Pattern of Retained Contrast on Immediate Postprocedure Computed tomography (CT) After Particle Embolization of Liver Tumors Predicts Subsequent Treatment Response

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

Wang Xiaodong, E-mail: wangxde@gmail.com; Erinjeri, Joseph P., E-mail: erinjerj@mskcc.org; Jia Xiaoyu, E-mail: jiax@mskcc.org

2013-08-01

PurposeTo determine if the pattern of retained contrast on immediate postprocedure computed tomography (CT) after particle embolization of hepatic tumors predicts modified Response Evaluation Criteria in Solid Tumors (mRECIST) response.Materials and MethodsThis study was approved by the Institutional Review Board with a waiver of authorization. One hundred four liver tumors were embolized with spherical embolic agents (Embospheres, Bead Block, LC Bead) and polyvinyl alcohol. Noncontrast CT was performed immediately after embolization to assess contrast retention in the targeted tumors, and treatment response was assessed by mRECIST criteria on follow-up CT (average time 9.0 {+-} 7.7 weeks after embolization). Tumor contrastmore » retention (TCR) was determined based on change in Hounsfield units (HUs) of the index tumors between the preprocedure and immediate postprocedure scans; vascular contrast retention (VCR) was rated; and defects in contrast retention (DCR) were also documented. The morphology of residual enhancing tumor on follow-up CT was described as partial, circumferential, or total. Association between TCR variables and tumor response were assessed using multivariate logistic regression.ResultsOf 104 hepatic tumors, 51 (49 %) tumors had complete response (CR) by mRECIST criteria; 23 (22.1 %) had partial response (PR); 21 (20.2 %) had stable disease (SD); and 9 (8.7 %) had progressive disease (PD). By multivariate analysis, TCR, VCR, and tumor size are independent predictors of CR (p = 0.02, 0.05, and 0.005 respectively). In 75 tumors, DCR was found to be an independent predictor of failure to achieve complete response (p < 0.0001) by imaging criteria.ConclusionTCR, VCR, and DCR on immediate posttreatment CT are independent predictors of CR by mRECIST criteria.« less

Rapid and early α-fetoprotein and des-γ-carboxy prothrombin responses to initial arterial infusion chemotherapy predict treatment outcomes of advanced hepatocellular carcinoma

PubMed Central

OYAMA, KENJI; KODA, MASAHIKO; SUGIHARA, TAKAAKI; KISHINA, MANABU; MIYOSHI, KENICHI; OKAMOTO, TOSHIAKI; HODOTSUKA, MASANORI; FUJISE, YUKI; MATONO, TOMOMITSU; TOKUNAGA, SHIHO; OKAMOTO, KINYA; HOSHO, KEIKO; OKANO, JUNICHI; MURAWAKI, YOSHIKAZU

2015-01-01

The aim of the present study was to predict the effects of transarterial infusion (TAI) chemotherapy based on early changes in α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) in patients with advanced hepatocellular carcinoma (HCC). Seventy-four patients who underwent TAI with cisplatin, 5-fluorouracil, mitomycin C and epirubicin for advanced HCC were enrolled. Antitumor responses were evaluated 6 months after TAI. Rapid and early responses were defined as the ratio of AFP or DCP after 1 week and 1 month compared to baseline. A total of 5, 10, 17 and 42 patients had complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD), respectively. Early AFP response was significantly lower in the CR+PR compared to the SD+PD groups (P<0.01). The early DCP response was significantly lower in the CR+PR compared to the SD+PD. The sensitivity and specificity of rapid and early AFP responses in the CR+PR were 0.78 and 0.72, and 0.80 and 0.73, respectively, and those of rapid and early DCP responses were 0.67 and 0.65, and 0.77 and 0.71, respectively. The combination of AFP and DCP responses had higher specificity compared to AFP or DCP alone responses. Patients were divided into responder and non-responder groups to evaluate the prediction of survival outcome. Early responders of AFP, DCP and AFP+DCP, who were divided based on the cut-off values of CR+PR survived significantly longer than the non-responders (P<0.05). In conclusion, rapid or early responses of AFP and/or DCP levels 1 and 4 weeks after TAI chemotherapy helped to predict the treatment effects. PMID:26137283

[Treatment of chronic refractory idiopathic thrombocytopenia purpura. 10 years experience at the Salvador Zubiran National Institute of Nutrition].

PubMed

Pita-Ramírez, L; Hurtado-Monroy, R; Labardini-Méndez, J

1992-01-01

A total of 126 patients with chronic idiopathic thrombocytopenic purpura were diagnosed from January 1980 to January 1990 in our institute. In this group of patients, 21 were refractory to prednisone therapy, splenectomy or both, or had had a relapse after a good response with these treatments. They were given other therapies. There was enough information for evaluation in 16 of the 21 patients. The treatment responses were classified according to the post-therapy platelet counts: complete response (CR) = > 150 x 10(9)/L for more than three months; partial response (PR) = 50-150 x 10(9)/L for more than three months; any response (AR) = CR + PR; no response (NR) = < 50 x 10(9)/L. There were 15 women and one male. The median age was 41 years (range 11 to 65). 6-mercaptopurine was given in all patients with CR = 31.2%, PR = 18.8%, AR = 50% and NR = 50%. Seven patients received cyclophosphamide with CR = 28.6%, PR = 14.3%, AR = 42.9% and NR = 57%. Vincristine was given in four patients with only one PR. Interferon alpha 2B was given in four patients with two transitory PR. One patient received colchicine and vitamin C without response. It is concluded that 6-mercaptopurine and cyclophosphamide are useful drugs in refractory thrombocytopenic purpura.

Peptide vaccine immunotherapy biomarkers and response patterns in pediatric gliomas

PubMed Central

Müller, Sören; Agnihotri, Sameer; Shoger, Karsen E.; Myers, Max I.; Chaparala, Srilakshmi; Villanueva, Clarence R.; Chattopadhyay, Ansuman; Butterfield, Lisa H.; Okada, Hideho; Pollack, Ian F.

2018-01-01

Low-grade gliomas (LGGs) are the most common brain tumor affecting children. We recently reported an early phase clinical trial of a peptide-based vaccine, which elicited consistent antigen-specific T cell responses in pediatric LGG patients. Additionally, we observed radiologic responses of stable disease (SD), partial response (PR), and near-complete/complete response (CR) following therapy. To identify biomarkers of clinical response in peripheral blood, we performed RNA sequencing on PBMC samples collected at multiple time points. Patients who showed CR demonstrated elevated levels of T cell activation markers, accompanied by a cytotoxic T cell response shortly after treatment initiation. At week 34, patients with CR demonstrated both IFN signaling and Poly-IC:LC adjuvant response patterns. Patients with PR demonstrated a unique, late monocyte response signature. Interestingly, HLA-V expression, before or during therapy, and an early monocytic hematopoietic response were strongly associated with SD. Finally, low IDO1 and PD-L1 expression before treatment and early elevated levels of T cell activation markers were associated with prolonged progression-free survival. Overall, our data support the presence of unique peripheral immune patterns in LGG patients associated with different radiographic responses to our peptide vaccine immunotherapy. Future clinical trials, including our ongoing phase II LGG vaccine immunotherapy, should monitor these response patterns. PMID:29618666

Partial DNA-guided Cas9 enables genome editing with reduced off-target activity

PubMed Central

Yin, Hao; Song, Chun-Qing; Suresh, Sneha; Kwan, Suet-Yan; Wu, Qiongqiong; Walsh, Stephen; Ding, Junmei; Bogorad, Roman L; Zhu, Lihua Julie; Wolfe, Scot A; Koteliansky, Victor; Xue, Wen; Langer, Robert; Anderson, Daniel G

2018-01-01

CRISPR–Cas9 is a versatile RNA-guided genome editing tool. Here we demonstrate that partial replacement of RNA nucleotides with DNA nucleotides in CRISPR RNA (crRNA) enables efficient gene editing in human cells. This strategy of partial DNA replacement retains on-target activity when used with both crRNA and sgRNA, as well as with multiple guide sequences. Partial DNA replacement also works for crRNA of Cpf1, another CRISPR system. We find that partial DNA replacement in the guide sequence significantly reduces off-target genome editing through focused analysis of off-target cleavage, measurement of mismatch tolerance and genome-wide profiling of off-target sites. Using the structure of the Cas9–sgRNA complex as a guide, the majority of the 3′ end of crRNA can be replaced with DNA nucleotide, and the 5 - and 3′-DNA-replaced crRNA enables efficient genome editing. Cas9 guided by a DNA–RNA chimera may provide a generalized strategy to reduce both the cost and the off-target genome editing in human cells. PMID:29377001

Oligoclonal bands in patients with multiple myeloma: Its emergence per se could not be translated to improved survival

PubMed Central

Fujisawa, Manabu; Seike, Keisuke; Fukumoto, Kouta; Suehara, Yasuhito; Fukaya, Masafumi; Sugihara, Hiroki; Takeuchi, Masami; Matsue, Kosei

2014-01-01

The emergence of oligoclonal bands (OB) has been reported in patients with multiple myeloma (MM) after stem cell transplantation (SCT) or successful chemotherapy. However, their clinical relevance remains unclear. We reviewed the clinical records of MM patients from January 2006 to May 2014. Treatment response was evaluated by International Working Group (IMWG) criteria. Serum immunofixation tests were performed at least every 3 months if the patient achieved more than very good partial response (VGPR). Free light chain (FLC) and minimal residual disease measurement by multicolor flow cytometry (MFC) were performed to evaluate the response to treatment. Among the 163 patients included in the study, 40 developed OB. Detection rates of OB in patients with complete response (CR), VGPR and partial response (PR) or less were 51.8, 36.3 and 0%, respectively. Patients with OB showed better progression-free survival (PFS) and overall survival (OS) rates than those without OB (P = 0.028 and P < 0.001, respectively). However, if the patients were limited to ≥VGPR or CR, development of OB did not affect PFS (P = 0.621 and P = 0.646, respectively) or OS (P = 0.189 and P = 0.766, respectively). OB was observed in 60% of patients after SCT, and in 36.6% of patients with more than VGPR without SCT (P < 0.001). Patients with OB tended to have less minimal residual disease than those without OB (P = 0.054) and its presence may affect the stringent CR criteria. In conclusion, the emergence of OB was seen exclusively in patients with favorable responses, but its emergence per se could not be translated to improved survival. PMID:25182124

oligoclonal bands in patients with multiple myeloma: its emergence per se could not be translated to improved survival.

PubMed

Fujisawa, Manabu; Seike, Keisuke; Fukumoto, Kouta; Suehara, Yasuhito; Fukaya, Masafumi; Sugihara, Hiroki; Takeuchi, Masami; Matsue, Kosei

2014-11-01

The emergence of oligoclonal bands (OB) has been reported in patients with multiple myeloma (MM) after stem cell transplantation (SCT) or successful chemotherapy. However, their clinical relevance remains unclear. We reviewed the clinical records of MM patients from January 2006 to May 2014. Treatment response was evaluated by International Working Group (IMWG) criteria. Serum immunofixation tests were performed at least every 3 months if the patient achieved more than very good partial response (VGPR). Free light chain (FLC) and minimal residual disease measurement by multicolor flow cytometry (MFC) were performed to evaluate the response to treatment. Among the 163 patients included in the study, 40 developed OB. Detection rates of OB in patients with complete response (CR), VGPR and partial response (PR) or less were 51.8, 36.3 and 0%, respectively. Patients with OB showed better progression-free survival (PFS) and overall survival (OS) rates than those without OB (P = 0.028 and P < 0.001, respectively). However, if the patients were limited to ≥VGPR or CR, development of OB did not affect PFS (P = 0.621 and P = 0.646, respectively) or OS (P = 0.189 and P = 0.766, respectively). OB was observed in 60% of patients after SCT, and in 36.6% of patients with more than VGPR without SCT (P < 0.001). Patients with OB tended to have less minimal residual disease than those without OB (P = 0.054) and its presence may affect the stringent CR criteria. In conclusion, the emergence of OB was seen exclusively in patients with favorable responses, but its emergence per se could not be translated to improved survival. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Photodynamic therapy and fluorescence diagnostics of breast cancer metastases with photosense and alasense

NASA Astrophysics Data System (ADS)

Vakoulovskaya, Elena G.; Shental, Victor V.; Letyagin, Victor P.; Brjezovsky, Vitaly J.; Oumnova, L. V.; Vorozhtsov, Georgy N.; Philinov, V.; Stranadko, Eugeny P.

2002-06-01

Photodynamic Therapy (PDT) and fluorescent diagnostics (FD) using photosensitizers Photosense (Aluminium Phtalocyanine, (NIOPIC, Russia)(PS) and Alasense have been provided in 101 patients with breast cancer as a multicenter study. All patients had recurrences of breast cancer (skin metastases) after combined treatment, chemotherapy and radiotherapy. FD of tumor with detecting of subclinical sites, accumulation of PS in tumor, adjacent tissue, skin before and during PDT was fulfilled. Multiple surface irradiations were carried on with interval 24-72 hours (semiconductive laser - (lambda) =672+2nm) in light does 100J/cm2 and total light does 300-900 J/cm2. 2 months after PDT we had overall response rate of 86,87% with complete response (CR) in 51,48% and partial response in 35,39%. During year after PDT in 52 patients with CR we had CR in 36,6% local recurrences in 23,1%, progression (distant (lung or bone) metastasis) in 40,4% of cases. Our experience show pronounced efficacy of PDT for skin metastases of breast cancer.

Long-term results of autologous hematopoietic cell transplantation for peripheral T cell lymphoma: the Stanford experience.

PubMed

Chen, Andy I; McMillan, Alex; Negrin, Robert S; Horning, Sandra J; Laport, Ginna G

2008-07-01

The peripheral T cell lymphomas (PTCL) carry a worse prognosis compared to B cell non-Hodgkin lymphoma. There is no uniform standard therapy for PTCL, and autologous hematopoietic cell transplant (AHCT) is often offered as consolidation in first remission or at relapse because of the poor outcomes with conventional therapy. We conducted a retrospective review of patients who underwent AHCT for PTCL from 1989 to 2006. Fifty-three cases were identified consisting of systemic anaplastic large cell (n = 18), PTCL unspecified (n = 17), angioimmunoblastic (n = 9), nasal type extranodal NK/T (n = 7), hepatosplenic (n = 2), and adult T cell leukemia/lymphoma (n = 1). Fifteen patients were transplanted in first complete or partial response (CR1/PR1), 32 in second or beyond CR or PR (CR2/PR2+), and 11 with primary refractory disease (REF). With a median follow-up was 5 years (range: 1.0-11.5), the 5-year progression-free survival (PFS) and overall survival (OS) were 25% and 48%, respectively. Disease status at AHCT had a significant impact on PFS and OS. The 5-year PFS for patients in CR1/PR1, CR2/PR2+, and REF was 51%, 12%, and 0%, respectively, and the corresponding figures for OS were 76%, 40%, and 30%, respectively. The pretransplant factors that impacted survival were disease status and the number of prior regimens. Histology, age, sex, stage, B symptoms, bone marrow involvement, and duration of first response did not significantly affect PFS or OS. Based on these results, AHCT as consolidation therapy in first complete or partial response may offer a durable survival benefit. However, AHCT with conventional salvage chemotherapy has minimal durable benefit in patients with relapsed or refractory PTCL, and thus novel strategies and/or allogeneic HCT should be more aggressively explored in lieu of AHCT for relapsed/ refractory PTCL.

Pharmacological basis for the medicinal use of black pepper and piperine in gastrointestinal disorders.

PubMed

Mehmood, Malik Hassan; Gilani, Anwarul Hassan

2010-10-01

Dried fruits of Piper nigrum (black pepper) are commonly used in gastrointestinal disorders. The aim of this study was to rationalize the medicinal use of pepper and its principal alkaloid, piperine, in constipation and diarrhea using in vitro and in vivo assays. When tested in isolated guinea pig ileum, the crude extract of pepper (Pn.Cr) (1–10 mg/mL) and piperine (3–300 μM) caused a concentration-dependent and atropine-sensitive stimulant effect. In rabbit jejunum, Pn.Cr (0.01–3.0 mg/mL) and piperine (30–1,000 μM) relaxed spontaneous contractions, similar to loperamide and nifedipine. The relaxant effect of Pn.Cr and piperine was partially inhibited in the presence of naloxone (1 μM) similar to that of loperamide, suggesting the naloxone-sensitive effect in addition to the Ca(2+) channel blocking (CCB)-like activity, which was evident by its relaxant effect on K+ (80 mM)-induced contractions. The CCB activity was confirmed when pretreatment of the tissue with Pn.Cr (0.03–0.3 mg/mL) or piperine (10–100 μM) caused a rightward shift in the concentration–response curves of Ca(2+), similar to loperamide and nifedipine. In mice, Pn.Cr and piperine exhibited a partially atropine-sensitive laxative effect at lower doses, whereas at higher doses it caused antisecretory and antidiarrheal activities that were partially inhibited in mice pretreated with naloxone (1.5 mg/kg), similar to loperamide. This study illustrates the presence of spasmodic (cholinergic) and antispasmodic (opioid agonist and Ca(2+) antagonist) effects, thus providing the possible explanation for the medicinal use of pepper and piperine in gastrointestinal motility disorders.

A phase I trial of two sequence-specific schedules of decitabine and vorinostat in patients with acute myeloid leukemia

PubMed Central

How, Jonathan; Minden, Mark D.; Brian, Leber; Chen, Eric X.; Brandwein, Joseph; Schuh, Andre C.; Schimmer, Aaron D.; Gupta, Vikas; Webster, Sheila; Degelder, Tammy; Haines, Patricia; Stayner, Lee-Anne; McGill, Shauna; Wang, Lisa; Piekarz, Richard; Wong, Tracy; Siu, Lillian L.; Espinoza-Delgado, Igor; Holleran, Julianne L.; Egorin, Merrill J.; Yee, Karen W. L.

2015-01-01

This phase I trial evaluated two schedules of escalating vorinostat in combination with decitabine every 28 days: (i) sequential or (ii) concurrent. There were three dose-limiting toxicities: grade 3 fatigue and generalized muscle weakness on the sequential schedule (n = 1) and grade 3 fatigue on the concurrent schedule (n = 2). The maximum tolerated dose was not reached on both planned schedules. The overall response rate (ORR) was 23% (three complete response [CR], two CR with incomplete incomplete blood count recovery [CRi], one partial response [PR] and two morphological leukemic free state [MLFS]). The ORR for all and previously untreated patients in the sequential arm was 13% (one CRi; one MLFS) and 0% compared to 30% (three CR; one CRi; one PR; one MLFS) and 36% in the concurrent arm (p = 0.26 for both), respectively. Decitabine plus vorinostat was safe and has clinical activity in patients with previously untreated acute myeloid leukemia. Responses appear higher with the concurrent dose schedule. Cumulative toxicities may limit long-term usage on the current dose/schedules. PMID:25682963

Point Defect Structure of Cr203

DTIC Science & Technology

1987-10-01

Calculation of Electron Hole Mobility ........................ 104 6.2.3 Construction of the Defect Concentration vs. Oxygen Pressure Diagram...1000’ to 16000C ............ 123 7.7 Calculated diffusion coefficient vs. oxygen partial pressure diagram for pure Cr203 at 1100 0 C...127 7.10 Calculated parabolic rate constant vs. oxygen partial pressure diagram for pure Cr203 at

Patterns of relapse and outcome of elderly multiple myeloma patients treated as front-line therapy with novel agents combinations☆

PubMed Central

Lopez, Aurelio; Mateos, Maria-Victoria; Oriol, Albert; Valero, Marta; Martínez, Joaquín; Lorenzo, Jose Ignacio; Perez, Montserrat; Martinez, Rafael; de Paz, Raquel; Granell, Miguel; De Arriba, Felipe; Blanchard, M. Jesús; Peñalver, Francisco Javier; Bello, Jose Luis; Martin, Maria Luisa; Bargay, Joan; Blade, Joan; Lahuerta, Juan Jose; San Miguel, Jesús F.; de la Rubia, Javier

2015-01-01

We report the characteristics of relapse, treatment response, and outcomes of 145 elderly patients with multiple myeloma in first relapse after front-line treatment with VMP or VTP. Reappearance of CRAB symptoms (113 patients) and more aggressive forms of disease (32 patients) were the most common patterns of relapse. After second-line therapy, 75 (51.7%) patients achieved at partial response and 16 (11%) complete response (CR). Overall survival was longer among patients receiving VMP as front-line induction (21.4 vs. 14.4 months, P=0.037), in patients achieving CR (28.3 vs. 14.8 months; P=0.04), and in patients without aggressive relapse (28.6 vs. 7.6 months; P=0.0007). PMID:26500850

Rapamycin Partially Mimics the Anticancer Effects of Calorie Restriction in a Murine Model of Pancreatic Cancer

PubMed Central

Lashinger, Laura M.; Malone, Lauren M.; Brown, Graham W.; Daniels, Elizabeth A.; Goldberg, Jason A.; Otto, Glen; Fischer, Susan M.; Hursting, Stephen D.

2011-01-01

Etiologic factors for pancreatic cancer, the fourth deadliest malignant neoplasm in the United States, include obesity and abnormal glucose metabolism. Calorie restriction (CR) and rapamycin each affect energy metabolism and cell survival pathways via inhibition of mammalian target of rapamycin (mTOR) signaling. Using a Panc02 murine pancreatic cancer cell transplant model in 45 male C57BL/6 mice, we tested the hypothesis that rapamycin mimics the effects of CR on pancreatic tumor growth. A chronic regimen of CR, relative to an ad libitum-fed control diet, produced global metabolic effects such as reduced body weight (20.6±1.6g vs. 29.3±2.3g; p<0.0001), improved glucose responsiveness, and decreased circulating levels of insulin-like growth factor (IGF)-1 (126±8ng/mL vs. 199±11ng/mL; p=0.0006) and leptin (1.14±0.2 ng/mL vs. 5.05±1.2 ng/mL; p=0.01). In contrast, rapamycin treatment (2.5mg/kg i.p. every other day, initiated in mice following 20 weeks of ad libitum control diet consumption), relative to control diet, produced no significant change in body weight, IGF-1 or leptin levels, but decreased glucose responsiveness. Pancreatic tumor volume was significantly reduced in the CR group (221±107mm3; p<0.001) and, to a lesser extent, the rapamycin group (374±206mm3; p=0.04) relative to controls (550±147mm3), and this differential inhibition correlated with expression of the proliferation marker Ki-67. Both CR and rapamycin decreased phosphorylation of mTOR, p70/S6K and S6 ribosomal protein, but only CR decreased phosphorylation of Akt, GSK-3β, ERK/MAPK, and STAT-3TYR705. These findings suggest rapamycin partially mimics the anticancer effects of calorie restriction on tumor growth in a murine model of pancreatic cancer. PMID:21593197

Measurable Residual Disease at Induction Redefines Partial Response in Acute Myeloid Leukemia and Stratifies Outcomes in Patients at Standard Risk Without NPM1 Mutations

PubMed Central

Freeman, Sylvie D.; Hills, Robert K.; Virgo, Paul; Khan, Naeem; Couzens, Steve; Dillon, Richard; Gilkes, Amanda; Upton, Laura; Nielsen, Ove Juul; Cavenagh, James D.; Jones, Gail; Khwaja, Asim; Cahalin, Paul; Thomas, Ian; Grimwade, David; Burnett, Alan K.; Russell, Nigel H.

2018-01-01

Purpose We investigated the effect on outcome of measurable or minimal residual disease (MRD) status after each induction course to evaluate the extent of its predictive value for acute myeloid leukemia (AML) risk groups, including NPM1 wild-type (wt) standard risk, when incorporated with other induction response criteria. Methods As part of the NCRI AML17 trial, 2,450 younger adult patients with AML or high-risk myelodysplastic syndrome had prospective multiparameter flow cytometric MRD (MFC-MRD) assessment. After course 1 (C1), responses were categorized as resistant disease (RD), partial remission (PR), and complete remission (CR) or complete remission with absolute neutrophil count < 1,000/µL or thrombocytopenia < 100,000/μL (CRi) by clinicians, with CR/CRi subdivided by MFC-MRD assay into MRD+ and MRD−. Patients without high-risk factors, including Flt3 internal tandem duplication wt/−NPM1-wt subgroup, received a second daunorubicin/cytosine arabinoside induction; course 2 (C2) was intensified for patients with high-risk factors. Results Survival outcomes from PR and MRD+ responses after C1 were similar, particularly for good- to standard-risk subgroups (5-year overall survival [OS], 27% RD v 46% PR v 51% MRD+ v 70% MRD−; P < .001). Adjusted analyses confirmed significant OS differences between C1 RD versus PR/MRD+ but not PR versus MRD+. CRi after C1 reduced OS in MRD+ (19% CRi v 45% CR; P = .001) patients, with a smaller effect after C2. The prognostic effect of C2 MFC-MRD status (relapse: hazard ratio [HR], 1.88 [95% CI, 1.50 to 2.36], P < .001; survival: HR, 1.77 [95% CI, 1.41 to 2.22], P < .001) remained significant when adjusting for C1 response. MRD positivity appeared less discriminatory in poor-risk patients by stratified analyses. For the NPM1-wt standard-risk subgroup, C2 MRD+ was significantly associated with poorer outcomes (OS, 33% v 63% MRD−, P = .003; relapse incidence, 89% when MRD+ ≥ 0.1%); transplant benefit was more apparent in patients with MRD+ (HR, 0.72; 95% CI, 0.31 to 1.69) than those with MRD− (HR, 1.68 [95% CI, 0.75 to 3.85]; P = .16 for interaction). Conclusion MFC-MRD can improve outcome stratification by extending the definition of partial response after first induction and may help predict NPM1-wt standard-risk patients with poor outcome who benefit from transplant in the first CR. PMID:29601212

Open-label Bendamustine Monotherapy for Pediatric Patients With Relapsed or Refractory Acute Leukemia: Efficacy and Tolerability

PubMed Central

Brown, Patrick; Megason, Gail; Ahn, Hyo Seop; Cho, Bin; Kirov, Ivan; Frankel, Lawrence; Aplenc, Richard; Bensen-Kennedy, Debra; Munteanu, Mihaela; Weaver, Jennifer; Harker-Murray, Paul

2014-01-01

This open-label, single-arm, phase I/II, dose-escalation study was designed to determine the recommended phase II dose (RP2D), pharmacokinetics, tolerability, and efficacy of bendamustine in pediatric patients (age ranging from 1 to 20 y) with histologically proven relapsed/refractory acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML). Patients (27 with ALL, 16 with AML) received intravenous bendamustine on days 1 and 2 of each treatment cycle. Phase I involved planned dose escalation of bendamustine to establish the RP2D for phase II. Objectives included overall response rate, duration of response, and tolerability. Eleven patients were treated in phase I, and the RP2D was 120 mg/m2. In phase II, 32 patients received bendamustine 120 mg/m2. Two patients with ALL (bendamustine 90 mg/m2) experienced complete response (CR). Among patients who received bendamustine 120 mg/m2, 2 experienced partial response (PR); 7 had stable disease. The overall response rate (CR+CR without platelet recovery [CRp]) was 4.7% and biological activity rate (CR+CRp+PR) was 9.3%. No AML patients responded. The most common adverse events were anemia, neutropenia, thrombocytopenia, pyrexia, nausea, vomiting, and diarrhea. Bendamustine monotherapy has acceptable tolerability in heavily pretreated children with relapsed/refractory ALL or AML and appears to have some activity in ALL, warranting further studies in combination trials. PMID:24072240

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

Igidbashian, Levon, E-mail: levonig@hotmail.co; Fortin, Bernard; Guertin, Louis

Purpose: To evaluate the role of neck dissection (ND) after chemoradiation therapy (CRT) for head and neck squamous cell carcinoma (HNSCC) with N3 disease. Methods and Materials: From March 1998 to September 2006, 70 patients with HNSCC and N3 neck disease were treated with concomitant CRT as primary therapy. Response to treatment was assessed using clinical examination and computed tomography 6 to 8 weeks posttreatment. Neck dissection was not routinely performed and considered for those with less than complete response. Of the patients, 26 (37.1%) achieved clinical complete response (cCR) after CRT. A total of 31 (44.3%) underwent ND aftermore » partial response (cPR-ND). Thirteen patients (29.5%) did not achieve cCR and did not undergo ND for the following reasons: incomplete response/progression at primary site, refusal/contraindication to surgery, metastatic progression, or death. These patients were excluded from the analysis. Outcomes were computed using Kaplan-Meier curves and were compared with log rank tests. Results: Comparing the cCR and cPR-ND groups at 2 years, the disease-free survival was respectively 62.7% and 84.9% (p = 0.048); overall survival was 63.0% and 79.4% (p = 0.26), regional relapse-free survival was 87.8% and 96.0% (p = 0.21); and distant disease-free survival was 67.1% and 92.6% (p = 0.059). In the cPR-ND group, 71.0% had no pathologic evidence of disease (PPV of 29.0%). Conclusions: Patients with N3 disease achieving regional cPR and primary cCR who underwent ND seemed to have better outcomes than patients achieving global cCR without ND. Clinical assessment with computed tomography is not adequate for evaluating response to treatment. Because of the inherent limitations of our study, further confirmatory studies are warranted.« less

A mutation in the interferon regulatory element of HBV may influence the response of interferon treatment in chronic hepatitis B patients.

PubMed

Lu, Jia-Jie; Chen, En-Qiang; Yang, Jia-Hong; Zhou, Tao-You; Liu, Li; Tang, Hong

2012-01-10

A functional interferon regulatory element (IRE) has been found in the EnhI/X promoter region of hepatitis B virus (HBV) genome. The purpose of this study is to compare the gene order of responder and non-responder to interferon therapy in patients with chronic hepatitis B (CHB), so as to evaluate the relationship between IRE mutation and the response to interferon treatment for CHB patients. Synthetic therapeutic effect is divided into complete response (CR), partial response (PR) and non-response (NR). Among the 62 cases included in this study, 40 cases (64.5%) were in the response group (CR and PR) and 22 (35.5%) cases were in the NR group. Wild type sequence of HBV IRE TTTCACTTTC were found in 35 cases (56.5%), and five different IRE gene sequences. included TTTtACTTTC, TTTCAtTTTC, TTTtAtTTTC, TTTtACTTTt and cTTtACcTTC, were found in 22 cases (35.5%), 1 case (1.6%), 1 case (1.6%), 2 cases (3.2%) and 1 case (1.6%) respectively. There were 41.9%cases (26/62) with forth base C→T mutation, consisted of 32.5% (13/40) cases in response group and 59.1% (13/22) cases in NR group. Among the 35 cases with IRE sequences, there were 67.5% (27/40) cases in response group and 36.4% (8/22) in NR group, and the difference in IRE sequences between two groups was statistic significantly (P = 0.027). The result suggested that there is likely relationship between the forth base mutation (C→T) of IRE region and the response of HBV to Interferon therapy, and this mutation may partially decrease the inhibition effect of interferon on HBV. The forth base C→T mutation in IRE element of HBV may partially influence the response of Interferon treatment in CHB patients.

Treatment of feline lymphoma using a 12-week, maintenance-free combination chemotherapy protocol in 26 cats.

PubMed

Limmer, S; Eberle, N; Nerschbach, V; Nolte, I; Betz, D

2016-08-01

The aim of this prospective clinical trial was to investigate the efficacy and toxicity of a short-term, maintenance-free chemotherapy protocol in feline lymphoma. Twenty-six cats with confirmed diagnosis of high-/intermediate-grade lymphoma were treated with a 12-week protocol consisting of cyclic administration of l-asparaginase, vincristine, cyclophosphamide, doxorubicin and prednisolone. Complete (CR) and partial remission (PR) rates were 46 and 27%, respectively. Median duration of first CR was 394 days compared with a median PR duration of 41 days. No factor was identified to significantly influence the likelihood to reach CR. Overall survival amounted to 78 days (range: 9-2230 days). Median survival in CR cats was 454 days and in PR cats was 82 days. Toxicosis was mainly low grade with anorexia seen most frequently. In cats achieving CR, maintenance-free chemotherapy may be sufficient to attain long-term remission and survival. Factors aiding in prognosticating the likelihood for CR, strategies enhancing response and targeting chemotherapy-induced anorexia need to be identified in future. © 2014 John Wiley & Sons Ltd.

Temperature Dependent Electrical Transport Properties of Ni-Cr and Co-Cr Binary Alloys

NASA Astrophysics Data System (ADS)

Thakore, B. Y.; Suthar, P. H.; Khambholja, S. G.; Gajjar, P. N.; Bhatt, N. K.; Jani, A. R.

2011-12-01

The temperature dependent electrical transport properties viz. electrical resistivity and thermal conductivity of Ni10Cr90 and Co20Cr80 alloys are computed at various temperatures. The electrical resistivity has been calculated according to Faber-Ziman model combined with Ashcroft-Langreth partial structure factors. In the present work, to include the ion-electron interaction, we have used a well tested local model potential. For exchange-correlation effects, five different forms of local field correction functions due to Hartree (H), Taylor (T), Ichimaru and Utsumi (IU), Farid et al (F) and Sarkar et al (S) are used. The present results due to S function are in good agreement with the experimental data as compared to results obtained using other four functions. The S functions satisfy compressibility sum rule in long wave length limit more accurately as compared to T, IU and F functions, which may be responsible for better agreement of results, obtained using S function. Also, present result confirms the validity of present approach in determining the transport properties of alloys like Ni-Cr and Co-Cr.

Intermittent versus daily calorie restriction: which diet regimen is more effective for weight loss?

PubMed

Varady, K A

2011-07-01

Dietary restriction is an effective strategy for weight loss in obese individuals. The most common form of dietary restriction implemented is daily calorie restriction (CR), which involves reducing energy by 15-60% of usual caloric intake every day. Another form of dietary restriction employed is intermittent CR, which involves 24 h of ad libitum food consumption alternated with 24 h of complete or partial food restriction. Although both diets are effective for weight loss, it remains unknown whether one of these interventions produces superior changes in body weight and body composition when compared to the other. Accordingly, this review examines the effects of daily CR versus intermittent CR on weight loss, fat mass loss and lean mass retention in overweight and obese adults. Results reveal similar weight loss and fat mass loss with 3 to 12 weeks' intermittent CR (4-8%, 11-16%, respectively) and daily CR (5-8%, 10-20%, respectively). In contrast, less fat free mass was lost in response to intermittent CR versus daily CR. These findings suggest that these diets are equally as effective in decreasing body weight and fat mass, although intermittent CR may be more effective for the retention of lean mass. © 2011 The Author. obesity reviews © 2011 International Association for the Study of Obesity.

Retreatment of recurrent carcinoma of the head and neck by afterloading interstitial 192Ir implant

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

Emami, B.; Marks, J.E.

From January 1975 to December 1980, 25 patients with persistent or recurrent carcinomas of the head and neck were retreated for palliation at the Division of Radiation Oncology, Mallinckrodt Institute of Radiology. These patients had all undergone extensive previous treatment by surgery and/or radiation. All were retreated with 192Ir interstitial implant with or without external radiation and/or surgical excision. Of 25 patients, 13 had complete response (CR) and 6 had partial response for a follow-up period of 1 to 7 years. Of 13 patients with CR, 6 are alive with no evidence of disease (NED) and two died NED. Detailedmore » results are presented and the new strategy for such patients is discussed.« less

Gene expression patterns in formalin-fixed, paraffin-embedded core biopsies predict docetaxel chemosensitivity in breast cancer patients.

PubMed

Chang, Jenny C; Makris, Andreas; Gutierrez, M Carolina; Hilsenbeck, Susan G; Hackett, James R; Jeong, Jennie; Liu, Mei-Lan; Baker, Joffre; Clark-Langone, Kim; Baehner, Frederick L; Sexton, Krsytal; Mohsin, Syed; Gray, Tara; Alvarez, Laura; Chamness, Gary C; Osborne, C Kent; Shak, Steven

2008-03-01

Previously, we had identified gene expression patterns that predicted response to neoadjuvant docetaxel. Other studies have validated that a high Recurrence Score (RS) by the 21-gene RT-PCR assay is predictive of worse prognosis but better response to chemotherapy. We investigated whether tumor expression of these 21 genes and other candidate genes can predict response to docetaxel. Core biopsies from 97 patients were obtained before treatment with neoadjuvant docetaxel (4 cycles, 100 mg/m2 q3 weeks). Three 10-microm FFPE sections were submitted for quantitative RT-PCR assays of 192 genes that were selected from our previous work and the literature. Of the 97 patients, 81 (84%) had sufficient invasive cancer, 80 (82%) had sufficient RNA for QRTPCR assay, and 72 (74%) had clinical response data. Mean age was 48.5 years, and the median tumor size was 6 cm. Clinical complete responses (CR) were observed in 12 (17%), partial responses in 41 (57%), stable disease in 17 (24%), and progressive disease in 2 patients (3%). A significant relationship (P<0.05) between gene expression and CR was observed for 14 genes, including CYBA. CR was associated with lower expression of the ER gene group and higher expression of the proliferation gene group from the 21 gene assay. Of note, CR was more likely with a high RS (P=0.008). We have established molecular profiles of sensitivity to docetaxel. RT-PCR technology provides a potential platform for a predictive test of docetaxel chemosensitivity using small amounts of routinely processed material.

Radioembolization for Unresectable Intrahepatic Cholangiocarcinoma: Review of Safety, Response Evaluation Criteria in Solid Tumors 1.1 Imaging Response and Survival.

PubMed

Swinburne, Nathaniel C; Biederman, Derek M; Besa, Cecilia; Tabori, Nora E; Fischman, Aaron M; Patel, Rahul S; Nowakowski, Francis Scott; Gunasekaran, Ganesh; Schwartz, Myron E; Lookstein, Robert A; Kim, Edward

2017-06-01

The optimal palliative treatment for unresectable intrahepatic cholangiocarcinoma (ICC) remains controversial. While selective internal radiation therapy (SIRT) using yttrium-90 microspheres is a well-accepted treatment for hepatocellular carcinoma, data related to its use for locally advanced ICC remain relatively scarce. Twenty-nine patients (mean age 66 ± 11 years; 15 female) with unresectable biopsy-proven ICC treated with SIRT between June 2008 and April 2015 were retrospectively evaluated for post-treatment toxicity, overall survival, and imaging response using response evaluation criteria in solid tumors (RECIST) 1.1 criteria. RECIST 1.1 response was evaluable following 26 treatments [complete response (CR):0, partial response (PR):3; stable disease (SD):16, progression of disease (PD):7]. Objective response rate (CR+PR) was 12%. Disease control rate (CR+PR+SD) was 73%. Median time to progression was 5.6 [95% confidence interval (CI): 0-12.0] months. Median survival following SIRT was 9.1 (95% CI: 1.7-16.4) months. Post-treatment survival was prolonged in patients with absence of extrahepatic disease (p = 0.03) and correlated with RECIST 1.1 response (p = 0.02). Toxicities were limited to grade I severity and occurred following 27% of treatments. These findings support the safe, effective use of SIRT for unresectable ICC. Post-treatment survival is prolonged in patients with absence of extrahepatic disease at baseline. RECIST 1.1 response following SIRT for ICC is predictive of survival.

Hydrogen sulfide interacts with calcium signaling to enhance the chromium tolerance in Setaria italica.

PubMed

Fang, Huihui; Jing, Tao; Liu, Zhiqiang; Zhang, Liping; Jin, Zhuping; Pei, Yanxi

2014-12-01

The oscillation of intracellular calcium (Ca(2+)) concentration is a primary event in numerous biological processes in plants, including stress response. Hydrogen sulfide (H2S), an emerging gasotransmitter, was found to have positive effects in plants responding to chromium (Cr(6+)) stress through interacting with Ca(2+) signaling. While Ca(2+) resemblances H2S in mediating biotic and abiotic stresses, crosstalk between the two pathways remains unclear. In this study, Ca(2+) signaling interacted with H2S to produce a complex physiological response, which enhanced the Cr(6+) tolerance in foxtail millet (Setaria italica). Results indicate that Cr(6+) stress activated endogenous H2S synthesis as well as Ca(2+) signaling. Moreover, toxic symptoms caused by Cr(6+) stress were strongly moderated by 50μM H2S and 20mM Ca(2+). Conversely, treatments with H2S synthesis inhibitor and Ca(2+) chelators prior to Cr(6+)-exposure aggravated these toxic symptoms. Interestingly, Ca(2+) upregulated expression of two important factors in metal metabolism, MT3A and PCS, which participated in the biosynthesis of heavy metal chelators, in a H2S-dependent manner to cope with Cr(6+) stress. These findings also suggest that the H2S dependent pathway is a component of the Ca(2+) activating antioxidant system and H2S partially contributes Ca(2+)-activating antioxidant system. Copyright © 2014 Elsevier Ltd. All rights reserved.

Nanometre-scale 3D defects in Cr2AlC thin films.

PubMed

Chen, Y T; Music, D; Shang, L; Mayer, J; Schneider, J M

2017-04-20

MAX-phase Cr 2 AlC containing thin films were synthesized by magnetron sputtering in an industrial system. Nanometre-scale 3D defects are observed near the boundary between regions of Cr 2 AlC and of the disordered solid solution (CrAl) x C y . Shrinkage of the Cr-Cr interplanar distance and elongation of the Cr-Al distance in the vicinity of the defects are detected using transmission electron microscopy. The here observed deformation surrounding the defects was described using density functional theory by comparing the DOS of bulk Cr 2 AlC with the DOS of a strained and unstrained Cr 2 AlC(0001) surface. From the partial density of states analysis, it can be learned that Cr-C bonds are stronger than Cr-Al bonds in bulk Cr 2 AlC. Upon Cr 2 AlC(0001) surface formation, both bonds are weakened. While the Cr-C bonds recover their bulk strength as Cr 2 AlC(0001) is strained, the Cr-Al bonds experience only a partial recovery, still being weaker than their bulk counterparts. Hence, the strain induced bond strengthening in Cr 2 AlC(0001) is larger for Cr d - C p bonds than for Cr d - Al p bonds. The here observed changes in bonding due to the formation of a strained surface are consistent with the experimentally observed elongation of the Cr-Al distance in the vicinity of nm-scale 3D defects in Cr 2 AlC thin films.

Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia

PubMed Central

Porter, David L.; Hwang, Wei-Ting; Frey, Noelle V.; Lacey, Simon F.; Shaw, Pamela A.; Loren, Alison W.; Bagg, Adam; Marcucci, Katherine T.; Shen, Angela; Gonzalez, Vanessa; Ambrose, David; Grupp, Stephan A.; Chew, Anne; Zheng, Zhaohui; Milone, Michael C.; Levine, Bruce L.; Melenhorst, Jan J.; June, Carl H.

2018-01-01

Patients with multiply relapsed or refractory chronic lymphocytic leukemia (CLL) have a poor prognosis. Chimeric antigen receptor (CAR)–modified T cells targeting CD19 have the potential to improve on the low complete response rates with conventional therapies by inducing sustained remissions in patients with refractory B cell malignancies. We previously reported preliminary results on three patients with refractory CLL. We report the mature results from our initial trial using CAR-modified T cells to treat 14 patients with relapsed and refractory CLL. Autologous T cells transduced with a CD19-directed CAR (CTL019) lentiviral vector were infused into patients with relapsed/refractory CLL at doses of 0.14 × 108 to 11 × 108 CTL019 cells (median, 1.6 × 108 cells). Patients were monitored for toxicity, response, expansion, and persistence of circulating CTL019 T cells. The overall response rate in these heavily pretreated CLL patients was 8 of 14 (57%), with 4 complete remissions (CR) and 4 partial remissions (PR). The in vivo expansion of the CAR T cells correlated with clinical responses, and the CAR T cells persisted and remained functional beyond 4 years in the first two patients achieving CR. No patient in CR has relapsed. All responding patients developed B cell aplasia and experienced cytokine release syndrome, coincident with T cell proliferation. Minimal residual disease was not detectable in patients who achieved CR, suggesting that disease eradication may be possible in some patients with advanced CLL. PMID:26333935

Polyethylenimine functionalized Fe3O4/steam-exploded rice straw composite as an efficient adsorbent for Cr(VI) removal

NASA Astrophysics Data System (ADS)

Zhang, Shengli; Wang, Zhikai; Chen, Haoyu; Kai, Chengcheng; Jiang, Man; Wang, Qun; Zhou, Zuowan

2018-05-01

Polyethyleneimine functionalized Fe3O4/steam-exploded rice straw composite (Fe3O4-PEI-SERS), which combines magnetic separation with adsorption of PEI functionalized biosorbent, was successfully prepared via a simple glutaraldehyde crosslinking method. Its adsorption potential for the removal of Cr(VI) was systematically studied in batch mode. Results showed that Cr(VI) adsorption on Fe3O4-PEI-SESERS was highly pH-dependent, and the optimum pH was 2.0. The time to reach equilibrium was related to initial Cr(VI) concentration and was 1 and 6 h for 200 and 300 mg/L of Cr(VI), respectively. The adsorption system followed pseudo-second-order kinetic model and Langmuir isotherm. Its maximum adsorption capacity was 280.11, 317.46 and 338.98 mg/g at 25, 35 and 45 °C, respectively. The competitive uptake from coexisting ions (K+, Na+, Cu2+, Cl- and NO3-) was insignificant except SO42-. After six adsorption/desorption cycles, the adsorbent retained good adsorption capacity. The Cr(VI) removal involved its partial reduction into Cr(III). Due to the properties of high adsorption capacity, strong magnetic responsiveness, good reusability and Cr(VI) detoxification, the Fe3O4-PEI-SESERS has a potential application in Cr(VI) removal from wastewater.

Amplification and overexpression of topoisomerase IIalpha predict response to anthracycline-based therapy in locally advanced breast cancer.

PubMed

Coon, John S; Marcus, Elizabeth; Gupta-Burt, Shalina; Seelig, Steven; Jacobson, Kris; Chen, Shande; Renta, Vivian; Fronda, Geraldo; Preisler, Harvey D

2002-04-01

The putative association between erbB-2 overexpression and favorable response to anthracyline-based therapy in breast cancer is controversial, and the mechanism unclear. We sought to determine whether coamplification and overexpression of the topoisomerase IIalpha gene, near erbB-2 on chromosome 17, and a known anthracycline target, may underlie the association. Thirty-five patients who had locally advanced breast cancer (LABC) and who had received neoadjuvant, anthracycline-based therapy were studied. Copy number of topoisomerase IIalpha and erbB-2 was determined by fluorescence in situ hybridization, and expression by immunohistochemistry. Of 8 patients with erbB-2 amplification, 5 had a complete response (CR) or minimal residual disease (MRD), 3 had a partial response (PR), and none had stable (StD) or progressive disease (PD) at the time of mastectomy, versus 3 CR or MRD, 16 PR, and 8 StD or PD for patients without amplification (P = 0.008). In contrast, erbB-2 overexpression was not significantly associated with response (P = 0.114). Of 6 patients with topoisomerase IIalpha amplification, 4 had CR or MRD, 2 PR, and none StD or PD, versus 4 CR or MRD, 17 PR, and 8 StD or PD for patients without amplification (P = 0.034). All of the tumors with topoisomerase IIalpha amplification also had erbB-2 amplification, but not vice versa. Overexpression of topoisomerase IIalpha (9 patients) was also associated with favorable response (P = 0.021). Coamplification of erbB-2 and topoisomerase IIalpha is significantly associated with favorable local response to anthracycline-based therapy in LABC. The expression data favor a plausible mechanism based on topoisomerase IIalpha biology.

Temperature Dependent Electrical Transport Properties of Ni-Cr and Co-Cr Binary Alloys

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

Thakore, B. Y.; Khambholja, S. G.; Bhatt, N. K.

2011-12-12

The temperature dependent electrical transport properties viz. electrical resistivity and thermal conductivity of Ni{sub 10}Cr{sub 90} and Co{sub 20}Cr{sub 80} alloys are computed at various temperatures. The electrical resistivity has been calculated according to Faber-Ziman model combined with Ashcroft-Langreth partial structure factors. In the present work, to include the ion-electron interaction, we have used a well tested local model potential. For exchange-correlation effects, five different forms of local field correction functions due to Hartree (H), Taylor (T), Ichimaru and Utsumi (IU), Farid et al (F) and Sarkar et al (S) are used. The present results due to S function aremore » in good agreement with the experimental data as compared to results obtained using other four functions. The S functions satisfy compressibility sum rule in long wave length limit more accurately as compared to T, IU and F functions, which may be responsible for better agreement of results, obtained using S function. Also, present result confirms the validity of present approach in determining the transport properties of alloys like Ni-Cr and Co-Cr.« less

Improved Follow-Up and Response Monitoring of Thoracic Cage Involvement in Multiple Myeloma Using a Novel CT Postprocessing Software: The Lessons We Learned.

PubMed

Bier, Georg; Mustafa, Deedar Farhad; Kloth, Christopher; Weisel, Katja; Ditt, Hendrik; Nikolaou, Konstantin; Horger, Marius

2016-01-01

The purpose of this study is to evaluate the benefit of using novel CT postprocessing software that generates unfolded rib images for more-accurate evaluation of multiple myeloma (MM) at follow-up, response monitoring, and visualization of treatment-related bone changes. Between January 2012 and February 2015, 40 consecutive patients with MM underwent repeated whole-body reduced-dose CT at our institution. The results were retrospectively evaluated and compared with established hematologic markers. Unfolded rib reformatted images were compared with 5- and 1-mm-thick slices with regard to bone changes, bone marrow attenuation, and bone sclerosis. Hematologic response categories at follow-up were complete response (CR; n = 2), very good partial response (VGPR; n = 1), partial response (PR; n = 9), stable disease (n = 9), and progressive disease (PD; n = 19). The number of lesions increased in 11 patients (all with PD), decreased in two patients (both with CR), and stayed unchanged in 27 patients. The size of the lesions increased in 14 patients (all with PD), decreased in five patients (two with CR, two with PR, and one with stable disease), and remained unchanged in 21 patients. There was a mean (± SD) difference of 27.99 ± 19.71 HU in bone marrow attenuation for patients with PD (p < 0.0001) and -31.24 ± 13.57 HU in the responders group (p = 0.002), whereas patients with stable disease showed stable bone marrow attenuation at follow-up (mean, -3.37 ± 10.55 HU). Increased bone sclerosis was detected in 12 patients (all of whom were receiving therapy). The sensitivity and specificity of unfolded rib images, 5-mm slices, and 1-mm slices were, respectively, 78.9% and 100%, 52.6% and 100%, and 63.2% and 100% for accurate bone response assessment; 100% and 95.2%, 94.74% and 42.9%, and 89.47% and 47.62% for bone marrow attenuation; and 100% and 100%, 58.3% and 100%, and 91.67% and 100% for sclerosis. For therapy response assessment, unfolded rib reading is more accurate than transverse CT slices.

Hexavalent chromium damages chamomile plants by alteration of antioxidants and its uptake is prevented by calcium.

PubMed

Kováčik, Jozef; Babula, Petr; Hedbavny, Josef; Klejdus, Bořivoj

2014-05-30

Toxicity of low (3μM) and high (60 and 120μM) concentrations of hexavalent chromium/Cr(VI) in chamomile plants was studied. Fluorescence staining confirmed reduction of Cr(VI) to Cr(III). Cr was mainly accumulated in the roots with translocation factor <0.007. Notwithstanding this, both shoots and roots revealed increase in oxidative stress and depletion of glutathione, total thiols, ascorbic acid and activities of glutathione reductase and partially ascorbate peroxidase mainly at 120μM Cr. Though some protective mechanisms were detected (elevation of nitric oxide, enhancement of GPX activity and increase in phenols and lignin), this was not sufficient to counteract the oxidative damage. Consequently, soluble proteins, tissue water content and biomass production were considerably depleted. Surprising increase in some mineral nutrients in roots (Ca, Fe, Zn and Cu) was also detected. Subsequent experiment confirmed that exogenous calcium suppressed oxidative symptoms and Cr uptake but growth of chamomile seedlings was not improved. Alteration of naturally present reductants could be a reason for Cr(III) signal detected using specific fluorescence reagent: in vitro assay confirmed disappearance of ascorbic acid in equimolar mixture with dichromate (>96% at pH 4 and 7) while such response of glutathione was substantially less visible. Copyright © 2014 Elsevier B.V. All rights reserved.

Reinduction therapy for adult acute leukemia with adriamycin, vincristine, and prednisone: a Southwest Oncology Group study.

PubMed

Elias, L; Shaw, M T; Raab, S O

1979-08-01

In an attempt to improve remissions and survivals in previously treated patients with adult acute leukemia, we gave Adriamycin, vincristine, and prednisone for induction therapy, followed by 6-mercaptopurine and methotrexate for maintenance therapy to patients attaining complete remission (CR). The study group consisted of 18 patients with acute myeloblastic leukemia (AML), ten with acute lymphoblastic leukemia, and one with acute undifferentiated leukemia. Only one patient had previously received Adriamycin. Overall, there were ten CRs and two partial remissions. The five CRs and one partial remission in patients with AML occurred among those with one prior induction attempt; none of the eight AML patients with more than one prior induction attempt responded. The actuarial median duration of CR was 15 weeks and was similar for AML and acute lymphoblastic leukemia patients. Responders had a longer median survival (30 weeks) than nonresponders (9 weeks). Thus, although a reasonable number of responses in previously treated patients were obtained with this program, improvements in maintenance therapy are clearly needed.

A Planned Neck Dissection Is Not Necessary in All Patients With N2-3 Head-and-Neck Cancer After Sequential Chemoradiotherapy

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

Soltys, Scott G., E-mail: sgsoltys@stanford.edu; Choi, Clara Y.H.; Fee, Willard E.

2012-07-01

Purpose: To assess the role of a planned neck dissection (PND) after sequential chemoradiotherapy for patients with head-and-neck cancer with N2-N3 nodal disease. Methods and Materials: We reviewed 90 patients with N2-N3 head-and-neck squamous cell carcinoma treated between 1991 and 2001 on two sequential chemoradiotherapy protocols. All patients received induction and concurrent chemotherapy with cisplatin and 5-fluorocuracil, with or without tirapazamine. Patients with less than a clinical complete response (cCR) in the neck proceeded to a PND after chemoradiation. The primary endpoint was nodal response. Clinical outcomes and patterns of failure were analyzed. Results: The median follow-up durations for livingmore » and all patients were 8.3 years (range, 1.5-16.3 year) and 5.4 years (range, 0.6-16.3 years), respectively. Of the 48 patients with nodal cCR whose necks were observed, 5 patients had neck failures as a component of their recurrence [neck and primary (n = 2); neck, primary, and distant (n = 1); neck only (n = 1); neck and distant (n = 1)]. Therefore, PND may have benefited only 2 patients (4%) [neck only failure (n = 1); neck and distant failure (n = 1)]. The pathologic complete response (pCR) rate for those with a clinical partial response (cPR) undergoing PND (n = 30) was 53%. The 5-year neck control rates after cCR, cPR{yields}pCR, and cPR{yields}pPR were 90%, 93%, and 78%, respectively (p = 0.36). The 5-year disease-free survival rates for the cCR, cPR{yields}pCR, and cPR{yields}pPR groups were 53%, 75%, and 42%, respectively (p = 0.04). Conclusion: In our series, patients with N2-N3 neck disease achieving a cCR in the neck, PND would have benefited only 4% and, therefore, is not recommended. Patients with a cPR should be treated with PND. Residual tumor in the PND specimens was associated with poor outcomes; therefore, aggressive therapy is recommended. Studies using novel imaging modalities are needed to better assess treatment response.« less

The Tumour Response to Induction Chemotherapy has Prognostic Value for Long-Term Survival Outcomes after Intensity-Modulated Radiation Therapy in Nasopharyngeal Carcinoma.

PubMed

Peng, Hao; Chen, Lei; Zhang, Yuan; Li, Wen-Fei; Mao, Yan-Ping; Liu, Xu; Zhang, Fan; Guo, Rui; Liu, Li-Zhi; Tian, Li; Lin, Ai-Hua; Sun, Ying; Ma, Jun

2016-04-21

The prognostic value of the tumour response to induction chemotherapy (IC) for long-term survival outcomes after intensity-modulated radiation therapy in nasopharyngeal carcinoma (NPC) remains unknown. We retrospectively reviewed 1811 consecutive patients with newly diagnosed NPC treated using IMRT, and 399 eligible patients with pre- and post-induction chemotherapy magnetic resonance images were recruited. The clinicopathological features of patients with different tumour responses were compared using the Chi-square test or Fisher's exact test. Prognostic value was assessed using a multivariate Cox proportional hazards model. After IC, 101/399 (25.3%) patients had a complete tumour response overall (CR), 262 (65.7%) had a partial response (PR) and 36 (9.0%) had stable disease (SD). The 4-year disease-free survival (DFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS) rates for CR vs. PR vs. SD were 90.0% vs. 79.0% vs. 58.2% (CR vs. PR: P1 = 0.007; CR vs. SD: P2 < 0.001; PR vs. SD: P3 = 0.004), 95.7% vs. 88.7% vs. 70.2% (P1 = 0.017, P2 < 0.001, P3 = 0.005), 92.0% vs. 87.4% vs. 74.3% (P1 = 0.162, P2 = 0.005, P3 = 0.029) and 95.9% vs. 88.8% vs. 81.8% (P1 = 0.024, P2 = 0.006, P3 = 0.268), respectively. Multivariate analysis identified that the tumour response to IC was an independent prognostic factor for DFS, OS and LRRFS.

Geometry of α-Cr2O3(0001) as a Function of H2O Partial Pressure

PubMed Central

2015-01-01

Surface X-ray diffraction has been employed to elucidate the surface structure of α-Cr2O3(0001) as a function of water partial pressure at room temperature. In ultra high vacuum, following exposure to ∼2000 Langmuir of H2O, the surface is found to be terminated by a partially occupied double layer of chromium atoms. No evidence of adsorbed OH/H2O is found, which is likely due to either adsorption at minority sites, or X-ray induced desorption. At a water partial pressure of ∼30 mbar, a single OH/H2O species is found to be bound atop each surface Cr atom. This adsorption geometry does not agree with that predicted by ab initio calculations, which may be a result of some differences between the experimental conditions and those modeled. PMID:26877825

Complete response of a recurrent-metastatic liposarcoma with dedifferentiated histological features following the administration of trabectedin and review of literature.

PubMed

Kus, Tulay; Aktas, Gokmen; Kalender, Mehmet Emin; Tutar, Ediz; Ulker, Esra; Camci, Celaletdin

2015-01-01

The present case report defines a rare case of a liposarcoma with bone metastasis resulting in a complete remission (CR) following trabectedin treatment. The patient was referred with abdominal swelling and pain. A retroperitoneal mass was detected and described as dedifferentiated liposarcoma (DDLS). The mass was surgically removed and consequently adjuvant chemotherapy was administered. Three months after the completion of chemotherapy, patient presented with bone metastasis in thoracic and lumbar vertebrae. Vertebroplasty and radiotherapy (RT) was performed. After these therapies, bone pain persisted and bone scintigraphy showed increased activity in L4, T11, and T12 vertebrae. Zoledronic acid was added to trabectedin treatment. CR has been detected on bone scintigraphy and positron emission tomography-computed tomography (PET-CT) after 18 weeks. Previous cases about liposarcoma treated with trabectedin were mostly about the myxoid/round cell type (former name, currently known as myxoid liposarcoma (MLS)) and mostly reported partial responses. In this study, trabectedin was used for the treatment of a metastatic retroperitoneal DDLS and a CR was achieved.

Effect of arachidonic acid metabolites on CR1 expression by B-lymphocytes.

PubMed

Cook, J M; Guibert, F; Delebassee, S; Gualde, N

1989-01-01

The effect of arachidonic acid metabolites on the expression of the receptor for the C3b/C4b fragment of complement (CR1) by human B-lymphocytes was investigated. Kinetic experiments to determine CR1 expression over time indicated that the maximal receptor number occurred at 2 h, followed by a return to baseline values. Addition of 10(-4) M puromycin to the cells suggested that the increase was due to the expression of an intracellular pool and not de novo synthesis of new receptor molecules. B-lymphocytes were incubated with arachidonic acid, 15-hydroxyeicosatetraenoic acid, leukotrienes B4 or C4 or prostaglandin E2 (PGE2). The quantity of membrane antigenic binding sites was determined before and after incubation. The lipoxygenase metabolites did not alter CR1 numbers. In contrast, PGE2 significantly decreased (P less than 0.05) the quantity of CR1 expressed. In kinetic experiments, PGE2 blocked the maximal expression of CR1 seen at 2 h, indicating that it prevents the appearance of an intracellular pool of receptor. These results show that CR1 number on B-lymphocytes can be altered by at least one arachidonic acid metabolite. This may offer a partial explanation for the inhibitory effects of PGE2 on B-cell proliferation and immunoglobulin secretion since CR1 is implicated in B-lymphocyte differentiation and specific antibody response.

Do circulating long non-coding RNAs (lncRNAs) (LincRNA-p21, GAS 5, HOTAIR) predict the treatment response in patients with head and neck cancer treated with chemoradiotherapy?

PubMed

Fayda, Merdan; Isin, Mustafa; Tambas, Makbule; Guveli, Murat; Meral, Rasim; Altun, Musa; Sahin, Dilek; Ozkan, Gozde; Sanli, Yasemin; Isin, Husniye; Ozgur, Emre; Gezer, Ugur

2016-03-01

Long non-coding RNAs (lncRNAs) have been shown to be aberrantly expressed in head and neck cancer (HNC). The aim of the present study was to evaluate plasma levels of three lncRNA molecules (lincRNA-p21, GAS5, and HOTAIR) in the treatment response in HNC patients treated with radical chemoradiotherapy (CRT). Forty-one patients with HNC were enrolled in the study. Most of the patients had nasopharyngeal carcinoma (n = 27, 65.9 %) and locally advanced disease. Blood was drawn at baseline and treatment evaluation 4.5 months after therapy. lncRNAs in plasma were measured by semiquantitative PCR. Treatment response was evaluated according to clinical examination, RECIST and PERCIST criteria based on magnetic resonance imaging (MRI), and positron emission tomography with computed tomography (PET/CT) findings. Complete response (CR) rates were 73.2, 36.6, and 50 % for clinical investigation, PET/CT-, or MRI-based response evaluation, respectively. Predictive value of lncRNAs was investigated in patients with CR vs. those with partial response (PR)/progressive disease (PD). We found that post-treatment GAS5 levels in patients with PR/PD were significantly higher compared with patients with CR based on clinical investigation (p = 0.01). Receiver operator characteristic (ROC) analysis showed that at a cutoff value of 0.3 of GAS5, sensitivity and specificity for clinical tumor response were 82 and 77 %, respectively. Interestingly, pretreatment GAS5 levels were significantly increased in patients with PR/PD compared to those with CR upon MRI-based response evaluation (p = 0.042). In contrast to GAS5, pretreatment or post-treatment lincRNA-p21 and HOTAIR levels were not informative for treatment response. Our results suggest that circulating GAS5 could be a biomarker in predicting treatment response in HNC patients.

Prediction of Neck Dissection Requirement After Definitive Radiotherapy for Head-and-Neck Squamous Cell Carcinoma

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

Thariat, Juliette; Department of Radiation Oncology/IBDC CNRS UMR, Cancer Center Antoine-Lacassagne, University Nice Sophia-Antipolis, Nice, Cedex 2; Ang, K. Kian

2012-03-01

Background: This analysis was undertaken to assess the need for planned neck dissection in patients with a complete response (CR) of involved nodes after irradiation and to determine the benefit of a neck dissection in those with less than CR by tumor site. Methods: Our cohort included 880 patients with T1-4, N1-3M0 squamous cell carcinoma of the oropharynx, larynx, or hypopharynx who received treatment between 1994 and 2004. Survival curves were calculated by the Kaplan-Meier Method, comparisons of rates with the log-rank test and prognostic factors by Cox's proportional hazard model. Results: Nodal CR occurred in 377 (43%) patients, ofmore » whom 365 patients did not undergo nodal dissection. The 5-year actuarial regional control rate of patients with CR was 92%. Two hundred sixty-eight of the remaining patients (53%) underwent neck dissections. The 5-year actuarial regional control rate for patients without a CR was 84%. Those who had a neck dissection fared better with 5-year actuarial regional control rates of 90% and 76% for those operated and those not operated (p < 0.001). Variables associated with poorer regional control rates included higher T and N stage, non-oropharynx cancers, non-CR, both clinical and pathological. Conclusions: With 92% 5-year neck control rate without neck dissection after CR, there is little justification for systematic neck dissection. The addition of a neck dissection resulted in higher neck control after partial response though patients with viable tumor on pathology specimens had poorer outcomes. The identification of that subgroup that benefits from additional treatment remains a challenge.« less

Chromium isotope heterogeneity in the mantle

NASA Astrophysics Data System (ADS)

Xia, Jiuxing; Qin, Liping; Shen, Ji; Carlson, Richard W.; Ionov, Dmitri A.; Mock, Timothy D.

2017-04-01

To better constrain the Cr isotopic composition of the silicate Earth and to investigate potential Cr isotopic fractionation during high temperature geological processes, we analyzed the Cr isotopic composition of different types of mantle xenoliths from diverse geologic settings: fertile to refractory off-craton spinel and garnet peridotites, pyroxenite veins, metasomatised spinel lherzolites and associated basalts from central Mongolia, spinel lherzolites and harzburgites from North China, as well as cratonic spinel and garnet peridotites from Siberia and southern Africa. The δ53CrNIST 979 values of the peridotites range from - 0.51 ± 0.04 ‰ (2SD) to + 0.75 ± 0.05 ‰ (2SD). The results show a slight negative correlation between δ53Cr and Al2O3 and CaO contents for most mantle peridotites, which may imply Cr isotopic fractionation during partial melting of mantle peridotites. However, highly variable Cr isotopic compositions measured in Mongolian peridotites cannot be caused by partial melting alone. Instead, the wide range in Cr isotopic composition of these samples most likely reflects kinetic fractionation during melt percolation. Chemical diffusion during melt percolation resulted in light Cr isotopes preferably entering into the melt. Two spinel websterite veins from Mongolia have extremely light δ53Cr values of - 1.36 ± 0.04 ‰ and - 0.77 ± 0.06 ‰, respectively, which are the most negative Cr isotopic compositions yet reported for mantle-derived rocks. These two websterite veins may represent crystallization products from the isotopically light melt that may also metasomatize some peridotites in the area. The δ53Cr values of highly altered garnet peridotites from southern Africa vary from - 0.35 ± 0.04 ‰ (2SD) to + 0.12 ± 0.04 ‰ (2SD) and increase with increasing LOI (Loss on Ignition), reflecting a shift of δ53Cr to more positive values by secondary alteration. The Cr isotopic composition of the pristine, fertile upper mantle is estimated as δ53Cr = - 0.14 ± 0.12 ‰, after corrections for the effects of partial melting and metasomatism. This value is in line with that estimated for the BSE (- 0.12 ± 0.10 ‰) previously.

Exposure to Hexavalent Chromium Resulted in Significantly Higher Tissue Chromium Burden Compared With Trivalent Chromium Following Similar Oral Doses to Male F344/N Rats and Female B6C3F1 Mice

PubMed Central

Collins, Bradley J.; Stout, Matthew D.; Levine, Keith E.; Kissling, Grace E.; Fennell, Timothy R.; Walden, Ramsey; Abdo, Kamal; Pritchard, John B.; Fernando, Reshan A.; Burka, Leo T.; Hooth, Michelle J.

2010-01-01

In National Toxicology Program 2-year studies, hexavalent chromium [Cr(VI)] administered in drinking water was clearly carcinogenic in male and female rats and mice, resulting in small intestine epithelial neoplasms in mice at a dose equivalent to or within an order of magnitude of human doses that could result from consumption of chromium-contaminated drinking water, assuming that dose scales by body weight3/4 (body weight raised to the 3/4 power). In contrast, exposure to trivalent chromium [Cr(III)] at much higher concentrations may have been carcinogenic in male rats but was not carcinogenic in mice or female rats. As part of these studies, total chromium was measured in tissues and excreta of additional groups of male rats and female mice. These data were used to infer the uptake and distribution of Cr(VI) because Cr(VI) is reduced to Cr(III) in vivo, and no methods are available to speciate tissue chromium. Comparable external doses resulted in much higher tissue chromium concentrations following exposure to Cr(VI) compared with Cr(III), indicating that a portion of the Cr(VI) escaped gastric reduction and was distributed systemically. Linear or supralinear dose responses of total chromium in tissues were observed following exposure to Cr(VI), indicating that these exposures did not saturate gastric reduction capacity. When Cr(VI) exposure was normalized to ingested dose, chromium concentrations in the liver and glandular stomach were higher in mice, whereas kidney concentrations were higher in rats. In vitro studies demonstrated that Cr(VI), but not Cr(III), is a substrate of the sodium/sulfate cotransporter, providing a partial explanation for the greater absorption of Cr(VI). PMID:20843897

Exposure to hexavalent chromium resulted in significantly higher tissue chromium burden compared with trivalent chromium following similar oral doses to male F344/N rats and female B6C3F1 mice.

PubMed

Collins, Bradley J; Stout, Matthew D; Levine, Keith E; Kissling, Grace E; Melnick, Ronald L; Fennell, Timothy R; Walden, Ramsey; Abdo, Kamal; Pritchard, John B; Fernando, Reshan A; Burka, Leo T; Hooth, Michelle J

2010-12-01

In National Toxicology Program 2-year studies, hexavalent chromium [Cr(VI)] administered in drinking water was clearly carcinogenic in male and female rats and mice, resulting in small intestine epithelial neoplasms in mice at a dose equivalent to or within an order of magnitude of human doses that could result from consumption of chromium-contaminated drinking water, assuming that dose scales by body weight(3/4) (body weight raised to the 3/4 power). In contrast, exposure to trivalent chromium [Cr(III)] at much higher concentrations may have been carcinogenic in male rats but was not carcinogenic in mice or female rats. As part of these studies, total chromium was measured in tissues and excreta of additional groups of male rats and female mice. These data were used to infer the uptake and distribution of Cr(VI) because Cr(VI) is reduced to Cr(III) in vivo, and no methods are available to speciate tissue chromium. Comparable external doses resulted in much higher tissue chromium concentrations following exposure to Cr(VI) compared with Cr(III), indicating that a portion of the Cr(VI) escaped gastric reduction and was distributed systemically. Linear or supralinear dose responses of total chromium in tissues were observed following exposure to Cr(VI), indicating that these exposures did not saturate gastric reduction capacity. When Cr(VI) exposure was normalized to ingested dose, chromium concentrations in the liver and glandular stomach were higher in mice, whereas kidney concentrations were higher in rats. In vitro studies demonstrated that Cr(VI), but not Cr(III), is a substrate of the sodium/sulfate cotransporter, providing a partial explanation for the greater absorption of Cr(VI).

Instructions for the use of the CIVM-Jet 4C finite-strain computer code to calculate the transient structural responses of partial and/or complete arbitrarily-curved rings subjected to fragment impact

NASA Technical Reports Server (NTRS)

Rodal, J. J. A.; French, S. E.; Witmer, E. A.; Stagliano, T. R.

1979-01-01

The CIVM-JET 4C computer program for the 'finite strain' analysis of 2 d transient structural responses of complete or partial rings and beams subjected to fragment impact stored on tape as a series of individual files. Which subroutines are found in these files are described in detail. All references to the CIVM-JET 4C program are made assuming that the user has a copy of NASA CR-134907 (ASRL TR 154-9) which serves as a user's guide to (1) the CIVM-JET 4B computer code and (2) the CIVM-JET 4C computer code 'with the use of the modified input instructions' attached hereto.

Comparison of Ifosfamide, Carboplatin and Etoposide versus Etoposide, Steroid, and Cytarabine Cisplatin as Salvage Chemotherapy in Patients with Refractory or Relapsed Hodgkin's lymphoma

PubMed Central

Mehrzad, Valiollah; Ashrafi, Farzaneh; Farrashi, Ali Reza; Pourmarjani, Reyhaneh; Dehghani, Mehdi; Shahsanaei, Armindokht

2017-01-01

Background: Refractory or relapsed Hodgkin's disease (HD) occurs in 10-50% of patients. The treatment of choice for these patients is high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT). Response to salvage chemotherapy (SCT) partial remission (PR) is necessary before HDCT with ASCT. However, its applicability is restricted mostly to patients responding to salvage chemotherapy. Optimal salvage regimen for these patients is unclear. In this study, our aim was to compare the efficacy profiles of ifosfamide, carboplatin, and etoposide (ICE) and etoposide-steroid-cytarabine-cisplatin (ESHAP) (cytosine arabinoside, cisplatin, and dexamethasone) regimens in the salvage treatment of relapsed or refractory HD. Materials and Methods: In this retrospective analysis, 114 patients with primary refractory or relapsed HD who received ICE or ESHAP salvage regimen were included. Results: Of 114 patients, 47 (41.2%) were females and the median age was 31.5 years. Response could be evaluated in 114 patients. Of 114 patients, 38 (33%) achieved complete remission (CR) and 21 (18.4%) achieved PR, leading to an overall response rate (ORR: CR + PR) of 51.4%. In the evaluable ICE group (n = 41), rates of CR, PR, and ORR were 21.9%, 17.1%, and 39% and in the ESHAP group (n = 73), rates of CR, PR, and ORR were 39.7%, 19.2%, and 58.9% (for ORR, P = 0.04), respectively. Conclusion: In patients with relapsed or refractory HD, treatment with ESHAP seems to have higher rates of response than ICE regimen does. PMID:28401077

Comparative Evaluation of Marginal Accuracy of a Cast Fixed Partial Denture Compared to Soldered Fixed Partial Denture Made of Two Different Base Metal Alloys and Casting Techniques: An In vitro Study.

PubMed

Jei, J Brintha; Mohan, Jayashree

2014-03-01

The periodontal health of abutment teeth and the durability of fixed partial denture depends on the marginal adaptation of the prosthesis. Any discrepancy in the marginal area leads to dissolution of luting agent and plaque accumulation. This study was done with the aim of evaluating the accuracy of marginal fit of four unit crown and bridge made up of Ni-Cr and Cr-Co alloys under induction and centrifugal casting. They were compared to cast fixed partial denture (FPD) and soldered FPD. For the purpose of this study a metal model was fabricated. A total of 40 samples (4-unit crown and bridge) were prepared in which 20 Cr-Co samples and 20 Ni-Cr samples were fabricated. Within these 20 samples of each group 10 samples were prepared by induction casting technique and other 10 samples with centrifugal casting technique. The cast FPD samples obtained were seated on the model and the samples were then measured with travelling microscope having precision of 0.001 cm. Sectioning of samples was done between the two pontics and measurements were made, then the soldering was made with torch soldering unit. The marginal discrepancy of soldered samples was measured and all findings were statistically analysed. The results revealed minimal marginal discrepancy with Cr-Co samples when compared to Ni-Cr samples done under induction casting technique. When compared to cast FPD samples, the soldered group showed reduced marginal discrepancy.

Marginal Zone Dural Lymphoma: the Memorial Sloan Kettering Cancer Center and University of Miami Experiences

PubMed Central

de la Fuente, Macarena I.; Haggiagi, Aya; Moul, Adrienne; Young, Robert J.; Sidani, Charif; Markoe, Arnold; Vega, Francisco; DeAngelis, Lisa M.; Lossos, Izidore S.

2017-01-01

Dural lymphoma (DL) is a rare type of primary CNS lymphoma arising from the dura mater. The optimal treatment is uncertain. A retrospective review was performed on 26 DL patients. Seventeen patients underwent resection and 9 had a biopsy. 23 patients could be assessed for a response to treatment after surgery. 13 received focal radiotherapy (RT), 6 whole brain RT (WBRT), 3 chemotherapy alone and 1 chemotherapy followed by WBRT. 22 achieved complete response (CR) and one a partial response (PR). Four patients relapsed (2 local and 2 systemic). Median follow up was 64 months, with median PFS and OS not reached. Three year PFS was 89% (95% CI 0.64–0.97). All patients are alive at last follow-up, demonstrating that DL is an indolent tumor with long survival. CR is achievable with focal therapy in the majority of cases, but there is a risk for relapses and long-term follow-up is recommended. PMID:27649904

Central and peripheral effects of chronic food restriction and weight restoration in the rat.

PubMed

Kinzig, Kimberly P; Hargrave, Sara L; Tao, Erin E

2009-02-01

Previous studies have demonstrated that some endocrine consequences of long-term caloric restriction persist after weight restoration in human subjects. Here we evaluate effects of chronic food restriction in rats that were restricted to 70% of control kcal for 4 wk and subsequently weight restored. Measures were taken from rats at 80% (chronically restricted; CR), 90% (partially weight restored; PR), 100% (fully weight restored; FR), and after 4 wk at 100% body weight of controls (extended weight restored; ER). Plasma insulin and leptin were decreased, and ghrelin was increased in CR compared with controls. Leptin and ghrelin normalized with weight restoration at PR, FR, and ER; however, baseline insulin was not normalized until the ER state. Hypothalamic mRNA expression levels for proopiomelanocortin (POMC), agouti-related protein (AgRP), and neuropeptide Y (NPY) revealed significantly less POMC mRNA expression in CR and PR rats, and significantly less arcuate NPY mRNA in PR and FR. In the dorsomedial hypothalamus, CR, PR, and FR rats had significantly increased NPY expression that was not normalized until the ER state. In response to a test meal, insulin and ghrelin release patterns were altered through the FR stage, and ghrelin remained affected at ER. Collectively, these data demonstrate that mere weight restoration is not sufficient to normalize hypothalamic gene expression levels and endocrine responses to a meal, and that meal-related ghrelin responses persist despite weight restoration for up to 4 wk.

NMR-based metabolomics approach to study the chronic toxicity of crude ricin from castor bean kernels on rats.

PubMed

Guo, Pingping; Wang, Junsong; Dong, Ge; Wei, Dandan; Li, Minghui; Yang, Minghua; Kong, Lingyi

2014-07-29

Ricin, a large, water soluble toxic glycoprotein, is distributed majorly in the kernels of castor beans (the seeds of Ricinus communis L.) and has been used in traditional Chinese medicine (TCM) or other folk remedies throughout the world. The toxicity of crude ricin (CR) from castor bean kernels was investigated for the first time using an NMR-based metabolomic approach complemented with histopathological inspection and clinical chemistry. The chronic administration of CR could cause kidney and lung impairment, spleen and thymus dysfunction and diminished nutrient intake in rats. An orthogonal signal correction partial least-squares discriminant analysis (OSC-PLSDA) of metabolomic profiles of rat biofluids highlighted a number of metabolic disturbances induced by CR. Long-term CR treatment produced perturbations on energy metabolism, nitrogen metabolism, amino acid metabolism and kynurenine pathway, and evoked oxidative stress. These findings could explain well the CR induced nephrotoxicity and pulmonary toxicity, and provided several potential biomarkers for diagnostics of these toxicities. Such a (1)H NMR based metabolomics approach showed its ability to give a systematic and holistic view of the response of an organism to drugs and is suitable for dynamic studies on the toxicological effects of TCM.

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

Cai Ling; Sun Yat-sen University Cancer Center, Guangzhou, Guangdong; Stauder, Michael C.

Purpose: Primary bone lymphoma (PBL) represents less than 1% of all malignant lymphomas. In this study, we assessed the disease profile, outcome, and prognostic factors in patients with Stages I and II PBL. Patients and Methods: Thirteen Rare Cancer Network (RCN) institutions enrolled 116 consecutive patients with PBL treated between 1987 and 2008 in this study. Eighty-seven patients underwent chemoradiotherapy (CXRT) without (78) or with (9) surgery, 15 radiotherapy (RT) without (13) or with (2) surgery, and 14 chemotherapy (CXT) without (9) or with (5) surgery. Median RT dose was 40 Gy (range, 4-60). The median number of CXT cyclesmore » was six (range, 2-8). Median follow-up was 41 months (range, 6-242). Results: The overall response rate at the end of treatment was 91% (complete response [CR] 74%, partial response [PR] 17%). Local recurrence or progression was observed in 12 (10%) patients and systemic recurrence in 17 (15%). The 5-year overall survival (OS), lymphoma-specific survival (LSS), and local control (LC) were 76%, 78%, and 92%, respectively. In univariate analyses (log-rank test), favorable prognostic factors for OS and LSS were International Prognostic Index (IPI) score {<=}1 (p = 0.009), high-grade histology (p = 0.04), CXRT (p = 0.05), CXT (p = 0.0004), CR (p < 0.0001), and RT dose >40 Gy (p = 0.005). For LC, only CR and Stage I were favorable factors. In multivariate analysis, IPI score, RT dose, CR, and CXT were independently influencing the outcome (OS and LSS). CR was the only predicting factor for LC. Conclusion: This large multicenter retrospective study confirms the good prognosis of early-stage PBL treated with combined CXRT. An adequate dose of RT and complete CXT regime were associated with better outcome.« less

Pre-operative assessment of residual disease in locally advanced breast cancer patients: A sequential study by quantitative diffusion weighted MRI as a function of therapy.

PubMed

Agarwal, Khushbu; Sharma, Uma; Sah, Rani G; Mathur, Sandeep; Hari, Smriti; Seenu, Vurthaluru; Parshad, Rajinder; Jagannathan, Naranamangalam R

2017-10-01

The potential of diffusion weighted imaging (DWI) in assessing pathologic response and surgical margins in locally advanced breast cancer patients (n=38) undergoing neoadjuvant chemotherapy was investigated. DWI was performed at pre-therapy (Tp0), after I (Tp1) and III (Tp3) NACT at 1.5T. Apparent diffusion coefficient (ADC) of whole tumor (ADC WT ), solid tumor (ADC ST ), intra-tumoral necrosis (ADC Nec ) was determined. Further, ADC of 6 consecutive shells (5mm thickness each) including tumor margin to outside tumor margins (OM1 to OM5) was calculated and the data analyzed to define surgical margins. Of 38 patients, 6 were pathological complete responders (pCR), 19 partial responders (pPR) and 13 were non-responders (pNR). Significant increase was observed in ADC ST and ADC WT in pCR and pPR following therapy. Pre-therapy ADC was significantly lower in pCR compared to pPR and pNR indicating the heterogeneous nature of tumor which may affect drug perfusion and consequently the response. ADC of outside margins (OM1, OM2, and OM3) was significantly different among pCR, pPR and pNR at Tp3 which may serve as response predictive parameter. Further, at Tp3, ADC of outside margins (OM1, OM2, and OM3) was significantly lower compared to that seen at Tp0 in pCR, indicating the presence of residual disease in these shells. Pre-surgery information may serve as a guide to define cancer free margins and the extent of residual disease which may be useful in planning breast conservation surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

Standardizing of Pathology in Patients Receiving Neoadjuvant Chemotherapy.

PubMed

Bossuyt, Veerle; Symmans, W Fraser

2016-10-01

The use of neoadjuvant systemic therapy for the treatment of breast cancer patients is increasing. Pathologic response in the form of pathologic complete response (pCR) and grading systems of partial response, such as the residual cancer burden (RCB) system, gives valuable prognostic information for patients and is used as a primary endpoint in clinical trials. The breast cancer and pathology communities are responding with efforts to standardize pathology in patients receiving neoadjuvant chemotherapy. In this review, we summarize the challenges that postneoadjuvant systemic therapy surgical specimens pose and how pathologists and the multidisciplinary team can work together to optimize handling of these specimens. Multidisciplinary communication is essential. A single, standardized approach to macroscopic and microscopic pathologic examination makes it possible to provide reliable response information. This approach employs a map of tissue sections to correlate clinical, gross, microscopic, and imaging findings in order to report the presence of pCR (ypT0 ypN0 and ypT0/is ypN0) versus residual disease, the ypT and ypN stage using the current AJCC/UICC staging system, and the RCB.

Temozolomide in patients with glioblastoma at second relapse after first line nitrosourea-procarbazine failure: a phase II study.

PubMed

Brandes, Alba A; Ermani, Mario; Basso, Umberto; Paris, Myriam K; Lumachi, Franco; Berti, Franco; Amistà, Pietro; Gardiman, Marina; Iuzzolino, Paolo; Turazzi, Sergio; Monfardini, Silvio

2002-01-01

To investigate the efficacy of temozolomide (TMZ) in relationship to progression free survival at 6 months (PFS-6), median time to progression (TTP), response rate and toxicity, a phase II study was conducted in patients with recurrent glioblastoma multiforme (GBM) following surgery plus radiotherapy and a first-line regimen based on nitrosourea, procarbazine and vincristine. Forty-two patients with GBM were administered TMZ at the dose of 150 mg/m(2)/daily for 5 days every 4 weeks. The PFS-6 and at 12 months (PFS-12) was 24% (95% Confidence Interval [CI] = 14-42%) and 8% (CI = 2-27%), respectively, with a median TTP of 11.7 weeks (CI = 9-22 weeks). The response was assessed in all 42 patients; we observed 2 complete responses (CR) (4.7%), 6 partial responses (PR) (14.3%), and 9 stable disease (SD) (21.4%), with CR+PR = 19% (CI = 7-31%). TMZ as a second line regimen is a valid option in patients with heavily pretreated GBM. Copyright 2002 S. Karger AG, Basel

Combined local and systemic bleomycin administration in electrochemotherapy to reduce the number of treatment sessions

PubMed Central

Tellado, Matias; Olaiz, Nahuel; Michinski, Sebastian; Marshall, Guillermo

2016-01-01

Background Electrochemotherapy (ECT), a medical treatment widely used in human patients for tumor treatment, increases bleomycin toxicity by 1000 fold in the treated area with an objective response rate of around 80%. Despite its high response rate, there are still 20% of cases in which the patients are not responding. This could be ascribed to the fact that bleomycin, when administered systemically, is not reaching the whole tumor mass properly because of the characteristics of tumor vascularization, in which case local administration could cover areas that are unreachable by systemic administration. Patients and methods We propose combined bleomycin administration, both systemic and local, using companion animals as models. We selected 22 canine patients which failed to achieve a complete response after an ECT treatment session. Eleven underwent another standard ECT session (control group), while 11 received a combined local and systemic administration of bleomycin in the second treatment session. Results According to the WHO criteria, the response rates in the combined administration group were: complete response (CR) 54% (6), partial response (PR) 36% (4), stable disease (SD) 10% (1). In the control group, these were: CR 0% (0), PR 19% (2), SD 63% (7), progressive disease (PD) 18% (2). In the combined group 91% objective responses (CR+PR) were obtained. In the control group 19% objective responses were obtained. The difference in the response rate between the treatment groups was significant (p < 0.01). Conclusions Combined local and systemic bleomycin administration was effective in previously to ECT non responding canine patients. The results indicate that this approach could be useful and effective in specific population of patients and reduce the number of treatment sessions needed to obtain an objective response. PMID:27069450

Long-Term Response and Remission with Pixantrone in Patients with Relapsed or Refractory Aggressive Non-Hodgkin Lymphoma: Post-Hoc Analysis of the Multicenter, Open-Label, Randomized PIX301 Trial.

PubMed

Pettengell, Ruth; Coiffier, Bertrand; Egorov, Anton; Singer, Jack; Sivcheva, Lilia

2018-06-01

Pixantrone is recommended in relapsed and refractory non-Hodgkin lymphoma (NHL) or heavily pretreated NHL patients. Its conditional approval in Europe was based on results from the open-label, randomized, phase 3 PIX301 study, comparing pixantrone monotherapy with physician's choice of treatment in 140 patients with relapsed or refractory aggressive NHL. This post-hoc analysis of the PIX301 study investigated possible correlations between patient characteristics and clinical response in 17 patients (24%) treated with pixantrone who achieved a complete response (CR) or an unconfirmed complete response (CRu) at study end. These patients (10 male and 7 female) had a median age of 61 (range 41-75) years, and the most common diagnoses were diffuse large B-cell lymphoma (n = 10) and transformed indolent lymphoma (n = 4). Most had received two prior lines of therapy (n = 12). There was wide variation in the time from diagnosis to study entry (219-4777 days). Among the 17 patients who achieved a CR/CRu with pixantrone, 6 had stable or progressive disease as a response to their last regimen, 7 had a partial response, and 4 had a CR/CRu. Four patients from the pixantrone group survived without progression for more than 400 days. Prior response to previous therapies did not appear to affect long-term response to pixantrone. These observations suggest that pixantrone monotherapy in patients with multiply relapsed or refractory aggressive NHL who had received at least two prior therapies can be associated with durable responses and long-term remission, and this may be unrelated to the clinical response to the last therapy.

Photodynamic therapy and fluorescent diagnostics of head and neck cancer with second-generation photosensitizers

NASA Astrophysics Data System (ADS)

Vakulovskaya, Elena G.

2005-08-01

Photodynamic Therapy (PDT) and fluorescent diagnostics (FD) using Photosense was provided in 50 patients with head and neck cancer T1-3 stage, in 89 patients with skin cancer, using Radaclorine (RC) in 42 patients with T1-4 stage basal cell carcinoma (BCC),in 6 patients with oral cancer. Detection of borders of tumor, intensity of accumulation of photosensitizers in tumor, normal tissues were done by Spectral-fluorescent Complex. We"ve got fluorescence o fa 11 tumors and additional fluorescence zones were found with cytological verification. We used semiconductive lasers: Milon - h = 660+2nm, light dose 200 - 300 J/cm2 and Biospec (h=672+2nm), multiple laser surface and interstitial irradiation with total 1 ight d ose till 4 00-600 Ji cm2. A fter P DT with P S in head and neck cancer we"ve had complete response (CR) in 66.0% and partial response (PR) in 30.0%, with RC CR in BCC T1- 2NOMO - 92.9%, in recurrrencies CR - 60,6%, PR - 39,4%. The efficacy of PDT with PS was higher (CR - 86.7%, PR - 13,3%) and the recurrence rate in 6 months lower. Our experience show pronounced efficacy of PDT for head and neck tumors of different localization and histology, FD is providing diagnostically significant information, demonstrated high sensitivity and specificity.

Depth of Response in Multiple Myeloma: A Pooled Analysis of Three PETHEMA/GEM Clinical Trials

PubMed Central

Vidriales, Maria-Belen; Cordón, Lourdes; Cedena, Maria-Teresa; Puig, Noemi; Martinez-Lopez, Joaquin; Rosiñol, Laura; Gutierrez, Norma C.; Martín-Ramos, María-Luisa; Oriol, Albert; Teruel, Ana-Isabel; Echeveste, María-Asunción; de Paz, Raquel; de Arriba, Felipe; Hernandez, Miguel T.; Palomera, Luis; Martinez, Rafael; Martin, Alejandro; Alegre, Adrian; De la Rubia, Javier; Orfao, Alberto; Mateos, María-Victoria; Blade, Joan; San-Miguel, Jesus F.

2017-01-01

Purpose To perform a critical analysis on the impact of depth of response in newly diagnosed multiple myeloma (MM). Patients and Methods Data were analyzed from 609 patients who were enrolled in the GEM (Grupo Español de Mieloma) 2000 and GEM2005MENOS65 studies for transplant-eligible MM and the GEM2010MAS65 clinical trial for elderly patients with MM who had minimal residual disease (MRD) assessments 9 months after study enrollment. Median follow-up of the series was 71 months. Results Achievement of complete remission (CR) in the absence of MRD negativity was not associated with prolonged progression-free survival (PFS) and overall survival (OS) compared with near-CR or partial response (median PFS, 27, 27, and 29 months, respectively; median OS, 59, 64, and 65 months, respectively). MRD-negative status was strongly associated with prolonged PFS (median, 63 months; P < .001) and OS (median not reached; P < .001) overall and in subgroups defined by prior transplantation, disease stage, and cytogenetics, with prognostic superiority of MRD negativity versus CR particularly evident in patients with high-risk cytogenetics. Accordingly, Harrell C statistics showed higher discrimination for both PFS and OS in Cox models that included MRD (as opposed to CR) for response assessment. Superior MRD-negative rates after different induction regimens anticipated prolonged PFS. Among 34 MRD-negative patients with MM and a phenotypic pattern of bone marrow involvement similar to monoclonal gammopathy of undetermined significance at diagnosis, the probability of “operational cure” was high; median PFS was 12 years, and the 10-year OS rate was 94%. Conclusion Our results demonstrate that MRD-negative status surpasses the prognostic value of CR achievement for PFS and OS across the disease spectrum, regardless of the type of treatment or patient risk group. MRD negativity should be considered as one of the most relevant end points for transplant-eligible and elderly fit patients with MM. PMID:28498784

Depth of Response in Multiple Myeloma: A Pooled Analysis of Three PETHEMA/GEM Clinical Trials.

PubMed

Lahuerta, Juan-Jose; Paiva, Bruno; Vidriales, Maria-Belen; Cordón, Lourdes; Cedena, Maria-Teresa; Puig, Noemi; Martinez-Lopez, Joaquin; Rosiñol, Laura; Gutierrez, Norma C; Martín-Ramos, María-Luisa; Oriol, Albert; Teruel, Ana-Isabel; Echeveste, María-Asunción; de Paz, Raquel; de Arriba, Felipe; Hernandez, Miguel T; Palomera, Luis; Martinez, Rafael; Martin, Alejandro; Alegre, Adrian; De la Rubia, Javier; Orfao, Alberto; Mateos, María-Victoria; Blade, Joan; San-Miguel, Jesus F

2017-09-01

Purpose To perform a critical analysis on the impact of depth of response in newly diagnosed multiple myeloma (MM). Patients and Methods Data were analyzed from 609 patients who were enrolled in the GEM (Grupo Español de Mieloma) 2000 and GEM2005MENOS65 studies for transplant-eligible MM and the GEM2010MAS65 clinical trial for elderly patients with MM who had minimal residual disease (MRD) assessments 9 months after study enrollment. Median follow-up of the series was 71 months. Results Achievement of complete remission (CR) in the absence of MRD negativity was not associated with prolonged progression-free survival (PFS) and overall survival (OS) compared with near-CR or partial response (median PFS, 27, 27, and 29 months, respectively; median OS, 59, 64, and 65 months, respectively). MRD-negative status was strongly associated with prolonged PFS (median, 63 months; P < .001) and OS (median not reached; P < .001) overall and in subgroups defined by prior transplantation, disease stage, and cytogenetics, with prognostic superiority of MRD negativity versus CR particularly evident in patients with high-risk cytogenetics. Accordingly, Harrell C statistics showed higher discrimination for both PFS and OS in Cox models that included MRD (as opposed to CR) for response assessment. Superior MRD-negative rates after different induction regimens anticipated prolonged PFS. Among 34 MRD-negative patients with MM and a phenotypic pattern of bone marrow involvement similar to monoclonal gammopathy of undetermined significance at diagnosis, the probability of "operational cure" was high; median PFS was 12 years, and the 10-year OS rate was 94%. Conclusion Our results demonstrate that MRD-negative status surpasses the prognostic value of CR achievement for PFS and OS across the disease spectrum, regardless of the type of treatment or patient risk group. MRD negativity should be considered as one of the most relevant end points for transplant-eligible and elderly fit patients with MM.

Cidofovir for BK virus-associated hemorrhagic cystitis: a retrospective study.

PubMed

Cesaro, Simone; Hirsch, Hans H; Faraci, Maura; Owoc-Lempach, Joanna; Beltrame, Angela; Tendas, Andrea; Baltadakis, Ioannis; Dalle, Jean-Hughes; Koc, Yener; Toporski, Jacek; Styczynski, Jan; Yesilipek, M Akif; Heinz, Werner; Caniglia, Maurizio; Rascon, Jelena; Fauser, Axel A; Michallet, Mauricette; Lopez-Corral, Lucia; Neuburger, Stefan; Tridello, Gloria; Einsele, Herman

2009-07-15

BK virus-associated hemorrhagic cystitis (BKV-HC) is a severe complication after allogeneic hematopoietic stem cell transplantation (HSCT), but antiviral treatment for this condition has not been evaluated. We conducted a retrospective survey on the safety and outcome of cidofovir treatment for patients with BKV-HC in centers affiliated with the European Group for Blood and Marrow Transplantation. From 1 April 2004 to 31 December 2007, 62 patients received a diagnosis of BKV-HC after a median interval of 35 days after HSCT (range, 3-577 days). Fifty-seven patients (92%) received intravenous cidofovir, whereas 5 patients received cidofovir intravesically. Complete response (CR) was recorded in 38 (67%) of 57 patients with HC treated with intravenous cidofovir, whereas partial response (PR) was documented in 7 patients (12%). CR was documented in 3 patients and PR in 1 patient with HC treated with intravesical cidofovir. A reduction of 1-3 logs in BKV load was documented in 8 of the 10 patients achieving CR. Mild-to-moderate toxic effects were recorded in 18 of 57 patients who received intravenous cidofovir administration. In a multivariate analysis, the factors significantly associated with response to cidofovir were the stem cell source (P = .01) and the use of total body irradiation (P = .03). After a median follow-up of 287 days, overall survival and total treatment-related mortality rates were 63% and 40% for patients achieving CR, compared with 14% and 72% for patients with PR or no response to cidofovir, respectively (P = .001 and P = .001, respectively). Cidofovir may be a potentially effective therapy for BKV-HC, but evidence supporting its use requires randomized controlled trials.

Effects of Impression Material, Impression Tray Type, and Type of Partial Edentulism on the Fit of Cobalt-Chromium Partial Denture Frameworks on Initial Clinical Insertion: A Retrospective Clinical Evaluation.

PubMed

Baig, Mirza Rustum; Akbar, Jaber Hussain; Qudeimat, Muawia; Omar, Ridwaan

2018-02-15

To evaluate the effects of impression material, impression tray type, and type of partial edentulism (ie, Kennedy class) on the accuracy of fit of cobalt-chromium (Co-Cr) partial removable dental prostheses (PRDP) in terms of the number of fabricated frameworks required until the attainment of adequate fit. Electronic case documentations of 120 partially edentulous patients provided with Co-Cr PRDP treatment for one or both arches were examined. Statistical analyses of data were performed using analysis of variance and Tukey honest significant difference test to compare the relationships between the different factors and the number of frameworks that needed to be fabricated for each patient (α = .05). Statistical analysis of data derived from 143 records (69 maxillary and 74 mandibular) revealed no significant correlation between impression material, tray type, or Kennedy class and the number of construction attempts for the pooled or individual arch data (P ≥ .05). In PRDP treatment, alginate can be chosen as a first-choice material, and metal stock trays can be a preferred option for making final impressions to fabricate Co-Cr frameworks.

Chromium basalts - Experimental determination of redox states and partitioning among synthetic silicate phases

NASA Technical Reports Server (NTRS)

Schreiber, H. D.; Haskin, L. A.

1976-01-01

Experiments were performed on silicate compositions in the forsterite-anorthite-silica and forsterite-anorthite-diopside systems to determine the relative amounts of Cr(II), Cr(III), and Cr(VI) over a wide range of oxygen partial pressures from 10 to the -10th to 1 atm at 1500 and 1550 C. Redox states were measured by visible absorption spectroscopy and electron paramagnetic resonance spectroscopy and titration. It was found that Cr is present almost exclusively as Cr(III) in terrestrial basaltic liquids and as a mixture of Cr(III) and Cr(II) in lunar basaltic liquids.

Effects of the partial substitution of Ni by Cr on the transport, magnetic, and magnetocaloric properties of Ni 50Mn 37In 13

DOE PAGES

Pandey, Sudip; Quetz, Abdiel; Aryal, Anil; ...

