of CFA into the right hind metatarsal footpad. JSTF was administered orally at the dose of 125,250 and 500 mg/kg on 14 days after the induction of adjuvant arthritis. Tripterygium glycoside (20 mg/kg) was used as a positive control. Paw swelling, arthritic score, body weight loss, serum cytokines, inflammatory mediators, and histological change were measured. Results: We found that JSTF could ameliorate paw swelling of CFA rats, and significantly inhibit arthritic score (P < 0.05). The overproduction of tumor necrosis factor alpha and interleukin 1beta were remarkably suppressed in the serum of JSTF (125,500 mg/kg) treated rats (P < 0.05). Histopathological studies also showed a marked decrease of synovial inflammatory infiltration and synovial lining hyperplasia in the joints of JSTF-treated animals. Six flavonoids were isolated and from JSTF by various chromatographic methods and identified as follows: Catechin, quercitrin, isoquercitrin, isoscutellarein 7-O-β-D-xylopyranoside, isoscutellarein 7-O-β-D-xylopyranose-(1 → 3)-α-L-rhamnoside, and rutin. Conclusions: These results suggest the potential therapeutically effect of JSTF as an anti-arthritis agent toward CFA-induced arthritis in rats, and verified therapeutic applications of J. sabina on RA in folk medicine. SUMMARY Twigs and leaves of Juniperus sabina L. have been traditionally used as the medicinal herb in China for the treatment of rheumatoid arthritisJSTF could ameliorate paw swelling of CFA rats, and significantly inhibit arthritic scoreHistopathological studies showed a marked decrease of synovial inflammatory infiltration and synovial lining hyperplasia in the joints of JSTF-treated animalsSix flavonoids were isolated and from JSTF including: Catechin, quercitrin, isoquercitrin, isoscutellarein 7-O-β-D-xylopyranoside, isoscutellarein 7-O-β-D-xylopyranose-(1 → 3)-α-L- rhamnoside, and rutin. Abbreviations used: JSTF: Total flavonoids from Juniperus sabina; CFA: Complete Freund's Adjuvant; TG: Tripterygium glycoside; TNF-α: Tumor necrosis factor alpha; IL-1β: Interleukin 1beta; IL-6: Interleukin 6; H and E: Hematoxylin and eosin. PMID:27601846

HannaH phase III randomised study: Association of total pathological complete response with event-free survival in HER2-positive early breast cancer treated with neoadjuvant-adjuvant trastuzumab after 2 years of treatment-free follow-up.

PubMed

Jackisch, Christian; Hegg, Roberto; Stroyakovskiy, Daniil; Ahn, Jin-Seok; Melichar, Bohuslav; Chen, Shin-Cheh; Kim, Sung-Bae; Lichinitser, Mikhail; Starosławska, Elżbieta; Kunz, Georg; Falcon, Silvia; Chen, Shou-Tung; Crepelle-Fléchais, Aulde; Heinzmann, Dominik; Shing, Mona; Pivot, Xavier

2016-07-01

In the phase III, open-label, randomised HannaH study, fixed-dose neoadjuvant-adjuvant subcutaneous trastuzumab for human epidermal growth factor receptor 2 (HER2)-positive early breast cancer was non-inferior to standard weight-based intravenous infusion in terms of serum trough concentration and pathological complete response (pCR). Evidence suggests that pCR, particularly total pCR (tpCR), is likely to predict clinical benefit. We report associations between tpCR and event-free survival (EFS) from HannaH (the largest population from a single study of patients presenting with newly diagnosed HER2-positive breast cancer treated with neoadjuvant-adjuvant trastuzumab to date) plus long-term efficacy and safety. Eligible patients received four cycles of neoadjuvant docetaxel followed by four cycles of fluorouracil/epirubicin/cyclophosphamide administered concurrently with 3-weekly subcutaneous (600 mg fixed dose) or intravenous trastuzumab (8 mg/kg loading, 6 mg/kg maintenance doses). Post-surgery, patients received adjuvant trastuzumab as randomised to complete 1 year of standard treatment. In exploratory analyses, we used Cox regression to assess associations between tpCR and EFS. EFS rates per subgroup were estimated using the Kaplan-Meier method. Three-year EFS rates were 76% for subcutaneous and 73% for intravenous trastuzumab (unstratified hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.69-1.30; intention-to-treat population). Three-year overall survival rates were 92% for subcutaneous and 90% for intravenous trastuzumab (unstratified HR 0.76, 95% CI 0.44-1.32). tpCR was associated with a reduced risk of an EFS event: subcutaneous arm HR 0.38 (95% CI 0.22-0.65); intravenous arm HR 0.32 (95% CI 0.18-0.60). Results were similar for subgroups, including oestrogen receptor status. The few additional adverse events occurring during treatment-free follow-up were balanced between arms. Long-term efficacy supports the established non-inferiority of subcutaneous trastuzumab, and its safety profile remains consistent with the known intravenous profile. In each of HannaH's treatment arms, tpCR was associated with improved EFS, adding to evidence that tpCR is associated with clinical benefit in HER2-positive early breast cancer. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Complete Protection against Influenza Virus H1N1 Strain A/PR/8/34 Challenge in Mice Immunized with Non-Adjuvanted Novirhabdovirus Vaccines

PubMed Central

Rouxel, Ronan N.; Mérour, Emilie; Biacchesi, Stéphane; Brémont, Michel

2016-01-01

Novirhabdoviruses like Viral Hemorrhagic Septicemia Virus (VHSV) and Infectious Hematopoietic Necrosis Virus (IHNV) are fish-infecting Rhabdoviruses belonging to the Mononegavirales order. By reverse genetics, we previously showed that a recombinant VHSV expressing the West Nile Virus (WNV) E glycoprotein could serve as a vaccine platform against WNV. In the current study, we aimed to evaluate the potential of the Novirhabdovirus platform as a vaccine against influenza virus. Recombinant Novirhabdoviruses, rVHSV-HA and rIHNV-HA, expressing at the viral surface the hemagglutinin HA ectodomain were generated and used to immunized mice. We showed that mice immunized with either, rVHSV-HA or rIHNV-HA, elicited a strong neutralizing antibody response against influenza virus. A complete protection was conferred to the immunized mice when challenged with a lethal dose of influenza H1N1 A/PR/8/34 virus. Furthermore we showed that although acting as inert antigen in mice, since naturally inactivated over 20°C, mice immunized with rVHSV-HA or rIHNV-HA in the absence of adjuvant were also completely protected from a lethal challenge. Novirhabdoviruses platform are of particular interest as vaccines for mammals since they are cost effective to produce, relatively easy to generate and very effective to protect immunized animals. PMID:27711176

Photodynamic therapy using Photofrin and Foscan and the treatment of malignancies of the head and neck

NASA Astrophysics Data System (ADS)

Biel, Merrill A.

1998-05-01

One hundred thirty patients with neoplastic diseases of the larynx, oral cavity, pharynx and skin have been treated with photodynamic therapy (PDT) with follow-up to 79 months. Those patients with primary or recurrent leukoplakia, carcinoma-in- situ (CIS) and T1 carcinomas obtained a complete response after one PDT treatment and 87% remain free of disease. Sixteen patients with deeply invasive T2 and T3 carcinomas were treated with PDT. Of those sixteen, ten obtained a complete response, but six have recurred locally. Although a response can be achieved with PDT in the larger solid tumors, it is not a consistent complete response because of the depth of invasion of the tumor. This is due to the inability to adequately deliver laser light to the depths of the tumor bed. Fourteen patients with massive recurrences of squamous cell carcinomas were treated with intraoperative adjuvant PDT following tumor resection. Two patients developed a local recurrence within the field of treatment. PDT is highly effective for the curative treatment of early carcinomas (CIS, T1) of the head and neck. T2 and T3 superficial carcinomas, with invasion less than 0.5 cm, are also curatively treated with PDT with significantly reduced morbidity compared to conventional modes of treatment. Also, intraoperative adjuvant PDT may increase cure rates of large infiltrating carcinomas of the head and neck.

Carbohydrate-based vaccine adjuvants - discovery and development.

PubMed

Hu, Jing; Qiu, Liying; Wang, Xiaoli; Zou, Xiaopeng; Lu, Mengji; Yin, Jian

2015-10-01

The addition of a suitable adjuvant to a vaccine can generate significant effective adaptive immune responses. There is an urgent need for the development of novel po7tent and safe adjuvants for human vaccines. Carbohydrate molecules are promising adjuvants for human vaccines due to their high biocompatibility and good tolerability in vivo. The present review covers a few promising carbohydrate-based adjuvants, lipopolysaccharide, trehalose-6,6'-dibehenate, QS-21 and inulin as examples, which have been extensively studied in human vaccines in a number of preclinical and clinical studies. The authors discuss the current status, applications and strategies of development of each adjuvant and different adjuvant formulation systems. This information gives insight regarding the exciting prospect in the field of carbohydrate-based adjuvant research. Carbohydrate-based adjuvants are promising candidates as an alternative to the Alum salts for human vaccines development. Furthermore, combining two or more adjuvants in one formulation is one of the effective strategies in adjuvant development. However, further research efforts are needed to study and develop novel adjuvants systems, which can be more stable, potent and safe. The development of synthetic carbohydrate chemistry can improve the study of carbohydrate-based adjuvants.

Chemoradiotherapy enhanced the efficacy of radiotherapy in nasopharyngeal carcinoma patients: a network meta-analysis

PubMed Central

He, Jian; Wu, Ping; Tang, Yaoyun; Liu, Sulai; Xie, Chubo; Luo, Shi; Zeng, Junfeng; Xu, Jing; Zhao, Suping

2017-01-01

Object A Bayesian network meta-analysis (NMA) was conducted to estimate the overall survival (OS) and complete response (CR) performance in nasopharyngeal carcinoma (NPC) patients who have been given the treatment of radiotherapy, concurrent chemoradiotherapy (C), adjuvant chemotherapy (A), neoadjuvant chemotherapy (N), concurrent chemoradiotherapy with adjuvant chemotherapy (C+A), concurrent chemoradiotherapy with neoadjuvant chemotherapy (C+N) and neoadjuvant chemotherapy with adjuvant chemotherapy (N+A). Methods Literature search was conducted in electronic databases. Hazard ratios (HRs) accompanied their 95% confidence intervals (95%CIs) or 95% credible intervals (95%CrIs) were applied to measure the relative survival benefit between two comparators. Meanwhile odd ratios (ORs) with their 95% CIs or CrIs were given to present CR data from individual studies. RESULTS Totally 52 qualified studies with 10,081 patients were included in this NMA. In conventional meta-analysis (MA), patients with N+C exhibited an average increase of 9% in the 3-year OS in relation to those with C+A. As for the NMA results, five therapies were associated with a significantly reduced HR when compared with the control group when concerning 5-year OS. C, C+A and N+A also presented a decreased HR compared with A. There was continuity among 1-year, 3-year and 5-year OS status. Cluster analysis suggested that the three chemoradiotherapy appeared to be divided into the most compete group which is located in the upper right corner of the cluster plot. Conclusion In view of survival rate and complete response, the NMA results revealed that C, C+A and C+N showed excellent efficacy. As a result, these 3 therapies were supposed to be considered as the first-line treatment according to this NMA. PMID:28418901

Anti-arthritic activity of Xanthium strumarium L. extract on complete Freund׳s adjuvant induced arthritis in rats.

PubMed

Lin, Bing; Zhao, Yong; Han, Ping; Yue, Wei; Ma, Xue-Qin; Rahman, Khalid; Zheng, Cheng-Jian; Qin, Lu-Ping; Han, Ting

2014-08-08

Xanthium strumarium L. fruit (Xanthiu fruit) has been traditionally used as a medicinal herb in China for the treatment of many ailments including rheumatoid arthritis. However, the anti-arthritic activity of Xanthium strumarium fruit has still not been demonstrated. In the present study, we confirmed that the extract of Xanthium strumarium (EXS) prevents rheumatoid arthritis induced by Complete Freund׳s Adjuvant (CFA) in rats. Male Wistar rats (160±10 g) were immunized by intradermal injection of 0.1 mL of CFA into the left hind metatarsal footpad. EXS was administered orally at a dose of 300 and 75 mg/kg once a day after the induction of adjuvant arthritis. Methotrexate (3 mg/kg, twice a week) was used as a positive control. Paw swelling, arthritic score, body weight loss, spleen index, thymus index, serum cytokines, inflammatory mediators and histological change were measured. The chemical profile of EXS was analyzed by HPLC-DAD. We found that the EXS significantly suppressed paw swelling and arthritic score, increased body weight loss and decreased the thymus index. The overproduction of TNF-α and IL-1β were remarkably suppressed in the serum of all EXS-treated rats, and in contrast IL-10 was markedly increased. The level of COX-2 and 5-LOX was also decreased with EXS treatment. Ten phenolic acid derivatives were identified from 14 detected peaks by HPLC-DAD with the reference substances and verified by LC-MS. These results suggest the potential effect of EXS as an anti-arthritis agent towards CFA-induced arthritis in rats. Xanthium strumarium has the potential to be regarded as a candidate for use in general therapeutics and as an immune-modulatory medicine in rheumatoid arthritis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Suppression of antitumour protective cytotoxic T lymphocyte responses to a human papillomavirus 16 E7 DNA vaccine by coinjection of interleukin-12 complementary DNA: involvement of nitric oxide in immune suppression

PubMed Central

Sin, Jeong-Im

2009-01-01

Interleukin-12 (IL-12) has been shown to enhance cellular immunity in vitro and in vivo. The beneficial roles of IL-12 as a DNA vaccine adjuvant have been commonly observed. Here the impact of IL-12 complementary DNA (cDNA) as an adjuvant for a human papillomavirus (HPV) type 16 E7 DNA vaccine is investigated in a mouse tumour model. Coinjection of E7 DNA vaccine with IL-12 cDNA completely suppressed antigen-specific cytotoxic T-lymphocyte (CTL) responses, leading to a complete loss of antitumour protection from a tumour cell challenge. In addition, antigen-specific antibody and T helper cell proliferative responses were also suppressed by IL-12 cDNA coinjection. This inhibition was observed over different IL-12 cDNA doses. Furthermore, separate leg injections of IL-12 and E7 cDNAs suppressed antigen-specific CTL and tumour protective responses, but not antibody and T helper cell proliferative responses, suggesting different pathways for suppression of these two separate responses. Further knockout animal studies demonstrated that interferon-γ and nitric oxide are not directly associated with suppression of antigen-specific antibody responses by IL-12 cDNA coinjection. However, nitric oxide was found to be involved in suppression of antigen-specific CTL and tumour protective responses by IL-12 cDNA coinjection. These data suggest that coinjection of IL-12 cDNA results in suppression of E7-specific CTL responses through nitric oxide, leading to a loss of antitumour resistance in this DNA vaccine model. This study further shows that the adjuvant effect of IL-12 is dependent on the antigen types tested. PMID:19740332

Suppression of antitumour protective cytotoxic T lymphocyte responses to a human papillomavirus 16 E7 DNA vaccine by coinjection of interleukin-12 complementary DNA: involvement of nitric oxide in immune suppression.

PubMed

Sin, Jeong-Im

2009-09-01

Interleukin-12 (IL-12) has been shown to enhance cellular immunity in vitro and in vivo. The beneficial roles of IL-12 as a DNA vaccine adjuvant have been commonly observed. Here the impact of IL-12 complementary DNA (cDNA) as an adjuvant for a human papillomavirus (HPV) type 16 E7 DNA vaccine is investigated in a mouse tumour model. Coinjection of E7 DNA vaccine with IL-12 cDNA completely suppressed antigen-specific cytotoxic T-lymphocyte (CTL) responses, leading to a complete loss of antitumour protection from a tumour cell challenge. In addition, antigen-specific antibody and T helper cell proliferative responses were also suppressed by IL-12 cDNA coinjection. This inhibition was observed over different IL-12 cDNA doses. Furthermore, separate leg injections of IL-12 and E7 cDNAs suppressed antigen-specific CTL and tumour protective responses, but not antibody and T helper cell proliferative responses, suggesting different pathways for suppression of these two separate responses. Further knockout animal studies demonstrated that interferon-gamma and nitric oxide are not directly associated with suppression of antigen-specific antibody responses by IL-12 cDNA coinjection. However, nitric oxide was found to be involved in suppression of antigen-specific CTL and tumour protective responses by IL-12 cDNA coinjection. These data suggest that coinjection of IL-12 cDNA results in suppression of E7-specific CTL responses through nitric oxide, leading to a loss of antitumour resistance in this DNA vaccine model. This study further shows that the adjuvant effect of IL-12 is dependent on the antigen types tested.

Virtual reality bringing a new reality to postthoracotomy lung cancer patients via a home-based exercise intervention targeting fatigue while undergoing adjuvant treatment.

