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

Favorite, Jeffrey A.

In transport theory, adjoint-based partial derivatives with respect to mass density are constant-volume derivatives. Likewise, adjoint-based partial derivatives with respect to surface locations (i.e., internal interface locations and the outer system boundary) are constant-density derivatives. This study derives the constant-mass partial derivative of a response with respect to an internal interface location or the outer system boundary and the constant-mass partial derivative of a response with respect to the mass density of a region. Numerical results are given for a multiregion two-dimensional (r-z) cylinder for three very different responses: the uncollided gamma-ray flux at an external detector point, k effmore » of the system, and the total neutron leakage. Finally, results from the derived formulas compare extremely well with direct perturbation calculations.« less

Use of rituximab as a treatment for systemic lupus erythematosus: retrospective review

PubMed Central

Machado, Roberta Ismael Lacerda; Scheinberg, Morton Aaron; de Queiroz, Maria Yvone Carlos Formiga; de Brito, Danielle Christinne Soares Egypto; Guimarães, Maria Fernanda Brandao de Resende; Giovelli, Raquel Altoé; Freire, Eutilia Andrade Medeiros

2014-01-01

ABSTRACT Objective: To report the experience in three Brazilian institutions with the use of rituximab in patients with different clinical forms of lupus erythematosus systemic in activity. Methods: The study consisted of a sample of 17 patients with LES, who were already being treated, but that at some stage of the disease showed refractory symptoms. The patients were subdivided into groups according to the clinical manifestation, and the responses for the use of rituximab were rated as complete, partial or no response. Data were collected through a spreadsheet, and used specific parameters for each group. The treatment was carried on by using therapeutic dose of 1g, and repeating the infusion within an interval of 15 days. Results: The clinical responses to rituximab of the group only hematological and of the group only osteoarticular were complete in all cases. In the renal group there was a clinical complete response, two partial and one absent. In the renal and hematological group complete response, there was one death and a missing response. The pulmonary group presented a complete response and two partial. Conclusion: The present study demonstrated that rituximab can bring benefits to patients with lupus erythematosus systemic, with good tolerability and mild side effects; it presented, however, variable response according to the system affected. PMID:24728244

A Two-Decision Model for Responses to Likert-Type Items

ERIC Educational Resources Information Center

Thissen-Roe, Anne; Thissen, David

2013-01-01

Extreme response set, the tendency to prefer the lowest or highest response option when confronted with a Likert-type response scale, can lead to misfit of item response models such as the generalized partial credit model. Recently, a series of intrinsically multidimensional item response models have been hypothesized, wherein tendency toward…

Motion in partially and fully cross-linked F-actin networks

NASA Astrophysics Data System (ADS)

Morris, Eliza; Ehrlicher, Allen; Weitz, David

2012-02-01

Single molecule experiments have measured stall forces and procession rates of molecular motors on isolated cytoskeletal fibers in Newtonian fluids. But in the cell, these motors are transporting cargo through a highly complex cytoskeletal network. To compare these single molecule results to the forces exerted by motors within the cell, an evaluation of the response of the cytoskeletal network is needed. Using magnetic tweezers and fluorescence confocal microscopy we observe and quantify the relationship between bead motion and filament response in F-actin networks both partially and fully cross-linked with filamin We find that when the transition from full to partial cross-linking is brought about by a decrease in cross-linker concentration there is a simultaneous decline in the elasticity of the network, but the response of the bead remains qualitatively similar. However, when the cross-linking is reduced through a shortening of the F-actin filaments the bead response is completely altered. The characteristics of the altered bead response will be discussed here.

Model Selection Indices for Polytomous Items

ERIC Educational Resources Information Center

Kang, Taehoon; Cohen, Allan S.; Sung, Hyun-Jung

2009-01-01

This study examines the utility of four indices for use in model selection with nested and nonnested polytomous item response theory (IRT) models: a cross-validation index and three information-based indices. Four commonly used polytomous IRT models are considered: the graded response model, the generalized partial credit model, the partial credit…

Acquisition with partial and continuous reinforcement in pigeon autoshaping.

PubMed

Gottlieb, Daniel A

2004-08-01

Contemporary time accumulation models make the unique prediction that acquisition of a conditioned response will be equally rapid with partial and continuous reinforcement, if the time between conditioned stimuli is held constant. To investigate this, acquisition of conditioned responding was examined in pigeon autoshaping under conditions of 100% and 25% reinforcement, holding intertrial interval constant. Contrary to what was predicted, evidence for slowed acquisition in partially reinforced animals was observed with several response measures. However, asymptotic performance was superior with 25% reinforcement. A switching of reinforcement contingencies after initial acquisition did not immediately affect responding. After further sessions, partial reinforcement augmented responding, whereas continuous reinforcement did not, irrespective of an animal's reinforcement history. Subsequent training with a novel stimulus maintained the response patterns. These acquisition results generally support associative, rather than time accumulation, accounts of conditioning.

Impaired consciousness in partial seizures is bimodally distributed

PubMed Central

Cunningham, Courtney; Chen, William C.; Shorten, Andrew; McClurkin, Michael; Choezom, Tenzin; Schmidt, Christian P.; Chu, Victoria; Bozik, Anne; Best, Cameron; Chapman, Melissa; Furman, Moran; Detyniecki, Kamil; Giacino, Joseph T.

2014-01-01

Objective: To investigate whether impaired consciousness in partial seizures can usually be attributed to specific deficits in the content of consciousness or to a more general decrease in the overall level of consciousness. Methods: Prospective testing during partial seizures was performed in patients with epilepsy using the Responsiveness in Epilepsy Scale (n = 83 partial seizures, 30 patients). Results were compared with responsiveness scores in a cohort of patients with severe traumatic brain injury evaluated with the JFK Coma Recovery Scale–Revised (n = 552 test administrations, 184 patients). Results: Standardized testing during partial seizures reveals a bimodal scoring distribution, such that most patients were either fully impaired or relatively spared in their ability to respond on multiple cognitive tests. Seizures with impaired performance on initial test items remained consistently impaired on subsequent items, while other seizures showed spared performance throughout. In the comparison group, we found that scores of patients with brain injury were more evenly distributed across the full range in severity of impairment. Conclusions: Partial seizures can often be cleanly separated into those with vs without overall impaired responsiveness. Results from similar testing in a comparison group of patients with brain injury suggest that the bimodal nature of Responsiveness in Epilepsy Scale scores is not a result of scale bias but may be a finding unique to partial seizures. These findings support a model in which seizures either propagate or do not propagate to key structures that regulate overall arousal and thalamocortical function. Future investigations are needed to relate these behavioral findings to the physiology underlying impaired consciousness in partial seizures. PMID:24727311

Impaired consciousness in partial seizures is bimodally distributed.

PubMed

Cunningham, Courtney; Chen, William C; Shorten, Andrew; McClurkin, Michael; Choezom, Tenzin; Schmidt, Christian P; Chu, Victoria; Bozik, Anne; Best, Cameron; Chapman, Melissa; Furman, Moran; Detyniecki, Kamil; Giacino, Joseph T; Blumenfeld, Hal

2014-05-13

To investigate whether impaired consciousness in partial seizures can usually be attributed to specific deficits in the content of consciousness or to a more general decrease in the overall level of consciousness. Prospective testing during partial seizures was performed in patients with epilepsy using the Responsiveness in Epilepsy Scale (n = 83 partial seizures, 30 patients). Results were compared with responsiveness scores in a cohort of patients with severe traumatic brain injury evaluated with the JFK Coma Recovery Scale-Revised (n = 552 test administrations, 184 patients). Standardized testing during partial seizures reveals a bimodal scoring distribution, such that most patients were either fully impaired or relatively spared in their ability to respond on multiple cognitive tests. Seizures with impaired performance on initial test items remained consistently impaired on subsequent items, while other seizures showed spared performance throughout. In the comparison group, we found that scores of patients with brain injury were more evenly distributed across the full range in severity of impairment. Partial seizures can often be cleanly separated into those with vs without overall impaired responsiveness. Results from similar testing in a comparison group of patients with brain injury suggest that the bimodal nature of Responsiveness in Epilepsy Scale scores is not a result of scale bias but may be a finding unique to partial seizures. These findings support a model in which seizures either propagate or do not propagate to key structures that regulate overall arousal and thalamocortical function. Future investigations are needed to relate these behavioral findings to the physiology underlying impaired consciousness in partial seizures.

Piloting a Polychotomous Partial-Credit Scoring Procedure in a Multiple-Choice Test

ERIC Educational Resources Information Center

Tsopanoglou, Antonios; Ypsilandis, George S.; Mouti, Anna

2014-01-01

Multiple-choice (MC) tests are frequently used to measure language competence because they are quick, economical and straightforward to score. While degrees of correctness have been investigated for partially correct responses in combined-response MC tests, degrees of incorrectness in distractors and the role they play in determining the…

A FLEXIBLE APPROACH FOR EVALUATING FIXED RATIO MIXTURES OF FULL AND PARTIAL AGONISTS FOR MIXTURES OF MANY CHEMICALS.

EPA Science Inventory

Detecting interaction in chemical mixtures can be complicated by differences in the shapes of the dose-response curves of the individual components (e.g. mixtures of full and partial agonists with differing response maxima). We present an analysis scheme where flexible single che...

Constrained and Unconstrained Partial Adjacent Category Logit Models for Ordinal Response Variables

ERIC Educational Resources Information Center

Fullerton, Andrew S.; Xu, Jun

2018-01-01

Adjacent category logit models are ordered regression models that focus on comparisons of adjacent categories. These models are particularly useful for ordinal response variables with categories that are of substantive interest. In this article, we consider unconstrained and constrained versions of the partial adjacent category logit model, which…

Photosynthetic light response of flooded cherrybark oak (Quercus pagoda) seedlings grown in two light regimes

Treesearch

Emile S. Gardiner; Ken W. Krauss

2001-01-01

Two-year-old cherrybark oak (Quercus pagoda Raf.) seedlings raised in full or partial (27 percent) sunlight were flooded for 30 days to study the effects of light availability and root inundation on photosynthetic light response. Compared with seedlings receiving full sunlight, seedlings receiving partial sunlight developed leaves...

[Personal experience with VP-16 in the treatment of malignant lymphomas at the Chemotherapy Clinic of the Oncology Center--M. Skłodowskiej-Curie Institute in Warsaw].

PubMed

Pałucka, A; Walewski, J; Siedlecki, P; Zborzil, J

1990-01-01

Eighteen patients with advanced malignant lymphomas who had progressed with previous chemotherapy were treated with LEPP (chlorambucil, VP-16, procarbazine, prednisone). One complete response and 5 partial remissions were observed, yielding an overall response rate of 33%, with median response duration of about 2 months. Twenty three patients with advanced Hodgkin's disease all who had progressed with previous chemotherapy (MOPP and ABVD) and 19 of them also after radiation therapy were treated with third line salvage chemotherapy consisting of OPEC (VP- 16, chlorambucil, vincristine and prednisone). Two complete response and 3 partial remissions were obtained for overall response rate of 21% with median duration of about 9 months.

Partial polarizer filter

NASA Technical Reports Server (NTRS)

Title, A. M. (Inventor)

1978-01-01

A birefringent filter module comprises, in seriatum. (1) an entrance polarizer, (2) a first birefringent crystal responsive to optical energy exiting the entrance polarizer, (3) a partial polarizer responsive to optical energy exiting the first polarizer, (4) a second birefringent crystal responsive to optical energy exiting the partial polarizer, and (5) an exit polarizer. The first and second birefringent crystals have fast axes disposed + or -45 deg from the high transmitivity direction of the partial polarizer. Preferably, the second crystal has a length 1/2 that of the first crystal and the high transmitivity direction of the partial polarizer is nine times as great as the low transmitivity direction. To provide tuning, the polarizations of the energy entering the first crystal and leaving the second crystal are varied by either rotating the entrance and exit polarizers, or by sandwiching the entrance and exit polarizers between pairs of half wave plates that are rotated relative to the polarizers. A plurality of the filter modules may be cascaded.

How partial reinforcement of food cues affects the extinction and reacquisition of appetitive responses. A new model for dieting success?

PubMed

van den Akker, Karolien; Havermans, Remco C; Bouton, Mark E; Jansen, Anita

2014-10-01

Animals and humans can easily learn to associate an initially neutral cue with food intake through classical conditioning, but extinction of learned appetitive responses can be more difficult. Intermittent or partial reinforcement of food cues causes especially persistent behaviour in animals: after exposure to such learning schedules, the decline in responding that occurs during extinction is slow. After extinction, increases in responding with renewed reinforcement of food cues (reacquisition) might be less rapid after acquisition with partial reinforcement. In humans, it may be that the eating behaviour of some individuals resembles partial reinforcement schedules to a greater extent, possibly affecting dieting success by interacting with extinction and reacquisition. Furthermore, impulsivity has been associated with less successful dieting, and this association might be explained by impulsivity affecting the learning and extinction of appetitive responses. In the present two studies, the effects of different reinforcement schedules and impulsivity on the acquisition, extinction, and reacquisition of appetitive responses were investigated in a conditioning paradigm involving food rewards in healthy humans. Overall, the results indicate both partial reinforcement schedules and, possibly, impulsivity to be associated with worse extinction performance. A new model of dieting success is proposed: learning histories and, perhaps, certain personality traits (impulsivity) can interfere with the extinction and reacquisition of appetitive responses to food cues and they may be causally related to unsuccessful dieting. Copyright © 2014 Elsevier Ltd. All rights reserved.

Note: Nonpolar solute partial molar volume response to attractive interactions with water.

PubMed

Williams, Steven M; Ashbaugh, Henry S

2014-01-07

The impact of attractive interactions on the partial molar volumes of methane-like solutes in water is characterized using molecular simulations. Attractions account for a significant 20% volume drop between a repulsive Weeks-Chandler-Andersen and full Lennard-Jones description of methane interactions. The response of the volume to interaction perturbations is characterized by linear fits to our simulations and a rigorous statistical thermodynamic expression for the derivative of the volume to increasing attractions. While a weak non-linear response is observed, an average effective slope accurately captures the volume decrease. This response, however, is anticipated to become more non-linear with increasing solute size.

Note: Nonpolar solute partial molar volume response to attractive interactions with water

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

Williams, Steven M.; Ashbaugh, Henry S., E-mail: hanka@tulane.edu

2014-01-07

The impact of attractive interactions on the partial molar volumes of methane-like solutes in water is characterized using molecular simulations. Attractions account for a significant 20% volume drop between a repulsive Weeks-Chandler-Andersen and full Lennard-Jones description of methane interactions. The response of the volume to interaction perturbations is characterized by linear fits to our simulations and a rigorous statistical thermodynamic expression for the derivative of the volume to increasing attractions. While a weak non-linear response is observed, an average effective slope accurately captures the volume decrease. This response, however, is anticipated to become more non-linear with increasing solute size.

Metabolic response of rectal cancer assessed by 18-FDG PET following chemoradiotherapy is prognostic for patient outcome.

PubMed

Yeung, J M C; Kalff, V; Hicks, R J; Drummond, E; Link, E; Taouk, Y; Michael, M; Ngan, S; Lynch, A C; Heriot, A G

2011-05-01

Complete pathological response has proven prognostic benefits in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy. Sequential 18-FDG PET may be an early surrogate for pathological response to chemoradiotherapy. The aim of this study was to identify whether metabolic response measured by FDG PET following chemoradiotherapy is prognostic for tumor recurrence and survival following neoadjuvant therapy and surgical treatment for primary rectal cancer. Patients with primary rectal cancer treated by long-course neoadjuvant chemoradiotherapy followed by surgery had FDG PET performed before and 4 weeks after treatment, before surgical resection was performed. Retrospective chart review was undertaken for patient demographics, tumor staging, recurrence rates, and survival. : Between 2000 and 2007, 78 patients were identified (53 male, 25 female; median age, 64 y). After chemoradiotherapy, 37 patients (47%) had a complete metabolic response, 26 (33%) had a partial metabolic response, and 14 (18%) had no metabolic response as assessed by FDG PET (1 patient had missing data). However, only 4 patients (5%) had a complete pathological response. The median postoperative follow-up period was 3.1 years during which 14 patients (19%) had a recurrence: 2 local, 9 distant, and 3 with both local and distant. The estimated percentage without recurrence was 77% at 5 years (95% CI 66%-89%). There was an inverse relationship between FDG PET metabolic response and the incidence of recurrence within 3 years (P = .04). Kaplan-Meier analysis of FDG PET metabolic response and overall survival demonstrated a significant difference in survival among patients in the 3 arms: complete, partial, and no metabolic response (P = .04); the patients with complete metabolic response had the best prognosis. Complete or partial metabolic response on PET following neoadjuvant chemoradiotherapy and surgery predicts a lower local recurrence rate and improved survival compared with patients with no metabolic response. Metabolic response may be used to stratify prognosis in patients with rectal cancer.

In response to partial plant shading, the lack of phytochrome A does not directly induce leaf senescence but alters the fine-tuning of chlorophyll biosynthesis

PubMed Central

Brouwer, Bastiaan; Gardeström, Per; Keech, Olivier

2014-01-01

Phytochrome is thought to control the induction of leaf senescence directly, however, the signalling and molecular mechanisms remain unclear. In the present study, an ecophysiological approach was used to establish a functional connection between phytochrome signalling and the physiological processes underlying the induction of leaf senescence in response to shade. With shade it is important to distinguish between complete and partial shading, during which either the whole or only a part of the plant is shaded, respectively. It is first shown here that, while PHYB is required to maintain chlorophyll content in a completely shaded plant, only PHYA is involved in maintaining the leaf chlorophyll content in response to partial plant shading. Second, it is shown that leaf yellowing associated with strong partial shading in phyA-mutant plants actually correlates to a decreased biosynthesis of chlorophyll rather than to an increase of its degradation. Third, it is shown that the physiological impact of this decreased biosynthesis of chlorophyll in strongly shaded phyA-mutant leaves is accompanied by a decreased capacity to adjust the Light Compensation Point. However, the increased leaf yellowing in phyA-mutant plants is not accompanied by an increase of senescence-specific molecular markers, which argues against a direct role of PHYA in inducing leaf senescence in response to partial shade. In conclusion, it is proposed that PHYA, but not PHYB, is essential for fine-tuning the chlorophyll biosynthetic pathway in response to partial shading. In turn, this mechanism allows the shaded leaf to adjust its photosynthetic machinery to very low irradiances, thus maintaining a positive carbon balance and repressing the induction of leaf senescence, which can occur under prolonged periods of shade. PMID:24604733

Low-Dose Radiotherapy in Indolent Lymphoma

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

Rossier, Christine; Schick, Ulrike; Miralbell, Raymond

Purpose: To assess the response rate, duration of response, and overall survival after low-dose involved-field radiotherapy in patients with recurrent low-grade lymphoma or chronic lymphocytic leukemia (CLL). Methods and Materials: Forty-three (24 women, 19 men) consecutive patients with indolent lymphoma or CLL were treated with a total dose of 4 Gy (2 x 2 Gy) using 6- 18-MV photons. The median age was 73 years (range, 39-88). Radiotherapy was given either after (n = 32; 75%) or before (n = 11; 25%) chemotherapy. The median time from diagnosis was 48 months (range, 1-249). The median follow-up period was 20 monthsmore » (range, 1-56). Results: The overall response rate was 90%. Twelve patients (28%) had a complete response, 15 (35%) had a partial response, 11 (26%) had stable disease, and 5 (11%) had progressive disease. The median overall survival for patients with a positive response (complete response/partial response/stable disease) was 41 months; for patients with progressive disease it was 6 months (p = 0.001). The median time to in-field progression was 21 months (range, 0-24), and the median time to out-field progression was 8 months (range, 0-40). The 3-year in-field control was 92% in patients with complete response (median was not reached). The median time to in-field progression was 9 months (range, 0.5-24) in patients with partial response and 6 months (range, 0.6-6) in those with stable disease (p < 0.05). Younger age, positive response to radiotherapy, and no previous chemotherapy were the best factors influencing the outcome. Conclusions: Low-dose involved-field radiotherapy is an effective treatment in the management of patients with recurrent low-grade lymphoma or CLL.« less

Partial clinical response to anakinra in severe palmoplantar pustular psoriasis.

PubMed

Tauber, M; Viguier, M; Alimova, E; Petit, A; Lioté, F; Smahi, A; Bachelez, H

2014-09-01

Palmoplantar pustular psoriasis is a clinical psoriasis variant characterised by a high impact on quality of life and poor response to biologics approved for plaque type psoriasis.The recombinant interleukin-1 (IL-1) receptor antagonist anakinra has been recently used for the treatment of isolated refractory cases of generalised pustular psoriasis with contrasted results. To report the clinical response in two patients treated with anakinra as salvage therapy in two patients with severe palmoplantar pustular psoriasis refractory to currently available antipsoriatic systemic therapies. Anakinra was given subcutaneously at the daily dose of 100 mg, and clinical response was evaluated using the palmoplantar psoriasis area and severity index (PPPASI). Only partial and transient responses were observed in both patients, who had to stop anakinra due to lack of efficacy and to side effects. Anakinra appears to provide only partial clinical improvement in refractory palmoplantar pustular psoriasis. Prospective clinical studies on larger populations are warranted to investigate more accurately both efficacy and safety of IL-1-inhibiting strategies in pustular psoriasis. © 2014 British Association of Dermatologists.

A Multidimensional Partial Credit Model with Associated Item and Test Statistics: An Application to Mixed-Format Tests

ERIC Educational Resources Information Center

Yao, Lihua; Schwarz, Richard D.

2006-01-01

Multidimensional item response theory (IRT) models have been proposed for better understanding the dimensional structure of data or to define diagnostic profiles of student learning. A compensatory multidimensional two-parameter partial credit model (M-2PPC) for constructed-response items is presented that is a generalization of those proposed to…

A Study of Reverse-Worded Matched Item Pairs Using the Generalized Partial Credit and Nominal Response Models

ERIC Educational Resources Information Center

Matlock Cole, Ki Lynn; Turner, Ronna C.; Gitchel, W. Dent

2018-01-01

The generalized partial credit model (GPCM) is often used for polytomous data; however, the nominal response model (NRM) allows for the investigation of how adjacent categories may discriminate differently when items are positively or negatively worded. Ten items from three different self-reported scales were used (anxiety, depression, and…

Identification of non-response to treatment using narrative data in an electronic health record inflammatory bowel disease cohort

PubMed Central

Ananthakrishnan, Ashwin N.; Cagan, Andrew; Cai, Tianxi; Gainer, Vivian S.; Shaw, Stanley Y; Savova, Guergana; Churchill, Susanne; Karlson, Elizabeth W.; Murphy, Shawn N.; Liao, Katherine P.; Kohane, Isaac

2016-01-01

Introduction Electronic health records (EHR), increasingly a part of healthcare, provide a wealth of untapped narrative free text data that has the potential to accurately inform clinical outcomes. Methods From a validated cohort of patients with Crohn’s disease (CD) or ulcerative colitis (UC), we identified patients with ≥ 1 coded or narrative mention of monoclonal antibodies to tumor necrosis factor α (anti-TNF). Chart review by ascertained true use of therapy, time of initiation and cessation of treatment, as well as clinical response stratified as non-response, partial, or complete response at one year. Internal consistency was assessed in an independent validation cohort. Results A total of 3,087 patients had a mention of an anti-TNF. Actual therapy initiation was within 60 days of the first coded mention in 74% of patients. In the derivation cohort, 18% of anti-TNF starts were classified as non-response at 1 year, 21% as partial, and 56% as complete response. On multivariate analysis, the number of narrative mentions of diarrhea (OR 1.08, 95% CI 1.02 – 1.14) and fatigue (OR 1.16, 95% CI 1.02 – 1.32) were independently associated with non-response at 1 year (AUC 0.82). A likelihood of non-response score comprising a weighted sum of both demonstrated a good dose response relationship across non-responders (2.18), partial (1.20), and complete (0.50) responders (p < 0.0001) and correlated well with need for surgery or hospitalizations. Conclusions Narrative data in an EHR offers considerable potential to define temporally evolving disease outcomes such as non-response to treatment. PMID:26332313

Electroconvulsive therapy in pregnant patients.

PubMed

Bulbul, Feridun; Copoglu, Umit Sertan; Alpak, Gokay; Unal, Ahmet; Demir, Bahadır; Tastan, Mehmet Fatih; Savas, Haluk A

2013-01-01

In this study, the aim was to evaluate the clinical characteristics of patients that received electroconvulsive therapy (ECT) during pregnancy due to psychiatric disorders, evaluate the safety and efficacy of ECT in pregnant women, and evaluate the overall status of mothers and babies during the postpartum period. The study included 33 patients who were admitted as inpatients with the indication of ECT due to pregnancy and concurrent psychiatric disorders. Upon ECT administration, a complete response to treatment was seen in 84.21% of patients with major depression (n=16), a partial response to treatment in 15.78% of patients (n=3), a complete response to treatment in 91.66% of patients with bipolar disorder (n=11), a partial response to treatment in 8.33% of the patients(n=1), and a full response to treatment in 50% of patients with schizophrenia (n=1) and a partial response to treatment in 50% of patients with schizophrenia (n=1) were obtained. We had after birth information of 27 infants from total 33. It was learned that two of them had disease, one was stillbirth and 24 of them did not have any health problems. ECT administration during pregnancy to treat psychiatric disorders was found to be an effective treatment method. No risk of preterm birth in mothers treated with ECT during pregnancy was detected. © 2013.

A flowing liquid test system for assessing the linearity and time-response of rapid fibre optic oxygen partial pressure sensors.

PubMed

Chen, R; Hahn, C E W; Farmery, A D

2012-08-15

The development of a methodology for testing the time response, linearity and performance characteristics of ultra fast fibre optic oxygen sensors in the liquid phase is presented. Two standard medical paediatric oxygenators are arranged to provide two independent extracorporeal circuits. Flow from either circuit can be diverted over the sensor under test by means of a system of rapid cross-over solenoid valves exposing the sensor to an abrupt change in oxygen partial pressure, P O2. The system is also capable of testing the oxygen sensor responses to changes in temperature, carbon dioxide partial pressure P CO2 and pH in situ. Results are presented for a miniature fibre optic oxygen sensor constructed in-house with a response time ≈ 50 ms and a commercial fibre optic sensor (Ocean Optics Foxy), when tested in flowing saline and stored blood. Copyright © 2012 Elsevier B.V. All rights reserved.

Refractory gastroesophageal reflux disease

PubMed Central

Subramanian, Charumathi Raghu; Triadafilopoulos, George

2015-01-01

Gastroesophageal reflux disease (GERD) is a condition that develops when the reflux of stomach contents into the esophagus causes troublesome symptoms, esophageal injury, and/or complications. Use of proton pump inhibitors (PPI) remains the standard therapy for GERD and is effective in most patients. Those whose symptoms are refractory to PPIs should be evaluated further and other treatment options should be considered, according to individual patient characteristics. Response to PPIs could be total (no symptoms), partial (residual breakthrough symptoms), or absent (no change in symptoms). Patients experiencing complete response do not usually need further management. Patients with partial response can be treated surgically or by using emerging endoscopic therapies. Patients who exhibit no response to PPI need further evaluation to rule out other causes. PMID:25274499

Multicenter study of combination DEP regimen as a salvage therapy for adult refractory hemophagocytic lymphohistiocytosis.

PubMed

Wang, Yini; Huang, Wenqiu; Hu, Liangding; Cen, Xinan; Li, Lihong; Wang, Jijun; Shen, Jianliang; Wei, Na; Wang, Zhao

2015-11-05

Hemophagocytic lymphohistiocytosis (HLH) is a refractory immune disorder with a significant risk of death. Although standard therapy has dramatically improved survival in HLH patients, approximately 30%, especially adults, show no response to current treatment strategies. This prospective study aimed to investigate the efficacy of liposomal doxorubicin treatment combined with etoposide and methylprednisolone (doxorubicin-etoposide-methylprednisolone; DEP) as a salvage therapy for adult refractory HLH. Adult patients who did not achieve at least partial response 2 weeks after initial standard HLH therapy were enrolled in this study between June 2013 and June 2014. Response to salvage therapy was assessed at 2 and 4 weeks after initiation of DEP therapy and patients were followed until death or until November 2014. Sixty-three refractory HLH patients were enrolled, including 29 cases of lymphoma-associated HLH, 22 cases of Epstein-Barr virus-associated HLH, and 4 cases of familial HLH. There were 8 cases with unknown underlying diseases. Seventeen cases (27.0%) achieved complete response and 31 cases (49.2%) achieved partial response. The overall response was 76.2% (48/63). Patients who showed no response to DEP died within 4 weeks after salvage therapy. Twenty-nine of the 48 patients who achieved partial or complete response survived to subsequent chemotherapy, allogenic hematopoietic stem cell transplantation, or splenectomy. Our study suggests that DEP regimen is an effective salvage regimen for adult refractory HLH, which can prolong patient survival as we continue to understand the responsible mechanisms and bridge the gap between HLH and its underlying diseases. This study was registered in the Chinese Clinical Trials Registry Platform (http://www.chictr.org.cn/) as ChiCTR-IPC-14005514. © 2015 by The American Society of Hematology.

Corporate social responsibility: an assessment of the enlightened self-interest model.

PubMed

Keim, G D

1978-01-01

Much recent discussion of corporate social responsibility has concerned operationality. Many activities subsumed under corporate social responsibility can be shown to be public or partially public goods. The theory of public goods can clarify and explain some complex problems of operationalizing the social responsibility doctrine. An examination of philanthropy provides some behavioral applications.

Efficacy of infliximab rescue therapy in patients with chronic refractory pouchitis: a multicenter study.

PubMed

Barreiro-de Acosta, M; García-Bosch, O; Souto, R; Mañosa, M; Miranda, J; García-Sanchez, V; Gordillo, J; Chacon, S; Loras, C; Carpio, D; Maroto, N; Menchén, L; Rojas-Feria, M; Sierra, M; Villoria, A; Marin-Jimenez, I

2012-05-01

Despite medical therapy, 30% of patients with ulcerative colitis (UC) need to undergo surgery. Around 50% of patients with proctocolectomy with ileal pouch-anal anastomosis (IPAA) develop complications of the pouch. Clinical evidence for the use of infliximab (IFX) in refractory pouchitis is limited. The aim of this study was to report efficacy of IFX in these patients. A retrospective, multicenter study was designed. Patients older than 18 years with chronic refractory pouchitis treated with IFX (5 mg/kg) were included. Short-term IFX efficacy was evaluated at week 8 and mid-term efficacy at weeks 26 and 52. Complete response was defined as cessation of diarrhea and urgency and partial response as marked clinical improvement but persisting symptoms. The modified Pouchitis Disease Activity Index (mPDAI) without endoscopy was calculated when available. Thirty-three consecutive UC patients with chronic refractory pouchitis were included (18 male, mean age 45 years, range 21-67). At week 8, 21% patients achieved complete response and 63% showed partial clinical response. At weeks 26 and 52, 33% and 27% achieved complete response and 33% and 18% showed partial clinical response, respectively. Thirteen patients (39%) withdrew treatment (four for lack of efficacy, four for loss of response and five for adverse events). None of the potential factors analyzed had an influence on response to IFX. IFX was effective in the short- and mid-term in patients with chronic refractory pouchitis. However, medication had to be discontinued in a high number of patients. Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.

Context-dependent sequential effects of target selection for action.

PubMed

Moher, Jeff; Song, Joo-Hyun

2013-07-11

Humans exhibit variation in behavior from moment to moment even when performing a simple, repetitive task. Errors are typically followed by cautious responses, minimizing subsequent distractor interference. However, less is known about how variation in the execution of an ultimately correct response affects subsequent behavior. We asked participants to reach toward a uniquely colored target presented among distractors and created two categories to describe participants' responses in correct trials based on analyses of movement trajectories; partial errors referred to trials in which observers initially selected a nontarget for action before redirecting the movement and accurately pointing to the target, and direct movements referred to trials in which the target was directly selected for action. We found that latency to initiate a hand movement was shorter in trials following partial errors compared to trials following direct movements. Furthermore, when the target and distractor colors were repeated, movement time and reach movement curvature toward distractors were greater following partial errors compared to direct movements. Finally, when the colors were repeated, partial errors were more frequent than direct movements following partial-error trials, and direct movements were more frequent following direct-movement trials. The dependence of these latter effects on repeated-task context indicates the involvement of higher-level cognitive mechanisms in an integrated attention-action system in which execution of a partial-error or direct-movement response affects memory representations that bias performance in subsequent trials. Altogether, these results demonstrate that whether a nontarget is selected for action or not has a measurable impact on subsequent behavior.

Clinical profile and treatment outcome of older (>75 years) patients with systemic AL amyloidosis

PubMed Central

Sachchithanantham, Sajitha; Offer, Mark; Venner, Christopher; Mahmood, Shameem A.; Foard, Darren; Rannigan, Lisa; Lane, Thirusha; Gillmore, Julian D.; Lachmann, Helen J.; Hawkins, Philip N.; Wechalekar, Ashutosh D.

2015-01-01

Systemic AL amyloidosis, a disease with improving outcomes using novel therapies, is increasingly recognized in the elderly but treatment and outcomes have not been systematically studied in this group of patients in whom comorbidities and frailty may compound morbidity and mortality. We report the outcomes of 295 patients with systemic AL amyloidosis ≥75 years seen at the UK National Amyloidosis Centre from 2005–2012. The median age was 78.5 years. The median overall survival was 20 months. Two hundred and thirty-eight patients received chemotherapy and 57 elected for supportive care only (overall survival – 24 and 8.4 months, respectively). On intention-to-treat analysis, 44% achieved a hematologic response including a very good partial response or better in 23%. The median overall survival was 6.2 years in patients achieving very good partial response or better at the 6-month landmark analysis and 1.5 years in non-responders. Factors independently indicating a poor prognosis were: cardiac involvement, performance status ≥2; systolic blood pressure <100 mmHg and, on landmark analysis, achieving less than a very good partial response. Treatment of systemic AL amyloidosis in the elderly is challenging. Deep clonal responses are associated with excellent survival and organ responses. Achieving a response to the first-line regimen appears particularly important as outcomes of non-responders are similar to those of untreated patients. Prospective trials with lower toxicity, outpatient treatment regimens are needed. PMID:26294730

A Review and Comparison of Mouse and Rat Responses to Micro Gravity, Hyper Gravity and Simulated Models of Partial Gravity; Species Differences, Gaps in the Available Data, and Consideration of the Advantages and Caveats of Each Model for Spaceflight

NASA Technical Reports Server (NTRS)

Donovan, F. M.; Gresser, A. L.; Sato, Kevin Y.; Taylor, Elizabeth M.

2018-01-01

Laboratory strains of mice and rat are widely used to study mammalian responses to stimulus, and both have been studied under a variety of gravity conditions, including space flight. We compared results obtained from exposure to spaceflight and microgravity, hyper gravity via centrifugation, earth gravity, and models of simulated partial gravity (hind-limb unloading and partial weight bearing treatments). We examined the reported changes in survival, body mass, circadian rhythm (body temperature and activity levels), behavior, bone, muscle, immune, cardio-vasculature, vestibular, reproduction and neonate survival, microbiome, and the visual system. Not all categories have published data for both species, some have limited data, and there are variations in experiment design that allow for only relative comparisons to be considered. The data reveal species differences in both the level of gravity required to obtain a response, degree of response, and in temporal expression of responses. Examination of the data across the gravity levels allows consideration of the hypothesis that gravitational responses follow a continuum, and organ specific differences are noted. In summary, we present advantages and caveats of each model system as pertains to gravitational biology research and identify gaps in our knowledge of how these mammals respond to gravity.

Thin film devices used as oxygen partial pressure sensors

NASA Technical Reports Server (NTRS)

Canady, K. S.; Wortman, J. J.

1970-01-01

Electrical conductivity of zinc oxide films to be used in an oxygen partial pressure sensor is measured as a function of temperature, oxygen partial pressure, and other atmospheric constituents. Time response following partial pressure changes is studied as a function of temperature and environmental changes.

Diagnosis of Middle Atmosphere Climate Sensitivity by the Climate Feedback Response Analysis Method

NASA Technical Reports Server (NTRS)

Zhu, Xun; Yee, Jeng-Hwa; Cai, Ming; Swartz, William H.; Coy, Lawrence; Aquila, Valentina; Talaat, Elsayed R.

2014-01-01

We present a new method to diagnose the middle atmosphere climate sensitivity by extending the Climate Feedback-Response Analysis Method (CFRAM) for the coupled atmosphere-surface system to the middle atmosphere. The Middle atmosphere CFRAM (MCFRAM) is built on the atmospheric energy equation per unit mass with radiative heating and cooling rates as its major thermal energy sources. MCFRAM preserves the CFRAM unique feature of an additive property for which the sum of all partial temperature changes due to variations in external forcing and feedback processes equals the observed temperature change. In addition, MCFRAM establishes a physical relationship of radiative damping between the energy perturbations associated with various feedback processes and temperature perturbations associated with thermal responses. MCFRAM is applied to both measurements and model output fields to diagnose the middle atmosphere climate sensitivity. It is found that the largest component of the middle atmosphere temperature response to the 11-year solar cycle (solar maximum vs. solar minimum) is directly from the partial temperature change due to the variation of the input solar flux. Increasing CO2 always cools the middle atmosphere with time whereas partial temperature change due to O3 variation could be either positive or negative. The partial temperature changes due to different feedbacks show distinctly different spatial patterns. The thermally driven globally averaged partial temperature change due to all radiative processes is approximately equal to the observed temperature change, ranging from 0.5 K near 70 km from the near solar maximum to the solar minimum.

Effects of oxygen on responses to heating in two lizard species sampled along an elevational gradient.

PubMed

DuBois, P Mason; Shea, Tanner K; Claunch, Natalie M; Taylor, Emily N

2017-08-01

Thermal tolerance is an important variable in predictive models about the effects of global climate change on species distributions, yet the physiological mechanisms responsible for reduced performance at high temperatures in air-breathing vertebrates are not clear. We conducted an experiment to examine how oxygen affects three variables exhibited by ectotherms as they heat-gaping threshold, panting threshold, and loss of righting response (the latter indicating the critical thermal maximum)-in two lizard species along an elevational (and therefore environmental oxygen partial pressure) gradient. Oxygen partial pressure did not impact these variables in either species. We also exposed lizards at each elevation to severely hypoxic gas to evaluate their responses to hypoxia. Severely low oxygen partial pressure treatments significantly reduced the gaping threshold, panting threshold, and critical thermal maximum. Further, under these extreme hypoxic conditions, these variables were strongly and positively related to partial pressure of oxygen. In an elevation where both species overlapped, the thermal tolerance of the high elevation species was less affected by hypoxia than that of the low elevation species, suggesting the high elevation species may be adapted to lower oxygen partial pressures. In the high elevation species, female lizards had higher thermal tolerance than males. Our data suggest that oxygen impacts the thermal tolerance of lizards, but only under severely hypoxic conditions, possibly as a result of hypoxia-induced anapyrexia. Copyright © 2017. Published by Elsevier Ltd.

Pressure dependence of the electro-optic response function in partially exposed polymer dispersed ferroelectric liquid crystals

NASA Technical Reports Server (NTRS)

Parmar, D. S.; Holmes, H. K.

1993-01-01

Ferroelectric liquid crystals in a new configuration, termed partially exposed polymer dispersed ferroelectric liquid crystal (PEPDFLC), respond to external pressures and demonstrate pressure-induced electro-optic switching response. When the PEPDFLC thin film is sandwiched between two transparent conducting electrodes, one a glass plate and the other a flexible sheet such as polyvenylidene fluoride, the switching characteristics of the thin film are a function of the pressure applied to the flexible transparent electrode and the bias voltage across the electrodes. Response time measurements reveal a linear dependence of the change in electric field with external pressure.

Conformal gravity holography in four dimensions.

PubMed

Grumiller, Daniel; Irakleidou, Maria; Lovrekovic, Iva; McNees, Robert

2014-03-21

We formulate four-dimensional conformal gravity with (anti-)de Sitter boundary conditions that are weaker than Starobinsky boundary conditions, allowing for an asymptotically subleading Rindler term concurrent with a recent model for gravity at large distances. We prove the consistency of the variational principle and derive the holographic response functions. One of them is the conformal gravity version of the Brown-York stress tensor, the other is a "partially massless response". The on shell action and response functions are finite and do not require holographic renormalization. Finally, we discuss phenomenologically interesting examples, including the most general spherically symmetric solutions and rotating black hole solutions with partially massless hair.

Investigating the LGBTQ Responsive Model for Supervision of Group Work

ERIC Educational Resources Information Center

Luke, Melissa; Goodrich, Kristopher M.

2013-01-01

This article reports an investigation of the LGBTQ Responsive Model for Supervision of Group Work, a trans-theoretical supervisory framework to address the needs of lesbian, gay, bisexual, transgender, and questioning (LGBTQ) persons (Goodrich & Luke, 2011). Findings partially supported applicability of the LGBTQ Responsive Model for Supervision…

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.

Enzymatic recontouring of auricular cartilage in a rabbit model.

PubMed

Massengill, Phillip L; Goco, Paulino E; Norlund, L Layne; Muir-Padilla, Jeanne

2005-01-01

To evaluate the effectiveness of contouring auricular cartilage in a rabbit model using biologically active enzymes injected subcutaneously. The first phase determined the most effective volume and concentration required to affect the cartilage. To accomplish this task, we used ex vivo rabbit ears from a slaughterhouse. In the second phase, we injected 1 mL of hyaluronidase (150 U per milliliter of isotonic sodium chloride solution [saline]), elastase (1 mg per milliliter of saline), or saline into the ears of live rabbits. The study took place at the Madigan Army Medical Center (Tacoma, Wash), and included 10 animals. In each rabbit, we injected the test compound in one ear and saline in the other ear (control). We injected hyaluronidase in 5 ears and elastase in 5 ears. After injection, the ears were contoured and splinted for 4 weeks. In the third phase, we changed the injection pathway in 5 animals. At 4 weeks, 4 (80%) of the 5 ears injected with hyaluronidase showed full response and 1 (20%) had a partial response. Of the 5 ears injected with elastase, 4 (80%) showed a full response while 1 (20%) demonstrated a partial response. There was a response in all 10 of the ears injected with a test compound. Of the 10 control ears, 3 (30%) showed a partial response. At 6 weeks, approximately 6 (30%) of the ears had maintained contour demonstrating a full response. The difference between the test ears and the control ears was statistically significant (P = .006). Compared with the control ears, the results were statistically significant for elastase (P = .004) and hyaluronidase (P = .02). Overall, both agents demonstrated a subjective and objective response compared with control ears. This study demonstrates that bioactive enzymes and splinting can be effective in correcting ear deformities in a rabbit model.

Increasing bone sclerosis during bortezomib therapy in multiple myeloma patients: results of a reduced-dose whole-body MDCT study.

PubMed

Schulze, Maximilian; Weisel, Katja; Grandjean, Caroline; Oehrlein, Katharina; Zago, Manola; Spira, Daniel; Horger, Marius

2014-01-01

The objective of our study was to assess the frequency, location, extent, and patterns of bone sclerosis occurring in patients with multiple myeloma (MM) during bortezomib-based therapy. From June 2003 through December 2011, 593 whole-body reduced-dose MDCT studies were performed of 79 consecutive patients receiving bortezomib. The median surveillance time was 21 months (range, 3-67 months). Baseline studies were compared with follow-up studies during therapy (follow-up 1), at the end of therapy (follow-up 2), and 12 months after cessation of bortezomib therapy (follow-up 3). We recorded any sclerotic change occurring inside or along the margins of the osteolytic lesions, in the cancellous bone, or inside preexistent medullary or extramedullary lesions. The time point of occurrence of bone sclerosis was correlated with the best hematologic response category. Fourteen (17.7%) patients developed focal (n = 11) or diffuse (n = 3) bone sclerosis. The time window from bortezomib initiation to radiographic detection of bone sclerosis was 8 months (SD, 7 months). Sclerosis occurred at multiple sites (n = 7) or at an isolated site (n = 7). On subsequent whole-body reduced-dose MDCT studies, sclerosis further increased in seven (50%) patients. Hematologic best response during bortezomib treatment was complete response (n = 1), very good partial response (n = 2), partial response (n = 8), and stable disease (n = 3). Radiologic response at the time of sclerosis detection was partial response (n = 8), stable disease (n = 2), and progressive disease (n = 4). Bone remineralization may occur during bortezomib-based therapy for MM in a substantial proportion of patients. The extent, location, and patterns of sclerosis differ among patients and are unpredictable. Sclerosis was documented even in patients showing suboptimal hematologic response.

Sparse partial least squares regression for simultaneous dimension reduction and variable selection

PubMed Central

Chun, Hyonho; Keleş, Sündüz

2010-01-01

Partial least squares regression has been an alternative to ordinary least squares for handling multicollinearity in several areas of scientific research since the 1960s. It has recently gained much attention in the analysis of high dimensional genomic data. We show that known asymptotic consistency of the partial least squares estimator for a univariate response does not hold with the very large p and small n paradigm. We derive a similar result for a multivariate response regression with partial least squares. We then propose a sparse partial least squares formulation which aims simultaneously to achieve good predictive performance and variable selection by producing sparse linear combinations of the original predictors. We provide an efficient implementation of sparse partial least squares regression and compare it with well-known variable selection and dimension reduction approaches via simulation experiments. We illustrate the practical utility of sparse partial least squares regression in a joint analysis of gene expression and genomewide binding data. PMID:20107611

Gene expression changes in the coccolithophore Emiliania huxleyi after 500 generations of selection to ocean acidification

PubMed Central

Lohbeck, Kai T.; Riebesell, Ulf; Reusch, Thorsten B. H.

2014-01-01

Coccolithophores are unicellular marine algae that produce biogenic calcite scales and substantially contribute to marine primary production and carbon export to the deep ocean. Ongoing ocean acidification particularly impairs calcifying organisms, mostly resulting in decreased growth and calcification. Recent studies revealed that the immediate physiological response in the coccolithophore Emiliania huxleyi to ocean acidification may be partially compensated by evolutionary adaptation, yet the underlying molecular mechanisms are currently unknown. Here, we report on the expression levels of 10 candidate genes putatively relevant to pH regulation, carbon transport, calcification and photosynthesis in E. huxleyi populations short-term exposed to ocean acidification conditions after acclimation (physiological response) and after 500 generations of high CO2 adaptation (adaptive response). The physiological response revealed downregulation of candidate genes, well reflecting the concomitant decrease of growth and calcification. In the adaptive response, putative pH regulation and carbon transport genes were up-regulated, matching partial restoration of growth and calcification in high CO2-adapted populations. Adaptation to ocean acidification in E. huxleyi likely involved improved cellular pH regulation, presumably indirectly affecting calcification. Adaptive evolution may thus have the potential to partially restore cellular pH regulatory capacity and thereby mitigate adverse effects of ocean acidification. PMID:24827439

BDR in newly diagnosed patients with WM: final analysis of a phase 2 study after a minimum follow-up of 6 years.

PubMed

Gavriatopoulou, Maria; García-Sanz, Ramón; Kastritis, Efstathios; Morel, Pierre; Kyrtsonis, Marie-Christine; Michalis, Eurydiki; Kartasis, Zafiris; Leleu, Xavier; Palladini, Giovanni; Tedeschi, Alessandra; Gika, Dimitra; Merlini, Giampaolo; Sonneveld, Pieter; Dimopoulos, Meletios A

2017-01-26

In this phase 2 multicenter trial, we evaluated the efficacy of the combination of bortezomib, dexamethasone, and rituximab (BDR) in 59 previously untreated symptomatic patients with Waldenström macroglobulinemia (WM), most of which were of advanced age and with adverse prognostic factors. BDR consisted of a single 21-day cycle of bortezomib alone (1.3 mg/m 2 IV on days 1, 4, 8, and 11), followed by weekly IV bortezomib (1.6 mg/m 2 on days 1, 8, 15, and 22) for 4 additional 35-day cycles, with IV dexamethasone (40 mg) and IV rituximab (375 mg/m 2 ) on cycles 2 and 5, for a total treatment duration of 23 weeks. On intent to treat, 85% responded (3% complete response, 7% very good partial response, 58% partial response). After a minimum follow-up of 6 years, median progression-free survival was 43 months and median duration of response for patients with at least partial response was 64.5 months. Overall survival at 7 years was 66%. No patient had developed secondary myelodysplasia, whereas transformation to high-grade lymphoma occurred in 3 patients who had received chemoimmunotherapy after BDR. Thus, BDR is a very active, fixed-duration, chemotherapy-free regimen, inducing durable responses and with a favorable long-term toxicity profile (www.ClinicalTrials.gov #NCT00981708). © 2017 by The American Society of Hematology.

Response rates and survival times for cats with lymphoma treated with the University of Wisconsin-Madison chemotherapy protocol: 38 cases (1996-2003).

PubMed

Milner, Rowan J; Peyton, Jamie; Cooke, Kirsten; Fox, Leslie E; Gallagher, Alexander; Gordon, Patti; Hester, Juli

2005-10-01

To determine response rates and survival times for cats with lymphoma treated with the University of Wisconsin-Madison chemotherapy protocol. Retrospective study. 38 cats with lymphoma. Medical records were reviewed, and information on age, sex, breed, FeLV and FIV infection status, anatomic form, clinical stage, and survival time was obtained. Immunophenotyping was not performed. Mean +/- SD age of the cats was 10.9 +/- 4.4 years. Overall median survival time was 210 days (interquartile range, 90 to 657 days), and overall duration of first remission was 156 days (interquartile range, 87 to 316 days). Age, sex, anatomic form, and clinical stage were not significantly associated with duration of first remission or survival time. Eighteen of the 38 (47%) cats had complete remission, 14 (37%) had partial remission, and 6 (16%) had no response. Duration of first remission was significantly longer for cats with complete remission (654 days) than for cats with partial remission (114 days). Median survival time for cats with complete remission (654 days) was significantly longer than median survival time for cats with partial remission (122 days) and for cats with no response (11 days). Results suggested that a high percentage of cats with lymphoma will respond to treatment with the University of Wisconsin-Madison chemotherapy protocol. Age, sex, anatomic form, and clinical stage were not significantly associated with duration of first response or survival time, but initial response to treatment was.

Ethylene is not involved in adaptive responses to flooding in the Amazonian wild rice species Oryza grandiglumis.

PubMed

Okishio, Takuma; Sasayama, Daisuke; Hirano, Tatsuya; Akimoto, Masahiro; Itoh, Kazuyuki; Azuma, Tetsushi

2015-02-01

The Amazonian wild rice Oryza grandiglumis has two contrasting adaptation mechanisms to flooding submergence: a quiescence response to complete submergence at the seedling stage and an escape response based on internodal elongation to partial submergence at the mature stage. We investigated possible factors that trigger these responses. In stem segments excised from mature O. grandiglumis plants, complete submergence only slightly promoted internodal elongation with increased ethylene levels in the internodes, while partial submergence substantially promoted internodal elongation without increased ethylene levels in the internodes. Incubation of non-submerged stem segments under a continuous flow of humidified ethylene-free air promoted internodal elongation to the same extent as that observed for partially submerged segments. Applied ethylene had little effect on the internodal elongation of non-submerged segments irrespective of humidity conditions. These results indicate that the enhanced internodal elongation of submerged O. grandiglumis plants is not triggered by ethylene accumulated during submergence but by the moist surroundings provided by submergence. The growth of shoots in O. grandiglumis seedlings was not promoted by ethylene or complete submergence, as is the case in O. sativa cultivars possessing the submergence-tolerant gene SUB1A. However, because the genome of O. grandiglumis lacks the SUB1A gene, the quiescence response of O. grandiglumis seedlings to complete submergence may be regulated by a mechanism distinct from that involved in the response of submergence-tolerant O. sativa cultivars. Copyright © 2014 Elsevier GmbH. All rights reserved.

An Empirical Assessment of the Effects of Affective Response in the Measurement of Organizational Climate.

ERIC Educational Resources Information Center

Schnake, Mel E.

1983-01-01

Examined whether an affective response affects the dimensionality of perceptual measures of organizational climate, in a study of 8,938 employees who completed an organizational climate questionnaire and a measure of job satisfaction. Results suggested that partialing job satisfaction out of responses improved the dimensionality of the climate…

Effectiveness of infliximab after adalimumab failure in Crohn's disease.

PubMed

Chaparro, María; Andreu, Montserrat; Barreiro-de Acosta, Manuel; García-Planella, Esther; Ricart, Elena; Domènech, Eugeni; Esteve, María; Merino, Olga; Nos, Pilar; Peñalva, Mireia; Gisbert, Javier P

2012-10-07

To evaluate the effectiveness of infliximab as a second-line therapy in Crohn's disease patients after adalimumab failure. A historical cohort study in a community-based gastroenterology practice evaluated Crohn's disease patients treated with infliximab (induction plus maintenance) after adalimumab failure. Patients were identified using a large Spanish database (ENEIDA). We included 15 Crohn's disease patients who received infliximab after adalimumab failure. Five patients discontinued adalimumab due to loss of response, 3 due to adverse events and 7 due to partial response. After infliximab therapy was started, all patients who had interrupted adalimumab due to loss of efficacy regained response. All patients who discontinued adalimumab due to adverse events responded to infliximab and maintained this response; one of these patients had an uneventful course on infliximab, but 2 developed adverse events. None of the 7 patients who interrupted adalimumab due to partial response reached remission with infliximab. Switching from adalimumab to infliximab may be useful in patients who develop adverse effects or loss of response, however, the benefit of infliximab in primary nonresponders was not established.

Effectiveness of infliximab after adalimumab failure in Crohn's disease

PubMed Central

Chaparro, María; Andreu, Montserrat; Barreiro-de Acosta, Manuel; García-Planella, Esther; Ricart, Elena; Domènech, Eugeni; Esteve, María; Merino, Olga; Nos, Pilar; Peñalva, Mireia; Gisbert, Javier P

2012-01-01

AIM: To evaluate the effectiveness of infliximab as a second-line therapy in Crohn’s disease patients after adalimumab failure. METHODS: A historical cohort study in a community-based gastroenterology practice evaluated Crohn’s disease patients treated with infliximab (induction plus maintenance) after adalimumab failure. Patients were identified using a large Spanish database (ENEIDA). RESULTS: We included 15 Crohn’s disease patients who received infliximab after adalimumab failure. Five patients discontinued adalimumab due to loss of response, 3 due to adverse events and 7 due to partial response. After infliximab therapy was started, all patients who had interrupted adalimumab due to loss of efficacy regained response. All patients who discontinued adalimumab due to adverse events responded to infliximab and maintained this response; one of these patients had an uneventful course on infliximab, but 2 developed adverse events. None of the 7 patients who interrupted adalimumab due to partial response reached remission with infliximab. CONCLUSION: Switching from adalimumab to infliximab may be useful in patients who develop adverse effects or loss of response, however, the benefit of infliximab in primary nonresponders was not established. PMID:23066316

Effect of some blocking drugs on the pressor response to physostigmine in the rat

PubMed Central

Gokhale, S. D.; Gulati, O. D.; Joshi, N. Y.

1963-01-01

Bretylium and guanethidine blocked the pressor effect of physostigmine and potentiated the responses to adrenaline and noradrenaline on the blood pressure of the rat. Morphine and atropine in small doses blocked the pressor effect of physostigmine without interfering with the actions of adrenaline and noradrenaline. Chlorpromazine in small doses (0.5 to 2.5 mg/kg) blocked the pressor effect of physostigmine and potentiated the responses to noradrenaline whilst those to adrenaline remained unaltered. 3,6-Di(3-diethylaminopropoxy)pyridazine di(methiodide) (Win 4981) blocked the pressor effect of physostigmine and, in its early stages, this block was partially reversed by choline chloride. N-Diethylaminoethyl-N-isopentyl-N'N'-diisopropylurea (P-286), in a dose that reduced the effect of dimethylphenylpiperazinium, had no effect on the pressor response to physostigmine or on the responses to adrenaline and noradrenaline. Hexamethonium, even in large doses (100 mg/kg), only blocked partially the effect of physostigmine while mecamylamine produced a complete block; the responses to adrenaline and noradrenaline were potentiated in both instances. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6 PMID:14081658

O6-Methylguanine DNA Methyltransferase Status Does Not Predict Response or Resistance to Alkylating Agents in Well-Differentiated Pancreatic Neuroendocrine Tumors.

PubMed

Raj, Nitya; Klimstra, David S; Horvat, Natally; Zhang, Liying; Chou, Joanne F; Capanu, Marinela; Basturk, Olca; Do, Richard Kinh Gian; Allen, Peter J; Reidy-Lagunes, Diane

2017-07-01

Alkylating agents have activity in well-differentiated pancreatic neuroendocrine tumors (WD panNETs). In glioblastoma multiforme, decreased activity of O-methylguanine DNA methyltransferase (MGMT) predicts response; in panNETs, MGMT relevance is unknown. We identified patients with WD panNETs treated with alkylating agents, determined best overall response by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, and performed MGMT activity testing. Fifty-six patients were identified; 26 (46%) of the 56 patients experienced partial response, 24 (43%) of 56 experienced stable disease, and 6 (11%) of 56 experienced progression of disease. O-methylguanine DNA methyltransferase status was available for 36 tumors. For tumors with partial response, 10 (67%) of 15 were MGMT deficient, and 5 (33%) of 15 were MGMT intact. For tumors with stable disease, 7 (47%) of 15 were MGMT deficient, and 8 (53%) of 15 were MGMT intact. For tumors with progression of disease, 3 (50%) of 6 were MGMT deficient, and 3 (50%) of 6 were MGMT intact. We observed response and resistance to alkylating agents in MGMT-deficient and MGMT-intact tumors. O-methylguanine DNA methyltransferase status should not guide alkylating agent therapy in WD panNETs.

Cullin 5 Expression in the Rat: Cellular and Tissue Distribution, and Changes in Response to Water Deprivation and Hemorrhagic Shock

DTIC Science & Technology

2003-02-28

of Health p53 tumor suppressor PBS phosphate buffered saline PCO2 partial pressure of carbon dioxide PO2 partial pressure of oxygen PCR...buffered saline TTBS tween-20 tris buffered saline TonEBP tonicity-response enhancer binding protein TSNRP TriService Nursing Research Program...growth and metabolism (Hochstrasser, 1995; Deshaies, 1999). Although traditionally seen as no more than a means of eliminating no longer needed

Coherent detection of frequency-hopped quadrature modulations in the presence of jamming. II - QPR Class I modulation. [Quadrature Partial Response

NASA Technical Reports Server (NTRS)

Simon, M. K.

1981-01-01

This paper considers the performance of quadrature partial response (QPR) in the presence of jamming. Although a QPR system employs a single sample detector in its receiver, while quadrature amplitude shift keying (or quadrature phase shift keying) requires a matched-filter type of receiver, it is shown that the coherent detection performances of the two in the presence of the intentional jammer have definite similarities.

Treatment of Bowen Disease With Photodynamic Therapy and the Advantages of Sequential Topical Imiquimod.

PubMed

Victoria-Martínez, A M; Martínez-Leborans, L; Ortiz-Salvador, J M; Pérez-Ferriols, A

2017-03-01

Photodynamic therapy (PDT) has been shown to be useful and effective in the treatment of actinic keratosis, Bowen disease, and basal cell carcinoma. We present a series of 13 Bowen disease lesions treated using PDT. Complete responses were achieved in 11 (84%) of the lesions after 3 months of treatment; at 18 months, complete responses were seen in 9 (70%) of the lesions. Patients who presented a partial response or recurrence were treated with topical 5% imiquimod and achieved complete responses. The lesions that presented partial response or recurrence were the largest lesions, between 3 and 5cm in diameter. PDT in monotherapy or combined sequentially with imiquimod is an excellent and well-tolerated therapeutic option for Bowen disease. The treatment has few adverse effects and shows satisfactory results, particularly in multiple large lesions in areas of difficult surgical reconstruction or in elderly patients with a high surgical risk. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

A Data-Driven Response Virtual Sensor Technique with Partial Vibration Measurements Using Convolutional Neural Network.

PubMed

Sun, Shan-Bin; He, Yuan-Yuan; Zhou, Si-Da; Yue, Zhen-Jiang

2017-12-12

Measurement of dynamic responses plays an important role in structural health monitoring, damage detection and other fields of research. However, in aerospace engineering, the physical sensors are limited in the operational conditions of spacecraft, due to the severe environment in outer space. This paper proposes a virtual sensor model with partial vibration measurements using a convolutional neural network. The transmissibility function is employed as prior knowledge. A four-layer neural network with two convolutional layers, one fully connected layer, and an output layer is proposed as the predicting model. Numerical examples of two different structural dynamic systems demonstrate the performance of the proposed approach. The excellence of the novel technique is further indicated using a simply supported beam experiment comparing to a modal-model-based virtual sensor, which uses modal parameters, such as mode shapes, for estimating the responses of the faulty sensors. The results show that the presented data-driven response virtual sensor technique can predict structural response with high accuracy.

Dynamic representation of partially occluded objects in primate prefrontal and visual cortex

PubMed Central

Choi, Hannah; Shea-Brown, Eric

2017-01-01

Successful recognition of partially occluded objects is presumed to involve dynamic interactions between brain areas responsible for vision and cognition, but neurophysiological evidence for the involvement of feedback signals is lacking. Here, we demonstrate that neurons in the ventrolateral prefrontal cortex (vlPFC) of monkeys performing a shape discrimination task respond more strongly to occluded than unoccluded stimuli. In contrast, neurons in visual area V4 respond more strongly to unoccluded stimuli. Analyses of V4 response dynamics reveal that many neurons exhibit two transient response peaks, the second of which emerges after vlPFC response onset and displays stronger selectivity for occluded shapes. We replicate these findings using a model of V4/vlPFC interactions in which occlusion-sensitive vlPFC neurons feed back to shape-selective V4 neurons, thereby enhancing V4 responses and selectivity to occluded shapes. These results reveal how signals from frontal and visual cortex could interact to facilitate object recognition under occlusion. PMID:28925354

A Data-Driven Response Virtual Sensor Technique with Partial Vibration Measurements Using Convolutional Neural Network

PubMed Central

Sun, Shan-Bin; He, Yuan-Yuan; Zhou, Si-Da; Yue, Zhen-Jiang

2017-01-01

Measurement of dynamic responses plays an important role in structural health monitoring, damage detection and other fields of research. However, in aerospace engineering, the physical sensors are limited in the operational conditions of spacecraft, due to the severe environment in outer space. This paper proposes a virtual sensor model with partial vibration measurements using a convolutional neural network. The transmissibility function is employed as prior knowledge. A four-layer neural network with two convolutional layers, one fully connected layer, and an output layer is proposed as the predicting model. Numerical examples of two different structural dynamic systems demonstrate the performance of the proposed approach. The excellence of the novel technique is further indicated using a simply supported beam experiment comparing to a modal-model-based virtual sensor, which uses modal parameters, such as mode shapes, for estimating the responses of the faulty sensors. The results show that the presented data-driven response virtual sensor technique can predict structural response with high accuracy. PMID:29231868

Partial response to proton pump inhibitor therapy for GERD: observational study of patient characteristics, burden of disease, and costs in the USA.

PubMed

Stålhammar, Nils-Olov; Spiegel, Brennan M; Granstedt Löfman, Helena; Karlsson, Maria; Wahlqvist, Peter; Næsdal, Jørgen; Nelson, M Todd; Despiégel, Nicolas

2012-01-01

Disease burden and associated costs are not well understood among patients with gastroesophageal reflux disease (GERD) who have persistent symptoms despite optimized proton pump inhibitor (PPI) therapy. The aim of this study was to investigate disease burden and costs of GERD in partial responders to PPI therapy. The Partial Response to PPI treatment: the Cost to Society and the Burden to the Patient in the US (REMAIN US) study was a 12-month, multicenter, noninterventional, observational study of 552 partial PPI responders in the USA. Participating sites were comprised of family practice (n = 30), internal medicine (n = 8), and specialist (gastroenterologist) centers (n = 15). GERD symptoms, health-related quality of life (HRQL), and impact on productivity were evaluated from patient-reported outcome instruments. Resource utilization data were also collected. Patients had a high symptom burden, impaired HRQL, and reduced productivity while at work and in daily activities, despite optimized PPI therapy. Mean annual GERD-related costs were US$9944 per patient, comprising total direct costs and mean productivity loss costs of US$4068 and US$5876 per patient, respectively. Patients with GERD and a partial response to PPI therapy have considerable direct and indirect costs, along with substantial impairments in HRQL and productivity.

Investigation into the acute effects of total and partial energy restriction on postprandial metabolism among overweight/obese participants.

PubMed

Antoni, Rona; Johnston, Kelly L; Collins, Adam L; Robertson, M Denise

2016-03-28

The intermittent energy restriction (IER) approach to weight loss involves short periods of substantial (75-100 %) energy restriction (ER) interspersed with normal eating. This study aimed to characterise the early metabolic response to these varying degrees of ER, which occurs acutely and prior to weight loss. Ten (three female) healthy, overweight/obese participants (36 (SEM 5) years; 29·0 (sem 1·1) kg/m2) took part in this acute three-way cross-over study. Participants completed three 1-d dietary interventions in a randomised order with a 1-week washout period: isoenergetic intake, partial 75 % ER and total 100 % ER. Fasting and postprandial (6-h) metabolic responses to a liquid test meal were assessed the following morning via serial blood sampling and indirect calorimetry. Food intake was also recorded for two subsequent days of ad libitum intake. Relative to the isoenergetic control, postprandial glucose responses were increased following total ER (+142 %; P=0·015) and to a lesser extent after partial ER (+76 %; P=0·051). There was also a delay in the glucose time to peak after total ER only (P=0·024). Both total and partial ER interventions produced comparable reductions in postprandial TAG responses (-75 and -59 %, respectively; both P<0·05) and 3-d energy intake deficits of approximately 30 % (both P=0·015). Resting and meal-induced thermogenesis were not significantly affected by either ER intervention. In conclusion, our data demonstrate the ability of substantial ER to acutely alter postprandial glucose-lipid metabolism (with partial ER producing the more favourable overall response), as well as incomplete energy-intake compensation amongst overweight/obese participants. Further investigations are required to establish how metabolism adapts over time to the repeated perturbations experienced during IER, as well as the implications for long-term health.

A note on monotonicity of item response functions for ordered polytomous item response theory models.

PubMed

Kang, Hyeon-Ah; Su, Ya-Hui; Chang, Hua-Hua

2018-03-08

A monotone relationship between a true score (τ) and a latent trait level (θ) has been a key assumption for many psychometric applications. The monotonicity property in dichotomous response models is evident as a result of a transformation via a test characteristic curve. Monotonicity in polytomous models, in contrast, is not immediately obvious because item response functions are determined by a set of response category curves, which are conceivably non-monotonic in θ. The purpose of the present note is to demonstrate strict monotonicity in ordered polytomous item response models. Five models that are widely used in operational assessments are considered for proof: the generalized partial credit model (Muraki, 1992, Applied Psychological Measurement, 16, 159), the nominal model (Bock, 1972, Psychometrika, 37, 29), the partial credit model (Masters, 1982, Psychometrika, 47, 147), the rating scale model (Andrich, 1978, Psychometrika, 43, 561), and the graded response model (Samejima, 1972, A general model for free-response data (Psychometric Monograph no. 18). Psychometric Society, Richmond). The study asserts that the item response functions in these models strictly increase in θ and thus there exists strict monotonicity between τ and θ under certain specified conditions. This conclusion validates the practice of customarily using τ in place of θ in applied settings and provides theoretical grounds for one-to-one transformations between the two scales. © 2018 The British Psychological Society.

[Treatment of interstitial cystitis by intravesical instillation of hyaluronic acid: A prospective study on 31 patients].

PubMed

Van Agt, S; Gobet, F; Sibert, L; Leroi, A-M; Grise, P

2011-03-01

We evaluate the efficacy of hyaluronate acid instillation for treatment of interstitial cystitis (IC). From March 2008 to May 2009, a prospective study included 31 patients. We used the new definition of IC established by the ICS in 2002. Patients have a urinalysis, a cystoscopy, a hydrodistension test and bladder biopsies. The urodynamic evaluation was not systematic. Patients received weekly six instillations of 40mg (50ml) intravesical hyaluronate acid. We evaluated the efficacy and safety of treatment with two specific questionnaires of interstitial cystitis filled before and after 6 weeks of treatment: the O'Leary-Sant and Pelvic pain and Urgency/Frequency (PUF). Four groups were defined: good response, partial response, poor response and no response. They were composed by 14 patients (45%), two (7%), seven (22%) and eight patients (26%). We obtained 52% positive response (good response and partial response) after 6 weeks of treatment. Patients with cystoscopy and histology abnormal had a response rate of 60%. No serious side effects were observed. Hyaluronate acid has a place in the treatment of interstitial cystitis with an efficiency comparable to other treatments and good tolerance. The response rate to treatment can be improved by better selection of patients, particularly those having a cystoscopy and histology abnormal. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Response of the Water Level in a Well to Earth Tides and Atmospheric Loading Under Unconfined Conditions

NASA Astrophysics Data System (ADS)

Rojstaczer, Stuart; Riley, Francis S.

1990-08-01

The response of the water level in a well to Earth tides and atmospheric loading under unconfined conditions can be explained if the water level is controlled by the aquifer response averaged over the saturated depth of the well. Because vertical averaging tends to diminish the influence of the water table, the response is qualitatively similar to the response of a well under partially confined conditions. When the influence of well bore storage can be ignored, the response to Earth tides is strongly governed by a dimensionless aquifer frequency Q'u. The response to atmospheric loading is strongly governed by two dimensionless vertical fluid flow parameters: a dimensionless unsaturated zone frequency, R, and a dimensionless aquifer frequency Qu. The differences between Q'u and Qu are generally small for aquifers which are highly sensitive to Earth tides. When Q'u and Qu are large, the response of the well to Earth tides and atmospheric loading approaches the static response of the aquifer under confined conditions. At small values of Q'u and Qu, well response to Earth tides and atmospheric loading is strongly influenced by water table drainage. When R is large relative to Qu, the response to atmospheric loading is strongly influenced by attenuation and phase shift of the pneumatic pressure signal in the unsaturated zone. The presence of partial penetration retards phase advance in well response to Earth tides and atmospheric loading. When the theoretical response of a phreatic well to Earth tides and atmospheric loading is fit to the well response inferred from cross-spectral estimation, it is possible to obtain estimates of the pneumatic diffusivity of the unsaturated zone and the vertical hydraulic conductivity of the aquifer.

Effect of inadequate response to treatment in patients with depression.

PubMed

Knoth, Russell L; Bolge, Susan C; Kim, Edward; Tran, Quynh-Van

2010-08-01

To assess the effects of inadequate response to antidepressant treatment on healthcare resource utilization and on work productivity in patients diagnosed as having major depressive disorder (MDD). This study used data from the 2006 US National Health and Wellness Survey, a cross-sectional survey of adults 18 years and older. Patients who self-reported a confirmed diagnosis of depression and were currently taking antidepressant medication were included in the analyses. Adequacy of antidepressant treatment response was determined from responses to the mental health domain of the 8-Item Short Form Health Survey (SF-8). Logistic regression analyses adjusted for demographics, comorbidity, and component scores on the SF-8 were used to determine the associations between inadequacy of treatment response and health outcomes. Of 5988 patients who met the inclusion criteria for the study, 30.9% were classified as antidepressant treatment responders, 31.2% were partial responders, and 37.9% were nonresponders. Partial response and nonresponse to treatment were associated with greater likelihood of emergency department utilization (odds ratios [ORs], 1.26 and 1.54, respectively; P <.01 for both) and hospitalization (OR, 1.23; P = .05 and OR, 1.39; P <.01, respectively). Similarly, partial response and nonresponse were associated with lower likelihood of current employment (OR, 0.83; P = .01 and OR, 0.63; P <.01, respectively) and with greater likelihood of work productivity loss among the employed (ORs, 1.42 and 1.99, respectively; P <.01 for both). Patients with MDD who failed to respond to antidepressant treatment as evidenced by poor self-reported mental health status used more healthcare resources, were less likely to be employed, and had more work productivity loss than those who responded to antidepressant therapy.

Mirror neuron activation as a function of explicit learning: changes in mu-event-related power after learning novel responses to ideomotor compatible, partially compatible, and non-compatible stimuli.