2017-03-15

Here, the structural, magnetic, and magnetotransport properties of Ni 50-xCr xMn 37In 13 Heusler alloys have been synthesized and investigated by x-ray diffraction (XRD), field and pressure dependent magnetization, and electrical resistivity measurements. The partial substitution of Ni by Cr in Ni 50Mn 37In 13 significantly improves the magnetocaloric effect in the vicinity of the martensitic transition (T M). This system also shows a large negative entropy change at the Curie temperature (T C), making it a candidate material for application in a refrigeration cycle that exploits both positive and negative magnetic entropy changes. The refrigeration capacity (RC) values atmore » T M and T C increase significantly by more than 20 % with Cr substitution. The application of hydrostatic pressure increases the temperature stability of the martensitic phase in Ni 45Cr 5Mn 37In 13. The influence of Cr substitution on the transport properties of Ni 48Cr 2Mn 37In 13 is discussed. An asymmetric magnetoresistance, i.e., a spin-valve-like behavior, has been observed near T M for Ni 48Cr 2Mn 37In 13.« less

Effects of the partial substitution of Ni by Cr on the transport, magnetic, and magnetocaloric properties of Ni 50Mn 37In 13

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

Pandey, Sudip; Quetz, Abdiel; Aryal, Anil

Here, the structural, magnetic, and magnetotransport properties of Ni 50-xCr xMn 37In 13 Heusler alloys have been synthesized and investigated by x-ray diffraction (XRD), field and pressure dependent magnetization, and electrical resistivity measurements. The partial substitution of Ni by Cr in Ni 50Mn 37In 13 significantly improves the magnetocaloric effect in the vicinity of the martensitic transition (T M). This system also shows a large negative entropy change at the Curie temperature (T C), making it a candidate material for application in a refrigeration cycle that exploits both positive and negative magnetic entropy changes. The refrigeration capacity (RC) values atmore » T M and T C increase significantly by more than 20 % with Cr substitution. The application of hydrostatic pressure increases the temperature stability of the martensitic phase in Ni 45Cr 5Mn 37In 13. The influence of Cr substitution on the transport properties of Ni 48Cr 2Mn 37In 13 is discussed. An asymmetric magnetoresistance, i.e., a spin-valve-like behavior, has been observed near T M for Ni 48Cr 2Mn 37In 13.« less

Baseline Predictors for Success Following Strategy-Based Cognitive Remediation Group Training in Schizophrenia.

PubMed

Farreny, Aida; Aguado, Jaume; Corbera, Silvia; Ochoa, Susana; Huerta-Ramos, Elena; Usall, Judith

2016-08-01

Our aim was to examine predictive variables associated with the improvement in cognitive, clinical, and functional outcomes after outpatient participation in REPYFLEC strategy-based Cognitive Remediation (CR) group training. In addition, we investigated which factors might be associated with some long-lasting effects at 6 months' follow-up. Predictors of improvement after CR were studied in a sample of 29 outpatients with schizophrenia. Partial correlations were computed between targeted variables and outcomes of response to explore significant associations. Subsequently, we built linear regression models for each outcome variable and predictors of improvement. The improvement in negative symptoms at posttreatment was linked to faster performance in the Trail Making Test B. Disorganization and cognitive symptoms were related to changes in executive function at follow-up. Lower levels of positive symptoms were related to durable improvements in life skills. Levels of symptoms and cognition were associated with improvements following CR, but the pattern of resulting associations was nonspecific.

Impact of saline aquifer water on surface and shallow pit corrosion of martensitic stainless steels during exposure to CO2 environment (CCS)

NASA Astrophysics Data System (ADS)

Pfennig, Anja; Kranzmann, Axel

2018-05-01

Pipe steels suitable for carbon capture and storage technology (CCS) require resistance against the corrosive environment of a potential CCS-site, e.g. heat, pressure, salinity of the aquifer, CO2-partial pressure. Samples of different mild and high alloyed stainless injection-pipe steels partially heat treated: 42CrMo4, X20Cr13, X46Cr13, X35CrMo4 as well as X5CrNiCuNb16-4 were kept at T=60 °C and ambient pressure as well as p=100 bar for 700 h - 8000 h in a CO2-saturated synthetic aquifer environment similar to possible geological on-shore CCS-sites in the northern German Basin. Main corrosion products are FeCO3 and FeOOH. Corrosion rates obtained at 100 bar are generally much lower than those measured at ambient pressure. Highest surface corrosion rates are 0.8 mm/year for 42CrMo4 and lowest 0.01 mm/year for X5CrNiCuNb16-4 in the vapour phase at ambient pressure. At 100 bar the highest corrosion rates are 0.01 mm/year for 42CrMo4, X20Cr13 (liquid phase), X46Cr13 and less than 0.01 mm/year for X35CrMo4 and X5CrNiCuNb16-4 after 8000 h of exposure with no regard to atmosphere. Martensitic microstructure offers good corrosion resistance.

Effectiveness of evaluating tumor vascularization using 3D power Doppler ultrasound with high-definition flow technology in the prediction of the response to neoadjuvant chemotherapy for T2 breast cancer: a preliminary report

NASA Astrophysics Data System (ADS)

Shia, Wei-Chung; Chen, Dar-Ren; Huang, Yu-Len; Wu, Hwa-Koon; Kuo, Shou-Jen

2015-10-01

The aim of this study was to evaluate the effectiveness of advanced ultrasound (US) imaging of vascular flow and morphological features in the prediction of a pathologic complete response (pCR) and a partial response (PR) to neoadjuvant chemotherapy for T2 breast cancer. Twenty-nine consecutive patients with T2 breast cancer treated with six courses of anthracycline-based neoadjuvant chemotherapy were enrolled. Three-dimensional (3D) power Doppler US with high-definition flow (HDF) technology was used to investigate the blood flow in and morphological features of the tumors. Six vascularity quantization features, three morphological features, and two vascular direction features were selected and extracted from the US images. A support vector machine was used to evaluate the changes in vascularity after neoadjuvant chemotherapy, and pCR and PR were predicted on the basis of these changes. The most accurate prediction of pCR was achieved after the first chemotherapy cycle, with an accuracy of 93.1% and a specificity of 85.5%, while that of a PR was achieved after the second cycle, with an accuracy of 79.31% and a specificity of 72.22%. Vascularity data can be useful to predict the effects of neoadjuvant chemotherapy. Determination of changes in vascularity after neoadjuvant chemotherapy using 3D power Doppler US with HDF can generate accurate predictions of the patient response, facilitating early decision-making.

Whole Cell Therapeutic Vaccine Modified With Hyper-IL6 for Combinational Treatment of Nonresected Advanced Melanoma.

PubMed

Mackiewicz, Jacek; Karczewska-Dzionk, Aldona; Laciak, Maria; Kapcinska, Malgorzata; Wiznerowicz, Maciej; Burzykowski, Tomasz; Zakowska, Monika; Rose-John, Stefan; Mackiewicz, Andrzej

2015-05-01

Active specific immunotherapy of cancer requires an efficient induction and effector phase. The induction covers potent activation of anti-tumor response, whereas effector breaks the immunosuppression. We report efficacy of therapeutic melanoma vaccine (AGI-101H) used alone in advanced disease as a candidate for further combined treatment. In adjuvant setting in patients with resected metastases AGI-101H combined with surgery of recurring disease demonstrated long-term survival. Seventy-seven patients with nonresectable melanoma (8% IIIB, 21% IIIC, 71% IV) were enrolled. AGI-101H was administered 8× every 2 weeks, and then every month. At progression, maintenance was continued or induction was repeated and followed by maintenance. Median follow-up was 139.3 months. The median overall survival (OS) was 17.3 months; in patients with WHO 0-1 was 20.3 months. Complete response (CR) and partial response (PR) were observed in 19.4% and 9% of pts. Disease control rate was 54.5% of pts. The median CR+PR duration was 32 months. Reinduction was performed in 36.3% patients following disease progression with 46.6% of CR+PR. No grade 3/4 adverse events were observed. Treatment with AGI-101H of melanoma patients is safe and effective. AGI-101H is a good candidate for combinatorial treatment with immune check-points inhibitors or tumor hypoxia normalizators. EudraCT Number 2008-003373-40.

A phase 1 dose-escalation study of the oral histone deacetylase inhibitor abexinostat in combination with standard hypofractionated radiotherapy in advanced solid tumors

PubMed Central

Deutsch, Eric; Moyal, Elizabeth Cohen-Jonathan; Gregorc, Vanesa; Zucali, Paolo Andrea; Menard, Jean; Soria, Jean-Charles; Kloos, Ioana; Hsu, Jeff; Luan, Ying; Liu, Emily; Vezan, Remus; Graef, Thorsten; Rivera, Sofia

2017-01-01

Current treatments for advanced solid tumors tend to be only palliative. Although radiotherapy is administered with a curative intent, radioresistance and dose-limiting toxicities pose limitations to treatment. Abexinostat, an oral pan-histone deacetylase inhibitor, demonstrated enhanced sensitivity to radiation in various solid tumor cell lines. We conducted an exploratory, phase 1, dose-escalation study of abexinostat in combination with standard hypofractionated radiotherapy in patients with advanced solid tumors treated in a palliative setting. Among 58 treated patients, the median age was 61.5 years (range, 20-82); 47% of the patients had M1 stage disease, and 95% had received previous chemotherapy alone or chemotherapy in combination with surgery and/or radiotherapy. The recommended phase 2 dose was determined to be 90 mg/m2 (140 mg). Of the 51 patients evaluable for response, best overall response was 8% (1 complete response [CR], 3 partial responses [PRs]), and best loco-regional response was 12% (1 CR and 5 PRs) at a median follow-up of 16 weeks. Of note, patients with target or non-target brain lesions showed encouraging responses, with 1 patient achieving a best loco-regional response of CR. Treatment-emergent grade ≥3 adverse events (AEs) were few, with most common being thrombocytopenia (17%), lymphopenia (12%), and hypokalemia (7%). Six patients (10%) discontinued treatment due to AEs. No grade ≥3 prolongation of the QTc interval was observed, with no treatment discontinuations due to this AE. Oral abexinostat combined with radiotherapy was well tolerated in patients with advanced solid tumors. The combination may have potential for treatment of patients with brain lesions. PMID:28915584

Effect of complete or partial proteinuria recovery on long-term outcomes of lupus nephritis.

PubMed

Medina-Rosas, Jorge; Fung, William A; Su, Jiandong; Touma, Zahi

2018-02-01

We aimed to evaluate the effect of complete recovery (CR), partial recovery (PR), and no recovery (NR) of proteinuria at 2 years from the diagnosis of LN on long-term renal and extra-renal outcomes. Patients with LN and proteinuria attending the Lupus Center from 1970 to 2015 were analyzed. At 2 years from diagnosis of LN, patients were divided into three groups (CR, PR, and NR), and long-term outcomes were studied up to 15 years or last visit available. CR was defined as resolution of proteinuria, PR as a reduction ≥50% in baseline proteinuria, and NR as a reduction <50% compared to baseline. Long-term outcomes examined included renal outcomes [low eGFR, ESRD, and composite renal (low eGFR, ESRD, and dialysis/transplant)], cardiovascular outcomes, damage, and death. Kaplan-Meier plots, time-independent and time-dependent Cox proportional hazards models were applied to examine the effect of CR, PR, or NR on long-term outcomes. Of 277 patients, 71.8% achieved CR, 18.4% PR, and 9.8% NR at 2 years. CR compared to NR and CR compared to PR were protective against low eGFR and composite renal outcome in time-independent and time-dependent analyses. CR compared to PR protected against damage in the time-independent analysis. Overall, the comparison of CR and PR favored CR for long-term renal outcomes. CR at 2 years from diagnosis of LN protected against renal outcomes (low eGFR, ESRD/dialysis, and transplant). CR is more favorable compared to PR and clinicians should aim for CR to improve long-term outcomes in LN. Copyright © 2018 Elsevier Inc. All rights reserved.

Significant efficacy of 2-chlorodeoxyadenosine{+/-} rituximab in the treatment of splenic marginal zone lymphoma (SMZL): extended follow-up.

PubMed

Cervetti, G; Galimberti, S; Pelosini, M; Ghio, F; Cecconi, N; Petrini, M

2013-09-01

Splenic marginal zone lymphoma with or without villous lymphocytes (SLVL/SMZL) is an indolent lymphoma that typically affects elderly patients and that has a median survival >10 years. It presents with marked splenomegaly. Treatment is required in symptomatic cases. Splenectomy remains one of the first-line options in patients fit for surgery. The best pharmacological strategy has not yet been identified for poor surgical risk cases. Among different possible chemotherapeutic approaches, purine analogs, alone or in association with Rituximab, seem to be a valid therapeutic choice. Fifty SMZL patients were treated with Cladribine ± anti-CD20 monoclonal antibody. Forty-seven of 50 patients were evaluable for response. ORR was 87%: 24 of 47 patients (51%) achieved a complete hematological response (CR), 17 of 47 (36%) a partial response (PR) and 6 (13%) resulted unresponsive. Interestingly, 15 of 24 cases (62%) in CR achieved also a molecular remission. After a median follow-up of 48 months, 7 of 41 responsive cases relapsed and the 5-year PFS was 80%. These data confirm the efficacy of this schedule emphasizing the impact of minimal residual disease even in the outcome of SMZL patients.

Biochemical surface modification of Co-Cr-Mo.

PubMed

Puleo, D A

1996-01-01

Because of the limited mechanical properties of tissue substitutes formed by culturing cells on polymeric scaffolds, other approaches to tissue engineering must be explored for applications that require complete and immediate ability to bear weight, e.g. total joint replacements. Biochemical surface modification offers a way to partially regulate events at the bone-implant interface to obtain preferred tissue responses. Tresyl chloride, gamma-aminopropyltriethoxysilane (APS) and p-nitrophenyl chloroformate (p-NPC) immobilization schemes were used to couple a model enzyme, trypsin, on bulk samples of Co-Cr-Mo. For comparison, samples were simply adsorbed with protein. The three derivatization schemes resulted in different patterns and levels of activity. Tresyl chloride was not effective in immobilizing active enzyme on Co-Cr-Mo. Aqueous silanization with 12.5% APS resulted in optimal immobilized activity. Activity on samples derivatized with 0.65 mg p-NPC cm-2 was four to five times greater than that on samples simple adsorbed with enzyme or optimally derivatized with APS and was about eight times that on tresylated samples. This work demonstrates that, although different methods have different effectiveness, chemical derivatization can be used to alter the amount and/or stability of biomolecules immobilized on the surface of Co-Cr-Mo.

Retreatment with brentuximab vedotin in patients with CD30-positive hematologic malignancies

PubMed Central

2014-01-01

Background Brentuximab vedotin is a CD30-directed antibody-drug conjugate. Retreatment with brentuximab vedotin monotherapy was investigated in patients with CD30-positive Hodgkin lymphoma (HL) or systemic anaplastic large cell lymphoma (ALCL) who relapsed after achieving complete or partial remission (CR or PR) with initial brentuximab vedotin therapy in a previous study (ClinicalTrials.gov NCT00947856). Methods Twenty-one patients with HL and 8 patients with systemic ALCL were retreated; 3 patients with systemic ALCL were retreated twice. Patients generally received brentuximab vedotin 1.8 mg/kg intravenously approximately every 3 weeks over 30 minutes as an outpatient infusion. The primary objectives of this study were to assess safety and to estimate antitumor activity of brentuximab vedotin retreatment. Results The objective response rate was 60% (30% CR) in HL patients and 88% (63% CR) in systemic ALCL patients. The estimated median duration of response for patients with an objective response was 9.5 months (range, 0.0+ to 28.0+ months) at the time of study closure. Of the 19 patients with objective response, 7 patients had not had an event of disease progression or death at the time of study closure; duration of response for these patients ranged from 3.5 to 28 months. Of the 11 patients with CR, 45% had response durations of over 1 year. Adverse events (AEs) occurring in ≥25% of patients during the retreatment period were generally similar in type and frequency to those observed in the pivotal trials of brentuximab vedotin monotherapy, with the exception of peripheral neuropathy, which is known to have a cumulative effect. Grade 3 or higher events were observed in 48% of patients; these were generally transient and managed by dose modifications or delays. Deaths due to AEs occurred in 3 HL patients; none were considered to be related to brentuximab vedotin retreatment. Discussion With the exception of a higher rate of peripheral motor neuropathy, retreatment with brentuximab vedotin was associated with similar side effects seen in the pivotal trials. Conclusions Retreatment with brentuximab vedotin monotherapy is associated with response rates in 68% (39% CR) of patients with relapsed HL and systemic ALCL. Trial registration United States registry and results database ClinicalTrials.gov NCT00947856. PMID:24642247

In vitro investigation of marginal accuracy of implant-supported screw-retained partial dentures.

PubMed

Koke, U; Wolf, A; Lenz, P; Gilde, H

2004-05-01

Mismatch occurring during the fabrication of implant-supported dentures may induce stress to the peri-implant bone. The purpose of this study was to investigate the influence of two different alloys and the fabrication method on the marginal accuracy of cast partial dentures. Two laboratory implants were bonded into an aluminium block so that the distance between their longitudinal axes was 21 mm. Frameworks designed for screw-retained partial dentures were cast either with pure titanium (rematitan) or with a CoCr-alloy (remanium CD). Two groups of 10 frameworks were cast in a single piece. The first group was made of pure titanium, and the second group of a CoCr-alloy (remanium CD). A third group of 10 was cast in two pieces and then laser-welded onto a soldering model. This latter group was also made of the CoCr-alloy. All the frameworks were screwed to the original model with defined torque. Using light microscopy, marginal accuracy was determined by measuring vertical gaps at eight defined points around each implant. Titanium frameworks cast in a single piece demonstrated mean vertical gaps of 40 microm (s.d. = 11 microm) compared with 72 microm (s.d. = 40 microm) for CoCr-frameworks. These differences were not significant (U-test, P = 0.124) because of a considerable variation of the values for CoCr-frameworks (minimum: 8 microm and maximum: 216 microm). However, frameworks cast in two pieces and mated with a laser showed significantly better accuracy in comparison with the other experimental groups (mean: 17 microm +/- 6; P < 0.01). (i) The fit of implant-supported partial dentures cast with pure titanium in a single piece is preferable to that of those made with the CoCr-alloy and (ii) the highest accuracy can be achieved by using a two-piece casting technique combined with laser welding. Manufacturing the framework pieces separately and then welding them together provides the best marginal fit.

THE IMPACT OF LATE-LIFE ANXIETY AND DEPRESSION ON COGNITIVE FLEXIBILITY AND COGNITIVE RESTRUCTURING SKILL ACQUISITION.

PubMed

Johnco, Carly; Wuthrich, Viviana M; Rapee, Ronald M

2015-10-01

Studies examining treatment moderators and mediators in late-life anxiety and depression are sparse. Executive functioning skills decrease with age, and are poorer in the context of anxiety and depression. One of the key cognitive behavioral therapy techniques for anxiety and depression is cognitive restructuring (CR), which teaches people to identify and dispute maladaptive thoughts. There is evidence that cognitive flexibility (CF), one aspect of executive functioning, has a negative impact on CR skill acquisition in nonclinical older adults, and this warrants extension in a clinical sample. This study assessed CR skill acquisition in a clinical sample of 47 older adults with anxiety and depression and 53 nonclinical controls during an experimental paradigm, and investigated the influence of CF on this relationship. A battery of neuropsychological tests assessing CF were administered and CR was learned during a brief intervention. The clinical sample showed poorer CF on some measures, as well as poorer CR quality and efficacy (reduction in subjective distress). CF partially mediated the relationship between clinical status and CR quality, and between clinical status and CR efficacy. These results provide preliminary evidence that older adults with anxiety and depression are worse at learning and benefiting from CR with a brief intervention and this is partially due to having poorer CF skills. These findings warrant further examination in a treatment context to assess whether CR skill acquisition improves over treatment. © 2015 Wiley Periodicals, Inc.

Successful Management of Decitabine prior to Full-Dose Idarubicin and Cytarabine in the Treatment of Refractory/Recurrent Acute Myeloid Leukemia.

PubMed

Zhao, Hongyu; Xu, Li; Yang, Yongjian; Shao, Jianhua; Chen, Ping; Dong, Xuebin; Gu, Linping; Li, Daqi

2017-01-01

To investigate the safety and efficacy of the triple therapy of decitabine, idarubicin, and cytarabine in the treatment of refractory or recurrent acute myeloid leukemia (R/R AML). We conducted a single-center retrospective study in which decitabine treatment was administered prior to full-dose idarubicin and cytarabine (D-IA) for 21 R/R AML patients. After 1 cycle of D-IA, 10/21 (47.6%) patients experienced a complete remission (CR) and 2/21 (9.5%) showed a partial response. There was a 1-month response rate (RR) in 12/21 patients (57.14%); these patients achieved CR after 2 cycles of D-IA. Five of these 12 (40%) patients then received sequential allogeneic stem cell transplantation. At the last follow-up date, 9/21 (42.8%) patients had survived, and 7/21 (33.3%) were in continuous CR. Hematological toxicity and infections were the most prominent toxicities of this regimen. Other toxicities included nausea, vomiting, bleeding, and liver enzyme abnormalities. No mortalities were recorded due to treatment-related toxicity during remission. The combination was well tolerated, and the RR was encouraging. Our study suggests that D-IA may offer a novel and potentially effective treatment regimen for R/R AML patients. © 2017 S. Karger AG, Basel.

Increasing transcriptome response of serpins during the ontogenetic stages in the salmon louse Caligus rogercresseyi (Copepoda: Caligidae).

PubMed

Maldonado-Aguayo, W; Gallardo-Escárate, C

2014-06-01

Serine protease inhibitors, or serpins, target serine proteases, and are important regulators of intra- and extracellular proteolysis. For parasite survival, parasite-derived protease inhibitors have been suggested to play essential roles in evading the host's immune system and protecting against exogenous host proteases. The aim of this work was to identify serpins via high throughput transcriptome sequencing and elucidate their potential functions during the lifecycle of the salmon louse Caligus rogercresseyi. Eleven putative, partial serpin sequences in the C. rogercresseyi transcriptome were identified and denoted as Cr-serpins 1 to 11. Comparative analysis of the deduced serpin-like amino acid sequences revealed a highly conserved reactive center loop region. Interestingly, P1 residues suggest putative functions involved with the trypsin/subtilisin, elastase, or subtilisin inhibitors, which evidenced increasing gene expression profiles from the copepodid to adult stage in C. rogercresseyi. Concerning this, Cr-serpin 10 was mainly expressed in the copepodid stage, while Cr-serpins 3, 4, 5, and 11 were mostly expressed in chalimus and adult stages. These results suggest that serpins could be involved in evading the immune response of the host fish. The identification of these serpins furthers the understanding of the immune system in this important ectoparasite species. Copyright © 2014 Elsevier B.V. All rights reserved.

Structural, magnetic and phonon properties of Cr(III)-doped perovskite metal formate framework [(CH{sub 3}){sub 2}NH{sub 2}][Mn(HCOO){sub 3}

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

Mączka, Mirosław, E-mail: m.maczka@int.pan.wroc.pl; Gągor, Anna; Hermanowicz, Krzysztof

2016-05-15

We have incorporated Cr(III) into [(CH{sub 3}){sub 2}NH{sub 2}][Mn(HCOO){sub 3}] (DMMn) multiferroic metal organic framework (MOF). The highest concentration of Cr(III) in the synthesized samples reached 15.9 mol%. The obtained samples were characterized by powder and single-crystal X-ray diffraction, DSC, magnetic susceptibility, dielectric, EPR, Raman and IR methods. These methods and the performed chemical analysis revealed that electrical charge neutrality after substitution of Cr(III) for Mn(II) is maintained by partial replacement of dimethylammonium (DMA{sup +}) cations by neutral HCOOH molecules. These changes in the chemical composition are responsible for weakening of the hydrogen bonds and decreased flexibility of the framework.more » This in turn leads to lowering of the ferroelectric phase transition temperature, observed around 185 K for undoped DMMn and around 155 K for the sample containing 3.1 mol% of Cr(III), and lack of macroscopic phase transition for the samples with Cr(III) content of 8.2 and 15.9 mol %. Another interesting effect observed for the studied samples is pronounced strengthening of the weak ferromagnetism of in Cr(III)-doped samples, associated with slight decrease of the ferromagnetic ordering temperature from 8.5 K for DMMn to 7.0 K for the sample with 15.9 mol % Cr(III) content. - Graphical abstract: Incorporation of Cr(III) into [(CH3)2NH2[Mn(HCOO)3] framework increases the magnetization. - Highlights: • Chromium(III) substitutes for Mn(II) in the studied MOF. • Charge neutrality is maintained by replacing DMA{sup +} cations by neutral HCOOH molecules. • Compounds with 8.2 and 15.9% of Cr(III) show no phase transition above 100 K. • Doping with Cr(III) increases magnetization.« less

Adipogenic Signaling in Rat White Adipose Tissue: Modulation by Aging and Calorie Restriction

PubMed Central

Zhu, Min; Lee, Garrick D.; Ding, Liusong; Hu, Jingping; Qiu, Guang; de Cabo, Rafa; Bernier, Michel; Ingram, Donald K.; Zou, Sige

2007-01-01

Alterations in adipogenesis could have significant impact on several aging processes. We previously reported that calorie restriction (CR) in rats significantly increases the level of circulating adiponectin, a distinctive marker of differentiated adipocytes, leading to a concerted modulation in the expression of key transcription target genes and, as a result, to increased fatty acid oxidation and reduced deleterious lipid accumulation in other tissues. These findings led us to investigate further the effects of aging on adipocytes and to determine how CR modulates adipogenic signaling in vivo. CR for 2 and 25 months, significantly increased the expression of PPARγ, C/EBPβ and Cdk-4, and partially attenuated age-related decline in C/EBPα expression relative to rats fed ad libitum (AL). As a result, adiponectin was upregulated at both mRNA and protein levels, resulting in activation of target genes involved in fatty acid oxidation and fatty acid synthesis, and greater responsiveness of adipose tissue to insulin. Moreover, CR significantly decreased the ratio of C/EBPß isoforms LAP/LIP, suggesting the suppression of gene transcription associated with terminal differentiation while facilitating preadipocytes proliferation. Morphometric analysis revealed a greater number of small adipocytes in CR relative to AL feeding. Immunostaining confirmed that small adipocytes were more strongly positive for adiponectin than the large ones. Overall these results suggest that CR increased the expression of adipogenic factors, and maintained the differentiated state of adipocytes, which is critically important for adiponectin biosynthesis and insulin sensitivity. PMID:17624709

Partially filled intermediate band of Cr-doped GaN films

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

Sonoda, S.

2012-05-14

We investigated the band structure of sputtered Cr-doped GaN (GaCrN) films using optical absorption, photoelectron yield spectroscopy, and charge transport measurements. It was found that an additional energy band is formed in the intrinsic band gap of GaN upon Cr doping, and that charge carriers in the material move in the inserted band. Prototype solar cells showed enhanced short circuit current and open circuit voltage in the n-GaN/GaCrN/p-GaN structure compared to the GaCrN/p-GaN structure, which validates the proposed concept of an intermediate-band solar cell.

Does Response to Induction Chemotherapy Predict Survival for Locally Advanced Non-Small-Cell Lung Cancer? Secondary Analysis of RTOG 8804/8808

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

McAleer, Mary Frances, E-mail: mfmcalee@mdanderson.or; Moughan, Jennifer M.S.; Byhardt, Roger W.

2010-03-01

Purpose: Induction chemotherapy (ICT) improves survival compared with radiotherapy (RT) alone in locally advanced non-small-cell lung cancer (LANSCLC) patients with good prognostic factors. Concurrent chemoradiotherapy (CCRT) is superior to ICT followed by RT. The question arises whether ICT response predicts the outcome of patients subsequently treated with CCRT or RT. Methods and Materials: Between 1988 and 1992, 194 LANSCLC patients were treated prospectively with ICT (two cycles of vinblastine and cisplatin) and then CCRT (cisplatin plus 63 Gy for 7 weeks) in the Radiation Therapy Oncology Group 8804 trial (n = 30) or ICT and then RT (60 Gy/6 wk)more » on Radiation Therapy Oncology Group 8808 trial (n = 164). Of the 194 patients, 183 were evaluable and 141 had undergone a postinduction assessment. The overall survival (OS) of those with complete remission (CR) or partial remission (PR) was compared with that of patients with stable disease (SD) or progressive disease (PD) after ICT. Results: Of the 141 patients, 6, 30, 99, and 6 had CR, PR, SD, and PD, respectively. The log-rank test showed a significant difference (p <0.0001) in OS when the response groups were compared (CR/PR vs. SD/PD). On univariate and multivariate analyses, a trend was seen toward a response to ICT with OS (p = 0.097 and p = 0.06, respectively). A squamous histologic type was associated with worse OS on univariate and multivariate analyses (p = 0.031 and p = 0.018, respectively). SD/PD plus a squamous histologic type had a hazard ratio of 2.25 vs. CR/PR plus a nonsquamous histologic type (p = 0.007) on covariate analysis. Conclusion: The response to ICT was associated with a significant survival difference when the response groups were compared. A response to ICT showed a trend toward, but was not predictive of, improved OS in LANSCLC patients. Patients with SD/PD after ICT and a squamous histologic type had the poorest OS. These data suggest that patients with squamous LANSCLC might benefit from immediate RT or CCRT.« less

Perceiving Cardiac Rehabilitation Staff as Mainly Responsible for Exercise: A Dilemma for Future Self-Management.

PubMed

Flora, Parminder K; McMahon, Casey J; Locke, Sean R; Brawley, Lawrence R

2018-03-01

Cardiac rehabilitation (CR) exercise therapy facilitates patient recovery and better health following a cardiovascular event. However, post-CR adherence to self-managed (SM)-exercise is suboptimal. Part of this problem may be participants' view of CR staff as mainly responsible for help and program structure. Does post-CR exercise adherence for those perceiving high CR staff responsibility suffer as a consequence? Participants in this prospective, observational study were followed over 12 weeks of CR and one month afterward. High perceived staff responsibility individuals were examined for a decline in the strength of adherence-related social cognitions and exercise. Those high and low in perceived staff responsibility were also compared. High perceived staff responsibility individuals reported significant declines in anticipated exercise persistence (d = .58) and number of different SM-exercise options (d = .44). High versus low responsibility comparisons revealed a significant difference in one-month post-CR SM-exercise volume (d = .67). High perceived staff responsibility individuals exercised half of the amount of low responsibility counterparts at one month post-CR. Perceived staff responsibility and CR SRE significantly predicted SM-exercise volume, R 2 adj = .10, and persistence, R 2 adj = .18, one month post-CR. Viewing helpful well-trained CR staff as mainly responsible for participant behavior may be problematic for post-CR exercise maintenance among those more staff dependent. © 2017 The International Association of Applied Psychology.

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

Aghaei, Faranak; Tan, Maxine; Liu, Hong

Purpose: To identify a new clinical marker based on quantitative kinetic image features analysis and assess its feasibility to predict tumor response to neoadjuvant chemotherapy. Methods: The authors assembled a dataset involving breast MR images acquired from 68 cancer patients before undergoing neoadjuvant chemotherapy. Among them, 25 patients had complete response (CR) and 43 had partial and nonresponse (NR) to chemotherapy based on the response evaluation criteria in solid tumors. The authors developed a computer-aided detection scheme to segment breast areas and tumors depicted on the breast MR images and computed a total of 39 kinetic image features from bothmore » tumor and background parenchymal enhancement regions. The authors then applied and tested two approaches to classify between CR and NR cases. The first one analyzed each individual feature and applied a simple feature fusion method that combines classification results from multiple features. The second approach tested an attribute selected classifier that integrates an artificial neural network (ANN) with a wrapper subset evaluator, which was optimized using a leave-one-case-out validation method. Results: In the pool of 39 features, 10 yielded relatively higher classification performance with the areas under receiver operating characteristic curves (AUCs) ranging from 0.61 to 0.78 to classify between CR and NR cases. Using a feature fusion method, the maximum AUC = 0.85 ± 0.05. Using the ANN-based classifier, AUC value significantly increased to 0.96 ± 0.03 (p < 0.01). Conclusions: This study demonstrated that quantitative analysis of kinetic image features computed from breast MR images acquired prechemotherapy has potential to generate a useful clinical marker in predicting tumor response to chemotherapy.« less

Phase 2 randomized study of bortezomib-melphalan-prednisone with or without siltuximab (anti–IL-6) in multiple myeloma

PubMed Central

San-Miguel, Jesús; Bladé, Joan; Shpilberg, Ofer; Grosicki, Sebastian; Maloisel, Frédéric; Min, Chang-Ki; Polo Zarzuela, Marta; Robak, Tadeusz; Prasad, Sripada V. S. S.; Tee Goh, Yeow; Laubach, Jacob; Spencer, Andrew; Mateos, María-Victoria; Palumbo, Antonio; Puchalski, Tom; Reddy, Manjula; Uhlar, Clarissa; Qin, Xiang; van de Velde, Helgi; Xie, Hong; Orlowski, Robert Z.

2014-01-01

Because interleukin-6 (IL-6) is considered important in the proliferation of early multiple myeloma (MM), we hypothesized that the addition of the anti-IL-6 monoclonal antibody siltuximab to the bortezomib-melphalan-prednisone (VMP) regimen would improve outcomes in transplant-ineligible patients with newly diagnosed MM. One hundred and six patients were randomized to receive 9 cycles of VMP or VMP plus siltuximab (11 mg/kg every 3 weeks) followed by siltuximab maintenance. Baseline characteristics were well balanced except for immunoglobulin A subtype and 17p deletions. With a complete response (CR) rate of 27% on siltuximab plus VMP (S+VMP) and 22% on VMP, the study did not confirm its hypothesis that the addition of siltuximab would increase the CR rate by at least 10%. Overall response rate was 88% on S+VMP and 80% on VMP, and at least very good partial response rates were 71% and 51% (P = .0382), respectively. Median progression-free survival (17 months) and 1-year overall survival (88%) were identical in the 2 arms. Grade ≥3 adverse-event incidence was 92% on S+VMP and 81% on VMP (P = .09), with trends toward more hematologic events and infections on S+VMP. Maintenance therapy with siltuximab was well tolerated. In conclusion, the addition of siltuximab to VMP did not improve the CR rate or long-term outcomes. This study was registered at http://clinicaltrials.gov as #NCT00911859. PMID:24833354

Increased pathological complete response rate after a long-term neoadjuvant letrozole treatment in postmenopausal oestrogen and/or progesterone receptor-positive breast cancer

PubMed Central

Allevi, G; Strina, C; Andreis, D; Zanoni, V; Bazzola, L; Bonardi, S; Foroni, C; Milani, M; Cappelletti, M R; Gussago, F; Aguggini, S; Giardini, R; Martinotti, M; Fox, S B; Harris, A L; Bottini, A; Berruti, A; Generali, D

2013-01-01

Background: The objective of this study was to determine the optimal scheduling of 2.5 mg daily letrozole in neoadjuvant breast cancer patients to obtain pathological complete response (pathCR) and assess Ki-67 expression as an early predictor of response. Patients and methods: This single institution study comprised 120 oestrogen receptor (ER)-positive postmenopausal women with primary breast cancer (clinical stage ⩾T2, N0–1), from three sequential cohorts (cohort A of 40, cohort B of 40 and cohort C of 40 patients, respectively) based on different duration of the neoadjuvant letrozole. Biological markers such as ER, progesterone receptor, HER2 and Ki-67 expression were tested at diagnosis and at definitive surgery. Results: A total of 89 patients (75.4%) achieved an objective response with 44 (37.3%) clinical CRs and 45 (38.1%) partial responses. The clinical CRs were significantly observed in cohort C (23 out of 40 patients, 57.5%) and B (16 out of 38 patients, 42.1%) compared with cohort A (5 out of 40 patients, 12.5%) (P-value for trend <0.001). Letrozole induced a similar significant reduction in Ki-67 index after treatment in all cohorts. The pathCR rate was significantly more frequent in cohort C (7 out of 40 patients, 17.5%) than in cohort A (1 out of 40 patients, 2.5%) and B (2 out of 40 patients, 5.0%) (P-value for trend <0.04). Conclusion: One-year neoadjuvant letrozole therapy leads to a higher pathCR rate and may be the optimal length of drug exposure. PMID:23579222

Effect of free Cr content on corrosion behavior of 3Cr steels in a CO2 environment

NASA Astrophysics Data System (ADS)

Li, Wei; Xu, Lining; Qiao, Lijie; Li, Jinxu

2017-12-01

The corrosion behavior of 3Cr steels with three microstructures (martensite, bainite, combined ferrite and pearlite) in simulated oil field formation water with a CO2 partial pressure of 0.8 MPa was investigated. The relationships between Cr concentrations in corrosion scales and corrosion rates were studied. The precipitated phases that contained Cr were observed in steels of different microstructures, and free Cr content levels were compared. The results showed that steel with the martensite microstructure had the highest free Cr content, and thus had the highest corrosion resistance. The free Cr content of bainite steel was lower than that of martensite steel, and the corrosion rate of bainite steel was higher than that of martensite steel. Because large masses of Cr were combined in ferrite and pearlite steel, the corrosion rates of ferrite and pearlite steel were the highest. Free Cr content in steel affects its corrosion behavior greatly.

Synthesis, structure, and magnetic characterization of Cr{sub 4}US{sub 8}

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

Ward, Matthew D.; Chan, Ian Y.; Malliakas, Christos D.

The compound Cr{sub 4}US{sub 8} has been synthesized at 1073 K and its crystal structure has been determined at 100 K. The structure is modulated with a two-fold commensurate supercell. The subcell may be indexed in an orthorhombic cell but weak supercell reflections lead to the monoclinic superspace group P2{sub 1}/c(α0γ)0s with two Cr sites, one U site, and four S sites. The structure comprises a three-dimensional framework of CrS{sub 6} octahedra with channels that are partially occupied by U atoms. Each U atom in these channels is coordinated by eight S atoms in a bicapped trigonal-prismatic arrangement. The magneticmore » behavior of Cr{sub 4}US{sub 8} is complex. At temperatures above ~120 K at all measured fields, there is little difference between field-cooled and zero field-cooled data and χ(T) decreases monotonously with temperature, which is reminiscent of the Curie–Weiss law. At lower temperatures, the temperature dependence of χ(T) is complex and strongly dependent on the magnetic field strength. - Graphical abstract: Structure of Cr{sub 4}US{sub 8} viewed down the a axis. - Highlights: • At 1073 K Cr{sub 4}US{sub 8} was synthesized and at 100 K its crystal structure was determined. • The 3D structure comprises CrS{sub 6} octahedra with channels partially occupied by U. • The magnetic behavior of Cr{sub 4}US{sub 8} is complex.« less

Platelet aggregation caused by a partially purified jellyfish toxin from Carybdea rastonii.

PubMed

Azuma, H; Sekizaki, S; Satoh, A; Nakajima, T; Ishikawa, M

1986-01-01

A partially purified toxin (pCrTX) was obtained from the tentacles of the jellyfish, Carybdea rastonii. When pCrTX (3 X 10(-8) - 3 X 10(-7) g/ml) was added to citrated platelet-rich plasma, aggregation was produced in a concentration-dependent manner. Scanning electron microscopic examination revealed that both pCrTX and collagen produced aggregates of platelets possessing many pseudopods. The concentration which produced 50% aggregation for pCrTX was 1.8 X 10(-7) g/ml, as compared to 2.3 X 10(-6) g/ml for collagen. The pCrTX-induced aggregation was only slightly inhibited by indomethacin and quinacrine in concentrations sufficient to inhibit arachidonic acid- and collagen-induced aggregation. pCrTX was less active in washed platelets suspended in Ca2+ free medium, whereas the pCrTX-induced aggregation was significantly augmented in the presence of Ca2+. The augmentation of aggregation by Ca2+ was only slightly attenuated by pretreatment with 100 microM verapamil. pCrTX significantly increased the concentration of cytoplasmic free Ca2+ ([Ca2+]i) and depolarized the platelet membrane in concentrations that produced aggregation. The increase in [Ca2+]i caused by pCrTX was little affected by verapamil. The depolarization by pCrTX was unchanged in the presence or absence of Ca2+, or by sodium or potassium transport inhibitors. The movement of 22Na+ into platelets was significantly increased by pCrTX. This increase in the movement of 22N+ into platelets was unaffected by tetrodotoxin. On the other hand, pCrTX-induced aggregation, depolarization and the increase in [Ca2+]i were all significantly attenuated in low Na+ medium. These results suggest that pCrTX causes a massive depolarization by increasing cation permeability indiscriminately and this generalized depolarization permits an inward movement of calcium down an electrochemical gradient which, in turn triggers platelet aggregation.

Impact of Sequencing Targeted Therapies With High-dose Interleukin-2 Immunotherapy: An Analysis of Outcome and Survival of Patients With Metastatic Renal Cell Carcinoma From an On-going Observational IL-2 Clinical Trial: PROCLAIMSM.

PubMed

Clark, Joseph I; Wong, Michael K K; Kaufman, Howard L; Daniels, Gregory A; Morse, Michael A; McDermott, David F; Agarwala, Sanjiv S; Lewis, Lionel D; Stewart, John H; Vaishampayan, Ulka; Curti, Brendan; Gonzalez, René; Lutzky, Jose; Rudraptna, Venkatesh; Cranmer, Lee D; Jeter, Joanne M; Hauke, Ralph J; Miletello, Gerald; Milhem, Mohammed M; Amin, Asim; Richart, John M; Fishman, Mayer; Hallmeyer, Sigrun; Patel, Sapna P; Van Veldhuizen, Peter; Agarwal, Neeraj; Taback, Bret; Treisman, Jonathan S; Ernstoff, Marc S; Perritt, Jessica C; Hua, Hong; Rao, Tharak B; Dutcher, Janice P; Aung, Sandra

2017-02-01

This analysis describes the outcome for patients who received targeted therapy (TT) prior to or following high-dose interleukin-2 (HD IL-2). Patients with renal cell carcinoma (n = 352) receiving HD IL-2 were enrolled in Proleukin R Observational Study to Evaluate the Treatment Patterns and Clinical Response in Malignancy (PROCLAIM SM ) beginning in 2011. Statistical analyses were performed using datasets as of September 24, 2015. Overall, there were 4% complete response (CR), 13% partial response (PR), 39% stable disease (SD), and 43% progressive disease (PD) with HD IL-2. The median overall survival (mOS) was not reached in patients with CR, PR, or SD, and was 15.5 months in patients with PD (median follow-up, 21 months). Sixty-one patients had prior TT before HD IL-2 with an overall response rate (ORR) to HD IL-2 of 19% (1 CR, 9 PR) and an mOS of 22.1 months. One hundred forty-nine patients received TT only after HD IL-2 with an mOS of 35.5 months. One hundred forty-two patients had no TT before or after HD IL-2, and mOS was not reached. The mOS was 8.5 months in PD patients who received HD IL-2 without follow-on TT and 29.7 months in PD patients who received follow-on TT after HD IL-2. HD IL-2 as sole front-line therapy, in the absence of added TT, shows extended clinical benefit (CR, PR, and SD). Patients with PD after HD IL-2 appear to benefit from follow-on TT. Patients who progressed on TT and received follow-on HD IL-2 experienced major clinical benefit. HD IL-2 therapy should be considered in eligible patients. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

[High dosage therapy with stem cell transplantation in neuroendocrine carcinoma].

PubMed

Buxhofer, V; Ruckser, R; Kier, P; Habertheuer, K H; Zelenka, P; Tatzreiter, G; Dorner, S; Vedovelli, H; Sebesta, C; Hinterberger, W

2000-01-01

Neuroendocrine carcinoma and small-cell lung cancer (SCLC) are highly responsive to chemo- and radiotherapy. Nevertheless, most patients (pts.) experience relapse. At the 2nd department of medicine in the Donauspital, 4 pts. with neuroendocrine carcinomas of different primary sites underwent high-dose chemotherapy with autologous stem-cell transplantation (ASTx). Pt. 1 suffered from neuroendocrine lung cancer, pt. 2 from a small-cell carcinoma of the pancreas. Pt. 3 had a metastatic small-cell abdominal bulky tumor and pt. 4 presented with neuroendocrine carcinoma of the prostate. After 4-6 cycles induction chemotherapy pts. were consolidated with 1 cycle of HDCht and ASTx. Prior to HDCht pt. 1 and pt. 2 were in complete remission (CR) and pt. 3 and pt. 4 in partial remission. Pt. 3 converted in CR after HDCht. He is still in CR with a disease-free survival of 23 month after ASTx and 30 month after diagnosis. Pt. 1, 2 and 4 died from relapse 10, 16 and 5 month after ASTx and 16, 22 and 9 month after diagnosis. Pts. with neuroendocrine carcinomas might be suitable candidates for HDCht and ASTx.

PD1 blockade with pembrolizumab is highly effective in relapsed or refractory NK/T-cell lymphoma failing l-asparaginase.

PubMed

Kwong, Yok-Lam; Chan, Thomas S Y; Tan, Daryl; Kim, Seok Jin; Poon, Li-Mei; Mow, Benjamin; Khong, Pek-Lan; Loong, Florence; Au-Yeung, Rex; Iqbal, Jabed; Phipps, Colin; Tse, Eric

2017-04-27

Natural killer (NK)/T-cell lymphomas failing L-asparaginse regimens have no known salvage and are almost invariably fatal. Seven male patients with NK/T-cell lymphoma (median age, 49 years; range, 31-68 years) for whom a median of 2 (range, 1-5) regimens (including l-asparaginase regimens and allogeneic hematopoietic stem-cell transplantation [HSCT] in 2 cases) failed were treated with the anti-programmed death 1 (PD1) antibody pembrolizumab. All patients responded, according to various clinical, radiologic (positron emission tomography), morphologic, and molecular (circulating Epstein-Barr virus [EBV] DNA) criteria. Two patients achieved complete response (CR) in all parameters. Three patients achieved clinical and radiologic CRs, with two having molecular remission (undetectable EBV DNA) but minimal EBV-encoded RNA-positive cells in lesions comprising predominantly CD3 + CD4 + and CD3 + CD8 + T cells (which ultimately disappeared, suggesting they represented pseudoprogression) and one having detectable EBV DNA despite morphologic CR. Two patients achieved partial response (PR). After a median of 7 (range, 2-13) cycles of pembrolizumab and a follow-up of a median of 6 (range, 2-10) months, all five CR patients were still in remission. The only adverse event was grade 2 skin graft-versus-host disease in one patient with previous allogeneic HSCT. Expression of the PD1 ligand was strong in 4 patients (3 achieving CR) and weak in 1 (achieving PR). PD1 blockade with pembrolizumab was a potent strategy for NK/T-cell lymphomas failing l-asparaginase regimens. © 2017 by The American Society of Hematology.

Randomized phase 2/3 trial of CpG oligodeoxynucleotide PF-3512676 alone or with dacarbazine for patients with unresectable stage III and IV melanoma.

PubMed

Weber, Jeffrey S; Zarour, Hassan; Redman, Bruce; Trefzer, Uwe; O'Day, Steven; van den Eertwegh, Alfons J M; Marshall, Ernest; Wagner, Stefan

2009-09-01

The primary objective of this phase 2 study was to assess the objective response rate (complete response [CR] + partial responses [PR]), by Response Evaluation Criteria in Solid Tumors, of PF-3512676, a CpG oligodeoxynucleotide, alone in 2 doses or in combination with dacarbazine (DTIC) in patients with unresectable stage IIIB/C or stage IV malignant melanoma, with the aim of selecting an arm to take forward to a phase 3 portion of the study. A total of 184 patients were randomized to 1 of 4 treatments: PF-3512676 10 mg (low dose), at 40 mg (high dose), 40 mg plus DTIC (850 mg/m(2)), or DTIC (850 mg/m(2)) alone. Patients received PF-3512676 subcutaneously weekly in a 3-week cycle and received DTIC intravenously on the first week of the cycle. The objective response rate (PR or CR, confirmed or unconfirmed) in the 40 mg + DTIC arm was 16% (7 patients) compared with 8% (3 patients) with DTIC alone. One (2%) patient in the 10-mg and 0 patients in the 40-mg arms achieved an objective response. Best response of CR or PR or stable disease (SD), with no minimum duration defined for SD, was achieved by 15 (33%) patients in the 40 mg + DTIC arm, 15 (38%) patients in the DTIC-only arm, 8 (17%) patients in the 10-mg arm, and 9 (20%) patients in the 40-mg arm. The most frequently reported adverse events were classified as local injection site reactions or systemic flu-like symptoms, specifically fatigue, rigors, and pyrexia. PF-3512676 at the doses used was generally well tolerated. The modest objective response rates observed in all arms did not warrant continuation to the phase 3 portion of the study.

A Catharanthus roseus BPF-1 homologue interacts with an elicitor-responsive region of the secondary metabolite biosynthetic gene Str and is induced by elicitor via a JA-independent signal transduction pathway.

PubMed

van der Fits, L; Zhang, H; Menke, F L; Deneka, M; Memelink, J

2000-11-01

Plants respond to pathogen attack by induction of various defence responses, including the biosynthesis of protective secondary metabolites. In Catharanthus roseus, the elicitor-induced expression of the terpenoid indole alkaloid biosynthetic gene Strictosidine synthase (Str) is mediated via the plant stress hormonejasmonate. In the promoters of several defence-related genes, cis-acting elements have been identified that are important for transcriptional regulation upon stress signals. Here we show that an upstream region in the Str promoter confers responsiveness to partially purified yeast elicitor and jasmonate. Yeast one-hybrid screening with this element as a bait identified a MYB-like protein, which shows high homology to parsley box P-binding factor-1 (PcBPF-1). In vitro analyses showed that the Str promoter fragment contained a novel binding site for BPF-1-like proteins with higher binding affinity than the previously described box P. CrBPF-1 mRNA accumulated rapidly in elicitor-treated C. roseus suspension cells, whereas no induction was observed with jasmonate. Inhibitor studies indicated that CrBPF-1 plays a role in an elicitor-responsive but jasmonate-independent signal transduction pathway, acting downstream of protein phosphorylation and calcium influx.

Development of a New Subclavian Arterial Infusion Chemotherapy Method for Locally or Recurrent Advanced Breast Cancer Using an Implanted Catheter-Port System After Redistribution of Arterial Tumor Supply

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

Takizawa, Kenji, E-mail: taki-lrl@vy.catv.ne.jp; Shimamoto, Hiroshi, E-mail: hshima@k8.dion.ne.jp; Ogawa, Yukihisa, E-mail: yukky-p406c@nifty.com

Locally or recurrent advanced breast cancers can receive arterial blood supply from various arteries, such as the internal thoracic artery (ITA), the lateral thoracic artery, and the other small arterial branches originating from the subclavian artery. Failure to catheterize and subsequent formation of collateral arterial blood supply from various arteries are some of the reasons why the response to conventional selective transarterial infusion chemotherapy is limited and variable. To overcome this problem, we developed a new subclavian arterial infusion chemotherapy method using an implanted catheter-port system after redistribution of arterial tumor blood supply by embolizing the ITA. We named thismore » technique ('redistributed subclavian arterial infusion chemotherapy' (RESAIC)). Using RESAIC, patients can be treated on an outpatient basis for extended periods of time. Eleven patients underwent RESAIC, and the complete remission and partial response rate in 10 evaluable patients was 90%: complete remission [CR] n = 4, partial remission n = 4, stable disease n = 1, and not evaluable n = 1. Three of four patients with CR had no distant metastasis, and modified radical mastectomy was performed 1 month after conclusion of RESAIC. The resected specimens showed no residual cancer cells, and pathologically confirmed complete remission was diagnosed in each of these cases. Although temporary grade-3 myelosuppression was seen in three patients who were previously treated by systemic chemotherapy, there was no other drug-induced toxicity or procedure-related complications. RESAIC produced a better response and showed no major complications compared with other studies despite the advanced stage of the cancers.« less

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

Wu, Fen; Sun, Hong; Kluz, Thomas

Hexavalent chromium [Cr(VI)] is a human carcinogen that results in the generation of reactive oxygen species (ROS) and a variety of DNA lesions leading to cell death. Epigallocatechin-3-gallate (EGCG), the major polyphenol present in green tea, possesses potent antioxidative activity capable of protecting normal cells from various stimuli-induced oxidative stress and cell death. Here we demonstrated that co-treatment with EGCG protected human normal bronchial epithelial BEAS-2B cells from Cr(VI)-induced cell death in a dose-dependent manner. Cr(VI) induces apoptosis as the primary mode of cell death. Co-treatment of BEAS-2B cells with EGCG dose-dependently suppressed Cr(VI)-induced apoptosis. Fluorescence microscopic analyses and quantitativemore » measurement revealed that EGCG significantly decreased intracellular levels of ROS induced by Cr(VI) exposure. Using a well-established K{sup +}/SDS precipitation assay, we further showed that EGCG was able to dose-dependently reduce DNA–protein cross-links (DPC), lesions that could be partially attributed to Cr(VI)-induced oxidative stress. Finally, analyses of Affymetrix microarray containing 28,869 well-annotated genes revealed that, among the 3412 genes changed more than 1.5-fold by Cr(VI) treatment, changes of 2404 genes (70%) were inhibited by pretreatment of EGCG. Real-time PCR confirmed the induction of 3 genes involved in cell death and apoptosis by Cr(VI), which was eliminated by EGCG. In contrast, Cr(VI) reduced the expression of 3 genes related to cellular defense, and this reduction was inhibited by EGCG. Our results indicate that EGCG protects BEAS-2B cells from Cr(VI)-induced cytotoxicity presumably by scavenging ROS and modulating a subset of genes. EGCG, therefore, might serve as a potential chemopreventive agent against Cr(VI) carcinogenesis. -- Highlights: ► EGCG protected human normal bronchial epithelial BEAS-2B cells from Cr(VI)-induced cell death and apoptosis. ► EGCG significantly decreased intracellular levels of ROS induced by Cr(VI) exposure. ► EGCG reduced DNA-protein cross-links, lesions that could be partially attributed to Cr(VI)-induced oxidative stress. ► EGCG modulated 70% of the gene expression changes induced by Cr(VI) exposure.« less

Magnetocaloric effects and electrical resistivity of Ni2Mn0.55CoxCr0.45-xGa - A Heusler alloy system exhibiting a partially-decoupled first-order phase transition

NASA Astrophysics Data System (ADS)

Brock, Jeffrey; Khan, Mahmud

2018-05-01

The phase transitions and associated magnetocaloric properties of the Ni2Mn0.55CoxCr0.45-xGa (0 ≤ x ≤ 0.25) Heusler alloy system have been investigated. All samples exhibit a first-order martensitic phase transition, evidenced by a sharp drop in the resistivity versus temperature data and a thermomagnetic irreversibility in the dc magnetization data of the respective samples. Large magnetic entropy changes have also been observed near the phase transitions. The martensitic transformation temperature increases as Cr is partially replaced with Co. Additionally, this substitution leads to a partial decoupling of the magnetic and structural phase transitions, dramatically suppressing any magnetic hysteresis losses. Furthermore, the change in electrical resistivity during the phase transition remains relatively constant across the system, despite major changes in the degree of structural disorder and magnetostructural phase transition coupling. Detailed experimental results and conjectures as to the origin of these behaviors have been provided.

Laser welding of removable partial denture frameworks.

PubMed

Brudvik, James S; Lee, Seungbum; Croshaw, Steve N; Reimers, Donald L; Reimers, Dave L

2008-01-01

To identify and measure distortions inherent in the casting process of a Class III mandibular cobalt-chromium (Co-Cr) framework to illustrate the problems faced by the laboratory technician and the clinician and to measure the changes that occur during the correction of the fit discrepancy using laser welding. Five identical castings of a Co-Cr alloy partial denture casting were made and measured between 3 widely separated points using the x, y, and z adjustments of a Nikon Measurescope. The same measurements were made after each of the following clinical and laboratory procedures: sprue removal, sectioning of the casting into 3 parts through the posterior meshwork, fitting the segments to the master cast, picking up the segments using resin, and laser welding of the 3 segments. Measurements of all 5 castings showed a cross-arch decrease after sprue removal, an increase after fitting the segments to the master cast, and a slight decrease after resin pickup and laser welding. Within the limitations of this study, the findings suggest that precise tooth-frame relations can be established by resin pickup and laser welding of segments of Co-Cr removable partial denture frameworks.

Chemometrics-assisted simultaneous determination of cobalt(II) and chromium(III) with flow-injection chemiluminescence method

NASA Astrophysics Data System (ADS)

Li, Baoxin; Wang, Dongmei; Lv, Jiagen; Zhang, Zhujun

2006-09-01

In this paper, a flow-injection chemiluminescence (CL) system is proposed for simultaneous determination of Co(II) and Cr(III) with partial least squares calibration. This method is based on the fact that both Co(II) and Cr(III) catalyze the luminol-H 2O 2 CL reaction, and that their catalytic activities are significantly different on the same reaction condition. The CL intensity of Co(II) and Cr(III) was measured and recorded at different pH of reaction medium, and the obtained data were processed by the chemometric approach of partial least squares. The experimental calibration set was composed with nine sample solutions using orthogonal calibration design for two component mixtures. The calibration curve was linear over the concentration range of 2 × 10 -7 to 8 × 10 -10 and 2 × 10 -6 to 4 × 10 -9 g/ml for Co(II) and Cr(III), respectively. The proposed method offers the potential advantages of high sensitivity, simplicity and rapidity for Co(II) and Cr(III) determination, and was successfully applied to the simultaneous determination of both analytes in real water sample.

A regional-scale study of chromium and nickel in soils of northern California, USA

USGS Publications Warehouse

Morrison, J.M.; Goldhaber, M.B.; Lee, L.; Holloway, J.M.; Wanty, R.B.; Wolf, R.E.; Ranville, J.F.

2009-01-01

A soil geochemical survey was conducted in a 27,000-km2 study area of northern California that includes the Sierra Nevada Mountains, the Sacramento Valley, and the northern Coast Range. The results show that soil geochemistry in the Sacramento Valley is controlled primarily by the transport and weathering of parent material from the Coast Range to the west and the Sierra Nevada to the east. Chemically and mineralogically distinctive ultramafic (UM) rocks (e.g. serpentinite) outcrop extensively in the Coast Range and Sierra Nevada. These rocks and the soils derived from them have elevated concentrations of Cr and Ni. Surface soil samples derived from UM rocks of the Sierra Nevada and Coast Range contain 1700-10,000 mg/kg Cr and 1300-3900 mg/kg Ni. Valley soils west of the Sacramento River contain 80-1420 mg/kg Cr and 65-224 mg/kg Ni, reflecting significant contributions from UM sources in the Coast Range. Valley soils on the east side contain 30-370 mg/kg Cr and 16-110 mg/kg Ni. Lower Cr and Ni concentrations on the east side of the valley are the result of greater dilution by granitic sources of the Sierra Nevada. Chromium occurs naturally in the Cr(III) and Cr(VI) oxidation states. Trivalent Cr is a non-toxic micronutrient, but Cr(VI) is a highly soluble toxin and carcinogen. X-ray diffraction and scanning electron microscopy of soils with an UM parent show Cr primarily occurs within chromite and other mixed-composition spinels (Al, Mg, Fe, Cr). Chromite contains Cr(III) and is highly refractory with respect to weathering. Comparison of a 4-acid digestion (HNO3, HCl, HF, HClO4), which only partially dissolves chromite, and total digestion by lithium metaborate (LiBO3) fusion, indicates a lower proportion of chromite-bound Cr in valley soils relative to UM source soils. Groundwater on the west side of the Sacramento Valley has particularly high concentrations of dissolved Cr ranging up to 50 ??g L-1 and averaging 16.4 ??g L-1. This suggests redistribution of Cr during weathering and oxidation of Cr(III)-bearing minerals. It is concluded that regional-scale transport and weathering of ultramafic-derived constituents have resulted in enrichment of Cr and Ni in the Sacramento Valley and a partial change in the residence of Cr.

Electron energy loss spectroscopy analysis of lithium deintercalated Li5/3-xTi7/3CrO7

NASA Astrophysics Data System (ADS)

Díaz-Carrasco, P.; Moreau, P.; Guyomard, D.; Kuhn, A.; García-Alvarado, F.

2006-05-01

Electron energy loss spectroscopy has been used to investigate the average oxidation state of Cr in both electrochemically and chemically delithiathed Li5/3-xTi7/3CrO7. The O K edge, Ti L2,3 and Cr L2,3 edge were monitored. Upon removal of Li ions, the oxygen K edge shows a continuous change while the Cr L edges remain almost unchanged. The Cr 2p multiplet was compared with reference samples (Cr2O3, CrO2 and K2Cr2O7) in order to assess on the sensitivity of the Cr L-edge to the oxidation state of chromium ion. The similarity between the Cr L spectra of Cr2O3 and CrO2 makes the valence analysis difficult in Li5/3-xTi7/3CrO7 but the presence of CrVI is excluded in oxidized samples. However, evolution of the low energy loss spectra observed in the 10 15 eV region confirms the modification of the electronic structure and partial oxidation of CrIII to CrIV.

Topotecan-Vincristine-Doxorubicin in Stage 4 High-Risk Neuroblastoma Patients Failing to Achieve a Complete Metastatic Response to Rapid COJEC: A SIOPEN Study.

PubMed

Amoroso, Loredana; Erminio, Giovanni; Makin, Guy; Pearson, Andrew D J; Brock, Penelope; Valteau-Couanet, Dominique; Castel, Victoria; Pasquet, Marlène; Laureys, Genevieve; Thomas, Caroline; Luksch, Roberto; Ladenstein, Ruth; Haupt, Riccardo; Garaventa, Alberto

2018-01-01

Metastatic response to induction therapy for high-risk neuroblastoma is a prognostic factor. In the International Society of Paediatric Oncology Europe Neuroblastoma (SIOPEN) HR-NBL-1 protocol, only patients with metastatic complete response (CR) or partial response (PR) with ≤ three abnormal skeletal areas on iodine 123-metaiodobenzylguanidine ([ 123 I]mIBG) scintigraphy and no bone marrow disease proceed to high dose therapy (HDT). In this study, topotecan-vincristine-doxorubicin (TVD) was evaluated in patients failing to achieve these criteria, with the aim of improving the metastatic response rate. Patients with metastatic high-risk neuroblastoma who had not achieved the SIOPEN criteria for HDT after induction received two courses of topotecan 1.5 mg/m 2 /day for 5 days, followed by a 48-hour infusion of vincristine, 2 mg/m 2 , and doxorubicin, 45 mg/m 2 . Sixty-three patients were eligible and evaluable. Following two courses of TVD, four (6.4%) patients had an overall CR, while 28 (44.4%) had a PR with a combined response rate of 50.8% (95% confidence interval [CI], 37.9 to 63.6). Of these, 23 patients achieved a metastatic CR or a PR with ≤ 3 mIBG skeletal areas and no bone marrow disease (36.5%; 95% CI, 24.7 to 49.6) and were eligible to receive HDT. Toxicity was mostly haematological, affecting 106 of the 126 courses (84.1%; 95% CI, 76.5 to 90.0), and dose reduction was necessary in six patients. Stomatitis was the second most common nonhematological toxicity, occurring in 20 patients (31.7%). TVD was effective in improving the response rate of high-risk neuroblastoma patients after induction with COJEC enabling them to proceed to HDT. However, the long-term benefits of TVD needs to be determined in randomized clinical trials.

Topotecan-Vincristine-Doxorubicin in Stage 4 High-Risk Neuroblastoma Patients Failing to Achieve a Complete Metastatic Response to Rapid COJEC: A SIOPEN Study

PubMed Central

Amoroso, Loredana; Erminio, Giovanni; Makin, Guy; Pearson, Andrew D. J.; Brock, Penelope; Valteau-Couanet, Dominique; Castel, Victoria; Pasquet, Marlène; Laureys, Genevieve; Thomas, Caroline; Luksch, Roberto; Ladenstein, Ruth; Haupt, Riccardo; Garaventa, Alberto

2018-01-01

Purpose Metastatic response to induction therapy for high-risk neuroblastoma is a prognostic factor. In the International Society of Paediatric Oncology Europe Neuroblastoma (SIOPEN) HR-NBL-1 protocol, only patients with metastatic complete response (CR) or partial response (PR) with ≤ three abnormal skeletal areas on iodine 123-metaiodobenzylguanidine ([123I]mIBG) scintigraphy and no bone marrow disease proceed to high dose therapy (HDT). In this study, topotecan-vincristine-doxorubicin (TVD) was evaluated in patients failing to achieve these criteria, with the aim of improving the metastatic response rate. Materials and Methods Patients with metastatic high-risk neuroblastoma who had not achieved the SIOPEN criteria for HDT after induction received two courses of topotecan 1.5 mg/m2/day for 5 days, followed by a 48-hour infusion of vincristine, 2 mg/m2, and doxorubicin, 45 mg/m2. Results Sixty-three patients were eligible and evaluable. Following two courses of TVD, four (6.4%) patients had an overall CR, while 28 (44.4%) had a PR with a combined response rate of 50.8% (95% confidence interval [CI], 37.9 to 63.6). Of these, 23 patients achieved a metastatic CR or a PR with ≤ 3 mIBG skeletal areas and no bone marrow disease (36.5%; 95% CI, 24.7 to 49.6) and were eligible to receive HDT. Toxicity was mostly haematological, affecting 106 of the 126 courses (84.1%; 95% CI, 76.5 to 90.0), and dose reduction was necessary in six patients. Stomatitis was the second most common nonhematological toxicity, occurring in 20 patients (31.7%). Conclusion TVD was effective in improving the response rate of high-risk neuroblastoma patients after induction with COJEC enabling them to proceed to HDT. However, the long-term benefits of TVD needs to be determined in randomized clinical trials. PMID:28324923

Low-Dose Radiation Therapy (2 Gy × 2) in the Treatment of Orbital Lymphoma

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

Fasola, Carolina E.; Jones, Jennifer C.; Huang, Derek D.

2013-08-01

Purpose: Low-dose radiation has become increasingly used in the management of indolent non-Hodgkin lymphoma (NHL), but has not been studied specifically for cases of ocular adnexal involvement. The objective of this study is to investigate the effectiveness of low-dose radiation in the treatment of NHL of the ocular adnexa. Methods and Materials: We reviewed the records of 20 NHL patients with 27 sites of ocular adnexal involvement treated with low-dose radiation consisting of 2 successive fractions of 2 Gy at our institution between 2005 and 2011. The primary endpoint of this study is freedom from local relapse (FFLR). Results: Atmore » a median follow-up time of 26 months (range 7-92), the overall response rate for the 27 treated sites was 96%, with a complete response (CR) rate of 85% (n=23) and a partial response rate of 11% (n=3). Among all treated sites with CR, the 2-year FFLR was 100%, with no in-treatment field relapses. The 2-year freedom from regional relapse rate was 96% with 1 case of relapse within the ipsilateral orbit (outside of the treatment field). This patient underwent additional treatment with low-dose radiation of 4 Gy to the area of relapse achieving a CR and no evidence of disease at an additional 42 months of follow-up. Orbital radiation was well tolerated with only mild acute side effects (dry eye, conjunctivitis, transient periorbital edema) in 30% of treated sites without any reports of long-term toxicity. Conclusions: Low-dose radiation with 2 Gy × 2 is effective and well tolerated in the treatment of indolent NHL of the ocular adnexa with high response rates and durable local control with the option of reirradiation in the case of locoregional relapse.« less

Bendamustine in Combination With Gemcitabine and Vinorelbine Is an Effective Regimen As Induction Chemotherapy Before Autologous Stem-Cell Transplantation for Relapsed or Refractory Hodgkin Lymphoma: Final Results of a Multicenter Phase II Study.

PubMed

Santoro, Armando; Mazza, Rita; Pulsoni, Alessandro; Re, Alessandro; Bonfichi, Maurizio; Zilioli, Vittorio Ruggero; Salvi, Flavia; Merli, Francesco; Anastasia, Antonella; Luminari, Stefano; Annechini, Giorgia; Gotti, Manuel; Peli, Annalisa; Liberati, Anna Marina; Di Renzo, Nicola; Castagna, Luca; Giordano, Laura; Carlo-Stella, Carmelo

2016-09-20

This multicenter, open-label, phase II study evaluated the combination of bendamustine, gemcitabine, and vinorelbine (BeGEV) as induction therapy before autologous stem-cell transplantation (ASCT) in patients with relapsed or refractory Hodgkin lymphoma (HL). Patients with HL who were refractory to or had relapsed after one previous chemotherapy line were eligible. The primary end point was complete response (CR) rate after four cycles of therapy. Secondary end points were: overall response rate, stem-cell mobilization activity, and toxicity. Progression-free and overall survival were also evaluated. In total, 59 patients were enrolled. After four cycles of therapy, 43 patients (73%) achieved CR, and six (10%) achieved partial response, for an overall response rate of 83%. The most common grade 3 to 4 nonhematologic toxicities included febrile neutropenia (n = 7) and infection (n = 4). Regarding hematologic toxicities, grade 3 to 4 thrombocytopenia and neutropenia were each experienced by eight patients (13.5%). CD34+ cells were successfully harvested in 55 of 57 evaluable patients, and 43 of 49 responding patients underwent ASCT. With a median follow-up of 29 months, the 2-year progression-free and overall survival rates for the total population were 62.2% and 77.6%, respectively. The same figures for patients undergoing autograft were 80.8% and 89.3%, respectively. This phase II study demonstrates that BeGEV is an effective salvage regimen able to induce CR in a high proportion of patients with relapsed or refractory HL before ASCT. These data provide a strong rationale for further development of the BeGEV regimen. © 2016 by American Society of Clinical Oncology.

[Post-therapeutic evolution and prognostic factors of intestinal lymphomas, Retrospective analysis of 42 cases].

PubMed

Sánchez-Fayos, M P; Hernández Guío, C; Rivas, M C; Outeiriño, J; González-Campos, C; Lobo, F

1993-12-01

To evaluate in retrospect the response to therapy and long-term evolution of a series of primitive intestinal lymphomas. The series was comprised of 42 patients diagnosed in our hospital during 1960-1962. The mean age was 34.5 years (range, 3-73), the M/F ratio was 21/21, and the histopathology distributes as follows: high grade (HG), 24 cases, low grade (LG), 12 cases, and mixed (LG/HG), 6 cases. B/T immunophenotype: 40/2. Staging: IE1,29 cases, IIE2-IV, 11 cases. The treatment applied in the series was classified in various types: ample surgical resection (aSR), 21 cases; partial surgical resection (pSR), 9 cases; abdominal radiation therapy (RT), 7 cases; monochemotherapy (MCT), 7 cases, and polychemotherapy (PCT), 28 cases. The correlation of clinicobiological variables with immediate response to treatment was evaluated by means of the chi square test, and the acturial post-therapeutic survival curves in accordance to the life tables, differences being calculated by the log rank test. Small intestine was the commonest site of involvement, 31 cases; ileocecal region, 7 cases; colon, 2 cases, and colon plus small intestine, 2 cases. Regardless of therapy type, complete remission (CR) was attained in 20 patients (47.5%), partial remission in 5; 11 cases were unresponsive (26.5%) and early death occurred in 6 instances (14.2%). The acturial post-therapeutic survival offered an 8-year expectancy of 47%. The correlation between immediate complete response and 16 clinico-biologic variables showed favourable significance for tumoral proliferation index (i.e., Pc10-positive cells < 15%) and for therapeutic regimens including PCT+aSR. On the other hand, the necessity of emergency surgery for diagnosis was a poor-risk factor. The correlation between a post-therapeutic survival and 19 other variables showed the following as favorable data: female sex, tumour proliferative index (i.e., Pc10-positive cells < 15%), the use of PCT+aSR, and attaining CR. Poor-risk factors were the need of emergency surgery, multicentric lymphomatous involvement and serum LDH rates 350 UI/L. Although immediate response (CR) and long-term results (survival) were better in the patients with favourable histology (LG+LG/HG) and in those with loco-regional disease (stages IE-IE1), the differences had no statistical significance, possibly due to the low number of cases. 1) Even though these findings should be carefully evaluated, dut to lack of homogeneity of the series and the fact of being a retrospective study, the rate of CR in this series (47.5%) is similar to that of current studies. 2) Female sex, type of therapy, multifocal involvement, the need of emergency surgery and high LDH levels have significant value in univariate analyses.

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

Choudhary, Renu; Department of Physics and Astronomy and NCMN, University of Nebraska, Lincoln, NE 68588; Kharel, Parashu

Disordered CoFeCrAl and CoFeCrSi{sub 0.5}Al{sub 0.5} alloys have been investigated experimentally and by first-principle calculations. The melt-spun and annealed samples all exhibit Heusler-type superlattice peaks, but the peak intensities indicate a substantial degree of B2-type chemical disorder. Si substitution reduces the degree of this disorder. Our theoretical analysis also considers several types of antisite disorder (Fe-Co, Fe-Cr, Co-Cr) in Y-ordered CoFeCrAl and partial substitution of Si for Al. The substitution transforms the spin-gapless semiconductor CoFeCrAl into a half-metallic ferrimagnet and increases the half-metallic band gap by 0.12 eV. Compared CoFeCrAl, the moment of CoFeCrSi{sub 0.5}Al{sub 0.5} is predicted to increasemore » from 2.01 μ{sub B} to 2.50 μ{sub B} per formula unit, in good agreement with experiment.« less

Laboratory investigations of the effects of nitrification-induced acidification on Cr cycling in vadose zone material partially derived from ultramafic rocks

USGS Publications Warehouse

Mills, Christopher T.; Goldhaber, Martin B.

2012-01-01

Sacramento Valley (California, USA) soils and sediments have high concentrations of Cr(III) because they are partially derived from ultramafic material. Some Cr(III) is oxidized to more toxic and mobile Cr(VI) by soil Mn oxides. Valley soils typically have neutral to alkaline pH at which Cr(III) is highly immobile. Much of the valley is under cultivation and is both fertilized and irrigated. A series of laboratory incubation experiments were conducted to assess how cultivation might impact Cr cycling in shallow vadose zone material from the valley. The first experiments employed low (7.1 mmol N per kg soil) and high (35 mmol N kg− 1) concentrations of applied (NH4)2SO4. Initially, Cr(VI) concentrations were up to 45 and 60% greater than controls in low and high incubations, respectively. After microbially-mediated oxidation of all NH4+, Cr(VI) concentrations dropped below control values. Increased nitrifying bacterial populations (estimated by measurement of phospholipid fatty acids) may have increased the Cr(VI) reduction capacity of the vadose zone material resulting in the observed decreases in Cr(VI). Another series of incubations employed vadose zone material from a different location to which low (45 meq kg− 1) and high (128 meq kg− 1) amounts of NH4Cl, KCl, and CaCl2 were applied. All treatments, except high concentration KCl, resulted in mean soil Cr(VI) concentrations that were greater than the control. High concentrations of water-leachable Ba2 + (mean 38 μmol kg− 1) in this treatment may have limited Cr(VI) solubility. A final set of incubations were amended with low (7.1 mmol N kg− 1) and high (35 mmol N kg− 1) concentrations of commercial liquid ammonium polyphosphate (APP) fertilizer which contained high concentrations of Cr(III). Soil Cr(VI) in the low APP incubations increased to a concentration of 1.8 μmol kg− 1 (5 × control) over 109 days suggesting that Cr(III) added with the APP fertilizer was more reactive than naturally-occurring soil Cr(III).

RedOx-controlled sorption of iodine anions by hydrotalcite composites

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

Levitskaia, Tatiana G.; Chatterjee, Sayandev; Arey, Bruce W.

2016-01-01

The radioactive contaminant iodine-129 (I-129) is one of the top risk drivers at radiological waste disposal and contaminated groundwater sites where nuclear material fabrication or reprocessing has occurred. Currently there are very few options available to treat I-129 in the groundwater, which is partially related to its complex biogeochemical behavior in the subsurface and occurrence in the multiple chemical forms. We hypothesize that layered hydrotalcite materials containing redox active transition metal ions offer a potential solution, benefiting from the simultaneous adsorption of iodate (IO3-) and iodide (I-) anions, which exhibit different electronic and structural properties and therefore may require dissimilarmore » hosts. To test this hypothesis, Cr3+- based materials were selected based on the rationale that Cr3+ readily reduces IO3- in solution. It was combined with either redox-active Co2+ or redox-inactive Ni2+ so that two model materials were prepared by hydrothermal synthesis including Co2+-Cr3+ and Ni2+-Cr3+(M-Cr). Obtained M-Cr materials comprised of Co2+-Cr3+ or Ni2+-Cr3+ layered hydrotalcite and small fractions of Co3O4 spinel or Ni(OH)2 theophrastite phases were structurally characterized before and after uptake of periodate (IO4-), IO3-, and I- anions. It was found that the IO3- uptake is driven by its chemical reduction to I2 and I-. Interestingly, in the Co2+-Cr3+ hydrotalcite, Co2+ and not Cr3+ serves as a reductant while in the Ni2+-Cr3+ hydrotalcite Cr3+ is responsible for the reduction of IO3-. A different uptake mechanism was identified for the IO4- anion. The Co2+-Cr3+ hydrotalcite phase efficiently uptakes IO4- by a diffusion-limited ion exchange mechanism and is not accompanied by the redox process, while Cr3+ in the Ni2+-Cr3+ hydrotalcite reduces IO4- to IO3-, I2 and I-. Iodide exhibited high affinity only to the Co-Cr material. The Co-Cr material performed remarkably well for the removal of IO3-, I- and total iodine from the groundwater collected from the US DOE Hanford site, WA, USA outperforming non-redox active hydrotalcites (e.g., Mg2+-Al3+) reported previously. This work demonstrates that redox-controlled sorption can be a highly effective method for the treatment of anions based on elements with mobile oxidation states. Further, multiple anions of interest could be simultaneously removed through combination of approaches.« less

Evaluation of ifosfamide salvage therapy for metastatic canine osteosarcoma.

PubMed

Batschinski, K; Dervisis, N G; Kitchell, B E

2014-12-01

A retrospective study was performed to assess toxicity and response rate of ifosfamide salvage treatment for dogs diagnosed with metastatic osteosarcoma (OSA). Dogs diagnosed with OSA and previously treated with standard chemotherapy were included in the study. Nineteen dogs met the inclusion criteria, and 17 dogs were evaluable for response. Ifosfamide doses ranged from 375 to 425 mg m(-2) (median dose 375 mg m(-2)), with a median of two doses administered per dog (range 1-7 doses). The overall response to ifosfamide was 11.8% [complete response (CR) = 1/17, partial response (PR) = 1/17, stable disease (SD) = 2/17, progressive disease (PD) = 13/17]. Two dogs were hospitalized due to ifosfamide toxicosis. The median survival duration from the first dose of ifosfamide to death was 95 days. Ifosfamide was well tolerated, but minor anti-tumour activity was observed. © 2012 Blackwell Publishing Ltd.

Local atomic structure of Fe/Cr multilayers: Depth-resolved method

NASA Astrophysics Data System (ADS)

Babanov, Yu. A.; Ponomarev, D. A.; Devyaterikov, D. I.; Salamatov, Yu. A.; Romashev, L. N.; Ustinov, V. V.; Vasin, V. V.; Ageev, A. L.

2017-10-01

A depth-resolved method for the investigation of the local atomic structure by combining data of X-ray reflectivity and angle-resolved EXAFS is proposed. The solution of the problem can be divided into three stages: 1) determination of the element concentration profile with the depth z from X-ray reflectivity data, 2) determination of the X-ray fluorescence emission spectrum of the element i absorption coefficient μia (z,E) as a function of depth and photon energy E using the angle-resolved EXAFS data Iif (E , ϑl) , 3) determination of partial correlation functions gij (z , r) as a function of depth from μi (z , E) . All stages of the proposed method are demonstrated on a model example of a multilayer nanoheterostructure Cr/Fe/Cr/Al2O3. Three partial pair correlation functions are obtained. A modified Levenberg-Marquardt algorithm and a regularization method are applied.

Clinical factors of response in patients with advanced ovarian cancer participating in early phase clinical trials.

PubMed

George, Angela; Kristeleit, Rebecca; Rafii, Saeed; Michie, Caroline O; Bowen, Rebecca; Michalarea, Vasiliki; van Hagen, Tom; Wong, Mabel; Rallis, Grigorios; Molife, L Rhoda; Lopez, Juanita; Banerji, Udai; Banerjee, Susana N; Gore, Martin E; de Bono, Johann S; Kaye, Stan B; Yap, Timothy A

2017-05-01

Drug resistance to conventional anticancer therapies is almost inevitable in patients with advanced ovarian cancer (AOC), limiting their available treatment options. Novel phase I trial therapies within a dedicated drug development unit may represent a viable alternative; however, there is currently little evidence for patient outcomes in such patients. To address this, we undertook a retrospective review of patients with AOC allocated to phase I trials in the Drug Development Unit at Royal Marsden Hospital (RMH) between June 1998 and October 2010. A total of 200 AOC patients with progressive disease were allocated to ≥1 trial each, with a total of 281 allocations. Of these, 135 (68%) patients commenced ≥1 trial (mean 1.4 [1-8]), totaling 216 allocated trials; 65 (32%) patients did not start due to deterioration resulting from rapidly progressive disease (63 patients) or patient choice (2 patients). Response Evaluation Criteria in Solid Tumours (RECIST) complete/partial responses (CR/PR) were observed in 43 (20%) of those starting trials, including those on poly(ADP-ribose) polymerase (PARP) inhibitors (18/79 [23%]), antiangiogenics (9/65 [14%]) and chemotherapy combinations (14/43 [33%]). Factors associated with CR/PR included: fewer prior treatments, platinum-sensitive disease, CR/PR with prior therapy, (the United States-based) Eastern Cooperative Oncology Group (ECOG) performance status score, fewer metastatic sites, higher albumin and haemoglobin levels, lower white cell counts and baseline CA125 levels, germline BRCA1/2 mutations and better RMH Prognostic Score. Mean survival was 32° months for patients who achieved CR/PR. Treatments were generally well tolerated. Most patients with AOC (134/200 [67%]) received ≥1 subsequent line of therapy after phase I trials. Our data suggest that phase I trial referrals should be considered earlier in the AOC treatment pathway and before the onset of rapid disease progression particularly with the emergence of promising novel agents in the era of precision medicine. Copyright © 2017 Elsevier Ltd. All rights reserved.

The efficacy of radiation therapy in the treatment of Graves' orbitopathy.

PubMed

Matthiesen, Chance; Thompson, J Spencer; Thompson, David; Farris, Bradley; Wilkes, Byron; Ahmad, Salahuddin; Herman, Terence; Bogardus, Carl

2012-01-01

To review our institutional outcomes of patients treated with radiation therapy (RT) for Graves' orbitopathy (GO), assess the role of orbital reirradiation, and identify prognostic factors of complete response (CR). This is a retrospective review of 211 patients who presented with a diagnosis of GO and received RT between January 2000-2010. RT dose was 20 Gy in 10 fractions. Patient median age was 51 years (range, 15-84 years), median follow-up was 11 months (range, 1-88 months). Patient symptoms included any combination of proptosis (90.9%), extraocular muscle dysfunction (78.9%), soft tissue signs (68.4%), and diplopia (58.4%). Corticosteroids were used as first-line therapy in 20.6% of patients. Among those who achieved either CR or partial response (PR), prognostic factors were evaluated. Stabilization of disease without recurrence was clinically achieved overall in 202 patients (96.7%). At the completion of RT, 176 patients (84.2%) reported a symptomatic improvement of pretreatment symptoms. CR of GO symptoms was achieved using multiple treatment modalities, including RT by 93 patients (44.5%), of which 32 patients received RT only. Corticosteroids were discontinued in 97.8% of patients who received them as initial therapy. Surgical intervention following radiotherapy was required for 144 (68.9%) of all patients. Fourteen patients received orbital reirradiation for persistent or recurrent symptoms. Five of these achieved a CR, and the other nine achieved disease stabilization but retained persistent ocular symptoms. Long-term side effects of RT included dry eyes (12%). Of the prognostic factors we investigated, only gender predicted CR, which was less common in men (33.9%) than in women (49.7%) p = 0.0471. Orbital radiation for GO is an established treatment modality for patients. Orbital reirradiation is beneficial for patients who do not respond to initial RT or experience symptom recurrence without an apparent risk of increased morbidity. Copyright © 2012 Elsevier Inc. All rights reserved.

The Impact of Cross-track Infrared Sounder (CrIS) Cloud-Cleared Radiances on Hurricane Joaquin (2015) and Matthew (2016) Forecasts

NASA Astrophysics Data System (ADS)

Wang, Pei; Li, Jun; Li, Zhenglong; Lim, Agnes H. N.; Li, Jinlong; Schmit, Timothy J.; Goldberg, Mitchell D.

2017-12-01

Hyperspectral infrared (IR) sounders provide high vertical resolution atmospheric sounding information that can improve the forecast skill in numerical weather prediction. Commonly, only clear radiances are assimilated, because IR sounder observations are highly affected by clouds. A cloud-clearing (CC) technique, which removes the cloud effects from an IR cloudy field of view (FOV) and derives the cloud-cleared radiances (CCRs) or clear-sky equivalent radiances, can be an alternative yet effective way to take advantage of the thermodynamic information from cloudy skies in data assimilation. This study develops a Visible Infrared Imaging Radiometer Suite (VIIRS)-based CC method for deriving Cross-track Infrared Sounder (CrIS) CCRs under partially cloudy conditions. Due to the lack of absorption bands on VIIRS, two important quality control steps are implemented in the CC process. Validation using VIIRS clear radiances indicates that the CC method can effectively obtain the CrIS CCRs for FOVs with partial cloud cover. To compare the impacts from assimilation of CrIS original radiances and CCRs, three experiments are carried out on two storm cases, Hurricane Joaquin (2015) and Hurricane Matthew (2016), using Gridpoint Statistical Interpolation assimilation system and Weather Research and Forecasting-Advanced Research Version models. At the analysis time, more CrIS observations are assimilated when using CrIS CCRs than with CrIS original radiances. Comparing temperature, specific humidity, and U/V winds with radiosondes indicates that the data impacts are growing larger with longer time forecasts (beyond 72 h forecast). Hurricane track forecasts also show improvements from the assimilation of CrIS CCRs due to better weather system forecasts. The impacts of CCRs on intensity are basically neutral with mixed positive and negative results.

Simultaneous PET/MRI in assessing the response to chemo/radiotherapy in head and neck carcinoma: initial experience.

PubMed

Romeo, Valeria; Iorio, Brigida; Mesolella, Massimo; Ugga, Lorenzo; Verde, Francesco; Nicolai, Emanuele; Covello, Mario

2018-06-19

The purpose of the study was to assess by simultaneous positron emission tomography/magnetic resonance imaging (PET/MRI) the response to chemotherapy (CHT) and/or radiotherapy (RT) in patients with head and neck squamous cell carcinoma (HNSCC). Five patients with HNSCC underwent simultaneous PET/MRI examination before and after CHT and/or RT. Standard uptake volume (SUV), apparent diffusion coefficient (ADC), Ktrans, Kep, Ve, and iAUC pre- and post-treatment values were extracted and compared. The response to treatment was assessed according to RECIST criteria and classified as complete response (CR), partial response (PR), stable disease (SD), and progression disease (PD). In patient 1, PR was observed with increased ADC, Ktrans, and Ve values and reduction of SUV, iAUC, and Kep values; during clinical and instrumental follow-up, the patient experienced disease progression. Patient 2, classified as PR, showed increased ADC values and reduction of SUV and all perfusion parameters; follow-up demonstrated disease stability. Patient 3, considered as SD, showed increase of ADC and all perfusion values with a mild decrease of SUV; PD was observed during clinical and instrumental follow-up. Patients 4 and 5 showed a CR with no detectable tumor lesions at post-treatment PET/MRI examination, confirmed by 1-year follow-up. Multiparametric evaluation with simultaneous PET/MRI could be a useful tool to assess and predict the response to CHT and/or RT in patients with HNSCC.

Rescaling of temporal expectations during extinction

PubMed Central

Drew, Michael R.; Walsh, Carolyn; Balsam, Peter D

2016-01-01

Previous research suggests that extinction learning is temporally specific. Changing the CS duration between training and extinction can facilitate the loss of the CR within the extinction session but impairs long-term retention of extinction. In two experiments using conditioned magazine approach with rats, we examined the relation between temporal specificity of extinction and CR timing. In Experiment 1 rats were trained on a 12-s, fixed CS-US interval and then extinguished with CS presentations that were 6, 12, or 24 s in duration. The design of Experiment 2 was the same except rats were trained using partial rather than continuous reinforcement. In both experiments, extending the CS duration in extinction facilitated the diminution of CRs during the extinction session, but shortening the CS duration failed to slow extinction. In addition, extending (but not shortening) the CS duration caused temporal rescaling of the CR, in that the peak CR rate migrated later into the trial over the course of extinction training. This migration partially accounted for the faster loss of the CR when the CS duration was extended. Results are incompatible with the hypothesis that extinction is driven by cumulative CS exposure and suggest that temporally extended nonreinforced CS exposure reduces conditioned responding via temporal displacement rather than through extinction per se. PMID:28045291

Low-Degree Partial Melting Experiments of CR and H Chondrite Compositions: Implications for Asteroidal Magmatism Recorded in GRA 06128 and GRA 06129 T

NASA Technical Reports Server (NTRS)

Usui, T.; Jones, John H.; Mittlefehldt, D. W.

2010-01-01

Studies of differentiated meteorites have revealed a diversity of differentiation processes on their parental asteroids; these differentiation mechanisms range from whole-scale melting to partial melting without the core formation [e.g., 1]. Recently discovered paired achondrites GRA 06128 and GRA 06129 (hereafter referred to as GRA) represent unique asteroidal magmatic processes. These meteorites are characterized by high abundances of sodic plagioclase and alkali-rich whole-rock compositions, implying that they could originate from a low-degree partial melt from a volatile-rich oxidized asteroid [e.g., 2, 3, 4]. These conditions are consistent with the high abundances of highly siderophile elements, suggesting that their parent asteroid did not segregate a metallic core [2]. In this study, we test the hypothesis that low-degree partial melts of chondritic precursors under oxidizing conditions can explain the whole-rock and mineral chemistry of GRA based on melting experiments of synthesized CR- and H-chondrite compositions.

Does laboratory cue reactivity correlate with real-world craving and smoking responses to cues?

PubMed

Shiffman, Saul; Li, Xiaoxue; Dunbar, Michael S; Tindle, Hilary A; Scholl, Sarah M; Ferguson, Stuart G

2015-10-01

Laboratory cue reactivity (CR) assessments are used to assess smokers' responses to cues. Likewise, EMA recording is used to characterize real-world response to cues. Understanding the relationship between CR and EMA responses addresses the ecological validity of CR. In 190 daily smokers not currently quitting, craving and smoking responses to cues were assessed in laboratory CR and by real-world EMA recording. Separate CR sessions involved 5 smoking-relevant cues (smoking, alcohol, negative affect, positive affect, smoking prohibitions), and a neutral cue. Subjects used EMA to monitor smoking situations for 3 weeks, completing parallel situational assessments (presence of others smoking, alcohol consumption, negative affect, positive affect, and smoking prohibitions, plus current craving) in smoking and non-smoking occasions (averaging 70 and 60 occasions each). Analyses correlated CR craving and smoking cue responses with EMA craving and smoking correlations with similar cues. Although some cues did not show main effects on average craving or smoking, a wide range of individual differences in response to cues was apparent in both CR and EMA data, providing the necessary context to assess their relationship. Laboratory CR measures of cue response were not correlated with real-world cue responses assessed by EMA. The average correlation was 0.03; none exceeded 0.32. One of 40 correlations examined was significantly greater than 0. Laboratory CR measures do not correlate with EMA-assessed craving or smoking in response to cues, suggesting that CR measures are not accurate predictors of how smokers react to relevant stimuli in the real world. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Nano-sized Fe2O3/Fe3O4 facilitate anaerobic transformation of hexavalent chromium in soil-water systems.

PubMed

Zhang, Yaxian; Li, Hua; Gong, Libo; Dong, Guowen; Shen, Liang; Wang, Yuanpeng; Li, Qingbiao

2017-07-01

The purpose of this study is to investigate the effects of nano-sized or submicro Fe 2 O 3 /Fe 3 O 4 on the bioreduction of hexavalent chromium (Cr(VI)) and to evaluate the effects of nano-sized Fe 2 O 3 /Fe 3 O 4 on the microbial communities from the anaerobic flooding soil. The results indicated that the net decreases upon Cr(VI) concentration from biotic soil samples amended with nano-sized Fe 2 O 3 (317.1±2.1mg/L) and Fe 3 O 4 (324.0±22.2mg/L) within 21days, which were approximately 2-fold of Cr(VI) concentration released from blank control assays (117.1±5.6mg/L). Furthermore, the results of denaturing gradient gel electrophoresis (DGGE) and high-throughput sequencing indicated a greater variety of microbes within the microbial community in amendments with nano-sized Fe 2 O 3 /Fe 3 O 4 than the control assays. Especially, Proteobacteria occupied a predominant status on the phylum level within the indigenous microbial communities from chromium-contaminated soils. Besides, some partial decrease of soluble Cr(VI) in abiotic nano-sized Fe 2 O 3 /Fe 3 O 4 amendments was responsible for the adsorption of nano-sized Fe 2 O 3 /Fe 3 O 4 to soluble Cr(VI). Hence, the presence of nano-sized Fe 2 O 3 /Fe 3 O 4 could largely facilitate the mobilization and biotransformation of Cr(VI) from flooding soils by adsorption and bio-mediated processes. Copyright © 2017. Published by Elsevier B.V.

Effects of the impurity-host interactions on the nonradiative processes in ZnS:Cr

NASA Astrophysics Data System (ADS)

Tablero, C.

2010-11-01

There is a great deal of controversy about whether the behavior of an intermediate band in the gap of semiconductors is similar or not to the deep-gap levels. It can have significant consequences, for example, on the nonradiative recombination. In order to analyze the behavior of an intermediate band, we have considered the effect of the inward and outward displacements corresponding to breathing and longitudinal modes of Cr-doped ZnS and on the charge density for different processes involved in the nonradiative recombination using first-principles. This metal-doped zinc chalcogenide has a partially filled band within the host semiconductor gap. In contrast to the properties exhibited by deep-gap levels in other systems, we find small variations in the equilibrium configurations, forces, and electronic density around the Cr when the nonradiative recombination mechanisms modify the intermediate band charge. The charge density around the impurity is equilibrated in response to the perturbations in the equilibrium nuclear configuration and the charge of the intermediate band. The equilibration follows a Le Chatelier principle through the modification of the contribution from the impurity to the intermediate band and to the valence band. The intermediate band introduced by Cr in ZnS for the concentrations analyzed makes the electronic capture difficult and later multiphonon emission in the charge-transfer processes, in accordance with experimental results.

Icotinib and whole-brain radiotherapy for the treatment in patients with brain metastases from EGFR-mutant nonsmall cell lung cancer

PubMed Central

Jiang, Ai-Ying; Zhang, Jing; Luo, Hai-Long; Gao, Feng; Lv, Yu-Feng

2018-01-01

Abstract This study aimed to explore the effect and toxicity of icotinib and whole-brain radiotherapy (IWBRT) for the treatment of brain metastases from nonsmall cell lung cancer (BMNSCLC) with epidermal growth factor receptor (EGFR)-mutant among Chinese Han population. A total of 55 patients with EGFR-mutant BMNSCLC were included. They received orally icotinib (125 mg/tablet, 125 mg each time, 3 times daily) until disease progression. In addition, they also underwent whole-brain radiotherapy (3-Gy fractions once daily, 5 days weekly for a total dose of 30 Gy) in an attempt to extend their survival time. The outcomes consisted of complete response (CR), partial response (PR), stable disease (SD), progress disease (PD), overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). In addition, toxicity was also recorded in this study. The CR, PR, SD, PD, ORR, PFS, and OS were 38.2%, 52.8%, 5.4%, 3.6%, 90.1%, 12.5%, and 48.0% months, respectively. In addition, mild toxicity was observed in this study. This study demonstrated that IWBRT is efficacious with acceptable toxicity for patients with EGFR-mutant BMNSCLC among Chinese Han population. PMID:29642161

Icotinib and whole-brain radiotherapy for the treatment in patients with brain metastases from EGFR-mutant nonsmall cell lung cancer: A retrospective study.

PubMed

Jiang, Ai-Ying; Zhang, Jing; Luo, Hai-Long; Gao, Feng; Lv, Yu-Feng

2018-04-01

This study aimed to explore the effect and toxicity of icotinib and whole-brain radiotherapy (IWBRT) for the treatment of brain metastases from nonsmall cell lung cancer (BMNSCLC) with epidermal growth factor receptor (EGFR)-mutant among Chinese Han population.A total of 55 patients with EGFR-mutant BMNSCLC were included. They received orally icotinib (125 mg/tablet, 125 mg each time, 3 times daily) until disease progression. In addition, they also underwent whole-brain radiotherapy (3-Gy fractions once daily, 5 days weekly for a total dose of 30 Gy) in an attempt to extend their survival time. The outcomes consisted of complete response (CR), partial response (PR), stable disease (SD), progress disease (PD), overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). In addition, toxicity was also recorded in this study.The CR, PR, SD, PD, ORR, PFS, and OS were 38.2%, 52.8%, 5.4%, 3.6%, 90.1%, 12.5%, and 48.0% months, respectively. In addition, mild toxicity was observed in this study.This study demonstrated that IWBRT is efficacious with acceptable toxicity for patients with EGFR-mutant BMNSCLC among Chinese Han population.

CHOP plus etoposide and gemcitabine (CHOP-EG) as front-line chemotherapy for patients with peripheral T cell lymphomas.

PubMed

Kim, Jong Gwang; Sohn, Sang Kyun; Chae, Yee Soo; Kim, Dong Hwan; Baek, Jin Ho; Lee, Kyu Bo; Lee, Je-Jung; Chung, Ik-Joo; Kim, Hyeoung-Joon; Yang, Deok-Hwan; Lee, Won-Sik; Joo, Young-Don; Sohn, Chang-Hak

2006-07-01

The present study evaluated the feasibility of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) plus etoposide and gemcitabine (CHOP-EG) as front-line chemotherapy in patients with peripheral T cell lymphomas (PTCLs). Twenty-six patients with newly diagnosed PTCLs were enrolled into the pilot study. Treatment consisted of classical CHOP plus etoposide 100 mg/m(2) intravenously (i.v.) on day 1 and gemcitabine 600 mg/m(2) i.v. on day 1 in a 3 week interval. Fifteen complete responses (CR, 57.7%) or one unconfirmed complete response (uCR, 3.8%) and four partial responses (PR, 15.4%) were confirmed, giving an overall response rate of 76.9% (95% CI, 58.3-96.3%). Median survival has not yet been reached, while median event free survival was 215 days at a median follow-up duration of 383 days. Estimated overall survival at 1 year was 69.6%. The most severe haematological adverse event was neutropaenia, which occurred with a grade 4 intensity in 14 patients (53.8%). Additionally, febrile neutropaenia was observed in four patients (15.4%). However, there was no treatment-related death. The CHOP-EG regimen was found to be feasible in patients with PTCLs. For further investigation on the role of gemcitabine in the treatment of PTCLs, a more large scale phase II or phase III study is warranted.

Addition of cyclophosphamide and higher doses of dexamethasone do not improve outcomes of patients with AL amyloidosis treated with bortezomib.

PubMed

Kastritis, E; Gavriatopoulou, M; Roussou, M; Fotiou, D; Ziogas, D C; Migkou, M; Eleutherakis-Papaiakovou, E; Panagiotidis, I; Kanellias, N; Psimenou, E; Papadopoulou, E; Pamboucas, C; Manios, E; Gakiopoulou, H; Ntalianis, A; Tasidou, A; Giannouli, S; Terpos, E; Dimopoulos, M A

2017-06-16

Bortezomib, in combination with dexamethasone (VD) or with the addition of cyclophosphamide (VCD), is highly effective in patients with amyloid light-chain (AL) amyloidosis. Currently, VCD is considered as a primary regimen for patients with AL, but it is not clear whether the addition of cyclophosphamide to VD further and significantly improves efficacy, given the substantial activity of bortezomib itself. We retrospectively compared the outcomes of 101 patients with AL amyloidosis who received VD (n=59) or VCD (n=42) in two consecutive periods. Early mortality after adjustment for Mayo stage was similar. On intent to treat, a hematologic response rate was 68% for patients treated with VD and 78% for VCD (P=0.26), while complete response+very good partial response (CR+VGPR) rate was 47.5% and 35%, respectively. Higher doses of dexamethasone or twice-weekly bortezomib were not associated with significantly higher CR+VGPR rates. Organ responses occurred in similar rates between the two groups. Median survival was similar (33 vs 36 months, P=0.45) even after adjustment for Mayo stage and dose and schedule of bortezomib and dexamethasone. In conclusion, bortezomib even with low doses of dexamethasone is effective for the treatment of AL amyloidosis; higher doses of dexamethasone and addition of cyclophosphamide do not seem to have a profound effect on efficacy and survival.