PubMed

Hoffman, Amy J; Brintnall, Ruth Ann; Brown, Jean K; von Eye, Alexander; Jones, Lee W; Alderink, Gordon; Ritz-Holland, Deborah; Enter, Mark; Patzelt, Lawrence H; VanOtteren, Glenn M

2014-01-01

Little is known about rehabilitation for postthoracotomy non-small cell lung cancer (NSCLC) patients. This research uses a perceived self-efficacy-enhancing light-intensity exercise intervention targeting a priority symptom, cancer-related fatigue (CRF), for postthoracotomy NSCLC patients. This article reports on phase II of a 2-phase study. Phase I focused on initiation and tolerance of exercise during the 6 weeks immediately after thoracotomy, whereas phase II addressed maintenance of exercise for an additional 10 weeks including participants initiating and completing chemotherapy and/or radiation therapy. The objective of this study was to investigate the feasibility, acceptability, and preliminary efficacy of an exercise intervention for postthoracotomy NSCLC patients to include those initiating and completing adjuvant therapy. A single-arm design composed of 7 participants postthoracotomy for NSCLC performed light-intensity exercises using an efficacy-enhancing virtual-reality approach using the Nintendo Wii Fit Plus. Despite most participants undergoing chemotherapy and/or radiation therapy, participants adhered to the intervention at a rate of 88% with no adverse events while giving the intervention high acceptability scores on conclusion. Likewise, participants' CRF scores improved from initiation through the conclusion of the intervention with perceived self-efficacy for walking at a light intensity continuously for 60 minutes, improving significantly upon conclusion over presurgery values. Postthoracotomy NSCLC patients maintained exercise for an additional 10 weeks while undergoing adjuvant therapy showing rehabilitation potential because the exercise intervention was feasible, safe, well tolerated, and highly acceptable showing positive changes in CRF self-management. A randomized controlled trial is needed to further investigate these relationships.

Corrigendum to "Long-term results of a phase II study of gemcitabine and cisplatin chemotherapy combined with intensity-modulated radiotherapy in locoregionally advanced nasopharyngeal carcinoma" [Oral Oncol. 73 (2017) 118-123].

PubMed

Wu, Mingyao; Ou, Dan; He, Xiayun; Hu, Chaosu

2017-11-01

To evaluate long-term results of a phase II study of induction and adjuvant gemcitabine and cisplatin (GP) chemotherapy with intensity-modulated radiotherapy (IMRT) in locoregionally advanced nasopharyngeal carcinoma (NPC). One hundred and twelve patients (Stage III: 65, IVA-B: 47) with locoregionally advanced NPC were enrolled in this study. All patients received induction chemotherapy consisting of 1000 mg/m 2 gemcitabine on day 1 and 8, and cisplatin 25 mg/m 2 on day 1-3, every 3 weeks for 2 cycles. Adjuvant chemotherapy for 2 cycles of the same regime was given 28 days after the end of IMRT. The IMRT technique was utilized for all patients. In total, 97.3% patients completed 2 cycles of induction chemotherapy. The overall response rate (RR) of cervical lymph nodes was 89.0%. Acute toxicities were mainly grade 1-2 myleosuppression and vomiting. And 83.9% patients completed 2 cycles of adjuvant chemotherapy. All patients finished IMRT with RR at the end of IMRT for nasopharynx, lymph nodes of neck and retropharyngeal area being 99.1%, 97.9% and 97.7%, respectively. The 5-year local control, regional control, distant metastasis-free and overall survival rates were 93.2%, 92.3%, 89.0% and 82.1%, respectively. The 5-year overall survival of stage III and IVA-B were 87.0%, and 75.5%, respectively. The incidence of grade 3-4 acute radiotherapy-related mucositis was 28.6%. Severe late toxicities were uncommon. IMRT combined with GP for locoregionally advanced NPC is well tolerated, effective, and convenient, and warrants further studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Impact of neoadjuvant chemotherapy and postoperative adjuvant chemotherapy cycles on survival of patients with advanced-stage ovarian cancer

PubMed Central

Chung, Young Shin; Kim, Yun-Ji; Lee, Inha; Nam, Eun Ji; Kim, Sunghoon; Kim, Sang Wun; Kim, Young Tae

2017-01-01

Background There is currently no consensus regarding the optimal number of chemotherapy cycles to be administered before and after interval debulking surgery (IDS) in patients with advanced ovarian cancer. This study aimed to evaluate the impact of the number of neoadjuvant chemotherapy (NAC) and postoperative adjuvant chemotherapy (POAC) cycles on the survival of patients with advanced ovarian cancer undergoing NAC/IDS/POAC. Methods We retrospectively reviewed data from 203 patients who underwent NAC/IDS/POAC at Yonsei Cancer Hospital between 2006 and 2016. All patients underwent taxane plus carboplatin chemotherapy for NAC and POAC. The patient outcomes were analyzed according to the number of NAC, POAC, and total chemotherapy (NAC+POAC) cycles. Results Patients who received fewer than 6 cycles of total chemotherapy (n = 8) had poorer progression-free survival (PFS) and overall survival (OS) than those completing at least 6 cycles (p = 0.005 and p<0.001, respectively). Among patients who completed at least 6 cycles of total chemotherapy (n = 189), Kaplan-Meier analysis revealed no significant difference in either PFS or OS according to the number of NAC cycles (1–3 vs. ≥4; p = 0.136 and p = 0.267, respectively). Among patients who experienced complete remission after 3 cycles of POAC (n = 98), the addition of further POAC cycles did not improve the PFS or OS (3 vs. ≥4; p = 0.641 and p = 0.104, respectively). Conclusion IDS after 4 cycles of NAC may be a safe and effective option when completing 6 cycles of total chemotherapy. Furthermore, the addition of more than 3 cycles of POAC does not appear to influence the survival of patients achieving completion remission after 3 cycles of POAC. PMID:28873393

Impact of neoadjuvant chemotherapy and postoperative adjuvant chemotherapy cycles on survival of patients with advanced-stage ovarian cancer.

PubMed

Chung, Young Shin; Kim, Yun-Ji; Lee, Inha; Lee, Jung-Yun; Nam, Eun Ji; Kim, Sunghoon; Kim, Sang Wun; Kim, Young Tae

2017-01-01

There is currently no consensus regarding the optimal number of chemotherapy cycles to be administered before and after interval debulking surgery (IDS) in patients with advanced ovarian cancer. This study aimed to evaluate the impact of the number of neoadjuvant chemotherapy (NAC) and postoperative adjuvant chemotherapy (POAC) cycles on the survival of patients with advanced ovarian cancer undergoing NAC/IDS/POAC. We retrospectively reviewed data from 203 patients who underwent NAC/IDS/POAC at Yonsei Cancer Hospital between 2006 and 2016. All patients underwent taxane plus carboplatin chemotherapy for NAC and POAC. The patient outcomes were analyzed according to the number of NAC, POAC, and total chemotherapy (NAC+POAC) cycles. Patients who received fewer than 6 cycles of total chemotherapy (n = 8) had poorer progression-free survival (PFS) and overall survival (OS) than those completing at least 6 cycles (p = 0.005 and p<0.001, respectively). Among patients who completed at least 6 cycles of total chemotherapy (n = 189), Kaplan-Meier analysis revealed no significant difference in either PFS or OS according to the number of NAC cycles (1-3 vs. ≥4; p = 0.136 and p = 0.267, respectively). Among patients who experienced complete remission after 3 cycles of POAC (n = 98), the addition of further POAC cycles did not improve the PFS or OS (3 vs. ≥4; p = 0.641 and p = 0.104, respectively). IDS after 4 cycles of NAC may be a safe and effective option when completing 6 cycles of total chemotherapy. Furthermore, the addition of more than 3 cycles of POAC does not appear to influence the survival of patients achieving completion remission after 3 cycles of POAC.

Effects of adjuvants for human use in systemic lupus erythematosus (SLE)-prone (New Zealand black/New Zealand white) F1 mice.

PubMed

Favoino, E; Favia, E I; Digiglio, L; Racanelli, V; Shoenfeld, Y; Perosa, F

2014-01-01

The safety of four different adjuvants was assessed in lupus-prone New Zealand black/New Zealand white (BW)F1 mice. Four groups of mice were injected intraperitoneally with incomplete Freund's adjuvant (IFA), complete Freund's adjuvant (CFA), squalene (SQU) or aluminium hydroxide (ALU). An additional group received plain phosphate-buffered saline (PBS) (UNT group). Mice were primed at week 9 and boosted every other week up to week 15. Proteinuria became detectable at weeks 17 (IFA group), 24 (CFA group), 28 (SQU and ALU groups) and 32 (UNT group). Different mean values were obtained among the groups from weeks 17 to 21 [week 17: one-way analysis of variance (anova) P = 0·016; weeks 18 and 19: P = 0·048; weeks 20 and 21: P = 0·013] being higher in the IFA group than the others [Tukey's honestly significant difference (HSD) post-test P < 0·05]. No differences in anti-DNA antibody levels were observed among groups. Anti-RNP/Sm antibody developed at week 19 in only one CFA-treated mouse. Mean mouse weight at week 18 was lower in the ALU group than the IFA (Tukey's HSD post-test P = 0·04), CFA (P = 0·01) and SQU (P < 0·0001) groups, while the mean weight in the SQU group was higher than in the IFA (P = 0·009), CFA (P = 0·013) and UNT (P = 0·005) groups. The ALU group weight decreased by almost half between weeks 29 and 31, indicating some toxic effect of ALU in the late post-immunization period. Thus, SQU was the least toxic adjuvant as it did not (i) accelerate proteinuria onset compared to IFA; (ii) induce toxicity compared to ALU or (iii) elicit anti-RNP/Sm autoantibody, as occurred in the CFA group. © 2013 British Society for Immunology.

Evaluation of Liposome, Heat-Killed Mycobacterium w, and Alum Adjuvants in the Protection Offered by Different Combinations of Recombinant HA, NP proteins, and M2e Against Homologous H5N1 Virus.

PubMed

Ingle, Nilesh B; Virkar, Rashmi G; Agnihotri, Kalpana; Sharma, Kapil S; Lole, Kavita S; Arankalle, Vidya A

2016-10-01

Continued evolution of highly pathogenic H5N1 viruses causing high mortality in humans obviates need for broadly cross-reactive vaccines. For this, hemagglutinin (HA) inducing specific protective antibodies, highly conserved nucleoprotein (NP), and ectodomain of matrix (M2e) protein, either singly or in combination, were evaluated in BALB/c mice. Recombinant HA and NP (baculovirus system) and M2e (synthetic peptide) and 3 adjuvants, that is, liposomes, Mw (heat killed Mycobacterium w), and alum were utilized for the homologous virus challenge. Additional immunogens included liposome-encapsulated HA/NP proteins and corresponding DNAs. Mice groups received two doses of respective formulations given at 3-week intervals and challenged intranasally with 100LD50 of H5N1 virus strain. Dynamics of weight loss, lung viral load, titres of IgG-anti-HA, NP, and M2e antibodies (ELISA), and IgG-subtype analysis was done. Two doses of all the formulations led to 100% seroconversion against the immunogens evaluated (100% seroconversion after the first dose in majority). Antibody titres against the components were dependent on the adjuvant and combination. HA-driven Th2 response with all the adjuvants, balanced Th1/Th2 response to NP protein, and Th2-bias with alum were noted. Low anti-M2e antibody titres did not allow subtype analysis. On challenge, complete protection was observed with Mw-HA, alum-HA+NP, Lipo-HA+NP+M2e, alum-HA+NP+M2e, and HA-DP formulations with 12-fold, 8-fold, 720-fold, 17-fold, and no reduction, respectively, in lung viral load. In conclusion, the results identify several adjuvant-immunogen combinations conferring 100% protection in mice that need further evaluation in higher animals.

Adjuvant leuprolide with or without docetaxel in patients with high-risk prostate cancer after radical prostatectomy (TAX-3501): important lessons for future trials.

PubMed

Schweizer, Michael T; Huang, Peng; Kattan, Michael W; Kibel, Adam S; de Wit, Ronald; Sternberg, Cora N; Epstein, Jonathan I; Eisenberger, Mario A

2013-10-15

The current trial evaluated 2 common therapies for patients with advanced prostate cancer, docetaxel and hormonal therapy (HT), in the surgical adjuvant setting. TAX-3501 was a randomized, phase 3, adjuvant study post-radical prostatectomy (RP) in high-risk patients with prostate cancer (n=228) comparing 18 months of HT with (CHT) without docetaxel chemotherapy either immediately (I) or deferred (D). High-risk disease was defined as a 5-year freedom-from-disease-progression rate of ≤ 60% as predicted by a post-RP nomogram. Progression-free survival (PFS), including prostate-specific antigen disease recurrence, was the primary endpoint. The authors also assessed the accuracy of the nomogram and analyzed testosterone recovery in 108 patients treated with HT who had at least 1 posttreatment testosterone value. Between December 2005 and September 2007, 228 patients were randomized between the treatment cohorts. TAX-3501 was terminated prematurely because of enrollment challenges, leaving it underpowered to detect differences in PFS. After a median follow-up of 3.4 years (interquartile range, 2.3-3.8 years), 39 of 228 patients (17%) demonstrated PSA disease progression, and metastatic disease progression occurred in 1 patient. The median time to baseline testosterone recovery after the completion of treatment was prolonged at 487 days (95% confidence interval, 457-546 days). The nomogram's predicted versus observed freedom from disease progression was significantly different for the combination D(HT) and D(CHT) group (P<.00001). TAX-3501 illustrated several difficulties involved in conducting postoperative adjuvant systemic trials in men with high-risk prostate cancer: the lack of consensus regarding patient selection and treatment, the need for long follow-up time, nonvalidated intermediate endpoints, evolving standard approaches, and the need for long-term research support. Except for selected patients at very high-risk of disease recurrence and death, surgical adjuvant trials in patients with prostate cancer may not be feasible. Copyright © 2013 American Cancer Society.

Incompletely obliterated cranial arteriovenous fistulae are safely and effectively treated with adjuvant ε-aminocaproic acid.

PubMed

Howard, Brian M; Grossberg, Jonathan A; Prater, Adam; Cawley, C Michael; Dion, Jacques E; Tong, Frank C

2018-07-01

Administration of ε-aminocaproic acid (εACA), as adjuvant therapy following incompletely embolized cranial dural arteriovenous (dAVFs) and direct carotid artery to cavernous sinus fistulae (CCFs), is a strategy to promote post-procedural thrombosis. However, the efficacy of εACA to treat incompletely obliterated dAVFs and CCFs has not been published. The purpose of this study was to determine if administration of εACA following incomplete embolization of cranial dAVFs or CCFs was associated with an increased likelihood of cure on follow-up imaging compared with patients not given adjuvant εACA. A retrospective cohort study was performed. All patients who underwent treatment of a dAVF or CCF at our institution between 1998 and 2016 were reviewed (n=262). Patients with residual shunting following the first attempted endovascular embolization were included in the analysis (n=52). The study groups were those treated with εACA following incomplete obliteration of the fistula and those who were not. The primary outcome was obliteration of the fistula on initial follow-up imaging. Complication rates between cohorts were compared. 20 (38%) patients with incompletely obliterated fistulae were treated with adjuvant εACA. A trend towards an improved rate of complete obliteration on initial follow-up imaging was observed in the group treated with εACA (55% vs 34% in the group not treated with εACA, p=0.14). No difference in clinical outcomes or thromboembolic complications was observed between the groups. In summary, these data suggest that administration of εACA is a safe adjuvant therapy in the management of cranial dAVFs and CCFs that are incompletely treated endovascularly. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

18β-glycyrrhetinic acid induces immunological adjuvant activity of Th1 against Candida albicans surface mannan extract.

PubMed

Kim, Jeonghyeon; Joo, Inkyung; Kim, Hayan; Han, Yongmoon

2013-08-15

The aim of this study was to determine the immunological adjuvant effect of 18β-glycyrrhetinic acid (GA) isolated from Glycyrrhizae radix. In the experiments, BALB/c mice were immunized on days 1 and 22 intraperitoneally (i.p.) with an emulsion form of Candida albicans surface mannan extract (SM) mixed with either Incomplete Freund's Adjuvant [SM/IFA], or Complete Freund's Adjuvant [SM/CFA] or GA mixed with IFA [SM/GA/IFA]. One week after the second immunization, polyclonal sera were collected from these animals in order to determine IgG isotypes and cytokine profiles in the sera. After the collection, the spleen samples were collected to determine the degree of T cell proliferation. Additionally, the DTH (delayed type hypersensitivity) response was examined by measuring the footpad swelling of immunized mice. Data resulting from the T cell proliferation test showed that SM/GA/IFA enhanced the proliferation the most. The enhancement was about 85% more compared to SM/IFA (p<0.05). IgG isotypes and cytokine profiles displayed that SM/GA/IFA induced the most abundant production of total IgG with the highest IgG2a/IgG1 ratio (1.31) and greatest IFN-γ secretion. In contrast, SM/CFA resulted in an IgG2a/IgG1 ratio less than 1 and SM/IFA produced a dominant induction of IL-4, but almost no IFN-γ secretion. Together, these observations revealed that GA developed a greater Th1 immune response than Th2 response. The DTH determination confirmed that GA-addition induced dominant Th1 immunity - displaying the highest footpad-swelling followed by SM/CFA and BSA/IFA, respectively. All of this data indicates that GA has a Th1-immunological adjuvant activity, which would be beneficial in the treatment of Th1-disordered disease due to C. albicans. Copyright © 2013 Elsevier GmbH. All rights reserved.