PubMed

Behmer, Lawrence P; Fournier, Lisa R

2016-11-01

Questions regarding the malleability of the mirror neuron system (MNS) continue to be debated. MNS activation has been reported when people observe another person performing biological goal-directed behaviors, such as grasping a cup. These findings support the importance of mapping goal-directed biological behavior onto one's motor repertoire as a means of understanding the actions of others. Still, other evidence supports the Associative Sequence Learning (ASL) model which predicts that the MNS responds to a variety of stimuli after sensorimotor learning, not simply biological behavior. MNS activity develops as a consequence of developing stimulus-response associations between a stimulus and its motor outcome. Findings from the ideomotor literature indicate that stimuli that are more ideomotor compatible with a response are accompanied by an increase in response activation compared to less compatible stimuli; however, non-compatible stimuli robustly activate a constituent response after sensorimotor learning. Here, we measured changes in the mu-rhythm, an EEG marker thought to index MNS activity, predicting that stimuli that differ along dimensions of ideomotor compatibility should show changes in mirror neuron activation as participants learn the respective stimulus-response associations. We observed robust mu-suppression for ideomotor-compatible hand actions and partially compatible dot animations prior to learning; however, compatible stimuli showed greater mu-suppression than partially or non-compatible stimuli after explicit learning. Additionally, non-compatible abstract stimuli exceeded baseline only after participants explicitly learned the motor responses associated with the stimuli. We conclude that the empirical differences between the biological and ASL accounts of the MNS can be explained by Ideomotor Theory. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Gene expression changes in the coccolithophore Emiliania huxleyi after 500 generations of selection to ocean acidification.

PubMed

Lohbeck, Kai T; Riebesell, Ulf; Reusch, Thorsten B H

2014-07-07

Coccolithophores are unicellular marine algae that produce biogenic calcite scales and substantially contribute to marine primary production and carbon export to the deep ocean. Ongoing ocean acidification particularly impairs calcifying organisms, mostly resulting in decreased growth and calcification. Recent studies revealed that the immediate physiological response in the coccolithophore Emiliania huxleyi to ocean acidification may be partially compensated by evolutionary adaptation, yet the underlying molecular mechanisms are currently unknown. Here, we report on the expression levels of 10 candidate genes putatively relevant to pH regulation, carbon transport, calcification and photosynthesis in E. huxleyi populations short-term exposed to ocean acidification conditions after acclimation (physiological response) and after 500 generations of high CO2 adaptation (adaptive response). The physiological response revealed downregulation of candidate genes, well reflecting the concomitant decrease of growth and calcification. In the adaptive response, putative pH regulation and carbon transport genes were up-regulated, matching partial restoration of growth and calcification in high CO2-adapted populations. Adaptation to ocean acidification in E. huxleyi likely involved improved cellular pH regulation, presumably indirectly affecting calcification. Adaptive evolution may thus have the potential to partially restore cellular pH regulatory capacity and thereby mitigate adverse effects of ocean acidification. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

FDG-PET metabolic response predicts outcomes in anal cancer managed with chemoradiotherapy.

PubMed

Day, F L; Link, E; Ngan, S; Leong, T; Moodie, K; Lynch, C; Michael, M; Winton, E de; Hogg, A; Hicks, R J; Heriot, A

2011-08-09

The aim was to investigate the correlation between (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) metabolic response to chemoradiotherapy and clinical outcomes in squamous cell carcinoma (SCC) of the anus. A total of 48 patients with biopsy-proven anal SCC underwent FDG-PET scans at baseline and post chemoradiotherapy (54 Gy, concurrent 5-FU/mitomycin). Kaplan-Meier analysis was used to determine survival outcomes according to FDG-PET metabolic response. In all, 79% patients (n=38) had a complete metabolic response (CMR) at all sites of disease, 15% (n=7) had a CMR in regional nodes but only partial response in the primary tumour (overall partial metabolic response (PMR)) and 6% (n=3) had progressive distant disease despite CMR locoregionally (overall no response (NR)). The 2-year progression-free survival (PFS) was 95% for patients with a CMR, 71% for PMR and 0% for NR (P<0.0001). The 5-year overall survival (OS) was 88% in CMR, 69% in PMR and 0% in NR (P<0.0001). Cox proportional hazards regression analyses for PFS and OS found significant associations for incomplete (PMR+NR) vs complete FDG-PET response to treatment only, (HR 4.1 (95% CI: 1.5-11.5, P=0.013) and 6.7 (95% CI: 2.1-21.6, P=0.002), respectively). FDG-PET metabolic response to chemoradiotherapy in anal cancer is significantly associated with PFS and OS, and in this cohort incomplete FDG-PET response was a stronger predictor than T or N stage.

Treatment With Bortezomib-based Therapy, Followed by Autologous Stem Cell Transplantation, Improves Outcomes in Light Chain Amyloidosis: A Retrospective Study.

PubMed

Jain, Tania; Kosiorek, Heidi E; Kung, Shu T; Shah, Vishal S; Dueck, Amylou C; Gonzalez-Calle, Veronica; Luft, Susan; Reeder, Craig B; Adams, Roberta; Noel, Pierre; Larsen, Jeremy T; Mikhael, Joseph; Bergsagel, Leif; Stewart, A Keith; Fonseca, Rafael

2018-05-04

The hematologic response is critical in patients with light chain amyloidosis because a good response is known to improve organ response and overall survival. We present a retrospective analysis to compare the hematologic and organ response in patients who received bortezomib-based therapy before autologous stem cell transplantation (ASCT) versus those who received non-bortezomib-based therapy before ASCT and those who underwent ASCT at diagnosis. Of a total of 63 patients who underwent ASCT for light chain amyloidosis, 34 received bortezomib-based therapy before ASCT (Bor-ASCT) and 29 did not receive bortezomib therapy (non-Bor-ASCT). A greater number of patients had involvement of ≥ 3 organs and cardiac involvement in the Bor-ASCT group, suggesting a greater risk at baseline in the Bor-ASCT group. At 3, 6, and 12 months after ASCT, the hematologic response was better in the Bor-ASCT group, with a statistically significance difference at 6 months (partial response or better in 82% vs. 20%; P = .002) and 12 months (partial response or better in 76% vs. 33%; P = .02). Organ responses (66% vs. 21%; P < .001) and median overall survival (not reached vs. 53 months; P = .001) were also greater in the Bor-ASCT group. Our study has shown that bortezomib-based therapy before ASCT improves the hematologic response, organ response and overall survival, potentially by decreasing the light chain load before ASCT. Copyright © 2018 Elsevier Inc. All rights reserved.

Calibration of ultra-high frequency (UHF) partial discharge sensors using FDTD method

NASA Astrophysics Data System (ADS)

Ishak, Asnor Mazuan; Ishak, Mohd Taufiq

2018-02-01

Ultra-high frequency (UHF) partial discharge sensors are widely used for conditioning monitoring and defect location in insulation system of high voltage equipment. Designing sensors for specific applications often requires an iterative process of manufacturing, testing and mechanical modifications. This paper demonstrates the use of finite-difference time-domain (FDTD) technique as a tool to predict the frequency response of UHF PD sensors. Using this approach, the design process can be simplified and parametric studies can be conducted in order to assess the influence of component dimensions and material properties on the sensor response. The modelling approach is validated using gigahertz transverse electromagnetic (GTEM) calibration system. The use of a transient excitation source is particularly suitable for modeling using FDTD, which is able to simulate the step response output voltage of the sensor from which the frequency response is obtained using the same post-processing applied to the physical measurement.

On the transmission of partial information: inferences from movement-related brain potentials

NASA Technical Reports Server (NTRS)

Osman, A.; Bashore, T. R.; Coles, M. G.; Donchin, E.; Meyer, D. E.

1992-01-01

Results are reported from a new paradigm that uses movement-related brain potentials to detect response preparation based on partial information. The paradigm uses a hybrid choice-reaction go/nogo procedure in which decisions about response hand and whether to respond are based on separate stimulus attributes. A lateral asymmetry in the movement-related brain potential was found on nogo trials without overt movement. The direction of this asymmetry depended primarily on the signaled response hand rather than on properties of the stimulus. When the asymmetry first appeared was influenced by the time required to select the signaled hand, and when it began to differ on go and nogo trials was influenced by the time to decide whether to respond. These findings indicate that both stimulus attributes were processed in parallel and that the asymmetry reflected preparation of the response hand that began before the go/nogo decision was completed.

Tenofovir-Based Alternate Therapies for Chronic Hepatitis B Patients with Partial Virological Response to Entecavir

PubMed Central

Lu, Louis; Yip, Benjamin; Trinh, Huy; Pan, Calvin Q.; Han, Steven-Huy B.; Wong, Christopher C.; Li, Jiayi; Chan, Stanley; Krishnan, Gomathi; Wong, Clifford C.; Nguyen, Mindie H.

2014-01-01

Entecavir (ETV) is a first-line antiviral therapy for treating chronic hepatitis B (CHB); however, some patients have suboptimal response to ETV. Currently, there are limited data on how to approach these patients. Therefore our aim was to compare the effectiveness of two alternate therapies – tenofovir (TDF) monotherapy and combination therapy of ETV+TDF – in CHB patients with ETV partial virological response. We conducted a retrospective study of 68 patients who had partial virological response to ETV, defined as having detectable HBV DNA following at least 12 months of ETV, and were switched to TDF monotherapy (n=25) or ETV+TDF (n=43). Patients were seen in 7 US liver/community-based clinics and started on ETV between 2005-2009. The majority of patients were male; the vast majority were Asian and had positive hepatitis B e antigen (HBeAg). Patients in both groups had similar pre-treatment characteristics. Complete viral suppression (CVS) rates with TDF monotherapy and ETV+TDF were similar after 6 months (71% vs. 83, p=0.23) and 12 months (86% vs. 84%, p=0.85), and there was no statistically significant difference in CVS rates even when only patients with higher HBV DNA levels at switch (>1,000 IU/mL) were evaluated. Multivariate analysis indicated that ETV+TDF was not an independent predictor of CVS compared to TDF monotherapy (OR=1.19, p=0.63). In conclusion, TDF monotherapy and ETV+TDF are comparable in achieving CVS in CHB patients with partial virological response to ETV. Long-term alternate therapy with one pill (TDF monotherapy) vs. two pills (ETV+TDF) could lead to lower non-adherence rates and better treatment outcomes. PMID:25417914

Whole-plant versus leaf-level regulation of photosynthetic responses after partial defoliation in Eucalyptus globulus saplings.

PubMed

Eyles, Alieta; Pinkard, Elizabeth A; Davies, Noel W; Corkrey, Ross; Churchill, Keith; O'Grady, Anthony P; Sands, Peter; Mohammed, Caroline

2013-04-01

Increases in photosynthetic capacity (A1500) after defoliation have been attributed to changes in leaf-level biochemistry, water, and/or nutrient status. The hypothesis that transient photosynthetic responses to partial defoliation are regulated by whole-plant (e.g. source-sink relationships or changes in hydraulic conductance) rather than leaf-level mechanisms is tested here. Temporal variation in leaf-level gas exchange, chemistry, whole-plant soil-to-leaf hydraulic conductance (KP), and aboveground biomass partitioning were determined to evaluate mechanisms responsible for increases in A1500 of Eucalyptus globulus L. potted saplings. A1500 increased in response to debudding (B), partial defoliation (D), and combined B&D treatments by up to 36% at 5 weeks after treatment. Changes in leaf-level factors partly explained increases in A1500 of B and B&D treatments but not for D treatment. By week 5, saplings in B, B&D, and D treatments had similar leaf-specific KP to control trees by maintaining lower midday water potentials and higher transpiration rate per leaf area. Whole-plant source:sink ratios correlated strongly with A1500. Further, unlike KP, temporal changes in source:sink ratios tracked well with those observed for A1500. The results indicate that increases in A1500 after partial defoliation treatments were largely driven by an increased demand for assimilate by developing sinks rather than improvements in whole-plant water relations and changes in leaf-level factors. Three carbohydrates, galactional, stachyose, and, to a lesser extent, raffinose, correlated strongly with photosynthetic capacity, indicating that these sugars may function as signalling molecules in the regulation of longer term defoliation-induced gas exchange responses.

Whole-plant versus leaf-level regulation of photosynthetic responses after partial defoliation in Eucalyptus globulus saplings

PubMed Central

Eyles, Alieta

2013-01-01

Increases in photosynthetic capacity (A1500) after defoliation have been attributed to changes in leaf-level biochemistry, water, and/or nutrient status. The hypothesis that transient photosynthetic responses to partial defoliation are regulated by whole-plant (e.g. source–sink relationships or changes in hydraulic conductance) rather than leaf-level mechanisms is tested here. Temporal variation in leaf-level gas exchange, chemistry, whole-plant soil-to-leaf hydraulic conductance (KP), and aboveground biomass partitioning were determined to evaluate mechanisms responsible for increases in A1500 of Eucalyptus globulus L. potted saplings. A1500 increased in response to debudding (B), partial defoliation (D), and combined B&D treatments by up to 36% at 5 weeks after treatment. Changes in leaf-level factors partly explained increases in A1500 of B and B&D treatments but not for D treatment. By week 5, saplings in B, B&D, and D treatments had similar leaf-specific KP to control trees by maintaining lower midday water potentials and higher transpiration rate per leaf area. Whole-plant source:sink ratios correlated strongly with A1500. Further, unlike KP, temporal changes in source:sink ratios tracked well with those observed for A1500. The results indicate that increases in A1500 after partial defoliation treatments were largely driven by an increased demand for assimilate by developing sinks rather than improvements in whole-plant water relations and changes in leaf-level factors. Three carbohydrates, galactional, stachyose, and, to a lesser extent, raffinose, correlated strongly with photosynthetic capacity, indicating that these sugars may function as signalling molecules in the regulation of longer term defoliation-induced gas exchange responses. PMID:23382548

Photodynamic therapy of non-melanoma skin cancers

NASA Astrophysics Data System (ADS)

Ikram, M.; Khan, R. U.; Firdous, S.; Atif, M.; Nawaz, M.

2011-02-01

In this prospective study duly approved from Institutional Ethics Review Committee for research in medicine, PAEC General Hospital Islamabad, Pakistan, we investigate the efficacy, safety and tolerability along with cosmetic outcome of topical 5-aminolaevulinic acid photodynamic therapy for superficial nonmelanoma skin cancers (NMSCs) and their precursors. Patients with Histological diagnosis of NMSCs and their precursors were assessed for PDT, after photographic documentation of the lesions and written consent, underwent two (2) sessions of PDT in one month (4 weeks) according to standard protocol. A freshly prepared 20% 5-ALA in Unguentum base was applied under occlusive dressing for 4-6 h as Drug Light Interval (DLI) and irradiated with light of 630 nm wavelength from a diode laser at standard dose of 90 J/cm2. Approximately 11% patients reported pain during treatment which was managed in different simple ways. In our study we regularly followed up the patients for gross as well as histopathological response and recurrence free periods during median follow-up of 24 months. Regarding Basal cell carcinomas complete response was observed in 86.2% (25/29), partial response in 10.3% (3/29) and recurrence during first year in 3.5% (1/29) lesions. All the lesions which showed partial response or recurrence were nBCCs. Regarding Actinic Keratosis complete response was observed in 95.3% (20/21), partial response in 4.7% (1/21) while Bowen's disease showed 100% (2/2) results. 81.8% (9/11) Squamous Cell Carcinomas showed complete, 9% (1/11) partial response and 9% (1/11) presented with recurrence after 3 months. We observed excellent and good cosmetic results along with tumor clearance in our study. Treatment sessions were well tolerated with high level of patient's satisfaction and only minor side effects of pain during treatment sessions and inflammatory changes post photodynamic therapy were observed. We concluded that 5-ALA PDT is an effective and safe emerging treatment modality for management of superficial non-melanoma skin cancers and their precursors with better cosmetic outcome and minor side effects.

In Situ Poling and Imidization of Amorphous Piezoelectric Polyimides

NASA Technical Reports Server (NTRS)

Park, Cheol; Ounaies, Zoubeida; Wise, Kristopher E.; Harrison, Joycelyn S.; Bushnell, Dennis M. (Technical Monitor)

2002-01-01

An amorphous piezoelectric polyimide containing polar functional groups has been developed using a combination of experimental and molecular modeling for potential use in high temperature applications. This amorphous polyimide, (Beta-CN)APB/ODPA, has exhibited good thermal stability and piezoelectric response at temperatures up to 150C. Density functional calculations predicted that a partially cured amic acid (open imide ring) possesses a dipole moment four times larger than the fully imidized closed ring. In situ poling and imidization of the partially cured (Beta-CN)APB/ODPA, was studied in an attempt to maximize the degree of dipolar orientation and the resultant piezoelectric response. A positive corona poling was used to minimize localized arcing during poling and to allow use of higher poling fields without dielectric breakdown. The dielectric relaxation strength, remanent polarization, and piezoelectric response were evaluated as a function of the poling profile. The partially cured, corona poled polymers exhibited higher dielectric relaxation strength (delta varepsilon), remanent polarization (Pr) and piezoelectric strain coefficient (d33) than the fully cured, conventionally poled ones.

Nanocrystalline films for gas-reactive applications

DOEpatents

Eastman, Jeffrey A.; Thompson, Loren J.

2004-02-17

A gas sensor for detection of oxidizing and reducing gases, including O.sub.2, CO.sub.2, CO, and H.sub.2, monitors the partial pressure of a gas to be detected by measuring the temperature rise of an oxide-thin-film-coated metallic line in response to an applied electrical current. For a fixed input power, the temperature rise of the metallic line is inversely proportional to the thermal conductivity of the oxide coating. The oxide coating contains multi-valent cation species that change their valence, and hence the oxygen stoichiometry of the coating, in response to changes in the partial pressure of the detected gas. Since the thermal conductivity of the coating is dependent on its oxygen stoichiometry, the temperature rise of the metallic line depends on the partial pressure of the detected gas. Nanocrystalline (<100 nm grain size) oxide coatings yield faster sensor response times than conventional larger-grained coatings due to faster oxygen diffusion along grain boundaries rather than through grain interiors.

Exercise capacity is associated with endothelin-1 release during emotional excitement in coronary artery disease patients.

PubMed

Tulppo, Mikko P; Piira, Olli-Pekka; Hautala, Arto J; Kiviniemi, Antti M; Miettinen, Johanna A; Huikuri, Heikki V

2014-08-01

Endothelin-1 (ET-1), a potent vasoconstrictor, IL-6, and catecholamines are increased and heart rate variability [SD of normal to normal R-R intervals (SDNN)] decreased during emotional excitement, but individual responses vary. We tested the hypothesis that exercise capacity is associated with physiological responses caused by real-life emotional excitement. We measured the plasma levels of ET-1, IL-6, catecholamines, heart rate, and SDNN in enthusiastic male ice hockey spectators (n = 51; age, 59 ± 9 years) with stable coronary artery disease (CAD) at baseline and during the Finnish National Ice Hockey League's final play-off matches. Maximal exercise capacity (METs) by bicycle exercise test and left ventricular ejection fraction (LVEF) were measured on a separate day. ET-1 response from baseline to emotional excitement correlated with maximal METs (r = -0.30; P = 0.040). In a linear stepwise regression analysis age, body mass index (BMI), METs, LVEF, basal ET-1, and subjective experience of excitement were entered the model as independent variables to explain ET-1 response. This model explained 27% of ET-1 response (P = 0.003). Maximal METs were most strongly correlated with ET-1 response (β = -0.45; partial correlation r = -0.43; P = 0.002), followed by BMI (β = -0.31; partial correlation r = -0.31; P = 0.033) and LVEF (β = -0.30; partial correlation r = -0.33; P = 0.023). Exercise capacity may protect against further cardiovascular events in CAD patients, because it is associated with reduced ET-1 release during emotional excitement. Copyright © 2014 the American Physiological Society.

Comparison of the effects of single and daily repeated immobilization stress on resting activity and heterotypic sensitization of the hypothalamic-pituitary-adrenal axis.

PubMed

Daviu, Núria; Rabasa, Cristina; Nadal, Roser; Armario, Antonio

2014-03-01

Acute exposure to severe stressors causes marked activation of the hypothalamic-pituitary-adrenal (HPA) axis that is reflected on the day after higher resting levels of HPA hormones and sensitization of the HPA response to novel (heterotypic) stressors. However, whether a single exposure to a severe stressor or daily repeated exposure to the same (homotypic) stressor modifies these responses to the same extent has not been studied. In this experiment, we studied this issue in adult male Sprague-Dawley rats daily exposed for seven days to a severe stressor such as immobilization on boards (IMO). A first exposure to 1 h IMO resulted in a marked activation of the HPA axis as reflected in plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone, and such activation was significantly reduced after the seventh IMO. On the day after the first IMO, higher resting levels of ACTH and corticosterone and sensitization of their responses to a short exposure to an open-field (OF) were observed, together with a marked hypoactivity in this environment. Repeated exposure to IMO partially reduced hypoactivity, the increase in resting levels of HPA hormones and the ACTH responsiveness to the OF on the day after the last exposure to IMO. In contrast, corticosterone response was gradually increased, suggesting partial dissociation from ACTH. These results indicate that daily repeated exposure to the same stressor partially reduced the HPA response to the homotypic stressor as well as the sensitization of HPA axis activity observed the day after chronic stress cessation.

Partial Exemption of Certain Chemical Substances from Reporting Additional Chemical Data

EPA Pesticide Factsheets

This Federal Register notice amends the list of chemical substances that are partially exempt from reporting additional information by adding six chemicals in response to a petition the Agency received.

Adaptation and inhibition underlie responses to time-varying interaural phase cues in a model of inferior colliculus neurons.

PubMed

Borisyuk, Alla; Semple, Malcolm N; Rinzel, John

2002-10-01

A mathematical model was developed for exploring the sensitivity of low-frequency inferior colliculus (IC) neurons to interaural phase disparity (IPD). The formulation involves a firing-rate-type model that does not include spikes per se. The model IC neuron receives IPD-tuned excitatory and inhibitory inputs (viewed as the output of a collection of cells in the medial superior olive). The model cell possesses cellular properties of firing rate adaptation and postinhibitory rebound (PIR). The descriptions of these mechanisms are biophysically reasonable, but only semi-quantitative. We seek to explain within a minimal model the experimentally observed mismatch between responses to IPD stimuli delivered dynamically and those delivered statically (McAlpine et al. 2000; Spitzer and Semple 1993). The model reproduces many features of the responses to static IPD presentations, binaural beat, and partial range sweep stimuli. These features include differences in responses to a stimulus presented in static or dynamic context: sharper tuning and phase shifts in response to binaural beats, and hysteresis and "rise-from-nowhere" in response to partial range sweeps. Our results suggest that dynamic response features are due to the structure of inputs and the presence of firing rate adaptation and PIR mechanism in IC cells, but do not depend on a specific biophysical mechanism. We demonstrate how the model's various components contribute to shaping the observed phenomena. For example, adaptation, PIR, and transmission delay shape phase advances and delays in responses to binaural beats, adaptation and PIR shape hysteresis in different ranges of IPD, and tuned inhibition underlies asymmetry in dynamic tuning properties. We also suggest experiments to test our modeling predictions: in vitro simulation of the binaural beat (phase advance at low beat frequencies, its dependence on firing rate), in vivo partial range sweep experiments (dependence of the hysteresis curve on parameters), and inhibition blocking experiments (to study inhibitory tuning properties by observation of phase shifts).

Grade of Membership Response Time Model for Detecting Guessing Behaviors

ERIC Educational Resources Information Center

Pokropek, Artur

2016-01-01

A response model that is able to detect guessing behaviors and produce unbiased estimates in low-stake conditions using timing information is proposed. The model is a special case of the grade of membership model in which responses are modeled as partial members of a class that is affected by motivation and a class that responds only according to…

Preliminary Predictors of within-Session Adherence to Exposure and Response Prevention in Pediatric Obsessive-Compulsive Disorder

ERIC Educational Resources Information Center

Morgan, Jessica; Caporino, Nicole E.; De Nadai, Alessandro S.; Truax, Tatyana; Lewin, Adam B.; Jung, Leah; Park, Jennifer M.; Khan, Yasmeen Ali; Murphy, Tanya K.; Storch, Eric A.

2013-01-01

Background: Cognitive-behavioral therapy with exposure and response prevention (ERP) is an effective treatment for pediatric OCD; however, up to 30 % of children are treatment non-responders and as many as 40% are partial responders. Although poor treatment adherence has been linked to attenuated response in adults with OCD, little research has…

Monitoring the effects of partial cutting and gap size on microclimate and vegetation responses in northern hardwood forests in Wisconsin

Treesearch

Terry F. Strong; Ron M. Teclaw; John C. Zasada

1997-01-01

Silviculture modifies the environment. Past monitoring of silvicultural practices has been usually limited to vegetation responses, but parallel monitoring of the environment is needed to better predict these responses. In an example of monitoring temperatures in two studies of northern hardwood forests in Wisconsin, we found that different silvicultural practices...

Decreased responsiveness following lithium discontinuation in bipolar disorder: A naturalistic observation study.

PubMed

Cakir, Sibel; Yazıcı, Olcay; Post, Robert M

2017-01-01

Lithium is a cornerstone in treatment of bipolar disorder. Findings are conflicting as to whether acquired unresponsiveness occurs following the discontinuation. Retrospective life chart data were evaluated to investigate the incidence of loss of response. Sixty-five patients chosen from a larger cohort, followed with prospective life charts, who discontinued lithium and had a second lithium treatment. Patients who had at least 2 mood episodes when they were drug naïve to describe the natural frequency of illness and 3 mood episodes before the discontinuation were included. The type of response was defined as excellent, partial, or poor according to mirror design method. Eighteen of 65 patients (27.6%) had a decreased response to lithium following its discontinuation. Nine of these patients (13.8%) were unresponsive and nine patients (13.8%) had attenuated response to second lithium treatment. The mean time of discontinuation was longer in the patients who show decreased response (245.8+268.2 vs. 117.9+149.8 days, p=.01). Those who had episode recurrences during the discontinuation were more likely to show reduced responsiveness upon re-treatment. After discontinuation of lithium treatment, more than a quarter of the patients showed an attenuated response or unresponsiveness, and initial partial responders more likely to show unresponsiveness than excellent responders. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

NEUROTROPHIN MEDIATION OF ALLERGIC AIRWAYS RESPONSES TO INHALED DIESEL PARTICLES IN MICE

EPA Science Inventory

Neurotrophins, including nerve growth factor (NGF) partially mediate many features of allergic airways disease including airway hyper-responsiveness. Diesel exhaust particulates (DEP) associated with the combustion of diesel fuel exacerbate many of these allergic airways respons...

Hot, humid air increases cellular influx during the late-phase response to nasal challenge with antigen.

PubMed

Assanasen, P; Baroody, F M; Naureckas, E; Naclerio, R M

2001-12-01

Inhalation of hot, humid air (HHA: 37 degrees C, > 95% relative humidity (RH)) partially inhibits the early response to nasal challenge with antigen. To investigate whether HHA inhibited the late-phase response to nasal challenge with antigen and increased hyper-responsiveness of the nasal mucosa to histamine. Twenty subjects with seasonal allergic rhinitis, outside of their allergy season, participated in a randomized, 2-way cross-over study. The subjects continuously breathed room air (25 degrees C, 30% RH) or HHA delivered via a face mask during the entire experiment. Subjects were challenged intranasally with antigen 1 h after beginning conditioning. The response was monitored by symptoms and nasal lavage at 2-h intervals after the last antigen challenge. Eight hours after antigen challenge, nasal challenge with histamine was performed. Exposure to HHA significantly increased nasal mucosal temperature from baseline without affecting nasal secretion osmolality. HHA significantly inhibited antigen-induced sneezes, congestion, pruritus, and human serum albumin levels during the early response to antigen challenge. HHA exposure, however, was associated with an 8-fold increase in the eosinophil influx and a 15-fold increase in the levels of eosinophil cationic protein during the late-phase response compared to room air. There were no significant differences in nasal hyper-responsiveness to histamine during either exposure. HHA partially decreases the early response to nasal challenge with antigen, but dramatically increases eosinophil influx. Increasing eosinophil number had no effects on the hyper-responsiveness to histamine. We speculate that the physical conditions of air differentially impact the stages of allergic inflammation.

Measures of Partial Knowledge and Unexpected Responses in Multiple-Choice Tests

ERIC Educational Resources Information Center

Chang, Shao-Hua; Lin, Pei-Chun; Lin, Zih-Chuan

2007-01-01

This study investigates differences in the partial scoring performance of examinees in elimination testing and conventional dichotomous scoring of multiple-choice tests implemented on a computer-based system. Elimination testing that uses the same set of multiple-choice items rewards examinees with partial knowledge over those who are simply…

Synthesis and in Vitro and in Vivo Characterization of Highly β1-Selective β-Adrenoceptor Partial Agonists

PubMed Central

2013-01-01

β-Adrenoceptor antagonists boast a 50-year use for symptomatic control in numerous cardiovascular diseases. One might expect highly selective antagonists are available for the human β-adrenoceptor subtype involved in these diseases, yet few truly β1-selective molecules exist. To address this clinical need, we re-evaluated LK 204-545 (1),1 a selective β1-adrenoceptor antagonist, and discovered it possessed significant partial agonism. Removal of 1’s aromatic nitrile afforded 19, a ligand with similar β1-adrenoceptor selectivity and partial agonism (log KD of −7.75 and −5.15 as an antagonist of functional β1- and β2-mediated responses, respectively, and 34% of the maximal response of isoprenaline (β1)). In vitro β-adrenoceptor selectivity and partial agonism of 19 were mirrored in vivo. We designed analogues of 19 to improve affinity, selectivity, and partial agonism. Although partial agonism could not be fully attenuated, SAR suggests that an extended alkoxyalkoxy side chain, alongside substituents at the meta- or para-positions of the phenylurea, increases ligand affinity and β1-selectivity. PMID:23614528

Cardiovascular autonomic adaptation in lunar and martian gravity during parabolic flight.

PubMed

Widjaja, Devy; Vandeput, Steven; Van Huffel, Sabine; Aubert, André E

2015-06-01

Weightlessness has a well-known effect on the autonomic control of the cardiovascular system. With future missions to Mars in mind, it is important to know what the effect of partial gravity is on the human body. We aim to study the autonomic response of the cardiovascular system to partial gravity levels, as present on the Moon and on Mars, during parabolic flight. ECG and blood pressure were continuously recorded during parabolic flight. A temporal analysis of blood pressure and heart rate to changing gravity was conducted to study the dynamic response. In addition, cardiovascular autonomic control was quantified by means of heart rate (HR) and blood pressure (BP) variability measures. Zero and lunar gravity presented a biphasic cardiovascular response, while a triphasic response was noted during martian gravity. Heart rate and blood pressure are positively correlated with gravity, while the general variability of HR and BP, as well as vagal indices showed negative correlations with increasing gravity. However, the increase in vagal modulation during weightlessness is not in proportion when compared to the increase during partial gravity. Correlations were found between the gravity level and modulations in the autonomic nervous system during parabolic flight. Nevertheless, with future Mars missions in mind, more studies are needed to use these findings to develop appropriate countermeasures.

Modeling crown structural responses to competing vegetation control, thinning, fertilization, and Swiss needle cast in coastal Douglas-fir of the Pacific Northwest, USA.

Treesearch

A.R. Weiskittel; D.A. Maguire; R.A. Monserud

2007-01-01

Crown structure is a key variable influencing stand productivity, but its reported response to various stand factors has differed. This can be partially attributed to lack of a unified study on crown response to intensive management or stand health. In this analysis of several Douglas-fir (Pseudotsuga menziesii var. menziesii [...

Stress Responses among Divorcing Men and Women

ERIC Educational Resources Information Center

Chiriboga, David A.; Cutler, Loraine

1977-01-01

Explores behavioral and emotional responses during the divorce process. Men and women (N=252) were interviewed about traumas and advantages associated with stages of divorce already experienced. Results only partially substantiate finding by Goode that final separation is perceived as most traumatic. (Author)

DIESEL PARTICLE INSTILLATION ENHANCES INFLAMMATORY AND NEUROTROPHIN RESPONSES IN THE LUNGS OF ALLERGIC BALB/C MICE

EPA Science Inventory

Neurotrophins, including nerve growth factor (NGF) partially mediate many features of allergic airways disease including airways resistance and inflammation. Antibody blockade of NGF attenuates airways resistance associated with the allergen-specific airways responses in mice. ...

Genomic analysis of soybean defense response to Sclerotinia sclerotiorum

USDA-ARS?s Scientific Manuscript database

We have conducted microarray studies on changes in soybean transcript levels in response to Sclerotinia sclerotiorum infection. These stem inoculations enabled us to identify genes that are differentially expressed in soybean plants in partially resistant versus susceptible varieties. We are expandi...

Thin film oxygen partial pressure sensor

NASA Technical Reports Server (NTRS)

Wortman, J. J.; Harrison, J. W.; Honbarrier, H. L.; Yen, J.

1972-01-01

The development is described of a laboratory model oxygen partial pressure sensor using a sputtered zinc oxide thin film. The film is operated at about 400 C through the use of a miniature silicon bar. Because of the unique resistance versus temperature relation of the silicon bar, control of the operational temperature is achieved by controlling the resistance. A circuit for accomplishing this is described. The response of sputtered zinc oxide films of various thicknesses to oxygen, nitrogen, argon, carbon dioxide, and water vapor caused a change in the film resistance. Over a large range, film conductance varied approximately as the square root of the oxygen partial pressure. The presence of water vapor in the gas stream caused a shift in the film conductance at a given oxygen partial pressure. A theoretical model is presented to explain the characteristic features of the zinc oxide response to oxygen.

MYC Amplification as a Predictive Factor of Complete Pathologic Response to Docetaxel-based Neoadjuvant Chemotherapy for Breast Cancer.

PubMed

Pereira, Cynthia Brito Lins; Leal, Mariana Ferreira; Abdelhay, Eliana Saul Furquim Werneck; Demachki, Sâmia; Assumpção, Paulo Pimentel; de Souza, Mirian Carvalho; Moreira-Nunes, Caroline Aquino; Tanaka, Adriana Michiko da Silva; Smith, Marília Cardoso; Burbano, Rommel Rodríguez

2017-06-01

Neoadjuvant chemotherapy is a standard treatment for stage II and III breast cancer. The identification of biomarkers that may help in the prediction of response to neoadjuvant therapies is necessary for a more precise definition of the best drug or drug combination to induce a better response. We assessed the role of Ki67, hormone receptors expression, HER2, MYC genes and their protein status, and KRAS codon 12 mutations as predictor factors of pathologic response to anthracycline-cyclophosphamide (AC) followed by taxane docetaxel (T) neoadjuvant chemotherapy (AC+T regimen) in 51 patients with invasive ductal breast cancer. After neoadjuvant chemotherapy, 82.4% of patients showed pathologic partial response, with only 9.8% showing pathologic complete response. In multivariate analysis, MYC immunoreactivity and high MYC gain defined as MYC/nucleus ≥ 5 were significant predictor factors for pathologic partial response. Using the receiver operating characteristic curve analysis, the ratio of 2.5 MYC/CEP8 (sensitivity of 80% and specificity of 89.1%) or 7 MYC/nuclei copies (sensitivity of 80% and specificity of 73.9%) as the best cutoff in predicting a pathologic complete response was identified. Thus, MYC may have a role in chemosensitivity to AC and/or docetaxel drugs. Additionally, MYC amplification may be a predictor factor of pathologic response to the AC+T regimen in patients with breast cancer. Moreover, patients with an increased number of MYC copies showed pathologic complete response to this neoadjuvant treatment more frequently. The analysis of MYC amplification may help in the identification of patients that may have a better response to AC+T treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

Individualized Radiation Dose Escalation Based on the Decrease in Tumor FDG Uptake and Normal Tissue Constraints Improve Survival in Patients With Esophageal Carcinoma.

PubMed

Ma, Jinbo; Wang, Zhaoyang; Wang, Chengde; Chen, Ercheng; Dong, Yaozong; Song, Yipeng; Wang, Wei; You, Dong; Jiang, Wei; Zang, Rukun

2017-02-01

To determine whether individualized radiation dose escalation after planned chemoradiation based on the decrease in tumor and normal tissue constraints can improve survival in patients with esophageal carcinoma. From August 2005 to December 2010, 112 patients with squamous esophageal carcinoma were treated with radical concurrent chemoradiation. Patients received positron emission tomography-computer tomography scan twice, before radiation and after radiation dose of 50.4 Gy. All patients were noncomplete metabolic response groups according to the Response Evaluation Criteria in solid tumors. Only 52 patients with noncomplete metabolic response received individualized dose escalation based on tumor and normal tissue constraints. Survival and treatment failure were observed and analyzed using SPSS (13.0). The rate of complete metabolic response for patients with noncomplete metabolic response after dose escalation reached 17.3% (9 of 52). The 2-year overall survival rates for patients with noncomplete metabolic response in the conventional and dose-escalation groups were 20.5% and 42.8%, respectively( P = .001). The 2-year local control rates for patients were 35.7% and 76.2%, respectively ( P = .002). When patients were classified into partial metabolic response and no metabolic response, 2-year overall survival rates for patients with partial metabolic response were significantly different in conventional and dose-escalation groups (33.8% vs 78.4%; P = .000). The 2-year overall survival rates for patients with no metabolic response in two groups (8.6% vs 15.1%) did not significantly differ ( P = .917). Individualized radiation dose escalation has the potential to improve survival in patients with esophageal carcinoma according to increased rate of complete metabolic response. However, further trials are needed to confirm this and to identify patients who may benefit from dose escalation.

Tumor response ratio predicts overall survival in breast cancer patients treated with neoadjuvant chemotherapy.

PubMed

Miller, Marian; Ottesen, Rebecca A; Niland, Joyce C; Kruper, Laura; Chen, Steven L; Vito, Courtney

2014-10-01

Neoadjuvant chemotherapy (NAC) is commonly used to treat locally advanced breast cancer. Pathologic complete response (pCR) predicts improved overall survival (OS); however, prognosis of patients with partial response remains unclear. We evaluated whether tumor response ratio (TRR) is a better predictor of OS than current staging methods. Using the National Comprehensive Cancer Network Breast Cancer Outcomes Database, we identified patients with stage I-III breast cancer who had NAC and pretreatment imaging at City of Hope (1997-2010). Patient demographics, tumor characteristics, and OS were analyzed. TRR was calculated as residual in-breast disease divided by size on pre-NAC imaging. Four TRR groups were stratified; TRR 0 (pCR), TRR > 0-0.4 (strong partial response, SPR), TRR > 0.4-1.0 (weak partial response, WPR), or TRR > 1.0 (tumor growth, TG). OS was estimated by the Kaplan-Meier method and tested by the log-rank test. Cox regression was performed to evaluate associations between OS and TRR in a multivariable analysis while controlling for potential confounders. There were 218 eligible patients identified; 59 (27 %) had pCR, 61 (28 %) SPR, 72 (33 %) WPR, and 26 (12 %) TG. Five-year OS decreased continuously with increasing TRR:pCR (90 %), SPR (79 %), WPR (66 %), and TG (60 %). TRR was the only measure that significantly predicted OS (p = 0.0035); pathologic stage (p = 0.23) and pre-NAC clinical tumor stage (cT) (p = 0.87) were not significant. TRR continued to be statistically significant by multivariable analysis (p = 0.016). TRR takes into account both pretreatment and residual disease and more accurately predicts OS than pathologic stage and pre-NAC cT. TRR may be useful to more accurately assess prognosis and OS in breast cancer patients undergoing NAC.

Immunohistochemical expression of CD-10, BCL-6 and MUM-1 antibodies and immediate clinical response in patients of diffuse large B-cell lymphomas after six cycles of chemotherapy.

PubMed

Hassan, Usman; Ishtiaq, Sheeba; Hussain, Mudassar

2014-10-01

To determine the expression of CD-10, BCL-6 and MUM-1 in patients with diffuse large B-cell lymphoma (DLBCL) and its association with immediate clinical response after six cycles of CHOP chemotherapy. Analytical study. Armed Forces Institute of Pathology (AFIP), Rawalpindi in collaboration with Nuclear medicine, Oncology and Radiotherapy Institute (NORI), Islamabad from September 2010 to September 2011. CD-10, BCL-6 and MUM-1 antibodies were applied on cases diagnosed as DLBCL. Immediate clinical response was noted after 6 cycles of chemotherapy with the help of oncologist and divided into complete response, partial response, stable disease and relapse/ progression. Patient's age, results of expression of CD-10, BCL-6 and MUM-1 and results of immediate clinical response to chemotherapy were noted. Regarding analysis of prognostic markers (CD-10, BCL-6 and MUM-1), chi-square test was used for immediate clinical response to chemotherapy in DLBCL. CD-10 was positive in 40% cases, BCL-6 in 58.7% cases and MUM-1 was positive in 46.7% cases. About 41.3% of patients showed complete response, 10.6% partial response, 17.3% stable disease and 30.8% showed relapse/progression. CD-10 expression in DLBCL was associated with better immediate clinical response (p=0.011) whereas MUM-1 expression in DLBCL was associated with poor immediate clinical response (p<0.0001). However, there was no statistically significant association of BCL-6 with immediate clinical response (p=0.22). DLBCL shows expression of CD-10, BCL-6 and MUM-1 in nearly fifty percent of the cases. CD-10 is associated with good whereas MUM is associated with poor response. However, there was no association of BCL-6 with immediate clinical response.

Response of the water level in a well to Earth tides and atmospheric loading under unconfined conditions

USGS Publications Warehouse

Rojstaczer, Stuart; Riley, Francis S.

1990-01-01

The response of the water level in a well to Earth tides and atmospheric loading under unconfined conditions can be explained if the water level is controlled by the aquifer response averaged over the saturated depth of the well. Because vertical averaging tends to diminish the influence of the water table, the response is qualitatively similar to the response of a well under partially confined conditions. When the influence of well bore storage can be ignored, the response to Earth tides is strongly governed by a dimensionless aquifer frequency Q′u. The response to atmospheric loading is strongly governed by two dimensionless vertical fluid flow parameters: a dimensionless unsaturated zone frequency, R, and a dimensionless aquifer frequency Qu. The differences between Q′u and Qu are generally small for aquifers which are highly sensitive to Earth tides. When Q′u and Qu are large, the response of the well to Earth tides and atmospheric loading approaches the static response of the aquifer under confined conditions. At small values of Q′u and Qu, well response to Earth tides and atmospheric loading is strongly influenced by water table drainage. When R is large relative to Qu, the response to atmospheric loading is strongly influenced by attenuation and phase shift of the pneumatic pressure signal in the unsaturated zone. The presence of partial penetration retards phase advance in well response to Earth tides and atmospheric loading. When the theoretical response of a phreatic well to Earth tides and atmospheric loading is fit to the well response inferred from cross-spectral estimation, it is possible to obtain estimates of the pneumatic diffusivity of the unsaturated zone and the vertical hydraulic conductivity of the aquifer.

Pollution Response Systems Analysis

DOT National Transportation Integrated Search

1978-01-01

This study was initiated as part of the U.S. Coast Guard effort to provide adequate response within six hours for a spill of up to 100,000 ton of oil in U.S. waters. The guidelines and assumptions for the study are described, and partial results are ...

The Active Role of the Ocean in the Temporal Evolution of Climate Sensitivity

DOE PAGES

Garuba, Oluwayemi A.; Lu, Jian; Liu, Fukai; ...

2017-11-30

Here, the temporal evolution of the effective climate sensitivity is shown to be influenced by the changing pattern of sea surface temperature (SST) and ocean heat uptake (OHU), which in turn have been attributed to ocean circulation changes. A set of novel experiments are performed to isolate the active role of the ocean by comparing a fully coupled CO 2 quadrupling community Earth System Model (CESM) simulation against a partially coupled one, where the effect of the ocean circulation change and its impact on surface fluxes are disabled. The active OHU is responsible for the reduced effective climate sensitivity andmore » weaker surface warming response in the fully coupled simulation. The passive OHU excites qualitatively similar feedbacks to CO 2 quadrupling in a slab ocean model configuration due to the similar SST spatial pattern response in both experiments. Additionally, the nonunitary forcing efficacy of the active OHU (1.7) explains the very different net feedback parameters in the fully and partially coupled responses.« less

The Active Role of the Ocean in the Temporal Evolution of Climate Sensitivity

NASA Astrophysics Data System (ADS)

Garuba, Oluwayemi A.; Lu, Jian; Liu, Fukai; Singh, Hansi A.

2018-01-01

The temporal evolution of the effective climate sensitivity is shown to be influenced by the changing pattern of sea surface temperature (SST) and ocean heat uptake (OHU), which in turn have been attributed to ocean circulation changes. A set of novel experiments are performed to isolate the active role of the ocean by comparing a fully coupled CO2 quadrupling community Earth System Model (CESM) simulation against a partially coupled one, where the effect of the ocean circulation change and its impact on surface fluxes are disabled. The active OHU is responsible for the reduced effective climate sensitivity and weaker surface warming response in the fully coupled simulation. The passive OHU excites qualitatively similar feedbacks to CO2 quadrupling in a slab ocean model configuration due to the similar SST spatial pattern response in both experiments. Additionally, the nonunitary forcing efficacy of the active OHU (1.7) explains the very different net feedback parameters in the fully and partially coupled responses.

The Active Role of the Ocean in the Temporal Evolution of Climate Sensitivity

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

Garuba, Oluwayemi A.; Lu, Jian; Liu, Fukai

Here, the temporal evolution of the effective climate sensitivity is shown to be influenced by the changing pattern of sea surface temperature (SST) and ocean heat uptake (OHU), which in turn have been attributed to ocean circulation changes. A set of novel experiments are performed to isolate the active role of the ocean by comparing a fully coupled CO 2 quadrupling community Earth System Model (CESM) simulation against a partially coupled one, where the effect of the ocean circulation change and its impact on surface fluxes are disabled. The active OHU is responsible for the reduced effective climate sensitivity andmore » weaker surface warming response in the fully coupled simulation. The passive OHU excites qualitatively similar feedbacks to CO 2 quadrupling in a slab ocean model configuration due to the similar SST spatial pattern response in both experiments. Additionally, the nonunitary forcing efficacy of the active OHU (1.7) explains the very different net feedback parameters in the fully and partially coupled responses.« less

Understanding tree growth responses after partial cuttings: A new approach

PubMed Central

Rossi, Sergio; Lussier, Jean-Martin; Walsh, Denis; Morin, Hubert

2017-01-01

Forest ecosystem management heads towards the use of partial cuttings. However, the wide variation in growth response of residual trees remains unexplained, preventing a suitable prediction of forest productivity. The aim of the study was to assess individual growth and identify the driving factors involved in the responses of residual trees. Six study blocks in even-aged black spruce [Picea mariana (Mill.) B.S.P.] stands of the eastern Canadian boreal forest were submitted to experimental shelterwood and seed-tree treatments. Individual-tree models were applied to 1039 trees to analyze their patterns of radial growth during the 10 years after partial cutting by using the nonlinear Schnute function on tree-ring series. The trees exhibited different growth patterns. A sigmoid growth was detected in 32% of trees, mainly in control plots of older stands. Forty-seven percent of trees located in the interior of residual strips showed an S-shape, which was influenced by stand mortality, harvested intensity and dominant height. Individuals showing an exponential pattern produced the greatest radial growth after cutting and were edge trees of younger stands with higher dominant height. A steady growth decline was observed in 4% of trees, represented by the individuals suppressed and insensitive to the treatment. The analyses demonstrated that individual nonlinear models are able to assess the variability in growth within the stand and the factors involved in the occurrence of the different growth patterns, thus improving understanding of the tree responses to partial cutting. This new approach can sustain forest management strategies by defining the best conditions to optimize the growth yield of residual trees. PMID:28222200

Understanding tree growth responses after partial cuttings: A new approach.

PubMed

Montoro Girona, Miguel; Rossi, Sergio; Lussier, Jean-Martin; Walsh, Denis; Morin, Hubert

2017-01-01

Forest ecosystem management heads towards the use of partial cuttings. However, the wide variation in growth response of residual trees remains unexplained, preventing a suitable prediction of forest productivity. The aim of the study was to assess individual growth and identify the driving factors involved in the responses of residual trees. Six study blocks in even-aged black spruce [Picea mariana (Mill.) B.S.P.] stands of the eastern Canadian boreal forest were submitted to experimental shelterwood and seed-tree treatments. Individual-tree models were applied to 1039 trees to analyze their patterns of radial growth during the 10 years after partial cutting by using the nonlinear Schnute function on tree-ring series. The trees exhibited different growth patterns. A sigmoid growth was detected in 32% of trees, mainly in control plots of older stands. Forty-seven percent of trees located in the interior of residual strips showed an S-shape, which was influenced by stand mortality, harvested intensity and dominant height. Individuals showing an exponential pattern produced the greatest radial growth after cutting and were edge trees of younger stands with higher dominant height. A steady growth decline was observed in 4% of trees, represented by the individuals suppressed and insensitive to the treatment. The analyses demonstrated that individual nonlinear models are able to assess the variability in growth within the stand and the factors involved in the occurrence of the different growth patterns, thus improving understanding of the tree responses to partial cutting. This new approach can sustain forest management strategies by defining the best conditions to optimize the growth yield of residual trees.

Affective-associative two-process theory: a neurocomputational account of partial reinforcement extinction effects.

PubMed

Lowe, Robert; Almér, Alexander; Billing, Erik; Sandamirskaya, Yulia; Balkenius, Christian

2017-12-01

The partial reinforcement extinction effect (PREE) is an experimentally established phenomenon: behavioural response to a given stimulus is more persistent when previously inconsistently rewarded than when consistently rewarded. This phenomenon is, however, controversial in animal/human learning theory. Contradictory findings exist regarding when the PREE occurs. One body of research has found a within-subjects PREE, while another has found a within-subjects reversed PREE (RPREE). These opposing findings constitute what is considered the most important problem of PREE for theoreticians to explain. Here, we provide a neurocomputational account of the PREE, which helps to reconcile these seemingly contradictory findings of within-subjects experimental conditions. The performance of our model demonstrates how omission expectancy, learned according to low probability reward, comes to control response choice following discontinuation of reward presentation (extinction). We find that a PREE will occur when multiple responses become controlled by omission expectation in extinction, but not when only one omission-mediated response is available. Our model exploits the affective states of reward acquisition and reward omission expectancy in order to differentially classify stimuli and differentially mediate response choice. We demonstrate that stimulus-response (retrospective) and stimulus-expectation-response (prospective) routes are required to provide a necessary and sufficient explanation of the PREE versus RPREE data and that Omission representation is key for explaining the nonlinear nature of extinction data.

Effect of radiation therapy on bronchial obstruction due to bronchogenic carcinoma

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

Chetty, K.G.; Moran, E.M.; Sassoon, C.S.

1989-03-01

We evaluated the effect of radiation therapy in 57 patients with obstruction of a large bronchus with NSCC. Response with aeration of the atelectatic lung was seen in 12 patients (21 percent). Three patients (5 percent) showed partial response with persistent partial atelectasis, and nine patients (16 percent) showed good response with complete aeration of the atelectatic lung. In these patients the response appeared to be related to the dose of radiation. All of the patients who responded received more than 50 Gy. The difference in the response rate related to the dose of radiation was statistically significant (p lessmore » than 0.05). The rates were similar with all histologic types of NSCC. Regardless of the clinical response observed, bronchoscopy performed two to four months after completion of radiation therapy in 14 patients revealed persistent endobronchial tumor. There was no significant relationship between the persistence of endobronchial tumor, the dose of radiation therapy, and the tumor's histologic type. Of the 12 patients with radiographic improvement in atelectasis, fibrotic changes developed in four (33 percent) patients and pneumonitis in two (17 percent). Progression of disease with distant metastases occurred in 58 percent (seven) of the 12 patients who showed a clinical response of their bronchial obstruction. The median time to survival was nearly identical in responders and nonresponders.« less

Knowing the future: partial foreknowledge effects on the programming of prosaccades and antisaccades.

PubMed

Abegg, Mathias; Manoach, Dara S; Barton, Jason J S

2011-01-01

Foreknowledge about the demands of an upcoming trial may be exploited to optimize behavioural responses. In the current study we systematically investigated the benefits of partial foreknowledge--that is, when some but not all aspects of a future trial are known in advance. For this we used an ocular motor paradigm with horizontal prosaccades and antisaccades. Predictable sequences were used to create three partial foreknowledge conditions: one with foreknowledge about the stimulus location only, one with foreknowledge about the task set only, and one with foreknowledge about the direction of the required response only. These were contrasted with a condition of no-foreknowledge and a condition of complete foreknowledge about all three parameters. The results showed that the three types of foreknowledge affected saccadic efficiency differently. While foreknowledge about stimulus-location had no effect on efficiency, task foreknowledge had some effect and response-foreknowledge was as effective as complete foreknowledge. Foreknowledge effects on switch costs followed a similar pattern in general, but were not specific for switching of the trial attribute for which foreknowledge was available. We conclude that partial foreknowledge has a differential effect on efficiency, most consistent with preparatory activation of a motor schema in advance of the stimulus, with consequent benefits for both switched and repeated trials. Copyright © 2010 Elsevier Ltd. All rights reserved.

Dialogue between E. coli free radical pathways and the mitochondria of C. elegans.

PubMed

Govindan, J Amaranath; Jayamani, Elamparithi; Zhang, Xinrui; Mylonakis, Eleftherios; Ruvkun, Gary

2015-10-06

The microbial world presents a complex palette of opportunities and dangers to animals, which have developed surveillance and response strategies to hints of microbial intent. We show here that the mitochondrial homeostatic response pathway of the nematode Caenorhabditis elegans responds to Escherichia coli mutations that activate free radical detoxification pathways. Activation of C. elegans mitochondrial responses could be suppressed by additional mutations in E. coli, suggesting that C. elegans responds to products of E. coli to anticipate challenges to its mitochondrion. Out of 50 C. elegans gene inactivations known to mediate mitochondrial defense, we found that 7 genes were required for C. elegans response to a free radical producing E. coli mutant, including the bZip transcription factor atfs-1 (activating transcription factor associated with stress). An atfs-1 loss-of-function mutant was partially resistant to the effects of free radical-producing E. coli mutant, but a constitutively active atfs-1 mutant growing on wild-type E. coli inappropriately activated the pattern of mitochondrial responses normally induced by an E. coli free radical pathway mutant. Carbonylated proteins from free radical-producing E. coli mutant may directly activate the ATFS-1/bZIP transcription factor to induce mitochondrial stress response: feeding C. elegans with H2O2-treated E. coli induces the mitochondrial unfolded protein response, and inhibition of a gut peptide transporter partially suppressed C. elegans response to free radical damaged E. coli.

Phenobarbital for Neonatal Seizures: Response Rate and Predictors of Refractoriness.

PubMed

Spagnoli, Carlotta; Seri, Stefano; Pavlidis, Elena; Mazzotta, Silvia; Pelosi, Annalisa; Pisani, Francesco

2016-10-01

Background Phenobarbital is the first-line choice for neonatal seizures treatment, despite a response rate of approximately 45%. Failure to respond to acute anticonvulsants is associated with poor neurodevelopmental outcome, but knowledge on predictors of refractoriness is limited. Objective To quantify response rate to phenobarbital and to establish variables predictive of its lack of efficacy. Methods We retrospectively evaluated newborns with electrographically confirmed neonatal seizures admitted between January 1999 and December 2012 to the neonatal intensive care unit of Parma University Hospital (Italy), excluding neonates with status epilepticus. Response was categorized as complete (cessation of clinical and electrographic seizures after phenobarbital administration), partial (reduction but not cessation of electrographic seizures with the first bolus, response to the second bolus), or absent (no response after the second bolus). Multivariate analysis was used to identify independent predictors of refractoriness. Results Out of 91 newborns receiving phenobarbital, 57 (62.6%) responded completely, 15 (16.5%) partially, and 19 (20.9%) did not respond. Seizure type (p = 0.02), background electroencephalogram (EEG; p ≤ 0.005), and neurologic examination (p  ≤  0.005) correlated with response to phenobarbital. However, EEG (p  ≤  0.02) and seizure type (p  ≤  0.001) were the only independent predictors. Conclusion Our results suggest a prominent role of neurophysiological variables (background EEG and electrographic-only seizure type) in predicting the absence of response to phenobarbital in high-risk newborns. Georg Thieme Verlag KG Stuttgart · New York.

The Effects of Partial Reinforcement in the Acquisition and Extinction of Recurrent Serial Patterns.

ERIC Educational Resources Information Center

Dockstader, Steven L.

The purpose of these 2 experiments was to determine whether sequential response pattern behavior is affected by partial reinforcement in the same way as other behavior systems. The first experiment investigated the partial reinforcement extinction effects (PREE) in a sequential concept learning task where subjects were required to learn a…

Stepwise Analysis of Differential Item Functioning Based on Multiple-Group Partial Credit Model.

ERIC Educational Resources Information Center

Muraki, Eiji

1999-01-01

Extended an Item Response Theory (IRT) method for detection of differential item functioning to the partial credit model and applied the method to simulated data using a stepwise procedure. Then applied the stepwise DIF analysis based on the multiple-group partial credit model to writing trend data from the National Assessment of Educational…

(131)I-MIBG therapy for malignant paraganglioma and phaeochromocytoma: systematic review and meta-analysis.

PubMed

van Hulsteijn, L T; Niemeijer, N D; Dekkers, O M; Corssmit, E P M

2014-04-01

(131)I-MIBG therapy can be used for palliative treatment of malignant paraganglioma and phaeochromocytoma. The main objective of this study was to perform a systematic review and meta-analysis assessing the effect of (131)I-MIBG therapy on tumour volume in patients with malignant paraganglioma/phaeochromocytoma. A literature search was performed in December 2012 to identify potentially relevant studies. Main outcomes were the pooled proportions of complete response, partial response and stable disease after radionuclide therapy. A meta-analysis was performed with an exact likelihood approach using a logistic regression with a random effect at the study level. Pooled proportions with 95% confidence intervals (CI) were reported. Seventeen studies concerning a total of 243 patients with malignant paraganglioma/phaeochromocytoma were treated with (131)I-MIBG therapy. The mean follow-up ranged from 24 to 62 months. A meta-analysis of the effect of (131)I-MIBG therapy on tumour volume showed pooled proportions of complete response, partial response and stable disease of, respectively, 0·03 (95% CI: 0·06-0·15), 0·27 (95% CI: 0·19-0·37) and 0·52 (95% CI: 0·41-0·62) and for hormonal response 0·11 (95% CI: 0·05-0·22), 0·40 (95% CI: 0·28-0·53) and 0·21 (95% CI: 0·10-0·40), respectively. Separate analyses resulted in better results in hormonal response for patients with paraganglioma than for patients with phaeochromocytoma. Data on the effects of (131)I-MIBG therapy on malignant paraganglioma/phaeochromocytoma suggest that stable disease concerning tumour volume and a partial hormonal response can be achieved in over 50% and 40% of patients, respectively, treated with (131)I-MIBG therapy. It cannot be ruled out that stable disease reflects not only the effect of MIBG therapy, but also (partly) the natural course of the disease. © 2013 John Wiley & Sons Ltd.

Phase II study of the safety and antitumor activity of the hypoxia-activated prodrug TH-302 in combination with doxorubicin in patients with advanced soft tissue sarcoma.

PubMed

Chawla, Sant P; Cranmer, Lee D; Van Tine, Brian A; Reed, Damon R; Okuno, Scott H; Butrynski, James E; Adkins, Douglas R; Hendifar, Andrew E; Kroll, Stew; Ganjoo, Kristen N

2014-10-10

TH-302, a prodrug of the cytotoxic alkylating agent bromo-isophosphoramide mustard, is preferentially activated in hypoxic conditions. This phase II study investigated TH-302 in combination with doxorubicin, followed by single-agent TH-302 maintenance therapy in patients with first-line advanced soft tissue sarcoma (STS) to assess progression-free survival (PFS), response rate, overall survival, safety, and tolerability. In this open-label phase II study, TH-302 300 mg/m(2) was administered intravenously on days 1 and 8 with doxorubicin 75 mg/m(2) on day 1 of each 21-day cycle. After six cycles, patients with stable and/or responding disease could receive maintenance monotherapy with TH-302. Ninety-one patients initiated TH-302 plus doxorubicin induction treatment. The PFS rate at 6 months (primary efficacy measure) was 58% (95% CI, 46% to 68%). Median PFS was 6.5 months (95% CI, 5.8 to 7.7 months); median overall survival was 21.5 months (95% CI, 16.0 to 26.2 months). Best tumor responses were complete response (n = 2 [2%]) and partial response (n = 30 [34%]). During TH-302 maintenance (n = 48), five patients improved from stable disease to partial response, and one patient improved from partial to complete response. The most common adverse events during induction were fatigue, nausea, and skin and/or mucosal toxicities as well as anemia, thrombocytopenia, and neutropenia. These were less severe and less frequent during maintenance. There was no evidence of TH-302-related hepatic, renal, or cardiac toxicity. PFS, overall survival, and tumor response compared favorably with historical outcomes achieved with other first-line chemotherapies for advanced STS. A phase III study of TH-302 is ongoing (NCT01440088). © 2014 by American Society of Clinical Oncology.

Mediators of a brief hypnosis intervention to control side effects in breast surgery patients: Response expectancies and emotional distress

PubMed Central

Montgomery, Guy H.; Hallquist, Michael N.; Schnur, Julie B.; David, Daniel; Silverstein, Jeffrey H.; Bovbjerg, Dana H.

2010-01-01

Hypnosis is widely recognized as an empirically supported intervention to improve postsurgical outcomes. However, to date, no research has examined mediators of hypnotic benefit among surgery patients. The present study was designed to test the hypotheses that response expectancies and emotional distress would mediate the effects of an empirically validated presurgical hypnosis intervention on postsurgical side effects (i.e., pain, nausea, and fatigue). In a sample of 200 women undergoing breast conserving surgery (mean age = 48.50 years), structural equation modeling revealed the following: 1) hypnotic effects on postsurgical pain were partially mediated by pain expectancy (p< .0001), but not by distress (p=.12); 2) hypnotic effects on postsurgical nausea were partially mediated by presurgical distress (p=.02), but not by nausea expectancy (p=.10); 3) hypnotic effects on postsurgical fatigue were partially mediated by both fatigue expectancy (p=.0001) and presurgical distress (p=.02). These results improve understanding of the underlying mechanisms responsible for hypnotic phenomena in the surgical setting, and suggest that future hypnotic interventions target patient expectancies and distress to improve postsurgical recovery. PMID:20099953

The Effects of Cold Exposure on Wet Aircraft Passengers: A Review

DTIC Science & Technology

1994-05-01

Gauquelin, G. Hormonal responses adrenal medulla. In Guyton A.C. Textbook ofMedi- to exercise during moderate cold exposure in young cal...The physiological responses to partial wetting and subscqumnt exposure to cold environmental conditions have not been studied. The effects of cold... responses to maintain thermal balance. Body heat balance is one of the most well regulated The preoptic area of the hypothalamus has recep- control

Durable responses and reversible toxicity of high-dose interleukin-2 treatment of melanoma and renal cancer in a Community Hospital Biotherapy Program.

PubMed

Payne, Roxanne; Glenn, Lyn; Hoen, Helena; Richards, Beverley; Smith, John W; Lufkin, Robert; Crocenzi, Todd S; Urba, Walter J; Curti, Brendan D

2014-01-01

High-dose interleukin-2 (IL-2) has been FDA-approved for over 20 years, but it is offered only at a small number of centers with expertise in its administration. We analyzed the outcomes of patients receiving high-dose IL-2 in relation to the severity of toxicity to ascertain if response or survival were adversely affected. A retrospective analysis of the outcomes of 500 patients with metastatic renal cell carcinoma (RCC) (n = 186) or melanoma (n = 314) treated with high-dose IL-2 between 1997 and 2012 at Providence Cancer Center was performed. IL-2 was administered at a dose of 600,000 international units per kg by IV bolus every 8 hours for up to 14 doses. A second cycle was administered 16 days after the first and patients with tumor regression could receive additional cycles. Survival and anti-tumor response were analyzed by diagnosis, severity of toxicity, number of IL-2 cycles and subsequent therapy. The objective response rate in melanoma was 28% (complete 12% and partial 16%), and in RCC was 24% (complete 7% and partial 17%). The 1-, 2- and 3-year survivals were 59%, 41% and 31%, for melanoma and 75%, 56% and 44%, for RCC, respectively. The proportion of patients with complete or partial response in both melanoma and RCC was higher in patients who a) required higher phenylephrine doses to treat hypotension (p < 0.003), b) developed acidosis (bicarbonate < 19 mmol (p < 0.01)), or c) thrombocytopenia (<50, 50-100, >100,000 platelets; p < 0.025). The proportion achieving a complete or partial response was greater in patients with melanoma who received 5 or more compared with 4 or fewer IL-2 cycles (p < 0.0001). The incidence of death from IL-2 was less than 1% and was not higher in patients who required phenylephrine. High-dose IL-2 can be administered safely; severe toxicity including hypotension is reversible and can be managed in a community hospital. The tumor response and survival reported here are superior to the published literature and support treating patients to their individualized maximum tolerated dose. IL-2 should remain part of the treatment paradigm in selected patients with melanoma and RCC.

Toxicity and response in cats with neoplasia treated with toceranib phosphate.

PubMed

Harper, Aaron; Blackwood, Laura

2017-06-01

Objectives Toceranib phosphate is a tyrosine kinase inhibitor licensed for the treatment of non-resectable Patnaik grade II/III recurrent cutaneous mast cell tumours in dogs. There is no information in cats regarding the tolerated dose, toxicity or tumour response of this drug. The aim of this study was to analyse retrospectively a cohort of cats with advanced neoplasia treated with toceranib to identify toxicity and response. Methods The medical records of the Small Animal Teaching Hospital were reviewed. Cats were included if they had received toceranib for at least 2 weeks for the treatment of histologically or cytologically confirmed neoplastic disease, and had at least one set of monitoring blood tests (haematology, biochemistry) performed after baseline tests. Toxicity was graded according to the Veterinary Comparative Oncology Group - common terminology criteria for adverse events(VCOG-CTCAE) and response was measured according to Response Evaluation In Solid Tumors (RECIST) criteria. Results Fourteen cats met the inclusion criteria, the majority of which (13/14) had received previous therapy (surgery, radiotherapy, chemotherapy). The most common tumour types were mast cell tumours or malignant epithelial tumours. Toxicity occurred in 10/14 cats - 10 cats had mild myelosuppression or gastrointestinal effects. Two cats developed severe hepatoxicity. One cat died from congestive heart failure, although whether this was related to toceranib therapy is unknown. Regarding response, one cat achieved complete response; two cats achieved partial response and five cats achieved stable disease: overall biological response rate was 57.1%. All of the cats that achieved either partial or complete response were treated for mast cell disease. Overall median duration of response was 90 days (range 14-570 days). None of the cats with squamous cell carcinoma achieved a response. Conclusions and relevance Toceranib phosphate is generally well tolerated in cats, with toxicity limited to mild gastrointestinal or myelosuppressive effects in the majority of cases (10/14) in this study; however, hepatotoxicity is a concern. Response to treatment in this small cohort was similar to that reported in dogs.

USE OF SEDIMENT PROFILE IMAGERY TO ESTIMATE NEAR-BOTTOM DISSOLVED OXYGEN REGIMES

EPA Science Inventory

The U.S. EPA, Atlantic Ecology Division is developing empirical stressor-response models for nitrogen pollution in partially enclosed coastal systems using dissolved oxygen (DO) as one of the system responses. We are testing a sediment profile image camera as a surrogate indicat...

49 CFR 234.106 - Partial activation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Partial activation. 234.106 Section 234.106 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION GRADE CROSSING SIGNAL SYSTEM SAFETY AND STATE ACTION PLANS Response to Reports...

49 CFR 234.106 - Partial activation.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Partial activation. 234.106 Section 234.106 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION GRADE CROSSING SIGNAL SYSTEM SAFETY AND STATE ACTION PLANS Response to Reports...

Using Covert Response Activation to Test Latent Assumptions of Formal Decision-Making Models in Humans.

PubMed

Servant, Mathieu; White, Corey; Montagnini, Anna; Burle, Borís

2015-07-15

Most decisions that we make build upon multiple streams of sensory evidence and control mechanisms are needed to filter out irrelevant information. Sequential sampling models of perceptual decision making have recently been enriched by attentional mechanisms that weight sensory evidence in a dynamic and goal-directed way. However, the framework retains the longstanding hypothesis that motor activity is engaged only once a decision threshold is reached. To probe latent assumptions of these models, neurophysiological indices are needed. Therefore, we collected behavioral and EMG data in the flanker task, a standard paradigm to investigate decisions about relevance. Although the models captured response time distributions and accuracy data, EMG analyses of response agonist muscles challenged the assumption of independence between decision and motor processes. Those analyses revealed covert incorrect EMG activity ("partial error") in a fraction of trials in which the correct response was finally given, providing intermediate states of evidence accumulation and response activation at the single-trial level. We extended the models by allowing motor activity to occur before a commitment to a choice and demonstrated that the proposed framework captured the rate, latency, and EMG surface of partial errors, along with the speed of the correction process. In return, EMG data provided strong constraints to discriminate between competing models that made similar behavioral predictions. Our study opens new theoretical and methodological avenues for understanding the links among decision making, cognitive control, and motor execution in humans. Sequential sampling models of perceptual decision making assume that sensory information is accumulated until a criterion quantity of evidence is obtained, from where the decision terminates in a choice and motor activity is engaged. The very existence of covert incorrect EMG activity ("partial error") during the evidence accumulation process challenges this longstanding assumption. In the present work, we use partial errors to better constrain sequential sampling models at the single-trial level. Copyright © 2015 the authors 0270-6474/15/3510371-15$15.00/0.

Marginal ridge fracture resistance, microleakage and pulpal response to glass ionomer/glass cermet partial tunnel restorations.

PubMed

Prabhu, N T; Munshi, A K; Shetty, T R

1997-01-01

Sixty sound premolars which were to be extracted for orthodontic treatment purposes were restored either with glass ionomer cement or glass cermet cements after partial tunnel preparation, and prior to the extraction after a time interval of 30 and 60 days respectively. The teeth were then subjected to marginal ridge fracture resistance, microleakage study using dye penetration and histological evaluation of the pulpal response to these materials. Both the materials exhibited increase in marginal ridge fracture resistance at 60 days, with minimal degree of microleakage and were biologically compatible with the dental pulp.

Public Use of Academic Libraries in Virginia.

ERIC Educational Resources Information Center

McCulley, Lucretia; Ream, Dan

1988-01-01

The directors of 40 academic libraries in Virginia were surveyed to obtain information on their practices relating to public access, services, and fees in their libraries. Complete or partial responses were received from 21 libraries in private institutions and 14 from state-supported institutions. These responses indicate that all of the…

Development of new physical activity and sedentary behavior change self-efficacy questionnaires using item response modeling

USDA-ARS?s Scientific Manuscript database

Theoretically, increased levels of physical activity self-efficacy (PASE) should lead to increased physical activity, but few studies have reported this effect among youth. This failure may be at least partially attributable to measurement limitations. In this study, Item Response Modeling (IRM) was...

Accounting for Cheating: An Evolving Theory and Emergent Themes

ERIC Educational Resources Information Center

Brent, Edward; Atkisson, Curtis

2011-01-01

This study examines student responses to the question, "What circumstances, if any, could make cheating justified?" It then assesses how well those responses can be classified by existing theories and categories that emerge from a qualitative analysis of the data. Results show considerable support for techniques of neutralization, partial support…

BLOCKADE OF TRKA OR P75 NEUROTROPHIN RECEPTORS ATTENUATES DIESEL PARTICULATE-INDUCED ENHANCEMENT OF ALLERGIC AIRWAYS RESPONSES IN BALB/C MICE

EPA Science Inventory

Neurotrophins, including nerve growth factor (NGF) partially mediate many features of allergic airways disease including airway resistance. Exposure to diesel exhaust particles (DEP) associated with the combustion of diesel fuel exacerbates allergic airways responses. We tested t...

[Prediction of the molecular response to pertubations from single cell measurements].