Response assessment of bevacizumab therapy in GBM with integrated 11C-MET-PET/MRI: a feasibility study.

PubMed

Deuschl, Cornelius; Moenninghoff, Christoph; Goericke, Sophia; Kirchner, Julian; Köppen, Susanne; Binse, Ina; Poeppel, Thorsten D; Quick, Harald H; Forsting, Michael; Umutlu, Lale; Herrmann, Ken; Hense, Joerg; Schlamann, Marc

2017-08-01

The objective of this study was to evaluate the potential of integrated 11C-MET PET/MR for response assessment of relapsed glioblastoma (GBM) receiving bevacizumab treatment. Eleven consecutive patients with relapsed GBM were enrolled for an integrated 11C-MET PET/MRI at baseline and at follow-up. Treatment response for MRI was evaluated according to Response Assessment in Neuro-oncology (RANO) criteria and integrated 11C-MET PET was assessed by the T/N ratio. MRI showed no patient with complete response (CR), six of 11 patients with PR, four of 11 patients with SD, and one of 11 patients with progressive disease (PD). PET revealed metabolic response in five of the six patients with partial response (PR) and in two of the four patients with stable disease (SD), whereas metabolic non-response was detected in one of the six patients with PR, in two of the four patients with SD, and in the one patient with PD. Morphological imaging was predictive for PFS and OS when response was defined as CR, PR, SD, and non-response as PD. Metabolic imaging was predictive when using T/N ratio reduction of >25 as discriminator. Based on the morphologic and metabolic findings of this study a proposal for applying integrated PET/MRI for treatment response in relapsed GBM was developed, which was significantly predictive for PFS and OS (P = 0.010 respectively 0,029, log). This study demonstrates the potential of integrated 11C-MET-PET/MRI for response assessment of GBM and the utility of combined assessment of morphologic and metabolic information with the proposal for assessing relapsed GBM.

First principles calculation of elastic and magnetic properties of Cr-based full-Heusler alloys

NASA Astrophysics Data System (ADS)

Aly, Samy H.; Shabara, Reham M.

2014-06-01

We present an ab-initio study of the elastic and magnetic properties of Cr-based full-Heusler alloys within the first-principles density functional theory. The lattice constant, magnetic moment, bulk modulus and density of states are calculated using the full-potential nonorthogonal local-orbital minimum basis (FPLO) code in the Generalized Gradient Approximation (GGA) scheme. Only the two alloys Co2CrSi and Fe2CrSi are half-metallic with energy gaps of 0.88 and 0.55 eV in the spin-down channel respectively. We have predicted the metallicity state for Fe2CrSb, Ni2CrIn, Cu2CrIn, and Cu2CrSi alloys. Fe2CrSb shows a strong pressure dependent, e.g. exhibits metallicity at zero pressure and turns into a half-metal at P≥10 GPa. The total and partial magnetic moments of these alloys were studied under higher pressure, e.g. in Co2CrIn, the total magnetic moment is almost unchanged under higher pressure up to 500 GPa.

VB-CHEP chemotherapy regimen for aggressive non-Hodgkin's lymphomas.

PubMed

Yalçin, S; Kars, A; Ozişik, Y; Tekuzman, G; Ozyilkan, O; Celik, I; Barişta, I; Güllü, I; Güler, N; Baltali, E; Firat, D

1998-10-01

Despite intensive search for the optimal combination chemotherapy for aggressive non-Hodgkin's lymphoma (NHL), the CHOP (cyclophosphamide, adriamycin, vincristine and prednisolone) regimen is still the standard therapy. We investigated the clinical efficacy of a new combination regimen consisting of vincristine, bleomycin-cyclophosphamide, adriamycin, etoposide and prednisolone (VB-CHEP) in patients with aggressive NHL. A total of 29 patients with aggressive NHL was enrolled into the protocol. Eight patients were consolidated with cisplatin and cytarabine and 5 patients received radiotherapy for bulky disease. Objective response was achieved in 82.8% of the patients. Complete remission (CR) and partial remission rates were 72.4%, and 10.3%, respectively. CR rate was significantly lower in patients with advanced stage, extranodal disease and bone marrow involvement. Median follow-up time is 34+ months; 17 patients are disease-free while 12 died and only 2 patients with CR have relapsed so far. Median response duration is 29+ months and the median survival is 48+ months. The survival rate is 69% in the first year and 66% in the second year. A total of 152 cycles were evaluated for toxicity. Major hematological toxicity was myelosuppression and neutropenia, detected in 50.65%, was mostly grades 1-2. Neutropenic fever occurred in only 11 cycles. The side effects of the consolidation therapy were also acceptable. We conclude that the VB-CHEP regimen with consolidation therapy for high-risk patients may be an effective treatment for advanced stage aggressive NHL.

Minimal-change disease in adolescents and adults: epidemiology and therapeutic response

PubMed Central

Keskar, Vaibhav; Jamale, Tukaram Ekanath; Kulkarni, Manjunath Jeevanna; Kiggal Jagadish, Pradeep; Fernandes, Gwendolyn; Hase, Niwrutti

2013-01-01

Background Epidemiology of minimal-change disease (MCD) in adults differs from that in children and is not studied well in Indian population. Methods We retrospectively studied the records of 61 adult patients with MCD to assess clinical, laboratory and histopathological features, and to evaluate the response to treatment, course and complications of the disease and therapy. Results The male to female ratio was 1.17:1. Mean age was 30.46 years. Of the total, 6.55% had hypertension; 13.11% had microhaematuria. After initial treatment with steroids, 68.85% had complete remission (CR) and 13.1% had partial remission (PR). Twelve of 14 (85.71%) steroid-resistant cases had CR or PR after alternative immunosuppression with cyclophosphamide, or mycophenolate mofetil. Of all patients, 44.2% had at least one relapse; 8.19% were frequently relapsing and 26.22% were steroid dependent. After a mean follow-up of 149.9 weeks, 38 (61.29%) patients were in CR and 16 (26.22%) in PR with a mean proteinuria of 1.28 g/day, 3 being treated for relapse. Mean serum creatinine was 89.28 μmol/L (1.01 mg/dL). Fourteen (22.95%) had acute kidney injury (AKI). All but two recovered completely. Conclusions This single-centre study with a medium-term follow-up shows that majority of patients respond to steroids or alternative immunosuppressants. AKI is common and may not be completely reversible in some cases. PMID:26064510

Next Generation Flow for highly sensitive and standardized detection of minimal residual disease in multiple myeloma.

PubMed

Flores-Montero, J; Sanoja-Flores, L; Paiva, B; Puig, N; García-Sánchez, O; Böttcher, S; van der Velden, V H J; Pérez-Morán, J-J; Vidriales, M-B; García-Sanz, R; Jimenez, C; González, M; Martínez-López, J; Corral-Mateos, A; Grigore, G-E; Fluxá, R; Pontes, R; Caetano, J; Sedek, L; Del Cañizo, M-C; Bladé, J; Lahuerta, J-J; Aguilar, C; Bárez, A; García-Mateo, A; Labrador, J; Leoz, P; Aguilera-Sanz, C; San-Miguel, J; Mateos, M-V; Durie, B; van Dongen, J J M; Orfao, A

2017-10-01

Flow cytometry has become a highly valuable method to monitor minimal residual disease (MRD) and evaluate the depth of complete response (CR) in bone marrow (BM) of multiple myeloma (MM) after therapy. However, current flow-MRD has lower sensitivity than molecular methods and lacks standardization. Here we report on a novel next generation flow (NGF) approach for highly sensitive and standardized MRD detection in MM. An optimized 2-tube 8-color antibody panel was constructed in five cycles of design-evaluation-redesign. In addition, a bulk-lysis procedure was established for acquisition of ⩾10 7 cells/sample, and novel software tools were constructed for automatic plasma cell gating. Multicenter evaluation of 110 follow-up BM from MM patients in very good partial response (VGPR) or CR showed a higher sensitivity for NGF-MRD vs conventional 8-color flow-MRD -MRD-positive rate of 47 vs 34% (P=0.003)-. Thus, 25% of patients classified as MRD-negative by conventional 8-color flow were MRD-positive by NGF, translating into a significantly longer progression-free survival for MRD-negative vs MRD-positive CR patients by NGF (75% progression-free survival not reached vs 7 months; P=0.02). This study establishes EuroFlow-based NGF as a highly sensitive, fully standardized approach for MRD detection in MM which overcomes the major limitations of conventional flow-MRD methods and is ready for implementation in routine diagnostics.

Heterogeneity of Cr in Mytilus edulis: Implications for the Cr isotope system as a paleo-redox proxy

NASA Astrophysics Data System (ADS)

Bruggmann, Sylvie; Klaebe, Robert; Frei, Robert

2017-04-01

Changes in 53Cr/52Cr (δ53Cr) values recorded by biogenic carbonates are emerging as a proxy for variations in the redox state of the Earth's oceans and atmosphere (e.g. [1], [2]). We investigate the ability of modern carbonate shells (Mytilus edulis) to record the δ53Cr composition of ambient seawater in order to assess their utility as a paleo-redox proxy. Samples of cultivated M. edulis from the Kiel Fjord, Germany, were analyzed for their δ53Cr composition and Cr concentrations [Cr] using TIMS. To disentangle the pathway of Cr into the carbonate shell, a series of step-digestions of their organic outer sheaths (periostraca) and their intra-layer composition were performed. Bulk analyses of specimens with intact periostraca returned 16 to 34 ppb Cr with δ53Cr values ranging from 0.28 to 0.65 ± 0.1 (2SE) and thus fall within the range of surface seawater from the Baltic Sea (0.3 - 0.6 \\permil [3]). Partial removal of periostraca resulted in lower [Cr] (5 to 17 ppb) and δ53Cr values (-0.05 ± 0.15 \\permil). These results show a positive correlation between the amount of organic matter present in a sample and both [Cr] and δ53Cr (n = 9). With nearly complete removal of periostraca, the remaining [Cr] is significantly lower (less than 5 ppb) and can only be accessed by incineration of the carbonate shell. The correlation between [Cr], δ53Cr and the amount of periostracum present in bulk samples indicates that a significant proportion of preserved Cr may be associated with the organic outer sheath. The Cr endmember accessed after incineration is less likely associated with the carbonate crystal lattice. Instead, the δ53Cr values obtained after incineration are similar to those reported from terrestrial rocks, suggesting the influence of detrital particles. Alternatively, Cr may be reduced and subsequently re-oxidized during the mineralization of biogenic carbonates [4]. Seasonal changes in primary productivity in seawater may further influence the shell's Cr isotopic composition [3]. A detailed understanding of the processes causing the observed heterogeneity of [Cr] and δ53Cr in modern carbonate shells is crucial for the use of the Cr isotope system as a potential paleo-redox proxy. [1] Bonnand, P., James, R. H., Parkinson, I. J., Connelly, D. P., and Fairchild, I. J. (2013). The chromium isotopic composition of seawater and marine carbonates. Earth and Planetary Science Letters, 382:10-20. [2] Holmden, C., Jacobsen, A. D., Sageman, B. B., Hurgten, M. T. (2016). Response of the Cr isotope proxy to Cretaceous Ocean Anoxic Event 2 in a pelagic carbonate succession from the Western Interior Seaway. Geochimica et Cosmochimica Acta, 186:227-295. [3] Paulukat, C., Gilleaudeau, G. J., Chernyavskiy, P., Frei, R. (2016). The Cr-isotope signature of surface seawater -A global perspective. Chemical Geology, 444:101-109. [4] Pereira, N. S., Voegelin, A. R., Paulukat, C., Sial, A. N., Ferreira, V. P., and Frei, R. (2015). Chromium-isotope signatures in scleractinian corals from the Rocas Atoll, Tropical South Atlantic. Geobiology 1-14.

CrMAPK3 regulates the expression of iron-deficiency-responsive genes in Chlamydomonas reinhardtii.

PubMed

Fei, Xiaowen; Yu, Junmei; Li, Yajun; Deng, Xiaodong

2017-05-16

Under iron-deficient conditions, Chlamydomonas exhibits high affinity for iron absorption. Nevertheless, the response, transmission, and regulation of downstream gene expression in algae cells have not to be investigated. Considering that the MAPK pathway is essential for abiotic stress responses, we determined whether this pathway is involved in iron deficiency signal transduction in Chlamydomonas. Arabidopsis MAPK gene sequences were used as entry data to search for homologous genes in Chlamydomonas reinhardtii genome database to investigate the functions of mitogen-activated protein kinase (MAPK) gene family in C. reinhardtii under iron-free conditions. Results revealed 16 C. reinhardtii MAPK genes labeled CrMAPK2-CrMAPK17 with TXY conserved domains and low homology to MAPK in yeast, Arabidopsis, and humans. The expression levels of these genes were then analyzed through qRT-PCR and exposure to high salt (150 mM NaCl), low nitrogen, or iron-free conditions. The expression levels of these genes were also subjected to adverse stress conditions. The mRNA levels of CrMAPK2, CrMAPK3, CrMAPK4, CrMAPK5, CrMAPK6, CrMAPK8, CrMAPK9, and CrMAPK11 were remarkably upregulated under iron-deficient stress. The increase in CrMAPK3 expression was 43-fold greater than that in the control. An RNA interference vector was constructed and transformed into C. reinhardtii 2A38, an algal strain with an exogenous FOX1:ARS chimeric gene, to silence CrMAPK3. After this gene was silenced, the mRNA levels and ARS activities of FOX1:ARS chimeric gene and endogenous CrFOX1 were decreased. The mRNA levels of iron-responsive genes, such as CrNRAMP2, CrATX1, CrFTR1, and CrFEA1, were also remarkably reduced. CrMAPK3 regulates the expression of iron-deficiency-responsive genes in C. reinhardtii.

Safety and efficacy of azacitidine in Belgian patients with high-risk myelodysplastic syndromes, acute myeloid leukaemia, or chronic myelomonocytic leukaemia: results of a real-life, non-interventional post-marketing survey.

PubMed

Beguin, Y; Selleslag, D; Meers, S; Graux, C; Bries, G; Deeren, D; Vrelust, I; Ravoet, C; Theunissen, K; Voelter, V; Potier, H; Trullemans, F; Noens, L; Mineur, P

2015-02-01

We evaluated azacitidine (Vidaza(®)) safety and efficacy in patients with myelodysplastic syndrome (MDS), acute myeloid leukaemia (AML), and chronic myelomonocytic leukaemia (CMML), in a real-life setting. Treatment response, dose, and schedule were assessed. This non-interventional, post-marketing survey included 49/50 patients receiving azacitidine at 14 Belgian haematology centres from 2010-2012. Treatment-emergent adverse events (TEAEs), including treatment-related TEAEs, and serious TEAEs (TESAEs) were recorded throughout the study. Treatment response [complete response (CR), partial response (PR), haematological improvement (HI), stable disease (SD), treatment failure (TF)) and transfusion-independence (TI) were evaluated at completion of a 1-year observation period (1YOP) or at treatment discontinuation, and overall survival (OS), at study conclusion. The median age of patients was 74·7 (range: 43·9-87·8) years; 69·4% had MDS, 26·5% had primary or secondary AML, and 4·1% had CMML. Treatment-related TEAEs, grade 3-4 TEAEs, and TESAEs were reported in 67·3%, 28·6%, and 18·4% of patients, respectively. During 1YOP, patients received a median of 7 (1-12) treatment cycles. Treatment response was assessed for 38/49 patients. Among MDS and CMML patients (n = 29), 41·4% had CR, PR, or HI, 41·4% had SD, and 17·2% had TF. Among AML patients (n = 9), 44·4% had CR or PR, 33·3% had SD, and 22·2% had TF. TI was observed in 14/32 (43·8%) patients who were transfusion-dependent at baseline. Median (95% confidence interval) OS was 490 (326-555) days; 1-year OS estimate was 0·571 (0·422-0·696). Our data support previous findings that azacitidine has a clinically acceptable safety profile and shows efficacy.

Accelerated Echo Planer J-resolved Spectroscopic Imaging of Putamen and Thalamus in Obstructive Sleep Apnea.

PubMed

Sarma, Manoj K; Macey, Paul M; Nagarajan, Rajakumar; Aysola, Ravi; Harper, Ronald M; Thomas, M Albert

2016-09-06

Obstructive sleep apnea syndrome (OSAS) leads to neurocognitive and autonomic deficits that are partially mediated by thalamic and putamen pathology. We examined the underlying neurochemistry of those structures using compressed sensing-based 4D echo-planar J-resolved spectroscopic imaging (JRESI), and quantified values with prior knowledge fitting. Bilaterally increased thalamic mI/Cr, putamen Glx/Cr, and Glu/Cr, and bilaterally decreased thalamic and putamen tCho/Cr and GABA/Cr occurred in OSAS vs healthy subjects (p < 0.05). Increased right thalamic Glx/Cr, Glu/Cr, Gln/Cr, Asc/Cr, and decreased GPC/Cr and decreased left thalamic tNAA/Cr, NAA/Cr were detected. The right putamen showed increased mI/Cr and decreased tCho/Cr, and the left, decreased PE/Cr ratio. ROC curve analyses demonstrated 60-100% sensitivity and specificity for the metabolite ratios in differentiating OSAS vs. Positive correlations were found between: left thalamus mI/Cr and baseline oxygen saturation (SaO2); right putamen tCho/Cr and apnea hypopnea index; right putamen GABA/Cr and baseline SaO2; left putamen PE/Cr and baseline SaO2; and left putamen NAA/Cr and SaO2 nadir (all p < 0.05). Negative correlations were found between left putamen PE/Cr and SaO2 nadir. These findings suggest underlying inflammation or glial activation, with greater alterations accompanying lower oxygen saturation. These metabolite levels may provide biomarkers for future neurochemical interventions by pharmacologic or other means.

Preliminary evidence for biologic activity of toceranib phosphate (Palladia(®)) in solid tumours.

PubMed

London, C; Mathie, T; Stingle, N; Clifford, C; Haney, S; Klein, M K; Beaver, L; Vickery, K; Vail, D M; Hershey, B; Ettinger, S; Vaughan, A; Alvarez, F; Hillman, L; Kiselow, M; Thamm, D; Higginbotham, M L; Gauthier, M; Krick, E; Phillips, B; Ladue, T; Jones, P; Bryan, J; Gill, V; Novasad, A; Fulton, L; Carreras, J; McNeill, C; Henry, C; Gillings, S

2012-09-01

The purpose of this study was to provide an initial assessment of the potential biologic activity of toceranib phosphate (Palladia®, Pfizer Animal Health, Madison, NJ, USA) in select solid tumours in dogs. Cases in which toceranib was used to treat dogs with apocrine gland anal sac adenocarcinoma (AGASACA), metastatic osteosarcoma (OSA), thyroid carcinoma, head and neck carcinoma and nasal carcinoma were included. Clinical benefit (CB) was observed in 63/85 (74%) dogs including 28/32 AGASACA [8 partial response (PR), 20 stable disease (SD)], 11/23 OSAs (1 PR and 10 SD), 12/15 thyroid carcinomas (4 PR and 8 SD), 7/8 head and neck carcinomas [1 complete response (CR), 5 PR and 1 SD] and 5/7 (1 CR and 4 SD) nasal carcinomas. For dogs experiencing CB, the median dose of toceranib was 2.8 mg kg(-1) , 36/63 (58.7%) were dosed on a Monday/Wednesday/Friday basis and 47/63 (74.6%) were treated 4 months or longer. Although these data provide preliminary evidence that toceranib exhibits CB in dogs with certain solid tumours, future prospective studies are necessary to define its true activity. © 2011 Blackwell Publishing Ltd.

Outcome of Radiation Monotherapy for High-risk Patients with Stage I Esophageal Cancer.

PubMed

Shirakawa, Yasuhiro; Noma, Kazuhiro; Maeda, Naoaki; Tanabe, Shunsuke; Kuroda, Shinji; Kagawa, Shunsuke; Katsui, Kuniaki; Katayama, Norihisa; Kanazawa, Susumu; Fujiwara, Toshiyoshi

2017-04-01

Currently, chemoradiation is the most widely used nonsurgical treatment for esophageal cancer. However, some patients, particularly the very elderly or those with severe vital organ dysfunction, face difficulty with the chemotherapy component. We therefore examined the outcome of radiation therapy (RT) alone for patients with esophageal cancer at our facility. Between January 2005 and December 2014, 84 patients underwent RT at our hospital, and 78 of these patients received concomitant chemotherapy. The remaining 6 patients underwent RT alone; these patients were considered to be high-risk and to have no lymph node metastasis (stage I). Five of them received irradiation up to a curative dose: 4 showed a complete response (CR) and 1 showed a partial response (PR). Of the patients exhibiting CR, 3 are currently living recurrence-free, whereas 1 patient underwent endoscopic submucosal dissection (ESD) as salvage therapy for local recurrence, with no subsequent recurrence. High-risk stage I esophageal cancer patients can be treated radically with RT alone under certain conditions. In the future, to broaden the indications for RT monotherapy to include some degree of advanced cancers, a novel concurrent therapy should be identified.

[Effects of pathological assessment of endometrial tissue in fertility-sparing treatment with progestin for endometrial carcinoma of stage I a and complex atypical hyperplasia].

PubMed

Gong, Qinglin; Chen, Xiaoduan; Xie, Xing

2014-09-01

To assess the efficacy and pathological change of fertility-sparing treatment with progestin for endometrial carcinoma (EC) of stage I a and complex atypical hyperplasia (CAH) and to observe the prognosis of the treatment. Nine EC patients of stage I a and 21 CAH patients aged under 40 years who desired childbearing and retaining their fertility were enrolled into this study. All patients were given a daily oral high-dose of progestin with duration of treatment ranging from 6 to 9 months. Diagnostic curettage was performed every 3 months as a modality for seeing the histologic change of neoplastic tissues and endometrial tissue. A careful and long- term follow- up is necessary for patients with complete response (CR). During the first period of fertility-sparing management, according to histologic change, 5 EC patients and 18 CAH patients showed CR with no evidence of endometrial adenocarcinoma or hyperplasia, 2 EC patients and 2 CAH patients showed partial response with a regression to complex or simple hyperplasia without atypia, 2 EC patients and 1 CAH patient showed stable disease or progressive disease. Accordingly, a total of 26 patients showed CR (26 of 30 patients). The median time to CR was 6 months (range, 3 to 21 months) of progestin treatment. The median follow-up time was 55.5 months (range, 24 to 104 months) and all patients were alive. During follow-up, among the 26 patients with CR, 3 of 6 EC patients achieved CR recurred disease after a median time interval of 10 months (range, 6 to 51 months), 7 of 20 CAH patients achieved CR had recurrent disease after a median time interval of 12 months (range, 6 to 55 months). Four of 7 CAH with recurrent disease achieved CR to progestin re-treatment. Eight of 26 patients achieved CR continued a further 3 or 6 months of consolidation therapy, 3 of them had recurrent disease, the remaining 18 stopped progesterone treatment after CR and 7 patients had recurrent disease; there was no significant statistical difference between the two groups (P = 1.000). EC patients succeeded in 4 pregnancies, CAH patients succeeded in 10 pregnancies, they gave birth to 16 healthy babies in all. EC of stage I a and CAH had slow progression of symptoms. Progestin treatment in EC of stage I a and CAH patients was effective. A careful and long-term follow-up is required because of the substantial high rate of recurrence. Progestin re-treatment in most patients with recurrent endometrial cancer is effective and safe.

Phase I/II evaluation of RV1001, a novel PI3Kδ inhibitor, in spontaneous canine lymphoma.

PubMed

Gardner, Heather L; Rippy, Sarah B; Bear, Misty D; Cronin, Kim L; Heeb, Heather; Burr, Holly; Cannon, Claire M; Penmetsa, Kumar V; Viswanadha, Srikant; Vakkalanka, Swaroop; London, Cheryl A

2018-01-01

RV1001 is a novel, potent, and selective PI3Kδ inhibitor. The purpose of this study was to evaluate the safety and efficacy of RV1001 in canine Non-Hodgkin lymphoma (NHL). Inhibition of endogenous pAKT by RV1001 in primary canine NHL cells was determined by Western blotting. A phase I study of RV1001 was performed in 21 dogs with naïve and drug resistant T and B-cell NHL to assess safety, pharmacokinetic profile, and response to therapy. The objective response rate was 62% (complete response (CR) n = 3; partial response (PR) n = 10), and responses were observed in both naïve and chemotherapy-resistant B and T cell NHL. This study provided the recommended starting dose for a phase II, non-pivotal, exploratory, open label multi-centered clinical trial in 35 dogs with naïve and drug resistant T and B-cell NHL, to further define the efficacy and safety profile of RV1001. The objective response rate in the phase II study was 77% (CR n = 1; PR n = 26). Clinical toxicities were primarily hepatobiliary and gastrointestinal, and were responsive to dose modifications and/or temporary drug discontinuation. Hepatotoxicity was the primary dose limiting toxicity. RV1001 exhibits good oral bioavailability, an acceptable safety profile, and biologic activity with associated inhibition of pAKT in dogs with B and T cell NHL. Data from these studies can be leveraged to help inform the design of future studies involving isoform-selective PI3K inhibitors in humans.

Baseline clinical predictors of antitumor response to the PARP inhibitor olaparib in germline BRCA1/2 mutated patients with advanced ovarian cancer.

PubMed

Rafii, Saeed; Gourley, Charlie; Kumar, Rajiv; Geuna, Elena; Ern Ang, Joo; Rye, Tzyvia; Chen, Lee-May; Shapira-Frommer, Ronnie; Friedlander, Michael; Matulonis, Ursula; De Greve, Jacques; Oza, Amit M; Banerjee, Susana; Molife, L Rhoda; Gore, Martin E; Kaye, Stan B; Yap, Timothy A

2017-07-18

The PARP inhibitor olaparib was recently granted Food and Drug Administration (FDA) accelerated approval in patients with advanced BRCA1/2 mutation ovarian cancer. However, antitumor responses are observed in only approximately 40% of patients and the impact of baseline clinical factors on response to treatment remains unclear. Although platinum sensitivity has been suggested as a marker of response to PARP inhibitors, patients with platinum-resistant disease still respond to olaparib. 108 patients with advanced BRCA1/2 mutation ovarian cancers were included. The interval between the end of the most recent platinum chemotherapy and PARPi (PTPI) was used to predict response to olaparib independent of conventional definition of platinum sensitivity. RECIST complete response (CR) and partial response (PR) rates were 35% in patients with platinum-sensitive versus 13% in platinum-resistant (p<0.005). Independent of platinum sensitivity status, the RECIST CR/PR rates were 42% in patients with PTPI greater than 52 weeks and 18% in patients with PTPI less than 52 weeks (p=0.016). No association was found between baseline clinical factors such as FIGO staging, debulking surgery, BRCA1 versus BRCA2 mutations, prior history of breast cancer and prior chemotherapy for breast cancer, and the response to olaparib. We conducted an international multicenter retrospective study to investigate the association between baseline clinical characteristics of patients with advanced BRCA1/2 mutation ovarian cancers from eight different cancer centers and their antitumor response to olaparib. PTPI may be used to refine the prediction of response to PARP inhibition based on the conventional categorization of platinum sensitivity.

Gemcitabine and docetaxel in relapsed and unresectable high-grade osteosarcoma and spindle cell sarcoma of bone.

PubMed

Palmerini, E; Jones, R L; Marchesi, E; Paioli, A; Cesari, M; Longhi, A; Meazza, C; Coccoli, L; Fagioli, F; Asaftei, S; Grignani, G; Tamburini, A; Pollack, S M; Picci, P; Ferrari, S

2016-04-20

Few new compounds are available for relapsed osteosarcoma. We retrospectively evaluated the activity of gemcitabine (G) plus docetaxel (D) in patients with relapsed high-grade osteosarcoma and high-grade spindle cell sarcoma of bone (HGS). Patients receiving G 900 mg/m(2) d 1, 8; D 75 mg/m(2) d 8, every 21 days were eligible. Primary end-point: progression-free survival (PFS) at 4 months; secondary end-point: overall survival (OS) and response rate. Fifty-one patients were included, with a median age of 17 years (8-71), 26 (51%) were pediatric patients. GD line of treatment: 2nd in 14 patients, ≥3rd in 37. 25 (49%) patients had metastases limited to lungs, 26 (51%) multiple sites. 40 (78%) osteosarcoma, 11 (22%) HGS. Eight (16%) patients achieved surgical complete response (sCR2) after GD. Four-month PFS rate was 46%, and significantly better for patients with ECOG 0 (ECOG 0: 54% vs ECOG 1: 43% vs ECOG 2: 0%; p = 0.003), for patients undergoing metastasectomy after GD (sCR2 75% vs no-sCR2 40 %, p = 0.02) and for osteosarcoma (osteosarcoma 56% vs HGS 18%; p = 0.05), with no differences according to age, line of treatment, and pattern of metastases. Forty-six cases had RECIST measurable disease: 6 (13%) patients had a partial response (PR), 20 (43%) had stable disease (SD) and 20 (43%) had progressive disease (PD). The 1-year OS was 30%: 67% for PR, 54% for SD and 20% for PD (p = 0.005). GD is an active treatment for relapsed high-grade osteosarcoma, especially for ECOG 0 patients, and should be included in the therapeutic armamentarium of metastatic osteosarcoma.

Diffusion of cations in chromia layers grown on iron-base alloys

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

Lobnig, R.E.; Hennesen, K.; Grabke, H.J.

Diffusion of the cations Cr, Fe, Mn, and Ni in Cr{sub 2}O{sub 3} has been investigated at 1,173 K. The diffusion measurements were performed on chromia layers grown on the model alloys Fe-20Cr and Fe-20Cr-12Ni in order to consider effects of small amounts of dissolved alien cations in Cr{sub 2}O{sub 3}. The samples were diffusion annealed in H{sub 2}-H{sub 2}O at an oxygen partial pressure close to the Cr{sub 2}O{sub 3}/Cr equilibrium. For all tracers the lattice-diffusion coefficients are 3-5 orders of magnitude smaller than the grain-boundary diffusion coefficients. The lattice diffusivity of Mn is about two orders of magnitudemore » greater than the other lattice-diffusion coefficients, especially in Cr{sub 2}O{sub 3} grown on Fe-20Cr-12Ni. The values of the diffusion coefficients for Cr, Fe, and Ni are in the same range. Diffusion of the tracers in Cr{sub 2}O{sub 3} grown on different alloys did not show significant differences with the exception of Mn.« less

Long-term disease-free survivors with cytogenetically normal acute myeloid leukemia and MLL partial tandem duplication: a Cancer and Leukemia Group B study

PubMed Central

Ruppert, Amy S.; Marcucci, Guido; Mrózek, Krzysztof; Paschka, Peter; Langer, Christian; Baldus, Claudia D.; Wen, Jing; Vukosavljevic, Tamara; Powell, Bayard L.; Carroll, Andrew J.; Kolitz, Jonathan E.; Larson, Richard A.; Caligiuri, Michael A.; Bloomfield, Clara D.

2007-01-01

The clinical impact of MLL partial tandem duplication (MLL-PTD) was evaluated in 238 adults aged 18 to 59 years with cytogenetically normal (CN) de novo acute myeloid leukemia (AML) who were treated intensively on similar Cancer and Leukemia Group B protocols 9621 and 19808. Twenty-four (10.1%) patients harbored an MLL-PTD. Of those, 92% achieved complete remission (CR) compared with 83% of patients without MLL-PTD (P = .39). Neither overall survival nor disease-free survival significantly differed between the 2 groups (P = .67 and P = .55, respectively). Thirteen MLL-PTD+ patients relapsed within 1.4 years of achieving CR. MLL-PTD+ patients who relapsed more often had other adverse CN-AML–associated molecular markers. In contrast with previously reported studies, 9 (41%) MLL-PTD+ patients continue in long-term first remission (CR1; range, 2.5-7.7 years). Intensive consolidation therapy that included autologous peripheral stem-cell transplantation during CR1 may have contributed to the better outcome of this historically poor-prognosis group of CN-AML patients with MLL-PTD. PMID:17341662

Erythropoietin plus granulocyte colony-stimulating factor in the treatment of myelodysplastic syndromes. Identification of a subgroup of responders. The Spanish Erythropathology Group.

PubMed

Remacha, A F; Arrizabalaga, B; Villegas, A; Manteiga, R; Calvo, T; Julià, A; Fernández Fuertes, I; González, F A; Font, L; Juncà, J; del Arco, A; Malcorra, J J; Equiza, E P; de Mendiguren, B P; Romero, M

1999-12-01

Anemia leading to transfusion is probably the most important problem in patients with myelodysplastic syndromes (MDS). Human recombinant erythropoietin (rHuEpo) and granulocyte colony-stimulating factor (G-CSF) have been used to treat patients with anemia of MDS, but fewer than 50% respond. The aim of this work was to evaluate the benefit of rHuEpo +/- G-CSF treatment and to isolate the response predictive variables in a group of selected patients with MDS. A non-randomized multicenter trial was carried out in 32 patients with MDS. The inclusion criteria were age >= 18 years, refractory anemia (RA) or refractory anemia with ringed sideroblasts, Hb <= 100 g/L or receiving transfusions and serum erythropoietin <= 250 U/L. These patients were treated with subcutaneous rHuEpo (300 U/kg) three times a week for 8 weeks. In the case of partial response (PR) or no response (NR) subcutaneosly administered G-CSF (1 microg/kg) three times a week was added to the rHuEpo for 8 more weeks. If the patient achieved complete response (CR) or PR in the second phase, he was included in a follow-up phase of 24 weeks in which the dose of growth factors was tapered down. Several variables, including the score published by the Scandinavian-American group, were used as possible predictive variables. An erythroid response was observed in 16 patients (50%); in 12 it was a CR and in 4 it was a PR. During the period of rHuEpo administration, 7 CR and 4 PR (34.4%) were documented. Of the 14 patients in whom G-CSF was added to rHuEpo, 7 (50%) responded (3 CR and 4 PR). No major side-effects associated with growth factors were observed. The multivariate analysis showed that of the different variables evaluated only the Scandinavian-American response score was significant with a relative probability of response of 11.8 (95% confident intervals: 2.5-53) when this score was > +1 (77% of cases responded). In contrast, when this score was <= 1 only 15 % of the cases responded. Use of the Scandinavian-American response score is to be recommended in a patient-oriented approach to treating MDS cases with the Epo and G-CSF. Treatment with rHuEpo and G-CSF is safe, its main drawback being its cost. However, a long-term study evaluating the regimen's cost-benefit ratio is warranted.

Characterization of new polymer-grafted protein cation exchangers developed by partial neutralization of carboxyl groups derivatized by modification of poly(ethylenimine)-Sepharose with succinic anhydride.

PubMed

Zhao, Yangyang; Dong, Xiaoyan; Yu, Linling; Liu, Yang; Sun, Yan

2018-05-18

Previously, we have studied protein adsorption and chromatographic behaviors on poly(ethylenimine) (PEI)-grafted Sepharose FF anion-exchange resins, and found that protein uptake rates increased greatly when PEI grafting density reached over a critical ionic capacity (cIC) due to the occurrence of the "chain delivery" effect. Moreover, by partial charge neutralization of starting resin FF-PEI-L740 (IC = 740 mmol/L, larger than the cIC) with sodium acetate to FF-PEI-R440, it exhibited a three-fold increase in uptake rate over FF-PEI-L740. In this work, to take the advantages of PEI and extend the applications of the PEI-grafted resins in cation-exchange chromatography, a series of cation exchangers of five different ICs were developed. First, the charged of FF-PEI-L740 was reversed from positive to negative by reaction with excess succinic anhydride, which created a cation-exchanger with an IC of 970 mmol/L (FF-FEI-C970). FF-PEI-C970 was further modified with ethanolamine for partial charge neutralizations, leading to the preparation of four charge-reduced cation exchangers with IC values (in mmol/L) of 780, 630, 560 and 430, which were denoted as FF-PEI-CR780, -CR630 -CR560 and -CR430, respectively. Protein adsorption and chromatographic behaviors were investigated using lysozyme (Lys) as the model protein. It was found that, the resins of high and moderate IC values (IC ≥ 560 mmol/L) afforded adsorption capacities up to over 230 mg/mL. Besides, the uptake rate, represented by the effective pore diffusivity (D e/ D 0 ), exhibited significant increase from 0.067 (FF-PEI-C970 and FF-PEI-CR780) to 0.343 (FF-PEI-CR630 and FF-PEI-CR560) and then to 1.035 (FF-PEI-CR430) with decreasing IC. It was considered that decreasing IC led to the decreased protein binding sites (binding strength), which encouraged the occurrence of the "chain delivery" effect. Moreover, the resins of high and moderate IC values, particularly, the resins of moderate IC values (FF-PEI-CR630 and FF-PEI-CR560), presented both high adsorption capacities and uptake kinetics at 0-100 mmol/L NaCl. Besides, dynamic binding capacity achieved 150 mg/mL for the resins of moderate IC values at 0 mmol/L NaCl concentration, and afforded >110 mg/mL for the resin of high IC values at 0-100 mmol/L NaCl concentration. The results proved the excellent IEC performance of the PEI-derived cation exchangers. Copyright © 2018 Elsevier B.V. All rights reserved.

Development study of compositions for advanced wrought nickel-base superalloys

NASA Technical Reports Server (NTRS)

Kent, W. B.

1972-01-01

Using NASA IIb as a base composition, the effects of five key elements (carbon, tungsten, tantalum, aluminum, and hafnium) on resultant properties were investigated in an effort to optimize the composition and derive new wrought high temperature alloys with improved strength characteristics. A total of nineteen compositions were melted, extruded, and rolled to bar stock using thermomechanical processing. Both full and partial solution heat treatments were developed for the compositions. Tensile properties from room temperature to 1800 deg F, stress and creep rupture properties to 1800 deg F, and thermal stability characteristics were evaluated. NASA IIb-7 exhibited the best response to the partial solution heat treatment for optimum properties up to 1200 deg F. The alloy contained 0.13C, 9.0 Cr, 9.0 Co, 2.0 Mo, 7.5 W, 10.0 Ta, 3.5 Al, 0.75 Ti, 0.02 B, 0.10 Zr, 0.50 V, 1.0 Hf, and balance nickel.

Morphological and transcriptional responses of Lycopersicon esculentum to hexavalent chromium in agricultural soil.

PubMed

Li, Shi-Guo; Hou, Jing; Liu, Xin-Hui; Cui, Bao-Shan; Bai, Jun-Hong

2016-07-01

The carcinogenic, teratogenic, and mutagenic effects of hexavalent chromium (Cr[VI]) on living organisms through the food chain raise the immediate need to assess the potential toxicological impacts of Cr(VI) on human health. Therefore, the concentration-dependent responses of 12 Cr(VI)-responsive genes selected from a high-throughput Lycopersicon esculentum complementary DNA microarray were examined at different Cr concentrations. The results indicated that most of the genes were differentially expressed from 0.1 mg Cr/kg soil, whereas the lowest-observable-adverse-effect concentrations of Cr(VI) were 1.6 mg Cr/kg soil, 6.4 mg Cr/kg soil, 3.2 mg Cr/kg soil, and 0.4 mg Cr/kg soil for seed germination, root elongation, root biomass, and root morphology, respectively, implying that the transcriptional method was more sensitive than the traditional method in detecting Cr(VI) toxicity. Dose-dependent responses were observed for the relative expression of expansin (p = 0.778), probable chalcone-flavonone isomerase 3 (p = -0.496), and 12S seed storage protein CRD (p = -0.614); therefore, the authors propose the 3 genes as putative biomarkers in Cr(VI)-contaminated soil. Environ Toxicol Chem 2016;35:1751-1758. © 2015 SETAC. © 2015 SETAC.

The influence of heat treatments on several types of base-metal removable partial denture alloys.

PubMed

Morris, H F; Asgar, K; Rowe, A P; Nasjleti, C E

1979-04-01

Four removable partial denture alloys, Vitallium (Co-Cr alloy), Dentillium P.D. (Fe-Cr alloy), Durallium L.G. (Co-Cr-Ni alloy), and Ticonium 100 (Ni-Cr alloy), were evaluated in the as-cast condition and after heat treatment for 15 minutes at 1,300 degrees, 1,600 degrees, 1,900 degrees, and 2,200 degrees F followed by quenching in water. The following properties were determined and compared for each alloy at each heat treatment condition: the yield strengths at 0.01%, 0.1%, and 0.2% offsets, the ultimate tensile strength, the percent elongation, the modulus of elasticity, and the Knoop microhardness. The results were statistically analyzed. Photomicrographs were examined for each alloy and test condition. The following conclusions were made: 1. The "highest values" were exhibited by the as-cast alloy. 2. Heat treatment of the partial denture alloys tested resulted in reductions in strength, while the elongations varied. This study demonstrates that, in practice, one should avoid (a) prolonged "heat-soaking" while soldering and (b) grinding or polishing of the casting until the alloy is "red hot". 3. Durallium L.G. was the least affected by the various heat treatment conditions. 4. Conventional reporting of the yield strength at 0.2% offset, the ultimate tensile strength, and percent elongation are not adequate to completely describe and compare the mechanical behavior of alloys. The reporting of the yield strength at 0.01% offset, in addition to the other reported properties, will provide a more complete description of the behavior of the dental alloys.

Palliation by Low-Dose Local Radiation Therapy for Indolent Non-Hodgkin Lymphoma

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

Chan, Elisa K.; Fung, Sharon; Gospodarowicz, Mary

Purpose: The purpose of this study was to assess the efficacy of a 2 Multiplication-Sign 2 Gy (total dose, 4 Gy) palliative radiation therapy (RT) regimen for treating patients with indolent non-Hodgkin lymphoma (NHL) in terms of response rate, response duration, and symptom relief. Methods and Materials: A retrospective chart review was conducted. Between 2003 and 2007, 54 patients with NHL were treated to 85 anatomical sites with a 2 Multiplication-Sign 2 Gy palliative regimen. Local response was assessed by clinical and/or radiographic data. Symptoms before and after treatment for each site treated were obtained from clinical notes in patientmore » medical records. Median follow-up time was 1.3 years. Results: For the 54 patients, the median age at time of treatment was 71.1 years old, and 57% of them were male. Of the 85 disease sites treated, 56% of sites had indolent histology, 28% of sites were diagnosed with chronic lymphocytic leukemia (CLL), 13% of sites had aggressive histology, and 2% of sites were shown to have other histology. Overall response rate (ORR) was 81% (49% complete response [CR], 32% partial response [PR]). The 2-year rate for freedom from local progression was 50% (95% CI, 37%-61%). The ORR for follicular lymphoma, Mucosa associated lymphoid tissue (MALT), and marginal zone lymphoma (MZL) histology was 88%, compared with a 59% rate for CLL histology (p = 0.005). While the ORR was similar for tumors of different sizes, the CR rate for patients with tumors <5 cm tended to be higher than those with tumors >10 cm (CR rate of 57% vs. 27%, respectively; p = 0.06). For the 48 sites with clearly documented symptoms at pretreatment, 92% of sites improved after low-dose RT. Conclusions: Short-course low-dose palliative radiotherapy (2 Multiplication-Sign 2 Gy) is an effective treatment that results in high response rates for indolent non-Hodgkin lymphoma. This treatment regimen provides effective symptomatic relief for tumor bulk of all sizes.« less

Fabrication and analysis of Cr-doped ZnO nanoparticles from the gas phase.

PubMed

Schneider, L; Zaitsev, S V; Jin, W; Kompch, A; Winterer, M; Acet, M; Bacher, G

2009-04-01

High quality Cr-doped ZnO nanoparticles from the gas phase were prepared and investigated with respect to their structural, optical and magnetic properties. The extended x-ray absorption fine structure and the x-ray absorption near edge structure of the particles verify that after nanoparticle preparation Cr is incorporated as Cr3+ ) at least partially on sites with a 4-fold oxygen configuration, most likely on a Zn site, into the wurtzite lattice. Despite the fact that Cr is known to act as an efficient non-radiative loss centre for near band gap emission (NBE), a pronounced NBE is obtained up to room temperature even for a nominal Cr concentration of 10 at.%. Annealing at 1000 degrees C results in a significant improvement of the photoluminescence efficiency and a reduced PL linewidth down to 2.9 meV at low temperatures while the structural and magnetic data indicate the formation of ZnCr2O4 clusters.

Randomized phase II trial of carboplatin versus paclitaxel and carboplatin in platinum-sensitive recurrent advanced ovarian carcinoma: a GEICO (Grupo Espanol de Investigacion en Cancer de Ovario) study.

PubMed

González-Martín, A J; Calvo, E; Bover, I; Rubio, M J; Arcusa, A; Casado, A; Ojeda, B; Balañá, C; Martínez, E; Herrero, A; Pardo, B; Adrover, E; Rifá, J; Godes, M J; Moyano, A; Cervantes, A

2005-05-01

The aim of this study was to determine whether the response rate for the paclitaxel-carboplatin combination is superior to carboplatin alone in the treatment of patients with platinum-sensitive recurrent ovarian carcinoma. Patients with recurrent ovarian carcinoma, 6 months after treatment with a platinum-based regimen and with no more than two previous chemotherapy lines, were randomized to receive carboplatin area under the curve (AUC) 5 (arm A) or paclitaxel 175 mg/m(2) + carboplatin AUC 5 (arm B). The primary end point was objective response, following a 'pick up the winner' design. Secondary end points included time to progression (TTP), overall survival, tolerability and quality of life (QoL). Eighty-one patients were randomized and included in the intention-to-treat analysis. The response rate in arm B was 75.6% [26.8% complete response (CR) + 48.8% partial response (PR)] [95% confidence interval (CI) 59.7% to 87.6%] and 50% in arm A (20% CR + 30% PR) (95% CI 33.8% to 66.2%). No significant differences were observed in grade 3-4 hematological toxicity. Conversely, mucositis, myalgia/arthralgia and peripheral neurophaty were more frequent in arm B. Median TTP was 49.1 weeks in arm B (95% CI 36.9-61.3) and 33.7 weeks in arm A (95% CI 25.8-41.5). No significant differences were found in the QoL analysis. Paclitaxel-carboplatin combination is a tolerable regimen with a higher response rate than carboplatin monotherapy in platinum-sensitive recurrent ovarian carcinoma.

The response of CR-39 nuclear track detector to 1-9 MeV protons

DOE PAGES

Sinenian, N.; Rosenberg, M. J.; Manuel, M.; ...

2011-10-28

The response of CR-39 nuclear track detector (TasTrak®) to protons in the energy range of 0.92-9.28 MeV has been studied. Previous studies of the CR-39 response to protons have been extended by examining the piece-to-piece variability in addition to the effects of etch time and etchant temperature; it is shown that the shape of the CR-39 response curve to protons can vary from piece-to-piece. The effects due to the age of CR-39 have also been studied using 5.5 MeV alpha particles over a 5-year period. Track diameters were found to degrade with the age of the CR-39 itself rather thanmore » the age of the tracks, consistent with previous studies utilizing different CR-39 over shorter time periods.« less

Photodynamic therapy for premalignant lesions of the vulva and vagina: A long-term follow-up study.

PubMed

Choi, Min Chul; Kim, Mi Sun; Lee, Gee Hoon; Jung, Sang Geun; Park, Hyun; Joo, Won Duk; Lee, Chan; Lee, Je Ho; Hwang, Yoon Young; Kim, Seung Jo

2015-07-14

We aimed to evaluate responses to photodynamic therapy (PDT) and its long-term efficacy in preserving normal anatomy and function in women with premalignant lesions of the lower genital tract. Fifteen patients received PDT for vulvar intraepithelial neoplasia (VIN), vaginal intraepithelial neoplasia (VAIN), or vulvar Paget's disease between January 2003 and December 2013. Patients underwent colposcopy and/or vulvoscopy for assessment of lesions. Surface photoillumination with a 630-nm red laser light was applied to the lesions 48 hours after intravenous injection of 2 mg/kg photosensitizer (PSZ; Photogem®). The light dose to the lesions was 150 J/cm 2 . The median age of the 15 patients (VIN II: 3, VIN III: 4, VAIN II: 2, VAIN III: 3, Paget's disease: 3) was 42.3 years. The complete response (CR) rate was 80% (12/15) at the 3-month follow-up and 71.4% (10/14) at the 1-year follow-up. There were two cases of persistent disease at the 3-month follow-up. One patient with persistent disease underwent partial vulvectomy three times for repetitive recurrence, and the other received secondary PDT with topical 5-aminolevulinic acid (5-ALA) and subsequently showed no evidence of disease (NED). Another patient achieved 90% remission through a combination of additional alternative treatments after showing partial response (PR). In two cases of CR, recurrence was observed at the 1-year follow-up. Regarding adverse events, photosensitivity reactions such as facial edema and urticaria occurred in 13.3% (2/15) and perineal pain occurred in one patient. PDT may be an effective alternative treatment for premalignant lesions of the female lower genital tract to preserve normal anatomy and sexual function without therapeutic impairment. Lasers Surg. Med. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Clinicopathological findings, treatment response and predictors of long-term outcome in a cohort of lupus nephritis patients managed according to the Euro-lupus regime: a retrospective analysis in Sri Lanka.

PubMed

Herath, Nalaka; Ratnatunga, Neelakanthi; Weerakoon, Kosala; Wazil, Abdul; Nanayakkara, Nishantha

2017-02-02

Despite the improvement in survival of patients with lupus nephritis (LN) globally, there is sparse data from Sri Lanka (SL). The current study aims to describe the clinicopathological findings, treatment response and predictors of long-term outcome of patients with WHO class III-IV LN in SL, managed according to the Euro-lupus regime. Of 72 patients, 64 were females. In half of them, LN was diagnosed within the 1st year of the illness. The most common presenting feature was sub-nephrotic proteinuria. Sixteen and twenty patients had nephrotic syndrome and abnormal renal function respectively at the time of diagnosis. Fifty-four patients (75%) responded to the Euro-lupus regimen [CR, 20 (28%); PR, 34(47%)]. Later at 6 months, 65 patients (90%) achieved remission [CR, 31(43%); PR, 34 (47%)]. Seven patients experienced treatment failure. During the total duration of follow up, 54 patients remained in complete or partial remission, 26 developed renal relapses, and 19 suffered severe infective episodes. Renal relapses were more common in people who achieved partial remission than complete remission. The long term renal outcome was not associated with age, sex, severity of proteinuria, class of LN or initial renal function. Patients who achieved remission at 6 months had a good long-term outcome. The demographic and clinical features of WHO class III and IV LN in Sri Lankan patients were similar to that reported in the global literature. 75% of patients responded to the Euro-lupus regimen. Therefore, this regime is a suitable initial regimen for LN patients in SL. Good long-term renal outcome can be predicted by early response to therapy. Further studies are necessary to explore better treatment options for patients who fail to achieve remission during initial therapy.

Apoptosis of lymphocytes in the presence of Cr(V) complexes: role in Cr(VI)-induced toxicity.

PubMed

Vasant, C; Balamurugan, K; Rajaram, R; Ramasami, T

2001-08-03

Cr(VI) compounds have been declared as a potent occupational carcinogen by IARC (1990) through epidemiological studies among workers in chrome plating, stainless-steel, and pigment industries. Studies relating to the role of intermediate oxidation states such as Cr(V) and Cr(IV) in Cr(VI)-induced carcinogenicity are gaining importance. In this study, issues relating to toxicity elicited by Cr(V) have been addressed and comparisons made with those relating to Cr(VI) employing human peripheral blood lymphocytes. Lymphocytes have been isolated from heparinized blood by Ficoll-Hypaque density gradient centrifugation and exposed to Cr(V) complexes viz. sodium bis(2-ethyl-2-hydroxybutyrato)oxochromate(V), Na[Cr(V)O(ehba)(2)], 1 and sodium bis(2-hydroxy-2-methylbutyrato)oxochromate(V), Na[Cr(V)O(hmba)(2)], 2 and Cr(VI). The phytohemagglutinin (PHA)-induced proliferation of lymphocytes has been found to be inhibited by the two complexes of Cr(V) and chromate Cr(VI) in a time- and concentration-dependent manner. Viability of cells decreases in the presence of Cr(V). Apoptosis appears to be the mode of cell death in the presence of both Cr(V) and Cr(VI). Pretreatment of cells with antioxidants before exposure to chromium(V) complexes reverse apoptosis partially. Possibility for the formation and implication of reactive oxygen species in Cr(V)-induced apoptosis of human lymphocyte cells has been indicated in this investigation. The intermediates of Cr(V) and radical species in the biotoxic pathways elicited by Cr(VI) seems feasible. Copyright 2001 Academic Press.

Occurrence and Speciation of Polymeric Chromium(III), Monomeric Chromium(III) and Chromium(VI) in Environmental Samples

PubMed Central

HU, LIGANG; CAI, YONG; JIANG, GUIBIN

2016-01-01

Laboratory experiments suggest that polymeric Cr(III) could exist in aqueous solution for a relative long period of time. However, the occurrence of polymeric Cr(III) has not been reported in environmental media due partially to the lack of method for speciating polymeric Cr. We observed an unknown Cr species during the course of study on speciation of Cr in the leachates of chromated-copper-arsenate (CCA)-treated wood. Efforts were made to identify structure of the unknown Cr species. Considering the forms of Cr existed in the CCA-treated woods, we mainly focused our efforts to determine if the unknown species were polymeric Cr(III), complex of Cr/As or complex of Cr with dissolved organic matter (DOM). In order to evaluate whether polymeric Cr(III) largely exist in wood leachates, high performance liquid chromatography coupled with inductively coupled mass spectrometry (HPLC-ICPMS was used) for simultaneous speciation of monomeric Cr(III), polymeric Cr(III), and Cr(VI). In addition to wood leachates where polymeric Cr (III) ranged from 39.1 to 67.4 %, occurrence of the unknown Cr species in other environmental matrices, including surface waters, tap and waste waters, was also investigated. It was found that polymeric Cr(III) could exist in environmental samples containing μg/L level of Cr, at a level up to 60% of total Cr, suggesting that polymeric Cr(III) could significantly exist in natural environments. Failure in quantifying polymeric Cr(III) would lead to the underestimation of total Cr and bias in Cr speciation. The environmental implication of the presence of polymeric Cr(III) species in the environment deserves further study. PMID:27156211

Response monitoring of breast cancer patients receiving neoadjuvant chemotherapy using quantitative ultrasound, texture, and molecular features

PubMed Central

Gangeh, Mehrdad; Tadayyon, Hadi; Sadeghi-Naini, Ali; Gandhi, Sonal; Wright, Frances C.; Slodkowska, Elzbieta; Curpen, Belinda; Tran, William; Czarnota, Gregory J.

2018-01-01

Background Pathological response of breast cancer to chemotherapy is a prognostic indicator for long-term disease free and overall survival. Responses of locally advanced breast cancer in the neoadjuvant chemotherapy (NAC) settings are often variable, and the prediction of response is imperfect. The purpose of this study was to detect primary tumor responses early after the start of neoadjuvant chemotherapy using quantitative ultrasound (QUS), textural analysis and molecular features in patients with locally advanced breast cancer. Methods The study included ninety six patients treated with neoadjuvant chemotherapy. Breast tumors were scanned with a clinical ultrasound system prior to chemotherapy treatment, during the first, fourth and eighth week of treatment, and prior to surgery. Quantitative ultrasound parameters and scatterer-based features were calculated from ultrasound radio frequency (RF) data within tumor regions of interest. Additionally, texture features were extracted from QUS parametric maps. Prior to therapy, all patients underwent a core needle biopsy and histological subtypes and biomarker ER, PR, and HER2 status were determined. Patients were classified into three treatment response groups based on combination of clinical and pathological analyses: complete responders (CR), partial responders (PR), and non-responders (NR). Response classifications from QUS parameters, receptors status and pathological were compared. Discriminant analysis was performed on extracted parameters using a support vector machine classifier to categorize subjects into CR, PR, and NR groups at all scan times. Results Of the 96 patients, the number of CR, PR and NR patients were 21, 52, and 23, respectively. The best prediction of treatment response was achieved with the combination mean QUS values, texture and molecular features with accuracies of 78%, 86% and 83% at weeks 1, 4, and 8, after treatment respectively. Mean QUS parameters or clinical receptors status alone predicted the three response groups with accuracies less than 60% at all scan time points. Recurrence free survival (RFS) of response groups determined based on combined features followed similar trend as determined based on clinical and pathology. Conclusions This work demonstrates the potential of using QUS, texture and molecular features for predicting the response of primary breast tumors to chemotherapy early, and guiding the treatment planning of refractory patients. PMID:29298305

The role of complement receptor positive and complement receptor negative B cells in the primary and secondary immune response to thymus independent type 2 and thymus dependent antigens.

PubMed

Lindsten, T; Yaffe, L J; Thompson, C B; Guelde, G; Berning, A; Scher, I; Kenny, J J

1985-05-01

Both complement receptor positive (CR+) and complement receptor negative (CR-) B cells have been shown to be involved in the primary immune response to PC-Hy (phosphocholine conjugated hemocyanin), a thymus dependent (TD) antigen which preferentially induces antibody secretion in Lyb-5+ B cells during a primary adoptive transfer assay. CR+ and CR- B cells also responded in a primary adoptive transfer assay to TNP-Ficoll, a thymus independent type 2 (TI-2) antigen which activates only Lyb-5+ B cells. When the secondary immune response to PC-Hy and TNP-Ficoll were analyzed, it was found that most of the immune memory to both antigens was present in the CR- B cell subset. The CR- B cell subset also dominated the secondary immune response to PC-Hy in immune defective (CBA/N X DBA/2N)F1 male mice. These data indicate that CR- B cells dominate the memory response in both the Lyb-5+ and Lyb-5- B cell subsets of normal and xid immune defective mice and suggest that Lyb-5+ and Lyb-5- B cells can be subdivided into CR+ and CR- subsets.

Successive reactive liquid flow episodes in a layered intrusion (Unit 9, Rum Eastern Layered Intrusion, Scotland)

NASA Astrophysics Data System (ADS)

Leuthold, Julien; Blundy, Jon; Holness, Marian

2014-05-01

We will present a detailed microstructural and geochemical study of reactive liquid flow in Unit 9 of the Rum Eastern Layered Intrusion. In the study region, Unit 9 comprises an underlying lens-like body of peridotite overlain by a sequence of troctolite and gabbro (termed allivalite), with some local and minor anorthosite. The troctolite is separated from the overlying gabbro by a distinct, sub-horizontal, undulose horizon (the major wavy horizon). Higher in the stratigraphy is another, similar, horizon (the minor wavy horizon) that separates relatively clinopyroxene-poor gabbro from an overlying gabbro. To the north of the peridotite lens, both troctolite and gabbro grade into poikilitic gabbro. Clinopyroxene habit in the allivalite varies from thin rims around olivine in troctolite, to equigranular crystals in gabbro, to oikocrysts in the poikilitic gabbro. The poikilitic gabbros contain multiple generations of clinopyroxene, with Cr-rich (~1.1 wt.% Cr2O3), anhedral cores with moderate REE concentrations (core1) overgrown by an anhedral REE-depleted second generation with moderate Cr (~0.7 wt.% Cr2O3) (core2). These composite cores are rimmed by Cr-poor (~0.2 wt.% Cr2O3) and REE-poor to moderate clinopyroxene. We interpret these microstructures as a consequence of two separate episodes of partial melting triggered by the intrusion of hot olivine-phyric picrite to form the discontinuous lenses that comprise the Unit 9 peridotite. Loss of clinopyroxene-saturated partial melt from the lower part of the allivalite immediately following the early stages of sill intrusion resulted in the formation of clinopyroxene-poor gabbro. The spatial extent of clinopyroxene loss is marked by the minor wavy horizon. A further partial melting event stripped out almost all clinopyroxene from the lowest allivalite, to form a troctolite, with the major wavy horizon marking the extent of melting during this second episode. The poikilitic gabbro formed from clinopyroxene-saturated melt moving upwards and laterally through the cumulate pile. The Rum layered intrusion is an open intrusive complex, composed of individual partially molten zones, evolving independently. The Rum layered intrusion offers a direct overview of processes taking place in shallow intra-plate and ridge magma chambers. Intrusion of hot magma into a pre-existing cumulate pile results in the modification both the incoming liquid and the host-rock cumulates. Our study highlights the necessity of considering this type of process when modelling the geochemistry of lavas erupted from magma chambers subject to repeated replenishment.

Modelling in vivo creatine/phosphocreatine in vitro reveals divergent adaptations in human muscle mitochondrial respiratory control by ADP after acute and chronic exercise.

PubMed

Ydfors, Mia; Hughes, Meghan C; Laham, Robert; Schlattner, Uwe; Norrbom, Jessica; Perry, Christopher G R

2016-06-01

Mitochondrial respiratory sensitivity to ADP is thought to influence muscle fitness and is partly regulated by cytosolic-mitochondrial diffusion of ADP or phosphate shuttling via creatine/phosphocreatine (Cr/PCr) through mitochondrial creatine kinase (mtCK). Previous measurements of respiration in vitro with Cr (saturate mtCK) or without (ADP/ATP diffusion) show mixed responses of ADP sensitivity following acute exercise vs. less sensitivity after chronic exercise. In human muscle, modelling in vivo 'exercising' [Cr:PCr] during in vitro assessments revealed novel responses to exercise that differ from detections with or without Cr (±Cr). Acute exercise increased ADP sensitivity when measured without Cr but had no effect ±Cr or with +Cr:PCr, whereas chronic exercise increased sensitivity ±Cr but lowered sensitivity with +Cr:PCr despite increased markers of mitochondrial oxidative capacity. Controlling in vivo conditions during in vitro respiratory assessments reveals responses to exercise that differ from typical ±Cr comparisons and challenges our understanding of how exercise improves metabolic control in human muscle. Mitochondrial respiratory control by ADP (Kmapp ) is viewed as a critical regulator of muscle energy homeostasis. However, acute exercise increases, decreases or has no effect on Kmapp in human muscle, whereas chronic exercise surprisingly decreases sensitivity despite greater mitochondrial content. We hypothesized that modelling in vivo mitochondrial creatine kinase (mtCK)-dependent phosphate-shuttling conditions in vitro would reveal increased sensitivity (lower Kmapp ) after acute and chronic exercise. The Kmapp was determined in vitro with 20 mm Cr (+Cr), 0 mm Cr (-Cr) or 'in vivo exercising' 20 mm Cr/2.4 mm PCr (Cr:PCr) on vastus lateralis biopsies sampled from 11 men before, immediately after and 3 h after exercise on the first, fifth and ninth sessions over 3 weeks. Dynamic responses to acute exercise occurred throughout training, whereby the first session did not change Kmapp with in vivo Cr:PCr despite increases in -Cr. The fifth session decreased sensitivity with Cr:PCr or +Cr despite no change in -Cr. Chronic exercise increased sensitivity ±Cr in association with increased electron transport chain content (+33-62% complexes I-V), supporting classic proposals that link increased sensitivity to oxidative capacity. However, in vivo Cr:PCr reveals a perplexing decreased sensitivity, contrasting the increases seen ±Cr. Functional responses occurred without changes in fibre type or proteins regulating mitochondrial-cytosolic energy exchange (mtCK, VDAC and ANT). Despite the dynamic responses seen with ±Cr, modelling in vivo phosphate-shuttling conditions in vitro reveals that ADP sensitivity is unchanged after high-intensity exercise and is decreased after training. These findings challenge our understanding of how exercise regulates skeletal muscle energy homeostasis. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Durable Complete Response After Discontinuation of Pembrolizumab in Patients With Metastatic Melanoma.

PubMed

Robert, Caroline; Ribas, Antoni; Hamid, Omid; Daud, Adil; Wolchok, Jedd D; Joshua, Anthony M; Hwu, Wen-Jen; Weber, Jeffrey S; Gangadhar, Tara C; Joseph, Richard W; Dronca, Roxana; Patnaik, Amita; Zarour, Hassane; Kefford, Richard; Hersey, Peter; Zhang, Jin; Anderson, James; Diede, Scott J; Ebbinghaus, Scot; Hodi, F Stephen

2017-12-28

Purpose Pembrolizumab provides durable antitumor activity in metastatic melanoma, including complete response (CR) in about 15% of patients. Data are limited on potential predictors of CR and patient disposition after pembrolizumab discontinuation after CR. We describe baseline characteristics and long-term follow-up in patients who experienced CR with pembrolizumab in the KEYNOTE-001 study ( ClinicalTrials.gov identifier: NCT01295827). Patients and Methods Patients with ipilimumab-naive or -treated advanced/metastatic melanoma received one of three dose regimens of pembrolizumab. Eligible patients who received pembrolizumab for ≥ 6 months and at least two treatments beyond confirmed CR could discontinue therapy. Response was assessed every 12 weeks by central Response Evaluation Criteria in Solid Tumors version 1.1. For this analysis, CR was defined per investigator assessment, immune-related response criteria, and potential predictors of CR were evaluated using univariate and multivariate analyses. Results Of 655 treated patients, 105 (16.0%) achieved CR after median follow-up of 43 months. At data cutoff, 92 patients (87.6%) had CR, with median follow-up of 30 months from first CR. Fourteen (13.3%) patients continued to receive treatment for a median of ≥ 40 months. Pembrolizumab was discontinued by 91 patients (86.7%), including 67 (63.8%) who proceeded to observation without additional anticancer therapy. The 24-month disease-free survival rate from time of CR was 90.9% in all 105 patients with CR and 89.9% in the 67 patients who discontinued pembrolizumab after CR for observation. Tumor size and programmed death-ligand 1 status were among the baseline factors independently associated with CR by univariate analysis. Conclusion Patients with metastatic melanoma can have durable complete remission after discontinuation of pembrolizumab, and the low incidence of relapse after median follow-up of approximately 2 years from discontinuation provides hope for a cure for some patients. The mechanisms underlying durable CR require further investigation.

Multicenter phase II study of weekly docetaxel, cisplatin, and S-1 (TPS) induction chemotherapy for locally advanced squamous cell cancer of the head and neck.

PubMed

Bae, Woo Kyun; Hwang, Jun Eul; Shim, Hyun Jeong; Cho, Sang Hee; Lee, Ki Hyeong; Han, Hye Suk; Song, Eun-Kee; Yun, Hwan Jung; Cho, In Sung; Lee, Joon Kyoo; Lim, Sang-Chul; Chung, Woong-Ki; Chung, Ik-Joo

2013-03-06

The purpose of this study was to evaluate the efficacy and tolerability of weekly docetaxel, cisplatin, and S-1 (weekly TPS) as induction chemotherapy for patients with locally advanced head and neck squamous cell carcinoma (HNSCC). A total of 35 patients with previously untreated, locally advanced HNSCC were enrolled. Seven patients (20%) were diagnosed with stage III HNSCC and 28 patients (80%) were diagnosed with stage IV. Induction treatment included 30 mg/m(2) docetaxel on day 1 and 8, 60 mg/m(2) cisplatin on day 1, and 70 mg/m(2) S-1 on days 1 to 14. The regimen was repeated every 21 days. After three courses of induction chemotherapy, patients received concurrent chemoradiotherapy. Among the 35 patients, 30 (85.7%) completed induction chemotherapy. The response to induction chemotherapy was as follows: nine patients (25.7%) achieved a complete response (CR) and the overall response rate (ORR) was 85.7%. Grades 3-4 toxicity during induction therapy included neutropenia (28.5%), neutropenic fever (8.5%), and diarrhea (17.1%). After completion of concurrent chemoradiotherapy, the CR rate was 62.8% and the partial response (PR) was 22.8%. Estimates of progression-free and overall survival at 2 years were 73.2% and 79.3%, respectively. Weekly TPS is a promising regimen that is well-tolerated, causes minimal myelosuppression and is effective as an outpatient regimen for locally advanced HNSCC. ClinicalTrials.gov: NCT01645748.

Ifosfamide and cisplatin as neoadjuvant chemotherapy for advanced cervical carcinoma.

PubMed

Leone, B; Vallejo, C; Perez, J; Cuevas, M A; Machiavelli, M; Lacava, J; Focaccia, G; Ferreyra, R; Suttora, G; Romero, A; Castaldi, J; Arroyo, A; Rabinovich, M

1996-04-01

A phase II trial was performed to evaluate the efficacy and toxicity of a combination of cisplatin (CDDP) and ifosfamide (IFX) as neoadjuvant chemotherapy in advanced cervical carcinoma (ACC). Between August 1991 and September 1993, 57 untreated patients with stages IIB to IVA were entered into this study. Median age was 44 years (range, 25 to 74 years). The distribution by stages (International Federation of Gynecology and Obstetrics) was as follows: IIB, 31 patients; IIIB, 21 patients; and IVA, 5 patients. Therapy consisted of IFX 2000 mg/m(2) 1-h i.v. infusion days 1 to 3; mesna 400 mg/m(2) i.v. bolus at hours 0 and 4, and 800 mg p.o. at hour 8; and CDDP 100 mg/m(2) on day 3. Cycles were repeated every 28 days for a total of three courses. Both staging and response assessment were performed by a multidisciplinary team. An objective response was observed in 30 of 56 patients (54%; 95% confidence interval, 41 to 67%). Four patients (7%) had a complete response (CR) and 26(46%) had a partial response (PR). Patients with CR or operable PR underwent surgery, otherwise received definitive radiotherapy. Toxicity was mild to moderate. There were no toxicity related deaths. These results indicate that IFX/CDDP is an active combination for ACC with mild toxicity. The results of phase III studies that evaluate the real impact of neoadjuvant chemotherapy are awaited.

Primary Mediastinal Large B-Cell Lymphoma: Results of Intensive Chemotherapy Regimens (MACOP-B/VACOP-B) Plus Involved Field Radiotherapy on 53 Patients. A Single Institution Experience

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

Mazzarotto, Renzo; Boso, Caterina; Vianello, Federica

2007-07-01

Purpose: The optimal therapy for primary mediastinal large B-cell lymphoma (PMLBCL) remains undefined. The superiority of intensive chemotherapy regimens (Methotrexate, Doxorubicin, Cyclophosphamide, Vincristine, Prednisone, Bleomycin [MACOP-B]/Etoposide, Doxorubicin, Cyclophosphamide, Vincristine, Prednisone, Bleomycin [VACOP-B]) over Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (CHOP)-like chemotherapy is upheld by some authors. The role of radiotherapy is still debated. In the absence of randomized trials, we report clinical findings and treatment response in 53 consecutive patients treated with intensive chemotherapy and mediastinal involved-field radiation therapy (IFRT). Methods and Material: Fifty-three consecutive patients with PMLBCL were retrospectively analyzed. Planned treatment consisted of induction chemotherapy (I-CT; Prednisone, Methotrexate, Doxorubicin, Cyclophosphamide,more » Etoposide-Mechloroethamine, Vincristine, Procarbazine, Prednisone [ProMACE-MOPP] in the first 2 patients, MACOP-B in the next 11, and VACOP-B in the last 40) followed by IFRT. Planned treatment was concluded in 43 of 53 patients; in 10 patients, I-CT was not immediately followed by IFRT. Among these 10 patients, 6 received high-dose chemotherapy (HD-CT) followed by IFRT, 2 received HD-CT, and 2 received no further treatment. Results: After a median follow-up of 93.9 months (range, 6-195 months), 45 of 53 patients (84.9%) were alive without disease. Eight patients died: 7 of PMLBCL and 1 of toxicity during HD-CT. The 5-year disease-free survival (DFS) and overall survival rates were 93.42% and 86.6%, respectively. The response rates after I-CT were complete response (CR) in 20 (37.73%) and partial response (PR) in 30 (56.60%); 3 patients (5.66%) were considered nonresponders. Among patients in PR after chemotherapy, 92% obtained a CR after IFRT. Conclusions: Our report confirms the efficacy of intensive chemotherapy plus mediastinal IFRT. IFRT plays a pivotal role in inducing CR in patients in PR after chemotherapy.« less

Supratentorial primitive neuroectodermal tumors (S-PNET) in children: A prospective experience with adjuvant intensive chemotherapy and hyperfractionated accelerated radiotherapy

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

Massimino, Maura; Gandola, Lorenza; Spreafico, Filippo

Purpose: Supratentorial primitive neuroectodermal tumors (S-PNET) are rare and have a grim prognosis, frequently taking an aggressive course with local relapse and metastatic spread. We report the results of a mono-institutional therapeutic trial. Methods and Materials: We enrolled 15 consecutive patients to preradiation chemotherapy (CT) consisting of high-dose methotrexate, high-dose etoposide, high-dose cyclophosphamide, and high-dose carboplatin, craniospinal irradiation (CSI) with hyperfractionated accelerated radiotherapy (HART) plus focal boost, maintenance with vincristine/lomustine or consolidation with high-dose thiotepa followed by autologous stem-cell rescue. Results: Median age was 9 years; 7 were male, 8 female. Site of disease was pineal in 3, elsewhere inmore » 12. Six patients were had no evidence of disease after surgery (NED). Of those with evidence of disease after surgery (ED), 2 had central nervous system spread. Of the 9 ED patients, 2 had complete response (CR) and 2 partial response (PR) after CT, 4 stable disease, and 1 progressive disease. Of the 7 ED patients before radiotherapy, 1 had CR, 4 PR, and 2 minor response, thus obtaining a 44% CR + PR after CT and 71% after HART. Because of rapid progression in 2 of the first 5 patients, high-dose thiotepa was systematically adopted after HART in the subsequent 10 patients. Six of 15 patients relapsed (4 locally, 1 locally with dissemination, 1 with dissemination) a mean of 6 months after starting CT, 2 developed second tumors; 5 of 6 relapsers died at a median of 13 months. Three-year progression-free survival, event-free survival, and overall survival were 54%, 34%, and 61%, respectively. Conclusion: Hyperfractionated accelerated RT was the main tool in obtaining responses in S-PNET; introducing the myeloablative phase improved the prognosis (3/10 vs. 3/5 relapses), though the outcome remained unsatisfactory despite the adoption of this intensive treatment.« less

Paclitaxel, Ifosfamide, and Cisplatin Efficacy for First-Line Treatment of Patients With Intermediate- or Poor-Risk Germ Cell Tumors

PubMed Central

Hu, James; Dorff, Tanya B.; Lim, Kristina; Patil, Sujata; Woo, Kaitlin M.; Carousso, Maryann; Hughes, Amanda; Sheinfeld, Joel; Bains, Manjit; Daneshmand, Siamak; Ketchens, Charlene; Bajorin, Dean F.; Bosl, George J.; Quinn, David I.; Motzer, Robert J.

2016-01-01

Purpose Paclitaxel, ifosfamide, and cisplatin (TIP) achieved complete responses (CRs) in two thirds of patients with advanced germ cell tumors (GCTs) who relapsed after first-line chemotherapy with cisplatin and etoposide with or without bleomycin. We tested the efficacy of first-line TIP in patients with intermediate- or poor-risk disease. Patients and Methods In this prospective, multicenter, single-arm phase II trial, previously untreated patients with International Germ Cell Cancer Collaborative Group poor-risk or modified intermediate-risk GCTs received four cycles of TIP (paclitaxel 240 mg/m2 over 2 days, ifosfamide 6 g/m2 over 5 days with mesna support, and cisplatin 100 mg/m2 over 5 days) once every 3 weeks with granulocyte colony-stimulating factor support. The primary end point was the CR rate. Results Of the first 41 evaluable patients, 28 (68%) achieved a CR, meeting the primary efficacy end point. After additional accrual on an extension phase, total enrollment was 60 patients, including 40 (67%) with poor risk and 20 (33%) with intermediate risk. Thirty-eight (68%) of 56 evaluable patients achieved a CR and seven (13%) achieved partial responses with negative markers (PR-negative) for a favorable response rate of 80%. Five of seven achieving PR-negative status had seminoma and therefore did not undergo postchemotherapy resection of residual masses. Estimated 3-year progression-free survival and overall survival rates were 72% (poor risk, 63%; intermediate risk, 90%) and 91% (poor risk, 87%; intermediate risk, 100%), respectively. Grade 3 to 4 toxicities consisted primarily of reversible hematologic or electrolyte abnormalities, including neutropenic fever in 18%. Conclusion TIP demonstrated efficacy as first-line therapy for intermediate- and poor-risk GCTs with an acceptable safety profile. Given higher rates of favorable response, progression-free survival, and overall survival compared with prior first-line studies, TIP warrants further study in this population. PMID:27185842

T cell-independent and T cell-dependent immunoglobulin G responses to polyomavirus infection are impaired in complement receptor 2-deficient mice.

PubMed

Szomolanyi-Tsuda, Eva; Seedhom, Mina O; Carroll, Michael C; Garcea, Robert L

2006-08-15

Polyomavirus (PyV) infection induces protective T cell-independent (TI) IgM and IgG antibody responses in T cell-deficient mice, but these responses are not generated by immunization with viral proteins or virus like particles. We hypothesized that innate signals contribute to the generation of isotype-switched antiviral antibody responses. We studied the role of complement receptor (CR2) engagement in TI and T cell-dependent (TD) antibody responses to PyV using CR2-deficient mice. Antiviral IgG responses were reduced by 80-40% in CR2-/- mice compared to wild type. Adoptive transfer experiments demonstrated the need for CR2 not only in TD, but also in TI IgG responses to PyV. Transfer of CR2-/- B lymphocytes to SCID mice resulted in TI antiviral IgG responses that corresponded to 10% of that seen in wild-type B cell-reconstituted mice. Thus, our studies revealed a profound dependence of TI and TD antiviral antibody responses on CR2-mediated signals in PyV-infected mice, where the viral antigen is abundant and persistent.

Vascular mechanisms underlying the hypotensive effect of Rumex acetosa.

PubMed

Qamar, Hafiz Misbah-Ud-Din; Qayyum, Rahila; Salma, Umme; Khan, Shamim; Khan, Taous; Shah, Abdul Jabbar

2018-12-01

Rumex acetosa L. (Polygonaceae) is well known in traditional medicine for its therapeutic efficacy as an antihypertensive. The study investigates antihypertensive potential of crude methanol extract (Ra.Cr) and fractions of Rumex acetosa in normotensive and hypertensive rat models and probes the underlying vascular mechanisms. Ra.Cr and its fractions were tested in vivo on normotensive and hypertensive Sprague-Dawley rats under anaesthesia for blood pressure lowering effect. In vitro experiments on rat and Oryctolagus cuniculus rabbit aortae were employed to probe the underlying vasorelaxant mechanism. In normotensive rats under anaesthesia, Ra.Cr caused fall in MAP (40 mmHg) at 50 mg/kg with % fall of 27.88 ± 4.55. Among the fractions tested, aqueous fraction was more potent at the dose of 50 mg/kg with % fall of 45.63 ± 2.84. In hypertensive rats under similar conditions, extract and fractions showed antihypertensive effect at same doses while aqueous fraction being more potent, exhibited 68.53 ± 4.45% fall in MAP (70 mmHg). In isolated rat aortic rings precontracted with phenylephrine (PE), Ra.Cr and fractions induced endothelium-dependent vasorelaxation, which was partially blocked in presence of l-NAME, indomethacin and atropine. In isolated rabbit aortic rings pre-contracted with PE and K + -(80 mM), Ra.Cr induced vasorelaxation and shifted Ca 2+ concentration-response curves to the right and suppressed PE peak formation, similar to verapamil, in Ca 2+ -free medium. The data indicate that l-NAME and atropine-sensitive endothelial-derived NO and COX enzyme inhibitors and Ca 2+ entry blocking-mediated vasodilator effect of the extract explain its antihypertensive potential.

Conflict resolution and adaptation in normal aging: the role of verbal intelligence and cognitive reserve.

PubMed

Puccioni, Olga; Vallesi, Antonino

2012-12-01

The present study investigated effects of cognitive aging on conflict resolution (the ability to suppress prepotent and distracting, irrelevant information) and conflict adaptation (the adjustment of conflict resolution based on previously experienced conflict level). In addition, it aimed at investigating whether Cognitive Reserve (CR) and intelligence play a compensatory role against age-related deficits in both factors. A color-word Stroop task with no feature repetitions (i.e., neither the word nor the color was repeated in two subsequent trials) was administered to 23 older adults with no dimentia (65-79 years old) and 22 younger controls (18-34 years old), in addition to measures of intelligence and CR. Older adults' performance was characterized by general slowing. However, response slowing inversely correlated with intelligence, education, and a cognitive-reserve index. The Stroop effect (i.e., response-time (RT) difference between incongruent and congruent conditions) was larger in older adults than in younger controls, and in the older group only, it negatively correlated with verbal IQ. With this feature-repetitions-free Stroop task, we confirmed the presence of some conflict adaptation effects, which, however, were spared by aging. Altogether, these findings show that older adults can cope better with age-related impairment in verbal interference resolution, if they have enough intelligence resources in a related (verbal) domain, whereas CR plays a role in general performance speed only. We therefore suggest that general and specific accounts of cognitive aging may apply to different processing stages, which are influenced by partially different compensatory factors. 2013 APA, all rights reserved

Chromium genotoxicity: a double-edged sword

PubMed Central

Nickens, Kristen P.; Patierno, Steven R.; Ceryak, Susan

2010-01-01

Certain forms of hexavalent chromium [Cr(VI)] are known respiratory carcinogens that induce a broad spectrum of DNA damage. Cr(VI)-carcinogenesis may be initiated or promoted through several mechanistic processes including, the intracellular metabolic reduction of Cr(VI) producing chromium species capable of interacting with DNA to yield genotoxic and mutagenic effects, Cr(VI)-induced inflammatory/immunological responses, and alteration of survival signaling pathways. Cr(VI) enters the cell through nonspecific anion channels, and is metabolically reduced by agents including ascorbate, glutathione, and cysteine to Cr(V), Cr(IV), and Cr(III). Cr(III) has a weak membrane permeability capacity and is unable to cross the cell membrane, thereby trapping it within the cell where it can bind to DNA and produce genetic damage leading to genomic instability. Structural genetic lesions produced by the intracellular reduction of Cr(VI) include DNA adducts, DNA strand breaks, DNA-protein crosslinks, oxidized bases, abasic sites, and DNA inter- and intrastrand crosslinks. The damage induced by Cr(VI) can lead to dysfunctional DNA replication and transcription, aberrant cell cycle checkpoints, dysregulated DNA repair mechanisms, microsatelite instability, inflammatory responses, and the disruption of key regulatory gene networks responsible for the balance of cell survival and cell death, which may all play an important role in Cr(VI) carcinogenesis. Several lines of evidence have indicated that neoplastic progression is a result of consecutive genetic/epigenetic changes that provide cellular survival advantages, and ultimately lead to the conversion of normal human cells to malignant cancer cells. This review is based on studies that provide a glimpse into Cr(VI) carcinogenicity via mechanisms including Cr(VI)-induced death-resistance, the involvement of DNA repair mechanisms in survival after chromium exposure, and the activation of survival signaling cascades in response to Cr(VI) genotoxicity. PMID:20430016

Usefulness of Interim FDG-PET After Induction Chemotherapy in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck Receiving Sequential Induction Chemotherapy Followed by Concurrent Chemoradiotherapy

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

Yoon, Dok Hyun; Cho, Yoojin; Kim, Sang Yoon

2011-09-01

Purpose: Induction chemotherapy (ICT) has been used to select patients for organ preservation and determine subsequent treatments in patients with locally advanced squamous cell carcinoma of the head and neck (LASCCHN). Still, the clinical outcomes of LASCCHN patients who showed response to ICT are heterogeneous. We evaluated the efficacy of interim 18-fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) after ICT in this specific subgroup of LASCCHN patients who achieved partial response (PR) after ICT to predict clinical outcomes after concurrent chemoradiotherapy (CCRT). Methods and Materials: Twenty-one patients with LASCCHN who showed PR to ICT by Response Evaluation Criteria In Solid Tumors beforemore » definitive CCRT were chosen in this retrospective analysis. FDG-PET was performed before and 2-4 weeks after ICT to assess the extent of disease at baseline and the metabolic response to ICT, respectively. We examined the correlation of the metabolic response by the percentage decrease of maximum standardized uptake value (SUVmax) on the primary tumor or lymph node after ICT or a specific threshold of SUVmax on interim FDG-PET with clinical outcomes including complete response (CR) rate to CCRT, progression-free survival (PFS), and overall survival (OS). Results: A SUVmax of 4.8 on interim FDG-PET could predict clinical CR after CCRT (100% vs. 20%, p = 0.001), PFS (median, not reached vs. 8.5 mo, p < 0.001), and OS (median, not reached vs. 12.0 months, p = 0.001) with a median follow-up of 20.3 months in surviving patients. A 65% decrease in SUVmax after ICT from baseline also could predict clinical CR after CCRT (100% vs. 33.3%, p = 0.003), PFS (median, not reached vs. 8.9 months, p < 0.001) and OS (median, not reached vs. 24.4 months, p = 0.001) of the patients. Conclusion: These data suggest that interim FDG-PET after ICT might be a useful determinant to predict clinical outcomes in patients with LASCCHN receiving sequential ICT followed by CCRT.« less

Three-dimensional power Doppler ultrasound in the early assessment of response to concurrent chemo-radiotherapy for advanced cervical cancer.

PubMed

Xu, Yan; Zhu, Lijing; Ru, Tong; Wang, Huanhuan; He, Jian; Zhou, Zhengyang; Yang, Xiaofeng

2017-09-01

Background Three-dimensional power Doppler ultrasound (3D-PDU) imaging has been widely applied to the differentiation of benign and malignant cervical lesions; however, its potential value for predicting response to chemo-radiotherapy has not been fully explored. Purpose To investigate the feasibility of 3D-PDU imaging in predicting treatment response in patients receiving concurrent chemo-radiotherapy (CCRT) for advanced cervical cancer. Material and Methods Fifty-two patients with advanced cervical cancer who received CCRT underwent 3D-PDU examinations at four timepoints: pre-therapy (baseline), 1 week and 2 weeks during, as well as immediately post CCRT. Final tumor response was determined by change in tumor size using magnetic resonance imaging (MRI). Cervical tumor volumes and vascular indices were calculated and compared with the clinical outcome. Results Of the 52 patients, 32 patients who completed all four examinations were included in the analyses: 21 were classified as complete response (CR) and 11 as partial response (PR). During the treatment, the CR group showed that 3D vascular indices (VI and VFI) significantly increased at 1 week ( P = 0.028, P = 0.017, respectively) then decreased at 2 weeks and obviously decreased at therapy completion (both P < 0.001), whereas tumors significantly decreased in volume at 2 weeks after therapy initiation ( P < 0.05). However, no significant differences in 3D vascular indices values were seen in the PR group during the treatment course (all P > 0.05). Conclusion Prospective longitudinal 3D-PDU imaging may have potentials in monitoring early therapeutic response to CCRT in patients with cervical cancer.

Concurrent IMRT and weekly cisplatin followed by GDP chemotherapy in newly diagnosed, stage IE to IIE, nasal, extranodal NK/T-Cell lymphoma.

PubMed

Ke, Q-H; Zhou, S-Q; Du, W; Liang, G; Lei, Y; Luo, F

2014-12-12

On the basis of the benefits of frontline radiation in early-stage, extranodal natural killer (NK)/T-cell lymphoma (ENKTL), we conducted the trial of concurrent chemoradiotherapy (CCRT) followed by three cycles of gemcitabine, dexamethasone and cisplatin (GDP). Thirty-two patients with newly diagnosed, stage IE to IIE, nasal ENKTL received CCRT (that is, all patients received intensity-modulated radiotherapy 56 Gy and cisplatin 30 mg/m(2) weekly, 3-5 weeks). Three cycles of GDP (gemcitabine 1000 mg/m(2) intravenously (i.v.) on days 1 and 8, dexamethasone 40 mg orally on days 1-4 and cisplatin 75 mg/m(2) i.v. on day 1 (GDP), every 21 days as an outpatient were scheduled after CCRT. All patients completed CCRT, which resulted in 100% response that included 24 complete responses (CRs) and eight partial responses. The CR rate after CCRT was 75.0% (that is, 24 of 32 responses). Twenty-eight of the 32 patients completed the planned three cycles of GDP, whereas four patients did not because they withdrew (n = 1) or because they had an infection (n = 3). The overall response rate and the CR rate were 90.6% (that is, 29 of 32 responses) and 84.4% (that is, 27 of 32 responses), respectively. Only two patient experienced grade 3 toxicity during CCRT (nausea), whereas 13 of the 30 patients experienced grade 4 neutropenia. The estimated 3-year overall survival and progression-free rates were 87.50% and 84.38%, respectively. In conclusion, CCRT followed by GDP chemotherapy can be a feasible and effective treatment strategy for stage IE to IIE nasal ENKTL.

Neuropsychological profile and clinical effects of arginine treatment in children with creatine transport deficiency

PubMed Central

2012-01-01

Background SLC6A8, an X-linked gene, encodes the creatine transporter (CRTR) and its mutations lead to cerebral creatine (Cr) deficiency which results in mental retardation, speech and language delay, autistic-like behaviour and epilepsy (CRTR-D, OMIM 300352). CRTR-D represents the most frequent Cr metabolism disorder but, differently from Cr synthesis defects, that are partially reversible by oral Cr supplementation, does not respond to Cr treatment even if precociously administrated. The precursors of Cr are the non-essential amino acids Glycine (Gly) and Arginine (Arg), which have their own transporters at the brain–blood barrier level and, therefore, their supplementation appears an attractive and feasible therapeutic option aimed at stimulating Cr endogenous synthesis and, in this way, at overcoming the block of Cr transport within the brain. However, until now the effects of Arg and/or Gly supplementation on Cr brain levels and behaviour have been controversial. Methods In this study five Italian male patients affected by CRTR-D were supplemented with oral L-Arg at a dosage of 300 mg/kg/day divided into 3 doses, for 24–36 months. Biochemical and plasmatic amino acids examinations and thyroid hormone dosages were periodically performed. Moreover, Proton and Phosphorus Magnetic Resonance Spectroscopy (MRS) was monitored during follow-up in concurrence with neuropsychological evaluations. Results During L-Arg treatment a clinical improvement in motor skills and to a lesser extent in communication and attention was observed. In addition, all patients had a reduction in the number and frequency of epileptic seizures. Daily living skills appeared also to be positively influenced by L-Arg treatment. Moreover, Total Cr and especially PhosphoCr, evaluated by proton and phosphorus spectroscopy, showed a mild increase, although well below the normal range. Conclusion This study provides information to support the effectiveness of L-Arg supplement treatment in CTRT-D patients; in fact the syndromic pattern of cognitive and linguistic deficit presented by CRTR-D patients was partially altered by L-Arg supplementation especially at a qualitative clinical level. Oral L-Arg may represent not only a protective factor towards a further cognitive decline, but can lead to the acquisition of new skills. PMID:22713831

Maternal caloric restriction partially rescues the deleterious effects of advanced maternal age on offspring

PubMed Central

Gribble, Kristin E; Jarvis, George; Bock, Martha; Mark Welch, David B

2014-01-01

While many studies have focused on the detrimental effects of advanced maternal age and harmful prenatal environments on progeny, little is known about the role of beneficial non-Mendelian maternal inheritance on aging. Here, we report the effects of maternal age and maternal caloric restriction (CR) on the life span and health span of offspring for a clonal culture of the monogonont rotifer Brachionus manjavacas. Mothers on regimens of chronic CR (CCR) or intermittent fasting (IF) had increased life span compared with mothers fed ad libitum (AL). With increasing maternal age, life span and fecundity of female offspring of AL-fed mothers decreased significantly and life span of male offspring was unchanged, whereas body size of both male and female offspring increased. Maternal CR partially rescued these effects, increasing the mean life span of AL-fed female offspring but not male offspring and increasing the fecundity of AL-fed female offspring compared with offspring of mothers of the same age. Both maternal CR regimens decreased male offspring body size, but only maternal IF decreased body size of female offspring, whereas maternal CCR caused a slight increase. Understanding the genetic and biochemical basis of these different maternal effects on aging may guide effective interventions to improve health span and life span. PMID:24661622

Application of Sequential Extractions and X-ray Absorption Spectroscopy to Determine the Speciation of Chromium in Northern New Jersey Marsh Soils Developed in Chromite ore Processing Residue (COPR)

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

Elzinga, E.; Cirmo, A

2010-01-01

The Cr speciation in marsh soils developed in weathering chromite ore processing residue (COPR) was characterized using sequential extractions and synchrotron microbeam and bulk X-ray absorption spectroscopic (XAS) analyses. The sequential extractions suggested substantial Cr associated with reducible and oxidizable soil components, and significant non-extractable residual Cr. Notable differences in Cr speciation estimates from three extraction schemes underscore the operationally defined nature of Cr speciation provided by these methods. Micro X-ray fluorescence maps and {mu}-XAS data indicated the presence of {micro}m-sized chromite particles scattered throughout the weathered COPR matrix. These particles derive from the original COPR material, and have relativelymore » high resistance towards weathering, and therefore persist even after prolonged leaching. Bulk XAS data further indicated Cr(III) incorporated in Fe(OH){sub 3}, and Cr(III) associated with organic matter. The low Cr contents of the weathered material (200-850 ppm) compared to unweathered COPR (20,000-60,000 ppm) point to substantial Cr leaching during COPR weathering, with partial repartitioning of released Cr into secondary Fe(OH){sub 3} phases and organics. The effects of anoxia on Cr speciation, and the potential of active COPR weathering releasing Cr(VI) deeper in the profile require further study.« less

Source identification of eight hazardous heavy metals in agricultural soils of Huizhou, Guangdong Province, China.

PubMed

Cai, Limei; Xu, Zhencheng; Ren, Mingzhong; Guo, Qingwei; Hu, Xibang; Hu, Guocheng; Wan, Hongfu; Peng, Pingan

2012-04-01

One hundred and four surface samples and 40 profiles samples in agricultural soils collected from Huizhou in south-east China were monitored for total contents of 8 heavy metals, and analyzed by multivariate statistical techniques and enrichment factor (EF), in order to investigate their origins. The results indicate that the concentrations of Cu, Zn, Ni, Cr, Pb, Cd, As and Hg in soils are 16.74, 57.21, 14.89, 27.61, 44.66, 0.10, 10.19 and 0.22 mg/kg, respectively. Compared to the soil background contents in Guangdong Province, the mean concentrations of Hg, Cd, Zn, Pb and As in soil of Huizhou are higher, especially Hg and Cd, which are 2.82 and 1.79 times the background values, respectively. Cr, Ni, Cu, partially, Zn and Pb mainly originate from a natural source. Cd, As, partially, Zn mainly come from agricultural practices. However, Hg, partially, Pb originate mainly from industry and traffic sources. Copyright © 2011 Elsevier Inc. All rights reserved.

Parametrization of local CR automorphisms by finite jets and applications

NASA Astrophysics Data System (ADS)

Lamel, Bernhard; Mir, Nordine

2007-04-01

For any real-analytic hypersurface Msubset {C}^N , which does not contain any complex-analytic subvariety of positive dimension, we show that for every point pin M the local real-analytic CR automorphisms of M fixing p can be parametrized real-analytically by their ell_p jets at p . As a direct application, we derive a Lie group structure for the topological group operatorname{Aut}(M,p) . Furthermore, we also show that the order ell_p of the jet space in which the group operatorname{Aut}(M,p) embeds can be chosen to depend upper-semicontinuously on p . As a first consequence, it follows that given any compact real-analytic hypersurface M in {C}^N , there exists an integer k depending only on M such that for every point pin M germs at p of CR diffeomorphisms mapping M into another real-analytic hypersurface in {C}^N are uniquely determined by their k -jet at that point. Another consequence is the following boundary version of H. Cartan's uniqueness theorem: given any bounded domain Ω with smooth real-analytic boundary, there exists an integer k depending only on partial Ω such that if H\\colon Ωto Ω is a proper holomorphic mapping extending smoothly up to partial Ω near some point pin partial Ω with the same k -jet at p with that of the identity mapping, then necessarily H=Id . Our parametrization theorem also holds for the stability group of any essentially finite minimal real-analytic CR manifold of arbitrary codimension. One of the new main tools developed in the paper, which may be of independent interest, is a parametrization theorem for invertible solutions of a certain kind of singular analytic equations, which roughly speaking consists of inverting certain families of parametrized maps with singularities.

Reproducibility over a 1-month period of 1H-MR spectroscopic imaging NAA/Cr ratios in clinically stable multiple sclerosis patients.

PubMed

Mostert, J P; Blaauw, Y; Koch, M W; Kuiper, A J; Hoogduin, J M; De Keyser, J

2008-08-01

N-acetylaspartate/creatine (NAA/Cr) ratios, assessed with proton magnetic resonance spectroscopy, are increasingly used as a surrogate marker for axonal dysfunction and degeneration in multiple sclerosis (MS). The purpose of this study was to test short-time reproducibility of NAA/Cr ratios in patients with clinically stable MS. In 35 MS patients we analysed NAA/Cr ratios obtained with (1)H-MR spectroscopic imaging at the centrum semiovale either with lateral ventricles partially included (group 1; n=15) or more cranially with no ventricles included (group 2; n=20). To test short-term reproducibility of the NAA/Cr measurements, patients were scanned twice 4 weeks apart. We determined mean NAA/Cr and Cho/Cr ratios of 12 grey matter and 24 white matter voxels. Mean NAA/Cr ratios of both the white and grey matter did not change after 4 weeks. Overall 4-week reproducibility of the NAA/Cr ratio, expressed as coefficient of variation, was 4.8% for grey matter and 3.5% for white matter. Reproducibility of cranial scanning of the ventricles was slightly better than with cerebrospinal fluid included. Our study shows good short-term reproducibility of NAA/Cr ratio measurements in the centrum semiovale, which supports the reliability of this technique for longitudinal studies.

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

Briggs, Samuel A.; Edmondson, Philip D.; Littrell, Kenneth C.

Here, FeCrAl alloys are currently under consideration for accident-tolerant fuel cladding applications in light water reactors owing to their superior high-temperature oxidation and corrosion resistance compared to the Zr-based alloys currently employed. However, their performance could be limited by precipitation of a Cr-rich α' phase that tends to embrittle high-Cr ferritic Fe-based alloys. In this study, four FeCrAl model alloys with 10–18 at.% Cr and 5.8–9.3 at.% Al were neutron-irradiated to nominal damage doses up to 7.0 displacements per atom at a target temperature of 320 °C. Small angle neutron scattering techniques were coupled with atom probe tomography to assessmore » the composition and morphology of the resulting α' precipitates. It was demonstrated that Al additions partially destabilize the α' phase, generally resulting in precipitates with lower Cr contents when compared with binary Fe-Cr systems. The precipitate morphology evolution with dose exhibited a transient coarsening regime akin to previously observed behavior in aged Fe-Cr alloys. Similar behavior to predictions of the LSW/UOKV models suggests that α' precipitation in irradiated FeCrAl is a diffusion-limited process with coarsening mechanisms similar to those in thermally aged high-Cr ferritic alloys.« less

Contemporary experience with high-dose interleukin-2 therapy and impact on survival in patients with metastatic melanoma and metastatic renal cell carcinoma.