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

Morganti, Alessio G.; Unit of Radiotherapy, Unit of General Oncology, Fondazione Giovanni Paolo II, Campobasso; Falconi, Massimo

Purpose: To determine the impact of chemoradiation therapy (CRT) on overall survival (OS) after resection of pancreatic adenocarcinoma. Methods and Materials: A multicenter retrospective review of 955 consecutive patients who underwent complete resection with macroscopically negative margins (R0-1) for invasive carcinoma (T1-4; N0-1; M0) of the pancreas was performed. Exclusion criteria included metastatic or unresectable disease at surgery, macroscopic residual disease (R2), treatment with intraoperative radiation therapy (IORT), and a histological diagnosis of no ductal carcinoma, or postoperative death (within 60 days of surgery). In all, 623 patients received postoperative radiation therapy (RT), 575 patients received concurrent chemotherapy (CT), and 462more » patients received adjuvant CT. Results: Median follow-up was 21.0 months. Median OS after adjuvant CRT was 39.9 versus 24.8 months after no adjuvant CRT (P<.001) and 27.8 months after CT alone (P<.001). Five-year OS was 41.2% versus 24.8% with and without postoperative CRT, respectively. The positive impact of CRT was confirmed by multivariate analysis (hazard ratio [HR] = 0.72; confidence interval [CI], 0.60-0.87; P=.001). Adverse prognostic factors identified by multivariate analysis included the following: R1 resection (HR = 1.17; CI = 1.07-1.28; P<.001), higher pT stage (HR = 1.23; CI = 1.11-1.37; P<.001), positive lymph nodes (HR = 1.27; CI = 1.15-1.41; P<.001), and tumor diameter >20 mm (HR = 1.14; CI = 1.05-1.23; P=.002). Multivariate analysis also showed a better prognosis in patients treated in centers with >10 pancreatic resections per year (HR = 0.87; CI = 0.78-0.97; P=.014) Conclusion: This study represents the largest comparative study on adjuvant therapy in patients after resection of carcinoma of the pancreas. Overall survival was better in patients who received adjuvant CRT.« less

No effect of bipolar interferential electrotherapy and pulsed ultrasound for soft tissue shoulder disorders: a randomised controlled trial

PubMed Central

van der Heijden, G. J M G; Leffers, P.; Wolters, P.; Verheijden, J.; van Mameren, H.; Houben, J.; Bouter, L.; Knipschild, P.

1999-01-01

OBJECTIVE—To assess the efficacy of bipolar interferential electrotherapy (ET) and pulsed ultrasound (US) as adjuvants to exercise therapy for soft tissue shoulder disorders (SD).
METHODS—Randomised placebo controlled trial with a two by two factorial design plus an additional control group in 17 primary care physiotherapy practices in the south of the Netherlands. Patients with shoulder pain and/or restricted shoulder mobility, because of a soft tissue impairment without underlying specific or generalised condition, were enrolled if they had not recovered after six sessions of exercise therapy in two weeks. They were randomised to receive (1) active ET plus active US; (2) active ET plus dummy US; (3) dummy ET plus active US; (4) dummy ET plus dummy US; or (5) no adjuvants. Additionally, they received a maximum of 12 sessions of exercise therapy in six weeks. Measurements at baseline, 6 weeks and 3, 6, 9, and 12 months later were blinded for treatment. Outcome measures: recovery, functional status, chief complaint, pain, clinical status, and range of motion.
RESULTS—After written informed consent 180 patients were randomised: both the active treatments were given to 73 patients, both the dummy treatments to 72 patients, and 35 patients received no adjuvants. Prognosis of groups appeared similar at baseline. Blinding was successfully maintained. At six weeks seven patients (20%) without adjuvants reported very large improvement (including complete recovery), 17 (23%) and 16 (22%) with active and dummy ET, and 19 (26%) and 14 (19%) with active and dummy US. These proportions increased to about 40% at three months, but remained virtually stable thereafter. Up to 12 months follow up the 95% CI for differences between groups for all outcomes include zero.
CONCLUSION—Neither ET nor US prove to be effective as adjuvants to exercise therapy for soft tissue SD.

 PMID:10460185

Prophylactic inguinal-femoral irradiation as an alternative to primary lymphadenectomy in treatment of vulvar carcinoma.

PubMed

Hallak, Sorana; Ladi, Luz; Sorbe, Bengt

2007-11-01

In a complete geographic series of 294 cases of primary vulvar carcinomas prophylactic inguinal-femoral irradiation was used as a standard postoperative therapy. Inguinal lymph node dissection was performed in only 27 cases (9%) and was not part of the standard surgery. The histology was squamous cell carcinoma in 269 cases (92%). The primary surgery was total vulvectomy, partial vulvectomy, or local resection of the tumor. The main type of radiotherapy was adjuvant inguinal irradiation. Two separate, symmetrical and rectangular inguinal fields were irradiated with combined photon and electron beams. In the complete series 127 recurrences (43%) were recorded. Local (24%) and regional recurrences (19%) were most frequent. Type of surgery was not associated with the risk of tumor recurrence. The 5-year overall survival rate was 53% and the relapse-free survival (RFS) rate was 55%. Tumor grade was significantly (P=0.007) associated with the RFS. The inguinal RFS rate was 75% both for patients treated with adjuvant inguinal irradiation without lymphadenectomy and patients treated with primary lymph adenectomy +/- inguinal irradiation. Postoperative complications were recorded in 22%. Postoperative complications occurred most frequently in the subgroup undergoing inguinal lymphadenectomy. Chronic lymph edemas were the most serious late tissue reactions.

Soluble Dietary Fibers Can Protect the Small Intestinal Mucosa Without Affecting the Anti-inflammatory Effect of Indomethacin in Adjuvant-Induced Arthritis Rats.

PubMed

Satoh, Hiroshi; Matsumoto, Hiroki; Hirakawa, Tomoe; Wada, Naoki

2016-01-01

How to prevent the small intestinal damage induced by NSAIDs is an urgent issue to be resolved. In the present study, we examined the effects of soluble dietary fibers on both anti-inflammatory and ulcerogenic effects of indomethacin in arthritic rats. Male Wistar rats weighing 180-220 g were used. Arthritis was induced by injecting Freund's complete adjuvant (killed M. tuberculosis) into the plantar region of the right hindpaw. The animals were fed a regular powder diet for rats or a diet supplemented with soluble dietary fibers such as pectin or guar gum. Indomethacin was administered once a day for 3 days starting 14 days after the adjuvant injection, when marked arthritis was observed. The volumes of the hindpaw were measured before and after indomethacin treatment to evaluate the effect of indomethacin on edema. The lesions in the small intestine were examined 24 h after the final dosing of indomethacin. Hindpaw volume was increased about 3 times 14 days after injection of the adjuvant. Indomethacin (3-10 mg/kg, p.o.) decreased hindpaw volume dose-dependently, but caused severe lesions in the small intestine at doses of 6 and 10 mg/kg. The addition of pectin (1-10 %) or guar gum (10 %) to the diet markedly decreased the lesion formation without affecting the anti-edema action of indomethacin. The same effects of pectin were observed when indomethacin was administered subcutaneously. It is suggested that soluble dietary fibers can prevent intestinal damage induced by NSAIDs without affecting the anti-inflammatory effect of these agents.

Long-term recovery of normal sexual function in testicular cancer survivors.

PubMed

Capogrosso, Paolo; Boeri, Luca; Ferrari, Matteo; Ventimiglia, Eugenio; La Croce, Giovanni; Capitanio, Umberto; Briganti, Alberto; Damiano, Rocco; Montorsi, Francesco; Salonia, Andrea

2016-01-01

Testicular cancer (TC) is the most common solid cancer in men between the third and fourth decade of life. Due to successful treatment approaches, TC survivors (TCSs) have long life expectancy, but with numerous potential long-term sequelae, including sexual dysfunction. We investigated predictors of long-term normal sexual function (SF) recovery in TCSs. Sociodemographic, medical, and psychometric data were analyzed in 143 Caucasian-European TCSs, who underwent orchiectomy at a single institution. Health-significant comorbidities were scored with the Charlson Comorbidity Index (CCI). Patients completed the International Index of Erectile Function (IIEF). Statistical models tested the association between predictors (including age at surgery, body mass index, CCI, and adjuvant therapy: radiotherapy [RT], chemotherapy [CT], CT followed by retroperitoneal lymph node dissection [RPLND] and RPLND alone) and the long-term recovery of normal SF (defined as IIEF-erectile function [EF] ≥26, and sexual desire [SD], intercourse satisfaction [IS] orgasmic function [OF], and overall satisfaction [OS] domain scores in the upper tertiles). At a mean follow-up of 86 months, 35 (25.5%) TCSs had erectile dysfunction (ED), with 16 (11.2%) experiencing severe ED. Median time of EF recovery was 60, 60, and 70 months after CT, RT, and RPLND, respectively. Only adjuvant RT emerged as an independent predictor of nonrecovery of normal EF (HR: 0.55, P= 0.01). Neither adjuvant CT nor CT plus RPLND or RPLND alone significantly impaired the recovery of normal erections. Adjuvant therapy was not associated with impaired recovery of normal sexuality as a whole, considering the IIEF-SD, -OF, -IS, and OS domains.

Xylopia aethiopica (Annonaceae) fruit extract suppresses Freund's adjuvant-induced arthritis in Sprague-Dawley rats.

PubMed

Obiri, David D; Osafo, Newman; Ayande, Patrick G; Antwi, Aaron O

2014-03-28

Xylopia aethiopica is used in a decoction of the dried fruit to treat bronchitis, asthma, arthritis, rheumatism, headache, neuralgia and colic pain. The aim of the study is to evaluate the anti-arthritic effects of a 70% aqueous ethanol extract of the fruit of Xylopia aethiopica in a chronic inflammatory model. Adjuvant arthritis was induced in Sprague-Dawley rats by intraplantar injection of Complete Freund's adjuvant into the right hind paw. Foot volume was measured by water displacement plethysmometry. The oedema component of inflammation was evaluated as the percentage change in paw swelling and the total oedema induced calculated as area under the time course curves. In addition to X-ray radiography, histopathology of ankle joints supported by haematological analysis was used to assess the anti-arthritic action of the extract of Xylopia aethiopica (XAE). Xylopia aethiopica extract (100, 300 and 600 mg kg(-1)) modified the time course curve significantly reducing hind paw oedema in the ipsilateral paw at all dose levels when administered both prophylactically and therapeutically. In addition XAE significantly suppressed the systemic spread of the arthritis from the ipsilateral to the contralateral limbs. The radiological pictures of the joints particularly metatarsal, phalanges and the ankle joint space of rats in the XAE-treated group showed protective effect against adjuvant-induced arthritis while histopathology revealed significant reduction in mononuclear infiltration, pannus formation and bone erosion. The haematological analysis in the test animals revealed significant improvement relative to the CFA model group. Xylopia aethiopica XAE suppresses joint inflammation and destruction in arthritic rats. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Expansion of CD11b+Ly6Ghigh and CD11b+CD49d+ myeloid cells with suppressive potential in mice with chronic inflammation and light-at-night-induced circadian disruption.

PubMed

Perfilyeva, Yuliya V; Abdolla, Nurshat; Ostapchuk, Yekaterina O; Tleulieva, Raikhan; Krasnoshtanov, Vladimir C; Belyaev, Nikolai N

2017-08-01

Myeloid-derived suppressor cells (MDSCs) are important negative regulators of immune processes in cancer and other pathological conditions. We suggested that MDSCs play a key role in pathogenesis of chronic inflammation, which precedes and, to a certain extent, induces carcinogenesis. The present study aimed at investigation of MDSCs arising during chronic inflammation and light-at-night (LN)-induced stress, which is shown to accelerate chronic diseases. 67 CD-1 mice and in vitro MDSC cultures. Adjuvant arthritis was induced by a subdermal injection of complete Freund's adjuvant. LN was induced by illumination of 750 lx at night. Flow cytometry for evaluation of cell phenotypes and MTT standard test for cell proliferation were used. Increased levels of splenic CD11b + Ly6G high and CD11b + CD49d + myeloid cells possessing suppressive potential in mice with adjuvant arthritis are shown. LN amplifies the process of CD11b + Ly6G high expansion in mice with adjuvant arthritis. Expression of CD62L and CD195 is elevated on the myeloid cells during exposure to LN. Our study raises the possibility that CD11b + Ly6G high and CD11b + CD49d + MDSCs play an important role in the induction of immunosuppressive environment typical for chronic inflammation. Also, LN can affect immune responses during chronic inflammation through recruitment of MDSCs from the bone marrow.

Compatibility of ASO3-adjuvanted H1N1pdm09 and seasonal trivalent influenza vaccines in adults: results of a randomized, controlled trial.

PubMed

Scheifele, David W; Ward, Brian J; Dionne, Marc; Vanderkooi, Otto G; Loeb, Mark; Coleman, Brenda L; Li, Yan

2012-07-06

When Canada chose a novel adjuvanted vaccine to combat the 2009 influenza pandemic, seasonal trivalent inactivated vaccine (TIV) was also available but compatibility of the two had not been assessed. To compare responses after concurrent or sequential administration of these vaccines, adults 20-59 years old were randomly assigned (1:1) to receive ASO3-adjuvanted H1N1pdm09 vaccine (Arepanrix, GSK, Quebec City, Quebec), with TIV (Vaxigrip, Sanofi Pasteur, Toronto) given concurrently or 21 days later. Blood was obtained at baseline and 21 days after each vaccination to measure hemagglutination inhibition (HAI) titers. Adverse effects were assessed using symptom diaries and personal interviews. 282 participants completed the study (concurrent vaccines 145, sequential vaccines 137). HAI titers to H1N1pdm09 were ≥ 40 at baseline in 15-18% of participants and following vaccination in 91-92%. Initially seropositive subjects (titer ≥ 10) had lower H1N1pdm09 geometric mean HAI titers (GMT) after concurrent than separate vaccinations (320.0 vs 476.5, p=0.039) but both exceeded GM responses of initially naïve participants, which were unaffected by concurrent TIV. Responses to TIV were not lower after concurrent than separate vaccination. Adverse event rates were not increased by concurrent vaccinations above those with H1N1pdm09 vaccine alone. This adjuvanted H1N1pdm09 vaccine was immunogenic and compatible with concurrently administered TIV. Copyright © 2012 Elsevier Ltd. All rights reserved.

Results of NCCTG N0275 (Alliance) - a phase II trial evaluating resection followed by adjuvant radiation therapy for patients with desmoplastic melanoma.

PubMed

Rule, William G; Allred, Jacob B; Pockaj, Barbara A; Markovic, Svetomir N; DiCaudo, David J; Erickson, Lori A; Deming, Richard L; Schild, Steven E

2016-08-01

To examine, in a prospective fashion, the utilization and efficacy of adjuvant radiation therapy (RT) in patients with resected desmoplastic melanoma (DM). Adult patients with resected, margin-negative, and nonmetastatic DM were eligible for this single-arm prospective phase II study. Patients were to receive postoperative RT, 30 Gy in five fractions, to the operative bed with 2- to 3-cm margins (depending on the tumor location). Nodal basin RT was not allowed. The primary study endpoint was the 2-year local recurrence rate (LRR). Secondary endpoints included the incidence of regional and distant metastatic disease, progression-free survival, overall survival (OS), and treatment-related toxicity. Twenty patients with a single de novo DM lesion meeting trial eligibility criteria were enrolled and treated. The 2-year LRR was 10%, with two patients demonstrating a LR within 2 years of completion of protocol therapy. No regional or distant failures occurred. OS at 2 and 5 years was 95 and 77%, respectively. There were no grade 3 or higher acute or late adverse events that were related to the protocol therapy. Adjuvant RT after wide local excision (WLE) for DM is efficacious and well tolerated. It should be considered for DM patients after margin-negative WLE. Additional study is needed to further refine low-risk patient populations that can potentially have adjuvant RT omitted as part of the treatment plan. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Military Standard: Technical Reviews and Audits for Systems, Equipments, and Computer Software

DTIC Science & Technology

1985-06-04

Concept Exploration or Demonstration and Validation phase. Such reviews may De conducted at any time but normal’y -dill be conducted after the...method of re•olutiun shall also De reviewed." All proposed environmental tests shall De reviewe• for compatibility wi•h the specified na•ura...accepted. See Attachment _ for comments. Attached is a list of de `iciencies. Signature(s) of FCA Team Member(s) "Sub-Team Chairperscn 0. Figure 3 Page 5 of

Bisphosphonates as adjuvant therapy for breast cancer.

PubMed

Burkinshaw, Roger; Coleman, Robert

2006-01-01

Great strides have been made over the last 20 years in the treatment of breast cancer and despite an increasing incidence, the number of deaths has fallen sharply since the late 1980s. The advent of new therapies, including taxanes and aromatase inhibitors, and exciting results announced recently using trastuzumab in the adjuvant treatment of HER2-positive patients should decrease this even further. However, although most patients present with disease that appears to be localized to the breast, a significant proportion of women will eventually develop metastatic breast cancer. Therefore, the detection and treatment of micrometastatic disease represents perhaps the most important remaining challenge in breast cancer management, and is the focus of extensive ongoing research. Bone is the most frequent site of distant relapse, accounting for approximately 40% of all first recurrences. In addition to the well recognized release of bone cell-activating factors from the tumor, it is now appreciated that the release of bone-derived growth factors and cytokines from resorbing bone can attract cancer cells to the bone surface and facilitate their growth and proliferation. Bisphosphonates are potent inhibitors of bone osteolysis and the inhibition of bone resorption could therefore have an effect on the development and progression of metastatic bone disease. They could represent an adjuvant therapeutic strategy of potential importance. Clinical trial results with the early bisphosphonate, clodronate, have proved inconclusive. A large, randomized, controlled trial has recently completed accrual and should provide the definitive answer to the question of the role of clodronate in this setting. More potent second- and third-generation bisphosphonates have also shown enhanced antitumor effects in preclinical evaluation and further studies are required to determine whether this antitumor potential of bisphosphonates translates to the clinical setting. Adjuvant bisphosphonates are, therefore, currently only recommended in the research setting and clinical trials evaluating the adjuvant use of these newer compounds are currently recruiting or being established. This article will review in more detail the rationale for the adjuvant use of bisphosphonates, the results of early trials, the progress of the later trials and the potential future role of bisphosphonates in the adjuvant treatment of breast cancer. In addition, it is increasingly acknowledged that many cancer treatments have detrimental effects on bone and can increase the risk of fracture. The increasing use of aromatase inhibitors, in particular, will become a major cause of treatment-induced bone loss. This bone loss can be prevented with bisphosphonate treatment and this will also be discussed.