PubMed

Remacle, Françoise; Levine, Raphael D

2014-12-01

The response of protein signalization networks to perturbations is analysed from single cell measurements. This experimental approach allows characterizing the fluctuations in protein expression levels from cell to cell. The analysis is based on an information theoretic approach grounded in thermodynamics leading to a quantitative version of Le Chatelier principle which allows to predict the molecular response. Two systems are investigated: human macrophages subjected to lipopolysaccharide challenge, analogous to the immune response against Gram-negative bacteria and the response of the proteins involved in the mTOR signalizing network of GBM cancer cells to changes in partial oxygen pressure. © 2014 médecine/sciences – Inserm.

Topical Modulation of the Burn Wound Inflammatory Response to Improve Short and Long Term Outcomes

DTIC Science & Technology

2017-10-01

casualty, treatment, organ failure, systemic inflammatory response syndrome , thermal injury, wound model, intervention 3. ACCOMPLISHMENTS:   What...thickness burns have a blister response. Using human eye or H&E studies, we did not observe any blisters in the pig model. However, the OCT...the deeper the partial thickness burn, the bigger the blister, until it gets close to full-thickness burns. The full-thickness burns are dry and

Polytomous versus Dichotomous Scoring on Multiple-Choice Examinations: Development of a Rubric for Rating Partial Credit

ERIC Educational Resources Information Center

Grunert, Megan L.; Raker, Jeffrey R.; Murphy, Kristen L.; Holme, Thomas A.

2013-01-01

The concept of assigning partial credit on multiple-choice test items is considered for items from ACS Exams. Because the items on these exams, particularly the quantitative items, use common student errors to define incorrect answers, it is possible to assign partial credits to some of these incorrect responses. To do so, however, it becomes…

Engine-Operating Load Influences Diesel Exhaust Composition and Cardiopulmonary and Immune Responses

PubMed Central

Campen, Matthew J.; Harrod, Kevin S.; Seagrave, JeanClare; Seilkop, Steven K.; Mauderly, Joe L.

2011-01-01

Background: The composition of diesel engine exhaust (DEE) varies by engine type and condition, fuel, engine operation, and exhaust after treatment such as particle traps. DEE has been shown to increase inflammation, susceptibility to infection, and cardiovascular responses in experimentally exposed rodents and humans. Engines used in these studies have been operated at idle, at different steady-state loads, or on variable-load cycles, but exposures are often reported only as the mass concentration of particulate matter (PM), and the effects of different engine loads and the resulting differences in DEE composition are unknown. Objectives: We assessed the impacts of load-related differences in DEE composition on models of inflammation, susceptibility to infection, and cardiovascular toxicity. Methods: We assessed inflammation and susceptibility to viral infection in C57BL/6 mice and cardiovascular toxicity in APOE–/– mice after being exposed to DEE generated from a single-cylinder diesel generator operated at partial or full load. Results: At the same PM mass concentration, partial load resulted in higher proportions of particle organic carbon content and a smaller particle size than did high load. Vapor-phase hydrocarbon content was greater at partial load. Compared with high-load DEE, partial-load DEE caused greater responses in heart rate and T-wave morphology, in terms of both magnitude and rapidity of onset of effects, consistent with previous findings that systemic effects may be driven largely by the gas phase of the exposure atmospheres. However, high-load DEE caused more lung inflammation and greater susceptibility to viral infection than did partial load. Conclusions: Differences in engine load, as well as other operating variables, are important determinants of the type and magnitude of responses to inhaled DEE. PM mass concentration alone is not a sufficient basis for comparing or combining results from studies using DEE generated under different conditions. PMID:21524982

Physiological and behavioral stress parameters in calves in response to partial scrotal resection, orchidectomy, and Burdizzo castration.

PubMed

Pieler, D; Peinhopf, W; Becher, A C; Aurich, J E; Rose-Meierhöfer, S; Erber, R; Möstl, E; Aurich, C

2013-10-01

Establishing artificial cryptorchids by partial scrotal resection without removing the testicles is a technique for castration of bull calves that recently has gained new interest. In contrast to orchidectomy and Burdizzo castration, the stress response of calves to shortening of the scrotum is unknown. In this study, partial scrotal resection in bull calves was compared with orchidectomy, Burdizzo castration, and controls without intervention (n=10 per group, ages 56 ± 3 d). Procedures were performed under xylazine sedation and local anesthesia. We hypothesized that partial scrotal resection is least stressful. Salivary cortisol, heart rate, heart rate variability, behavior, and locomotion were analyzed. Cortisol concentration peaked 60 min after start of the procedures. Cortisol release was at least in part xylazine induced and none of the experimental procedures released additional cortisol. Heart rate increased in calves of all groups with initial handling, but immediately after xylazine sedation decreased to 30% below initial values and was not modified by surgical procedures. The heart rate variability variables standard deviation of beat-to-beat interval and root mean square of successive beat-to-beat differences increased when calves were placed on the surgery table but effects were similar in calves submitted to surgeries and control calves. Locomotion increased, whereas lying time decreased in response to all surgeries. Locomotion increase was most pronounced after orchidectomy. Plasma fibrinogen concentrations increased after orchidectomy only. With adequate pain medication, orchidectomy, Burdizzo castration, and partial scrotal resection do not differ with regard to acute stress and, by inference, pain. Partial scrotal resection when carried out under xylazine sedation and local anesthesia thus is an acceptable castration technique in bull calves. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

The behavioural importance of dynamically activated descending inhibition from the nucleus reticularis gigantocellularis pars alpha.

PubMed

Azami, J; Green, D L; Roberts, M H; Monhemius, R

2001-05-01

We have recently demonstrated (J Physiol 506 (1998) 459) that the dynamic activation of descending inhibition of the nociceptive response of spinal multireceptive cells occurs in the nucleus reticularis gigantocellularis pars alpha (GiA). In the same paper we have shown that Lamina I dorsal horn cells are responsible for activating this inhibition via a pathway which runs in the contralateral dorsolateral funiculus. The effects of dynamically activating this system by noxious stimulation on behavioural responses to noxious stimuli have not been established. Here we demonstrate the effects of GiA on the behavioural response during application of standardized noxious stimuli. As this system is activated in response to noxious stimulation (J Physiol 506 (1998) 459), it is possible that chronic pain states may also activate GiA. We have therefore investigated this possibility in animals following partial sciatic nerve ligation (an animal model of chronic pain; Pain 43 (1990) 205). Male Wistar rats (280-310 g) were anaesthetized with halothane (0.5-2% in O(2)). Guide cannulae for microinjections were stereotaxically placed above GiA. In one group of animals the sciatic nerve was partially ligated. Animals were allowed to recover for 4-6 days. The responses of each animal during the formalin test (Pain 4 (1977) 161) and the tail flick test (Pain 12 (1982) 229) were recorded on different days. Microinjections (0.5 microl) of either gamma-aminobutyric acid (GABA, 200 mM), D-L homocysteic acid (DLH, 25 mM) or 0.9% saline (as control) into GiA were performed during these tests in a randomized, blind manner. In animals without sciatic nerve ligation, microinjection of GABA to GiA did not significantly affect the animal's response during the tail flick test. However microinjection of DLH significantly increased the latency of tail flick from 6.2 +/- 0.8 to 8.4 +/- 0.5 s for up to 15 min (n = 7, P < 0.01, Mann-Whitney U-test). Microinjection of GABA to GiA increased the behavioural response to formalin between 10 and 20 min post-injection, while microinjection of DLH reduced this response at all time points except 10 min post-injection (n = 8, P < 0.05, Mann-Whitney U-test). In animals with sciatic nerve ligation, microinjections (0.5 microl) of either GABA (200 mM), or saline (as control) into GiA contralateral to the partial sciatic ligation were performed during these tests in a randomized, blind manner. Partial sciatic ligation significantly reduced the behavioural response to contralaterally applied formalin from 15 min post-injection onwards, compared to controls without sciatic nerve ligation. Microinjection of GABA to GiA significantly increased the behavioural response to formalin from 20 to 50 min post-injection. The inactivation of GiA only causes behavioural effects in nociceptive tests of a long enough duration to activate the system (i.e. the formalin test but not the tail flick test). Chemical activation of the system affects both tests. These data strongly support the concept of an important analgesic system which is activated in response to noxious stimulation, and subsequently acts to reduce behavioural responses to noxious stimuli.

Genetic stability of physiological responses to defoliation in a eucalypt and altered chemical defence in regrowth foliage.

PubMed

Borzak, Christina L; Potts, Brad M; Barry, Karen M; Pinkard, Elizabeth A; O'Reilly-Wapstra, Julianne M

2017-02-01

Defoliation may initiate physiological recovery and chemical defence mechanisms that allow a plant to improve fitness after damage. Such responses may result in changes in plant resource allocation that influence growth and foliar chemistry. In this study, we investigated the nature and stability of the defoliation response of juvenile plants from three divergent populations of Eucalyptus globulus Labill. A partial defoliation treatment that removed all upper crown leaves and the apical buds was applied to plants sourced from eight families from each of three populations representing contrasting chemical resistance to mammalian herbivory. Growth, photosynthetic rate and chlorophyll content were assessed pre-defoliation and periodically up to 12 weeks post-defoliation. The content of key plant primary and secondary metabolites was assessed pre-defoliation, at 12 weeks post-defoliation in the old foliage (positioned below the point of defoliation) and in the new foliage of the control plants and regrowth (from axillary buds) on the defoliated plants. There were clear treatment impacts on physiological responses, growth and foliar chemical traits, but despite significant constitutive differences in physiology, growth and chemistry the three E. globulus populations did not vary in their response to foliage loss. Distinct physiological responses to defoliation were observed with treatment plants showing significant up-regulation of photosynthetic rate and increased chlorophyll content in the old foliage remaining in the lower crown. There was a significant increase in the concentrations of a number of foliar chemical compounds in the regrowth arising from previously dormant axillary buds compared with new growth derived from apical meristems. There were changes in biomass allocation; defoliated plants had increased branching and leaf biomass, with changes in regrowth morphology to increase light capture. This study argues for multiple responses of E. globulus juveniles to defoliation involving apical bud loss, including elevated chemical defences matched with increased growth. From a chemical defence perspective, these responses create an enhanced chemical mosaic to the herbivore, with leaves remaining after partial browsing potentially being more palatable than the regrowth. This study demonstrates the multiple independent strategies plants may use to respond to partial defoliation and emphasizes the dynamic interplay between growth and defence in the recovery response. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Influence of dopaminergic medication on automatic postural responses and balance impairment in Parkinson's disease.

PubMed

Bloem, B R; Beckley, D J; van Dijk, J G; Zwinderman, A H; Remler, M P; Roos, R A

1996-09-01

It is still unclear why balance impairment in Parkinson's disease (PD) often responds insufficiently to dopaminergic medication. We have studied this issue in 23 patients with idiopathic PD and 24 healthy controls. Our specific purposes were (a) to investigate the contribution of abnormal automatic postural responses to balance impairment in PD and (b) to assess the influence of dopaminergic medication on abnormal automatic postural responses and balance impairment. Standing subjects received 4 degrees "toe-up" rotational perturbations of a supporting forceplate. We bilaterally recorded posturally destabilizing medium latency (ML) responses from the stretched gastrocnemius muscles and functionally corrective long latency (LL) responses from the shortened tibialis anterior (TA) muscles. We also assessed changes in the center of foot pressure (CFP) and the center of gravity (COG). All patients were tested in the "off" and "on" phases. All controls were tested and retested after 1 h. During the off phase, we found enlarged ML amplitudes and diminished LL amplitudes in patients, together with a markedly increased posterior displacement of the COG. The abnormal ML and LL responses were partially responsible for the increased body sway in patients because the initial forward (destabilizing) displacement of the CFP was increased, while the subsequent backward displacement of the CFP (a measure of the corrective braking action of LL responses) was delayed. Abnormal late automatic or possibly more voluntary postural corrections also contributed substantially to the increased body sway. During the on phase, ML amplitudes were reduced in patients but remained increased compared with controls. LL amplitudes no longer differed between both groups due to a modest, possibly dopamine-related increase in patients and a simultaneous decrease in controls. The abnormal CFP displacement was only partially improved by dopaminergic medication. The later postural corrections were not improved at all. Consequently, the increased posterior COG displacement was not ameliorated during the on phase. We conclude that (a) a combination of abnormal automatic and perhaps more voluntary postural corrections contributes to increased body sway in PD and (b) dopaminergic medication fails to improve balance impairment in PD because early automatic postural responses are only partially corrected, while later occurring postural corrections are not improved at all. These electrophysiological results support clinical observations and suggest that nondopaminergic lesions play a significant role in the pathophysiology of postural abnormalities in PD.

29 CFR 4206.1 - Purpose and scope.

Code of Federal Regulations, 2010 CFR

2010-07-01

... protects the other employers in the plan from becoming responsible for unfunded vested benefits properly..., for adjusting the partial or complete withdrawal liability of an employer that previously partially withdrew from the same multiemployer plan. Section 4206(b)(1) provides that when an employer that has...

Spatiotemporal dynamics underlying object completion in human ventral visual cortex.

PubMed

Tang, Hanlin; Buia, Calin; Madhavan, Radhika; Crone, Nathan E; Madsen, Joseph R; Anderson, William S; Kreiman, Gabriel

2014-08-06

Natural vision often involves recognizing objects from partial information. Recognition of objects from parts presents a significant challenge for theories of vision because it requires spatial integration and extrapolation from prior knowledge. Here we recorded intracranial field potentials of 113 visually selective electrodes from epilepsy patients in response to whole and partial objects. Responses along the ventral visual stream, particularly the inferior occipital and fusiform gyri, remained selective despite showing only 9%-25% of the object areas. However, these visually selective signals emerged ∼100 ms later for partial versus whole objects. These processing delays were particularly pronounced in higher visual areas within the ventral stream. This latency difference persisted when controlling for changes in contrast, signal amplitude, and the strength of selectivity. These results argue against a purely feedforward explanation of recognition from partial information, and provide spatiotemporal constraints on theories of object recognition that involve recurrent processing. Copyright © 2014 Elsevier Inc. All rights reserved.

Inductive sensor performance in partial discharges and noise separation by means of spectral power ratios.

PubMed

Ardila-Rey, Jorge Alfredo; Rojas-Moreno, Mónica Victoria; Martínez-Tarifa, Juan Manuel; Robles, Guillermo

2014-02-19

Partial discharge (PD) detection is a standardized technique to qualify electrical insulation in machines and power cables. Several techniques that analyze the waveform of the pulses have been proposed to discriminate noise from PD activity. Among them, spectral power ratio representation shows great flexibility in the separation of the sources of PD. Mapping spectral power ratios in two-dimensional plots leads to clusters of points which group pulses with similar characteristics. The position in the map depends on the nature of the partial discharge, the setup and the frequency response of the sensors. If these clusters are clearly separated, the subsequent task of identifying the source of the discharge is straightforward so the distance between clusters can be a figure of merit to suggest the best option for PD recognition. In this paper, two inductive sensors with different frequency responses to pulsed signals, a high frequency current transformer and an inductive loop sensor, are analyzed to test their performance in detecting and separating the sources of partial discharges.

Anti-inflammatory activity of Bromelia hieronymi: comparison with bromelain.

PubMed

Errasti, María E; Caffini, Néstor O; Pelzer, Lilian E; Rotelli, Alejandra E

2013-03-01

Some plant proteases (e. g., papain, bromelain, ficin) have been used as anti-inflammatory agents for some years, and especially bromelain is still being used as alternative and/or complementary therapy to glucocorticoids, nonsteroidal antirheumatics, and immunomodulators. Bromelain is an extract rich in cysteine endopeptidases obtained from Ananas comosus. In this study the anti-inflammatory action of a partially purified extract of Bromelia hieronymi fruits, whose main components are cysteine endopeptidases, is presented. Different doses of a partially purified extract of B. hieronymi were assayed on carrageenan-induced and serotonine-induced rat paw edema, as well as in cotton pellet granuloma model. Doses with equal proteolytic activity of the partially purified extract and bromelain showed significantly similar anti-inflammatory responses. Treatment of the partially purified extract and bromelain with E-64 provoked loss of anti-inflammatory activity on carrageenan-induced paw edema, a fact which is consistent with the hypothesis that the proteolytic activity would be responsible for the anti-inflammatory action. Georg Thieme Verlag KG Stuttgart · New York.

Prospective study of rabbit antithymocyte globulin and cyclosporine for aplastic anemia from the EBMT Severe Aplastic Anaemia Working Party.

PubMed

Marsh, Judith C; Bacigalupo, Andrea; Schrezenmeier, Hubert; Tichelli, Andre; Risitano, Antonio M; Passweg, Jakob R; Killick, Sally B; Warren, Alan J; Foukaneli, Theodora; Aljurf, Mahmoud; Al-Zahrani, H A; Höchsmann, Britta; Schafhausen, Philip; Roth, Alexander; Franzke, Anke; Brummendorf, Tim H; Dufour, Carlo; Oneto, Rosi; Sedgwick, Philip; Barrois, Alain; Kordasti, Shahram; Elebute, Modupe O; Mufti, Ghulam J; Socie, Gerard

2012-06-07

Rabbit antithymocyte globulin (rATG; thymoglobulin, Genzyme) in combination with cyclosporine, as first-line immunosuppressive therapy, was evaluated prospectively in a multicenter, European, phase 2 pilot study, in 35 patients with aplastic anemia. Results were compared with 105 age- and disease severity-matched patients from the European Blood and Marrow Transplant registry, treated with horse ATG (hATG; lymphoglobulin) and cyclosporine. The primary end point was response at 6 months. At 3 months, no patients had achieved a complete response to rATG. Partial response occurred in 11 (34%). At 6 months, complete response rate was 3% and partial response rate 37%. There were 10 deaths after rATG (28.5%) and 1 after subsequent HSCT. Infections were the main cause of death in 9 of 10 patients. The best response rate was 60% for rATG and 67% for hATG. For rATG, overall survival at 2 years was 68%, compared with 86% for hATG (P = .009). Transplant-free survival was 52% for rATG and 76% for hATG (P = .002). On multivariate analysis, rATG (hazard ratio = 3.9, P = .003) and age more than 37 years (hazard ratio = 4.7, P = .0008) were independent adverse risk factors for survival. This study was registered at www.clinicaltrials.gov as NCT00471848.

Preliminary individualized chemotherapy for malignant astrocytomas based on O6-methylguanine-deoxyribonucleic acid methyltransferase methylation analysis.

PubMed

Watanabe, Takao; Katayama, Yoichi; Ogino, Akiyoshi; Ohta, Takashi; Yoshino, Atsuo; Fukushima, Takao

2006-08-01

O(6)-methylguanine-deoxyribonucleic acid methyltransferase gene (MGMT) methylation is apparently correlated with responsiveness to nitrosourea chemotherapy, suggesting this alkylating agent should be effective against MGMT-methylated tumors. MGMT appears not to be linked to platinum resistance, so platinum chemotherapy should be used for MGMT-unmethylated tumors. This study was a preliminary trial of individualized chemotherapy based on MGMT methylation status in a total of 20 patients with newly diagnosed malignant astrocytomas (9 anaplastic astrocytomas and 11 glioblastomas multiforme). The procarbazine, 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-2(2-chloroethyl)-3-nitrosourea, and vincristine (PAV) regimen was administered to seven patients with MGMT-methylated tumors, and the carboplatin and etoposide (CE) regimen was administered to 13 patients with MGMT-unmethylated tumors. Objective response to the PAV therapy was noted in all three patients with measurable residual tumor (2 complete responses and 1 partial response). Five of the seven patients continued to be disease-free after initiation of the PAV therapy. Objective response to the CE therapy was seen in only one of seven patients with measurable residual tumor (1 partial response). Three of the 13 patients were free from progression, whereas the remaining 10 patients showed early progression. The PAV regimen is effective against MGMT-methylated malignant astrocytomas, but the CE regimen is not useful at the given dose and schedule in MGMT-unmethylated tumors.

Response Assessment in Paediatric Phase I Trials According to RECIST Guidelines: Survival Outcomes, Patterns of Progression and Relevance of Changes in Tumour Measurements.

PubMed

Carceller, Fernando; Bautista, Francisco J; Fowkes, Lucy A; Marshall, Lynley V; Sirvent, Sara I; Chisholm, Julia C; Pearson, Andrew D J; Koh, Dow-Mu; Moreno, Lucas

2016-08-01

RECIST guidelines constitute the reference for radiological response assessment in most paediatric trials of anticancer agents. However, these criteria have not been validated in children. We evaluated the outcomes and patterns of progression of children/adolescents enrolled in phase I trials in two paediatric drug development units. Patients aged ≤21 assessed with RECIST (v1.0 or v1.1) were eligible. Clinico-radiological data were analysed using Mann-Whitney U and log-rank tests to correlate response categories and sum of longest diameters (SLD) with time-to-event variables and overall survival (OS). Sixty-one patients (71 enrolments) were evaluated; median age: 12.7 years (range, 3.1-20.9). Overall, 7% achieved complete/partial response (n = 5) and 31% disease stabilisation (n = 22). Median (95% CI) OS (in months) was 29.1 (27.6-30.6) with complete/partial response, 8.9 (2.0-15.8) with stable disease and 2.8 (2.3-3.3) with disease progression (P < 0.001); 32.6% patients with measurable disease presented exclusive progression of existing non-target lesions and/or new lesions. The change in SLD at best response showed a linear correlation with duration of response (r = -0.605; P = 0.004) and time on trial (r = -0.61; P = 0.003), but the change in SLD at progression did not correlate with time to progression (r = -0.219; P = 0.206). Response assessment according to RECIST correlated with OS in children/adolescents treated on phase I trials. The reduction in SLD at best response correlated with more prolonged responses. Tumour size did not constitute an optimal method to assess disease progression in one third of patients with measurable disease. Further refinement of current response assessment guidelines will enable the development of paediatric-specific radiological criteria. © 2016 Wiley Periodicals, Inc.

Primary Therapy of Waldenström Macroglobulinemia With Bortezomib, Dexamethasone, and Rituximab: WMCTG Clinical Trial 05-180

PubMed Central

Treon, Steven P.; Ioakimidis, Leukothea; Soumerai, Jacob D.; Patterson, Christopher J.; Sheehy, Patricia; Nelson, Marybeth; Willen, Michael; Matous, Jeffrey; Mattern, John; Diener, Jakow G.; Keogh, George P.; Myers, Thomas J.; Boral, Andy; Birner, Ann; Esseltine, Dixie L.; Ghobrial, Irene M.

2009-01-01

Purpose We examined the activity of bortezomib, dexamethasone, and rituximab (BDR) in patients with symptomatic, untreated Waldenström macroglobulinemia (WM). Patients and Methods A cycle of therapy consisted of bortezomib 1.3 mg/m2 intravenously; dexamethasone 40 mg on days 1, 4, 8, and 11; and rituximab 375 mg/m2 on day 11. Patients received four consecutive cycles for induction therapy and then four more cycles, each given 3 months apart, for maintenance therapy. Twenty-three patients received a median of seven cycles of treatment. Results Median bone marrow disease involvement declined from 55% to 10% (P = .0004), serum immunoglobulin M levels declined from 4,830 to 1,115 mg/dL (P < .0001), and hematocrit increased from 29.8% to 38.2% (P = .0002) at best response. The overall response rates and major response rates were 96% and 83% with three complete responses, two near complete responses, three very good partial responses, 11 partial responses, and three minor responses. Responses occurred at a median of 1.4 months. With a median follow-up of 22.8 months, 18 of 23 patients remained free of disease progression. Peripheral neuropathy was the most common toxicity, and it resolved to grade ≤ 1 in 13 of 16 patients at a median of 6.0 months. Four of the first seven treated patients developed herpes zoster, resulting in the institution of prophylactic antiviral therapy. Conclusion The results demonstrate that BDR produces rapid and durable responses, along with high rates of response and complete remissions in WM. Herpes zoster prophylaxis is necessary with BDR, and reversible peripheral neuropathy was the most common toxicity leading to premature discontinuation of bortezomib in 61% of patients. Exploration of alternative schedules for bortezomib administration that includes weekly dosing should be pursued. PMID:19506160

The effect of dilatancy on the unloading behavior of Mt. Helen tuff

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

Attia, A.V.; Rubin, M.B.

1993-11-01

In order to understand the role of rock dilatancy in modeling the response of partially saturated rock formations to underground nuclear explosions, we have developed a thermodynamically consistent model for a porous material, partially saturated with fluid. This model gives good predictions of the unloading behavior of dry, partially saturated, and fully saturated Mt. Helen tuff, as measured by Heard.

Toddlers' Social-Emotional Competence in the Contexts of Maternal Emotion Socialization and Contingent Responsiveness in a Low-Income Sample

ERIC Educational Resources Information Center

Brophy-Herb, Holly E.; Schiffman, Rachel F.; Bocknek, Erika London; Dupuis, Sara B.; Fitzgerald, Hiram E.; Horodynski, Mildred; Onaga, Esther; Van Egeren, Laurie A.; Hillaker, Barbara

2011-01-01

Early social-emotional development occurs in the context of parenting, particularly via processes such as maternal emotion socialization and parent-child interactions. Results from structural equation modeling indicated that maternal contingent responsiveness partially mediated the relationship between maternal emotion socialization of toddlers (N…

Bi-Factor Multidimensional Item Response Theory Modeling for Subscores Estimation, Reliability, and Classification

ERIC Educational Resources Information Center

Md Desa, Zairul Nor Deana

2012-01-01

In recent years, there has been increasing interest in estimating and improving subscore reliability. In this study, the multidimensional item response theory (MIRT) and the bi-factor model were combined to estimate subscores, to obtain subscores reliability, and subscores classification. Both the compensatory and partially compensatory MIRT…

Application of Response Surface Methodology on Leaching of Iron from Partially Laterised Khondalite Rocks: A Bauxite Mining Waste

NASA Astrophysics Data System (ADS)

Swain, Ranjita; Bhima Rao, R.

2018-04-01

In the present investigation, response surface methodology (RSM) is used for a quadratic model that continuously controls the process parameters. This model is used to optimize the removal of iron oxide from Partially Laterised Khondalite (PLK) rocks which is influenced by several independent variables namely acid concentration, time and temperature. Second order response functions are produced for leaching of iron oxide from PLK rocks-a bauxite mining waste. In RSM, Box-Behnken design is used for the process optimization to achieve maximum removal of iron oxide. The influence of the process variables of leaching of iron oxide is presented in the form of 3-D response graphs. The results of this investigation reveals that 3 M hydrochloric acid concentration, 240 min time and 373 K temperature are found to be the best conditions for removal of 99% Fe2O3. The product obtain at this condition contain 80% brightness which is suitable for ceramic and filler industry applications. The novelity of the work is that the waste can be a value added product after suitable physical beneficiation and chemical treatment.

Partial hypopituitarism and Langerhans cell histiocytosis

PubMed Central

Balaguruswamy, S; Chattington, P D

2011-01-01

A case of multisystem Langerhans cell histiocytosis with pituitary involvement nearly 20 years after initial presentation. A 48-year-old man had histiocytosis X 22 years ago initially involving the groin; subsequently his external auditory meatus, scalp, gum, mandibular bone, perineum and axilla were involved and treated. The pituitary gland was involved 4 years ago. A thyrotropin-releasing hormone test showed delayed response suggestive of hypothalamic disease. Prolactin levels were normal. A gonadotropin-releasing hormone test showed impaired testosterone and gonadotrophin response in keeping with pituitary disease. A glucagon stimulation test showed an impaired growth hormone response but a normal cortisol increase. MRI pituitary showed an empty sella. There was no evidence of diabetes insipidus. Bone mineral densitometry was normal. He has partial hypopituitarism needing thyroxine and testosterone replacement. He also developed type 2 diabetes mellitus 9 years ago. He is closely monitored for any development of diabetes insipidus and the need for growth hormone supplementation. PMID:22715201

What You Don't Know Can Hurt You: Missing Data and Partial Credit Model Estimates

PubMed Central

Thomas, Sarah L.; Schmidt, Karen M.; Erbacher, Monica K.; Bergeman, Cindy S.

2017-01-01

The authors investigated the effect of Missing Completely at Random (MCAR) item responses on partial credit model (PCM) parameter estimates in a longitudinal study of Positive Affect. Participants were 307 adults from the older cohort of the Notre Dame Study of Health and Well-Being (Bergeman and Deboeck, 2014) who completed questionnaires including Positive Affect items for 56 days. Additional missing responses were introduced to the data, randomly replacing 20%, 50%, and 70% of the responses on each item and each day with missing values, in addition to the existing missing data. Results indicated that item locations and person trait level measures diverged from the original estimates as the level of degradation from induced missing data increased. In addition, standard errors of these estimates increased with the level of degradation. Thus, MCAR data does damage the quality and precision of PCM estimates. PMID:26784376

Dynamic calibration of fast-response probes in low-pressure shock tubes

NASA Astrophysics Data System (ADS)

Persico, G.; Gaetani, P.; Guardone, A.

2005-09-01

Shock tube flows resulting from the incomplete burst of the diaphragm are investigated in connection with the dynamic calibration of fast-response pressure probes. As a result of the partial opening of the diaphragm, pressure disturbances are observed past the shock wave and the measured total pressure profile deviates from the envisaged step signal required by the calibration process. Pressure oscillations are generated as the initially normal shock wave diffracts from the diaphragm's orifice and reflects on the shock tube walls, with the lowest local frequency roughly equal to the ratio of the sound speed in the perturbed region to the shock tube diameter. The energy integral of the perturbations decreases with increasing distance from the diaphragm, as the diffracted leading shock and downwind reflections coalesce into a single normal shock. A procedure is proposed to calibrate fast-response pressure probes downwind of a partially opened shock tube diaphragm.

Tropical rainforest response to marine sky brightening climate engineering

NASA Astrophysics Data System (ADS)

Muri, Helene; Niemeier, Ulrike; Kristjánsson, Jón Egill

2015-04-01

Tropical forests represent a major atmospheric carbon dioxide sink. Here the gross primary productivity (GPP) response of tropical rainforests to climate engineering via marine sky brightening under a future scenario is investigated in three Earth system models. The model response is diverse, and in two of the three models, the tropical GPP shows a decrease from the marine sky brightening climate engineering. Partial correlation analysis indicates precipitation to be important in one of those models, while precipitation and temperature are limiting factors in the other. One model experiences a reversal of its Amazon dieback under marine sky brightening. There, the strongest partial correlation of GPP is to temperature and incoming solar radiation at the surface. Carbon fertilization provides a higher future tropical rainforest GPP overall, both with and without climate engineering. Salt damage to plants and soils could be an important aspect of marine sky brightening.

Belgium: risk adjustment and financial responsibility in a centralised system.

PubMed

Schokkaert, Erik; Van de Voorde, Carine

2003-07-01

Since 1995 Belgian sickness funds are partially financed through a risk adjustment system and are held partially financially responsible for the difference between their actual and their risk-adjusted expenditures. However, they did not get the necessary instruments for exerting a real influence on expenditures and the health insurance market has not been opened for new entrants. At the same time the sickness funds have powerful tools for risk selection, because they also dominate the market for supplementary health insurance. The present risk-adjustment system is based on the results of a regression analysis with aggregate data. The main proclaimed purpose of this system is to guarantee a fair treatment to all the sickness funds. Until now the danger of risk selection has not been taken seriously. Consumer mobility has remained rather low. However, since the degree of financial responsibility is programmed to increase in the near future, the potential profits from cream skimming will increase.

Immunomodulatory activity of a protein isolated from garlic extract on delayed type hypersensitivity.

PubMed

Ghazanfari, Tooba; Hassan, Zuhair M; Ebrahimi, Marzieh

2002-10-01

Garlic is known as a potent spice and a medicine with broad therapeutic properties ranging from antibacterial to anticancer, and anticoagulant. One major protein has been isolated and purified; it is the 14-kDa glycoprotein. This protein has shown to have immunomodulatory effects. In this study, two sources of garlic (freshly prepared and commercial tablet) were used. Both sources of garlic were augmented delayed type hypersensitivity (DTH) response, the optimum enhancement were detected at 20 mg/kg. Histological studies indicate that 20 mg/kg caused a hyperplasia and hypertrophy of periarteriolar lymphoid sheath of spleen and paracortical zone of lymph nodes. Partial purified fraction could increase the DTH response comparing to garlic extract, and purified protein could highly increase the DTH response comparing to both garlic extract and partial purified fraction. Garlic at all doses employed did not exhibit any effect on enhancement of antibody titer to SRBC.

UV absorption control of thin film growth

DOEpatents

Biefeld, Robert M.; Hebner, Gregory A.; Killeen, Kevin P.; Zuhoski, Steven P.

1991-01-01

A system for monitoring and controlling the rate of growth of thin films in an atmosphere of reactant gases measures the UV absorbance of the atmosphere and calculates the partial pressure of the gases. The flow of reactant gases is controlled in response to the partial pressure.

Response of MDOF strongly nonlinear systems to fractional Gaussian noises.

PubMed

Deng, Mao-Lin; Zhu, Wei-Qiu

2016-08-01

In the present paper, multi-degree-of-freedom strongly nonlinear systems are modeled as quasi-Hamiltonian systems and the stochastic averaging method for quasi-Hamiltonian systems (including quasi-non-integrable, completely integrable and non-resonant, completely integrable and resonant, partially integrable and non-resonant, and partially integrable and resonant Hamiltonian systems) driven by fractional Gaussian noise is introduced. The averaged fractional stochastic differential equations (SDEs) are derived. The simulation results for some examples show that the averaged SDEs can be used to predict the response of the original systems and the simulation time for the averaged SDEs is less than that for the original systems.

Proceedings of the International Conference on Cyclic Nucleotides, Calcium and Protein Phosphorylation (6th) Held in Bethesda, Maryland on September 2-7, 1986. Advances in Second Messenger and Phosphorprotein Research. Volume 21A. Abstracts Volume

DTIC Science & Technology

1988-11-16

oxoireamorine. Oxotremorine inhibited Ach release for a shorter duration. The ACh release-inhibition induced by 50 PH Aech-M was only acutely blocked...and the partial agonist oxotresorine in the presence of 59K of Lit. Carbacbol showed a 10-fold lover ECS0-value (3.7liM) and oxotremorine a 3-fold...however, only a decrease in the maximal response was seen. In both tissues, the maximal, response of the partial agonist oxotremorine was suppressed

Response of MDOF strongly nonlinear systems to fractional Gaussian noises

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

Deng, Mao-Lin; Zhu, Wei-Qiu, E-mail: wqzhu@zju.edu.cn

2016-08-15

In the present paper, multi-degree-of-freedom strongly nonlinear systems are modeled as quasi-Hamiltonian systems and the stochastic averaging method for quasi-Hamiltonian systems (including quasi-non-integrable, completely integrable and non-resonant, completely integrable and resonant, partially integrable and non-resonant, and partially integrable and resonant Hamiltonian systems) driven by fractional Gaussian noise is introduced. The averaged fractional stochastic differential equations (SDEs) are derived. The simulation results for some examples show that the averaged SDEs can be used to predict the response of the original systems and the simulation time for the averaged SDEs is less than that for the original systems.

Response of Partially Saturated Non-cohesive Soils

NASA Astrophysics Data System (ADS)

Świdziński, Waldemar; Mierczyński, Jacek; Mikos, Agata

2017-12-01

This paper analyses and discusses experimental results of undrained triaxial tests. The tests were performed on non-cohesive partially saturated soil samples subjected to monotonic and cyclic loading. The tests were aimed at determining the influence of saturation degree on soil's undrained response (shear strength, excess pore pressure generation). The saturation of samples was monitored by checking Skempton's parameter B. Additionally, seismic P-wave velocity measurements were carried out on samples characterized by various degrees of saturation. The tests clearly showed that liquefaction may also take place in non-cohesive soils that are not fully saturated and that the liquefaction potential of such soils strongly depends on the B parameter.

Cardiorespiratory dynamic response to mental stress: a multivariate time-frequency analysis.

PubMed

Widjaja, Devy; Orini, Michele; Vlemincx, Elke; Van Huffel, Sabine

2013-01-01

Mental stress is a growing problem in our society. In order to deal with this, it is important to understand the underlying stress mechanisms. In this study, we aim to determine how the cardiorespiratory interactions are affected by mental arithmetic stress and attention. We conduct cross time-frequency (TF) analyses to assess the cardiorespiratory coupling. In addition, we introduce partial TF spectra to separate variations in the RR interval series that are linearly related to respiration from RR interval variations (RRV) that are not related to respiration. The performance of partial spectra is evaluated in two simulation studies. Time-varying parameters, such as instantaneous powers and frequencies, are derived from the computed spectra. Statistical analysis is carried out continuously in time to evaluate the dynamic response to mental stress and attention. The results show an increased heart and respiratory rate during stress and attention, compared to a resting condition. Also a fast reduction in vagal activity is noted. The partial TF analysis reveals a faster reduction of RRV power related to (3 s) than unrelated to (30 s) respiration, demonstrating that the autonomic response to mental stress is driven by mechanisms characterized by different temporal scales.

Do interoceptive awareness and interoceptive responsiveness mediate the relationship between body appreciation and intuitive eating in young women?

PubMed

Oswald, Alana; Chapman, Janine; Wilson, Carlene

2017-02-01

The extent to which an individual appreciates their own body is recognised as a proximal predictor of intuitive eating, but the mechanisms underlying this relationship are less clearly understood. This study tested whether two partially independent, self-reported facets of interoceptive ability: 'interoceptive awareness' (defined as the ability to detect internal bodily cues) and 'interoceptive responsiveness' (the way in which individuals value and respond to these cues) mediated the relationship between body appreciation and three subscales of intuitive eating: 'unconditional permission to eat'; 'reliance on internal hunger and satiety cues', and 'eating for physical rather than emotional reasons'. Multiple mediation analyses of data from an online survey of Australian college women (n = 200) showed that: (1) interoceptive awareness partially mediated the relationship between body appreciation and 'reliance on internal hunger and satiety cues', and (2) interoceptive responsiveness partially mediated the relationship between all three subscales of intuitive eating. Although preliminary, this work lends support to the theoretical framework of the acceptance model of intuitive eating and extends it by suggesting that the different facets of intuitive eating may have distinct underlying mechanisms. Copyright © 2016 Elsevier Ltd. All rights reserved.

Serum amyloid protein A concentration in cryopyrin-associated periodic syndromes patients treated with interleukin-1 beta antagonist.

PubMed

Pastore, Serena; Paloni, Giulia; Caorsi, Roberta; Ronfani, Luca; Taddio, Andrea; Lepore, Loredana

2014-01-01

Cryopyrin-associated periodic syndromes (CAPS) are a group of chronic, relapsing autoinflammatory disorders which may be complicated by systemic AA amyloidosis. The aim of our study was to evaluate serum amyloid protein A (SAA) level in CAPS patients treated with Interleukin-1beta (IL-1β) antagonist and to correlate its level with treatment response. All patients of CAPS Italian Register treated with IL-1β inhibitor were enrolled. SAA levels before starting therapy, and at last visit were evaluated. Patients were then divided in complete responders and partial responders. Twenty-five patients were enrolled. SAA level before starting therapy was increased (median 118.5 mg/L, IQR 96.4-252.8; normal value <6.4 mg/L), while at last visit SAA was significantly reduced (median 4.3 mg/L, IQR 2.3-12.7) (p<0.001). However 12 patients still presented SAA levels beyond normal range, 10/25 patients (40%) showed a complete response to treatment. Conversely, 15 patients presented only a partial response, of which 12 for increased SAA value and 3 for increased CRP value. Patients with partial response had SAA values significantly higher than patients with complete response (median 12.6 mg/L; IQR 8.3-20.0 vs. 2.7 mg/L; IQR 1.6-4.1, p<0.001). Our results confirm the long term efficacy of anti IL-1β treatment in CAPS and the decrease of SAA levels; however 48% of patients still presented SAA elevation despite treatment. The real risk of these patients in developing amyloidosis is not clear but the persistent increase of SAA needs a close follow-up.

Improving sneaky-sex in a low oxygen environment: reproductive and physiological responses of male mosquito fish to chronic hypoxia.

PubMed

Carter, Alecia J; Wilson, Robbie S

2006-12-01

Few studies have examined the adaptive significance of reversible acclimation responses. The aerobic performance and mating behaviour of the sexually coercive male eastern mosquito fish (Gambusia holbrooki) offers an excellent model system for testing the benefits of reversible acclimation responses to mating success. We exposed male mosquito fish to normoxic or hypoxic conditions for 4 weeks and tested their maximum sustained swimming performance and their ability to obtain coercive matings under both normoxic and hypoxic conditions. We predicted that hypoxia-acclimated males would possess greater swimming and mating performance in hypoxic conditions than normoxic-acclimated males, and vice versa when tested in normoxia. Supporting our predictions, we found the sustained swimming performance of male mosquito fish was greater in a hypoxic environment following long-term exposure to low partial pressures of oxygen. However, the benefits of acclimation responses to mating performance were dependent on whether they were tested in the presence or absence of male-male competition. In a non-competitive environment, male mosquito fish acclimated to hypoxic conditions spent a greater amount of time following females and obtained more copulations than normoxic-acclimated males when tested in low partial pressures of oxygen. When males were competed against each other for copulations, we found no influence of long-term exposure to different partial pressures of oxygen on mating behaviour. Thus, despite improvements in the aerobic capacity of male mosquito fish following long-term acclimation to hypoxic conditions, these benefits did not always manifest themselves in improved mating performance. This study represents one of the first experimental tests of the benefits of reversible acclimation responses, and indicates that the ecological significance of physiological plasticity may be more complicated than previously imagined.

Disease Evolution and Response to Rapamycin in Activated Phosphoinositide 3-Kinase δ Syndrome: The European Society for Immunodeficiencies-Activated Phosphoinositide 3-Kinase δ Syndrome Registry

PubMed Central

Maccari, Maria Elena; Abolhassani, Hassan; Aghamohammadi, Asghar; Aiuti, Alessandro; Aleinikova, Olga; Bangs, Catherine; Baris, Safa; Barzaghi, Federica; Baxendale, Helen; Buckland, Matthew; Burns, Siobhan O.; Cancrini, Caterina; Cant, Andrew; Cathébras, Pascal; Cavazzana, Marina; Chandra, Anita; Conti, Francesca; Coulter, Tanya; Devlin, Lisa A.; Edgar, J. David M.; Faust, Saul; Fischer, Alain; Garcia-Prat, Marina; Hammarström, Lennart; Heeg, Maximilian; Jolles, Stephen; Karakoc-Aydiner, Elif; Kindle, Gerhard; Kiykim, Ayca; Kumararatne, Dinakantha; Grimbacher, Bodo; Longhurst, Hilary; Mahlaoui, Nizar; Milota, Tomas; Moreira, Fernando; Moshous, Despina; Mukhina, Anna; Neth, Olaf; Neven, Benedicte; Nieters, Alexandra; Olbrich, Peter; Ozen, Ahmet; Schmid, Jana Pachlopnik; Picard, Capucine; Prader, Seraina; Rae, William; Reichenbach, Janine; Rusch, Stephan; Savic, Sinisa; Scarselli, Alessia; Scheible, Raphael; Sediva, Anna; Sharapova, Svetlana O.; Shcherbina, Anna; Slatter, Mary; Soler-Palacin, Pere; Stanislas, Aurelie; Suarez, Felipe; Tucci, Francesca; Uhlmann, Annette; van Montfrans, Joris; Warnatz, Klaus; Williams, Anthony Peter; Wood, Phil; Kracker, Sven; Condliffe, Alison Mary; Ehl, Stephan

2018-01-01

Activated phosphoinositide 3-kinase (PI3K) δ Syndrome (APDS), caused by autosomal dominant mutations in PIK3CD (APDS1) or PIK3R1 (APDS2), is a heterogeneous primary immunodeficiency. While initial cohort-descriptions summarized the spectrum of clinical and immunological manifestations, questions about long-term disease evolution and response to therapy remain. The prospective European Society for Immunodeficiencies (ESID)-APDS registry aims to characterize the disease course, identify outcome predictors, and evaluate treatment responses. So far, 77 patients have been recruited (51 APDS1, 26 APDS2). Analysis of disease evolution in the first 68 patients pinpoints the early occurrence of recurrent respiratory infections followed by chronic lymphoproliferation, gastrointestinal manifestations, and cytopenias. Although most manifestations occur by age 15, adult-onset and asymptomatic courses were documented. Bronchiectasis was observed in 24/40 APDS1 patients who received a CT-scan compared with 4/15 APDS2 patients. By age 20, half of the patients had received at least one immunosuppressant, but 2–3 lines of immunosuppressive therapy were not unusual before age 10. Response to rapamycin was rated by physician visual analog scale as good in 10, moderate in 9, and poor in 7. Lymphoproliferation showed the best response (8 complete, 11 partial, 6 no remission), while bowel inflammation (3 complete, 3 partial, 9 no remission) and cytopenia (3 complete, 2 partial, 9 no remission) responded less well. Hence, non-lymphoproliferative manifestations should be a key target for novel therapies. This report from the ESID-APDS registry provides comprehensive baseline documentation for a growing cohort that will be followed prospectively to establish prognostic factors and identify patients for treatment studies. PMID:29599784

Disease Evolution and Response to Rapamycin in Activated Phosphoinositide 3-Kinase δ Syndrome: The European Society for Immunodeficiencies-Activated Phosphoinositide 3-Kinase δ Syndrome Registry.

PubMed

Maccari, Maria Elena; Abolhassani, Hassan; Aghamohammadi, Asghar; Aiuti, Alessandro; Aleinikova, Olga; Bangs, Catherine; Baris, Safa; Barzaghi, Federica; Baxendale, Helen; Buckland, Matthew; Burns, Siobhan O; Cancrini, Caterina; Cant, Andrew; Cathébras, Pascal; Cavazzana, Marina; Chandra, Anita; Conti, Francesca; Coulter, Tanya; Devlin, Lisa A; Edgar, J David M; Faust, Saul; Fischer, Alain; Garcia-Prat, Marina; Hammarström, Lennart; Heeg, Maximilian; Jolles, Stephen; Karakoc-Aydiner, Elif; Kindle, Gerhard; Kiykim, Ayca; Kumararatne, Dinakantha; Grimbacher, Bodo; Longhurst, Hilary; Mahlaoui, Nizar; Milota, Tomas; Moreira, Fernando; Moshous, Despina; Mukhina, Anna; Neth, Olaf; Neven, Benedicte; Nieters, Alexandra; Olbrich, Peter; Ozen, Ahmet; Schmid, Jana Pachlopnik; Picard, Capucine; Prader, Seraina; Rae, William; Reichenbach, Janine; Rusch, Stephan; Savic, Sinisa; Scarselli, Alessia; Scheible, Raphael; Sediva, Anna; Sharapova, Svetlana O; Shcherbina, Anna; Slatter, Mary; Soler-Palacin, Pere; Stanislas, Aurelie; Suarez, Felipe; Tucci, Francesca; Uhlmann, Annette; van Montfrans, Joris; Warnatz, Klaus; Williams, Anthony Peter; Wood, Phil; Kracker, Sven; Condliffe, Alison Mary; Ehl, Stephan

2018-01-01

Activated phosphoinositide 3-kinase (PI3K) δ Syndrome (APDS), caused by autosomal dominant mutations in PIK3CD (APDS1) or PIK3R1 (APDS2), is a heterogeneous primary immunodeficiency. While initial cohort-descriptions summarized the spectrum of clinical and immunological manifestations, questions about long-term disease evolution and response to therapy remain. The prospective European Society for Immunodeficiencies (ESID)-APDS registry aims to characterize the disease course, identify outcome predictors, and evaluate treatment responses. So far, 77 patients have been recruited (51 APDS1, 26 APDS2). Analysis of disease evolution in the first 68 patients pinpoints the early occurrence of recurrent respiratory infections followed by chronic lymphoproliferation, gastrointestinal manifestations, and cytopenias. Although most manifestations occur by age 15, adult-onset and asymptomatic courses were documented. Bronchiectasis was observed in 24/40 APDS1 patients who received a CT-scan compared with 4/15 APDS2 patients. By age 20, half of the patients had received at least one immunosuppressant, but 2-3 lines of immunosuppressive therapy were not unusual before age 10. Response to rapamycin was rated by physician visual analog scale as good in 10, moderate in 9, and poor in 7. Lymphoproliferation showed the best response (8 complete, 11 partial, 6 no remission), while bowel inflammation (3 complete, 3 partial, 9 no remission) and cytopenia (3 complete, 2 partial, 9 no remission) responded less well. Hence, non-lymphoproliferative manifestations should be a key target for novel therapies. This report from the ESID-APDS registry provides comprehensive baseline documentation for a growing cohort that will be followed prospectively to establish prognostic factors and identify patients for treatment studies.

Inhibition of Mutated, Activated BRAF in Metastatic Melanoma

PubMed Central

Flaherty, Keith T.; Puzanov, Igor; Kim, Kevin B.; Ribas, Antoni; McArthur, Grant A.; Sosman, Jeffrey A.; O'Dwyer, Peter J.; Lee, Richard J.; Grippo, Joseph F.; Nolop, Keith; Chapman, Paul B.

2013-01-01

Background The identification of somatic mutations in the gene encoding the serine–threonine protein kinase B-RAF (BRAF) in the majority of melanomas offers an opportunity to test oncogene-targeted therapy for this disease. Methods We conducted a multicenter, phase 1, dose-escalation trial of PLX4032 (also known as RG7204), an orally available inhibitor of mutated BRAF, followed by an extension phase involving the maximum dose that could be administered without adverse effects (the recommended phase 2 dose). Patients received PLX4032 twice daily until they had disease progression. Pharmacokinetic analysis and tumor-response assessments were conducted in all patients. In selected patients, tumor biopsy was performed before and during treatment to validate BRAF inhibition. Results A total of 55 patients (49 of whom had melanoma) were enrolled in the dose-escalation phase, and 32 additional patients with metastatic melanoma who had BRAF with the V600E mutation were enrolled in the extension phase. The recommended phase 2 dose was 960 mg twice daily, with increases in the dose limited by grade 2 or 3 rash, fatigue, and arthralgia. In the dose-escalation cohort, among the 16 patients with melanoma whose tumors carried the V600E BRAF mutation and who were receiving 240 mg or more of PLX4032 twice daily, 10 had a partial response and 1 had a complete response. Among the 32 patients in the extension cohort, 24 had a partial response and 2 had a complete response. The estimated median progression-free survival among all patients was more than 7 months. Conclusions Treatment of metastatic melanoma with PLX4032 in patients with tumors that carry the V600E BRAF mutation resulted in complete or partial tumor regression in the majority of patients. (Funded by Plexxikon and Roche Pharmaceuticals.) PMID:20818844

Monetary policy and the effects of oil price shocks on the Japanese economy

NASA Astrophysics Data System (ADS)

Lee, Byung Rhae

1998-12-01

The evidence of output decreases and price level increases following oil price shocks in the Japanese economy is presented in this paper. These negative effects of oil shocks are better explained by Hamilton's (1996) net oil price increase measure (NOPI) than by other oil measures. The fact that an oil shock has a statistically significant effect on the call money rate and real output and that the call money rate also has a statistically significant effect on real output appears to explain that the effects of oil price shocks on economic activity are partially attributed to contractionary monetary policy responses. The asymmetric effects of positive and negative oil shocks are also found in the Japanese economy and this asymmetry can also be partially explained by monetary policy responses. To assess the relative contribution of oil shocks and endogenous monetary policy responses to the economic downturns, I shut off the responses of the call money rate to oil shocks utilizing the impulse response results from the VAR model. Then, I re-run the VAR with the adjusted call money rate series. The empirical results show that around 30--40% of the negative effects of oil price shocks on the Japanese economy can be accounted for by oil shock induced monetary tightening.

Hematopoietic responses under protracted exposures to low daily dose gamma irradiation

NASA Astrophysics Data System (ADS)

Seed, T. M.; Fritz, T. E.; Tolle, D. V.; Jackson, W. E.

In attempting to evaluate the possible health consequences of chronic ionizing radiation exposure during extended space travel (e.g., Mars Mission), ground-based experimental studies of the clinical and pathological responses of canines under low daily doses of 60Co gamma irradiation (0.3-26.3 cGy d -1) have been examined. Specific reference was given to responses of the blood forming system. Results suggest that the daily dose rate of 7.5 cGy d -1 represents a threshold below which the hematopoietic system can retain either partial or full trilineal cell-producing capacity (erythropoiesis, myelopoiesis, and megakaryopoiesis) for extended periods of exposure (> 1yr). Trilineal capacity was fully retained for several years of exposure at the lowest dose-rate tested (0.3 cGy d -1) but was completely lost within several hundred days at the highest dose-rate (26.3 cGy d -1). Retention of hematopoietic capacity under chronic exposure has been demonstrated to be mediated by hematopoietic progenitors with acquired radioresistance and repair functions, altered cytogenetics, and cell-cycle characteristics. Radiological, biological, and temporal parameters responsible for these vital acquisitions by hematopoietic progenitors have been partially characterized. These parameters, along with threshold responses, are described and discussed in relation to potential health risks of the space traveler under chronic stress of low-dose irradiation.

Predictive Coding in Area V4: Dynamic Shape Discrimination under Partial Occlusion

PubMed Central

Choi, Hannah; Pasupathy, Anitha; Shea-Brown, Eric

2018-01-01

The primate visual system has an exquisite ability to discriminate partially occluded shapes. Recent electrophysiological recordings suggest that response dynamics in intermediate visual cortical area V4, shaped by feedback from prefrontal cortex (PFC), may play a key role. To probe the algorithms that may underlie these findings, we build and test a model of V4 and PFC interactions based on a hierarchical predictive coding framework. We propose that probabilistic inference occurs in two steps. Initially, V4 responses are driven solely by bottom-up sensory input and are thus strongly influenced by the level of occlusion. After a delay, V4 responses combine both feedforward input and feedback signals from the PFC; the latter reflect predictions made by PFC about the visual stimulus underlying V4 activity. We find that this model captures key features of V4 and PFC dynamics observed in experiments. Specifically, PFC responses are strongest for occluded stimuli and delayed responses in V4 are less sensitive to occlusion, supporting our hypothesis that the feedback signals from PFC underlie robust discrimination of occluded shapes. Thus, our study proposes that area V4 and PFC participate in hierarchical inference, with feedback signals encoding top-down predictions about occluded shapes. PMID:29566355

The dynamic range of response set activation during action sequencing.

PubMed

Behmer, Lawrence P; Crump, Matthew J C

2017-03-01

We show that theories of response scheduling for sequential action can be discriminated on the basis of their predictions for the dynamic range of response set activation during sequencing, which refers to the momentary span of activation states for completed and to-be-completed actions in a response set. In particular, theories allow that future actions in a plan are partially activated, but differ with respect to the width of the range, which refers to the number of future actions that are partially activated. Similarly, theories differ on the width of the range for recently completed actions that are assumed to be rapidly deactivated or gradually deactivated in a passive fashion. We validate a new typing task for measuring momentary activation states of actions across a response set during action sequencing. Typists recruited from Amazon Mechanical Turk copied a paragraph by responding to a "go" signal that usually cued the next letter but sometimes cued a near-past or future letter (n-3, -2, -1, 0, +2, +3). The activation states for producing letters across go-signal positions can be inferred from RTs and errors. In general, we found evidence of graded parallel activation for future actions and rapid deactivation of more distal past actions. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

ESCAschool study: trial protocol of an adaptive treatment approach for school-age children with ADHD including two randomised trials.

PubMed

Döpfner, Manfred; Hautmann, Christopher; Dose, Christina; Banaschewski, Tobias; Becker, Katja; Brandeis, Daniel; Holtmann, Martin; Jans, Thomas; Jenkner, Carolin; Millenet, Sabina; Renner, Tobias; Romanos, Marcel; von Wirth, Elena

2017-07-24

The ESCAschool study addresses the treatment of school-age children with attention-deficit/hyperactivity disorder (ADHD) in a large multicentre trial. It aims to investigate three interrelated topics: (i) Clinical guidelines often recommend a stepped care approach, including different treatment strategies for children with mild to moderate and severe ADHD symptoms, respectively. However, this approach has not yet been empirically validated. (ii) Behavioural interventions and neurofeedback have been shown to be effective, but the superiority of combined treatment approaches such as medication plus behaviour therapy or medication plus neurofeedback compared to medication alone remains questionable. (iii) Growing evidence indicates that telephone-assisted self-help interventions are effective in the treatment of ADHD. However, larger randomised controlled trials (RCTs) are lacking. This report presents the ESCAschool trial protocol. In an adaptive treatment design, two RCTs and additional observational treatment arms are considered. The target sample size of ESCAschool is 521 children with ADHD. Based on their baseline ADHD symptom severity, the children will be assigned to one of two groups (mild to moderate symptom group and severe symptom group). The adaptive design includes two treatment phases (Step 1 and Step 2). According to clinical guidelines, different treatment protocols will be followed for the two severity groups. In the moderate group, the efficacy of telephone-assisted self-help for parents and teachers will be tested against waitlist control in Step 1 (RCT I). The severe group will receive pharmacotherapy combined with psychoeducation in Step 1. For both groups, treatment response will be determined after Step 1 treatment (no, partial or full response). In severe group children demonstrating partial response to medication, in Step 2, the efficacy of (1) counselling, (2) behaviour therapy and (3) neurofeedback will be tested (RCT II). All other treatment arms in Step 2 (severe group: no or full response; moderate group: no, partial or full response) are observational. The ESCAschool trial will provide evidence-based answers to several important questions for clinical practice following a stepped care approach. The adaptive study design will also provide new insights into the effects of additional treatments in children with partial response. German Clinical Trials Register (DRKS) DRKS00008973 . Registered 18 December 2015.

Relationship between the Temporal Changes in Positron-Emission-Tomography-Imaging-Based Textural Features and Pathologic Response and Survival in Esophageal Cancer Patients.

PubMed

Yip, Stephen S F; Coroller, Thibaud P; Sanford, Nina N; Mamon, Harvey; Aerts, Hugo J W L; Berbeco, Ross I

2016-01-01

Although change in standardized uptake value (SUV) measures and PET-based textural features during treatment have shown promise in tumor response prediction, it is unclear which quantitative measure is the most predictive. We compared the relationship between PET-based features and pathologic response and overall survival with the SUV measures in esophageal cancer. Fifty-four esophageal cancer patients received PET/CT scans before and after chemoradiotherapy. Of these, 45 patients underwent surgery and were classified into complete, partial, and non-responders to the preoperative chemoradiation. SUVmax and SUVmean, two cooccurrence matrix (Entropy and Homogeneity), two run-length matrix (RLM) (high-gray-run emphasis and Short-run high-gray-run emphasis), and two size-zone matrix (high-gray-zone emphasis and short-zone high-gray emphasis) textures were computed. The relationship between the relative difference of each measure at different treatment time points and the pathologic response and overall survival was assessed using the area under the receiver-operating-characteristic curve (AUC) and Kaplan-Meier statistics, respectively. All Textures, except Homogeneity, were better related to pathologic response than SUVmax and SUVmean. Entropy was found to significantly distinguish non-responders from the complete (AUC = 0.79, p = 1.7 × 10(-4)) and partial (AUC = 0.71, p = 0.01) responders. Non-responders can also be significantly differentiated from partial and complete responders by the change in the run-length and size-zone matrix textures (AUC = 0.71-0.76, p ≤ 0.02). Homogeneity, SUVmax, and SUVmean failed to differentiate between any of the responders (AUC = 0.50-0.57, p ≥ 0.46). However, none of the measures were found to significantly distinguish between complete and partial responders with AUC <0.60 (p = 0.37). Median Entropy and RLM textures significantly discriminated patients with good and poor survival (log-rank p < 0.02), while all other textures and survival were poorly related (log-rank p > 0.25). For the patients studied, temporal changes in Entropy and all RLM were better correlated with pathological response and survival than the SUV measures. The hypothesis that these metrics can be used as clinical predictors of better patient outcomes will be tested in a larger patient dataset in the future.

A Single-Center Experience With Isolated Limb Infusion: An Interventional Oncology Opportunity.

PubMed

DeFoe, Adam; Heckman, Andrew; Slater, Dick; Silva-Lopez, Edibaldo; Foster, Jason; Bowden, Thom; Vargo, Christopher

2017-03-01

This retrospective review details our experience with isolated limb infusion for the treatment of melanoma, squamous cell carcinoma, and sarcoma in-transit metastases performed entirely in the interventional radiology suite. Eleven patients were treated over a 3-year period. Treatment response was assessed clinically and with PET/CT. Eight patients had either complete or partial response, giving an overall response rate of 72%. Isolated limb infusion can efficiently be performed entirely in the interventional radiology suite.

Phase II study of 4'-(9-acridinylamino) methanesulfon-m- anisidide (AMSA) in metastatic melanoma.

PubMed

Legha, S S; Hall, S W; Powell, K C; Burgess, M A; Benjamin, R S; Gutterman, J U; Bodey, G P

1980-01-01

A phase II study of AMSA in previously treated patients with metastatic malignant melanoma was conducted. The dose schedule of AMSA was 40 mg/m2/day for 3 days repeated at 3-week intervals. Among the 30 evaluable patients, one achieved a complete response, one a partial response, and four had minor responses. Side effects included mild nausea and vomiting and moderate degree of myelosuppression. AMSA has poor activity against previously treated metastatic melanoma.

Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE for Metastatic Neuroendocrine Tumor Occurring in Association with Multiple Endocrine Neoplasia Type 1 and Cushing's Syndrome.

PubMed

Naik, Chinna; Basu, Sandip

2017-01-01

Neuroendocrine tumor (NET) occurring in association with other endocrine syndromes forms a distinct entity. The aim was to assess the therapy response profile of the routine peptide receptor radionuclide therapy (PRRT) in this relatively uncommon but clinically challenging subgroup of patients. A retrospective analysis was undertaken from the case records from those who were treated with 177 Lu-DOTATATE for metastatic NET. In addition to assessing the therapeutic efficacy, emphasis was also given to study lesional sites and scan pattern. A total of 5 cases were found: In this series of five cases, four belonged to multiple endocrine neoplasia type 1 (MEN1) syndrome; in these four MEN1 syndrome patients, the primary site of NET was thymic region ( n = 1), duodenum ( n = 1), and pancreas ( n = 2). The fifth case was of Cushing's syndrome with the primary site of NET in the thymus. A good symptomatic response was observed in all MEN1 syndrome cases (100%) and progression of symptoms in the patient with Cushing's syndrome. The biochemical response (assessed by measurement of tumor marker serum chromogranin A) demonstrated very good partial response (defined by more than 75% reduction of tumor marker) in 2 MEN1 cases and Cushing's syndrome, good partial response (25-75% reduction of tumor marker) in the remaining 2 MEN1 cases. Scan wise (assessed by technetium [ 99m Tc]-hydrazinonicotinamide [HYNIC]-tektrotyd [TOC]/ 68 Ga-DOTA-NOC/TATE positron emission tomography-computed tomography [PET-CT] and fluorodeoxyglucose [FDG] PET-CT) partial response was observed in 3 MEN1 cases, stable disease was noted in one MEN1 case and disease progression was noted in the patient with Cushing's syndrome. The change in FDG uptake was found to be an important sensitive scan parameter in the treatment evaluation of NETs compared to somatostatin receptor-based imaging in the cases with low MiB1 index. In our series, good palliative response to 177 Lu-DOTA-octreotate (DOTATATE) PRRT was observed in most NET patients associated with MEN1 syndrome without any major hematological or renal toxicity.

Cognitive Behavioral Analysis System of Psychotherapy and Brief Supportive Psychotherapy for Augmentation of Antidepressant Nonresponse in Chronic Depression

PubMed Central

Kocsis, James H.; Gelenberg, Alan J.; Rothbaum, Barbara O.; Klein, Daniel N.; Trivedi, Madhukar H.; Manber, Rachel; Keller, Martin B.; Leon, Andrew C.; Wisniewski, Steven R.; Arnow, Bruce A.; Markowitz, John C.; Thase, Michael E.

2012-01-01

Context Previous studies have found that few chronically depressed patients remit with antidepressant medications alone. Objective To determine the role of adjunctive psychotherapy in the treatment of chronically depressed patients with less than complete response to an initial medication trial. Design This trial compared 12 weeks of (1) continued pharmacotherapy and augmentation with cognitive behavioral analysis system of psychotherapy (CBASP), (2) continued pharmacotherapy and augmentation with brief supportive psychotherapy (BSP), and (3) continued optimized pharmacotherapy (MEDS) alone. We hypothesized that adding CBASP would produce higher rates of response and remission than adding BSP or continuing MEDS alone. Setting Eight academic sites. Participants Chronically depressed patients with a current DSM-IV–defined major depressive episode and persistent depressive symptoms for more than 2 years. Interventions Phase 1 consisted of open-label, algorithm-guided treatment for 12 weeks based on a history of antidepressant response. Patients not achieving remission received next-step pharmacotherapy options with or without adjunctive psychotherapy (phase 2). Individuals undergoing psychotherapy were randomized to receive either CBASP or BSP stratified by phase 1 response, ie, as nonresponders (NRs) or partial responders (PRs). Main Outcome Measures Proportions of remitters, PRs, and NRs and change on Hamilton Scale for Depression (HAM-D) scores. Results In all, 808 participants entered phase 1, of which 491 were classified as NRs or PRs and entered phase 2 (200 received CBASP and MEDS, 195 received BSP and MEDS, and 96 received MEDS only). Mean HAM-D scores dropped from 25.9 to 17.7 in NRs and from 15.2 to 9.9 in PRs. No statistically significant differences emerged among the 3 treatment groups in the proportions of phase 2 remission (15.0%), partial response (22.5%), and non-response (62.5%) or in changes on HAM-D scores. Conclusions Although 37.5% of the participants experienced partial response or remitted in phase 2, neither form of adjunctive psychotherapy significantly improved outcomes over that of a flexible, individualized pharmacotherapy regimen alone. A longitudinal assessment of later-emerging benefits is ongoing. Trial Registration clinicaltrials.gov Identifier: NCT00057551 PMID:19884606

Experimental evidence for partial spatial coherence in imaging Mueller polarimetry.

PubMed

Ossikovski, Razvigor; Arteaga, Oriol; Yoo, Sang Hyuk; Garcia-Caurel, Enric; Hingerl, Kurt

2017-11-15

We demonstrate experimentally the validity of the partial spatial coherence formalism in Mueller polarimetry and show that, in a finite spatial resolution experiment, the measured response is obtained through convolving the theoretical one with the instrument function. The reported results are of primary importance for Mueller imaging systems.

Fitting and Testing Conditional Multinormal Partial Credit Models

ERIC Educational Resources Information Center

Hessen, David J.

2012-01-01

A multinormal partial credit model for factor analysis of polytomously scored items with ordered response categories is derived using an extension of the Dutch Identity (Holland in "Psychometrika" 55:5-18, 1990). In the model, latent variables are assumed to have a multivariate normal distribution conditional on unweighted sums of item…

ISOLATION OF JUVENILE HORMONES ESTERASE AND ITS PARTIAL CDNA CLONE FROM THE BEETLE, TENEBRIO MOLITOR. (R825433)

EPA Science Inventory

Juvenile hormone esterase (JHE) plays an essential role in insect development. It is partially responsible for the clearance of juvenile hormone (JH) which regulates various aspects of insect development and reproduction. Because of its role in regulating JH titer, this enzyme...

Photosynthetic Light Response of Bottomland Oak Seedlings Raised Under Partial Sunlight

Treesearch

Emile S. Gardiner

2002-01-01

Seedlings of cherrybark oak (Quercus pagoda Rafinesque), Nuttall oak (Quercus nuttallii Palmer) and overcup oak (Quercus lyrata Walter) were grown under two light levels, partial (20 percent) or full sunlight, to study physiological acclimation of leaves to low light availability. Shifts in leaf morphology were...

Evidence for partial overlap of male olfactory cues in lampreys

USGS Publications Warehouse

Buchinger, Tyler J.; Li, Ke; Huertas, Mar; Baker, Cindy F.; Jia, Liang; Hayes, Michael C.; Li, Weiming; Johnson, Nicholas S.

2016-01-01

Animals rely on a mosaic of complex information to find and evaluate mates. Pheromones, often comprised of multiple components, are considered to be particularly important for species-recognition in many species. While the evolution of species-specific pheromone blends is well-described in many insects, very few vertebrate pheromones have been studied in a macro-evolutionary context. Here, we report a phylogenetic comparison of multi-component male odours that guide reproduction in lampreys. Chemical profiling of sexually mature males from eleven species of lamprey, representing six of ten genera and two of three families, indicated the chemical profiles of sexually mature male odours are partially shared among species. Behavioural assays conducted with four species sympatric in the Laurentian Great Lakes indicated asymmetric female responses to heterospecific odours, where Petromyzon marinus were attracted to male odour collected from all species tested but other species generally preferred only the odour of conspecifics. Electro-olfactogram recordings from P. marinusindicated that although P. marinus exhibited behavioural responses to odours from males of all species, at least some of the compounds that elicited olfactory responses were different in conspecific male odours compared to heterospecific male odours. We conclude that some of the compounds released by sexually mature males are shared among species and elicit olfactory and behavioural responses in P. marinus, and suggest that our results provide evidence for partial overlap of male olfactory cues among lampreys. Further characterization of the chemical identities of odour components is needed to confirm shared pheromones among species.

Social Information Processing Mediates the Intergenerational Transmission of Aggressiveness in Romantic Relationships

PubMed Central

Fite, Jennifer E.; Bates, John E.; Holtzworth-Munroe, Amy; Dodge, Kenneth A.; Nay, Sandra Y.; Pettit, Gregory S.

2012-01-01

This study explored the K. A. Dodge (1986) model of social information processing as a mediator of the association between interparental relationship conflict and subsequent offspring romantic relationship conflict in young adulthood. The authors tested 4 social information processing stages (encoding, hostile attributions, generation of aggressive responses, and positive evaluation of aggressive responses) in separate models to explore their independent effects as potential mediators. There was no evidence of mediation for encoding and attributions. However, there was evidence of significant mediation for both the response generation and response evaluation stages of the model. Results suggest that the ability of offspring to generate varied social responses and effectively evaluate the potential outcome of their responses at least partially mediates the intergenerational transmission of relationship conflict. PMID:18540765

Novel therapy in multiple myeloma.

PubMed

Avilés, Agustin; Neri, Natividad; Nambo, M Jesús; Cleto, Sergio; Castañeda, Claudia; González, Martha; Talavera, Alejandra; Huerta-Guzmán, Judith

2005-10-01

Treatment in patients with multiple myeloma remain to be defined. Younger patients (defined as a cut-off level < 65 years old) will be treated with chemotherapy and transplant procedures. However, most patients > 65 years old are not candidates for this therapeutic approach and the use of intensive chemotherapy could be associated to severe toxicity. We developed an new, not-cytotoxic regimen with dexamethasone 30 mg/m(2), iv, days 1 to 4, all trans retinoic acid 45 mg/m(2), po, days 5 to 14 and interferon alfa 2a 4.5 MU, sc, daily, days 5 to 14 (DAI regimen) administered every 28 days in number of 6 cycles, at this point patients were restaging, if they showed complete response, objective response or partial response they were conducted to received thalidomide 100-200 mg po, daily and dexamethasone 10 mg/2, po days 1 to 4 at monthly intervals, for 18 months. Forty one patients were enrolled in an Phase II study. In an intent to treat analysis all patients were evaluable. Complete response was observed in 18 cases (43%), objective response in 10 patients (24%) and partial response in 5 patients (12%), overall response rate was 80%. Eight patients were considered failures. At an median of 36 months, no relapse of progression disease has been observed, thus actuarial curves at 3-years showed that event free survival is 100% and overall survival is 91%. Toxicity was mild, all patients received the planned dose in time. This regimen appear to be useful in older patients with multiple myeloma, the response rate is higher and toxicity was mild. Controlled clinical trials comparing with conventional chemotherapy will be conducted to define the role of this therapeutic approach.