PubMed

Alva, Ajjai; Daniels, Gregory A; Wong, Michael K K; Kaufman, Howard L; Morse, Michael A; McDermott, David F; Clark, Joseph I; Agarwala, Sanjiv S; Miletello, Gerald; Logan, Theodore F; Hauke, Ralph J; Curti, Brendan; Kirkwood, John M; Gonzalez, Rene; Amin, Asim; Fishman, Mayer; Agarwal, Neeraj; Lowder, James N; Hua, Hong; Aung, Sandra; Dutcher, Janice P

2016-12-01

High-dose interleukin-2 (HD IL-2) was approved for treatment of metastatic renal cell carcinoma (mRCC) in 1992 and for metastatic melanoma (mM) in 1998, in an era predating targeted therapies and immune checkpoint inhibitors. The PROCLAIM SM registry was established to collect and analyze data for patients treated with HD IL-2 in the current era. This analysis includes 170 patients with mM and 192 patients with mRCC treated between 2005 and 2012 with survival data current as of July 27, 2015. For patients with mM, complete response (CR) was observed in 5 %, partial response (PR) in 10 %, stable disease (SD) in 22 %, and 63 % had progressive disease (PD). The median overall survival (mOS) for these patients was 19.6 months, with a median follow-up of 43.1 months. The mOS was not reached for patients achieving CR or PR, and was 33.4 months for patients with SD. For patients with mRCC, 6 % achieved CR, 9 % had PR, 22 % had SD, and 62 % had PD. The mOS was 41 months, with a median follow-up of 46.6 months. The mOS for patients who had CR and PR was not reached and was 49.6 months for patients with SD. There were no treatment-related deaths among 362 patients. The duration of mOS for patients with mM and mRCC is longer than historically reported. These data support a continued role for IL-2 in the treatment of eligible patients with mM or mRCC and warrant further evaluation of HD IL-2 in combination or sequence with other therapeutic agents.

Microstructural and opto-electrical properties of chromium nitride films implanted with vanadium ions

NASA Astrophysics Data System (ADS)

Novaković, M.; Traverse, A.; Popović, M.; Lieb, K. P.; Zhang, K.; Bibić, N.

2012-07-01

We report on modifications of 280-nm thin polycrystalline CrN layers caused by vanadium ion implantation. The CrN layers were deposited at 150°C by d.c. reactive sputtering on Si(100) wafers and then implanted at room temperature with 80-keV V+ ions to fluences of 1×1017 and 2×1017 ions/cm2. Rutherford backscattering spectroscopy, cross-sectional transmission electron microscopy, and X-ray diffraction were used to characterize changes in the structural properties of the films. Their optical and electrical properties were analyzed by infrared spectroscopy in reflection mode and electrical resistivity measurements. CrN was found to keep its cubic structure under the conditions of vanadium ion implantation used here. The initially partially non-metallic CrN layer displays metallic character under implantation, which may be related to the possible formation of Cr1-x V x N.

Phase relations in the Fe-Ni-Cr-S system and the sulfidation of an austenitic stainless steel

NASA Technical Reports Server (NTRS)

Jacob, K. T.; Rao, D. B.; Nelson, H. G.

1977-01-01

The stability fields of various sulfide phases that form on Fe-Cr, Fe-Ni, Ni-Cr and Fe-Cr-Ni alloys were developed as a function of temperature and the partial pressure of sulfur. The calculated stability fields in the ternary system were displayed on plots of log P sub S sub 2 versus the conjugate extensive variable which provides a better framework for following the sulfidation of Fe-Cr-Ni alloys at high temperatures. Experimental and estimated thermodynamic data were used in developing the sulfur potential diagrams. Current models and correlations were employed to estimate the unknown thermodynamic behavior of solid solutions of sulfides and to supplement the incomplete phase diagram data of geophysical literature. These constructed stability field diagrams were in excellent agreement with the sulfide phases and compositions determined during a sulfidation experiment.

Physico-mechanical properties and prosthodontic applications of Co-Cr dental alloys: a review of the literature

PubMed Central

2014-01-01

Cobalt-Chromium (Co-Cr) alloys are classified as predominantly base-metal alloys and are widely known for their biomedical applications in the orthopedic and dental fields. In dentistry, Co-Cr alloys are commonly used for the fabrication of metallic frameworks of removable partial dentures and recently have been used as metallic substructures for the fabrication of porcelain-fused-to-metal restorations and implant frameworks. The increased worldwide interest in utilizing Co-Cr alloys for dental applications is related to their low cost and adequate physico-mechanical properties. Additionally, among base-metal alloys, Co-Cr alloys are used more frequently in many countries to replace Nickel-Chromium (Ni-Cr) alloys. This is mainly due to the increased concern regarding the toxic effects of Ni on the human body when alloys containing Ni are exposed to the oral cavity. This review article describes dental applications, metallurgical characterization, and physico-mechanical properties of Co-Cr alloys and also addresses their clinical and laboratory behavior in relation to those properties. PMID:24843400

Corrosion behavior of ODS steels with several chromium contents in hot nitric acid solutions

NASA Astrophysics Data System (ADS)

Tanno, Takashi; Takeuchi, Masayuki; Ohtsuka, Satoshi; Kaito, Takeji

2017-10-01

Oxide dispersion strengthened (ODS) steel cladding tubes have been developed for fast reactors. Tempered martensitic ODS steels with 9 and 11 wt% of chromium (9Cr-, 11Cr-ODS steel) are the candidate material in research being carried out at JAEA. In this work, fundamental immersion tests and electrochemical tests of 9 to 12Cr-ODS steels were systematically conducted in various nitric acid solutions at 95 °C. The corrosion rate decreased exponentially with effective solute chromium concentration (Creff) and nitric acid concentration. Addition of vanadium (V) and ruthenium (Ru) also decreased the corrosion rate. The combination of low Creff and dilute nitric acid could not avoid the active mass dissolution during active domain at the beginning of immersion, and the corrosion rate was high. Higher Creff decreased the partial anodic current during the active domain and assisted the passivation of the surface of the steel. Concentrated nitric acid and addition of Ru and V increased partial cathodic current and shifted the corrosion potential to noble side. These effects should have prevented the active mass dissolution and decreased the corrosion rate.

Combination chemoimmunotherapy with pentostatin, cyclophosphamide, and rituximab shows significant clinical activity with low accompanying toxicity in previously untreated B chronic lymphocytic leukemia

PubMed Central

Kay, Neil E.; Geyer, Susan M.; Call, Timothy G.; Shanafelt, Tait D.; Zent, Clive S.; Jelinek, Diane F.; Tschumper, Renee; Bone, Nancy D.; Dewald, Gordon W.; Lin, Thomas S.; Heerema, Nyla A.; Smith, Lisa; Grever, Michael R.; Byrd, John C.

2007-01-01

Building on the prior work of use of pentostatin in chronic lymphocytic leukemia (CLL), we initiated a trial of combined pentostatin (2 mg/m2), cyclophosphamide (600 mg/m2), and rituximab (375 mg/m2) for 65 symptomatic, previously untreated patients. Of 64 evaluable patients, 34 (53%) were high Rai risk, 71% were nonmutated for the immunoglobulin heavy-chain variable region gene, 34% were CD38+, and 34% were ZAP-70+. Thirty patients (52%) had one anomaly detected by fluorescence in situ (FISH) hybridization, and 21 (36%) had complex FISH defects. Thirty-eight patients (58%) had grade 3+ hematologic toxicity but minimal transfusion needs and no major infections. Responses occurred in 58 patients (91%), with 26 (41%) complete responses (CRs), 14 (22%) nodular partial responses (nodular PRs), and 18 (28%) partial responses (PRs). Many patients with a CR also lacked evidence of minimal residual disease by 2-color flow cytometry. Examination of prognostic factors demonstrated poor response in the 3 patients with del(17p). In contrast, we found this regimen was equally effective in young versus older (> 70 years) patients and in del(11q22.3) versus other favorable prognostic factors. Thus, this novel regimen of pentostatin, cyclophosphamide, and rituximab for previously untreated patients with CLL demonstrated significant clinical activity despite poor risk-based prognoses, achievement of minimal residual disease in some, and modest toxicity. PMID:17008537

Removal of Cr(VI) ions by sewage sludge compost biomass from aqueous solutions: Reduction to Cr(III) and biosorption

NASA Astrophysics Data System (ADS)

Chen, Huixia; Dou, Junfeng; Xu, Hongbin

2017-12-01

Sewage sludge compost biomass was used as a novel biosorbent to remove hexavalent chromium from water. Surface area analysis, scanning electron microscopy, fourier-transform infrared spectroscopy, energy-dispersive X-ray spectroscopy, and point zero charge was applied to study the microstructure, compositions and chemical bonding states of the biomass adsorbent. Effects of contact time, biomass dosage, agitation speed, pH, the initial concentration of Cr(VI) and Cr(Ⅲ) on its adsorption removal were also performed in the batch experiments. A model describing adsorption, desorption and reduction phenomena during the sorption process has been referenced to model Cr(VI) sorption onto sewage sludge compost biomass. The result of characterization test shows that adsorption of Cr(VI) onto sewage sludge compost biomass followed by the partial reduction to Cr(Ⅲ) by biomass groups such as hydroxyl, carboxyl, and amino groups. The absorption kinetics model in the description of adsorption-coupled reduction of Cr(VI) fits successfully the kinetic data obtained at different temperatures and describes the kinetics profile of total, hexavalent and trivalent chromium. The study shows that sewage sludge compost biomass could be used as a potential biosorbent for removal of hexavalent chromium from wastewaters.

Electronic, thermoelectric, and magneto-dielectric properties of Ca1-xNaxCr2O4

NASA Astrophysics Data System (ADS)

Kolodiazhnyi, Taras; Sakurai, Hiroya

2013-06-01

We report on electronic, thermoelectric, and magneto-dielectric properties of Ca1-xNaxCr2O4 series with a calcium ferrite-type structure prepared by high-pressure-high-temperature synthesis. Dielectric spectroscopy down to 2 K confirms that both CaCr2O4 and NaCr2O4 end members have an insulating ground state notwithstanding the fact that the latter compound has a mixed valence Cr3+/Cr4+ structure. A crossover from positive to negative charge carriers occurs in NaCr2O4 at T≈230 K. Partial substitution of Ca for Na brings about a change from n to p type carriers at ca. x =0.75. A strong suppression of thermal conductivity below TN=21 K was found in CaCr2O4 indicating a scattering of acoustic phonons from a long wave-length cycloidal magnetic excitations. A pronounced dielectric anomaly at Néel temperature adds CaCr2O4 to the multiferroic family of compounds. Lattice contribution to dielectric properties of NaCr2O4 at TN=125 K is screened by high electric conductivity. An onset of the magnetocapacitance above 3 T correlates with the spin-flop transition in NaCr2O4 at a critical field of 3.5 T. A strong non-saturated magnetocapacitance in this compound cannot be entirely attributed to the colossal magnetoresistance.

A combined APT and SANS investigation of α' phase precipitation in neutron-irradiated model FeCrAl alloys

DOE PAGES

Briggs, Samuel A.; Edmondson, Philip D.; Littrell, Kenneth C.; ...

2017-03-01

Here, FeCrAl alloys are currently under consideration for accident-tolerant fuel cladding applications in light water reactors owing to their superior high-temperature oxidation and corrosion resistance compared to the Zr-based alloys currently employed. However, their performance could be limited by precipitation of a Cr-rich α' phase that tends to embrittle high-Cr ferritic Fe-based alloys. In this study, four FeCrAl model alloys with 10–18 at.% Cr and 5.8–9.3 at.% Al were neutron-irradiated to nominal damage doses up to 7.0 displacements per atom at a target temperature of 320 °C. Small angle neutron scattering techniques were coupled with atom probe tomography to assessmore » the composition and morphology of the resulting α' precipitates. It was demonstrated that Al additions partially destabilize the α' phase, generally resulting in precipitates with lower Cr contents when compared with binary Fe-Cr systems. The precipitate morphology evolution with dose exhibited a transient coarsening regime akin to previously observed behavior in aged Fe-Cr alloys. Similar behavior to predictions of the LSW/UOKV models suggests that α' precipitation in irradiated FeCrAl is a diffusion-limited process with coarsening mechanisms similar to those in thermally aged high-Cr ferritic alloys.« less

Major Element Geochemistry of Peridotites from Santa Elena Ophiolite Complex, NW Costa Rica and Their Tectonic Implications

NASA Astrophysics Data System (ADS)

Wright, S.; Snow, J. E.; Gazel, E.; Sisson, V.

2010-12-01

The Santa Elena Ophiolite Complex (SEOC) is located on the west coast of Northern Costa Rica, near the Nicaraguan border. It consists primarily of preserved oceanic crustal rocks and underlying upper mantle thrust onto an accretionary complex. The petrogenesis and tectonic origin of this complex have widely been interpreted to be either a preserved mantle portion of the Caribbean Large Igneous Province (CLIP) as it drifted between North and South America from the Galapagos hotpot into the present day Caribbean Ocean around 80 Ma or as the mantle section to the nearby Nicoya complex. Previous structural work suggests that SEOC is a supra-subduction complex, not related to the CLIP or Nicoya. Our preliminary results agree. Mantle peridotites collected from the Santa Elena Ophiolite Complex consist primarily of spinel lherzolite (61 %) with minor amounts of harzburgite and dunite (22 % and 16 % respectively). Spinel Cr# [molar Cr / (Cr+Al)*100] is widely accepted to constrain mantle partial melting and lithospheric melt stagnation. Cr# of spinels within Santa Elena lherzolites fall between 12 and 35, suggesting an extent of 3 % to 13 % partial melting. Cr# of harzburgites range from 35 to 39, suggesting 13 % to 14 % partial melting. This range of partial melting suggests only modest depletion of this exposed portion of the ancient uppermost mantle. TiO2 concentrations of the lherzolite and harzburgite range from 0.004% to 0.128%, with the exception of one sample, SE10 - 17 (0.258%), and fall within the normal melting trend for mantle peridotites. The presence of dunite indicates that melt flow and associated melt - rock reaction with the surrounding peridotite took place within this portion of the mantle. A Cr# of 84.5 from one of these dunite samples indicate that significant melt rock reaction with refractory melts took place. Such results are rarely found in mid-ocean ridge abyssal peridotite settings, and are currently found primarily in forearc tectonic settings. However, due to the overall "normal" TiO2 concentrations in all but one spinel peridotite requires that if melt flow did occur, that the melt be nearly depleted in titanium. The relatively low Cr#'s and TiO2 concentrations of spinel in these peridotites that suggest low degrees of partial melting along with the paleo presence of melt flow and melt-rock reaction by low titanium melts, such as boninites, point toward a young fore-arc model for the tectonic origin of this ophiolite body rather than a preserved mantle portion of the CLIP. Additionally, two lines of evidence suggest SEOC was emplaced prior to the collision of the CLIP with North and South America. The SEOC is 1) capped by a Campanian (83.5 - 70.6 Ma) rudist limestone and 2) lies uncomformably atop Cenomanian (93.6 - 99.6 Ma) radiolarite beds. This suggests that the mantle portion of the SEOC was emplaced and exposed at the Caribbean ocean floor prior to the Late Cretaceous (Campanian), but no earlier than the Cenomanian. This combined tectonic and geochemical evidence suggests SEOC may be a portion of the proto-arc that existed between the Americas in the Cretaceous prior to assault by the CLIP.

Temperature-dependent selective oxidation processes for Ni-5Cr and Ni-4Al

DOE PAGES

Kruska, Karen; Schreiber, Daniel K.; Olszta, Matthew J.; ...

2018-05-09

The selective oxidation of Ni-5Cr and Ni-4 Al alloys is evaluated during high (800 °C) and low (420 °C) temperature exposures with the oxygen partial pressure moderated by a Ni/NiO powder buffer. Internal oxidation of Cr and Al is observed throughout the matrix and at grain boundaries at 800 °C accompanied by the ejection of Ni onto the surface for both. At 420 °C, matrix internal oxidation was eliminated and only Ni-4 Al exhibited intergranular (IG) oxidation. Surprisingly, a protective surface oxide rapidly formed for Ni-5Cr blocking IG oxidation. Finally, this is contradictory to results in 330–360 °C hydrogenated watermore » environments where both alloys show IG oxidation.« less

Temperature-dependent selective oxidation processes for Ni-5Cr and Ni-4Al

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

Kruska, Karen; Schreiber, Daniel K.; Olszta, Matthew J.

The selective oxidation of Ni-5Cr and Ni-4 Al alloys is evaluated during high (800 °C) and low (420 °C) temperature exposures with the oxygen partial pressure moderated by a Ni/NiO powder buffer. Internal oxidation of Cr and Al is observed throughout the matrix and at grain boundaries at 800 °C accompanied by the ejection of Ni onto the surface for both. At 420 °C, matrix internal oxidation was eliminated and only Ni-4 Al exhibited intergranular (IG) oxidation. Surprisingly, a protective surface oxide rapidly formed for Ni-5Cr blocking IG oxidation. Finally, this is contradictory to results in 330–360 °C hydrogenated watermore » environments where both alloys show IG oxidation.« less

Platelet aggregation caused by Carybdea rastonii toxins (CrTX-I, II and III) obtained from a jellyfish, Carybdea rastonii.

PubMed

Azuma, H; Sekizaki, S; Satoh, A; Nakajima, T

1986-05-01

The pharmacological mechanisms of platelet aggregation induced by highly toxic proteins (CrTX-I, CrTX-II, and CrTX-III) obtained from tentacles of a jellyfish, Carybdea rastonii, were investigated. When the partially purified toxin (pCrTX) and CrTXs were added to the citrated platelet-rich plasma (PRP), aggregation was produced in a concentration-dependent manner. The activity of CrTXs was approximately 100 times more potent than pCrTX. The CrTXs-induced aggregation was little affected by indomethacin and quinacrine at concentrations sufficient to inhibit arachidonic acid- and collagen-induced aggregation. The CrTXs-induced aggregation in washed platelets was significantly augmented in the presence of Ca2+. The pretreatment with verapamil failed to modify this augmentation of aggregation. The concentration of cytoplasmic-free calcium ([Ca2+]i) of platelets was increased by CrTXs at the same concentrations that produced aggregation. This effect of CrTXs was again little affected by verapamil. CrTXs at the same concentrations as those that produced aggregation and increased [Ca2+]i caused depolarization of platelets, which was unchanged after pretreatment with sodium or potassium transport inhibitors. CrTX-I significantly increased the 22Na flux into platelets and this effect of CrTX-I was unaffected by tetrodotoxin. The CrTX-I-induced aggregation, depolarization, and increase in [Ca2+]i were all significantly attenuated in the low Na+ medium. These results suggest that CrTXs cause a massive depolarization by increasing cation permeability and this generalized depolarization permits an inward movement of Ca2+ down its electrochemical gradient which, in turn, triggers platelet aggregation.

Anti-HER2 CD4(+) T-helper type 1 response is a novel immune correlate to pathologic response following neoadjuvant therapy in HER2-positive breast cancer.

PubMed

Datta, Jashodeep; Berk, Erik; Xu, Shuwen; Fitzpatrick, Elizabeth; Rosemblit, Cinthia; Lowenfeld, Lea; Goodman, Noah; Lewis, David A; Zhang, Paul J; Fisher, Carla; Roses, Robert E; DeMichele, Angela; Czerniecki, Brian J

2015-05-23

A progressive loss of circulating anti-human epidermal growth factor receptor-2/neu (HER2) CD4(+) T-helper type 1 (Th1) immune responses is observed in HER2(pos)-invasive breast cancer (IBC) patients relative to healthy controls. Pathologic complete response (pCR) following neoadjuvant trastuzumab and chemotherapy (T + C) is associated with decreased recurrence and improved prognosis. We examined differences in anti-HER2 Th1 responses between pCR and non-pCR patients to identify modifiable immune correlates to pathologic response following neoadjuvant T + C. Anti-HER2 Th1 responses in 87 HER2(pos)-IBC patients were examined using peripheral blood mononuclear cells pulsed with 6 HER2-derived class II peptides via IFN-γ ELISPOT. Th1 response metrics were anti-HER2 responsivity, repertoire (number of reactive peptides), and cumulative response across 6 peptides (spot-forming cells [SFC]/10(6) cells). Anti-HER2 Th1 responses of non-pCR patients (n = 4) receiving adjuvant HER2-pulsed type 1-polarized dendritic cell (DC1) vaccination were analyzed pre- and post-immunization. Depressed anti-HER2 Th1 responses observed in treatment-naïve HER2(pos)-IBC patients (n = 22) did not improve globally in T + C-treated HER2(pos)-IBC patients (n = 65). Compared with adjuvant T + C receipt, neoadjuvant T + C - utilized in 61.5 % - was associated with higher anti-HER2 Th1 repertoire (p = 0.048). While pCR (n = 16) and non-pCR (n = 24) patients did not differ substantially in demographic/clinical characteristics, pCR patients demonstrated dramatically higher anti-HER2 Th1 responsivity (94 % vs. 33 %, p = 0.0002), repertoire (3.3 vs. 0.3 peptides, p < 0.0001), and cumulative response (148.2 vs. 22.4 SFC/10(6), p < 0.0001) versus non-pCR patients. After controlling for potential confounders, anti-HER2 Th1 responsivity remained independently associated with pathologic response (odds ratio 8.82, p = 0.016). This IFN-γ(+) immune disparity was mediated by anti-HER2 CD4(+)T-bet(+)IFN-γ(+) (i.e., Th1) - not CD4(+)GATA-3(+)IFN-γ(+) (i.e., Th2) - phenotypes, and not attributable to non-pCR patients' immune incompetence, host-level T-cell anergy, or increased immunosuppressive populations. In recruited non-pCR patients, anti-HER2 Th1 repertoire (3.7 vs. 0.5, p = 0.014) and cumulative response (192.3 vs. 33.9 SFC/10(6), p = 0.014) improved significantly following HER2-pulsed DC1 vaccination. Anti-HER2 CD4(+) Th1 response is a novel immune correlate to pathologic response following neoadjuvant T + C. In non-pCR patients, depressed Th1 responses are not immunologically "fixed" and can be restored with HER2-directed Th1 immune interventions. In such high-risk patients, combining HER2-targeted therapies with strategies to boost anti-HER2 Th1 immunity may improve outcomes and mitigate recurrence.

Reductive solidification/stabilization of chromate in municipal solid waste incineration fly ash by ascorbic acid and blast furnace slag.

PubMed

Zhou, Xian; Zhou, Min; Wu, Xian; Han, Yi; Geng, Junjun; Wang, Teng; Wan, Sha; Hou, Haobo

2017-09-01

Fly ash is a hazardous byproduct of municipal solid waste incineration (MSWI). Cementitious material that is based on ground-granulated blast furnace slag (GGBFS) has been tested and proposed as a binder to stabilize Pb, Cd, and Zn in MSWI fly ash (FA). Cr, however, still easily leaches from MSWI FA. Different reagents, such as ascorbic acid (VC), NaAlO 2 , and trisodium salt nonahydrate, were investigated as potential Cr stabilizers. The results of the toxicity characteristic leaching procedure (TCLP) showed that VC significantly improved the stabilization of Cr via the reduction of Cr(VI) to Cr(III). VC, however, could interfere with the hydration process. Most available Cr was transformed into stable Cr forms at the optimum VC content of 2 wt%. Cr leaching was strongly pH dependent and could be represented by a quintic polynomial model. The results of X-ray diffraction and scanning electron microscopy-energy dispersive analysis revealed that hollow spheres in raw FA were partially filled with hydration products, resulting in the dense and homogeneous microstructure of the solidified samples. The crystal structures of C-S-H and ettringite retained Zn and Cr ions. In summary, GGBFS-based cementitious material with the low addition of 2 wt% VC effectively immobilizes Cr-bearing MSWI FA. Copyright © 2017. Published by Elsevier Ltd.

Maternal caloric restriction partially rescues the deleterious effects of advanced maternal age on offspring.

PubMed

Gribble, Kristin E; Jarvis, George; Bock, Martha; Mark Welch, David B

2014-08-01

While many studies have focused on the detrimental effects of advanced maternal age and harmful prenatal environments on progeny, little is known about the role of beneficial non-Mendelian maternal inheritance on aging. Here, we report the effects of maternal age and maternal caloric restriction (CR) on the life span and health span of offspring for a clonal culture of the monogonont rotifer Brachionus manjavacas. Mothers on regimens of chronic CR (CCR) or intermittent fasting (IF) had increased life span compared with mothers fed ad libitum (AL). With increasing maternal age, life span and fecundity of female offspring of AL-fed mothers decreased significantly and life span of male offspring was unchanged, whereas body size of both male and female offspring increased. Maternal CR partially rescued these effects, increasing the mean life span of AL-fed female offspring but not male offspring and increasing the fecundity of AL-fed female offspring compared with offspring of mothers of the same age. Both maternal CR regimens decreased male offspring body size, but only maternal IF decreased body size of female offspring, whereas maternal CCR caused a slight increase. Understanding the genetic and biochemical basis of these different maternal effects on aging may guide effective interventions to improve health span and life span. © 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Multiple episodes of partial melting, depletion, metasomatism and enrichment processes recorded in the heterogeneous upper mantle sequence of the Neotethyan Eldivan ophiolite, Turkey

NASA Astrophysics Data System (ADS)

Uysal, Ibrahim; Ersoy, E. Yalçın; Dilek, Yildirim; Kapsiotis, Argyrios; Sarıfakıoğlu, Ender

2016-03-01

The Eldivan ophiolite along the Izmir-Ankara-Erzincan suture zone in north-central Anatolia represents a remnant of the Neotethyan oceanic lithosphere. Its upper mantle peridotites include three lithologically and compositionally distinct units: clinopyroxene (cpx)-harzburgite and lherzolite (Group-1), depleted harzburgite (Group-2), and dunite (Group-3). Relics of primary olivine and pyroxene occur in the less refractory harzburgites, and fresh chromian spinel (Cr-spinel) is ubiquitous in all peridotites. The Eldivan peridotites reflect a petrogenetic history evolving from relatively fertile (lherzolite and cpx-harzburgite) toward more depleted (dunite) compositions through time, as indicated by (i) a progressive decrease in the modal cpx distribution, (ii) a progressive increase in the Cr#s [Cr / (Cr + Al)] of Cr-spinel (0.15-0.78), and (iii) an increased depletion in the whole-rock abundances of some magmaphile major oxides (Al2O3, CaO, SiO2 and TiO2) and incompatible trace elements (Zn, Sc, V and Y). The primitive mantle-normalized REE patterns of the Group-1 and some of the Group-2 peridotites display LREE depletions. Higher YbN and lower SmN/YbN ratios of these rocks are compatible with their formation after relatively low degrees (9-25%) of open-system dynamic melting (OSDM) of a Depleted Mid-ocean ridge Mantle (DMM) source, which was then fluxed with small volumes of oceanic mantle-derived melt [fluxing ratio (β): 0.7-1.2%]. Accessory Cr-spinel compositions (Cr# = 015-0.53) of these rocks are consistent with their origin as residual peridotites beneath a mid-ocean ridge axis. Part of the Group-2 harzburgites exhibit lower YbN and higher SmN/YbN ratios, LREE-enriched REE patterns, and higher Cr-spinel Cr#s ranging between 0.54 and 0.61. Trace element compositions of these peridotites can be modeled by approximately 15% OSDM of a previously 17% depleted DMM, which was then fluxed (β: 0.4%) with subduction-influenced melt. The Group-3 dunite samples contain Cr-spinel with elevated Cr#s (0.73-0.78) and low-TiO2 contents (< 0.13 wt.%), implying higher degrees of melting (21-24%) of an already depleted DMM that was triggered by infiltration of low-Ti boninite melt with fluxing rates of 0.4-4.0%. The existence of interstitial, idiomorphic Cr-spinel (high Cr# and low Ti) in the Group-3 dunites is consistent with this interpretation. The occurrence of both MOR- and SSZ-type peridotites in the Eldivan ophiolite suggests that its heterogeneous upper mantle was produced as a result of different partial melting and melt-rock reaction processes in different tectonic settings within the Neotethyan realm.

Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation for High-Grade Gliomas in Children and Adolescents

PubMed Central

2017-01-01

With the aim to investigate the outcome of tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) for high-grade gliomas (HGGs), we retrospectively reviewed the medical records of 30 patients with HGGs (16 glioblastomas, 7 anaplastic astrocytomas, and 7 other HGGs) between 2006 and 2015. Gross or near total resection was possible in 11 patients. Front-line treatment after surgery was radiotherapy (RT) in 14 patients and chemotherapy in the remaining 16 patients including 3 patients less than 3 years of age. Eight of 12 patients who remained progression free and 5 of the remaining 18 patients who experienced progression during induction treatment underwent the first HDCT/auto-SCT with carboplatin + thiotepa + etoposide (CTE) regimen and 11 of them proceeded to the second HDCT/auto-SCT with cyclophosphamide + melphalan (CyM) regimen. One patient died from hepatic veno-occlusive disease (VOD) during the second HDCT/auto-SCT; otherwise, toxicities were manageable. Four patients in complete response (CR) and 3 of 7 patients in partial response (PR) or second PR at the first HDCT/auto-SCT remained event free: however, 2 patients with progressive tumor experienced progression again. The probabilities of 3-year overall survival (OS) after the first HDCT/auto-SCT in 11 patients in CR, PR, or second PR was 58.2% ± 16.9%. Tumor status at the first HDCT/auto-SCT was the only significant factor for outcome after HDCT/auto-SCT. There was no difference in survival between glioblastoma and other HGGs. This study suggests that the outcome of HGGs in children and adolescents after HDCT/auto-SCT is encouraging if the patient could achieve CR or PR before HDCT/auto-SCT. PMID:28049229

Tumor RNA disruption predicts survival benefit from breast cancer chemotherapy.

PubMed

Parissenti, Amadeo M; Guo, Baoqing; Pritzker, Laura B; Pritzker, Kenneth P H; Wang, Xiaohui; Zhu, Mu; Shepherd, Lois E; Trudeau, Maureen E

2015-08-01

In a prior substudy of the CAN-NCIC-MA.22 clinical trial (ClinicalTrials.gov identifier NCT00066443), we observed that neoadjuvant chemotherapy reduced tumor RNA integrity in breast cancer patients, a phenomenon we term "RNA disruption." The purpose of the current study was to assess in the full patient cohort the relationship between mid-treatment tumor RNA disruption and both pCR post-treatment and, subsequently, disease-free survival (DFS) up to 108 months post-treatment. To meet these objectives, we developed the RNA disruption assay (RDA) to quantify RNA disruption and stratify it into 3 response zones of clinical importance. Zone 1 is a level of RNA disruption inadequate for pathologic complete response (pCR); Zone 2 is an intermediate level, while Zone 3 has high RNA disruption. The same RNA disruption cut points developed for pCR response were then utilized for DFS. Tumor RDA identified >fourfold more chemotherapy non-responders than did clinical response by calipers. pCR responders were clustered in RDA Zone 3, irrespective of tumor subtype. DFS was about 2-fold greater for patients with tumors in Zone 3 compared to Zone 1 patients. Kaplan-Meier survival curves corroborated these findings that high tumor RNA disruption was associated with increased DFS. DFS values for patients in zone 3 that did not achieve a pCR were similar to that of pCR recipients across tumor subtypes, including patients with hormone receptor positive tumors that seldom achieve a pCR. RDA appears superior to pCR as a chemotherapy response biomarker, supporting the prospect of its use in response-guided chemotherapy.

Nucleoside analogues in the therapy of Langerhans cell histiocytosis: a survey of members of the histiocyte society and review of the literature.

PubMed

Weitzman, S; Wayne, A S; Arceci, R; Lipton, J M; Whitlock, J A

1999-11-01

Previous reports have suggested activity of the nucleoside analogues 2-chlorodeoxyadenosine (2-CdA) and 2'-deoxycoformycin (2'-DCF) in Langerhans cell histiocytosis (LCH). To assess the efficacy of 2-CdA and 2'-DCF as salvage therapy for LCH, a survey of members of the Histiocyte Society and a literature review were undertaken. Twenty-three patients treated with 2-CdA and 4 treated with 2'-DCF were found, age range 2 months to 49 years. All 15 survey patients had multiorgan involvement, and 14 were heavily pretreated. Doses of 2-CdA ranged from 0.1 mg/kg/day continuous infusion for 5-7 days (majority of patients) to 13 mg/m(2)/day for 5 days, for 1-6 courses. One of the 15 patients had an early death, 5 had no response (NR), 3 had partial response (PR), and 6 achieved complete response (CR). Among 8 published patients, 7 achieved stable CR and 1 NR. Among 4 patients treated with 2'-DCF (4 mg/m(2)/week for 8 weeks then q 2 weekly), 2 achieved CR for 16+ and 18+ months and 2 PR for 2 and 5 months. Toxicity consisted mainly of combined myelo- and immunosuppression but no significant infections occurred and there were no toxic deaths. A cumulative thrombocytopenia was noted, which in 1 case took up to 6 months to resolve. Transient gastrointestinal toxicity and elevation of liver enzymes was seen, and 2 patients developed renal tubular acidosis. The peripheral neuropathy reported in adult patients receiving high doses was not seen. 2-CdA and 2'-DCF appear to have a useful role in LCH and are worthy of prospective trial in patients unresponsive to routine therapy. Copyright 1999 Wiley-Liss, Inc.

Results of a Phase II Trial of Gemcitabine plus Doxorubicin in Patients with Recurrent Head and Neck Cancers: Serum C18-ceramide as a Novel Biomarker for Monitoring Response

PubMed Central

Saddoughi, Sahar A.; Garrett-Mayer, Elizabeth; Chaudhary, Uzair; O’Brien, Paul; Afrin, Larry; Day, Terry A.; Gillespie, M. Boyd; Sharma, Anand; Wilhoit, Christina; Bostick, Robin; Senkal, Can E.; Hannun, Yusuf A.; Bielawski, Jacek; Simon, George; Shirai, Keisuke; Ogretmen, Besim

2011-01-01

Purpose Here we report a phase II clinical trial, which was designed to test a novel hypothesis that treatment with GEM/DOX would be efficacious via reconstitution of C18-ceramide signaling in HNSCC patients for whom first-line platinum-based therapy failed. Experimental Design Patients received GEM (1,000 mg/m2) and DOX (25 mg/m2) on days 1 and 8, every 21 days, until disease progression. After completion of 2 treatment cycles, patients were assessed radiographically, and serum samples were taken for sphingolipid measurements. Results We enrolled 18 patients in the trial, who were evaluable for toxicity, and 17 for response. The most common toxicity was neutropenia, observed in 9 of 18 patients, and there were no major non-hematological toxicities. Of the 17 patients, 5 patients had progressive disease (PD), 1 had complete response (CR), 3 exhibited partial response (PR), and 8 had stable disease (SD). The median progression-free survival (PFS) was 1.6 months (95% CI, 1.4, 4.2) with a median survival of 5.6 months (95% CI, 3.8, 18.2). Remarkably, serum sphingolipid analysis revealed significant differences in patterns of C18-ceramide elevation in patients with CR/PR/SD in comparison to patients with PD, indicating the reconstitution of tumor suppressor ceramide generation by GEM/DOX treatment. Conclusions Our data suggest that the GEM/DOX combination could represent an effective treatment for some patients with recurrent or metastatic HNSCC, and that serum C18-ceramide elevation might be a novel serum biomarker of chemotherapy response. PMID:21791630

Volatile products from the interaction of KCl(g) with Cr2O3 and LaCrO3 in oxidizing environments

NASA Technical Reports Server (NTRS)

Kohl, F. J.; Miller, R. A.; Stearns, C. A.; Fryburg, G. C.; Dillard, J. G.

1977-01-01

Cooled target collection techniques and high pressure mass spectrometric sampling were used to measure the relative rates of oxidative vaporization and to identify the volatile products emanating from samples of chromia and Mg-doped lanthanum chromite. The materials were exposed to partial pressures of KCl with and without H2O in one atmosphere of slowly flowing oxygen at elevated temperatures. Chromia and fresh samples of lanthanum chromite exhibited enhanced rates of oxidative vaporization upon exposure to these reactants. Mass spectrometric identification showed that the enhancements resulted from the heterogeneous formation of complex molecules of the type KCl sub 1,2,3 CrO3 and KOH sub l,2 CrO3. Lanthanum chromite that had undergone prolonged oxidative vaporization exhibited no enhanced oxidation upon exposure to the reactants.

Long-Term Cr Poisoning Effect on LSCF-GDC Composite Cathodes Sintered at Different Temperatures

DOE PAGES

Xiong, Chunyan; Taillon, Joshua A.; Pellegrinelli, Christopher; ...

2016-07-19

Here, the impact of sintering temperature on Cr-poisoning of solid oxide fuel cell (SOFC) cathodes was systematically studied. La 0.6Sr 0.4Fe 0.8Co 0.2O 3-δ - Ce 0.9Gd 0.1O 2-δ symmetric cells were aged at 750°C in synthetic air with the presence of Crofer 22 APU, a common high temperature interconnect, over 200 hours and electrochemical impedance spectroscopy (EIS) was used to determine the degradation process. Both the ohmic resistance (R Ω) and polarization resistance (R P) of LSCF-GDC cells, extracted from EIS spectra, for different sintering temperatures increase as a function of aging time. Furthermore, the Cr-related degradation rate increasesmore » with decreased cathode sintering temperature. The polarization resistance of cathode sintered at lower temperature (950°C) increases dramatically while aging with the presence of Cr and also significantly decreases the oxygen partial pressure dependence after aging. The degradation rate shows a positive correlation to the concentration of Cr. The results indicate that decreased sintering temperature increases the total surface area, leading to more available sites for Sr-Cr-O nucleation and thus greater Cr degradation.« less

The effect of mass transfer parameterization and ice retention on the scavenging and redistribution of SO2 by a deep convective cloud.

PubMed

Vučković, Vladan; Vujović, Dragana

2017-02-01

A chemistry module with the aqueous chemistry coupled with the complex 3D nonhydrostatic atmospheric model is used to investigate how the representation of gas-aqueous mass transfer and ice retention affect the SO 2 redistribution in the presence of a convective cloud. Gas uptake to the liquid water is calculated using both Henry's law equilibrium (HE) and kinetic mass transport (KMT). The constant retention coefficients for SO 2 (k ret  = 0.46) and for H 2 O 2 (k ret  = 0.64) are used. It is shown that the amount of SO 2 in the air at higher altitudes (10-12 km) is greater when partial retention (PR) is included. All values of k ret between 0 and 1 represented the partial retention (PR), while complete retention (CR) means the entire mass of the gas from the solution remained in the ice phase (k ret  = 1). Total mass of SO 2 in the air in the entire domain was greater in the case of PR than in the case when the CR was assumed (at the end of the integration time, 0.11% for HE and 0.61% for KMT) and in KMT than in the HE case (0.9% for CR and 1.4% for PR). The amount of SO 2 in the ice phase was lower in the case of PR for both HE and KMT. The highest concentrations of S(IV) in rainwater were in the case of HE-CR, while the smallest values were in the case of KMT-PR. Total precipitation of S(IV) in PR exhibits 90% relative to CR, if HE was assumed. When KMT was used, PR gives 81.7% S(IV) relative to CR. Scavenging was the highest in the HE-CR case and the lowest in the KMT-PR case. If HE is assumed, averaged cumulative mass (ACM) of S(IV) precipitation per unit of domain surface for the CR case was 11.1% greater than in the PR case (if KMT was assumed, this difference was greater, 22.4%). Similarly, ACM for HE is 24.1% greater than KMT for the CR case and 36.8% for the PR case.

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

Roy, Ram Vinod; Pratheeshkumar, Poyil; Son, Yong-O

Hexavalent chromium (Cr(VI)) is classified as a human carcinogen. Cr(VI) has been associated with adenocarcinomas and squamous cell carcinoma of the lung. The present study shows that acute Cr(VI) treatment in human bronchial epithelial cells (BEAS-2B) increased inflammatory responses (TNF-α, COX-2, and NF-кB/p65) and expression of Nrf2. Cr(VI)-induced generation of reactive oxygen species (ROS) are responsible for increased inflammation. Despite the fact that Nrf2 is a master regulator of response to oxidative stress, silencing of Nrf2 in the acute Cr(VI) treatment had no effect on Cr(VI)-induced inflammation. In contrast, in Cr(VI)-transformed (CrT) cells, Nrf2 is constitutively activated. Knock-down of thismore » protein resulted in decreased inflammation, while silencing of SOD2 and CAT had no effect in the expression of these inflammatory proteins. Results obtained from the knock-down of Nrf2 in CrT cells are very different from the results obtained in the acute Cr(VI) treatment. In BEAS-2B cells, knock-down of Nrf2 had no effect in the inflammation levels, while in CrT cells a decrease in the expression of inflammation markers was observed. These results indicate that before transformation, ROS plays a critical role while Nrf2 not in Cr(VI)-induced inflammation, whereas after transformation (CrT cells), Nrf2 is constitutively activated and this protein maintains inflammation while ROS not. Constitutively high levels of Nrf2 in CrT binds to the promoter regions of COX-2 and TNF-α, leading to increased inflammation. Collectively, our results demonstrate that before cell transformation ROS are important in Cr(VI)-induced inflammation and after transformation a constitutively high level of Nrf2 is important. - Highlights: • Cr(VI)-induced ROS increased inflammation, while Nrf2 had no effect. • In the CrT cells knock-down of Nrf2 resulted in decreased inflammation. • Mechanistic differences in regulating Cr(VI)-induced inflammation.« less

Regulation of Dynamic Behavior of Retinal Microglia by CX3CR1 Signaling

PubMed Central

Liang, Katharine J.; Lee, Jung Eun; Wang, Yunqing D.; Ma, Wenxin; Fontainhas, Aurora M.; Fariss, Robert N.; Wong, Wai T.

2009-01-01

PURPOSE Microglia in the central nervous system display a marked structural dynamism in their processes in the resting state. This dynamic behavior, which may play a constitutive surveying role in the uninjured neural parenchyma, is also highly responsive to tissue injury. The role of CX3CR1, a chemokine receptor expressed in microglia, in regulating microglia morphology and dynamic behavior in the resting state and after laser-induced focal injury was examined. METHODS Time-lapse confocal imaging of retinal explants was used to evaluate the dynamic behavior of retinal microglia labeled with green fluorescent protein (GFP). Transgenic mice in which CX3CR1 signaling was ablated (CX3CR1GFP/GFP/CX3CR1−/−) and preserved (CX3CR1+/GFP/CX3CR1+/−) were used. RESULTS Retinal microglial density, distribution, cellular morphology, and overall retinal tissue anatomy were not altered in young CX3CR1−/− animals. In the absence of CX3CR1, retinal microglia continued to exhibit dynamic motility in their processes. However, rates of process movement were significantly decreased, both under resting conditions and in response to tissue injury. In addition, microglia migration occurring in response to focal laser injury was also significantly slowed in microglia lacking CX3CR1. CONCLUSIONS CX3CR1 signaling in retinal microglia, though not absolutely required for the presence of microglial dynamism, plays a role in potentiating the rate of retinal microglial process dynamism and cellular migration. CX3CL1 signaling from retinal neurons and endothelial cells likely modulates dynamic microglia behavior so as to influence the level of microglial surveillance under basal conditions and the rate of dynamic behavior in response to tissue injury. PMID:19443728

Modeling hexavalent chromium removal in a Bacillus sp. fixed-film bioreactor.

PubMed

Nkhalambayausi-Chirwa, Evans M; Wang, Yi-Tin

2004-09-30

A one-dimensional diffusion-reaction model was developed to simulate Cr(VI) reduction in a Bacillus sp. pure culture biofilm reactor with glucose as a sole supplied carbon and energy source. Substrate utilization and Cr(VI) reduction in the biofilm was best represented by a system of (second-order) partial differential equations (PDEs). The PDE system was solved by the (fourth-order) Runge-Kutta method adjusted for mass transport resistance using the (second-order) Crank-Nicholson and Backward Euler finite difference methods. A heuristic procedure (genetic search algorithm) was used to find global optimum values of Cr(VI) reduction and substrate utilization rate kinetic parameters. The fixed-film bioreactor system yielded higher values of the maximum specific Cr(VI) reduction rate coefficient and Cr(VI) reduction capacity (kmc = 0.062 1/h, and Rc = 0.13 mg/mg, respectively) than previously determined in batch reactors (kmc = 0.022 1/h and Rc = 0.012 mg/mg). The model predicted effluent Cr(VI) concentration well with 98.9% confidence (sigmay2 = 2.37 mg2/L2, N = 119) and effluent glucose with 96.4 % confidence (sigmay(w)2 = 5402 mg2/L2, N = 121, w = 100) over a wide range of Cr(VI) loadings (10-498 mg Cr(VI)/L/d). Copyright 2004 Wiley Periodicals, Inc.

Synthesis and study of electronic state of Sr2CrO2Co2As2 with CoAs conduction layers

NASA Astrophysics Data System (ADS)

Suzuki, Atsushi; Ohta, Hiroto; Aruga Katori, Hiroko

2017-06-01

We successfully synthesized a new member of compounds with the CoAs layer, Sr2CrO2Co2As2, and its partially substituted systems Sr2CrO2(Tmx Co1- x )2As2 (Tm = Fe, Ni), and measured magnetization and electric resistivity of these polycrystalline compounds. As a result of magnetic measurement for Sr2CrO2Co2As2, magnetic moments of Co do not construct an itinerant electronic ferromagnetism unlike other compounds with the CoPn (Pn=P and As) layers. Both Sr2CrO2(Tmx Co1- x )2As2 with Tm = Fe and Ni also do not show an itinerant electronic ferromagnetism down to 2 K. For each solid solution of Sr2CrO2(Fe x Co1- x )2As2 with x > 0.0, ρ weakly increases with the decrease of T at low temperature region, indicating that the mixed occupancy of Cr and Fe within the conducting layers occurs in Sr2CrO2(Fe x Co1- x )2As2. We conclude that the absence of ferromagnetism in Sr2CrO2Co2As2 is due to the self-electron-doping from Cr to the conduction bands and the attempt to recover the ferromagnetism by the hole-doping effect is prevented by the mixed occupancy of Cr and Fe in Sr2CrO2 (Fe x Co1- x )2As2 with x > 0.0. The result of our structural analysis supports that the disappearance of itinerant electronic ferromagnetism in Sr2CrO2Co2As2 is due to the self-electron-doping from Cr.

The oxidation of Cr(III) to Cr(VI) in the environment by atmospheric oxygen during the bush fires.

PubMed

Panichev, N; Mabasa, W; Ngobeni, P; Mandiwana, K; Panicheva, S

2008-05-30

The presence of Cr(VI) in soils and plants of remote unpolluted areas can be explained by partial oxidation of Cr(III) with atmospheric oxygen during seasonable bush fires, which are rather frequent event in South Africa. Experiments with thermal treatment of a veld grass, Hyperthelia dissoluta, in muffle furnace at high temperature, followed by electrothermal atomic absorption spectrometry (ETAAS) determination of chromium, show a remarkable increase in Cr(VI) concentration from initial 2.5 to 23.2% after the treatment of grass ash at 500 degrees C and to 58.1% at 900 degrees C. Before ETAAS determination, the two chromium species of interest were separated by the treatment of samples with 0.1M Na2CO3. Thermodynamic calculations confirm the possibility of Cr(III) to Cr(VI) oxidation with atmospheric oxygen at high temperature in alkaline media, which is typical for vegetation ash. Analysis of field samples show that percent of Cr(VI), in respect to the total amount of chromium increased from initial 2.5% in grass to 9.3% in ash of grass. Without oxidation the percent of Cr(VI) in grass and ash of grass should be a constant value. After the fire Cr(VI) concentration in top soil (0-3 cm) increased from 0.3+/-0.05 to 1.8+/-0.5 microg g(-1) and the total Cr from 26+/-9 to 69+/-14 microg g(-1). The reason for the appearance of additional amount of Cr on top soil can be explained by condensation of chromium species from flame and shouldering ash on a soil surface. The results of studies demonstrate that Cr(VI) is formed by Cr(III) oxidation with atmospheric oxygen at high temperature during bush fires.

Biofilm Shows Spatially Stratified Metabolic Responses to Contaminant Exposure

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

Cao, Bin; Majors, Paul D.; Ahmed, B.

2012-11-01

The objective of this study was to elucidate the spatiotemporal responses of live S. oneidensis MR-1 biofilms to U(VI) (uranyl, UO22+) and Cr(VI) (chromate, CrO42-), important environmental contaminants at DOE contaminated sites. Toward this goal, we applied noninvasive nuclear magnetic resonance (NMR) imaging, diffusion, relaxation and spectroscopy techniques to monitor in situ spatiotemporal responses of S. oneidensis biofilms to U(VI) and Cr(VI) exposure in terms of changes in biofilm structures, diffusion properties, and cellular metabolism. Exposure to U(VI) or Cr(VI) did not appear to change the overall biomass distribution but caused changes in the physicochemical microenvironments inside the biofilm asmore » indicated by diffusion measurements. Changes in the diffusion properties of the biofilms in response to U(VI) and Cr(VI) exposure imply a novel function of the extracellular polymeric substances (EPS) affecting the biotransformation and transport of contaminants in the environment. In the presence of U(VI) or Cr(VI), the anaerobic metabolism of lactate was inhibited significantly, although the biofilms were still capable of reducing U(VI) and Cr(VI). Local concentrations of Cr(III)aq in the biofilm suggested relatively high Cr(VI) reduction activities at the top of the biofilm, near the medium-biofilm interface. The depth-resolved metabolic activities of the biofilm suggested higher diversion effects of gluconeogenesis and C1 metabolism pathways at the bottom of the biofilm and in the presence of U(VI). This study provides a noninvasive means to investigate spatiotemporal responses of biofilms, including surface-associated microbial communities in engineering, natural and medical settings, to various environmental perturbations including exposure to environmental contaminants and antimicrobials.« less

Mild caloric restriction up-regulates the expression of prohibitin: A proteome study

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

Takahashi, Shoko; Masuda, Junko; Shimagami, Hiroshi

2011-02-18

Research highlights: {yields} Proteomic analysis was performed to elucidate physiological alterations induced by mild CR. {yields} The results suggest good reproducibility and possibility to grasp the important response of CR. {yields} The increase in prohibitin abundance was observed in CR groups by proteomic analysis. {yields} We hypothesize that prohibitin might be involved in the longevity induced by CR. -- Abstract: Caloric restriction (CR) is well known to expand lifespan in a variety of species and to retard many age-related diseases. The effects of relatively mild CR on the proteome profile in relation to lifespan have not yet been reported, despitemore » the more extensive studies of the stricter CR conditions. Thus, the present study was conducted to elucidate the protein profiles in rat livers after mild CR for a relatively short time. Young growing rats were fed CR diets (10% and 30% CR) for 1 month. We performed the differential proteomic analysis of the rat livers using two-dimensional electrophoresis combined with MALDI-TOF mass spectrometry. The most remarkable protein among the differentially expressed proteins was found to be prohibitin, the abundance of which was increased by 30% CR. Prohibitin is a ubiquitously expressed protein shown to suppress cell proliferation and to be related to longevity. The increase in prohibitin was observed both in 10% and 30% CR by Western blot analysis. Furthermore, induction of AMP-activated kinase (AMPK) protein, related to the actions of prohibitin in promoting longevity, was observed. The increased prohibitin level in response to subtle CR suggests that this increase may be one of the early events leading to the expansion of lifespan in response to CR.« less

Role of follow-up endoscopic examination in treatment response assessment for patients with gastric diffuse large B cell lymphoma.

PubMed

Yoon, Seung Bae; Lee, In Seok; Lee, Ha Ni; Kim, Eunyoung; Kim, Woohyeon; Lee, Han Hee; Lee, Bo-In; Choi, Myung-Gyu; Jung, Seung Eun; Choi, Byung Ock; Park, Gyeong Sin; Cho, Seok-Goo

2016-09-01

According to lymphoma guidelines, gastric diffuse large B cell lymphoma (DLBCL) patients should undergo regular computed tomography (CT) and/or positron emission tomography (PET) examinations to assess treatment response. Endoscopic examinations are not indicated in the guidelines. The aim of this study was to investigate the utility of endoscopic examinations during and after treatment for DLBCL. We reviewed the patients diagnosed with gastric DLBCL at Seoul St. Mary's Hospital. All patients underwent endoscopy and radiologic examinations at every follow-up appointment. Radiologic response was defined according to World Health Organization criteria and endoscopic response was determined based on the Groupe d'Etude des Lymphomes de l'Adult grading system that is widely used in post-treatment evaluation of gastric MALT lymphoma. Forty-five patients were analyzed. Within a median follow-up period of 34 months, 35 patients achieved both radiologic and endoscopic complete remission (CR). The median times to endoscopic and radiologic CR were not significantly different (21 versus 16 weeks, p = 0.118). However, in 25 patients with stage I disease, endoscopic CR [median (range), 20 (11-36)] was achieved later than radiologic CR [median (range), 13 (8-36)] (p = 0.027). Among 40 patients who achieved radiologic CR, 35 patients who also achieved endoscopic CR maintained remission during the follow-up. Two of the five patients who achieved radiologic CR without endoscopic CR experienced recurrence. In gastric DLBCL patients, endoscopic response does not always correlate with radiologic response and might predict disease recurrence. We suggest that follow-up endoscopic examination with biopsy should be performed in addition to radiologic examination.

The development of an energy-independent personnel neutron dosimeter using CR-39

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

Doremus, S.W.

The addition of specialized (n,{alpha}) radiators to a standard polyethylene/CR-39 (PE/CR-39) neutron dosimetry system was evaluated for improved response to low energy neutrons. Specialized radiators consisting of poly(vinyl alcohol) complexed with boron (natural and enriched boron-10) and poly(acrylic acid) complexed with lithium (enriched lithium-6) were evaluated. The complexion of boron with poly(vinyl alcohol) was accomplished by incorporation or surface coating. The complexion of lithium with poly(acrylic acid) was exclusively performed by incorporation. The dosimeter was designed such that the specialized radiator was in contact with the CR-39 detector (i.e., the specialized radiator was sandwiched between the CR-39 detector and polyethylenemore » radiator). The neutron response of this dosimetry system was investigated using {sup 252}Cf (moderated and bare) spontaneous fission neutrons. Detectors were chemically etched and then read with a Nikon OPTIPHOT microscope. The mean response (tracks {center dot} field{sup {minus}1}) of detectors treated with specialized (n,{alpha}) radiators were evaluated against PE/CR-39 controls. The results of this investigation demonstrate that PE/CR-39 dosimeters equipped with specialized (n,{alpha}) radiators have a noticeable response to low energy neutrons that in many instances is significantly greater than that of the controls. The addition of specialized radiators to this dosimetry system did not effect (diminish) its response to fast neutrons.« less

Long-term follow-up and salvage surgery in patients with T2N0M0 squamous cell carcinoma of the glottic larynx who received concurrent chemoradiation therapy with carboplatin (CBDCA) - AUC 1.5 vs AUC 2.0.

PubMed

Furusaka, Tohru; Matsuda, Hiroshi; Saito, Tsutomu; Katsura, Yoshihisa; Ikeda, Minoru

2012-11-01

Patients who received concurrent chemoradiation therapy with carboplatin were followed up on a long-term basis. In 25 patients treated with carboplatin at an AUC of 2.0 mg/ml, the complete response (CR), 10-year survival, and 10-year larynx preservation rates were 96.0%, 91.1%, and 75.2%, respectively, and the safety margin for partial laryngectomy was 4 mm from the gross tumor. To perform long-term follow-up of the therapeutic outcomes of concurrent chemoradiation therapy and salvage surgery to determine the additive and synergistic effects of anticancer drugs combined with chemoradiotherapy. Fifty male patients (aged 33-76 years) with untreated T2N0M0 squamous cell carcinoma of the glottic larynx were included. Carboplatin was intravenously administered once a week for 4 weeks. Radiotherapy was delivered by an external beam of 4 MV linac X-ray (total = 66 Gy). The AUC 1.5 combination group showed overall response, CR, 5-year survival, 10-year survival, 5-year larynx preservation, and 10-year larynx preservation rates of 100.0%, 68.0%, 83.4%, 77.0%, 75.2%, and 75.2%, respectively. The AUC 2.0 combination group showed corresponding rates of 100%, 96.0%, 95.7%, 91.1%, 82.9%, and 72.7%, respectively. The most common side effects of grade 3 or more were leukopenia, neutropenia, and mucositis (stomatitis), and all were reversible. Thirteen patients (52.0%) in the AUC 1.5 combination group and nine patients (36.0%) in the AUC 2.0 combination group required salvage surgery. Histologically, concurrent chemoradiation therapy with carboplatin caused more severe cancer tissue degeneration. Pathological examinations indicated that the safety margin for partial laryngectomy was 4 mm from the gross tumor.

Comparative efficacy and safety of selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors in older adults: a network meta-analysis.

PubMed

Thorlund, Kristian; Druyts, Eric; Wu, Ping; Balijepalli, Chakrapani; Keohane, Denis; Mills, Edward

2015-05-01

To establish the comparative efficacy and safety of selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors in older adults using the network meta-analysis approach. Systematic review and network meta-analysis. Individuals aged 60 and older. Data on partial response (defined as at least 50% reduction in depression score from baseline) and safety (dizziness, vertigo, syncope, falls, loss of consciousness) were extracted. A Bayesian network meta-analysis was performed on the efficacy and safety outcomes, and relative risks (RRs) with 95% credible intervals (CrIs) were produced. Fifteen randomized controlled trials were eligible for inclusion in the analysis. Citalopram, escitalopram, paroxetine, duloxetine, venlafaxine, fluoxetine, and sertraline were represented. Reporting on partial response and dizziness was sufficient to conduct a network meta-analysis. Reporting on other outcomes was sparse. For partial response, sertraline (RR=1.28), paroxetine (RR=1.48), and duloxetine (RR=1.62) were significantly better than placebo. The remaining interventions yielded RRs lower than 1.20. For dizziness, duloxetine (RR=3.18) and venlafaxine (RR=2.94) were statistically significantly worse than placebo. Compared with placebo, sertraline had the lowest RR for dizziness (1.14) and fluoxetine the second lowest (1.31). Citalopram, escitalopram, and paroxetine all had RRs between 1.4 and 1.7. There was clear evidence of the effectiveness of sertraline, paroxetine, and duloxetine. There also appears to be a hierarchy of safety associated with the different antidepressants, although there appears to be a dearth of reporting of safety outcomes. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.

Thermoregulatory, Cardiovascular, and Metabolic Responses to Mild Caloric Restriction in the Brown Norway Rat

EPA Science Inventory

Caloric restriction (CR) has been demonstrated to prolong the life span of a variety of species. CR-induced reduction in core temperature (Tc) is considered a key mechanism responsible for prolonging life span in rodents; however, little is known on the regulation of CR-induced h...

Quality of life in responders after palliative radiation therapy for painful bone metastases using EORTC QLQ-C30 and EORTC QLQ-BM22: results of a Brazilian cohort.

PubMed

Mendez, Lucas C; Raman, Srinivas; Wan, Bo Angela; da Silva, José Luiz Padilha; Moraes, Fábio Y; Lima, Kennya M L B; Silva, Maurício F; Diz, Maria Del Pilar Estevez; Chow, Edward; Marta, Gustavo Nader

2017-08-01

Bone metastases cause pain, suffering and impaired quality of life (QoL). Palliative radiotherapy (RT) and/or chemotherapy are effective methods in controlling pain, reducing analgesics use and improving QoL. This study goal was to investigate the changes in QoL scores among patients who responded to palliative treatment. A prospective study evaluating the role of radiation therapy in a public academic hospital in São Paulo-Brazil recorded patients' opioid use, pain score, Portuguese version of QLQ-BM22 and QLQ-C30 before and 2 months after radiotherapy. Analgesic use and pain score were used to calculate international pain response category. Overall response was defined as the sum of complete response (CR) and partial response (PR). CR was defined as pain score of 0 with no increase in analgesic intake whereas PR was defined as pain reduction ≥2 without analgesic increase or analgesic reduction in ≥25% without increase in pain at the treated site. From September 2014 to October 2015, 25 patients with bone metastases responded to RT or chemotherapy (1 CR, 24 PR). There were 8 male and 17 female patients. The median age of the 25 patients was 59 (range, 22 to 80) years old. Patient's primary cancer site was breast [11], prostate [5], lung [2], others [7]. For QLQ-BM 22, the mean scores of 4 categories at baseline were: pain site (PS) 39, pain characteristics (PC) 61, function interference (FI) 49 and psycho-social aspects (PA) 57. At 2 month follow up, the scores were PS 27, PC 37, FI 70 and PA 59. Statistical significant improvement (P<0.05) was seen in PS, PC, FI but not PA. In the QLQ-C30, the scores were not statistically different for all categories, except for pain that demonstrated a 33 point decrease in the median pain score domain (66 to 33). Responders to RT at 2 months presented improvement in BM22 and C30 pain domains, and also improvement in functional interference domain of the BM22 questionnaire.

Combination chemotherapy with 5-fluorouracil, oral Idarubicin, and cyclophosphamide (FIC) in metastatic breast cancer--an open phase II study.

PubMed

Kolarić, K; Potrebica, V; Vukas, D; Mechl, Z; Sopkova, B

1988-01-01

Phase II studies of p.o. Idarubicin administration, a new daunorubicin analogue (4-demethoxy-daunorubicin), have shown antitumor activity in 23%-31% of previously treated metastatic breast cancer patients, while in untreated patients a response rate of 41% was observed. Our Phase II study has shown an overall response of 23% [1 complete response (CR), 9 partial response (PR), 10/43] with a daily dose of 15 mg/m2 p.o. on days 1,2,3. On the basis of these results we have recently included Idarubicin in combination chemotherapy of breast cancer, substituting Adriamycin by Idarubicin in an FAC schedule. Of 50 consecutive metastatic breast cancer patients who entered the study, 42 patients who received greater than 2 cycles were evaluable. There were 22 premenopausal and 20 postmenopausal patients (mean = 51 years). In 25 patients a performance status of 0-2 (ECOG) was registered and in 17 patients it was 3. Previous radiation had been administered in 34, hormonal therapy in 18, and adjuvant chemotherapy (CMF 5, CMFVP 3) in 8 patients; 22 patients had predominant metastatic sites in soft tissues, 18 in visceral organs, and 2 in the bones. The FIC schedule was administered as follows: 5-fluorouracil 500 mg/m2 i.v. days 1 and 8, Idarubicin 15 mg/m2 p.o. days 1, 2 and 3, and cyclophosphamide 500 mg/m2 i.v. day 1. An objective response was observed in 23 (5 CR, 18 PR) out of 42 patients (53%, CR 12%). Soft tissue metastases responded in 55% (12/22), visceral organs in 61% (11/18), and no response was observed in bone lesions (0/2). The median remission duration was 8 months (3-16+). Toxicity was mild, expressed mainly in the form of nausea/vomiting, grade I and II in 64% of the patients. Alopecia was very mild (grade I and II in 23% of the patients). Leukopenia grade I-II was observed in 21% of the patients. In 4 patients reversible ECG changes occurred. Left ventricular ejection fraction did not show any pathological changes. The Idarubicin-containing combination chemotherapy we have used has the following characteristics: easier administration (p.o. anthracycline, no risk of tissue extravasation), lower toxicity (cardiotoxicity, alopecia, and myelosuppression in particular), and a notable antitumor activity.

Photodynamic therapy and fluorescent diagnostics of skin cancer with radochlorine and photosense: comparing efficacy and toxicity

NASA Astrophysics Data System (ADS)

Vakulovskaya, Elena G.; Kemov, Yuriy V.; Zalevsky, Igor D.; Reshetnikov, Andrew V.; Umnova, Loubov V.; Vorozhcsov, Georgiu N.

2004-06-01

Photodynamic therapy (PDT) and fluorescent diagnostics (FD) with Radaclorine (RadaPharma, Russia) (RC) have been provided in 32 patients with T1-4 stage basal cell carcinoma (BCC) and in 81 patients with Photsense. Pharmacocynetic studies with detecting the borders of tumor growth and intensity of accumulation of photosensizers in tumor, normal tissues and visualization have been done by Spectral-fluorescent Complex and spectranalyser LESA-01 (He-Ne-laser, λ=633nm). We've got fluorescence of all tumors and additional fluorescence zones were found, cytological verification of BCC was got in most of cases. The fluorescent signs of RC in normal skin were found till 5 days after injection. As a source of light for PDT we used simeconductive lasers: Milon - λ = 660+2nm, light dose was 200-300 J/cm2 and Biospec (λ+672+2nm), multiple laser surface and interstitial irradiation was performed 24 hours after PS injection with total light dose till 400-600 J/cm2. 2 months after PDT with RC complete response (CR) in 65.6% of cases, partial response-in 34.4% of cases. The efficacy of PDT with PS was higher (CR-84.0%, PR-14.8%). Our experience show pronounced efficacy of PDT with RC for BCC without side effects and very short skin toxicity.

Characterization of sour cherry isolates of plum pox virus from the Volga Basin in Russia reveals a new cherry strain of the virus.

PubMed

Glasa, Miroslav; Prikhodko, Yuri; Predajňa, Lukáš; Nagyová, Alžbeta; Shneyder, Yuri; Zhivaeva, Tatiana; Subr, Zdeno; Cambra, Mariano; Candresse, Thierry

2013-09-01

Plum pox virus (PPV) is the causal agent of sharka, the most detrimental virus disease of stone fruit trees worldwide. PPV isolates have been assigned into seven distinct strains, of which PPV-C regroups the genetically distinct isolates detected in several European countries on cherry hosts. Here, three complete and several partial genomic sequences of PPV isolates from sour cherry trees in the Volga River basin of Russia have been determined. The comparison of complete genome sequences has shown that the nucleotide identity values with other PPV isolates reached only 77.5 to 83.5%. Phylogenetic analyses clearly assigned the RU-17sc, RU-18sc, and RU-30sc isolates from cherry to a distinct cluster, most closely related to PPV-C and, to a lesser extent, PPV-W. Based on their natural infection of sour cherry trees and genomic characterization, the PPV isolates reported here represent a new strain of PPV, for which the name PPV-CR (Cherry Russia) is proposed. The unique amino acids conserved among PPV-CR and PPV-C cherry-infecting isolates (75 in total) are mostly distributed within the central part of P1, NIa, and the N terminus of the coat protein (CP), making them potential candidates for genetic determinants of the ability to infect cherry species or of adaptation to these hosts. The variability observed within 14 PPV-CR isolates analyzed in this study (0 to 2.6% nucleotide divergence in partial CP sequences) and the identification of these isolates in different localities and cultivation conditions suggest the efficient establishment and competitiveness of the PPV-CR in the environment. A specific primer pair has been developed, allowing the specific reverse-transcription polymerase chain reaction detection of PPV-CR isolates.

Selective Detection of NO2 Using Cr-Doped CuO Nanorods

PubMed Central

Kim, Kang-Min; Jeong, Hyun-Mook; Kim, Hae-Ryong; Choi, Kwon-Il; Kim, Hyo-Joong; Lee, Jong-Heun

2012-01-01

CuO nanosheets, Cr-doped CuO nanosheets, and Cr-doped CuO nanorods were prepared by heating a slurry containing Cu-hydroxide/Cr-hydroxide. Their responses to 100 ppm NO2, C2H5OH, NH3, trimethylamine, C3H8, and CO were measured. For 2.2 at% Cr-doped CuO nanorods, the response (Ra/Rg, Ra: resistance in air, Rg: resistance in gas) to 100 ppm NO2 was 134.2 at 250 °C, which was significantly higher than that of pure CuO nano-sheets (Ra/Rg = 7.5) and 0.76 at% Cr-doped CuO nanosheets (Ra/Rg = 19.9). In addition, the sensitivity for NO2 was also markedly enhanced by Cr doping. Highly sensitive and selective detection of NO2 in 2.2 at% Cr-doped CuO nanorods is explained in relation to Cr-doping induced changes in donor density, morphology, and catalytic effects. PMID:22969384

Characterization of commercial off-the shelf regenerable sorbent to scrub carbon dioxide in a portable life support system

NASA Astrophysics Data System (ADS)

Arai, Tatsuya; Fricker, John

2018-06-01

A resin bead Mitsubishi DIAION™ CR20 was identified and characterized as a first commercial off-the shelf regenerable carbon dioxide (CO2) sorbent candidate for space life support system applications at room temperature. The CO2 adsorption rates and capacities of CR20 at varying CO2 partial pressures were obtained. The data were used to numerically simulate CO2 adsorption by a swingbed, a pair of two sorbent beds that alternately adsorb and desorb CO2 in a space suit portable life support system (PLSS). The result demonstrated that a reasonable volume of CR20 would be able to continuously adsorb CO2 with bed-swing interval of 4 min at 300-W metabolic rate, and that commercial off-the shelf CR20 would have similar performance of CO2 adsorption to the proprietary swingbed sorbent SA9T for PLSS applications.

Structure Study of Magnetic Thin Films for Voltage Controlled Spintronics by Scanning Transmission Electron Microscopy Experiment and Density Functional Theory Calculations

NASA Astrophysics Data System (ADS)

Sun, Congli

We have studied magnetic thin films for voltage controlled magnetic tunnel junctions (MTJs) by advanced scanning transmission electron microscopy (STEM) and density functional theory (DFT) simulations. MTJs are the prototypical spintronic device and manipulation of magnetism by electrical means is among the most promising approaches to novel voltage-controlled spin electronics. The voltage controlled magnetic effect can be achieved across many different materials systems, all of which depend on high-quality thin films with minimum crystallographic defects. Cr2O3 is antiferromagnetic in bulk but ferromagnetic on the (0001) surface. Bulk Cr2O3 has two degenerate antiferromagnetic states with opposite (0001) surface spin polarization. As Cr2O3 is also magnetoelectric, the degenerate antiferromagnetic states can be lifted by manipulating the free-energy gain DeltaF = aEH. Therefore, the surface ferromagnetism can be controlled by applied electric field. We have observed vertical grain boundaries in Cr2O 3/Al2O3 systems that are related with a 60° in-plane rotation by diffraction contrast TEM image. STEM as a function of scattering angle points out a simultaneous ⅓[101¯0] basal plane shift. Local boundary electron energy loss spectroscopy (EELS) shows a pre-peak on the O K-edge, indicating a reduced bandgap along the boundary that provides potential breakdown paths in Cr2O3 thin films. B doping of Cr2O3 is known to increase the Neel temperature. B was found to form either BCr4 tetrahedra or BO 3 triangles in the Cr2O3 lattice, with sigma * and pi* bonds exhibiting different energy loss features. Modeling the experimental spectra as a linear combination of simulated B K edges reproduces the experimental pi* / sigma * ratios for 12 to 43 % of the B in the sample occupying BCr 4 sites. Simulated BCr4 fraction / total B as a function of oxygen partial pressures supports the EELS results and indicates further increase of Neel temperature can be achieved by optimizing oxygen partial pressures.

Predicting pathological complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a systematic review.

PubMed

Ryan, J E; Warrier, S K; Lynch, A C; Ramsay, R G; Phillips, W A; Heriot, A G

2016-03-01

Approximately 20% of patients treated with neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer achieve a pathological complete response (pCR) while the remainder derive the benefit of improved local control and downstaging and a small proportion show a minimal response. The ability to predict which patients will benefit would allow for improved patient stratification directing therapy to those who are likely to achieve a good response, thereby avoiding ineffective treatment in those unlikely to benefit. A systematic review of the English language literature was conducted to identify pathological factors, imaging modalities and molecular factors that predict pCR following chemoradiotherapy. PubMed, MEDLINE and Cochrane Database searches were conducted with the following keywords and MeSH search terms: 'rectal neoplasm', 'response', 'neoadjuvant', 'preoperative chemoradiation', 'tumor response'. After review of title and abstracts, 85 articles addressing the prediction of pCR were selected. Clear methods to predict pCR before chemoradiotherapy have not been defined. Clinical and radiological features of the primary cancer have limited ability to predict response. Molecular profiling holds the greatest potential to predict pCR but adoption of this technology will require greater concordance between cohorts for the biomarkers currently under investigation. At present no robust markers of the prediction of pCR have been identified and the topic remains an area for future research. This review critically evaluates existing literature providing an overview of the methods currently available to predict pCR to nCRT for locally advanced rectal cancer. The review also provides a comprehensive comparison of the accuracy of each modality. Colorectal Disease © 2015 The Association of Coloproctology of Great Britain and Ireland.

Removable partial denture alloys processed by laser-sintering technique.

PubMed

Alageel, Omar; Abdallah, Mohamed-Nur; Alsheghri, Ammar; Song, Jun; Caron, Eric; Tamimi, Faleh

2018-04-01

Removable partial dentures (RPDs) are traditionally made using a casting technique. New additive manufacturing processes based on laser sintering has been developed for quick fabrication of RPDs metal frameworks at low cost. The objective of this study was to characterize the mechanical, physical, and biocompatibility properties of RPD cobalt-chromium (Co-Cr) alloys produced by two laser-sintering systems and compare them to those prepared using traditional casting methods. The laser-sintered Co-Cr alloys were processed by the selective laser-sintering method (SLS) and the direct metal laser-sintering (DMLS) method using the Phenix system (L-1) and EOS system (L-2), respectively. L-1 and L-2 techniques were 8 and 3.5 times more precise than the casting (CC) technique (p < 0.05). Co-Cr alloys processed by L-1 and L-2 showed higher (p < 0.05) hardness (14-19%), yield strength (10-13%), and fatigue resistance (71-72%) compared to CC alloys. This was probably due to their smaller grain size and higher microstructural homogeneity. All Co-Cr alloys exhibited low porosity (2.1-3.3%); however, pore distribution was more homogenous in L-1 and L-2 alloys when compared to CC alloys. Both laser-sintered and cast alloys were biocompatible. In conclusion, laser-sintered alloys are more precise and present better mechanical and fatigue properties than cast alloys for RPDs. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1174-1185, 2018. © 2017 Wiley Periodicals, Inc.

Investigation by Monte Carlo simulation of substitution doping in the Double Perovskite Sr2CrRe1-xWxO6

NASA Astrophysics Data System (ADS)

El Rhazouani, O.; Benyoussef, A.

2018-01-01

Re-substitution doping by W has been investigated in the Double Perovskite (DP) Sr2CrRe1-xWxO6 for x ranging from 10 to 90% by using a Monte Carlo Simulation (MCS) in the framework of Ising model. Exchange couplings used in the simulation have been approximated in previous work for experimental Curie temperatures (TC). Doping effect on: partial and total magnetization, magnetic susceptibility, internal energy, specific heat, and Curie temperature has been studied. A sharp drop of partial magnetizations at 40% of W-concentration has been noticed at the magnetic transition. Apparition of a non-monotonic behavior of the total magnetization at 20% of W-concentration. Effect of doping on the stability of the compound has been emphasized. A quasilinear decrease of TC has been observed by increasing the concentration percentage of substitution doping by W.

Crystal structure and electrical conductivity of lanthanum-calcium chromites-titanates La 1-xCa xCr 1-yTi yO 3-δ ( x=0-1, y=0-1)

NASA Astrophysics Data System (ADS)

Vashook, V.; Vasylechko, L.; Zosel, J.; Gruner, W.; Ullmann, H.; Guth, U.

2004-10-01

Five series of perovskite-type compounds in the system La1-xCaxCr1-yTiyO3 with the nominal compositions y = 0 , x = 0 - 0.5 ; y = 0.2 , x = 0.2 - 0.8 ; y = 0.5 , x = 0.5 - 1.0 ; y = 0.8 , x = 0.6 - 1.0 and y = 1 , x = 0.8 - 1 were synthesized by a ceramic technique in air (final heating 1350 °C). On the basis of the X-ray analysis of the samples with (Ca/Ti)⩾1, the phase diagram of the CaTiO3-LaCrIIIO3-CaCrIVO3 quasi-ternary system was constructed. Extended solid solution with a wide homogeneity range is formed in the quasi-ternary system CaCrIVO3-CaTiO3-LaCrIIIO3. The solid solution La(1-x‧-y)Ca(x‧+y)CrIVx‧CrIII(1-x‧-y)TiyO3 exists by up to 0.6-0.7 mol fractions of CaCrIVO3 (x‧ < 0.6 - 0.7) at the experimental conditions. The crystal structure of the compounds is orthorhombic in the space group Pbnm at room temperature. The lattice parameters and the average interatomic distances of the samples within the solid solution ranges decrease uniformly with increasing Ca content. Outside the quasi-ternary system, the nominal compositions La0.1Ca0.9TiO3, La0.2Ca0.8TiO3, La0.4Ca0.6Cr0.2Ti0.8O3 and La0.3Ca0.7Cr0.2Ti0.8O3 in the system La1-xCaxCr1-yTiyO3 were found as single phases with an orthorhombic structure. In the temperature range between 850 and 1000 °C, the synthesized single-phase compositions are stable at pO2=6×10-16-0.21×105 Pa. Oxygen stoichiometry and electrical conductivity of the separate compounds were investigated as functions of temperature and oxygen partial pressure. The chemical stability of these oxides with respect to oxygen release during thermal dissociation decreases with increasing Ca-content. At 900 °C and oxygen partial pressure 1×10-15-0.21×105 Pa, the compounds with x > y (acceptor doped) are p-type semiconductors and those with x < y (donor doped) and x = y are n-type semiconductors. The type and level of electrical conductivity are functions of the concentration ratios of cations occupying the B-sites of the perovskite structures: [Cr3+]/[Cr4+] and [Ti4+]/[Ti3+]. The maximum electrical conductivity at 900 °C and pO2=10-15 Pa was found for the composition La0.1Ca0.9TiO3 (near 50 S/cm) and in air at 900 °C for La0.5Ca0.5CrO3 (close to 100 S/cm).

Bioremediation of chromium by the yeast Pichia guilliermondii: toxicity and accumulation of Cr (III) and Cr (VI) and the influence of riboflavin on Cr tolerance.

PubMed

Ksheminska, Helena; Jaglarz, Anita; Fedorovych, Daria; Babyak, Lyubov; Yanovych, Dmytro; Kaszycki, Pawel; Koloczek, Henryk

2003-01-01

A comparative study has been made on the sensitivity of the yeast Pichia guilliermondii to Cr (III) and Cr (VI) as well as on the Cr uptake potential at growth-inhibitory concentrations of chromium. The strains used in the study were either isolated from natural sources or obtained from a laboratory strain collection. The results show that most of the natural strains were more tolerant to chromium and were able to grow in the presence of 5 mM Cr (III) or 0.5 mM Cr (VI), that is at concentrations which substantially inhibited the growth of laboratory strains. The cellular Cr content after treatment was similar for both strain types and ranged from 1.2-4.0 mg/g d.w. and 0.4-0.9 mg/g d.w., for Cr (III) and Cr (VI) forms, respectively, however, in one case of a natural strain it reached the value of 10 mg Cr (III)/g dry mass. Natural-source strains were grouped into four groups based on the yeasts' differential response to Cr (III) and Cr (VI). Hexavalent Cr-resistant mutants of a P. giuilliermondii laboratory strain, which revealed markedly changed capabilities of chromium accumulation, were obtained by means of UV-induced mutagenesis. Cr (VI) treatment triggered oversynthesis of riboflavin and the addition of exogenous riboflavin increased P. guilliermondii resistance to both Cr (III) and Cr (VI). Electrophoretic protein profiles revealed the induction and/or suppression of several proteins in response to toxic Cr (VI) levels.

Mn-Cr dating of Fe- and Ca-rich olivine from 'quenched' and 'plutonic' angrite meteorites using Secondary Ion Mass Spectrometry

NASA Astrophysics Data System (ADS)

McKibbin, Seann J.; Ireland, Trevor R.; Amelin, Yuri; Holden, Peter

2015-05-01

Angrite meteorites are suitable for Mn-Cr relative dating (53Mn decays to 53Cr with a half life of 3.7 Myr) using Secondary Ion Mass Spectrometry (SIMS) because they contain olivine and kirschsteinite with very high 55Mn/52Cr ratios arising from very low Cr concentrations. Discrepant Mn-Cr and U-Pb time intervals between the extrusive or 'quenched' angrite D'Orbigny and some slowly cooled or 'plutonic' angrites suggests that some have been affected by secondary disturbances, but this seems to have occurred in quenched rather than in slow-cooled plutonic angrites, where such disturbance or delay of isotopic closure might be expected. Using SIMS, we investigate the Mn-Cr systematics of quenched angrites to higher precision than previously achieved by this method and extend our investigation to non-quenched (plutonic or sub-volcanic) angrites. High values of 3.54 (±0.18) × 10-6 and 3.40 (±0.19) × 10-6 (2-sigma) are found for the initial 53Mn/55Mn of the quenched angrites D'Orbigny and Sahara 99555, which are preserved by Cr-poor olivine and kirschsteinite. The previously reported initial 53Mn/55Mn value of D'Orbigny obtained from bulk-rock and mineral separates is slightly lower and was probably controlled by Cr-rich olivine. Results can be interpreted in terms of the diffusivity of Cr in this mineral. Very low Cr concentrations in Ca-rich olivine and kirschsteinite are probably charge balanced by Al; this substitutes for Si and likely diffuses at a very slow rate because Si is the slowest-diffusing cation in olivine. Diffusion in Cr-rich Mg-Fe olivine is probably controlled by cation vacancies because of deficiency in charge-balancing Al and is therefore more prone to disturbance. The higher initial 53Mn/55Mn found by SIMS for extrusive angrites is more likely to reflect closure of Cr in kirschsteinite at the time of crystallisation, simultaneous with closure of U-Pb and Hf-W isotope systematics for these meteorites obtained from pyroxenes. For the younger angrites Northwest Africa (NWA) 4590 and 4801 we have found initial 53Mn/55Mn values which are consistent with more precise work, at 0.90 (±0.4) × 10-6 and 0.13 (±1.1) × 10-6 respectively. Our work shows that SIMS can usefully constrain and distinguish the ages of angrites of different petrologic groups. In reviewing the petrology of angrites, we suggest that NWA 2999, 4590, and 4801 underwent a secondary partial melting and Cr (+/-Pb) disturbance event that the sub-volcanic Lewis Cliff 86010, and perhaps the plutonic Angra dos Reis, did not. With our higher initial 53Mn/55Mn for D'Orbigny and Sahara 99555 as well as previous data, a combined quenched angrite initial 53Mn/55Mn of 3.47 (±0.12) × 10-6 (2-sigma, MSWD 1.00) yields consistent Mn-Cr and U-Pb intervals between these angrites and Lewis Cliff 86010. Discrepant Mn-Cr timescales for other plutonic and sub-volcanic angrites represents resetting during the secondary partial melting event at ∼4557.2 Ma and indicates a relative order of disturbance of isotope systems: Mn-Cr in olivine before U-Pb in pyroxene, with Hf-W in pyroxene being the most resistant.

Association of fecal calprotectin concentrations with disease severity, response to treatment, and other biomarkers in dogs with chronic inflammatory enteropathies

PubMed Central

Berghoff, Nora; Mansell, Joanne; Grützner, Niels; Parnell, Nolie K.; Gurtner, Corinne; Suchodolski, Jan S.; Steiner, Jörg M.

2018-01-01

Background Calprotectin is a marker of inflammation, but its clinical utility in dogs with chronic inflammatory enteropathies (CIE) is unknown. Objective Evaluation of fecal calprotectin in dogs with biopsy‐confirmed CIE. Animals 127 dogs. Methods Prospective case‐control study. Dogs were assigned a canine chronic enteropathy clinical activity index (CCECAI) score, and histologic lesions severity was assessed. Fecal calprotectin, fecal S100A12, and serum C‐reactive protein (CRP) were measured. Food‐ or antibiotic‐responsive cases (FRE/ARE, n = 13) were distinguished from steroid‐/immunosuppressant‐responsive or ‐refractory cases (SRE/IRE, n = 20). Clinical response to treatment in SRE/IRE dogs was classified as complete remission (CR), partial response (PR), or no response (NR). Results Fecal calprotectin correlated with CCECAI (ρ = 0.27, P = .0065) and fecal S100A12 (ρ = 0.90, P < .0001), some inflammatory criteria, and cumulative inflammation scores, but not serum CRP (ρ = 0.16, P = .12). Dogs with SRE/IRE had higher fecal calprotectin concentrations (median: 2.0 μg/g) than FRE/ARE dogs (median: 1.4 μg/g), and within the SRE/IRE group, dogs with PR/NR had higher fecal calprotectin (median: 37.0 μg/g) than dogs with CR (median: 1.6 μg/g). However, both differences did not reach statistical significance (both P = .10). A fecal calprotectin ≥15.2 μg/g separated both groups with 80% sensitivity (95% confidence interval [95%CI]: 28%‐100%) and 75% specificity (95%CI: 43%‐95%). Conclusions and Clinical Importance Fecal calprotectin could be a useful surrogate marker of disease severity in dogs with CIE, but larger longitudinal studies are needed to evaluate its utility in predicting the response to treatment. PMID:29460444

Hexavalent chromium induced stress and metabolic responses in hybrid willows.

PubMed

Yu, Xiao-Zhang; Gu, Ji-Dong; Huang, Shen-Zhuo

2007-04-01

Metabolic responses to hexavalent chromium (Cr(6+)) stress and the uptake and translocation of Cr(6+ )were investigated using pre-rooted hybrid willows (Salix matsudana Koidz x Salix alba L.) exposed to hydroponic solution spiked with K(2)CrO(4) at 24.0 +/- 1 degrees C for 192 h. Various physiological parameters of the plants were monitored to determine toxicity from Cr(6+ )exposure. At Cr(6+) treatments of 50% higher than that of the non-treated control plants. As Cr concentrations were increased further, a slight increase in the transpiration rate was also observed compared with the controls. Negligible difference in the chlorophyll contents in leaves between the treated and the non-treated control plants was measured, except for willows exposed to 1.05 mg Cr/l. The response of soluble proteins in leaves of willows to Cr treatments was remarkable. Cr-induced toxicity appeared in all treatments resulting in reduced activities of catalase (CAT) and peroxidase (POD) compared to the controls. Superoxide dismutases (SOD) activity in the leaf cells showed a positive increase after Cr exposure. Of all selected parameters, soluble proteins in leaves were the most sensitive to Cr(6+ )doses, showing a significant linear correlation negatively (R (2) = 0.931). Uptake of Cr(6+) by willows grown in flasks was found to increase linearly with the added Cr(6+ )(a zero order kinetics), as indicated by the high R (2) (0.9322). Recovery of Cr in different parts of plant materials varied significantly with roots being the dominant site of Cr accumulation. Although the translocation to shoots was detected, the amount of Cr translocated to shoots was considerably small. The capacity of willows to assimilate Cr(6+ )was also evaluated using detached leaves and roots in sealed glass vessels in vivo. Uptake of Cr by roots was mediated possibly through an active transport mechanism, whereas the cuticle of leaves was the major obstacle to uptake Cr from the hydroponic solution. In addition, both cysteine and ascorbic acid showed a remarkable potential to reduce Cr(6+) at a neutral pH. Results indicated that the added Cr did not cause deleterious effects on plant physiological functions over a 192-h period of exposure. Significant removal of Cr from the hydroponic solution was observed in the presence of hybrid willows. The data also suggest that phytoremediation of Cr(6+) is possible and ecologically safe due to the minor translocation of Cr to aerial tissues.

Predictors of response, progression-free survival, and overall survival using NANT Response Criteria (v1.0) in relapsed and refractory high-risk neuroblastoma.

PubMed

Villablanca, Judith G; Ji, Lingyun; Shapira-Lewinson, Adi; Marachelian, Araz; Shimada, Hiroyuki; Hawkins, Randall A; Pampaloni, Miguel; Lai, Hollie; Goodarzian, Fariba; Sposto, Richard; Park, Julie R; Matthay, Katherine K

2018-05-01

The New Approaches to Neuroblastoma Therapy Response Criteria (NANTRC) were developed to optimize response assessment in patients with recurrent/refractory neuroblastoma. Response predictors and associations of the NANTRC version 1.0 (NANTRCv1.0) and prognostic factors with outcome were analyzed. A retrospective analysis was performed of patients with recurrent/refractory neuroblastoma enrolled from 2000 to 2009 on 13 NANT Phase 1/2 trials. NANTRC overall response integrated CT/MRI (Response Evaluation Criteria in Solid Tumors [RECIST]), metaiodobenzylguanidine (MIBG; Curie scoring), and percent bone marrow (BM) tumor (morphology). Fourteen (6.9%) complete response (CR) and 14 (6.9%) partial response (PR) occurred among 203 patients evaluable for response. Five-year progression-free survival (PFS) was 16 ± 3%; overall survival (OS) was 27 ± 3%. Disease sites at enrollment included MIBG-avid lesions (100% MIBG trials; 84% non-MIBG trials), measurable CT/MRI lesions (48%), and BM (49%). By multivariable analysis, Curie score of 0 (P < 0.001), lower Curie score (P = 0.003), no measurable CT/MRI lesions (P = 0.044), and treatment on peripheral blood stem cell (PBSC) supported trials (P = 0.005) were associated with achieving CR/PR. Overall response of stable disease (SD) or better was associated with better OS (P < 0.001). In multivariable analysis, MYCN amplification (P = 0.037) was associated with worse PFS; measurable CT/MRI lesions (P = 0.041) were associated with worse OS; prior progressive disease (PD; P < 0.001/P < 0.001), Curie score ≥ 1 (P < 0.001; P = 0.001), higher Curie score (P = 0.048/0.037), and treatment on non-PBSC trials (P = < 0.001/0.003) were associated with worse PFS and OS. NANTRCv1.0 response of at least SD is associated with better OS in patients with recurrent/refractory neuroblastoma. Patient and tumor characteristics may predict response and outcome. Identifying these variables can optimize Phase 1/2 trial design to select novel agents for further testing. © 2018 Wiley Periodicals, Inc.

Chemical Properties And Toxicity of Chromium(III) Nutritional Supplements

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

Levina, A.; Lay, P.A.

2009-05-19

The status of Cr(III) as an essential micronutrient for humans is currently under question. No functional Cr(III)-containing biomolecules have been definitively described as yet, and accumulated experience in the use of Cr(III) nutritional supplements (such as [Cr(pic){sub 3}], where pic = 2-pyridinecarboxylato) has shown no measurable benefits for nondiabetic people. Although the use of large doses of Cr(III) supplements may lead to improvements in glucose metabolism for type 2 diabetics, there is a growing concern over the possible genotoxicity of these compounds, particularly of [Cr(pic){sub 3}]. The current perspective discusses chemical transformations of Cr(III) nutritional supplements in biological media, withmore » implications for both beneficial and toxic actions of Cr(III) complexes, which are likely to arise from the same biochemical mechanisms, dependent on concentrations of the reactive species. These species include: (1) partial hydrolysis products of Cr(III) nutritional supplements, which are capable of binding to biological macromolecules and altering their functions; and (2) highly reactive Cr(VI/V/IV) species and organic radicals, formed in reactions of Cr(III) with biological oxidants. Low concentrations of these species are likely to cause alterations in cell signaling (including enhancement of insulin signaling) through interactions with the active centers of regulatory enzymes in the cell membrane or in the cytoplasm, while higher concentrations are likely to produce genotoxic DNA lesions in the cell nucleus. These data suggest that the potential for genotoxic side-effects of Cr(III) complexes may outweigh their possible benefits as insulin enhancers, and that recommendations for their use as either nutritional supplements or antidiabetic drugs need to be reconsidered in light of these recent findings.« less

Regulatory effect of dietary intake of chromium propionate on the response of monocyte-derived macrophages from Holstein cows in mid lactation.

PubMed

Garcia, M; Qu, Y; Scholte, C M; O'Connor, D; Rounds, W; Moyes, K M

2017-08-01

Chromium (Cr) has been reported to enhance immune function and improve insulin sensitivity and performance in beef and dairy cattle. However, its effect on bovine macrophage inflammatory and metabolic response is unknown. The objective of this study was to characterize the effect of dietary Cr on the inflammatory and metabolic response of polarized macrophages ex vivo. Twelve primiparous and 16 multiparous healthy Holstein cows in mid lactation (143 ± 37 d in milk) were enrolled in this study. Cows were fed a common total mixed ration once per day that was top-dressed with 200 g of ground corn containing 1 of 2 dietary treatments: control (CTL, no Cr supplementation) or Cr propionate (CrP, 8 mg of Cr/cow per day) for 35 d. At d 1, 17, and 35 of treatment, blood monocytes were isolated and cultured to obtain 3 monocyte-derived macrophage (MDM) phenotypes: M0 (non-polarized), M1 (pro-inflammatory; IFN-γ polarized) and M2 (anti-inflammatory; IL-4 polarized). The experiment was set in a randomized complete block design. Neither dry matter intake nor milk yield was affected by treatment. Plasma concentrations of metabolites and the metabolic and inflammatory response of MDM in spent media were not affected by treatment. Neither the whole blood cell population nor the specific proportion of leukocytes was affected by the main effect of treatment. However, we did observe a trend for fewer circulating neutrophils in cows fed CrP than in cows fed CTL for 35 d, which may be partly attributable to a greater influx of neutrophils into peripheral tissues, a reduced pro-inflammatory response during disease, or both; this warrants future study. Expression of IGFI was increased in MDM-M0, and expression of CXCL11 tended to increase in MDM-M2 from cows fed CrP compared with cows fed CTL. Expression of SLC2A3 also tended to increase in MDM-M2 from cows fed CrP compared with cows fed CTL at 17 d. Our results suggest that CrP has minimal effect on the inflammatory and metabolic response of MDM for Holstein dairy cows in mid lactation. Future studies are warranted to evaluate the differential regulation of Cr on the inflammatory and metabolic response of leukocytes from dairy cows at different stages of lactation and parity. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Phase transformations in a Cu−Cr alloy induced by high pressure torsion

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

Korneva, Anna, E-mail: a.korniewa@imim.pl; Straumal, Boris; Institut für Nanotechnologie, Karlsruher Institut für Technologie, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen

2016-04-15

Phase transformations induced by high pressure torsion (HPT) at room temperature in two samples of the Cu-0.86 at.% Cr alloy, pre-annealed at 550 °C and 1000 °C, were studied in order to obtain two different initial states for the HPT procedure. Observation of microstructure of the samples before HPT revealed that the sample annealed at 550 °C contained two types of Cr precipitates in the Cu matrix: large particles (size about 500 nm) and small ones (size about 70 nm). The sample annealed at 1000 °C showed only a little fraction of Cr precipitates (size about 2 μm). The subsequentmore » HPT process resulted in the partial dissolution of Cr precipitates in the first sample and dissolution of Cr precipitates with simultaneous decomposition of the supersaturated solid solution in another. However, the resulting microstructure of the samples after HPT was very similar from the standpoint of grain size, phase composition, texture analysis and hardness measurements. - Highlights: • Cu−Cr alloy with two different initial states was deformed by HPT. • Phase transformations in the deformed materials were studied. • SEM, TEM and X-ray diffraction techniques were used for microstructure analysis. • HPT leads to formation the same microstructure independent of the initial state.« less

On the mechanism of Cr (VI)-induced carcinogenesis: dose dependence of uptake and cellular responses.

PubMed

Liu, K; Husler, J; Ye, J; Leonard, S S; Cutler, D; Chen, F; Wang, S; Zhang, Z; Ding, M; Wang, L; Shi, X

2001-06-01

Cr (VI) compounds are widely used industrial chemicals and are recognized human carcinogens. The mechanisms of carcinogenesis associated with these compounds remain to be investigated. The present study focused on dose-dependence of Cr (VI)-induced uptake and cellular responses. The results show that Cr (VI) is able to enter the cells (human lung epithelial cell line A549) at low concentration (< 10 microM) and that the Cr (VI) uptake appears to be a combination of saturable transport and passive diffusion. Electron spin resonance (ESR) trapping measurements showed that upon stimulation with Cr (VI), A549 cells were able to generate reactive oxygen species (ROS). The amount of ROS generated depended on the Cr (VI) concentration. ROS generation involved NADPH-dependent flavoenzymes. Cr (VI) affected the following cellular parameters in a dose-dependent manner, (a) activation of nuclear transcription factors NF-kappaB, and p53, (b) DNA damage, (c) induction of cell apoptosis, and (d) inhibition of cell proliferation. The activation of transcription factors was assessed by electrophoretic mobility shift assay and western blot analysis, DNA damage by single cell gel electrophoresis assay, cell apoptosis by DNA fragmentation assay, and cell proliferation by a non-radioactive ELISA kit. At the concentration range used in the present study, no thresholds were found in all of these cell responses to Cr (VI). The results may guide further research to better understand and evaluate the risk of Cr (VI)-induced carcinogenesis at low levels of exposure.

Determination of solute site occupancies within γ' precipitates in nickel-base superalloys via orientation-specific atom probe tomography

DOE PAGES

Meher, Subhashish; Rojhirunsakool, Tanaporn; Nandwana, Peeyush; ...

2015-04-28

In this study, the analytical limitations in atom probe tomography such as resolving a desired set of atomic planes, for solving complex materials science problems, have been overcome by employing a well-developed unique and reproducible crystallographic technique, involving synergetic coupling of orientation microscopy with atom probe tomography. The crystallographic information in atom probe reconstructions has been utilized to determine the solute site occupancies in Ni-Al-Cr based superalloys accurately. The structural information in atom probe reveals that both Al and Cr occupy the same sub-lattice within the L1 2-ordered g precipitates to form Ni 3(Al,Cr) precipitates in a Ni-14Al-7Cr(at.%) alloy. Interestingly,more » the addition of Co, which is a solid solution strengthener, to a Ni-14Al-7Cr alloy results in the partial reversal of Al site occupancy within g precipitates to form (Ni,Al) 3(Al,Cr,Co) precipitates. This unique evidence of reversal of Al site occupancy, resulting from the introduction of other solutes within the ordered structures, gives insights into the relative energetics of different sub-lattice sites when occupied by different solutes.« less

Adrenocorticotropic hormone analog use for podocytopathies.

PubMed

Filippone, Edward J; Dopson, Shirley J; Rivers, Denise M; Monk, Rebeca D; Udani, Suneel M; Jafari, Golriz; Huang, Solomon C; Melhem, Arafat; Assioun, Bassim; Schmitz, Paul G

2016-01-01

Adrenocorticotropic hormone is being increasingly studied for treatment of various glomerulopathies, most notably membranous nephropathy. Less data are available regarding its use in idiopathic nephrotic syndrome (INS) secondary to minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS). We report here our experience with H.P. Acthar(®) Gel (repository corticotropin injection) as first-line or subsequent therapy in patients with INS. Data were taken from three patients with MCD and ten patients with FSGS from around the US, who were treated with Acthar Gel as initial or subsequent therapy. Treatment was solely at the discretion of the primary nephrologist without a specific protocol. A complete response (CR) was defined as final urine protein-to-creatinine ratio <500 mg/g and a partial response (PR) as 50% decrease without rise of serum creatinine. Side effects and tolerability were noted. All three patients with MCD received Acthar Gel as second-line or later immunosuppressive (IS) therapy and all responded (one CR and two PRs). Two of the ten patients with FSGS received Acthar Gel as first-line IS therapy, while the other eight had failed multiple agents. Four of the ten patients with FSGS had responses, including two CRs and two PRs. The three patients with MCD tolerated therapy well without side effects. Five patients with FSGS tolerated therapy well, while five had various steroid-like side effects, resulting in therapy discontinuation in two patients. Acthar Gel is a viable alternative IS agent for treatment of INS in patients intolerant or resistant to conventional therapy. More data are needed to better define its appropriate place.