Status of Wrought FeCrAl-UO 2 Capsules Irradiated in the Advanced Test Reactor

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

Field, Kevin G.; Harp, J.; Core, G.

2017-07-01

Candidate cladding materials for accident tolerant fuel applications require extensive testing and validation prior to commercial deployment within the nuclear power industry. One class of cladding materials, FeCrAl alloys, is currently undergoing such effort. Within these activities is a series of irradiation programs within the Advanced Test Reactor. These programs are developed to aid in commercial maturation and understand the fundamental mechanisms controlling the cladding performance during normal operation of a typical light water reactor. Three different irradiation programs are on-going; one designed as a simple proof-of-principle concept, the other to evaluate the susceptibility of FeCrAl to fuel-cladding chemical interaction,more » and the last to fully simulate the conditions of a pressurized water reactor experimentally. To date, nondestructive post-irradiation examination has been completed on the rodlet deemed FCA-L3 from the simple proof-of-concept irradiation program. Initial results show possible breach of the rodlet under irradiation but further studies are needed to conclusively determine whether breach has occurred and the underlying reasons for such a possible failure. Further work includes characterizing additional rodlets following irradiation.« less

Role of adjuvant chemoradiotherapy in T4N0 stage IV head and neck cancer: A National Cancer Database analysis.

PubMed

Kirke, Diana N; Qureshi, Muhammad M; Kamran, Sophia C; Ezzat, Waleed; Jalisi, Scharukh; Salama, Andrew; Everett, Peter C; Truong, Minh Tam

2018-06-01

The purpose of this study was to evaluate the role of postoperative adjuvant radiotherapy (surgery + adjuvant RT) versus adjuvant chemoradiotherapy (surgery + adjuvant CRT) in patients with T4N0M0, stage IV head and neck squamous cell carcinoma (HNSCC). Between 1998 and 2011, 3518 and 885 patients were treated with surgery + adjuvant RT and surgery + adjuvant CRT, respectively. Three-year overall survival (OS) rates were determined and crude and adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were computed. Median follow-up was 41.8 months with 2193 reported deaths. The 3-year OS was 67.5% for surgery + adjuvant RT and 70.5% for surgery + adjuvant CRT (P = .013). For negative margins, the corresponding 3-year OS was 70.1% and 74.9% (P = .005). For positive margins, the corresponding 3-year OS was 56.0% and 60.6% (P = .079). On multivariate analysis, the beneficial effect for adjuvant CRT over adjuvant RT was not significant (HR 0.90; CI 0.79-1.03; P = .124). In this cohort of patients with T4N0 HNSCC treated with surgery, there was no observed survival benefit of adjuvant CRT over adjuvant RT on multivariate analysis. © 2018 Wiley Periodicals, Inc.

Phase II Trial of Preoperative Radiation With Concurrent Capecitabine, Oxaliplatin, and Bevacizumab Followed by Surgery and Postoperative 5-Fluorouracil, Leucovorin, Oxaliplatin (FOLFOX), and Bevacizumab in Patients With Locally Advanced Rectal Cancer: 5-Year Clinical Outcomes ECOG-ACRIN Cancer Research Group E3204.

PubMed

Landry, Jerome C; Feng, Yang; Prabhu, Roshan S; Cohen, Steven J; Staley, Charles A; Whittington, Richard; Sigurdson, Elin Ruth; Nimeiri, Halla; Verma, Udit; Benson, Al Bowen

2015-06-01

The 5-year oncologic outcomes from the trial regimen were excellent. However, the neoadjuvant and surgical toxicity of this regimen was significant and was the primary reason for the low compliance with adjuvant systemic therapy.Due to the lack of an improvement in the pathologic complete response rate, the substantial associated toxicity, and the negative phase III trials of adjuvant bevacizumab in colon cancer, this regimen will not be pursued for further study. The addition of bevacizumab to chemotherapy improves overall survival for metastatic colorectal cancer. We initiated a phase II trial to evaluate preoperative capecitabine, oxaliplatin, and bevacizumab with radiation therapy (RT) followed by surgery and postoperative 5-fluorouracil, leucovorin, oxaliplatin (FOLFOX), and bevacizumab for locally advanced rectal cancer. The purpose of this report is to describe the 5-year oncologic outcomes of this regimen. In a phase II Simon two-stage design study, we evaluated preoperative treatment with capecitabine (825 mg/m(2) b.i.d. Monday-Friday), oxaliplatin (50 mg/m(2) weekly), bevacizumab (5 mg/kg on days 1, 15, and 29), and RT (50.4 Gy). Surgery was performed by 8 weeks after RT. Beginning 8-12 weeks after surgery, patients received FOLFOX plus bevacizumab (5 mg/kg) every 2 weeks for 12 cycles (oxaliplatin stopped after 9 cycles). The primary endpoint was a pathologic complete response (path-CR) rate of 30%. Fifty-seven patients with resectable T3/T4 rectal adenocarcinoma were enrolled between 2006 and 2010. Of 57 enrolled patients, 53 were eligible and included in the analysis. Forty-eight (91%) patients completed preoperative therapy, all of whom underwent curative surgical resection. Nine patients (17%) achieved path-CR. There were 29 worst grade 3 events, 8 worst grade 4 events, and 2 patient deaths, 1 of which was attributed to study therapy. Twenty-six patients (54%) began adjuvant chemotherapy. After a median follow-up period of 41 months, the 5-year overall survival (OS) rate for all patients was 80%. Only 2 patients experienced cancer recurrence: 1 distant (liver) and 1 loco-regional (pelvic lymph nodes), respectively. Both of these patients are still alive. The 5-year relapse-free survival rate was 81%. Despite the path-CR primary endpoint of this trial not being reached, the 5-year OS and recurrence-free survival rates were excellent. However, the neoadjuvant and surgical toxicity of this regimen was significant and was the primary reason for the low compliance with adjuvant systemic therapy. Because of the lack of an improvement in the path-CR rate, the substantial associated toxicity, and the negative phase III trials of adjuvant bevacizumab in colon cancer, this regimen will not be pursued for further study. ©AlphaMed Press; the data published online to support this summary is the property of the authors.

A systematic review and meta-analysis on the safety of newly adjuvanted vaccines among children.

PubMed

Stassijns, Jorgen; Bollaerts, Kaatje; Baay, Marc; Verstraeten, Thomas

2016-02-03

New adjuvants such as the AS- or the MF59-adjuvants improve vaccine efficacy and facilitate dose-sparing. Their use in influenza and malaria vaccines has resulted in a large body of evidence on their clinical safety in children. We carried out a systematic search for safety data from published clinical trials on newly adjuvanted vaccines in children ≤10 years of age. Serious adverse events (SAEs), solicited AEs, unsolicited AEs and AEs of special interest were evaluated for four new adjuvants: the immuno-stimulants containing adjuvant systems AS01 and AS02, and the squalene containing oil-in-water emulsions AS03 and MF59. Relative risks (RR) were calculated, comparing children receiving newly adjuvanted vaccines to children receiving other vaccines with a variety of antigens, both adjuvanted and unadjuvanted. Twenty-nine trials were included in the meta-analysis, encompassing 25,056 children who received at least one dose of the newly adjuvanted vaccines. SAEs did not occur more frequently in adjuvanted groups (RR 0.85, 95%CI 0.75-0.96). Our meta-analyses showed higher reactogenicity following administration of newly adjuvanted vaccines, however, no consistent pattern of solicited AEs was observed across adjuvant systems. Pain was the most prevalent AE, but often mild and of short duration. No increased risks were found for unsolicited AEs, febrile convulsions, potential immune mediated diseases and new onset of chronic diseases. Our meta-analysis did not show any safety concerns in clinical trials of the newly adjuvanted vaccines in children ≤10 years of age. An unexplained increase of meningitis in one Phase III AS01-adjuvanted malaria trial and the link between narcolepsy and the AS03-adjuvanted pandemic vaccine illustrate that continued safety monitoring is warranted. Copyright © 2015 Elsevier Ltd. All rights reserved.

Advances in aluminum hydroxide-based adjuvant research and its mechanism.

PubMed

He, Peng; Zou, Yening; Hu, Zhongyu

2015-01-01

In the past few decades, hundreds of materials have been tried as adjuvant; however, only aluminum-based adjuvants continue to be used widely in the world. Aluminum hydroxide, aluminum phosphate and alum constitute the main forms of aluminum used as adjuvants. Among these, aluminum hydroxide is the most commonly used chemical as adjuvant. In spite of its wide spread use, surprisingly, the mechanism of how aluminum hydroxide-based adjuvants exert their beneficial effects is still not fully understood. Current explanations for the mode of action of aluminum hydroxide-based adjuvants include, among others, the repository effect, pro-phagocytic effect, and activation of the pro-inflammatory NLRP3 pathway. These collectively galvanize innate as well as acquired immune responses and activate the complement system. Factors that have a profound influence on responses evoked by aluminum hydroxide-based adjuvant applications include adsorption rate, strength of the adsorption, size and uniformity of aluminum hydroxide particles, dosage of adjuvant, and the nature of antigens. Although vaccines containing aluminum hydroxide-based adjuvants are beneficial, sometimes they cause adverse reactions. Further, these vaccines cannot be stored frozen. Until recently, aluminum hydroxide-based adjuvants were known to preferentially prime Th2-type immune responses. However, results of more recent studies show that depending on the vaccination route, aluminum hydroxide-based adjuvants can enhance both Th1 as well as Th2 cellular responses. Advances in systems biology have opened up new avenues for studying mechanisms of aluminum hydroxide-based adjuvants. These will assist in scaling new frontiers in aluminum hydroxide-based adjuvant research that include improvement of formulations, use of nanoparticles of aluminum hydroxide and development of composite adjuvants.

Advances in aluminum hydroxide-based adjuvant research and its mechanism

PubMed Central

He, Peng; Zou, Yening; Hu, Zhongyu

2015-01-01

In the past few decades, hundreds of materials have been tried as adjuvant; however, only aluminum-based adjuvants continue to be used widely in the world. Aluminum hydroxide, aluminum phosphate and alum constitute the main forms of aluminum used as adjuvants. Among these, aluminum hydroxide is the most commonly used chemical as adjuvant. In spite of its wide spread use, surprisingly, the mechanism of how aluminum hydroxide-based adjuvants exert their beneficial effects is still not fully understood. Current explanations for the mode of action of aluminum hydroxide-based adjuvants include, among others, the repository effect, pro-phagocytic effect, and activation of the pro-inflammatory NLRP3 pathway. These collectively galvanize innate as well as acquired immune responses and activate the complement system. Factors that have a profound influence on responses evoked by aluminum hydroxide-based adjuvant applications include adsorption rate, strength of the adsorption, size and uniformity of aluminum hydroxide particles, dosage of adjuvant, and the nature of antigens. Although vaccines containing aluminum hydroxide-based adjuvants are beneficial, sometimes they cause adverse reactions. Further, these vaccines cannot be stored frozen. Until recently, aluminum hydroxide-based adjuvants were known to preferentially prime Th2-type immune responses. However, results of more recent studies show that depending on the vaccination route, aluminum hydroxide-based adjuvants can enhance both Th1 as well as Th2 cellular responses. Advances in systems biology have opened up new avenues for studying mechanisms of aluminum hydroxide-based adjuvants. These will assist in scaling new frontiers in aluminum hydroxide-based adjuvant research that include improvement of formulations, use of nanoparticles of aluminum hydroxide and development of composite adjuvants. PMID:25692535

Vaccine adjuvant technology: from mechanistic concepts to practical applications.

PubMed

Degen, Winfried G J; Jansen, Theo; Schijns, Virgil E J C

2003-04-01

Distinct types of immune responses are required for efficient elimination of different pathogens. Programming of the desired type of immune response by safe nonreplicating vaccines requires suitable vaccine adjuvants. Adjuvants largely determine the magnitude and quality of immune responses specific for the coadministered antigen. Unfortunately, rational vaccine design requiring a rational choice of vaccine adjuvant, is hampered by a lack of knowledge about the mechanism(s) of vaccine adjuvant activity. The current review addresses different critical immunological processes possibly explaining adjuvant functions. In addition, we discuss traditional vaccine adjuvant formulations and their possible mode of action. Finally, we reflect on the latest technologies for the identification of novel adjuvants using molecular analysis of immune activation and functional genomics.

Metronomic chemotherapy for non-metastatic triple negative breast cancer: Selection is the key

PubMed Central

Rabanal, Connie; Ruiz, Rossana; Neciosup, Silvia; Gomez, Henry

2017-01-01

Triple negative breast cancer (TNBC) accounts for 15%-20% of all breast cancer, and is still defined as what it is not. Currently, TNBC is the only type of breast cancer for which there are no approved targeted therapies and maximum tolerated dose chemotherapy with taxanes and anthracycline-containing regimens is still the standard of care in both the neoadjuvant and adjuvant settings. In the last years, metronomic chemotherapy (MC) is being explored as an alternative to improve outcomes in TNBC. In the neoadjuvant setting, purely metronomic and hybrid approaches have been developed with the objective of increasing complete pathologic response (pCR) and prolonging disease free survival. These regimens proved to be very effective achieving pCR rates between 47%-60%, but at the cost of great toxicity. In the adjuvant setting, MC is used to intensify adjuvant chemotherapy and, more promisingly, as maintenance therapy for high-risk patients, especially those with no pCR after neoadjuvant chemotherapy. Considering the dismal prognosis of TNBC, any strategy that potentially improves outcomes, specially being the oral agents broadly available and inexpensive, should be considered and certainly warrants further exploration. Finally, the benefit of MC needs to be validated in properly designed clinical trials were the selection of the population is the key. PMID:29291168

TGFBI expression is an independent predictor of survival in adjuvant-treated lung squamous cell carcinoma patients.

PubMed

Pajares, M J; Agorreta, J; Salvo, E; Behrens, C; Wistuba, I I; Montuenga, L M; Pio, R; Rouzaut, A

2014-03-18

Transforming growth factor β-induced protein (TGFBI) is a secreted protein that mediates cell anchoring to the extracellular matrix. This protein is downregulated in lung cancer, and when overexpressed, contributes to apoptotic cell death. Using a small series of stage IV non-small cell lung cancer (NSCLC) patients, we previously suggested the usefulness of TGFBI as a prognostic and predictive factor in chemotherapy-treated late-stage NSCLC. In order to validate and extend these results, we broaden the analysis and studied TGFBI expression in a large series of samples obtained from stage I-IV NSCLC patients. TGFBI expression was assessed by immunohistochemistry in 364 completely resected primary NSCLC samples: 242 adenocarcinomas (ADCs) and 122 squamous cell carcinomas (SCCs). Kaplan-Meier curves, log-rank tests and the Cox proportional hazards model were used to analyse the association between TGFBI expression and survival. High TGFBI levels were associated with longer overall survival (OS, P<0.001) and progression-free survival (PFS, P<0.001) in SCC patients who received adjuvant platinium-based chemotherapy. Moreover, multivariate analysis demonstrated that high TGFBI expression is an independent predictor of better survival in patients (OS: P=0.030 and PFS: P=0.026). TGFBI may be useful for the identification of a subset of NSCLC who may benefit from adjuvant therapy.

Neoadjuvant or adjuvant therapy for resectable esophageal cancer: is there a standard of care?

PubMed

Almhanna, Khaldoun; Shridhar, Ravi; Meredith, Kenneth L

2013-04-01

Carcinoma of the esophagus is an aggressive and lethal disease with an increasing incidence worldwide. Despite changes in the treatment approach over the past two decades and even following complete resection, most patients will eventually relapse and die as a result of their disease. Several clinical trials evaluated different modalities in treating locally advanced esophageal cancer; however, because of stage migration and the changes in disease epidemiology, applying these trials to clinical practice has become a daunting task. We searched Medline and conference abstracts for randomized studies published in the past three decades. We restricted our search to articles published in English. Neoadjuvant chemoradiotherapy followed by surgical resection is an accepted standard of care in the United States for patients with locally advanced esophageal cancer. Esophagectomy remains an essential component of treatment and can lead to improved overall survival, especially when performed at high-volume institutions. The role of adjuvant chemotherapy following curative resection in patients who underwent neoadjuvant chemotherapy and radiation remains unclear. Several questions still need to be answered regarding the use of neoadjuvant or adjuvant therapy for patients with resectable esophageal cancer. The optimal chemotherapy regimen has not yet been identified for these patients, although newer therapies show promise.