Ipilimumab for Patients With Advanced Mucosal Melanoma

PubMed Central

Postow, Michael A.; Luke, Jason J.; Bluth, Mark J.; Ramaiya, Nikhil; Panageas, Katherine S.; Lawrence, Donald P.; Ibrahim, Nageatte; Flaherty, Keith T.; Sullivan, Ryan J.; Ott, Patrick A.; Callahan, Margaret K.; Harding, James J.; D'Angelo, Sandra P.; Dickson, Mark A.; Schwartz, Gary K.; Chapman, Paul B.; Gnjatic, Sacha; Wolchok, Jedd D.; Hodi, F. Stephen

2013-01-01

The outcome of patients with mucosal melanoma treated with ipilimumab is not defined. To assess the efficacy and safety of ipilimumab in this melanoma subset, we performed a multicenter, retrospective analysis of 33 patients with unresectable or metastatic mucosal melanoma treated with ipilimumab. The clinical characteristics, treatments, toxicities, radiographic assessment of disease burden by central radiology review at each site, and mutational profiles of the patients' tumors were recorded. Available peripheral blood samples were used to assess humoral immunity against a panel of cancer-testis antigens and other antigens. By the immune-related response criteria of the 30 patients who underwent radiographic assessment after ipilimumab at approximately week 12, there were 1 immune-related complete response, 1 immune-related partial response, 6 immune-related stable disease, and 22 immune-related progressive disease. By the modified World Health Organization criteria, there were 1 immune-related complete response, 1 immune-related partial response, 5 immune-related stable disease, and 23 immune-related progressive disease. Immune-related adverse events (as graded by Common Terminology Criteria for Adverse Events version 4.0) consisted of six patients with rash (four grade 1, two grade 2), three patients with diarrhea (one grade 1, two grade 3), one patient with grade 1 thyroiditis, one patient with grade 3 hepatitis, and 1 patient with grade 2 hypophysitis. The median overall survival from the time of the first dose of ipilimumab was 6.4 months (range: 1.8–26.7 months). Several patients demonstrated serologic responses to cancer-testis antigens and other antigens. Durable responses to ipilimumab were observed, but the overall response rate was low. Additional investigation is necessary to clarify the role of ipilimumab in patients with mucosal melanoma. PMID:23716015

Ipilimumab for patients with advanced mucosal melanoma.

PubMed

Postow, Michael A; Luke, Jason J; Bluth, Mark J; Ramaiya, Nikhil; Panageas, Katherine S; Lawrence, Donald P; Ibrahim, Nageatte; Flaherty, Keith T; Sullivan, Ryan J; Ott, Patrick A; Callahan, Margaret K; Harding, James J; D'Angelo, Sandra P; Dickson, Mark A; Schwartz, Gary K; Chapman, Paul B; Gnjatic, Sacha; Wolchok, Jedd D; Hodi, F Stephen; Carvajal, Richard D

2013-06-01

The outcome of patients with mucosal melanoma treated with ipilimumab is not defined. To assess the efficacy and safety of ipilimumab in this melanoma subset, we performed a multicenter, retrospective analysis of 33 patients with unresectable or metastatic mucosal melanoma treated with ipilimumab. The clinical characteristics, treatments, toxicities, radiographic assessment of disease burden by central radiology review at each site, and mutational profiles of the patients' tumors were recorded. Available peripheral blood samples were used to assess humoral immunity against a panel of cancer-testis antigens and other antigens. By the immune-related response criteria of the 30 patients who underwent radiographic assessment after ipilimumab at approximately week 12, there were 1 immune-related complete response, 1 immune-related partial response, 6 immune-related stable disease, and 22 immune-related progressive disease. By the modified World Health Organization criteria, there were 1 immune-related complete response, 1 immune-related partial response, 5 immune-related stable disease, and 23 immune-related progressive disease. Immune-related adverse events (as graded by Common Terminology Criteria for Adverse Events version 4.0) consisted of six patients with rash (four grade 1, two grade 2), three patients with diarrhea (one grade 1, two grade 3), one patient with grade 1 thyroiditis, one patient with grade 3 hepatitis, and 1 patient with grade 2 hypophysitis. The median overall survival from the time of the first dose of ipilimumab was 6.4 months (range: 1.8-26.7 months). Several patients demonstrated serologic responses to cancer-testis antigens and other antigens. Durable responses to ipilimumab were observed, but the overall response rate was low. Additional investigation is necessary to clarify the role of ipilimumab in patients with mucosal melanoma.

Felix Hoppe-Seyler Lecture 1997. Protective antibody responses against viruses.

PubMed

Zinkernagel, R M

1997-08-01

Neutralizing antibody responses against the acute cytopathic vesicular stomatitis virus (VSV) have been studied in mice to evaluate their general characteristics including specificity, self-/non-self discrimination and memory. IgM responses are generated very early, by day 3 to 4, in a T helper cell-independent fashion and without VSV having polyclonal activating capacities. The order of the glycoprotein tips on the virus envelope (multiple, 8-10 nm distance, paracrystalline) exhibiting the neutralizing determinants are key to this prompt response. These paracrystalline identical multimeric antigens are characteristic of infectious agents and are always reacted against by B cells. Self-antigens that are accessible to B cells in the intact host are either monomeric in serum or mobile multimers on cell surfaces; these configurations need contact dependent or contact independent T help, respectively. Because T help is tolerant against self-antigens, no anti-self B cell responses are usually induced against monomeric self-antigens. If collagen or DNA (rigid multimeric self-antigens) become accessible, however, they may become targets of auto-antibody responses. The antibody repertoire against VSV is partially contained in the germline and partially is generated by somatic mutation; they seem not to undergo affinity-maturation. In any case protection against lethal infection is dependent upon strictly T helper cell dependent IgG generated by day 6 to 7 and reaches a protective level of about 1-10 micrograms/ml. Interesting affinity/avidity and onrate above a minimal threshold are of no apparent advantage for protection in vivo. Maintenance of these antibody levels by antigen depots, and not the presence of memory B cells alone, is key to providing protective immunological memory. Collectively these data suggest that studying biologically important protective antibody responses may modify some of the parameters that have been defined by studying hapten specific antibody responses.

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

Phase II Study of Dutasteride for Recurrent Prostate Cancer During Androgen Deprivation Therapy

PubMed Central

Shah, Satyan K.; Trump, Donald L.; Sartor, Oliver; Tan, Wei; Wilding, Gregory E.; Mohler, James L.

2010-01-01

Purpose We determined the response rate to and safety of a dual 5α-reductase inhibitor, dutasteride, in men with castration recurrent prostate cancer. Materials and Methods A total of 28 men with asymptomatic castration recurrent prostate cancer were treated with 3.5 mg dutasteride daily (luteinizing hormone-releasing hormone treatment continued), and evaluated monthly for response and toxicity. Eligibility included appropriate duration antiandrogen withdrawal, baseline prostate specific antigen 2.0 ng/ml or greater and a new lesion on bone scan, increase in measurable disease using Response Evaluation Criteria in Solid Tumors criteria, or 2 or more consecutive prostate specific antigen measurements increased over baseline. Outcomes were progression, stable disease, partial response (prostate specific antigen less than 50% of enrollment for 4 or more weeks) or complete response. Results There were 25 evaluable men with a mean age of 70 years (range 57 to 88), a mean prostate specific antigen of 61.9 ng/ml (range 5.0 to 488.9) and mean Gleason score 8 (range 6 to 10), 15 of whom had bone metastases. Eight men had 10 grade 3 or higher adverse events using National Cancer Institute Common Terminology Criteria, all of which were judged to be unrelated to treatment. Of the 25 men 14 had disease progression by 2 months, 9 had stable (2.5, 3, 3, 4, 4, 5, 5, 8.5, 9 months) disease, 2 had a partial response and none had a complete response. Overall median time to progression was 1.87 months (range 1 to 10, 95% CI 1.15–3.91). Conclusions Dutasteride rarely produces biochemical responses in men with castration recurrent prostate cancer. However, further study is warranted given its favorable safety profile. PMID:19091347

Partial cutting of western hemlock and sitka spruce in southeast Alaska.

Treesearch

Wilbur A. Farr; A.S. Harris

1971-01-01

This study of response to partial cutting over a 17-year period in a 96-year-old stand of western hemlock-Sitka spruce at Karta Bay, Alaska, showed that crop trees left after partial cutting were able to increase or maintain &out the same rate of diameter growth as before thinning, but growth in diameter of trees in an unthinned stand followed the norma2 pattern of...

Population response of the northern red-backed vole (Clethrionomys rutilus) to differentially cut white spruce forest.

Treesearch

Stephen D. West; R. Glenn Ford; John C. Zasada

1980-01-01

The population response of the northern red-backed vole (Clethrionomys rutilus) to a differentially cut white spruce (Picea glauca) forest 30 km southwest of Fairbanks, Alaska, was monitored by simultaneous livetrapping in a clearcut, in a partially cut or shelterwood area, and in an area of uncut forest. During the first...

Use of Mutant-Assisted Gene Identification and Characterization (MAGIC) to identify novel genetic loci that modify the maize hypersensitive response

USDA-ARS?s Scientific Manuscript database

The partially-dominant, autoactive maize disease resistance gene Rp1-D21 causes hypersensitive response (HR) lesions to form spontaneously on the leaves and stem in the absence of pathogen recognition. The maize nested association mapping (NAM) population consists of 25 200-line subpopulations each...

Translational Response of Toe-Restrained Retaining Walls to Earthquake Ground Motions Using CorpsWallSlip (CWSlip)

DTIC Science & Technology

2007-06-01

corresponding software developed for the translational response of rock- founded retaining walls buttressed at their toe by a reinforced concrete slab...by a Reinforced Concrete Slab ...........................................................................................................32 2.1...2.5 New translational analysis model of a wall retaining a partially submerged backfill and buttressed by a reinforced concrete slab

Responsibility, Authority, and Accountability in School-Based and Non-School-Based Management: Principals' Coping Strategies

ERIC Educational Resources Information Center

Grinshtain, Yael; Gibton, Dan

2018-01-01

Purpose: The purpose of this paper is to understand how primary school principals in Israel cope with the gaps between authority and responsibility in their work, deriving from partially implemented decentralization processes, and how this relates to school-based management (SBM) and accountability principles. Design/methodology/approach: Using…

Initial Experiences with Machine-Assisted Reconsiderative Test Scoring: A New Method for Partial Credit and Multiple Correct Responses.

ERIC Educational Resources Information Center

Anderson, Paul S.

Initial experiences with computer-assisted reconsiderative scoring are described. Reconsiderative scoring occurs when student responses are received and reviewed by the teacher before points for correctness are assigned. Manually scored completion-style questions are reconsiderative. A new method of machine assistance produces an item analysis on…

A Person Fit Test for IRT Models for Polytomous Items

ERIC Educational Resources Information Center

Glas, C. A. W.; Dagohoy, Anna Villa T.

2007-01-01

A person fit test based on the Lagrange multiplier test is presented for three item response theory models for polytomous items: the generalized partial credit model, the sequential model, and the graded response model. The test can also be used in the framework of multidimensional ability parameters. It is shown that the Lagrange multiplier…

Generalized Path Analysis and Generalized Simultaneous Equations Model for Recursive Systems with Responses of Mixed Types

ERIC Educational Resources Information Center

Tsai, Tien-Lung; Shau, Wen-Yi; Hu, Fu-Chang

2006-01-01

This article generalizes linear path analysis (PA) and simultaneous equations models (SiEM) to deal with mixed responses of different types in a recursive or triangular system. An efficient instrumental variable (IV) method for estimating the structural coefficients of a 2-equation partially recursive generalized path analysis (GPA) model and…

75 FR 34260 - Federal Acquisition Regulation; FAR Case 2005-040, Electronic Subcontracting Reporting System (eSRS)

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-16

... documented as past performance for future acquisitions.'' Response: Partially concur. The Councils do not... in FAR 19.704(a)(2) should be revised to read ``Submit a new commercial plan, 30 working days before... performance. Response: Non-concur. Although it is essential that the Central Contractor Registration, the...

Student Response to a Partial Inversion of an Organic Chemistry Course for Non-Chemistry Majors

ERIC Educational Resources Information Center

Rein, Kathleen S.; Brookes, David T.

2015-01-01

We report the student response to a two-year transformation of a one-semester organic chemistry course for nonchemistry majors. The transformed course adopted a peer led team learning approach and incorporated case studies. Student attitudes toward the course transformation were assessed throughout the semester, and adjustments to the methods were…

Heritability of HR and BP Response To Exercise Training in the HERITAGE Family Study.

ERIC Educational Resources Information Center

Rice, Treva; Gagnon, Jacques; Leon, Arthur S.; Skinner, James S.; Wilmore, Jack H.; Bouchard, Claude; Rao, D. C.

2002-01-01

Assessed the heritability of response to exercise training in resting blood pressure (BP) and heart rate (HR) among sedentary Caucasians comprising 98 families who completed an exercise training program. Results indicated that the trainability of systolic BP and HR in families with elevated BP was partially determined by genetic factors. Diastolic…

Responses of an Insect Folivore and Its Parastoids to Multiyear Experimental Defoliation of Aspen

Treesearch

Dylan Parry; Daniel A. Herms; William J. Mattson

2003-01-01

Foliage quality may decline in deciduous trees following defoliation, thus affecting the insect generation responsible for the herbivory (rapid induced resistance, RIR), or future generations (delayed induced resistance, DIR). During outbreaks, trees often suffer partial or complete defoliation for two or more successive years, yet most studies have examined induced...

Maximum Marginal Likelihood Estimation of a Monotonic Polynomial Generalized Partial Credit Model with Applications to Multiple Group Analysis.

PubMed

Falk, Carl F; Cai, Li

2016-06-01

We present a semi-parametric approach to estimating item response functions (IRF) useful when the true IRF does not strictly follow commonly used functions. Our approach replaces the linear predictor of the generalized partial credit model with a monotonic polynomial. The model includes the regular generalized partial credit model at the lowest order polynomial. Our approach extends Liang's (A semi-parametric approach to estimate IRFs, Unpublished doctoral dissertation, 2007) method for dichotomous item responses to the case of polytomous data. Furthermore, item parameter estimation is implemented with maximum marginal likelihood using the Bock-Aitkin EM algorithm, thereby facilitating multiple group analyses useful in operational settings. Our approach is demonstrated on both educational and psychological data. We present simulation results comparing our approach to more standard IRF estimation approaches and other non-parametric and semi-parametric alternatives.

User's guide to computer program CIVM-JET 4B to calculate the transient structural responses of partial and/or complete structural rings to engine-rotor-fragment impact

NASA Technical Reports Server (NTRS)

Stagliano, T. R.; Spilker, R. L.; Witmer, E. A.

1976-01-01

A user-oriented computer program CIVM-JET 4B is described to predict the large-deflection elastic-plastic structural responses of fragment impacted single-layer: (a) partial-ring fragment containment or deflector structure or (b) complete-ring fragment containment structure. These two types of structures may be either free or supported in various ways. Supports accommodated include: (1) point supports such as pinned-fixed, ideally-clamped, or supported by a structural branch simulating mounting-bracket structure and (2) elastic foundation support distributed over selected regions of the structure. The initial geometry of each partial or complete ring may be circular or arbitrarily curved; uniform or variable thicknesses of the structure are accommodated. The structural material is assumed to be initially isotropic; strain hardening and strain rate effects are taken into account.

Partial information can be transmitted in an auditory channel: inferences from lateralized readiness potentials.

PubMed

Gong, Diankun; Hu, Jiehui; Yao, Dezhong

2012-04-01

With the two-choice go/no-go paradigm, we investigated whether timbre attribute can be transmitted as partial information from the stimulus identification stage to the response preparation stage in auditory tone processing. We manipulated two attributes of the stimulus: timbre (piano vs. violin) and acoustic intensity (soft vs. loud) to ensure an earlier processing of timbre than intensity. We associated the timbre attribute more with go trials. Results showed that lateralized readiness potentials (LRPs) were consistently elicited in no-go trials. This showed that the timbre attribute had been transmitted to the response preparation stage before the intensity attribute was processed in the stimuli identification stage. Such a result provides evidence for the continuous model and asynchronous discrete coding (ADC) model in information processing. We suggest that partial information can be transmitted in an auditory channel. Copyright © 2011 Society for Psychophysiological Research.

Investigations of student understanding of entropy and of mixed second-order partial derivatives in upper-level thermodynamics

NASA Astrophysics Data System (ADS)

Bucy, Brandon R.

While much of physics education research (PER) has traditionally been conducted in introductory undergraduate courses, researchers have begun to study student understanding of physics concepts at the upper-level. In this dissertation, we describe investigations conducted in advanced undergraduate thermodynamics courses. We present and discuss results pertaining to student understanding of two topics: entropy and the role of mixed second-order partial derivatives in thermodynamics. Our investigations into student understanding of entropy consisted of an analysis of written student responses to researcher-designed diagnostic questions. Data gathered in clinical interviews is employed to illustrate and extend results gathered from written responses. The question sets provided students with several ideal gas processes, and asked students to determine and compare the entropy changes of these processes. We administered the question sets to students from six distinct populations, including students enrolled in classical thermodynamics, statistical mechanics, thermal physics, physical chemistry, and chemical engineering courses, as well as a sample of physics graduate students. Data was gathered both before and after instruction in several samples. Several noteworthy features of student reasoning are identified and discussed. These features include student ideas about entropy prior to instruction, as well as specific difficulties and other aspects of student reasoning evident after instruction. As an example, students from various populations tended to emphasize either the thermodynamic or the statistical definition of entropy. Both approaches present students with a unique set of benefits as well as challenges. We additionally studied student understanding of partial derivatives in a thermodynamics context. We identified specific difficulties related to the mixed second partial derivatives of a thermodynamic state function, based on an analysis of student responses to homework and exam problems. Students tended to set these partial derivatives identically equal to zero. Students also displayed difficulties in relating the physical description of a material property to a corresponding mathematical statement involving partial derivatives. We describe the development of a guided-inquiry tutorial activity designed to address these specific difficulties. This tutorial focused on the graphical interpretation of partial derivatives. Preliminary results suggest that the tutorial was effective in addressing several student difficulties related to partial derivatives.

Role of the autonomic nervous system in rat liver regeneration.

PubMed

Xu, Cunshuan; Zhang, Xinsheng; Wang, Gaiping; Chang, Cuifang; Zhang, Lianxing; Cheng, Qiuyan; Lu, Ailing

2011-05-01

To study the regulatory role of autonomic nervous system in rat regenerating liver, surgical operations of rat partial hepatectomy (PH) and its operation control (OC), sympathectomy combining partial hepatectomy (SPH), vagotomy combining partial hepatectomy (VPH), and total liver denervation combining partial hepatectomy (TDPH) were performed, then expression profiles of regenerating livers at 2 h after operation were detected using Rat Genome 230 2.0 array. It was shown that the expressions of 97 genes in OC, 230 genes in PH, 253 genes in SPH, 187 genes in VPH, and 177 genes in TDPH were significantly changed in biology. The relevance analysis showed that in SPH, genes involved in stimulus response, immunity response, amino acids and K(+) transport, amino acid catabolism, cell adhesion, cell proliferation mediated by JAK-STAT, Ca(+), and platelet-derived growth factor receptor, cell growth and differentiation through JAK-STAT were up-regulated, while the genes involved in chromatin assembly and disassembly, and cell apoptosis mediated by MAPK were down-regulated. In VPH, the genes associated with chromosome modification-related transcription factor, oxygen transport, and cell apoptosis mediated by MAPK pathway were up-regulated, but the genes associated with amino acid catabolism, histone acetylation-related transcription factor, and cell differentiation mediated by Wnt pathway were down-regulated. In TDPH, the genes related to immunity response, growth and development of regenerating liver, cell growth by MAPK pathway were up-regulated. Our data suggested that splanchnic and vagal nerves could regulate the expressions of liver regeneration-related genes.

Comparison of Th1- and Th2-associated immune reactivities stimulated by single versus multiple vaccination of mice with irradiated Schistosoma mansoni cercariae

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

Caulada-Benedetti, Z.; Al-Zamel, F.; Sher, A.

1991-03-01

Mice immunized against Schistosoma mansoni by a single percutaneous exposure to radiation-attenuated parasite larvae demonstrate partial resistance to challenge infection that has been shown to correlate with development of cell-mediated immunity, whereas mice hyperimmunized by multiple exposure to attenuated larvae produce antibodies capable of transferring partial protection to naive recipients. Measurement of Ag-specific lymphokine responses in these animals suggested that the difference in resistance mechanisms may be due to the differential induction of Th subset response by the two immunization protocols. Thus, upon Ag stimulation, singly immunized mice predominantly demonstrated responses associated with Th1 reactivity, including IL-2 and IFN-gamma production,more » whereas multiply immunized animals showed increased IL-5, IL-4, and IgG1 antibody production associated with enhanced Th2 response. These responses demonstrated some degree of organ compartmentalization, with splenocytes demonstrating higher Th1-related lymphokine production and cells from draining lymph nodes showing stronger proliferation and Th2 type reactivity. However, hyperimmunized mice also continued to demonstrate substantial Th1-associated immune reactivity. Moreover, in vivo Ag challenge elicited activated larvacidal macrophages in hyperimmunized animals. These observations indicate that protective cell-mediated mechanisms associated with induction of CD4+ Th1 cell reactivity predominate in singly vaccinated mice. Further vaccination stimulates Th2 responses, such as enhanced IgG1 production, that may also contribute to protective immunity.« less

Chemotherapy for neuroendocrine tumors: the Beatson Oncology Centre experience.

PubMed

Hatton, M Q; Reed, N S

1997-01-01

The role of chemotherapy in malignant neuroendocrine tumours is difficult to assess because of their rarity and variation in biological behaviour. We present a retrospective review of chemotherapy given to 18 patients with metastatic and one with locally advanced neuroendocrine tumours. There were eight poorly differentiated neuroendocrine tumours, six thyroid medullary carcinomas, two phaeochromocytomas, two pancreatic islet cell tumours and one undifferentiated neuroblastoma. Four patients were given 3-weekly dacarbazine, vincristine and cyclophosphamide (DOC) chemotherapy. In eight patients, this regimen was modified by substituting the dacarbazine and cisplatin and etoposide (OPEC). A further six patients were treated with dacarbazine reintroduced into the 3-weekly regimen (DOPEC). The remaining patient received cisplatin and etoposide. There were two complete responses (both with OPEC) and eight partial responses (two with DOC, three with OPEC and three with DOPEC). Five patients had stable disease and four progressed. Four received further chemotherapy on relapse, producing one complete and one partial response. The median response duration to initial chemotherapy was 10 months (range 3-34). The median survival was 12 months (range 1-42). The main toxicity was haematological, with grade 3-4 neutropenia in 12 patients; eight suffered episodes of sepsis. One death was treatment related. Other toxicity was mild although three patients discontinued vincristine with grade 2 neurotoxicity. The response rate and side effects of these three regimens appear comparable. We conclude that, although these patient numbers are small, combination chemotherapy produces an encouraging response rate (53%; 95% CI 30-75) in malignant neuroendocrine tumours, with acceptable toxicity.

Infrared neural stimulation (INS) inhibits electrically evoked neural responses in the deaf white cat

NASA Astrophysics Data System (ADS)

Richter, Claus-Peter; Rajguru, Suhrud M.; Robinson, Alan; Young, Hunter K.

2014-03-01

Infrared neural stimulation (INS) has been used in the past to evoke neural activity from hearing and partially deaf animals. All the responses were excitatory. In Aplysia californica, Duke and coworkers demonstrated that INS also inhibits neural responses [1], which similar observations were made in the vestibular system [2, 3]. In deaf white cats that have cochleae with largely reduced spiral ganglion neuron counts and a significant degeneration of the organ of Corti, no cochlear compound action potentials could be observed during INS alone. However, the combined electrical and optical stimulation demonstrated inhibitory responses during irradiation with infrared light.

Iron-Deficiency Anemia After Partial Gastrectomy

PubMed Central

Geokas, M. C.; McKenna, R. D.

1967-01-01

Although the mechanism for its development is not well understood, iron-deficiency anemia is a well-recognized consequence of partial gastrectomy. The reported incidence varies considerably, depending upon the criteria used to define anemia, and other factors. Rapid emptying of the gastric remnant, intestinal “hurry”, and borderline dietary-iron intake, with or without concomitant blood loss, produce malabsorption of some forms of iron that appears to be responsible for development of the deficiency. The diagnosis rests on hematological findings in the peripheral blood, the evaluation of iron stores, epithelial changes, and the response to adequate treatment. Oral iron therapy can be both effective and inexpensive and should form the mainstay of treatment. PMID:6019057

Detecting Math Anxiety with a Mixture Partial Credit Model

ERIC Educational Resources Information Center

Ölmez, Ibrahim Burak; Cohen, Allan S.

2017-01-01

The purpose of this study was to investigate a new methodology for detection of differences in middle grades students' math anxiety. A mixture partial credit model analysis revealed two distinct latent classes based on homogeneities in response patterns within each latent class. Students in Class 1 had less anxiety about apprehension of math…

Inductive Sensor Performance in Partial Discharges and Noise Separation by Means of Spectral Power Ratios

PubMed Central

Ardila-Rey, Jorge Alfredo; Rojas-Moreno, Mónica Victoria; Martínez-Tarifa, Juan Manuel; Robles, Guillermo

2014-01-01

Partial discharge (PD) detection is a standardized technique to qualify electrical insulation in machines and power cables. Several techniques that analyze the waveform of the pulses have been proposed to discriminate noise from PD activity. Among them, spectral power ratio representation shows great flexibility in the separation of the sources of PD. Mapping spectral power ratios in two-dimensional plots leads to clusters of points which group pulses with similar characteristics. The position in the map depends on the nature of the partial discharge, the setup and the frequency response of the sensors. If these clusters are clearly separated, the subsequent task of identifying the source of the discharge is straightforward so the distance between clusters can be a figure of merit to suggest the best option for PD recognition. In this paper, two inductive sensors with different frequency responses to pulsed signals, a high frequency current transformer and an inductive loop sensor, are analyzed to test their performance in detecting and separating the sources of partial discharges. PMID:24556674

The effects of ALG on the murine immune response to sheep erythrocytes

PubMed Central

Anderson, Hilary R.; Dresser, D. W.; Iverson, G. M.; Lance, E. M.; Wortis, H. H.; Zebra, J.

1972-01-01

Antilymphocyte globulin (ALG), and to a lesser extent normal rabbit globulin (NRG), when given to mice prior to immunization with sheep-RBC suppress both the γM and γG2a responses. Globulin injected after the antigen suppresses the γG2a response, augments the γG1 response and has little effect on the γM response. These effects are also observed in mice partially paralysed to rabbit γ globulin. In another system—the response to hapten—protein conjugates precursors of antibody producing cells were found to be more resistant to ALS treatment in vivo than were helper cells. It is concluded that the suppressive effects of ALG treatment are largely due to the direct action of ALG on helper cells (T-cells). The mechanism of the adjuvant-like effect is unclear. PMID:4550853

An Investigation of the Accuracy of Alternative Methods of True Score Estimation in High-Stakes Mixed-Format Examinations.

ERIC Educational Resources Information Center

Klinger, Don A.; Rogers, W. Todd

2003-01-01

The estimation accuracy of procedures based on classical test score theory and item response theory (generalized partial credit model) were compared for examinations consisting of multiple-choice and extended-response items. Analysis of British Columbia Scholarship Examination results found an error rate of about 10 percent for both methods, with…

76 FR 51398 - Notice of Proposed Partial Consent Decree Under the Comprehensive Environmental Response...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-18

... Environmental Response, Compensation, and Liability Act and the Clean Air Act Notice is hereby given that on....C. 9607, and Sections 112(r) and 114(a) of the Clean Air Act (``CAA''), 42 U.S.C. 7412(r), 7414(a), with respect to the Danversport Superfund Site, a former inks and paint products manufacturing facility...

Canopy arthropod response to density and distribution of green trees retained after partial harvest.

Treesearch

Timothy D. Schowalter; Yanli Zhang; Robert A. Progar

2005-01-01

We measured canopy arthropod responses to six contrasting green-tree retention treatments at six locations (blocks) in western Oregon and Washington as part of the Demonstration of Ecosystem Management Options (DEMO) study. Treatments were 100% retention (uncut), 75% retention with three 1-ha harvested gaps, 40% dispersed retention, 40% aggregated retention with five 1...

Silvicultural management within streamside management zones of intermittent streams: effects on decomposition, productivity, nutrient cycling, and channel vegetation

Treesearch

R. Governo; B. G. Lockaby; Robert B. Rummer; C. Colson

2004-01-01

The purpose of this watershed study on three intermittent streams was to evaluate responses of riparian processes to three streamside management zone (SMZ) treatments; no harvest, clearcut, and partial hawest (50% basal area removal). Riparian response variables measured included litter$all, leaf litter decomposition, understory vegetation, soil temperature and water...

Enhancing the Future Strategic Corporal

DTIC Science & Technology

2006-01-01

with greater firepower than ever before, the Strategic Corporal will be charged with greater responsibility than ever before, while the potential for...translation of “Strategic Corporal ”, and the article responsible for popularizing the term, see General Charles C. Krulak, “The Strategic Corporal ...Quantico, Virginia 22134-5068 FUTURE WAR PAPER ENHANCING THE FUTURE STRATEGIC CORPORAL SUBMITTED IN PARTIAL FULFILLMENT OF THE

Phase II trial of cystemustine, a new nitrosourea, as treatment of high-grade brain tumors in adults.

PubMed

Roche, H; Cure, H; Adenis, A; Fargeot, P; Terret, C; Lentz, M A; Madelmont, J C; Fumoleau, P; Hanausk, A; Chollet, P

2000-09-01

This study included 39 patients (37 evaluable, of whom 30 patients with recurrent gliomas and 7 patients with gliomas untreated by radiotherapy); they were enrolled into a phase II trial using a new nitrosourea, cystemustine, administrated every 2 weeks at 60 mg/m2 as a 15 min-infusion. Pathology at inclusion was (WHO classification): 14 glioblastomas, 20 grade 3-4 astrocytomas and 3 grade 3 oligodendrogliomas. Four partial responses have been obtained, giving an overall response rate of 10.8%. Four additional patients had a partial response, which for various reasons was not confirmed 4 weeks later; 12 patients had a stable disease for at least 8 weeks, 15 patients had progressive disease. Of the 4 responses, 2 were with a grade 3 oligodendroglioma and 2 glioblastoma. Toxicity (WHO grading) was mainly hematological: leukopenia (16.2% grade 3-4), neutropenia (29.7% grade 3-4), thrombopenia (27% grade 3-4). No other toxicity greater than grade 2 was observed. In conclusion, cystemustine at 60 mg/m2 has moderate clinical activity in relapsing glioma. Our results warrant further investigation of this agent with an increased dose or modified scheme.

Phase I trial of bortezomib and dacarbazine in melanoma and soft tissue sarcoma.

PubMed

Poklepovic, Andrew; Youssefian, Leena E; Youseffian, Leena; Winning, Mary; Birdsell, Christine A; Crosby, Nancy A; Ramakrishnan, Viswanathan; Ernstoff, Marc S; Roberts, John D

2013-08-01

Preclinical studies in human melanoma cell lines and murine xenograft tumor models suggest that the proteasome inhibitor bortezomib enhances the activity of the cytotoxic agent dacarbazine. We performed a phase I trial of bortezomib and dacarbazine in melanoma, soft tissue sarcoma, and amine precursor uptake and decarboxylation tumors. The primary objective was to identify recommended phase II doses for the combination. Bortezomib and dacarbazine were both administered intravenously once weekly. All patients received prophylactic antiemetics. Dose escalation proceeded using a standard 3 + 3 design. Response was assessed according to NCI RECIST v1.0. Twenty eight patients were enrolled to six dose levels. Bortezomib 1.6 mg/m(2) and dacarbazine 580 mg/m(2) are the recommended phase II weekly doses. The combination was generally well tolerated. Among 15 patients with melanoma there was one durable complete response in a patient with an exon-11 cKIT mutation, and one partial response. Among 12 patients with soft tissue sarcoma there was one partial response. Bortezomib 1.6 mg/m(2) and dacarbazine 580 mg/m(2) administered intravenously once weekly is well tolerated and has at least minimal activity in melanoma and soft tissue sarcoma.

Extrarenal perivascular epithelioid cell tumors (PEComas) respond to mTOR inhibition: Clinical and molecular correlates

PubMed Central

Dickson, Mark A.; Schwartz, Gary K.; Antonescu, Cristina R.; Kwiatkowski, David J.; Malinowska, Izabela A.

2012-01-01

Perivascular epithelioid cell tumors (PEComas) are a group of rare mesenchymal tumors that typically show both melanocytic and smooth muscle cell features. Some types of PEComa are seen at high frequency in tuberous sclerosis complex (TSC). The TSC1 and TSC2 genes are commonly mutated in both TSC-associated and sporadic PEComas, and mTOR signaling pathway activation is also common in these tumors. Preliminary reports have indicated that the mTOR inhibitors sirolimus and related drugs have activity in some patients with non-TSC-associated PEComa. Here we report on the use of these medications in the treatment of five consecutive patients with extrarenal non-pulmonary PEComas seen at one institution. Three complete responses, one partial response and one case of progression were seen. Molecular studies identified TSC2 aberrations in four of these patients, and TFE3 translocation was excluded in the resistant case. A review of all published cases as well as those reported here indicates that partial or complete response was seen in 6 of 11 PEComas, with 5 of the 6 having a complete response. These findings highlight the consistent though incomplete activity of mTOR inhibitors in the treatment of PEComas. PMID:22927055

Perceptual and Motor Inhibition in Adolescents/Young Adults with Childhood-Diagnosed ADHD

PubMed Central

Bedard, Anne-Claude V.; Trampush, Joey W.; Newcorn, Jeffrey H.; Halperin, Jeffrey M.

2010-01-01

Objective This study examined perceptual and motor inhibition in a longitudinal sample of adolescents/young adults who were diagnosed with ADHD in childhood, and as a function of the relative persistence of ADHD. Method Ninety-eight participants diagnosed with ADHD in childhood were re-evaluated approximately 10 years later. Eighty-five never-ADHD controls similar in age, IQ, sociodemographic background, and gender distribution served as a comparison group. Participants were administered a psychiatric interview and the Stimulus and Response Conflict Tasks (Nassauer & Halperin, 2003). Results Participants with childhood ADHD demonstrated slower and less accurate responses to both control and conflict conditions relative to the comparison group, as well as more variable responses in both conditions of the motor inhibition task; there was no specific effect of childhood ADHD on perceptual or motor inhibition. ADHD persisters and partial remitters did not differ in overall accuracy, speed or variability in responding, but relative to partial remitters, persisters demonstrated greater slowing in response to perceptual conflict. Conclusions These findings are consistent with theories positing state regulation, but not inhibitory control deficits in the etiology of ADHD, and suggest that improved perceptual inhibition may be associated with better outcome for ADHD. PMID:20604617

Hyberbaric oxygen as sole treatment for severe radiation - induced haemorrhagic cystitis

PubMed Central

Dellis, Athanasios; Papatsoris, Athanasios; Kalentzos, Vasileios; Deliveliotis, Charalambos; Skolarikos, Andreas

2017-01-01

ABSTRACT Purpose To examine the safety and efficacy of hyperbaric oxygen as the primary and sole treatment for severe radiation-induced haemorrhagic cystitis. Materials and methods Hyperbaric oxygen was prospectively applied as primary treatment in 38 patients with severe radiation cystitis. Our primary endpoint was the incidence of complete and partial response to treatment, while the secondary endpoints included the duration of response, the correlation of treatment success-rate to the interval between the onset of haematuria and initiation of therapy, blood transfusion need and total radiation dose, the number of sessions to success, the avoidance of surgery and the overall survival. Results All patients completed therapy without complications with a mean follow-up of 29.33 months. Median number of sessions needed was 33. Complete and partial response rate was 86.8% and 13.2%, respectively. All 33 patients with complete response received therapy within 6 months of the haematuria onset. One patient needed cystectomy, while 33 patients were alive at the end of follow-up. Conclusions Our study suggests the early primary use of hyperbaric oxygen for radiation-induced severe cystitis as an effective and safe treatment option. PMID:28338304

Auditory biological marker of concussion in children

PubMed Central

Kraus, Nina; Thompson, Elaine C.; Krizman, Jennifer; Cook, Katherine; White-Schwoch, Travis; LaBella, Cynthia R.

2016-01-01

Concussions carry devastating potential for cognitive, neurologic, and socio-emotional disease, but no objective test reliably identifies a concussion and its severity. A variety of neurological insults compromise sound processing, particularly in complex listening environments that place high demands on brain processing. The frequency-following response captures the high computational demands of sound processing with extreme granularity and reliably reveals individual differences. We hypothesize that concussions disrupt these auditory processes, and that the frequency-following response indicates concussion occurrence and severity. Specifically, we hypothesize that concussions disrupt the processing of the fundamental frequency, a key acoustic cue for identifying and tracking sounds and talkers, and, consequently, understanding speech in noise. Here we show that children who sustained a concussion exhibit a signature neural profile. They have worse representation of the fundamental frequency, and smaller and more sluggish neural responses. Neurophysiological responses to the fundamental frequency partially recover to control levels as concussion symptoms abate, suggesting a gain in biological processing following partial recovery. Neural processing of sound correctly identifies 90% of concussion cases and clears 95% of control cases, suggesting this approach has practical potential as a scalable biological marker for sports-related concussion and other types of mild traumatic brain injuries. PMID:28005070

The persistence of cognitive deficits in remitted and unremitted ADHD: a case for the state-independence of response inhibition

PubMed Central

McAuley, Tara; Crosbie, Jennifer; Charach, Alice; Schachar, Russell

2014-01-01

Background Response inhibition, working memory, and response variability are possible endophenotypes of ADHD based on their association with the disorder and evidence of heritability. One of the critical although rarely studied criteria for a valid endophenotype is that it persists despite waxing and waning of the overt manifestations of the disorder, a criterion known as state-independence. This study examined whether these aspects of cognition exhibit state-independence in ADHD. Methods One hundred and seventy-nine children diagnosed with ADHD in a rigorous baseline assessment were contacted for follow-up assessment in adolescence. Of this sample, 130 (73%) were reascertained. At follow-up, children previously diagnosed with ADHD were identified as remittent (n = 24), persistent (n = 64), or in partial remission (n = 42) based on symptoms and impairment of the disorder. Response inhibition, working memory, and response variability were assessed both in childhood (baseline) and adolescence (follow-up) and were compared with age-matched controls (40 children and 28 adolescents) seen at either time point. Results Relative to controls, ADHD children showed baseline deficits in response inhibition, working memory, and response variability. Only the group difference in response inhibition remained significant in adolescence. In general, cognitive performance among ADHD participants improved with age and did so regardless of changes in ADHD symptoms and impairment. Within the ADHD group, however, cognitive performance in childhood and in adolescence did not differ amongst those with persistent, remittent, and partially remittent forms of the disorder. Conclusions Results demonstrate that response inhibition not only distinguishes ADHD children from their unaffected peers but is also state-independent, such that deficits remain present irrespective of changes in the disease phenotype. In other words, inhibitory deficits measured in childhood persist into adolescence even when the ADHD phenotype remits. These findings provide further evidence that the ability to stop prepotent actions is an endophenotype of ADHD. PMID:24261515

Fecal S100A12 concentration predicts a lack of response to treatment in dogs affected with chronic enteropathy.

PubMed

Heilmann, Romy M; Volkmann, Maria; Otoni, Cristiane C; Grützner, Niels; Kohn, Barbara; Jergens, Albert E; Steiner, Jörg M

2016-09-01

S100A12 is a potential biomarker of gastrointestinal inflammation in dogs and fecal S100A12 concentrations are correlated with disease severity and outcome. The aim of the present study was to investigate whether there was any association between pre-treatment fecal S100A12 concentrations in dogs affected with chronic enteropathy (CE) and the response to treatment. Dogs affected with CE were recruited into the study and were classified as antibiotic-responsive diarrhea (ARD; n = 9), food-responsive diarrhea (FRD; n = 30) or idiopathic inflammatory bowel disease (IBD; n = 25). They were also grouped based on their response to treatment as complete remission (n = 35), partial response (n = 25) or no response (n = 4). Fecal S100A12 concentrations, measured by ELISA, were elevated in dogs affected with IBD compared with those from dogs affected with FRD (P = 0.010) or ARD (P = 0.025). Dogs with IBD that did not respond to treatment (n = 4) had significantly greater fecal S100A12 concentrations than dogs in complete remission (P = 0.009). Measurement of fecal S100A12 at the time of diagnosis discriminated between dogs with IBD that were refractory to therapy (≥2700 ng/g fecal S100A12) from those with at least a partial response (<2700 ng/g fecal S100A12), with a sensitivity of 100% and a specificity of 76%. These preliminary results suggest that testing of fecal S100A12 may be useful for predicting the lack of response to treatment in dogs affected with CE. The utility of serial fecal S100A12 measurements for monitoring dogs undergoing treatment for CE warrants further investigation. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Prospective Clinical Trial Combining Radiation Therapy With Systemic Immunotherapy in Metastatic Melanoma

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

Hiniker, Susan M., E-mail: shiniker@stanford.edu; Reddy, Sunil A.; Maecker, Holden T.

Purpose: Local radiation therapy (RT) combined with systemic anti-cytotoxic T-lymphocyte–associated protein-4 immunotherapy may enhance induction of systemic antimelanoma immune responses. The primary objective of the present trial was to assess the safety and efficacy of combining ipilimumab with RT in patients with stage IV melanoma. The secondary objectives included laboratory assessment of induction of antimelanoma immune responses. Methods and Materials: In our prospective clinical trial, 22 patients with stage IV melanoma were treated with palliative RT and ipilimumab for 4 cycles. RT to 1 to 2 disease sites was initiated within 5 days after starting ipilimumab. Patients had ≥1 nonirradiated metastasismore » measuring ≥1.5 cm available for response assessment. Tumor imaging studies were obtained at baseline, 2 to 4 weeks after cycle 4 of ipilimumab, and every 3 months until progression. Laboratory immune response parameters were measured before and during treatment. Results: Combination therapy was well-tolerated without unexpected toxicities. Eleven patients (50.0%) experienced clinical benefit from therapy, including complete and partial responses and stable disease at median follow-up of 55 weeks. Three patients (27.3%) achieved an ongoing systemic complete response at a median follow-up of 55 weeks (range 32-65), and 3 (27.3%) had an initial partial response for a median of 40 weeks. Analysis of immune response data suggested a relationship between elevated CD8-activated T-cells and response. Conclusion: This is the second prospective clinical trial of treatment of metastatic melanoma using the combination of RT and systemic immunotherapy and the first using this sequence of therapy. The results from the present trial demonstrate that a subset of patients may benefit from combination therapy, arguing for continued clinical investigation of the use of RT combined with immunotherapy, including programmed cell death 1 inhibitors, which might have the potential to be even more effective in combination with RT.« less

Prospective pilot study of high-dose (10 mg/kg/day) liposomal amphotericin B (L-AMB) for the initial treatment of mucormycosis.

PubMed

Lanternier, F; Poiree, S; Elie, C; Garcia-Hermoso, D; Bakouboula, P; Sitbon, K; Herbrecht, R; Wolff, M; Ribaud, P; Lortholary, O

2015-11-01

Mucormycosis incidence is increasing and is associated with a high rate of mortality. Although lipid-based formulations of amphotericin B are the recommended first-line treatment, only one prospective trial in a limited number of patients has been performed to evaluate this regimen. Patients with proven or probable mucormycosis were included between June 2007 and March 2011. Patients were scheduled to receive 10 mg/kg/day liposomal amphotericin B (L-AMB) monotherapy for 1 month and surgery was performed when appropriate. The primary outcome was response rate at week 4 or at the end of treatment (EOT) if before week 4, evaluated by an independent committee. ClinicalTrials.gov Identifier: NCT00467883. Forty patients were enrolled. Response was analysed in 33 patients at week 4. Most patients had a haematological malignancy as their primary underlying disease (53%). Seventy-one percent of patients underwent therapeutic surgery. The response rate at week 4 or at EOT was 36%, with 18% partial responses and 18% complete responses. The response rate at week 12 was 45%, with 13% partial responses and 32% complete responses. Overall mortality was 38% at week 12 and 53% at week 24. Serum creatinine doubled in 16 (40%) patients and returned to normal levels within 12 weeks in 10/16 (63%). High-dose L-AMB for mucormycosis, in combination with surgery in 71% of cases, was associated with an overall response rate of 36% at week 4 and 45% at week 12 and creatinine level doubling in 40% of patients (transient in 63%). These results may serve as the basis for future clinical trials. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Results of a minimally invasive technique for treatment of unicameral bone cysts.

PubMed

Mik, Gökçe; Arkader, Alexandre; Manteghi, Alexander; Dormans, John P

2009-11-01

Unicameral bone cysts are benign bone lesions commonly seen in pediatric patients. Several treatment methods have been described with variable results and high recurrence rates. We previously reported short-term success of a minimally invasive technique that includes combining percutaneous decompression and grafting with medical-grade calcium sulfate pellets. The purpose of this study was to review the additional long-term results with a minimum followup of 24 months (average, 37 months; range, 24-70 months). We identified 55 patients with an average age of 10.8 years (range, 1.3-18 years). Forty-one of 55 lesions occurred in the humerus and femur. Forty-four of 55 (80%) patients had a partial or complete response after initial surgery; of these, seven obtained a partial or complete response after a repeat surgery (cumulative healing rate, 94%). Two patients underwent a third surgery (cumulative healing rate, 98%). One underwent a third repeat surgery (cumulative healing rate, 100%). There were no major complications associated with the procedure. Two patients had a superficial infection that resolved with oral antibiotics. Although some patients required a repeat procedure, complete or partial response at a minimum 24 months' followup was achieved in all patients. Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Predictive sensor method and apparatus

NASA Technical Reports Server (NTRS)

Nail, William L. (Inventor); Koger, Thomas L. (Inventor); Cambridge, Vivien (Inventor)

1990-01-01

A predictive algorithm is used to determine, in near real time, the steady state response of a slow responding sensor such as hydrogen gas sensor of the type which produces an output current proportional to the partial pressure of the hydrogen present. A microprocessor connected to the sensor samples the sensor output at small regular time intervals and predicts the steady state response of the sensor in response to a perturbation in the parameter being sensed, based on the beginning and end samples of the sensor output for the current sample time interval.

Partially converted stereoscopic images and the effects on visual attention and memory

NASA Astrophysics Data System (ADS)

Kim, Sanghyun; Morikawa, Hiroyuki; Mitsuya, Reiko; Kawai, Takashi; Watanabe, Katsumi

2015-03-01

This study contained two experimental examinations of the cognitive activities such as visual attention and memory in viewing stereoscopic (3D) images. For this study, partially converted 3D images were used with binocular parallax added to a specific region of the image. In Experiment 1, change blindness was used as a presented stimulus. The visual attention and impact on memory were investigated by measuring the response time to accomplish the given task. In the change blindness task, an 80 ms blank was intersected between the original and altered images, and the two images were presented alternatingly for 240 ms each. Subjects were asked to temporarily memorize the two switching images and to compare them, visually recognizing the difference between the two. The stimuli for four conditions (2D, 3D, Partially converted 3D, distracted partially converted 3D) were randomly displayed for 20 subjects. The results of Experiment 1 showed that partially converted 3D images tend to attract visual attention and are prone to remain in viewer's memory in the area where moderate negative parallax has been added. In order to examine the impact of a dynamic binocular disparity on partially converted 3D images, an evaluation experiment was conducted that applied learning, distraction, and recognition tasks for 33 subjects. The learning task involved memorizing the location of cells in a 5 × 5 matrix pattern using two different colors. Two cells were positioned with alternating colors, and one of the gray cells was moved up, down, left, or right by one cell width. Experimental conditions was set as a partially converted 3D condition in which a gray cell moved diagonally for a certain period of time with a dynamic binocular disparity added, a 3D condition in which binocular disparity was added to all gray cells, and a 2D condition. The correct response rates for recognition of each task after the distraction task were compared. The results of Experiment 2 showed that the correct response rate in the partial 3D condition was significantly higher with the recognition task than in the other conditions. These results showed that partially converted 3D images tended to have a visual attraction and affect viewer's memory.

Bounded influence function based inference in joint modelling of ordinal partial linear model and accelerated failure time model.

PubMed

Chakraborty, Arindom

2016-12-01

A common objective in longitudinal studies is to characterize the relationship between a longitudinal response process and a time-to-event data. Ordinal nature of the response and possible missing information on covariates add complications to the joint model. In such circumstances, some influential observations often present in the data may upset the analysis. In this paper, a joint model based on ordinal partial mixed model and an accelerated failure time model is used, to account for the repeated ordered response and time-to-event data, respectively. Here, we propose an influence function-based robust estimation method. Monte Carlo expectation maximization method-based algorithm is used for parameter estimation. A detailed simulation study has been done to evaluate the performance of the proposed method. As an application, a data on muscular dystrophy among children is used. Robust estimates are then compared with classical maximum likelihood estimates. © The Author(s) 2014.

Treatment of advanced soft tissue sarcomas with ifosfamide and doxorubicin combination chemotherapy.

PubMed

Barişta, I; Tekuzman, G; Yalçin, S; Güllü, I; Güler, N; Ozişik, Y; Kars, A; Celik, I; Türker, A; Altundağ, K; Zengin, N; Uner, A; Baltali, E; Firat, D

2000-01-01

Our objective was to assess the efficacy of a standard dose ifosfamide and doxorubicin containing regimen in the treatment of advanced soft tissue sarcomas. Forty consecutive patients with a median age of 35.5 years were treated. Ifosfamide was administered at a dose of 2.5 g/m(2)/day as 72-hour continuous infusion with mesna at the same dosage and schedule. Doxorubicin was given at the dose of 60 mg/m(2)/day as 2-hour infusion on day 1. Six patients had a complete response (15%), and 9 (22.5%) had a partial response, fourteen patients (35%) stable disease, and 11 (27.5%) did not respond to chemotherapy. The median duration of response was 13 and 5 months for the complete and partial responders, respectively. The median survival was 37 months. Febrile neutropenia was encountered in 9 cases (22.5%). The present ifosfamide and doxorubicin combination is a moderately effective and well-tolerable regimen in the treatment of advanced soft tissue sarcomas. Copyright 2000 Wiley-Liss, Inc.

Using Transcranial Magnetic Stimulation to Evaluate the Motor Pathways After an Intraoperative Spinal Cord Injury and to Predict the Recovery of Intraoperative Transcranial Electrical Motor Evoked Potentials: A Case Report.

PubMed

Grover, Helen J; Thornton, Rachel; Lutchman, Lennel N; Blake, Julian C

2016-06-01

The authors report a case of unilateral loss of intraoperative transcranial electrical motor evoked potentials (TES MEP) associated with a spinal cord injury during scoliosis correction and the subsequent use of extraoperative transcranial magnetic stimulation to monitor the recovery of spinal cord function. The authors demonstrate the absence of TES MEPs and absent transcranial magnetic stimulation responses in the immediate postoperative period, and document the partial recovery of transcranial magnetic stimulation responses, which corresponded to partial recovery of TES MEPs. Intraoperative TES MEPs were enhanced using spatial facilitation technique, which enabled the patient to undergo further surgery to stabilize the spine and correct her scoliosis. This case report supports evidence of the use of extraoperative transcranial magnetic stimulation to predict the presence of intraoperative TES responses and demonstrates the usefulness of spatial facilitation to monitor TES MEPs in a patient with a preexisting spinal cord injury.

Disgust and Anger Relate to Different Aggressive Responses to Moral Violations

PubMed Central

Molho, Catherine; Tybur, Joshua M.; Güler, Ezgi; Balliet, Daniel; Hofmann, Wilhelm

2017-01-01

In response to the same moral violation, some people report experiencing anger, and others report feeling disgust. Do differences in emotional responses to moral violations reflect idiosyncratic differences in the communication of outrage, or do they reflect differences in motivational states? Whereas equivalence accounts suggest that anger and disgust are interchangeable expressions of condemnation, sociofunctional accounts suggest that they have distinct antecedents and consequences. We tested these accounts by investigating whether anger and disgust vary depending on the costs imposed by moral violations and whether they differentially correspond with aggressive tendencies. Results across four studies favor a sociofunctional account: When the target of a moral violation shifts from the self to another person, anger decreases, but disgust increases. Whereas anger is associated with high-cost, direct aggression, disgust is associated with less costly indirect aggression. Finally, whether the target of a moral violation is the self or another person influences direct aggression partially via anger and influences indirect aggression partially via disgust. PMID:28485700

Significant partial response of metastatic intra-abdominal and pelvic round cell liposarcoma to a small-molecule VEGFR-2 tyrosine kinase inhibitor apatinib: A case report.

PubMed

Dong, Min; Bi, Jingwang; Liu, Xiaohong; Wang, Baocheng; Wang, Jun

2016-08-01

Myxoid/round cell liposarcoma is the second most common subtype of liposarcoma. Chemotherapy and radiotherapy have a limited efficacy for treating advanced myxoid/round cell liposarcoma, with relatively serious side effects. We herein present a 68-year-old Chinese woman initially diagnosed with advanced multiple intra-abdominal and pelvic round cell liposarcoma.She refused to receive cytotoxic chemotherapy and received apatinib as the first-line therapy, a novel tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2 that has been used in the treatment of patients with metastatic gastric cancer who progressed with 2 or more chemotherapy regimens. This patient was partially responsive to apatinib with a dose of 500 mg daily. No serious drug-related side effects were observed. Our findings indicate that some cases of liposarcoma may be responsive to antiangiogenic agent apatinib. Randomized clinical studies are needed to further confirm the efficacy and safety of apatinib in the clinical treatment of liposarcoma.

Electronic structure, dielectric response, and surface charge distribution of RGD (1FUV) peptide.

PubMed

Adhikari, Puja; Wen, Amy M; French, Roger H; Parsegian, V Adrian; Steinmetz, Nicole F; Podgornik, Rudolf; Ching, Wai-Yim

2014-07-08

Long and short range molecular interactions govern molecular recognition and self-assembly of biological macromolecules. Microscopic parameters in the theories of these molecular interactions are either phenomenological or need to be calculated within a microscopic theory. We report a unified methodology for the ab initio quantum mechanical (QM) calculation that yields all the microscopic parameters, namely the partial charges as well as the frequency-dependent dielectric response function, that can then be taken as input for macroscopic theories of electrostatic, polar, and van der Waals-London dispersion intermolecular forces. We apply this methodology to obtain the electronic structure of the cyclic tripeptide RGD-4C (1FUV). This ab initio unified methodology yields the relevant parameters entering the long range interactions of biological macromolecules, providing accurate data for the partial charge distribution and the frequency-dependent dielectric response function of this peptide. These microscopic parameters determine the range and strength of the intricate intermolecular interactions between potential docking sites of the RGD-4C ligand and its integrin receptor.

Partial pneumonectomy of telomerase null mice carrying shortened telomeres initiates cell growth arrest resulting in a limited compensatory growth response

PubMed Central

Jackson, Sha-Ron; Lee, Jooeun; Reddy, Raghava; Williams, Genevieve N.; Kikuchi, Alexander; Freiberg, Yael; Warburton, David

2011-01-01

Telomerase mutations and significantly shortened chromosomal telomeres have recently been implicated in human lung pathologies. Natural telomere shortening is an inevitable consequence of aging, which is also a risk factor for development of lung disease. However, the impact of shortened telomeres and telomerase dysfunction on the ability of lung cells to respond to significant challenge is still largely unknown. We have previously shown that lungs of late generation, telomerase null B6.Cg-Terctm1Rdp mice feature alveolar simplification and chronic stress signaling at baseline, a phenocopy of aged lung. To determine the role telomerase plays when the lung is challenged, B6.Cg-Terctm1Rdp mice carrying shortened telomeres and wild-type controls were subjected to partial pneumonectomy. We found that telomerase activity was strongly induced in alveolar epithelial type 2 cells (AEC2) of the remaining lung immediately following surgery. Eighty-six percent of wild-type animals survived the procedure and exhibited a burst of early compensatory growth marked by upregulation of proliferation, stress response, and DNA repair pathways in AEC2. In B6.Cg-Terctm1Rdp mice carrying shortened telomeres, response to pneumonectomy was characterized by decreased survival, diminished compensatory lung growth, attenuated distal lung progenitor cell response, persistent DNA damage, and cell growth arrest. Overall, survival correlated strongly with telomere length. We conclude that functional telomerase and properly maintained telomeres play key roles in both long-term survival and the early phase of compensatory lung growth following partial pneumonectomy. PMID:21460122

Hematopoietic responses under protracted exposures to low daily dose gamma irradiation.

PubMed

Seed, T M; Fritz, T E; Tolle, D V; Jackson, W E

2002-01-01

In attempting to evaluate the possible health consequences of chronic ionizing radiation exposure during extended space travel (e.g., Mars Mission), ground-based experimental studies of the clinical and pathological responses of canines under low daily doses of 60Co gamma irradiation (0.3-26.3 cGy d-1) have been examined. Specific reference was given to responses of the blood forming system. Results suggest that the daily dose rate of 7.5 cGy d-1 represents a threshold below which the hematopoietic system can retain either partial or full trilineal cell-producing capacity (erythropoiesis, myelopoiesis, and megakaryopoiesis) for extended periods of exposure (>1 yr). Trilineal capacity was fully retained for several years of exposure at the lowest dose-rate tested (0.3 cGy d-1) but was completely lost within several hundred days at the highest dose-rate (26.3 cGy d-1). Retention of hematopoietic capacity under chronic exposure has been demonstrated to be mediated by hematopoietic progenitors with acquired radioresistance and repair functions, altered cytogenetics, and cell-cycle characteristics. Radiological, biological, and temporal parameters responsible for these vital acquisitions by hematopoietic progenitors have been partially characterized. These parameters, along with threshold responses, are described and discussed in relation to potential health risks of the space traveler under chronic stress of low-dose irradiation. Published by Elsevier Science Ltd on behalf of COSPAR.

Patient-ventilator asynchrony affects pulse pressure variation prediction of fluid responsiveness.

PubMed

Messina, Antonio; Colombo, Davide; Cammarota, Gianmaria; De Lucia, Marta; Cecconi, Maurizio; Antonelli, Massimo; Corte, Francesco Della; Navalesi, Paolo

2015-10-01

During partial ventilatory support, pulse pressure variation (PPV) fails to adequately predict fluid responsiveness. This prospective study aims to investigate whether patient-ventilator asynchrony affects PPV prediction of fluid responsiveness during pressure support ventilation (PSV). This is an observational physiological study evaluating the response to a 500-mL fluid challenge in 54 patients receiving PSV, 27 without (Synch) and 27 with asynchronies (Asynch), as assessed by visual inspection of ventilator waveforms by 2 skilled blinded physicians. The area under the curve was 0.71 (confidence interval, 0.57-0.83) for the overall population, 0.86 (confidence interval, 0.68-0.96) in the Synch group, and 0.53 (confidence interval, 0.33-0.73) in the Asynch group (P = .018). Sensitivity and specificity of PPV were 78% and 89% in the Synch group and 36% and 46% in the Asynch group. Logistic regression showed that the PPV prediction was influenced by patient-ventilator asynchrony (odds ratio, 8.8 [2.0-38.0]; P < .003). Of the 27 patients without asynchronies, 12 had a tidal volume greater than or equal to 8 mL/kg; in this subgroup, the rate of correct classification was 100%. Patient-ventilator asynchrony affects PPV performance during partial ventilatory support influencing its efficacy in predicting fluid responsiveness. Copyright © 2015 Elsevier Inc. All rights reserved.

Factors influencing response to ingenol mebutate therapy for actinic keratosis of face and scalp

PubMed Central

Skroza, Nevena; Proietti, Ilaria; Bernardini, Nicoletta; Balduzzi, Veronica; Mambrin, Alessandra; Marchesiello, Anna; Tolino, Ersilia; Zuber, Sara; La Torre, Giuseppe; Potenza, Concetta

2017-01-01

AIM To determine factors independently influencing response to ingenol mebutate therapy and assess efficacy on clinical setting of non-hypertrophic non-hyperkeratotic actinic keratosis (AK). METHODS Consecutive patients affected by non-hypertrophic non-hyperkeratotic AKs of the face or scalp were enrolled to receive ingenol mebutate 0.015% gel on a selected skin area of 25 cm2 for 3 consecutive days. Local skin reactions were calculated at each follow up visit using a validated composite score. Efficacy was evaluated by the comparison of clinical and dermoscopic pictures before the treatment and at day 57, and classified as complete, partial and poor response. RESULTS A number of 130 patients were enrolled, of which 101 (77.7%) were treated on the face, while 29 (22.3%) on the scalp. The great majority of our study population (n = 119, 91.5%) reached at least a 75% clearance of AKs and, in particular, 58 patients (44.6%) achieved a complete response while 61 (46.9%) a partial one. Logistic backward multivariate analysis showed that facial localization, level of local skin reaction (LSR) at day 2, the highest LSR values and level of crusts at day 8 were factors independently associated with the achievement of a complete response. CONCLUSION Ingenol mebutate 0.015% gel, when properly applied, is more effective on the face than on the scalp and efficacy is directly associated to LSR score. PMID:29067277

Responses to crizotinib in patients with ALK-positive lung adenocarcinoma who tested immunohistochemistry (IHC)-positive and fluorescence in situ hybridization (FISH)-negative.

PubMed

Ma, Di; Wang, Zheng; Yang, Lin; Mu, Xinlin; Wang, Yan; Zhao, Xinming; Li, Junling; Lin, Dongmei

2016-09-27

Although the Ventana immunohistochemistry (IHC) platform for detecting anaplastic lymphoma kinase gene (ALK) (D5F3) expression was recently approved by the US Food and Drugs Administration (FDA), fluorescence in situ hybridization (FISH) is still the "gold-standard" method recommended by the US National Comprehensive Cancer Network (NCCN) guideline for NSCLC. We evaluated 6 ALK-positive lung adenocarcinoma patients who tested Ventana IHC-positive and FISH-negative and assessed their clinical responses to the ALK tyrosine kinase inhibitor (TKI) crizotinib. Histologic and cytologic specimens from the 6 patients were stained with Ventana anti-ALK(D5F3) rabbit monoclonal primary antibody using the OptiView™ DAB IHC detection kit and OptiView™ amplification kit on a Ventana BenchMark XT processor. In addition, they were also tested by FISH, qRT-PCR, next-generation sequencing (NGS), and RNAscope ISH analysis. All patients received crizotinib treatment and their follow-up clinical data were recorded. The objective response rate achieved with crizotinib therapy was 66.7% (4/6 partial responses and 2/6 stable disease). One patient in whom a new fusion type (EML4->EXOC6B->ALK fusion) was identified obtained a partial response. These findings indicate that patients with ALK-positive lung adenocarcinoma who test Ventana IHC-positive and FISH-negative may still respond to crizotinib therapy.

Rethinking responsibility in offenders with acquired paedophilia: punishment or treatment?

PubMed

Gilbert, Frédéric; Focquaert, Farah

2015-01-01

This article reviews the current neurobiological literature on the aetiology of developmental and acquired paedophilia and examines what the consequences could be in terms of responsibility and treatment for the latter. Addressing the question of responsibility and punishment of offenders with acquired paedophilia from a neurobiological perspective is controversial. Consequently it is essential to avoid hasty conclusions based strictly on neurobiological abnormality justifications. This study establishes a distinction between developmental and acquired paedophilia. The article investigates whether offenders who fulfil the diagnosis of acquired paedophilia should be held fully responsible, particularly in cases where the offender's conduct appears to result from volitionally controlled behaviour that is seemingly incompatible with a neurological cause. Moreover, the article explores how responsibility can be compromised when offenders with acquired paedophilia have (partially) preserved moral knowledge despite their sexual disorder. The article then examines the option of offering mandatory treatment as an alternative to imprisonment for offenders with acquired paedophilia. Furthermore, the article addresses the ethical issues related to offering any form of quasi-coercive treatment as a condition of release. This study concludes that decisions to fully or partially excuse an individual who fulfil the diagnosis of acquired paedophilia should take all relevant information into account, both neurobiological and other environmental evidence, and should proceed on a careful case by case analysis before sentencing or offering treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

A rigorous computational approach to linear response

NASA Astrophysics Data System (ADS)

Bahsoun, Wael; Galatolo, Stefano; Nisoli, Isaia; Niu, Xiaolong

2018-03-01

We present a general setting in which the formula describing the linear response of the physical measure of a perturbed system can be obtained. In this general setting we obtain an algorithm to rigorously compute the linear response. We apply our results to expanding circle maps. In particular, we present examples where we compute, up to a pre-specified error in the L∞ -norm, the response of expanding circle maps under stochastic and deterministic perturbations. Moreover, we present an example where we compute, up to a pre-specified error in the L 1-norm, the response of the intermittent family at the boundary; i.e. when the unperturbed system is the doubling map. This work was mainly conducted during a visit of SG to Loughborough University. WB and SG would like to thank The Leverhulme Trust for supporting mutual research visits through the Network Grant IN-2014-021. SG thanks the Department of Mathematical Sciences at Loughborough University for hospitality. WB thanks Dipartimento di Matematica, Universita di Pisa. The research of SG and IN is partially supported by EU Marie-Curie IRSES ‘Brazilian-European partnership in Dynamical Systems’ (FP7-PEOPLE-2012-IRSES 318999 BREUDS). IN was partially supported by CNPq and FAPERJ. IN would like to thank the Department of Mathematics at Uppsala University and the support of the KAW grant 2013.0315.

Baseline Severity as Predictor of Change in St George’s Respiratory Questionnaire Scores in Trials of Long-acting Bronchodilators with COPD Patients

PubMed Central

Jones, Paul W.; Gelhorn, Heather; Karlsson, Niklas; Menjoge, Shailendra; Müllerova, Hana; Rennard, Stephen I.; Tal-Singer, Ruth; Wilson, Hilary; Merrill, Debora; Tabberer, Maggie

2017-01-01

Background: In trials oflong-acting bronchodilators, health status is an important trial outcome, however the influence of baseline severity on response measured by St George’s Respiratory Questionnaire (SGRQ) is not known. We have compared SGRQ changes between patients with chronic obstructive pulmonary disease (COPD) of mild-moderate severity or dyspnea (Global initiative for chronic Obstructive Lung disease [GOLD] grades 1 and 2; modified Medical Research Council [mMRC] grades 1 and 2) to those with severe-very severe severity or dyspnea (GOLD grades 3 and 4; mMRC grades 3 and 4). Methods: Combined individual patient data from the COPD Biomarkers Qualification Consortium database (trials of long-acting bronchodilators) were used comprising of patients from short-term (≤1-year duration; n=10802) and medium-term (2-4 years’ duration; n=8963) studies. A repeated measures analysis of variance (ANOVA) was used to determine the effects of baseline severity (GOLD/mMRC) on SGRQ response to treatment. All treatment arms were combined. Results: In short-term studies, milder patients showed a greater response than those with more severe disease in terms of GOLD grade (partial Eta2 = 0.03, p < 0.0001) and mMRC grade (partial Eta2 = 0.05, p < 0.0001). Similar results were seen in the medium-term studies (partial Eta2 = 0.02, p < 0.0001; mMRC: partial Eta2 = 0.05, p < 0.0001,). Conclusions: Patients with less severe airflow limitation and less severe dyspnea showed larger improvements in SGRQ score than more severely obstructed or dyspneic patients. Although these severity influences are small (2%-5% of the variance in SGRQ score), they do suggest that pre-specified separate analyses are warranted to test for differences in response, based on baseline severity. PMID:28848922

A novel comparative pattern count analysis reveals a chronic ethanol-induced dynamic shift in immediate early NF-κB genome-wide promoter binding during liver regeneration.

PubMed

Kuttippurathu, Lakshmi; Patra, Biswanath; Hoek, Jan B; Vadigepalli, Rajanikanth

2016-03-01

Liver regeneration after partial hepatectomy is a clinically important process that is impaired by adaptation to chronic alcohol intake. We focused on the initial time points following partial hepatectomy (PHx) to analyze the genome-wide binding activity of NF-κB, a key immediate early regulator. We investigated the effect of chronic alcohol intake on immediate early NF-κB genome-wide localization, in the adapted state as well as in response to partial hepatectomy, using chromatin immunoprecipitation followed by promoter microarray analysis. We found many ethanol-specific NF-κB binding target promoters in the ethanol-adapted state, corresponding to the regulation of biosynthetic processes, oxidation-reduction and apoptosis. Partial hepatectomy induced a diet-independent shift in NF-κB binding loci relative to the transcription start sites. We employed a novel pattern count analysis to exhaustively enumerate and compare the number of promoters corresponding to the temporal binding patterns in ethanol and pair-fed control groups. The highest pattern count corresponded to promoters with NF-κB binding exclusively in the ethanol group at 1 h post PHx. This set was associated with the regulation of cell death, response to oxidative stress, histone modification, mitochondrial function, and metabolic processes. Integration with the global gene expression profiles to identify putative transcriptional consequences of NF-κB binding patterns revealed that several of ethanol-specific 1 h binding targets showed ethanol-specific differential expression through 6 h post PHx. Motif analysis yielded co-incident binding loci for STAT3, AP-1, CREB, C/EBP-β, PPAR-γ and C/EBP-α, likely participating in co-regulatory modules with NF-κB in shaping the immediate early response to PHx. We conclude that adaptation to chronic ethanol intake disrupts the NF-κB promoter binding landscape with consequences for the immediate early gene regulatory response to the acute challenge of PHx.

Frontal midline theta and the error-related negativity: neurophysiological mechanisms of action regulation.

PubMed

Luu, Phan; Tucker, Don M; Makeig, Scott

2004-08-01

The error-related negativity (ERN) is an event-related potential (ERP) peak occurring between 50 and 100 ms after the commission of a speeded motor response that the subject immediately realizes to be in error. The ERN is believed to index brain processes that monitor action outcomes. Our previous analyses of ERP and EEG data suggested that the ERN is dominated by partial phase-locking of intermittent theta-band EEG activity. In this paper, this possibility is further evaluated. The possibility that the ERN is produced by phase-locking of theta-band EEG activity was examined by analyzing the single-trial EEG traces from a forced-choice speeded response paradigm before and after applying theta-band (4-7 Hz) filtering and by comparing the averaged and single-trial phase-locked (ERP) and non-phase-locked (other) EEG data. Electrical source analyses were used to estimate the brain sources involved in the generation of the ERN. Beginning just before incorrect button presses in a speeded choice response paradigm, midfrontal theta-band activity increased in amplitude and became partially and transiently phase-locked to the subject's motor response, accounting for 57% of ERN peak amplitude. The portion of the theta-EEG activity increase remaining after subtracting the response-locked ERP from each trial was larger and longer lasting after error responses than after correct responses, extending on average 400 ms beyond the ERN peak. Multiple equivalent-dipole source analysis suggested 3 possible equivalent dipole sources of the theta-bandpassed ERN, while the scalp distribution of non-phase-locked theta amplitude suggested the presence of additional frontal theta-EEG sources. These results appear consistent with a body of research that demonstrates a relationship between limbic theta activity and action regulation, including error monitoring and learning.