Adrenocorticotropic hormone analog use for podocytopathies

PubMed Central

Filippone, Edward J; Dopson, Shirley J; Rivers, Denise M; Monk, Rebeca D; Udani, Suneel M; Jafari, Golriz; Huang, Solomon C; Melhem, Arafat; Assioun, Bassim; Schmitz, Paul G

2016-01-01

Background Adrenocorticotropic hormone is being increasingly studied for treatment of various glomerulopathies, most notably membranous nephropathy. Less data are available regarding its use in idiopathic nephrotic syndrome (INS) secondary to minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS). We report here our experience with H.P. Acthar® Gel (repository corticotropin injection) as first-line or subsequent therapy in patients with INS. Methods Data were taken from three patients with MCD and ten patients with FSGS from around the US, who were treated with Acthar Gel as initial or subsequent therapy. Treatment was solely at the discretion of the primary nephrologist without a specific protocol. A complete response (CR) was defined as final urine protein-to-creatinine ratio <500 mg/g and a partial response (PR) as 50% decrease without rise of serum creatinine. Side effects and tolerability were noted. Results All three patients with MCD received Acthar Gel as second-line or later immunosuppressive (IS) therapy and all responded (one CR and two PRs). Two of the ten patients with FSGS received Acthar Gel as first-line IS therapy, while the other eight had failed multiple agents. Four of the ten patients with FSGS had responses, including two CRs and two PRs. The three patients with MCD tolerated therapy well without side effects. Five patients with FSGS tolerated therapy well, while five had various steroid-like side effects, resulting in therapy discontinuation in two patients. Conclusion Acthar Gel is a viable alternative IS agent for treatment of INS in patients intolerant or resistant to conventional therapy. More data are needed to better define its appropriate place. PMID:27418857

Combustion synthesis of complex oxides

NASA Astrophysics Data System (ADS)

Ming, Qimin

Advanced ceramic materials have numerous applications in electronic engineering, chemical engineering, and semiconductor industry. The synthesis of these materials at an economical cost is the bottleneck in the application of these materials. Self-propagating High-temperature Synthesis (SHS) is a new technique for producing these materials for exothermic systems by a combustion wave that propagates and produces high purity products. The full potential of SHS to produce advanced materials has not yet been utilized. In this study, we used SHS to prepare two types of complex oxides: La 1-xSrxCrO3, La0.89Sr0.1 MnO3, powders, used to make interconnect and cathode of solid oxide fuel cells; and chromium- and gallium-doped La1-xSr xFeO3-delta, mixed ionic and electronic conductive powders used to manufacture ceramic membranes for oxygen separation. A thermodynamic feasibility analysis shows that the oxidation of Cr is the main source of heat generation of La1-xSrxCrO 3, which maintains a stable reaction front. Replacing part of the metallic Cr in the reaction mixture by its oxides decreases the combustion temperature and front propagating velocity and modifies the product morphology. The oxygen needed for the Cr oxidation is provided by the decomposition of CrO3 , SrO2, or NaClO4. The predicted and observed combustion temperatures are in reasonable agreement. TG/DTA analyses of La1-xSrxCrO3 indicated that SHS stability was strongly affected by the transport of oxygen between the two regions, in which oxygen was generated by the decomposition of either NaClO4 or CrO3 and that in which it was consumed by the oxidation of Cr. Partial melting at the high combustion temperature during SHS of La 1-xSrxMnO3 increased product homogeneity. The electrical conductivity at 1000°C in air of SHS-produced cathode material (of 180 O-1·cm-1) matches that of the commercial product made by other processes. However, the SHS process provides much higher productivity and decreases processing time and the consumption of the electrical power. SrFeO3-x and LaCrO3 were the main intermediates and products for SHS of chromium-doped La0.2Sr0.8FeO 3-delta. The final structure was a solid solution of Fe and Sr rich oxides and La and Cr rich oxides. Decreasing the reactant particle size increased the homogeneity of the SHS product and increased the velocity of the propagating combustion front. The SHS produced La0.2Sr 0.8Cr0.2Fe0.8O3-delta had a maximal electrical conductivity of 8.8 O-1·cm -1 at 560°C in a pure oxygen. The material, having the highest stability in reducing conditions, had a moderate oxygen permeation rate of 3.35 x 10-9 mol/s·cm2 at 980°C in an oxygen partial pressure gradient from air to 4 x 10 -5 atm. The homogeneity and particle size of the combustion product of gallium-doped La0.5Sr0.5FeO3-delta may be increased by decreasing the cooling rate of the sample, either by increasing the sample diameter or by controlling the post-combustion temperature. The perovskite oxide maintained its cubic structure at all temperatures (from 20 to 1000°C) in air. However, decomposition occurred at 860°C under a simulated synthesis gas environment (22%CH4+21%CO2+57%H2, oxygen partial pressure of about 10-21 atm). Its maximal electrical conductivity was 142 O-1·cm-1 at 580°C under oxygen pressure of 1 atm. This material is suitable for use as a membrane in synthesis gas production, since the thermal expansions in air and reducing conditions are rather close at high temperatures.

Critical analysis of the stringent complete response in multiple myeloma: contribution of sFLC and bone marrow clonality

PubMed Central

Paiva, Bruno; López-Anglada, Lucía; Mateos, María-Victoria; Cedena, Teresa; Vidríales, María-Belén; Sáez-Gómez, María Auxiliadora; Contreras, Teresa; Oriol, Albert; Rapado, Inmaculada; Teruel, Ana-Isabel; Cordón, Lourdes; Blanchard, María Jesús; Bengoechea, Enrique; Palomera, Luis; de Arriba, Felipe; Cueto-Felgueroso, Cecilia; Orfao, Alberto; Bladé, Joan; San Miguel, Jesús F.; Lahuerta, Juan José

2015-01-01

Stringent complete response (sCR) criteria are used in multiple myeloma as a deeper response category compared with CR, but prospective validation is lacking, it is not always clear how evaluation of clonality is performed, and is it not known what the relative clinical influence is of the serum free light chain ratio (sFLCr) and bone marrow (BM) clonality to define more sCR. To clarify this controversy, we focused on 94 patients that reached CR, of which 69 (73%) also fulfilled the sCR criteria. Patients with sCR displayed slightly longer time to progression (median, 62 vs 53 months, respectively; P = .31). On analyzing this contribution to the prognosis of sFLCr or clonality, it was found that the sFLCr does not identify patients in CR at distinct risk; by contrast, low-sensitive multiparametric flow cytometry (MFC) immunophenotyping (2 colors), which is equivalent to immunohistochemistry, identifies a small number of patients (5 cases) with high residual tumor burden and dismal outcome; nevertheless, using traditional 4-color MFC, persistent clonal BM disease was detectable in 36% of patients, who, compared with minimal residual disease-negative cases, had a significantly inferior outcome. These results show that the current definition of sCR should be revised. PMID:26089396

Rituximab with pentostatin or cladribine: an effective combination treatment for hairy cell leukemia after disease recurrence.

PubMed

Else, Monica; Dearden, Claire E; Matutes, Estella; Forconi, Francesco; Lauria, Francesco; Ahmad, Humayun; Kelly, Susan; Liyanage, Anandika; Ratnayake, Vijitha; Shankari, Jagadeesan; Whalley, Ioana; Catovsky, Daniel

2011-06-01

The purine analogs pentostatin and cladribine are effective treatments for hairy cell leukemia (HCL). However, alternative treatments are needed for patients with recurrent disease. We reviewed retrospectively data from 18 patients who were retreated with either pentostatin (n = 12) or cladribine (n = 6) in combination with rituximab, after 1-6 (median 2) previous treatments with either purine analog as a single agent. All 18 patients responded to therapy, with a complete response (CR) rate of 89%. This compared favorably with CR rates of 68% after second-line therapy and 47% after third-line therapy in 88 patients retreated one or more times with a purine analog alone. Toxicity with the combination treatment was minimal. At a median follow-up of 36 months (range 5-83 months) all 16 complete responders remained in CR, while one partial responder developed recurrent disease at 10 months. The estimated recurrence rate at 3 years was 7%. This compares with 21% after second-line therapy and 42% after third-line therapy in the 88 patients retreated with a purine analog alone. Furthermore, it was a marked improvement on the 55% recurrence at 3 years previously seen in these same 18 patients after their own first-line treatment with single-agent pentostatin or cladribine (p = 0.006). The combination of a purine analog with rituximab was safe and effective for patients with recurrent HCL. The results suggest an added benefit compared with single-agent purine analog therapy.

Modacrylic anion-exchange fibers for Cr(VI) removal from chromium-plating rinse water in batch and flow-through column experiments.

PubMed

Lee, Seung-Chan; Kang, Jin-Kyu; Sim, Eun-Hye; Choi, Nag-Choul; Kim, Song-Bae

2017-11-10

The aim of this study was to investigate Cr(VI) removal from chromium-plating rinse water using modacrylic anion-exchange fibers (KaracaronTM KC31). Batch experiments were performed with synthetic Cr(VI) solutions to characterize the KC31 fibers in Cr(VI) removal. Cr(VI) removal by the fibers was affected by solution pH; the Cr(VI) removal capacity was the highest at pH 2 and decreased gradually with a pH increase from 2 to 12. In regeneration and reuse experiments, the Cr(VI) removal capacity remained above 37.0 mg g -1 over five adsorption-desorption cycles, demonstrating that the fibers could be successfully regenerated with NaCl solution and reused. The maximum Cr(VI) removal capacity was determined to be 250.3 mg g -1 from the Langmuir model. In Fourier-transform infrared spectra, a Cr = O peak newly appeared at 897 cm -1 after Cr(VI) removal, whereas a Cr-O peak was detected at 772 cm -1 due to the association of Cr(VI) ions with ion-exchange sites. X-ray photoelectron spectroscopy analyses demonstrated that Cr(VI) was partially reduced to Cr(III) after the ion exchange on the surfaces of the fibers. Batch experiments with chromium-plating rinse water (Cr(VI) concentration = 1178.8 mg L -1 ) showed that the fibers had a Cr(VI) removal capacity of 28.1-186.4 mg g -1 under the given conditions (fiber dose = 1-10 g L -1 ). Column experiments (column length = 10 cm, inner diameter = 2.5 cm) were conducted to examine Cr(VI) removal from chromium-plating rinse water by the fibers under flow-through column conditions. The Cr(VI) removal capacities for the fibers at flow rates of 0.5 and 1.0 mL min -1 were 214.8 and 171.5 mg g -1 , respectively. This study demonstrates that KC31 fibers are effective in the removal of Cr(VI) ions from chromium-plating rinse water.

Effect of NiFeCr seed and capping layers on exchange bias and planar Hall voltage response of NiFe/Au/IrMn trilayer structures

NASA Astrophysics Data System (ADS)

Talantsev, Artem; Elzwawy, Amir; Kim, CheolGi

2018-05-01

Thin films and cross junctions, based on NiFe/Au/IrMn structures, were grown on Ta and NiFeCr seed layers by magnetron sputtering. The effects of substitution of Ta with NiFeCr in seed and capping layers on an exchange bias field are studied. A threefold improvement of the exchange bias value in the structures, grown with NiFeCr seed and capping layers, is demonstrated. The reasons for this effect are discussed. Formation of clusters in the NiFeCr capping layer is proved by atomic force microscopy technique. Ta replacement on NiFeCr in the capping layer results in the enhancement of magnetoresistive response and a reduction of noise.

Novel rabies virus-neutralizing epitope recognized by human monoclonal antibody: fine mapping and escape mutant analysis.

PubMed

Marissen, Wilfred E; Kramer, R Arjen; Rice, Amy; Weldon, William C; Niezgoda, Michael; Faber, Milosz; Slootstra, Jerry W; Meloen, Rob H; Clijsters-van der Horst, Marieke; Visser, Therese J; Jongeneelen, Mandy; Thijsse, Sandra; Throsby, Mark; de Kruif, John; Rupprecht, Charles E; Dietzschold, Bernhard; Goudsmit, Jaap; Bakker, Alexander B H

2005-04-01

Anti-rabies virus immunoglobulin combined with rabies vaccine protects humans from lethal rabies infections. For cost and safety reasons, replacement of the human or equine polyclonal immunoglobulin is advocated, and the use of rabies virus-specific monoclonal antibodies (MAbs) is recommended. We produced two previously described potent rabies virus-neutralizing human MAbs, CR57 and CRJB, in human PER.C6 cells. The two MAbs competed for binding to rabies virus glycoprotein. Using CR57 and a set of 15-mer overlapping peptides covering the glycoprotein ectodomain, a neutralization domain was identified between amino acids (aa) 218 and 240. The minimal binding region was identified as KLCGVL (aa 226 to 231), with key residues K-CGV- identified by alanine replacement scanning. The critical binding region of this novel nonconformational rabies virus epitope is highly conserved within rabies viruses of genotype 1. Subsequently, we generated six rabies virus variants escaping neutralization by CR57 and six variants escaping CRJB. The CR57 escape mutants were only partially covered by CRJB, and all CRJB-resistant variants completely escaped neutralization by CR57. Without exception, the CR57-resistant variants showed a mutation at key residues within the defined minimal binding region, while the CRJB escape viruses showed a single mutation distant from the CR57 epitope (N182D) combined with mutations in the CR57 epitope. The competition between CR57 and CRJB, the in vitro escape profile, and the apparent overlap between the recognized epitopes argues against including both CR57 and CRJB in a MAb cocktail aimed at replacing classical immunoglobulin preparations.

Antiferromagnetic structure and electronic properties of BaCr2As2 and BaCrFeAs2

NASA Astrophysics Data System (ADS)

Filsinger, Kai A.; Schnelle, Walter; Adler, Peter; Fecher, Gerhard H.; Reehuis, Manfred; Hoser, Andreas; Hoffmann, Jens-Uwe; Werner, Peter; Greenblatt, Martha; Felser, Claudia

2017-05-01

Recent theoretical studies suggest that superconductivity may be found in doped chromium pnictides with crystal structures similar to their iron counterparts. Here, we report a comprehensive study on the magnetic arsenides BaCr2As2 and BaCrFeAs2 (space group I 4 /m m m ), which are possible mother compounds with d4 and d5 electron configurations, respectively. DFT-based calculations of the electronic structure evidence metallic antiferromagnetic ground states for both compounds. By powder neutron diffraction, we confirm for BaCr2As2 a robust ordering in the antiferromagnetic G -type structure at TN=580 K with μCr=1.9 μB . Anomalies in the lattice parameters point to magnetostructural coupling effects. In BaCrFeAs2, the Cr and Fe atoms randomly occupy the transition-metal site and G -type order is found below 265 K with μCr /Fe=1.1 μB . 57Fe Mössbauer spectroscopy demonstrates that only a small ordered moment is associated with the Fe atoms, in agreement with electronic structure calculations leading to μFe˜0 . The temperature dependence of the hyperfine field does not follow that of the total moments. Both compounds are metallic but show large enhancements of the linear specific heat. Electrical transport in BaCrFeAs2 is dominated by the atomic disorder and the partial magnetic disorder of Fe. Our results indicate that Néel-type order is unfavorable for Fe moments and thus it is destabilized with increasing Fe content.

A prospective phase II trial of response adapted whole brain radiotherapy after high dose methotrexate based chemotherapy in patients with newly diagnosed primary central nervous system lymphoma-analysis of acute toxicity profile and early clinical outcome.

PubMed

Adhikari, Narayan; Biswas, Ahitagni; Gogia, Ajay; Sahoo, Ranjit Kumar; Garg, Ajay; Nehra, Ashima; Sharma, Mehar Chand; Bhasker, Suman; Singh, Manmohan; Sreenivas, Vishnubhatla; Chawla, Rohan; Joshi, Garima; Kumar, Lalit; Chander, Subhash

2018-04-09

The treatment of primary CNS lymphoma (PCNSL) comprises high dose methotrexate (HDMTX) based chemotherapy followed by whole brain radiotherapy (WBRT), the major drawback of which is long term neurotoxicity. We intended to assess the feasibility of response adapted WBRT in PCNSL in the Indian setting. We screened 32 patients and enrolled 22 eligible patients with PCNSL from 2015 to 2017 in a prospective phase II trial. The patients underwent five 2-weekly cycles of induction chemotherapy with rituximab, methotrexate, vincristine, procarbazine. Patients with complete response(CR) to induction chemotherapy were given reduced dose WBRT 23.4 Gy/13 fractions/2.5 weeks while those with partial response (PR), stable or progressive disease (SD or PD) were given standard dose WBRT 45 Gy/25 fractions/5 weeks. Thereafter two cycles of consolidation chemotherapy with cytarabine were given. The primary endpoints of the study were assessment of response rate (RR) and progression free survival (PFS). The secondary endpoints of the study were assessment of overall survival (OS), toxicity profile of treatment and serial changes in quality of life and neuropsychological parameters. Out of 19 patients who completed HDMTX based chemotherapy, 10 (52.63%) patients achieved CR, 8 (42.11%) patients had PR and 1 patient had PD. After a median follow-up period of 11.25 months, the estimated median OS was 19 months. The actuarial rates of PFS and OS were respectively 94.1 and 68.2% at 1 year and 50.2 and 48.5% at 2 years. Three patients in reduced dose WBRT arm had recurrence and two of them died of progressive disease, whereas there was no recurrence or disease related death in standard dose WBRT arm. On univariate analysis of PFS, age ≤ 50 years and use of standard dose WBRT (45 Gy) led to significantly improved outcome (p value 0.03 and 0.02 respectively). In patients with PCNSL, reduced dose WBRT after CR to HDMTX based chemotherapy may lead to suboptimal clinical outcome due to higher risk of recurrence, progression and early death. Trial Registration No CTRI/2015/10/006268.

Lacosamide Isothiocyanate-based Agents: Novel Agents to Target and Identify Lacosamide Receptors

PubMed Central

Park, Ki Duk; Morieux, Pierre; Salomé, Christophe; Cotten, Steven W.; Reamtong, Onrapak; Eyers, Claire; Gaskell, Simon J.; Stables, James P.; Liu, Rihe; Kohn, Harold

2009-01-01

(R)-Lacosamide ((R)-2, (R)-N-benzyl 2-acetamido-3-methoxypropionamide), has recently gained regulatory approval for the treatment of partial-onset seizures in adults. Whole animal pharmacological studies have documented that (R)-2 function is unique. A robust strategy is advanced for the discovery of interacting proteins associated with function and toxicity of (R)-2 through the use of (R)-2 analogs, 3, that contain “affinity bait (AB)” and “chemical reporter (CR)” functional groups. In 3, covalent modification of the interacting proteins proceeds at the AB moiety, and detection or isolation of the selectively captured protein occurs through the bioorthogonal CR group upon reaction with an appropriate probe. We report the synthesis, pharmacological evaluation, and interrogation of the mouse soluble brain proteome using 3 where the AB group is an isothiocyanate moiety. One compound, (R)-N-(4-isothiocyanato)benzyl 2-acetamido-3-(prop-2-ynyloxy)propionamide ((R)-9), exhibited excellent seizure protection in mice and, like (R)-2, anticonvulsant activity principally resided in the (R)-stereoisomer. Several proteins were preferentially labeled by (R)-9 compared with (S)-9, including collapsin response mediator protein 2. PMID:19795888

Increasing Weldability of Service-Aged Reformer Tubes by Partial Solution Annealing

NASA Astrophysics Data System (ADS)

Mostafaei, M.; Shamanian, M.; Purmohamad, H.; Amini, M.

2016-04-01

A dissimilar joint of 25Cr-35Ni/30Cr-48Ni (HP/HV) heat-resistant steels was evaluated. The investigations indicated that the as-cast HP alloy contained M7C3, M23C6, and NbC carbides and HV alloy with 5 wt.% tungsten, contained M23C6 and M6C carbides embedded in an austenitic matrix. After 8 years of ex-service aging at 1050 °C, the ductility of HP/HV reformer tubes was decreased dramatically, and thus, the repair welding of the aged HP/HV dissimilar joint was at a risk. In order to repair the aged reformer tubes and increase weldability properties, a new partial solution annealing treatment was designed. Mechanical testing results showed that partial solution annealing at 1200 °C for 6 h increased the elongation and toughness of the aged HP and HV alloys drastically. Also, a mechanism for constitutional liquation cracking in the heat-affected zones (HAZ) of the HP/HV dissimilar joint was proposed. In the HAZ of the aged HP/HV welded joint, the cracks around the locally melted carbides were initiated and propagated during carbides solidification at the cooling cycle of welding associated with the decrease in the ductility of the aged HP and HV alloys. In addition, Varestraint weldability test showed that the susceptibility to hot cracking was decreased with partial solution annealing.

Comparative study of circumferential clasp retention force for titanium and cobalt-chromium removable partial dentures.

PubMed

Rodrigues, Renata Cristina Silveira; Ribeiro, Ricardo Faria; de Mattos, Maria da Gloria Chiarello; Bezzon, Osvaldo Luiz

2002-09-01

The interest in using titanium to fabricate removable partial denture (RPD) frameworks has increased, but there are few studies to support its use. The objective of this study was to compare circumferential RPD clasps made of commercially pure titanium and identical clasps made of 2 different cobalt (Co)-chromium (Cr) alloys by testing insertion/removal and radiographically inspecting the casts for defects. On refractory casts that represent a partially edentulous mandibular right hemi-arch segment, 36 frameworks were cast from commercially pure titanium (n = 12) and 2 Co-Cr alloys (n = 12 each) with identical prefabricated patterns and the manufacturer-designated investment and casting technique. Each group was divided into 2 subgroups, corresponding to .25-mm and .50-mm undercuts, respectively. No polishing procedures were performed to ensure uniformity. Only nodules and burs were carefully removed with tungsten burs under magnification when necessary. The specimens were radiographed and subjected to an insertion/removal test simulating 5 years of framework use. The data were subjected to analysis of variance and the Tukey complementary test (P<.01) to compare the retentive forces of RPDs made with the different materials. The Student t test (P<.01) was used to compare the retentive forces of RPDs fabricated with the same alloy with different undercuts. A total of 20% of the titanium specimens demonstrated porosity, showing casting difficulties, and any defect detected on the clasps determined the sample replacement. For Co-Cr alloys, casting difficulties were not found. The data were subjected to analysis of variance and the Tukey complementary test to compare materials for the same undercut. For the .25-mm undercut, no significant difference was found between Magnum and Rematitan alloys; they were both different from the Remanium alloy (P<.01). For the.50-mm undercut, no significant difference was found between Co-Cr alloys; they were both different from Rematitan alloy (P<.01). The Student t test used to compare the same alloys with different undercuts showed no significant difference between Remanium with .25-mm and .50-mm undercuts. For Magnum and Rematitan alloys, there was a significant difference between different undercuts (P=.01). Within the limitations of this simulation study, the results suggest that commercially pure titanium clasps maintained retention over a simulated 5-year period, with lower retention force than identical Co-Cr clasps.

Hypoxia decreases creatine uptake in cardiomyocytes, while creatine supplementation enhances HIF activation.

PubMed

Santacruz, Lucia; Arciniegas, Antonio Jose Luis; Darrabie, Marcus; Mantilla, Jose G; Baron, Rebecca M; Bowles, Dawn E; Mishra, Rajashree; Jacobs, Danny O

2017-08-01

Creatine (Cr), phosphocreatine (PCr), and creatine kinases (CK) comprise an energy shuttle linking ATP production in mitochondria with cellular consumption sites. Myocytes cannot synthesize Cr: these cells depend on uptake across the cell membrane by a specialized creatine transporter (CrT) to maintain intracellular Cr levels. Hypoxia interferes with energy metabolism, including the activity of the creatine energy shuttle, and therefore affects intracellular ATP and PCr levels. Here, we report that exposing cultured cardiomyocytes to low oxygen levels rapidly diminishes Cr transport by decreasing V max and K m Pharmacological activation of AMP-activated kinase (AMPK) abrogated the reduction in Cr transport caused by hypoxia. Cr supplementation increases ATP and PCr content in cardiomyocytes subjected to hypoxia, while also significantly augmenting the cellular adaptive response to hypoxia mediated by HIF-1 activation. Our results indicate that: (1) hypoxia reduces Cr transport in cardiomyocytes in culture, (2) the cytoprotective effects of Cr supplementation are related to enhanced adaptive physiological responses to hypoxia mediated by HIF-1, and (3) Cr supplementation increases the cellular ATP and PCr content in RNCMs exposed to hypoxia. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Retention and release of hexavalent and trivalent chromium by chitosan, olive stone activated carbon, and their blend.

PubMed

Ba, Seydou; Alagui, Abdelhakim; Hajjaji, Mohamed

2018-05-07

Shrimp shells and waste of olive stones were used as feedstock for the preparation of chitosan and activated carbon. The adsorption of Cr VI and Cr III species in aqueous solution by the materials prepared and their blend were studied by using the well-known kinetic and isotherm models, Fourier transform infrared spectroscopy and scanning electron microscope. It was demonstrated that the rates of adsorption were controlled by diffusion inside particles and throughout the liquid film, and adsorption occurred spontaneously (- 26 < ∆G° < - 15 kJ/mol) in the range of 298-333 K, except for that involving Cr III species and activated carbon. The maximum amounts of Cr species retained by the composite (146 mg of Cr VI /g and 33 mg of Cr III /g at 298 K) were three times greater than those of the basic constituents. Adsorption was markedly affected by temperature and pH, and Cr VI species were substantially desorbed in acid mediums, particularly in acetic acid solution. The recovery of Cr III species varied according to the adsorbent and the solution used. The immobilization of Cr VI species (HCrO 4 - and CrO 4 2- ) and Cr III species (Cr(OH) 2 + and Cr 3 (OH) 4 5+ ) by chitosan was accomplished by means of amine moieties and hydroxyls of D-glucosamine units of the biopolymer. The adsorption of Cr VI species on activated carbon involved π electrons of aromatic rings as well as oxygenated sites (C-OH, C=O, C-O-C). In such a condition, Cr VI was partially reduced into Cr III . For the composite, the amino functional groups of chitosan and hydroxyls of both constituents were implicated in the linkage of the biopolymer and activated carbon, and the C-O-H and C-O-C functional groups of chitosan were involved in the retention of Cr VI species. For Cr III species, adsorption occurred preferentially on hydroxyls of the components, and consequently, the chains of the biopolymer recovered some flexibility.

Canine stifle joint biomechanics associated with tibial plateau leveling osteotomy predicted by use of a computer model.

PubMed

Brown, Nathan P; Bertocci, Gina E; Marcellin-Little, Denis J

2014-07-01

To evaluate effects of tibial plateau leveling osteotomy (TPLO) on canine stifle joint biomechanics in a cranial cruciate ligament (CrCL)-deficient stifle joint by use of a 3-D computer model simulating the stance phase of gait and to compare biomechanics in TPLO-managed, CrCL-intact, and CrCL-deficient stifle joints. Computer simulations of the pelvic limb of a Golden Retriever. A previously developed computer model of the canine pelvic limb was used to simulate TPLO stabilization to achieve a tibial plateau angle (TPA) of 5° (baseline value) in a CrCL-deficient stifle joint. Sensitivity analysis was conducted for tibial fragment rotation of 13° to -3°. Ligament loads, relative tibial translation, and relative tibial rotation were determined and compared with values for CrCL-intact and CrCL-deficient stifle joints. TPLO with a 5° TPA converted cranial tibial translation to caudal tibial translation and increased loads placed on the remaining stifle joint ligaments, compared with results for a CrCL-intact stifle joint. Lateral collateral ligament load was similar, medial collateral ligament load increased, and caudal cruciate ligament load decreased after TPLO, compared with loads for a CrCL-deficient stifle joint. Relative tibial rotation after TPLO was similar to that of a CrCL-deficient stifle joint. Stifle joint biomechanics were affected by TPLO fragment rotation. In the model, stifle joint biomechanics were partially improved after TPLO, compared with CrCL-deficient stifle joint biomechanics, but TPLO did not fully restore CrCL-intact stifle joint biomechanics. Overrotation of the tibial fragment negatively influenced stifle joint biomechanics by increasing caudal tibial translation.

Hexavalent chromium targets mitochondrial respiratory chain complex I to induce reactive oxygen species-dependent caspase-3 activation in L-02 hepatocytes.

PubMed

Xiao, Fang; Li, Yanhong; Dai, Lu; Deng, Yuanyuan; Zou, Yue; Li, Peng; Yang, Yuan; Zhong, Caigao

2012-09-01

Hexavalent chromium [Cr(VI)], which is used for various industrial applications, such as leather tanning and chroming, can cause a number of human diseases including inflammation and cancer. Cr(VI) exposure leads to severe damage to the liver, but the mechanisms involved in Cr(VI)-mediated toxicity in the liver are unclear. The present study provides evidence that Cr(VI) enhances reactive oxygen species (ROS) accumulation by inhibiting the mitochondrial respiratory chain complex (MRCC) I. Cr(VI) did not affect the expression levels of antioxidative proteins such as superoxide dismutase (SOD), catalase and thioredoxin (Trx), indicating that the antioxidative system was not involved in Cr(VI)-induced ROS accumulation. We found that ROS mediated caspase-3 activation partially depends on the downregulation of the heat shock protein (HSP) 70 and 90. In order to confirm our hypothesis that ROS plays a key role in Cr(VI)-mediated cytotoxicity, we used N-acetylcysteine (NAC) to inhibit the accumulation of ROS. NAC successfully blocked the inhibition of HSP70 and HSP90 as well as the activation of caspase-3, suggesting that ROS is essential in Cr(VI)-induced caspase-3 activation. By applying different MRCC substrates as electron donors, we also confirmed that Cr(VI) could accept the electrons leaked from MRCC I and the reduction occurs at MRCC I. In conclusion, the present study demonstrates that Cr(VI) induces ROS-dependent caspase-3 activation by inhibiting MRCC I activity, and MRCC I has been identified as a new target and a new mechanism for the apoptosis-inducing activity displayed by Cr(VI).

The stable Cr isotopic compositions of chondrites and silicate planetary reservoirs

NASA Astrophysics Data System (ADS)

Schoenberg, Ronny; Merdian, Alexandra; Holmden, Chris; Kleinhanns, Ilka C.; Haßler, Kathrin; Wille, Martin; Reitter, Elmar

2016-06-01

The depletion of chromium in Earth's mantle (∼2700 ppm) in comparison to chondrites (∼4400 ppm) indicates significant incorporation of chromium into the core during our planet's metal-silicate differentiation, assuming that there was no significant escape of the moderately volatile element chromium during the accretionary phase of Earth. Stable Cr isotope compositions - expressed as the ‰-difference in 53Cr/52Cr from the terrestrial reference material SRM979 (δ53/52CrSRM979 values) - of planetary silicate reservoirs might thus yield information about the conditions of planetary metal segregation processes when compared to chondrites. The stable Cr isotopic compositions of 7 carbonaceous chondrites, 11 ordinary chondrites, 5 HED achondrites and 2 martian meteorites determined by a double spike MC-ICP-MS method are within uncertainties indistinguishable from each other and from the previously determined δ53/52CrSRM979 value of -0.124 ± 0.101‰ for the igneous silicate Earth. Extensive quality tests support the accuracy of the stable Cr isotope determinations of various meteorites and terrestrial silicates reported here. The uniformity in stable Cr isotope compositions of samples from planetary silicate mantles and undifferentiated meteorites indicates that metal-silicate differentiation of Earth, Mars and the HED parent body did not cause measurable stable Cr isotope fractionation between these two reservoirs. Our results also imply that the accretionary disc, at least in the inner solar system, was homogeneous in its stable Cr isotopic composition and that potential volatility loss of chromium during accretion of the terrestrial planets was not accompanied by measurable stable isotopic fractionation. Small but reproducible variations in δ53/52CrSRM979 values of terrestrial magmatic rocks point to natural stable Cr isotope variations within Earth's silicate reservoirs. Further and more detailed studies are required to investigate whether silicate differentiation processes, such as partial mantle melting and crystal fractionation, can cause stable Cr isotopic fractionation on Earth and other planetary bodies.

Safety and Antitumor Activity of Pembrolizumab in Patients with Estrogen Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer.

PubMed

Rugo, Hope S; Delord, Jean-Pierre; Im, Seock-Ah; Ott, Patrick A; Piha-Paul, Sarina A; Bedard, Philippe L; Sachdev, Jasgit; Tourneau, Christophe Le; van Brummelen, Emilie M J; Varga, Andrea; Salgado, Roberto; Loi, Sherene; Saraf, Sanatan; Pietrangelo, Dina; Karantza, Vassiliki; Tan, Antoinette R

2018-03-20

Purpose: We investigated the safety and antitumor activity of the anti-programmed death 1 monoclonal antibody pembrolizumab in patients with estrogen receptor-positive (ER + )/human epidermal growth factor receptor 2-negative (HER2 - ) advanced breast cancer with programmed death ligand 1-positive (PD-L1-positive) tumors in the phase Ib open-label, multicohort KEYNOTE-028 (NCT02054806) study. Experimental Design: Patients with ER + /HER2 - advanced breast cancer with PD-L1-positive tumors (combined positive score ≥1) received pembrolizumab (10 mg/kg every 2 weeks) up to 2 years or until confirmed progression/intolerable toxicity. Primary endpoints were safety and overall response rate (ORR), based on Response Evaluation Criteria in Solid Tumors, version 1 (RECIST v1.1) as assessed by investigator review. Results: Between April 2014 and January 2015, 25 patients were enrolled. Median number of prior therapies for breast cancer, including endocrine agents, was 9 (range, 3-15). Median follow-up was 9.7 months (range, 0.7-31.8 months). Three patients experienced partial response (PR) and none experienced complete response (CR), resulting in an ORR of 12.0% (95% CI, 2.5%-31.2%); 16% of patients had stable disease (SD) and clinical benefit rate (CR + PR + [SD for ≥24 weeks]) was 20% (95% CI, 7-41). Median duration of response was 12.0 months (range, 7.4-15.9 months). The incidence of treatment-related adverse events was 64%; nausea (20%) and fatigue (12%) were most common and were predominantly grade 1/2. No treatment-related discontinuations or deaths occurred. Conclusions: Pembrolizumab was well tolerated with modest but durable overall response in certain patients with previously treated, advanced, PD-L1-positive, ER + /HER2 - breast cancer. Clin Cancer Res; 1-8. ©2018 AACR. ©2018 American Association for Cancer Research.

Shock Wave Response of Iron-based In Situ Metallic Glass Matrix Composites

PubMed Central

Khanolkar, Gauri R.; Rauls, Michael B.; Kelly, James P.; Graeve, Olivia A.; Hodge, Andrea M.; Eliasson, Veronica

2016-01-01

The response of amorphous steels to shock wave compression has been explored for the first time. Further, the effect of partial devitrification on the shock response of bulk metallic glasses is examined by conducting experiments on two iron-based in situ metallic glass matrix composites, containing varying amounts of crystalline precipitates, both with initial composition Fe49.7Cr17.7Mn1.9Mo7.4W1.6B15.2C3.8Si2.4. The samples, designated SAM2X5-600 and SAM2X5-630, are X-ray amorphous and partially crystalline, respectively, due to differences in sintering parameters during sample preparation. Shock response is determined by making velocity measurements using interferometry techniques at the rear free surface of the samples, which have been subjected to impact from a high-velocity projectile launched from a powder gun. Experiments have yielded results indicating a Hugoniot Elastic Limit (HEL) to be 8.58 ± 0.53 GPa for SAM2X5-600 and 11.76 ± 1.26 GPa for SAM2X5-630. The latter HEL result is higher than elastic limits for any BMG reported in the literature thus far. SAM2X5-600 catastrophically loses post-yield strength whereas SAM2X5-630, while showing some strain-softening, retains strength beyond the HEL. The presence of crystallinity within the amorphous matrix is thus seen to significantly aid in strengthening the material as well as preserving material strength beyond yielding. PMID:26932846

Shock Wave Response of Iron-based In Situ Metallic Glass Matrix Composites.

PubMed

Khanolkar, Gauri R; Rauls, Michael B; Kelly, James P; Graeve, Olivia A; Hodge, Andrea M; Eliasson, Veronica

2016-03-02

The response of amorphous steels to shock wave compression has been explored for the first time. Further, the effect of partial devitrification on the shock response of bulk metallic glasses is examined by conducting experiments on two iron-based in situ metallic glass matrix composites, containing varying amounts of crystalline precipitates, both with initial composition Fe49.7Cr17.7Mn1.9Mo7.4W1.6B15.2C3.8Si2.4. The samples, designated SAM2X5-600 and SAM2X5-630, are X-ray amorphous and partially crystalline, respectively, due to differences in sintering parameters during sample preparation. Shock response is determined by making velocity measurements using interferometry techniques at the rear free surface of the samples, which have been subjected to impact from a high-velocity projectile launched from a powder gun. Experiments have yielded results indicating a Hugoniot Elastic Limit (HEL) to be 8.58 ± 0.53 GPa for SAM2X5-600 and 11.76 ± 1.26 GPa for SAM2X5-630. The latter HEL result is higher than elastic limits for any BMG reported in the literature thus far. SAM2X5-600 catastrophically loses post-yield strength whereas SAM2X5-630, while showing some strain-softening, retains strength beyond the HEL. The presence of crystallinity within the amorphous matrix is thus seen to significantly aid in strengthening the material as well as preserving material strength beyond yielding.

The impact of physical training on endothelial function in myocardial infarction survivors: pilot study.

PubMed

Peller, Michał; Balsam, Paweł; Główczyńska, Renata; Ossoliński, Krzysztof; Gilarowska, Anna; Kołtowski, Łukasz; Grabowski, Marcin; Filipiak, Krzysztof J; Opolski, Grzegorz

Endothelial dysfunction (ED) may indirectly influence the outcome of patients with coronary artery disease. To assess the influence of cardiac rehabilitation (CR) on endothelial function in patients after ST-segment elevation myocardial infarction (STEMI). Twenty-nine patients scheduled for CR were included in the study. CR began at least four weeks after STEMI and consisted of 12 or 24 training sessions. Endothelial function assessment was performed before and after CR, using reactive hyperaemia peripheral arterial tonometry. Before the CR, ED was diagnosed in 16 of 29 (55.2%) patients. A total of 25 patients had two assessments of endothelial function: before and after CR. In univariate analysis the factors of negative response of endothelial function to CR were: higher baseline hyperaemia index (lnRHI) (odds ratio [OR] for positive response to CR 0.01; 95% confidence interval [CI] 0.00-0.33; p = 0.01) and higher peak serum troponin I level during index hospitalisation (OR 0.97; 95% CI 0.94-1.00; p = 0.04). The independent, negative predictor of response to CR was lnRHI (OR 0.01; 95% CI 0.01-0.16; p = 0.03). Patients training for 24 sessions (n = 16) had similar lnRHI changes to those of patients training for 12 sessions (n = 9); [0.16 (-0.06)-0.30 vs. 0.10 (0.05-0.15); p = 0.44, respectively]. ED is a frequent abnormality in STEMI survivors. Despite the lack of statistically significant improvement of endothelial function after CR in the analysed group of patients, some factors can influence the efficacy of this type of physical activity. The best effect of CR on endothelial function was observed in patients with baseline ED.

Prolonged Particulate Hexavalent Chromium Exposure Suppresses Homologous Recombination Repair in Human Lung Cells

PubMed Central

Browning, Cynthia L.; Qin, Qin; Kelly, Deborah F.; Prakash, Rohit; Vanoli, Fabio; Jasin, Maria

2016-01-01

Abstract Genomic instability is one of the primary models of carcinogenesis and a feature of almost all cancers. Homologous recombination (HR) repair protects against genomic instability by maintaining high genomic fidelity during the repair of DNA double strand breaks. The defining step of HR repair is the formation of the Rad51 nucleofilament, which facilitates the search for a homologous sequence and invasion of the template DNA strand. Particulate hexavalent chromium (Cr(VI)), a human lung carcinogen, induces DNA double strand breaks and chromosome instability. Since the loss of HR repair increases Cr(VI)-induced chromosome instability, we investigated the effect of extended Cr(VI) exposure on HR repair. We show acute (24 h) Cr(VI) exposure induces a normal HR repair response. In contrast, prolonged (120 h) exposure to particulate Cr(VI) inhibited HR repair and Rad51 nucleofilament formation. Prolonged Cr(VI) exposure had a profound effect on Rad51, evidenced by reduced protein levels and Rad51 mislocalization to the cytoplasm. The response of proteins involved in Rad51 nuclear import and nucleofilament formation displayed varying responses to prolonged Cr(VI) exposure. BRCA2 formed nuclear foci after prolonged Cr(VI) exposure, while Rad51C foci formation was suppressed. These results suggest that particulate Cr(VI), a major chemical carcinogen, inhibits HR repair by targeting Rad51, causing DNA double strand breaks to be repaired by a low fidelity, Rad51-independent repair pathway. These results further enhance our understanding of the underlying mechanism of Cr(VI)-induced chromosome instability and thus, carcinogenesis. PMID:27449664

Magnons and magnetodielectric effects in CoCr2O4 : Raman scattering studies

NASA Astrophysics Data System (ADS)

Sethi, A.; Byrum, T.; McAuliffe, R. D.; Gleason, S. L.; Slimak, J. E.; Shoemaker, D. P.; Cooper, S. L.

2017-05-01

Magnetoelectric materials have generated wide technological and scientific interest because of the rich phenomena these materials exhibit, including the coexistence of magnetic and ferroelectric orders, magnetodielectric behavior, and exotic hybrid excitations such as electromagnons. The multiferroic spinel material CoCr2O4 is a particularly interesting example of a multiferroic material, because evidence for magnetoelectric behavior in the ferrimagnetic phase seems to conflict with traditional noncollinear-spin-driven mechanisms for inducing a macroscopic polarization. With the overall goal of clarifying the magnetodielectric behavior previously reported below TC in CoCr2O4 , in this paper we report an inelastic light scattering study of the magnon and phonon spectrum of CoCr2O4 as simultaneous functions of temperature, pressure, and magnetic field. Below the Curie temperature (TC=94 K ) of CoCr2O4 we observe a ω ˜16 cm-1 q =0 magnon having T1g-symmetry, which has the transformation properties of an axial vector. The anomalously large Raman intensity of the T1g-symmetry magnon is characteristic of materials with a large magneto-optical response and likely arises from large magnetic fluctuations that strongly modulate the dielectric response in CoCr2O4 . The Raman susceptibility of the T1g-symmetry magnon exhibits a strong magnetic-field dependence that is consistent with the magnetodielectric response observed in CoCr2O4 , suggesting that magnetodielectric behavior in CoCr2O4 primarily arises from the field-dependent suppression of magnetic fluctuations that are strongly coupled to long-wavelength phonons. Increasing the magnetic anisotropy in CoCr2O4 with applied pressure decreases the magnetic-field dependence of the T1g-symmetry magnon Raman susceptibility, suggesting that strain can be used to control the magnetodielectric response in CoCr2O4 .

Low Estrogen Receptor (ER)-Positive Breast Cancer and Neoadjuvant Systemic Chemotherapy: Is Response Similar to Typical ER-Positive or ER-Negative Disease?

PubMed

Landmann, Alessandra; Farrugia, Daniel J; Zhu, Li; Diego, Emilia J; Johnson, Ronald R; Soran, Atilla; Dabbs, David J; Clark, Beth Z; Puhalla, Shannon L; Jankowitz, Rachel C; Brufsky, Adam M; Ahrendt, Gretchen M; McAuliffe, Priscilla F; Bhargava, Rohit

2018-05-08

Pathologic complete response (pCR) rate after neoadjuvant chemotherapy was compared between 141 estrogen receptor (ER)-negative (43%), 41 low ER+ (13%), 47 moderate ER+ (14%), and 98 high ER+ (30%) tumors. Human epidermal growth factor receptor 2-positive cases, cases without semiquantitative ER score, and patients treated with neoadjuvant endocrine therapy alone were excluded. The pCR rate of low ER+ tumors was similar to the pCR rate of ER- tumors (37% and 26% for low ER and ER- respectively, P = .1722) but significantly different from the pCR rate of moderately ER+ (11%, P = .0049) and high ER+ tumors (4%, P < .0001). Patients with pCR had an excellent prognosis regardless of the ER status. In patients with residual disease (no pCR), the recurrence and death rate were higher in ER- and low ER+ cases compared with moderate and high ER+ cases. Low ER+ breast cancers are biologically similar to ER- tumors. Semiquantitative ER H-score is an important determinant of response to neoadjuvant chemotherapy.

RNA Disruption and Drug Response in Breast Cancer Primary Systemic Therapy.

PubMed

Pritzker, Kenneth; Pritzker, Laura; Generali, Daniele; Bottini, Alberto; Cappelletti, Maria Rosa; Guo, Baoqing; Parissenti, Amadeo; Trudeau, Maureen

2015-05-01

As there is now evidence that switching clinical nonresponders early in primary systemic therapy to alternate treatment regimens can enhance survival in some breast cancer patients, the need for a robust intermediate endpoint that can guide treatment response across all tumor subtypes is urgent. Recently, chemotherapy drugs have been shown to induce a decrease in RNA quality in tumor cells from breast cancer biopsies in some patients at midtherapy, and that this has been associated with subsequent achievement of pathological complete response (pCR). The decrease in RNA quality has been shown to be associated with RNA disruption; aberrant RNA bands visualized by RNA electrophoresis have been associated with subsequent tumor cell death. The objectives of these studies are to show that a new assay based on induction of RNA disruption in tumor cells by chemotherapy can stratify at midtherapy, pCR responders from non-pCR responders irrespective of clinical response and to present early evidence that clinically useful RNA disruption can be detected as early as 14 days after initiation of treatment. RNA disruption in tumor cells was quantified by analysis of the RNA electrophoresis banding pattern and expressed as an RNA disruption index (RDI). To develop the RNA disruption assay (RDA), RDI was correlated with clinical outcome (pCR) from the NCIC-CTG MA.22 breast cancer clinical trial (ClinicalTrials.gov NCT00066443). RDA Zones were established by stratifying patients using RDI values into Zone 1, Zone 2, and Zone 3. Zone 3 included seven out of eight pCR responders, whereas Zone 1 contained no pCR responders. An intermediate zone (Zone 2) was established which contained one pCR. Subsequently, to determine early drug response, RNA disruption was examined by RDI after 14 days exposure to trastuzumab, zoledronic acid, or letrozole + cyclophosphamide ± sorafenib therapy. In MA.22, RDA stratified 23 of 85 patients in Zone 1 as pCR nonresponders, 24 patients in Zone 2, an intermediate zone, and 38 patients in Zone 3, pCR responders and non-pCR patients who share RDI comparable to those achieving pCR. In the early response studies, after 14 days exposure to chemotherapy, some RNA disruption as measured by RDI elevation could be detected in 3/12 trastuzumab, 7/15 zoledronic acid, 5/29 letrozole + cyclophosphamide, and 5/23 letrozole + cyclophosphamide + sorafenib patients. RDA is a novel intermediate endpoint that has promise for clinical utility for breast cancers early in response-guided primary systemic therapy. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Critical analysis of the stringent complete response in multiple myeloma: contribution of sFLC and bone marrow clonality.

PubMed

Martínez-López, Joaquín; Paiva, Bruno; López-Anglada, Lucía; Mateos, María-Victoria; Cedena, Teresa; Vidríales, María-Belén; Sáez-Gómez, María Auxiliadora; Contreras, Teresa; Oriol, Albert; Rapado, Inmaculada; Teruel, Ana-Isabel; Cordón, Lourdes; Blanchard, María Jesús; Bengoechea, Enrique; Palomera, Luis; de Arriba, Felipe; Cueto-Felgueroso, Cecilia; Orfao, Alberto; Bladé, Joan; San Miguel, Jesús F; Lahuerta, Juan José

2015-08-13

Stringent complete response (sCR) criteria are used in multiple myeloma as a deeper response category compared with CR, but prospective validation is lacking, it is not always clear how evaluation of clonality is performed, and is it not known what the relative clinical influence is of the serum free light chain ratio (sFLCr) and bone marrow (BM) clonality to define more sCR. To clarify this controversy, we focused on 94 patients that reached CR, of which 69 (73%) also fulfilled the sCR criteria. Patients with sCR displayed slightly longer time to progression (median, 62 vs 53 months, respectively; P = .31). On analyzing this contribution to the prognosis of sFLCr or clonality, it was found that the sFLCr does not identify patients in CR at distinct risk; by contrast, low-sensitive multiparametric flow cytometry (MFC) immunophenotyping (2 colors), which is equivalent to immunohistochemistry, identifies a small number of patients (5 cases) with high residual tumor burden and dismal outcome; nevertheless, using traditional 4-color MFC, persistent clonal BM disease was detectable in 36% of patients, who, compared with minimal residual disease-negative cases, had a significantly inferior outcome. These results show that the current definition of sCR should be revised. © 2015 by The American Society of Hematology.

Cr2O3 nanoparticle-functionalized WO3 nanorods for ethanol gas sensors

NASA Astrophysics Data System (ADS)

Choi, Seungbok; Bonyani, Maryam; Sun, Gun-Joo; Lee, Jae Kyung; Hyun, Soong Keun; Lee, Chongmu

2018-02-01

Pristine WO3 nanorods and Cr2O3-functionalized WO3 nanorods were synthesized by the thermal evaporation of WO3 powder in an oxidizing atmosphere, followed by spin-coating of the nanowires with Cr2O3 nanoparticles and thermal annealing in an oxidizing atmosphere. Scanning electron microscopy was used to examine the morphological features and X-ray diffraction was used to study the crystallinity and phase formation of the synthesized nanorods. Gas sensing tests were performed at different temperatures in the presence of test gases (ethanol, acetone, CO, benzene and toluene). The Cr2O3-functionalized WO3 nanorods sensor showed a stronger response to these gases relative to the pristine WO3 nanorod sensor. In particular, the response of the Cr2O3-functionalized WO3 nanorods sensor to 200 ppm ethanol gas was 5.58, which is approximately 4.4 times higher that of the pristine WO3 nanorods sensor. Furthermore, the Cr2O3-functionalized WO3 nanorods sensor had a shorter response and recovery time. The pristine WO3 nanorods had no selectivity toward ethanol gas, whereas the Cr2O3-functionalized WO3 nanorods sensor showed good selectivity toward ethanol. The gas sensing mechanism of the Cr2O3-functionalized WO3 nanorods sensor toward ethanol is discussed in detail.

Impact of x-ray dose on the response of CR-39 to 1–5.5 MeV alphas

DOE PAGES

Rojas-Herrera, J.; Rinderknecht, H. G.; Zylstra, A. B.; ...

2015-03-01

The CR-39 nuclear track detector is used in many nuclear diagnostics fielded at inertial confinement fusion (ICF) facilities. Large x-ray uences generated by ICF experiments may impact the CR-39 response to incident charged particles. To determine the impact of x-ray exposure on the CR-39 response to alpha particles, a thick-target bremsstrahlung x-ray generator was used to expose CR-39 to various doses of 8 keV Cu-K α and K β x-rays. The CR-39 detectors were then exposed to 1-5.5 MeV alphas from an Am-241 source. The regions of the CR-39 exposed to x-rays showed a smaller track diameter than those notmore » exposed to x-rays: for example, a dose of 3.0 ± 0.1 Gy causes a decrease of (19 ± 2)% in the track diameter of a 5.5 MeV alpha particle, while a dose of 60.0 ± 1.3 Gy results in a decrease of (45 ± 5)% in the track diameter. The reduced track diameters were found to be predominantly caused by a comparable reduction in the bulk etch rate of the CR-39 with x-ray dose. A residual effect depending on alpha particle energy is characterized using an empirical formula.« less

Low dose decitabine in very high risk relapsed or refractory acute myeloid leukaemia in children and young adults.

PubMed

Phillips, Christine L; Davies, Stella M; McMasters, Richard; Absalon, Michael; O'Brien, Maureen; Mo, Jun; Broun, Randall; Moscow, Jeffrey A; Smolarek, Teresa; Garzon, Ramiro; Blum, William; Schwind, Sebastian; Marcucci, Guido; Perentesis, John P

2013-05-01

Low-dose decitabine has encouraging activity and tolerability in adults with acute myeloid leukaemia (AML), but paediatric experience is lacking. We report our retrospective experience with decitabine in eight children and young adults (median age 4 years) with refractory/relapsed AML, who had failed multiple regimens or were not candidates for standard retrieval regimens due to prior toxicities. Three of eight patients (38%) had complete response (CR; 1 each of CR, CR with incomplete platelet recovery and CR with incomplete count recovery). Best responses were observed after a median of 2.5 cycles (range 1-4 cycles). Four patients received subsequent allogeneic stem cell transplant, and two remain in long-term CR. © 2013 Blackwell Publishing Ltd.

Personalised treatment for cognitive dysfunction in individuals with schizophrenia spectrum disorders.

PubMed

Medalia, Alice; Saperstein, Alice M; Hansen, Marie C; Lee, Seonjoo

2018-06-01

Cognitive deficits are a well-recognised issue for individuals diagnosed with schizophrenia spectrum disorders. Despite positive group findings for the use of cognitive remediation (CR) interventions, there are substantial individual differences in response to treatment. In addition, the aggregate CR literature reports low moderate effect sizes for cognitive and functional outcomes. Based on personalised medicine theory, this paper uses extant CR literature to examine the individual characteristics determined to predict treatment response. These characteristics, which fall into the broad categories of cognitive, psychological, and biological can be used as tailoring variables to personalise CR to an individual's unique profile. Personalisation through the use of these tailoring variables has the potential to improve the delivery of CR to maximise treatment outcomes.

Selective Internal Oxidation as a Mechanism for Intergranular Stress Corrosion Cracking of Ni-Cr-Fe Alloys

NASA Astrophysics Data System (ADS)

Capell, Brent M.; Was, Gary S.

2007-06-01

The mechanism of selective internal oxidation (SIO) for intergranular stress corrosion cracking (IGSCC) of nickel-base alloys has been investigated through a series of experiments using high-purity alloys and a steam environment to control the formation of NiO on the surface. Five alloys (Ni-9Fe, Ni-5Cr, Ni-5Cr-9Fe, Ni-16Cr-9Fe, and Ni-30Cr-9Fe) were used to investigate oxidation and intergranular cracking behavior for hydrogen-to-water vapor partial pressure ratios (PPRs) between 0.001 and 0.9. The Ni-9Fe, Ni-5Cr, and Ni-5Cr-9Fe alloys formed a uniform Ni(OH)2 film at PPRs less than 0.09, and the higher chromium alloys formed chromium-rich oxide films over the entire PPR range studied. Corrosion coupon results show that grain boundary oxides extended for significant depths (>150 nm) below the sample surface for all but the highest Cr containing alloy. Constant extension rate tensile (CERT) test results showed that intergranular cracking varied with PPR and cracking was more pronounced at a PPR value where nonprotective Ni(OH)2 was able to form and a link between the nonprotective Ni(OH)2 film and the formation of grain boundary oxides is suggested. The observation of grain boundary oxides in stressed and unstressed samples as well as the influence of alloy content on IG cracking and oxidation support SIO as a mechanism for IGSCC.

Spin-phonon coupling and exchange interaction in Gd substituted YFe0.5Cr0.5O3

NASA Astrophysics Data System (ADS)

Singh, Karan; Sharma, Mohit K.; Mukherjee, K.

2018-02-01

We report the evolution of physical properties due to partial substitution of Gd on the Y site in a mixed metal oxide YFe0.5Cr0.5O3. This compound exhibits negative magnetization at low applied fields. Our investigations on Y1-xGdxFe0.5Cr0.5O3 (x = 0.0, 0.2, 0.4 and 0.6) compounds is carried out through magnetization and Raman spectroscopy studies. It is observed that even with 20% Gd substitution, the negative magnetization observed in YFe0.5Cr0.5O3 is suppressed. Due to magnetic rare earth ion Gd3+, additional exchange interaction of the form Gd-O-Fe/Cr dominates the magnetic interaction arising due to the transition metal ions. This results in positive magnetization in Gd-substituted compounds. Temperature dependent Raman spectroscopy along with magnetization studies revealed that the observed shifts of Raman mode is due to spin-phonon coupling. Hardening of Raman mode observed below 240 K in YFe0.5Cr0.5O3 weakens and softening of phonon modes was observed for Y0.4Gd0.6Fe0.5Cr0.5O3 compound. This implies that additional magnetic interactions due to Gd ions play a dominating role in dictating the behavior of the Gd-substituted compounds.

The Role of Azacitidine in the Treatment of Elderly Patients with Acute Myeloid Leukemia: Results of a Retrospective Multicenter Study

PubMed Central

Tombak, Anıl; Uçar, Mehmet Ali; Akdeniz, Aydan; Tiftik, Eyüp Naci; Gören Şahin, Deniz; Akay, Olga Meltem; Yıldırım, Murat; Nevruz, Oral; Kis, Cem; Gürkan, Emel; Medeni Solmaz, Şerife; Özcan, Mehmet Ali; Yıldırım, Rahşan; Berber, İlhami; Erkurt, Mehmet Ali; Tuğlular, Tülin Fıratlı; Tarkun, Pınar; Yavaşoğlu, İrfan; Doğu, Mehmet Hilmi; Sarı, İsmail; Merter, Mustafa; Özcan, Muhit; Yıldızhan, Esra; Kaynar, Leylagül; Mehtap, Özgür; Uysal, Ayşe; Şahin, Fahri; Salim, Ozan; Sungur, Mehmet Ali

2016-01-01

Objective: In this study, we aimed to investigate the efficacy and safety of azacitidine (AZA) in elderly patients with acute myeloid leukemia (AML), including patients with >30% bone marrow (BM) blasts. Materials and Methods: In this retrospective multicenter study, 130 patients of ≥60 years o ld who were ineligible for intensive chemotherapy or had progressed despite conventional treatment were included. Results: The median age was 73 years and 61.5% of patients had >30% BM blasts. Patients received AZA for a median of four cycles (range: 1-21). Initial overall response [including complete remission (CR)/CR with incomplete recovery/partial remission] was 36.2%. Hematologic improvement (HI) of any kind was documented in 37.7% of all patients. HI was also documented in 27.1% of patients who were unresponsive to treatment. Median overall survival (OS) was 18 months for responders and 12 months for nonresponders (p=0.005). In the unresponsive patient group, any HI improved OS compared to patients without any HI (median OS was 14 months versus 10 months, p=0.068). Eastern Cooperative Oncology Group performance status of <2, increasing number of AZA cycles (≥5 courses), and any HI predicted better OS. Age, AML type, and BM blast percentage had no impact. Conclusion: We conclude that AZA is effective and well tolerated in elderly comorbid AML patients, irrespective of BM blast count, and HI should be considered a sufficient response to continue treatment with AZA. PMID:27095141

Clinical Characteristics of Monomorphic Post-transplant Lymphoproliferative Disorders

PubMed Central

Park, Byeong-Bae; Suh, Cheolwon; Won, Jong-Ho; Lee, Won-Sik; Shin, Ho-Jin

2010-01-01

Post-transplant lymphoproliferative disorders (PTLD) are a heterogeneous group of lymphoproliferative disorders associated with immunosuppression and Epstein-Barr virus infection. PTLD is classified into three major categories: early lesions, polymorphic PTLD, and monomorphic PTLD. The majority of monomorphic PTLD cases are non-Hodgkin's lymphoma of B-cell origin. This retrospective study was conducted to investigate the incidence, clinical manifestation, treatment, and outcomes of monomorphic PTLD among 5,817 recipients of solid organ or allogeneic hematopoietic stem cell transplantation from five institutions. Fourteen patients with monomorphic PTLD were identified (male:female 11:3; median age 42.6 yr, range 24-60). The overall incidence rate was 0.24%. The most common disease type was diffuse large B cell lymphoma (n=7). The median time between the transplant and diagnosis of PTLD was 85.8 months. However, all cases of PTLD after allogeneic hematopoietic stem cell transplantation occurred within 1 yr after transplantation. Ten of the 14 patients had EBV-positive tumor. Fourteen patients received combination systemic chemotherapy and four patients were treated with radiation therapy. Ten patients achieved a complete response (CR) and two patients a partial response (PR). The median follow-up period for surviving patients was 36.6 months. Nine patients remain alive (eight CR, one PR). Nine of 11 solid organ transplantations preserved graft function. The present study indicates a lower incidence rate and a longer median time before the development of PTLD than those of previous reports. Careful monitoring was needed after allogeneic hematopoietic stem cell transplantation for PTLD. PMID:20357991

Mobilization of Cr(VI) from chromite ore processing residue through acid treatment.

PubMed

Tinjum, James M; Benson, Craig H; Edil, Tuncer B

2008-02-25

Batch leaching studies on chromite ore processing residue (COPR) were performed using acids to investigate leaching of hexavalent chromium, Cr(VI), with respect to particle size, reaction time, and type of acid (HNO(3) and H(2)SO(4)). Aqueous Cr(VI) is maximized at approximately 0.04 mol Cr(VI) per kg of dry COPR at pH 7.6-8.1. Cr(VI) mobilized more slowly for larger particles, and the pH increased with time and increased more rapidly for smaller particles, suggesting that rate limitations occur in the solid phase. With H(2)SO(4), the pH stabilized at a higher value (8.8 for H(2)SO(4) vs. 8.0 for HNO(3)) and more rapidly (16 h vs. 30 h), and the differences in pH for different particle sizes were smaller. The acid neutralization capacity (ANC) of COPR is very large (8 mol HNO(3) per kg of dry COPR for a stable eluate pH of 7.5). Changes to the elemental and mineralogical composition and distribution in COPR particles after mixing with acid indicate that Cr(VI)-bearing solids dissolved. However, concentrations of Cr(VI) >2800 mg kg(-1) (>50% of the pre-treatment concentration) were still found after mixing with acid, regardless of the particle size, reaction time, or type of acid used. The residual Cr(VI) appears to be partially associated with poorly-ordered Fe and Al oxyhydroxides that precipitated in the interstitial areas of COPR particles. Remediation strategies that use HNO(3) or H(2)SO(4) to neutralize COPR or to maximize Cr(VI) in solution are likely to require extensive amounts of acid, may not mobilize all of the Cr(VI), and may require extended contact time, even under well-mixed conditions.

Metabolome of Vanilla planifolia (Orchidaceae) and related species under Cymbidium mosaic virus (CymMV) infection.

PubMed

Palama, Tony Lionel; Grisoni, Michel; Fock-Bastide, Isabelle; Jade, Katia; Bartet, Laetitia; Choi, Young Hae; Verpoorte, Robert; Kodja, Hippolyte

2012-11-01

The genus Vanilla which belongs to the Orchidaceae family comprises more than 110 species of which two are commercially cultivated (Vanilla planifolia and Vanilla xtahitensis). The cured pods of these species are the source of natural vanilla flavor. In intensive cultivation systems the vines are threatened by viruses such as Cymbidium mosaic virus (CymMV). In order to investigate the effect of CymMV on the growth and metabolome of vanilla plants, four accessions grown in intensive cultivation systems under shadehouse, CR01 (V. planifolia), CR17 (V. xtahitensis), CR03 (V. planifolia × V. xtahitensis) and CR18 (Vanilla pompona), were challenged with an isolate of CymMV. CymMV infected plants of CR01, CR03 and CR17 had a reduced growth compared to healthy plants, while there was no significant difference in the growth of CR18 vines. Interestingly, CR18 had qualitatively more phenolic compounds in leaves and a virus titre that diminished over time. No differences in the metabolomic profiles of the shadehouse samples obtained by nuclear magnetic resonance (NMR) were observed between the virus infected vs. healthy plants. However, using in- vitro V. planifolia plants, the metabolomic profiles were affected by virus infection. Under these controlled conditions the levels of amino acids and sugars present in the leaves were increased in CymMV infected plants, compared to uninfected ones, whereas the levels of phenolic compounds and malic acid were decreased. The metabolism, growth and viral status of V. pompona accession CR18 contrasted from that of the other species suggesting the existence of partial resistance to CymMV in the vanilla germplasm. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Novel Rabies Virus-Neutralizing Epitope Recognized by Human Monoclonal Antibody: Fine Mapping and Escape Mutant Analysis†

PubMed Central

Marissen, Wilfred E.; Kramer, R. Arjen; Rice, Amy; Weldon, William C.; Niezgoda, Michael; Faber, Milosz; Slootstra, Jerry W.; Meloen, Rob H.; Clijsters-van der Horst, Marieke; Visser, Therese J.; Jongeneelen, Mandy; Thijsse, Sandra; Throsby, Mark; de Kruif, John; Rupprecht, Charles E.; Dietzschold, Bernhard; Goudsmit, Jaap; Bakker, Alexander B. H.

2005-01-01

Anti-rabies virus immunoglobulin combined with rabies vaccine protects humans from lethal rabies infections. For cost and safety reasons, replacement of the human or equine polyclonal immunoglobulin is advocated, and the use of rabies virus-specific monoclonal antibodies (MAbs) is recommended. We produced two previously described potent rabies virus-neutralizing human MAbs, CR57 and CRJB, in human PER.C6 cells. The two MAbs competed for binding to rabies virus glycoprotein. Using CR57 and a set of 15-mer overlapping peptides covering the glycoprotein ectodomain, a neutralization domain was identified between amino acids (aa) 218 and 240. The minimal binding region was identified as KLCGVL (aa 226 to 231), with key residues K-CGV- identified by alanine replacement scanning. The critical binding region of this novel nonconformational rabies virus epitope is highly conserved within rabies viruses of genotype 1. Subsequently, we generated six rabies virus variants escaping neutralization by CR57 and six variants escaping CRJB. The CR57 escape mutants were only partially covered by CRJB, and all CRJB-resistant variants completely escaped neutralization by CR57. Without exception, the CR57-resistant variants showed a mutation at key residues within the defined minimal binding region, while the CRJB escape viruses showed a single mutation distant from the CR57 epitope (N182D) combined with mutations in the CR57 epitope. The competition between CR57 and CRJB, the in vitro escape profile, and the apparent overlap between the recognized epitopes argues against including both CR57 and CRJB in a MAb cocktail aimed at replacing classical immunoglobulin preparations. PMID:15795253

Can Cr( iii ) substitute for Al( iii ) in the structure of boehmite?

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

Chatterjee, Sayandev; Conroy, Michele A.; Smith, Frances N.

2016-01-01

The dissolution of boehmite is a technical issue for the Al industry because of its recalcitrant nature. In fact, a similar problem exists with boehmite in nuclear waste sludge at the Hanford site in eastern Washington State, USA. Dissolution of Al phases is required to reduce the waste loadings in the final borosilicate glass waste form. Although not the most common Al-bearing species in the sludge, boehmite may become a rate limiting step in the processing of the wastes. Hanford boehmite is an order of magnitude more resistant to dissolution in hot caustic solutions than expected from surface-normalized rates. Wemore » are exploring potential intrinsic and extrinsic effects that may limit boehmite reactivity; one clue comes from microstructural analyses that indicate an association of Cr with Al in the Hanford nuclear waste. Hence, in this first paper, we investigated the potential role of chromium on the reactivity of boehmite in caustic solution. An important finding was that irrespective of the synthesis pathway, amount of Cr(III), or the resultant morphology, there was no evidence for Cr incorporation in the bulk structure, in agreement with QM calculations. In fact, electron microscopic (EM) and spectroscopic analyses showed that Cr was enriched at the (101) edges of the boehmite. However, Cr had no measurable effect on the morphology during the synthesis step. In contrast, comparison of the morphologies of the synthetic Cr-doped and pure boehmite samples after exposure to caustic solutions provided evidence that Cr inhibited the corrosion. TEM showed that Cr was not homogeneously distributed at the surface. Consequently, Cr may have partially passivated the surface by blocking discrete energetic sites on the lateral surfaces of boehmite.« less

Monoclonal antibody-purged bone marrow transplantation therapy for multiple myeloma.

PubMed

Anderson, K C; Andersen, J; Soiffer, R; Freedman, A S; Rabinowe, S N; Robertson, M J; Spector, N; Blake, K; Murray, C; Freeman, A

1993-10-15

Forty patients with plasma cell dyscrasias underwent high-dose chemoradiotherapy and either anti-B-cell monoclonal antibody (MoAb)-treated autologous, anti-T-cell MoAb-treated HLA-matched sibling allogeneic or syngeneic bone marrow transplantation (BMT). The majority of patients had advanced Durie-Salmon stage myeloma at diagnosis, all were pretreated with chemotherapy, and 17 had received prior radiotherapy. At the time of BMT, all patients demonstrated good performance status with Karnofsky score of 80% or greater and had less than 10% marrow tumor cells; 34 patients had residual monoclonal marrow plasma cells and 38 patients had paraprotein. Following high-dose chemoradiotherapy, there were 18 complete responses (CR), 18 partial responses, one non-responder, and three toxic deaths. Granulocytes greater than 500/microL and untransfused platelets greater than 20,000/microL were noted at a median of 23 (range, 12 to 46) and 25 (range, 10 to 175) days posttransplant (PT), respectively, in 24 of the 26 patients who underwent autografting. In the 14 patients who received allogeneic or syngeneic grafts, granulocytes greater than 500/microL and untransfused platelets greater than 20,000/microL were noted at a median of 19 (range, 12 to 24) and 16 (range, 5 to 32) days PT, respectively. With 24 months median follow-up for survival after autologous BMT, 16 of 26 patients are alive free from progression at 2+ to 55+ months PT; of these, 5 patients remain in CR at 6+ to 55+ months PT. With 24 months median follow-up for survival after allogeneic and syngeneic BMT, 8 of 14 patients are alive free from progression at 8+ to 34+ months PT; of these, 5 patients remain in CR at 8+ to 34+ months PT. This therapy has achieved high response rates and prolonged progression-free survival in some patients and proven to have acceptable toxicity. However, relapses post-BMT, coupled with slow engraftment post-BMT in heavily pretreated patients, suggest that such treatment strategies should be used earlier in the disease course. To define the role of BMT in the treatment of myeloma, its efficacy should be compared with that of conventional chemotherapy in a randomized trial.

Investigation of equilibrium and kinetics of Cr(VI) adsorption by dried Bacillus cereus using response surface methodology.

PubMed

Yang, Kai; Zhang, Jing; Yang, Tao; Wang, Hongyu

2016-01-01

In this study, response surface methodology (RSM) based on three-variable-five-level central composite rotatable design was used to analyze the effects of combined and individual operating parameters (biomass dose, initial concentration of Cr(VI) and pH) on the Cr(VI) adsorption capacity of dried Bacillus cereus. A quadratic polynomial equation was obtained to predict the adsorbed Cr(VI) amount. Analysis of variance showed that the effect of biomass dose was the key factor in the removal of Cr(VI). The maximum adsorbed Cr(VI) amount (30.93 mg g(-1)) was found at 165.30 mg L(-1), 2.96, and 3.01 g L(-1) for initial Cr(VI) concentration, pH, and biosorbent dosage, respectively. The surface chemical functional groups and microstructure of unloaded and Cr(VI)-loaded dried Bacillus cereus were identified by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM), respectively. Besides, the results gained from these studies indicated that Langmuir isotherm and the second-order rate expression were suitable for the removal of Cr(VI) from wastewater. The results revealed RSM was an effective method for optimizing biosorption process, and dried Bacillus cereus had a remarkable performance on the removal of Cr(VI) from wastewater.

Efficacy of vincristine and etoposide with escalating cyclophosphamide in poor-prognosis pediatric brain tumors1

PubMed Central

Ziegler, David S.; Cohn, Richard J.; McCowage, Geoffrey; Alvaro, Frank; Oswald, Cecilia; Mrongovius, Robert; White, Les

2006-01-01

The objective of this study was to assess the efficacy of the VETOPEC regimen, a regimen of vincristine and etoposide with escalating doses of cyclophosphamide (CPA), in pediatric patients with high-risk brain tumors. Three consecutive studies by the Australia and New Zealand Children’s Cancer Study Group—VETOPEC I, Baby Brain 91, and VETOPEC II—have used a specific chemotherapy regimen of vincristine (VCR), etoposide (VP-16) and escalating CPA in patients with relapsed, refractory, or high-risk solid tumors. Patients in the VETOPEC II cohort were treated with very high dose CPA with peripheral blood stem cell (PBSC) rescue. We analyzed the subset of patients with high-risk brain tumors treated with these intensive VETOPEC-based protocols to assess the response, toxicity, and survival. We also assessed whether the use of very high dose chemotherapy with stem cell rescue improved the response rate or affected toxicity. Seventy-one brain tumor patients were treated with VETOPEC-based protocols. Of the 54 patients evaluable for tumor response, 17 had a complete response (CR) and 20 a partial response (PR) to treatment, which yielded an overall response rate of 69%. The CR + PR was 83% (19/23) for medulloblastomas, 56% (5/9) for primitive neuroectodermal tumors, 55% (6/11) for grade 3 and 4 astrocytomas, and 80% (6/8) for ependymomas. At a median follow-up of 36 months, overall survival for the entire cohort of 71 patients was 32%, with event-free survival of 13%. There were no toxic deaths within the PBSC-supported VETOPEC II cohort, despite higher CPA doses, compared with 7% among the non-PBSC patients. This regimen produces high response rates in a variety of very poor prognosis pediatric brain tumors. The maximum tolerated dose of CPA was not reached. Higher escalation in doses of CPA did not deliver a further improvement in response. With PBSC rescue in the VETOPEC II study, hematologic toxicity was no longer a limiting factor. The response rates observed support further development of this chemotherapy regimen. PMID:16443948

Proteomic responses of BEAS-2B cells to nontoxic and toxic chromium: Protein indicators of cytotoxicity conversion.

PubMed

Bruno, Maribel; Ross, Jeffrey; Ge, Yue

2016-12-15

Hexavalent chromium (Cr (VI)) is an environmental human carcinogen which primarily targets lungs. Among a variety of toxic mechanisms, disruption of biological pathways via translational and post-translational modifications represents a key mechanism through which Cr (VI) induces cytotoxicity and carcinogenesis. To identify those disruptions which are altered in response to cytotoxic Cr (VI) exposures, we measured and compared cytotoxicity and changes in expression and phosphorylation status of 15 critical biochemical pathway regulators in human BEAS-2B cells exposed for 48h to a non-toxic concentration (0.3μM) and a toxic concentration (1.8μM) of Cr (VI) by ELISA techniques. In addition, 43 functional proteins which may be altered in response to pathway signaling changes were identified using two dimensional electrophoresis (2-DE) and mass spectrometry. The proteins and fold changes observed in cells exposed to the non-toxic dose of Cr (VI) (0.3μM) were not necessarily the same as those found in the toxic one (1.8μM). A subset of signaling proteins that were correlated with the cytotoxic responses of human BEAS-2B cells to Cr (VI) treatments were identified. These proteins include regulators of glycolysis, glycogen synthase kinase 3 beta (GSK3β) and phosphoprotein 70 ribosomal protein s6 kinase (p70S6K), a signaling protein associated with oxidative stress and inflammation responses, JNK and metal regulatory transcription factor 1 (MTF-1), and a source of ubiquitin for signaling targeted protein degradation, polyubiquitin C (UBC). In addition, two dimensional gel electrophoresis (2-DE) was applied to identify key alterations in biochemical pathways differentiating between cytotoxic and non-cytotoxic exposures to Cr (VI), including glycolysis and gluconeogenesis, protein degradation, inflammation, and oxidative stress. Published by Elsevier Ireland Ltd.

[The design of Co-Cr-Mo alloy combining the framework with porcelain fused to metal restorations and determination of the mechanical properties].

PubMed

Chao, Yong-lie; Lui, Chang-hong; Li, Ning; Yang, Xiao-yu

2005-02-01

To investigate a kind of Co-Cr-Mo alloys used for both porcelain fused to metal (PFM) restorations and casting framework of removable partial dentures. The Co-Cr-Mo alloy underwent the design for elementary compositions of the alloys and the production from the raw materials by means of a vacuum melt furnace. The strength, hardness, plasticity and casting ability of the alloy were examined with metal tensile test. Vickers hardness test and grid casting were examined respectively. The microstructure of the Co-Cr-Mo alloy was also inspected by scanning electron microscope and X-ray diffraction analysis. The elementary composition of DA9-4 alloy mainly consisted of Co 54%-67%, Cr 21%-26%, Mo 5%-8%, W 5%-8%, Si 1%-3%, Mn 0.1%-0.25% and trace elements. The yield strength of the alloy was 584 MPa, while the tensile strength was 736 MPa. The coefficient of expansion was 15.0%, the Vickers hardness reached 322, and the casting ratio exibited 100%. The DA9-4 Co-Cr-Mo alloy used for PFM and framework shown in this paper can meet the clinical demands and have reached the objects of the experiment plan.

Hydrogen permeation characteristics of some Fe-Cr-Al alloys

NASA Astrophysics Data System (ADS)

Van Deventer, E. H.; Maroni, V. A.

1983-01-01

Hydrogen permeation data are reported for two Fe-Cr-Al alloys, Type-405 SS (Cr 14-A1 0.2) and a member of the Fecralloy family of alloys (Cr 16-A1 5). The hydrogen permeability of each alloy (in a partially oxidized condition) was measured over a period of several weeks at randomly selected temperatures (between 150 and 850°C) and upstream H 2 pressures (between 2 and 1.5 × 10 4 Pa). The permeabilities showed considerable scatter with both time and temperature and were 10 2 to 10 3 times lower than those of pure iron, even in strongly reducing environments. The exponent, n, for the relationship between upstream H 2 pressure, P, and permeability, φ, ( φ ~ Pn) was closer to 0.7 than to the expected 0.5, indicating a process limited by surface effects (e.g., surface oxide films) as opposed to bulk material effects. Comparison of these results with prior permeation measurements on other Fe-Cr-Al alloys, on Fe-Cr alloys, and on pure iron shows that the presence of a few weight percent aluminum offers the best prospects for achieving low tritium permeabilities with martensitic and ferritic steels used in fusion-reactor first wall and blanket applications.

Prolonged Particulate Hexavalent Chromium Exposure Suppresses Homologous Recombination Repair in Human Lung Cells.

PubMed

Browning, Cynthia L; Qin, Qin; Kelly, Deborah F; Prakash, Rohit; Vanoli, Fabio; Jasin, Maria; Wise, John Pierce

2016-09-01

Genomic instability is one of the primary models of carcinogenesis and a feature of almost all cancers. Homologous recombination (HR) repair protects against genomic instability by maintaining high genomic fidelity during the repair of DNA double strand breaks. The defining step of HR repair is the formation of the Rad51 nucleofilament, which facilitates the search for a homologous sequence and invasion of the template DNA strand. Particulate hexavalent chromium (Cr(VI)), a human lung carcinogen, induces DNA double strand breaks and chromosome instability. Since the loss of HR repair increases Cr(VI)-induced chromosome instability, we investigated the effect of extended Cr(VI) exposure on HR repair. We show acute (24 h) Cr(VI) exposure induces a normal HR repair response. In contrast, prolonged (120 h) exposure to particulate Cr(VI) inhibited HR repair and Rad51 nucleofilament formation. Prolonged Cr(VI) exposure had a profound effect on Rad51, evidenced by reduced protein levels and Rad51 mislocalization to the cytoplasm. The response of proteins involved in Rad51 nuclear import and nucleofilament formation displayed varying responses to prolonged Cr(VI) exposure. BRCA2 formed nuclear foci after prolonged Cr(VI) exposure, while Rad51C foci formation was suppressed. These results suggest that particulate Cr(VI), a major chemical carcinogen, inhibits HR repair by targeting Rad51, causing DNA double strand breaks to be repaired by a low fidelity, Rad51-independent repair pathway. These results further enhance our understanding of the underlying mechanism of Cr(VI)-induced chromosome instability and thus, carcinogenesis. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Gene expression profiles in paraffin-embedded core biopsy tissue predict response to chemotherapy in women with locally advanced breast cancer.

PubMed

Gianni, Luca; Zambetti, Milvia; Clark, Kim; Baker, Joffre; Cronin, Maureen; Wu, Jenny; Mariani, Gabriella; Rodriguez, Jaime; Carcangiu, Marialuisa; Watson, Drew; Valagussa, Pinuccia; Rouzier, Roman; Symmans, W Fraser; Ross, Jeffrey S; Hortobagyi, Gabriel N; Pusztai, Lajos; Shak, Steven

2005-10-10

We sought to identify gene expression markers that predict the likelihood of chemotherapy response. We also tested whether chemotherapy response is correlated with the 21-gene Recurrence Score assay that quantifies recurrence risk. Patients with locally advanced breast cancer received neoadjuvant paclitaxel and doxorubicin. RNA was extracted from the pretreatment formalin-fixed paraffin-embedded core biopsies. The expression of 384 genes was quantified using reverse transcriptase polymerase chain reaction and correlated with pathologic complete response (pCR). The performance of genes predicting for pCR was tested in patients from an independent neoadjuvant study where gene expression was obtained using DNA microarrays. Of 89 assessable patients (mean age, 49.9 years; mean tumor size, 6.4 cm), 11 (12%) had a pCR. Eighty-six genes correlated with pCR (unadjusted P < .05); pCR was more likely with higher expression of proliferation-related genes and immune-related genes, and with lower expression of estrogen receptor (ER) -related genes. In 82 independent patients treated with neoadjuvant paclitaxel and doxorubicin, DNA microarray data were available for 79 of the 86 genes. In univariate analysis, 24 genes correlated with pCR with P < .05 (false discovery, four genes) and 32 genes showed correlation with P < .1 (false discovery, eight genes). The Recurrence Score was positively associated with the likelihood of pCR (P = .005), suggesting that the patients who are at greatest recurrence risk are more likely to have chemotherapy benefit. Quantitative expression of ER-related genes, proliferation genes, and immune-related genes are strong predictors of pCR in women with locally advanced breast cancer receiving neoadjuvant anthracyclines and paclitaxel.

Cumulative Risk and Physiological Stress Responses in African American Adolescents.

PubMed

Kliewer, Wendy; Robins, Jo Lynne W

2017-07-01

To investigate associations between components of cumulative risk (CR) and physiological stress responses in African American adolescents and evaluate emotion regulation as a mediator and sex as a moderator of these associations. Cortisol and salivary alpha amylase (sAA) were collected in adolescents ( N = 205; 55% female; 12.1 ± 1.6 years at baseline) as part of a longitudinal study of stress and adjustment in families. CR was assessed at baseline and emotion regulation was assessed at baseline and 2 years later at Wave 3 (W3) using caregiver and adolescent reports. Cortisol and sAA responses to the social competence interview were assessed at W3. Repeated-measures analyses of variance predicting cortisol and controlling for time of day, adolescent age, medication usage, and pubertal status revealed significant interactions of time with both psychosocial and sociodemographic risk. In both analyses, youths with higher levels of risk showed a steeper decline in cortisol than youths with lower levels of risk. In parallel analyses predicting sAA, time interacted with psychosocial but not with sociodemographic risk. There were no interactions with sex in any of the analyses. Although CR was associated with changes in emotion regulation, there was no evidence that these changes accounted for the observed CR-stress response associations. These findings illustrate the potential importance of disentangling CR and suggest that additional work is needed to help explicate why and how CR is associated with specific physiological responses to stress.

Adsorption and desorption of hexavalent chromium in an alluvial aquifer near Telluride, Colorado

USGS Publications Warehouse

Stollenwerk, K.G.; Grove, D.B.

1985-01-01

A laboratory investigation of reactions between hexavalent chromium [Cr(VI)] and alluvium was conducted to evaluate reactions of Cr(VI) contaminating an alluvial aquifer near Telluride, CO and to determine the mechanisms responsible for these reactions. Uncontaminated alluvium and groundwater (spiked with CrO42-) from the study site were used in batch and column experiments. Results of these experiments show that Cr(VI) was adsorbed by the alluvium. Distribution coefficients from batch experiments ranged from 52 L/kg at an equilibrium CrO42- concentration of 0.4 ??mol/L to 1.7 L/kg at an equilibrium concentration of 1400 ??mol/L. The zero point of charge for the alluvium was approximately 8.3, and the alluvium had a positive net charge at the groundwater pH of 6.8. Visual and chemical evidence indicated that Fe oxide and hydroxide coatings on the alluvial particles principally were responsible for the absorption of Cr(VI). During column experiments, Cr(VI) initially was desorbed easily from the alluvium by Cr-free groundwater; however, the rate of desorption decreased rapidly, and > 60 pore volumes of groundwater were required to decrease the effluent concentration of Cr(VI) to 3 ??mol/L [drinking water standard for Cr(VI) = 1 ??mol/L]. The quantity of Cr(VI) adsorbed varied with the type and concentration of other anions in solution.

Controlling Tumor Progression with Cyclophosphamide, Vincristine, and Dacarbazine Treatment Improves Survival in Patients with Metastatic and Unresectable Malignant Pheochromocytomas/Paragangliomas.

PubMed

Asai, Shiko; Katabami, Takuyuki; Tsuiki, Mika; Tanaka, Yasushi; Naruse, Mitsuhide

2017-04-01

Evidence has not been established to support that combination chemotherapy with cyclophosphamide, vincristine, and dacarbazine (CVD) improves survival in patients with malignant pheochromocytoma and paraganglioma (M-PPGL). To investigate the efficacy of CVD for this disease, we retrospectively analyzed data of 23 patients with metastatic and unresectable M-PPGL (mean age, 41.7 ± 15.4 years) who received at least 2 cycles of this regimen. The follow-up period after initiation of CVD ranged from 0.3 to 13.7 years, with a median of 3.3 years. CVD therapy achieved a complete tumor response (CR) in 1 patient (4%), a partial response (PR) in 5 (22%), stable disease (SD) in 5 (22%), and progressive disease (PD) in 13 (52%), respectively. All of the responders (CR and PR) but 6% of the non-responders (SD and PD) showed substantial biochemical improvement. The progression-free survival period in the responders was significantly longer than in the non-responders (p < 0.01). Although the overall survival and survival after the diagnosis of M-PPGL were longer in the responders than the non-responders, the difference was not statistically significant (p = 0.08). The progression-free and overall survival period were significantly longer in the non-progression group (CR, PR, and SD) than in the progression group (PD) (1.7 ± 3.3 vs. 0.3 ± 0.3 years, p < 0.01, and 4.6 ± 3.6 vs. 2.0 ± 3.7 years, p = 0.01, respectively). It is therefore suggested that CVD chemotherapy could be useful in controlling tumor progression and improving survival in patients with metastatic and progressive M-PPGL.

Radiation therapy for hypersalivation: a prospective study in 50 amyotrophic lateral sclerosis patients.

PubMed

Assouline, Avi; Levy, Antonin; Abdelnour-Mallet, Maya; Gonzalez-Bermejo, Jesus; Lenglet, Timothée; Le Forestier, Nadine; Salachas, François; Bruneteau, Gaelle; Meininger, Vincent; Delanian, Sylvie; Pradat, Pierre-François

2014-03-01

This study aimed to evaluate the efficiency and the tolerance of radiation therapy (RT) on salivary glands in a large series of amyotrophic lateral sclerosis (ALS) patients with hypersalivation. Fifty ALS patients that had medically failure pretreatment were included in this prospective study. RT was delivered through a conventional linear accelerator with 6-MV photons and 2 opposed beams fields including both submandibular glands and two-thirds of both parotid glands. Total RT dose was 10 Gy in 2 fractions (n=30) or 20 Gy in 4 fractions (n=20). RT efficacy was assessed with the 9-grade Sialorrhea Scoring Scale (SSS), recently prospectively validated as the most effective and sensitive tool to measure sialorrhea in ALS patients. At the end of RT, all patients had improved: 46 had a complete response (92% CR, SSS 1-3) and 4 had a partial response (8% PR, SSS 4-5). A significant lasting salivary reduction was observed 6 months after RT completion: there was 71% CR and 26% PR, and there was a significant SSS reduction versus baseline (P<10(-6)). There was no grade 3 to 4 toxicity, and most side effects (34%) occurred during RT. Nine patients (18%) underwent a second salivary gland RT course, with a 3-months mean delay from the first RT, resulting in a SSS decrease (-77%). Both RT dose regimens induced a significant SSS decrease with no significant toxicity. There were, however, more patients with CR/PR in the 20-Gy protocol (P=.02), and 8 of 9 patients (89%) receiving a second RT course had previously been treated within the 10-Gy protocol. Radiation therapy of 20 Gy in 4 fractions is an efficient and safe treatment for ALS patients with sialorrhea. A shorter RT course (10 Gy in 2 fractions) may be proposed in patients in poor medical condition. Copyright © 2014 Elsevier Inc. All rights reserved.

Rituximab in treatment of idiopathic glomerulopathy.

PubMed

El-Reshaid, Kamel; Sallam, Hossameldin Tawfik; Hakim, Abbass Ali; Al-Attiyah, Rajaa

2012-09-01

The aim of our study was to assess the role of rituximab (Mabthera) in the treatment of patients with corticosteroid-resistant and calcineurin-inhibitors ± cellcept refractory idiopathic nephrotic syndrome (INS). A total of 83 patients who had required the previous treatment for a minimum of two years were included in the study. Our protocol included the use of rituximab in four-weekly slow infusions. Five patients were excluded as they could not tolerate rituximab infusion for allergic reaction. As expected, none of the patients had a decline in the total circulating lymphocyte counts yet all had achieved decline of their initially normal CD20 to < 0.5% one month after infusion. The decline persisted for eight to ten months later. In the minimal change disease (MCD) group, 31 of the 32 patients had complete remission (CR) and were off any immunosuppressive therapy and one of the previous non-responders (NR) did not respond. Excluding two patients who had required retreatment, the others remained in CR (17 up to 28 months and six up to 36 months). Treatment with rituximab resulted in amelioration of NS in 17 of the 18 patients with focal segmental glomerulosclerosis (FSGS), while only one patient remained NR. Although renal function remained stable, proteinuria reappeared by eight to 12 months. Retreatment with rituximab resulted in a similar response with stable kidney function. In the 28 patients with membranous glomerulopathy (MG), 24 had achieved CR. Two patients failed to respond and two had partial remission. By 12 months, all patients relapsed. The response was within one month following treatment in patient with MCD, but was gradual within three months in FSGS and MG. Relapsers in all groups responded in a similar pattern to repeat dosing with the drug subsequently. Our prospective study represents an adequate number of patients with biopsy-proven subgroups of INS in both children and adults with long-term follow-up of treatment with rituximab. The drug is effective and safe for treatment of patients refractory to the conventional agents.

Radiation Therapy for Hypersalivation: A Prospective Study in 50 Amyotrophic Lateral Sclerosis Patients

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

Assouline, Avi, E-mail: avi.assouline@ccpsc.fr; Department of Radiation Oncology, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique - Hôpitaux de Paris; Levy, Antonin

Purpose: This study aimed to evaluate the efficiency and the tolerance of radiation therapy (RT) on salivary glands in a large series of amyotrophic lateral sclerosis (ALS) patients with hypersalivation. Methods and Materials: Fifty ALS patients that had medically failure pretreatment were included in this prospective study. RT was delivered through a conventional linear accelerator with 6-MV photons and 2 opposed beams fields including both submandibular glands and two-thirds of both parotid glands. Total RT dose was 10 Gy in 2 fractions (n=30) or 20 Gy in 4 fractions (n=20). RT efficacy was assessed with the 9-grade Sialorrhea Scoring Scalemore » (SSS), recently prospectively validated as the most effective and sensitive tool to measure sialorrhea in ALS patients. Results: At the end of RT, all patients had improved: 46 had a complete response (92% CR, SSS 1-3) and 4 had a partial response (8% PR, SSS 4-5). A significant lasting salivary reduction was observed 6 months after RT completion: there was 71% CR and 26% PR, and there was a significant SSS reduction versus baseline (P<10{sup −6}). There was no grade 3 to 4 toxicity, and most side effects (34%) occurred during RT. Nine patients (18%) underwent a second salivary gland RT course, with a 3-months mean delay from the first RT, resulting in a SSS decrease (−77%). Both RT dose regimens induced a significant SSS decrease with no significant toxicity. There were, however, more patients with CR/PR in the 20-Gy protocol (P=.02), and 8 of 9 patients (89%) receiving a second RT course had previously been treated within the 10-Gy protocol. Conclusion: Radiation therapy of 20 Gy in 4 fractions is an efficient and safe treatment for ALS patients with sialorrhea. A shorter RT course (10 Gy in 2 fractions) may be proposed in patients in poor medical condition.« less

Antibiotic treatment as sole management of Helicobacter pylori-negative gastric MALT lymphoma: a single center experience with prolonged follow-up.

PubMed

Raderer, Markus; Wöhrer, Stefan; Kiesewetter, Barbara; Dolak, Werner; Lagler, Heimo; Wotherspoon, Andrew; Muellauer, Leonhard; Chott, Andreas

2015-06-01

Relatively little is known about the long-term outcome of patients with Helicobacter pylori (HP)-negative gastric lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) with antibiotic therapy as sole management. We have analyzed all patients with HP-negative gastric MALT lymphoma undergoing antibiotic therapy as sole management of their disease. HP negativity was defined as negative histology, breath test and serology, and response to treatment, survival and long-term outcome was assessed together with clinico-pathological characteristics including t(11; 18) (q21; q21) translocation. Out of 97 patients with gastric MALT lymphoma, 24 were HP-negative, and 13 (5 females and 8 males) underwent only antibiotic management for initial therapy. Eight had stage I and five were found to have stage II disease, with three patients suffering from an underlying autoimmune disease. Antibiotic therapy consisted of standard HP eradication regimens consisting of clarithromycin in all patients, along with metronidazole in seven and amoxicillin in six plus a proton-pump inhibitor. After a median follow-up of 95 months (42-, 181+), 12/13 patients are alive. Six patients with stage I disease achieved an objective response (five complete (CR) and one partial remission, 46 %), four had stable disease (lasting 11-27 months), and three progressed. All patients with stable disease received chemotherapy, but only one patient due to clear cut progression. One patient relapsed 23 months after initial CR, and achieved a second CR with antibiotics now lasting 87 months. These results indicate that a relevant percentage of patients with HP-negative gastric MALT lymphoma may benefit from antibiotic therapy and do not require additional oncological therapies. Our data suggest that the remissions seen in these patients might be durable as evidenced by prolonged follow-up in our series.

An Evolutionarily Conserved DOF-CONSTANS Module Controls Plant Photoperiodic Signaling1[OPEN

PubMed Central

2015-01-01

The response to daylength is a crucial process that evolved very early in plant evolution, entitling the early green eukaryote to predict seasonal variability and attune its physiological responses to the environment. The photoperiod responses evolved into the complex signaling pathways that govern the angiosperm floral transition today. The Chlamydomonas reinhardtii DNA-Binding with One Finger (CrDOF) gene controls transcription in a photoperiod-dependent manner, and its misexpression influences algal growth and viability. In short days, CrDOF enhances CrCO expression, a homolog of plant CONSTANS (CO), by direct binding to its promoter, while it reduces the expression of cell division genes in long days independently of CrCO. In Arabidopsis (Arabidopsis thaliana), transgenic plants overexpressing CrDOF show floral delay and reduced expression of the photoperiodic genes CO and FLOWERING LOCUS T. The conservation of the DOF-CO module during plant evolution could be an important clue to understanding diversification by the inheritance of conserved gene toolkits in key developmental programs. PMID:25897001

MOPP chemotherapy for treatment of resistant lymphoma in dogs: a retrospective study of 117 cases (1989-2000).

PubMed

Rassnick, Kenneth M; Mauldin, Glenna E; Al-Sarraf, Renee; Mauldin, G Neal; Moore, Antony S; Mooney, Samantha C

2002-01-01

The purpose of this retrospective study was to evaluate the efficacy and toxicity of the MOPP chemotherapy protocol (mechlorethamine, vincristine, procarbazine, and prednisone) as a rescue regimen in dogs with lymphoma. One hundred seventeen dogs that had resistance to previously administered chemotherapy were evaluated. Before treatment with MOPP, all dogs received a median of 6 chemotherapy drugs for a median duration of 213 days. Thirty-one percent (36 of 117) had a complete response (CR) to MOPP for a median of 63 days, and 34% (40 of 117) had a partial response (PR) for a median of 47 days. Sixteen percent (19 of 117) had stable disease (SD) for a median of 33 days. Predictors for response to MOPP were not identified. Gastrointestinal (GI) toxicity occurred in 28% (33 of 117) of the dogs, and 13% (15 dogs) required hospitalization. Five dogs developed septicemia, and 2 died as a result. MOPP was an effective treatment for dogs with resistant lymphoma and was well tolerated by the majority of affected dogs.

Hypofractionated Palliative Radiotherapy with Concurrent Radiosensitizing Chemotherapy for Advanced Head and Neck Cancer Using the "QUAD-SHOT Regimen".

PubMed

Gamez, Mauricio E; Agarwal, Manuj; Hu, Kenneth S; Lukens, John N; Harrison, Louis B

2017-02-01

To analyze the outcomes using the hypofractionated palliative radiotherapy regimen "QUAD-Shot" with concurrent radiosensitizing chemotherapy for advanced head and neck cancer. We analyzed twenty-one patients with newly-diagnosed or recurrent head and neck cancer treated with palliative hypofractionated concurrent chemoradiation using the QUAD-Shot regimen. All patients received at least one cycle of RT, with sixteen patients (76%) completing all three cycles. 85.7 % of patients had objective response to therapy with five patients (23.8%) demonstrating complete response (CR) and thirteen patients (61.9%) demonstrating partial response (PR). Palliation of symptoms was achieved in all (100%) of the sixteen patients that completed the three cycles. Median overall survival and median progression-free survival were 7 and 4 months, respectively. QUAD-Shot palliative radiation therapy coupled with radiosensitizing chemotherapy is efficacious and well-tolerated in patients with newly-diagnosed or recurrent head and neck cancer not amenable to curative therapy. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

The effect of elevated blood cortisol levels on the extinction of a conditioned stress response in rainbow trout.

PubMed

Barreto, R E; Volpato, G L; Pottinger, T G

2006-09-01

Following previously published observations that a conditioned response (CR) was lost more quickly by rainbow trout (Oncorhynchus mykiss) exhibiting a high responsiveness to stressors than by low responding individuals this study was designed to investigate the effects of exogenous cortisol on the retention of a CR in unselected rainbow trout. Fish held in isolation were conditioned over a 10-day period by pairing an innocuous signal (conditioned stimulus, CS: a water jet played on the surface of the tank water) with a mild stressor (unconditioned stimulus, US: 30 min of confinement). This resulted in a brief elevation of plasma cortisol levels (the CR) when the fish was exposed to the CS only. The effect of exogenous cortisol on the retention of the CR was evaluated by comparing the performance of fish that received cortisol-containing slow-release intraperitoneal implants, with fish receiving vehicle-only implants. Retention of the CR was assessed at intervals up to 35 days after conditioning ceased. The CR was considered to be evident when 30 min following presentation of the CS, mean plasma cortisol levels were significantly higher in conditioned than untrained fish. On day 1 both cortisol-implanted and vehicle-implanted conditioned fish exhibited a CR. However, from day 5 onwards the CR was observed only in the vehicle-implanted and conditioned group. This finding indicates that administration of cortisol accelerated the extinction of the CR in the cortisol-implanted fish, suggesting that elevated plasma cortisol levels can impair memory processes in rainbow trout.

Identification of rice genes associated with cosmic-ray response via co-expression gene network analysis.

PubMed

Hwang, Sun-Goo; Kim, Dong Sub; Hwang, Jung Eun; Han, A-Reum; Jang, Cheol Seong

2014-05-15

In order to better understand the biological systems that are affected in response to cosmic ray (CR), we conducted weighted gene co-expression network analysis using the module detection method. By using the Pearson's correlation coefficient (PCC) value, we evaluated complex gene-gene functional interactions between 680 CR-responsive probes from integrated microarray data sets, which included large-scale transcriptional profiling of 1000 microarray samples. These probes were divided into 6 distinct modules that contained 20 enriched gene ontology (GO) functions, such as oxidoreductase activity, hydrolase activity, and response to stimulus and stress. In particular, modules 1 and 2 commonly showed enriched annotation categories such as oxidoreductase activity, including enriched cis-regulatory elements known as ROS-specific regulators. These results suggest that the ROS-mediated irradiation response pathway is affected by CR in modules 1 and 2. We found 243 ionizing radiation (IR)-responsive probes that exhibited similarities in expression patterns in various irradiation microarray data sets. The expression patterns of 6 randomly selected IR-responsive genes were evaluated by quantitative reverse transcription polymerase chain reaction following treatment with CR, gamma rays (GR), and ion beam (IB); similar patterns were observed among these genes under these 3 treatments. Moreover, we constructed subnetworks of IR-responsive genes and evaluated the expression levels of their neighboring genes following GR treatment; similar patterns were observed among them. These results of network-based analyses might provide a clue to understanding the complex biological system related to the CR response in plants. Copyright © 2014 Elsevier B.V. All rights reserved.