Annual Research Progress Report for Department of Clinical Investigation (Madigan Army Medical Center), October 1990 - September 1991

DTIC Science & Technology

1991-09-01

approach ethically difficult to justify. Untreated observation until 2 years post injury follows for both groups. Information pertaining to seizure ...completing adjuvant therapy, except for tamoxifen and DES. Patients with a history of deep vein thrombosis, cerebral embolus, stroke , congestive heart...Controlled Hypertensive Patients Arthur Herpolsheimer Pulmonary Function of Preeclamptic Women CPT, MC Receiving Intravenous Magnesium Sulfate Seizure

Phase I/II combined chemoimmunotherapy with carcinoembryonic antigen-derived HLA-A2-restricted CAP-1 peptide and irinotecan, 5-fluorouracil, and leucovorin in patients with primary metastatic colorectal cancer.

PubMed

Weihrauch, Martin R; Ansén, Sascha; Jurkiewicz, Elke; Geisen, Caroline; Xia, Zhinan; Anderson, Karen S; Gracien, Edith; Schmidt, Manuel; Wittig, Burghardt; Diehl, Volker; Wolf, Juergen; Bohlen, Heribert; Nadler, Lee M

2005-08-15

We conducted a phase I/II randomized trial to evaluate the clinical and immunologic effect of chemotherapy combined with vaccination in primary metastatic colorectal cancer patients with a carcinoembryonic antigen-derived peptide in the setting of adjuvants granulocyte macrophage colony-stimulating factor, CpG-containing DNA molecules (dSLIM), and dendritic cells. HLA-A2-positive patients with confirmed newly diagnosed metastatic colorectal cancer and elevated serum carcinoembryonic antigen (CEA) were randomized to receive three cycles of standard chemotherapy (irinotecan/high-dose 5-fluorouracil/leucovorin) and vaccinations with CEA-derived CAP-1 peptide admixed with different adjuvants [CAP-1/granulocyte macrophage colony-stimulating factor/interleukin-2 (IL-2), CAP-1/dSLIM/IL-2, and CAP-1/IL-2]. After completion of chemotherapy, patients received weekly vaccinations until progression of disease. Immune assessment was done at baseline and after three cycles of combined chemoimmunotherapy. HLA-A2 tetramers complexed with the peptides CAP-1, human T-cell lymphotrophic virus type I TAX, cytomegalovirus (CMV) pp65, and EBV BMLF-1 were used for phenotypic immune assessment. IFN-gamma intracellular cytokine assays were done to evaluate CTL reactivity. Seventeen metastatic patients were recruited, of whom 12 completed three cycles. Therapy resulted in five complete response, one partial response, five stable disease, and six progressive disease. Six grade 1 local skin reactions and one mild systemic reaction to vaccination treatment were observed. Overall survival after a median observation time of 29 months was 17 months with a survival rate of 35% (6 of 17) at that time. Eight patients (47%) showed elevation of CAP-1-specific CTLs. Neither of the adjuvants provided superiority in eliciting CAP-1-specific immune responses. During three cycles of chemotherapy, EBV/CMV recall antigen-specific CD8+ cells decreased by an average 14%. The presented chemoimmunotherapy is a feasible and safe combination therapy with clinical and immunologic efficacy. Despite concurrent chemotherapy, increases in CAP-1-specific T cells were observed in 47% of patients after vaccination.

[A Distal Bile Duct Carcinoma Patient Who Underwent Surgical Resection for Liver Metastasis].

PubMed

Komiyama, Sosuke; Izumiya, Yasuhito; Kimura, Yu; Nakashima, Shingo; Kin, Syuichi; Kawakami, Sadao

2018-03-01

A 70-year-old man with distal bile duct carcinoma underwent a subtotal stomach-preserving pancreaticoduodenectomy without adjuvant chemotherapy. One and a half years after the surgery, elevated levels of serum SPan-1(38.1 U/mL)were observed and CT scans demonstrated a solitary metastasis, 25mm in size, in segment 8 of the liver. The patient received 2 courses of gemcitabine-cisplatin combination chemotherapy. No new lesions were detected after chemotherapy and the patient underwent a partial liver resection of segment 8. The pathological examination revealed a metachronous distant metastasis originating from the bile duct carcinoma. Subsequently, the patient received S-1 adjuvant chemotherapy for 6 months. Following completion of all therapies, the patient survived without tumor recurrence for 3 years and 10 months after the initial operation. Thus, surgical interventions might be effective in improving prognosis among selected patients with postoperative liver metastasis of bile duct carcinoma.

Ductal Carcinoma in Situ: Clinical Perspective.

PubMed

Kühn, Thorsten

2010-08-01

Ductal carcinoma is situ (DCIS) is the fastest growing subtype of breast cancer, mainly because of improved screening activities. In contrast to invasive disease, DCIS is a local process with excellent survival rates. Current treatment strategies include surgery, radiotherapy (RT) and anti-hormonal treatment. The selection of an individual risk-adapted therapeutic approach remains controversial. This relates especially to the extent of surgery and the therapeutic index of adjuvant RT and tamoxifen. Several new trials have been published or updated recently that address important clinical issues. There is an urgent need to get more insight into the biological behaviour of different subtypes of DCIS, and develop more targeted and individualized treatment strategies. So far, surgery appears to be the most effective treatment modality. A morphology-based treatment model that allows complete resection of certain DCIS lesions without further adjuvant measures has not been evaluated prospectively and deserves further evaluation.

The Interplay between QSAR/QSPR Studies and Partial Order Ranking and Formal Concept Analyses

PubMed Central

Carlsen, Lars

2009-01-01

The often observed scarcity of physical-chemical and well as toxicological data hampers the assessment of potentially hazardous chemicals released to the environment. In such cases Quantitative Structure-Activity Relationships/Quantitative Structure-Property Relationships (QSAR/QSPR) constitute an obvious alternative for rapidly, effectively and inexpensively generatng missing experimental values. However, typically further treatment of the data appears necessary, e.g., to elucidate the possible relations between the single compounds as well as implications and associations between the various parameters used for the combined characterization of the compounds under investigation. In the present paper the application of QSAR/QSPR in combination with Partial Order Ranking (POR) methodologies will be reviewed and new aspects using Formal Concept Analysis (FCA) will be introduced. Where POR constitutes an attractive method for, e.g., prioritizing a series of chemical substances based on a simultaneous inclusion of a range of parameters, FCA gives important information on the implications associations between the parameters. The combined approach thus constitutes an attractive method to a preliminary assessment of the impact on environmental and human health by primary pollutants or possibly by a primary pollutant well as a possible suite of transformation subsequent products that may be both persistent in and bioaccumulating and toxic. The present review focus on the environmental – and human health impact by residuals of the rocket fuel 1,1-dimethylhydrazine (heptyl) and its transformation products as an illustrative example. PMID:19468330

Adaptive control method for core power control in TRIGA Mark II reactor

NASA Astrophysics Data System (ADS)

Sabri Minhat, Mohd; Selamat, Hazlina; Subha, Nurul Adilla Mohd

2018-01-01

The 1MWth Reactor TRIGA PUSPATI (RTP) Mark II type has undergone more than 35 years of operation. The existing core power control uses feedback control algorithm (FCA). It is challenging to keep the core power stable at the desired value within acceptable error bands to meet the safety demand of RTP due to the sensitivity of nuclear research reactor operation. Currently, the system is not satisfied with power tracking performance and can be improved. Therefore, a new design core power control is very important to improve the current performance in tracking and regulate reactor power by control the movement of control rods. In this paper, the adaptive controller and focus on Model Reference Adaptive Control (MRAC) and Self-Tuning Control (STC) were applied to the control of the core power. The model for core power control was based on mathematical models of the reactor core, adaptive controller model, and control rods selection programming. The mathematical models of the reactor core were based on point kinetics model, thermal hydraulic models, and reactivity models. The adaptive control model was presented using Lyapunov method to ensure stable close loop system and STC Generalised Minimum Variance (GMV) Controller was not necessary to know the exact plant transfer function in designing the core power control. The performance between proposed adaptive control and FCA will be compared via computer simulation and analysed the simulation results manifest the effectiveness and the good performance of the proposed control method for core power control.

Rational design of small molecules as vaccine adjuvants.

PubMed

Wu, Tom Y-H; Singh, Manmohan; Miller, Andrew T; De Gregorio, Ennio; Doro, Francesco; D'Oro, Ugo; Skibinski, David A G; Mbow, M Lamine; Bufali, Simone; Herman, Ann E; Cortez, Alex; Li, Yongkai; Nayak, Bishnu P; Tritto, Elaine; Filippi, Christophe M; Otten, Gillis R; Brito, Luis A; Monaci, Elisabetta; Li, Chun; Aprea, Susanna; Valentini, Sara; Calabrό, Samuele; Laera, Donatello; Brunelli, Brunella; Caproni, Elena; Malyala, Padma; Panchal, Rekha G; Warren, Travis K; Bavari, Sina; O'Hagan, Derek T; Cooke, Michael P; Valiante, Nicholas M

2014-11-19

Adjuvants increase vaccine potency largely by activating innate immunity and promoting inflammation. Limiting the side effects of this inflammation is a major hurdle for adjuvant use in vaccines for humans. It has been difficult to improve on adjuvant safety because of a poor understanding of adjuvant mechanism and the empirical nature of adjuvant discovery and development historically. We describe new principles for the rational optimization of small-molecule immune potentiators (SMIPs) targeting Toll-like receptor 7 as adjuvants with a predicted increase in their therapeutic indices. Unlike traditional drugs, SMIP-based adjuvants need to have limited bioavailability and remain localized for optimal efficacy. These features also lead to temporally and spatially restricted inflammation that should decrease side effects. Through medicinal and formulation chemistry and extensive immunopharmacology, we show that in vivo potency can be increased with little to no systemic exposure, localized innate immune activation and short in vivo residence times of SMIP-based adjuvants. This work provides a systematic and generalizable approach to engineering small molecules for use as vaccine adjuvants. Copyright © 2014, American Association for the Advancement of Science.

Photodynamic therapy and the treatment of malignancies of the head and neck

NASA Astrophysics Data System (ADS)

Biel, Merrill A.; Boss, Ellen E.

1996-04-01

Seventy-nine patients with neoplastic diseases of the larynx, oral cavity, pharynx, and skin have been treated with photodynamic therapy (PDT) with follow-up to 65 months. Patients with carcinoma-in-situ (CIS) and T1 carcinomas obtained a complete response after one PDT treatment. All but two patients remain free of disease. Four patients with T2 and T3 superficial carcinomas were treated with PDT. One patient developed recurrence with 51- month follow-up. Eleven patients with deeply invasive T2, T3, and T4 carcinomas were treated with PDT. Of those eleven, eight obtained a complete response, but five have recurred locally. A response can be achieved with PDT, although not a consistent complete response because of the depth of invasion of the tumor. This is due to the inability to adequately deliver laser light to the depths of the tumor bed. Eight patients with massive neck recurrences of squamous cell carcinomas were treated with intraoperative adjuvant PDT following tumor resection. Only one patient developed recurrence with 30-month follow-up. PDT is highly effective for the curative treatment of early carcinomas (CIS, T1) of the head and neck. T2 and T3 superficial carcinomas, with invasion less than 0.5 cm, are also curatively treated with PDT with significantly reduced morbidity compared to conventional modes of treatment. Also, intraoperative adjuvant PDT may increase cure rates of large infiltrating carcinomas of the head and neck.

Dendritic cell-targeting DNA-based mucosal adjuvants for the development of mucosal vaccines

PubMed Central

Kataoka, Kosuke; Fujihashi, Kohtaro

2009-01-01

In order to establish effective mucosal immunity against various mucosal pathogens, vaccines must be delivered via the mucosal route and contain effective adjuvant(s). Since mucosal adjuvants can simply mix with the antigen, it is relatively easy to adapt them for different types of vaccine development. Even in simple admixture vaccines, the adjuvant itself must be prepared without any complications. Thus, CpG oligodeoxynucleotides or plasmids encoding certain cDNA(s) would be potent mucosal adjuvant candidates when compared with other substances that can be used as mucosal adjuvants. The strategy of a DNA-based mucosal adjuvant facilitates the targeting of mucosal dendritic cells, and thus is an effective and safe approach. It would also provide great flexibility for the development of effective vaccines for various mucosal pathogens. PMID:19722892

Assessment of squalene adjuvanted and non-adjuvanted vaccines against pandemic H1N1 influenza in children 6 months to 17 years of age

PubMed Central

Vesikari, Timo; Pepin, Stéphanie; Kusters, Inca; Hoffenbach, Agnès; Denis, Martine

2012-01-01

Vaccines were urgently needed in 2009 against A/H1N1 pandemic influenza. Based on the H5N1 experience, it was originally thought that 2 doses of an adjuvanted vaccine were needed for adequate immunogenicity. We tested H1N1 vaccines with or without AF03, a squalene-based adjuvant, in children. Two randomized, open-label, trials were conducted. Participants 3–17 y received two injections of 3.8 µg or 7.5 µg hemagglutinin (HA) with adjuvant or 15 µg HA without adjuvant. Participants aged 6–35 mo received two injections of 1.9 µg or 3.8 µg HA with full or half dose adjuvant or 7.5 µg HA without adjuvant. All subjects 3 to 17 y reached seroprotection (hemagglutination inhibition (HI) titer ≥ 40) after the first dose of the adjuvanted vaccine, and 94% and 98% in the 3–8 and 9–17 y groups respectively with the non-adjuvanted vaccine. In children aged 6–35 mo responses were modest after one dose, but after two doses virtually all children were seroprotected regardless of HA or adjuvant dose. In this age group, antibody titers were 5 to 7 times higher after adjuvanted than non-adjuvanted vaccine. The higher responses with the adjuvanted vaccine were also reflected as better antibody persistence. There was no clustering of adverse events that would be suggestive of a safety signal. While a single injection was sufficient in subjects from 3 y, in children aged 6–35 mo two injections of this A/H1N1 pandemic influenza vaccine were required. Formulation of this vaccine with adjuvant provided a significant advantage for immunogenicity in the latter age group. PMID:22906943

Cosmeceutical Effects of Galactomannan Fraction from Arenga pinnata Fruits In vitro

PubMed Central

Yanti; Madriena; Ali, Soegianto

2017-01-01

Background: Cosmeceuticals refer to natural cosmetics with medical-like benefits due to their bioactive contents. Sugar palm fruit (Arenga pinnata) extract has been claimed for its anti-aging effect in vitro. However, its active compounds for cosmeceuticals is still unclear. Objective: This study was aimed to extract galactomannan from A. pinnata fruits and test its efficacy for tyrosinase inhibition, antioxidant, and anti-photoaging activities in vitro. Materials and Methods: Galactomannan from A. pinnata fruits was extracted by freeze drying and identified for its chemical compounds by using pyrolysis gas chromatography-mass spectrometry (py-GC/MS). Galactomannan was tested for its tyrosinase inhibition in both cell-based (melanocytes) and enzymatic assays, antioxidant activity using ferrous ion chelating assay (FCA) assay, and anti-photoaging activity for inhibiting the gene expression of matrix metalloproteinase-1 (MMP-1) and MMP-13 in macrophages using quantitative real-time polymerase chain reaction (qRT-PCR) analysis. Results: Identification of galactomannan fraction from A. pinnata fruits by py-GC/MS mainly consisted of oxonium ion and glucosides. For cellular assay, galactomannan at 5 μg/mL inhibited >50% of tyrosinase activity in melanocytes induced by phorbol myristate acetate. At the enzymatic level, galactomannan at similar concentration showed less tyrosinase activity inhibition (~20%). FCA results showed that galactomannan at 10 μg/mL exerted >50% of antioxidant activity. The qRT-PCR data indicated that galactomannan at 5 μg/mL inhibited >50% of MMP-1 and MMP-13 gene expressions in ultraviolet B-treated macrophages. Conclusion: Galactomannan fraction from A. pinnata fruits has efficacy for enlightening effect, antioxidant, and anti-photoaging activity in the dose-independent pattern, indicating its cosmeceutical effects for skin healthcare. SUMMARY A. pinnata fruit containing galactomannan has cosmeceutical potentials through enlightening effect, antioxidant, and anti-photoaging activity in vitro.Galactomannan fraction has inhibitory effect on tyrosinase activity in both cellular melanocytes and enzymatic systems.Galactomannan fraction has strong protection against UVB-irradiation effect by inhibiting collagenase genes (MMP-1 and MMP-13) in macrophages. Abbreviations Used: Py-GC/MS: Pyrolysis-Gas Chromatography-Mass Spectrometry; FCA: Ferrous chelating activity; MMP: Matrix metalloproteinase; qRT-PCR: Quantitative Real-Time Polymerase Chain Reaction; PMA: Phorbol myristate acetate; UV: Ultraviolet; RPMI: Roswell Park Memorial Institute; DMEM: Dulbecco's modified eagle media; FBS: Fetal bovine serum; PBS: Phosphate buffered saline; MTT: 3-(4,5-diethylthiazol-2-yl)-2,5-dipheniltetrazolium bromide; L-DOPA: L-3,4-dihydroxyphenylalanine; EDTA: Ethylenediaminetetraacetic acid; GAPDH: Glyceraldehyde 3-phosphate dehydrogenase; DPPH: 1,1-diphenyl-2-picryl-hydrazyl; SPF: Sun protection factor PMID:28250652

Combined-modality treatment for advanced oral tongue squamous cell carcinoma

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

Fan, K.-H.; Lin, C.-Y.; Kang, C.-J.