Efficacy of TACE in TIPS Patients: Comparison of Treatment Response to Chemoembolization for Hepatocellular Carcinoma in Patients With and Without a Transjugular Intrahepatic Portosystemic Shunt

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

Kuo, Yuo-Chen, E-mail: yuo-chen.kuo@ucsf.edu; Kohi, Maureen P., E-mail: maureen.kohi@ucsf.edu; Naeger, David M., E-mail: david.naeger@ucsf.edu

Purpose: To compare treatment response after transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) in patients with and without a transjugular intrahepatic portosystemic shunt (TIPS). Materials and Methods: A retrospective review of patients who underwent conventional TACE for HCC between January 2005 and December 2009 identified 10 patients with patent TIPS. From the same time period, 23 patients without TIPS were selected to control for comparable Model for End-Stage Liver Disease and Child-Pugh-Turcotte scores. The two groups showed similar distribution of Barcelona Clinic Liver Cancer and United Network of Organ Sharing stages. Target HCC lesions were evaluated according to the modifiedmore » response evaluation criteria in solid tumors (mRECIST) guidelines. Transplantation rate, time to tumor progression, and overall survival (OS) were documented. Results: After TACE, the rate of complete response was significantly greater in non-TIPS patients compared with TIPS patients (74 vs. 30 %, p = 0.03). Objective response rate (complete and partial response) trended greater in the non-TIPS group (83 vs. 50 %, p = 0.09). The liver transplantation rate was 80 and 74 % in the TIPS and non-TIPS groups, respectively (p = 1.0). Time to tumor progression was similar (p = 0.47) between the two groups. OS favored the non-TIPS group (p = 0.01) when censored for liver transplantation. Conclusion: TACE is less effective in achieving complete or partial response using mRECIST criteria in TIPS patients compared with those without a TIPS. Nevertheless, similar clinical outcomes may be achieved, particularly in TIPS patients who are liver-transplantation candidates.« less

Eribulin mesylate (halichondrin B Analog E7389) in platinum-resistant and platinum-sensitive ovarian cancer: a two-cohort, phase II study

PubMed Central

Hensley, Martee L.; Kravetz, Sara; Jia, Xiaoyu; Iasonos, Alexia; Tew, William; Pereira, Lauren; Sabbatini, Paul; Whalen, Christin; Aghajanian, Carol A.; Zarwan, Corinne; Berlin, Suzanne

2011-01-01

Background Eribulin mesylate is a tubulin inhibitor with activity superior to paclitaxel in NIH:OVCAR-3 human epithelial ovarian cancer xenograft models. We sought to assess the efficacy of eribulin in platinum-resistant and platinum-sensitive recurrent ovarian cancer. Methods Patients with recurrent measurable epithelial ovarian cancer, ≤2 prior cytotoxic regimens, and adequate organ function were enrolled into two separate cohorts: 1) Platinum resistant (progression-free interval from last platinum-based therapy <6 months); and 2) Platinum sensitive (progression-free interval from last platinum-based therapy ≥6 months). Treatment: Eribulin 1.4 mg/m2 over 15 minutes by vein on days 1 and 8, every 21 days. Efficacy was determined by objective response by computed tomography. Results Platinum-resistant cohort: Thirty-seven patients enrolled. Thirty-six patients were evaluable for response and toxicity. Two patients achieved partial response (PR, 5.5%). Sixteen (44%) had a best response of stable disease. Median progression-free survival was 1.8 months (95% confidence interval, 1.4–2.8 months). Platinum-sensitive cohort: Thirty-seven patients enrolled, and all were evaluable for response. Seven patients achieved partial response (PR, 19%). Median progression-free survival was 4.1 months (95% confidence interval, 2.8–5.8 months). The major toxicity was grade 3 or 4 neutropenia (42% in platinum-resistant patients; 54% in platinum-sensitive patients). Conclusions Eribulin achieved objective response in 5.5% of women with platinum-resistant recurrent ovarian cancer and in 19% of women with platinum-sensitive disease. Median progression-free survival was 1.8 months in the platinum-resistant group and 4.1 months in the platinum-sensitive group. PMID:21935916

Multiple host defense defects in failure of C57BL/6 ep/ep (pale ear) mice to resolve visceral Leishmania donovani infection.

PubMed Central

Murray, H W; Hariprashad, J; McDermott, D F; Stoeckle, M Y

1996-01-01

Euthymic C57BL/L ep/ep (pale ear [PE]) mice halt the visceral replication of intracellular Leishmania donovani but fail to properly resolve infection. A previous study identified an isolated defect in tissue granuloma formation in these mice; CD4+ and CD8+ cell number, gamma interferon (IFN-gamma) production, and macrophage antimicrobial activity in vitro were all intact. New in vivo results reported here suggest a considerably more complex immune defect, with evidence indicating (i) enhanced control over L. donovani after transfer of normal C57BL/6 spleen cells, (ii) a partially suppressive Th2 cell-associated response mediated by interleukin-4 (IL-4) but not reversed by CD4+ cell depletion, (iii) absent responses to endogenous Th1 cell lymphokines (IFN-gamma and IL-2) but preserved responsiveness to endogenous tumor necrosis factor alpha, (iv) absent responses to exogenous treatment with recognized antileishmanial cytokines (IFN-gamma, IL-2, IL-12, and granulocyte-macrophage colony-stimulating factor [GM-CSF]) not corrected by transfer of C57BL/6 spleen cells, and (v) a deficient response to antimony chemotherapy. Defective hepatic granuloma formation was not corrected by transfer of C57BL/6 spleen cells or by anti-IL-4 administration. While treatment with IL-2 and GM-CSF modified the tissue reaction and induced selected effector cells to encase tissue macrophages, no antileishmanial activity resulted. Together, these observations suggest that the failure of PE mice to resolve visceral L. donovani infection likely represents expression of multiple suboptimal immune responses and/or partial defects, probably involving a combination of T-cell dysfunction, a Th2 cell response, and target cell (macrophage) hyporesponsiveness. PMID:8557335

B cell immunopoiesis: visualizing the impact of CD40 engagement on the course of T cell-independent immune responses in an Ig transgenic system.

PubMed

Erickson, L D; Vogel, L A; Cascalho, M; Wong, J; Wabl, M; Durell, B G; Noelle, R J

2000-11-01

This study tracks the fate of antigen-reactive B cells through follicular and extrafollicular responses and addresses the function of CD40 in these processes. The unique feature of this system is the use of transgenic B cells in which the heavy chain locus has been altered by site-directed insertion of a rearranged V(H) DJ(H) exon such that they are able to clonally expand, isotype-switch and follow a normal course of differentiation upon immunization. These Ig transgenic B cells when adoptively transferred into non-transgenic (Tg) mice in measured amounts expanded and differentiated distinctively in response to T cell-independent (TI) or T cell-dependent (TD) antigens. The capacity of these Tg B cells to faithfully recapitulate the humoral immune response to TI and TD antigens provides the means to track clonal B cell behavior in vivo. Challenge with TI antigen in the presence of agonistic anti-CD40 mAb resulted in well-defined alterations of the TI response. In vivo triggering of Tg B cells with TI antigen and CD40 caused an increase in the levels IgG produced and a broadening of the Ig isotype profile, characteristics which partially mimic TD responses. Although some TD characteristics were induced by TI antigen and CD40 triggering, the Tg B cells failed to acquire a germinal center phenotype and failed to generate a memory response. Therefore, TD-like immunity can be only partially reconstituted with CD40 agonists and TI antigens, suggesting that there are additional signals required for germinal center formation and development of memory.

Overcoming the response plateau in multiple myeloma: a novel bortezomib-based strategy for secondary induction and high-yield CD34+ stem cell mobilization.

PubMed

Niesvizky, Ruben; Mark, Tomer M; Ward, Maureen; Jayabalan, David S; Pearse, Roger N; Manco, Megan; Stern, Jessica; Christos, Paul J; Mathews, Lena; Shore, Tsiporah B; Zafar, Faiza; Pekle, Karen; Xiang, Zhaoying; Ely, Scott; Skerret, Donna; Chen-Kiang, Selina; Coleman, Morton; Lane, Maureen E

2013-03-15

This phase II study evaluated bortezomib-based secondary induction and stem cell mobilization in 38 transplant-eligible patients with myeloma who had an incomplete and stalled response to, or had relapsed after, previous immunomodulatory drug-based induction. Patients received up to six 21-day cycles of bortezomib plus dexamethasone, with added liposomal doxorubicin for patients not achieving partial response or better by cycle 2 or very good partial response or better (≥VGPR) by cycle 4 (DoVeD), followed by bortezomib, high-dose cyclophosphamide, and filgrastim mobilization. Gene expression/signaling pathway analyses were conducted in purified CD34+ cells after bortezomib-based mobilization and compared against patients who received only filgrastim ± cyclophosphamide. Plasma samples were similarly analyzed for quantification of associated protein markers. The response rate to DoVeD relative to the pre-DoVeD baseline was 61%, including 39% ≥ VGPR. Deeper responses were achieved in 10 of 27 patients who received bortezomib-based mobilization; postmobilization response rate was 96%, including 48% ≥ VGPR, relative to the pre-DoVeD baseline. Median CD34+ cell yield was 23.2 × 10(6) cells/kg (median of 1 apheresis session). After a median follow-up of 46.6 months, median progression-free survival was 47.1 months from DoVeD initiation; 5-year overall survival rate was 76.4%. Grade ≥ 3 adverse events included thrombocytopenia (13%), hand-foot syndrome (11%), peripheral neuropathy (8%), and neutropenia (5%). Bortezomib-based mobilization was associated with modulated expression of genes involved in stem cell migration. Bortezomib-based secondary induction and mobilization could represent an alternative strategy for elimination of tumor burden in immunomodulatory drug-resistant patients that does not impact stem cell yield.

Visual Enhancement of Laparoscopic Partial Nephrectomy With 3-Charge Coupled Device Camera: Assessing Intraoperative Tissue Perfusion and Vascular Anatomy by Visible Hemoglobin Spectral Response

DTIC Science & Technology

2010-10-01

open nephron spanng surgery a single institution expenence. J Ural 2005; 174: 855 21 Bhayan• SB, Aha KH Pmto PA et al Laparoscopic partial...noninvasively assess laparoscopic intraoperative changes in renal tissue perfusion during and after warm ischemia. Materials and Methods: We analyzed select...TITLE AND SUBTITLE Visual Enhancement of Laparoscopic Partial Nephrectomy With 3-Charge Coupled Device Camera: Assessing Intraoperative Tissue

Oxygen partial pressure effects on the RF sputtered p-type NiO hydrogen gas sensors

NASA Astrophysics Data System (ADS)

Turgut, Erdal; Çoban, Ömer; Sarıtaş, Sevda; Tüzemen, Sebahattin; Yıldırım, Muhammet; Gür, Emre

2018-03-01

NiO thin films were grown by Radio Frequency (RF) Magnetron Sputtering method under different oxygen partial pressures, which are 0.6 mTorr, 1.3 mTorr and 2.0 mTorr. The effects of oxygen partial pressures on the thin films were analyzed through Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM), X-ray Diffraction (XRD), X-ray Photoelectron Spectroscopy (XPS) and Hall measurements. The change in the surface morphology of the thin films has been observed with the SEM and AFM measurements. While nano-pyramids have been obtained on the thin film grown at the lowest oxygen partial pressure, the spherical granules lower than 60 nm in size has been observed for the samples grown at higher oxygen partial pressures. The shift in the dominant XRD peak is realized to the lower two theta angle with increasing the oxygen partial pressures. XPS measurements showed that the Ni2p peak involves satellite peaks and two oxidation states of Ni, Ni2+ and Ni3+, have been existed together with the corresponding splitting in O1s spectrum. P-type conductivity of the grown NiO thin films are confirmed by the Hall measurements with concentrations on the order of 1013 holes/cm-3. Gas sensor measurements revealed minimum of 10% response to the 10 ppm H2 level. Enhanced responsivity of the gas sensor devices of NiO thin films is shown as the oxygen partial pressure increases.

Advanced probabilistic methods for quantifying the effects of various uncertainties in structural response

NASA Technical Reports Server (NTRS)

Nagpal, Vinod K.

1988-01-01

The effects of actual variations, also called uncertainties, in geometry and material properties on the structural response of a space shuttle main engine turbopump blade are evaluated. A normal distribution was assumed to represent the uncertainties statistically. Uncertainties were assumed to be totally random, partially correlated, and fully correlated. The magnitude of these uncertainties were represented in terms of mean and variance. Blade responses, recorded in terms of displacements, natural frequencies, and maximum stress, was evaluated and plotted in the form of probabilistic distributions under combined uncertainties. These distributions provide an estimate of the range of magnitudes of the response and probability of occurrence of a given response. Most importantly, these distributions provide the information needed to estimate quantitatively the risk in a structural design.

Parent Ratings of ADHD Symptoms: Generalized Partial Credit Model Analysis of Differential Item Functioning across Gender

ERIC Educational Resources Information Center

Gomez, Rapson

2012-01-01

Objective: Generalized partial credit model, which is based on item response theory (IRT), was used to test differential item functioning (DIF) for the "Diagnostic and Statistical Manual of Mental Disorders" (4th ed.), inattention (IA), and hyperactivity/impulsivity (HI) symptoms across boys and girls. Method: To accomplish this, parents completed…

A Note on the Equivalence between Observed and Expected Information Functions with Polytomous IRT Models

ERIC Educational Resources Information Center

Magis, David

2015-01-01

The purpose of this note is to study the equivalence of observed and expected (Fisher) information functions with polytomous item response theory (IRT) models. It is established that observed and expected information functions are equivalent for the class of divide-by-total models (including partial credit, generalized partial credit, rating…

Detecting Random, Partially Random, and Nonrandom Minnesota Multiphasic Personality Inventory-2 Protocols

ERIC Educational Resources Information Center

Pinsoneault, Terry B.

2007-01-01

The ability of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2; J. N. Butcher et al., 2001) validity scales to detect random, partially random, and nonrandom MMPI-2 protocols was investigated. Investigations included the Variable Response Inconsistency scale (VRIN), F, several potentially useful new F and VRIN subscales, and F-sub(b) - F…

Distinguishing between the Partial-Mapping Preparation Hypothesis and the Failure-to-Engage Hypothesis of Residual Switch Costs

ERIC Educational Resources Information Center

Lindsen, Job P.; de Jong, Ritske

2010-01-01

Lien, Ruthruff, Remington, & Johnston (2005) reported residual switch cost differences between stimulus-response (S-R) pairs and proposed the partial-mapping preparation (PMP) hypothesis, which states that advance preparation will typically be limited to a subset of S-R pairs because of structural capacity limitations, to account for these…

Long-term response of oak-hickory regeneration to partial harvest and repeated fires: influence of light and moisture

Treesearch

Louis R. Iverson; Todd F. Hutchinson; Matthew P. Peters; Daniel A. Yaussy

2017-01-01

By tracking oak-hickory (Quercus-Carya) regeneration for 13 yr across management-manipulated light and topographically driven moisture gradients after partial harvest and three prescribed fires, we document best-case conditions to promote advanced oak regeneration, and thereby provide a promising management tool to reverse the downward spiral in...

First-principles calculation of the bulk photovoltaic effect in bismuth ferrite.

PubMed

Young, Steve M; Zheng, Fan; Rappe, Andrew M

2012-12-07

We compute the bulk photovoltaic effect (BPVE) in BiFeO(3) using first-principles shift current theory, finding good agreement with experimental results. Furthermore, we reconcile apparently contradictory observations: by examining the contributions of all photovoltaic response tensor components and accounting for the geometry and ferroelectric domain structure of the experimental system, we explain the apparent lack of BPVE response in striped polydomain samples that is at odds with the significant response observed in monodomain samples. We reveal that the domain-wall-driven response in striped polydomain samples is partially mitigated by the BPVE, suggesting that enhanced efficiency could be obtained in materials with cooperative rather than antagonistic interaction between the two mechanisms.

Complete Metabolic Response of Advanced Melanoma to Vemurafenib Assessed with FDG-PET-CT at 85 Hours.

PubMed

Pascal, Pierre; Dercle, Laurent; Weyts, Kathleen; Meyer, Nicolas; Courbon, Fréderic

2018-05-01

Vemurafenib improves the management of advanced melanoma due to selective inhibition of the mutated BRAF V600E kinase. FDG-PET-CT is a tool for the evaluation of the biologic impact of inhibiting mutant BRAF. With vemurafenib at day 15, all the patients had at least partial metabolic response. Reductions in uptake correlate with longer progression free survival. In this case, incomplete information provided by the patient led to the performance of his third PET 85 hours after the introduction of vemurafenib. This early case of complete metabolic response suggests that FDG-PET-CT is a useful marker of early biologic response to vemurafenib.

Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins

PubMed Central

Postmus, Iris; Trompet, Stella; Deshmukh, Harshal A.; Barnes, Michael R.; Li, Xiaohui; Warren, Helen R.; Chasman, Daniel I.; Zhou, Kaixin; Arsenault, Benoit J.; Donnelly, Louise A.; Wiggins, Kerri L.; Avery, Christy L.; Griffin, Paula; Feng, QiPing; Taylor, Kent D.; Li, Guo; Evans, Daniel S.; Smith, Albert V.; de Keyser, Catherine E.; Johnson, Andrew D.; de Craen, Anton J. M.; Stott, David J.; Buckley, Brendan M.; Ford, Ian; Westendorp, Rudi G. J.; Eline Slagboom, P.; Sattar, Naveed; Munroe, Patricia B.; Sever, Peter; Poulter, Neil; Stanton, Alice; Shields, Denis C.; O’Brien, Eoin; Shaw-Hawkins, Sue; Ida Chen, Y.-D.; Nickerson, Deborah A.; Smith, Joshua D.; Pierre Dubé, Marie; Matthijs Boekholdt, S.; Kees Hovingh, G.; Kastelein, John J. P.; McKeigue, Paul M.; Betteridge, John; Neil, Andrew; Durrington, Paul N.; Doney, Alex; Carr, Fiona; Morris, Andrew; McCarthy, Mark I.; Groop, Leif; Ahlqvist, Emma; Bis, Joshua C.; Rice, Kenneth; Smith, Nicholas L.; Lumley, Thomas; Whitsel, Eric A.; Stürmer, Til; Boerwinkle, Eric; Ngwa, Julius S.; O’Donnell, Christopher J.; Vasan, Ramachandran S.; Wei, Wei-Qi; Wilke, Russell A.; Liu, Ching-Ti; Sun, Fangui; Guo, Xiuqing; Heckbert, Susan R; Post, Wendy; Sotoodehnia, Nona; Arnold, Alice M.; Stafford, Jeanette M.; Ding, Jingzhong; Herrington, David M.; Kritchevsky, Stephen B.; Eiriksdottir, Gudny; Launer, Leonore J.; Harris, Tamara B.; Chu, Audrey Y.; Giulianini, Franco; MacFadyen, Jean G.; Barratt, Bryan J.; Nyberg, Fredrik; Stricker, Bruno H.; Uitterlinden, André G.; Hofman, Albert; Rivadeneira, Fernando; Emilsson, Valur; Franco, Oscar H.; Ridker, Paul M.; Gudnason, Vilmundur; Liu, Yongmei; Denny, Joshua C.; Ballantyne, Christie M.; Rotter, Jerome I.; Adrienne Cupples, L.; Psaty, Bruce M.; Palmer, Colin N. A.; Tardif, Jean-Claude; Colhoun, Helen M.; Hitman, Graham; Krauss, Ronald M.; Wouter Jukema, J; Caulfield, Mark J.; Donnelly, Peter; Barroso, Ines; Blackwell, Jenefer M.; Bramon, Elvira; Brown, Matthew A.; Casas, Juan P.; Corvin, Aiden; Deloukas, Panos; Duncanson, Audrey; Jankowski, Janusz; Markus, Hugh S.; Mathew, Christopher G.; Palmer, Colin N. A.; Plomin, Robert; Rautanen, Anna; Sawcer, Stephen J.; Trembath, Richard C.; Viswanathan, Ananth C.; Wood, Nicholas W.; Spencer, Chris C. A.; Band, Gavin; Bellenguez, Céline; Freeman, Colin; Hellenthal, Garrett; Giannoulatou, Eleni; Pirinen, Matti; Pearson, Richard; Strange, Amy; Su, Zhan; Vukcevic, Damjan; Donnelly, Peter; Langford, Cordelia; Hunt, Sarah E.; Edkins, Sarah; Gwilliam, Rhian; Blackburn, Hannah; Bumpstead, Suzannah J.; Dronov, Serge; Gillman, Matthew; Gray, Emma; Hammond, Naomi; Jayakumar, Alagurevathi; McCann, Owen T.; Liddle, Jennifer; Potter, Simon C.; Ravindrarajah, Radhi; Ricketts, Michelle; Waller, Matthew; Weston, Paul; Widaa, Sara; Whittaker, Pamela; Barroso, Ines; Deloukas, Panos; Mathew, Christopher G.; Blackwell, Jenefer M.; Brown, Matthew A.; Corvin, Aiden; McCarthy, Mark I.; Spencer, Chris C. A.

2014-01-01

Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response. PMID:25350695

Effects of endogenous pyrogen and prostaglandin E2 on hypothalamic neurons in rat brain slices.

PubMed

Watanabe, T; Morimoto, A; Murakami, N

1987-06-01

We investigated the effects of endogenous pyrogen and prostaglandin E2 (PGE2) on the preoptic and anterior hypothalamic (POAH) neurons using brain slice preparations from the rat. Partially purified endogenous pyrogen did not change the activities of most of the neurons in the POAH region when applied locally through a micropipette attached to the recording electrode in proximity to the neurons. This indicates that partially purified endogenous pyrogen does not act directly on the neuronal activity in the POAH region. The partially purified endogenous pyrogen, applied into a culture chamber containing a brain slice, facilitated the activities in 24% of the total neurons tested, regardless of the thermal specificity of the neurons. Moreover, PGE2 added to the culture chamber facilitated 48% of the warm-responsive, 33% of the cold-responsive, and 29% of the thermally insensitive neurons. The direction of change in neuronal activity induced by partially purified endogenous pyrogen appears to be almost the same as that induced by PGE2 when these substances were applied by perfusion to the same neuron in the culture chamber. These results suggest that partially purified pyrogen applied to the perfusate of the culture chamber stimulates some constituents of brain tissue to synthesize and release prostaglandin, which in turn affects the neuronal activity of the POAH region.

Understanding the transmission dynamics of respiratory syncytial virus using multiple time series and nested models.

PubMed

White, L J; Mandl, J N; Gomes, M G M; Bodley-Tickell, A T; Cane, P A; Perez-Brena, P; Aguilar, J C; Siqueira, M M; Portes, S A; Straliotto, S M; Waris, M; Nokes, D J; Medley, G F

2007-09-01

The nature and role of re-infection and partial immunity are likely to be important determinants of the transmission dynamics of human respiratory syncytial virus (hRSV). We propose a single model structure that captures four possible host responses to infection and subsequent reinfection: partial susceptibility, altered infection duration, reduced infectiousness and temporary immunity (which might be partial). The magnitude of these responses is determined by four homotopy parameters, and by setting some of these parameters to extreme values we generate a set of eight nested, deterministic transmission models. In order to investigate hRSV transmission dynamics, we applied these models to incidence data from eight international locations. Seasonality is included as cyclic variation in transmission. Parameters associated with the natural history of the infection were assumed to be independent of geographic location, while others, such as those associated with seasonality, were assumed location specific. Models incorporating either of the two extreme assumptions for immunity (none or solid and lifelong) were unable to reproduce the observed dynamics. Model fits with either waning or partial immunity to disease or both were visually comparable. The best fitting structure was a lifelong partial immunity to both disease and infection. Observed patterns were reproduced by stochastic simulations using the parameter values estimated from the deterministic models.

An Application of Unfolding and Cumulative Item Response Theory Models for Noncognitive Scaling: Examining the Assumptions and Applicability of the Generalized Graded Unfolding Model

ERIC Educational Resources Information Center

Sgammato, Adrienne N.

2009-01-01

This study examined the applicability of a relatively new unidimensional, unfolding item response theory (IRT) model called the generalized graded unfolding model (GGUM; Roberts, Donoghue, & Laughlin, 2000). A total of four scaling methods were applied. Two commonly used cumulative IRT models for polytomous data, the Partial Credit Model and…

Evaluation of an Arabic Version of Children's Self-Report Social Skills Scale (CS[superscript 4]) Based on Item Response Theory

ERIC Educational Resources Information Center

Hussein, Mohamed Habashy

2010-01-01

The present study examined the psychometric properties of the Arabic version of Children's Self-report Social Skills Scale (CS[superscript 4]) using a generalized partial credit model (GPCM). Data from 722 primary school children (401 boys and 321 girls) responses, in Egypt, were analyzed using GPCM. The results indicated that the 21 items are…

Regeneration response to tornado and salvage harvesting in a bottomland forest

Treesearch

John L. Nelson; John W. Groninger; Loretta L. Battaglia; Charles M. Ruffner

2010-01-01

A direct hit from an F4 tornado on May 2003, followed by a partial salvage logging operation at Mermet Lake State Conservation Area on the Ohio River bottoms of southern IL have provided a rare opportunity to assess the responses of a bottomland hardwood forest to severe wind and soil disturbances. The study area encompasses 700 acres and is representative of many...

Stormflow response to roadbuilding and partial cutting in small streams of northern California

Treesearch

Robert R. Ziemer

1981-01-01

To assess the influence of road building and logging on storm flow response, a pair of watersheds were studied at Caspar Creek near Fort Bragg in northern California from 1963 to 1975. Selection cutting and tractor yarding of 85-year-old second-growth redwood and Douglas-fir forest did not significantly affect large peak streamflows. The first streamflow peaks in the...

17 CFR 240.13e-100 - Schedule 13E-3, Transaction statement under section 13(e) of the Securities Exchange Act of 1934...

Code of Federal Regulations, 2010 CFR

2010-04-01

.... If an item is inapplicable or the answer is in the negative, so state. The statement published, sent or given to security holders may omit negative and not applicable responses, except that responses to.... Information contained in exhibits to the statement may be incorporated by reference in answer or partial...

An Analysis of Cross Racial Identity Scale Scores Using Classical Test Theory and Rasch Item Response Models

ERIC Educational Resources Information Center

Sussman, Joshua; Beaujean, A. Alexander; Worrell, Frank C.; Watson, Stevie

2013-01-01

Item response models (IRMs) were used to analyze Cross Racial Identity Scale (CRIS) scores. Rasch analysis scores were compared with classical test theory (CTT) scores. The partial credit model demonstrated a high goodness of fit and correlations between Rasch and CTT scores ranged from 0.91 to 0.99. CRIS scores are supported by both methods.…

How college students conceptualize and practice responsible drinking.

PubMed

Barry, Adam E; Goodson, Patricia

2011-01-01

This study sought to employ a mixed-methods approach to (a) qualitatively explore responsible drinking beliefs and behaviors among a sample of college students, and (b) quantitatively assess the prevalence of those behaviors. Convenience samples, drawn from currently enrolled students attending a large public university in Texas, comprised 13 participants in the qualitative phase and a random sample of 729 students for the quantitative phase. A partially mixed sequential dominant status design (qual → QUAN) was employed. PARTICIPANTS associated 7 distinct themes with drinking responsibly; however, embedded inside these themes were numerous potentially harmful elements. Quantitative findings supported the qualitative themes, also highlighting gender and ethnic differences. Males believed responsible drinking behaviors should occur with significantly less frequency than females, whereas Whites attached less relative necessity to certain responsible drinking behaviors. This study represents an initial attempt to determine specific, evidence-based characteristics of responsible drinking.

Investigating the effectiveness of response strategies for vulnerabilities to corruption in the chinese public construction sector.

PubMed

Shan, Ming; Chan, Albert P C; Le, Yun; Hu, Yi

2015-06-01

Response strategy is a key for preventing widespread corruption vulnerabilities in the public construction sector. Although several studies have been devoted to this area, the effectiveness of response strategies has seldom been evaluated in China. This study aims to fill this gap by investigating the effectiveness of response strategies for corruption vulnerabilities through a survey in the Chinese public construction sector. Survey data obtained from selected experts involved in the Chinese public construction sector were analyzed by factor analysis and partial least squares-structural equation modeling. Analysis results showed that four response strategies of leadership, rules and regulations, training, and sanctions, only achieved an acceptable level in preventing corruption vulnerabilities in the Chinese public construction sector. This study contributes to knowledge by improving the understanding of the effectiveness of response strategies for corruption vulnerabilities in the public construction sector of developing countries.

Immunity against Helminths: Interactions with the Host and the Intercurrent Infections

PubMed Central

Moreau, Emmanuelle; Chauvin, Alain

2010-01-01

Helminth parasites are of considerable medical and economic importance. Studies of the immune response against helminths are of great interest in understanding interactions between the host immune system and parasites. Effector immune mechanisms against tissue-dwelling helminths and helminths localized in the lumen of organs, and their regulation, are reviewed. Helminth infections are characterized by an association of Th2-like and Treg responses. Worms are able to persist in the host and are mainly responsible for chronic infection despite a strong immune response developed by the parasitized host. Two types of protection against the parasite, namely, premune and partial immunities, have been described. Immune responses against helminths can also participate in pathogenesis. Th2/Treg-like immunomodulation allows the survival of both host and parasite by controlling immunopathologic disorders and parasite persistence. Consequences of the modified Th2-like responses on co-infection, vaccination, and inflammatory diseases are discussed. PMID:20150967

Image Processing, Coding, and Compression with Multiple-Point Impulse Response Functions.

NASA Astrophysics Data System (ADS)

Stossel, Bryan Joseph

1995-01-01

Aspects of image processing, coding, and compression with multiple-point impulse response functions are investigated. Topics considered include characterization of the corresponding random-walk transfer function, image recovery for images degraded by the multiple-point impulse response, and the application of the blur function to image coding and compression. It is found that although the zeros of the real and imaginary parts of the random-walk transfer function occur in continuous, closed contours, the zeros of the transfer function occur at isolated spatial frequencies. Theoretical calculations of the average number of zeros per area are in excellent agreement with experimental results obtained from computer counts of the zeros. The average number of zeros per area is proportional to the standard deviations of the real part of the transfer function as well as the first partial derivatives. Statistical parameters of the transfer function are calculated including the mean, variance, and correlation functions for the real and imaginary parts of the transfer function and their corresponding first partial derivatives. These calculations verify the assumptions required in the derivation of the expression for the average number of zeros. Interesting results are found for the correlations of the real and imaginary parts of the transfer function and their first partial derivatives. The isolated nature of the zeros in the transfer function and its characteristics at high spatial frequencies result in largely reduced reconstruction artifacts and excellent reconstructions are obtained for distributions of impulses consisting of 25 to 150 impulses. The multiple-point impulse response obscures original scenes beyond recognition. This property is important for secure transmission of data on many communication systems. The multiple-point impulse response enables the decoding and restoration of the original scene with very little distortion. Images prefiltered by the random-walk transfer function yield greater compression ratios than are obtained for the original scene. The multiple-point impulse response decreases the bit rate approximately 40-70% and affords near distortion-free reconstructions. Due to the lossy nature of transform-based compression algorithms, noise reduction measures must be incorporated to yield acceptable reconstructions after decompression.

Revisiting the slow force response: the role of the PKG signaling pathway in the normal and the ischemic heart.

PubMed

Castro-Ferreira, Ricardo; Neves, João Sérgio; Ladeiras-Lopes, Ricardo; Leite-Moreira, André M; Neiva-Sousa, Manuel; Almeida-Coelho, João; Ferreira-Martins, João; F Leite-Moreira, Adelino

2014-09-01

The myocardial response to acute stretch consists of a two-phase increase in contractility: an acute increase by the Frank-Starling mechanism and a gradual and time-dependent increase in force generated known as the slow force response (SFR). The SFR is actively modulated by different signaling pathways, but the role of protein kinase G (PKG) signaling is unknown. In this study we aim to characterize the role of the PKG signaling pathway in the SFR under normal and ischemic conditions. Rabbit papillary muscles were stretched from 92 to 100% of maximum length (Lmax) under basal conditions, in the absence (1) or presence of: a PKG agonist (2) and a PKG inhibitor (3); under ischemic conditions in the absence (4) or presence of: a PKG agonist (5); a nitric oxide (NO) donor (6) and a phosphodiesterase 5 (PDE5) inhibitor (7). Under normoxia, the SFR was significantly attenuated by inhibition of PKG and remained unaltered with PKG activation. Ischemia induced a progressive decrease in myocardial contractility after stretch. Neither the PKG agonist nor the NO donor altered the myocardial response to stretch under ischemic conditions. However, the use of a PDE5 inhibitor in ischemia partially reversed the progressive deterioration in contractility. PKG activity is essential for the SFR. During ischemia, a progressive decline in the force is observed in response to acute myocardial stretch. This dysfunctional response can be partially reversed by the use of PDE5 inhibitors. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Minimally cultured or selected autologous tumor-infiltrating lymphocytes after a lympho-depleting chemotherapy regimen in metastatic melanoma patients.

PubMed

Besser, Michal J; Shapira-Frommer, Ronnie; Treves, Avraham J; Zippel, Dov; Itzhaki, Orit; Schallmach, Ester; Kubi, Adva; Shalmon, Bruria; Hardan, Izhar; Catane, Raphael; Segal, Eran; Markel, Gal; Apter, Sara; Nun, Alon Ben; Kuchuk, Iryna; Shimoni, Avichai; Nagler, Arnon; Schachter, Jacob

2009-05-01

Adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TIL) and high-dose interleukin-2 (IL-2), after nonmyeloablative chemotherapy, has been shown to result in tumor regression in half of refractory metastatic melanoma patients. In the present study, we describe 2 separate clinical protocols. Twelve patients were treated with "Selected"-TIL, as previously reported and 8 patients with the modified version of "Young"-TIL. Selected-TIL protocol required the establishment of multiple T-cell cultures from 1 patient and in vitro selection of cultures secreting interferon-gamma upon antigenic stimulation. In contrast, Young-TIL are minimally cultured T cells with superior in vitro features that do not require further selection. Two of 12 Selected-TIL patients experienced objective clinical responses (1 complete response, 1 partial response). Out of 8 treated Young-TIL patients, 1 experienced complete response, 2 partial response, and 4 patients had disease stabilization. Twenty-one of 33 enrolled Selected-TIL patients were excluded from the protocol, mainly as cultures failed the interferon-gamma selection criteria or due to clinical deterioration, compared with only 3 Young-TIL patients. Expected bone marrow suppression and high-dose IL-2 toxicity were transient. There was no treatment-related mortality. This study vindicates the feasibility and effectiveness of TIL technology and calls for further efforts to implement and enhance this modality. The use of minimally cultured, unselected Young-TIL enables the treatment of most enrolled patients. Although the cohort of Young-TIL patients treated so far is rather small and the follow-up short, the response rate is encouraging.

Radiofrequency ablation of renal cell carcinoma: a follow up of outcomes.

PubMed

Curry, David; Yassin, Musaab; Thwaini, Ali; Pahuja, Ajay; Alanbuki, Ammar H; Rajan, Thiagarajan Nambi; Loan, Willie

2014-02-01

To present the oncological outcomes in a series of patients with cT1a renal cell carcinoma (RCC) treated with radiofrequency ablation (RFA) and its effect on the glomerular filtration rate (GFR). Forty-five patients (48 renal units) treated at the Belfast City Hospital, over 4 years. Average age is 61.5 years (range 41-80). Eighteen patients (22 renal units) were included with American Society of Anesthesiologists (ASA) II and III. The rest were ASA I. Average tumor size was 2.63 cm (range 1.2 cm-6 cm). Renal function before and after RFA was recorded by means of the estimated glomerular filtration rate (eGFR) and the changes are presented. Oncological outcomes were established from follow up imaging. A satisfactory response was defined by disappearance or a persistence of non-enhancing lesion of smaller size at follow up. A partial response was defined by a persistent but non-enhancing similar size lesion. A failed response was defined by enlarging or persistently enhancing lesions. Mean follow up was 30.6 months (4-60 months). A good response was found in 33 (74%) patients. A partial response was found in 3 (8%) patients and failed response was identified in 8 (18%) patients. The average reduction in eGFR was 11 mL/min. Two patients had a 50% reduction in their eGFR. No patient required dialysis following treatment. RFA presents safe treatment choice for patients with RCC, particularly those that are high risk surgical candidates and those who refuse surgery. Short term results suggest good oncological outcomes and preservation of renal function.

Prolonged duration of response in lenvatinib responders with thyroid cancer.

PubMed

Gianoukakis, Andrew G; Dutcus, Corina E; Batty, Nicolas; Guo, Matthew; Baig, Mahadi

2018-06-01

We present an updated analysis of lenvatinib in radioiodine-refractory differentiated thyroid cancer (RR-DTC) with new duration of response (DOR) data unavailable for the primary analysis. In this randomized, double-blind, multicenter, placebo-controlled phase 3 study, patients ≥18 years old with measurable, pathologically confirmed RR-DTC with independent radiologic confirmation of disease progression within the previous 13 months were randomized 2:1 to oral lenvatinib 24 mg/day or placebo. The main outcome measures for this analysis are DOR and progression-free survival (PFS). The median DOR for all lenvatinib responders (patients with complete or partial responses; objective response rate: 60.2%; 95% confidence interval (CI) 54.2-66.1) was 30.0 months (95% CI 18.4-36.7) and was generally similar across subgroups. DOR was shorter in patients with greater disease burden and with brain and liver metastases. Updated median PFS was longer in the overall lenvatinib group vs placebo (19.4 vs 3.7 months; hazard ratio (HR) 0.24; 99% CI 0.17-0.35; nominal P  < 0.0001). In lenvatinib responders, median PFS was 33.1 months (95% CI 27.8-44.6) vs 7.9 months (95% CI 5.8-10.7) in non-responders. The median DOR of 30.0 months seen with patients who achieved complete or partial responses with lenvatinib (60.2%) demonstrates that lenvatinib responders can have prolonged, durable and clinically meaningful responses. Prolonged PFS (33.1 months) was also observed in these lenvatinib responders. © 2018 The authors.

Low-dose mitomycin C, etoposide, and cisplatin for invasive vulvar Paget's disease.

PubMed

Watanabe, Yoh; Hoshiai, H; Ueda, H; Nakai, H; Obata, K; Noda, K

2002-01-01

We report the effect of low-dose mitomycin C, etoposide, and cisplatin (low-dose MEP) therapy for three patients with invasive vulvar Paget's disease (invasive VPD) who declined radical vulvectomy and skin grafting. One patient achieved a complete response, while the other two showed partial responses (PR) without grade 3 or 4 adverse effects. The two patients with PR were undergone partial vulvectomy and inguinal lymph node dissection. All patients have no sign of recurrence for 10 months after chemotherapy. Our present results suggest that low-dose MEP is an effective and safe chemotherapy for invasive VPD and low-dose MEP may significantly improve postoperative quality of life in patients with invasive VPD by avoiding extensive vulvar resection and skin grafting.

Modeling and optimization aspects of radiation induced grafting of 4-vinylpyridene onto partially fluorinated films

NASA Astrophysics Data System (ADS)

Nasef, Mohamed Mahmoud; Ahmad Ali, Amgad; Saidi, Hamdani; Ahmad, Arshad

2014-01-01

Modeling and optimization aspects of radiation induced grafting (RIG) of 4-vinylpyridine (4-VP) onto partially fluorinated polymers such as poly(ethylene-co-tetrafluoroethene) (ETFE) and poly(vinylidene fluoride) (PVDF) films were comparatively investigated using response surface method (RSM). The effects of independent parameters: absorbed dose, monomer concentration, grafting time and reaction temperature on the response, grafting yield (GY) were correlated through two quadratic models. The results of this work confirm that RSM is a reliable tool not only for optimization of the reaction parameters and prediction of GY in RIG processes, but also for the reduction of the number of the experiments, monomer consumption and absorbed dose leading to an improvement of the overall reaction cost.

Association Between Response to Acid-Suppression Therapy and Efficacy of Antireflux Surgery in Patients With Extraesophageal Reflux.

PubMed

Krill, Joseph T; Naik, Rishi D; Higginbotham, Tina; Slaughter, James C; Holzman, Michael D; Francis, David O; Garrett, C Gaelyn; Vaezi, Michael F

2017-05-01

The effectiveness of antireflux surgery (ARS) varies among patients with extraesophageal manifestations of gastroesophageal reflux disease (GERD). By studying a cohort of patients with primary extraesophageal symptoms and abnormal physiologic markers for GERD, we aimed to identify factors associated with positive outcomes from surgery, and compare outcomes to those with typical esophageal manifestations of GERD. We performed a retrospective cohort study to compare adult patients with extraesophageal and typical reflux symptoms who underwent de novo ARS from 2004 through 2012 at a tertiary care center. All 115 patients (79 with typical GERD and 36 with extraesophageal manifestations of GERD) had evidence of abnormal distal esophageal acid exposure based on pH testing or endoscopy. The principle outcome was time to primary symptom recurrence after surgery, based on patient reports of partial or total recurrence of symptoms at follow-up visits. Patients were followed up for a median duration of 66 months (interquartile range, 52-77 mo). The median time to recurrence of symptoms in the overall cohort was 68 months (11.5 months in the extraesophageal cohort vs >132 months in the typical cohort). Symptom recurrence after ARS was associated with having primarily extraesophageal symptoms (adjusted hazard ratio, 2.34; 95% confidence interval, 1.31-4.17) and poor preoperative symptom response to acid-suppression therapy (AST) (hazard ratio, 3.85; 95% confidence interval, 2.05-7.22). Patients with primary extraesophageal symptoms who had a full or partial preoperative AST response experienced lower rates of symptom recurrence compared to patients with poor AST response (P < .01). The rate of symptom recurrence was lowest among patients with primary typical reflux symptoms who had a partial or full symptom response to AST (P < .01). The severity of acid reflux on pH testing, symptom indices, severity of esophagitis, and hiatal hernia size were not associated with symptom response. In a retrospective study, we found the effectiveness of ARS to be less predictable in patients with extraesophageal symptoms of GERD than in patients with typical GERD. Response to AST before surgery was associated with ARS effectiveness in patients with extraesophageal reflux symptoms. Caution should be exercised when advocating ARS for patients with extraesophageal symptoms that do not respond to AST. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

CB1 receptor mediated analgesia from the Nucleus Reticularis Gigantocellularis pars alpha is activated in an animal model of neuropathic pain.

PubMed

Monhemius, R; Azami, J; Green, D L; Roberts, M H

2001-07-20

Cannabinoids are known to suppress responses to noxious stimulation in animals and man. Recent research has suggested a role for endogenous cannabinoids in the descending inhibition of dorsal horn cells via a supraspinal site of action. We have recently demonstrated [J. Physiol. 506(2) (1998) 459] that the nucleus reticularis gigantocellularis pars alpha (GiA) is a major source of such descending modulation, and importantly, that this system is activated in response to noxious stimulation. We have therefore investigated the role of CB1 receptor activation in mediating the antinociceptive effects of activation of GiA in models of acute and chronic pain. Microinjections (0.5 microl 60% DMSO) of either WIN 55,212-2 (5 microg, selective CB1 agonist), SR141716A (50 microg, competitive CB1 antagonist), both compounds together, or vehicle alone into GiA were performed prior to these tests in a randomised, blind manner. In control animals, WIN 55,212-2 markedly increased withdrawal latencies in the tail flick test and reduced responses to subcutaneous formalin. These effects were blocked by co-administration of SR141716A. These data suggest that activation of cannabinoid CB1 receptor subtypes in GiA leads to behavioural analgesia. In animals with partial sciatic nerve ligation, microinjection of drugs and injection of formalin were performed contralaterally to the site of ligation. Partial sciatic nerve ligation significantly reduced behavioural responses to contralaterally applied formalin. Microinjection of SR141716A to GiA reversed this inhibition of responses to formalin in animals with partial sciatic nerve ligation. These data provide evidence that endogenous CB1 receptor ligands are involved in GiA mediated antinociception, and that this system is important for the modulation of nociceptive transmission in an animal model of chronic neuropathic pain.

End-of-Treatment Positron Emission Tomography After Uniform First-Line Therapy of B-Cell Posttransplant Lymphoproliferative Disorder Identifies Patients at Low Risk of Relapse in the Prospective German PTLD Registry.

PubMed

Zimmermann, Heiner; Denecke, Timm; Dreyling, Martin H; Franzius, Christiane; Reinke, Petra; Subklewe, Marion; Amthauer, Holger; Kneba, Michael; Riess, Hanno; Trappe, Ralf U

2018-05-01

Fluorine-18 fluorodeoxyglucose (18F-FDG)-positron emission tomography (PET) is a recommended standard in the staging and response assessment of 18F-FDG-avid lymphoma. Posttransplant lymphoproliferative disorder (PTLD) can be detected by 18F-FDG-PET at diagnosis with high sensitivity and specificity. However, the role of response assessment by end-of-treatment (EOT) PET has only been addressed in small case series. We performed a retrospective, multicenter study of 37 patients with CD20-positive PTLD after solid organ transplantation treated with uniform, up-to-date, first-line protocols in the prospective German PTLD registry who had received EOT 18F-FDG-PET between 2006 and 2014. Median follow-up was 5.0 years. Any nonphysiological 18F-FDG uptake (Deauville score greater 2) was interpreted as PET-positive. By computed tomography (CT) final staging, 18 of 37 patients had a complete response, 18 had a partial response and 1 patient had stable disease. EOT PET was negative in 24 of 37 patients and positive in 13 of 37 patients. The positive predictive value of EOT PET for PTLD relapse was 38%, and the negative predictive value was 92%. Time to progression (TTP) and progression-free-survival were significantly longer in the PET negative group (P = 0.019 and P = 0.013). In the 18 patients in a partial response by CT staging, we noted highly significant differences in overall survival (P = 0.001), time to progression (P = 0.007), and progression-free survival (P < 0.001) by EOT PET. Even without baseline imaging, EOT PET in PTLD identifies patients at low risk of relapse and offers clinically relevant information, particularly in patients in a partial remission by CT staging.

Agonist Met antibodies define the signalling threshold required for a full mitogenic and invasive program of Kaposi's Sarcoma cells.

PubMed

Bardelli, Claudio; Sala, Marilena; Cavallazzi, Umberto; Prat, Maria

2005-09-09

We previously showed that the Kaposi Sarcoma line KS-IMM express a functional Met tyrosine kinase receptor, which, upon HGF stimulation, activates motogenic, proliferative, and invasive responses. In this study, we investigated the signalling pathways activated by HGF, as well as by Met monoclonal antibodies (Mabs), acting as full or partial agonists. The full agonist Mab mimics HGF in all biological and biochemical aspects. It elicits the whole spectrum of responses, while the partial agonist Mab induces only wound healing. These differences correlated with a more prolonged and sustained tyrosine phosphorylation of the receptor and MAPK evoked by HGF and by the full agonist Mab, relative to the partial agonist Mab. Since Gab1, JNK and PI 3-kinase are activated with same intensity and kinetics by HGF and by the two agonist antibodies, it is concluded that level and duration of MAPK activation by Met receptor are crucial for the induction of a full HGF-dependent mitogenic and invasive program in KS cells.

An N-methyl-D-aspartate receptor-independent excitatory action of partial reduction of extracellular [Mg2+] in CA1-region of rat hippocampal slices.

PubMed

Hamon, B; Stanton, P K; Heinemann, U

1987-03-31

Partial reduction of [Mg2+]o from 2 to 1 mM markedly enhanced neuronal responses evoked by Schaffer collateral-commissural fiber stimulation in the CA1-region of rat hippocampal slices. The amplitude of extracellular population potentials recorded in the CA1-pyramidal cell layer and maximum dV/dt of extracellular population EPSP's recorded in the CA1-pyramidal apical dendritic layer were both increased. However, unlike findings from slices where Mg2+ was completely removed from the bathing medium, there was no spontaneous or evoked epileptiform activity, and the N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovalerate (2-APV) did not antagonize the enhancement of evoked responses. These results indicate that, in addition to the participation of NMDA receptors in the epileptiform activity observed when Mg2+ is completely removed from the bathing medium, there is also an NMDA receptor-independent excitatory action of partial reduction of [Mg2+]o in hippocampal slices.

The roles of prostaglandin endoperoxides, thromboxane A2 and adenosine diphosphate in collagen-induced aggregation in man and the rat.

PubMed Central

Emms, H.; Lewis, G. P.

1986-01-01

The effects of aspirin, carboxyheptylimidazole (CHI) and creatine phosphate/creatine phosphokinase (CP/CPK) on platelet aggregation and thromboxane B2 (TxB2) formation induced by collagen have been examined in vitro. Platelets from two species, man and the rat, have been used. In man, aspirin and CHI abolished TxB2 production but only partially inhibited aggregation. CP/CPK partially inhibited aggregation and TxB2 formation. In the rat, aspirin and CHI abolished TxB2 formation but had no effect on aggregation. CP/CPK completely inhibited aggregation and partially inhibited TxB2 generation. In man, collagen-induced aggregation is largely dependent on ADP and to a lesser extent on arachidonate metabolites whereas, in the rat, ADP alone mediates aggregation induced by this agonist. The results with CP/CPK suggest that TxB2 formation is dependent either on the prior release of platelet ADP or on aggregation itself rather than being responsible for the aggregation response. PMID:3082399

Exotic species enhance response diversity to land-use change but modify functional composition.

PubMed

Stavert, Jamie R; Pattemore, David E; Gaskett, Anne C; Beggs, Jacqueline R; Bartomeus, Ignasi

2017-08-16

Two main mechanisms may buffer ecosystem functions despite biodiversity loss. First, multiple species could share similar ecological roles, thus providing functional redundancy. Second, species may respond differently to environmental change (response diversity). However, ecosystem function would be best protected when functionally redundant species also show response diversity. This linkage has not been studied directly, so we investigated whether native and exotic pollinator species with similar traits (functional redundancy) differed in abundance (response diversity) across an agricultural intensification gradient. Exotic pollinator species contributed most positive responses, which partially stabilized overall abundance of the pollinator community. However, although some functionally redundant species exhibited response diversity, this was not consistent across functional groups and aggregate abundances within each functional group were rarely stabilized. This shows functional redundancy and response diversity do not always operate in concert. Hence, despite exotic species becoming increasingly dominant in human-modified systems, they cannot replace the functional composition of native species. © 2017 The Author(s).

A comparison of analysis methods to estimate contingency strength.

PubMed

Lloyd, Blair P; Staubitz, Johanna L; Tapp, Jon T

2018-05-09

To date, several data analysis methods have been used to estimate contingency strength, yet few studies have compared these methods directly. To compare the relative precision and sensitivity of four analysis methods (i.e., exhaustive event-based, nonexhaustive event-based, concurrent interval, concurrent+lag interval), we applied all methods to a simulated data set in which several response-dependent and response-independent schedules of reinforcement were programmed. We evaluated the degree to which contingency strength estimates produced from each method (a) corresponded with expected values for response-dependent schedules and (b) showed sensitivity to parametric manipulations of response-independent reinforcement. Results indicated both event-based methods produced contingency strength estimates that aligned with expected values for response-dependent schedules, but differed in sensitivity to response-independent reinforcement. The precision of interval-based methods varied by analysis method (concurrent vs. concurrent+lag) and schedule type (continuous vs. partial), and showed similar sensitivities to response-independent reinforcement. Recommendations and considerations for measuring contingencies are identified. © 2018 Society for the Experimental Analysis of Behavior.

Explaining between-race differences in African-American and European-American women's responses to breast density notification.

PubMed

Manning, Mark; Albrecht, Terrance L; Yilmaz-Saab, Zeynep; Penner, Louis; Norman, Andria; Purrington, Kristen

2017-12-01

Prior research shows between-race differences in women's knowledge and emotions related to having dense breasts, thus suggesting that between-race differences in behavioral decision-making following receipt of breast density (BD) notifications are likely. Guided by the theory of planned behavior, this study examined differences in emotion-related responses (i.e., anxiety, worry, confusion) and behavioral cognition (e.g., intentions, behavioral attitudes) following receipt of BD notifications among African American (AA) and European American (EA) women. This study also examined whether race-related perceptions (i.e., discrimination, group-based medical mistrust), relevant knowledge and socioeconomic status (SES) explained the between race differences. Michigan women (N = 457) who presented for routine screening mammogram and had dense breasts, no prior breast cancer diagnoses, and had screen-negative mammograms were recruited from July, 2015 to March 2016. MANOVA was used to examine between race differences in psychological responses (i.e., emotional responses and behavioral cognition), and a multi-group structural regression model was used to examine whether race-related constructs, knowledge and SES mediated the effect of race on emotional responses and behavioral cognition. Prior awareness of BD was accounted for in all analyses. AA women generally reported more negative psychological responses to receiving BD notifications regardless of prior BD awareness. AA women had more favorable perceptions related to talking to their physicians about the BD notifications. Generally, race-related perceptions, SES, and related knowledge partially accounted for the effect of race on psychological response. Race-related perceptions and SES partially accounted for the differences in behavioral intentions. Between-race differences in emotional responses to BD notifications did not explain differences in women's intentions to discuss BD notifications with their physicians. Future examinations are warranted to examine whether there are between-race differences in actual post-BD notification behaviors and whether similar race-related variables account for differences. Copyright © 2017. Published by Elsevier Ltd.

CUDC-907 in relapsed/refractory diffuse large B-cell lymphoma, including patients with MYC-alterations: results from an expanded phase I trial.

PubMed

Oki, Yasuhiro; Kelly, Kevin R; Flinn, Ian; Patel, Manish R; Gharavi, Robert; Ma, Anna; Parker, Jefferson; Hafeez, Amir; Tuck, David; Younes, Anas

2017-11-01

CUDC-907 is a first-in-class, oral small molecule inhibitor of both HDAC (class I and II) and PI3K (class Iα, β, and δ) enzymes, with demonstrated anti-tumor activity in multiple pre-clinical models, including MYC-driven ones. In this report, we present the safety and preliminary activity results of CUDC-907, with and without rituximab, in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), with a particular focus on those with MYC-altered disease. Thirty-seven DLBCL patients were enrolled, 14 with confirmed MYC-altered disease. Twenty-five patients received monotherapy treatment, and 12 received the combination of CUDC-907 with rituximab. CUDC-907 monotherapy and combination demonstrated similar safety profiles consisting primarily of Grade 1/2 hematologic and gastrointestinal events. The most frequently reported Grade ≥3 treatment-related events were thrombocytopenia, neutropenia, diarrhea, fatigue, and anemia. Eleven responses (5 complete responses and 6 partial responses) were reported, for a response rate of 37% (11 out of 30) in evaluable patients [30% (11 out of 37) including all patients]. The objective response rate in evaluable MYC-altered DLBCL patients was 64% (7 out of 11; 4 complete responses and 3 partial responses), while it was 29% (2 out of 7) in MYC unaltered, and 17% (2 out of 12) in those with unknown MYC status. Median duration of response was 11.2 months overall; 13.6 months in MYC-altered patients, 6.0 months in MYC unaltered, and 7.8 months in those with MYC status unknown. The tolerable safety profile and encouraging evidence of durable anti-tumor activity, particularly in MYC-altered patients, support the continued development of CUDC-907 in these populations of high unmet need. ( clinicaltrials.gov identifier: 01742988 ). Copyright© Ferrata Storti Foundation.

Outcome of Patients Treated With a Single-Fraction Dose of Palliative Radiation for Cutaneous T-Cell Lymphoma

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

Thomas, Tarita O.; Agrawal, Priya; Guitart, Joan

2013-03-01

Purpose: Cutaneous T-cell lymphoma (CTCL) is a radiosensitive tumor. Presently, treatment with radiation is given in multiple fractions. The current literature lacks data that support single-fraction treatment for CTCL. This retrospective review assesses the clinical response in patients treated with a single fraction of radiation. Methods and Materials: This study reviewed the records of 58 patients with CTCL, primarily mycosis fungoides, treated with a single fraction of palliative radiation therapy (RT) between October 1991 and January 2011. Patient and tumor characteristics were reviewed. Response rates were compared using Fisher's exact test and multiple logistic regressions. Survival rates were determined usingmore » the Kaplan-Meier method. Cost-effectiveness analysis was performed to assess the cost of a single vs a multifractionated treatment regimen. Results: Two hundred seventy individual lesions were treated, with the majority (97%) treated with ≥700 cGy; mean follow-up was 41.3 months (range, 3-180 months). Response rate by lesion was assessed, with a complete response (CR) in 255 (94.4%) lesions, a partial response in 10 (3.7%) lesions, a partial response converted to a CR after a second treatment in 4 (1.5%) lesions, and no response in 1 (0.4%) lesion. The CR in lower extremity lesions was lower than in other sites (P=.0016). Lesions treated with photons had lower CR than those treated with electrons (P=.017). Patients with lesions exhibiting large cell transformation and tumor morphology had lower CR (P=.04 and P=.035, respectively). Immunophenotype did not impact response rate (P=.23). Overall survival was significantly lower for patients with Sézary syndrome (P=.0003) and erythroderma (P<.0001). The cost of multifractionated radiation was >200% higher than that for single-fraction radiation. Conclusions: A single fraction of 700 cGy-800 cGy provides excellent palliation for CTCL lesions and is cost effective and convenient for the patient.« less

Medial collateral ligament injuries and subsequent load on the anterior cruciate ligament: a biomechanical evaluation in a cadaveric model.

PubMed

Battaglia, Michael J; Lenhoff, Mark W; Ehteshami, John R; Lyman, Stephen; Provencher, Matthew T; Wickiewicz, Thomas L; Warren, Russell F

2009-02-01

Numerous studies have documented the effect of complete medial collateral ligament injury on anterior cruciate ligament loads; few have addressed how partial medial collateral ligament disruption affects knee kinematics. To determine knee kinematics and subsequent change in anterior cruciate ligament load in a partial and complete medial collateral ligament injury model. Controlled laboratory study. Ten human cadaveric knees were sequentially tested by a robot with the medial collateral ligament intact, in a partial injury model, and in a complete injury model with a universal force-moment sensor measuring system. Tibial translation, rotation, and anterior cruciate ligament load were measured under 3 conditions: anterior load (125 N), valgus load (10 N x m), and internal-external rotation torque (4 N x m; all at 0 degrees and 30 degrees of flexion). Anterior and posterior translation did not statistically increase with a partial or complete medial collateral ligament injury at 0 degrees and 30 degrees of flexion. In response to a 125 N anterior load, at 0 degrees , the anterior cruciate ligament load increased 8.7% (from 99.5 to 108.2 N; P = .006) in the partial injury and 18.3% (117.7 N; P < .001) in the complete injury; at 30 degrees , anterior cruciate ligament load was increased 12.3% (from 101.7 to 114.2 N; P = .001) in the partial injury and 20.6% (122.7 N; P < .001) in the complete injury. In response to valgus torque (10 N x m) at 30 degrees , anterior cruciate ligament load was increased 55.3% (30.4 to 47.2 N; P = .044) in the partial injury model and 185% (86.8 N; P = .001) in the complete injury model. In response to internal rotation torque (4 N.m) at 30 degrees , anterior cruciate ligament load was increased 29.3% (27.6 to 35.7 N; P = .001) in the partial injury model and 65.2% (45.6 N; P < .001) in the complete injury model. The amount of internal rotation at 30 degrees of flexion was significantly increased in the complete injury model (22.8 degrees ) versus the intact state (19.5 degrees ; P < .001). Partial and complete medial collateral ligament tears significantly increased the load on the anterior cruciate ligament. In a partial tear, the resultant load on the anterior cruciate ligament was increased at 30 degrees of flexion and with valgus load and internal rotation torque. Patients may need to be protected from valgus and internal rotation forces after anterior cruciate ligament reconstruction in the setting of a concomitant partial medial collateral ligament tear. This information may help clinicians understand the importance of partial injuries of the medial collateral ligament with a combined anterior cruciate ligament injury complex.

Conflict in object affordance revealed by grip force

PubMed Central

McBride, Jennifer; Sumner, Petroc; Husain, Masud

2011-01-01

Viewing objects can result in automatic, partial activation of motor plans associated with them—“object affordance”. Here, we recorded grip force simultaneously from both hands in an object affordance task to investigate the effects of conflict between coactivated responses. Participants classified pictures of objects by squeezing force transducers with their left or right hand. Responses were faster on trials where the object afforded an action with the same hand that was required to make the response (congruent trials) compared to the opposite hand (incongruent trials). In addition, conflict between coactivated responses was reduced if it was experienced on the preceding trial, just like Gratton adaptation effects reported in “conflict” tasks (e.g., Eriksen flanker). This finding suggests that object affordance demonstrates conflict effects similar to those shown in other stimulus–response mapping tasks and thus could be integrated into the wider conceptual framework on overlearnt stimulus–response associations. Corrected erroneous responses occurred more frequently when there was conflict between the afforded response and the response required by the task, providing direct evidence that viewing an object activates motor plans appropriate for interacting with that object. Recording continuous grip force, as here, provides a sensitive way to measure coactivated responses in affordance tasks. PMID:21824035

Aging causes decreased resistance to multiple stresses and a failure to activate specific stress response pathways.

PubMed

Dues, Dylan J; Andrews, Emily K; Schaar, Claire E; Bergsma, Alexis L; Senchuk, Megan M; Van Raamsdonk, Jeremy M

2016-04-01

In this work, we examine the relationship between stress resistance and aging. We find that resistance to multiple types of stress peaks during early adulthood and then declines with age. To dissect the underlying mechanisms, we use C. elegans transcriptional reporter strains that measure the activation of different stress responses including: the heat shock response, mitochondrial unfolded protein response, endoplasmic reticulum unfolded protein response, hypoxia response, SKN-1-mediated oxidative stress response, and the DAF-16-mediated stress response. We find that the decline in stress resistance with age is at least partially due to a decreased ability to activate protective mechanisms in response to stress. In contrast, we find that any baseline increase in stress caused by the advancing age is too mild to detectably upregulate any of the stress response pathways. Further exploration of how worms respond to stress with increasing age revealed that the ability to mount a hormetic response to heat stress is also lost with increasing age. Overall, this work demonstrates that resistance to all types of stress declines with age. Based on our data, we speculate that the decrease in stress resistance with advancing age results from a genetically-programmed inactivation of stress response pathways, not accumulation of damage.

Aging causes decreased resistance to multiple stresses and a failure to activate specific stress response pathways

PubMed Central

Bergsma, Alexis L.; Senchuk, Megan M.; Van Raamsdonk, Jeremy M.

2016-01-01

In this work, we examine the relationship between stress resistance and aging. We find that resistance to multiple types of stress peaks during early adulthood and then declines with age. To dissect the underlying mechanisms, we use C. elegans transcriptional reporter strains that measure the activation of different stress responses including: the heat shock response, mitochondrial unfolded protein response, endoplasmic reticulum unfolded protein response, hypoxia response, SKN-1-mediated oxidative stress response, and the DAF-16-mediated stress response. We find that the decline in stress resistance with age is at least partially due to a decreased ability to activate protective mechanisms in response to stress. In contrast, we find that any baseline increase in stress caused by the advancing age is too mild to detectably upregulate any of the stress response pathways. Further exploration of how worms respond to stress with increasing age revealed that the ability to mount a hormetic response to heat stress is also lost with increasing age. Overall, this work demonstrates that resistance to all types of stress declines with age. Based on our data, we speculate that the decrease in stress resistance with advancing age results from a genetically-programmed inactivation of stress response pathways, not accumulation of damage. PMID:27053445

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

41 CFR 301-72.300 - What procedures must we establish to collect unused, partially used, and exchanged tickets?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 41 Public Contracts and Property Management 4 2010-07-01 2010-07-01 false What procedures must we establish to collect unused, partially used, and exchanged tickets? 301-72.300 Section 301-72.300 Public Contracts and Property Management Federal Travel Regulation System TEMPORARY DUTY (TDY) TRAVEL ALLOWANCES AGENCY RESPONSIBILITIES 72-AGENCY...

Asynchronous partial contact motion due to internal resonance in multiple degree-of-freedom rotordynamics

NASA Astrophysics Data System (ADS)

Shaw, A. D.; Champneys, A. R.; Friswell, M. I.

2016-08-01

Sudden onset of violent chattering or whirling rotor-stator contact motion in rotational machines can cause significant damage in many industrial applications. It is shown that internal resonance can lead to the onset of bouncing-type partial contact motion away from primary resonances. These partial contact limit cycles can involve any two modes of an arbitrarily high degree-of-freedom system, and can be seen as an extension of a synchronization condition previously reported for a single disc system. The synchronization formula predicts multiple drivespeeds, corresponding to different forms of mode-locked bouncing orbits. These results are backed up by a brute-force bifurcation analysis which reveals numerical existence of the corresponding family of bouncing orbits at supercritical drivespeeds, provided the damping is sufficiently low. The numerics reveal many overlapping families of solutions, which leads to significant multi-stability of the response at given drive speeds. Further, secondary bifurcations can also occur within each family, altering the nature of the response and ultimately leading to chaos. It is illustrated how stiffness and damping of the stator have a large effect on the number and nature of the partial contact solutions, illustrating the extreme sensitivity that would be observed in practice.

Effect of surfactant and partial liquid ventilation treatment on gas exchange and lung mechanics in immature lambs: influence of gestational age.

PubMed

Rey-Santano, Carmen; Mielgo, Victoria; Gastiasoro, Elena; Valls-i-Soler, Adolfo; Murgia, Xabier

2013-01-01

Surfactant (SF) and partial liquid ventilation (PLV) improve gas exchange and lung mechanics in neonatal RDS. However, variations in the effects of SF and PLV with degree of lung immaturity have not been thoroughly explored. Experimental Neonatal Respiratory Physiology Research Unit, Cruces University Hospital. Prospective, randomized study using sealed envelopes. 36 preterm lambs were exposed (at 125 or 133-days of gestational age) by laparotomy and intubated. Catheters were placed in the jugular vein and carotid artery. All the lambs were assigned to one of three subgroups given: 20 mL/Kg perfluorocarbon and managed with partial liquid ventilation (PLV), surfactant (Curosurf®, 200 mg/kg) or (3) no pulmonary treatment (Controls) for 3 h. Cardiovascular parameters, blood gases and pulmonary mechanics were measured. In 125-day gestation lambs, SF treatment partially improved gas exchange and lung mechanics, while PLV produced significant rapid improvements in these parameters. In 133-day lambs, treatments with SF or PLV achieved similarly good responses. Neither surfactant nor PLV significantly affected the cardiovascular parameters. SF therapy response was more effective in the older gestational age group whereas the effectiveness of PLV therapy was not gestational age dependent.

Correlation of Fin Buffet Pressures on an F/A-18 with Scaled Wind-Tunnel Measurements

NASA Technical Reports Server (NTRS)

Moses, Robert W.; Shah, Gautam H.

1999-01-01

Buffeting is an aeroelastic phenomenon occurring at high angles of attack that plagues high performance aircraft, especially those with twin vertical tails. Previous wind-tunnel and flight tests were conducted to characterize the buffet loads on the vertical tails by measuring surface pressures, bending moments, and accelerations. Following these tests, buffeting responses were computed using the measured buffet pressures and compared to the measured buffeting responses. The calculated results did not match the measured data because the assumed spatial correlation of the buffet pressures was not correct. A better understanding of the partial (spatial) correlation of the differential buffet pressures on the tail was necessary to improve the buffeting predictions. Several wind-tunnel investigations were conducted for this purpose. When compared, the results of these tests show that the partial correlation scales with flight conditions. One of the remaining questions is whether the wind-tunnel data is consistent with flight data. Presented herein, cross-spectra and coherence functions calculated from pressures that were measured on the High Alpha Research Vehicle indicate that the partial correlation of the buffet pressures in flight agrees with the partial correlation observed in the wind tunnel.

Topical treatment of actinic keratoses with low-dose 5-fluorouracil in combination with salicylic acid--pilot study.

PubMed

Schlaak, Max; Simon, Jan C

2010-03-01

Actinic keratoses (AK) are carcinomas in situ and can progress to invasive squamous cell carcinomas. Treatment of actinic keratoses can be achieved by physical ablation, chemotherapeutic agents, immunomodulators or photodynamic therapy. We conducted a proof of concept study with 15 patients. Overall 66 actinic keratoses were treated with 5-FU (0.5%) and salicylic acid (10%) for 4 weeks (3 times per week). After 12 weeks complete response of 47 AK (77%), partial response of 13 AK (21%) and non-response of 1 AK (2%) were achieved. Treatment was well tolerated and efficient.

Narrative means to manage responsibility in life narratives across adolescence.

PubMed

De Silveira, Cybèle; Habermas, Tilmann

2011-01-01

Adolescence is a passage from dependence to adult responsibility. Alongside identity development, social-cognitive development, and the ability to construct a life story, adolescents become increasingly aware of both their potential responsibility in an expanded sphere of life and of complex, contextual influences on their lives. This was partially tested in a cross-sectional study, both in terms of linguistic means and content expressed in life narratives. Indicators were defined for narrative agency, grading of responsibility, serendipity, and turning points, and tested for age differences in relative frequencies in 102 life narratives from age groups of 8, 12, 16, and 20 years, balanced for gender. Narrative grading of responsibility, serendipity, and turning points increased throughout adolescence. The relative frequency of narrative agency, in contrast, remained constant across age groups. Results are interpreted in the context of adolescent development of narrative identity.

Impaired antibody response against T-dependent antigens in rhino mice.

PubMed

Takaoki, M; Kawaji, H

1980-05-01

The antibody response in rhino mice, which carry a mutant gene hrrh, to thymus-dependent (TD) or thymus-independent (TI) antigens was compared with that of phenotypically normal littermates. The magnitude of antibody response to TD antigens in rhino mice decreased as they grew up, whereas the antibody response to TI antigens in rhino mice was indistinguishable from that of littermates. A transfer of thymus cells from littermates to rhino mice resulted in the partial restoration of the responsiveness to TD antigens. The experiments employing adoptive transfer of spleen cells from rhino mice to the irradiated normal mice suggested that the hyporesponsiveness of TD antigens of adult rhino mice was mainly due to the defect in the T helper cell activities rather than either the increase of the suppressor cells or defects in other cell types.

Response Inhibition, Peer Preference and Victimization, and Self-Harm: Longitudinal Associations in Young Adult Women with and without ADHD.

PubMed

Meza, Jocelyn I; Owens, Elizabeth B; Hinshaw, Stephen P

2016-02-01

Self-harm (suicidal ideation and attempts; non-suicidal self-injuries behavior) peaks in adolescence and early-adulthood, with rates higher for women than men. Young women with childhood psychiatric diagnoses appear to be at particular risk, yet more remains to be learned about the key predictors or mediators of self-harm outcomes. Our aims were to examine, with respect to self-harm-related outcomes in early adulthood, the predictive validity of childhood response inhibition, a cardinal trait of attention-deficit hyperactivity disorder (ADHD), as well as the potential mediating effects of social preference and peer victimization, ascertained in early adolescence. Participants were an ethnically and socioeconomically diverse sample of 228 girls with and without ADHD, an enriched sample for deficits in response inhibition. Childhood response inhibition (RI) predicted young-adult suicide ideation (SI), suicide attempts (SA), and non-suicidal self-injury (NSSI), over and above full-scale IQ, mother's education, household income, and age. Importantly, teacher-rated social preference in adolescence was a partial mediator of the RI-SI/SA linkages; self-reported peer victimization in adolescence emerged as a significant partial mediator of the RI-NSSI linkage. We discuss implications for conceptual models of self-harm and for needed clinical services designed to detect and reduce self-harm.

The Spectrum of Replication Errors in the Absence of Error Correction Assayed Across the Whole Genome of Escherichia coli.

PubMed

Niccum, Brittany A; Lee, Heewook; MohammedIsmail, Wazim; Tang, Haixu; Foster, Patricia L

2018-06-15

When the DNA polymerase that replicates the Escherichia coli chromosome, DNA Pol III, makes an error, there are two primary defenses against mutation: proofreading by the epsilon subunit of the holoenzyme and mismatch repair. In proofreading deficient strains, mismatch repair is partially saturated and the cell's response to DNA damage, the SOS response, may be partially induced. To investigate the nature of replication errors, we used mutation accumulation experiments and whole genome sequencing to determine mutation rates and mutational spectra across the entire chromosome of strains deficient in proofreading, mismatch repair, and the SOS response. We report that a proofreading-deficient strain has a mutation rate 4,000-fold greater than wild-type strains. While the SOS response may be induced in these cells, it does not contribute to the mutational load. Inactivating mismatch repair in a proofreading-deficient strain increases the mutation rate another 1.5-fold. DNA polymerase has a bias for converting G:C to A:T base pairs, but proofreading reduces the impact of these mutations, helping to maintain the genomic G:C content. These findings give an unprecedented view of how polymerase and error-correction pathways work together to maintain E. coli' s low mutation rate of 1 per thousand generations. Copyright © 2018, Genetics.

Immunization of C57BL/6 Mice with GRA2 Combined with MPL Conferred Partial Immune Protection against Toxoplasma gondii

PubMed

Babaie, Jalal; Amiri, Samira; Homayoun, Robab; Azimi, Ebrahim; Mohabati, Reyhaneh; Berizi, Mahboobe; Sadaie, M. Reza; Golkar, Majid

2018-01-01

We have previously reported that immunization with GRA2 antigen of Toxoplasma gondii induces protective immunity in CBA/J (H2k) and BALB/c mice (H2d). We aimed to examine whether immunization of a distinct strain of rodent with recombinant dense granule antigens (GRA2) combined with monophosphorryl lipid A (MPL) adjuvant elicits protective immune response against T. gondii. C57BL/6 (H2b haplotype) mice were immunized with GRA2, formulated in MPL adjuvant. Strong humoral response, predominantly of IgG1 subclass and cellular response, IFN-γ, was detected at three weeks post immunization. Mice immunized with GRA2 had significantly (p < 0.01) fewer brain cysts than those in the adjuvant group, upon challenge infection. Despite the production of a strong antibody response, IFN-γ production and brain cyst reduction were not significant when the immunized mice were infected four months after the immunization. We can conclude that GRA2 immunization partially protects against T. gondii infection in C57BL/6 mice, though the potency and longevity of this antigen as a standalone vaccine may vary in distinct genetic backgrounds. This observation further emphasizes the utility of GRA2 for incorporation into a multi-antigenic vaccine against T. gondii.