Systematic review of FDG-PET prediction of complete pathological response and survival in rectal cancer.

PubMed

Memon, Sameer; Lynch, A Craig; Akhurst, Timothy; Ngan, Samuel Y; Warrier, Satish K; Michael, Michael; Heriot, Alexander G

2014-10-01

Advances in the management of rectal cancer have resulted in an increased application of multimodal therapy with the aim of tailoring therapy to individual patients. Complete pathological response (pCR) is associated with improved survival and may be potentially managed without radical surgical resection. Over the last decade, there has been increasing interest in the ability of functional imaging to predict complete response to treatment. The aim of this review was to assess the role of (18)F-flurordeoxyglucose positron emission tomography (FDG-PET) in prediction of pCR and prognosis in resectable locally advanced rectal cancer. A search of the MEDLINE and Embase databases was conducted, and a systematic review of the literature investigating positron emission tomography (PET) in the prediction of pCR and survival in rectal cancer was performed. Seventeen series assessing PET prediction of pCR were included in the review. Seven series assessed postchemoradiation SUVmax, which was significantly different between response groups in all six studies that assessed this. Nine series assessed the response index (RI) for SUVmax, which was significantly different between response groups in seven series. Thirteen studies investigated PET response for prediction of survival. Metabolic complete response assessed by SUV2max or visual response and RISUVmax showed strong associations with disease-free survival (DFS) and overall survival (OS). SUV2max and RISUVmax appear to be useful FDG-PET markers for prediction of pCR and these parameters also show strong associations with DFS and OS. FDG-PET may have a role in outcome prediction in patients with advanced rectal cancer.

Biometric Fusion Demonstration System Scientific Report

DTIC Science & Technology

2004-03-01

verification and facial recognition , searching watchlist databases comprised of full or partial facial images or voice recordings. Multiple-biometric...17 2.2.1.1 Fingerprint and Facial Recognition ............................... 17...iv DRDC Ottawa CR 2004 – 056 2.2.1.2 Iris Recognition and Facial Recognition ........................ 18

A Study of Relationship of Atheroembolic Risk Factors with Postoperative Recovery in Renal Function after Partial Nephrectomy in Patients Staged T1-2 Renal Cell Carcinoma during Median 4-Year Follow-up.

PubMed

Kim, Sung Han; Kang, Kyung Min; Yu, Ami; Lee, Jung Hoon; Nam, Byung Ho; Lee, Eun Sik

2016-01-01

The objective of this study is to evaluate the relationship of atheroembolic risk factors with postoperative recovery of renal function after on-clamp partial nephrectomy (PN) with warm ischemia in patients with staged T1-2 renal cell carcinoma (RCC). A total of 234 patients from 2004 to 2012 were included, and their clinicopathologic and operative parameters, including atheroembolic risk factors were reviewed retrospectively. Renal function, as determined by estimated glomerular filtration rate (eGFR) and measurement of serum creatinine level (Cr) at each scheduled follow-up for a median four years, was compared between the high-risk (HR) group (n=49, ≥ five risk factors) and the low-risk (LR) group (n=185, < five risk factors). Except for baseline renal function and number of risk factors for atheroembolism, differences in characteristics between groups were comparatively insignificant. At 3 months after the operation, Cr and eGFR differed significantly between the two groups (p < 0.05), but no differences were observed afterward. Significant deterioration from baseline in Cr and eGFR was observed in both groups at 1 month after the operation, with a greater change in the HR group (p < 0.05). From measurement to measurement, significantly faster deterioration in Cr and eGFR was observed in the HR group than in the LR group until 6 months after the operation (Cr: LR, 0.02 mg/dL and HR, 0.13 mg/dL; eGFR: LR, 1.50 mL/min/1.73 m(2) and HR, 6.38 mL/min/1.73 m(2); p < 0.05). The presence of atheroembolic risk factors may negatively influence postoperative recovery of renal function after PN in patients with localized RCC.

Improving the fit of implant prosthetics: an in vitro study.

PubMed

Yannikakis, Stavros; Prombonas, Anthony

2013-01-01

Accurate and passive fit between a prosthesis and its supporting implants has been considered a prerequisite for successful long-term osseointegration. The objective of this in vitro study was to evaluate the strain development during tightening of a five-unit screw-retained superstructure constructed using five different methods. Five-unit screw-retained fixed partial prostheses (n = 25) were fabricated on three implants embedded in an epoxy resin block using five different methods: (1) cobalt-chromium (Co-Cr), plastic cylinders, one-piece cast; (2) Co-Cr, plastic cylinders, framework sectioned, preceramic laser-welding soldering; (3) gold-platinum (Au-Pt), gold cylinders, one-piece cast; (4) Au-Pt, gold cylinders, framework sectioned, preceramic laser-welding soldering; (5) Co-Cr, one-piece cast, and cementation to "passive abutments" (Southern Implants) after final finishing and polishing. Strain gauges (SG) were attached to the fixed partial prosthesis (FPP) and to the resin block to measure the stress created during screw tightening. The combination of Co-Cr alloy and plastic cylinders in a one-piece cast showed such an inadequate fit among the fabricated methods that this group was excluded from the remainder of the experiment. Specimens of Au-Pt cast on gold cylinders in one piece showed higher strain development than the other groups used in this study, with strains ranging from 223.1 to 2,198.1 Μm/m. Sectioning and soldering significantly improved the overall fit. FPPs of Co-Cr in a one-piece cast cemented to "passive abutments" produced the best level of fit, with the least strain development in the prosthesis and the resin block (59 to 204.6 Μm/m). Absolute fit of superstructures on implants is not possible using conventional laboratory procedures. Cementing FPPs onto prefabricated cylinders directly onto the implants significantly reduces strain development compared to the other fabrication methods.

Irinotecan and temozolomide in recurrent Ewing sarcoma: an analysis in 51 adult and pediatric patients.

PubMed

Palmerini, E; Jones, R L; Setola, E; Picci, P; Marchesi, E; Luksch, R; Grignani, G; Cesari, M; Longhi, A; Abate, M E; Paioli, A; Szucs, Z; D'ambrosio, L; Scotlandi, K; Fagioli, F; Asaftei, S; Ferrari, S

2018-03-13

Data on temozolomide (TEM) and irinotecan (IRI) activity in recurrent Ewing sarcoma (EWS), especially in adult patients, are limited. Patients receiving TEM 100 mg/m 2 /day oral, and IRI 40 mg/m 2 /day intravenous, days 1-5, every 21 days, were included in this multi-institutional retrospective study. Disease control rate (DCR) [overall response rate (ORR) [complete response (CR) + partial response (PR)] + stable disease (SD)], 6-months progression-free survival (6-mos PFS) and 1-year overall survival (OS) were assessed. The median age of the 51 patients was 21 years (range 3-65 years): 34 patients (66%) were adults (≥18 years of age), 24 (48%) had ECOG 1 and 35 (69%) were presented with multiple site recurrence. TEMIRI was used at first relapse/progression in 13 (25%) patients, while the remainder received TEMIRI for second or greater relapse/progression. Fourteen (27%) patients had received prior myeloablative therapy with busulfan and melphalan. We observed five (10%) CR, 12 (24%) PR and 19 (37%) SD, with a DCR of 71%. 6-mos PFS was 49% (95% CI 35-63) and it was significantly influenced by ECOG (6-mos PFS 64% [95% CI 45-83] for ECOG 0, 34% [95% CI 14-54] for ECOG ≥1; p = .006) and LDH (6-mos PFS 62% [95% CI 44-79] for normal LDH, 22% [95% CI 3-42] for high LDH; p = .02), with no difference according to line of treatment, age and metastatic pattern. One-year OS was 55% (95% CI 39-70), with RECIST response (p = .001) and ECOG (p = .0002) independently associated with outcome. Grade 3 and 4 toxicity included neutropenia in 12% of patients, thrombocytopenia in 4%, diarrhea in 4%. This series confirms the activity of TEMIRI in both adults and pediatric patients. This schedule offers a 71% DCR, independently of the line of chemotherapy. Predictive factors of response are ECOG and LDH.

Environmental Controls on the Carbon Isotope Composition of Ecosystem Respired Carbon Dioxide in Contrasting Forest Ecosystems in Canada and USA

NASA Astrophysics Data System (ADS)

Alstad, K.; Lai, C.; Flanagan, L. B.; Ehleringer, J. R.

2006-12-01

Our objective was to compare the carbon isotope composition of respired CO2 (δ13CR) from 11 forest ecosystems in Canada and USA and to examine differences among forests in their response to seasonal variation in photosynthetic photon flux density (PPFD), soil and air temperature, vapor pressure deficit (VPD), precipitation, and soil moisture during May-October 2004. We proposed that variations in δ13CR can be used as a proxy for short-term changes in photosynthetic discrimination and associated shifts in integrated ecosystem-level ci/ca. Our analyses included comparisons of δ13CR responses for three functional groups: deciduous, boreal, and coastal forests. The δ13CR values were well predicted for each group based on the six environmental variables considered, where the highest R2 values determined for the coastal, deciduous, and boreal groups were 0.81, 0.80, and 0.56, respectively. Consistent with several previous studies, the highest correlations between δ13CR and shifts in environmental conditions were achieved when the environmental variables were averaged for 2-, 3- or 4-days previous to δ13CR sample collection. The relationships we observed between δ13CR and environmental factors were consistent with known leaf-level responses, and this was especially apparent within each functional group. However, there were differences among the functional groups for the strength and/or significance of the relationships between δ13CR and particular environmental factors. For example, while VPD and soil temperature were significant determinants of variation in δ13CR in the boreal group, PPFD was not a significant factor and there was only a weak relationship observed between δ13CR and changes in soil moisture. By contrast, in the coastal group, variation in δ13CR was very strongly correlated with changes in PPFD, and there was no significant relationship with VPD. At a single site comparisons made between years suggested the potential application of δ13CR values to assess year-to-year variation in ecosystem physiological responses to changing environmental conditions, but also showed that all environmental factors influencing carbon isotope discrimination during photosynthetic gas exchange need to be considered in such an analysis.

Nitrification inhibition by hexavalent chromium Cr(VI)--Microbial ecology, gene expression and off-gas emissions.

PubMed

Kim, Young Mo; Park, Hongkeun; Chandran, Kartik

2016-04-01

The goal of this study was to investigate the responses in the physiology, microbial ecology and gene expression of nitrifying bacteria to imposition of and recovery from Cr(VI) loading in a lab-scale nitrification bioreactor. Exposure to Cr(VI) in the reactor strongly inhibited nitrification performance resulting in a parallel decrease in nitrate production and ammonia consumption. Cr(VI) exposure also led to an overall decrease in total bacterial concentrations in the reactor. However, the fraction of ammonia oxidizing bacteria (AOB) decreased to a greater extent than the fraction of nitrite oxidizing bacteria (NOB). In terms of functional gene expression, a rapid decrease in the transcript concentrations of amoA gene coding for ammonia oxidation in AOB was observed in response to the Cr(VI) shock. In contrast, transcript concentrations of the nxrA gene coding for nitrite oxidation in NOB were relatively unchanged compared to Cr(VI) pre-exposure levels. Therefore, Cr(VI) exposure selectively and directly inhibited activity of AOB, which indirectly resulted in substrate (nitrite) limitation to NOB. Significantly, trends in amoA expression preceded performance trends both during imposition of and recovery from inhibition. During recovery from the Cr(VI) shock, the high ammonia concentrations in the bioreactor resulted in an irreversible shift towards AOB populations, which are expected to be more competitive in high ammonia environments. An inadvertent impact during recovery was increased emission of nitrous oxide (N2O) and nitric oxide (NO), consistent with recent findings linking AOB activity and the production of these gases. Therefore, Cr(VI) exposure elicited multiple responses on the microbial ecology, gene expression and both aqueous and gaseous nitrogenous conversion in a nitrification process. A complementary interrogation of these multiple responses facilitated an understanding of both direct and indirect inhibitory impacts on nitrification. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comprehensive Review on the Surrogate Endpoints of Efficacy Proposed or Hypothesized in the Scientific Community Today.

PubMed

von Minckwitz, Gunter; Fontanella, Caterina

2015-05-01

An intermediate endpoint is a surrogate marker of treatment efficacy assessed earlier than the true outcome of interest. A suitable intermediate endpoint in neoadjuvant trials of specific breast cancer subtypes is pathological complete response (pCR) rate, defined as no invasive (+/-noninvasive) residual cancer in breast and nodes at surgery. On the basis of available evidence, Food and Drug Administration the US allowed to use of pCR as a surrogate endpoint for accelerated approval process. However, surrogacy to long-term outcome remains an unresolved issue. Literature data provide indications that triple-negative, HER2-positive, and high-grade hormone receptor-positive breast cancer subtypes achieved the highest pCR rate; the prognostic impact of pCR on survival is established only for these aggressive subtypes. In the German experience, early response after two to four cycles of neoadjuvant treatment strongly correlated with both pCR rate and long-term outcome. Therefore, early response may be considered a predictive marker for pCR and used for driving clinical trial design. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Pathologic Complete Response Predicts Recurrence-Free Survival More Effectively by Cancer Subset: Results From the I-SPY 1 TRIAL—CALGB 150007/150012, ACRIN 6657

PubMed Central

Esserman, Laura J.; Berry, Donald A.; DeMichele, Angela; Carey, Lisa; Davis, Sarah E.; Buxton, Meredith; Hudis, Cliff; Gray, Joe W.; Perou, Charles; Yau, Christina; Livasy, Chad; Krontiras, Helen; Montgomery, Leslie; Tripathy, Debasish; Lehman, Constance; Liu, Minetta C.; Olopade, Olufunmilayo I.; Rugo, Hope S.; Carpenter, John T.; Dressler, Lynn; Chhieng, David; Singh, Baljit; Mies, Carolyn; Rabban, Joseph; Chen, Yunn-Yi; Giri, Dilip; van 't Veer, Laura; Hylton, Nola

2012-01-01

Purpose Neoadjuvant chemotherapy for breast cancer provides critical information about tumor response; how best to leverage this for predicting recurrence-free survival (RFS) is not established. The I-SPY 1 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis) was a multicenter breast cancer study integrating clinical, imaging, and genomic data to evaluate pathologic response, RFS, and their relationship and predictability based on tumor biomarkers. Patients and Methods Eligible patients had tumors ≥ 3 cm and received neoadjuvant chemotherapy. We determined associations between pathologic complete response (pCR; defined as the absence of invasive cancer in breast and nodes) and RFS, overall and within receptor subsets. Results In 221 evaluable patients (median tumor size, 6.0 cm; median age, 49 years; 91% classified as poor risk on the basis of the 70-gene prognosis profile), 41% were hormone receptor (HR) negative, and 31% were human epidermal growth factor receptor 2 (HER2) positive. For 190 patients treated without neoadjuvant trastuzumab, pCR was highest for HR-negative/HER2-positive patients (45%) and lowest for HR-positive/HER2-negative patients (9%). Achieving pCR predicted favorable RFS. For 172 patients treated without trastuzumab, the hazard ratio for RFS of pCR versus no pCR was 0.29 (95% CI, 0.07 to 0.82). pCR was more predictive of RFS by multivariate analysis when subtype was taken into account, and point estimates of hazard ratios within the HR-positive/HER2-negative (hazard ratio, 0.00; 95% CI, 0.00 to 0.93), HR-negative/HER2-negative (hazard ratio, 0.25; 95% CI, 0.04 to 0.97), and HER2-positive (hazard ratio, 0.14; 95% CI, 0.01 to 1.0) subtypes are lower. Ki67 further improved the prediction of pCR within subsets. Conclusion In this biologically high-risk group, pCR differs by receptor subset. pCR is more highly predictive of RFS within every established receptor subset than overall, demonstrating that the extent of outcome advantage conferred by pCR is specific to tumor biology. PMID:22649152

Investigation of DOTA-Metal Chelation Effects on the Chemical Shift of 129 Xe

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

Jeong, Keunhong; Slack, Clancy C.; Vassiliou, Christophoros C.

2015-09-17

Recent work has shown that xenon chemical shifts in cryptophane-cage sensors are affected when tethered chelators bind to metals. Here in this paper, we explore the xenon shifts in response to a wide range of metal ions binding to diastereomeric forms of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) linked to cryptophane-A. The shifts induced by the binding of Ca 2+, Cu 2+, Ce 3+, Zn 2+, Cd 2+, Ni 2+, Co 2+, Cr 2+, Fe 3+, and Hg 2+ are distinct. In addition, the different responses of the diastereomers for the same metal ion indicate that shifts are affected by partial folding withmore » a correlation between the expected coordination number of the metal in the DOTA complex and the chemical shift of 129Xe. Lastly, these sensors may be used to detect and quantify many important metal ions, and a better understanding of the basis for the induced shifts could enhance future designs.« less

Long-term survival in primary CNS lymphoma treated by high-dose methotrexate monochemotherapy: role of STAT6 activation as prognostic determinant.

PubMed

Yang, Seung-Ho; Lee, Kun Soo; Kim, Il Sup; Hong, Jae Taek; Sung, Jae Hoon; Son, Byung Chul; Lee, Sang Won; Hong, Yong-Kil

2009-03-01

We report a single-center experience of 16 immunocompetent patients diagnosed with primary central nervous system lymphoma and treated with monochemotherapy with high-dose methotrexate (MTX) and deferred radiotherapy. MTX was given at a dose of 8.0 g/m2 for induction and at a dose of 3.5-8.0 g/m2 for maintenance. There were eight complete responses (CR), one partial response, one stable disease, and six patients whose tumors progressed in spite of the chemotherapy. At final follow-up, five of five CRs were alive and well without radiotherapy, with median follow-up of 26 months. Overall survival in eight non-CRs treated with the subsequent radiotherapy was 36 months. In the immunohistochemical study, STAT6 was positively expressed in 8 out of 13 cases. They included all non-CRs and two CRs. This observation suggests that STAT6 expression can be used as a prognostic determinant for MTX chemotherapy.

Paroxysmal nocturnal haemoglobinuria phenotype cells and leucocyte subset telomere length in childhood acquired aplastic anaemia.

PubMed

Tutelman, Perri R; Aubert, Geraldine; Milner, Ruth A; Dalal, Bakul I; Schultz, Kirk R; Deyell, Rebecca J

2014-03-01

The significance of paroxysmal nocturnal haemoglobinuria (PNH(pos) ) cells and leucocyte subset telomere lengths in paediatric aplastic anaemia (AA) is unknown. Among 22 children receiving immunosuppressive therapy (IST) for AA, 73% (16/22) were PNH(pos) , of whom 94% achieved at least a partial response (PR) to IST; 11/16 (69%) achieved complete response (CR). Only 2/6 (33%) PNH(neg) patients achieved PR. PNH(pos) patients were less likely to fail IST compared to PNH(neg) patients (odds ratio 0·033; 95% confidence interval 0·002-0·468; P = 0·012). Children with AA had short granulocyte (P = 7·8 × 10(-9) ), natural killer cell (P = 6·0 × 10(-4) ), naïve T lymphocyte (P = 0·002) and B lymphocyte (P = 0·005) telomeres compared to age-matched normative data. © 2013 John Wiley & Sons Ltd.

Interim heterogeneity changes measured using entropy texture features on T2-weighted MRI at 3.0 T are associated with pathological response to neoadjuvant chemotherapy in primary breast cancer.

PubMed

Henderson, Shelley; Purdie, Colin; Michie, Caroline; Evans, Andrew; Lerski, Richard; Johnston, Marilyn; Vinnicombe, Sarah; Thompson, Alastair M

2017-11-01

To investigate whether interim changes in hetereogeneity (measured using entropy features) on MRI were associated with pathological residual cancer burden (RCB) at final surgery in patients receiving neoadjuvant chemotherapy (NAC) for primary breast cancer. This was a retrospective study of 88 consenting women (age: 30-79 years). Scanning was performed on a 3.0 T MRI scanner prior to NAC (baseline) and after 2-3 cycles of treatment (interim). Entropy was derived from the grey-level co-occurrence matrix, on slice-matched baseline/interim T2-weighted images. Response, assessed using RCB score on surgically resected specimens, was compared statistically with entropy/heterogeneity changes and ROC analysis performed. Association of pCR within each tumour immunophenotype was evaluated. Mean entropy percent differences between examinations, by response category, were: pCR: 32.8%, RCB-I: 10.5%, RCB-II: 9.7% and RCB-III: 3.0%. Association of ultimate pCR with coarse entropy changes between baseline/interim MRI across all lesions yielded 85.2% accuracy (area under ROC curve: 0.845). Excellent sensitivity/specificity was obtained for pCR prediction within each immunophenotype: ER+: 100%/100%; HER2+: 83.3%/95.7%, TNBC: 87.5%/80.0%. Lesion T2 heterogeneity changes are associated with response to NAC using RCB scores, particularly for pCR, and can be useful across all immunophenotypes with good diagnostic accuracy. • Texture analysis provides a means of measuring lesion heterogeneity on MRI images. • Heterogeneity changes between baseline/interim MRI can be linked with ultimate pathological response. • Heterogeneity changes give good diagnostic accuracy of pCR response across all immunophenotypes. • Percentage reduction in heterogeneity is associated with pCR with good accuracy and NPV.

Spontaneous mutations in CYC8 and MIG1 suppress the short chronological lifespan of budding yeast lacking SNF1/AMPK

PubMed Central

Maqani, Nazif; Fine, Ryan D.; Shahid, Mehreen; Li, Mingguang; Enriquez-Hesles, Elisa; Smith, Jeffrey S.

2018-01-01

Chronologically aging yeast cells are prone to adaptive regrowth, whereby mutants with a survival advantage spontaneously appear and re-enter the cell cycle in stationary phase cultures. Adaptive regrowth is especially noticeable with short-lived strains, including those defective for SNF1, the homolog of mammalian AMP-activated protein kinase (AMPK). SNF1 becomes active in response to multiple environmental stresses that occur in chronologically aging cells, including glucose depletion and oxidative stress. SNF1 is also required for the extension of chronological lifespan (CLS) by caloric restriction (CR) as defined as limiting glucose at the time of culture inoculation. To identify specific downstream SNF1 targets responsible for CLS extension during CR, we screened for adaptive regrowth mutants that restore chronological longevity to a short-lived snf1∆ parental strain. Whole genome sequencing of the adapted mutants revealed missense mutations in TPR motifs 9 and 10 of the transcriptional co-repressor Cyc8 that specifically mediate repression through the transcriptional repressor Mig1. Another mutation occurred in MIG1 itself, thus implicating the activation of Mig1-repressed genes as a key function of SNF1 in maintaining CLS. Consistent with this conclusion, the cyc8 TPR mutations partially restored growth on alternative carbon sources and significantly extended CLS compared to the snf1∆ parent. Furthermore, cyc8 TPR mutations reactivated multiple Mig1-repressed genes, including the transcription factor gene CAT8, which is responsible for activating genes of the glyoxylate and gluconeogenesis pathways. Deleting CAT8 completely blocked CLS extension by the cyc8 TPR mutations on CLS, identifying these pathways as key Snf1-regulated CLS determinants.

Imatinib in systemic mastocytosis: a phase IV clinical trial in patients lacking exon 17 KIT mutations and review of the literature

PubMed Central

Alvarez-Twose, Iván; Matito, Almudena; Morgado, José Mário; Sánchez-Muñoz, Laura; Jara-Acevedo, María; García-Montero, Andrés; Mayado, Andrea; Caldas, Carolina; Teodósio, Cristina; Muñoz-González, Javier Ignacio; Mollejo, Manuela; Escribano, Luis; Orfao, Alberto

2017-01-01

Resistance to imatinib has been recurrently reported in systemic mastocytosis (SM) carrying exon 17 KIT mutations. We evaluated the efficacy and safety of imatinib therapy in 10 adult SM patients lacking exon 17 KIT mutations, 9 of which fulfilled criteria for well-differentiated SM (WDSM). The World Health Organization 2008 disease categories among WDSM patients were mast cell (MC) leukemia (n = 3), indolent SM (n = 3) and cutaneous mastocytosis (n = 3); the remainder case had SM associated with a clonal haematological non-MC disease. Patients were given imatinib for 12 months −400 or 300 mg daily depending on the presence vs. absence of > 30% bone marrow (BM) MCs and/or signs of advanced disease–. Absence of exon 17 KIT mutations was confirmed in highly-purified BM MCs by peptide nucleic acid-mediated PCR, while mutations involving other exons were investigated by direct sequencing of purified BM MC DNA. Complete response (CR) was defined as resolution of BM MC infiltration, skin lesions, organomegalies and MC-mediator release-associated symptoms, plus normalization of serum tryptase. Criteria for partial response (PR) included ≥ 50% reduction in BM MC infiltration and improvement of skin lesions and/or organomegalies. Treatment was well-tolerated with an overall response rate of 50%, including early and sustained CR in four patients, three of whom had extracellular mutations of KIT, and PR in one case. This later patient and all non-responders (n = 5) showed wild-type KIT. These results together with previous data from the literature support the relevance of the KIT mutational status in selecting SM patients who are candidates for imatinib therapy. PMID:28978170

Imatinib in systemic mastocytosis: a phase IV clinical trial in patients lacking exon 17 KIT mutations and review of the literature.

PubMed

Alvarez-Twose, Iván; Matito, Almudena; Morgado, José Mário; Sánchez-Muñoz, Laura; Jara-Acevedo, María; García-Montero, Andrés; Mayado, Andrea; Caldas, Carolina; Teodósio, Cristina; Muñoz-González, Javier Ignacio; Mollejo, Manuela; Escribano, Luis; Orfao, Alberto

2017-09-15

Resistance to imatinib has been recurrently reported in systemic mastocytosis (SM) carrying exon 17 KIT mutations. We evaluated the efficacy and safety of imatinib therapy in 10 adult SM patients lacking exon 17 KIT mutations, 9 of which fulfilled criteria for well-differentiated SM (WDSM). The World Health Organization 2008 disease categories among WDSM patients were mast cell (MC) leukemia ( n = 3), indolent SM ( n = 3) and cutaneous mastocytosis ( n = 3); the remainder case had SM associated with a clonal haematological non-MC disease. Patients were given imatinib for 12 months -400 or 300 mg daily depending on the presence vs. absence of > 30% bone marrow (BM) MCs and/or signs of advanced disease-. Absence of exon 17 KIT mutations was confirmed in highly-purified BM MCs by peptide nucleic acid-mediated PCR, while mutations involving other exons were investigated by direct sequencing of purified BM MC DNA. Complete response (CR) was defined as resolution of BM MC infiltration, skin lesions, organomegalies and MC-mediator release-associated symptoms, plus normalization of serum tryptase. Criteria for partial response (PR) included ≥ 50% reduction in BM MC infiltration and improvement of skin lesions and/or organomegalies. Treatment was well-tolerated with an overall response rate of 50%, including early and sustained CR in four patients, three of whom had extracellular mutations of KIT , and PR in one case. This later patient and all non-responders ( n = 5) showed wild-type KIT . These results together with previous data from the literature support the relevance of the KIT mutational status in selecting SM patients who are candidates for imatinib therapy.

Electrochemical treatment of lung cancer

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

Xin, Y.L.; Xue, F.Z.; Ge, B.S.

1997-03-01

A pilot study of electrochemical treatment (ECT) as a therapy for 386 patients with nonsmall cell lung cancer was undertaken. There were 103 stage 2 cases, 89 stage 3a cases, 122 stage 3b cases, and 72 stage 4 cases. Two ECT methods were used. For peripherally located lung cancer, platinum electrodes were inserted transcutaneously into the tumor under x-ray or CT guidance. For central type lung cancer or for those inoperable during thoracotomy, electrodes were inserted intraoperatively directly into the cancer. Voltage was 6--8 V, current was 40--100 mA, and electric charge was 100 coulombs per cm of tumor diameter.more » The number of electrodes was determined from the size of cancer mass, because the diameter of effective area around each electrode is approximately 3 cm. The short-term (6 months after ECT) results of the 386 lung cancer cases were: complete response (CR), 25.6% (99/386); partial response (PR), 46.4% (179/386); no change (NC), 15.3% (59/386); and progressive disease (PD), 12.7% (49/386). The total effective rate (CR + PR) was 72% (278/386). The 1, 3, and 5 year overall survival rates were 86.3% (333/386), 58.8% (227/386), and 29.5% (114/386), respectively. The main complication was traumatic pneumothorax, with an incidence rate of 14.8% (57/386). These clinical results show that ECT is simple, safe, effective, and minimally traumatic. ECT provides an alternative method for treating lung cancers that are conventionally inoperable, that are not responsive to chemotherapy or radiotherapy, or that cannot be resected after thoracotomy. Long-term survival rates suggest that ECT warrants further investigation.« less

[Feasibility and short-term efficacy of simplified intensity-modulated radiotherapy and concurrent chemotherapy for neck and upper thoracic esophageal carcinoma].

PubMed

Zhu, Wei-Guo; Yu, Chang-Hua; Han, Ji-Hua; Li, Tao; Zhou, Xi-Lei; Tao, Guang-Zhou

2009-12-01

For neck and upper thoracic esophageal carcinoma, three dimensional conformal radiation therapy (3D-CRT) does not necessarily meet all clinical requirements while intensity modulated radiation therapy (IMRT) may take up a lot of labour power and material resources. This study was to explore the feasibility of simplified IMPT(sIMRT) and concurrent chemotherapy for neck and upper thoracic esophageal carcinoma, and to investigate the acute toxicities and short-term efficacy of this treatment modality. sIMRT plans were designed for 30 patients with neck and upper thoracic esophageal carcinoma. Two target volumes were defined: PTV1, which was designed to irradiate to 64 Gy (2.13 Gy x 30 fractions); PTV2, which was given to 54 Gy (1.8 Gy x 30). The sIMRT plan included five equiangular coplanar beams. All patients concurrently received DDP+5-FU regimen with radiotherapy on d1-5 and d29-33. Chemotherapy was repeated for two cycles 28 days after radiotherapy. The treatment was completed for all patients within 6 weeks, and only one patient had Grade 3 acute bronchitis. The complete response (CR) rate was 90.0% (27/30) and the partial response (PR) rate 10.0% (3/30). Overall response was 100% for esophageal lesions and the CR rate 76.5% (13/17). The PR rate was 23.5% (4/17) in lymph node lesions. The major toxicities observed were Grades I-II leukocytopenia. sIMRT can generate desirable dose distribution for neck and upper thoracic esophageal carcinoma, which is similar to sophisticated IMRT but obviously better than 3D-CRT. The short-term efficacy of sIMRT is satisfactory and its acute toxicities are tolerable.

Clinical outcome and prognostic markers for patients with gynecologic malignancies in phase 1 clinical trials: a single institution experience from 1999 to 2010.

PubMed

Hou, June Y; Aparo, Santiago; Ghalib, Mohammad; Chaudhary, Imran; Shah, Umang; Swami, Umang; Einstein, Mark; Goldberg, Gary L; Mani, Sridhar; Goel, Sanjay

2013-10-01

There is a scarcity of outcome data regarding phase 1 trials for patients with gynecologic malignancy. The objective of this study was to assess toxicity, clinical benefit and prognosticators in gynecologic oncology patients participating in phase 1 trials. All phase 1 oncology trials conducted at Albert Einstein Cancer Center from 1999 to 2010 were reviewed and extracted for relevant demographic and clinical data concerning patients with gynecologic malignancy. Cox-proportional and logistic regression modeling were used for multivariate analysis. 120 distinct patients with gynecologic malignancy participated in 41 trials, constituting 30.6% of all phase 1 patients enrolled in the same time period. The median age is 59 years. Out of the 184 patients enrolled, 160 individual responses were evaluable. Seventeen DLT events (9.2%) occurred, including 1 (0.5%) treatment-related mortality. There were 27.2%≥ grade 3 hematologic and 24.4% non-hematologic toxicity. Eighty patients had stable disease (SD, 50%), including 21.9% with SD ≥ 4 months, 11 (6.3%) with partial response (PR), and 3 (1.9%) achieving complete response (CR). The clinical benefit rate (CBR=SD+CR+PR) was 58.1%. Albumin (Alb)≤ 3.5 g/dL and abnormal ANC were independent negative prognosticators of survival. We also found a continuous correlation between changes in Albumin (p=0.02) and LDH (p=0.02) and odds of achieving CBR≥4month. Our clinical outcome and safety data suggested that phase 1 trials may be a reasonable option for patients with advanced and recurrent gynecologic cancer. The potential prognosticators identified should be further validated in larger trials. © 2013.

Cross sections for the production of fragments with Z greater than or equal to 8 by fragmentation of Z greater than or equal to 9 and less than or equal to 26 nuclei

NASA Technical Reports Server (NTRS)

Heinrich, W.; Drechsel, H.; Brechtmann, C.; Beer, J.

1985-01-01

Charge changing nuclear collisions in plastic nuclear track detectors were studied using a new experimental technique of automatic track measurement for etched tracks in plastic detectors. Partial cross sections for the production of fragments of charge Z approximately 8 were measured for projectile nuclei of charge 9 approximately Z approximately 26 in the detector material CR39 and in silver. for this purpose three independent experiments were performed using Bevalac beams. The first one was an exposure of a stack of CR39 plastic plates to 1.8 GeV/nucl. Ar-40 nuclei. The second one was an exposure of another CR39 stack of 1.7 GeV/nucl. Fe-56 projectiles. In the third experiment a mixed stack of CR39 plates and silver foils was irradiated with 1.7 GeV/nucl. Fe-56 nuclei. Thus the measurement of nuclear cross sections in a light target (CR39 = C12H18O7) and as well in a heavy target (silver) was possible.

Metabolite ratios to assumed stable creatine level may confound the quantification of proton brain MR spectroscopy.

PubMed

Li, Belinda S Y; Wang, Hao; Gonen, Oded

2003-10-01

In localized brain proton MR spectroscopy ((1)H-MRS), metabolites' levels are often expressed as ratios, rather than as absolute concentrations. Frequently, their denominator is the creatine [Cr], which level is explicitly assumed to be stable in normal as well as in many pathologic states. The rationale is that ratios self-correct for imager and localization method differences, gain instabilities, regional susceptibility variations and partial volume effects. The implicit assumption is that these benefits are worth their cost(w)-(w) propagation of the individual variation of each of the ratio's components. To test this hypothesis, absolute levels of N-acetylaspartate [NAA], choline [Cho] and [Cr] were quantified in various regions of the brains of 8 volunteers, using 3-dimensional (3D) (1)H-MRS at 1.5 T. The results show that in over 50% of approximately 2000 voxels examined, [NAA]/[Cr] and [Cho]/[Cr] exhibited higher coefficients of variations (CV) than [NAA] and [Cho] individually. Furthermore, in approximately 33% of these voxels, the ratios' CVs exceeded even the combined constituents' CVs. Consequently, basing metabolite quantification on ratios and assuming stable [Cr] introduces more variability into (1)H-MRS than it prevents. Therefore, its cost exceeds the benefit.

Experimental investigation of in-situ transformations of the M 7C3 carbide in the cast Fe-Cr-Ni alloy

NASA Astrophysics Data System (ADS)

Kraposhin, V. S.; Kondrat'ev, S. Yu.; Talis, A. L.; Anastasiadi, G. P.

2017-03-01

The microstructure and the phase composition of a heat-resistant Fe-Cr-Ni alloy (0. 45C-25Cr-35Ni) has been investigated in the cast state and after annealing at 1150°C for 2-100 h. After a 2-h high-temperature annealing, the fragmentation of the crystal structure of the eutectic M 7C3 carbides into domains of 500 nm in size with a partial transition into M 23C6 carbides is observed. After a 100-h holding, the complete transition of the hexagonal M 7C3 carbides into M 23C6 with a face-centered cubic structure occurs. The carbide transition M 7C3 → M 23 can be considered to be an in situ transformation.

A comparison of white-collar jobs in regard to mental health consultation rates in a health care center operated by a Japanese company.

PubMed

Soeda, Shuji; Hayashi, Takeshi; Sugawara, Yoichi; Takano, Tomoki; Terao, Takeshi; Nakamura, Jun

2003-04-01

The aim of this study was to compare the consultation rates (CR) of workers performing several types of white-collar jobs. We collected data from the database inputted at the first consultation to a health care center from April 1996 to March 1999. We found that the CR of engineer group was 2.3 times higher than that of employees involved in research and development group. We speculate that this is partially due to the portion, which is not small, of computer systems engineer (SE) comprising this group; SE has previously been mentioned as a particularly stressful occupation in Japan. Since the result of this study is preliminary, we need to conduct a further study taking into account that multiple factors affect CR.

GLOBAL SIMULATIONS OF GALACTIC WINDS INCLUDING COSMIC-RAY STREAMING

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

Ruszkowski, Mateusz; Yang, H.-Y. Karen; Zweibel, Ellen, E-mail: mateuszr@umich.edu, E-mail: hsyang@astro.umd.edu, E-mail: zweibel@astro.wisc.edu

2017-01-10

Galactic outflows play an important role in galactic evolution. Despite their importance, a detailed understanding of the physical mechanisms responsible for the driving of these winds is lacking. In an effort to gain more insight into the nature of these flows, we perform global three-dimensional magnetohydrodynamical simulations of an isolated Milky Way-size starburst galaxy. We focus on the dynamical role of cosmic rays (CRs) injected by supernovae, and specifically on the impact of the streaming and anisotropic diffusion of CRs along the magnetic fields. We find that these microphysical effects can have a significant effect on the wind launching andmore » mass loading factors, depending on the details of the plasma physics. Due to the CR streaming instability, CRs propagating in the interstellar medium scatter on self-excited Alfvén waves and couple to the gas. When the wave growth due to the streaming instability is inhibited by some damping process, such as turbulent damping, the coupling of CRs to the gas is weaker and their effective propagation speed faster than the Alfvén speed. Alternatively, CRs could scatter from “extrinsic turbulence” that is driven by another mechanism. We demonstrate that the presence of moderately super-Alfvénic CR streaming enhances the efficiency of galactic wind driving. Cosmic rays stream away from denser regions near the galactic disk along partially ordered magnetic fields and in the process accelerate more tenuous gas away from the galaxy. For CR acceleration efficiencies broadly consistent with the observational constraints, CRs reduce the galactic star formation rates and significantly aid in launching galactic winds.« less

Nomogram predicting response after chemoradiotherapy in rectal cancer using sequential PETCT imaging: a multicentric prospective study with external validation.

PubMed

van Stiphout, Ruud G P M; Valentini, Vincenzo; Buijsen, Jeroen; Lammering, Guido; Meldolesi, Elisa; van Soest, Johan; Leccisotti, Lucia; Giordano, Alessandro; Gambacorta, Maria A; Dekker, Andre; Lambin, Philippe

2014-11-01

To develop and externally validate a predictive model for pathologic complete response (pCR) for locally advanced rectal cancer (LARC) based on clinical features and early sequential (18)F-FDG PETCT imaging. Prospective data (i.a. THUNDER trial) were used to train (N=112, MAASTRO Clinic) and validate (N=78, Università Cattolica del S. Cuore) the model for pCR (ypT0N0). All patients received long-course chemoradiotherapy (CRT) and surgery. Clinical parameters were age, gender, clinical tumour (cT) stage and clinical nodal (cN) stage. PET parameters were SUVmax, SUVmean, metabolic tumour volume (MTV) and maximal tumour diameter, for which response indices between pre-treatment and intermediate scan were calculated. Using multivariate logistic regression, three probability groups for pCR were defined. The pCR rates were 21.4% (training) and 23.1% (validation). The selected predictive features for pCR were cT-stage, cN-stage, response index of SUVmean and maximal tumour diameter during treatment. The models' performances (AUC) were 0.78 (training) and 0.70 (validation). The high probability group for pCR resulted in 100% correct predictions for training and 67% for validation. The model is available on the website www.predictcancer.org. The developed predictive model for pCR is accurate and externally validated. This model may assist in treatment decisions during CRT to select complete responders for a wait-and-see policy, good responders for extra RT boost and bad responders for additional chemotherapy. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Evaluation with 3.0-T MR imaging: predicting the pathological response of triple-negative breast cancer treated with anthracycline and taxane neoadjuvant chemotherapy.

PubMed

Kim, Min Jung; Kim, Eun-Kyung; Park, Seho; Moon, Hee Jung; Kim, Seung Il; Park, Byeong-Woo

2015-09-01

Triple-negative breast cancer (TNBC) which expresses neither hormonal receptors nor HER-2 is associated with poor prognosis and shorter survival. Several studies have suggested that TNBC patients attaining pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) show a longer survival than those without pCR. To assess the accuracy of 3.0-T breast magnetic resonance imaging (MRI) in predicting pCR and to evaluate the clinicoradiologic factors affecting the diagnostic accuracy of 3.0-T breast MRI in TNBC patients treated with anthracycline and taxane (ACD). This retrospective study was approved by the institutional review board; patient consent was not required. Between 2009 and 2012, 35 TNBC patients with 3.0-T breast MRI prior to (n = 26) or after (n = 35) NAC were included. MRI findings were reviewed according to pCR to chemotherapy. The diagnostic accuracy of 3.0-T breast MRI for predicting pCR and the clinicoradiological factors affecting MRI accuracy and response to NAC were analyzed. 3.0-T MRI following NAC with ACD accurately predicted pCR in 91.4% of TNBC patients. The residual tumor size between pathology and 3.0-T MRI in non-pCR cases showed a higher correlation in the Ki-67-positive TNBC group (r = 0.947) than in the Ki-67 negative group (r = 0.375) with statistical trends (P = 0.069). Pre-treatment MRI in the non-pCR group compared to the pCR group showed a larger tumor size (P = 0.030) and non-mass presentation (P = 0.015). 3.0-T MRI in TNBC patients following NAC with ACD showed a high accuracy for predicting pCR to NAC. Ki-67 can affect the diagnostic accuracy of 3.0-T MRI for pCR to NAC with ACD in TNBC patients. © The Foundation Acta Radiologica 2014.

Treatment of advanced refractory sarcomas with ifosfamide and etoposide combination chemotherapy.

PubMed

Yalçin, S; Güllü, I; Barişta, I; Tekuzman, G; Ozişik, Y; Celik, I; Kars, A

1998-01-01

Chemotherapy options for resistant advanced-stage sarcomas are limited and in most cases disappointing. In a phase II study, we treated 26 consecutive patients with refractory advanced sarcoma with ifosfamide and etoposide combination chemotherapy. All patients had received prior doxorubicin- and/or cyclophosphamide-based chemotherapies. Seventeen patients were male and 9 were female. The patients' median age was 35 years (range: 19-67 years). A total of 24 patients were eligible for evaluation of responses. Seven patients had a complete response (CR) (29.1%), 3 had a partial response (PR) (12.5%), 3 had stable disease (SD) (12.5%), and 11 had progressive disease (PD) (45.9%). An overall 41.6% objective response was achieved. Median time to treatment failure was 13.3 months. A total of 108 cycles of therapy were evaluable for evaluation of toxicity. Myelosuppression, observed in 55.5% of the treatment courses, was the major dose-limiting toxicity. Nausea and vomiting, seen in 64% of the courses, were the most important nonhematological side effects. Alopecia was almost universal. Hemorrhagic cystitis was observed in only 1 patient. We have concluded that the combination of ifosfamide, mesna, and etoposide is effective in advanced refractory sarcomas, and has acceptable toxicity.

Differential antioxidative enzyme responses of Jatropha curcas L. to chromium stress.

PubMed

Yadav, Santosh Kumar; Dhote, Monika; Kumar, Phani; Sharma, Jitendra; Chakrabarti, Tapan; Juwarkar, Asha A

2010-08-15

Chromium (Cr) tolerant and accumulation capability of Jatropha curcas L. was tested in Cr spiked soil amended with biosludge and biofertilizer. Plants were cultivated in soils containing 0, 25, 50, 100 and 250 mg kg(-1) of Cr for one year with and without amendment. Plant tissue analysis showed that combined application of biosludge and biofertilizer could significantly reduce Cr uptake and boost the plant biomass, whereas biofertilizer alone did not affect the uptake and plant growth. Antioxidative responses of catalase (CAT), ascorbate peroxidase (APX) and glutathione S-transferase (GST) were increased with increasing Cr concentration in plant. Hyperactivity of the CAT and GST indicated that antioxidant enzymes played an important role in protecting the plant from Cr toxicity. However, APX took a little part in detoxification of H(2)O(2) due to its sensitivity to Cr. Therefore, reduced APX activity was recorded. Reduced glutathione (GSH) activity was recorded in plant grown on/above 100 mg kg(-1) of Cr in soil. The study concludes that J. curcas could grow under chromium stress. Furthermore, the results encouraged that J. curcas is a suitable candidate for the restoration of Cr contaminated soils with the concomitant application of biosludge and biofertilizer. Copyright 2010 Elsevier B.V. All rights reserved.

Caloric restriction enhances fear extinction learning in mice.

PubMed

Riddle, Megan C; McKenna, Morgan C; Yoon, Yone J; Pattwell, Siobhan S; Santos, Patricia Mae G; Casey, B J; Glatt, Charles E

2013-05-01

Fear extinction learning, the ability to reassess a learned cue of danger as safe when it no longer predicts aversive events, is often dysregulated in anxiety disorders. Selective serotonin reuptake inhibitors (SSRI's) enhance neural plasticity and their ability to enhance fear extinction learning may explain their anxiolytic properties. Caloric restriction (CR) has SSRI-like effects on neural plasticity and anxiety-related behavior. We implemented CR in mice to determine its effects on conditioned-fear responses. Wild type and serotonin transporter (SERT) knockout mice underwent CR for 7 days leading to significant weight loss. Mice were then tested for cued fear learning and anxiety-related behavior. CR markedly enhanced fear extinction learning and its retention in adolescent female mice, and adults of both sexes. These effects of CR were absent in SERT knockout mice. Moreover, CR phenocopied behavioral and molecular effects of chronic fluoxetine, but there was no additive effect of CR in fluoxetine-treated mice. These results demonstrate that CR enhances fear extinction learning through a SERT-dependent mechanism. These results may have implications for eating disorders such as anorexia nervosa (AN), in which there is a high prevalence of anxiety before the onset of dietary restriction and support proposals that in AN, CR is a motivated effort to control dysregulated fear responses and elevated anxiety.

An exploratory study on low-concentration hexavalent chromium adsorption by Fe(III)-cross-linked chitosan beads

PubMed Central

Zhang, Yuanjing; Qian, Jin; Xin, Xu; Hu, Sihai; Zhang, Shuai; Wei, Jianguo

2017-01-01

In this study, Fe(III)-cross-linked chitosan beads (Fe(III)-CBs) were synthesized and employed to explore the characteristics and primary mechanism of their hexavalent chromium (Cr(VI)) adsorption under low concentration Cr(VI) (less than 20.0 mg l−1) and a pH range from 2.0 to 8.0. Batch tests were conducted to determine the Cr(VI) adsorption capacity and kinetics, and the effects of pH and temperature on the adsorption under low concentration Cr(VI) and a pH range from 2.0 to 8.0. Scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy and X-ray photoelectron spectroscopy were employed to explore the characteristics of Fe(III)-CBs and their Cr(VI) adsorption mechanisms. The results show that, unlike the adsorption of other absorbents, the Cr(VI) adsorption was efficient in a wide pH range from 2.0 to 6.0, and well described by the pseudo-first-order model and the Langmuir–Freundlich isotherm model. The capacity of Cr(VI) adsorption by Fe(III)-CBs was as high as 166.3 mg g−1 under temperature 25°C and pH 6.0. The desorption test was also carried out by 0.1 mol l−1 NaOH solution for Fe(III)-CBs regeneration. It was found that Fe(III)-CBs could be re-used for five adsorption–desorption cycles without significant decrease in Cr(VI) adsorption capacity. Ion exchange was confirmed between functional groups (i.e. amino group) and Cr(VI) anions (i.e. CrO42−). The amino-like functional groups played a key role in Cr(VI) distribution on the Fe(III)-CBs surface; Cr(VI) adsorbed on Fe(III)-CBs was partially reduced to Cr(III) with alcoholic group served as electron donor, and then formed another rate-limiting factor. So, Fe(III)-CBs has a good prospect in purifying low concentration Cr(VI) water with a pH range from 2.0 to 6.0. PMID:29291084

The effects of graded levels of calorie restriction: III. Impact of short term calorie and protein restriction on mean daily body temperature and torpor use in the C57BL/6 mouse

PubMed Central

Mitchell, Sharon E.; Delville, Camille; Konstantopedos, Penelope; Derous, Davina; Green, Cara L.; Chen, Luonan; Han, Jing-Dong J.; Wang, Yingchun; Promislow, Daniel E.L.; Douglas, Alex; Lusseau, David; Speakman, John R.

2015-01-01

A commonly observed response in mammals to calorie restriction (CR) is reduced body temperature (Tb). We explored how the Tb of male C57BL/6 mice responded to graded CR (10 to 40%), compared to the response to equivalent levels of protein restriction (PR) over 3 months. Under CR there was a dynamic change in daily Tb over the first 30–35 days, which stabilized thereafter until day 70 after which a further decline was noted. The time to reach stability was dependent on restriction level. Body mass negatively correlated with Tb under ad libitum feeding and positively correlated under CR. The average Tb over the last 20 days was significantly related to the levels of body fat, structural tissue, leptin and insulin-like growth factor-1. Some mice, particularly those under higher levels of CR, showed periods of daily torpor later in the restriction period. None of the changes in Tb under CR were recapitulated by equivalent levels of PR. We conclude that changes in Tb under CR are a response only to the shortfall in calorie intake. The linear relationship between average Tb and the level of restriction supports the idea that Tb changes are an integral aspect of the lifespan effect. PMID:26286956

Bone marrow chimeric mice reveal a role for CX₃CR1 in maintenance of the monocyte-derived cell population in the olfactory neuroepithelium.

PubMed

Vukovic, Jana; Blomster, Linda V; Chinnery, Holly R; Weninger, Wolfgang; Jung, Steffen; McMenamin, Paul G; Ruitenberg, Marc J

2010-10-01

Macrophages in the olfactory neuroepithelium are thought to play major roles in tissue homeostasis and repair. However, little information is available at present about possible heterogeneity of these monocyte-derived cells, their turnover rates, and the role of chemokine receptors in this process. To start addressing these issues, this study used Cx₃cr1(gfp) mice, in which the gene sequence for eGFP was knocked into the CX₃CR1 gene locus in the mutant allele. Using neuroepithelial whole-mounts from Cx₃cr1(gfp/+) mice, we show that eGFP(+) cells of monocytic origin are distributed in a loose network throughout this tissue and can be subdivided further into two immunophenotypically distinct subsets based on MHC-II glycoprotein expression. BM chimeric mice were created using Cx₃cr1(gfp/+) donors to investigate turnover of macrophages (and other monocyte-derived cells) in the olfactory neuroepithelium. Our data indicate that the monocyte-derived cell population in the olfactory neuroepithelium is actively replenished by circulating monocytes and under the experimental conditions, completely turned over within 6 months. Transplantation of Cx₃cr1(gfp/gfp) (i.e., CX₃CR1-deficient) BM partially impaired the replenishment process and resulted in an overall decline of the total monocyte-derived cell number in the olfactory epithelium. Interestingly, replenishment of the CD68(low)MHC-II(+) subset appeared minimally affected by CX₃CR1 deficiency. Taken together, the established baseline data about heterogeneity of monocyte-derived cells, their replenishment rates, and the role of CX₃CR1 provide a solid basis to further examine the importance of different monocyte subsets for neuroregeneration at this unique frontier with the external environment.

Low Diversity in the Mitogenome of Sperm Whales Revealed by Next-Generation Sequencing

PubMed Central

Alexander, Alana; Steel, Debbie; Slikas, Beth; Hoekzema, Kendra; Carraher, Colm; Parks, Matthew; Cronn, Richard; Baker, C. Scott

2013-01-01

Large population sizes and global distributions generally associate with high mitochondrial DNA control region (CR) diversity. The sperm whale (Physeter macrocephalus) is an exception, showing low CR diversity relative to other cetaceans; however, diversity levels throughout the remainder of the sperm whale mitogenome are unknown. We sequenced 20 mitogenomes from 17 sperm whales representative of worldwide diversity using Next Generation Sequencing (NGS) technologies (Illumina GAIIx, Roche 454 GS Junior). Resequencing of three individuals with both NGS platforms and partial Sanger sequencing showed low discrepancy rates (454-Illumina: 0.0071%; Sanger-Illumina: 0.0034%; and Sanger-454: 0.0023%) confirming suitability of both NGS platforms for investigating low mitogenomic diversity. Using the 17 sperm whale mitogenomes in a phylogenetic reconstruction with 41 other species, including 11 new dolphin mitogenomes, we tested two hypotheses for the low CR diversity. First, the hypothesis that CR-specific constraints have reduced diversity solely in the CR was rejected as diversity was low throughout the mitogenome, not just in the CR (overall diversity π = 0.096%; protein-coding 3rd codon = 0.22%; CR = 0.35%), and CR phylogenetic signal was congruent with protein-coding regions. Second, the hypothesis that slow substitution rates reduced diversity throughout the sperm whale mitogenome was rejected as sperm whales had significantly higher rates of CR evolution and no evidence of slow coding region evolution relative to other cetaceans. The estimated time to most recent common ancestor for sperm whale mitogenomes was 72,800 to 137,400 years ago (95% highest probability density interval), consistent with previous hypotheses of a bottleneck or selective sweep as likely causes of low mitogenome diversity. PMID:23254394

Low diversity in the mitogenome of sperm whales revealed by next-generation sequencing.

PubMed

Alexander, Alana; Steel, Debbie; Slikas, Beth; Hoekzema, Kendra; Carraher, Colm; Parks, Matthew; Cronn, Richard; Baker, C Scott

2013-01-01

Large population sizes and global distributions generally associate with high mitochondrial DNA control region (CR) diversity. The sperm whale (Physeter macrocephalus) is an exception, showing low CR diversity relative to other cetaceans; however, diversity levels throughout the remainder of the sperm whale mitogenome are unknown. We sequenced 20 mitogenomes from 17 sperm whales representative of worldwide diversity using Next Generation Sequencing (NGS) technologies (Illumina GAIIx, Roche 454 GS Junior). Resequencing of three individuals with both NGS platforms and partial Sanger sequencing showed low discrepancy rates (454-Illumina: 0.0071%; Sanger-Illumina: 0.0034%; and Sanger-454: 0.0023%) confirming suitability of both NGS platforms for investigating low mitogenomic diversity. Using the 17 sperm whale mitogenomes in a phylogenetic reconstruction with 41 other species, including 11 new dolphin mitogenomes, we tested two hypotheses for the low CR diversity. First, the hypothesis that CR-specific constraints have reduced diversity solely in the CR was rejected as diversity was low throughout the mitogenome, not just in the CR (overall diversity π = 0.096%; protein-coding 3rd codon = 0.22%; CR = 0.35%), and CR phylogenetic signal was congruent with protein-coding regions. Second, the hypothesis that slow substitution rates reduced diversity throughout the sperm whale mitogenome was rejected as sperm whales had significantly higher rates of CR evolution and no evidence of slow coding region evolution relative to other cetaceans. The estimated time to most recent common ancestor for sperm whale mitogenomes was 72,800 to 137,400 years ago (95% highest probability density interval), consistent with previous hypotheses of a bottleneck or selective sweep as likely causes of low mitogenome diversity.

Trivalent chromium induces oxidative stress in goldfish brain.

PubMed

Lushchak, Oleh V; Kubrak, Olha I; Torous, Ihor M; Nazarchuk, Tetyana Yu; Storey, Kenneth B; Lushchak, Volodymyr I

2009-03-01

Although information on the effects of Cr(6+) in biological systems is abundant, Cr(3+) has received less attention. Toxic effects of chromium compounds are partially associated with activation of redox processes. Recently we found that Cr(6+) induced oxidative stress in goldfish tissues and the glutathione system was shown to play a protective role. The present study aimed to investigate free radical processes in brain of goldfish exposed to CrCl(3). Trivalent chromium at a concentration of 50 mg L(-1) was lethal and therefore we chose to examine sublethal dosages of 1.0-10.0 mg L(-1) in aquarium water. The levels of lipid peroxides and protein carbonyls (measures of oxidative damage to lipids and proteins) in brain increased after 96 h exposure of goldfish to Cr(3+). However, exposure to 1.0-10.0 mg L(-1) Cr(3+) decreased total glutathione concentration in brain by approximately 50-60%. Oxidized glutathione levels also fell by approximately 40-60% except at the 10.0 mg L(-1) dosage where they decreased by 85%. Therefore, 10.0 mg L(-1) Cr(3+) significantly reduced the ratio [GSSG]/[totalGSH] to 35% of the control value. Chromium treatment did not affect the activity of superoxide dismutase, but reduced the activities of catalase by 55-62% and glutathione-S-transferase by 14-21%. The activities of glucose-6-phosphate dehydrogenase and glutathione reductase were unchanged under any experimental conditions used. Therefore, it can be concluded that although Cr(3+) exposure induced oxidative stress in goldfish brain, it failed to enhance the efficiency of the antioxidant system in the organ.

Evaluation of anticollagen type I antibody titers in synovial fluid of both stifle joints and the left shoulder joint of dogs with unilateral cranial cruciate disease.

PubMed

de Bruin, Tanya; de Rooster, Hilde; van Bree, Henri; Cox, Eric

2007-03-01

To evaluate anticollagen type I antibodies in synovial fluid of the affected stifle joint, the contralateral stifle joint, and the left shoulder joint of dogs with unilateral cranial cruciate ligament (CrCL) rupture during an extended period of 12 to 18 months. 13 client-owned dogs with CrCL rupture and 2 sham-operated dogs. All dogs were examined and arthrocentesis of all 3 joints was performed every 6 months after surgery. Synovial fluid samples were tested for anticollagen type I antibodies by use of an ELISA. Dogs with partial CrCL rupture had higher antibody titers than dogs with complete rupture. Six of 13 dogs ruptured the contralateral CrCL during the study, whereby higher antibody titers were found for the stifle joints than for the shoulder joint. Seronegative dogs or dogs with extremely low antibody titers and 2 dogs with high antibody titers did not sustain a CrCL rupture in the contralateral stifle joint. In most dogs that had a CrCL rupture of the contralateral stifle joint, a distinct antibody titer gradient toward the stifle joints was detected, suggesting that there was a local inflammatory process in these joints. However, only a small number of sham-operated dogs were used to calculate the cutoff values used to determine the anticollagen type I antibody titers in these patients. Synovial fluid antibodies against collagen type I alone do not initiate CrCL rupture because not all dogs with high antibody titers sustained a CrCL rupture in the contralateral stifle joint.

Effluent concentration and removal efficiency of nine heavy metals in secondary treatment plants in Shanghai, China.

PubMed

Feng, Jingjing; Chen, Xiaolin; Jia, Lei; Liu, Qizhen; Chen, Xiaojia; Han, Deming; Cheng, Jinping

2018-04-10

Wastewater treatment plants (WWTPs) are the most common form of industrial and municipal wastewater control. To evaluate the performance of wastewater treatment and the potential risk of treated wastewater to aquatic life and human health, the influent and effluent concentrations of nine toxic metals were determined in 12 full-scale WWTPs in Shanghai, China. The performance was evaluated based on national standards for reclamation and aquatic criteria published by US EPA, and by comparison with other full-scale WWTPs in different countries. Potential sources of heavy metals were recognized using partial correlation analysis, hierarchical clustering, and principal component analysis (PCA). Results indicated significant treatment effect on As, Cd, Cr, Cu, Hg, Mn, Pb, and Zn. The removal efficiencies ranged from 92% (Cr) to 16.7% (Hg). The results indicated potential acute and/or chronic effect of Cu, Ni, Pb, and Zn on aquatic life and potential harmful effect of As and Mn on human health for the consumption of water and/or organism. The results of partial correlation analysis, hierarchical clustering based on cosine distance, and PCA, which were consistent with each other, suggested common source of Cd, Cr, Cu, and Pb and common source of As, Hg, Mn, Ni, and Zn. Hierarchical clustering based on Jaccard similarity suggested common source of Cd, Hg, and Ni, which was statistically proved by Fisher's exact test.

Evaluation of metal ion release from Ti6Al4V and Co-Cr-Mo casting alloys: in vivo and in vitro study.

PubMed

El Sawy, Amal A; Shaarawy, Mohammed A

2014-02-01

The aim of this study was to evaluate the amount of ions released from Ti6Al4V and Co-Cr-Mo alloys both in vivo and in vitro. Twenty-one discs of each alloy were constructed and divided into seven groups. Three specimens from each group were immersed in a buffered saline solution over a period of 1, 3, 5, 7, 14, 21, and 28 days. Twenty-eight participants were also included in the study, where the study group consisted of 14 mandibular partially edentulous patients, and the control group consisted of 14 volunteers. The study group was further divided into two equal groups: the first group received removable partial dentures (RPDs) constructed from Co-Cr-Mo alloy, while the second group received RPDs constructed from Ti6Al4V alloy. Saliva samples were collected from each participant over the same study period. The conditioning media and saliva samples were analyzed using a spectrophotometer. One-way ANOVA and Tukey tests were used for statistical analysis (p < 0.05). The concentrations of metal ions released from the studied alloys were significantly higher in the in vitro than in the in vivo study group during the follow-up periods. A statistically significant increase in ion concentrations of the different elements for both alloys was found with time (p < 0.05). The amounts of released metallic ions from Co-Cr-Mo and Ti6Al4V alloys were higher in the buffered saline solutions than in the studied saliva samples and control groups; however, these amounts were still within the physiological limit of trace elements in the human body. © 2013 by the American College of Prosthodontists.

The structure, surface topography and mechanical properties of Si-C-N films fabricated by RF and DC magnetron sputtering

NASA Astrophysics Data System (ADS)

Shi, Zhifeng; Wang, Yingjun; Du, Chang; Huang, Nan; Wang, Lin; Ning, Chengyun

2011-12-01

Silicon carbon nitride thin films were deposited on Co-Cr alloy under varying deposition conditions such as sputtering power and the partial pressure ratio of N2 to Ar by radio frequency and direct current magnetron sputtering techniques. The chemical bonding configurations, surface topography and hardness were characterized by means of X-ray photoelectron spectroscopy, atomic force microscopy and nano-indentation technique. The sputtering power exhibited important influence on the film composition, chemical bonding configurations and surface topography, the electro-negativity had primary effects on chemical bonding configurations at low sputtering power. A progressive densification of the film microstructure occurring with the carbon fraction was increased. The films prepared by RF magnetron sputtering, the relative content of the Si-N bond in the films increased with the sputtering power increased, and Si-C and Si-Si were easily detachable, and C-O, N-N and N-O on the film volatile by ion bombardment which takes place very frequently during the film formation process. With the increase of sputtering power, the films became smoother and with finer particle growth. The hardness varied between 6 GPa and 11.23 GPa depending on the partial pressure ratio of N2 to Ar. The tribological characterization of Co-Cr alloy with Si-C-N coating sliding against UHMWPE counter-surface in fetal bovine serum, shows that the wear resistance of the Si-C-N coated Co-Cr alloy/UHMWPE sliding pair show much favourable improvement over that of uncoated Co-Cr alloy/UHMWPE sliding pair. This study is important for the development of advanced coatings with tailored mechanical and tribological properties.

Dandelion Taraxacum linearisquameum does not reflect soil metal content in urban localities.

PubMed

Kováčik, Jozef; Dudáš, Matej; Hedbavny, Josef; Mártonfi, Pavol

2016-11-01

Accumulation of selected heavy metals (Cd, Pb, Ni, Cr, Fe, and Zn) and phenolic metabolites (total soluble phenols, cichoric and caftaric acid) in dandelion organs (leaves, roots, inflorescences/anthodia) collected from six localities within the industrial town Košice (eastern Slovakia) were studied. Localities from the vicinity of a steel factory (Cd, Fe) and heavy traffic (Pb, Ni, Cr, Zn) contained the highest amount of individual metals in the soil but a significant correlation between soil and organ metal content was found only for Cr in the leaves (r 2  = 0.7679). The amount of Cd and partially Pb differed among localities in all organs and especially in the leaves and anthodia, indicating probably the impact of atmospheric pollution. The bioaccumulation factor was <1 for almost all metals, suggesting that given dandelion species is not metal accumulator. Translocation factor did not reach values close to or over 1 only for Cd, indicating a root-to-shoot movement of Pb, Ni and Zn though the impact of air pollution on leaves cannot be excluded. A strong correlation between leaf Cd and leaf total phenols, cichoric and caftaric acids was observed (r 2  = 0.7926, 0.8682 and 0.8830, respectively), indicating that phenolic metabolites act in the protection of dandelion against Cd excess. Overall, our data indicate low pollution of urban soil by Cd (5.53-113.8 ng g -1 ) and partially by Cr and the suitability of above-ground organs of dandelion species for the monitoring of air pollution mainly by Cd. Copyright © 2016 Elsevier Ltd. All rights reserved.

Chromium Enhances Insulin Responsiveness via AMPK

PubMed Central

Hoffman, Nolan J.; Penque, Brent A.; Habegger, Kirk M.; Sealls, Whitney; Tackett, Lixuan; Elmendorf, Jeffrey S.

2014-01-01

Trivalent chromium (Cr3+) is known to improve glucose homeostasis. Cr3+ has been shown to improve plasma membrane-based aspects of glucose transporter GLUT4 regulation and increase activity of the cellular energy sensor 5′ AMP-activated protein kinase (AMPK). However, the mechanism(s) by which Cr3+ improves insulin responsiveness and whether AMPK mediates this action is not known. In this study we tested if Cr3+ protected against physiological hyperinsulinemia-induced plasma membrane cholesterol accumulation, cortical filamentous actin (F-actin) loss and insulin resistance in L6 skeletal muscle myotubes. In addition, we performed mechanistic studies to test our hypothesis that AMPK mediates the effects of Cr3+ on GLUT4 and glucose transport regulation. Hyperinsulinemia-induced insulin-resistant L6 myotubes displayed excess membrane cholesterol and diminished cortical F-actin essential for effective glucose transport regulation. These membrane and cytoskeletal abnormalities were associated with defects in insulin-stimulated GLUT4 translocation and glucose transport. Supplementing the culture medium with pharmacologically relevant doses of Cr3+ in the picolinate form (CrPic) protected against membrane cholesterol accumulation, F-actin loss, GLUT4 dysregulation and glucose transport dysfunction. Insulin signaling was neither impaired by hyperinsulinemic conditions nor enhanced by CrPic, whereas CrPic increased AMPK signaling. Mechanistically, siRNA-mediated depletion of AMPK abolished the protective effects of CrPic against GLUT4 and glucose transport dysregulation. Together these findings suggest that the micronutrient Cr3+, via increasing AMPK activity, positively impacts skeletal muscle cell insulin sensitivity and glucose transport regulation. PMID:24725432

The effects of graded levels of calorie restriction: XI. Evaluation of the main hypotheses underpinning the life extension effects of CR using the hepatic transcriptome.

PubMed

Derous, Davina; Mitchell, Sharon E; Wang, Lu; Green, Cara L; Wang, Yingchun; Chen, Luonan; Han, Jing-Dong J; Promislow, Daniel E L; Lusseau, David; Douglas, Alex; Speakman, John R

2017-07-31

Calorie restriction (CR) may extend longevity by modulating the mechanisms involved in aging. Different hypotheses have been proposed for its main mode of action. We quantified hepatic transcripts of male C57BL/6 mice exposed to graded levels of CR (0% to 40% CR) for three months, and evaluated the responses relative to these various hypotheses. Of the four main signaling pathways implied to be linked to the impact of CR on lifespan (insulin/insulin like growth factor 1 (IGF-1), nuclear factor-kappa beta (NF-ĸB), mechanistic target of rapamycin (mTOR) and sirtuins (SIRTs)), all the pathways except SIRT were altered in a manner consistent with increased lifespan. However, the expression levels of SIRT4 and SIRT7 were decreased with increasing levels of CR. Changes consistent with altered fuel utilization under CR may reduce reactive oxygen species production, which was paralleled by reduced protection. Downregulated major urinary protein (MUP) transcription suggested reduced reproductive investment. Graded CR had a positive effect on autophagy and xenobiotic metabolism, and was protective with respect to cancer signaling. CR had no significant effect on fibroblast growth factor-21 (FGF21) transcription but affected transcription in the hydrogen sulfide production pathway. Responses to CR were consistent with several different hypotheses, and the benefits of CR on lifespan likely reflect the combined impact on multiple aging related processes.

The effects of graded levels of calorie restriction: XI. Evaluation of the main hypotheses underpinning the life extension effects of CR using the hepatic transcriptome

PubMed Central

Derous, Davina; Mitchell, Sharon E.; Wang, Lu; Green, Cara L.; Wang, Yingchun; Chen, Luonan; Han, Jing-Dong J.; Promislow, Daniel E.L.; Lusseau, David; Douglas, Alex; Speakman, John R.

2017-01-01

Calorie restriction (CR) may extend longevity by modulating the mechanisms involved in aging. Different hypotheses have been proposed for its main mode of action. We quantified hepatic transcripts of male C57BL/6 mice exposed to graded levels of CR (0% to 40% CR) for three months, and evaluated the responses relative to these various hypotheses. Of the four main signaling pathways implied to be linked to the impact of CR on lifespan (insulin/insulin like growth factor 1 (IGF-1), nuclear factor-kappa beta (NF-ĸB), mechanistic target of rapamycin (mTOR) and sirtuins (SIRTs)), all the pathways except SIRT were altered in a manner consistent with increased lifespan. However, the expression levels of SIRT4 and SIRT7 were decreased with increasing levels of CR. Changes consistent with altered fuel utilization under CR may reduce reactive oxygen species production, which was paralleled by reduced protection. Downregulated major urinary protein (MUP) transcription suggested reduced reproductive investment. Graded CR had a positive effect on autophagy and xenobiotic metabolism, and was protective with respect to cancer signaling. CR had no significant effect on fibroblast growth factor-21 (FGF21) transcription but affected transcription in the hydrogen sulfide production pathway. Responses to CR were consistent with several different hypotheses, and the benefits of CR on lifespan likely reflect the combined impact on multiple aging related processes. PMID:28768896

A Multi-responsive Regenerable Europium-Organic Framework Luminescent Sensor for Fe3+ , CrVI Anions, and Picric Acid.

PubMed

Liu, Wei; Huang, Xin; Xu, Cong; Chen, Chunyang; Yang, Lizi; Dou, Wei; Chen, Wanmin; Yang, Huan; Liu, Weisheng

2016-12-23

A novel luminescent microporous lanthanide metal-organic framework (Ln-MOF) based on a urea-containing ligand has been successfully assembled. Structural analysis revealed that the framework features two types of 1D channels, with urea N-H bonds projecting into the pores. Luminescence studies have revealed that the Ln-MOF exhibits high sensitivity, good selectivity, and a fast luminescence quenching response towards Fe 3+ , Cr VI anions, and picric acid. In particular, in the detection of Cr 2 O 7 2- and picric acid, the Ln-MOF can be simply and quickly regenerated, thus exhibiting excellent recyclability. To the best of our knowledge, this is the first example of a multi-responsive luminescent Ln-MOF sensor for Fe 3+ , Cr VI anions, and picric acid based on a urea derivative. This Ln-MOF may potentially be used as a multi-responsive regenerable luminescent sensor for the quantitative detection of toxic and harmful substances. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Lung Inflammation, Injury, and Proliferative Response after Repetitive Particulate Hexavalent Chromium Exposure

PubMed Central

Beaver, Laura M.; Stemmy, Erik J.; Schwartz, Arnold M.; Damsker, Jesse M.; Constant, Stephanie L.; Ceryak, Susan M.; Patierno, Steven R.

2009-01-01

Background Chronic inflammation is implicated in the development of several human cancers, including lung cancer. Certain particulate hexavalent chromium [Cr(VI)] compounds are well-documented human respiratory carcinogens that release genotoxic soluble chromate and are associated with fibrosis, fibrosarcomas, adenocarcinomas, and squamous cell carcinomas of the lung. Despite this, little is known about the pathologic injury and immune responses after repetitive exposure to particulate chromates. Objectives In this study we investigated the lung injury, inflammation, proliferation, and survival signaling responses after repetitive exposure to particulate chromate. Methods BALB/c mice were repetitively treated with particulate basic zinc chromate or saline using an intranasal exposure regimen. We assessed lungs for Cr(VI)-induced changes by bronchoalveolar lavage, histologic examination, and immunohistochemistry. Results Single exposure to Cr(VI) resulted in inflammation of lung tissue that persists for up to 21 days. Repetitive Cr(VI) exposure induced a neutrophilic inflammatory airway response 24 hr after each treatment. Neutrophils were subsequently replaced by increasing numbers of macrophages by 5 days after treatment. Repetitive Cr(VI) exposure induced chronic peribronchial inflammation with alveolar and interstitial pneumonitis dominated by lymphocytes and macrophages. Moreover, chronic toxic mucosal injury was observed and accompanied by increased airway pro-matrix metalloprotease-9. Injury and inflammation correlated with airways becoming immunoreactive for phosphorylation of the survival signaling protein Akt and the proliferation marker Ki-67. We observed a reactive proliferative response in epithelial cells lining airways of chromate-exposed animals. Conclusions These data illustrate that repetitive exposure to particulate chromate induces chronic injury and an inflammatory microenvironment that may promote Cr(VI) carcinogenesis. PMID:20049209

Changes on aggregation in mine waste amended with biochar and marble mud

NASA Astrophysics Data System (ADS)

Ángeles Muñoz, María; Guzmán, Jose; Zornoza, Raúl; Moreno-Barriga, Fabián; Faz, Ángel; Lal, Rattan

2016-04-01

Mining activities have produced large amounts of wastes over centuries accumulated in tailing ponds in Southeast Spain. Applications of biochar may have a high potential for reclamation of degraded soils. Distribution, size and stability of aggregates are important indices of soil physical quality. However, research data on aggregation processes at amended mining tailings with biochar are scanty. Therefore, the aim of this study was to determine the effects of seven different treatments involving biochar and marble mud (MM) on the aggregation in mine waste (MW). Seven different treatments were tested after 90 days of incubation in the laboratory. These treatments were the mix of MW and: biochar from solid pig manure (PM), biochar from cotton crop residues (CR), biochar from municipal solid waste (MSW), marble mud (MM), PM+MM, CR+MM, MSW+MM and control without amendment. High sand percentages were identified in the MW. The biochars made from wastes (PM, CR, MSW) were obtained through pyrolysis of feedstocks. The water stability of soil aggregates was studied. The data on total aggregation were corrected for the primary particles considering the sandy texture of the MW. Moreover, partial aggregation was determined for each fraction and the mean weight diameter (MWD) of aggregates was computed. Soil bulk density and total porosity were also determined. No significant differences were observed in total aggregation and MWD among treatments including the control. For the size range of >4.75 mm, there were significant differences in aggregates > 4.75 mm between CR+MM in comparison with that for CT. There were also significant differences between MSW and PM+MM for the 1-0.425 mm fraction, and between CT and MM and CR for 0.425-0.162 mm aggregate size fractions. Therefore, CR-derived biochar applied with MM enhanced stability of macro-aggregates. Furthermore, soil bulk density was also the lowest bulk density and total porosity the highest for the CR-derived biochar treatment because macro aggregate stability is largely responsible for macro-porosity. The decrease in bulk density may be an indication of a positive effect for mine waste reclamation. Conversely, no differences were observed among treatments in micro-aggregate stability. Apparently, low organic matter contents in MW needed to be co-amended with labile organic amendments to effectively increase soil aggregation. Furthermore, the presence of Fe hydroxides could also increase the micro-aggregation. Additional research is needed to understand the mechanisms of mine soil reclamation. Acknowledgement : This work has been funded by Fundación Séneca (Agency of Science and Technology of the Region of Murcia, Spain

Impact of Race, Ethnicity and BMI on Achievement of Pathologic Complete Response Following Neoadjuvant Chemotherapy for Breast Cancer: A Pooled Analysis of Four Prospective Alliance Clinical Trials (A151426)

PubMed Central

Warner, Erica T.; Ballman, Karla V.; Strand, Carrie; Boughey, Judy; Buzdar, Aman U.; Carey, Lisa A.; Sikov, William M.; Partridge, H.

2016-01-01

Purpose Previous studies demonstrated poor response to neoadjuvant systemic therapy (NST) for breast cancer among black women and women who are overweight or obese but this may be due to chemotherapy under dosing. We assessed associations of race, ethnicity and body mass index (BMI) with pathologic complete response (pCR) in clinical trial populations. Methods 1797 women enrolled in four NST trials (CALGB 40601, 40603; ACOSOG Z1041, Z1071) were included. Tumor subtypes were defined by estrogen receptor (ER) and HER2 status. Logistic regression generated odds ratios (OR) and 95% confidence intervals (CI) for the associations of race, ethnicity, and BMI with pCR adjusting for subtype, study arm, lymph node status, tumor size, and tumor grade. Results 253 (14.1%) were black, 199 (11.1%) Hispanic, 520 (28.9%) overweight, and 743 (41.4%) obese. Compared to whites, Blacks and Hispanics were more likely to be obese and Blacks were more likely to have triple-negative cancer. pCR rates differed significantly by tumor subtype. In multivariate analyses, neither race (black vs. white: OR: 1.18, 95% CI: 0.85–1.62) nor ethnicity (Hispanic vs. non-Hispanic: OR: 1.30, 95% CI: 0.67–2.53) were significant predictors of pCR overall or by subtype. Overweight and obese women had lower pCR rates in ER+/HER2+, but higher pCR rates in ER−/HER2+ cancers. Conclusions There was no difference in breast pCR according to race or ethnicity. Overall, there was no major difference in pCR rates by BMI. These findings suggest that pCR with optimally dosed NST is a function of tumor, rather than patient, biology. PMID:27449492

Impact of race, ethnicity, and BMI on achievement of pathologic complete response following neoadjuvant chemotherapy for breast cancer: a pooled analysis of four prospective Alliance clinical trials (A151426).

PubMed

Warner, Erica T; Ballman, Karla V; Strand, Carrie; Boughey, Judy C; Buzdar, Aman U; Carey, Lisa A; Sikov, William M; Partridge, Ann H

2016-08-01

Previous studies demonstrated poor response to neoadjuvant systemic therapy (NST) for breast cancer among black women and women who are overweight or obese, but this may be due to chemotherapy underdosing. We assessed associations of race, ethnicity, and body mass index (BMI) with pathologic complete response (pCR) in clinical trial populations. 1797 women enrolled in four NST trials (CALGB 40601, 40603; ACOSOG Z1041, Z1071) were included. Tumor subtypes were defined by estrogen receptor (ER) and HER2 status. Logistic regression generated odds ratios (OR) and 95 % confidence intervals (CI) for the associations of race, ethnicity, and BMI with in-breast pCR adjusting for subtype, study arm, lymph node status, tumor size, and tumor grade. 253 (14.1 %) were black, 199 (11.1 %) Hispanic, 520 (28.9 %) overweight, and 743 (41.4 %) obese. Compared to whites, Blacks and Hispanics were more likely to be obese and Blacks were more likely to have triple-negative cancer. pCR rates differed significantly by tumor subtype. In multivariate analyses, neither race (black vs white: OR 1.18, 95 % CI 0.85-1.62) nor ethnicity (Hispanic vs non-Hispanic; OR 1.30, 95 % CI 0.67-2.53) were significant predictors of pCR overall or by subtype. Overweight and obese women had lower pCR rates in ER+/HER2+, but higher pCR rates in ER-/HER2+ cancers. There was no difference in pCR according to race or ethnicity. Overall, there was no major difference in pCR rates by BMI. These findings suggest that pCR with optimally dosed NST is a function of tumor, rather than patient, biology.

The role of quantitative estrogen receptor status in predicting tumor response at surgery in breast cancer patients treated with neoadjuvant chemotherapy.

PubMed

Raphael, Jacques; Gandhi, Sonal; Li, Nim; Lu, Fang-I; Trudeau, Maureen

2017-07-01

Estrogen receptor (ER) negative (-) breast cancer (BC) patients have better tumor response rates than ER-positive (+) patients after neoadjuvant chemotherapy (NCT). We conducted a retrospective review using the institutional database "Biomatrix" to assess the value of quantitative ER status in predicting tumor response at surgery and to identify potential predictors of survival outcomes. Univariate followed by multivariable regression analyses were conducted to assess the association between quantitative ER and tumor response assessed as tumor size reduction and pathologic complete response (pCR). Predictors of recurrence-free survival (RFS) were identified using a cox proportional hazards model (CPH). A log-rank test was used to compare RFS between groups if a significant predictor was identified. 304 patients were included with a median follow-up of 43.3 months (Q1-Q3 28.7-61.1) and a mean age of 49.7 years (SD 10.9). Quantitative ER was inversely associated with tumor size reduction and pCR (OR 0.99, 95% CI 0.99-1.00, p = 0.027 and 0.98 95% CI 0.97-0.99, p < 0.0001, respectively). A cut-off of 60 and 80% predicted best the association with tumor size reduction and pCR, respectively. pCR was shown to be an independent predictor of RFS (HR 0.17, 95% CI 0.07-0.43, p = 0.0002) in all patients. At 5 years, 93% of patients with pCR and 72% of patients with residual tumor were recurrence-free, respectively (p = 0.0012). Quantitative ER status is inversely associated with tumor response in BC patients treated with NCT. A cut-off of 60 and 80% predicts best the association with tumor size reduction and pCR, respectively. Therefore, patients with an ER status higher than the cut-off might benefit from a neoadjuvant endocrine therapy approach. Patients with pCR had better survival outcomes independently of their tumor phenotype. Further prospective studies are needed to validate the clinical utility of quantitative ER as a predictive marker of tumor response.

Clinical and imaging features in different inner border-zone infarct patterns.

PubMed

Wang, Yujie; Wang, Jian

2015-03-01

The clinical and imaging features of different inner border-zone infarct patterns, corona radiata (CR) and centrum semiovale (CSO), is not quiet clear. Both are mostly reported together in previous studies. We intended to observe their clinical and imaging features. We observed 83 patients-47 cases with CR infarct lesion pattern and 36 cases with CSO. The lesion patterns were determined by diffusion-weighted imaging. Basic, clinical and radiologic features were compared between the patients with CR and CSO infarct lesion patterns. There was no significant difference between CR and CSO infarct patterns in terms of risk factors. However, patients with CR infarct had a higher initial National Institutes of Health Stroke Scale (NIHSS) score at admission (5.2 ± 2.3) than with CSO (3.9 ± 2.0, p = 0.009). Early clinical deterioration (OR, 2.42; 95% CI, 1.12-5.21; p = 0.024) and middle cerebral artery (MCA) stenosis (OR, 10.31; 95% CI, 3.30-32.19; p < 0.0001) were independently associated with the CR infarct lesion pattern. Partial infarct lesion shape (OR, 5.95; 95% CI, 1.40-25.33; p = 0.016) and internal carotid artery (ICA) stenosis (OR, 5.28; 95% CI, 1.92-14.51; p = 0.001) were independently correlated with the CSO infarct lesion pattern. Although CR and CSO infarct patterns might share common etiology and mechanisms, their clinical and imaging features are different.

Meta-analysis on the association between pathologic complete response and triple-negative breast cancer after neoadjuvant chemotherapy.

PubMed

Wu, Kunpeng; Yang, Qiaozhu; Liu, Yi; Wu, Aibing; Yang, Zhixiong

2014-04-15

Triple-negative breast cancer (TNBC) is a special subtype of breast cancer that is characterized by poor prognosis, strong tumor invasion and a high pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC). The pCR rate is a prognostic factor for TNBC. We aimed to evaluate the relationship between pCR and TNBC after NAC and originally tried to identify factors related to achieving pCR for TNBC using a meta-analysis. We systematically searched the literature for pCR and breast cancer after NAC and carefully identified eligibility criteria. The association between pCR and breast cancer subtypes was estimated using Review Manager, while pCR rates for TNBC and non-TNBC were determined using Meta-Analyst. This analysis included a total of 9,460 cases from 27 studies. The summary odds ratio estimating the relationship between pCR and breast cancer subtypes (TNBC vs non-TNBC) was 3.02 (95% confidence interval (CI), 2.66 to 3.42). The TNBC pCR rate was 28.9% (95% CI, 27.0 to 30.8%) and the non-TNBC was 12.5% (95% CI, 11.7 to 13.4%). From subgroup analyses, we identified the factors associated with the highest pCR rates for TNBC. TNBC has a higher pCR rate than non-TNBC. In the NAC setting, these factors of platinum-containing, more than six cycles, four kinds of drugs, 16 weeks' treatment duration and sequential chemotherapy may contribute to increasing the pCR rate.

Chromium precipitation from tanning spent liquors using industrial alkaline residues: A comparative study

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

Fonseca Almeida, M.A.; Boaventura, R.A.R.

1998-07-01

Chromium precipitation from spent tanning liquors using industrial alkaline tailings is described and removal efficiencies are compared with those obtained with traditional chemicals as NaOH, CaO and MgO: (1) using steelmaking dusts at dosages up to 70 g/l residual Cr remains {ge} 3.7 mg/l. Moreover Cr and mainly Pb are partially leached by the spent tanning liquor, therefore limiting the use of this industrial residue as Cr precipitant; (2) a dosage of 80 g/l (dry basis) of chemical sludge from a water treatment plant results in a removal efficiency of 99.97% Cr and residual Cr {le} 2 mg/l under experimentalmore » conditions that include stirring at 100 rpm for 1 h and settling for 23 h. Sedimentation time may be reduced to 2 h if stirring is extended to 2 h. Resulting sludge volume is about 400 ml/l. However, during Cr precipitation, Al is leached form the added product up to about 40 mg Al per liter of supernatant; (3) precipitation using acetylene production sludge only requires a dosage of 16 g/l (dry basis) to remove 99.96% Cr after stirring for 1 h and settling for 2 h. The soluble Cr concentration in the clarified effluent is {le} 2 mg/l and the sludge volume about 500 ml/l. This Cr level can also be achieved at a dosage of 14 g/l, provided the stirring time is increased to 3 h; (4) these results are comparable with those using either CaO or MgO at similar dosages; and (5) NaOH at dosages between 6.4 and 14 g/l proved to be not sufficiently effective for Cr precipitation. Although removal efficiencies up to 99.9% are achieved, residual Cr is always above 8.7 mg/l. Additionally, the resulting sludge is not very dense, thus leading to high sludge volume production.« less

Combined nano-biotechnology for in-situ remediation of mixed contamination of groundwater by hexavalent chromium and chlorinated solvents.

PubMed

Němeček, Jan; Pokorný, Petr; Lhotský, Ondřej; Knytl, Vladislav; Najmanová, Petra; Steinová, Jana; Černík, Miroslav; Filipová, Alena; Filip, Jan; Cajthaml, Tomáš

2016-09-01

The present report describes a 13month pilot remediation study that consists of a combination of Cr(VI) (4.4 to 57mg/l) geofixation and dechlorination of chlorinated ethenes (400 to 6526μg/l), achieved by the sequential use of nanoscale zerovalent iron (nZVI) particles and in situ biotic reduction supported by whey injection. The remediation process was monitored using numerous techniques, including physical-chemical analyses and molecular biology approaches which enabled both the characterization of the mechanisms involved in pollutant transformation and the description of the overall background processes of the treatment. The results revealed that nZVI was efficient toward Cr(VI) by itself and completely removed it from the groundwater (LOQ 0.05mg/l) and the subsequent application of whey resulted in a high removal of chlorinated ethenes (97 to 99%). The persistence of the reducing conditions, even after the depletion of the organic substrates, indicated a complementarity between nZVI and the whey phases in the combined technology as the subsequent application of whey phase partially assisted the microbial regeneration of the spent nZVI by promoting its reduction into Fe(II), which further supported remediation conditions at the site. Illumina sequencing and the detection of functional vcrA and bvcA genes documented a development in the reducing microbes (iron-reducing, sulfate-reducing and chlororespiring bacteria) that benefited under the conditions of the site and that was probably responsible for the high dechlorination and/or Cr(VI) reduction. The results of this study demonstrate the feasibility and high efficiency of the combined nano-biotechnological approach of nZVI and whey application in-situ for the removal of Cr(VI) and chlorinated ethenes from the groundwater of the contaminated site. Copyright © 2016 Elsevier B.V. All rights reserved.

Transition metal partially supported graphene: Magnetism and oscillatory electrostatic potentials

DOE PAGES

Liu, Xiaojie; Wang, Cai-Zhuang

2017-08-07

Using first-principles calculations here, we show that Mn and Cr layers under graphene exhibit almost zero magnetic moment due to anti-ferromagnetic order, while ferromagnetic coupling in Fe, Co, and Ni leads to large magnetic moment. The transition metal partially supported graphene, with a mixture of supported and pristine areas, exhibits an oscillatory electrostatic potential, thus alternating the electric field across the supported and pristine areas. Such an effect can be utilized to control mass transport and nanostructure self-organization on graphene at the atomic level.

Transition metal partially supported graphene: Magnetism and oscillatory electrostatic potentials

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

Liu, Xiaojie; Wang, Cai-Zhuang

Using first-principles calculations here, we show that Mn and Cr layers under graphene exhibit almost zero magnetic moment due to anti-ferromagnetic order, while ferromagnetic coupling in Fe, Co, and Ni leads to large magnetic moment. The transition metal partially supported graphene, with a mixture of supported and pristine areas, exhibits an oscillatory electrostatic potential, thus alternating the electric field across the supported and pristine areas. Such an effect can be utilized to control mass transport and nanostructure self-organization on graphene at the atomic level.

Flight Termination Systems Commonality Standard

DTIC Science & Technology

2014-09-01

input level is increased 60 dB from threshold. Corona : A visible electric discharge resulting from a partial electric breakdown of gases as the...4-49 Figure 4-10. Electrostatic Discharge Test...check channel telemetry output (EFTR) CDR critical design review CFS flight self- discharge in amp-hrs CR remaining capacity for determining

Modeling Cr-to-Tm and Cr-to-Tm-to-Ho energy transfer in YAG crystals

NASA Technical Reports Server (NTRS)

Swetits, John J.

1991-01-01

A systematic analysis of energy transfer processes in crystals of YAG doped with varying concentrations of Cr and Tm is described. Both spectral measurements and measurements of the temporal response to pulsed excitation are used to give independent determinations of the microscopic interaction parameter for Cr to Tm transfer. The different factors in influencing the temperature dependence of the Cr to Tm transfer are discussed. The dependence of the Tm cross-relaxation rate on Tm concentration is determined.

Effects of Cr(III) and CR(VI) on nitrification inhibition as determined by SOUR, function-specific gene expression and 16S rRNA sequence analysis of wastewater nitrifying enrichments

EPA Science Inventory

The effect of Cr(III) and Cr(VI) on ammonia oxidation, the transcriptional responses of functional genes involved in nitrification and changes in 16S rRNA level sequences were examined in nitrifying enrichment cultures. The nitrifying bioreactor was operated as a continuous react...

Allogeneic hematopoietic cell transplantation for consolidation of VGPR or CR for newly diagnosed multiple myeloma

PubMed Central

Nishihori, T; Ochoa-Bayona, JL; Kim, J; Pidala, J; Shain, K; Baz, R; Sullivan, D; Jim, HS; Anasetti, C; Alsina, M

2015-01-01

Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative approach in patients with multiple myeloma, but its use for consolidation of first remission has not yet been fully explored. Twenty-two myeloma patients with very good partial response (VGPR) or CR received allogeneic peripheral blood grafts as consolidation from HLA-matched donors between 2007 and 2012. Conditioning regimens were fludarabine (30 mg/m2 i.v. if with bortezomib and 40 mg/m2 i.v. when without bortezomib, ×4 days) plus melphalan (70 mg/m2 intravenously ×2 days) with (n = 13) or without (n = 9) bortezomib (1.3 mg/m2). The cumulative incidence of grades 2–4 acute GVHD at day 100 was 45% (95% CI: 24–65%) and moderate-to-severe chronic GVHD at 2 years was 46% (95% CI: 19–69%). With a median follow-up of 18 (range, 2–61) months, the 2-year PFS estimate is 74.8% (95% CI: 45–90%), which compares favorably with the 52% (95% CI: 35–66%) after autologous HCT for similar patients (a median follow-up of 30 (range, 9–55) months). We are conducting a phase 2 study to assess the efficacy of allogeneic HCT as post-remission therapy. PMID:23542223

An Evolutionarily Conserved DOF-CONSTANS Module Controls Plant Photoperiodic Signaling.

PubMed

Lucas-Reina, Eva; Romero-Campero, Francisco J; Romero, José M; Valverde, Federico

2015-06-01

The response to daylength is a crucial process that evolved very early in plant evolution, entitling the early green eukaryote to predict seasonal variability and attune its physiological responses to the environment. The photoperiod responses evolved into the complex signaling pathways that govern the angiosperm floral transition today. The Chlamydomonas reinhardtii DNA-Binding with One Finger (CrDOF) gene controls transcription in a photoperiod-dependent manner, and its misexpression influences algal growth and viability. In short days, CrDOF enhances CrCO expression, a homolog of plant CONSTANS (CO), by direct binding to its promoter, while it reduces the expression of cell division genes in long days independently of CrCO. In Arabidopsis (Arabidopsis thaliana), transgenic plants overexpressing CrDOF show floral delay and reduced expression of the photoperiodic genes CO and FLOWERING LOCUS T. The conservation of the DOF-CO module during plant evolution could be an important clue to understanding diversification by the inheritance of conserved gene toolkits in key developmental programs. © 2015 American Society of Plant Biologists. All Rights Reserved.

Exposure to Particulate Hexavalent Chromium Exacerbates Allergic Asthma Pathology

PubMed Central

Schneider, Brent C.; Constant, Stephanie L.; Patierno, Steven R.; Jurjus, Rosalyn A.; Ceryak, Susan M.

2011-01-01

Airborne hexavalent chromate, Cr(VI), has been identified by the Environmental Protection Agency as a possible health threat in urban areas, due to the carcinogenic potential of some of its forms. Particulate chromates are produced in many different industrial settings, with high levels of aerosolized forms historically documented. Along with an increased risk of lung cancer, a high incidence of allergic asthma has been reported in workers exposed to certain inhaled particulate Cr(VI) compounds. However, a direct causal association between Cr(VI) and allergic asthma has not been established. We recently showed that inhaled particulate Cr(VI) induces an innate neutrophilic inflammatory response in BALB/c mice. In the current studies we investigated how the inflammation induced by inhaled particulate Cr(VI) might alter the pathology of an allergic asthmatic response. We used a well-established mouse model of allergic asthma. Groups of ovalbumin protein (OVA)-primed mice were challenged either with OVA alone, or with a combination of OVA and particulate zinc chromate, and various parameters associated with asthmatic responses were measured. Co-exposure to particulate Cr(VI) and OVA mediated a mixed form of asthma in which both eosinophils and neutrophils are present in airways, tissue pathology is markedly exacerbated, and airway hyperresponsiveness is significantly increased. Taken together these findings suggest that inhalation of particulate forms of Cr(VI) may augment the severity of ongoing allergic asthma, as well as alter its phenotype. Such findings may have implications for asthmatics in settings in which airborne particulate Cr(VI) compounds are present at high levels. PMID:22178736

Effects of 200 keV Ar-ions irradiation on the structural and optical properties of reactively sputtered CrN films

NASA Astrophysics Data System (ADS)

Novaković, M.; Popović, M.; Zhang, K.; Rakočević, Z.; Bibić, N.

2016-12-01

Modification in structural and optical properties of chromium-nitride (CrN) films induced by argon ion irradiation and thermal annealings were investigated using various experimental techniques. CrN films deposited by d. c. reactive sputtering on Si substrate were implanted with 200 keV argon ions, at fluences of 5-20 × 1015 ions/cm2. As-implanted samples were then annealed in vacuum, for 2 h at 700 °C. Rutherford backscattering spectrometry, X-ray diffraction, cross-sectional (high-resolution) transmission electron microscopy and spectroscopic ellipsometry (SE) measurements were carried out in order to study structural and optical properties of the layers. After irradiation with 200 keV Ar ions a damaged surface layer of nanocrystalline structure was generated, which extended beyond the implantation profile, but left an undamaged bottom zone. Partial loss of columnar structure observed in implanted samples was recovered after annealing at 700 °C and CrN started to decompose to Cr2N. This layer geometry determined from transmission electron microscopy was inferred in the analysis of SE data using the combined Drude and Tauc-Lorentz model, and the variation of the optical bandgap was deduced. The results are discussed on the basis of the changes induced in the microstructure. It was found that the optical properties of the layers are strongly dependent on the defects' concentration of CrN.

Chi-square analysis of the reduction of ATP levels in L-02 hepatocytes by hexavalent chromium.

PubMed

Yuan, Yang; Peng, Li; Gong-Hua, Hu; Lu, Dai; Xia-Li, Zhong; Yu, Zhou; Cai-Gao, Zhong

2012-06-01

This study explored the reduction of adenosine triphosphate (ATP) levels in L-02 hepatocytes by hexavalent chromium (Cr(VI)) using chi-square analysis. Cells were treated with 2, 4, 8, 16, or 32 μM Cr(VI) for 12, 24, or 36 h. Methyl thiazolyl tetrazolium (MTT) experiments and measurements of intracellular ATP levels were performed by spectrophotometry or bioluminescence assays following Cr(VI) treatment. The chi-square test was used to determine the difference between cell survival rate and ATP levels. For the chi-square analysis, the results of the MTT or ATP experiments were transformed into a relative ratio with respect to the control (%). The relative ATP levels increased at 12 h, decreased at 24 h, and increased slightly again at 36 h following 4, 8, 16, 32 μM Cr(VI) treatment, corresponding to a "V-shaped" curve. Furthermore, the results of the chi-square analysis demonstrated a significant difference of the ATP level in the 32-μM Cr(VI) group (P < 0.05). The results suggest that the chi-square test can be applied to analyze the interference effects of Cr(VI) on ATP levels in L-02 hepatocytes. The decreased ATP levels at 24 h indicated disruption of mitochondrial energy metabolism and the slight increase of ATP levels at 36 h indicated partial recovery of mitochondrial function or activated glycolysis in L-02 hepatocytes.

Different threshold and bipolar resistive switching mechanisms in reactively sputtered amorphous undoped and Cr-doped vanadium oxide thin films

NASA Astrophysics Data System (ADS)

Rupp, Jonathan A. J.; Querré, Madec; Kindsmüller, Andreas; Besland, Marie-Paule; Janod, Etienne; Dittmann, Regina; Waser, Rainer; Wouters, Dirk J.

2018-01-01

This study investigates resistive switching in amorphous undoped and Cr-doped vanadium oxide thin films synthesized by sputtering deposition at low oxygen partial pressure. Two different volatile threshold switching characteristics can occur as well as a non-volatile bipolar switching mechanism, depending on device stack symmetry and Cr-doping. The two threshold switching types are associated with different crystalline phases in the conduction filament created during an initial forming step. The first kind of threshold switching, observed for undoped vanadium oxide films, was, by its temperature dependence, proven to be associated with a thermally triggered insulator-to-metal transition in a crystalline VO2 phase, whereas the threshold switch observed in chromium doped films is stable up to 90 °C and shows characteristics of an electronically induced Mott transition. This different behaviour for undoped versus doped films has been attributed to an increased stability of V3+ due to the Cr3+ doping (as evidenced by X-ray photoelectron spectroscopy analysis), probably favouring the creation of a crystalline Cr-doped V2O3 phase (rather than a Cr-doped VO2 phase) during the energetic forming step. The symmetric Pt/a-(VCr)Ox/Pt device showing high temperature stable threshold switching may find interesting applications as a possible new selector device for resistive switching memory (ReRAM) crossbar arrays.