Purpose: The aim of this study was to investigate prognostic factors in advanced-stage oral tongue cancer treated with postoperative adjuvant therapy and to identify indications for adjuvant concomitant chemoradiotherapy (CCRT). Methods and Materials: We retrospectively reviewed the records of 201 patients with advanced squamous cell carcinoma of the oral tongue managed between January 1995 and November 2002. All had undergone wide excision and neck dissection plus adjuvant radiotherapy or CCRT. Based on postoperative staging, 123 (61.2%) patients had Stage IV and 78 (38.8%) had Stage III disease. All patients were followed for at least 18 months after completion of radiotherapymore » or until death. The median follow-up was 40.4 months for surviving patients. The median dose of radiotherapy was 64.8 Gy (range, 58.8-72.8 Gy). Cisplatin-based regimens were used for chemotherapy. Results: The 3-year overall survival (OS) and recurrence-free survival (RFS) rates were 48% and 50.8%, respectively. Stage, multiple nodal metastases, differentiation, and extracapsular spread (ECS) significantly affected disease-specific survival on univariate analysis. On multivariate analysis, multiple nodal metastases, differentiation, ECS, and CCRT were independent prognostic factors. If ECS was present, only CCRT significantly improved survival (3-year RFS with ECS and with CCRT = 48.2% vs. without CCRT = 15%, p = 0.038). In the presence of other poor prognostic factors, results of the two treatment strategies did not significantly differ. Conclusions: Based on this study, ECS appears to be an absolute indication for adjuvant CCRT. CCRT can not be shown to be statistically better than radiotherapy alone in this retrospective series when ECS is not present.« less

Sentinel Lymph Node Biopsy in Endometrial Cancer: a New Standard of Care?

PubMed

Sullivan, Stephanie A; Rossi, Emma C

2017-09-18

Lymph node status is one of the most important factors in determining prognosis and the need for adjuvant treatment in endometrial cancer (EMCA). Unfortunately, full lymphadenectomy bears significant surgical and postoperative risks. The majority of patients with clinical stage I disease will not have metastatic disease; thus, a full lymphadenectomy only increases morbidity in this population of patients. The use of the sentinel lymph node (SLN) biopsy has emerged as an alternative to complete lymphadenectomy in EMCA. By removing the highest yield lymph nodes, the SLN biopsy has the same diagnostic ability as lymphadenectomy while minimizing morbidity. The sensitivity of sentinel lymph node identification with robotic fluorescence imaging for detecting metastatic endometrial and cervical cancer (FIRES) trial published this year is the largest prospective, multi-institution trial investigating the accuracy of the SLN biopsy for endometrial and cervical cancer. Results of this trial found an excellent sensitivity (97.2%) and false negative rate (3%) with the technique. The conclusions from the FIRES trial and those of a recent meta-analysis are that SLN biopsy has an acceptable diagnostic accuracy in detecting lymphatic metastases, and can replace lymphadenectomy for this diagnostic purpose. There remains controversy surrounding the SLN biopsy in high-risk disease and the use of adjuvant therapy in the setting of low volume disease detected with ultrastaging. Current data suggests that the technique is accurate in high-risk disease and that the increased detection of metastasis helps guide adjuvant therapy such that oncologic outcomes are likely not affected by forgoing a full lymphadenectomy. Further prospective study is needed to investigate the impact of low volume metastatic disease on oncologic outcomes and the need for adjuvant therapy in these patients.

U.S. Food and Drug Administration Approval: Neratinib for the Extended Adjuvant Treatment of Early Stage HER2-Positive Breast Cancer.

PubMed

Singh, Harpreet; Walker, Amanda J; Amiri-Kordestani, Laleh; Cheng, Joyce; Tang, Shenghui; Balcazar, Pamela; Barnett-Ringgold, Kimberly; Palmby, Todd R; Cao, Xianhua; Zheng, Nan; Liu, Qi; Yu, Jingyu; Pierce, William F; Daniels, Selena R; Sridhara, Rajeshwari; Ibrahim, Amna; Kluetz, Paul G; Blumenthal, Gideon M; Beaver, Julia A; Pazdur, Richard

2018-03-09

On July 17, 2017, the Food and Drug Administration (FDA) approved neratinib (NERLYNX, Puma Biotechnology, Inc) for the extended adjuvant treatment of adult patients with early-stage HER2-overexpressed/amplified breast cancer, to follow adjuvant trastuzumab-based therapy. Approval was based on data from ExteNET, a randomized, double-blind, placebo-controlled multicenter trial. Women with early-stage HER2-positive breast cancer and within two years of completing adjuvant trastuzumab were randomized to neratinib (n=1420) or placebo (n=1420) for one year. The primary endpoint was invasive disease-free survival (iDFS) defined as the time between randomization date to first occurrence of invasive recurrence (local/regional, ipsilateral or contralateral breast cancer), distance recurrence, or death from any cause, with two years and 28 days of follow up. The trial showed a statistically significant treatment effect favoring neratinib with a stratified hazard ratio of 0.66 (95% CI: 0.49, 0.90, p=0.008). Estimated iDFS rate at 2-years was 94.2% (95% CI: 92.6%, 95.4%) in patients treated with neratinib vs. 91.9% (95% CI: 90.2%, 93.2%) in those receiving placebo. Diarrhea was the most common adverse event (AE) with a 40% incidence of Grade 3 or 4 diarrhea and represents the most common AE leading to treatment discontinuation. Other frequent AEs (>10% incidence) were nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, and muscle spasms. Other than diarrhea, neratinib is associated with a low incidence of severe AEs; toxicities are generally reversible and manageable with dose interruptions, dose reductions, and/or standard medical care. This article summarizes FDA decision-making and data supporting the neratinib approval. Copyright ©2018, American Association for Cancer Research.

Adjuvant effects of aluminium hydroxide-adsorbed allergens and allergoids – differences in vivo and in vitro

PubMed Central

Heydenreich, B; Bellinghausen, I; Lund, L; Henmar, H; Lund, G; Adler Würtzen, P; Saloga, J

2014-01-01

Allergen-specific immunotherapy (SIT) is a clinically effective therapy for immunoglobulin (Ig)E-mediated allergic diseases. To reduce the risk of IgE-mediated side effects, chemically modified allergoids have been introduced. Furthermore, adsorbance of allergens to aluminium hydroxide (alum) is widely used to enhance the immune response. The mechanisms behind the adjuvant effect of alum are still not completely understood. In the present study we analysed the effects of alum-adsorbed allergens and allergoids on their immunogenicity in vitro and in vivo and their ability to activate basophils of allergic donors. Human monocyte derived dendritic cells (DC) were incubated with native Phleum pratense or Betula verrucosa allergen extract or formaldehyde-or glutaraldehyde-modified allergoids, adsorbed or unadsorbed to alum. After maturation, DC were co-cultivated with autologous CD4+ T cells. Allergenicity was tested by leukotriene and histamine release of human basophils. Finally, in-vivo immunogenicity was analysed by IgG production of immunized mice. T cell proliferation as well as interleukin (IL)-4, IL-13, IL-10 and interferon (IFN)-γ production were strongly decreased using glutaraldehyde-modified allergoids, but did not differ between alum-adsorbed allergens or allergoids and the corresponding unadsorbed preparations. Glutaraldehyde modification also led to a decreased leukotriene and histamine release compared to native allergens, being further decreased by adsorption to alum. In vivo, immunogenicity was reduced for allergoids which could be partly restored by adsorption to alum. Our results suggest that adsorption of native allergens or modified allergoids to alum had no consistent adjuvant effect but led to a reduced allergenicity in vitro, while we observed an adjuvant effect regarding IgG production in vivo. PMID:24528247

Adjuvant effects of aluminium hydroxide-adsorbed allergens and allergoids - differences in vivo and in vitro.

PubMed

Heydenreich, B; Bellinghausen, I; Lund, L; Henmar, H; Lund, G; Adler Würtzen, P; Saloga, J

2014-06-01

Allergen-specific immunotherapy (SIT) is a clinically effective therapy for immunoglobulin (Ig)E-mediated allergic diseases. To reduce the risk of IgE-mediated side effects, chemically modified allergoids have been introduced. Furthermore, adsorbance of allergens to aluminium hydroxide (alum) is widely used to enhance the immune response. The mechanisms behind the adjuvant effect of alum are still not completely understood. In the present study we analysed the effects of alum-adsorbed allergens and allergoids on their immunogenicity in vitro and in vivo and their ability to activate basophils of allergic donors. Human monocyte derived dendritic cells (DC) were incubated with native Phleum pratense or Betula verrucosa allergen extract or formaldehyde- or glutaraldehyde-modified allergoids, adsorbed or unadsorbed to alum. After maturation, DC were co-cultivated with autologous CD4(+) T cells. Allergenicity was tested by leukotriene and histamine release of human basophils. Finally, in-vivo immunogenicity was analysed by IgG production of immunized mice. T cell proliferation as well as interleukin (IL)-4, IL-13, IL-10 and interferon (IFN)-γ production were strongly decreased using glutaraldehyde-modified allergoids, but did not differ between alum-adsorbed allergens or allergoids and the corresponding unadsorbed preparations. Glutaraldehyde modification also led to a decreased leukotriene and histamine release compared to native allergens, being further decreased by adsorption to alum. In vivo, immunogenicity was reduced for allergoids which could be partly restored by adsorption to alum. Our results suggest that adsorption of native allergens or modified allergoids to alum had no consistent adjuvant effect but led to a reduced allergenicity in vitro, while we observed an adjuvant effect regarding IgG production in vivo. © 2014 British Society for Immunology.

Nipple-Sparing Mastectomy is Not Associated with a Delay of Adjuvant Treatment.

PubMed

Albright, Emily L; Schroeder, Mary C; Foster, Kendra; Sugg, Sonia L; Erdahl, Lillian M; Weigel, Ronald J; Lizarraga, Ingrid M

2018-07-01

High-volume single-institution studies support the oncologic safety of nipple sparing mastectomy (NSM). Concerns remain regarding the increased potential for complications, recurrence, and delays to subsequent adjuvant therapy. A national database was used to examine treatment and outcomes for NSM patients. Women undergoing unilateral NSM or skin sparing mastectomy (SSM) for stage 0-4 breast cancer from 2004 to 2013 were identified from the National Cancer Database. Demographic and oncologic characteristics, short-term outcomes and time to local and systemic treatment were compared. NSM was performed on 8173 patients: 8.7% were node positive, and for stage 1-4 disease, 10.6% were triple negative (TN) and 15.3% were HER2-positive. NSM patients were less likely than SSM patients to receive chemotherapy [CT] (37.4 vs. 43.4%) or radiation [PMRT] (15.6 vs. 16.9%), and were also more likely to present with clinically early-stage disease. NSM patients with high-risk features were more likely to receive CT in the neoadjuvant [NCT] than adjuvant setting [AC] (OR 3.76, 1.81, and 1.99 for clinical N2/3, TN, and HER2-positive disease, all p < 0.001). On multivariate analysis, NSM patients had a higher rate of pathologic complete response [pCR] (OR 1.41, p < 0.001). Readmission rate, positive margin rate and time to CT, PMRT or hormonal therapy were not increased for NSM compared to SSM patients. Over one third of NSM patients received chemotherapy and/or radiation. NSM patients with high-risk features were more likely to receive NAC and obtain a pCR. NSM patients did not experience worse outcomes or delayed adjuvant therapy compared to SSM.

Appendiceal Goblet Cell Carcinoids: Management Considerations from a Reference Peritoneal Tumour Service Centre and ENETS Centre of Excellence.

PubMed

Lamarca, Angela; Nonaka, Daisuke; Lopez Escola, Cristina; Hubner, Richard A; O'Dwyer, Sarah; Chakrabarty, Bipasha; Fulford, Paul; Valle, Juan W

2016-01-01

Appendix goblet cell carcinoids are known to share histological features of adenocarcinoma and neuroendocrine tumours. Due to their low incidence, quality evidence is lacking for the management of these patients. We performed a single-centre retrospective study of patients with a confirmed diagnosis of appendiceal goblet cell carcinoid (GCC; 1996-2014). Patients were divided into curative intent (CI) and palliative intent (PI) cohorts. Our primary end point was overall survival (OS). Seventy-four patients were eligible; 76% were treated with CI [surgery only (36%), cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC; 36%), adjuvant chemotherapy (20%) and a combination of CRS and HIPEC followed by adjuvant chemotherapy (9%)], and 23% had advanced-stage disease amenable to palliative treatment (chemotherapy or supportive care) only. Completion right hemicolectomy, performed in 64% of the CI cohort, did not impact on the relapse rate or disease-free survival. FOLFOX chemotherapy was used in both the adjuvant and palliative settings; safety was as expected, and we observed a high rate (60%) of disease control in the palliative cohort. The estimated median OS (all patients), disease-free survival (CI patients) and progression-free survival (PI patients) were 52.1 (95% CI 29.4-90.3), 75.9 (26.6-not reached) and 5.3 (0.6-5.7) months, respectively. Age and stage were independent factors associated with OS in the multivariable analysis. Tang classification showed a trend for impact on OS. No benefit from specific adjuvant approach was identified; however, selection bias for treatment approach was observed. Prospective trials are needed to define optimal approaches in GCC. All GCC patients should be managed by specialized centres due to their esoteric behaviour; we provide management considerations based on our experience and conclusions. © 2015 S. Karger AG, Basel.

Using tablet-based technology in patient education about systemic therapy options for early-stage breast cancer: a pilot study.

PubMed

Morgan, E R; Laing, K; McCarthy, J; McCrate, F; Seal, M D

2015-10-01

Patient education in early-stage breast cancer has been shown to improve patient well-being and quality of life, but it poses a challenge given the increasingly complex regimens and time constraints in clinical practice. Technology-aided teaching in the clinic could help to improve the understanding of adjuvant systemic therapy for patients. In this prospective pilot study, we used a clinician-administered, tablet-based teaching aid to teach patients with early-stage breast cancer about adjuvant systemic therapy. Participation was offered to newly diagnosed patients with early-stage breast cancer presenting for their first medical oncology visit at a provincial cancer centre. Participants were shown a tablet-based presentation describing procedures, rationales, risks, and benefits of adjuvant systemic therapy as an adjunct to a discussion with the medical oncologist. After the clinic visit, participants completed a questionnaire measuring satisfaction with the visit and knowledge of the treatment plan discussed. The 25 patients recruited for the study had a mean age of 57 years. An offer of upfront chemotherapy alone was made to 12 participants (48%), chemotherapy with trastuzumab to 4 (16%), and hormonal therapy to 9 (36%). Correct answers to all questions related to treatment knowledge were given by 22 patients (88%). Satisfaction with the clinic visit was high (mean satisfaction score: 4.53 ± 0.1 of a possible 5). We found that a tablet-based presentation about adjuvant systemic therapy was satisfactory to patients with early-stage breast cancer and that knowledge retention after the clinic visit was high. Tablet-based teaching could be a feasible and effective way of educating patients in the breast oncology clinic and warrants further investigation in randomized studies.

Long-Term Outcome With Catheter Ablation of Ventricular Tachycardia in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy.

PubMed

Santangeli, Pasquale; Zado, Erica S; Supple, Gregory E; Haqqani, Haris M; Garcia, Fermin C; Tschabrunn, Cory M; Callans, David J; Lin, David; Dixit, Sanjay; Hutchinson, Mathew D; Riley, Michael P; Marchlinski, Francis E

2015-12-01

Catheter ablation of ventricular tachycardia (VT) in arrhythmogenic right ventricular cardiomyopathy improves short-term VT-free survival. We sought to determine the long-term outcomes of VT control and need for antiarrhythmic drug therapy after endocardial (ENDO) and adjuvant epicardial (EPI) substrate modification in patients with arrhythmogenic right ventricular cardiomyopathy. We examined 62 consecutive patients with Task Force criteria for arrhythmogenic right ventricular cardiomyopathy referred for VT ablation with a minimum follow-up of 1 year. Catheter ablation was guided by activation/entrainment mapping for tolerated VT and pacemapping/targeting of abnormal substrate for unmappable VT. Adjuvant EPI ablation was performed when recurrent VT or persistent inducibility after ENDO-only ablation. Endocardial plus adjuvant EPI ablation was performed in 39 (63%) patients, including 13 who crossed over to ENDO-EPI after VT recurrence during follow-up, after ENDO-only ablation. Before ablation, 54 of 62 patients failed a mean of 2.4 antiarrhythmic drugs, including amiodarone in 29 (47%) patients. During follow-up of 56±44 months after the last ablation, VT-free survival was 71% with only a single VT episode in additional 9 patients (15%). At last follow-up, 39 (64%) patients were only on β-blockers or no treatment, 21 were on class 1 or 3 antiarrhythmic drugs (11 for atrial arrhythmias), and 2 were on amiodarone as a bridge to heart transplantation. The long-term outcome after ENDO and adjuvant EPI substrate ablation of VT in arrhythmogenic right ventricular cardiomyopathy is good. Most patients have complete VT control without amiodarone therapy and limited need for antiarrhythmic drugs. © 2015 American Heart Association, Inc.