Our experience with facial nerve monitoring in vestibular schwannoma surgery under partial neuromuscular blockade.

PubMed

Vega-Céliz, Jorge; Amilibia-Cabeza, Emili; Prades-Martí, José; Miró-Castillo, Nuria; Pérez-Grau, Marta; Pintanel Rius, Teresa; Roca-Ribas Serdà, Francesc

2015-01-01

Facial nerve monitoring is fundamental in the preservation of the facial nerve in vestibular schwannoma surgery. Our objective was to analyse the usefulness of facial nerve monitoring under partial neuromuscular blockade. This was a retrospective analysis of 69 patients operated in a tertiary hospital. We monitored 100% of the cases. In 75% of the cases, we could measure an electromyographic response after tumour resection. In 17 cases, there was an absence of electromyographic response. Fifteen of them had an anatomic lesion with loss of continuity of the facial nerve and, in 2 cases, there was a lesion with preservation of the nerve. Preoperative facial palsy (29% 7%; P=.0349), large tumour size (88 vs. 38%; P=.0276), and a non-functional audition (88 vs. 51%; P=.0276) were significantly related with an absence of electromyographic response. Facial nerve monitoring under neuromuscular blockade is possible and safe in patients without previous facial palsy. If the patient had an electromyographic response after tumour excision, they developed better facial function in the postoperative period and after a year of follow up. Copyright © 2014 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Patología Cérvico-Facial. All rights reserved.

Sustained Liver Glucose Release in Response to Adrenaline Can Improve Hypoglycaemic Episodes in Rats under Food Restriction Subjected to Acute Exercise

PubMed Central

Babata, Lucas K. R.; Pedrosa, Maria M. D.; Garcia, Rosângela F.; Peicher, Márcia V.; de Godoi, Vilma Aparecida Ferreira

2014-01-01

Background. As the liver is important for blood glucose regulation, this study aimed at relating liver glucose release stimulated by glucagon and adrenaline to in vivo episodes of hypoglycaemia. Methods. The blood glucose profile during an episode of insulin-induced hypoglycaemia in exercised and nonexercised male Wistar control (GC) and food-restricted (GR, 50%) rats and liver glucose release stimulated by glucagon and adrenaline were investigated. Results. In the GR, the hypoglycaemic episodes showed severe decreases in blood glucose, persistent hypoglycaemia, and less complete glycaemic recovery. An exercise session prior to the episode of hypoglycaemia raised the basal blood glucose, reduced the magnitude of the hypoglycaemia, and improved the recovery of blood glucose. In fed animals of both groups, liver glucose release was activated by glucagon and adrenaline. In fasted GR rats, liver glycogenolysis activated by glucagon was impaired, despite a significant basal glycogenolysis, while an adrenaline-stimulated liver glucose release was recorded. Conclusions. The lack of liver response to glucagon in the GR rats could be partially responsible for the more severe episodes of hypoglycaemia observed in vivo in nonexercised animals. The preserved liver response to adrenaline can partially account for the less severe hypoglycaemia in the food-restricted animals after acute exercise. PMID:24719616

Early in situ changes in chondrocyte biomechanical responses due to a partial meniscectomy in the lateral compartment of the mature rabbit knee joint.

PubMed

Fick, J M; P Ronkainen, A; Madden, R; Sawatsky, A; Tiitu, V; Herzog, W; Korhonen, R K

2016-12-08

We determined the biomechanical responses of chondrocytes to indentation at specific locations within the superficial zone of cartilage (i.e. patellar, femoral groove, femoral condylar and tibial plateau sites) taken from female New Zealand white rabbits three days after a partial meniscectomy in the lateral compartment of a knee joint. Confocal laser scanning microscopy combined with a custom indentation system was utilized to image chondrocyte responses at sites taken from ten contralateral and experimental knee joints. Cell volume, height, width and depth changes, global, local axial and transverse strains and Young׳s moduli were determined. Histological assessment was performed and proteoglycan content from the superficial zone of each site was determined. Relative to contralateral group cells, patellar, femoral groove and lateral femoral condyle cells in the experimental group underwent greater volume decreases (p < 0.05), due to smaller lateral expansions (with greater decreases in cell height only for the lateral femoral condyle cells; p < 0.05) whereas medial femoral and medial tibial plateau cells underwent smaller volume decreases (p < 0.05), due to less deformation in cell height (p < 0.05). Proteoglycan content was reduced in the patellar (p > 0.05), femoral groove, medial femoral condyle and medial tibial plateau experimental sites (p < 0.05). The findings suggest: (i) cell biomechanical responses to cartilage loading in the rabbit knee joint can become altered as early as 3 days after a partial meniscectomy, (ii) are site-specific, and (iii) occur before alterations in tissue mechanics or changes detectable with histology. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of (-)-OSU6162 and ACR16 on motor activity in rats, indicating a unique mechanism of dopaminergic stabilization.

PubMed

Rung, Johan P; Rung, Emilia; Helgeson, Lisa; Johansson, Anette M; Svensson, Kjell; Carlsson, Arvid; Carlsson, Maria L

2008-06-01

Dopaminergic stabilizers can be defined as drugs that stimulate or inhibit dopaminergic signalling depending on the dopaminergic tone. (-)-OSU6162 and ACR16 appear to possess such a profile. They have been proposed to act as partial dopamine receptor agonists or as antagonists with preferential action on dopaminergic autoreceptors. Previous studies have shown either stimulation or inhibition of behaviour in response to (-)-OSU6162 and ACR16, which has been suggested to reflect their dual effects on dopaminergic signalling. The aims of the present work are to (1) examine the relation between behavioural response to these drugs and activity baseline, and (2) test the suggested mechanisms of action by means of close comparisons with the known partial D2-receptor agonists (-)-3-PPP and aripiprazole, and the D2 autoreceptor preferring antagonist amisulpride with respect to effects on behaviour. From the results of these experiments it can be concluded that: (1) The direction of the response to (-)-OSU6162 and ACR16 is dependent on activity baseline, which in turn, under physiological conditions, is determined primarily by test arena size of and degree of habituation to the environment. (2) The effects of (-)-OSU6162 and ACR16 cannot be explained on the basis of either partial dopamine receptor agonism or preferential dopamine autoreceptor antagonism. Nevertheless, the current data suggest at least two different D2-receptor-associated targets which mediate opposite effects on activity. This result fits in with a mechanism proposed from a recent in vitro study, according to which (-)-OSU6162 has a dual action on dopamine D2 receptors, (a) an allosteric effect causing an enhanced response to dopamine, and (b) the previously proposed orthosteric effect antagonizing the action of dopamine.

Long-term survival based on pathologic response to neoadjuvant therapy in esophageal cancer.

PubMed

Tiesi, Gregory; Park, Wungki; Gunder, Meredith; Rubio, Gustavo; Berger, Michael; Ardalan, Bach; Livingstone, Alan; Franceschi, Dido

2017-08-01

Neoadjuvant treatment is standard for locally advanced esophageal cancer. However, whether the addition of radiation to neoadjuvant regimen improves survival remains unclear. The aim of this study was to compare survival in locally advanced esophageal cancer treated with neoadjuvant chemotherapy versus chemoradiation. A prospectively maintained database of esophagectomies (1999-2012) was analyzed. We identified 297 patients with locally advanced esophageal cancer that underwent either neoadjuvant chemotherapy (n = 231) or chemoradiation (n = 66) followed by esophagectomy. Pretreatment and pathologic staging were compared to assess response. Overall survival was recorded. Most patients in the chemotherapy and chemoradiation groups had pretreatment stage III disease (66.7% versus 65.2%; P = 0.44). Median follow-up was 79.3 and 64.9 mo for chemotherapy and chemoradiation cohorts, respectively. Complete response rate was higher in chemoradiation than chemotherapy groups (30.3% versus 13.8%; P < 0.001). Overall survival was similar between complete responders in both groups (median not reached versus 121.1 mo; chemotherapy versus chemoradiation). However, partial responders in the chemotherapy cohort had improved median survival (147.2 mo) versus those in the chemoradiation cohort (83.7 mo, P < 0.03). Within the chemotherapy-only group, partial responders had improved survival compared with nonresponders (P = 0.041); however, there was no difference in survival between partial and complete responders (P = 0.36). In patients undergoing esophagectomy for locally advanced esophageal cancer, neoadjuvant chemotherapy was associated with an equivalent overall survival, when compared with neoadjuvant chemoradiotherapy. Adding neoadjuvant radiation may enhance complete response rates but does not appear to be associated with improved survival. Copyright © 2017 Elsevier Inc. All rights reserved.

Dynamics of the h-LH and h-FSH response after the stimulation test with Gn-RH-LH/FSH in man.

PubMed

Klepsch, I; Grigorescu, A; Eşanu, C

1976-01-01

A study was carried out on a number of 17 subjects concerning the dynamics of LH and FSH response after stimulation with Gn-RH-LH/FSH. The results show a stimulation 10 minutes after quick i.v. injection of synthetic RH, with a peak at 20-30 minutes and a persistence of the response of up to 180 min. The variation of the response is proportional with the dose, the response to stimulation being higher for LH than for FSH. The response in the normal adult male is of 82-858% for LH and of 157-250% for FSH. In aged subjects there is an increased response capacity showing that the hypophysis still reacts at an advanced age, with variations depending on the individual characteristics. In Sheehan's syndrome the basal values of FSH and LH are low, with a slight response after stimulation with RH, suggesting the possibility of a partial regeneration of the hypophysis if any intact areas were left after the initial necrotic process.

Expression and function of somatostatin receptor subtype 1 in human growth hormone secreting pituitary tumors deriving from patients partially responsive or resistant to long-term treatment with somatostatin analogs.

PubMed

Matrone, C; Pivonello, R; Colao, A; Cappabianca, P; Cavallo, L M; Del Basso De Caro, M L; Taylor, J E; Culler, M D; Lombardi, G; Di Renzo, G F; Annunziato, L

2004-03-01

The role of somatostatin (SS) receptor subtype 1 (SSTR(1)) in mediating the inhibitory effect of SS on growth hormone (GH) secreting pituitary tumors has been recently demonstrated. In the present study, we evaluated the effect of the selective SSTR(1) agonist BIM-23745 on in vitro GH secretion in GH-secreting pituitary tumor cells, deriving from patients resistant or partially responsive to octreotide long-acting release (octreotide-LAR) or lanreotide therapy in vivo and expressing SSTR(1) mRNA. In addition, the inhibiting effect of BIM-23745 on the GH secretion was compared with that of octreotide. Our data demonstrate that (1) SSTR(1) receptor was present in 56.25% (9/16) of the GH-secreting adenomas examined; (2) in all GH-secreting pituitary tumors that expressed SSTR(1), BIM-23745 significantly inhibited GH secretion in vitro, and (3) when SSTR(1) subtype was present in tumors from patients resistant to octreotide-LAR or lanreotide therapy, BIM-23745 was able to inhibit the in vitro GH secretion. In conclusion, the results of the current study suggest that SS analogs selective for the SSTR(1) may represent a further useful approach for the treatment of acromegaly in patients resistant or partially responsive to octreotide-LAR or lanreotide treatment in vivo. Copyright 2004 S. Karger AG, Basel

Vibration analysis of partially cracked plate submerged in fluid

NASA Astrophysics Data System (ADS)

Soni, Shashank; Jain, N. K.; Joshi, P. V.

2018-01-01

The present work proposes an analytical model for vibration analysis of partially cracked rectangular plates coupled with fluid medium. The governing equation of motion for the isotropic plate based on the classical plate theory is modified to accommodate a part through continuous line crack according to simplified line spring model. The influence of surrounding fluid medium is incorporated in the governing equation in the form of inertia effects based on velocity potential function and Bernoulli's equations. Both partially and totally submerged plate configurations are considered. The governing equation also considers the in-plane stretching due to lateral deflection in the form of in-plane forces which introduces geometric non-linearity into the system. The fundamental frequencies are evaluated by expressing the lateral deflection in terms of modal functions. The assessment of the present results is carried out for intact submerged plate as to the best of the author's knowledge the literature lacks in analytical results for submerged cracked plates. New results for fundamental frequencies are presented as affected by crack length, fluid level, fluid density and immersed depth of plate. By employing the method of multiple scales, the frequency response and peak amplitude of the cracked structure is analyzed. The non-linear frequency response curves show the phenomenon of bending hardening or softening and the effect of fluid dynamic pressure on the response of the cracked plate.

Effects of RO 15-1788 on a running response rewarded on continuous or partial reinforcement schedules.

PubMed

Hawkins, M; Sinden, J; Martin, I; Gray, J A

1988-01-01

Two experiments were run in which rats were rewarded with food for running in a straight alley at one trial a day, followed by extinction of the running response. During acquisition of the response, reward was delivered either on a continuous reinforcement (CRF) or on a quasirandom 50% partial reinforcement (PRF) schedule. The groups given PRF were more resistant to extinction than those given CRF, the well-known partial reinforcement extinction effect. In Experiment 1 different groups of rats were injected during acquisition only with 1, 5 or 10 mg/kg of the benzodiazepine antagonist, RO 15-1788, or with placebo. In Experiment 2, 5 mg/kg RO 15-1788 or placebo were administered in a full cross-over design during acquisition, extinction or both. At the end of Experiment 2 only [3H]-flunitrazepam binding was measured in either the presence or absence of added gamma-aminobutyrate (GABA) in homogenates of hippocampi dissected from the animals that had received behavioural training. The drug affected running speeds during both acquisition and extinction in different ways depending upon the schedule of reinforcement (CRF or PRF) and also gave rise to enhanced GABA stimulation of [3H]-flunitrazepam binding. The results are discussed in relation to the hypothesis that the neurochemical pathways by which reinforcement schedules modify behaviour include a step influenced by benzodiazepine receptors.

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

Epidermal growth factor (EGF) stimulated Ca/sup 2 +/ mobilization in hepatocytes is abolished by phorbol esters, pertussis toxin and partial hepatectomy

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

Johnson, R.M.; Garrison, J.C.

1986-05-01

EGF has been demonstrated to increase free intracellular Ca/sup 2 +/ levels in isolated hepatocytes putatively by generation of the second messenger inositol trisphosphate (IP/sub 3/). Pretreatment of cells with phorbol 12-myristate 13-acetate (PMA) inhibited the EGF (66 nM) stimulated Ca/sup 2 +/ response as measured by quin2. Inhibition by PMA was maximal within 3 min and was concentration dependent (IC/sub 50/ = 13.5 nM). Four other active phorbol ester analogues blocked the Ca/sup 2 +/ response while inactive analogues did not. EGF was unable to increase intracellular Ca/sup 2 +/ levels in hepatocytes isolated from rats treated with pertussismore » toxin for 72 hrs. Neither PMA nor toxin pretreatment was able to inhibit the Ca/sup 2 +/ response to angiotensin II (Ang II). In hepatocytes isolated 24 hrs after partial hepatectomy, the Ca/sup 2 +/ response to EGF (as measured by phosphorylase activity, EC/sub 50/ = 5 nM) was completely abolished and remained attenuated for 7 days post-hepatectomy. The Ca/sup 2 +/ response to Ang II in this model system was also blunted but required 3 days for development of the full effect and within 7 days full activity is nearly restored. The results suggest that fundamental differences exist in the transduction mechanisms used by these two Ca/sup 2 +/-linked hormones to mobilize intracellular Ca/sup 2 +/ (and putatively increase IP/sub 3/ formation).« less

Active Female Maximal and Anaerobic Threshold Cardiorespiratory Responses to Six Different Water Aerobics Exercises.

PubMed

Antunes, Amanda H; Alberton, Cristine L; Finatto, Paula; Pinto, Stephanie S; Cadore, Eduardo L; Zaffari, Paula; Kruel, Luiz F M

2015-01-01

Maximal tests conducted on land are not suitable for the prescription of aquatic exercises, which makes it difficult to optimize the intensity of water aerobics classes. The aim of the present study was to evaluate the maximal and anaerobic threshold cardiorespiratory responses to 6 water aerobics exercises. Volunteers performed 3 of the exercises in the sagittal plane and 3 in the frontal plane. Twelve active female volunteers (aged 24 ± 2 years) performed 6 maximal progressive test sessions. Throughout the exercise tests, we measured heart rate (HR) and oxygen consumption (VO2). We randomized all sessions with a minimum interval of 48 hr between each session. For statistical analysis, we used repeated-measures 1-way analysis of variance. Regarding the maximal responses, for the peak VO2, abductor hop and jumping jacks (JJ) showed significantly lower values than frontal kick and cross-country skiing (CCS; p < .001; partial η(2) = .509), while for the peak HR, JJ showed statistically significantly lower responses compared with stationary running and CCS (p < .001; partial η(2) = .401). At anaerobic threshold intensity expressed as the percentage of the maximum values, no statistically significant differences were found among exercises. Cardiorespiratory responses are directly associated with the muscle mass involved in the exercise. Thus, it is worth emphasizing the importance of performing a maximal test that is specific to the analyzed exercise so the prescription of the intensity can be safer and valid.

Lack of effective systemic therapy for recurrent clear cell carcinoma of the ovary.

PubMed

Crotzer, David R; Sun, Charlotte C; Coleman, Robert L; Wolf, Judith K; Levenback, Charles F; Gershenson, David M

2007-05-01

Clear cell carcinoma of the ovary is an aggressive tumor characterized by relative chemoresistance and a poor prognosis. The purpose of this study was to review our experience with recurrent clear cell carcinoma of the ovary to evaluate its responsiveness to systemic cytotoxic and hormonal agents. All patients diagnosed with clear cell carcinoma of the ovary seen at our institution between 1990 and 2002 were identified and their medical records reviewed. Eligibility criteria were: 1) primary diagnosis of clear cell carcinoma of the ovary, 2) measurable recurrent disease, 3) treatment of recurrent disease with 1 or more systemic regimens, and 4) adequate clinical information. End points were clinical response, progression-free survival, and overall survival. Fifty-one patients treated for recurrent clear cell carcinoma were identified. The patients received a total of 105 regimens (344 cycles of therapy). Among patients with platinum-sensitive disease (n=22 regimens), 2 patients (9%) had partial responses to retreatment with carboplatin plus paclitaxel, and 4 (18%) had stable disease. Among patients with platinum-resistant disease (n=83 regimens), only 1 patient (1%) had a partial response - to gemcitabine - and 1 patient had stable disease in response to 2 different regimens-paclitaxel and gemcitabine. The median progression-free survival was 8 months, and the median overall survival was 18 months. Our findings suggest that recurrent clear cell carcinoma of the ovary is particularly chemoresistant. A continued search for more active, targeted agents is warranted.

Treatment of erosive oral lichen planus with local ultraviolet B phototherapy.

PubMed

Kassem, Riad; Yarom, Noam; Scope, Alon; Babaev, Meir; Trau, Henri; Pavlotzky, Felix

2012-05-01

Oral lichen planus (OLP) is a chronic inflammatory disease that can significantly affect the patient's quality of life. We sought to demonstrate the therapeutic efficacy of local ultraviolet (UV) B phototherapy in OLP. Patients with biopsy-confirmed erosive OLP recalcitrant to previous medical therapy were treated with the TheraLight UV 120-2 system (TheraLight Inc, Carlsbad, CA). Lesions were accessed directly using a flexible fiber guide. Local phototherapy was delivered 3 times a week, with gradual increase in UVB dose every other session. Affected oral mucosa was defined as the area showing erosions or symptomatic reticular lesions. Complete response was defined as reduction of at least 80% in the affected mucosal area, and partial response was defined as a reduction of 50% to 80% in the affected mucosal area. The primary end point was efficacy after 8 weeks of treatment. Fourteen patients were included in the study. Nine achieved complete response and 5 partial response after 8 weeks. Ten patients were continued on maintenance therapy and were able to maintain their response for another 29 weeks. None of the patients showed any serious side effects from local UVB therapy. The study was performed in a small series of patients at a single medical center. Further studies with larger patient samples are required to validate our findings. Local UVB phototherapy may be a promising treatment modality for erosive OLP. Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

40 CFR 281.24 - Memorandum of agreement.

Code of Federal Regulations, 2010 CFR

2010-07-01

... state roles and responsibilities in areas including, but not limited to: Implementation of partial state programs; enforcement; compliance monitoring; EPA oversight; and sharing and reporting of information. At...

Changes in Fish Assemblages following the Establishment of a Network of No-Take Marine Reserves and Partially-Protected Areas

PubMed Central

Kelaher, Brendan P.; Coleman, Melinda A.; Broad, Allison; Rees, Matthew J.; Jordan, Alan; Davis, Andrew R.

2014-01-01

Networks of no-take marine reserves and partially-protected areas (with limited fishing) are being increasingly promoted as a means of conserving biodiversity. We examined changes in fish assemblages across a network of marine reserves and two different types of partially-protected areas within a marine park over the first 5 years of its establishment. We used Baited Remote Underwater Video (BRUV) to quantify fish communities on rocky reefs at 20–40 m depth between 2008–2011. Each year, we sampled 12 sites in 6 no-take marine reserves and 12 sites in two types of partially-protected areas with contrasting levels of protection (n = 4 BRUV stations per site). Fish abundances were 38% greater across the network of marine reserves compared to the partially-protected areas, although not all individual reserves performed equally. Compliance actions were positively associated with marine reserve responses, while reserve size had no apparent relationship with reserve performance after 5 years. The richness and abundance of fishes did not consistently differ between the two types of partially-protected areas. There was, therefore, no evidence that the more regulated partially-protected areas had additional conservation benefits for reef fish assemblages. Overall, our results demonstrate conservation benefits to fish assemblages from a newly established network of temperate marine reserves. They also show that ecological monitoring can contribute to adaptive management of newly established marine reserve networks, but the extent of this contribution is limited by the rate of change in marine communities in response to protection. PMID:24454934

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.

Linear and nonlinear analysis of fluid slosh dampers

NASA Astrophysics Data System (ADS)

Sayar, B. A.; Baumgarten, J. R.

1982-11-01

A vibrating structure and a container partially filled with fluid are considered coupled in a free vibration mode. To simplify the mathematical analysis, a pendulum model to duplicate the fluid motion and a mass-spring dashpot representing the vibrating structure are used. The equations of motion are derived by Lagrange's energy approach and expressed in parametric form. For a wide range of parametric values the logarithmic decrements of the main system are calculated from theoretical and experimental response curves in the linear analysis. However, for the nonlinear analysis the theoretical and experimental response curves of the main system are compared. Theoretical predictions are justified by experimental observations with excellent agreement. It is concluded finally that for a proper selection of design parameters, containers partially filled with viscous fluids serve as good vibration dampers.

Optimization of composite coagulant made from polyferric chloride and tapioca starch in landfill leachate treatment

NASA Astrophysics Data System (ADS)

Shaylinda, M. Z. N.; Hamidi, A. A.; Mohd, N. A.; Ariffin, A.; Irvan, D.; Hazreek, Z. A. M.; Nizam, Z. M.

2018-04-01

In this research, the performance of polyferric chloride and tapioca flour as composite coagulants for partially stabilized leachate was investigated. Response surface methodology (RSM) was used to optimize the coagulation and flocculation process of partially stabilized leachate. Central composite design a standard design tool in RSM was applied to evaluate the interactions and effects of dose and pH. Dose 0.2 g/L Fe and pH 4.71 were the optimum value suggested by RSM. Experimental test based on the optimum condition, resulted in 95.9%, 94.6% and 50.4% of SS, color and COD removals, respectively. The percentage difference recorded between experimental and model responses was <5%. Therefore, it can be concluded that RSM was an appropriate optimization tool for coagulation and flocculation process.

Physiological responses to incremental exercise in the heat following internal and external precooling.

PubMed

James, C A; Richardson, A J; Watt, P W; Gibson, O R; Maxwell, N S

2015-06-01

Twelve males completed three incremental, discontinuous treadmill tests in the heat [31.9(1.0) °C, 61.9(8.9)%] to determine speed at two fixed blood lactate concentrations (2 and 3.5 mmol/L), running economy (RE), and maximum oxygen uptake ( V ˙ O 2 m a x ). Trials involved 20 min of either internal cooling (ICE, 7.5 g/kg ice slurry ingestion) or mixed-methods external cooling (EXT, cold towels, forearm immersion, ice vest, and cooling shorts), alongside no intervention (CON). Following precooling, participants ran 0.3 km/h faster at 2 mmol/L and 0.2 km/h faster at 3.5 mmol/L (P = 0.04, partial η(2)  = 0.27). Statistical differences were observed vs CON for ICE (P = 0.03, d = 0.15), but not EXT (P = 0.12, d = 0.15). There was no effect of cooling on RE (P = 0.81, partial η(2)  = 0.02), nor on V ˙ O 2 m a x (P = 0.69, partial η(2)  = 0.04). An effect for cooling on physiological strain index was observed (P < 0.01, partial η(2)  = 0.41), with differences vs CON for EXT (P = 0.02, d = 0.36), but not ICE (P = 0.06, d = 0.36). Precooling reduced thermal sensation (P < 0.01, partial η(2)  = 0.66) in both cooling groups (P < 0.01). Results indicate ICE and EXT provide similar physiological responses for exercise up to 30 min duration in the heat. Differing thermoregulatory responses are suggestive of specific event characteristics determining the choice of cooling. Precooling appears to reduce blood lactate accumulation and reduce thermoregulatory and perceptual strain during incremental exercise. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Radioembolization for Neuroendocrine Liver Metastases: Safety, Imaging, and Long-Term Outcomes

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

Memon, Khairuddin; Lewandowski, Robert J.; Mulcahy, Mary F.

2012-07-01

Purpose: To present long-term outcomes on the safety and efficacy of Yttrium-90 radioembolization in the treatment of unresectable hepatic neuroendocrine metastases refractory to standard-of-care therapy. Methods and Materials: This study was approved by our institutional review board and was compliant with the Health Insurance Portability and Accountability Act. Forty patients with hepatic neuroendocrine metastases were treated with {sup 90}Y radioembolization at a single center. Toxicity was assessed using National Cancer Institute Common Terminology Criteria v3.0. Response to therapy was assessed by World Health Organization (WHO) guidelines for size and European Association for the Study of the Liver disease (EASL) guidelinesmore » for necrosis. Time to response and overall survival were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed. Results: The median dose was 113 Gy (29-299 Gy). Clinical toxicities included fatigue (63%), nausea/vomiting (40%), abdominal pain (18%), fever (8%), diarrhea and weight loss (5%); Grade 3 and 4 bilirubin toxicities were experienced by 2 patients and 1 patient, respectively. Different responses were noted by WHO (complete response, 1.2%; partial response, 62.7%) and EASL (complete response, 20.5%; partial response, 43.4%). Median time to response was 4 and 4.9 months by lesion and patient, respectively. The 1-, 2-, and 3-year overall survival rates were 72.5%, 62.5%, and 45%, respectively. Eastern Cooperative Oncology Group (ECOG) performance score 0 (p < 0.0001), tumor burden {<=}25% (p = 0.0019), albumin {>=}3.5 g/dL (p = 0.017), and bilirubin {<=}1.2 mg/dL (p = 0.002) prognosticated survival on univariate analysis; only ECOG performance score 0 and bilirubin {<=}1.2 mg/dL prognosticated better survival outcome on multivariate analysis (p = 0.0001 and p = 0.02). Conclusion: Yttrium-90 therapy for hepatic neuroendocrine metastases leads to satisfactory tumor response and patient survival with low toxicity, in line with published national guidelines recommending radioembolization as a potential option for unresectable hepatic neuroendocrine metastases.« less

Response surface modeling of alfentanil-sevoflurane interaction on cardiorespiratory control and bispectral index.

PubMed

Dahan, A; Nieuwenhuijs, D; Olofsen, E; Sarton, E; Romberg, R; Teppema, L

2001-06-01

Respiratory depression is a serious side effect of anesthetics and opioids. The authors examined the influence of the combined administration of sevoflurane and alfentanil on ventilatory control, heart rate (HR), and Bispectral Index (BIS) in healthy volunteers. Step decreases in end-tidal partial pressure of oxygen from normoxia into hypoxia (approximately 50 mmHg) at constant end-tidal partial pressure of carbon dioxide (approximately 48 mmHg) were performed in nine male volunteers at various concentrations of alfentanil and sevoflurane, ranging from 0 to 50 ng/ml for alfentanil and from 0 to 0.4 end-tidal concentration (ET%) for sevoflurane, and with various combinations of alfentanil and sevoflurane. The alfentanil-sevoflurane interactions on normoxic resting (hypercapnic) ventilation (Vi), HR, hypoxic Vi, and HR responses and BIS were assessed by construction of response surfaces that related alfentanil and sevoflurane to effect using a population analysis. Concentration-effect relations were linear for alfentanil and sevoflurane. Synergistic interactions were observed for resting Vi and resting HR. Depression of Vi by 25% occurred at 38 +/- 11 ng/ml alfentanil (population mean +/- SE) and at 0.7 +/- 0.4 ET% sevoflurane. One possibility for 25% reduction when alfentanil and sevoflurane are combined is 13.4 ng/ml alfentanil plus 0.12 ET% sevoflurane. Additive interactions were observed for hypoxic Vi and HR responses and BIS. Depression of the hypoxic Vi response by 25% occurred at 16 +/- 1 ng/ml alfentanil and 0.14 +/- 0.05 ET% sevoflurane. The effect of sevoflurane on the BIS (25% reduction of BIS occurred at 0.45 +/- 0.08 ET%) was independent of the alfentanil concentration. Response surface modeling was used successfully to analyze the effect of interactions between two drugs on respiration. The combination of alfentanil and sevoflurane causes more depression of Vi and HR than does the summed effect of each drug administered separately. The effects of combining alfentanil and sevoflurane on hypoxic Vi and HR responses and BIS could be predicted from the separate dose-response curves. Over the dose range tested, the hypoxic response is more sensitive to the effects of anesthetics and opioids relative to resting ventilation.

[Measurement of 75Se-SeHCAT abdominal retention in the initial diagnosis of Bile Acid Absorption (BAM)].

PubMed

Notta, P C; Ramal, D; Maisterra, S; Rodríguez Gasen, A; Maymó, S; Sabaté, A; Girbau, A; Guardiola, J; Martín-Comín, J

2011-01-01

To evaluate the usefulness of the (75)SeHCAT abdominal retention (AR) measurement in the early diagnosis of diarrhea syndrome (DS). Thirty-seven patients with diarrhea syndrome within the first month of evolution were prospectively evaluated. The (75)Se-SeHCAT abdominal retention was measured 4 and 7 days post-administration of 0.01 mCi of (75)SeHCAT. The test was performed prior to treatment and at 3 months when the baseline study was positive. The test was considered positive if the RA was <25% at 4(th) and <10% on the 7th day. The patients were visited at 3 months. Depending on the response, 3 groups were established: a) complete response: normalization of stool frequency, b) partial response, decrease of frequency or c) no response. Group A: The AR of (75)Se-SEHCAT was normal in 21 patients. Six were diagnosed of colonic diverticulosis, 8 of irritable bowel syndrome, 1 of lymphocytic colitis, 1 of post-gastroenteritis syndrome, 1 of celiac disease and 1 of stenosis of the cardia. Four are still under study. Group B: The AR of (75)Se-SEHCAT decreased in 16 patients. All showed abnormal AR at day 7 and all but 1 at day 4. Following administration of cholestyramine resin, 8 (50%) presented partial response and 8 (50%) complete response. At 3 months, AR had increased at day 4 and 9 at day 7. The measurement of (75)SEHCAT abdominal retention allows the early diagnosis of bile acid malabsorption in 43% of the patients with DS. Measurement at 7 days seems more accurate than that at 4 days. Copyright © 2010 Elsevier España, S.L. y SEMNIM. All rights reserved.

Chemoembolization for Hepatocellular Carcinoma Supplied by a Lumbar Artery

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

Kim, Han Myun, E-mail: seoul49@naver.com; Kim, Hyo-Cheol, E-mail: angiointervention@gmail.com; Woo, Sungmin, E-mail: j-crew7@hotmail.com

PurposeTo describe the radiologic findings and imaging response of hepatocellular carcinoma (HCC) supplied by the lumbar artery.MethodsBetween April 2004 and December 2012, we encountered HCC supplied by a lumbar artery in 21 patients. Two investigators retrospectively reviewed clinical and radiological findings of HCC supplied by the lumbar artery using computed tomography (CT) scans and digital subtraction angiograms.ResultsPatients had received 1–27 sessions of previous chemoembolization procedures (mean 7.7 sessions, median 4 sessions). Mean tumor size was 5.3 cm. The locations of HCC supplied by lumbar artery were the bare area (n = 14, 67 %) and segment VI (n = 7, 33 %). Tumor-feeding arteries arose from themore » main lumbar artery (n = 7), proximal anterior division (n = 4), and distal anterior division (n = 14). In 20 patients, selective chemoembolization through the tumor-feeding arteries of the lumbar artery was achieved. In 1 patient, nonselective embolization at the main lumbar artery was performed. There was no complication such as skin necrosis or paralysis. On the first follow-up enhanced CT scan, target tumors fed by the lumbar artery showed complete response (n = 6), partial response (n = 4), stable disease (n = 3), and progressive disease (n = 8), but overall tumor response was partial response (n = 1) and progressive disease (n = 20).ConclusionWhen HCC is located in the inferior tip or bare area of the liver, a lumbar artery may supply the tumor. Although selective chemoembolization via the tumor-feeding vessel of the lumbar artery can be achieved in most cases, overall tumor response is commonly unfavorable.« less

Granulocytic myeloid-derived suppressor cells from human cord blood modulate T-helper cell response towards an anti-inflammatory phenotype.

PubMed

Köstlin, Natascha; Vogelmann, Margit; Spring, Bärbel; Schwarz, Julian; Feucht, Judith; Härtel, Christoph; Orlikowsky, Thorsten W; Poets, Christian F; Gille, Christian

2017-09-01

Infections are a leading cause of perinatal morbidity and mortality. The outstandingly high susceptibility to infections early in life is mainly attributable to the compromised state of the neonatal immune system. One important difference to the adult immune system is a bias towards T helper type 2 (Th2) responses in newborns. However, mechanisms regulating neonatal T-cell responses are incompletely understood. Granulocytic myeloid-derived suppressor cells (GR-MDSC) are myeloid cells with a granulocytic phenotype that suppress various functions of other immune cells and accumulate under physiological conditions during pregnancy in maternal and fetal blood. Although it has been hypothesized that GR-MDSC accumulation during fetal life could be important for the maintenance of maternal-fetal tolerance, the influence of GR-MDSC on the immunological phenotype of neonates is still unclear. Here, we investigated the impact of GR-MDSC isolated from cord blood (CB-MDSC) on the polarization of Th cells. We demonstrate that CB-MDSC inhibit Th1 responses and induced Th2 responses and regulatory T (Treg) cells. Th1 inhibition was cell-contact dependent and occurred independent of other cell types, while Th2 induction was mediated independently of cell contact through expression of ArgI and reactive oxygen species by CB-MDSC and partially needed the presence of monocytes. Treg cell induction by CB-MDSC also occurred cell-contact independently but was partially mediated through inducible nitric oxide synthase. These results point towards a role of MDSC in regulating neonatal immune responses. Targeting MDSC function in neonates could be a therapeutic opportunity to improve neonatal host defence. © 2017 John Wiley & Sons Ltd.

Promoter CpG island hypermethylation of the DNA repair enzyme MGMT predicts clinical response to dacarbazine in a phase II study for metastatic colorectal cancer.

PubMed

Amatu, Alessio; Sartore-Bianchi, Andrea; Moutinho, Catia; Belotti, Alessandro; Bencardino, Katia; Chirico, Giuseppe; Cassingena, Andrea; Rusconi, Francesca; Esposito, Anna; Nichelatti, Michele; Esteller, Manel; Siena, Salvatore

2013-04-15

O(6)-methylguanine-DNA-methyltransferase (MGMT) is a DNA repair protein removing mutagenic and cytotoxic adducts from O(6)-guanine in DNA. Approximately 40% of colorectal cancers (CRC) display MGMT deficiency due to the promoter hypermethylation leading to silencing of the gene. Alkylating agents, such as dacarbazine, exert their antitumor activity by DNA methylation at the O(6)-guanine site, inducing base pair mismatch; therefore, activity of dacarbazine could be enhanced in CRCs lacking MGMT. We conducted a phase II study with dacarbazine in CRCs who had failed standard therapies (oxaliplatin, irinotecan, fluoropyrimidines, and cetuximab or panitumumab if KRAS wild-type). All patients had tumor tissue assessed for MGMT as promoter hypermethylation in double-blind for treatment outcome. Patients received dacarbazine 250 mg/m(2) intravenously every day for four consecutive days, every 21 days, until progressive disease or intolerable toxicity. We used a Simon two-stage design to determine whether the overall response rate would be 10% or more. Secondary endpoints included association of response, progression-free survival, and disease control rate with MGMT status. Sixty-eight patients were enrolled from May 2011 to March 2012. Patients received a median of three cycles of dacarbazine (range 1-12). Grades 3 and 4 toxicities included: fatigue (41%), nausea/vomiting (29%), constipation (25%), platelet count decrease (19%), and anemia (18%). Overall, two patients (3%) achieved partial response and eight patients (12%) had stable disease. Disease control rate (partial response + stable disease) was significantly associated with MGMT promoter hypermethylation in the corresponding tumors. Objective clinical responses to dacarbazine in patients with metastatic CRC are confined to those tumors harboring epigenetic inactivation of the DNA repair enzyme MGMT.

Semiquantitative visual approach to scoring lung cancer treatment response using computed tomography: a pilot study.

PubMed

Gottlieb, Ronald H; Kumar, Prasanna; Loud, Peter; Klippenstein, Donald; Raczyk, Cheryl; Tan, Wei; Lu, Jenny; Ramnath, Nithya

2009-01-01

Our objective was to compare a newly developed semiquantitative visual scoring (SVS) method with the current standard, the Response Evaluation Criteria in Solid Tumors (RECIST) method, in the categorization of treatment response and reader agreement for patients with metastatic lung cancer followed by computed tomography. The 18 subjects (5 women and 13 men; mean age, 62.8 years) were from an institutional review board-approved phase 2 study that evaluated a second-line chemotherapy regimen for metastatic (stages III and IV) non-small cell lung cancer. Four radiologists, blinded to the patient outcome and each other's reads, evaluated the change in the patients' tumor burden from the baseline to the first restaging computed tomographic scan using either the RECIST or the SVS method. We compared the numbers of patients placed into the partial response, the stable disease (SD), and the progressive disease (PD) categories (Fisher exact test) and observer agreement (kappa statistic). Requiring the concordance of 3 of the 4 readers resulted in the RECIST placing 17 (100%) of 17 patients in the SD category compared with the SVS placing 9 (60%) of 15 patients in the partial response, 5 (33%) of the 15 patients in the SD, and 1 (6.7%) of the 15 patients in the PD categories (P < 0.0001). Interobserver agreement was higher among the readers using the SVS method (kappa, 0.54; P < 0.0001) compared with that of the readers using the RECIST method (kappa, -0.01; P = 0.5378). Using the SVS method, the readers more finely discriminated between the patient response categories with superior agreement compared with the RECIST method, which could potentially result in large differences in early treatment decisions for advanced lung cancer.

Lymphatic Malformation Architecture: Implications for Treatment With OK-432.

PubMed

Malic, Claudia C; Guilfoyle, Regan; Courtemanche, Rebecca J M; Arneja, Jugpal S; Heran, Manraj K S; Courtemanche, Douglas J

2017-10-01

Herein, the authors aim to describe their findings of novel architectural types of lymphatic malformations (LM) and explain the relationship between these architectures and OK-432 treatment outcomes. A retrospective review was conducted of all patients diagnosed with a LM treated with OK-432 at the Vascular Anomalies Clinic at BC Children's Hospital from December 2002 to January 2012. Twenty-seven patients were included in the study. Sixty percent of lesions were present by 2 years of age with the majority located in the head and neck (59%). The average number of sclerotherapy procedures was 1.4 per patient. Treatment under fluoroscopic guidance revealed 3 new LM architectures: open-cell microcystic, closed-cell microcystic, and lymphatic channel. Response to treatment was complete or good for 14/19 macrocystic and for 1/2 mixed lesions. Open-cell microcystic LMs gave a complete or good response for 3/3, which was attributed to OK-432 freely communicating between cysts. Closed-cell microcystic LM had localized cysts that did not allow OK-432 to freely communicate and were associated with partial responses, 2/2. The lymphatic channel had a partial response. There were 2 minor complications and 1 instance of recurrence. The identification of 3 new LM architectures expands the current accepted classification to include: open-cell microcystic, closed-cell microcystic, and lymphatic channels. The majority of complete responses to OK-432 were found with macrocystic lesions. Open-cell microcystic lesions respond better to OK-432 than closed-cell microcystic lesions, and lymphatic channels may respond to OK-432. These key architecture-response relationships have direct clinical implications for treatment with OK-432 sclerotherapy.

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.

Changing trends in prognostic factors for patients with multiple myeloma after autologous stem cell transplantation during the immunomodulator drug/proteasome inhibitor era

PubMed Central

Takamatsu, Hiroyuki; Honda, Sumihisa; Miyamoto, Toshihiro; Yokoyama, Kenji; Hagiwara, Shotaro; Ito, Toshiro; Tomita, Naoto; Iida, Shinsuke; Iwasaki, Toshihiro; Sakamaki, Hisashi; Suzuki, Ritsuro; Sunami, Kazutaka

2015-01-01

We evaluated the clinical significance of prognostic factors including the International Staging System (ISS) and modified European Group for Blood and Marrow Transplantation response criteria in 1650 Japanese patients with multiple myeloma (MM) who underwent upfront single autologous stem cell transplantation (ASCT). We categorized patients into two treatment cohorts: pre-novel agent era (1995–2006) and novel agent era (2008–2011). The combined percentage of pre-ASCT complete response and very good partial response cases (463 of 988, 47%) significantly increased during the novel agent era compared with the pre-novel agent era (164 of 527, 31%; P < 0.0001). The 2-year overall survival (OS) rate of 87% during the novel agent era was a significant improvement relative to that of 82% during the pre-novel agent era (P = 0.019). Although significant differences in OS were found among ISS stages during the pre-novel agent era, no significant difference was observed between ISS I and II (P = 0.107) during the novel agent era. The factors independently associated with a superior OS were female gender (P = 0.002), a good performance status (P = 0.024), lower ISS (P < 0.001), pre-ASCT response at least partial response (P < 0.001) and ASCT during the novel agent era (P = 0.017). These results indicate that the response rate and OS were significantly improved, and the ISS could not clearly stratify the prognoses of Japanese patients with MM who underwent upfront single ASCT during the novel agent era. PMID:25530023

Vancomycin Ophthalmic Ointment 1% for methicillin-resistant Staphylococcus aureus or methicillin-resistant Staphylococcus epidermidis infections: a case series

PubMed Central

Sotozono, Chie; Fukuda, Masahiko; Ohishi, Masao; Yano, Keiko; Origasa, Hideki; Saiki, Yoshinori; Shimomura, Yoshikazu; Kinoshita, Shigeru

2013-01-01

Objectives To investigate the efficacy and safety of Vancomycin Ophthalmic Ointment 1% (Toa Pharmaceutical Co., Ltd, Toyama, Japan) in patients with external ocular infections caused by methicillin-resistant Staphylococcus aureus (MRSA) or methicillin-resistant Staphylococcus epidermidis (MRSE). Design A case series. Setting This study was a multicentre, open-label, uncontrolled study in Japan approved as orphan drug status. Participants Patients with MRSA or MRSE external ocular infections unresponsive to the treatment of fluoroquinolone eye drops. Interventions Vancomycin Ophthalmic Ointment 1% was administered four times daily. Primary and secondary outcome measures The subjective and objective clinical scores and bacterial cultures were collected at days 0 (baseline), 3, 7 and 14. The primary outcome was clinical response evaluation (efficacy rate) determined as complete response, partial response, no response and worsening. Secondary outcome was the eradication of the bacteria. Safety was assessed by adverse events including cases in which neither MRSA nor MRSE was detected. Results Twenty-five cases with MRSA (20) or MRSE (5) infections were enrolled. Of these 25 cases, 4 discontinued the treatment due to the negative results for bacterial culture during screening or at baseline. Of the 21 cases with conjunctivitis (14), blepharitis (3), meibomitis (1), dacryocystitis (2) or keratitis (1), 14 (66.7%) cases were evaluated as being excellently (complete response, 2 cases) or well (partial response, 12 cases) treated. The eradication rates were 68.4% in MRSA (13 of 19 cases) and 100% in MRSE (2 of 2 cases). Ten adverse events occurred in 7 (28.0%) of 25 cases at the local administration site. Conclusions Vancomycin Ophthalmic Ointment 1% was considered to be useful for the treatment of intractable ocular MRSA/MRSE infections. PMID:23364319

Phase II trial of irinotecan in patients with metastatic colorectal carcinoma.

PubMed

Pitot, H C; Wender, D B; O'Connell, M J; Schroeder, G; Goldberg, R M; Rubin, J; Mailliard, J A; Knost, J A; Ghosh, C; Kirschling, R J; Levitt, R; Windschitl, H E

1997-08-01

To evaluate the objective tumor response rate and toxicities of patients with metastatic colorectal carcinoma treated with irinotecan hydrochloride (CPT-11). A total of 121 patients with advanced colorectal carcinoma--90 with prior fluorouracil (5-FU) exposure and 31 chemotherapeutically naive patients--were enrolled between May 1993 and June 1994. Patients were treated with CPT-11 at 125 mg/m2 intravenously weekly for 4 weeks followed by a 2-week rest. Among 90 patients with prior 5-FU chemotherapy, 12 partial responses were observed (response rate, 13.3%; 95% confidence interval [CI], 7.1% to 22.1%). Among 31 chemotherapy-naive patients, eight had partial responses (response rate, 25.8%; 95% CI, 11.9% to 44.6%). The median response duration as measured from time of initial treatment for the two groups was 7.7 months and 7.6 months, respectively. The major adverse reactions were gastrointestinal and hematologic. The incidence of grade 3 or 4 diarrhea was 36.4%, while the overall incidence of grade 3 or 4 leukopenia was 21.5% of patients. Only four of 121 patients (3.3%) developed neutropenic fever (grade 4 neutropenia with > or = grade 2 fever). The incidence of grade 4 leukopenia was higher in patients with prior pelvic radiotherapy (chi2 test P = .04), while the incidence of grade 3 or 4 diarrhea demonstrated no association with previous pelvic irradiation. According to the study design, CPT-11 showed promising activity in chemotherapy-naive patients with advanced colorectal carcinoma and modest activity in patients with prior 5-FU exposure. The toxicity with this schedule appears manageable with appropriate dose modification for individual patient tolerance and an intensive loperamide regimen for the management of diarrhea. Care should be taken when treating patients with prior pelvic radiotherapy because of the increased risk of neutropenia.

Approval summary: azacitidine for treatment of myelodysplastic syndrome subtypes.

PubMed

Kaminskas, Edvardas; Farrell, Ann; Abraham, Sophia; Baird, Amy; Hsieh, Li-Shan; Lee, Shwu-Luan; Leighton, John K; Patel, Hasmukh; Rahman, Atiqur; Sridhara, Rajeshwara; Wang, Yong-Cheng; Pazdur, Richard

2005-05-15

This article summarizes data submitted to the U.S. Food and Drug Administration for marketing approval of azacitidine as injectable suspension (Vidaza, Pharmion Corporation, Boulder, CO) for treatment of patients with myelodysplastic syndrome. In one phase 3 controlled trial, 191 study subjects were randomized to treatment with azacitidine or to observation; an additional 120 patients were treated with azacitidine in two phase 2 single arm studies. The primary efficacy end point was the overall response rate, defined as complete or partial normalization of peripheral blood counts and bone marrow blast percentages for at least 4 weeks. In the controlled trial, the overall response rate was 15.7% in the azacitidine treatment group; there were no responders in the observation group (P < 0.0001). Response rates were similar in the two single arm studies. During response patients stopped being red cell or platelet transfusion dependent. Median duration of responses was at least 9 months. An additional 19% of azacitidine-treated patients had less than partial responses, most becoming transfusion independent. The most common adverse events attributed to azacitidine were gastrointestinal, hematologic, local (injection site), and constitutional. There were no azacitidine-related deaths. On May 19, 2004 the U.S. Food and Drug Administration approved azacitidine as injectable suspension for treatment of patients with the following myelodysplastic syndrome subtypes: refractory anemia or refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia. Full prescribing information is available at http://www.fda.gov/cder/foi/label/2004/050794lbl.pdf. Azacitidine is the first agent approved for treatment of myelodysplastic syndrome.

Characterization of cholinergic muscarinic receptor-stimulated phosphoinositide metabolism in brain from immature rats

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

Balduini, W.; Murphy, S.D.; Costa, L.G.

Hydrolysis of phosphoinositides elicited by stimulation of cholinergic muscarinic receptors has been studied in brain from neonatal (7-day-old) rats in order to determine: (1) whether the neonatal rat could provide a good model system to study this signal-transduction pathway; and (2) whether potential differences with adult nerve tissue would explain the differential, age-related effects of cholinergic agonists. Accumulation of (3H) inositol phosphates in (3H)inositol prelabeled slices from neonatal and adult rats was measured as an index of phosphoinositide metabolism. Full (acetylcholine, methacholine, carbachol) and partial (oxotremorine, bethanechol) agonists had qualitatively similar, albeit quantitatively different, effects in neonatal and adult rats.more » Atropine and pirenzepine effectively blocked the carbachol-induced response with inhibition constants of 1.2 and 20.7 nM, respectively. In all brain areas, response to all agonists was higher in neonatal than adult rats, and in hippocampus and cerebral cortex the response was higher than in cerebellum or brainstem. The relative intrinsic activity of partial agonists was higher in the latter two areas (0.6-0.7) than in the former two (0.3-0.4). Carbachol-stimulated phosphoinositide metabolism in brain areas correlated well with the binding of (3H)QNB (r2 = 0.627) and, particularly, with (3H)pirenzepine (r2 = 0.911). In cerebral cortex the effect of carbachol was additive to that of norepinephrine and glutamate. The presence of calcium (250-500 microM) was necessary for maximal response to carbachol to be elicited; the EC50 value for Ca2+ was 65.4 microM. Addition of EDTA completely abolished the response. Removal of sodium ions from the incubation medium reduced the response to carbachol by 50%.« less

Transient quantum coherent response to a partially coherent radiation field.

PubMed

Sadeq, Zaheen S; Brumer, Paul

2014-02-21

The response of an arbitrary closed quantum system to a partially coherent electric field is investigated, with a focus on the transient coherences in the system. As a model we examine, both perturbatively and numerically, the coherences induced in a three level V system. Both rapid turn-on and pulsed turn-on effects are investigated. The effect of a long and incoherent pulse is also considered, demonstrating that during the pulse the system shows a coherent response which reduces after the pulse is over. Both the pulsed scenario and the thermally broadened CW case approach a mixed state in the long time limit, with rates dictated by the adjacent level spacings and the coherence time of the light, and via a mechanism that is distinctly different from traditional decoherence. These two excitation scenarios are also explored for a minimal "toy" model of the electronic levels in pigment protein complex PC645 by both a collisionally broadened CW laser and by a noisy pulse, where unexpectedly long transient coherence times are observed and explained. The significance of environmentally induced decoherence is noted.

Hypercorrection of high confidence errors in lexical representations.

PubMed

Iwaki, Nobuyoshi; Matsushima, Hiroko; Kodaira, Kazumasa

2013-08-01

Memory errors associated with higher confidence are more likely to be corrected than errors made with lower confidence, a phenomenon called the hypercorrection effect. This study investigated whether the hypercorrection effect occurs with phonological information of lexical representations. In Experiment 1, 15 participants performed a Japanese Kanji word-reading task, in which the words had several possible pronunciations. In the initial task, participants were required to read aloud each word and indicate their confidence in their response; this was followed by receipt of visual feedback of the correct response. A hypercorrection effect was observed, indicating generality of this effect beyond previous observations in memories based upon semantic or episodic representations. This effect was replicated in Experiment 2, in which 40 participants performed the same task as in Experiment 1. When the participant's ratings of the practical value of the words were controlled, a partial correlation between confidence and likelihood of later correcting the initial mistaken response was reduced. This suggests that the hypercorrection effect may be partially caused by an individual's recognition of the practical value of reading the words correctly.

Inhibition of polymorphonuclear leukocyte function by Legionella pneumophila exoproducts.

PubMed

Sahney, N N; Lambe, B C; Summersgill, J T; Miller, R D

1990-08-01

Total exoproducts (relative molecular mass greater than 10,000) from wild-type strains of Legionella pneumophila markedly inhibited human polymorphonuclear leukocyte (PMN) superoxide anion generation, at sub-lethal concentrations, in response to four stimuli [1.7, 0, 0.6 and 3.4% of control for zymosan activated particles (ZAP), phorbol myristate acetate (PMA), calcium ionophore (A 23187), and formyl-methionyl-leucyl-phenylalanine (fMLP), respectively]. PMN chemotaxis towards fMLP and spontaneous migration, were also dramatically inhibited (2.8 and 2.9% of buffer-treated controls, respectively). In contrast, total exoproducts from the cas-1 strain of L. pneumophila, a protease-deficient mutant generated by ethyl methane sulfonate mutagenesis, failed to inhibit PMN superoxide production in response to ZAP and PMA and only partially inhibited PMN response to A 23187 and fMLP. PMN spontaneous migration was unaffected by treatment with total exoproducts from the mutant, while directed chemotaxis was partially inhibited (51.4%). These data demonstrated that L. pneumophila total exoproducts, primarily protease had significant inhibitory effects on normal PMN function and may play an important contributory role in the pathogenesis of legionnaire's disease.

Significant partial response of metastatic intra-abdominal and pelvic round cell liposarcoma to a small-molecule VEGFR-2 tyrosine kinase inhibitor apatinib

PubMed Central

Dong, Min; Bi, Jingwang; Liu, Xiaohong; Wang, Baocheng; Wang, Jun

2016-01-01

Abstract Introduction: Myxoid/round cell liposarcoma is the second most common subtype of liposarcoma. Chemotherapy and radiotherapy have a limited efficacy for treating advanced myxoid/round cell liposarcoma, with relatively serious side effects. Case presentation: We herein present a 68-year-old Chinese woman initially diagnosed with advanced multiple intra-abdominal and pelvic round cell liposarcoma. She refused to receive cytotoxic chemotherapy and received apatinib as the first-line therapy, a novel tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2 that has been used in the treatment of patients with metastatic gastric cancer who progressed with 2 or more chemotherapy regimens. This patient was partially responsive to apatinib with a dose of 500 mg daily. No serious drug-related side effects were observed. Conclusion: Our findings indicate that some cases of liposarcoma may be responsive to antiangiogenic agent apatinib. Randomized clinical studies are needed to further confirm the efficacy and safety of apatinib in the clinical treatment of liposarcoma. PMID:27495042

A generalized partially linear mean-covariance regression model for longitudinal proportional data, with applications to the analysis of quality of life data from cancer clinical trials.

PubMed

Zheng, Xueying; Qin, Guoyou; Tu, Dongsheng

2017-05-30

Motivated by the analysis of quality of life data from a clinical trial on early breast cancer, we propose in this paper a generalized partially linear mean-covariance regression model for longitudinal proportional data, which are bounded in a closed interval. Cholesky decomposition of the covariance matrix for within-subject responses and generalized estimation equations are used to estimate unknown parameters and the nonlinear function in the model. Simulation studies are performed to evaluate the performance of the proposed estimation procedures. Our new model is also applied to analyze the data from the cancer clinical trial that motivated this research. In comparison with available models in the literature, the proposed model does not require specific parametric assumptions on the density function of the longitudinal responses and the probability function of the boundary values and can capture dynamic changes of time or other interested variables on both mean and covariance of the correlated proportional responses. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Electronic Structure, Dielectric Response, and Surface Charge Distribution of RGD (1FUV) Peptide

PubMed Central

Adhikari, Puja; Wen, Amy M.; French, Roger H.; Parsegian, V. Adrian; Steinmetz, Nicole F.; Podgornik, Rudolf; Ching, Wai-Yim

2014-01-01

Long and short range molecular interactions govern molecular recognition and self-assembly of biological macromolecules. Microscopic parameters in the theories of these molecular interactions are either phenomenological or need to be calculated within a microscopic theory. We report a unified methodology for the ab initio quantum mechanical (QM) calculation that yields all the microscopic parameters, namely the partial charges as well as the frequency-dependent dielectric response function, that can then be taken as input for macroscopic theories of electrostatic, polar, and van der Waals-London dispersion intermolecular forces. We apply this methodology to obtain the electronic structure of the cyclic tripeptide RGD-4C (1FUV). This ab initio unified methodology yields the relevant parameters entering the long range interactions of biological macromolecules, providing accurate data for the partial charge distribution and the frequency-dependent dielectric response function of this peptide. These microscopic parameters determine the range and strength of the intricate intermolecular interactions between potential docking sites of the RGD-4C ligand and its integrin receptor. PMID:25001596

Neurophysiology of perceived confidence.

PubMed

Graziano, Martin; Parra, Lucas C; Sigman, Mariano

2010-01-01

In a partial report paradigm, subjects observe during a brief presentation a cluttered field and after some time - typically ranging from 100 ms to a second - are asked to report a subset of the presented elements. A vast buffer of information is transiently available to be broadcasted which, if not retrieved in time, fades rapidly without reaching consciousness. An interesting feature of this experiment is that objective performance and subjective confidence is decoupled. This converts this paradigm in an ideal vehicle to understand the brain dynamics of the construction of confidence. Here we report a high-density EEG experiment in which we infer elements of the EEG response which are indicative of subjective confidence. We find that an early response during encoding partially correlates with perceived confidence. However, the bulk of the weight of subjective confidence is determined during a late, N400-like waveform, during the retrieval stage. This shows that we can find markers of access to internal, subjective states, that are uncoupled from objective response and stimulus properties of the task, and we propose that this can be used with decoding methods of EEG to infer subjective mental states.

Clostridial collagenase aggravates the systemic inflammatory response in rats with partial-thickness burns.

PubMed

Dokumcu, Zafer; Ergun, Orkan; Celik, Handan Ak; Aydemir, Sohret; Sezak, Murat; Ozok, Geylani; Celik, Ahmet

2008-11-01

Clostridial collagenase A (CCA) has been shown effective in degrading collagen in eschar tissue and promoting healing in partial-thickness burns. As there are also reports of fever, leukocytosis, increased C-reactive protein (CRP) levels and septic complications during treatment with CCA, we aimed to determine in rats whether CCA aggravates the systemic inflammatory response. Rats with partial-thickness burns were randomly divided into groups with either no dressing (ND), povidone-iodine dressing (PID) or CCA dressing (CCAD). Body weights and temperatures, blood leukocyte counts, and serum levels of CRP, interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha), were measured at 0, 3, and 24h and days 3 and 7 from burn. Wounds were cultured on days 1, 3 and 7 and burn depth was evaluated on day 1. Body weights for all groups were significantly lower after burn, with highest loss (25.5%) in the CCAD group. At 3h a significant drop in rectal temperature was noted in all groups. The CCAD group had higher rectal temperature levels than the PID group on days 3 and 7 (p<0.05). Changes in serum levels of CRP, IL-1 beta, IL-6 and TNF-alpha were not significant in the ND and PID groups; the CCAD group showed a significant rise in serum levels of CRP on day 1, of IL-6 on day 3 and of TNF-alpha on day 7. Wound infection was more common in CCAD group and increased on days 3 and 7, but this was insignificant. CCA aggravated the systemic inflammatory response in rats with partial-thickness burns, which is accompanied by a higher risk of infection.

Adakitic (tonalitic-trondhjemitic) magmas resulting from eclogite decompression and dehydration melting during exhumation in response to continental collision

NASA Astrophysics Data System (ADS)

Song, Shuguang; Niu, Yaoling; Su, Li; Wei, Chunjing; Zhang, Lifei

2014-04-01

Modern adakite or adakitic rocks are thought to result from partial melting of younger and thus warmer subducting ocean crust in subduction zones, with the melt interacting with or without mantle wedge peridotite during ascent, or from melting of thickened mafic lower crust. Here we show that adakitic (tonalitic-trondhjemitic) melts can also be produced by eclogite decompression during exhumation of subducted and metamorphosed oceanic/continental crust in response to continental collision, as exemplified by the adakitic rocks genetically associated with the early Paleozoic North Qaidam ultra-high pressure metamorphic (UHPM) belt on the northern margin of the Greater Tibetan Plateau. We present field evidence for partial melting of eclogite and its products, including adakitic melt, volumetrically significant plutons evolved from the melt, cumulate rocks precipitated from the melt, and associated granulitic residues. This “adakitic assemblage” records a clear progression from eclogite decompression and heating to partial melting, to melt fractionation and ascent/percolation in response to exhumation of the UHPM package. The garnetite and garnet-rich layers in the adakitic assemblage are of cumulate origin from the adakitic melt at high pressure, and accommodate much of the Nb-Ta-Ti. Zircon SHRIMP U-Pb dating shows that partial melting of the eclogite took place at ∼435-410 Ma, which postdates the seafloor subduction (>440 Ma) and temporally overlaps the UHPM (∼440-425 Ma). While the geological context and the timing of adakite melt formation we observe differ from the prevailing models, our observations and documentations demonstrate that eclogite melting during UHPM exhumation may be important in contributing to crustal growth.

Short-term intravenous citalopram augmentation in partial/nonresponders with major depression: a randomized placebo-controlled study.

PubMed

Altamura, Alfredo Carlo; Dell'Osso, Bernardo; Buoli, Massimiliano; Bosi, Monica; Mundo, Emanuela

2008-07-01

Approximately 30-45% of patients with major depressive episode (MDE) do not fully respond to standard recommended treatments and further strategies of intervention, including pharmacological augmentation, have been proposed for these patients. This study was aimed to evaluate the efficacy of short-term, low-dose (10 mg/day) intravenous (i.v.) citalopram augmentation versus placebo in a sample of patients with MDE and partial or no response to selective serotonin reuptake inhibitors (SSRIs). Thirty-six patients with a Diagnostic and Statistical Manual for Mental Disorders, 4th edition, text revision criteria MDE and partial or no response to oral SSRIs were selected and randomly assigned to citalopram (n=18) or to placebo (n=18) i.v. augmentation. The augmentation regimen lasted 5 consecutive days during which the patients were maintained on their current treatment with oral SSRIs. Analyses of variance with repeated measures on Hamilton Depression Rating Scale and Montgomery-Asberg Depression Rating Scale total scores, administered daily with blind-raters conditions, were done. With regard to the Hamilton Depression Rating Scale total scores, a significant time effect (F=42.02, P<0.0001) and timextreatment effect (F=21.17, P<0.0001) were found in favor of citalopram. Similar results were obtained from the analysis on Montgomery-Asberg Depression Rating Scale total scores: time effect (F=50.07, P<0.0001), timextreatment effect (F=19.91, P<0.0001), and treatment effect (F=4.07, P=0.05). Even though referred to a small sample, the present findings seem to suggest that short-term, low-dose, i.v. citalopram augmentation may be effective in depressed patients with partial or no response to oral SSRIs. Further controlled studies performed with double-blind conditions are warranted to confirm the present results.

Photosynthesis and growth response of almond to increased atmospheric ozone partial pressures

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

Retzlaff, W.A.; Williams, L.E.; DeJong, T.M.

Uniform nursery stock of five almond cultivars [Prunus dulcis (Mill) D.A. Webb syn. P. amygdalus Batsch, cv. Butte, Carmel, Mission, Nonpareil, and Sonora] propagated on peach (P. domstica L. Batsch.) rootstock were exposed to three different atmospheric ozone (O[sub 3]) partial pressures. The trees were planted in open-top fumigation chambers on 19 Apr. 1989 at the University of California Kearny Agricultural Center located in the San Joaquin Valley of California. Exposures of the trees to three atmospheric O[sub 3] partial pressures lasted from 1 June to 2 Nov. 1989. The mean 12-h [0800-2000 h Pacific Daylight Time (PDT)] O[sub 3]more » partial pressures measured in the open-top chambers during the experimental period were 0.038, 0.060, and 0.112 [mu]Pa Pa[sup [minus]1] O[sub 3] in the charcoal filtered, ambient, and ambient + O[sub 3] treatments, respectively. Leaf net CO[sub 2] assimilation, trunk cross-sectional area growth, and root, trunk, foliage, and total dry weight of Nonpareil were reduced by increased atmospheric O[sub 3] partial pressures. Mission was unaffected by O[sub 3] and Butte, Carmel, and Sonora were intermediate in their responses. Foliage of Nonpareil also abscised prematurely in the ambient and ambient + O[sub 3] treatments. The results indicate that there are almond cultivars that are sensitive to O[sub 3] exposure.« less

Growth responses of Neurospora crassa to increased partial pressures of the noble gases and nitrogen.

PubMed

Buchheit, R G; Schreiner, H R; Doebbler, G F

1966-02-01

Buchheit, R. G. (Union Carbide Corp., Tonawanda, N.Y.), H. R. Schreiner, and G. F. Doebbler. Growth responses of Neurospora crassa to increased partial pressures of the noble gases and nitrogen. J. Bacteriol. 91:622-627. 1966.-Growth rate of the fungus Neurospora crassa depends in part on the nature of metabolically "inert gas" present in its environment. At high partial pressures, the noble gas elements (helium, neon, argon, krypton, and xenon) inhibit growth in the order: Xe > Kr> Ar > Ne > He. Nitrogen (N(2)) closely resembles He in inhibitory effectiveness. Partial pressures required for 50% inhibition of growth were: Xe (0.8 atm), Kr (1.6 atm), Ar (3.8 atm), Ne (35 atm), and He ( approximately 300 atm). With respect to inhibition of growth, the noble gases and N(2) differ qualitatively and quantitatively from the order of effectiveness found with other biological effects, i.e., narcosis, inhibition of insect development, depression of O(2)-dependent radiation sensitivity, and effects on tissue-slice glycolysis and respiration. Partial pressures giving 50% inhibition of N. crassa growth parallel various physical properties (i.e., solubilities, solubility ratios, etc.) of the noble gases. Linear correlation of 50% inhibition pressures to the polarizability and of the logarithm of pressure to the first and second ionization potentials suggests the involvement of weak intermolecular interactions or charge-transfer in the biological activity of the noble gases.

Effects of partial sleep deprivation on slow waves during non-rapid eye movement sleep: A high density EEG investigation.

PubMed

Plante, David T; Goldstein, Michael R; Cook, Jesse D; Smith, Richard; Riedner, Brady A; Rumble, Meredith E; Jelenchick, Lauren; Roth, Andrea; Tononi, Giulio; Benca, Ruth M; Peterson, Michael J

2016-02-01

Changes in slow waves during non-rapid eye movement (NREM) sleep in response to acute total sleep deprivation are well-established measures of sleep homeostasis. This investigation utilized high-density electroencephalography (hdEEG) to examine topographic changes in slow waves during repeated partial sleep deprivation. Twenty-four participants underwent a 6-day sleep restriction protocol. Spectral and period-amplitude analyses of sleep hdEEG data were used to examine changes in slow wave energy, count, amplitude, and slope relative to baseline. Changes in slow wave energy were dependent on the quantity of NREM sleep utilized for analysis, with widespread increases during sleep restriction and recovery when comparing data from the first portion of the sleep period, but restricted to recovery sleep if the entire sleep episode was considered. Period-amplitude analysis was less dependent on the quantity of NREM sleep utilized, and demonstrated topographic changes in the count, amplitude, and distribution of slow waves, with frontal increases in slow wave amplitude, numbers of high-amplitude waves, and amplitude/slopes of low amplitude waves resulting from partial sleep deprivation. Topographic changes in slow waves occur across the course of partial sleep restriction and recovery. These results demonstrate a homeostatic response to partial sleep loss in humans. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Eruptive vellus hair cysts: report of a pediatric case with partial response to calcipotriene therapy.

PubMed

Erkek, Emel; Kurtipek, Gülcan Saylam; Duman, Deniz; Sanli, Cihat; Erdoğan, Sibel

2009-12-01

Eruptive vellus hair cysts (EVHCs) are characterized by asymptomatic, follicular, comedonelike papules usually located on the anterior chest and abdomen. We present a pediatric case of EVHC associated with attention deficit hyperactivity disorder that partially responded to calcipotriene cream within 2 months. Our aim is to refamiliarize clinicians with a common albeit frequently unrecognized disorder of vellus hair follicles.

Teaching a New Method of Partial Fraction Decomposition to Senior Secondary Students: Results and Analysis from a Pilot Study

ERIC Educational Resources Information Center

Man, Yiu-Kwong; Leung, Allen

2012-01-01

In this paper, we introduce a new approach to compute the partial fraction decompositions of rational functions and describe the results of its trials at three secondary schools in Hong Kong. The data were collected via quizzes, questionnaire and interviews. In general, according to the responses from the teachers and students concerned, this new…

The Persistence of Erroneous Familiarity in an Epileptic Male: Challenging Perceptual Theories of Deja Vu Activation

ERIC Educational Resources Information Center

O'Connor, Akira R.; Moulin, Christopher J. A.

2008-01-01

We report the case of a 39-year-old, temporal lobe epileptic male, MH. Prior to complex partial seizure, experienced up to three times a day, MH often experiences an aura experienced as a persistent sensation of deja vu. Data-driven theories of deja vu formation suggest that partial familiarity for the perceived stimulus is responsible for the…

Vitamin D, Breast Cancer, and Bone Health

DTIC Science & Technology

2011-05-01

Margarine, fortified 1 Tbs 60 15 Pudding prepared with fortified milk 0.5 cup 50 10 Ready-to- eat cereals, fortified 0.75-1 cup 40 10 Liver, beef ...Baum M. Retrospective analysis of time to recurrence in the ATAC trial according to hormone receptor status: an hypothesis-generating study. J Clin...NTx Cross-linked N-telopeptide of type I collagen PR Partial response PTH Parathyroid hormone RR Response rate SAE Serious adverse event SD

Zero-gravity venting of three refrigerants

NASA Technical Reports Server (NTRS)

Labus, T. L.; Aydelott, J. C.; Amling, G. E.

1974-01-01

An experimental investigation of venting cylindrical containers partially filled with initially saturated liquids under zero-gravity conditions was conducted in the NASA Lewis Research Center 5-second zero-gravity facility. The effect of interfacial mass transfer on the ullage pressure response during venting was analytically determined, based on a conduction analysis applied to an infinitely planer (flat) liquid-vapor interface. This pressure response was compared with both the experimental results and an adiabatic decompression computation.

The production of phantom partials due to nonlinearities in the structural components of the piano.

PubMed

Rokni, Eric; Neldner, Lauren M; Adkison, Camille; Moore, Thomas R

2017-10-01

Phantom partials are anomalous overtones in the spectrum of the piano sound that occur at sum and difference frequencies of the natural overtones of the string. Although they are commonly assumed to be produced by forced longitudinal waves in the string, analysis of the sound of a piano produced by mechanically vibrating the soundboard while all the strings are damped indicates that phantom partials can occur in the absence of string motion. The magnitude of the effect leads to the conclusion that nonlinearity in the non-string components may be responsible for some of the power in the phantom partials.

Gas selectivity of SILAR grown CdS nano-bulk junction

NASA Astrophysics Data System (ADS)

Jayakrishnan, R.; Nair, Varun G.; Anand, Akhil M.; Venugopal, Meera

2018-03-01

Nano-particles of cadmium sulphide were deposited on cleaned copper substrate by an automated sequential ionic layer adsorption reaction (SILAR) system. The grown nano-bulk junction exhibits Schottky diode behavior. The response of the nano-bulk junction was investigated under oxygen and hydrogen atmospheric conditions. The gas response ratio was found to be 198% for Oxygen and 34% for Hydrogen at room temperature. An increase in the operating temperature of the nano-bulk junction resulted in a decrease in their gas response ratio. A logarithmic dependence on the oxygen partial pressure to the junction response was observed, indicating a Temkin isothermal behavior. Work function measurements using a Kelvin probe demonstrate that the exposure to an oxygen atmosphere fails to effectively separate the charges due to the built-in electric field at the interface. Based on the benefits like simple structure, ease of fabrication and response ratio the studied device is a promising candidate for gas detection applications.