Ionic displacement induced ferroelectricity in multiferroic Cr doped ZnO

NASA Astrophysics Data System (ADS)

Tiwari, Jeetendra Kumar; Ali, Nasir; Ghosh, Subhasis

2018-05-01

Cr doped ZnO thin film was grown on quartz substrate using RF magnetron sputtering. Room temperature magnetic and ferroelectric properties of Cr doped ZnO were investigated. It is shown that ZnO becomes ferromagnetic upon Cr doping. It is considered that breaking of centrosymmetry due strain developed by doping of Cr should be responsible for the ferroelectricity. These films were characterized by X-ray diffraction (XRD), which shows that the films possess crystalline structure with preferred orientation along the (002) crystal plane and there is no extra peak due to Cr i.e. single phase.

Predicting response to primary chemotherapy: gene expression profiling of paraffin-embedded core biopsy tissue.

PubMed

Mina, Lida; Soule, Sharon E; Badve, Sunil; Baehner, Fredrick L; Baker, Joffre; Cronin, Maureen; Watson, Drew; Liu, Mei-Lan; Sledge, George W; Shak, Steve; Miller, Kathy D

2007-06-01

Primary chemotherapy provides an ideal opportunity to correlate gene expression with response to treatment. We used paraffin-embedded core biopsies from a completed phase II trial to identify genes that correlate with response to primary chemotherapy. Patients with newly diagnosed stage II or III breast cancer were treated with sequential doxorubicin 75 mg/M2 q2 wks x 3 and docetaxel 40 mg/M2 weekly x 6; treatment order was randomly assigned. Pretreatment core biopsy samples were interrogated for genes that might correlate with pathologic complete response (pCR). In addition to the individual genes, the correlation of the Oncotype DX Recurrence Score with pCR was examined. Of 70 patients enrolled in the parent trial, core biopsies samples with sufficient RNA for gene analyses were available from 45 patients; 9 (20%) had inflammatory breast cancer (IBC). Six (14%) patients achieved a pCR. Twenty-two of the 274 candidate genes assessed correlated with pCR (p < 0.05). Genes correlating with pCR could be grouped into three large clusters: angiogenesis-related genes, proliferation related genes, and invasion-related genes. Expression of estrogen receptor (ER)-related genes and Recurrence Score did not correlate with pCR. In an exploratory analysis we compared gene expression in IBC to non-inflammatory breast cancer; twenty-four (9%) of the genes were differentially expressed (p < 0.05), 5 were upregulated and 19 were downregulated in IBC. Gene expression analysis on core biopsy samples is feasible and identifies candidate genes that correlate with pCR to primary chemotherapy. Gene expression in IBC differs significantly from noninflammatory breast cancer.

Over-Expression of Superoxide Dismutase Ameliorates Cr(VI) Induced Adverse Effects via Modulating Cellular Immune System of Drosophila melanogaster

PubMed Central

Pragya, Prakash; Shukla, Arvind Kumar; Murthy, Ramesh Chandra; Abdin, Malik Zainul; Kar Chowdhuri, Debapratim

2014-01-01

The evolutionarily conserved innate immune system plays critical role for maintaining the health of an organism. However, a number of environmental chemicals including metals are known to exert adverse effects on immune system. The present study assessed the in vivo effect of a major environmental chemical, Cr(VI), on cellular immune response using Drosophila melanogaster and subsequently the protective role of superoxide dismutase (SOD) based on the comparable performance of the tested anti-oxidant enzymes. The immuno-modulatory potential of Cr(VI) was demonstrated by observing a significant reduction in the total hemocyte count along with impaired phagocytic activity in exposed organism. Concurrently, a significant increase in the percentage of Annexin V-FITC positive cells, activation of DEVDase activity, generation of free radical species along with inhibition of anti-oxidant enzyme activities was observed in the hemocytes of exposed organism. In addition, we have shown that ONOO− is primarily responsible for Cr(VI) induced adverse effects on Drosophila hemocytes along with O2 −. While generation of O2 −/ONOO− in Cr(VI) exposed Drosophila hemocytes was found to be responsible for the suppression of Drosophila cellular immune response, Cr(VI) induced alteration was significantly reduced by the over-expression of sod in Drosophila hemocytes. Overall, our results suggest that manipulation of one of the anti-oxidant genes, sod, benefits the organism from Cr(VI) induced alteration in cellular immunity. Further, this study demonstrates the applicability of D. melanogaster to examine the possible effects of environmental chemicals on innate immunity which can be extrapolated to higher organisms due to evolutionary conservation of innate immune system between Drosophila and mammals. PMID:24505420

[18F]fluoro-2-deoxyglucose-positron emission tomography for the assessment of histopathological response after preoperative chemoradiotherapy in advanced oral squamous cell carcinoma.

PubMed

Shimomura, Hiroyuki; Sasahira, Tomonori; Yamanaka, Yasutsugu; Kurihara, Miyako; Imai, Yuichiro; Tamaki, Shigehiro; Yamakawa, Nobuhiro; Shirone, Norihisa; Hasegawa, Masatoshi; Kuniyasu, Hiroki; Kirita, Tadaaki

2015-04-01

[(18)F]fluoro-2-deoxyglucose-positron emission tomography (FDG-PET) is widely used to evaluate tumor metabolic activity. The aim of this study was to evaluate the usefulness of FDG-PET in assessing the histopathological response to preoperative concurrent chemoradiotherapy (CRT) in patients with oral squamous cell carcinoma (OSCC). Forty-five patients with resectable advanced OSCC who had received preoperative CRT followed by tumor ablative surgery between January 2004 and December 2011 were included in the study. All patients underwent FDG-PET before and after preoperative CRT. The maximum standardized uptake value (SUVmax) before (pre-SUV) and after preoperative CRT (post-SUV) and the SUVmax reduction rate (ΔSUV %) were used to evaluate the response to preoperative CRT. Correlations among SUVmax, histopathological response, and expression of cancer antigen Ki-67 and hypoxia-inducible factor-1α (HIF-1α) were analyzed. Preoperative CRT significantly reduced intratumoral FDG uptake (P < 0.001). The pre-SUV and post-SUV were significantly lower in patients with a pathological complete response (pCR) than in those with a non-pCR (pre-SUV P = 0.037; post-SUV P = 0.001). ΔSUV % was higher in patients with pCR than in those with non-pCR (P = 0.029). The pre-SUV was significantly correlated with Ki-67 and HIF-1α expression in pretreatment biopsy specimens (Ki-67 P = 0.046, R = 0.292; HIF-1α P = 0.007, R = 0.385). The expression of both Ki-67 and HIF-1α was significantly lower in patients with pCR than in those with non-pCR (Ki-67 P < 0.001; HIF-1α P < 0.001). Low pre-SUV and post-SUV and high ΔSUV % may predict a good histopathological response to preoperative CRT. Ki-67 and HIF-1α expression in pretreatment biopsy specimens were predictors of histopathological response to preoperative CRT.

The effects of graded levels of calorie restriction: VI. Impact of short-term graded calorie restriction on transcriptomic responses of the hypothalamic hunger and circadian signaling pathways.

PubMed

Derous, Davina; Mitchell, Sharon E; Green, Cara L; Chen, Luonan; Han, Jing-Dong J; Wang, Yingchun; Promislow, Daniel E L; Lusseau, David; Speakman, John R; Douglas, Alex

2016-04-01

Food intake and circadian rhythms are regulated by hypothalamic neuropeptides and circulating hormones, which could mediate the anti-ageing effect of calorie restriction (CR). We tested whether these two signaling pathways mediate CR by quantifying hypothalamic transcripts of male C57BL/6 mice exposed to graded levels of CR (10 % to 40 %) for 3 months. We found that the graded CR manipulation resulted in upregulation of core circadian rhythm genes, which correlated negatively with circulating levels of leptin, insulin-like growth factor 1 (IGF-1), insulin, and tumor necrosis factor alpha (TNF-α). In addition, key components in the hunger signaling pathway were expressed in a manner reflecting elevated hunger at greater levels of restriction, and which also correlated negatively with circulating levels of insulin, TNF-α, leptin and IGF-1. Lastly, phenotypes, such as food anticipatory activity and body temperature, were associated with expression levels of both hunger genes and core clock genes. Our results suggest modulation of the hunger and circadian signaling pathways in response to altered levels of circulating hormones, that are themselves downstream of morphological changes resulting from CR treatment, may be important elements in the response to CR, driving some of the key phenotypic outcomes.

The effects of graded levels of calorie restriction: VI. Impact of short-term graded calorie restriction on transcriptomic responses of the hypothalamic hunger and circadian signaling pathways

PubMed Central

Green, Cara L.; Chen, Luonan; Han, Jing‐Dong J.; Wang, Yingchun; Promislow, Daniel E.L.; Lusseau, David; Speakman, John R.; Douglas, Alex

2016-01-01

Food intake and circadian rhythms are regulated by hypothalamic neuropeptides and circulating hormones, which could mediate the anti‐ageing effect of calorie restriction (CR). We tested whether these two signaling pathways mediate CR by quantifying hypothalamic transcripts of male C57BL/6 mice exposed to graded levels of CR (10 % to 40 %) for 3 months. We found that the graded CR manipulation resulted in upregulation of core circadian rhythm genes, which correlated negatively with circulating levels of leptin, insulin‐like growth factor 1 (IGF‐1), insulin, and tumor necrosis factor alpha (TNF‐α). In addition, key components in the hunger signaling pathway were expressed in a manner reflecting elevated hunger at greater levels of restriction, and which also correlated negatively with circulating levels of insulin, TNF‐α, leptin and IGF‐1. Lastly, phenotypes, such as food anticipatory activity and body temperature, were associated with expression levels of both hunger genes and core clock genes. Our results suggest modulation of the hunger and circadian signaling pathways in response to altered levels of circulating hormones, that are themselves downstream of morphological changes resulting from CR treatment, may be important elements in the response to CR, driving some of the key phenotypic outcomes. PMID:26945906

Interaction of growth hormone receptor/binding protein gene disruption and caloric restriction for insulin sensitivity and attenuated aging

PubMed Central

Arum, Oge; Saleh, Jamal; Boparai, Ravneet; Turner, Jeremy; Kopchick, John; Khardori, Romesh; Bartke, Andrzej

2014-01-01

The correlation of physiological sensitivity to insulin ( vis-à-vis glycemic regulation) and longevity is extensively established, creating a justifiable gerontological interest on whether insulin sensitivity is causative, or even predictive, of some or all phenotypes of slowed senescence (including longevity). The growth hormone receptor/ binding protein gene-disrupted (GHR-KO) mouse is the most extensively investigated insulin-sensitive, attenuated aging model. It was reported that, in a manner divergent from similar mutants, GHR-KO mice fail to respond to caloric restriction (CR) by altering their insulin sensitivity. We hypothesized that maximized insulin responsiveness is what causes GHR-KO mice to exhibit a suppressed survivorship response to dietary (including caloric) restriction; and attempted to refute this hypothesis by assessing the effects of CR on GHR-KO mice for varied slow-aging-associated phenotypes. In contrast to previous reports, we found GHR-KO mice on CR to be less responsive than their ad libitum (A.L.) counterparts to the hypoglycemia-inducing effects of insulin. Further, CR had negligible effects on the metabolism or cognition of GHR-KO mice. Therefore, our data suggest that the effects of CR on the insulin sensitivity of GHR-KO mice do not concur with the effects of CR on the aging of GHR-KO mice. PMID:25789159

Long-term effects of cardiac rehabilitation in elderly individuals with stable coronary artery disease.

PubMed

Mandic, Sandra; Stevens, Emily; Hodge, Claire; Brown, Casey; Walker, Robert; Body, Dianne; Barclay, Leanne; Nye, Edwin R; Williams, Michael J A

2016-01-01

To compare exercise capacity and cardiovascular response to exercise in elderly individuals with coronary artery disease (CAD) who attend ongoing community-based maintenance cardiac rehabilitation (CR) versus age- and gender-matched healthy "very active" (HVA; ≥ 2000 kcal/week) and healthy "less active" (HLA; <2000 kcal/week) individuals. Sixty-three participants (age: 72.3 ± 5.1 years; 62% men; n = 21 per group) completed the following assessments: (1) symptom-limited graded exercise test with expired gas analysis and bioimpedance assessment of cardiovascular function during exercise; (2) walking tests; (3) physical function; (4) anthropometry and (5) 12-month physical activity recall. The CR group achieved 98% (range: 73-154%) of age- and gender-predicted peak oxygen consumption for healthy individuals. Peak oxygen consumption was lower in CR compared to HVA but not HLA group (VO2peak: CR: 19.0 ± 4.5, HVA: 23.7 ± 2.9, HLA: 20.7 ± 4.7 ml ·kg(-1)ċmin(-1), p = 0.001 versus HVA; p = 0.390 versus HLA). Peak heart rate was lower in CR compared to both HVA and HLA. Walking test results and cardiovascular and physical function were not different between the groups. Elderly individuals with CAD participating in maintenance CR have similar exercise capacity and cardiorespiratory response to exercise compared to their age- and gender-matched less active healthy peers. The findings support referral of elderly patients to community-based CR. Fitness benefits of long-term maintenance cardiac rehabilitation (CR) programs remain unknown. Elderly individuals with coronary artery disease participating in maintenance CR have exercise capacity and cardiorespiratory response to exercise similar to their less active healthy peers. Maintenance CR may play an important role prolonging independent living in elderly individuals.

Comparison of Integrated Testlet and Constructed-Response Question Formats

ERIC Educational Resources Information Center

Slepkov, Aaron D.; Shiell, Ralph C.

2014-01-01

Constructed-response (CR) questions are a mainstay of introductory physics textbooks and exams. However, because of the time, cost, and scoring reliability constraints associated with this format, CR questions are being increasingly replaced by multiple-choice (MC) questions in formal exams. The integrated testlet (IT) is a recently developed…

Reliability, agreement, and responsiveness of a 6-minute walk/run test in patients with heart disease.

PubMed

Berghmans, Danielle D; Lenssen, Antoine F; Bastiaenen, Carolien H; Ilhan, Mustafa; Lencer, Nicole H; Roox, George M

2013-02-01

The 6-minute walk test (6 MWT) is widely used to assess exercise tolerance in cardiac rehabilitation (CR). However, previous research shows it to be insufficiently responsive, especially for patients with a relatively high maximal exercise tolerance at baseline. We therefore designed a 6-minute walk/run test (6 MWRT), which has the same duration as the 6 MWT but allows running. The objective of this study was to determine the test-retest reproducibility and responsiveness of this 6 MWRT. Responsiveness was investigated in a prospective cohort study among a group of patients entering CR at Maastricht University Medical Center, with a cross-sectional part to assess the test-retest reproducibility. Test-retest reproducibility (reliability and agreement) was investigated using the intraclass correlation (ICC) and a Bland-Altman plot of two measurements implemented in the first week of rehabilitation. Responsiveness of the 6 MWT and the 6 MWRT was calculated using the standard response mean (SRM) over a 6-week period. The first reproducibility analysis included 34 patients, the second 22 patients. The ICCs were 0.935 and 0.906, respectively, with limits of agreement of ± 79 and ± 61 m. The responsiveness analysis included 27 patients. The SRM values were 0.83 for the 6 MWT and 0.71 for the 6 MWRT. Although the 6 MWRT is a reproducible test in CR, its responsiveness is not superior to that of the 6 MWT. We therefore prefer the conventional 6 MWT as an evaluative measurement in CR and advise against using the 6 MWRT as (evaluative) measurement in CR for this purpose.

Predictions of a Large Magnetocaloric Effect in Co- and Cr-Substituted Heusler Alloys Using First-Principles and Monte Carlo Approaches

NASA Astrophysics Data System (ADS)

Sokolovskiy, Vladimir V.; Buchelnikov, Vasiliy D.; Zagrebin, Mikhail A.; Grünebohm, Anna; Entel, Peter

The effect of Co- and Cr-doping on magnetic and magnetocaloric poperties of Ni-Mn-(In, Ga, Sn, and Al) Heusler alloys has been theoretically studied by combining first principles with Monte Carlo approaches. The magnetic and magnetocaloric properties are obtained as a function of temperature and magnetic field using a mixed type of Potts and Blume-Emery-Griffiths model where the model parameters are obtained from ab initio calculations. The Monte Carlo calculations allowed to make predictions of a giant inverse magnetocaloric effect in partially new hypothetical magnetic Heusler alloys across the martensitic transformation.

Outcomes of Hispanic women with lymph-node positive, HER2 positive breast cancer treated with neoadjuvant chemotherapy and trastuzumab in Mexico.

PubMed

Villarreal-Garza, Cynthia; Soto-Perez-de-Celis, Enrique; Sifuentes, Erika; Ruano, Santiago; Baez-Revueltas, Berenice; Lara-Medina, Fernando; Arce-Salinas, Claudia; Alvarado-Miranda, Alberto; Chavarri-Guerra, Yanin; Caro-Sanchez, Claudia; Castañeda-Soto, Noel; Bargallo-Rocha, Enrique; Mohar, Alejandro

2015-06-01

Evidence regarding the outcomes of Hispanic women with breast cancer is lacking. We analyzed women with HER2+ disease treated with trastuzumab-based neoadjuvant chemotherapy in Mexico. 244 patients were included. Outcomes were compared between patients who achieved pathologic complete response (pCR) (n = 119), or less than pCR (n = 125). Patients with noninvasive (ypT0/is, ypN0) residual disease were also analyzed. 119 (48.8%) patients achieved pCR. pCR was the only factor associated with improved 3 year survival (98.1% vs 92.3%: P = 0.02). Survival was better in patients with ypT0/is, ypN0 response than in those with residual invasive disease (p < 0.01). 3 year survival was 98.1% for patients with pCR and 92.6% for patients with ypTis, ypN0 response (p = 0.64). Response rates to trastuzumab based neoadjuvant chemotherapy in Hispanics mimic that of other ethnic groups. This underlines the fact that access to treatment, rather than ethnicity, is the main prognostic factor in this population. Copyright © 2015 Elsevier Ltd. All rights reserved.

Luminescent sensing of Cu2+, CrO42- and photocatalytic degradation of methyl violet by Zn(II) metal-organic framework (MOF) having 5,5‧-(1H-2,3,5-triazole-1,4-diyl)diisophthalic acid ligand

NASA Astrophysics Data System (ADS)

Wu, Weiping; Li, Baohong; Gu, Chuying; Wang, Jun; Singh, Amita; Kumar, Abhinav

2017-11-01

A porous Zn(II) metal-organic framework (MOF) [Zn(H2L)(4,4‧-bipy)0.5]n (1) has been selected and its luminescence sensing for cations and anions as well as the photocatalytic property against methyl violet have been explored. Luminescence studies indicated that 1 could be an efficient multifunctional fluorescent material for highly sensitive detection of metal cation Cu2+ and anions CrO42-. The luminescence intensity of 1 was found to decrease proportionately with increase in the concentration of Cu2+ and CrO42-. Furthermore, the photocatalytic property of 1 for degradation of the methyl violet (MV) have been explored and a possible photocatalytic mechanism have been proposed using density of states (DOS) and partial DOS (pDOS) calculations.

On quasi-periodic variations of low-energy cosmic rays observed near earth.

PubMed

Kudela, Karel; Langer, Ronald

2015-06-01

Cosmic ray (CR) may partially, especially at high altitudes, contribute to the dosimetric characteristics. Along with irregular CR variations as Forbush decreases and solar particle events are, the quasi-periodic variations may be of some relevance too. A very short review (with references to original papers) of the present knowledge of various types of such variations is presented, namely (i) diurnal wave, (ii) ~27 d variability due to the solar rotation, (iii) Rieger-type periodicity, and (iv) quasi-biennial oscillations as well as waves on longer time scales related to solar activity and to polarity of magnetic field of the Sun. Variability is illustrated in measurements of secondary CR on the ground including the high-altitude observations at Lomnický štít. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

High Temperature Thermal Stability and Oxidation Resistance of Magnetron-sputtered Homogeneous CrAlON Coatings on 430 Steel

NASA Astrophysics Data System (ADS)

Kayani, A.; Wickey, K. J.; Nandasiri, M. I.; Moore, A.; Garratt, E.; AlFaify, S.; Gao, X.; Smith, R. J.; Buchanan, T. L.; Priyantha, W.; Kopczyk, M.; Gannon, P. E.; Gorokhovsky, V. I.

2009-03-01

The requirements of low cost and high-temperature corrosion resistance for bipolar interconnect plates in solid oxide fuel cell stacks has directed attention to the use of metal plates with oxidation resistant coatings. We have investigated the performance of steel plates with homogenous coatings of CrAlON (oxynitrides). The coatings were deposited using RF magnetron sputtering, with Ar as a sputtering gas. Oxygen in these coatings was not intentionally added. Oxygen might have come through contaminated nitrogen gas bottle, leak in the chamber or from the partial pressure of water vapors. Nitrogen was added during the growth process to get oxynitride coating. The Cr/Al composition ratio in the coatings was varied in a combinatorial approach. The coatings were subsequently annealed in air for up to 25 hours at 800° C. The composition of the coated plates and the rate of oxidation were characterized using Rutherford backscattering (RBS) and nuclear reaction analysis (NRA). From our results, we conclude that Al rich coatings are more susceptible to oxidation than Cr rich coatings.

Metal concentrations in sediments from tourist beaches of Miri City, Sarawak, Malaysia (Borneo Island).

PubMed

Nagarajan, R; Jonathan, M P; Roy, Priyadarsi D; Wai-Hwa, L; Prasanna, M V; Sarkar, S K; Navarrete-López, M

2013-08-15

Forty-three sediment samples were collected from the beaches of Miri City, Sarawak, Malaysia to identify the enrichment of partially leached trace metals (PLTMs) from six different tourist beaches. The samples were analyzed for PLTMs Fe, Mn, Cr, Co, Cu, Ni, Pb, Sr and Zn. The concentration pattern suggest that the southern side of the study area is enriched with Fe (1821-6097 μg g(-1)), Mn (11.57-90.22 μg g(-1)), Cr (51.50-311 μg g(-1)), Ni (18-51 μg g(-1)), Pb (8.81-84.05 μg g(-1)), Sr (25.95-140.49 μg g(-1)) and Zn (12.46-35.04 μg g(-1)). Compared to the eco-toxicological values, Cr>Effects range low (ERL), Lowest effect level (LEL), Severe effect level (SEL); Cu>Unpolluted sediments, ERL, LEL; Pb>Unpolluted sediments and Ni>ERL and LEL. Comparative results with other regions indicate that Co, Cr, Cu, Ni and Zn are higher, indicating an external input rather than natural process. Copyright © 2013 Elsevier Ltd. All rights reserved.

Single- versus Double-Scoring of Trend Responses in Trend Score Equating with Constructed-Response Tests. Research Report. ETS RR-10-12

ERIC Educational Resources Information Center

Tan, Xuan; Ricker, Kathryn L.; Puhan, Gautam

2010-01-01

This study examines the differences in equating outcomes between two trend score equating designs resulting from two different scoring strategies for trend scoring when operational constructed-response (CR) items are double-scored--the single group (SG) design, where each trend CR item is double-scored, and the nonequivalent groups with anchor…

Dopamine dependency for acquisition and performance of Pavlovian conditioned response

PubMed Central

Darvas, Martin; Wunsch, Amanda M.; Gibbs, Jeffrey T.; Palmiter, Richard D.

2014-01-01

During Pavlovian conditioning, pairing of a neutral conditioned stimulus (CS) with a reward leads to conditioned reward-approach responses (CRs) that are elicited by presentation of the CS. CR behaviors can be sign tracking, in which animals engage the CS, or goal tracking, in which animals go to the reward location. We investigated CR behaviors in mice with only ∼5% of normal dopamine in the striatum using a Pavlovian conditioning paradigm. These mice had severely impaired acquisition of the CR, which was ameliorated by pharmacological restoration of dopamine synthesis with l-dopa. Surprisingly, after they had learned the CR, its expression decayed only gradually in following sessions that were conducted without l-dopa treatment. To assess specific contributions of dopamine signaling in the dorsal or ventral striatum, we performed virus-mediated restoration of dopamine synthesis in completely dopamine-deficient (DD) mice. Mice with dopamine signaling only in the dorsal striatum did not acquire a CR, whereas mice with dopamine signaling only in in the ventral striatum acquired a CR. The CR in mice with dopamine signaling only in the dorsal striatum was restored by subjecting the mice to instrumental training in which they had to interact with the CS to obtain rewards. We conclude that dopamine is essential for learning and performance of CR behavior that is predominantly goal tracking. Furthermore, although dopamine signaling in the ventral striatum is sufficient to support a CR, dopamine signaling only in the dorsal striatum can also support a CR under certain circumstances. PMID:24550305

Creatine Monohydrate Supplementation Does Not Augment Fitness, Performance, or Body Composition Adaptations in Response to Four Weeks of High-Intensity Interval Training in Young Females.

PubMed

Forbes, Scott C; Sletten, Nathan; Durrer, Cody; Myette-Côté, Étienne; Candow, D; Little, Jonathan P

2017-06-01

High-intensity interval training (HIIT) has been shown to improve cardiorespiratory fitness, performance, body composition, and insulin sensitivity. Creatine (Cr) supplementation may augment responses to HIIT, leading to even greater physiological adaptations. The purpose of this study was to determine the effects of 4 weeks of HIIT (three sessions/week) combined with Cr supplementation in recreationally active females. Seventeen females (age = 23 ± 4 yrs; BMI = 23.4 ± 2.4) were randomly assigned to either Cr (Cr; 0.3 g・kg -1 ・d -1 for 5 d followed by 0.1 g・kg -1 ・d -1 for 23 days; n = 9) or placebo (PLA; n = 8). Before and after the intervention, VO 2peak , ventilatory threshold (VT), time-trial performance, lean body mass and fat mass, and insulin sensitivity were assessed. HIIT improved VO 2peak (Cr = +10.2%; PLA = +8.8%), VT (Cr = +12.7%; PLA = +9.9%), and time-trial performance (Cr = -11.5%; PLA = -11.6%) with no differences between groups (time main effects, all p < .001). There were no changes over time for fat mass (Cr = -0.3%; PLA = +4.3%), whole-body lean mass (Cr = +0.5%; PLA = -0.9%), or insulin resistance (Cr = +3.9%; PLA = +18.7%). In conclusion, HIIT is an effective way to improve cardiorespiratory fitness, VT, and time-trial performance. The addition of Cr to HIIT did not augment improvements in cardiorespiratory fitness, performance or body composition in recreationally active females.

Chromium enhances insulin responsiveness via AMPK.

PubMed

Hoffman, Nolan J; Penque, Brent A; Habegger, Kirk M; Sealls, Whitney; Tackett, Lixuan; Elmendorf, Jeffrey S

2014-05-01

Trivalent chromium (Cr(3+)) is known to improve glucose homeostasis. Cr(3+) has been shown to improve plasma membrane-based aspects of glucose transporter GLUT4 regulation and increase activity of the cellular energy sensor 5' AMP-activated protein kinase (AMPK). However, the mechanism(s) by which Cr(3+) improves insulin responsiveness and whether AMPK mediates this action is not known. In this study we tested if Cr(3+) protected against physiological hyperinsulinemia-induced plasma membrane cholesterol accumulation, cortical filamentous actin (F-actin) loss and insulin resistance in L6 skeletal muscle myotubes. In addition, we performed mechanistic studies to test our hypothesis that AMPK mediates the effects of Cr(3+) on GLUT4 and glucose transport regulation. Hyperinsulinemia-induced insulin-resistant L6 myotubes displayed excess membrane cholesterol and diminished cortical F-actin essential for effective glucose transport regulation. These membrane and cytoskeletal abnormalities were associated with defects in insulin-stimulated GLUT4 translocation and glucose transport. Supplementing the culture medium with pharmacologically relevant doses of Cr(3+) in the picolinate form (CrPic) protected against membrane cholesterol accumulation, F-actin loss, GLUT4 dysregulation and glucose transport dysfunction. Insulin signaling was neither impaired by hyperinsulinemic conditions nor enhanced by CrPic, whereas CrPic increased AMPK signaling. Mechanistically, siRNA-mediated depletion of AMPK abolished the protective effects of CrPic against GLUT4 and glucose transport dysregulation. Together these findings suggest that the micronutrient Cr(3+), via increasing AMPK activity, positively impacts skeletal muscle cell insulin sensitivity and glucose transport regulation. Copyright © 2014 Elsevier Inc. All rights reserved.

Morphological response contributes to patient selection for rescue liver resection in chemotherapy patients with initially un-resectable colorectal liver metastasis.

PubMed

Suzuki, Koichi; Muto, Yuta; Ichida, Kosuke; Fukui, Taro; Takayama, Yuji; Kakizawa, Nao; Kato, Takaharu; Hasegawa, Fumi; Watanabe, Fumiaki; Kaneda, Yuji; Kikukawa, Rina; Saito, Masaaki; Tsujinaka, Shingo; Futsuhara, Kazushige; Takata, Osamu; Noda, Hiroshi; Miyakura, Yasuyuki; Kiyozaki, Hirokazu; Konishi, Fumio; Rikiyama, Toshiki

2017-08-01

Morphological response is considered an improved surrogate to the Response Evaluation Criteria in Solid Tumors (RECIST) model with regard to predicting the prognosis for patients with colorectal liver metastases. However, its use as a decision-making tool for surgical intervention has not been examined. The present study assessed the morphological response in 50 patients who underwent chemotherapy with or without bevacizumab for initially un-resectable colorectal liver metastases. Changes in tumor morphology between heterogeneous with uncertain borders and homogeneous with clear borders were defined as an optimal response (OR). Patients were also assessed as having an incomplete response (IR), and an absence of marked changes was assessed as no response (NR). No significant difference was observed in progression-free survival (PFS) between complete response/partial response (CR/PR) and stable disease/progressive disease (SD/PD), according to RECIST. By contrast, PFS for OR/IR patients was significantly improved compared with that for NR patients (13.2 vs. 8.7 months; P=0.0426). Exclusion of PD enhanced the difference in PFS between OR/IR and NR patients (15.1 vs. 9.3 months; P<0.0001), whereas no difference was observed between CR/PR and SD. The rate of OR and IR in patients treated with bevacizumab was 47.4% (9/19), but only 19.4% (6/31) for patients that were not administered bevacizumab. Comparison of the survival curves between OR/IR and NR patients revealed similar survival rates at 6 months after chemotherapy, but the groups exhibited different survival rates subsequent to this period of time. Patients showing OR/IR within 6 months appeared to be oncologically stable and could be considered as candidates for surgical intervention, including rescue liver resection. Comparing the pathological and morphological features of the tumor with representative optimal response, living tumor cells were revealed to be distributed within the area of vascular reconstruction induced by bevacizumab, resulting in a predictive value for prognosis in the patients treated with bevacizumab. The present findings provided the evidence for physicians to consider patients with previously un-resectable metastatic colorectal cancer as candidates for surgical treatment. Morphological response is a useful decision-making tool for evaluating these patients for rescue liver resection following chemotherapy.

Hungry for life: How the arcuate nucleus and neuropeptide Y may play a critical role in mediating the benefits of calorie restriction.

PubMed

Minor, Robin K; Chang, Joy W; de Cabo, Rafael

2009-02-05

Laboratory studies consistently demonstrate extended lifespan in animals on calorie restriction (CR), where total caloric intake is reduced by 10-40% but adequate nutrition is otherwise maintained. CR has been further shown to delay the onset and severity of chronic diseases associated with aging such as cancer, and to extend the functional health span of important faculties like cognition. Less understood are the underlying mechanisms through which CR might act to induce such alterations. One theory postulates that CR's beneficial effects are intimately tied to the neuroendocrine response to low energy availability, of which the arcuate nucleus in the hypothalamus plays a pivotal role. Neuropeptide Y (NPY), a neurotransmitter in the front line of the arcuate response to low energy availability, is the primary hunger signal affected by CR and therefore may be a critical mechanism for lifespan extension.

Assessing pathological complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a systematic review.

PubMed

Ryan, J E; Warrier, S K; Lynch, A C; Heriot, A G

2015-10-01

Pathological complete response to neoadjuvant chemoradiotherapy is found in 20% of patients with rectal cancer undergoing long-course chemoradiotherapy. Some authors have suggested that these patients do not need to undergo surgery and can be managed with careful follow-up, with surgery only used in the event of clinical failure. Widespread adoption of this regimen is limited by the accuracy of methods to confirm a pathological complete response (pCR). A systematic search of PubMed, Medline and Cochrane databases was conducted to identify clinical, histological and radiological features in those patients with rectal cancer who achieved a pCR following chemoradiotherapy. Searches were conducted with the following keywords and MeSH search terms: 'rectal neoplasm', 'response', 'neoadjuvant', 'preoperative chemoradiation' and 'tumour response'. After review of title and abstracts, 89 articles addressing the assessment of pCR were identified. Histology and clinical assessment are the most effective methods of assessment of pCR, with histology considered the gold standard. Clinical assessment is limited to low rectal tumours and is open to significant inter-rater variability, while histological examination requires a surgical specimen. Diffusion-weighted MRI and (18) F-fluorodeoxyglucose positron emission tomography/CT demonstrate the greatest potential for the assessment of pCR, but both modalities have limited accuracy. Determination of a pCR is crucial if a nonoperative approach is to be undertaken proactively. Various methods are available, but currently they lack sufficient sensitivity and specificity to define management. This is likely to be an area of further research in the future. Colorectal Disease © 2015 The Association of Coloproctology of Great Britain and Ireland.

BK virus-hemorrhagic cystitis following allogeneic stem cell transplantation: Clinical characteristics and utility of leflunomide treatment.

PubMed

Park, Young Hoon; Lim, Joo Han; Yi, Hyeon Gyu; Lee, Moon Hee; Kim, Chul Soo

2016-04-18

BK virus-hemorrhagic cystitis (BKV-HC) is a potential cause of morbidity and mortality in patients having undergone allogeneic stem cell transplantation (Allo-SCT). We analyzed the clinical features of BKV-HC following Allo-SCT and reported the utility of leflunomide therapy for BKV-HC. From January 2005 to June 2014, among the 69 patients underwent Allo-SCT in our institution, the patients who experienced BKV-HC were investigated retrospectively. Hemorrhagic cystitis (HC) was observed in 30 patients (43.5%), and among them, 18 patients (26.1%) were identified as BKV-HC. The median age of the patients (12 males and 6 females) was 45 years (range, 13-63). Patients received Allo-SCT from acute myeloid leukemia (n=11), aplastic anemia (n=4), myelodysplastic syndrome (n=2), and non-Hodgkin lymphoma (n=1).The donor types were a HLA-matched sibling donor for 6 patients, HLA-matched unrelated donor for 9, and a haploidentical familial donor for 2. The median onset and duration of BKV-HC was on day 21 (range, 7-97) after transplantation and 22 days (range, 6-107). Eleven patients (62.1%) had grade I-II HC and seven patients (38.9%) had grade III-IV (high-grade) HC. Among the seven patients who had high-grade HC, one had complete response (CR), one partial response (PR), and five no response (NR). Among the five non-responders, one died of BKV-HC associated complications. The remaining four patients were treated with leflunomide, with achieving CR (n=2) and PR (n=2). The median duration from the start of leflunomide therapy to response was 13 days (range, 8-17 days). All patients tolerated the leflunomide treatment well, with three patients having mild gastrointestinal symptoms, including anorexia and abdominal bloating. BKV-HC was commonly observed in patients with HC following Allo-SCT. In high-grade BKV-HC patients who fail supportive care, leflunomide may be a feasible option without significant toxicity.

Phase II Study of Bevacizumab in Patients With HIV-Associated Kaposi's Sarcoma Receiving Antiretroviral Therapy

PubMed Central

Uldrick, Thomas S.; Wyvill, Kathleen M.; Kumar, Pallavi; O'Mahony, Deirdre; Bernstein, Wendy; Aleman, Karen; Polizzotto, Mark N.; Steinberg, Seth M.; Pittaluga, Stefania; Marshall, Vickie; Whitby, Denise; Little, Richard F.; Yarchoan, Robert

2012-01-01

Purpose Alternatives to cytotoxic agents are desirable for patients with HIV-associated Kaposi's sarcoma (KS). Vascular endothelial growth factor-A (VEGF-A) contributes to KS pathogenesis. We evaluated the humanized anti–VEGF-A monoclonal antibody, bevacizumab, in patients with HIV-KS. Patients and Methods Patients with HIV-KS who either experienced progression while receiving highly active antiretroviral therapy (HAART) for at least 1 month or did not regress despite HAART for at least 4 months were administered bevacizumab 15 mg/kg intravenously on days 1 and 8 and then every 3 weeks. The primary objective was assessment of antitumor activity using modified AIDS Clinical Trial Group (ACTG) criteria for HIV-KS. HIV-uninfected patients were also eligible and observed separately. Results Seventeen HIV-infected patients were enrolled. Fourteen patients had been receiving effective HAART for at least 6 months (median, 1 year). Thirteen patients had advanced disease (ACTG T1), 13 patients had received prior chemotherapy for KS, and seven patients had CD4 count less than 200 cells/μL. Median number of cycles was 10 (range, 1 to 37 cycles); median follow-up was 8.3 months (range, 3 to 36 months). Of 16 assessable patients, best tumor responses observed were complete response (CR) in three patients (19%), partial response (PR) in two patients (12%), stable disease in nine patients (56%), and progressive disease in two patients (12%). Overall response rate (CR + PR) was 31% (95% CI, 11% to 58.7%). Four of five responders had received prior chemotherapy for KS. Over 202 cycles, grade 3 to 4 adverse events at least possibly attributed to therapy included hypertension (n = 7), neutropenia (n = 5), cellulitis (n = 3), and headache (n = 2). Conclusion Bevacizumab is tolerated in patients with HIV-KS and has activity in a subset of patients. PMID:22430271

[Response and prognosis of patients with multiple myeloma induced by PAD/TAD].

PubMed

Zeng, Tianmei; He, Haiyan; Shi, Haotian; Xi, Hao; Du, Juan; Zhang, Chunyang; Jiang, Hua; Fu, Weijun; Zhou, Fan; Hou, Jian

2015-03-17

To evaluate the impact of cytogenetic grouping and autologous stem cell transplantation on the prognosis of patients with multiple myeloma (MM) induced by PAD (velcade+epirubicin+dexamethasone) and TAD (thalidomide+epirubicin+dexamethasone). A total of 191 patients with a definite diagnosis of MM were enrolled from May 2008 to December 2013 into this prospective study. They were non-randomly induced by PAD (n = 132) or TAD (n = 59) plus autologous stem cell transplantation or chemotherapy. Response and survival rates were also analyzed between two groups. The overall response rates of PAD and TAD groups were 84.4% (108/128) and 69.5% (41/59) (P = 0.011) respectively. The very good partial remission (VGPR) rates were 70.3% (90/128) and 32.2% (19/59) (P < 0.001) and near complete remission/complete remission (nCR/CR) rates 68.0% (87/128) and 25.4% (15/59) respectively (P < 0.001). Both progression-free survival (PFS) and overall survival (OS) showed no significant inter-group difference (P = 0.223, 0.989). The survival analysis of PAD group showed that FISH high-risk group had shorter PFS and OS than FISH low-risk group (15.2 vs 19.1 months for PFS, P = 0.098; 41.2 months vs non-attaining for OS, P = 0.017). In FISH high-risk group, patients consolidated with autologous stem cell transplantation showed longer PFS than those with chemotherapy (17.8 vs 14.6 months, P = 0.029) while the OS showed no difference (P = 0.840). In FISH low-risk group, no difference were observed in PFS and OS between patients with consolidation therapies alone (P = 0.131, 0.294). The response rates are higher in patients induced by PAD than by TAD. After PAD induction, cytogenetic grouping may further distinguish the prognosis of MM patients. For FISH high-risk patients, their PFS is prolonged by autologous stem cell transplantation.

Accumulation and detoxification dynamics of Chromium and antioxidant responses in juvenile rare minnow, Gobiocypris rarus.

PubMed

Yuan, Cong; Li, Meng; Zheng, Yao; Zhou, Ying; Wu, Feili; Wang, Zaizhao

2017-09-01

Hexavalent chromium (Cr 6+ ) compounds are hazardous via all exposure routes. To explore the dynamics of Cr accumulation and elimination and to reveal the mechanisms underlying detoxification and antioxidation in juvenile Gobiocypris rarus, one-month old G. rarus larvae were exposed to 0.1mgL -1 Cr 6+ for four weeks for accumulation and subsequently placed to clean water for another week for depuration. The contents of Cr were measured weekly in the whole body of G. rarus juveniles. The activities of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), glutathione S-transferase (GST) and glutathione reductase (GR), and contents of glutathione (GSH) and malonaldehyde (MDA), and transcripts of cat, Cu/Zn-sod, Mn-sod, gpx1, gstpi, gr, mt1, nrf2 and uba52 were determined. The results indicated that G. rarus juveniles had a strong ability to resist the Cr accumulation by Cr 6+ exposure and to remove Cr from the body in clean water. In addition, GST and MT proteins may be involved in the detoxification of Cr 6+ . Moreover, Cr 6+ -induced GST detoxification in G. rarus juveniles might be accomplished through the Nrf2-mediated regulation of gene expressions. The antioxidant enzyme systems exhibited a response mechanism of the protective enzymes in organisms when they are subjected to external environmental stress. Two weeks of Cr 6+ treatments could have led to the damage and consecutive degradation of antioxidant enzymes via ubiquitination, and MT proteins could be involved in protecting the activity of these enzymes. The capability of antioxidant enzyme systems to recover from the Cr 6+ -induced damage was strong in G. rarus juveniles after Cr 6+ was removed from the water. Copyright © 2017 Elsevier B.V. All rights reserved.

Eliminating minimal residual disease as a therapeutic end point: working toward cure for patients with CLL.

PubMed

Thompson, Philip A; Wierda, William G

2016-01-21

Deep remission and prolonged disease-free survival can be achieved with first-line chemoimmunotherapy (CIT), such as combined fludarabine, cyclophosphamide, and rituximab, in the majority of patients with chronic lymphocytic leukemia (CLL). More modest results are reported with less intense regimens like obinutuzumab plus chlorambucil. Clinical assessment has limited sensitivity in detecting residual disease responsible for subsequent relapse, even including morphologic bone marrow (BM) evaluation. Multicolor flow cytometry and polymerase chain reaction (PCR)-based methods can detect minimal residual disease (MRD) to a sensitivity of ≥1:10,000 (10(-4)). Achieving BM MRD-negative complete remission (CR) is associated with superior progression-free survival (PFS) and overall survival; MRD status is the single best posttreatment predictor of long-term outcomes after CIT. Newer oral B-cell receptor signaling pathway inhibitors are highly effective at controlling disease, but best monotherapy responses are typically partial remission, and patients must remain on treatment to maintain disease control. Therapeutic progress is still needed for CLL. We propose that targeting MRD provides opportunity to realize this progress. Achieving BM MRD-negative CR is a prerequisite for long-term unmaintained disease-free survival and potential for cure. We review available methodologies for detecting MRD and correlations with posttreatment outcomes. We discuss the potential utility of MRD to direct individualized therapy. Finally, we discuss the importance of MRD-negative status as a surrogate marker for longer PFS in clinical studies to allow more rapid determination of clinical benefit. © 2016 by The American Society of Hematology.

Postnatal exposure to chromium through mother’s milk accelerates follicular atresia in F1 offspring through increased oxidative stress and depletion of antioxidant enzymes

PubMed Central

Stanley, Jone A.; Sivakumar, Kirthiram K.; Nithy, Thamizh K.; Arosh, Joe A.; Hoyer, Patricia B.; Burghardt, Robert C.; Banu, Sakhila K.

2013-01-01

Hexavalent chromium, CrVI, is a heavy metal endocrine disruptor, known as a mutagen, teratogen, and a group A carcinogen. Environmental contamination with CrVI, including drinking water, has been increasing in more than 30 cities in the United States. CrVI is rapidly converted to CrIII intracellularly, and CrIII can cause DNA strand breaks and cancer or apoptosis through different mechanisms. Our previous study demonstrated that lactational exposure to chromium results in a delay or arrest in follicle development and a decrease in steroid hormone levels in F1 female rats, both of which are mitigated (partial inhibition) by vitamin C. The current study tested the hypothesis that lactational exposure to CrIII accelerates follicle atresia in F1 offspring by increasing reactive oxygen species (ROS) and decreasing cellular antioxidants. Results showed that lactational exposure to CrIII dose-dependently increased follicular atresia and decreased steroidogenesis in postnatal day 25, 45, and 65 rats. Vitamin C mitigated or inhibited the effects of CrIII at all doses. CrIII increased hydrogen peroxide and lipid hydroperoxide in plasma and ovary; decreased the antioxidant enzymes (AOXs) GPx1, GR, SOD, and catalase; and increased glutathione S-transferase in plasma and ovary. To understand the effects of CrVI on ROS and AOXs in granulosa (GC) and theca (TC) cell compartments in the ovary, ROS levels and mRNA expression of cytosolic and mitochondrial AOXs, such as SOD1, SOD2, catalase, GLRX1, GSTM1, GSTM2, GSTA4, GR, TXN1, TXN2, TXNRD2, and PRDX3, were studied in GCs and TCs and in a spontaneously immortalized granulosa cell line (SIGC). Overall, CrVI downregulated each of the AOXs; and vitamin C mitigated the effects of CrVI on these enzymes in GCs and SIGCs, but failed to mitigate CrVI effects on GSTM1, GSTM2, TXN1, and TXN2 in TCs. Thus, these data for the first time reveal that lactational exposure to CrIII accelerated follicular atresia and decreased steroidogenesis in F1 female offspring by altering the ratio of ROS and AOXs in the ovary. Vitamin C is able to protect the ovary from CrIII-induced oxidative stress and follicle atresia through protective effects on GCs rather than TCs. PMID:23470461

Chromium picolinate and chromium histidinate protects against renal dysfunction by modulation of NF-κB pathway in high-fat diet fed and Streptozotocin-induced diabetic rats.

PubMed

Selcuk, Mustafa Yavuz; Aygen, Bilge; Dogukan, Ayhan; Tuzcu, Zeynep; Akdemir, Fatih; Komorowski, James R; Atalay, Mustafa; Sahin, Kazim

2012-04-08

Diabetic nephropathy is one of major complications of diabetes mellitus. Although chromium is an essential element for carbohydrate and lipid metabolism, its effects on diabetic nephropathy are not well understood. The present study was conducted to investigate the effects of chromium picolinate (CrPic) and chromium histidinate (CrHis) on nuclear factor-kappa B (NF-κB) and nuclear factor-E2-related factor-2 (Nrf2) pathway in the rat kidney. Male Wistar rats were divided into six groups. Group I received a standard diet (8% fat) and served as a control; Group II was fed with a standard diet and received CrPic; Group III was fed with a standard diet and received CrHis; Group IV received a high fat diet (HFD, 40% fat) for 2 weeks and then were injected with streptozotocin (STZ) (HFD/STZ); Group V was treated as group IV (HFD/STZ) but supplemented with CrPic for 12 weeks. Group VI was treated as group IV (HFD/STZ) but supplemented with CrHis. The increased NF-κβ p65 in the HFD/STZ group was inhibited by CrPic and CrHis supplementation (P < 0.05). In STZ-treated rats, a significant decrease in levels of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) was found in kidney tissues when compared to control rats (P < 0.05). A significant increase in the levels of IκBα was observed in CrPic- and CrHis-treated rats when compared with STZ-treated rats. Renal Nrf2 levels were significantly decreased in diabetic rats compared with the control rats. There was a higher tendency for increase of kidney Nrf2 level and decrease in kidney NFκBp65 levels and 4- hydroxyl nonenal (4-HNE) protein adducts (P < 0.05) in diabetic rats. Our result show that in kidney tissue CrHis/CrPic increases Nrf2 level, parallelly decreases NF-κB and partially restores IκBα levels in HFD/STZ group, suggesting that CrPic and CrHis may play a role in antioxidant defense system via the Nrf2 pathway by reducing inflammation through NF-κβ p65 inhibition. Moreover, a greater reduction in NF-κB expression and greater increases in expressions of IκBα and Nrf2 in diabetic rats supplemented with CrHis than rats supplemented with CrPic suggest that CrHis has more favorable effects than CrPic.

Room-temperature ferromagnetic transitions and the temperature dependence of magnetic behaviors in FeCoNiCr-based high-entropy alloys

NASA Astrophysics Data System (ADS)

Na, Suok-Min; Yoo, Jin-Hyeong; Lambert, Paul K.; Jones, Nicholas J.

2018-05-01

High-entropy alloys (HEAs) containing multiple principle alloying elements exhibit unique properties so they are currently receiving great attention for developing innovative alloy designs. In FeCoNi-based HEAs, magnetic behaviors strongly depend on the addition of alloying elements, usually accompanied by structural changes. In this work, the effect of non-magnetic components on the ferromagnetic transition and magnetic behaviors in equiatomic FeCoNiCrX (X=Al, Ga, Mn and Sn) HEAs was investigated. Alloy ingots of nominal compositions of HEAs were prepared by arc melting and the button ingots were cut into discs for magnetic measurements as functions of magnetic field and temperature. The HEAs of FeCoNiCrMn and FeCoNiCrSn show typical paramagnetic behaviors, composed of solid solution FCC matrix, while the additions of Ga and Al in FeCoNiCr exhibit ferromagnetic behaviors, along with the coexistence of FCC and BCC phases due to spinodal decomposition. The partial phase transition in both HEAs with the additions of Ga and Al would enhance ferromagnetic properties due to the addition of the BCC phase. The saturation magnetization for the base alloy FeCoNiCr is 0.5 emu/g at the applied field of 20 kOe (TC = 104 K). For the HEAs of FeCoNiCrGa and FeCoNiCrAl, the saturation magnetization significantly increased to 38 emu/g (TC = 703 K) and 25 emu/g (TC = 277 K), respectively. To evaluate the possibility of solid solution FCC and BCC phases in FeCoNiCr-type HEAs, we introduced a parameter of valence electron concentration (VEC). The proposed rule for solid solution formation by the VEC was matched with FeCoNiCr-type HEAs.

Effects of chromium picolinate on glucose uptake in insulin-resistant 3T3-L1 adipocytes involve activation of p38 MAPK.

PubMed

Wang, Yi-qun; Yao, Ming-hui

2009-12-01

Chromium picolinate (CrPic) has been discovered as a supplemental or alternative medication for type 2 diabetes, but its mechanism of action is not well understood. The purpose of this study was to explore the possible anti-diabetic mechanisms of CrPic in insulin-resistant 3T3-L1 adipocytes; the insulin resistance was induced by treatment with high glucose and insulin for 24 h. The effects of CrPic on glucose metabolism and the glucose uptake-inducing activity of CrPic were investigated. Meanwhile, the effects of CrPic on glucose transporter 4 (GLUT4) translocation were visualized by immonofluorescence microscopy. In addition, its effects on insulin signaling pathways and mitogen-activated protein kinase (MAPK) signaling cascades were assessed by immunoblotting analysis and real-time PCR. The results showed that CrPic induced glucose metabolism and uptake, as well as GLUT4 translocation to plasma membrane (PM) in both control and insulin-resistant 3T3-L1 adipocytes without any changes in insulin receptor beta (IR-beta), protein kinase B (AKt), c-Cbl, extracellular signal-regulated kinase (ERK), c-Jun phosphorylation and c-Cbl-associated protein (CAP) mRNA levels. Interestingly, CrPic was able to increase the basal and insulin-stimulated levels of p38 MAPK activation in the control and insulin-resistant cells. Pretreatment with the specific p38 MAPK inhibitor SB203580 partially inhibited the CrPic-induced glucose transport, but CrPic-activated translocation of GLUT4 was not inhibited by SB203580. This study provides an experimental evidence of the effects of CrPic on glucose uptake through the activation of p38 MAPK and it is independent of the effect on GLUT4 translocation. The findings also suggest exciting new insights into the role of p38 MAPK in glucose uptake and GLUT4 translocation.

Caloric restriction induces heat shock response and inhibits B16F10 cell tumorigenesis both in vitro and in vivo.

PubMed

Novelle, Marta G; Davis, Ashley; Price, Nathan L; Ali, Ahmed; Fürer-Galvan, Stefanie; Zhang, Yongqing; Becker, Kevin; Bernier, Michel; de Cabo, Rafael

2015-04-01

Caloric restriction (CR) without malnutrition is one of the most consistent strategies for increasing mean and maximal lifespan and delaying the onset of age-associated diseases. Stress resistance is a common trait of many long-lived mutants and life-extending interventions, including CR. Indeed, better protection against heat shock and other genotoxic insults have helped explain the pro-survival properties of CR. In this study, both in vitro and in vivo responses to heat shock were investigated using two different models of CR. Murine B16F10 melanoma cells treated with serum from CR-fed rats showed lower proliferation, increased tolerance to heat shock and enhanced HSP-70 expression, compared to serum from ad libitum-fed animals. Similar effects were observed in B16F10 cells implanted subcutaneously in male C57BL/6 mice subjected to CR. Microarray analysis identified a number of genes and pathways whose expression profile were similar in both models. These results suggest that the use of an in vitro model could be a good alternative to study the mechanisms by which CR exerts its anti-tumorigenic effects.

Caloric restriction induces heat shock response and inhibits B16F10 cell tumorigenesis both in vitro and in vivo

PubMed Central

Novelle, Marta G.; Davis, Ashley; Price, Nathan L.; Ali, Ahmed; Fürer-Galvan, Stefanie; Zhang, Yongqing; Becker, Kevin; Bernier, Michel; de Cabo, Rafael

2015-01-01

Caloric restriction (CR) without malnutrition is one of the most consistent strategies for increasing mean and maximal lifespan and delaying the onset of age-associated diseases. Stress resistance is a common trait of many long-lived mutants and life-extending interventions, including CR. Indeed, better protection against heat shock and other genotoxic insults have helped explain the pro-survival properties of CR. In this study, both in vitro and in vivo responses to heat shock were investigated using two different models of CR. Murine B16F10 melanoma cells treated with serum from CR-fed rats showed lower proliferation, increased tolerance to heat shock and enhanced HSP-70 expression, compared to serum from ad libitum-fed animals. Similar effects were observed in B16F10 cells implanted subcutaneously in male C57BL/6 mice subjected to CR. Microarray analysis identified a number of genes and pathways whose expression profile were similar in both models. These results suggest that the use of an in vitro model could be a good alternative to study the mechanisms by which CR exerts its anti-tumorigenic effects. PMID:25948793

Electronic and optical properties of Cr-, B-doped, and (Cr, B)-codoped SrTiO3

NASA Astrophysics Data System (ADS)

Wu, Jiao; Huang, Wei-Qing; Yang, Ke; Wei, Zeng-Xi; Peng, P.; Huang, Gui-Fang

2017-04-01

Energy band engineering of semiconductors plays a crucial role in exploring high-efficiency visible-light response photocatalysts. Herein, we systematically study the electronic properties and optical response of Cr-, B-doped SrTiO3, and (Cr, B)-codoped SrTiO3 by using first-principles calculations to explore the mechanism for its superior photocatalytic activities in the visible light region. Special emphasis is placed on uncovering the synergy effects of nonmetal B dopant with metal Cr dopant at different cation sites. It is found that the electronic properties and optical absorption of SrTiO3 can be dramatically engineered by mono- or co-doping. In particular, the intermediate levels lying in the bandgap of the codoped SrTiO3 relay on the Cr impurity doped at Sr or Ti cation sites. Moreover, the (Cr@Sr, B@O)-SrTiO3 retains the charge balancing without the generation of unexpected oxygen vacancies, and is more desirable for solar light harvesting due to its higher absorption than others in the entire visible light. The findings can rationalize the available experimental results and are helpful in designing SrTiO3-based photocatalysts with high-efficiency performance.

Intergranular stress corrosion cracking and selective internal oxidation of nickel-chromium-iron alloys in hydrogenated steam

NASA Astrophysics Data System (ADS)

Capell, Brent M.

2005-07-01

Selective internal oxidation (SIO) is a mechanism of grain boundary embrittlement through the formation of intergranular oxides of Cr2O3. SIO is proposed as a mechanism to explain intergranular stress corrosion cracking (IGSCC) of Ni-base alloys in pressurized water reactor environments. The purpose of this work is to investigate SIO through a series of experiments using controlled-purity alloys in a controlled, low-pressure steam environment in which the oxygen potential is varied. Five alloys; Ni-9Fe, Ni-5Cr, LCr (Ni-5Cr-9Fe), CD85 (Ni-16Cr-9Fe) and HCr (Ni-30Cr-9Fe), were used in corrosion coupon exposure tests and constant extension rate tensile (CERT) tests at 550°C and 400°C in an environment consisting of a controlled mixture of hydrogen, water vapor and argon. The hydrogen-to-water vapor partial pressure ratio (PPR) was varied between 0.001 and 0.9 to control the oxygen partial pressure. The Ni-9Fe, Ni-5Cr and LCr alloys formed a uniform Ni(OH)2 film at PPR values less than 0.09 while CD85 and HCr formed Cr2O 3 oxide films over the entire PPR range. Corrosion coupon results also show the formation of highly localized oxide particles at grain boundaries. Focused ion beam analysis revealed that intergranular oxides were observed at significant depths (>150 nm) down grain boundaries and the oxide morphology depended on the alloy composition and PPR value. Diffusion of oxygen along the grain boundary accounted for the growth of intergranular oxides. CERT test results showed that intergranular cracking was caused by creep-induced microvoid coalescence only at 550°C and did not depend on PPR. At 400°C, the cracking behavior depended on the PPR and resulted in a mixture of creep-induced microvoid coalescence and brittle intergranular failure. The cracked boundary fraction was higher at a PPR value where a Ni(OH)2 surface film formed. Alloy composition influenced cracking and the cracked boundary fraction decreased as the alloy chromium content increased. The compositions of oxides at intergranular crack tips were similar to intergranular oxides in corrosion coupons and demonstrated a link between intergranular oxide formation and intergranular cracking. The observation of intergranular oxides as well as the influence of alloy content on IG cracking was found to support SIO as a mechanism for IGSCC.

Magnetic and low temperature phonon studies of CoCr2O4 powders doped with Fe(III) and Ni(II) ions

NASA Astrophysics Data System (ADS)

Ptak, M.; Mączka, M.; Pikul, A.; Tomaszewski, P. E.; Hanuza, J.

2014-04-01

Extensive temperature-dependent phonon studies and low-temperature magnetic measurements of CoCr2-xFexO4 (for x=0.5, 1 and 2) and Co0.9Ni0.1Cr2O4 polycrystalline powders are presented. The main aim of these studies was to obtain information on phonon and structural properties of these compounds as well as strength of spin-phonon coupling in the magnetically ordered phases. IR and Raman spectra show that doping of CoCr2O4 with Fe(III) ions leads to broadening of bands and appearance of new bands due to the formation of inverted spinel structure. In contrast to this behavior, doping with 10 mol% of Ni(II) ions leads to weak increase of band width only. Magnetization measured as a function of temperature and external magnetic field showed that magnetic properties of Co0.9Ni0.1Cr2O4 sample are similar to those reported for pure CoCr2O4, i.e., partial substitution of Ni(II) for Co(II) leads to slight shift of the ferrimagnetic phase transition at TC and spiral spin order transition at TS towards lower values. The change of crystallization preference induced by incorporation of increasing concentration of Fe(III) ions in the spinel lattice causes significant increase of TC and decrease of TS. The latter transition disappears completely for higher concentrations of Fe(III). The performed temperature-dependent IR studies revealed interesting anomalous behavior of phonons below TC for CoCr1.5Fe0.5O4 and Co0.9Ni0.1Cr2O4, which was attributed to spin-phonon coupling.

Memory is Not Enough: The Neurobiological Substrates of Dynamic Cognitive Reserve.

PubMed

Serra, Laura; Bruschini, Michela; Di Domenico, Carlotta; Gabrielli, Giulia Bechi; Marra, Camillo; Caltagirone, Carlo; Cercignani, Mara; Bozzali, Marco

2017-01-01

Changes in the residual memory variance are considered as a dynamic aspect of cognitive reserve (d-CR). We aimed to investigate for the first time the neural substrate associated with changes in the residual memory variance overtime in patients with amnestic mild cognitive impairment (aMCI). Thirty-four aMCI patients followed-up for 36 months and 48 healthy elderly individuals (HE) were recruited. All participants underwent 3T MRI, collecting T1-weighted images for voxel-based morphometry (VBM). They underwent an extensive neuropsychological battery, including six episodic memory tests. In patients and controls, factor analyses were used on the episodic memory scores to obtain a composite memory score (C-MS). Partial Least Square analyses were used to decompose the variance of C-MS in latent variables (LT scores), accounting for demographic variables and for the general cognitive efficiency level; linear regressions were applied on LT scores, striping off any contribution of general cognitive abilities, to obtain the residual value of memory variance, considered as an index of d-CR. LT scores and d-CR were used in discriminant analysis, in patients only. Finally, LT scores and d-CR were used as variable of interest in VBM analysis. The d-CR score was not able to correctly classify patients. In both aMCI patients and HE, LT1st and d-CR scores showed correlations with grey matter volumes in common and in specific brain areas. Using CR measures limited to assess memory function is likely less sensitive to detect the cognitive decline and predict the evolution of Alzheimer's disease. In conclusion, d-CR needs a measure of general cognition to identify conversion to Alzheimer's disease efficiently.

Effects of dietary organic chromium and vitamin C supplementation on performance, immune responses, blood metabolites, and stress status of laying hens subjected to high stocking density.

PubMed

Mirfendereski, E; Jahanian, R

2015-02-01

The present study was carried out to investigate the effects of dietary supplementation of chromium-methionine (CrMet) and vitamin C (VC) on performance, immune response, and stress status of laying hens subjected to high stocking density. A total of 360 Hy-Line W-36 leghorn hens (at 26 wk old) were used in a 2×3×2 factorial arrangement that had 2 cage densities (5 and 7 hens per cage), 3 Cr levels (0, 500, and 1,000 ppb as CrMet), and 2 dietary VC levels (0 and 500 ppm as L-ascorbic acid). The trial lasted for 12 wk. The first 2 wk were for adaptation (26 to 28 wk of age), and the remaining 10 wk served as the main recording period. In addition to performance, immune response to Newcastle disease virus (NDV) was assessed at d 7 and 14 postvaccination. Also, the birds' stress status was evaluated by analyzing appropriate plasma metabolites. The results showed that hens in cages with higher stocking density had lower hen-day egg production, egg mass, and feed intake compared with those in normal density cages (P<0.05). Dietary CrMet supplementation caused significant increases in egg production and egg mass (P<0.01). There were significant Cr × VC interactions related to egg production and feed conversion efficiency (P<0.01); dietary CrMet supplementation was more effective in improving egg production and feed conversion ratio in VC-unsupplemented diets. Although plasma concentrations of triglycerides and high-density lipoproteins were not influenced by dietary treatments, supplemental CrMet decreased plasma cholesterol levels (P<0.05). Plasma insulin and glucose levels of hens kept at a density of 7 hens/cage were significantly higher than those of hens in normal cage density (P<0.01), and dietary CrMet supplementation decreased plasma concentrations of insulin (P<0.001) and glucose (P<0.01), with higher impacts in high stocking density-challenged hens. While high stocking density caused a marked increase in plasma corticosterone (P<0.01), both supplemental CrMet and VC decreased it to near normal levels. There were significant stocking density×Cr interactions related to plasma insulin and corticosterone concentrations (P<0.01); supplemental CrMet was more effective in lowering these hormones in high stocking density-challenged hens. The high stocking density challenge suppressed NDV antibody response (P<0.001), while dietary supplementation of CrMet improved antibody titers against NDV at d 14 post vaccination particularly in hens kept at a density of 7 hens/cage (P<0.01). From the present observations, it can be concluded that CrMet can improve laying performance largely because it alleviates harmful responses to stressful conditions. © 2015 Poultry Science Association Inc.

Chromium in Drinking Water: Sources, Metabolism, and Cancer Risks

PubMed Central

2011-01-01

Drinking water supplies in many geographic areas contain chromium in the +3 and +6 oxidation states. Public health concerns are centered on the presence of hexavalent Cr that is classified as a known human carcinogen via inhalation. Cr(VI) has high environmental mobility and can originate from anthropogenic and natural sources. Acidic environments with high organic content promote the reduction of Cr(VI) to nontoxic Cr(III). The opposite process of Cr(VI) formation from Cr(III) also occurs, particularly in the presence of common minerals containing Mn(IV) oxides. Limited epidemiological evidence for Cr(VI) ingestion is suggestive of elevated risks for stomach cancers. Exposure of animals to Cr(VI) in drinking water induced tumors in the alimentary tract, with linear and supralinear responses in the mouse small intestine. Chromate, the predominant form of Cr(VI) at neutral pH, is taken up by all cells through sulfate channels and is activated nonenzymatically by ubiquitously present ascorbate and small thiols. The most abundant form of DNA damage induced by Cr(VI) is Cr-DNA adducts, which cause mutations and chromosomal breaks. Emerging evidence points to two-way interactions between DNA damage and epigenetic changes that collectively determine the spectrum of genomic rearrangements and profiles of gene expression in tumors. Extensive formation of DNA adducts, clear positivity in genotoxicity assays with high predictive values for carcinogenicity, the shape of tumor–dose responses in mice, and a biological signature of mutagenic carcinogens (multispecies, multisite, and trans-sex tumorigenic potency) strongly support the importance of the DNA-reactive mutagenic mechanisms in carcinogenic effects of Cr(VI). Bioavailability results and kinetic considerations suggest that 10–20% of ingested low-dose Cr(VI) escapes human gastric inactivation. The directly mutagenic mode of action and the incompleteness of gastric detoxification argue against a threshold in low-dose extrapolation of cancer risk for ingested Cr(VI). PMID:21766833

Highly Corrosion Resistant and Sandwich-like Si3N4/Cr-CrNx/Si3N4 Coatings Used for Solar Selective Absorbing Applications.

PubMed

Zhang, Ke; Du, Miao; Haoa, Lei; Meng, Jianping; Wang, Jining; Mi, Jing; Liu, Xiaopeng

2016-12-14

Highly corrosion resistant, layer-by-layer nanostructured Si 3 N 4 /Cr-CrN x /Si 3 N 4 coatings were deposited on aluminum substrate by DC/RF magnetron sputtering. Corrosion resistance experiments were performed in 0.5, 1.0, 3.0, and 5.0 wt % NaCl salt spray at 35 °C for 168 h. Properties of the coatings were comprehensively investigated in terms of optical property, surface morphology, microstructure, elemental valence state, element distribution, and potentiodynamic polarization. UV-vis-near-IR spectrophotometer and FTIR measurements show that the change process in optical properties of Si 3 N 4 /Cr-CrN x /Si 3 N 4 /Al coatings can be divided into three stages: a rapid active degradation stage, a steady passivation stage, and a transpassivation degradation stage. With the increase in the concentration of NaCl salt spray, solar absorptance and thermal emittance experienced a slight degradation. SEM images reveal that there is an increase in surface defects, such as microcracks and holes and -cracks. XRD and TEM measurements indicate that the phase structure changed partially and the content of CrO x and Al 2 O 3 has increased. Auger electron spectroscopy shows that the elements of Cr, N, and O have undergone a minor diffusion. Electrochemical polarization curves show that the as-deposited Si 3 N 4 /Cr-CrN x /Si 3 N 4 /Al coatings have excellent corrosion resistance of 3633.858 kΩ, while after corroding in 5.0 wt % NaCl salt spray for 168 h the corrosion resistance dropped to 13.759 kΩ. However, these coatings still have an outstanding performance of high solar absorptance of 0.924 and low thermal emittance of 0.090 after corroding in 3.0 wt % NaCl salt spray for 120 h. Thus, the Si 3 N 4 /Cr-CrN x /Si 3 N 4 /Al coating is a good choice for solar absorber coatings applied in the high-saline environment.

Chromate Reduction by a Pseudomonad Isolated from a Site Contaminated with Chromated Copper Arsenate

PubMed Central

McLean, Jeff; Beveridge, Terry J.

2001-01-01

A pseudomonad (CRB5) isolated from a decommissioned wood preservation site reduced toxic chromate [Cr(VI)] to an insoluble Cr(III) precipitate under aerobic and anaerobic conditions. CRB5 tolerated up to 520 mg of Cr(VI) liter−1 and reduced chromate in the presence of copper and arsenate. Under anaerobic conditions it also reduced Co(III) and U(VI), partially internalizing each metal. Metal precipitates were also found on the surface of the outer membrane and (sometimes) on a capsule. The results showed that chromate reduction by CRB5 was mediated by a soluble enzyme that was largely contained in the cytoplasm but also found outside of the cells. The crude reductase activity in the soluble fraction showed a Km of 23 mg liter−1 (437 μM) and a Vmax of 0.98 mg of Cr h−1 mg of protein−1 (317 nmol min−1 mg of protein−1). Minor membrane-associated Cr(VI) reduction under anaerobiosis may account for anaerobic reduction of chromate under nongrowth conditions with an organic electron donor present. Chromate reduction under both aerobic and anaerobic conditions may be a detoxification strategy for the bacterium which could be exploited to bioremediate chromate-contaminated or other toxic heavy metal-contaminated environments. PMID:11229894

The Effect of Year-to-Year Rater Variation on IRT Linking

ERIC Educational Resources Information Center

Yen, Shu Jing; Ochieng, Charles; Michaels, Hillary; Friedman, Greg

2005-01-01

Year-to-year rater variation may result in constructed response (CR) parameter changes, making CR items inappropriate to use in anchor sets for linking or equating. This study demonstrates how rater severity affected the writing and reading scores. Rater adjustments were made to statewide results using an item response theory (IRT) methodology…

Reinstatement of an Extinguished Fear Conditioned Response in Infant Rats

ERIC Educational Resources Information Center

Revillo, Damian A.; Trebucq, Gastón; Paglini, Maria G.; Arias, Carlos

2016-01-01

Although it is currently accepted that the extinction effect reflects new context-dependent learning, this is not so clear during infancy, because some studies did not find recovery of the extinguished conditioned response (CR) in rodents during this ontogenetic stage. However, recent studies have shown the return of an extinguished CR in infant…

Compliment Responses of Thai and Punjabi Speakers of English in Thailand

ERIC Educational Resources Information Center

Sachathep, Sukchai

2014-01-01

This variational pragmatics (VP) study investigates the similarities and differences of compliment responses (CR) between Thai and Punjabi speakers of English in Thailand, focusing on the strategies used in CR when the microsociolinguistic variables are integrated into the Discourse Completion Task (DCT). The participants were 20 Thai and 20…

Health benefits of air pollution abatement policy: Role of the shape of the concentration-response function.

PubMed

Pope, C Arden; Cropper, Maureen; Coggins, Jay; Cohen, Aaron

2015-05-01

There is strong evidence that fine particulate matter (aerodynamic diameter<2.5 μm; PM2.5) air pollution contributes to increased risk of disease and death. Estimates of the burden of disease attributable to PM2.5 pollution and benefits of reducing pollution are dependent upon the shape of the concentration response (C-R) functions. Recent evidence suggests that the C-R function between PM2.5 air pollution and mortality risk may be supralinear across wide ranges of exposure. Such results imply that incremental pollution abatement efforts may yield greater benefits in relatively clean areas than in highly polluted areas. The role of the shape of the C-R function in evaluating and understanding the costs and health benefits of air pollution abatement policy is explored. There remain uncertainties regarding the shape of the C-R function, and additional efforts to more fully understand the C-R relationships between PM2.5 and adverse health effects are needed to allow for more informed and effective air pollution abatement policies. Current evidence, however, suggests that there are benefits both from reducing air pollution in the more polluted areas and from continuing to reduce air pollution in cleaner areas. Estimates of the benefits of reducing PM2.5 air pollution are highly dependent upon the shape of the PM2.5-mortality concentration-response (C-R) function. Recent evidence indicates that this C-R function may be supralinear across wide ranges of exposure, suggesting that incremental pollution abatement efforts may yield greater benefits in relatively clean areas than in highly polluted areas. This paper explores the role of the shape of the C-R function in evaluating and understanding the costs and health benefits of PM2.5 air pollution abatement.

Fractionated gemtuzumab ozogamicin and standard dose cytarabine produced prolonged second remissions in patients over the age of 55 years with acute myeloid leukemia in late first relapse.

PubMed

Pilorge, Sylvain; Rigaudeau, Sophie; Rabian, Florence; Sarkozy, Clémentine; Taksin, Anne L; Farhat, Hassan; Merabet, Fathia; Ghez, Stéphanie; Raggueneau, Victoria; Terré, Christine; Garcia, Isabelle; Renneville, Aline; Preudhomme, Claude; Castaigne, Sylvie; Rousselot, Philippe

2014-04-01

Gemtuzumab ozogamicin (fGO), a humanized anti-CD33 monoclonal antibody linked to calicheamicin in combination with intensive chemotherapy gives high response rates in adult acute myeloid leukemia (AML) patients in relapse. However, reduced intensity chemotherapy in combination with fractionated GO has not been tested in aged relapsing patients. Patients from our institution with CD33+ AML aged 55 years or more in first late relapse (≥ 6 months) were proposed participation in a GO compassionate use program. Induction therapy consisted in fractionated GO (fGO; 3 mg/m², days 1, 4, 7) with standard-dose cytarabine (200 mg/m² /day, 7 days). Patients were consolidated with two courses of GO and intermediate dose cytarabine. Twenty-four patients (median age 68 years) received fGO with cytarabine. Median follow-up was 42 months. The response rate was 75%, including complete remission (CR) in 16 patients and CR with incomplete platelet recovery (CRp) in two patients. Two-year overall survival (OS) was 51% (95% CI: 28-69) and 2 years relapse-free survival (RFS) was 51% (95%CI: 25-72). Duration of second CR (CR2) was longer than first CR (CR1) in 9 out of 18 patients. Minimal residual disease (MRD) was negative in evaluable patients in CR2, particularly in NPM1 mutated cases. Toxicity was in line with that of the same fractionated single agent GO schedule. Fractionated GO with low intensity chemotherapy produced high response rates and prolonged CR2 in aged AML patients in first late relapse. Copyright © 2013 Wiley Periodicals, Inc.

Cryogenic strength improvement by utilizing room-temperature deformation twinning in a partially recrystallized VCrMnFeCoNi high-entropy alloy

PubMed Central

Jo, Y. H.; Jung, S.; Choi, W. M.; Sohn, S. S.; Kim, H. S.; Lee, B. J.; Kim, N. J.; Lee, S.

2017-01-01

The excellent cryogenic tensile properties of the CrMnFeCoNi alloy are generally caused by deformation twinning, which is difficult to achieve at room temperature because of insufficient stress for twinning. Here, we induced twinning at room temperature to improve the cryogenic tensile properties of the CrMnFeCoNi alloy. Considering grain size effects on the critical stress for twinning, twins were readily formed in the coarse microstructure by cold rolling without grain refinement by hot rolling. These twins were retained by partial recrystallization and played an important role in improving strength, allowing yield strengths approaching 1 GPa. The persistent elongation up to 46% as well as the tensile strength of 1.3 GPa are attributed to additional twinning in both recrystallized and non-recrystallization regions. Our results demonstrate that non-recrystallized grains, which are generally avoided in conventional alloys because of their deleterious effect on ductility, can be useful in achieving high-strength high-entropy alloys. PMID:28604656

CrATP interferes in the promastigote-macrophage interaction in Leishmania amazonensis infection.

PubMed

Ennes-Vidal, V; Castro, R O S; Britto, C; Barrabin, H; D'Avila-Levy, C M; Moreira, O C

2011-07-01

Recent have shown the relationship between Ecto-Nucleoside-Triphosphate-Diphosphohydrolases (Ecto-NTPDases or ecto-nucleotidases) and virulence and infectivity in trypanosomatids. In this work, the inhibition of the ecto-ATPase activities and promastigote growth of Leishmania amazonensis by CrATP was characterized. Furthermore, this compound was used to investigate the role of ecto-nucleotidase in the interaction of L. amazonensis with resident peritoneal macrophages obtained from BALB/c mice. CrATP partially inhibits the ecto-ATPase activity, presenting Ki values of 575·7±199·1 and 383·5±79·0 μm, in the presence or absence of 5 mm MgCl2, respectively. The apparent Kms for ATP (2·9±0·5 mm to Mg2+-dependent ecto-ATPase and 0·4±0·2 mm to Mg2+-independent ecto-ATPase activities) are not significantly altered by CrATP, suggesting a reversible non-competitive inhibition of both enzymes. When CrATP was added to the cultivation medium at 500 μm, it drastically inhibited the cellular growth. The interaction of promastigote forms of L. amazonensis with BALB/c peritoneal macrophages is strongly affected by CrATP. When the parasites were treated with 500 μm CrATP before interacting with macrophages, the adhesion and endocytic indices were strongly reduced to 53·0±14·8% and 39·8±1·1%, respectively. These results indicate that ecto-nucleotidase plays an important role in the infection process caused by Leishmania amazonensis.

GABA content within the ventromedial prefrontal cortex is related to trait anxiety.

PubMed

Delli Pizzi, Stefano; Padulo, Caterina; Brancucci, Alfredo; Bubbico, Giovanna; Edden, Richard A; Ferretti, Antonio; Franciotti, Raffaella; Manippa, Valerio; Marzoli, Daniele; Onofrj, Marco; Sepede, Gianna; Tartaro, Armando; Tommasi, Luca; Puglisi-Allegra, Stefano; Bonanni, Laura

2016-05-01

The ventromedial prefrontal cortex (vmPFC) plays a key role in emotion processing and regulation. vmPFC dysfunction may lead to disinhibition of amygdala causing high anxiety levels. γ-Aminobutyric acid (GABA) inter-neurons within vmPFC shape the information flow to amygdala. Thus, we hypothesize that GABA content within vmPFC could be relevant to trait anxiety. Forty-three healthy volunteers aged between 20 and 88 years were assessed for trait anxiety with the Subscale-2 of the State-Trait-Anxiety Inventory (STAI-Y2) and were studied with proton magnetic resonance spectroscopy to investigate GABA and Glx (glutamate+glutamine) contents within vmPFC. Total creatine (tCr) was used as internal reference. Partial correlations assessed the association between metabolite levels and STAI-Y2 scores, removing the effect of possible nuisance factors including age, educational level, volumes of gray matter and white matter within magnetic resonance spectroscopy voxel. We observed a positive relationship between GABA/tCr and STAI-Y2 scores. No significant relationships were found between Glx/tCr and STAI-Y2 and between tCr/water and STAI-Y2. No differences were found between males and females as regards to age, STAI-Y2, GABA/tCr, Glx/tCr, tCr/water, gray matter and white matter volumes. We suggest a close relationship between GABA content within vmPFC and trait anxiety providing new insights in the physiology of emotional brain. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

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

Seyler, Kyle L.; Zhong, Ding; Klein, Dahlia R.

Bulk chromium tri-iodide (CrI 3) has long been known as a layered van der Waals ferromagnet. However, its monolayer form was only recently isolated and confirmed to be a truly two-dimensional (2D) ferromagnet, providing a new platform for investigating light–matter interactions and magneto-optical phenomena in the atomically thin limit. Here in this paper, we report spontaneous circularly polarized photoluminescence in monolayer CrI 3 under linearly polarized excitation, with helicity determined by the monolayer magnetization direction. In contrast, the bilayer CrI 3 photoluminescence exhibits vanishing circular polarization, supporting the recently uncovered anomalous antiferromagnetic interlayer coupling in CrI 3 bilayers. Distinct frommore » the Wannier–Mott excitons that dominate the optical response in well-known 2D van der Waals semiconductors, our absorption and layer-dependent photoluminescence measurements reveal the importance of ligand-field and charge-transfer transitions to the optoelectronic response of atomically thin CrI 3. We attribute the photoluminescence to a parity-forbidden d–d transition characteristic of Cr 3+ complexes, which displays broad linewidth due to strong vibronic coupling and thickness-independent peak energy due to its localized molecular orbital nature.« less

Reduction of hexavalent chromium using Aerva lanata L.: elucidation of reduction mechanism and identification of active principles.

PubMed

Poonkuzhali, K; Rajeswari, V; Saravanakumar, T; Viswanathamurthi, P; Park, Seung-Moon; Govarthanan, M; Sathishkumar, P; Palvannan, T

2014-05-15

The effluent discharge treatment for controlling the environment from non biodegradable metal contaminants using plant extract is an efficient technique. The reduction of hexavalent chromium by abundantly available weed, Aerva lanata L. was investigated using batch equilibrium technique. The variables studied were Cr(VI) concentration, Aerva lanata L. dose, contact time, pH, temperature and agitation speed. Cyclic voltammetry and ICP-MS analysis confirmed the reduction of Cr(VI) to Cr(III). Electrochemical analysis proved that, the chromium has not been degraded and the valency of the chromium has only been changed. ICP-MS analysis shows that 100ng/L of hexavalent chromium was reduced to 97.01ng/L trivalent chromium. These results suggest that components present in the Aerva lanata L. are responsible for the reduction of Cr(VI) to Cr(III). The prime components ferulic acid, kaempherol and β-carboline present in the Aerva lanata L. may be responsible for the reduction of Cr(VI) as evident from LC-MS analysis. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of chromium on the immune system.

PubMed

Shrivastava, Richa; Upreti, R K; Seth, P K; Chaturvedi, U C

2002-09-06

Chromium is a naturally occurring heavy metal found commonly in the environment in trivalent, Cr(III), and hexavalent, Cr(VI), forms. Cr(VI) compounds have been declared as a potent occupational carcinogen among workers in chrome plating, stainless steel, and pigment industries. The reduction of Cr(VI) to Cr(III) results in the formation of reactive intermediates that together with oxidative stress oxidative tissue damage and a cascade of cellular events including modulation of apoptosis regulatory gene p53, contribute to the cytotoxicity, genotoxicity and carcinogenicity of Cr(VI)-containing compounds. On the other hand, chromium is an essential nutrient required to promote the action of insulin in body tissues so that the body can use sugars, proteins and fats. Chromium is of significant importance in altering the immune response by immunostimulatory or immunosuppressive processes as shown by its effects on T and B lymphocytes, macrophages, cytokine production and the immune response that may induce hypersensitivity reactions. This review gives an overview of the effects of chromium on the immune system of the body. Copyright 2002 Federation of European Microbiological Societies

Metabolomic Profiling of the Synergistic Effects of Melittin in Combination with Cisplatin on Ovarian Cancer Cells

PubMed Central

Alonezi, Sanad; Tusiimire, Jonans; Wallace, Jennifer; Dufton, Mark J.; Parkinson, John A.; Young, Louise C.; Clements, Carol J.; Park, Jin-Kyu; Jeon, Jong-Woon; Ferro, Valerie A.; Watson, David G.

2017-01-01

Melittin, the main peptide present in bee venom, has been proposed as having potential for anticancer therapy; the addition of melittin to cisplatin, a first line treatment for ovarian cancer, may increase the therapeutic response in cancer treatment via synergy, resulting in improved tolerability, reduced relapse, and decreased drug resistance. Thus, this study was designed to compare the metabolomic effects of melittin in combination with cisplatin in cisplatin-sensitive (A2780) and resistant (A2780CR) ovarian cancer cells. Liquid chromatography (LC) coupled with mass spectrometry (MS) was applied to identify metabolic changes in A2780 (combination treatment 5 μg/mL melittin + 2 μg/mL cisplatin) and A2780CR (combination treatment 2 μg/mL melittin + 10 μg/mL cisplatin) cells. Principal components analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) multivariate data analysis models were produced using SIMCA-P software. All models displayed good separation between experimental groups and high-quality goodness of fit (R2) and goodness of prediction (Q2), respectively. The combination treatment induced significant changes in both cell lines involving reduction in the levels of metabolites in the tricarboxylic acid (TCA) cycle, oxidative phosphorylation, purine and pyrimidine metabolism, and the arginine/proline pathway. The combination of melittin with cisplatin that targets these pathways had a synergistic effect. The melittin-cisplatin combination had a stronger effect on the A2780 cell line in comparison with the A2780CR cell line. The metabolic effects of melittin and cisplatin in combination were very different from those of each agent alone. PMID:28420117

TiO2-Based Nanomaterials for Gas Sensing-Influence of Anatase and Rutile Contributions.

PubMed

Zakrzewska, K; Radecka, M

2017-12-01

The paper deals with application of three nanomaterial systems: undoped TiO 2 , chromium-doped TiO 2 :Cr and TiO 2 -SnO 2 synthesized by flame spray synthesis (FSS) technique for hydrogen sensing. The emphasis is put on the role of anatase and rutile polymorphic forms of TiO 2 in enhancing sensitivity towards reducing gases. Anatase-to-rutile transformation is achieved by annealing of undoped TiO 2 in air at 700 °C, specific Cr doping and modification with SnO 2 . Undoped TiO 2 and TiO 2 -SnO 2 exhibit n-type behaviour and while TiO 2 : 5 at.% Cr is a p-type semiconductor. X-ray diffraction (XRD) has been applied to determine anatase-to-rutile weight ratio as well as anatase and rutile crystal size. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) have been used to characterize the structure and morphological parameters. Optical reflectometry enabled to find and compare the band gaps E g of anatase and rutile predominated compositions. Electrical properties, i.e. the electrical conductivity and values of constant phase element (CPE), have been established on the basis of impedance spectroscopy. Dynamic responses of the electrical resistance as a function of hydrogen concentration revealed that predominance of rutile in anatase/rutile mixture is beneficial for gas sensing. Partial transformation to rutile in all three material systems under study resulted in an increased sensitivity towards hydrogen. It is proposed that this effect can be explained in a similar way as in photocatalysis, i.e. by specific band alignment and electron transfer from rutile to anatase to facilitate oxygen preadsorption on the surface of anatase grains.

From mean-field localized magnetism to itinerant spin fluctuations in the "nonmetallic metal" FeCrAs

NASA Astrophysics Data System (ADS)

Plumb, K. W.; Stock, C.; Rodriguez-Rivera, J. A.; Castellan, J.-P.; Taylor, J. W.; Lau, B.; Wu, W.; Julian, S. R.; Kim, Young-June

2018-05-01

FeCrAs displays an unusual electrical response that is neither metallic in character nor divergent at low temperatures, as expected for an insulating response, and therefore it has been termed a "nonmetal metal." The anomalous resistivity occurs for temperatures below ˜900 K. We have carried out neutron scattering experiments on powder and single crystal samples to study the magnetic dynamics and critical fluctuations in FeCrAs. Magnetic neutron diffraction measurements find Cr3 + magnetic order setting in at TN=115 K ˜10 meV with a mean-field critical exponent. Using neutron spectroscopy we observe gapless, high velocity, magnetic fluctuations emanating from magnetic positions with propagation wave vector q⃗0=(1/3 ,1/3 ) , which persists up to at least 80 meV ˜927 K, an energy scale much larger than TN. Despite the mean-field magnetic order at low temperatures, the magnetism in FeCrAs therefore displays a response which resembles that of itinerant magnets at high energy transfers. We suggest that the presence of stiff high-energy spin fluctuations extending up to a temperature scale of ˜900 K is the origin of the unusual temperature dependence of the resistivity.

Effects of Sex, Strain, and Energy Intake on Hallmarks of Aging in Mice.

PubMed

Mitchell, Sarah J; Madrigal-Matute, Julio; Scheibye-Knudsen, Morten; Fang, Evandro; Aon, Miguel; González-Reyes, José A; Cortassa, Sonia; Kaushik, Susmita; Gonzalez-Freire, Marta; Patel, Bindi; Wahl, Devin; Ali, Ahmed; Calvo-Rubio, Miguel; Burón, María I; Guiterrez, Vincent; Ward, Theresa M; Palacios, Hector H; Cai, Huan; Frederick, David W; Hine, Christopher; Broeskamp, Filomena; Habering, Lukas; Dawson, John; Beasley, T Mark; Wan, Junxiang; Ikeno, Yuji; Hubbard, Gene; Becker, Kevin G; Zhang, Yongqing; Bohr, Vilhelm A; Longo, Dan L; Navas, Placido; Ferrucci, Luigi; Sinclair, David A; Cohen, Pinchas; Egan, Josephine M; Mitchell, James R; Baur, Joseph A; Allison, David B; Anson, R Michael; Villalba, José M; Madeo, Frank; Cuervo, Ana Maria; Pearson, Kevin J; Ingram, Donald K; Bernier, Michel; de Cabo, Rafael

2016-06-14

Calorie restriction (CR) is the most robust non-genetic intervention to delay aging. However, there are a number of emerging experimental variables that alter CR responses. We investigated the role of sex, strain, and level of CR on health and survival in mice. CR did not always correlate with lifespan extension, although it consistently improved health across strains and sexes. Transcriptional and metabolomics changes driven by CR in liver indicated anaplerotic filling of the Krebs cycle together with fatty acid fueling of mitochondria. CR prevented age-associated decline in the liver proteostasis network while increasing mitochondrial number, preserving mitochondrial ultrastructure and function with age. Abrogation of mitochondrial function negated life-prolonging effects of CR in yeast and worms. Our data illustrate the complexity of CR in the context of aging, with a clear separation of outcomes related to health and survival, highlighting complexities of translation of CR into human interventions. Published by Elsevier Inc.

Diagnosing cerebral visual impairment in children with good visual acuity.

PubMed

van Genderen, Maria; Dekker, Marjoke; Pilon, Florine; Bals, Irmgard

2012-06-01

To identify elements that could facilitate the diagnosis of cerebral visual impairment (CVI) in children with good visual acuity in the general ophthalmic clinic. We retrospectively investigated the clinical characteristics of 30 children with good visual acuity and CVI and compared them with those of 23 children who were referred with a suspicion of CVI, but proved to have a different diagnosis. Clinical characteristics included medical history, MRI findings, visual acuity, crowding ratio (CR), visual field assessment, and the results of ophthalmologic and orthoptic examination. We also evaluated the additional value of a short CVI questionnaire. Eighty-three percent of the children with an abnormal medical history (mainly prematurity and perinatal hypoxia) had CVI, in contrast with none of the children with a normal medical history. Cerebral palsy, visual field defects, and partial optic atrophy only occurred in the CVI group. 41% of the children with CVI had a CR ≥2.0, which may be related to dorsal stream dysfunction. All children with CVI, but also 91% of the children without CVI gave ≥3 affirmative answers on the CVI questionnaire. An abnormal pre- or perinatal medical history is the most important risk factor for CVI in children, and therefore in deciding which children should be referred for further multidisciplinary assessment. Additional symptoms of cerebral damage, i.e., cerebral palsy, visual field defects, partial optic atrophy, and a CR ≥2 may support the diagnosis. CVI questionnaires should not be used for screening purposes as they yield too many false positives.

Homologous Recombination Repair Signaling in Chemical Carcinogenesis: Prolonged Particulate Hexavalent Chromium Exposure Suppresses the Rad51 Response in Human Lung Cells

PubMed Central

Qin, Qin; Xie, Hong; Wise, Sandra S.; Browning, Cynthia L.; Thompson, Kelsey N.; Holmes, Amie L.; Wise, John Pierce

2014-01-01

The aim of this study was to focus on hexavalent chromium, [Cr(VI)], a chemical carcinogen and major public health concern, and consider its ability to impact DNA double strand break repair. We further focused on particulate Cr(VI), because it is the more potent carcinogenic form of Cr(VI). DNA double strand break repair serves to protect cells against the detrimental effects of DNA double strand breaks. For particulate Cr(VI), data show DNA double strand break repair must be overcome for neoplastic transformation to occur. Acute Cr(VI) exposures reveal a robust DNA double strand break repair response, however, longer exposures have not been considered. Using the comet assay, we found longer exposures to particulate zinc chromate induced concentration-dependent increases in DNA double strand breaks indicating breaks were occurring throughout the exposure time. Acute (24 h) exposure induced DNA double strand break repair signaling by inducing Mre11 foci formation, ATM phosphorylation and phosphorylated ATM foci formation, Rad51 protein levels and Rad51 foci formation. However, longer exposures reduced the Rad51 response. These data indicate a major chemical carcinogen can simultaneously induce DNA double strand breaks and alter their repair and describe a new and important aspect of the carcinogenic mechanism for Cr(VI). PMID:25173789

Mood and cortisol responses following tryptophan-rich hydrolyzed protein and acute stress in healthy subjects with high and low cognitive reactivity to depression.

PubMed

Firk, Christine; Markus, C Rob

2009-06-01

It is suggested that stress particularly in subjects with high cognitive reactivity (CR), a psychological vulnerability marker of depression, may increase or even induce serotonergic vulnerability, which in turn may lead to reduced serotonin (5-HT) function, decreased stress coping and an increased risk to develop depressive symptoms. The aim of the present study was to investigate the beneficial effects of 5-HT augmentation through a tryptophan-rich hydrolyzed protein (HP) on mood and stress coping in subjects with high and low CR. We hypothesized that subjects with high CR are more responsive to the beneficial effects of HP than subjects with low CR particularly after acute stress exposure. In a double-blind, crossover study, participants' mood and cortisol was assessed before and after acute stress exposure either following intake of HP or a standard casein protein (CP) as control condition. HP significantly increased positive mood in all subjects and dampened the cortisol response to acute stress. No differences were found between high and low CR subjects. To conclude, because dietary treatment with HP has beneficial effects on mood and physiological stress coping in both high and low CR subjects, HP may be a good dietary method for augmenting brain TRP and 5-HT and thus 5-HT linked stress resilience.

Configuration of automatic exposure control on mammography units for computed radiography to match patient dose of screen film systems

NASA Astrophysics Data System (ADS)

Yang, Chang-Ying Joseph; Huang, Weidong

2009-02-01

Computed radiography (CR) is considered a drop-in addition or replacement for traditional screen-film (SF) systems in digital mammography. Unlike other technologies, CR has the advantage of being compatible with existing mammography units. One of the challenges, however, is to properly configure the automatic exposure control (AEC) on existing mammography units for CR use. Unlike analogue systems, the capture and display of digital CR images is decoupled. The function of AEC is changed from ensuring proper and consistent optical density of the captured image on film to balancing image quality with patient dose needed for CR. One of the preferences when acquiring CR images under AEC is to use the same patient dose as SF systems. The challenge is whether the existing AEC design and calibration process-most of them proprietary from the X-ray systems manufacturers and tailored specifically for SF response properties-can be adapted for CR cassettes, in order to compensate for their response and attenuation differences. This paper describes the methods for configuring the AEC of three different mammography units models to match the patient dose used for CR with those that are used for a KODAK MIN-R 2000 SF System. Based on phantom test results, these methods provide the dose level under AEC for the CR systems to match with the dose of SF systems. These methods can be used in clinical environments that require the acquisition of CR images under AEC at the same dose levels as those used for SF systems.

Quantifying the Benefit of a Pathologic Complete Response After Neoadjuvant Chemoradiotherapy in the Treatment of Esophageal Cancer

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

Scheer, Richard V.; Fakiris, Achilles J.; Johnstone, Peter A.S., E-mail: pajohnst@iupui.edu

Purpose: To better define the benefit of a pathologic complete response (pCR) after neoadjuvant chemoradiotherapy in the treatment of esophageal and gastroesophageal cancer, we undertook a comprehensive review of the literature to derive a pooled analysis of crude survival data and quantify the survival benefit of pCR vs. residual disease at esophagectomy. Methods and Materials: In all, 22 articles were reviewed. Crude overall survival data, stratified by patients with pCR vs. those with residual disease at esophagectomy, were collected and analyzed using a chi-square analysis. The relative and absolute survival benefit of achieving a pCR were calculated and analyzed. Finally,more » stratified median survival times were also analyzed. Results: Overall survival for patients with pCR was 93.1%, 75.0%, and 50.0% at 2, 3, and 5 years, respectively, whereas it was 36.8%, 29.0%, and 22.6% for patients with residual tumor (p < 0.025). The mean relative survival benefit of pCR at 2, 3, and 5 years was 2.05, 2.35, and 2.84, respectively. The mean absolute survival benefit of pCR was 35.66%, 33.79%, and 33.20%, respectively. Median survival times for patients with pCR were significantly longer than for those with residual tumor (p = 0.011). Conclusion: In esophageal and gastroesophageal cancers, pCR seems to significantly increase overall survival in patients undergoing neoadjuvant chemoradiotherapy. Specifically, the data suggest that patients with pCR are two to three times more likely to survive than are those with residual tumor at esophagectomy. Moreover, these data suggest that 33-36% more patients survive when pCR is achieved than when it is not.« less

Hexavalent Chromium Cr(VI) Up-Regulates COX-2 Expression through an NFκB/c-Jun/AP-1–Dependent Pathway

PubMed Central

Zuo, Zhenghong; Cai, Tongjian; Li, Jingxia; Zhang, Dongyun; Yu, Yonghui

2012-01-01

Background: Hexavalent chromium [Cr(VI)] is recognized as a human carcinogen via inhalation. However, the molecular mechanisms by which Cr(VI) causes cancers are not well understood. Objectives: We evaluated cyclooxygenase-2 (COX-2) expression and the signaling pathway leading to this induction due to Cr(VI) exposure in cultured cells. Methods: We used the luciferase reporter assay and Western blotting to determine COX-2 induction by Cr(VI). We used dominant negative mutant, genetic knockout, gene knockdown, and chromatin immunoprecipitation approaches to elucidate the signaling pathway leading to COX-2 induction. Results: We found that Cr(VI) exposure induced COX-2 expression in both normal human bronchial epithelial cells and mouse embryonic fibroblasts in a concentration- and time-dependent manner. Deletion of IKKβ [inhibitor of transcription factor NFκB (IκB) kinase β; an upstream kinase responsible for nuclear factor κB (NFκB) activation] or overexpression of TAM67 (a dominant-negative mutant of c-Jun) dramatically inhibited the COX-2 induction due to Cr(VI), suggesting that both NFκB and c-Jun/AP-1 pathways were required for Cr(VI)-induced COX-2 expression. Our results show that p65 and c-Jun are two major components involved in NFκB and AP-1 activation, respectively. Moreover, our studies suggest crosstalk between NFκB and c-Jun/AP-1 pathways in cellular response to Cr(VI) exposure for COX-2 induction. Conclusion: We demonstrate for the first time that Cr(VI) is able to induce COX-2 expression via an NFκB/c-Jun/AP-1–dependent pathway. Our results provide novel insight into the molecular mechanisms linking Cr(VI) exposure to lung inflammation and carcinogenesis. PMID:22472290

Quantifying the benefit of a pathologic complete response after neoadjuvant chemoradiotherapy in the treatment of esophageal cancer.

PubMed

Scheer, Richard V; Fakiris, Achilles J; Johnstone, Peter A S

2011-07-15

To better define the benefit of a pathologic complete response (pCR) after neoadjuvant chemoradiotherapy in the treatment of esophageal and gastroesophageal cancer, we undertook a comprehensive review of the literature to derive a pooled analysis of crude survival data and quantify the survival benefit of pCR vs. residual disease at esophagectomy. In all, 22 articles were reviewed. Crude overall survival data, stratified by patients with pCR vs. those with residual disease at esophagectomy, were collected and analyzed using a chi-square analysis. The relative and absolute survival benefit of achieving a pCR were calculated and analyzed. Finally, stratified median survival times were also analyzed. Overall survival for patients with pCR was 93.1%, 75.0%, and 50.0% at 2, 3, and 5 years, respectively, whereas it was 36.8%, 29.0%, and 22.6% for patients with residual tumor (p < 0.025). The mean relative survival benefit of pCR at 2, 3, and 5 years was 2.05, 2.35, and 2.84, respectively. The mean absolute survival benefit of pCR was 35.66%, 33.79%, and 33.20%, respectively. Median survival times for patients with pCR were significantly longer than for those with residual tumor (p = 0.011). In esophageal and gastroesophageal cancers, pCR seems to significantly increase overall survival in patients undergoing neoadjuvant chemoradiotherapy. Specifically, the data suggest that patients with pCR are two to three times more likely to survive than are those with residual tumor at esophagectomy. Moreover, these data suggest that 33-36% more patients survive when pCR is achieved than when it is not. Copyright © 2011 Elsevier Inc. All rights reserved.