Dietary grape seed polyphenols repress neuron and glia activation in trigeminal ganglion and trigeminal nucleus caudalis

PubMed Central

2010-01-01

Background Inflammation and pain associated with temporomandibular joint disorder, a chronic disease that affects 15% of the adult population, involves activation of trigeminal ganglion nerves and development of peripheral and central sensitization. Natural products represent an underutilized resource in the pursuit of safe and effective ways to treat chronic inflammatory diseases. The goal of this study was to investigate effects of grape seed extract on neurons and glia in trigeminal ganglia and trigeminal nucleus caudalis in response to persistent temporomandibular joint inflammation. Sprague Dawley rats were pretreated with 200 mg/kg/d MegaNatural-BP grape seed extract for 14 days prior to bilateral injections of complete Freund's adjuvant into the temporomandibular joint capsule. Results In response to grape seed extract, basal expression of mitogen-activated protein kinase phosphatase 1 was elevated in neurons and glia in trigeminal ganglia and trigeminal nucleus caudalis, and expression of the glutamate aspartate transporter was increased in spinal glia. Rats on a normal diet injected with adjuvant exhibited greater basal levels of phosphorylated-p38 in trigeminal ganglia neurons and spinal neurons and microglia. Similarly, immunoreactive levels of OX-42 in microglia and glial fibrillary acidic protein in astrocytes were greatly increased in response to adjuvant. However, adjuvant-stimulated levels of phosphorylated-p38, OX-42, and glial fibrillary acidic protein were significantly repressed in extract treated animals. Furthermore, grape seed extract suppressed basal expression of the neuropeptide calcitonin gene-related peptide in spinal neurons. Conclusions Results from our study provide evidence that grape seed extract may be beneficial as a natural therapeutic option for temporomandibular joint disorders by suppressing development of peripheral and central sensitization. PMID:21143976

Lactobacillus GG as an immune adjuvant for live-attenuated influenza vaccine in healthy adults: a randomized double-blind placebo-controlled trial.

PubMed

Davidson, L E; Fiorino, A-M; Snydman, D R; Hibberd, P L

2011-04-01

Live-attenuated influenza vaccine (LAIV) protects against influenza by mucosal activation of the immune system. Studies in animals and adults have demonstrated that probiotics improve the immune response to mucosally delivered vaccines. We hypothesized that Lactobacillus GG (LGG) would function as an immune adjuvant to increase rates of seroconversion after LAIV administration. We conducted a randomized double-blind placebo-controlled pilot study to determine whether LGG improved rates of seroconversion after administration of LAIV. We studied 42 healthy adults during the 2007-2008 influenza season. All subjects received LAIV and then were randomized to LGG or placebo, twice daily for 28 days. Hemagglutinin inhibition titers were assessed at baseline, at day 28 and at day 56 to determine the rates of seroconversion. Subjects were assessed for adverse events throughout the study period. A total of 39 subjects completed the per-protocol analysis. Both LGG and LAIV were well tolerated. Protection rates against the vaccine H1N1 and B strains were suboptimal in subjects receiving LGG and placebo. For the H3N2 strain, 84% receiving LGG vs 55% receiving placebo had a protective titer 28 days after vaccination (odds of having a protective titer was 1.84 95% confidence interval 1.04-3.22, P=0.048). Lactobacillus GG is potential as an important adjuvant to improve influenza vaccine immunogenicity. Future studies of probiotics as immune adjuvants might need to specifically consider examining vaccine-naïve or sero-negative subjects, target mucosal immune responses or focus on groups known to have poor response to influenza vaccines. © 2011 Macmillan Publishers Limited All rights reserved

In a randomized, double-blind clinical trial, adjuvant atorvastatin improved symptoms of depression and blood lipid values in patients suffering from severe major depressive disorder.

PubMed

Haghighi, Mohammad; Khodakarami, Saeed; Jahangard, Leila; Ahmadpanah, Mohammad; Bajoghli, Hafez; Holsboer-Trachsler, Edith; Brand, Serge

2014-11-01

The administration of statins seems to be a promising new avenue in the treatment of patients suffering from major depressive disorder (MDD), though patients suffering from severe MDD remain unstudied in this respect. The aim of the present study was therefore to investigate, in a randomized double-blind clinical trial, the influence of adjuvant atorvastatin on symptoms of depression in patients with MDD. A total of 60 patients suffering from MDD (mean age: 32.25 years; 53% males) received a standard medication of 40 mg/d citalopram. Next, patients were randomly assigned either to the atorvastatin group (20 mg/d) or to the placebo group. Blood lipid values were assessed at baseline and on completion of the study 12 weeks later. Experts rated depressive symptoms via Hamilton Depression Rating Scales (HDRS) at baseline and 3, 6 and 12 weeks later. HDRS scores decreased over time; the significant Time by Group interaction showed that symptoms of depression decreased more in the atorvastatin than in the placebo group. Compared to the placebo group, in the atorvastatin group cholesterol, triglyceride, and Low Density Lipids (LDL) significantly decreased, and High Density Lipids (HDL) significantly increased over time. HDRS scores and blood lipid values were generally not associated. The pattern of results suggests that adjuvant atorvastatin favorably influences symptoms of depression among patients with severe MDD. Given that after 12 weeks of monotherapy and adjuvant atorvastatin patients were still moderately to severely depressed, more powerful treatment algorithms such as augmentation and change of medication are highly recommended. Copyright © 2014 Elsevier Ltd. All rights reserved.

Phase I Trial of Aflibercept (VEGF Trap) with Radiation Therapy and Concomitant and Adjuvant Temozolomide in Patients with High-Grade Gliomas

PubMed Central

Nayak, Lakshmi; de Groot, John; Wefel, Jeffrey S; Cloughesy, Timothy F; Lieberman, Frank; Chang, Susan M; Omuro, Antonio; Drappatz, Jan; Batchelor, Tracy T; DeAngelis, Lisa M; Gilbert, Mark R; Aldape, Kenneth D; Yung, Alfred WK; Fisher, Joy; Ye, Xiaobu; Chen, Alice; Grossman, Stuart; Prados, Michael; Wen, Patrick Y

2017-01-01

Background Anti-vascular endothelial growth factor (VEGF) therapy has shown promise in the treatment of high-grade gliomas (HGG). Aflibercept is a recombinant human fusion protein that acts as a soluble decoy receptor for VEGF-A, VEGF-B and placental growth factor (PlGF), depleting circulating levels of these growth factors. Methods The Adult Brain Tumor Consortium (ABTC) conducted a phase I trial of aflibercept and temozolomide (TMZ) in patients with newly diagnosed high-grade gliomas (HGG) with 2 dose levels and a 3+3 design. Three arms using aflibercept were examined; with radiation and concomitant temozolomide; with adjuvant temozolomide using the 5/28 regimen; and with adjuvant temozolomide using the 21/28 day regimen. Results Fifty-nine patients were enrolled, 21 in arm 1, 20 in arm 2 and 18 in arm 3. Median age was 56 years (24-69); median KPS 90 (60-100). The maximum tolerated dose (MTD) of aflibercept for all 3 arms was 4mg/kg every 2 weeks. Dose limiting toxicities (DLTs) at the MTD were: Arm 1: 0/21 patients; Arm 2: 2/20 patients (G3 deep vein thrombosis, G4 neutropenia; Arm 3: 3/18 patients (G4 biopsy-confirmed thrombotic microangiopathy, G3 rash, G4 thrombocytopenia). The median number of cycles of aflibercept was 5 (range, 1-16). All patients stopped treatment; 28 (47%) for disease progression, 21 (36%) for toxicities, 8 (14%) for other reasons, and 2 (3%) patients completed the full treatment course. Conclusions This study met its primary endpoint and the MTD of aflibercept with radiation and concomitant and adjuvant temozolomide is 4mg/kg every 2 weeks. PMID:28116649

Phase I trial of aflibercept (VEGF trap) with radiation therapy and concomitant and adjuvant temozolomide in patients with high-grade gliomas.

PubMed

Nayak, Lakshmi; de Groot, John; Wefel, Jeffrey S; Cloughesy, Timothy F; Lieberman, Frank; Chang, Susan M; Omuro, Antonio; Drappatz, Jan; Batchelor, Tracy T; DeAngelis, Lisa M; Gilbert, Mark R; Aldape, Kenneth D; Yung, Alfred W K; Fisher, Joy; Ye, Xiaobu; Chen, Alice; Grossman, Stuart; Prados, Michael; Wen, Patrick Y

2017-03-01

Anti-vascular endothelial growth factor (VEGF) therapy has shown promise in the treatment of high-grade gliomas (HGG). Aflibercept is a recombinant human fusion protein that acts as a soluble decoy receptor for VEGF-A, VEGF-B and placental growth factor, depleting circulating levels of these growth factors. The Adult Brain Tumor Consortium conducted a phase I trial of aflibercept and temozolomide (TMZ) in patients with newly diagnosed HGG with 2 dose levels and a 3+3 design. Three arms using aflibercept were examined; with radiation and concomitant temozolomide; with adjuvant temozolomide using the 5/28 regimen; and with adjuvant temozolomide using the 21/28 day regimen. Fifty-nine patients were enrolled, 21 in arm 1, 20 in arm 2 and 18 in arm 3. Median age was 56 years (24-69); median KPS 90 (60-100). The maximum tolerated dose (MTD) of aflibercept for all 3 arms was 4 mg/kg every 2 weeks. Dose limiting toxicities at the MTD were: Arm 1: 0/21 patients; Arm 2: 2/20 patients (G3 deep vein thrombosis, G4 neutropenia; Arm 3: 3/18 patients) (G4 biopsy-confirmed thrombotic microangiopathy, G3 rash, G4 thrombocytopenia). The median number of cycles of aflibercept was 5 (range, 1-16). All patients stopped treatment; 28 (47%) for disease progression, 21 (36%) for toxicities, 8 (14%) for other reasons, and 2 (3%) patients completed the full treatment course. This study met its primary endpoint and the MTD of aflibercept with radiation and concomitant and adjuvant temozolomide is 4 mg/kg every 2 weeks.

Phase II Study of Short-Course Radiotherapy Plus Concomitant and Adjuvant Temozolomide in Elderly Patients With Glioblastoma

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

Minniti, Giuseppe, E-mail: Giuseppe.Minniti@ospedalesantandrea.it; Department of Neurological Sciences, Neuromed Institute, Pozzilli; Lanzetta, Gaetano

Purpose: Radiotherapy (RT) and chemotherapy may prolong survival in older patients (age {>=}70 years) with glioblastoma multiforme (GBM), although the survival benefits remain poor. This Phase II multicenter study was designed to evaluate the efficacy and safety of an abbreviated course of RT plus concomitant and adjuvant temozolomide (TMZ) in older patients with GBM. Patients and Methods: Seventy-one eligible patients 70 years of age or older with newly diagnosed GBM and a Karnofsky performance status {>=}60 were treated with a short course of RT (40 Gy in 15 fractions over 3 weeks) plus TMZ at the dosage of 75 mg/m{supmore » 2} per day followed by 12 cycles of adjuvant TMZ (150-200 mg/m{sup 2} for 5 days during each 28-day cycle). The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival and toxicity. Results: The Median OS was 12.4 months, and the 1-year and 2-year OS rates were 58% and 20%, respectively. The median and 1-year rates of progression-free survival were 6 months and 20%, respectively. All patients completed the planned programme of RT. Grade 3 or 4 adverse events occurred in 16 patients (22%). Grade 3 and 4 neutropenia and/or thrombocytopenia occurred in 10 patients (15%), leading to the interruption of treatment in 6 patients (8%). Nonhematologic Grade 3 toxicity was rare, and included fatigue in 4 patients and cognitive disability in 1 patient. Conclusions: A combination of an abbreviated course of RT plus concomitant and adjuvant TMZ is well tolerated and may prolong survival in elderly patients with GBM. Future randomized studies need to evaluate the efficacy and toxicity of different schedules of RT in association with chemotherapy.« less

Safety and feasibility of adjuvant chemotherapy with S-1 in Japanese breast cancer patients after primary systemic chemotherapy: a feasibility study.

PubMed

Shigekawa, Takashi; Osaki, Akihiko; Sekine, Hiroshi; Sato, Nobuaki; Kanbayashi, Chizuko; Sano, Hiroshi; Takeuchi, Hideki; Ueda, Shigeto; Nakamiya, Noriko; Sugitani, Ikuko; Sugiyama, Michiko; Shimada, Hiroko; Hirokawa, Eiko; Takahashi, Takao; Saeki, Toshiaki

2015-04-10

Advanced breast cancer patients have a higher risk of postoperative recurrence than early-stage breast cancer patients. Recurrence is believed to be caused by the increase in micrometases, which were not eradicated by preoperative or postoperative chemotherapy. Therefore, a new therapeutic strategy that can improve treatment efficacy is mandatory for advanced breast cancer. S-1 was shown to be effective and safe in Japanese metastatic breast cancer patients treated with previous chemotherapy, including anthracyclines. Thus, in this study, we evaluated S-1 as adjuvant chemotherapy in breast cancer patients after standard primary systemic chemotherapy. The treatment consisted of 18 courses (a 2-week administration and a 1-week withdrawal; one year) administered at 80-120 mg/body/day. In cases judged to require postoperative radiotherapy, it was concurrently initiated on Day 1 of the study. If the estrogen receptor and/or human epidermal growth factor receptor 2 were positive, endocrine therapy and/or trastuzumab were permitted, concurrently. Of the 45 patients enrolled between September 2007 and September 2009 from 3 institutions, 43 patients were eligible. Thirty-two of the 43 (74.4%) patients received concurrent radiotherapy. Twenty-two of the 43 (51.2%) patients completed the scheduled courses of chemotherapy. The most common reasons for withdrawal of treatment were subjective symptoms, such as nausea, anorexia, or general fatigue during the first 9 courses of treatment in 9/43 (20.9%) patients, recurrence in 7/43 (16.3%) patients, and adverse events in 5/43 (11.6%) patients. The cumulative percentage of administration for 365 days was 66.4% (95% confidence interval: 50.8-79.1%). Although grade 3 neutropenia (9.3%), leukopenia (4.7%), and diarrhea (4.7%) were observed, they were manageable. No grade 4 adverse effects were observed. The percentage of Japanese breast cancer patients completing the 18-course treatment and the cumulative percentage of administration for 365 days using S-1 after standard primary systemic chemotherapy were similar with the results of another study of adjuvant chemotherapy for the Japanese gastric cancer patients with no severe adverse effects. A phase III trial investigating the usefulness of adjuvant S-1 is now ongoing in Japan, and it is expected that S-1 will have a significant survival benefit in breast cancer patients. UMIN000013469.

Modes of Action for Mucosal Vaccine Adjuvants

PubMed Central

2017-01-01

Abstract Vaccine adjuvants induce innate immune responses and the addition of adjuvants to the vaccine helps to induce protective immunity in the host. Vaccines utilizing live attenuated or killed whole pathogens usually contain endogenous adjuvants, such as bacterial cell wall products and their genomic nucleic acids, which act as pathogen-associated molecular patterns and are sufficient to induce adaptive immune responses. However, purified protein- or antigen-based vaccines, including component or recombinant vaccines, usually lose these endogenous innate immune stimulators, so the addition of an exogenous adjuvant is essential for the success of these vaccine types. Although this adjuvant requirement is mostly the same for parental and mucosal vaccines, the development of mucosal vaccine adjuvants requires the specialized consideration of adapting the adjuvants to characteristic mucosal conditions. This review provides a brief overview of mucosa-associated immune response induction processes, such as antigen uptake and dendritic cell subset-dependent antigen presentation. It also highlights several mucosal vaccine adjuvants from recent reports, particularly focusing on their modes of action. PMID:28436755

Modes of Action for Mucosal Vaccine Adjuvants.

PubMed

Aoshi, Taiki

Vaccine adjuvants induce innate immune responses and the addition of adjuvants to the vaccine helps to induce protective immunity in the host. Vaccines utilizing live attenuated or killed whole pathogens usually contain endogenous adjuvants, such as bacterial cell wall products and their genomic nucleic acids, which act as pathogen-associated molecular patterns and are sufficient to induce adaptive immune responses. However, purified protein- or antigen-based vaccines, including component or recombinant vaccines, usually lose these endogenous innate immune stimulators, so the addition of an exogenous adjuvant is essential for the success of these vaccine types. Although this adjuvant requirement is mostly the same for parental and mucosal vaccines, the development of mucosal vaccine adjuvants requires the specialized consideration of adapting the adjuvants to characteristic mucosal conditions. This review provides a brief overview of mucosa-associated immune response induction processes, such as antigen uptake and dendritic cell subset-dependent antigen presentation. It also highlights several mucosal vaccine adjuvants from recent reports, particularly focusing on their modes of action.

Autoimmune disorders after immunisation with Influenza A/H1N1 vaccines with and without adjuvant: EudraVigilance data and literature review.