Reconciling the Observed and Modeled Southern Hemisphere Circulation Response to Volcanic Eruptions

NASA Astrophysics Data System (ADS)

McGraw, M. C.; Barnes, E. A.; Deser, C.

2016-12-01

Confusion exists regarding the tropospheric circulation response to volcanic eruptions, with models and observations seeming to disagree on the sign of the response. The forced Southern Hemisphere circulation response to the eruptions of Pinatubo and El Chichon is shown to be a robust positive annular mode, using over 200 ensemble members from 38 climate models. It is demonstrated that the models and observations are not at odds, but rather, internal climate variability is large and can overwhelm the forced response. It is further argued that the state of ENSO can at least partially explain the sign of the observed anomalies, and may account for the perceived discrepancy between model and observational studies. The eruptions of both El Chichon and Pinatubo occurred during El Nino events, and it is demonstrated that the SAM anomalies following volcanic eruptions are weaker during El Nino events compared to La Nina events.

Task switching and response correspondence in the psychological refractory period paradigm

NASA Technical Reports Server (NTRS)

Lien, Mei-Ching; Schweickert, Richard; Proctor, Robert W.

2003-01-01

Three experiments examined the effects of task switching and response correspondence in a psychological refractory period paradigm. A letter task (vowel-consonant) and a digit task (odd-even) were combined to form 4 possible dual-task pairs in each trial: letter-letter, letter-digit, digit-digit, and digit-letter. Foreknowledge of task transition (repeat or switch) and task identity (letter or digit) was varied across experiments: no foreknowledge in Experiment 1, partial foreknowledge (task transition only) in Experiment 2, and full foreknowledge in Experiment 3. For all experiments, the switch cost for Task 2 was additive with stimulus onset asynchrony, and the response-correspondence effect for Task 2 was numerically smaller in the switch condition than in the repeat condition. These outcomes suggest that reconfiguration for Task 2 takes place after the central processing of Task 1 and that the crosstalk correspondence effect is due to response activation by way of stimulus-response associations.

Glucose and Insulin Secretory Response Patterns Following Diet and Tolazamide Therapy in Diabetes

PubMed Central

Turtle, J. R.

1970-01-01

Glucose and insulin secretory response patterns during glucose tolerance tests were determined in 28 maturity-onset diabetics, and the sequential effects of diet and a sulphonylurea, tolazamide, were assessed. Untreated diabetics showed hyperglycaemia, increased serum immunoreactive insulin response patterns, delayed insulin release, and relative insulin deficiency. Diet alone partially corrected the hyperglycaemia and serum immunoreactive insulin response but had no effect on the delayed insulin release or relative insulin deficiency. Tolazamide plus diet restored all values towards normal. The net effect of maintenance tolazamide therapy was to (1) restore the insulin secretory response pattern to normal, (2) reduce total pancreatic insulin output, and (3) improve the efficiency of insulin secretion. The results suggest that there is a rational basis for the use of sulphonylurea in all maturity-onset diabetics, including patients with mild carbohydrate intolerance and those who are apparently controlled by diet alone. PMID:5470087

Paradoxical response to dexamethasone and spontaneous hypocortisolism in Cushing's disease

PubMed Central

Lila, Anurag R; Sarathi, Vijaya; Bandgar, Tushar R; Shah, Nalini S

2013-01-01

Paradoxical response to dexamethasone and spontaneous development of hypocortisolism are rare features of Cushing's disease. We report a 13-year-old boy with Cushing's disease owing to a pituitary macroadenoma. On initial evaluation, he had partial suppression of serum cortisol by dexamethasone. He developed transient hypocortisolism after first adenomectomy, but the disease recurred after 1 year. Repeat evaluation showed recurrent hypercortisolism and paradoxical response to dexamethasone. He underwent second surgery and, postoperatively, hypercostisolism persisted even after 2 years of surgery. Repeat evaluations after 8 years of second surgery revealed persistent hypocortisolism despite residual tumour of same size and similar plasma adrenocorticotropic hormone (ACTH) levels. We have also shown that the paradoxical increase in serum cortisol was preceded by a paradoxical increase in ACTH. The paradoxical response persisted despite hypocortisolism. This patient with Cushing's disease had two very rare features: paradoxical response to dexamethasone and spontaneous development of hypocortisolism. PMID:23365169

Extra-auditory responses to long-term intermittent noise stimulation in humans.

PubMed

Fruhstorfer, B; Hensel, H

1980-12-01

Respiration, heart rate, cutaneous blood flow, and electroencephalogram (EEG) reactions to long-term intermittent noise exposure were recorded from 13 volunteers (20-29 yr) with normal hearing and vegetative reactivity. They received daily within 1 h 12 noise stimuli (16 s 100 dB (A) white noise) for 10 or 21 days, respectively. Most subjects reported partial subjective adaptation to the noise. Heart rate adapted within a session but did not change considerably during successive days. Vascular responses did not change during one session but diminished mainly during the first 10 days. Noise responses in the EEG remained constant, but a decrease in vigilance occurred during the whole experimental series. Respiration responses were unpredictable and showed no trend within the sessions. It was concluded that certain physiological responses adapt to loud noise but that the time course of adaptation is different. Therefore a general statement about physiological noise adaptation is not possible.

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.

Physical and ecological controllers of the microbial responses to drying and rewetting in soil

NASA Astrophysics Data System (ADS)

Leizeaga, Ainara; Meisner, Annelein; Bååth, Erland; Rousk, Johannes

2017-04-01

Soil moisture is one of the most powerful factors that regulate microbial activity in soil. The variation of moisture leads to drying-rewetting (DRW) events which are known to induce enormous dynamics in soil biogeochemistry; however, the microbial underpinnings are mostly unknown. Rewetting a dry soil can result in two response patterns of bacterial growth. In the Type 1 response, bacteria start growing immediately after rewetting with rates that increase in a linear fashion to converge with those prior to the DRW within hours. This growth response coincides with respiration rates that peak immediately after rewetting to then exponentially decrease. In the Type 2 response, bacterial growth remains very low after rewetting during a lag period of up to 20 hours. Bacteria then increase their growth rates exponentially to much higher rates than those before the DRW event. This growth response coincides with respiration rates that increase to high rates immediately after rewetting that then remain elevated and sometimes even increase further in sync with the growth increase. Previous studies have shown that (i) extended drying (ii) starving before DRW and (iii) inhibitors combined with drought could change the bacterial response from Type 1 to Type 2. This suggested that the response of bacteria upon rewetting could be related to the harshness of the disturbance as experienced by the microbes. In the present study, we set out to study if reduced harshness could change a Type 2 response into a Type 1 response. We hypothesized that (1) a reduced physical harshness of drying and (2) induced tolerance to drying in microbial communities could change a Type 2 response into a Type 1 growth response upon rewetting. To address this, two experiments were performed. First, soils were partially dried to different water contents and bacterial response upon rewetting was measured. Second, soils were exposed to repeated DRW cycles (< 9 cycles) and the bacterial response was followed after rewetting. A less harsh drying (partial drying) of a soil could change the growth responses to rewetting. The lag period decreased with less complete drying to eventually became 0, transitioning from a Type 2 to a Type 1. Even after a Type 1 response was induced, further reduction of harshness could also lead to a faster recovery of growth rates. Our results support the hypothesis: the physical harshness of drying can determine the microbial survival and thus the type of bacterial growth response. Subjecting soil to DRW cycles could also induce a change from a Type 2 to Type 1 growth response. This suggested that there was a community shift towards higher drought-tolerance. Thus, identical physical disturbance was less harsh for a community that has been subjected to more drying rewetting cycles. To predict how the microbial community's control of the soil C budget of ecosystems is affected warming-induced drought, our results demonstrate that both the physical characteristics of the disturbance and the community's tolerance to drought need to be considered.

Membrane fluidity controls redox-regulated cold stress responses in cyanobacteria.

PubMed

Maksimov, Eugene G; Mironov, Kirill S; Trofimova, Marina S; Nechaeva, Natalya L; Todorenko, Daria A; Klementiev, Konstantin E; Tsoraev, Georgy V; Tyutyaev, Eugene V; Zorina, Anna A; Feduraev, Pavel V; Allakhverdiev, Suleyman I; Paschenko, Vladimir Z; Los, Dmitry A

2017-09-01

Membrane fluidity is the important regulator of cellular responses to changing ambient temperature. Bacteria perceive cold by the transmembrane histidine kinases that sense changes in thickness of the cytoplasmic membrane due to its rigidification. In the cyanobacterium Synechocystis, about a half of cold-responsive genes is controlled by the light-dependent transmembrane histidine kinase Hik33, which also partially controls the responses to osmotic, salt, and oxidative stress. This implies the existence of some universal, but yet unknown signal that triggers adaptive gene expression in response to various stressors. Here we selectively probed the components of photosynthetic machinery and functionally characterized the thermodynamics of cyanobacterial photosynthetic membranes with genetically altered fluidity. We show that the rate of oxidation of the quinone pool (PQ), which interacts with both photosynthetic and respiratory electron transport chains, depends on membrane fluidity. Inhibitor-induced stimulation of redox changes in PQ triggers cold-induced gene expression. Thus, the fluidity-dependent changes in the redox state of PQ may universally trigger cellular responses to stressors that affect membrane properties.

Direct transcriptional activation of BT genes by NLP transcription factors is a key component of the nitrate response in Arabidopsis.

PubMed

Sato, Takeo; Maekawa, Shugo; Konishi, Mineko; Yoshioka, Nozomi; Sasaki, Yuki; Maeda, Haruna; Ishida, Tetsuya; Kato, Yuki; Yamaguchi, Junji; Yanagisawa, Shuichi

2017-01-29

Nitrate modulates growth and development, functioning as a nutrient signal in plants. Although many changes in physiological processes in response to nitrate have been well characterized as nitrate responses, the molecular mechanisms underlying the nitrate response are not yet fully understood. Here, we show that NLP transcription factors, which are key regulators of the nitrate response, directly activate the nitrate-inducible expression of BT1 and BT2 encoding putative scaffold proteins with a plant-specific domain structure in Arabidopsis. Interestingly, the 35S promoter-driven expression of BT2 partially rescued growth inhibition caused by reductions in NLP activity in Arabidopsis. Furthermore, simultaneous disruption of BT1 and BT2 affected nitrate-dependent lateral root development. These results suggest that direct activation of BT1 and BT2 by NLP transcriptional activators is a key component of the molecular mechanism underlying the nitrate response in Arabidopsis. Copyright © 2016 Elsevier Inc. All rights reserved.

Sequential therapy in advanced non-small-cell lung cancer with weekly paclitaxel followed by cisplatin-gemcitabine-vinorelbine. A phase II study.

PubMed

Feliu, J; Martin, G; Lizón, J; Chacón, J I; Dorta, J; de Castro, J; Rodríguez, A; Sánchez Heras, B; Torrego, J C; Espinosa, E; González Barón, M

2001-10-01

New effective therapies are needed to improve the outcome of patients with advanced non-small-cell lung cancer (NSCLC). The aim of this study was to assess the response rate and survival obtained with a sequential regimen of chemotherapy. Patients with newly diagnosed stage IIIb-IV NSCLC were included. They all had measurable disease and a good performance status (0-2 in the Eastern Cooperative Oncology Group scale). Chemotherapy consisted of weekly paclitaxel 150 mg/m2 x 6, followed two weeks later by cisplatin 100 mg/m2 on day 1, gemcitabine 1,000 mg/m2 on days 1 and 14, and vinorelbine 25 mg/m2 on days 1 and 14 (CGV). CGV was administered every 28 days for a maximum of six courses. Fifty-two patients were included, 19 (37%) with stage IIIb and 33 (63%) with stage IV disease. After therapy with weekly paclitaxel. 29 partial responses were obtained (56%, 95% confidence interval (95% CI): 38%-67%), whereas 15 patients had stable disease (29%) and eight had a progression (15%). After CGV, there were four complete remissions (8%) and 24 partial responses (46%), for an overall response rate of 54% (95% CI: 37%-65%). Eight patients had stable disease (15%) and 16 had a progression (31%). No patient progressing after paclitaxel responded to CGV, whereas 5 out of 15 patients with stable disease reached a partial response with CGV (33%). On the contrary, 5 out of 29 patients with a partial response to paclitaxel progressed after CGV (17%). Median survival has not been reached after a median follow-up of 14 months. Median time to progression was nine months. Fifty-six percent of patients remain alive at one year. Two hundred eighty-nine courses of paclitaxel and 170 of CGV were given, with a median of 5.5 and 3.4 per patient, respectively (ranges 2-6 and 0-6. respectively). WHO grade 3-4 toxicities for paclitaxel were: neutropenia in two patients (4/) and peripheral neuropathy in five (10%). Two patients had allergic reactions requiring paclitaxel withdrawal, whereas four (8%) had hyperglycemia >250 mg/ml. Grade 3-4 toxicities for CGV were: neutropenia in ten patients (20%), peripheral neuropathy in six (12%), anemia in four (8%), nausea/vomiting in five (10%). thrombocytopenia in two (4%), and fatigue in four (8%). Our results suggest that sequential chemotherapy with weekly paclitaxel followed by CGV is highly active in patients with advanced NSCLC and has an acceptable toxicity. This schedule deserves further evaluation in a phase III study.

Phase 2 trial of BCNU plus irinotecan in adults with malignant glioma1

PubMed Central

Reardon, David A.; Quinn, Jennifer A.; Rich, Jeremy N.; Gururangan, Sridharan; Vredenburgh, James; Sampson, John H.; Provenzale, James M.; Walker, Amy; Badruddoja, Michael; Tourt-Uhlig, Sandra; Herndon, James E.; Dowell, Jeannette M.; Affronti, Mary Lou; Jackson, Susanne; Allen, Deborah; Ziegler, Karen; Silverman, Steven; Bohlin, Cindy; Friedman, Allan H.; Bigner, Darell D.; Friedman, Henry S.

2004-01-01

In preclinical studies, BCNU, or 1,3-bis(2-chloroethyl)-1-nitrosourea, plus CPT-11 (irinotecan) exhibits schedule-dependent, synergistic activity against malignant glioma (MG). We previously established the maximum tolerated dose of CPT-11 when administered for 4 consecutive weeks in combination with BCNU administered on the first day of each 6-week cycle. We now report a phase 2 trial of BCNU plus CPT-11 for patients with MG. In the current study, BCNU (100 mg/m2) was administered on day 1 of each 6-week cycle. CPT-11 was administered on days 1, 8, 15, and 22 at 225 mg/m2 for patients receiving CYP3A1- or CYP3A4-inducing anticonvulsants and at 125 mg/m2 for those not on these medications. Newly diagnosed patients received up to 3 cycles before radiotherapy, while recurrent patients received up to 8 cycles. The primary end point of this study was radiographic response, while time to progression and overall survival were also assessed. Seventy-six patients were treated, including 37 with newly diagnosed tumors and 39 with recurrent disease. Fifty-six had glioblastoma multiforme, 18 had anaplastic astrocytoma, and 2 had anaplastic oligodendroglioma. Toxicities (grade ⩾3) included infections (13%), thromboses (12%), diarrhea (10%), and neutropenia (7%). Interstitial pneumonitis developed in 4 patients. Five newly diagnosed patients (14%; 95% CI, 5%–29%) achieved a radiographic response (1 complete response and 4 partial responses). Five patients with recurrent MG also achieved a response (1 complete response and 4 partial responses; 13%; 95% CI, 4%–27%). More than 40% of both newly diagnosed and recurrent patients achieved stable disease. Median time to progression was 11.3 weeks for recurrent glioblastoma multiforme patients and 16.9 weeks for recurrent anaplastic astrocytoma/anaplastic oligodendroglioma patients. We conclude that the activity of BCNU plus CPT-11 for patients with MG appears comparable to that of CPT-11 alone and may be more toxic. PMID:15134628

Predicting and managing primary and secondary non-response to rituximab using B-cell biomarkers in systemic lupus erythematosus

PubMed Central

Md Yusof, Md Yuzaiful; Shaw, Daniel; El-Sherbiny, Yasser M; Dunn, Emma; Rawstron, Andy C; Emery, Paul; Vital, Edward M

2017-01-01

Objective To assess factors associated with primary and secondary non-response to rituximab in systemic lupus erythematosus (SLE) and evaluate management of secondary non-depletion non-response (2NDNR). Methods 125 patients with SLE treated with rituximab over 12 years were studied prospectively. A major clinical response was defined as improvement of all active British Isles Lupus Assessment Group (BILAG)-2004 domains to grade C/better and no A/B flare. Partial responders were defined by one persistent BILAG B. B-cell subsets were measured using highly sensitive flow cytometry. Patients with 2NDNR, defined by infusion reaction and defective depletion, were treated with ocrelizumab or ofatumumab. Results 117 patients had evaluable data. In cycle 1 (C1), 96/117 (82%) achieved BILAG response (major=50%, partial=32%). In multivariable analysis, younger age (OR 0.97, 95% CI 0.94 to 1.00) and B-cell depletion at 6 weeks (OR 3.22, 95% CI 1.24 to 8.33) increased the odds of major response. Complete depletion was predicted by normal complement and lower pre-rituximab plasmablasts and was not associated with increased serious infection post-rituximab. Seventy-seven (with data on 72) C1 responders were retreated on clinical relapse. Of these, 61/72 (85%) responded in cycle 2 (C2). Of the 11 C2 non-responders, nine met 2NDNR criteria (incidence=12%) and tested positive for anti-rituximab antibodies. Lack of concomitant immunosuppressant and higher pre-rituximab plasmablasts predicted 2NDNR. Five were switched to ocrelizumab/ofatumumab, and all depleted and responded. Conclusion Treatment with anti-CD20 agents can be guided by B-cell monitoring and should aim to achieve complete depletion. 2NDNR is associated with anti-rituximab antibodies, and switching to humanised agents restores depletion and response. In SLE, alternative anti-CD20 antibodies may be more consistently effective. PMID:28684557

mRECIST criteria and contrast-enhanced US for the assessment of the response of hepatocellular carcinoma to transarterial chemoembolization

PubMed Central

Moschouris, Hippocrates; Malagari, Katerina; Papadaki, Marina G.; Kornezos, Ioannis; Stamatiou, Konstantinos; Anagnostopoulos, Antonios; Chatzimichael, Katerina; Kelekis, Nikolaos

2014-01-01

PURPOSE We aimed to evaluate the combination of the modified Response Evaluation Criteria In Solid Tumors (mRECIST) and contrast-enhanced ultrasonography (CEUS) as a tool for the assessment of hepatocellular carcinoma treated with transarterial chemoembolization. MATERIALS AND METHODS Forty-seven hepatocellular carcinoma patients (80 target tumors suitable for mRECIST measurements) were studied. They were treated with scheduled transarterial chemoembolization with doxorubicin-eluting microspheres every 5–7 weeks. Imaging follow-up (performed one month after each transarterial chemoembolization) included a standard, contrast-enhanced modality (computed tomography [CT] in 12 patients or magnetic resonance imaging [MRI] in 35 patients) and CEUS. The study focused on response evaluation after the third transarterial chemoembolization. CEUS required a bolus injection of an echo-enhancer and imaging with a dedicated, low mechanical index technique. The longest diameters of the enhancing target tumors were measured on the CEUS or CT/MRI, and mRECIST criteria were applied. Radiologic responses were correlated with overall survival and time to progression. RESULTS The measurements of longest diameters of the enhancing target tumors were easily performed in all patients. According to mRECIST-CEUS and mRECIST-CT/MRI, complete response was recorded in five and six patients, partial response in 22 and 21 patients, stable disease in 16 and 14 patients, and progressive disease in four and six patients, respectively. There was a high degree of concordance between CEUS and CT/MRI (kappa coefficient=0.84, P < 0.001). Responders (complete+partial response) according to mRECIST-CEUS had a significantly longer mean overall survival and time to progression compared to nonresponders (37.1 vs. 11.0 months, P < 0.001 and 24.6 vs. 10.9 months, P = 0.007, respectively). CONCLUSION The mRECIST-CEUS combination is feasible and has prognostic value in the assessment of hepatocellular carcinoma following transarterial chemoembolization. PMID:24317334

Safety and Efficacy of Pembrolizumab in Advanced, Programmed Death Ligand 1-Positive Cervical Cancer: Results From the Phase Ib KEYNOTE-028 Trial.

PubMed

Frenel, Jean-Sebastien; Le Tourneau, Christophe; O'Neil, Bert; Ott, Patrick A; Piha-Paul, Sarina A; Gomez-Roca, Carlos; van Brummelen, Emilie M J; Rugo, Hope S; Thomas, Shari; Saraf, Sanatan; Rangwala, Reshma; Varga, Andrea

2017-12-20

Purpose The KEYNOTE-028 trial ( ClinicalTrials.gov identifier: NCT02054806) was designed to assess the safety and efficacy of pembrolizumab in 20 programmed death ligand 1-positive, advanced solid tumor cohorts. Here, we present the results from the cohort of patients with advanced cervical cancer. Methods Patients were treated with pembrolizumab 10 mg/kg every 2 weeks for up to 24 months. Response was assessed every 8 weeks for the first 6 months and every 12 weeks thereafter. The primary end point was overall response rate per Response Evaluation Criteria in Solid Tumors, version 1.1, by investigator review. Safety was a secondary end point. Results Twenty-four patients were enrolled in the cervical cancer cohort. The median age was 42 years (range, 26 to 62 years), 22 patients (92%) had received prior radiation therapy, and 15 patients (63%) had received two or more lines of therapy, including bevacizumab (10 of 24 patients), for advanced disease. At the data cutoff, median follow-up duration was 11.0 months (range, 1.3 to 32.2 months). Overall response rate was 17% (95% CI, 5% to 37%); four patients (17%) achieved a confirmed partial response, and three patients (13%) had stable disease. Median duration of response for the four patients who achieved a partial response was 5.4 months (4.1 to 7.5 months). Treatment related adverse events (AEs) were experienced by 18 patients (75%); only rash (n = 5; 21%) and pyrexia (n = 4; 17%) and occurred in ≥ 10% of patients. Five patients experienced grade 3 treatment-related AEs. No grade 4 treatment-related AEs or deaths were observed. Conclusion In patients with programmed death ligand 1-positive advanced cervical cancer, pembrolizumab demonstrated antitumor activity and exhibited a safety profile consistent with that seen in other tumor types.

Overcoming the response plateau in multiple myeloma: A novel bortezomib-based strategy for secondary induction and high-yield CD34+ stem cell mobilization

PubMed Central

Niesvizky, Ruben; Mark, Tomer M.; Ward, Maureen; Jayabalan, David S.; Pearse, Roger N.; Manco, Megan; Stern, Jessica; Christos, Paul J.; Mathews, Lena; Shore, Tsiporah B.; Zafar, Faiza; Pekle, Karen; Xiang, Zhaoying; Ely, Scott; Skerret, Donna; Chen-Kiang, Selina; Coleman, Morton; Lane, Maureen E.

2014-01-01

Purpose This phase 2 study evaluated bortezomib-based secondary induction and stem cell mobilization in 38 transplant-eligible myeloma patients who had an incomplete and stalled response to, or had relapsed after, previous immunomodulatory drug-based induction. Experimental design Patients received up to six 21-day cycles of bortezomib plus dexamethasone, with added liposomal doxorubicin for patients not achieving partial response or better by cycle 2 or very good partial response or better (≥VGPR) by cycle 4 (DoVeD), followed by bortezomib, high-dose cyclophosphamide, and filgrastim mobilization. Gene expression/signaling pathway analyses were conducted in purified CD34+ cells post-bortezomib-based mobilization and compared against patients who received only filgrastim ± cyclophosphamide. Plasma samples were similarly analyzed for quantification of associated protein markers. Results The response rate to DoVeD relative to the pre-DoVeD baseline was 61%, including 39% ≥VGPR. Deeper responses were achieved in 10 of 27 patients who received bortezomib-based mobilization; post-mobilization response rate was 96%, including 48% ≥VGPR, relative to the pre-DoVeD baseline. Median CD34+ cell yield was 23.2 × 106 cells/kg (median of 1 apheresis session). After a median follow-up of 46.6 months, median progression-free survival was 47.1 months from DoVeD initiation;5-year overall survival rate was 76.4%. Grade ≥3 adverse events included thrombocytopenia (13%), hand-foot syndrome (11%), peripheral neuropathy (8%), and neutropenia (5%). Bortezomib-based mobilization was associated with modulated expression of genes involved in stem cell migration. Conclusion Bortezomib-based secondary induction and mobilization could represent an alternative strategy for elimination of tumor burden in immunomodulatory drug-resistant patients that does not impact stem cell yield. PMID:23357980

Genetic polymorphisms in 5-Fluorouracil-related enzymes predict pathologic response after neoadjuvant chemoradiation for rectal cancer.

PubMed

Nelson, Bailey; Carter, Jane V; Eichenberger, Maurice R; Netz, Uri; Galandiuk, Susan

2016-11-01

Many patients with rectal cancer undergo preoperative neoadjuvant chemoradiation, with approximately 70% exhibiting pathologic downstaging in response to treatment. Currently, there is no accurate test to predict patients who are likely to be complete responders to therapy. 5-Fluorouracil is used regularly in the neoadjuvant treatment of rectal cancer. Genetic polymorphisms affect the activity of thymidylate synthase, an enzyme involved in 5-Fluorouracil metabolism, which may account for observed differences in response to neoadjuvant treatment between patients. Detection of genetic polymorphisms might identify patients who are likely to have a complete response to neoadjuvant therapy and perhaps allow them to avoid operation. DNA was isolated from whole blood taken from patients with newly diagnosed rectal cancer who received neoadjuvant therapy (n = 50). Response to therapy was calculated with a tumor regression score based on histology from the time of operation. Polymerase chain reaction was performed targeting the promoter region of thymidylate synthase. Polymerase chain reaction products were separated using electrophoresis to determine whether patients were homozygous for a double-tandem repeat (2R), a triple-tandem repeat (3R), or were heterozygous (2R/3R). A single nucleotide polymorphism, 3G or 3C, also may be present in the second repeat unit of the triple-tandem repeat allele. Restriction fragment length polymorphism assays were performed in patients with at least one 3R allele using HaeIII. Patients with at least 1 thymidylate synthase 3G allele were more likely to have a complete or partial pathologic response to 5-Fluorouracil neoadjuvant therapy (odds ratio 10.4; 95% confidence interval, 1.3-81.6; P = .01) than those without at least one 3G allele. Identification of rectal cancer patients with specific genetic polymorphisms in enzymes involved in 5-Fluorouracil metabolism seems to predict the likelihood of complete or partial pathologic response to preoperative neoadjuvant therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Local and linear chemical reactivity response functions at finite temperature in density functional theory

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

Franco-Pérez, Marco, E-mail: francopj@mcmaster.ca, E-mail: ayers@mcmaster.ca, E-mail: jlgm@xanum.uam.mx, E-mail: avela@cinvestav.mx; Departamento de Química, Universidad Autónoma Metropolitana-Iztapalapa, Av. San Rafael Atlixco 186, México, D.F. 09340; Ayers, Paul W., E-mail: francopj@mcmaster.ca, E-mail: ayers@mcmaster.ca, E-mail: jlgm@xanum.uam.mx, E-mail: avela@cinvestav.mx

2015-12-28

We explore the local and nonlocal response functions of the grand canonical potential density functional at nonzero temperature. In analogy to the zero-temperature treatment, local (e.g., the average electron density and the local softness) and nonlocal (e.g., the softness kernel) intrinsic response functions are defined as partial derivatives of the grand canonical potential with respect to its thermodynamic variables (i.e., the chemical potential of the electron reservoir and the external potential generated by the atomic nuclei). To define the local and nonlocal response functions of the electron density (e.g., the Fukui function, the linear density response function, and the dualmore » descriptor), we differentiate with respect to the average electron number and the external potential. The well-known mathematical relationships between the intrinsic response functions and the electron-density responses are generalized to nonzero temperature, and we prove that in the zero-temperature limit, our results recover well-known identities from the density functional theory of chemical reactivity. Specific working equations and numerical results are provided for the 3-state ensemble model.« less

Local and linear chemical reactivity response functions at finite temperature in density functional theory.

PubMed

Franco-Pérez, Marco; Ayers, Paul W; Gázquez, José L; Vela, Alberto

2015-12-28

We explore the local and nonlocal response functions of the grand canonical potential density functional at nonzero temperature. In analogy to the zero-temperature treatment, local (e.g., the average electron density and the local softness) and nonlocal (e.g., the softness kernel) intrinsic response functions are defined as partial derivatives of the grand canonical potential with respect to its thermodynamic variables (i.e., the chemical potential of the electron reservoir and the external potential generated by the atomic nuclei). To define the local and nonlocal response functions of the electron density (e.g., the Fukui function, the linear density response function, and the dual descriptor), we differentiate with respect to the average electron number and the external potential. The well-known mathematical relationships between the intrinsic response functions and the electron-density responses are generalized to nonzero temperature, and we prove that in the zero-temperature limit, our results recover well-known identities from the density functional theory of chemical reactivity. Specific working equations and numerical results are provided for the 3-state ensemble model.

Progesterone modifies the responsivity of the amygdala-mPFC connection in male but not female Wistar rats.

PubMed

Contreras, Carlos M; Gutiérrez-García, Ana G

2017-05-10

Amygdala-medial prefrontal cortex (mPFC) connections partially regulate fear, anxiety, and the acquisition of conditioned fear. Progesterone exerts some effects on anxiety and fear. Currently unknown, however, are the actions of progesterone on the responsivity of amygdala-mPFC connections and possible sex differences. We performed single-unit extracellular recordings from the prelimbic (PL) and infralimbic (IL) cortices of the mPFC during stimulation of the basal amygdala (BA) in anesthetized male and diestrus female rats. Basal amygdala stimulation produced an initial excitatory paucisynaptic response that was similar between sexes and unaffected by progesterone. A long-lasting inhibitory response followed the initial brief excitatory response, which was more pronounced in the PL region in males. The unit activity ratio analysis indicated that progesterone negated the sex difference in the PL region response to BA stimulation. The results suggest that progesterone decreases the responsivity to amygdala stimulation, particularly in males compared with diestrus females, which may be related to sex differences in the strategies to cope with threatening situations. Copyright © 2017 Elsevier B.V. All rights reserved.

Photodynamic therapy influence on anti-cancer immunity

NASA Astrophysics Data System (ADS)

Isaeva, O. G.; Osipov, V. A.

2010-02-01

The system of partial differential equations describing tumor-immune dynamics with angiogenesis taken into account is presented. For spatially homogeneous case, the steady state analysis of the model is carried out. The effects of single photodynamic impact are numerically simulated. In the case of strong immune response we found that the photodynamic therapy (PDT) gives rise to the substantial shrinkage of tumor size which is accompanied by the increase of IL-2 concentration. On the contrary, the photodynamic stimulation of weak immune response is shown to be insufficient to reduce the tumor. These findings indicate the important role of anti-cancer immune response in the long-term tumor control after PDT.

Photodynamic therapy influence on anti-cancer immunity

NASA Astrophysics Data System (ADS)

Isaeva, O. G.; Osipov, V. A.

2009-10-01

The system of partial differential equations describing tumor-immune dynamics with angiogenesis taken into account is presented. For spatially homogeneous case, the steady state analysis of the model is carried out. The effects of single photodynamic impact are numerically simulated. In the case of strong immune response we found that the photodynamic therapy (PDT) gives rise to the substantial shrinkage of tumor size which is accompanied by the increase of IL-2 concentration. On the contrary, the photodynamic stimulation of weak immune response is shown to be insufficient to reduce the tumor. These findings indicate the important role of anti-cancer immune response in the long-term tumor control after PDT.

Feature Integration Across the Lifespan: Stickier Stimulus–Response Bindings in Children and Older Adults

PubMed Central

Hommel, Bernhard; Kray, Jutta; Lindenberger, Ulman

2010-01-01

Humans integrate the features of perceived events and of action plans into episodic event files. Here we investigated whether children (9–10 years), younger adults (20–31 years), and older adults (64–76 years) differ in the flexibility of managing (updating) event files. Relative to young adults, performance in children and older adults was more hampered by partial mismatches between present and previous stimulus–response relations, suggesting less efficient updating of episodic stimulus–response representations in childhood and old age. Results are discussed in relation to changes in cortical neurochemistry during maturation and senescence. PMID:22053159

Mediation and moderation of psychological pain treatments: response expectancies and hypnotic suggestibility.

PubMed

Milling, Leonard S; Reardon, John M; Carosella, Gina M

2006-04-01

The mediator role of response expectancies and the moderator role of hypnotic suggestibility were evaluated in the analogue treatment of pain. Approximately 1,000 participants were assessed for hypnotic suggestibility. Later, as part of a seemingly unrelated experiment, 188 of these individuals were randomly assigned to distraction, cognitive-behavioral package, hypnotic cognitive-behavioral package, hypnotic analgesia suggestion, placebo control, or no-treatment control conditions. Response expectancies partially mediated the effects of treatment on pain. Hypnotic suggestibility moderated treatment and was associated with the relief produced only by the hypnotic interventions. The results suggest that response expectancies are an important mechanism of hypnotic and cognitive-behavioral pain treatments and that hypnotic suggestibility is a trait variable that predicts hypnotic responding across situations, including hypnosis-based pain interventions. Copyright 2006 APA

Tablet based distributed intelligent load management

DOEpatents

Lu, Yan; Zhou, Siyuan

2018-01-09

A facility is connected to an electricity utility and is responsive to Demand Response Events. A plurality of devices is each individually connected to the electricity grid via an addressable switch connected to a secure network that is enabled to be individually switched off by a server. An occupant of a room in control of the plurality of devices provides via a Human Machine Interface on a tablet a preferred order of switching off the plurality of devices in case of a Demand Response Event. A configuration file based at least partially on the preferred order and on a severity of the Demand Response Events determines which devices which of the plurality devices will be switched off. The server accesses the configuration file and switches off the devices included in the configuration file.

Phenotypic Suppression of the Gibberellin-Insensitive Mutant (gai) of Arabidopsis.

PubMed Central

Wilson, R. N.; Somerville, C. R.

1995-01-01

The semidominant gibberellin-insensitive (gai) mutant of Arabidopsis thaliana shows impairment in multiple responses to the plant hormone gibberellin A3, which include effects on seed germination, stem elongation, apical dominance, and rapid flowering in short days. Results presented here show that the gai mutation also interferes with development of fertile flowers in continuous light. Mu-tagenesis of the gai mutant resulted in recovery of 17 independent mutants in which the gibberellin-insensitive phenotype is partially or completely suppressed. Sixteen of the suppressor mutations act semidominantly to restore gibberellin responsiveness. One representative of this class, the gar1 mutation, could not be genetically separated from the gai locus and is proposed to cause inactivation of the gai gene. The exceptional gar2 mutation partially suppresses the gai phenotype, is completely dominant, and is not linked to the gai locus. The gar2 mutation may define a new gene involved in gibberellin signaling. A recessive allele of the spindly (SPY) locus, spy-5, was also found to partially suppress the gai mutant phenotype. PMID:12228487

PPARγ partial agonist GQ-16 strongly represses a subset of genes in 3T3-L1 adipocytes

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

Milton, Flora Aparecida; Genomic Medicine, Houston Methodist Research Institute, Houston, TX; Cvoro, Aleksandra

Thiazolidinediones (TZDs) are peroxisome proliferator-activated receptor gamma (PPARγ) agonists that improve insulin resistance but trigger side effects such as weight gain, edema, congestive heart failure and bone loss. GQ-16 is a PPARγ partial agonist that improves glucose tolerance and insulin sensitivity in mouse models of obesity and diabetes without inducing weight gain or edema. It is not clear whether GQ-16 acts as a partial agonist at all PPARγ target genes, or whether it displays gene-selective actions. To determine how GQ-16 influences PPARγ activity on a gene by gene basis, we compared effects of rosiglitazone (Rosi) and GQ-16 in mature 3T3-L1more » adipocytes using microarray and qRT-PCR. Rosi changed expression of 1156 genes in 3T3-L1, but GQ-16 only changed 89 genes. GQ-16 generally showed weak effects upon Rosi induced genes, consistent with partial agonist actions, but a subset of modestly Rosi induced and strongly repressed genes displayed disproportionately strong GQ-16 responses. PPARγ partial agonists MLR24 and SR1664 also exhibit disproportionately strong effects on transcriptional repression. We conclude that GQ-16 displays a continuum of weak partial agonist effects but efficiently represses some negatively regulated PPARγ responsive genes. Strong repressive effects could contribute to physiologic actions of GQ-16. - Highlights: • GQ-16 is an insulin sensitizing PPARγ ligand with reduced harmful side effects. • GQ-16 displays a continuum of weak partial agonist activities at PPARγ-induced genes. • GQ-16 exerts strong repressive effects at a subset of genes. • These inhibitor actions should be evaluated in models of adipose tissue inflammation.« less

Clinical and functional outcomes of patients who experience partial response to citalopram: secondary analysis of STAR*D.

PubMed

Dennehy, Ellen B; Marangell, Lauren B; Martinez, James; Balasubramani, G K; Wisniewski, Stephen R

2014-05-01

We analyzed the public STAR*D database to better characterize the baseline clinical characteristics and functional outcomes of patients with major depressive disorder (MDD) who experienced partial response in order to better understand the burden associated with this outcome. Patients (n=2,876) received treatment with citalopram. The last available Quick Inventory of Depressive Symptoms (QIDS-SR) from the 12-week treatment period was used to assign subjects to one of three groups: remitters QIDS-SR≤5; non-responders QIDS-SR >5 and <25% reduction from baseline; and partial responders QIDS-SR >5 and ≥25% reduction from baseline. Baseline sociodemographic and clinical characteristics were compared across groups, as well as functional outcomes at Level 1 exit. RESULTS. Of the 2,876 patients, 943 patients (33%) were classified as remitters, 1069 (37%) as partial responders, and 854 (30%) as non-responders. The groups differed on a number of pre-treatment course of illness variables and comorbidities. In addition, remitters, partial responders, and non-responders all separated on posttreatment quality of life and functional outcomes at Level 1 exit. Partial responders demonstrated significant functional impairment at Level 1 exit, differing significantly from the patients who remitted on quality of life, mental and physical functioning, and social and work-related impairment. Adjusted outcomes showed similar differences. Differences in baseline rates of suicidality, comorbidity, and atypical presentations of depression were also observed between outcome groups. Given the substantial clinical and economic burden associated with functional impairment in depression, the need to fully treat partially responding patients to achieve depression remission and restoration of functioning is highlighted by this work.

Bread making technology influences postprandial glucose response: a review of the clinical evidence.

PubMed

Stamataki, Nikoleta S; Yanni, Amalia E; Karathanos, Vaios T

2017-04-01

Lowering postprandial glucose and insulin responses may have significant beneficial implications for prevention and treatment of metabolic disorders. Bread is a staple food consumed worldwide in a daily basis, and the use of different baking technologies may modify the glucose and insulin response. The aim of this review was to critically record the human studies examining the application of different bread making processes on postprandial glucose and insulin response to bread. Literature is rich of results which show that the use of sourdough fermentation instead of leavening with Saccharomyces cerevisiae is able to modulate glucose response to bread, whereas evidence regarding its efficacy on lowering postprandial insulin response is less clear. The presence of organic acids is possibly involved, but the exact mechanism of action is still to be confirmed. The reviewed data also revealed that the alteration of other processing conditions (method of cooking, proofing period, partial baking freezing technology) can effectively decrease postprandial glucose response to bread, by influencing physical structure and retrogradation of starch. The development of healthier bread products that benefit postprandial metabolic responses is crucial and suggested baking conditions can be used by the bread industry for the promotion of public health.

Cediranib for Metastatic Alveolar Soft Part Sarcoma

PubMed Central

Kummar, Shivaani; Allen, Deborah; Monks, Anne; Polley, Eric C.; Hose, Curtis D.; Ivy, S. Percy; Turkbey, Ismail B.; Lawrence, Scott; Kinders, Robert J.; Choyke, Peter; Simon, Richard; Steinberg, Seth M.; Doroshow, James H.; Helman, Lee

2013-01-01

Purpose Alveolar soft part sarcoma (ASPS) is a rare, highly vascular tumor, for which no effective standard systemic treatment exists for patients with unresectable disease. Cediranib is a potent, oral small-molecule inhibitor of all three vascular endothelial growth factor receptors (VEGFRs). Patients and Methods We conducted a phase II trial of once-daily cediranib (30 mg) given in 28-day cycles for patients with metastatic, unresectable ASPS to determine the objective response rate (ORR). We also compared gene expression profiles in pre- and post-treatment tumor biopsies and evaluated the effect of cediranib on tumor proliferation and angiogenesis using positron emission tomography and dynamic contrast-enhanced magnetic resonance imaging. Results Of 46 patients enrolled, 43 were evaluable for response at the time of analysis. The ORR was 35%, with 15 of 43 patients achieving a partial response. Twenty-six patients (60%) had stable disease as the best response, with a disease control rate (partial response + stable disease) at 24 weeks of 84%. Microarray analysis with validation by quantitative real-time polymerase chain reaction on paired tumor biopsies from eight patients demonstrated downregulation of genes related to vasculogenesis. Conclusion In this largest prospective trial to date of systemic therapy for metastatic ASPS, we observed that cediranib has substantial single-agent activity, producing an ORR of 35% and a disease control rate of 84% at 24 weeks. On the basis of these results, an open-label, multicenter, randomized phase II registration trial is currently being conducted for patients with metastatic ASPS comparing cediranib with another VEGFR inhibitor, sunitinib. PMID:23630200

With great control comes great responsibility: the relationship between perceived academic control, student responsibility, and self-regulation.

PubMed

Fishman, Evan J

2014-12-01

Students' perceived control over academic outcomes has been linked to their use of self-regulated strategies. However, students' sense of responsibility, or internal commitment to produce such outcomes, has not often been considered in this relationship. The purpose of this study was to examine the relationships between perceived academic control (PAC), student responsibility (SR), and knowledge building (KB). Participants were 152 undergraduate students enrolled in an educational technology course. An exploratory factor analysis was conducted to demonstrate the distinction between the PAC and SR constructs. A series of regression analyses were conducted to address the research hypotheses, and a bootstrap test was used to assess the mediating role of SR in the relationship between the PAC variables and KB. Initial evidence regarding the uniqueness of the PAC and SR constructs was provided. PAC (both primary control and secondary control [SC]) were positively and significantly related to SR. KB was positively and significantly related to SR, as was SC. Additionally, SR partially mediated the relationship between the PAC variables and KB. The findings showed that those who perceived the capability to achieve academic outcomes were more likely to feel internally obligated to produce such outcomes. The same was true for students who perceived the capability to psychologically adjust to academic situations. The results also demonstrated that students' sense of responsibility for academic outcomes played a partially mediating role in the relationship between their perceptions of control and reported use of self-regulated behaviour. © 2014 The British Psychological Society.

Partial validation of a French version of the ADHD-rating scale IV on a French population of children with ADHD and epilepsy. Factorial structure, reliability, and responsiveness.

PubMed

Mercier, Catherine; Roche, Sylvain; Gaillard, Ségolène; Kassai, Behrouz; Arzimanoglou, Alexis; Herbillon, Vania; Roy, Pascal; Rheims, Sylvain

2016-05-01

Attention deficit hyperactivity disorder (ADHD) is a well-known comorbidity in children with epilepsy. In English-speaking countries, the scores of the original ADHD-rating scale IV are currently used as main outcomes in various clinical trials in children with epilepsy. In French-speaking countries, several French versions are in use though none has been fully validated yet. We sought here for a partial validation of a French version of the ADHD-RS IV regarding construct validity, internal consistency (i.e., scale reliability), item reliability, and responsiveness in a group of French children with ADHD and epilepsy. The study involved 167 children aged 6-15years in 10 French neuropediatric units. The factorial structure and item reliability were assessed with a confirmatory factorial analysis for ordered categorical variables. The dimensions' internal consistency was assessed with Guttman's lambda 6 coefficient. The responsiveness was assessed by the change in score under methylphenidate and in comparison with a control group. The results confirmed the original two-dimensional factorial structure (inattention, hyperactivity/impulsivity) and showed a satisfactory reliability of most items, a good dimension internal consistency, and a good responsiveness of the total score and the two subscores. The studied French version of the ADHD-RS IV is thus validated regarding construct validity, reliability, and responsiveness. It can now be used in French-speaking countries in clinical trials of treatments involving children with ADHD and epilepsy. The full validation requires further investigations. Copyright © 2016 Elsevier Inc. All rights reserved.

Auditory cortical function during verbal episodic memory encoding in Alzheimer's disease.

PubMed

Dhanjal, Novraj S; Warren, Jane E; Patel, Maneesh C; Wise, Richard J S

2013-02-01

Episodic memory encoding of a verbal message depends upon initial registration, which requires sustained auditory attention followed by deep semantic processing of the message. Motivated by previous data demonstrating modulation of auditory cortical activity during sustained attention to auditory stimuli, we investigated the response of the human auditory cortex during encoding of sentences to episodic memory. Subsequently, we investigated this response in patients with mild cognitive impairment (MCI) and probable Alzheimer's disease (pAD). Using functional magnetic resonance imaging, 31 healthy participants were studied. The response in 18 MCI and 18 pAD patients was then determined, and compared to 18 matched healthy controls. Subjects heard factual sentences, and subsequent retrieval performance indicated successful registration and episodic encoding. The healthy subjects demonstrated that suppression of auditory cortical responses was related to greater success in encoding heard sentences; and that this was also associated with greater activity in the semantic system. In contrast, there was reduced auditory cortical suppression in patients with MCI, and absence of suppression in pAD. Administration of a central cholinesterase inhibitor (ChI) partially restored the suppression in patients with pAD, and this was associated with an improvement in verbal memory. Verbal episodic memory impairment in AD is associated with altered auditory cortical function, reversible with a ChI. Although these results may indicate the direct influence of pathology in auditory cortex, they are also likely to indicate a partially reversible impairment of feedback from neocortical systems responsible for sustained attention and semantic processing. Copyright © 2012 American Neurological Association.

Shindigs, brunches, and rodeos: the neural basis of event words.

PubMed

Bedny, Marina; Dravida, Swethasri; Saxe, Rebecca

2014-09-01

Events (e.g., "running" or "eating") constitute a basic type within human cognition and human language. We asked whether thinking about events, as compared to other conceptual categories, depends on partially independent neural circuits. Indirect evidence for this hypothesis comes from previous studies showing elevated posterior temporal responses to verbs, which typically label events. Neural responses to verbs could, however, be driven either by their grammatical or by their semantic properties. In the present experiment, we separated the effects of grammatical class (verb vs. noun) and semantic category (event vs. object) by measuring neural responses to event nouns (e.g., "the hurricane"). Participants rated the semantic relatedness of event nouns, as well as of two categories of object nouns-animals (e.g., "the alligator") and plants (e.g., "the acorn")-and three categories of verbs-manner of motion (e.g., "to roll"), emission (e.g., "to sparkle"), and perception (e.g., "to gaze"). As has previously been observed, we found larger responses to verbs than to object nouns in the left posterior middle (LMTG) and superior (LSTG) temporal gyri. Crucially, we also found that the LMTG responds more to event than to object nouns. These data suggest that part of the posterior lateral temporal response to verbs is driven by their semantic properties. By contrast, a more superior region, at the junction of the temporal and parietal cortices, responded more to verbs than to all nouns, irrespective of their semantic category. We concluded that the neural mechanisms engaged when thinking about event and object categories are partially dissociable.

Preoperative Intensity Modulated Radiation Therapy and Chemotherapy for Locally Advanced Vulvar Carcinoma: Analysis of Pattern of Relapse

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

Beriwal, Sushil, E-mail: beriwals@upmc.edu; Shukla, Gaurav; Shinde, Ashwin

2013-04-01

Purpose: To examine clinical outcomes and relapse patterns in locally advanced vulvar carcinoma treated using preoperative chemotherapy and intensity modulated radiation therapy (IMRT). Methods and Materials: Forty-two patients with stage I-IV{sub A} (stage I, n=3; stage II, n=13; stage III, n=23; stage IV{sub A}, n=3) vulvar cancer were treated with chemotherapy and IMRT via a modified Gynecological Oncology Group schema using 5-fluorouracil and cisplatin with twice-daily IMRT during the first and last weeks of treatment or weekly cisplatin with daily radiation therapy. Median dose of radiation was 46.4 Gy. Results: Thirty-three patients (78.6%) had surgery for resection of vulva; 13more » of these patients also had inguinal lymph node dissection. Complete pathologic response was seen in 48.5% (n=16) of these patients. Of these, 15 had no recurrence at a median time of 26.5 months. Of the 17 patients with partial pathological response, 8 (47.1%) developed recurrence in the vulvar surgical site within a median of 8 (range, 5-34) months. No patient had grade ≥3 chronic gastrointestinal/genitourinary toxicity. Of those having surgery, 8 (24.2%) developed wound infections requiring debridement. Conclusions: Preoperative chemotherapy/IMRT was well tolerated, with good pathologic response and clinical outcome. The most common pattern of recurrence was local in patients with partial response, and strategies to increase pathologic response rate with increasing dose or adding different chemotherapy need to be explored to help further improve outcomes.« less

Natural Killer Cell Functions during the Innate Immune Response to Pathogenic Streptococci

PubMed Central

Lemire, Paul; Galbas, Tristan; Thibodeau, Jacques; Segura, Mariela

2017-01-01

Dendritic cells (DCs) and NK cells play a crucial role in the first phase of host defense against infections. Group B Streptococcus (GBS) and Streptococcus suis are encapsulated streptococci causing severe systemic inflammation, leading to septicemia and meningitis. Yet, the involvement of NK cells in the innate immune response to encapsulated bacterial infection is poorly characterized. Here, it was observed that these two streptococcal species rapidly induce the release of IFN-γ and that NK cells are the major cell type responsible for this production during the acute phase of the infection. Albeit S. suis capacity to activate NK cells was lower than that of GBS, these cells partially contribute to S. suis systemic infection; mainly through amplification of the inflammatory loop. In contrast, such a role was not observed during GBS systemic infection. IFN-γ release by NK cells required the presence of DCs, which in turn had a synergistic effect on DC cytokine production. These responses were mainly mediated by direct DC-NK cell contact and partially dependent on soluble factors. Though IL-12 and LFA-1 were shown to be critical in S. suis-mediated activation of the DC-NK cell crosstalk, different or redundant molecular pathways modulate DC-NK interactions during GBS infection. The bacterial capsular polysaccharides also differently modulated NK cell activation. Together, these results demonstrated a role of NK cells in the innate immune response against encapsulated streptococcal infections; yet the molecular pathways governing NK activation seem to differ upon the pathogen and should not be generalized when studying bacterial infections. PMID:28706510

A self-photoprotection mechanism helps Stipa baicalensis adapt to future climate change

PubMed Central

Song, Xiliang; Zhou, Guangsheng; Xu, Zhenzhu; Lv, Xiaomin; Wang, Yuhui

2016-01-01

We examined the photosynthetic responses of Stipa baicalensis to relative long-term exposure (42 days) to the predicted elevated temperature and water availability changes to determine the mechanisms through which the plant would acclimate to future climate change. Two thermal regimes (ambient and +4 °C) and three irrigation levels (partial, normal and excess) were used in environmental control chambers. The gas exchange parameters, light response curves and A/Ci curves were determined. The elevated temperature and partial irrigation reduced the net photosynthetic rate due to a limitation in the photosynthetic capacity instead of the intercellular CO2 concentration. Partial irrigation decreased Rubisco activation and limited RuBP regeneration. The reduction in Vcmax increased with increasing temperature. Excess irrigation offset the negative effect of drought and led to a partial recovery of the photosynthetic capacity. Although its light use efficiency was restricted, the use of light and dark respiration by Stipa baicalensis was unchanged. We concluded that nonstomatal limitation was the primary reason for photosynthesis regulation in Stipa baicalensis under relative long-term climate change conditions. Although climate change caused reductions in the light use efficiency and photosynthetic rate, a self-photoprotection mechanism in Stipa baicalensis resulted in its high ability to maintain normal live activities. PMID:27161934

Role of mitochondrial dysfunction in neurotoxicity of MPP+: partial protection of PC12 cells by acetyl-L-carnitine.

PubMed

Virmani, Ashraf; Gaetani, Franco; Binienda, Zbigniew; Xu, Alex; Duhart, Helen; Ali, Syed F

2004-10-01

The damage to the central nervous system that is observed after administration of either methamphetamine (METH) or 1-methyl-4-phenylpyridinium (MPP+), the neurotoxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), is known to be linked to dopamine (DA). The underlying neurotoxicity mechanism for both METH and MPP+ seem to involve free radical formation and impaired mitochondrial function. The MPP+ is thought to selectively kill nigrostriatal dopaminergic neurons by inhibiting mitochondrial complex I, with cell death being attributed to oxidative stress damage to these vulnerable DA neurons. In the present study, MPP+ was shown to significantly inhibit the response to MTT by cultured PC12 cells. This inhibitory action of MPP+ could be partially reversed by the co-incubation of the cells with the acetylated form of carnitine, acetyl-L-carnitine (ALC). Since at least part of the toxic action of MPP+ is related to mitochondrial inhibition, the partial reversal of the inhibition of MTT response by ALC could involve a partial restoration of mitochondrial function. The role carnitine derivatives, such as ALC, play in attenuating MPP+ and METH-evoked toxicity is still under investigation to elucidate the contribution of mitochondrial dysfunction in mechanisms of neurotoxicity.

Tunability of RF-Responses by Plasmonic Dielectric Amplification Using Branched e- -Polarizable C60-Adducts on Magnetic (Postprint)

DTIC Science & Technology

2016-07-18

MAGNETIC (POSTPRINT) Min Wang, Tzuyang Yu, and Long Y. Chiang University of Massachusetts - Lowell Augustine Urbas and Zahyun Ku AFRL...TUNABILITY OF RF-RESPONSES BY PLASMONIC DIELECTRIC AMPLIFICATION USING BRANCHED E−‑ POLARIZABLE C60-ADDUCTS ON MAGNETIC (POSTPRINT) 5a. CONTRACT NUMBER...core–shell nanoparticles (NPs) consisting of a highly magnetic γ-FeOx@AuNP core and an e–-polarizable C60-DPAF adduct-derived partially bilayered

Efficacy, safety, and cost of pomalidomide in relapsed and refractory multiple myeloma.

PubMed

Gueneau, Pauline; Chretien, Marie-Lorraine; Cransac-Miet, Amelie; Aho, Ludwig Serge; Lafon, Ingrid; Favennec, Camille; Guy, Julien; Caillot, Denis; Boulin, Mathieu

2018-05-01

To investigate the efficacy, safety, and cost of a pomalidomide-dexamethasone regimen in patients with relapsed and refractory multiple myeloma (RRMM). All patients (n = 63) treated with pomalidomide-dexamethasone for RRMM in our university hospital between August 2013 and October 2015 were included. Pomalidomide was discontinued early due to progression (before the 4th cycle) in 17 (27%) patients. No case was discontinued for intolerance. The only independent factor that predicted early pomalidomide discontinuation was time from diagnosis to pomalidomide initiation <3 years. Overall response rate was 51% including complete response in 8%, very good partial response in 25%, and partial response in 19% patients. Thirteen (33%) patients showed stable disease. Median overall survival was 6.4 months in the 17 patients who discontinued pomalidomide early vs 26.8 months in the 14 patients with stable disease vs not achieved in the 32 responders (log-rank; P < 10 -3 ). The most common grade ≥3 adverse events were neutropenia (14%) and infections (25%). The incremental cost-effectiveness ratio of pomalidomide-dexamethasone compared with dexamethasone alone was estimated at €39 911 per life-year gained. The study demonstrated that pomalidomide-dexamethasone regimen has a long-term favorable safety-efficacy profile in RRMM patients. The survival benefit is substantial even in patients with stable disease. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Sequential promotion of normal and leukemic hemopoiesis by recombinant human granulocyte colony-stimulating factor during the course of myelodysplastic syndrome.

PubMed

Ueda, T; Kawai, Y; Sugiyama, T; Takeuchi, N; Yoshida, A; Iwasaki, H; Wano, Y; Tsutani, H; Kamada, N; Nakamura, T

1993-12-01

A 48-year-old man developed refractory anemia with excess of blasts in transformation. Complete response was achieved by low-dose ara-C therapy, but he relapsed 15 months later, with pancytopenia and 13.0% myeloblasts in normocellular marrow. He was treated unsuccessfully with prednisolone, metenolone, and 1-alpha-hydroxyvitamin D3 for 8 weeks. He then developed life-threatening pneumonia and was treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF Filgrastim; 125 micrograms/day s.c.). The pneumonia resolved and, interestingly, he achieved a partial response, with normal blood cell counts and only a few dysmyelopoietic cells in the marrow. However, thrombocytopenia progressed when rhG-CSF administration was tapered. When the dose was increased again, leukemic blasts were found to proliferate. When rhG-CSF was discontinued, blasts rapidly decreased in the peripheral blood. Chromosomal analysis revealed a complex abnormality during the first relapse, a normal 46,XY karyotype during the partial response, and recurrence of the same complex abnormality during leukemic transformation. The stimulation index of marrow mononuclear cells cultured with rhG-CSF increased with disease progression. These findings suggest that rhG-CSF initially stimulated the selective proliferation of normal hemopoietic cells, but the evolution or selection of a leukemic clone responsive to rhG-CSF appears to have occurred subsequently.

Favorable Response of Metastatic Merkel Cell Carcinoma to Targeted 177Lu-DOTATATE Therapy: Will PRRT Evolve to Become an Important Approach in Receptor-Positive Cases?

PubMed

Basu, Sandip; Ranade, Rohit

2016-06-01

This report illustrates an excellent partial response of Merkel cell carcinoma with multiple bilobar hepatic metastases to a single cycle of peptide receptor radionuclide therapy (PRRT) with (177)Lu-DOTATATE. This response, coupled with minimal side effects, warrants consideration of this therapy early in the disease course (rather than at an advanced stage after failure of other therapies) if the metastatic lesions exhibit adequate tracer avidity on somatostatin receptor-based imaging. Our patient showed progression of systemic disease after having undergone a second surgery and adjuvant radiotherapy to the head and neck, as well as chemotherapy, and hence was considered a candidate for PRRT. In a pretreatment study, the metastatic lesions demonstrated avidity to both somatostatin receptors and (18)F-FDG. Three months after the first cycle of treatment, when the patient was being evaluated for a second cycle, both imaging parameters showed evidence of a partial response that included nearly complete resolution of the two previously seen lesions. In view of the relatively good tolerability, minimal side effects, and targeted nature of the treatment, PRRT may evolve to become the first-line therapy for metastatic Merkel cell carcinoma and should be examined further in a larger number of patients. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Effect of partial supplementation of sun-dried Azolla as a protein source on the immunity and antioxidant status of commercial broilers.

PubMed

Chichilichi, Biswal; Mohanty, G P; Mishra, S K; Pradhan, C R; Behura, N C; Das, A; Behera, K

2015-09-01

The present study was conducted to evaluate the effect of partial supplementation of sun-dried Azolla as a protein source on the immunity of commercial broilers in coastal Odisha. A 180 day-old broiler chicks were distributed in six dietary treatments viz. C1: Basal diet, C2: Basal diet + enzyme, T1: Basal diet +5% protein from Azolla, T2: Basal diet + 5% protein from Azolla + enzyme, T3: Basal diet +10% protein from Azolla, and T4: Basal diet + 10% protein from Azolla + enzyme. Cutaneous basophilc hypersensitivity (CBH) and humoral immunity response were determined at the 38(th) day of age. At 42(nd) day, the weight of lymphoid organs, an antioxidant enzyme, and lipid peroxidation activity were determined. The CBH response did not differ significantly among the treated groups, but the sheep red blood cells response was significantly higher in T4. The weight of lymphoid organs or immune organs of all the treated groups did not differ significantly (p>0.05). The erythrocyte catalase level of T4 group was found to be significantly higher than rest of the treated groups except T3. It may be concluded that supplementation of Azolla at 10% of dietary protein requirement along with enzyme supplementation in an isonitrogenous diet showed a better immune response in broilers.

Effect of partial supplementation of sun-dried Azolla as a protein source on the immunity and antioxidant status of commercial broilers

PubMed Central

Chichilichi, Biswal; Mohanty, G. P.; Mishra, S. K.; Pradhan, C. R.; Behura, N. C.; Das, A.; Behera, K.

2015-01-01

Aim: The present study was conducted to evaluate the effect of partial supplementation of sun-dried Azolla as a protein source on the immunity of commercial broilers in coastal Odisha. Materials and Methods: A 180 day-old broiler chicks were distributed in six dietary treatments viz. C1: Basal diet, C2: Basal diet + enzyme, T1: Basal diet +5% protein from Azolla, T2: Basal diet + 5% protein from Azolla + enzyme, T3: Basal diet +10% protein from Azolla, and T4: Basal diet + 10% protein from Azolla + enzyme. Cutaneous basophilc hypersensitivity (CBH) and humoral immunity response were determined at the 38th day of age. At 42nd day, the weight of lymphoid organs, an antioxidant enzyme, and lipid peroxidation activity were determined. Results: The CBH response did not differ significantly among the treated groups, but the sheep red blood cells response was significantly higher in T4. The weight of lymphoid organs or immune organs of all the treated groups did not differ significantly (p>0.05). The erythrocyte catalase level of T4 group was found to be significantly higher than rest of the treated groups except T3. Conclusion: It may be concluded that supplementation of Azolla at 10% of dietary protein requirement along with enzyme supplementation in an isonitrogenous diet showed a better immune response in broilers. PMID:27047208

LIS1-associated classic lissencephaly: A retrospective, multicenter survey of the epileptogenic phenotype and response to antiepileptic drugs.

PubMed

Herbst, Saskia M; Proepper, Christiane R; Geis, Tobias; Borggraefe, Ingo; Hahn, Andreas; Debus, Otfried; Haeussler, Martin; von Gersdorff, Gero; Kurlemann, Gerhard; Ensslen, Matthias; Beaud, Nathalie; Budde, Joerg; Gilbert, Michael; Heiming, Ralf; Morgner, Rita; Philippi, Heike; Ross, Sophia; Strobl-Wildemann, Gertrud; Muelleder, Kerstin; Vosschulte, Paul; Morris-Rosendahl, Deborah J; Schuierer, Gerhard; Hehr, Ute

2016-04-01

Patients with LIS1-associated classic lissencephaly typically present with severe psychomotor retardation and drug-resistant epilepsy within the first year. To analyze the epileptogenic phenotype and response to antiepileptic therapy in LIS1-associated classic lissencephaly. Retrospective evaluation of 22 patients (8 months-24 years) with genetically and radiologically confirmed LIS1-associated classic lissencephaly in 16 study centers. All patients in our cohort developed drug-resistant epilepsy. In 82% onset of seizures was noted within the first six months of life, most frequently with infantile spasms. Later in infancy the epileptogentic phenotype became more variable and included different forms of focal seizures as well generalized as tonic-clonic seizures, with generalized tonic-clonic seizures being the predominant type. Lamotrigine and valproate were rated most successful with good or partial response rates in 88-100% of the patients. Both were evaluated significantly better than levetiracetam (p<0.05) and sulthiame (p<0.01) in the neuropediatric assessment and better than levetiracetam, sulthiame (p<0.05) and topiramate (p<0.01) in the family survey. Phenobarbital and vigabatrin achieved good or partial response in 62-83% of the patients. Our findings suggest that patients with LIS1-associated lissencephaly might benefit most from lamotrigine, valproate, vigabatrin or phenobarbital. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Comment on Birgegard and Sohlberg's (1999) suggestions for research in subliminal psychodynamic activation.

PubMed

Fudin, R

2000-06-01

Methodological changes in subliminal psychodynamic activation experiments based on the assumption that multiletter messages can be encoded automatically (Birgegard & Sohlberg, 1999) are questioned. Their contention that partial experimental messages and appropriate nonsense anagram controls (Fudin, 1986) need not be presented in every experiment is supported, with a reservation. If the difference between responses to the complete message and its control is significant in the predicted direction, then Fudin's procedure should be used. A nonsignificant difference between the response to each partial message and its control is needed to support the assumption of proponents of subliminal psychodynamic activation that successful outcomes are effected by the encoding of the meaning of a complete message. Experiments in subliminal psychodynamic activation can be improved if their methodologies take into account variables that may operate when subliminal stimuli are presented and encoded.

Liver failure induces a systemic inflammatory response. Prevention by recombinant N-terminal bactericidal/permeability-increasing protein.

PubMed Central

Boermeester, M. A.; Houdijk, A. P.; Meyer, S.; Cuesta, M. A.; Appelmelk, B. J.; Wesdorp, R. I.; Hack, C. E.; Van Leeuwen, P. A.

1995-01-01

The observed increased susceptibility of patients with fulminant hepatic failure for local and systemic infections has been hypothesized to be due to a failure for the hepatic clearance function and subsequent leaking of endogenous endotoxins into the systemic circulation. However, experimental evidence for such a systemic inflammation during liver failure due to endogenous endotoxemia is lacking. Therefore, we designed a study to clarify whether circulating endotoxins due to liver failure could lead to the development of systemic inflammations. In a rat model for liver failure induced by a two-thirds partial hepatectomy, we evaluated the course of circulating tumor necrosis factor and interleukin-6, changes in blood chemistry and hemodynamics, and histopathological changes in the lungs. Partially hepatectomized animals, but not sham-operated animals, demonstrated cardiac failure, increased levels of creatinin and urea, metabolic acidosis, high plasma levels of tumor necrosis factor and interleukin-6, and an influx of PMNs in the lungs-together indicating the development of a systemic inflammatory response. Continuous infusion of recombinant N-terminal bactericidal/permeability-increasing protein (rBPI23), a well described endotoxin-neutralizing protein, prevented these inflammatory reactions. Ex vivo experiments with rat plasma samples confirmed the presence of circulating endotoxins in partially hepatectomized rats as opposed to those treated with rBPI23. Thus, our results indicate that the early phase of liver failure induces a systemic inflammatory response triggered by circulating endotoxins, which can be prevented by perioperative infusion of rBPI23. Images Figure 2 PMID:7485405

shl, a New set of Arabidopsis mutants with exaggerated developmental responses to available red, far-red, and blue light.

PubMed

Pepper, A E; Seong-Kim, M; Hebst, S M; Ivey, K N; Kwak, S J; Broyles, D E

2001-09-01

The interaction of light perception with development is the subject of intensive genetic analysis in the model plant Arabidopsis. We performed genetic screens in low white light-a threshold condition in which photomorphogenetic signaling pathways are only partially active-for ethyl methane sulfonate-generated mutants with altered developmental phenotypes. Recessive mutants with exaggerated developmental responses were obtained in eight complementation groups designated shl for seedlings hyperresponsive to light. shl1, shl2, shl5, and shl3 shl4 (double mutant) seedlings showed limited or no phenotypic effects in darkness, but showed significantly enhanced inhibition of hypocotyl elongation in low-white, red, far-red, blue, and green light across a range of fluences. These results reflect developmental hyper-responsiveness to signals generated by both phytochrome and cryptochrome photoreceptors. The shl11 mutant retained significant phenotypic effects on hypocotyl length in both the phyA mutant and phyB mutant backgrounds but may be dependent on CRY1 for phenotypic expression in blue light. The shl2 phenotype was partially dependent on PHYB, PHYA, and CRY1 in red, far-red, and blue light, respectively. shl2 and, in particular, shl1 were partially dependent on HY5 activity for their light-hyperresponsive phenotypes. The SHL genes act (genetically) as light-dependent negative regulators of photomorphogenesis, possibly in a downstream signaling or developmental pathway that is shared by CRY1, PHYA, and PHYB and other photoreceptors (CRY2, PHYC, PHYD, and PHYE).

Partial oxidation of landfill leachate in supercritical water: Optimization by response surface methodology

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

Gong, Yanmeng; Wang, Shuzhong; Xu, Haidong

Highlights: • Partial oxidation of landfill leachate in supercritical water was investigated. • The process was optimized by Box–Behnken design and response surface methodology. • GY{sub H2}, TRE and CR could exhibit up to 14.32 mmol·gTOC{sup −1}, 82.54% and 94.56%. • Small amounts of oxidant can decrease the generation of tar and char. - Abstract: To achieve the maximum H{sub 2} yield (GY{sub H2}), TOC removal rate (TRE) and carbon recovery rate (CR), response surface methodology was applied to optimize the process parameters for supercritical water partial oxidation (SWPO) of landfill leachate in a batch reactor. Quadratic polynomial models formore » GY{sub H2}, CR and TRE were established with Box–Behnken design. GY{sub H2}, CR and TRE reached up to 14.32 mmol·gTOC{sup −1}, 82.54% and 94.56% under optimum conditions, respectively. TRE was invariably above 91.87%. In contrast, TC removal rate (TR) only changed from 8.76% to 32.98%. Furthermore, carbonate and bicarbonate were the most abundant carbonaceous substances in product, whereas CO{sub 2} and H{sub 2} were the most abundant gaseous products. As a product of nitrogen-containing organics, NH{sub 3} has an important effect on gas composition. The carbon balance cannot be reached duo to the formation of tar and char. CR increased with the increase of temperature and oxidation coefficient.« less

Evaluation of partial beta-adrenoceptor agonist activity.

PubMed

Lipworth, B J; Grove, A

1997-01-01

A partial beta-adrenoceptor (beta-AR) agonist will exhibit opposite agonist and antagonist activity depending on the prevailing degree of adrenergic tone or the presence of a beta-AR agonist with higher intrinsic activity. In vivo partial beta-AR agonist activity will be evident at rest with low endogenous adrenergic tone, as for example with chronotropicity (beta 1/beta 2), inotropicity (beta 1) or peripheral vasodilatation and finger tremor (beta 2). beta-AR blocking drugs which have partial agonist activity may exhibit a better therapeutic profile when used for hypertension because of maintained cardiac output without increased systemic vascular resistance, along with an improved lipid profile. In the presence of raised endogenous adrenergic tone such as exercise or an exogenous full agonist, beta-AR subtype antagonist activity will become evident in terms of effects on exercise induced heart rate (beta 1) and potassium (beta 2) responses. Reduction of exercise heart rate will occur to a lesser degree in the case of a beta-adrenoceptor blocker with partial beta 1-AR agonist activity compared with a beta-adrenoceptor blocker devoid of partial agonist activity. This may result in reduced therapeutic efficacy in the treatment of angina on effort when using beta-AR blocking drugs with partial beta 1-AR agonist activity. Effects on exercise hyperkalaemia are determined by the balance between beta 2-AR partial agonist activity and endogenous adrenergic activity. For predominantly beta 2-AR agonist such as salmeterol and salbutamol, potentiation of exercise hyperkalaemia occurs. For predominantly beta 2-AR antagonists such as carteolol, either potentiation or attenuation of exercise hyperkalaemia occurs at low and high doses respectively. beta 2-AR partial agonist activity may also be expressed as antagonism in the presence of an exogenous full agonist, as for example attenuation of fenoterol induced responses by salmeterol. Studies are required to investigate whether this phenomenon is relevant in the setting of acute severe asthma.

Assessment of simulated high-dose partial-body irradiation by PCC-R assay.

PubMed

Romero, Ivonne; García, Omar; Lamadrid, Ana I; Gregoire, Eric; González, Jorge E; Morales, Wilfredo; Martin, Cécile; Barquinero, Joan-Francesc; Voisin, Philippe

2013-09-01

The estimation of the dose and the irradiated fraction of the body is important information in the primary medical response in case of a radiological accident. The PCC-R assay has been developed for high-dose estimations, but little attention has been given to its applicability for partial-body irradiations. In the present work we estimated the doses and the percentage of the irradiated fraction in simulated partial-body radiation exposures at high doses using the PCC-R assay. Peripheral whole blood of three healthy donors was exposed to doses from 0-20 Gy, with ⁶⁰Co gamma radiation. To simulate partial body irradiations, irradiated and non-irradiated blood was mixed to obtain proportions of irradiated blood from 10-90%. Lymphocyte cultures were treated with Colcemid and Calyculin-A before harvest. Conventional and triage scores were performed for each dose, proportion of irradiated blood and donor. The Papworth's u test was used to evaluate the PCC-R distribution per cell. A dose-response relationship was fitted according to the maximum likelihood method using the frequencies of PCC-R obtained from 100% irradiated blood. The dose to the partially irradiated blood was estimated using the Contaminated Poisson method. A new D₀ value of 10.9 Gy was calculated and used to estimate the initial fraction of irradiated cells. The results presented here indicate that by PCC-R it is possible to distinguish between simulated partial- and whole-body irradiations by the u-test, and to accurately estimate the dose from 10-20 Gy, and the initial fraction of irradiated cells in the interval from 10-90%.