Response evaluation after primary systemic therapy of Her2 positive breast cancer – an observational cross-sectional study.

PubMed

Tőkés, Tímea; Szentmártoni, Gyöngyvér; Torgyík, László; Kajáry, Kornélia; Lengyel, Zsolt; Györke, Tamás; Molnár, Béla Á; Tőkés, Anna-Mária; Kulka, Janina; Dank, Magdolna

2015-04-01

To evaluate (I) trastuzumab-containing primary systemic therapy (PST) in human epidermal growth factor receptor 2 (Her2) overexpressing breast carcinomas.; (II) compare the patients who achieved and those who did not achieve pathological complete remission (pCR), and (III) analyze the accuracy of different clinical-imaging modalities in tumor response monitoring. 188 patients who received PST between 2008 and 2014 were reviewed and 43 Her2 overexpressing breast cancer patients (28 Luminal B/Her2-positive and 15 Her2-positive) were enrolled. 26 patients received mostly taxane-based PST without trastuzumab (Group 1) and 17 patients received trastuzumab-containing PST (Group 2). We compared the concordance between pCR and complete remission (CR) defined by breast-ultrasound, CR defined by standard 18F-fluoro-deoxy-glucose positron emission tomography and computerized tomography (FDG-PET/CT) criteria (Method 1) and CR defined by a novel, breast cancer specific FDG-PET/CT criteria (Method 2). Sensitivity (sens), specificity (spec), and positive (PPV) and negative predictive values (NPV) were calculated. Ten patients (38.5%) in Group 1 and eight (47%) in Group 2 achieved pCR. pCR was significantly more frequent in Her2-positive than in Luminal B/Her2-positive tumors in both Group 1: (P=0.043) and Group 2: (P=0.029). PET/CT evaluated by the breast cancer specific criteria (Method 2) differentiated pCR from non-pCR more accurately in both groups (Group 1: sens=77.8%, spec=%, PPV=100%, NPV=71.4%; Group 2: sens=87.5%, spec=62.5%, PPV=70%, NPV=83.3%) than standard PET/CT criteria (Method 1) (Group 1: sens=22.2% spec=100% PPV=100% NPV=41.7%; in Group 2: sens=37.5%, spec=87.5%, PPV=75% NPV=58.3%) or breast ultrasound (Group 1, sens=83.3% spec=25% PPV=62.5% NPV=50%; Group 2, sens=100% spec=12.5% PPV=41.6% NPV=100%). The benefit of targeted treatment with trastuzumab-containing PST in Her2 overexpressing breast cancer was defined in terms of pCR rate. Luminal B/Her2-positive subtype needs further subdivision to identify patients who would benefit from PST. Combined evaluation of tumor response by our novel, breast cancer specific FDG-PET/CT criteria accurately differentiated pCR from non-pCR patients.

The Role of 5-HT2A, 5-HT2C and mGlu2 Receptors in the Behavioral Effects of Tryptamine Hallucinogens N,N-Dimethyltryptamine and N,N-Diisopropyltryptamine in Rats and Mice

PubMed Central

Carbonaro, Theresa M.; Eshleman, Amy J.; Forster, Michael J.; Cheng, Kejun; Rice, Kenner C.; Gatch, Michael B.

2014-01-01

Rationale: Serotonin 5-HT2A and 5-HT2C receptors are thought to be the primary pharmacological mechanisms for serotonin-mediated hallucinogenic drugs, but recently there has been interest in metabotropic glutamate (mGluR2) receptors as contributors to the mechanism of hallucinogens. Objective: The present study assesses the role of these 5-HT and glutamate receptors as molecular targets for two tryptamine hallucinogens, N,N-dimethyltryptamine (DMT) and N,N-diisopropyltryptamine (DiPT). Methods: Drug discrimination, head twitch and radioligand binding assays were used. A 5-HT2AR inverse agonist (MDL100907), 5-HT2CR antagonist (SB242084) and mGluR2/3 agonist (LY379268) were tested for their ability to attenuate the discriminative stimulus effects of DMT and DiPT; an mGluR2/3 antagonist (LY341495) was tested for potentiation. MDL100907 was used to attenuate head twitches induced by DMT and DiPT. Radioligand binding studies and inosital-1-phosphate (IP-1) accumulation were performed at the 5-HT2CR for DiPT. Results: MDL100907 fully blocked the discriminative stimulus effects of DMT, but only partially blocked DiPT. SB242084 partially attenuated the discriminative stimulus effects of DiPT, but produced minimal attenuation of DMT’s effects. LY379268 produced potent, but only partial blockade of the discriminative stimulus effects of DMT. LY341495 facilitated DMT- and DiPT-like effects. Both compounds elicited head twitches (DiPT>DMT) which were blocked by MDL1000907. DiPT was a low potency full agonist at 5-HT2CR in vitro. Conclusions: The 5-HT2AR likely plays a major role in mediating the effects of both compounds. 5-HT2C and mGluR2 receptors likely modulate the discriminative stimulus effects of both compounds to some degree. PMID:24985890

The role of 5-HT2A, 5-HT 2C and mGlu2 receptors in the behavioral effects of tryptamine hallucinogens N,N-dimethyltryptamine and N,N-diisopropyltryptamine in rats and mice.

PubMed

Carbonaro, Theresa M; Eshleman, Amy J; Forster, Michael J; Cheng, Kejun; Rice, Kenner C; Gatch, Michael B

2015-01-01

Serotonin 5-HT2A and 5-HT2C receptors are thought to be the primary pharmacological mechanisms for serotonin-mediated hallucinogenic drugs, but recently there has been interest in metabotropic glutamate (mGluR2) receptors as contributors to the mechanism of hallucinogens. The present study assesses the role of these 5-HT and glutamate receptors as molecular targets for two tryptamine hallucinogens, N,N-dimethyltryptamine (DMT) and N,N-diisopropyltryptamine (DiPT). Drug discrimination, head twitch, and radioligand binding assays were used. A 5-HT2AR inverse agonist (MDL100907), 5-HT2CR antagonist (SB242084), and mGluR2/3 agonist (LY379268) were tested for their ability to attenuate the discriminative stimulus effects of DMT and DiPT; an mGluR2/3 antagonist (LY341495) was tested for potentiation. MDL100907 was used to attenuate head twitches induced by DMT and DiPT. Radioligand binding studies and inosital-1-phosphate (IP-1) accumulation were performed at the 5-HT2CR for DiPT. MDL100907 fully blocked the discriminative stimulus effects of DMT, but only partially blocked DiPT. SB242084 partially attenuated the discriminative stimulus effects of DiPT, but produced minimal attenuation of DMT's effects. LY379268 produced potent, but only partial blockade of the discriminative stimulus effects of DMT. LY341495 facilitated DMT- and DiPT-like effects. Both compounds elicited head twitches (DiPT>DMT) which were blocked by MDL1000907. DiPT was a low-potency full agonist at 5-HT2CR in vitro. The 5-HT2AR likely plays a major role in mediating the effects of both compounds. 5-HT2C and mGluR2 receptors likely modulate the discriminative stimulus effects of both compounds to some degree.

Maxillary overlay removable partial dentures for the restoration of worn teeth.

PubMed

Fonseca, Júlio; Nicolau, Pedro; Daher, Tony

2011-04-01

Prolonged tooth maintenance by a more aged population considerably increases the probability of dentists having to treat patients with high levels of tooth wear. Pathological tooth wear, caused primarily by parafunction, seems to be a growing problem that affects a large number of adult patients. The clinical report presents a case of a partially edentulous patient with an elevated degree of wear in the upper jaw caused by attrition and erosion, rehabilitated with a maxillary overlay removable partial denture (ORPD) consisting of a chrome-cobalt (Cr-Co) framework with anterior acrylic resin veneers, posterior cast overlays, and acrylic resin denture bases. Removable partial prosthesis is a treatment alternative when teeth are found to be severely worn or when the patient needs a simple and economical option. Because economics is a conditional factor of the treatment, the clinician should present different treatment alternatives to the patient, in which the overlay prosthesis can be considered.

VAC protocol for treatment of dogs with stage III hemangiosarcoma.

PubMed

Alvarez, Francisco J; Hosoya, Kenji; Lara-Garcia, Ana; Kisseberth, William; Couto, Guillermo

2013-01-01

Hemangiosarcomas (HSAs) are aggressive tumors with a high rate of metastasis. Clinical stage has been considered a negative prognostic factor for survival. The study authors hypothesized that the median survival time (MST) of dogs with metastatic (stage III) HSA treated with a vincristine, doxorubicin, and cyclophosphamide (VAC) chemotherapy protocol would not be different than those with stage I/II HSA. Sixty-seven dogs with HSA in different anatomic locations were evaluated retrospectively. All dogs received the VAC protocol as an adjuvant to surgery (n = 50), neoadjuvant (n = 3), or as the sole treatment modality (n = 14). There was no significant difference (P = 0.97) between the MST of dogs with stage III and stage I/II HSA. For dogs presenting with splenic HSA alone, there was no significant difference between the MST of dogs with stage III and stage I/II disease (P = 0.12). The overall response rate (complete response [CR] and partial response [PR]) was 86%). No unacceptable toxicities were observed. Dogs with stage III HSA treated with the VAC protocol have a similar prognosis to dogs with stage I/II HSA. Dogs with HSA and evidence of metastases at the time of diagnosis should not be denied treatment.

Patterns of intraspecific variability in the response to caloric restriction

PubMed Central

Gribble, Kristin E.; Kaido, Oksana; Jarvis, George; Mark Welch, David B.

2014-01-01

Caloric restriction (CR) is cited as the most robust means of increasing lifespan across a range of taxa, yet there is a high degree of variability in the response to CR, both within and between species. To examine the intraspecific evolutionary conservation of lifespan extension by CR, we tested the effects of chronic caloric restriction (CCR) at multiple food levels and of intermittent fasting (IF) in twelve isolates from the Brachionus plicatilis species complex of monogonont rotifers. While CCR generally increased or did not change lifespan and total fecundity, IF caused increased, unchanged, or decreased lifespan, depending upon the isolate, and decreased total fecundity in all but one isolate. Lifespan under ad libitum (AL) feeding varied among isolates and predicted the lifespan response to CR: longer-lived isolates under AL were less likely to have a significant increase in lifespan under CCR and were more likely to have a significantly shortened lifespan under IF. Lifespan under AL conditions and the response to CR were not correlated with hydroperiodicity of native habitat or with time in culture. Lack of trade-off between lifespan and fecundity under CCR, and differences in lifespan and fecundity under CCR and IF, even when average food intake was similar, suggest that longevity changes are not always directly determined by energy intake and that CCR and IF regimens extend lifespan through diverse genetic mechanisms. PMID:24384399

Patterns of intraspecific variability in the response to caloric restriction.

PubMed

Gribble, Kristin E; Kaido, Oksana; Jarvis, George; Mark Welch, David B

2014-03-01

Caloric restriction (CR) is cited as the most robust means of increasing lifespan across a range of taxa, yet there is a high degree of variability in the response to CR, both within and between species. To examine the intraspecific evolutionary conservation of lifespan extension by CR, we tested the effects of chronic caloric restriction (CCR) at multiple food levels and of intermittent fasting (IF) in twelve isolates from the Brachionus plicatilis species complex of monogonont rotifers. While CCR generally increased or did not change lifespan and total fecundity, IF caused increased, unchanged, or decreased lifespan, depending upon the isolate, and decreased total fecundity in all but one isolate. Lifespan under ad libitum (AL) feeding varied among isolates and predicted the lifespan response to CR: longer-lived isolates under AL were less likely to have a significant increase in lifespan under CCR and were more likely to have a significantly shortened lifespan under IF. Lifespan under AL conditions and the response to CR were not correlated with hydroperiodicity of native habitat or with time in culture. Lack of trade-off between lifespan and fecundity under CCR, and differences in lifespan and fecundity under CCR and IF, even when average food intake was similar, suggest that longevity changes are not always directly determined by energy intake and that CCR and IF regimens extend lifespan through diverse genetic mechanisms. Copyright © 2013 Elsevier Inc. All rights reserved.

Disruption of rcsB by a duplicated sequence in a curli-producing Escherichia coli O157:H7 results in differential gene expression in relation to biofilm formation, stress responses, and metabolism

USDA-ARS?s Scientific Manuscript database

Background: Escherichia coli O157:H7 (O157) strain 86-24, linked to a 1986 disease outbreak, displays biofilm- and curli-negative phenotypes that are correlated with the lack of Congo red (CR) binding and formation of white colonies (CR negative) on a CR negative containing medium. However, on a CR ...

Response of timepix detector with GaAs:Cr and Si sensor to heavy ions

NASA Astrophysics Data System (ADS)

Abu Al Azm, S. M.; Chelkov, G.; Kozhevnikov, D.; Guskov, A.; Lapkin, A.; Leyva Fabelo, A.; Smolyanskiy, P.; Zhemchugov, A.

2016-05-01

The response of the Timepix detector to neon ions with kinetic energy 77 and 158.4 MeV has been studied at the cyclotron U-400M of the JINR Flerov Laboratory of Nuclear Reaction. Sensors produced from gallium arsenide compensated by chromium and from silicon are used for these measurements. While in Timepix detector with Si sensor the well-known so-called "volcano effect" observed, in Timepix detector with GaAs:Cr sensor such effect was completely absent. In the work the behavior of the Timepix detector with GaAs:Cr sensor under irradiation with heavy ions is described in comparison with the detector based on Si sensor. Also the possible reason for absence of "volcano" effect in GaAs:Cr detector is proposed.

Time Course of the Rabbit's Conditioned Nictitating Membrane Movements during Acquisition, Extinction, and Reacquisition

ERIC Educational Resources Information Center

Kehoe, E. James; Ludvig, Elliot A.; Sutton, Richard S.

2014-01-01

The present experiment tested whether or not the time course of a conditioned eyeblink response, particularly its duration, would expand and contract, as the magnitude of the conditioned response (CR) changed massively during acquisition, extinction, and reacquisition. The CR duration remained largely constant throughout the experiment, while CR…

Transient photoconductivity in the ferromagnetic semiconductor CdCr2Se4

NASA Technical Reports Server (NTRS)

Walser, A. D.; Alfano, R. R.

1988-01-01

The transient photoconductive response time of the ferromagnetic semiconductor CdCr2Se4 was measured to be smaller than 90 ps, the response time of the scope. The measurements were performed at room temperature (300 K) for 0.53 and 1.06 microns excitations using a mode locked frequency-doubled YAG laser.

Combined abiotic and biotic in-situ reduction of hexavalent chromium in groundwater using nZVI and whey: A remedial pilot test.

PubMed

Němeček, Jan; Pokorný, Petr; Lacinová, Lenka; Černík, Miroslav; Masopustová, Zuzana; Lhotský, Ondřej; Filipová, Alena; Cajthaml, Tomáš

2015-12-30

The paper describes a pilot remediation test combining two Cr(VI) geofixation methods - chemical reduction by nanoscale zero-valent iron (nZVI) and subsequent biotic reduction supported by whey. Combination of the methods exploited the advantages of both - a rapid decrease in Cr(VI) concentrations by nZVI, which prevented further spreading of the contamination and facilitated subsequent use of the cheaper biological method. Successive application of whey as an organic substrate to promote biotic reduction of Cr(VI) after application of nZVI resulted in a further and long-term decrease in the Cr(VI) contents in the groundwater. The effect of biotic reduction was observed even in a monitoring well located at a distance of 22 m from the substrate injection wells after 10 months. The results indicated a reciprocal effect of both the phases - nZVI oxidized to Fe(III) during the abiotic phase was microbially reduced back to Fe(II) and acted as a reducing agent for Cr(VI) even when the microbial density was already low due to the consumed substrate. Community analysis with pyrosequencing of the 16S rRNA genes further confirmed partial recycling of nZVI in the form of Fe(II), where the results showed that the Cr(VI) reducing process was mediated mainly by iron-reducing and sulfate-reducing bacteria. Copyright © 2015 Elsevier B.V. All rights reserved.

Microstructure, Mechanical Properties, and Two-Body Abrasive Wear Behavior of Cold-Sprayed 20 vol.% Cubic BN-NiCrAl Nanocomposite Coating

NASA Astrophysics Data System (ADS)

Luo, Xiao-Tao; Yang, Er-Juan; Shang, Fu-Lin; Yang, Guan-Jun; Li, Chen-Xin; Li, Chang-Jiu

2014-10-01

20 vol.% cubic boron nitride (cBN) dispersoid reinforced NiCrAl matrix nanocomposite coating was prepared by cold spray using mechanically alloyed nanostructured composite powders. The as-sprayed nanocomposite coating was annealed at a temperature of 750 °C to enhance the inter-particle bonding. Microstructure of spray powders and coatings was characterized. Vickers microhardness of the coatings was measured. Two-body abrasive wear behavior of the coatings was examined on a pin-on-disk test. It was found that, in mechanically alloyed composite powders, nano-sized and submicro-sized cBN particles are uniformly distributed in nanocrystalline NiCrAl matrix. Dense coating was deposited by cold spray at a gas temperature of 650 °C with the same phases and grain size as those of the starting powder. Vickers hardness test yielded a hardness of 1063 HV for the as-sprayed 20 vol.% cBN-NiCrAl coating. After annealed at 750 °C for 5 h, unbonded inter-particle boundaries were partially healed and evident grain growth of nanocrystalline NiCrAl was avoided. Wear resistance of the as-sprayed 20 vol.% cBN-NiCrAl nanocomposite coating was comparable to the HVOF-sprayed WC-12Co coating. Annealing of the nanocomposite coating resulted in the improvement of wear resistance by a factor of ~33% owing to the enhanced inter-particle bonding. Main material removal mechanisms during the abrasive wear are also discussed.

Evaluation of a novel dextran-based flocculant on treatment of dye wastewater: Effect of kaolin particles.

PubMed

Zhao, Chuanliang; Zheng, Huaili; Sun, Yongjun; Zhang, Shixin; Liang, Jianjun; Liu, Yongzhi; An, Yanyan

2018-05-30

Graft modified flocculants have recently received increasing attention in the field of water treatment as they have the combinative advantages of synthetic and natural polymeric flocculants. In this work, surface-active monomer benzyl(methacryloyloxyethyl)dimethylammonium chloride (BMDAC) was selected to graft on dextran (DX) with high molecular weight (10.3 × 10 6  g/mol) produced through enzyme-catalyzed process in order to remove dissolved dyes from wastewater. The flocculant (DAB) was fabricated by ultrasound initiated polymerization technique, and the structure characterization of FTIR, 1 H/ 12 C NMR, XRD and XPS spectrum confirmed the successful grafting. Then the Congo red (CR) removal efficiency by DAB was optimized based on the flocculation conditions, including wastewater initial pH, flocculant dosage and initial dye concentration. The effect of suspended solids on the removal of dyes was evaluated in kaolin-CR simulated wastewater. The results indicated that the optimal removal efficiency of CR was 68.1% and 88.2% in single CR and kaolin-CR flocculation system, respectively. The improvement of removal efficiency was attributed to the fact that partial CR molecules were adsorbed onto kaolin particles before flocculation, and were synergistically flocculated accompanied by kaolin particles. Finally, the flocculation mechanism was discussed by a detailed investigation of the zeta potentials, FTIR and XPS spectra of flocs, which can provide important reference for optimizing the flocculation conditions and designing novel high-performance flocculants. Copyright © 2018. Published by Elsevier B.V.

Influence of chromium hyperdoping on the electronic structure of CH3NH3PbI3 perovskite: a first-principles insight.

PubMed

García, Gregorio; Palacios, Pablo; Menéndez-Proupin, Eduardo; Montero-Alejo, Ana L; Conesa, José C; Wahnón, Perla

2018-02-06

Organic-inorganic hybrid halide perovskites compounds are emerging as new materials with great potential for efficient solar cells. This paper explores the possibility of increasing their photovoltaic efficiency through sub-bandgap absorption by way of the in gap band (IGB) concept. Thus, we assess the formation of an in gap band as well as its effect on the absorption features of Organic-inorganic hybrid halide perovskites CH 3 NH 3 PbI 3 (MAPI). For this task, we use density functional theory (DFT) as well as many-body perturbation methods along to spin-orbit coupling (SOC) to study structural, energetic and electronic properties of partially Cr-substituted MAPI perovskites (CH 3 NH 3 Pb 1-x Cr x I 3 ). Our results reveal that Cr replacement does not lead to an important cell distortion, while the energetic of the substitution process evidences the possibility of obtaining Cr-substituted perovskite. The analysis of the electronic structure shows that Cr 3d-orbitals induce new electronic states in the host semiconductor bandgap, which fulfill the requirements to be considered as an IGB. Precise many-body perturbation methods in G 0 W 0 approach provided an accurate description on the electronic structures as well as the position of the IGB. In short, Pb replacement by Cr could be useful for improved absorption features through new sub-bandgap transitions across the in gap band.

Treatment of patients with multiple myeloma over 65 yr: more tolerability or better response?

PubMed

Tarkun, Pinar; Atalay, Figen; Atesoglu, Elif Birtas; Mehtap, Ozgur; Simsek, Melih; Terzi, Esra; Geduk, Ayfer; Balli, Fatih; Batman, Adnan; Baydemir, Canan; Hacihanefioglu, Abdullah

2015-05-01

Two-thirds of newly diagnosed patients with multiple myeloma (MM) are over 65 yr and/or physically unfit. Such patients are not eligible for high-dose chemotherapy or stem cell transplantation. The treatment aims in these patients should be to prolong survival by obtaining the best possible response, while maintaining good tolerability. The aim of our study was to evaluate the response to treatment and treatment-related toxicities in patients treated with conventional and novel protocols. The records of 138 elderly (≥65 yr) patients with MM were retrospectively evaluated. The median overall survival(OS) of the patients was 46 months. The median progression-free survival (PFS) was 18 months. The OS and PFS of the patients treated with the conventional protocols did not differ significantly from those treated with the novel protocols. The statistical analysis of the quality of the response to the treatment with the conventional and novel therapies showed that complete remission (CR), combined with a very good partial response (VGPR), was significantly higher in the latter. However, the toxicities were higher in the novel treatment group. The novel drug protocols significantly increased the quality of the responses of elderly patients with MM to therapy, but they did not increase the patients' tolerability. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chromium toxicity tolerance of Solanum nigrum L. and Parthenium hysterophorus L. plants with reference to ion pattern, antioxidation activity and root exudation.

PubMed

UdDin, Islam; Bano, Asghari; Masood, Sajid

2015-03-01

Chromium (Cr), being a highly toxic metal, adversely affects the mineral uptake and metabolic processes in plants when present in excess. The current study was aimed at investigating the Cr accumulation in various plant tissues and its relation to the antioxidation activity and root exudation. Plants were grown in soil spiked with different concentrations of Cr for three weeks in pots and analysed for different growth, antioxidants and ion attributes. Furthermore, plants treated with different concentrations of Cr in pots were shifted to rhizobox-like system for 48h and organic acids were monitored in the mucilage dissolved from the plant root surface, mirroring rhizospheric solution. The results revealed that the Cr application at 1mM increased the shoot fresh and dry weight and root dry weight of Solanum nigrum, whereas the opposite was observed for Parthenium hysterophorus when compared with lower levels of Cr (0.5mM) or control treatment. In both plant species, Cr and Cl concentrations were increased while Ca, Mg and K concentrations in root, shoot and root exudates were decreased with increasing levels of Cr. Higher levels of Cr treatments enhanced the activities of SOD, POD and proline content in leaves of S. nigrum, whereas lower levels of Cr treatment were found to have stimulatory effects in P. hysterophorus. P. hysterophorus exhibited highest exudation of organic acid contents. With increasing levels of Cr treatments, citric acid concentration in root exudates increased by 35% and 44% in S. nigrum, whereas 20% and 76% in P. hysterophorus. Cr toxicity was responsible for the shoot growth reduction of S. nigrum and P. hysterophorus, however, shoot growth response was different at different levels of applied Cr. Consequently, Cr stress negatively altered the plant physiology and biochemistry. However, the enhanced antioxidant production, Cl uptake and root exudation are the physiological and biochemical indicators for the plant adaptations in biotic systems polluted with Cr. Copyright © 2014 Elsevier Inc. All rights reserved.

Pathological complete response in patients with esophageal cancer after the trimodality approach: The association with baseline variables and survival-The University of Texas MD Anderson Cancer Center experience.

PubMed

Blum Murphy, Mariela; Xiao, Lianchum; Patel, Viren R; Maru, Dipen M; Correa, Arlene M; G Amlashi, Fatemeh; Liao, Zhongxing; Komaki, Ritsuko; Lin, Steven H; Skinner, Heath D; Vaporciyan, Ara; Walsh, Garrett L; Swisher, Stephen G; Sepesi, Boris; Lee, Jeffrey H; Bhutani, Manoop S; Weston, Brian; Hofstetter, Wayne L; Ajani, Jaffer A

2017-11-01

Reports are limited regarding clinical and pretreatment features that might predict a pathological complete response (pathCR) after treatment in patients with esophageal cancer (EC). This might allow patient selection for different strategies. This study examines the association of a pathCR with pretreatment variables, overall survival (OS), recurrence-free survival (RFS), and patterns of recurrence in a large cohort from a single institution. The baseline clinical features of 911 consecutive patients with EC who were treated with trimodality therapy from January 2000 to November 2013 were analyzed. A pathCR was defined as a surgical specimen with no residual carcinoma (primary or nodes). Logistic regressions were used to identify independent baseline features associated with a pathCR. We applied log-rank testing and Cox models to determine the association between a pathCR and the time-to-event outcomes (OS and RFS). Of 911 patients, 218 (23.9%) achieved a pathCR. The pathCR rate was 23.1% for adenocarcinoma and 32.2% for squamous cell carcinoma. A lower pathCR rate was observed for 1) older patients (>60 years), 2) patients with poorly differentiated tumors, 3) patients with signet ring cells (SRCs), and 4) patients with a higher T stage. Patients with a pathCR had longer OS and RFS than those without a pathCR (P = .0021 and P = .0011, respectively). Recurrences occurred more in non-pathCR patients. Distant metastases were the most common type of recurrence. PathCR patients developed brain metastases at a marginally higher rate than non-pathCR patients (P = .051). In this large cohort study, a pathCR is confirmed to be associated with better OS and RFS. The presence of a poorly differentiated tumor or SRCs reduces the likelihood of a pathCR. Future research should focus on molecular classifiers. Cancer 2017;123:4106-4113. © 2017 American Cancer Society. © 2017 American Cancer Society.

Effect of Cr, Ti, V, and Zr Micro-additions on Microstructure and Mechanical Properties of the Al-Si-Cu-Mg Cast Alloy

NASA Astrophysics Data System (ADS)

Shaha, S. K.; Czerwinski, F.; Kasprzak, W.; Friedman, J.; Chen, D. L.

2016-05-01

Uniaxial static and cyclic tests were used to assess the role of Cr, Ti, V, and Zr additions on properties of the Al-7Si-1Cu-0.5Mg (wt pct) alloy in as-cast and T6 heat-treated conditions. The microstructure of the as-cast alloy consisted of α-Al, eutectic Si, and Cu-, Mg-, and Fe-rich phases Al2.1Cu, Al8.5Si2.4Cu, Al5.2CuMg4Si5.1, and Al14Si7.1FeMg3.3. In addition, the micro-sized Cr/Zr/Ti/V-rich phases Al10.7SiTi3.6, Al6.7Si1.2TiZr1.8, Al21.4Si3.4Ti4.7VZr1.8, Al18.5Si7.3Cr2.6V, Al7.9Si8.5Cr6.8V4.1Ti, Al6.3Si23.2FeCr9.2V1.6Ti1.3, Al92.2Si16.7Fe7.6Cr8.3V1.8, and Al8.2Si30.1Fe1.6Cr18.8V3.3Ti2.9Zr were present. During solution treatment, Cu-rich phases were completely dissolved, while the eutectic silicon, Fe-, and Cr/Zr/Ti/V-rich intermetallics experienced only partial dissolution. Micro-additions of Cr, Zr, Ti, and V positively affected the alloy strength. The modified alloy in the T6 temper during uniaxial tensile tests exhibited yield strength of 289 MPa and ultimate tensile strength of 342 MPa, being significantly higher than that for the Al-Si-Cu-Mg base. Besides, the cyclic yield stress of the modified alloy in the T6 state increased by 23 pct over that of the base alloy. The fatigue life of the modified alloy was substantially longer than that of the base alloy tested using the same parameters. The role of Cr, Ti, V, and Zr containing phases in controlling the alloy fracture during static and cyclic loading is discussed.

The conceptualization and measurement of cognitive reserve using common proxy indicators: Testing some tenable reflective and formative models.

PubMed

Ikanga, Jean; Hill, Elizabeth M; MacDonald, Douglas A

2017-02-01

The examination of cognitive reserve (CR) literature reveals a lack of consensus regarding conceptualization and pervasive problems with its measurement. This study aimed at examining the conceptual nature of CR through the analysis of reflective and formative models using eight proxies commonly employed in the CR literature. We hypothesized that all CR proxies would significantly contribute to a one-factor reflective model and that educational and occupational attainment would produce the strongest loadings on a single CR factor. The sample consisted of 149 participants (82 male/67 female), with 18.1 average years of education and ages of 45-99 years. Participants were assessed for eight proxies of CR (parent socioeconomic status, intellectual functioning, level of education, health literacy, occupational prestige, life leisure activities, physical activities, and spiritual and religious activities). Primary statistical analyses consisted of confirmatory factor analysis (CFA) to test reflective models and structural equation modeling (SEM) to evaluate multiple indicators multiple causes (MIMIC) models. CFA did not produce compelling support for a unitary CR construct when using all eight of our CR proxy variables in a reflective model but fairly cogent evidence for a one-factor model with four variable proxies. A second three-factor reflective model based upon an exploratory principal components analysis of the eight proxies was tested using CFA. Though all eight indicators significantly loaded on their assigned factors, evidence in support of overall model fit was mixed. Based upon the results involving the three-factor reflective model, two alternative formative models were developed and evaluated. While some support was obtained for both, the model in which the formative influences were specified as latent variables appeared to best account for the contributions of all eight proxies to the CR construct. While the findings provide partial support for our hypothesis regarding CR as a one-dimensional reflective construct, the results strongly suggest that the construct is more complex than what can be captured in a reflective model alone. There is a need for theory to better identify and differentiate formative from reflective indicators and to articulate the mechanisms by which CR develops and operates.

Crystal structures and magnetic properties of lanthanide containing borates LnM(BO{sub 3}){sub 2} (Ln=Y, Ho–Lu; M=Sc, Cr)

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

Doi, Yoshihiro, E-mail: doi@sci.hokudai.ac.jp; Satou, Tatsuya; Hinatsu, Yukio

2013-10-15

The synthesis, crystal structures and magnetic properties of LnM(BO{sub 3}){sub 2} (Ln=Y, Ho–Lu; M=Sc, Cr) were investigated. The LnCr(BO{sub 3}){sub 2} compounds crystallize in the dolomite-type structure with space group R3{sup ¯}, in which the Ln and Cr ions occupy two octahedral sites. From the result of structural analysis, it was found that there is an anti-site disorder between these two sites and its chemical formula is more exactly Ln{sub 1−r}Cr{sub r}[Cr{sub 1−r}Ln{sub r}](BO{sub 3}){sub 2}. On the other hand, the LnSc(BO{sub 3}){sub 2} adopt the calcite-type structure with space group R3{sup ¯}c. The Ln and Sc ions randomly occupymore » an octahedral site and the chemical formula is represented as (Ln{sub 0.5}Sc{sub 0.5})BO{sub 3}. From the magnetic susceptibility and specific heat measurements, we found that all the LnCr(BO{sub 3}){sub 2} show an antiferromagnetic transition at 6.1–8.1 K. This transition is mainly due to the ordering of Cr{sup 3+} magnetic moments. Among the compounds with magnetic Ln{sup 3+} ions, only YbCr(BO{sub 3}){sub 2} shows an antiferromagnetic ordering of Ln{sup 3+} ion at 2.1 K. - Graphical abstract: The lanthanide containing borates LnM(BO{sub 3}){sub 2} (Ln=Y, Ho–Lu; M=Sc, Cr) have the dolomite-type (Ln=Cr) and calcite-type (Ln=Sc) structures. Both structures are similar to each other except for the difference in the partially or fully disordered arrangements of octahedral sites. At low temperatures, the LnCr(BO{sub 3}){sub 2} compounds show an antiferromagnetic transition due to a long-range ordering of Cr{sup 3+} moments. Among them only YbCr(BO{sub 3}){sub 2} shows an antiferromagnetic ordering of Ln{sup 3+} ion at 2.1 K. Display Omitted - Highlights: • Lanthanide containing borates LnM(BO{sub 3}){sub 2} (Ln=Y, Ho–Lu; M=Sc, Cr) have been synthesized. • LnCr(BO{sub 3}){sub 2} has the dolomite-type structure with an anti-site disorder between Ln and Cr sites. • LnSc(BO{sub 3}){sub 2} has the calcite-type structure in which the Ln and Cr randomly occupy the same site. • LnCr(BO{sub 3}){sub 2} shows an antiferromagnetic transition at 6.1–8.1 K due to the long-range magnetic ordering of Cr{sup 3+} moments. • Only YbCr(BO{sub 3}){sub 2} shows the two-step antiferromagnetic ordering: Cr{sup 3+} (6.1 K) and Yb{sup 3+} (2.1 K)« less

Pathway level alterations rather than mutations in single genes predict response to HER2-targeted therapies in the neo-ALTTO trial.

PubMed

Shi, W; Jiang, T; Nuciforo, P; Hatzis, C; Holmes, E; Harbeck, N; Sotiriou, C; Peña, L; Loi, S; Rosa, D D; Chia, S; Wardley, A; Ueno, T; Rossari, J; Eidtmann, H; Armour, A; Piccart-Gebhart, M; Rimm, D L; Baselga, J; Pusztai, L

2017-01-01

We performed whole-exome sequencing of pretreatment biopsies and examined whether genome-wide metrics of overall mutational load, clonal heterogeneity or alterations at variant, gene, and pathway levels are associated with treatment response and survival. Two hundred and three biopsies from the NeoALTTO trial were analyzed. Mutations were called with MuTect, and Strelka, using pooled normal DNA. Associations between DNA alterations and outcome were evaluated by logistic and Cox-proportional hazards regression. There were no recurrent single gene mutations significantly associated with pathologic complete response (pCR), except PIK3CA [odds ratio (OR) = 0.42, P = 0.0185]. Mutations in 33 of 714 pathways were significantly associated with response, but different genes were affected in different individuals. PIK3CA was present in 23 of these pathways defining a ‘trastuzumab resistance-network’ of 459 genes. Cases with mutations in this network had low pCR rates to trastuzumab (2/50, 4%) compared with cases with no mutations (9/16, 56%), OR = 0.035; P < 0.001. Mutations in the ‘Regulation of RhoA activity’ pathway were associated with higher pCR rate to lapatinib (OR = 14.8, adjusted P = 0.001), lapatinib + trastuzumab (OR = 3.0, adjusted P = 0.09), and all arms combined (OR = 3.77, adjusted P = 0.02). Patients (n = 124) with mutations in the trastuzumab resistance network but intact RhoA pathway had 2% (1/41) pCR rate with trastuzumab alone (OR = 0.026, P = 0.001) but adding lapatinib increased pCR rate to 45% (17/38, OR = 1.68, P = 0.3). Patients (n = 46) who had no mutations in either gene set had 6% pCR rate (1/15) with lapatinib, but had the highest pCR rate, 52% (8/15) with trastuzumab alone. Mutations in the RhoA pathway are associated with pCR to lapatinib and mutations in a PIK3CA-related network are associated with resistance to trastuzumab. The combined mutation status of these two pathways could define patients with very low response rate to trastuzumab alone that can be augmented by adding lapatinib or substituting trastuzumab with lapatinib.

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

Rojas-Herrera, J., E-mail: jimmy06@mit.edu; Rinderknecht, H. G.; Zylstra, A. B.

The CR-39 nuclear track detector is used in many nuclear diagnostics fielded at inertial confinement fusion (ICF) facilities. Large x-ray fluences generated by ICF experiments may impact the CR-39 response to incident charged particles. To determine the impact of x-ray exposure on the CR-39 response to alpha particles, a thick-target bremsstrahlung x-ray generator was used to expose CR-39 to various doses of 8 keV Cu-K{sub α} and K{sub β} x-rays. The CR-39 detectors were then exposed to 1–5.5 MeV alphas from an Am-241 source. The regions of the CR-39 exposed to x-rays showed a smaller track diameter than those notmore » exposed to x-rays: for example, a dose of 3.0 ± 0.1 Gy causes a decrease of (19 ± 2)% in the track diameter of a 5.5 MeV alpha particle, while a dose of 60.0 ± 1.3 Gy results in a decrease of (45 ± 5)% in the track diameter. The reduced track diameters were found to be predominantly caused by a comparable reduction in the bulk etch rate of the CR-39 with x-ray dose. A residual effect depending on alpha particle energy is characterized using an empirical formula.« less

Homologous Recombination and Translesion DNA Synthesis Play Critical Roles on Tolerating DNA Damage Caused by Trace Levels of Hexavalent Chromium

PubMed Central

Chen, Youjun; Zhou, Yi-Hui; Neo, Dayna; Clement, Jean; Takata, Minoru; Takeda, Shunichi; Sale, Julian; Wright, Fred A.; Swenberg, James A.; Nakamura, Jun

2016-01-01

Contamination of potentially carcinogenic hexavalent chromium (Cr(VI)) in the drinking water is a major public health concern worldwide. However, little information is available regarding the biological effects of a nanomoler amount of Cr(VI). Here, we investigated the genotoxic effects of Cr(VI) at nanomoler levels and their repair pathways. We found that DNA damage response analyzed based on differential toxicity of isogenic cells deficient in various DNA repair proteins is observed after a three-day incubation with K2CrO4 in REV1-deficient DT40 cells at 19.2 μg/L or higher as well as in TK6 cells deficient in polymerase delta subunit 3 (POLD3) at 9.8 μg/L or higher. The genotoxicity of Cr(VI) decreased ~3000 times when the incubation time was reduced from three days to ten minutes. TK mutation rate also significantly decreased from 6 day to 1 day exposure to Cr(VI). The DNA damage response analysis suggest that DNA repair pathways, including the homologous recombination and REV1- and POLD3-mediated error-prone translesion synthesis pathways, are critical for the cells to tolerate to DNA damage caused by trace amount of Cr(VI). PMID:27907204

Gas sensing behaviour of Cr{sub 2}O{sub 3} and W{sup 6+}: Cr{sub 2}O{sub 3} nanoparticles towards acetone

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

Kohli, Nipin, E-mail: nipinkohli82@yahoo.com; Hastir, Anita; Singh, Ravi Chand

2016-05-23

This paper reports the acetone gas sensing properties of Cr{sub 2}O{sub 3} and 2% W{sup 6+} doped Cr{sub 2}O{sub 3} nanoparticles. The simple cost-effective hydrolysis assisted co-precipitation method was adopted. Synthesized samples were characterized by X-ray diffraction (XRD) and field emission scanning electron microscopy (FESEM) techniques. XRD revealed that synthesized nanoparticles have corundum structure. The lattice parameters have been calculated by Rietveld refinement; and strain and crystallite size have been calculated by using the Williamson-Hall plots. For acetone gas sensing properties, the nanoparticles were applied as thick film onto alumina substrate and tested at different operating temperatures. The results showedmore » that the optimum operating temperature of both the gas sensors is 250°C. At optimum operating temperature, the response of Cr{sub 2}O{sub 3} and 2% W{sup 6+} doped Cr{sub 2}O{sub 3} gas sensor towards 100 ppm acetone was found to be 25.5 and 35.6 respectively. The investigations revealed that the addition of W{sup 6+} as a dopant enhanced the sensing response of Cr{sub 2}O{sub 3} nanoparticles appreciably.« less

MOR vs SSZ origin of the Aladaǧ ophiolite (S-Turkey): implications from clinopyroxene geochemistry

NASA Astrophysics Data System (ADS)

Saka, Samet; Uysal, Ibrahim; Seitz, Michael; Melih Akmaz, Recep

2017-04-01

The Aladaǧ ophiolite is located in the eastern Taurides, north of the city of Adana, southern Turkey. From bottom to top it is composed of mantle peridotites, ultramafic-mafic cumulates, isotropic (massive) gabbro and diabase dykes. Mantle peridotites, represented by varying degrees of serpentinized dunite, harzburgite and lherzolite, are divided into two subgroups according to spinel Cr# and Lanthanum Group Element (LGE) contents. Group-1 mantle peridotites contain spinel with low Cr# [100×Cr/(Cr+Al) = 13-47] values and relatively high heavy LGE contents whereas Group-2 mantle peridotites contain spinel with relatively higher Cr# (44-74) values and lower heavy LGE contents. Clinopyroxene in the Aladaǧ mantle peridotites are diopside in composition. Clinopyroxenes from the Group-1 samples have TiO2 contents up to 0.37 wt.% and Na2O contents up to 0.89 wt.%. Conversely, the Group-2 clinopyroxenes were relatively depleted compared to the Group-1 clinopyroxenes in terms of TiO2 (<0,1 wt.%) and Na2O (<0.56 wt.%) contents. The Al2O3 contents are between 0.36-5.75 wt.% for the Group-1 clinopyroxenes and this value is relatively low and range between 0.06-2.68 wt.% for the Group-2 clinopyroxenes. Chondrite-normalized LGE patterns of clinopyroxene in the Group-1 and the Group-2 samples differ from each other. While the Group-1 clinopyroxenes show almost flat HLGE to MLGE patterns (DyN/LuN= 0.35-1.30 avg; 0.75), the Group-2 clinopyroxenes are represented by a more significant depletion from HLGE to MLGE (DyN/LuN= 0.04-0.41 avg; 0.19). Ti and Dy contents of clinopyroxene from the Group-1 samples range between 320-2536 ppm and 0.43-2.4 ppm, respectively. However, the Group-2 clinopyroxenes contain rather lower Ti and Dy contents compared to Group-1 clinopyroxenes, varying from 34 to 289 ppm and 0.02 to 0.20 ppm, respectively. The major oxide composition and LGE patterns as well as Ti and Dy contents of the clinopyroxenes indicate that Group-1 samples are relatively lower-degree partial melting residue left after melting in the mid-ocean ridges, while the Group-2 samples are higher degree partial melting residue at suprasubduction zone. The high Ti versus Dy and Zr contents of Group-1 clinopyroxenes support that they are dry melting residues at mid-ocean ridge setting; however, lower Ti contents for a given Zr contents of Group-2 clinopyroxenes imply that these clinopyroxenes are formed as a result of hydrous partial melting. This study was supported by #114Y094 TUBITAK project

Mechanisms of chromium (VI)-induced apoptosis in anterior pituitary cells.

PubMed

Quinteros, Fernanda A; Machiavelli, Leticia I; Miler, Eliana A; Cabilla, Jimena P; Duvilanski, Beatriz H

2008-07-30

Hexavalent chromium (Cr (VI)) is a highly toxic metal. Exposure to Cr (VI) compounds may affect reproductive functions. Due to the importance of anterior pituitary hormones on reproductive physiology we have studied the effects of Cr (VI) on anterior pituitary. We previously demonstrated that, after in vivo Cr (VI) administration, Cr accumulates in the pituitary gland and affects prolactin secretion. In vitro, Cr (VI) causes apoptosis in anterior pituitary cells due to oxidative stress generation. To better understand the mechanisms involved in Cr (VI)-induced apoptosis we studied: (a) whether Cr (VI) affects the intracellular antioxidant response and (b) which of the apoptotic factors participates in Cr (VI) effect. Our results show that Cr (VI) treatment induces a decrease in catalase and glutathione peroxidase (GPx) activity but does not modify glutathione reductase (GR) activity. Cr (VI) exposure causes an increase of GSH levels. p53 and Bax mRNA are also upregulated by the metal. Pifithrin alpha, a p53 transcriptional inhibitor, increases Cr (VI) cytotoxicity, suggesting a role of p53 as a survival molecule. The antioxidant N-acetyl-cysteine (NAC) could prevent Bax mRNA increase and caspase 3 activation, confirming that Cr (VI)-induced apoptosis involves oxidative stress generation.

Efficacy and safety of cisplatin, dexamethasone, gemcitabine and pegaspargase (DDGP) regimen in newly diagnosed, advanced-stage extranodal natural killer/T-cell lymphoma: interim analysis of a phase 4 study NCT01501149

PubMed Central

Li, Ling; Li, Xin; Wang, Xinhua; Fu, Xiaorui; Ma, Wang; Qin, Yanru; Li, Wencai; Wu, Jingjing; Sun, Zhenchang; Zhang, Xudong; Nan, Feifei; Chang, Yu; Li, Zhaoming; Zhang, Dandan; Wang, Guannan; Yan, Jiaqin; Su, Liping; Wang, Jinghua; Xue, Hongwei; Young, Ken H.; Zhang, Mingzhi

2016-01-01

To explore a more effective treatment for newly diagnosed, advanced-stage extranodal natural killer/T-cell lymphoma, nasal type (ENKTL), we conducted a phase 4 study of the cisplatin, dexamethasone, gemcitabine, pegaspargase (DDGP) regimen. The primary end point was the 2-year progression-free survival (PFS) after the protocol treatment. Secondary endpoints included response rate (RR), overall survival (OS) and median survival time (MST). The interim analysis included data only from March 2011 to September 2013, who received six cycles of DDGP chemotherapy. A total of 25 eligible patients were enrolled. Seventeen patients (17/24, 70.83%) achieved complete response (CR) and four (4/24, 16.67%) achieved partial response (PR), three (3/24, 12.50%) had progressive disease (PD). The RR after treatment was 87.50%. After a median follow-up duration of 24.67 months (range 4-48 months). The 2-year PFS and OS rate were 61.80% (95% CI, 42.00% to 81.60%) and 68.50 % (95% CI, 48.70% to 88.30%), respectively. The MST was 36.55 months (95% CI, 29.41 months to 43.70 months). Grade 3/4 leukopenia occurred in fourteen patients (58.33%) and grade 3/4 thrombocytopenia occurred in eleven patients (45.83%). Twelve patients (50.00%) experienced Activated Partial Phromboplastin Ptime (APTT) elongation and fourteen patients (58.33%) experienced hypofibrinogenemia. In conclusion, DDGP regimen is an effective and tolerated treatment for newly diagnosed, advanced-stage ENKTL. This trial was registered at www.ClinicalTrials.gov as #NCT01501149. PMID:27384676

Patterns of relapse from a phase 3 Study of response-based therapy for intermediate-risk Hodgkin lymphoma (AHOD0031): a report from the Children's Oncology Group.

PubMed

Dharmarajan, Kavita V; Friedman, Debra L; Schwartz, Cindy L; Chen, Lu; FitzGerald, T J; McCarten, Kathleen M; Kessel, Sandy K; Iandoli, Matt; Constine, Louis S; Wolden, Suzanne L

2015-05-01

The study was designed to determine whether response-based therapy improves outcomes in intermediate-risk Hodgkin lymphoma. We examined patterns of first relapse in the study. From September 2002 to July 2010, 1712 patients <22 years old with stage I-IIA with bulk, I-IIAE, I-IIB, and IIIA-IVA with or without doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide were enrolled. Patients were categorized as rapid (RER) or slow early responders (SER) after 2 cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide (ABVE-PC). The SER patients were randomized to 2 additional ABVE-PC cycles or augmented chemotherapy with 21 Gy involved field radiation therapy (IFRT). RER patients were stipulated to undergo 2 additional ABVE-PC cycles and were then randomized to 21 Gy IFRT or no further treatment if complete response (CR) was achieved. RER without CR patients were non-randomly assigned to 21 Gy IFRT. Relapses were characterized without respect to site (initial, new, or both; and initial bulk or initial nonbulk), and involved field radiation therapy field (in-field, out-of-field, or both). Patients were grouped by treatment assignment (SER; RER/no CR; RER/CR/IFRT; and RER/CR/no IFRT). Summary statistics were reported. At 4-year median follow-up, 244 patients had experienced relapse, 198 of whom were fully evaluable for review. Those who progressed during treatment (n=30) or lacked relapse imaging (n=16) were excluded. The median time to relapse was 12.8 months. Of the 198 evaluable patients, 30% were RER/no CR, 26% were SER, 26% were RER/CR/no IFRT, 16% were RER/CR/IFRT, and 2% remained uncategorized. The 74% and 75% relapses involved initially bulky and nonbulky sites, respectively. First relapses rarely occurred at exclusively new or out-of-field sites. By contrast, relapses usually occurred at nodal sites of initial bulky and nonbulky disease. Although response-based therapy has helped define treatment for selected RER patients, it has not improved outcome for SER patients or facilitated refinement of IFRT volumes or doses. Copyright © 2015 Elsevier Inc. All rights reserved.

SU-E-J-271: Correlation of CT Number Change with Radiation Treatment Response for Pancreatic Cancer

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

Dalah, E; Tai, A; Oshima, K

Purpose: It has been reported recently that radiation can induce CT number (CTN) change during radiation therapy (RT) delivery. In the effort to explore whether CTN can be used to assess RT response, we analyze the relationship between the pathological treatment response (PTR) and the changes of CTN, MRI, and PET before and after the neoadjuvant chemoradiation (nCR) for pancreatic adenocarcinoma. Methods: The preand post-nCR CT, MRI, and PET data for a total of 8 patients with resectable, or borderline resectable pancreatic head adenocarcinoma treated with nCR were retrospectively analyzed. Radiographic characteristics were correlated to PTR data. The histograms, meansmore » and standard derivations (SD) of the CTNs in pancreatic head (CTNPH), the GTV defined by ADC (CTNGTV), and the rest of pancreatic head (CTNPH-CTNGTV) were compared. Changes before and after nCR were correlated with the corresponding changes of ADC, lean body mass normalized SUV (SUVlb), and PTR using Pearson’ s correlation coefficient test. Results: The average mean and SD in CTPH for all the patients analyzed were higher in post-nCR (53.17 ± 31.05 HU) compared to those at pre-nCR (28.09 ± 4.253 HU). The CTNGTV were generally higher than CTNPH and CTNPH-CTNGTV, though the differences were not significant. The post-nCR changes of mean CTN, ADC, and SUVlb values in pancreatic head were correlated with PTR (R=0.3273/P=0.5357, R=−0.5455/P<0.0001, and R=0.7638/P=0.0357, respectively). The mean difference in the maximum tumor dimension measured from CTN, ADC, and SUVlb as compared with pathological measurements was −2.1, −0.5, and 0.22 cm, respectively. Conclusion: The radiation-induced change of CTN in pancreas head after chemoradiation therapy of pancreatic cancer was observed, which may be related to treatment responses as assessed by biological imaging and pathology. More data are needed to determine whether the CTN can be used as a quantitative biomarker for response to neoadjuvant therapy.« less

An Exploratory Study on the Pathways of Cr (VI) Reduction in Sulfate-reducing Up-flow Anaerobic Sludge Bed (UASB) Reactor

PubMed Central

Qian, Jin; Wei, Li; Liu, Rulong; Jiang, Feng; Hao, Xiaodi; Chen, Guang-Hao

2016-01-01

Electroplating wastewater contains both Cr (VI) and sulfate. So Cr (VI) removal under sulfate-rich condition is quite complicated. This study mainly investigates the pathways for Cr (VI) removal under biological sulfate-reducing condition in the up-flow anaerobic sludge bed (UASB) reactor. Two potential pathways are found for the removal of Cr (VI). The first one is the sulfidogenesis-induced Cr (VI) reduction pathway (for 90% Cr (VI) removal), in which Cr (VI) is reduced by sulfide generated from biological reduction of sulfate. The second one leads to direct reduction of Cr (VI) which is utilized by bacteria as the electron acceptor (for 10% Cr (VI) removal). Batch test results confirmed that sulfide was oxidized to elemental sulfur instead of sulfate during Cr (VI) reduction. The produced extracellular polymeric substances (EPS) provided protection to the microbes, resulting in effective removal of Cr (VI). Sulfate-reducing bacteria (SRB) genera accounted for 11.1% of the total bacterial community; thus they could be the major organisms mediating the sulfidogenesis-induced reduction of Cr (VI). In addition, chromate-utilizing genera (e.g. Microbacterium) were also detected, which were possibly responsible for the direct reduction of Cr (VI) using organics as the electron donor and Cr (VI) as the electron acceptor. PMID:27021522

Quantitative contrast-enhanced ultrasound evaluation of pathological complete response in patients with locally advanced breast cancer receiving neoadjuvant chemotherapy.

PubMed

Wan, Cai-Feng; Liu, Xue-Song; Wang, Lin; Zhang, Jie; Lu, Jin-Song; Li, Feng-Hua

2018-06-01

To clarify whether the quantitative parameters of contrast-enhanced ultrasound (CEUS) can be used to predict pathological complete response (pCR) in patients with locally advanced breast cancer receiving neoadjuvant chemotherapy (NAC). Fifty-one patients with histologically proved locally advanced breast cancer scheduled for NAC were enrolled. The quantitative data for CEUS and the tumor diameter were collected at baseline and before surgery, and compared with the pathological response. Multiple logistic regression analysis was performed to examine quantitative parameters at CEUS and the tumor diameter to predict the pCR, and receiver operating characteristic (ROC) curve analysis was used as a summary statistic. Multiple logistic regression analysis revealed that PEAK (the maximum intensity of the time-intensity curve during bolus transit), PEAK%, TTP% (time to peak), and diameter% were significant independent predictors of pCR, and the area under the ROC curve was 0.932(Az 1 ), and the sensitivity and specificity to predict pCR were 93.7% and 80.0%. The area under the ROC curve for the quantitative parameters was 0.927(Az 2 ), and the sensitivity and specificity to predict pCR were 81.2% and 94.3%. For diameter%, the area under the ROC curve was 0.786 (Az 3 ), and the sensitivity and specificity to predict pCR were 93.8% and 54.3%. The values of Az 1 and Az 2 were significantly higher than that of Az 3 (P = 0.027 and P = 0.034, respectively). However, there was no significant difference between the values of Az 1 and Az 2 (P = 0.825). Quantitative analysis of tumor blood perfusion with CEUS is superior to diameter% to predict pCR, and can be used as a functional technique to evaluate tumor response to NAC. Copyright © 2018. Published by Elsevier B.V.

High-intensity focused ultrasound (HIFU) treatment for uterine fibroids: a meta-analysis.

PubMed

Ji, Yongshuo; Hu, Kaimeng; Zhang, Yu; Gu, Lijun; Zhu, Junqiu; Zhu, Linglin; Zhu, Yanfei; Zhao, Hong

2017-12-01

High-intensity focused ultrasound (HIFU) is a non-invasive uterine-preserving treatment alternative to hysterectomy for women with fibroids. We performed this meta-analysis to evaluate the efficacy of HIFU in the treatment of women with symptomatic fibroids comparing it to other approaches including medical treatment with mifepristone (Mife), traditional surgery with myomectomy or hysterectomy (MYC/HRM), and radiofrequency ablation (RF). 16 studies with 1725 women were included. The pooled data of HIFU comparing it to other methods in terms of complete or partial response rate (CR/PR) was not significantly better, but in subgroup analysis, the response rate was significantly higher than Mife, significantly lower than RF and comparable to MYC/HRM, respectively. For the endpoints of safety, the superiority of HIFU compared to MYC/HMR or Mife was found to be significant in terms of pain/discomfort, fever, transfusion, genital tract, gastrointestinal tract, and anesthesia-related complications, while no superiority was identified for skin burn, urinary tract, and nervous system complications. These results suggest that HIFU treatment of uterine leiomyomas leads to clinical improvement with few significant clinical complications and adverse events.

A retrospective study of feline gastric lymphoma in 16 chemotherapy-treated cats.

PubMed

Gustafson, Tanya L; Villamil, Armando; Taylor, Bonnie E; Flory, Andrea

2014-01-01

The purposes of this study were to describe cases of feline gastric lymphoma with regards to signalment, clinical presentation, laboratory and ancillary study findings, response to therapy, and outcomes and to identify prognostic variables. Sixteen cats with stage I and II gastric lymphoma treated with chemotherapy were included in this study. Seventy-five percent of cats experienced remission. Overall, first remission duration was 108 days. Response to treatment was prognostic as in other types of feline lymphoma. Cats with a complete remission (CR) had longer survival times compared with cats with a partial remission (PR). Sex and treatment with a rescue protocol were found to be prognostic with castrated males having longer survivals than spayed females. Cats that received rescue chemotherapy had shorter first remission durations than those that did not. Prior treatment with steroids and stage were not found to be significant prognostic variables. This study characterizes gastric lymphoma treated with chemotherapy in cats. Further studies are needed to determine the comparative efficacy of surgical and chemotherapeutic treatments for feline gastric lymphoma.

Treatment of feline intermediate- to high-grade lymphoma with a modified university of Wisconsin-Madison protocol: 119 cases (2004-2012).

PubMed

Collette, S A; Allstadt, S D; Chon, E M; Vernau, W; Smith, A N; Garrett, L D; Choy, K; Rebhun, R B; Rodriguez, C O; Skorupski, K A

2016-08-01

CHOP-based (cyclophosphamide, doxorubicin, vinca alkaloid, prednisolone) chemotherapy protocols are often recommended for treatment of feline lymphoma. While maintenance-free CHOP-based protocols have been published and readily used in dogs, there is limited literature regarding similar maintenance-free protocols in cats. The purpose of this study was to describe the outcome of cats with intermediate- to high-grade lymphoma that were prescribed a modified 25-week University of Wisconsin-Madison (UW-25) chemotherapy protocol. A secondary objective was examination of potential prognostic factors. One hundred and nineteen cats from five institutions treated with a UW-25-based protocol were included. The Kaplan-Meier median progression-free interval (PFI) and survival time (MST) were 56 and 97 (range 2-2019) days, respectively. Cats assessed as having a complete response (CR) to therapy had significantly longer PFI and MST than those with partial or no response (PFI 205 versus 54 versus 21 days, respectively, P < 0.0001 and MST 318 versus 85 versus 27 days, respectively, P < 0.0001). © 2015 John Wiley & Sons Ltd.

Postprandial metabolite profiles reveal differential nutrient handling after bariatric surgery compared with matched caloric restriction.

PubMed

Khoo, Chin Meng; Muehlbauer, Michael J; Stevens, Robert D; Pamuklar, Zehra; Chen, Jiegen; Newgard, Christopher B; Torquati, Alfonso

2014-04-01

Roux-en-Y gastric bypass (RYGB) surgery results in exaggerated postprandial insulin and incretin responses and increased susceptibility to hypoglycemia. We examined whether these features are due to caloric restriction (CR) or altered nutrient handling. We performed comprehensive analysis of postprandial metabolite responses during a 2-hour mixed-meal tolerance (MMT) test in 20 morbidly obese subjects with type 2 diabetes who underwent RYGB surgery or matched CR. Acylcarnitines and amino acids (AAs) were measured using targeted mass spectrometry. A linear mixed model was used to determine the main effect of interventions and interaction term to assess the effect of interventions on postprandial kinetics. Two weeks after these interventions, several gut hormones (insulin, glucose-dependent insulinotropic polypeptide, and glucagon-like peptide 1), glucose, and multiple AAs, including branched-chain and aromatic species, exhibited a more rapid rate of appearance and clearance in RYGB surgery subjects than in CR subjects during the MMT test. In the RYGB surgery group, changes in leucine/isoleucine, methionine, phenylalanine, and glucagon-like peptide 1 response were associated with changes in insulin response. Levels of alanine, pyruvate, and lactate decreased significantly at the later stages of meal challenge in RYGB surgery subjects but increased with CR. RYGB surgery results in improved metabolic flexibility (ie, greater disposal of glucose and AAs and more complete β-oxidation of fatty acids) compared with CR. The changes in the AA kinetics may augment the hormonal responses seen after RYGB surgery. The reduction in key gluconeogenic substrates in the postprandial state may contribute to increased susceptibility to hypoglycemic symptoms in RYGB surgery subjects.

Chemokine receptors CXCR2 and CX3CR1 differentially regulate functional responses of bone-marrow endothelial progenitors during atherosclerotic plaque regression.

PubMed

Herlea-Pana, Oana; Yao, Longbiao; Heuser-Baker, Janet; Wang, Qiongxin; Wang, Qilong; Georgescu, Constantin; Zou, Ming-Hui; Barlic-Dicen, Jana

2015-05-01

Atherosclerosis manifests itself as arterial plaques, which lead to heart attacks or stroke. Treatments supporting plaque regression are therefore aggressively pursued. Studies conducted in models in which hypercholesterolaemia is reversible, such as the Reversa mouse model we have employed in the current studies, will be instrumental for the development of such interventions. Using this model, we have shown that advanced atherosclerosis regression occurs when lipid lowering is used in combination with bone-marrow endothelial progenitor cell (EPC) treatment. However, it remains unclear how EPCs home to regressing plaques and how they augment atherosclerosis reversal. Here we identify molecules that support functional responses of EPCs during plaque resolution. Chemokines CXCL1 and CX3CL1 were detected in the vascular wall of atheroregressing Reversa mice, and their cognate receptors CXCR2 and CX3CR1 were observed on adoptively transferred EPCs in circulation. We tested whether CXCL1-CXCR2 and CX3CL1-CX3CR1 axes regulate functional responses of EPCs during plaque reversal. We show that pharmacological inhibition of CXCR2 or CX3CR1, or genetic inactivation of these two chemokine receptors interfered with EPC-mediated advanced atherosclerosis regression. We also demonstrate that CXCR2 directs EPCs to regressing plaques while CX3CR1 controls a paracrine function(s) of these cells. CXCR2 and CX3CR1 differentially regulate EPC functional responses during atheroregression. Our study improves understanding of how chemokines and chemokine receptors regulate plaque resolution, which could determine the effectiveness of interventions reducing complications of atherosclerosis. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Chemokine receptors CXCR2 and CX3CR1 differentially regulate functional responses of bone-marrow endothelial progenitors during atherosclerotic plaque regression

PubMed Central

Herlea-Pana, Oana; Yao, Longbiao; Heuser-Baker, Janet; Wang, Qiongxin; Wang, Qilong; Georgescu, Constantin; Zou, Ming-Hui; Barlic-Dicen, Jana

2015-01-01

Aims Atherosclerosis manifests itself as arterial plaques, which lead to heart attacks or stroke. Treatments supporting plaque regression are therefore aggressively pursued. Studies conducted in models in which hypercholesterolaemia is reversible, such as the Reversa mouse model we have employed in the current studies, will be instrumental for the development of such interventions. Using this model, we have shown that advanced atherosclerosis regression occurs when lipid lowering is used in combination with bone-marrow endothelial progenitor cell (EPC) treatment. However, it remains unclear how EPCs home to regressing plaques and how they augment atherosclerosis reversal. Here we identify molecules that support functional responses of EPCs during plaque resolution. Methods and results Chemokines CXCL1 and CX3CL1 were detected in the vascular wall of atheroregressing Reversa mice, and their cognate receptors CXCR2 and CX3CR1 were observed on adoptively transferred EPCs in circulation. We tested whether CXCL1–CXCR2 and CX3CL1–CX3CR1 axes regulate functional responses of EPCs during plaque reversal. We show that pharmacological inhibition of CXCR2 or CX3CR1, or genetic inactivation of these two chemokine receptors interfered with EPC-mediated advanced atherosclerosis regression. We also demonstrate that CXCR2 directs EPCs to regressing plaques while CX3CR1 controls a paracrine function(s) of these cells. Conclusion CXCR2 and CX3CR1 differentially regulate EPC functional responses during atheroregression. Our study improves understanding of how chemokines and chemokine receptors regulate plaque resolution, which could determine the effectiveness of interventions reducing complications of atherosclerosis. PMID:25765938

Phase II study of medroxyprogesterone acetate plus metformin as a fertility-sparing treatment for atypical endometrial hyperplasia and endometrial cancer.

PubMed

Mitsuhashi, A; Sato, Y; Kiyokawa, T; Koshizaka, M; Hanaoka, H; Shozu, M

2016-02-01

Metformin, widely used in the treatment of type 2 diabetes mellitus, reduces the risk of cancer and relapse after treatment. Fertility-sparing treatment for endometrial cancer (EC) with progestin is associated with a high chance of disease regression, and the high relapse rate continues to be a problem. We assessed the efficacy of metformin in preventing recurrence after medroxyprogesterone acetate (MPA) as fertility-sparing treatment for atypical endometrial hyperplasia (AEH) and EC. This phase II study enrolled 17 patients with AEH and 19 patients with EC limited to the endometrium (age, 20-40 years). MPA (400 mg/day) and metformin (750-2250 mg/day) were administered for 24-36 weeks to achieve a complete response (CR). Metformin was administered until conception, even after MPA discontinuation. The primary end point was relapse-free survival (RFS) after remission. We analyzed all efficacy end points in the full analysis set. The body mass index was ≥25 kg/m(2) in 27 patients (mean, 31 kg/m(2); range, 19-51 kg/m(2)), and the homeostasis model assessment for insulin resistance index was ≥2.5 in 24 patients (mean, 4.7; range, 0.7-21). Two patients showed progression at 12 weeks [6%; 95% confidence interval (CI) 2-18]. At 36 weeks, 29 (81%; 95% CI 65-90) patients achieved CR, and 5 (14%; 95% CI 6-29) patients achieved partial response. During a median follow-up of 38 months (range, 9-66 months) after remission, relapse was confirmed in three of the patients who had achieved CR (relapse rate, 10%). The 3-year estimated RFS rate was 89%. No patients experienced severe toxicity. Metformin inhibited disease relapse after MPA therapy. The combination of metformin and MPA in EC treatment should be studied further. UMIN 000002210. © The Author 2015. 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.

Oxidation and the Effects of High Temperature Exposures on Notched Fatigue Life of an Advanced Powder Metallurgy Disk Superalloy

NASA Technical Reports Server (NTRS)

Sudbrack, Chantal K.; Draper, Susan L.; Gorman, Timothy T.; Telesman, Jack; Gab, Timothy P.; Hull, David R.

2012-01-01

Oxidation and the effects of high temperature exposures on notched fatigue life were considered for a powder metallurgy processed supersolvus heat-treated ME3 disk superalloy. The isothermal static oxidation response at 704 C, 760 C, and 815 C was consistent with other chromia forming nickel-based superalloys: a TiO2-Cr2O3 external oxide formed with a branched Al2O3 internal subscale that extended into a recrystallized - dissolution layer. These surface changes can potentially impact disk durability, making layer growth rates important. Growth of the external scales and dissolution layers followed a cubic rate law, while Al2O3 subscales followed a parabolic rate law. Cr- rich M23C6 carbides at the grain boundaries dissolved to help sustain Cr2O3 growth to depths about 12 times thicker than the scale. The effect of prior exposures was examined through notched low cycle fatigue tests performed to failure in air at 704 C. Prior exposures led to pronounced debits of up to 99 % in fatigue life, where fatigue life decreased inversely with exposure time. Exposures that produced roughly equivalent 1 m thick external scales at the various isotherms showed statistically equivalent fatigue lives, establishing that surface damage drives fatigue debit, not exposure temperature. Fractographic evaluation indicated the failure mode for the pre-exposed specimens involved surface crack initiations that shifted with exposure from predominately single intergranular initiations with transgranular propagation to multi-initiations from the cracked external oxide with intergranular propagation. Weakened grain boundaries at the surface resulting from the M23C6 carbide dissolution are partially responsible for the intergranular cracking. Removing the scale and subscale while leaving a layer where M23C6 carbides were dissolved did not lead to a significant fatigue life improvement, however, also removing the M23C6 carbide dissolution layer led to nearly full recovery of life, with a transgranular initiation typical to that observed in unexposed specimens.

Response of Cr and Cr-Al coatings on Zircaloy-2 to high temperature steam

NASA Astrophysics Data System (ADS)

Zhong, Weicheng; Mouche, Peter A.; Heuser, Brent J.

2018-01-01

The oxidation behavior of chromium (Cr) and chromium-aluminum (CrAl) coatings with various compositions deposited on Zircaloy-2 to 700 °C high-temperature steam (HTS) exposure has been investigated. CrAl coatings with higher Al compositions demonstrate lower oxidation weight gain. A layer of γ-alumina developed on the CrAl coatings with Al composition over 43 at%, while Al2O3 and Cr2O3 developed on CrAl coatings with Al composition below 33 at%. Oxidation of Zircaloy-2 substrate was inhibited by the 1um coatings to 20 h HTS exposure. Coating constituent elements diffused into the substrate and formed intermetallic phases with the Zircaloy substrate. Thicker layers of intermetallic phases developed on the coatings with higher Al composition. The intermetallic phases included Fe and Ni, indicating the dissolution of second phase particles (SPPs) during HTS exposure.

The arcuate nucleus and NPY contribute to the antitumorigenic effect of calorie restriction

PubMed Central

Minor, Robin K.; López, Miguel; Younts, Caitlin M.; Jones, Bruce; Pearson, Kevin J.; Anson, R. Michael; Diéguez, Carlos; de Cabo, Rafael

2011-01-01

Summary Calorie restriction (CR) is known to have profound effects on tumor incidence. A typical consequence of CR is hunger, and we hypothesized that the neuroendocrine response to CR might in part mediate CR's antitumor effects. We tested CR under appetite suppression using two models: neuropeptide Y (NPY) knockout mice and monosodium glutamate (MSG)-injected mice. While CR was protective in control mice challenged with a two-stage skin carcinogenesis model, papilloma development was neither delayed nor reduced by CR in the MSG-treated and NPY knockout mice. Adiponectin levels were also not increased by CR in the appetite-suppressed mice. We propose that some of CR’s beneficial effects cannot be separated from those imposed on appetite, and that NPY neurons in the arcuate nucleus of the hypothalamus (ARC) are involved in the translation of reduced intake to downstream physiological and functional benefits. PMID:21385308

Neoadjuvant chemotherapy in breast cancer: prediction of pathologic response with PET/CT and dynamic contrast-enhanced MR imaging--prospective assessment.

PubMed

Tateishi, Ukihide; Miyake, Mototaka; Nagaoka, Tomoaki; Terauchi, Takashi; Kubota, Kazunori; Kinoshita, Takayuki; Daisaki, Hiromitsu; Macapinlac, Homer A

2012-04-01

To clarify whether fluorine 18 ((18)F) fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) and dynamic contrast-enhanced (DCE) magnetic resonance (MR) imaging performed after two cycles of neoadjuvant chemotherapy (NAC) can be used to predict pathologic response in breast cancer. Institutional human research committee approval and written informed consent were obtained. Accuracy after two cycles of NAC for predicting pathologic complete response (pCR) was examined in 142 women (mean age, 57 years: range, 43-72 years) with histologically proved breast cancer between December 2005 and February 2009. Quantitative PET/CT and DCE MR imaging were performed at baseline and after two cycles of NAC. Parameters of PET/CT and of blood flow and microvascular permeability at DCE MR were compared with pathologic response. Patients were also evaluated after NAC by using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 based on DCE MR measurements and European Organization for Research and Treatment of Cancer (EORTC) criteria and PET Response Criteria in Solid Tumors (PERCIST) 1.0 based on PET/CT measurements. Multiple logistic regression analyses were performed to examine continuous variables at PET/CT and DCE MR to predict pCR, and diagnostic accuracies were compared with the McNemar test. Significant decrease from baseline of all parameters at PET/CT and DCE MR was observed after NAC. Therapeutic response was obtained in 24 patients (17%) with pCR and 118 (83%) without pCR. Sensitivity, specificity, and accuracy to predict pCR were 45.5%, 85.5%, and 82.4%, respectively, with RECIST and 70.4%, 95.7%, and 90.8%, respectively, with EORTC and PERCIST. Multiple logistic regression revealed three significant independent predictors of pCR: percentage maximum standardized uptake value (%SUV(max)) (odds ratio [OR], 1.22; 95% confidence interval [CI]: 1.11, 1.34; P < .0001), percentage rate constant (%k(ep)) (OR, 1.07; CI: 1.03, 1.12; P = .002), and percentage area under the time-intensity curve over 90 seconds (%AUC(90)) (OR, 1.04; CI: 1.01, 1.07; P = .048). When diagnostic accuracies are compared, PET/CT is superior to DCE MR for the prediction of pCR (%SUV(max) [90.1%] vs %κ(ep) [83.8%] or %AUC(90) [76.8%]; P < .05). The sensitivities of %SUV(max) (66.7%), %k(ep) (51.7%), and %AUC(90) (50.0%) at (18)F-FDG PET/CT and DCE MR after two cycles of NAC are not acceptable, but the specificities (96.4%, 92.0%, and 95.2%, respectively) are high for stratification of pCR cases in breast cancer. © RSNA, 2012.

Postnatal exposure to chromium through mother's milk accelerates follicular atresia in F1 offspring through increased oxidative stress and depletion of antioxidant enzymes.

PubMed

Stanley, Jone A; Sivakumar, Kirthiram K; Nithy, Thamizh K; Arosh, Joe A; Hoyer, Patricia B; Burghardt, Robert C; Banu, Sakhila K

2013-08-01

Hexavalent chromium, CrVI, is a heavy metal endocrine disruptor, known as a mutagen, teratogen, and a group A carcinogen. Environmental contamination with CrVI, including drinking water, has been increasing in more than 30 cities in the United States. CrVI is rapidly converted to CrIII intracellularly, and CrIII can cause DNA strand breaks and cancer or apoptosis through different mechanisms. Our previous study demonstrated that lactational exposure to chromium results in a delay or arrest in follicle development and a decrease in steroid hormone levels in F1 female rats, both of which are mitigated (partial inhibition) by vitamin C. The current study tested the hypothesis that lactational exposure to CrIII accelerates follicle atresia in F1 offspring by increasing reactive oxygen species (ROS) and decreasing cellular antioxidants. Results showed that lactational exposure to CrIII dose-dependently increased follicular atresia and decreased steroidogenesis in postnatal day 25, 45, and 65 rats. Vitamin C mitigated or inhibited the effects of CrIII at all doses. CrIII increased hydrogen peroxide and lipid hydroperoxide in plasma and ovary; decreased the antioxidant enzymes (AOXs) GPx1, GR, SOD, and catalase; and increased glutathione S-transferase in plasma and ovary. To understand the effects of CrVI on ROS and AOXs in granulosa (GC) and theca (TC) cell compartments in the ovary, ROS levels and mRNA expression of cytosolic and mitochondrial AOXs, such as SOD1, SOD2, catalase, GLRX1, GSTM1, GSTM2, GSTA4, GR, TXN1, TXN2, TXNRD2, and PRDX3, were studied in GCs and TCs and in a spontaneously immortalized granulosa cell line (SIGC). Overall, CrVI downregulated each of the AOXs; and vitamin C mitigated the effects of CrVI on these enzymes in GCs and SIGCs, but failed to mitigate CrVI effects on GSTM1, GSTM2, TXN1, and TXN2 in TCs. Thus, these data for the first time reveal that lactational exposure to CrIII accelerated follicular atresia and decreased steroidogenesis in F1 female offspring by altering the ratio of ROS and AOXs in the ovary. Vitamin C is able to protect the ovary from CrIII-induced oxidative stress and follicle atresia through protective effects on GCs rather than TCs. Copyright © 2013 Elsevier Inc. All rights reserved.

Physiological responses and tolerance of kenaf (Hibiscus cannabinus L.) exposed to chromium.

PubMed

Ding, Han; Wang, Guodong; Lou, Lili; Lv, Jinyin

2016-11-01

Selection of kenaf species with chromium (Cr) tolerance and exploring the physiological mechanisms involved in Cr tolerance are crucial for application of these species to phyto-remediation. In the present study, a hydroponic experiment was conducted to investigate the variation in two kenaf cultivars, K39-2 and Zhe50-3 under Cr stress. At the same Cr concentration, the tolerance index (TI) of K39-2 was higher than that of Zhe50-3, indicating that K39-2 may be more tolerant to Cr than Zhe50-3. It was also observed that high concentration of chromium was accumulated both in the shoots and the roots of Hibiscus cannabinus L. The leaves of K39-2 accumulated 4760.28mgkg(-1) of dry weight under 1.50mM Cr stress, and the roots accumulated 11,958.33mgkg(-1). Physiological response shows that the antioxidant enzymes' superoxide dismutase (SOD), catalase activity (CAT) and peroxidase (POD) activities increased in the leaves and decreased in roots of the Cr-stressed plants nearly compared to the control. Moreover, the variation of antioxidant enzymes activities indicated Zhe50-3 was more vulnerable than K39-2, and the contents of the non-protein thiol pool (GSH, NPT and PCs) were higher in K39-2 than Zhe50-3 with the increased Cr concentration. Based on the observations above, it can be concluded that the well-coordinated physiological changes confer a greater Cr tolerance to K39-2 than Zhe50-3 under Cr exposure, and Hibiscus cannabinus L. has a great accumulation capacity for chromium. Copyright © 2016 Elsevier Inc. All rights reserved.

The Assignment of Raters to Items: Controlling for Rater Effects.

ERIC Educational Resources Information Center

Sykes, Robert C.; Heidorn, Mark; Lee, Guemin

A study was conducted to evaluate the effect of different modes (modalities) of assigning raters to test items. The impact on total constructed response (c.r.) score, and subsequently on total test score, of assigning a single versus multiple raters to an examination reading of a student's set of c.r. responses was evaluated for several mixed-item…

Chromium supplementation enhances the metabolic response of steers to lipopolysaccharide (LPS) challenge

USDA-ARS?s Scientific Manuscript database

The effect of chromium (Cr; KemTRACE®brandChromiumProprionate 0.04%, Kemin Industries) supplementation on the metabolic response to LPS challenge was examined. Steers (n=20; 235±4 kg body weight (BW)) received a premix that added 0 (Con) or 0.2 mg/kg Cr to the total diet (DM (dry matter) basis) for ...

Estimating the Effect on Grades of Using Multiple-Choice versus Constructive-Response Questions: Data from the Classroom

ERIC Educational Resources Information Center

Hickson, Stephen; Reed, W. Robert; Sander, Nicholas

2012-01-01

This study investigates the degree to which grades based solely on constructed-response (CR) questions differ from grades based solely on multiple-choice (MC) questions. If CR questions are to justify their higher costs, they should produce different grade outcomes than MC questions. We use a data set composed of thousands of observations on…

Global developmental delay in guanidionacetate methyltransferase deficiency: differences in formal testing and clinical observation.

PubMed

Verbruggen, Krijn T; Knijff, Wilma A; Soorani-Lunsing, Roelineke J; Sijens, Paul E; Verhoeven, Nanda M; Salomons, Gajja S; Goorhuis-Brouwer, Siena M; van Spronsen, Francjan J

2007-09-01

Guanidinoacetate N-methyltransferase (GAMT) deficiency is a defect in the biosynthesis of creatine (Cr). So far, reports have not focused on the description of developmental abilities in this disorder. Here, we present the result of formal testing of developmental abilities in a GAMT-deficient patient. Our patient, a 3-year-old boy with GAMT deficiency, presented clinically with a severe language production delay and nearly normal nonverbal development. Treatment with oral Cr supplementation led to partial restoration of the cerebral Cr concentration and a clinically remarkable acceleration of language production development. In contrast to clinical observation, formal testing showed a rather harmonic developmental delay before therapy and a general improvement, but no specific acceleration of language development after therapy. From our case, we conclude that in GAMT deficiency language delay is not always more prominent than delays in other developmental areas. The discrepancy between the clinical impression and formal testing underscores the importance of applying standardized tests in children with developmental delays. Screening for Cr deficiency by metabolite analysis of body fluids or proton magnetic resonance spectroscopy of the brain deficiency should be considered in any child with global developmental delay/mental retardation lacking clues for an alternative etiology.

Influence of Oxidation Treatments and Surface Finishing on the Electrochemical Behavior of Ni-20Cr HVOF Coatings

NASA Astrophysics Data System (ADS)

Ruiz-Luna, H.; Porcayo-Calderon, J.; Alvarado-Orozco, J. M.; Mora-García, A. G.; Martinez-Gomez, L.; Trápaga-Martínez, L. G.; Muñoz-Saldaña, J.

2017-12-01

The low-temperature electrochemical behavior of HVOF Ni-20Cr coatings was assessed. The coatings were evaluated in different conditions including as-sprayed, as-ground, and heat-treated in air and argon atmospheres. A detailed analysis of the coatings was carried out by means of XRD, SEM, and EPMA, prior and after the corrosion test. The corrosion rate was analyzed in a NaCl solution saturated with CO2. Results demonstrate that the use of a low-oxygen partial pressure favors the formation of a Cr2O3 layer on the surface of the coatings. According to the electrochemical results, the lower corrosion rates were obtained for the heat-treated coatings irrespective of the surface finishing, being the ground and argon heat-treated condition that shows the best corrosion performance. This behavior is due to the synergistic effect of the low-pressure heat treatment and the grinding processes. The grinding promotes a more homogeneous reaction area without surface heterogeneities such as voids, and the pre-oxidation treatment decreases the porosity content of the coating and also allows the growing of a Cr-rich oxide scale which acts as a barrier against the ions of the aqueous solution.

High temperature oxidation resistance of magnetron-sputtered homogeneous CrAlON coatings on 430 steel

NASA Astrophysics Data System (ADS)

Garratt, E.; Wickey, K. J.; Nandasiri, M. I.; Moore, A.; AlFaify, S.; Gao, X.; Kayani, A.; Smith, R. J.; Buchanan, T. L.; Priyantha, W.; Kopczyk, M.; Gannon, P. E.

2009-11-01

The requirements of low cost and high-temperature corrosion resistance for bipolar interconnect plates in solid oxide fuel cell stacks has directed attention to the use of metal plates with oxidation resistant coatings. We have investigated the performance of steel plates with homogenous coatings of CrAlON (oxynitrides). The coatings were deposited using RF magnetron sputtering, with Ar as a sputtering gas. Oxygen in these coatings was not intentionally added. Oxygen might have come through contaminated nitrogen gas bottle, leak in the chamber or from the partial pressure of water vapors. Nitrogen was added during the growth process to get oxynitride coating. The Cr/Al composition ratio in the coatings was varied in a combinatorial approach. The coatings were subsequently annealed in air for up to 25 hours at 800 oC. The composition of the coated plates and the rate of oxidation were characterized using Rutherford backscattering (RBS) and nuclear reaction analysis (NRA). Surface characterization was carried out using Atomic Force Microscopy (AFM) and surfaces of the coatings were found smooth on submicron scale. From our results, we conclude that Al rich coatings are more susceptible to oxidation than Cr rich coatings.

Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study.

PubMed

Topp, Max S; Gökbuget, Nicola; Stein, Anthony S; Zugmaier, Gerhard; O'Brien, Susan; Bargou, Ralf C; Dombret, Hervé; Fielding, Adele K; Heffner, Leonard; Larson, Richard A; Neumann, Svenja; Foà, Robin; Litzow, Mark; Ribera, Josep-Maria; Rambaldi, Alessandro; Schiller, Gary; Brüggemann, Monika; Horst, Heinz A; Holland, Chris; Jia, Catherine; Maniar, Tapan; Huber, Birgit; Nagorsen, Dirk; Forman, Stephen J; Kantarjian, Hagop M

2015-01-01

Adults with relapsed or refractory B-precursor acute lymphoblastic leukaemia have an unfavourable prognosis. Blinatumomab is a bispecific T-cell engager antibody construct targeting CD19, an antigen consistently expressed on B-lineage acute lymphoblastic leukaemia cells. We aimed to confirm the activity and safety profile of blinatumomab for acute lymphoblastic leukaemia. In a multicentre, single-arm, open-label phase 2 study, we enrolled adult patients with Philadelphia-chromosome-negative, primary refractory or relapsed (first relapse within 12 months of first remission, relapse within 12 months after allogeneic haemopoietic stem-cell transplantation [HSCT], or no response to or relapse after first salvage therapy or beyond) leukaemia. Patients received blinatumomab (9 μg/day for the first 7 days and 28 μg/day thereafter) by continuous intravenous infusion over 4 weeks every 6 weeks (up to five cycles), per protocol. The primary endpoint was complete remission (CR) or CR with partial haematological recovery of peripheral blood counts (CRh) within the first two cycles. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, number NCT01466179. Between Jan 13, 2012, and Oct 10, 2013, 189 patients were enrolled and treated with blinatumomab. After two cycles, 81 (43%, 95% CI 36-50) patients had achieved a CR or CRh: 63 (33%) patients had a CR and 18 (10%) patients had a CRh. 32 (40%) of patients who achieved CR/CRh underwent subsequent allogeneic HSCT. The most frequent grade 3 or worse adverse events were febrile neutropenia (48 patients, 25%), neutropenia (30 patients, 16%), and anaemia (27 patients, 14%). Three (2%) patients had grade 3 cytokine release syndrome. Neurologic events of worst grade 3 or 4 occurred in 20 (11%) and four (2%) patients, respectively. Three deaths (due to sepsis, Escherichia coli sepsis, and Candida infection) were thought to be treatment-related by the investigators. Single-agent blinatumomab showed antileukaemia activity in adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia characterised by negative prognostic factors. Further assessment of blinatumomab treatment earlier in the course of the disease and in combination with other treatment approaches is warranted. Amgen. Copyright © 2015 Elsevier Ltd. All rights reserved.

Docetaxel as neoadjuvant chemotherapy in patients with advanced cervical carcinoma.

PubMed

Vallejo, Carlos T; Machiavelli, Mario R; Pérez, Juan E; Romero, Alberto O; Bologna, Fabrina; Vicente, Hernán; Lacava, Juan A; Ortiz, Eduardo H; Cubero, Alberto; Focaccia, Guillermo; Suttora, Guillermo; Scenna, Mirna; Boughen, José M; Leone, Bernardo A

2003-10-01

The purpose of this study was to evaluate the efficacy and toxicity of docetaxel as single-agent neoadjuvant chemotherapy in locoregionally advanced cervical carcinoma. Between April 1998 and August 2000, 38 untreated patients with International Federation of Gynecology and Obstetrics stages IIB to IVA were entered onto this study. The median age was 44 years (range: 25-66 years). Stages: IIB 22 patients, IIIB 15 patients, and IVA 1 pt. Treatment consisted of docetaxel 100 mg/m2 IV infusion during 1 hour. Standard premedication with dexamethasone, diphenhydramine, and ranitidine was used. Cycles were repeated every 3 weeks for three courses, followed by radical surgery when it was judged appropriate, or definitive radiotherapy. Both staging and response assessment were performed by a multidisciplinary team. 106 cycles of therapy were administered; all patients were evaluable for TX, whereas 35 were evaluable for response (3 patients refused further treatment after the first cycle of therapy). Complete response (CR): 1 patient (3%); partial response: 11 patients (31%), for an overall objective response rate of 34% (95% CI: 15-53%); no change (NC): 16 patients (46%); and progressive disease: 7 patients (20%). Six patients (17%) underwent surgery and a pathologic CR was confirmed in 1 of them. The median time to treatment failure and the median survival have not been reached yet. The limiting toxicity was leukopenia in 25 patients (69%) (G1-G2: 14 patients, G3: 10 patients, and G4: 1 patient). Neutropenia: 28 patients (78%) (G1-G2: 10 patients, G3: 8 and G4: 10). Myalgias: 17 patients (47%) (G1-G2: 15 patients and G3: 2 patients). Emesis: 21 patients (55%) (G1-G2: 19 patients and G3: 2 patients). Alopecia G3: 13 patients (36%); rash cutaneous 26 patients (68%) (G1-G2: 22 patients and G3: 4 patients). There were no hypersensitivity reactions or fluid-retention syndrome. The received dose intensity was 91% of that projected. Docetaxel is an active drug against advanced cervical carcinoma with moderate toxicity. Further evaluation in association with other agents is clearly justified.

A Prospective Phase 2 Multicenter Study for the Efficacy of Radiation Therapy Following Incomplete Transarterial Chemoembolization in Unresectable Hepatocellular Carcinoma

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

Choi, Chihwan; Koom, Woong Sub; Kim, Tae Hyun

2014-12-01

Purpose: The purpose of this study was to investigate the efficacy and toxicity of radiation therapy (RT) following incomplete transarterial chemoembolization (TACE) in unresectable hepatocellular carcinoma (HCC). Methods and Materials: The study was designed as a prospective phase 2 multicenter trial. Patients with unresectable HCC, who had viable tumor after TACE of no more than 3 courses, were eligible. Three-dimensional conformal RT (3D-CRT) was added for HCC treatment with incomplete uptake of iodized oil, and the interval from TACE to RT was 4 to 6 weeks. The primary endpoint of this study was the tumor response after RT following incomplete TACEmore » in unresectable HCC. Secondary endpoints were patterns of failure, progression-free survival (PFS), time to tumor progression (TTP), overall survival (OS) rates at 2 years, and treatment-associated toxicity. Survival was calculated from the start of RT. Results: Between August 2008 and December 2010, 31 patients were enrolled. RT was delivered at a median dose of 54 Gy (range, 46-59.4 Gy) at 1.8 to 2 Gy per fraction. A best objective in-field response rate was achieved in 83.9% of patients, with complete response (CR) in 22.6% of patients and partial response in 61.3% of patients within 12 weeks post-RT. A best objective overall response rate was achieved in 64.5% of patients with CR in 19.4% of patients and PR in 45.1% of patients. The 2-year in-field PFS, PFS, TTP, and OS rates were 45.2%, 29.0%, 36.6%, and 61.3%, respectively. The Barcelona Clinic liver cancer stage was a significant independent prognostic factor for PFS (P=.023). Classic radiation-induced liver disease was not observed. There were no treatment-related deaths or hepatic failure. Conclusions: Early 3D-CRT following incomplete TACE is a safe and practical treatment option for patients with unresectable HCC.« less

Caloric restriction coupled with radiation decreases metastatic burden in triple negative breast cancer.

PubMed

Simone, Brittany A; Dan, Tu; Palagani, Ajay; Jin, Lianjin; Han, Sunny Y; Wright, Christopher; Savage, Jason E; Gitman, Robert; Lim, Meng Kieng; Palazzo, Juan; Mehta, Minesh P; Simone, Nicole L

2016-09-01

Metastatic breast cancer is devastating and triple negative breast cancers (TNBC) have a higher propensity for metastasis. Improved local control upfront in this aggressive cancer could potentially decrease its propensity toward metastasis. We sought to determine if using caloric restriction (CR) as a systemic therapy, combined with radiation therapy (IR) to the primary tumor, may impact metastatic disease. An orthotopic mouse model using a highly metastatic, luciferase-tagged TNBC cell line (4T1), was used to generate palpable tumors. Mice were then treated with CR, IR, and a combination of the two. In vivo imaging was performed for metastatic evaluation. Molecular evaluation of the tumors was performed, generating a mechanistic hypothesis for CR, which was then tested with pertinent pathway inhibition in the model. CR significantly increased the time to developing metastases, decreased the overall number and volume of lung metastases, and increased survival. CR decreased proliferation, increased apoptosis and globally downregulated the IGF-1R signaling pathway. Adding an IGF-1R/INSR inhibitor to local IR in vivo accomplished a decrease in metastases similar to CR plus IR, demonstrating the importance of the IGF-1R signaling pathway, and underscoring it as a possible mechanism for CR. CR decreased metastatic burden and therefore may complement cytotoxic therapies being used in the clinical setting for metastatic disease. Downregulation of the IGF-1R pathway, is in part responsible for this response and modulating IGF-1R directly resulted in similar improved progression-free survival. The novel use of CR has the potential to enhance clinical outcomes for patients with metastatic breast cancer.

Impact of complete response to chemotherapy on overall survival in advanced colorectal cancer: results from Intergroup N9741.

PubMed

Dy, Grace K; Krook, James E; Green, Erin M; Sargent, Daniel J; Delaunoit, Thierry; Morton, Roscoe F; Fuchs, Charles S; Ramanathan, Ramesh K; Williamson, Stephen K; Findlay, Brian P; Pockaj, Barbara A; Sticca, Robert P; Alberts, Steven R; Pitot, Henry C; Goldberg, Richard M

2007-08-10

To evaluate clinical characteristics and survival outcomes among patients with locally advanced or metastatic colorectal cancer who achieve a complete response (CR) to systemic treatment either alone or with multimodality approach. Data were collected retrospectively from CRC patients enrolled onto the phase III trial N9741, a National Cancer Institute-funded and Gastrointestinal Cancer Intergroup-sponsored study coordinated by the North Central Cancer Treatment Group. Patients were randomly assigned to combinations of oxaliplatin, fluorouracil (FU)/leucovorin (LV) and irinotecan. The three treatment arms consist of IFL (irinotecan + FU/LV), FOLFOX4 (oxaliplatin + FU/LV), and IROX (irinotecan + oxaliplatin). Median follow-up was 42.6 months. Sixty-two (4%) of 1,508 patients had a CR to chemotherapy alone, and an additional 32 (2%) had a CR after multimodality treatment. Factors associated with achieving CR with systemic chemotherapy alone included FOLFOX4 treatment, patients with assessable disease, or a single site of metastasis. Continuing protocol treatment beyond two cycles after documentation of CR was not associated with improved survival. The rate of curative intent resection was significantly higher for patients treated with oxaliplatin-containing regimens (P = .02). Median survival was similar between patients with CR after chemotherapy alone (44.3 months) or after multimodality approach (47.4 months; P = .81). FOLFOX4 was more likely to produce a CR than were IFL or IROX. Oxaliplatin regimens were more likely to result in successful surgical resections. Patients who have CR to systemic chemotherapy alone can achieve impressive survival outcomes similar to those seen among patients who attained a CR status after multimodality treatment.

RNA–protein binding interface in the telomerase ribonucleoprotein

PubMed Central

Bley, Christopher J.; Qi, Xiaodong; Rand, Dustin P.; Borges, Chad R.; Nelson, Randall W.; Chen, Julian J.-L.

2011-01-01

Telomerase is a specialized reverse transcriptase containing an intrinsic telomerase RNA (TR) which provides the template for telomeric DNA synthesis. Distinct from conventional reverse transcriptases, telomerase has evolved a unique TR-binding domain (TRBD) in the catalytic telomerase reverse transcriptase (TERT) protein, integral for ribonucleoprotein assembly. Two structural elements in the vertebrate TR, the pseudoknot and CR4/5, bind TERT independently and are essential for telomerase enzymatic activity. However, the details of the TR–TERT interaction have remained elusive. In this study, we employed a photoaffinity cross-linking approach to map the CR4/5-TRBD RNA–protein binding interface by identifying RNA and protein residues in close proximity. Photoreactive 5-iodouridines were incorporated into the medaka CR4/5 RNA fragment and UV cross-linked to the medaka TRBD protein fragment. The cross-linking RNA residues were identified by alkaline partial hydrolysis and cross-linked protein residues were identified by mass spectrometry. Three CR4/5 RNA residues (U182, U187, and U205) were found cross-linking to TRBD amino acids Tyr503, Phe355, and Trp477, respectively. This CR4/5 binding pocket is distinct and separate from the previously proposed T pocket in the Tetrahymena TRBD. Based on homologous structural models, our cross-linking data position the essential loop L6.1 adjacent to the TERT C-terminal extension domain. We thus propose that stem-loop 6.1 facilitates proper TERT folding by interacting with both TRBD and C-terminal extension. Revealing the telomerase CR4/5-TRBD binding interface with single-residue resolution provides important insights into telomerase ribonucleoprotein architecture and the function of the essential CR4/5 domain. PMID:22123986

Contact resonance atomic force microscopy imaging in air and water using photothermal excitation.

PubMed

Kocun, Marta; Labuda, Aleksander; Gannepalli, Anil; Proksch, Roger

2015-08-01

Contact Resonance Force Microscopy (CR-FM) is a leading atomic force microscopy technique for measuring viscoelastic nano-mechanical properties. Conventional piezo-excited CR-FM measurements have been limited to imaging in air, since the "forest of peaks" frequency response associated with acoustic excitation methods effectively masks the true cantilever resonance. Using photothermal excitation results in clean contact, resonance spectra that closely match the ideal frequency response of the cantilever, allowing unambiguous and simple resonance frequency and quality factor measurements in air and liquids alike. This extends the capabilities of CR-FM to biologically relevant and other soft samples in liquid environments. We demonstrate CR-FM in air and water on both stiff silicon/titanium samples and softer polystyrene-polyethylene-polypropylene polymer samples with the quantitative moduli having very good agreement between expected and measured values.

The Effects of Airway Microbiome on Corticosteroid Responsiveness in Asthma

PubMed Central

Goleva, Elena; Jackson, Leisa P.; Harris, J. Kirk; Robertson, Charles E.; Sutherland, E. Rand; Hall, Clifton F.; Good, James T.; Gelfand, Erwin W.; Martin, Richard J.

2013-01-01

Rationale: The role of airway microbiome in corticosteroid response in asthma is unknown. Objectives: To examine airway microbiome composition in patients with corticosteroid-resistant (CR) asthma and compare it with patients with corticosteroid-sensitive (CS) asthma and normal control subjects and explore whether bacteria in the airways of subjects with asthma may direct alterations in cellular responses to corticosteroids. Methods: 16S rRNA gene sequencing was performed on bronchoalveolar lavage (BAL) samples of 39 subjects with asthma and 12 healthy control subjects. In subjects with asthma, corticosteroid responsiveness was characterized, BAL macrophages were stimulated with pathogenic versus commensal microorganisms, and analyzed by real-time polymerase chain reaction for the expression of corticosteroid-regulated genes and cellular p38 mitogen-activated protein kinase (MAPK) activation. Measurements and Main Results: Of the 39 subjects with asthma, 29 were CR and 10 were CS. BAL microbiome from subjects with CR and CS asthma did not differ in richness, evenness, diversity, and community composition at the phylum level, but did differ at the genus level, with distinct genus expansions in 14 subjects with CR asthma. Preincubation of asthmatic airway macrophages with Haemophilus parainfluenzae, a uniquely expanded potential pathogen found only in CR asthma airways, resulted in p38 MAPK activation, increased IL-8 (P < 0.01), mitogen-activated kinase phosphatase 1 mRNA (P < 0.01) expression, and inhibition of corticosteroid responses (P < 0.05). This was not observed after exposure to commensal bacterium Prevotella melaninogenica. Inhibition of transforming growth factor-β–associated kinase-1 (TAK1), upstream activator of MAPK, but not p38 MAPK restored cellular sensitivity to corticosteroids. Conclusions: A subset of subjects with CR asthma demonstrates airway expansion of specific gram-negative bacteria, which trigger TAK1/MAPK activation and induce corticosteroid resistance. TAK1 inhibition restored cellular sensitivity to corticosteroids. PMID:24024497

Ligand-field helical luminescence in a 2D ferromagnetic insulator

DOE PAGES

Seyler, Kyle L.; Zhong, Ding; Klein, Dahlia R.; ...

2017-12-04

Bulk chromium tri-iodide (CrI 3) has long been known as a layered van der Waals ferromagnet. However, its monolayer form was only recently isolated and confirmed to be a truly two-dimensional (2D) ferromagnet, providing a new platform for investigating light–matter interactions and magneto-optical phenomena in the atomically thin limit. Here in this paper, we report spontaneous circularly polarized photoluminescence in monolayer CrI 3 under linearly polarized excitation, with helicity determined by the monolayer magnetization direction. In contrast, the bilayer CrI 3 photoluminescence exhibits vanishing circular polarization, supporting the recently uncovered anomalous antiferromagnetic interlayer coupling in CrI 3 bilayers. Distinct frommore » the Wannier–Mott excitons that dominate the optical response in well-known 2D van der Waals semiconductors, our absorption and layer-dependent photoluminescence measurements reveal the importance of ligand-field and charge-transfer transitions to the optoelectronic response of atomically thin CrI 3. We attribute the photoluminescence to a parity-forbidden d–d transition characteristic of Cr 3+ complexes, which displays broad linewidth due to strong vibronic coupling and thickness-independent peak energy due to its localized molecular orbital nature.« less