PubMed

Isai, Alina; Durand, Julie; Le Meur, Steven; Hidalgo-Simon, Ana; Kurz, Xavier

2012-11-19

All suspected autoimmune disorders (AID) reported as adverse reactions to EudraVigilance from 1 October 2009 to 31 December 2010 for adjuvanted (Celtura™, Fluval P™, Focetria™ and Pandemrix™) and non-adjuvanted (Cantgrip™, Celvapan™ and Panenza™) pandemic Influenza A/H1N1 vaccines were analysed to determine whether adjuvanted vaccines were associated with higher reporting of AID than non-adjuvanted ones. AID were identified based on the corresponding MedDRA High Level Group Term. Reports of type 1 diabetes mellitus and multiple sclerosis were also included in the analysis. Causality was assessed based on WHO causality assessment for adverse events following immunisation and Brighton Collaboration criteria for Guillain-Barré syndrome (GBS), idiopathic thrombocytopenic purpura and acute disseminated encephalomyelitis. Of the 50,221 adverse reactions received in EudraVigilance for A/H1N1 vaccines (adjuvanted: 46,173, non-adjuvanted: 4048), 314 were AID (adjuvanted: 276, non-adjuvanted: 38). GBS was the AID with the highest number of reports (125, adjuvanted: 109, non-adjuvanted: 16). Reporting ratios as calculated by the percentages of AID amongst all reported adverse reactions were 0.60% (95% CI: 0.53-0.67) and 0.94% (95% CI: 0.64-1.24) for adjuvanted and non-adjuvanted vaccines, and were 0.26% (95% CI: 0.22-0.31) and 0.37% (95% CI: 0.18-0.56) in a restricted analysis based on diagnostic certainty, causal relationship and plausible temporal association. Reporting rates for all reports of AID using the estimated number of vaccinees as denominator were 6.87 (95% CI: 6.06-7.68) and 9.98 (95% CI: 6.81-13.16) per million for adjuvanted and non-adjuvanted vaccines, and 3.01 (95% CI: 2.47-3.55) and 3.94 (95% CI: 1.95-5.94) per million in the restricted analysis. These results do not suggest a difference in the reporting of AID between adjuvanted and non-adjuvanted A/H1N1 vaccines. In a literature review performed on 31 August 2011, GBS was also the AID the most frequently discussed in association with A/H1N1 vaccination; reporting rates were generally within expected background rates. Copyright © 2012 Elsevier Ltd. All rights reserved.

NONINVASIVE FOLLICULAR TUMOR WITH PAPILLARY-LIKE NUCLEAR FEATURES: NOT A TEMPEST IN A TEAPOT.

PubMed

Agrawal, Nidhi; Abbott, Collette E; Liu, Cheng; Kang, Stella; Tipton, Laura; Patel, Kepal; Persky, Mark; King, Lizabeth; Deng, Fang-Ming; Bannan, Michael; Ogilvie, Jennifer B; Heller, Keith; Hodak, Steven P

2017-04-02

Encapsulated non-invasive follicular variant papillary thyroid cancer (ENIFVPTC) has recently been retermed noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). This designation specifically omits the word "cancer" to encourage conservative treatment since patients with NIFTP tumors have been shown to derive no benefit from completion thyroidectomy or adjuvant radio-active iodine (RAI) therapy. This was a retrospective study of consecutive cases of tumors from 2007 to 2015 that met pathologic criteria for NIFTP. The conservative management (CM) group included patients managed with lobectomy alone or appropriately indicated total thyroidectomy. Those included in the aggressive management (AM) group received either completion thyroidectomy or RAI or both. From 100 consecutive cases of ENIFVPTC reviewed, 40 NIFTP were included for the final analysis. Of these, 10 (27%) patients treated with initial lobectomy received completion thyroidectomy and 6 of 40 (16%) also received postsurgical adjuvant RAI. The mean per-patient cost of care in the AM group was $17,629 ± 2,865, nearly twice the $8,637 ± 309 costs in the CM group, and was largely driven by the cost of completion thyroidectomy and RAI. The term NIFTP has been recently promulgated to identify a type of thyroid neoplasm, formerly identified as a low-grade cancer, for which initial surgery represents adequate treatment. We believe that since the new NIFTP nomenclature intentionally omits the word "cancer," the clinical indolence of these tumors will be better appreciated, and cost savings will result from more conservative and appropriate clinical management. AM = aggressive management CM = conservative management ENIFVPTC = encapsulated noninvasive form of FVPTC FVPTC = follicular variant of papillary thyroid carcinoma NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features PTC = papillary thyroid carcinoma PTMC = papillary thyroid microcarcinoma RAI = radio-active iodine US = ultrasound.

From discovery to licensure, the Adjuvant System story.

PubMed

Garçon, Nathalie; Di Pasquale, Alberta

2017-01-02

Adjuvants are substances added to vaccines to improve their immunogenicity. Used for more than 80 years, aluminum, the first adjuvant in human vaccines, proved insufficient to develop vaccines that could protect against new challenging pathogens such as HIV and malaria. New adjuvants and new combinations of adjuvants (Adjuvant Systems) have opened the door to the delivery of improved and new vaccines against re-emerging and difficult pathogens. Adjuvant Systems concept started through serendipity. The access to new developments in technology, microbiology and immunology have been instrumental for the dicephering of what they do and how they do it. This knowledge opens the door to more rational vaccine design with implications for developing new and better vaccines.

Antioxidant Effect of Spirulina (Arthrospira) maxima on Chronic Inflammation Induced by Freund's Complete Adjuvant in Rats

PubMed Central

Gutiérrez-Rebolledo, Gabriel Alfonso; Galar-Martínez, Marcela; García-Rodríguez, Rosa Virginia; Chamorro-Cevallos, Germán A.; Hernández-Reyes, Ana Gabriela

2015-01-01

Abstract One of the major mechanisms in the pathogenesis of chronic inflammation is the excessive production of reactive oxygen and reactive nitrogen species, and therefore, oxidative stress. Spirulina (Arthrospira) maxima has marked antioxidant activity in vivo and in vitro, as well as anti-inflammatory activity in certain experimental models, the latter activity being mediated probably by the antioxidant activity of this cyanobacterium. In the present study, chronic inflammation was induced through injection of Freund's complete adjuvant (CFA) in rats treated daily with Spirulina (Arthrospira) maxima for 2 weeks beginning on day 14. Joint diameter, body temperature, and motor capacity were assessed each week. On days 0 and 28, total and differential leukocyte counts and serum oxidative damage were determined, the latter by assessing lipid peroxidation and protein carbonyl content. At the end of the study, oxidative damage to joints was likewise evaluated. Results show that S. maxima favors increased mobility, as well as body temperature regulation, and a number of circulating leukocytes, lymphocytes, and monocytes in specimens with CFA-induced chronic inflammation and also protects against oxidative damage in joint tissue as well as serum. In conclusion, the protection afforded by S. maxima against development of chronic inflammation is due to its antioxidant activity. PMID:25599112

Topical tranexamic acid as an adjuvant treatment in melasma: Side-by-side comparison clinical study.

PubMed

Chung, Jong Yoon; Lee, Jong Hee; Lee, Joo Heung

2016-08-01

Tranexamic acid (TNA) is a novel therapeutic agent for hyperpigmented skin disorders. The efficacy and safety of topical TNA in patients with melasma has not been heretofore studied. The main objective of this study is to evaluate the efficacy and safety of topical TNA combined with intense pulsed light (IPL) treatment in Asians with melasma. A randomized, split-face (internally controlled) study was conducted in 15 women who received four monthly sessions of IPL to both sides of the face. Topical TNA or vehicle was applied to a randomly assigned side during and after IPL treatment. Patients were followed up for 12 weeks after completing the IPL treatments. Baseline and follow-up melanin index (MI; measured by Mexameter®, Courage and Khazaka, Cologne, Germany) and modified melasma area and severity index (mMASI) scores were determined. Thirteen subjects completed the study without serious adverse events. MI and mMASI decreased significantly from baseline to 12 weeks after the last IPL treatment on the topical TNA side but not on the vehicle side. The efficacy of topical TNA in preventing rebound pigmentation after IPL treatment was also statistically significant. Topical TNA can be considered an effective and safe adjuvant to conventional treatment for melasma.

Ferulic acid ethyl ester diminished Complete Freund's Adjuvant-induced incapacitation through antioxidant and anti-inflammatory activity.

PubMed

Cunha, Francisco Valmor Macedo; Gomes, Bruno de Sousa; Neto, Benedito de Sousa; Ferreira, Alana Rodrigues; de Sousa, Damião Pergentino; de Carvalho e Martins, Maria do Carmo; Oliveira, Francisco de Assis

2016-01-01

Ferulic acid ethyl ester (FAEE) is a derivate from ferulic acid which reportedly has antioxidant effect; however, its role on inflammation was unknown. In this study, we investigated the orally administered FAEE anti-inflammatory activity on experimental inflammation models and Complete Freund's Adjuvant (CFA)-induced arthritis in rats. CFA-induced arthritis has been evaluated by incapacitation model and radiographic knee joint records at different observation time. FAEE (po) reduced carrageenan-induced paw edema (p < 0.001) within the 1st to 5th hours at 50 and 100 mg/kg doses. FAEE 50 and 100 mg/kg, po inhibited leukocyte migration into air pouch model (p < 0.001), and myeloperoxidase, superoxide dismutase, and catalase activities (p < 0.001) increased total thiol concentration and decreased the TNF-α and IL-1β concentrations, NO, and thiobarbituric acid reactive species. In the CFA-induced arthritis, FAEE 50 and 100 mg/kg significantly reduced the edema and the elevation paw time, a joint disability parameter, since second hour after arthritis induction (p < 0.001). FAEE presented rat joint protective activity in radiographic records (p < 0.001). The data suggest that the FAEE exerts anti-inflammatory activity by inhibiting leukocyte migration, oxidative stress reduction, and pro-inflammatory cytokines.

[Triple synchronous primary gynaecological tumours. A case report].

PubMed

Gutiérrez-Palomino, Laura; Romo-de Los Reyes, José María; Pareja-Megía, María Jesús; García-Mejido, José Antonio

2016-01-01

Synchronous multiple primary malignancies in the female genital tract are infrequent. From 50 to 70% of them corresponds to synchronous cancers of the endometrium and ovary. To our knowledge, this is only the third case report in the international literature of three concurrent gynaecological cancers of epithelial origin. A case is presented, as well as a literature review due to the infrequency of its diagnosis and the lack of information on the subject. A 49-year-old woman, with previous gynaecological history of ovarian endometriosis. She underwent a hysterectomy and bilateral oophorectomy, as she had been diagnosed with endometrial hyperplasia with atypia. The final histopathology reported synchronous ovarian, Fallopian tube, and endometrial cancer. An extension study and complete surgical staging was performed, both being negative. She received adjuvant treatment of chemotherapy and radiotherapy. She is currently free of disease. The aetiology is uncertain. There is controversy relating to increased susceptibility of synchronous neoplasms to pelvic endometriosis and inherited genetic syndromes. Its diagnosis needs to differentiate them from metastatic disease. Additionally, they are problematical from a clinical, diagnostic, therapeutic, and prognostic point of view. The presentation of more cases of triple synchronous cancers is necessary for a complete adjuvant and surgical treatment. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

Concurrent thermochemoradiotherapy for brain high-grade glioma

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

Ryabova, A. I., E-mail: ranigor@mail.ru; Novikov, V. A.; Startseva, Zh. A.

Despite the achievements in the current strategies for treatment, the prognosis in malignant glioma patients remains unsatisfactory. Hyperthermia is currently considered to be the most effective and universal modifier of radiotherapy and chemotherapy. Preliminary treatment outcomes for 28 patients with newly diagnosed (23) and recurrent (5) high-grade gliomas were presented. All the patients received multimodality treatment including surgery, thermoche-moradiotherapy followed by 4 cycles of adjuvant chemotherapy. All the patients endured thermochemoradiotherapy well. A complication, limited skin burn (II stage), was diagnosed in two cases and treated conservatively without treatment interruption. A month after thermochemoradiotherapy the results were as follows: completemore » regression was achieved in 4 cases, partial regression in 4 cases, stable disease in 14 cases and disease progression in 6 cases (one of them is pseudo-progression). After completing the adjuvant chemotherapy 2 more patients demonstrated complete response and 1 patient had disease progression. Introduction of local hyperthermia in multimodal therapy of malignant glioma does not impair the combined modality treatment tolerability of patients with malignant gliomas. A small number of studied patients and short follow-up time do not allow making reliable conclusions about the impact of local hyperthermia on the treatment outcomes; however, there is a tendency towards the increase in disease-free survival in the patients with newly diagnosed malignant gliomas.« less

Antioxidant Effect of Spirulina (Arthrospira) maxima on Chronic Inflammation Induced by Freund's Complete Adjuvant in Rats.

PubMed

Gutiérrez-Rebolledo, Gabriel Alfonso; Galar-Martínez, Marcela; García-Rodríguez, Rosa Virginia; Chamorro-Cevallos, Germán A; Hernández-Reyes, Ana Gabriela; Martínez-Galero, Elizdath

2015-08-01

One of the major mechanisms in the pathogenesis of chronic inflammation is the excessive production of reactive oxygen and reactive nitrogen species, and therefore, oxidative stress. Spirulina (Arthrospira) maxima has marked antioxidant activity in vivo and in vitro, as well as anti-inflammatory activity in certain experimental models, the latter activity being mediated probably by the antioxidant activity of this cyanobacterium. In the present study, chronic inflammation was induced through injection of Freund's complete adjuvant (CFA) in rats treated daily with Spirulina (Arthrospira) maxima for 2 weeks beginning on day 14. Joint diameter, body temperature, and motor capacity were assessed each week. On days 0 and 28, total and differential leukocyte counts and serum oxidative damage were determined, the latter by assessing lipid peroxidation and protein carbonyl content. At the end of the study, oxidative damage to joints was likewise evaluated. Results show that S. maxima favors increased mobility, as well as body temperature regulation, and a number of circulating leukocytes, lymphocytes, and monocytes in specimens with CFA-induced chronic inflammation and also protects against oxidative damage in joint tissue as well as serum. In conclusion, the protection afforded by S. maxima against development of chronic inflammation is due to its antioxidant activity.

Biochemical effects of nonylphenol polyethoxylate adjuvant, Diquat herbicide and their mixture on the three-spined stickleback (Gasterosteus aculeatus L.).

PubMed

Sanchez, W; Palluel, O; Lagadic, L; Aït-Aïssa, S; Porcher, J-M

2006-07-01

This study examined the response of 7-ethoxyresorufine-O-deethylase, glutathione-S-transferase, glutathione peroxidase, glutathione content, level of thiobarbituric acid reactive compounds and circulating vitellogenin, in three-spined sticklebacks after 21 days of exposure to Diquat herbicide, commercial nonylphenol polyethoxylate adjuvant and mixture between Diquat and adjuvant. The results showed that adjuvant exerted more important oxidative effects than Diquat and that mixture effects were unlike to single additivity. This study argues for ecotoxicological risk assessment of adjuvants and mixtures of adjuvants and pesticides.

Al adjuvants can be tracked in viable cells by lumogallion staining.

PubMed

Mile, Irene; Svensson, Andreas; Darabi, Anna; Mold, Matthew; Siesjö, Peter; Eriksson, Håkan

2015-07-01

The mechanism behind the adjuvant effect of aluminum salts is poorly understood notwithstanding that aluminum salts have been used for decades in clinical vaccines. In an aqueous environment and at a nearly neutral pH, the aluminum salts form particulate aggregates, and one plausible explanation of the lack of information regarding the mechanisms could be the absence of an efficient method of tracking phagocytosed aluminum adjuvants and thereby the intracellular location of the adjuvant. In this paper, we want to report upon the use of lumogallion staining enabling the detection of phagocytosed aluminum adjuvants inside viable cells. Including micromolar concentrations of lumogallion in the culture medium resulted in a strong fluorescence signal from cells that had phagocytosed the aluminum adjuvant. The fluorescence appeared as spots in the cytoplasm and by confocal microscopy and co-staining with probes presenting fluorescence in the far-red region of the spectrum, aluminum adjuvants could to a certain extent be identified as localized in acidic vesicles, i.e., lysosomes. Staining and detection of intracellular aluminum adjuvants was achieved not only by diffusion of lumogallion into the cytoplasm, thereby highlighting the presence of the adjuvant, but also by pre-staining the aluminum adjuvant prior to incubation with cells. Pre-staining of aluminum adjuvants resulted in bright fluorescent particulate aggregates that remained fluorescent for weeks and with only a minor reduction of fluorescence upon extensive washing or incubation with cells. Both aluminum oxyhydroxide and aluminum hydroxyphosphate, two of the most commonly used aluminum adjuvants in clinical vaccines, could be pre-stained with lumogallion and were easily tracked intracellularly after incubation with phagocytosing cells. Staining of viable cells using lumogallion will be a useful method in investigations of the mechanisms behind aluminum adjuvants' differentiation of antigen-presenting cells into inflammatory cells. Information will be gained regarding the phagosomal pathways and the events inside the phagosomes, and thereby the ultimate fate of phagocytosed aluminum adjuvants could be resolved. Copyright © 2015 Elsevier B.V. All rights reserved.

New generation adjuvants--from empiricism to rational design.

PubMed

O'Hagan, Derek T; Fox, Christopher B

2015-06-08

Adjuvants are an essential component of modern vaccine development. Despite many decades of development, only a few types of adjuvants are currently included in vaccines approved for human use. In order to better understand the reasons that development of some adjuvants succeeded while many others failed, we discuss some of the common attributes of successful first generation adjuvants. Next, we evaluate current trends in the development of second generation adjuvants, including the potential advantages of rationally designed synthetic immune potentiators appropriately formulated. Finally, we discuss desirable attributes of next generation adjuvants. Throughout, we emphasize that the importance of formulation and analytical characterization in all aspects of vaccine adjuvant development is often underappreciated. We highlight the formulation factors that must be evaluated in order to optimize interactions between vaccine antigens, immune potentiators, and particulate formulations, and the resulting effects on safety, biological activity, manufacturability, and stability. Copyright © 2015 Elsevier Ltd. All rights reserved.