Preoperative Single-Fraction Partial Breast Radiation Therapy: A Novel Phase 1, Dose-Escalation Protocol With Radiation Response Biomarkers

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

Horton, Janet K., E-mail: janet.horton@duke.edu; Blitzblau, Rachel C.; Yoo, Sua

Purpose: Women with biologically favorable early-stage breast cancer are increasingly treated with accelerated partial breast radiation (PBI). However, treatment-related morbidities have been linked to the large postoperative treatment volumes required for external beam PBI. Relative to external beam delivery, alternative PBI techniques require equipment that is not universally available. To address these issues, we designed a phase 1 trial utilizing widely available technology to 1) evaluate the safety of a single radiation treatment delivered preoperatively to the small-volume, intact breast tumor and 2) identify imaging and genomic markers of radiation response. Methods and Materials: Women aged ≥55 years with clinically node-negative,more » estrogen receptor–positive, and/or progesterone receptor–positive HER2−, T1 invasive carcinomas, or low- to intermediate-grade in situ disease ≤2 cm were enrolled (n=32). Intensity modulated radiation therapy was used to deliver 15 Gy (n=8), 18 Gy (n=8), or 21 Gy (n=16) to the tumor with a 1.5-cm margin. Lumpectomy was performed within 10 days. Paired pre- and postradiation magnetic resonance images and patient tumor samples were analyzed. Results: No dose-limiting toxicity was observed. At a median follow-up of 23 months, there have been no recurrences. Physician-rated cosmetic outcomes were good/excellent, and chronic toxicities were grade 1 to 2 (fibrosis, hyperpigmentation) in patients receiving preoperative radiation only. Evidence of dose-dependent changes in vascular permeability, cell density, and expression of genes regulating immunity and cell death were seen in response to radiation. Conclusions: Preoperative single-dose radiation therapy to intact breast tumors is well tolerated. Radiation response is marked by early indicators of cell death in this biologically favorable patient cohort. This study represents a first step toward a novel partial breast radiation approach. Preoperative radiation should be tested in future clinical trials because it has the potential to challenge the current treatment paradigm and provide a path forward to identify radiation response biomarkers.« 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.

7 CFR 4280.17 - Additional REDL terms.

Code of Federal Regulations, 2014 CFR

2014-01-01

... the Zero-Interest Loan to RBS even if the Ultimate Recipient does not repay the Intermediary. (b) The Intermediary is responsible for remitting any partial or full payment to RBS at the time the Ultimate Recipient...

7 CFR 4280.17 - Additional REDL terms.

Code of Federal Regulations, 2013 CFR

2013-01-01

... the Zero-Interest Loan to RBS even if the Ultimate Recipient does not repay the Intermediary. (b) The Intermediary is responsible for remitting any partial or full payment to RBS at the time the Ultimate Recipient...

7 CFR 4280.17 - Additional REDL terms.

Code of Federal Regulations, 2012 CFR

2012-01-01

... the Zero-Interest Loan to RBS even if the Ultimate Recipient does not repay the Intermediary. (b) The Intermediary is responsible for remitting any partial or full payment to RBS at the time the Ultimate Recipient...

7 CFR 4280.17 - Additional REDL terms.

Code of Federal Regulations, 2010 CFR

2010-01-01

... the Zero-Interest Loan to RBS even if the Ultimate Recipient does not repay the Intermediary. (b) The Intermediary is responsible for remitting any partial or full payment to RBS at the time the Ultimate Recipient...

7 CFR 4280.17 - Additional REDL terms.

Code of Federal Regulations, 2011 CFR

2011-01-01

... the Zero-Interest Loan to RBS even if the Ultimate Recipient does not repay the Intermediary. (b) The Intermediary is responsible for remitting any partial or full payment to RBS at the time the Ultimate Recipient...

49 CFR 234.106 - Partial activation.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION GRADE CROSSING SAFETY, INCLUDING SIGNAL SYSTEMS, STATE ACTION PLANS, AND EMERGENCY NOTIFICATION SYSTEMS Response to Credible Reports of Warning System Malfunction at Highway-Rail...

49 CFR 234.106 - Partial activation.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION GRADE CROSSING SAFETY, INCLUDING SIGNAL SYSTEMS, STATE ACTION PLANS, AND EMERGENCY NOTIFICATION SYSTEMS Response to Credible Reports of Warning System Malfunction at Highway-Rail...

49 CFR 234.106 - Partial activation.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION GRADE CROSSING SAFETY, INCLUDING SIGNAL SYSTEMS, STATE ACTION PLANS, AND EMERGENCY NOTIFICATION SYSTEMS Response to Credible Reports of Warning System Malfunction at Highway-Rail...

Rising Food Prices: Who's Responsible?

ERIC Educational Resources Information Center

Brown, Lester R.

1973-01-01

Rise in food prices can be partially attributed to the high food consumption level throughout Europe and North America, coupled with failure to evolve systems for more production of cattle, soybeans, and fisheries at lower cost. (PS)

Building physiological toughness: Some aversive events during extinction may attenuate return of fear.

PubMed

Culver, Najwa C; Stevens, Stephan; Fanselow, Michael S; Craske, Michelle G

2018-03-01

Although exposure therapy is an effective treatment for anxiety disorders, fear sometimes returns following successful therapy. Recent literature in animal models indicates that incorporating some aversive events into extinction training may offset these return of fear effects. The effect of occasional reinforced extinction trials was investigated in a sample of thirty-nine participants using a fear conditioning and extinction paradigm. Participants either underwent traditional extinction procedures during which the conditional stimulus which had been paired with the unconditional stimulus (US) during acquisition training (CS+) was presented alone with no presentations of the US or partially reinforced extinction during which there were several unpredicted CS+/US pairings. As measured by skin conductance responses, physiological fear responding remained elevated during extinction for participants who experienced partially reinforced extinction; however, these participants demonstrated protection from rapid reacquisition effects. Results from the subjective US-expectancy ratings did not provide evidence of protection against rapid reacquisition in the partially reinforced extinction group; however, there was evidence of protection from spontaneous recovery effects. Lastly, as measured by valence ratings, it was unclear whether partially reinforced extinction provided protection from fear recovery effects. Although participants who experienced partially reinforced extinction demonstrated protection from rapid reacquisition as measured by skin conductance responses, they also demonstrated significantly higher levels of physiological fear responding during extinction which made the results of the spontaneous recovery test more difficult to interpret. Occasional CS-US pairings during extinction may protect against return of fear effects. Clinical implications are discussed. Published by Elsevier Ltd.

Growth Responses of Neurospora crassa to Increased Partial Pressures of the Noble Gases and Nitrogen

PubMed Central

Buchheit, R. G.; Schreiner, H. R.; Doebbler, G. F.

1966-01-01

Buchheit, R. G. (Union Carbide Corp., Tonawanda, N.Y.), H. R. Schreiner, and G. F. Doebbler. Growth responses of Neurospora crassa to increased partial pressures of the noble gases and nitrogen. J. Bacteriol. 91:622–627. 1966.—Growth rate of the fungus Neurospora crassa depends in part on the nature of metabolically “inert gas” present in its environment. At high partial pressures, the noble gas elements (helium, neon, argon, krypton, and xenon) inhibit growth in the order: Xe > Kr> Ar ≫ Ne ≫ He. Nitrogen (N2) closely resembles He in inhibitory effectiveness. Partial pressures required for 50% inhibition of growth were: Xe (0.8 atm), Kr (1.6 atm), Ar (3.8 atm), Ne (35 atm), and He (∼ 300 atm). With respect to inhibition of growth, the noble gases and N2 differ qualitatively and quantitatively from the order of effectiveness found with other biological effects, i.e., narcosis, inhibition of insect development, depression of O2-dependent radiation sensitivity, and effects on tissue-slice glycolysis and respiration. Partial pressures giving 50% inhibition of N. crassa growth parallel various physical properties (i.e., solubilities, solubility ratios, etc.) of the noble gases. Linear correlation of 50% inhibition pressures to the polarizability and of the logarithm of pressure to the first and second ionization potentials suggests the involvement of weak intermolecular interactions or charge-transfer in the biological activity of the noble gases. PMID:5883104

Ambient ozone and pulmonary innate immunity

PubMed Central

Al-Hegelan, Mashael; Tighe, Robert M.; Castillo, Christian; Hollingsworth, John W.

2013-01-01

Ambient ozone is a criteria air pollutant that impacts both human morbidity and mortality. The effect of ozone inhalation includes both toxicity to lung tissue and alteration of the host immunologic response. The innate immune system facilitates immediate recognition of both foreign pathogens and tissue damage. Emerging evidence supports that ozone can modify the host innate immune response and that this response to inhaled ozone is dependent on genes of innate immunity. Improved understanding of the complex interaction between environmental ozone and host innate immunity will provide fundamental insight into the pathogenesis of inflammatory airways disease. We review the current evidence supporting that environmental ozone inhalation: (1) modifies cell types required for intact innate immunity, (2) is partially dependent on genes of innate immunity, (3) primes pulmonary innate immune responses to LPS, and (4) contributes to innate-adaptive immune system cross-talk. PMID:21132467

Atypical depressive symptoms as a predictor of treatment response to exercise in Major Depressive Disorder.

PubMed

Rethorst, Chad D; Tu, Jian; Carmody, Thomas J; Greer, Tracy L; Trivedi, Madhukar H

2016-08-01

Effective treatment of Major Depressive Disorder (MDD) will require the development of alternative treatments and the ability for clinicians to match patients with the treatment likely to produce the greatest effect. We examined atypical depression subtype as a predictor of treatment response to aerobic exercise augmentation in persons with non-remitted MDD. Our results revealed a small-to-moderate effect, particularly in a group assigned to high-dose exercise (semi-partial eta-squared =0.0335, p=0.0735), indicating that those with atypical depression tended to have larger treatment response to exercise. Through this hypothesis-generating analysis, we indicate the need for research to examine depression subtype, along with other demographic, clinical and biological factors as predictors of treatment response to exercise. Copyright © 2016 Elsevier B.V. All rights reserved.

Mechanism of action of nicotine in isolated iris sphincter preparations of rabbit.

PubMed Central

Hisayama, T.; Shinkai, M.; Takayanagi, I.; Morimoto, S.; Ishida, K.

1988-01-01

1. Nicotine produced a transient contraction of rabbit isolated iris sphincter muscle, a parasympathetic ganglion-free tissue. The response to nicotine was antagonized by hexamethonium, but was insensitive to tetrodotoxin (TTX). While single treatments with atropine, capsaicin or [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-substance P (rpwwL-SP) partially blocked the response, combined treatment abolished it. 2. Chronic treatment of animals with nicotine added to the drinking water (about 12 mg kg-1 per day) had no effect on the responsiveness to nicotine or the pharmacological properties of nicotine-induced contraction. 3. These results suggest that acetylcholine and tachykinin(s) released via sodium channel-independent mechanisms from nerve terminals of parasympathetic and primary sensory nerves, respectively, are involved in the nicotine-induced contractile response. PMID:3228672

Conscientiousness and Extraversion relate to responsiveness to tempo in dance.

PubMed

Carlson, Emily; Burger, Birgitta; London, Justin; Thompson, Marc R; Toiviainen, Petri

2016-10-01

Previous research has shown broad relationships between personality and dance, but the relationship between personality and specific structural features of music has not been explored. The current study explores the influence of personality and trait empathy on dancers' responsiveness to small tempo differences between otherwise musically identical stimuli, measured by difference in the amount in acceleration of key joints. Thirty participants were recorded using motion capture while dancing to excerpts from six popular songs that were time-stretched to be slightly faster or slower than their original tempi. Analysis revealed that higher conscientiousness and lower extraversion both correlated with greater responsiveness to tempo change. Partial correlation analysis revealed that conscientiousness remained significantly correlated with responsiveness when extraversion was controlled, but not vice versa. No effect of empathy was found. Implications are discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

Facing the new facts of retirement income adequacy.

PubMed

Mills, Marjorie S; Young, Michael L

2004-01-01

A range of new factors is responsible for the current problem with insufficient retirement resources. Changes inside and outside the organization share partial responsibility, as do employee behaviors. In addition, other factors simply have been overlooked as employers and employees think about retirement income adequacy. The authors describe the current situation, discuss the significant risks it creates for both employers and employees and advise employers on what they should do to help employees build a more secure future in retirement.

Pharmacologic Dose Testosterone to Treat Castration-Resistant Prostate Cancer: Mechanisms of Action and Drivers of Response

DTIC Science & Technology

2017-10-01

highly expressed in ovarian cancers, with approximately 44% to 82% of tumors staining positive for AR [139–141]. Polycystic ovarian syndrome (PCOS...stable disease, n = 3; partial response, n = 2) [167]. A case report has also reported favorable outcomes when ADT was combined with radiation therapy in a... syndrome . Obstet. Gynecol. 1996, 88, 554–559. [CrossRef] 143. Resta, L.; Russo, S.; Colucci, G.A.; Prat, J. Morphologic precursors of ovarian epithelial

Effects of VIE tagging and partial tissue sampling on the immune response of three-spined stickleback Gasterosteus aculeatus.

PubMed

Henrich, T; Hafer, N; Mobley, K B

2014-09-01

A 14 day experiment on effects of visible implant elastomer (VIE) tagging and spine-clipping of three-spined stickleback Gasterosteus aculeatus showed significant increases in immune response, particularly in the granulocyte:lymphocyte ratio, in both treatments and the sham control. A minimum two-week recovery after handling, anaesthesia, tagging and spine-clipping is recommended to minimize effect of manipulation on the immune system. © 2014 The Fisheries Society of the British Isles.

Task IV: Groundshock-Induced Hydrogeologic Response: Volume 2. Hydrologic Response of Deep Based Systems to Blast Loading

DTIC Science & Technology

1994-09-01

north-south. Width of the cap rock is approximately 1.5 miles, length about 3 miles and area about 4.4 square miles. According to Thordarson (1965...The volcanic tuffs making up the mesa are of moderately recent (Miocene) to very recent (Pliocene) origin. Thordarson (1965) identifies 11 layered tuff...various degrees of welded or partially welded tuff can be formed during cooling. The tuff units identified by Thordarson (1965) making up Rainier

Electrically-evoked frequency-following response (EFFR) in the auditory brainstem of guinea pigs.

PubMed

He, Wenxin; Ding, Xiuyong; Zhang, Ruxiang; Chen, Jing; Zhang, Daoxing; Wu, Xihong

2014-01-01

It is still a difficult clinical issue to decide whether a patient is a suitable candidate for a cochlear implant and to plan postoperative rehabilitation, especially for some special cases, such as auditory neuropathy. A partial solution to these problems is to preoperatively evaluate the functional integrity of the auditory neural pathways. For evaluating the strength of phase-locking of auditory neurons, which was not reflected in previous methods using electrically evoked auditory brainstem response (EABR), a new method for recording phase-locking related auditory responses to electrical stimulation, called the electrically evoked frequency-following response (EFFR), was developed and evaluated using guinea pigs. The main objective was to assess feasibility of the method by testing whether the recorded signals reflected auditory neural responses or artifacts. The results showed the following: 1) the recorded signals were evoked by neuron responses rather than by artifact; 2) responses evoked by periodic signals were significantly higher than those evoked by the white noise; 3) the latency of the responses fell in the expected range; 4) the responses decreased significantly after death of the guinea pigs; and 5) the responses decreased significantly when the animal was replaced by an electrical resistance. All of these results suggest the method was valid. Recording obtained using complex tones with a missing fundamental component and using pure tones with various frequencies were consistent with those obtained using acoustic stimulation in previous studies.

Holding a manual response sequence in memory can disrupt vocal responses that share semantic features with the manual response.

PubMed

Fournier, Lisa Renee; Wiediger, Matthew D; McMeans, Ryan; Mattson, Paul S; Kirkwood, Joy; Herzog, Theibot

2010-07-01

Holding an action plan in memory for later execution can delay execution of another action if the actions share a similar (compatible) feature. This compatibility interference (CI) occurs for actions that share the same response modality (e.g., manual response). We investigated whether CI can generalize to actions that utilize different response modalities (manual and vocal). In three experiments, participants planned and withheld a sequence of key-presses with the left- or right-hand based on the visual identity of the first stimulus, and then immediately executed a speeded, vocal response ('left' or 'right') to a second visual stimulus. The vocal response was based on discriminating stimulus color (Experiment 1), reading a written word (Experiment 2), or reporting the antonym of a written word (Experiment 3). Results showed that CI occurred when the manual response hand (e.g., left) was compatible with the identity of the vocal response (e.g., 'left') in Experiment 1 and 3, but not in Experiment 2. This suggests that partial overlap of semantic codes is sufficient to obtain CI unless the intervening action can be accessed automatically (Experiment 2). These findings are consistent with the code occupation hypothesis and the general framework of the theory of event coding (Behav Brain Sci 24:849-878, 2001a; Behav Brain Sci 24:910-937, 2001b).

Ifosfamide in the treatment of recurrent or disseminated lung cancer: a phase II study of two dose schedules.

PubMed

Costanzi, J J; Gagliano, R; Loukas, D; Panettiere, F J; Hokanson, J A

1978-05-01

Ifosfamide was administered to 21 patients with recurrent or disseminated lung cancer at a dose of 4.0 gm/M2 iv every 3 weeks. The response rate was 33% with an additional 14% showing no response or stable disease. At a dose of 1.2 gm/M2 daily for 5 days every 4 weeks, 57% of 14 patients responded with 35% showing no response or stable disease. The majority of the patients (28) had epidermoid carcinoma. Two (7%) had complete response with 9 (32%) showing partial responses. Other responses included 1/2 oat cell carcinomas and 3/6 large cell undifferentiated carcinomas. Toxicity was equal in both regimens for nausea, vomiting, increased serum LDH and neutropenia but the 5 day program had significantly less hemorrhagic cystitis. Survival was greatly influenced by response. There was no statistical difference in overall length of response between responders and the non responding/stable disease patients. But these two groups had a very significant survival advantage when compared to those patients with increasing disease. Similarly, there was a significant improvement in response duration for the low dosage regimen. Therefore, the low dose 5 day regimen is recommended because of its response rate, it has less hemorrhagic cystitis and it has better patient acceptance in that it can be given as an outpatient and does not require a Foley catheter.

Stakeholder consultation on tracking in UK veterinary degrees: part 2.

PubMed

Crowther, E; Hughes, K; Handel, I; Whittington, R; Pryce, M; Warman, S; Rhind, S; Baillie, S

2014-07-26

There is ongoing debate in the profession as to whether veterinary students should focus on one (or a small number of) species during their undergraduate training (ie, track). This paper presents the qualitative data from surveys evaluating UK stakeholder opinion on introducing partial tracking (whereby students continue to qualify able to practise in all species) and full tracking (students qualify in a limited number of species with restricted registration). Surveys were distributed to practitioners, students and university staff; 1061 responses were completed. Thematic framework analysis was conducted on the free-text responses; responses were coded to a hierarchical framework developed inductively from the data. Six major themes were identified: choice, flexibility, competency and knowledge, stakeholder implications, specialisation and 'what is a vet?'. The majority of the themes related to both full and partial tracking, usually being more pronounced in full tracking. The theme 'choice' is particularly important in light of the study's quantitative findings on students' awareness of the profession and their career aspirations (presented in a previous paper); should tracking be implemented, veterinary schools will need to take a proactive role in educating and assisting students while making career choices. British Veterinary Association.

Effects of behavioral response and vaccination policy on epidemic spreading--an approach based on evolutionary-game dynamics.

PubMed

Zhang, Hai-Feng; Wu, Zhi-Xi; Tang, Ming; Lai, Ying-Cheng

2014-07-11

How effective are governmental incentives to achieve widespread vaccination coverage so as to prevent epidemic outbreak? The answer largely depends on the complex interplay among the type of incentive, individual behavioral responses, and the intrinsic epidemic dynamics. By incorporating evolutionary games into epidemic dynamics, we investigate the effects of two types of incentives strategies: partial-subsidy policy in which certain fraction of the cost of vaccination is offset, and free-subsidy policy in which donees are randomly selected and vaccinated at no cost. Through mean-field analysis and computations, we find that, under the partial-subsidy policy, the vaccination coverage depends monotonically on the sensitivity of individuals to payoff difference, but the dependence is non-monotonous for the free-subsidy policy. Due to the role models of the donees for relatively irrational individuals and the unchanged strategies of the donees for rational individuals, the free-subsidy policy can in general lead to higher vaccination coverage. Our findings indicate that any disease-control policy should be exercised with extreme care: its success depends on the complex interplay among the intrinsic mathematical rules of epidemic spreading, governmental policies, and behavioral responses of individuals.

Radiation response of nanotwinned Cu under multiple-collision cascades

NASA Astrophysics Data System (ADS)

Wu, Lianping; Yu, Wenshan; Hu, Shuling; Shen, Shengping

2018-07-01

In this paper, multiple collision cascades (MCC) of nanotwinned (nt) Cu with three different twin spacings are performed to model the response of nt Cu upon a radiation dose of 1 displacements per atom (dpa). Considering the defects developed with high randomness in the material during a MCC process, each MCC in a nt Cu is conducted for eight times. This enables us to analyze some average properties of defect clusters in the radiated nt Cu with different twin spacings at the different radiation doses. We also analyze the microstructural evolution in the nt Cu during the MCC. Smaller size of defect clusters and lower defect density are seen in the nt Cu with smaller twin spacing. In addition, a number of defect clusters could be removed via their frequent interactions with the coherent twin boundaries (CTBs) during the MCC. This induces either the migration of CTBs or the healing of CTBs. Moreover, the potential formation and elimination mechanisms of stacking fault are found to be due to the climb of Frank partial dislocation and glide of Shockley partial dislocations. This study provides further evidence on the irradiation tolerance of CTBs and the self-healing capability of CTBs in response to radiation.

Norovirus Narita 104 Virus-Like Particles Expressed in Nicotiana benthamiana Induce Serum and Mucosal Immune Responses

PubMed Central

Mathew, Lolita George; Herbst-Kralovetz, Melissa M.; Mason, Hugh S.

2014-01-01

Narita 104 virus is a human pathogen belonging to the norovirus (family Caliciviridae) genogroup II. Noroviruses cause epidemic gastroenteritis worldwide. To explore the potential of developing a plant-based vaccine, a plant optimized gene encoding Narita 104 virus capsid protein (NaVCP) was expressed transiently in Nicotiana benthamiana using a tobacco mosaic virus expression system. NaVCP accumulated up to approximately 0.3 mg/g fresh weight of leaf at 4 days postinfection. Initiation of hypersensitive response-like symptoms followed by tissue necrosis necessitated a brief infection time and was a significant factor limiting expression. Transmission electron microscopy of plant-derived NaVCP confirmed the presence of fully assembled virus-like particles (VLPs). In this study, an optimized method to express and partially purify NaVCP is described. Further, partially purified NaVCP was used to immunize mice by intranasal delivery and generated significant mucosal and serum antibody responses. Thus, plant-derived Narita 104 VLPs have potential for use as a candidate subunit vaccine or as a component of a multivalent subunit vaccine, along with other genotype-specific plant-derived VLPs. PMID:24949472

Virus-like particles vaccine containing Clonorchis sinensis tegumental protein induces partial protection against Clonorchis sinensis infection.

PubMed

Lee, Dong-Hun; Kim, Ah-Ra; Lee, Su-Hwa; Quan, Fu-Shi

2017-12-29

Human clonorchiasis, caused by the infection of Clonorchis sinensis, is one of the major health problems in Southeast Asia. However, vaccine efficacy against C. sinensis infection remains largely unknown. In this study, for the first time, we generated virus-like particles (VLPs) vaccine containing the C. sinensis tegumental protein 22.3 kDa (CsTP 22.3) and the influenza matrix protein (M1) as a core protein, and investigated the vaccine efficacy in Sprague-Dawley rats. Intranasal immunization of VLPs vaccine induced C. sinensis-specific IgG, IgG2a and IgG2c in the sera and IgA responses in the feces and intestines. Notably, upon challenge infection with C. sinensis metacercariae, significantly lower adult worm loads (70.2%) were measured in the liver of rats immunized with VLPs, compared to those of naïve rats. Furthermore, VLPs immunization induced antibody secreting cells (ASC) responses and CD4+/CD8+ T cell responses in the spleen. Our results indicated that VLPs vaccine containing C. sinensis CsTP 22.3 kDa provided partial protection against C. sisnensis infection. Thus, VLPs could be a potential vaccine candidate against C. sinensis.

Effects of behavioral response and vaccination policy on epidemic spreading - an approach based on evolutionary-game dynamics

NASA Astrophysics Data System (ADS)

Zhang, Hai-Feng; Wu, Zhi-Xi; Tang, Ming; Lai, Ying-Cheng

2014-07-01

How effective are governmental incentives to achieve widespread vaccination coverage so as to prevent epidemic outbreak? The answer largely depends on the complex interplay among the type of incentive, individual behavioral responses, and the intrinsic epidemic dynamics. By incorporating evolutionary games into epidemic dynamics, we investigate the effects of two types of incentives strategies: partial-subsidy policy in which certain fraction of the cost of vaccination is offset, and free-subsidy policy in which donees are randomly selected and vaccinated at no cost. Through mean-field analysis and computations, we find that, under the partial-subsidy policy, the vaccination coverage depends monotonically on the sensitivity of individuals to payoff difference, but the dependence is non-monotonous for the free-subsidy policy. Due to the role models of the donees for relatively irrational individuals and the unchanged strategies of the donees for rational individuals, the free-subsidy policy can in general lead to higher vaccination coverage. Our findings indicate that any disease-control policy should be exercised with extreme care: its success depends on the complex interplay among the intrinsic mathematical rules of epidemic spreading, governmental policies, and behavioral responses of individuals.

11C-Choline-Pet Guided Stereotactic Body Radiation Therapy for Lymph Node Metastases in Oligometastatic Prostate Cancer.

PubMed

Franzese, Ciro; Lopci, Egesta; Di Brina, Lucia; D'Agostino, Giuseppe Roberto; Navarria, Pierina; Mancosu, Pietro; Tomatis, Stefano; Chiti, Arturo; Scorsetti, Marta

2017-10-21

aim is outcome of 11C-Choline-PET guided SBRT on lymph node metastases. patients with 1 - 4 lymph node metastases detected by 11C-choline-PET were treated with SBRT. Toxicity, treated metastases control and Progression Free Survival were computed. twenty-six patients, 38 lymph node metastases were irradiated. No grade ≥ 2 toxicity. Median PSA-nadir after RT was 1.02 ng/mL. Post-treatment 11C-Choline-PET showed metabolic complete response in 17 metastases (44,7%), partial response in 9 metastases (38%). SBRT is effective and safe for lymph node metastases. PET is important in identification of gross tumor and evaluation of the response.

Hyperthyroidism and acromegaly due to a thyrotropin- and growth hormone-secreting pituitary tumor. Lack of hormonal response to bromocriptine.

PubMed

Carlson, H E; Linfoot, J A; Braunstein, G D; Kovacs, K; Young, R T

1983-05-01

A 47-year-old woman with acromegaly and hyperthyroidism was found to have an inappropriately normal serum thyrotropin level (1.5 to 2.5 microU/ml) that responded poorly to thyrotropin-releasing hormone but showed partial responsiveness to changes in circulating thyroid hormones. Serum alpha-subunit levels were high-normal and showed a normal response to thyrotropin-releasing hormone. Growth hormone and thyrotropin hypersecretion persisted despite radiotherapy and bromocriptine treatment. Selective trans-sphenoidal removal of a pituitary adenoma led to normalization of both growth hormone and thyrotropin levels. Both thyrotropes and somatotropes were demonstrated in the adenoma by the immunoperoxidase technique and electron microscopy.

Response of plasma pancreatic and gastrointestinal hormones and growth hormone to oral and intravenous glucose and insulin hypoglycaemia in Chagas's disease.

PubMed

Long, R G; Albuquerque, R H; Prata, A; Barnes, A J; Adrian, T E; Christofides, N D; Bloom, S R

1980-09-01

Plasma hormonal responses to insulin hypoglycaemia and to oral and intravenous glucose were investigated in chagasic patients with severe bowel disease and compared with controls matched for age, sex, weight, and race. After intravenous insulin, plasma concentrations of pancreatic glucagon and pancreatic polypeptide (PP) were reduced in the patients with Chagas's disease. These subjects also showed a subnormal rise in plasma insulin after oral glucose. Other hormone responses did not differ significantly from those in the normal controls. These results are compatible with partial denervation of the pancreatic alpha, beta, and PP cells in patients with chronic gastrointestinal Chagas's disease.

Response of plasma pancreatic and gastrointestinal hormones and growth hormone to oral and intravenous glucose and insulin hypoglycaemia in Chagas's disease.

PubMed Central

Long, R G; Albuquerque, R H; Prata, A; Barnes, A J; Adrian, T E; Christofides, N D; Bloom, S R

1980-01-01

Plasma hormonal responses to insulin hypoglycaemia and to oral and intravenous glucose were investigated in chagasic patients with severe bowel disease and compared with controls matched for age, sex, weight, and race. After intravenous insulin, plasma concentrations of pancreatic glucagon and pancreatic polypeptide (PP) were reduced in the patients with Chagas's disease. These subjects also showed a subnormal rise in plasma insulin after oral glucose. Other hormone responses did not differ significantly from those in the normal controls. These results are compatible with partial denervation of the pancreatic alpha, beta, and PP cells in patients with chronic gastrointestinal Chagas's disease. PMID:6776017

Parental distress in response to childhood medical trauma: A mediation model.

PubMed

Currie, Roseanne; Anderson, Vicki A; McCarthy, Maria C; Burke, Kylie; Hearps, Stephen Jc; Muscara, Frank

2018-04-01

This study explored the relationship between individual and family-level risk in predicting longer-term parental distress following their child's unexpected diagnosis of serious illness. A mediation model was tested, whereby parents' pre-existing psychosocial risk predicts longer-term posttraumatic stress symptoms, indirectly through parents' acute stress response. One hundred and thirty-two parents of 104 children participated. Acute stress response partially mediated the relationship between psychosocial risk and posttraumatic stress symptoms, with a moderate indirect effect ( r 2 = .20, P M = .56, p < .001). Findings demonstrated that cumulative psychosocial risk factors predispose parents to acute stress and longer-term posttraumatic stress symptoms, highlighting the need for psychosocial screening in this population.

RECIST 1.1-Update and clarification: From the RECIST committee.

PubMed

Schwartz, Lawrence H; Litière, Saskia; de Vries, Elisabeth; Ford, Robert; Gwyther, Stephen; Mandrekar, Sumithra; Shankar, Lalitha; Bogaerts, Jan; Chen, Alice; Dancey, Janet; Hayes, Wendy; Hodi, F Stephen; Hoekstra, Otto S; Huang, Erich P; Lin, Nancy; Liu, Yan; Therasse, Patrick; Wolchok, Jedd D; Seymour, Lesley

2016-07-01

The Response Evaluation Criteria in Solid Tumours (RECIST) were developed and published in 2000, based on the original World Health Organisation guidelines first published in 1981. In 2009, revisions were made (RECIST 1.1) incorporating major changes, including a reduction in the number of lesions to be assessed, a new measurement method to classify lymph nodes as pathologic or normal, the clarification of the requirement to confirm a complete response or partial response and new methodologies for more appropriate measurement of disease progression. The purpose of this paper was to summarise the questions posed and the clarifications provided as an update to the 2009 publication. Copyright © 2016. Published by Elsevier Ltd.

TU-G-BRA-06: PET-Based Treatment Response Assessement for Neoadjuvent Chemoradiation for Pancreatic Adenocarcinoma

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

Dalah, E; Tai, A; Oshima, K

Purpose: To address the limitations of the conventional response evaluation criteria in solid tumors (RECIST), and validate PET response criteria in solid tumors (PERCIST1.0). We analyze the relationship between the pathological treatment response (PTR) and PERCIST1.0 for patients treated with neoadjuvent chemoradiation (nCR) for pancreatic adenocarcinoma. Methods: The pre- and post-nCR CT and PET data for a total of 8 patients with resectable, or borderline resectable pancreatic head adenocarcinoma treated with nCR were retrospectively analyzed. These data were compared with the PTR which were graded according to tumor cell destruction (cellularity), with Grade1, 2 or 3 (G1, G2 or G3)more » for good, moderate, and poor responses, respectively. RECIST-based PET (RECISTPET), and PERCIST1.0 were defined using lean body mass normalized SUV (nSUVlb). RECIST-based CT (RECISTCT) was defined by contouring the whole pancreas head (CTPH). Pre- and post-nSUVlb and SUVbw, PERCIST 1.0, were correlated with PTR using Pearson’s correlation coefficient test. Results: The average mean and SD in nSUVlb for all 8 patients analyzed were lower in post-nCR (1.35±0.34) compared to those at pre-nCR (1.38±0.20). Using PERCIST1.0, 5/8 patients showed stable metabolic disease (SMD), 2/8 partial metabolic response (PMR), and 1/8 progressive metabolic disease (PMD). Using RECISTPET 4/8 showed stable disease (STD), 4/8 partial response (PR), whereas 8/8 showed stable disease (STD) using RECISTCT. PTR were correlated with PERCIST1.0 (R=0.3780/P=0.6071). Pathological tumor size was correlated with RECISTCT (R=0.0727/P=0.8679), and RECISTPET, R=−0.3333/P=0.3798. Conclusion: Chemoradiation treatment response assessment based on metabolic tumor activities using PRECIST1.0 and RECISTPET appears to provide better agreement with pathological assessment as compared to the conventional CT-based assessment using RECISTCT. The integration of these additional radiographic metrics in assessing treatment response to nCR for pancreatic adenocarcinoma may provide a promising strategy to better select those patients most suitable for therapeutic intensification.« less

Efficacy and Biological Correlates of Response in a Phase 2 Study of Venetoclax Monotherapy in Patients with Acute Myelogenous Leukemia

PubMed Central

Konopleva, Marina; Pollyea, Daniel A.; Potluri, Jalaja; Chyla, Brenda; Hogdal, Leah; Busman, Todd; McKeegan, Evelyn; Salem, Ahmed Hamed; Zhu, Ming; Ricker, Justin L.; Blum, William; DiNardo, Courtney D.; Kadia, Tapan; Dunbar, Martin; Kirby, Rachel; Falotico, Nancy; Leverson, Joel; Humerickhouse, Rod; Mabry, Mack; Stone, Richard; Kantarjian, Hagop; Letai, Anthony

2017-01-01

We present a phase 2, single-arm study evaluating 800 mg daily venetoclax, a highly selective, oral small-molecule B-cell leukemia/lymphoma-2 (BCL-2) inhibitor in patients with high-risk relapsed/refractory acute myelogenous leukemia (AML) or unfit for intensive chemotherapy. Responses were evaluated following revised International Working Group (IWG) criteria. The overall response rate was 19%; an additional 19% of patients demonstrated anti-leukemic activity not meeting IWG criteria (partial bone marrow response and incomplete hematologic recovery). Twelve (38%) patients had isocitrate dehydrogenase 1/2 mutations, of whom 4 (33%) achieved complete response/complete response with incomplete blood count recovery. Six (19%) patients had BCL-2–sensitive protein index at screening, which correlated with time on study. BH3 profiling was consistent with on-target BCL-2 inhibition and identified potential resistance mechanisms. Common adverse events included nausea, diarrhea and vomiting (all grades), and febrile neutropenia and hypokalemia (grade 3/4). Venetoclax demonstrated activity and acceptable tolerability in patients with AML and adverse features. PMID:27520294

Checkpoint inhibition for advanced mucosal melanoma.

PubMed

Thierauf, Julia; Veit, Johannes A; Hess, Jochen; Treiber, Nicolai; Lisson, Catharina; Weissinger, Stephanie E; Bommer, Martin; Hoffmann, Thomas K

2017-04-01

Whereas anti-PD-1 therapy has demonstrated a significant and durable response against advanced cutaneous melanoma, conventional chemotherapies have shown only minor benefit against advanced mucosal melanoma. To investigate the efficacy of anti-PD-1 therapy in a small cohort of patients with mucosal melanoma of the head and neck. We analysed five patients with mucosal melanoma of the head and neck who received nivolumab or pembrolizumab, at an advanced stage. Expression of PD-L1 and PD-1 in all tumour samples was evaluated immunohistochemically. All patients received at least two cycles of nivolumab or pembrolizumab. The most severe adverse events were categorised as CTCAE (common terminology criteria for adverse events) Grade 2. All patients showed progressive disease after restaging at three and six months, and no partial or complete response was observed. Immunohistochemical staining demonstrated PD-L1 expression in less than 5% of tumour cells. Systemic therapy with either nivolumab or pembrolizumab showed no clinical response, however, tumour progression was identified in all patients using Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 and immune-related response criteria (irRC) to evaluate tumour response.

Effects of heat stress on baroreflex function in humans

NASA Technical Reports Server (NTRS)

Crandall, Craig G.; Cui, Jian; Wilson, Thad E.

2003-01-01

INTRODUCTION: Heat stress significantly reduces orthostatic tolerance in humans. The mechanism(s) causing this response remain unknown. The purpose of this review article is to present data pertaining to the hypothesis that reduced orthostatic tolerance in heat stressed individuals is a result of heat stress induced alterations in baroflex function. METHODS: In both normothermic and heat stressed conditions baroreflex responsiveness was assessed via pharmacological and non-pharmacological methods. In addition, the effects of heat stress on post-synaptic vasoconstrictor responsiveness were assessed. RESULTS: Generally, whole body heating did not alter baroreflex sensitivity defined as the gain of the linear portion of the baroreflex curve around the operating point. However, whole body heating shifted the baroreflex curve to the prevailing (i.e. elevated) heart rate and muscle sympathetic nerve activity. Finally, the heat stress impaired vasoconstrictor responses to exogenous administration of adrenergic agonists. CONCLUSION: Current data do not support the hypothesis that reduced orthostatic tolerance associated with heat stress in humans is due to impaired baroreflex responsiveness. This phenomenon may be partially due to the effects of heat stress on reducing vasoconstrictor responsiveness.

Synthetic biology and the prospects for responsible innovation.

PubMed

Macnaghten, Phil; Owen, Richard; Jackson, Roland

2016-11-30

In this article we provide a short review of the debate on responsible innovation and its intersection with synthetic biology, focusing on initiatives we have witnessed and been involved with in the UK. First, we describe the ways in which responsibility in science has been reconfigured institutionally, from an internal focus on the provision of objective and reliable knowledge, to a more external view that embraces the ways in which it has an impact on society. Secondly, we introduce a framework for responsible innovation as a (partial) response to this shift, highlighting its constituent dimensions and the capacities and competencies that are needed to put it into practice. Thirdly, we chart the development of social science research on synthetic biology, addressing its evolution from an 'ethical, legal and social implications' (ELSI) frame to a responsible innovation frame. Fourthly, we review findings from UK social science research with the synthetic biology community setting out challenges for productive collaboration. And finally, we conclude with suggestions on the need for changes in institutional governance. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

The Neural Basis of Contextual Influences on Face Categorization

PubMed Central

Freeman, Jonathan B.; Ma, Yina; Barth, Maria; Young, Steven G.; Han, Shihui; Ambady, Nalini

2015-01-01

From only brief exposure to a face, individuals spontaneously categorize another's race. Recent behavioral evidence suggests that visual context may affect such categorizations. We used fMRI to examine the neural basis of contextual influences on the race categorization of faces. Participants categorized the race of faces that varied along a White-Asian morph continuum and were surrounded by American, neutral, or Chinese scene contexts. As expected, the context systematically influenced categorization responses and their efficiency (response times). Neuroimaging results indicated that the retrosplenial cortex (RSC) and orbitofrontal cortex (OFC) exhibited highly sensitive, graded responses to the compatibility of facial and contextual cues. These regions showed linearly increasing responses as a face became more White when in an American context, and linearly increasing responses as a face became more Asian when in a Chinese context. Further, RSC activity partially mediated the effect of this face-context compatibility on the efficiency of categorization responses. Together, the findings suggest a critical role of the RSC and OFC in driving contextual influences on face categorization, and highlight the impact of extraneous cues beyond the face in categorizing other people. PMID:24006403

Comparative learning theory and its application in the training of horses.

PubMed

Cooper, J J

1998-11-01

Training can best be explained as a process that occurs through stimulus-response-reinforcement chains, whereby animals are conditioned to associate cues in their environment, with specific behavioural responses and their rewarding consequences. Research into learning in horses has concentrated on their powers of discrimination and on primary positive reinforcement schedules, where the correct response is paired with a desirable consequence such as food. In contrast, a number of other learning processes that are used in training have been widely studied in other species, but have received little scientific investigation in the horse. These include: negative reinforcement, where performance of the correct response is followed by removal of, or decrease in, intensity of a unpleasant stimulus; punishment, where an incorrect response is paired with an undesirable consequence, but without consistent prior warning; secondary conditioning, where a natural primary reinforcer such as food is closely associated with an arbitrary secondary reinforcer such as vocal praise; and variable or partial conditioning, where once the correct response has been learnt, reinforcement is presented according to an intermittent schedule to increase resistance to extinction outside of training.

Affective and physiological correlates of the perception of unimodal and bimodal emotional stimuli.

PubMed

Rosa, Pedro J; Oliveira, Jorge; Alghazzawi, Daniyal; Fardoun, Habib; Gamito, Pedro

2017-08-01

Despite the multisensory nature of perception, previous research on emotions has been focused on unimodal emotional cues with visual stimuli. To the best of our knowledge, there is no evidence on the extent to which incongruent emotional cues from visual and auditory sensory channels affect pupil size. To investigate the effects of audiovisual emotional information perception on the physiological and affective response, but also to determine the impact of mismatched cues in emotional perception on these physiological indexes. Pupil size, electrodermal activity and affective subjective responses were recorded while 30 participants were exposed to visual and auditory stimuli with varied emotional content in three different experimental conditions: pictures and sounds presented alone (unimodal), emotionally matched audio-visual stimuli (bimodal congruent) and emotionally mismatched audio-visual stimuli (bimodal incongruent). The data revealed no effect of emotional incongruence on physiological and affective responses. On the other hand, pupil size covaried with skin conductance response (SCR), but the subjective experience was partially dissociated from autonomic responses. Emotional stimuli are able to trigger physiological responses regardless of valence, sensory modality or level of emotional congruence.

5-HT1A Receptors on Mature Dentate Gyrus Granule Cells are Critical for the Antidepressant Response

PubMed Central

Samuels, Benjamin Adam; Anacker, Christoph; Hu, Alice; Levinstein, Marjorie R.; Pickenhagen, Anouchka; Tsetsenis, Theodore; Madroñal, Noelia; Donaldson, Zoe R.; Drew, Liam John; Dranovsky, Alex; Gross, Cornelius T.; Tanaka, Kenji F.; Hen, René

2015-01-01

Selective serotonin reuptake inhibitors (SSRIs) are widely used antidepressants, but the mechanisms by which they influence behavior are only partially resolved. Adult hippocampal neurogenesis is necessary for some of the responses to SSRIs, but it is unknown whether the mature dentate gyrus granule cells (mature DG GCs) also contribute. We deleted Serotonin 1A receptor (5HT1AR; a receptor required for the SSRI response) specifically from DG GCs and found that the effects of the SSRI fluoxetine on behavior and the Hypothalamic-Pituitary-Adrenal (HPA) axis were abolished. By contrast, mice lacking 5HT1ARs only in young adult born granule cells (abGCs) showed normal fluoxetine responses. Importantly, 5HT1AR deficient mice engineered to express functional 5HT1ARs only in DG GCs responded to fluoxetine, indicating that 5HT1ARs in DG GCs are sufficient to mediate an antidepressant response. Taken together, these data indicate that both mature DG GCs and young abGCs must be engaged for an antidepressant response. PMID:26389840

Targeting HER2 aberrations as actionable drivers in lung cancers: phase II trial of the pan-HER tyrosine kinase inhibitor dacomitinib in patients with HER2-mutant or amplified tumors

PubMed Central

Kris, M. G.; Camidge, D. R.; Giaccone, G.; Hida, T.; Li, B. T.; O'Connell, J.; Taylor, I.; Zhang, H.; Arcila, M. E.; Goldberg, Z.; Jänne, P. A.

2015-01-01

Background HER2 mutations and amplifications have been identified as oncogenic drivers in lung cancers. Dacomitinib, an irreversible inhibitor of HER2, EGFR (HER1), and HER4 tyrosine kinases, has demonstrated activity in cell-line models with HER2 exon 20 insertions or amplifications. Here, we studied dacomitinib in patients with HER2-mutant or amplified lung cancers. Patients and methods As a prespecified cohort of a phase II study, we included patients with stage IIIB/IV lung cancers with HER2 mutations or amplification. We gave oral dacomitinib at 30–45 mg daily in 28-day cycles. End points included partial response rate, overall survival, and toxicity. Results We enrolled 30 patients with HER2-mutant (n = 26, all in exon 20 including 25 insertions and 1 missense mutation) or HER2-amplified lung cancers (n = 4). Three of 26 patients with tumors harboring HER2 exon 20 mutations [12%; 95% confidence interval (CI) 2% to 30%] had partial responses lasting 3+, 11, and 14 months. No partial responses occurred in four patients with tumors with HER2 amplifications. The median overall survival was 9 months from the start of dacomitinib (95% CI 7–21 months) for patients with HER2 mutations and ranged from 5 to 22 months with amplifications. Treatment-related toxicities included diarrhea (90%; grade 3/4: 20%/3%), dermatitis (73%; grade 3/4: 3%/0%), and fatigue (57%; grade 3/4: 3%/0%). One patient died on study likely due to an interaction of dacomitinib with mirtazapine. Conclusions Dacomitinib produced objective responses in patients with lung cancers with specific HER2 exon 20 insertions. This observation validates HER2 exon 20 insertions as actionable targets and justifies further study of HER2-targeted agents in specific HER2-driven lung cancers. ClinicalTrials.gov NCT00818441. PMID:25899785

A social-cognitive perspective of terrorism risk perception and individual response in Canada.

PubMed

Lee, Jennifer E C; Lemyre, Louise

2009-09-01

The volume of research on terrorism has increased since the events of September 11, 2001. However, efforts to develop a contextualized model incorporating cognitive, social-contextual, and affective factors as predictors of individual responses to this threat have been limited. Therefore, the aim of this study was to evaluate a series of hypotheses drawn from such a model that was generated from a series of interviews with members of the Canadian public. Data of a national survey on perceived chemical, biological, radiological, nuclear, and explosives (CBRNE) terrorism threat and preparedness were analyzed. Results demonstrated that worry and behavioral responses to terrorism, such as individual preparedness, information seeking, and avoidance behaviors, were each a function of cognitive and social-contextual factors. As an affective response, worry about terrorism independently contributed to the prediction of behavioral responses above and beyond cognitive and social-contextual factors, and partially mediated the relationships of some of these factors with behavioral responses. Perceived coping efficacy emerged as the cognitive factor associated with the most favorable response to terrorism. Hence, findings highlight the importance of fostering a sense of coping efficacy to the effectiveness of strategies aimed at improving individual preparedness for terrorism.

Non-Time-Critical Removal Actions

EPA Pesticide Factsheets

Removal responses are used to address contamination that poses an immediate threat to human health and the environment. The documents below are a partial list of EPA's guidance for removals, with a focus on Non-Time-Critical Removal Actions (NTCRA).

76 FR 1412 - Notice of Intent To Grant Partially Exclusive Patent License; Lumedyne Technologies, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-10

...) described in Navy Case No. 98745--Method of Fabricating a Micro-Electro-Mechanical Apparatus for Generating Power Responsive to Mechanical Vibration//Navy Case No. 99735-- Apparatus for Generating Power...

Study on the capability of four-level partial response equalization in RSOA-based WDM-PON

NASA Astrophysics Data System (ADS)

Guo, Qi; Tran, An Vu

2010-12-01

The expected development of advanced video services with HDTV quality demands the delivery of more than Gb/s link to end users across the last mile connection. Future access networks are also required to have long reach for reduction in the number of central offices (CO). Fueled by those requirements, we propose a novel equalization scheme that increases the capacity and reach of the wavelength division multiplexing passive optical network (WDM-PON) based on a low bandwidth reflective semiconductor optical amplifier (RSOA). We investigate the characteristics of 10 Gb/s upstream transmission in WDM-PON using RSOA with only 1.2 GHz electrical bandwidth and various lengths of fiber. It is proven that the proposed four-level partial response equalizer (PRE) is capable of mitigating the impact of ISI in the received signals from optical network units (ONU) located 0 km to 75 km away from the optical line terminal (OLT).

A family of variable step-size affine projection adaptive filter algorithms using statistics of channel impulse response

NASA Astrophysics Data System (ADS)

Shams Esfand Abadi, Mohammad; AbbasZadeh Arani, Seyed Ali Asghar

2011-12-01

This paper extends the recently introduced variable step-size (VSS) approach to the family of adaptive filter algorithms. This method uses prior knowledge of the channel impulse response statistic. Accordingly, optimal step-size vector is obtained by minimizing the mean-square deviation (MSD). The presented algorithms are the VSS affine projection algorithm (VSS-APA), the VSS selective partial update NLMS (VSS-SPU-NLMS), the VSS-SPU-APA, and the VSS selective regressor APA (VSS-SR-APA). In VSS-SPU adaptive algorithms the filter coefficients are partially updated which reduce the computational complexity. In VSS-SR-APA, the optimal selection of input regressors is performed during the adaptation. The presented algorithms have good convergence speed, low steady state mean square error (MSE), and low computational complexity features. We demonstrate the good performance of the proposed algorithms through several simulations in system identification scenario.

Partial agonist therapy in schizophrenia: relevance to diminished criminal responsibility.

PubMed

Gavaudan, Gilles; Magalon, David; Cohen, Julien; Lançon, Christophe; Léonetti, Georges; Pélissier-Alicot, Anne-Laure

2010-11-01

Pathological gambling (PG), classified in the DSM-IV among impulse control disorders, is defined as inappropriate, persistent gaming for money with serious personal, family, and social consequences. Offenses are frequently committed to obtain money for gambling. Pathological gambling, a planned and structured behavioral disorder, has often been described as a complication of dopamine agonist treatment in patients with Parkinson's disease. It has never been described in patients with schizophrenia receiving dopamine agonists. We present two patients with schizophrenia, previously treated with antipsychotic drugs without any suggestion of PG, who a short time after starting aripiprazole, a dopamine partial agonist, developed PG and criminal behavior, which totally resolved when aripiprazole was discontinued. Based on recent advances in research on PG and adverse drug reactions to dopamine agonists in Parkinson's disease, we postulate a link between aripiprazole and PG in both our patients with schizophrenia and raise the question of criminal responsibility. © 2010 American Academy of Forensic Sciences.

Neural processing of amplitude and formant rise time in dyslexia.

PubMed

Peter, Varghese; Kalashnikova, Marina; Burnham, Denis

2016-06-01

This study aimed to investigate how children with dyslexia weight amplitude rise time (ART) and formant rise time (FRT) cues in phonetic discrimination. Passive mismatch responses (MMR) were recorded for a/ba/-/wa/contrast in a multiple deviant odd-ball paradigm to identify the neural response to cue weighting in 17 children with dyslexia and 17 age-matched control children. The deviant stimuli had either partial or full ART or FRT cues. The results showed that ART did not generate an MMR in either group, whereas both partial and full FRT cues generated MMR in control children while only full FRT cues generated MMR in children with dyslexia. These findings suggest that children, both controls and those with dyslexia, discriminate speech based on FRT cues and not ART cues. However, control children have greater sensitivity to FRT cues in speech compared to children with dyslexia. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

On the identification of continuous vibrating systems modelled by hyperbolic partial differential equations

NASA Technical Reports Server (NTRS)

Udwadia, F. E.; Garba, J. A.

1983-01-01

This paper deals with the identification of spatially varying parameters in systems of finite spatial extent which can be described by second order hyperbolic differential equations. Two questions have been addressed. The first deals with 'partial identification' and inquires into the possibility of retrieving all the eigenvalues of the system from response data obtained at one location x-asterisk epsilon (0, 1). The second deals with the identification of the distributed coefficients rho(x), a(x) and b(x). Sufficient conditions for unique identification of all the eigenvalues of the system are obtained, and conditions under which the coefficients can be uniquely identified using suitable response data obtained at one point in the spatial domain are determined. Application of the results and their usefulness is demonstrated in the identification of the properties of tall building structural systems subjected to dynamic load environments.

Diaphragm electrical activity during negative lower torso pressure in quadriplegic men.

PubMed

Banzett, R B; Inbar, G F; Brown, R; Goldman, M; Rossier, A; Mead, J

1981-09-01

We recorded the diaphragm electromyogram (EMG) of quadriplegic men before and during exposure of the lower torso to continuous negative pressure, which caused shortening of the inspiratory muscles by expanding the respiratory system by one tidal volume. The moving-time-averaged diaphragm EMG was larger during expansion of the respiratory system. When we repeated the experiment with subjects who breathed through a mouthpiece, we found qualitatively similar EMG changes and little or no change in tidal volume or end-tidal CO2 partial pressure. When the pressure was applied or removed rapidly, changes in EMG occurred within one or two breaths. Because end-tidal CO2 partial pressure did not increase, and because the response was rapid, we suggest that the response results from proprioceptive, rather than chemoreceptive, reflexes. As most of these men had complete spinal lesions at C6 or C7 the afferent pathways are likely to be vagal or phrenic.

Experience with rufinamide in a pediatric population: a single center's experience.

PubMed

Vendrame, Martina; Loddenkemper, Tobias; Gooty, Vasu D; Takeoka, Masanori; Rotenberg, Alexander; Bergin, Ann M; Eksioglu, Yaman Z; Poduri, Annapurna; Duffy, Frank H; Libenson, Mark; Bourgeois, Blaise F; Kothare, Sanjeev V

2010-09-01

Rufinamide is a new antiepileptic drug recently approved as adjunctive treatment for generalized seizures in Lennox-Gastaut syndrome. We undertook a retrospective analysis of 77 patients with refractory epilepsy and receiving rufinamide to evaluate the drug's efficacy, tolerability, safety, and dosing schedules. It appeared efficacious in diverse epilepsy syndromes, with the highest responder rate in focal cryptogenic epilepsies (81.1% of patients with >50% response rate), and in diverse seizure types, with the highest responder rate in tonic/atonic and partial seizures (48.6% and 46.7% of patients with >50% response rate, respectively). Rufinamide was well tolerated: only 13% of patients developed side effects necessitating drug withdrawal. These findings suggest that rufinamide may possess good efficacy and tolerability, and that its efficacy may extend to epilepsy syndromes beyond Lennox-Gastaut, including both partial and generalized epilepsy syndromes. Copyright 2010 Elsevier Inc. All rights reserved.

Saturated-unsaturated flow to a partially penetrating well with storage in a compressible aquifer

NASA Astrophysics Data System (ADS)

Mishra, P. K.; Neuman, S. P.

2010-12-01

Mishra and Neuman [2010] developed an analytical solution for flow to a partially penetrating well of zero radius in a compressible unconfined aquifer that allows inferring its saturated and unsaturated hydraulic properties from responses recorded in the saturated and/or the unsaturated zone. We extend their solution to the case of a finite diameter pumping well with storage. Both solutions account for horizontal as well as vertical flows throughout the system. We investigate the effects of storage in the pumping well and delayed piezometer response on drawdowns in the saturated and unsaturated zones as functions of position and time; validate our solution against numerical simulations of drawdown in a synthetic aquifer having unsaturated properties described by the van Genuchten - Mualem constitutive model; and use our solution to analyze drawdown data from a pumping test conducted at the Borden site in Ontario, Canada.

Photodynamic therapy in patients with recurrent gynecological carcinomas

NASA Astrophysics Data System (ADS)

Hetzel, Heinz; Mueller, Elisabeth; Kostron, Herwig

1993-03-01

Patients with recurrent gynecological carcinomas have a poor prognosis with a median survival time of 3 - 6 months. Four patients with recurrent vulva carcinomas, one patient with a recurrent breast cancer, and one with a recurrent cervical carcinoma underwent PDT after parenteral or topical sensitization with Photosan 3. Of those patients two women made a complete recovery with no evidence of disease 27 and 24 months after. One patient responded partially with two recurrences which were retreated twice after topical sensitization, she has survived 16 months. The remaining patients showed partial response and died 3 and 8 months after PDT. The energy delivered by an argon-dye-laser ranged between 225 and 750 J/cm2. Photosan 3 was given intravenously at a dose of 2.5 mg/kg body weight and was tolerated without any allergic reaction. A response rate of nearly 50% in recurrent gynecological malignancies encourages us to pursue PDT in gynecological diseases.

Methylphenidate has nonlinear dose effects on cued response inhibition in adults but not adolescents

PubMed Central

Simon, Nicholas W.; Moghaddam, Bita

2016-01-01

Ongoing development of the dopamine system during adolescence may provide a partial mechanism for behavioral and psychiatric vulnerabilities. Despite early evidence for a hyperactive adolescent dopaminergic system, recent data suggest that adolescent dopamine may be functionally hypoactive compared to in adults. While this distinction has been established in response to dopaminergic drugs and natural rewards, little is known about age-related differences in cognitive efficacy of dopaminergic drugs. Using a recently established Cued Response Inhibition Task, we tested the effects of acute systemic methylphenidate, commonly known as Ritalin, on response inhibition and response initiation in adolescent and adults rats. First, we replicated previous data that adolescents are able to inhibit a response to a cue on par with adults, but are slower to produce a rewarded response after a stop cue. Next, we observed that methylphenidate modulated response inhibition in adult rats, with low dose (0.3 mg/kg) improving inhibition, and high dose (3 mg/kg) impairing performance. This dose-response pattern is commonly observed with psychostimulant cognitive modulation. In adolescents, however, methylphenidate had no effect on response inhibition at any dose. Latency of response initiation after the stop cue was not affected by methylphenidate in either adult or adolescent rats. These data establish that dose-response of a commonly prescribed psychostimulant medication is different in adolescents and adults. They further demonstrate that healthy adolescent response inhibition is not as sensitive to psychostimulants as in adults, supporting the idea that the dopamine system is hypoactive in adolescence. PMID:27431940

Mechanical response of biopolymer double networks

NASA Astrophysics Data System (ADS)

Carroll, Joshua; Das, Moumita

We investigate a double network model of articular cartilage (AC) and characterize its equilibrium mechanical response. AC has very few cells and the extracellular matrix mainly determines its mechanical response. This matrix can be thought of as a double polymer network made of collagen and aggrecan. The collagen fibers are stiff and resist tension and compression forces, while aggrecans are flexible and control swelling and hydration. We construct a microscopic model made of two interconnected disordered polymer networks, with fiber elasticity chosen to qualitatively mimic the experimental system. We study the collective mechanical response of this double network as a function of the concentration and stiffness of the individual components as well as the strength of the connection between them using rigidity percolation theory. Our results may provide a better understanding of mechanisms underlying the mechanical resilience of AC, and more broadly may also lead to new perspectives on the mechanical response of multicomponent soft materials. This work was partially supported by a Cottrell College Science Award.

Personality and Differential Treatment Response in Major Depression: A Randomized Controlled Trial Comparing Cognitive-Behavioural Therapy and Pharmacotherapy

PubMed Central

Bagby, R Michael; Quilty, Lena C; Segal, Zindel V; McBride, Carolina C; Kennedy, Sidney H; Costa, Paul T

2008-01-01

Objective Effective treatments for major depressive disorder exist, yet some patients fail to respond, or achieve only partial response. One approach to optimizing treatment success is to identify which patients are more likely to respond best to which treatments. The objective of this investigation was to determine if patient personality characteristics are predictive of response to either cognitive-behavioural therapy (CBT) or pharmacotherapy (PHT). Method Depressed patients completed the Revised NEO Personality Inventory, which measures the higher-order domain and lower-order facet traits of the Five-Factor Model of Personality, and were randomized to receive either CBT or PHT. Result Four personality traits—the higher-order domain neuroticism and 3 lower-order facet traits: trust, straightforwardness, and tendermindedness—were able to distinguish a differential response rate to CBT, compared with PHT. Conclusion The assessment of patient dimensional personality traits can assist in the selection and optimization of treatment response for depressed patients. PMID:18616856

Stigma towards PLWHA: The Role of Internalized Homosexual Stigma in Latino Gay/Bisexual Male and Transgender Communities

PubMed Central

Ramirez-Valles, Jesus; Molina, Yamile; Dirkes, Jessica

2013-01-01

Stigma negatively affects the health of people living with HIV/AIDS (PLWHA). Negative attitudes and discriminatory actions towards PLWHA are thought to be based, among other factors, on stigma towards sexual minorities and beliefs about personal responsibility. Yet, there is little evidence to support these linkages and explain how they take place, especially among Latinos. This study analyzes attitudes towards PLWHA among 643 Latino gay/bisexual men and transgender (GBT) people. It examines whether discriminatory actions are predicted by beliefs about personal responsibility and internalized homosexual stigma. Results indicate that Discriminatory Actions towards PLWHA is associated with HIV/AIDS Personal Responsibility Beliefs and Internalized Homosexual Stigma. Further, HIV/AIDS Personal Responsibility Beliefs partially mediates the relationship between Internalized Homosexual Stigma and Discriminatory Actions towards PLWHA. Latino GBT persons who have internalized negative views about homosexuality may project those onto PLWHA. They may think PLWHA are responsible for their serostatus and, hence, deserving of rejection. PMID:23631713

Stigma towards PLWHA: the role of internalized homosexual stigma in Latino gay/bisexual male and transgender communities.

PubMed

Ramirez-Valles, Jesus; Molina, Yamile; Dirkes, Jessica

2013-06-01

Stigma negatively affects the health of people living with HIV/AIDS (PLWHA). Negative attitudes and discriminatory actions towards PLWHA are thought to be based, among other factors, on stigma towards sexual minorities and beliefs about personal responsibility. Yet, there is little evidence to support these linkages and explain how they take place, especially among Latinos. This study analyzes attitudes towards PLWHA among 643 Latino gay/bisexual men and transgender (GBT) people. It examines whether discriminatory actions are predicted by beliefs about personal responsibility and internalized homosexual stigma. Results indicate that Discriminatory Actions towards PLWHA is associated with HIV/AIDS Personal Responsibility Beliefs and Internalized Homosexual Stigma. Further, HIV/AIDS Personal Responsibility Beliefs partially mediates the relationship between Internalized Homosexual Stigma and Discriminatory Actions towards PLWHA. Latino GBT persons who have internalized negative views about homosexuality may project those onto PLWHA. They may think PLWHA are responsible for their serostatus and, hence, deserving of rejection.

Does Partner Responsiveness Predict Hedonic and Eudaimonic Well-Being? A 10-Year Longitudinal Study

PubMed Central

Selcuk, Emre; Gunaydin, Gul; Ong, Anthony D.; Almeida, David M.

2017-01-01

Motivated by attachment theory and recent conceptualizations of perceived partner responsiveness as a core feature of close relationships, the present study examined change in hedonic and eudaimonic well-being over a decade in a sample of more than 2,000 married adults across the United States. Longitudinal analyses revealed that perceived partner responsiveness— the extent to which individuals believe that their partner cares for, appreciates, and understands them—predicted increases in eudaimonic well-being a decade later. These results remained after controlling for initial hedonic and eudaimonic well-being, age, gender, extraversion, neuroticism, and perceived responsiveness of family and friends. Affective reactivity, measured via an 8-day diary protocol in a subset of the sample, partially mediated this longitudinal association. After controlling for covariates, perceived partner responsiveness did not prospectively predict hedonic well-being. These findings are the first to document the long-term benefits of perceived partner responsiveness on eudaimonic well-being. PMID:28592909

Individual differences in the processing of smoking-cessation video messages: An imaging genetics study.

PubMed

Shi, Zhenhao; Wang, An-Li; Aronowitz, Catherine A; Romer, Daniel; Langleben, Daniel D

2017-09-01

Studies testing the benefits of enriching smoking-cessation video ads with attention-grabbing sensory features have yielded variable results. Dopamine transporter gene (DAT1) has been implicated in attention deficits. We hypothesized that DAT1 polymorphism is partially responsible for this variability. Using functional magnetic resonance imaging, we examined brain responses to videos high or low in attention-grabbing features, indexed by "message sensation value" (MSV), in 53 smokers genotyped for DAT1. Compared to other smokers, 10/10 homozygotes showed greater neural response to High- vs. Low-MSV smoking-cessation videos in two a priori regions of interest: the right temporoparietal junction and the right ventrolateral prefrontal cortex. These regions are known to underlie stimulus-driven attentional processing. Exploratory analysis showed that the right temporoparietal response positively predicted follow-up smoking behavior indexed by urine cotinine. Our findings suggest that responses to attention-grabbing features in smoking-cessation messages is affected by the DAT1 genotype. Copyright © 2017. Published by Elsevier B.V.

Interaction in planning vocalizations and grasping.

PubMed

Tiainen, Mikko; Tiippana, Kaisa; Vainio, Martti; Komeilipoor, Naeem; Vainio, Lari

2017-08-01

Previous studies have shown a congruency effect between manual grasping and syllable articulation. For instance, a power grip is associated with syllables whose articulation involves the tongue body and/or large mouth aperture ([kɑ]) whereas a precision grip is associated with articulations that involve the tongue tip and/or small mouth aperture ([ti]). Previously, this effect has been observed in manual reaction times. The primary aim of the current study was to investigate whether this congruency effect also takes place in vocal responses and to investigate involvement of action selection processes in the effect. The congruency effect was found in vocal and manual responses regardless of whether or not the syllable or grip was known a priori, suggesting that the effect operates with minimal or absent action selection processes. In addition, the effect was observed in vocal responses even when the grip was only prepared but not performed, suggesting that merely planning a grip response primes the corresponding articulatory response. These results support the view that articulation and grasping are processed in a partially overlapping network.

Generalized analytic solutions and response characteristics of magnetotelluric fields on anisotropic infinite faults

NASA Astrophysics Data System (ADS)

Bing, Xue; Yicai, Ji

2018-06-01

In order to understand directly and analyze accurately the detected magnetotelluric (MT) data on anisotropic infinite faults, two-dimensional partial differential equations of MT fields are used to establish a model of anisotropic infinite faults using the Fourier transform method. A multi-fault model is developed to expand the one-fault model. The transverse electric mode and transverse magnetic mode analytic solutions are derived using two-infinite-fault models. The infinite integral terms of the quasi-analytic solutions are discussed. The dual-fault model is computed using the finite element method to verify the correctness of the solutions. The MT responses of isotropic and anisotropic media are calculated to analyze the response functions by different anisotropic conductivity structures. The thickness and conductivity of the media, influencing MT responses, are discussed. The analytic principles are also given. The analysis results are significant to how MT responses are perceived and to the data interpretation of the complex anisotropic infinite faults.

Subjective response as a consideration in the pharmacogenetics of alcoholism treatment.

PubMed

Roche, Daniel Jo; Ray, Lara A

2015-01-01

Currently available pharmacological treatments for alcoholism have modest efficacy and high individual variability in treatment outcomes, both of which have been partially attributed to genetic factors. One path to reducing the variability and improving the efficacy associated with these pharmacotherapies may be to identify overlapping genetic contributions to individual differences in both subjective responses to alcohol and alcoholism pharmacotherapy outcomes. As acute subjective response to alcohol is highly predictive of future alcohol related problems, identifying such shared genetic mechanisms may inform the development of personalized treatments that can effectively target converging pathophysiological mechanisms that convey risk for alcoholism. The focus of this review is to revisit the association between subjective response to alcohol and the etiology of alcoholism while also describing genetic contributions to this relationship, discuss potential pharmacogenetic approaches to target subjective response to alcohol in order to improve the treatment of alcoholism and examine conceptual and methodological issues associated with these topics, and outline future approaches to overcome these challenges.

Biphasic responses in multi-site phosphorylation systems.

PubMed

Suwanmajo, Thapanar; Krishnan, J

2013-12-06

Multi-site phosphorylation systems are repeatedly encountered in cellular biology and multi-site modification is a basic building block of post-translational modification. In this paper, we demonstrate how distributive multi-site modification mechanisms by a single kinase/phosphatase pair can lead to biphasic/partial biphasic dose-response characteristics for the maximally phosphorylated substrate at steady state. We use simulations and analysis to uncover a hidden competing effect which is responsible for this and analyse how it may be accentuated. We build on this to analyse different variants of multi-site phosphorylation mechanisms showing that some mechanisms are intrinsically not capable of displaying this behaviour. This provides both a consolidated understanding of how and under what conditions biphasic responses are obtained in multi-site phosphorylation and a basis for discriminating between different mechanisms based on this. We also demonstrate how this behaviour may be combined with other behaviour such as threshold and bistable responses, demonstrating the capacity of multi-site phosphorylation systems to act as complex molecular signal processors.

Correlation between standardized uptake value and apparent diffusion coefficient of neoplastic lesions evaluated with whole-body simultaneous hybrid PET/MRI.

PubMed

Rakheja, Rajan; Chandarana, Hersh; DeMello, Linda; Jackson, Kimberly; Geppert, Christian; Faul, David; Glielmi, Christopher; Friedman, Kent P

2013-11-01

The purpose of this study was to assess the correlation between standardized uptake value (SUV) and apparent diffusion coefficient (ADC) of neoplastic lesions in the use of a simultaneous PET/MRI hybrid system. Twenty-four patients with known primary malignancies underwent FDG PET/CT. They then underwent whole-body PET/MRI. Diffusion-weighted imaging was performed with free breathing and a single-shot spin-echo echo-planar imaging sequence with b values of 0, 350, and 750 s/mm(2). Regions of interest were manually drawn along the contours of neoplastic lesions larger than 1 cm, which were clearly identified on PET and diffusion-weighted images. Maximum SUV (SUVmax) on PET/MRI and PET/CT images, mean SUV (SUVmean), minimum ADC (ADCmin), and mean ADC (ADCmean) were recorded on PET/MR images for each FDG-avid neoplastic soft-tissue lesion with a maximum of three lesions per patient. Pearson correlation coefficient was used to asses the following relations: SUVmax versus ADCmin on PET/MR and PET/CT images, SUVmean versus ADCmean, and ratio of SUVmax to mean liver SUV (SUV ratio) versus ADCmin. A subanalysis of patients with progressive disease versus partial treatment response was performed with the ratio of SUVmax to ADCmin for the most metabolically active lesion. Sixty-nine neoplastic lesions (52 nonosseous lesions, 17 bone metastatic lesions) were evaluated. The mean SUVmax from PET/MRI was 7.0 ± 6.0; SUVmean, 5.6 ± 4.6; mean ADCmin, 1.10 ± 0.58; and mean ADCmean, 1.48 ± 0.72. A significant inverse Pearson correlation coefficient was found between PET/MRI SUVmax and ADCmin (r = -0.21, p = 0.04), between SUVmean and ADCmean (r = -0.18, p = 0.07), and between SUV ratio and ADCmin (r = -0.27, p = 0.01). A similar inverse Pearson correlation coefficient was found between the PET/CT SUVmax and ADCmin. Twenty of 24 patients had previously undergone PET/CT; five patients had a partial treatment response, and six had progressive disease according to Response Evaluation Criteria in Solid Tumors 1.1. The ratio between SUVmax and ADCmin was higher among patients with progressive disease than those with a partial treatment response. Simultaneous PET/MRI is a promising technology for the detection of neoplastic disease. There are inverse correlations between SUVmax and ADCmin and between SUV ratio and ADCmin. Correlation coefficients between SUVmax and ADCmin from PET/MRI were similar to values obtained with SUVmax from the same-day PET/CT. Given that both SUV and ADC are related to malignancy and that the correlation between the two biomarkers is relatively weak, SUV and ADC values may offer complementary information to aid in determination of prognosis and treatment response. The combined tumoral biomarker, ratio between SUVmax and ADCmin, may be useful for assessing progressive disease versus partial treatment response.