CpxR-Dependent Thermoregulation of Serratia marcescens PrtA Metalloprotease Expression and Its Contribution to Bacterial Biofilm Formation.

Science.gov (United States)

Bruna, Roberto E; Molino, María Victoria; Lazzaro, Martina; Mariscotti, Javier F; García Véscovi, Eleonora

2018-04-15

PrtA is the major secreted metalloprotease of Serratia marcescens Previous reports implicate PrtA in the pathogenic capacity of this bacterium. PrtA is also clinically used as a potent analgesic and anti-inflammatory drug, and its catalytic properties attract industrial interest. Comparatively, there is scarce knowledge about the mechanisms that physiologically govern PrtA expression in Serratia In this work, we demonstrate that PrtA production is derepressed when the bacterial growth temperature decreases from 37°C to 30°C. We show that this thermoregulation occurs at the transcriptional level. We determined that upstream of prtA , there is a conserved motif that is directly recognized by the CpxR transcriptional regulator. This feature is found along Serratia strains irrespective of their isolation source, suggesting an evolutionary conservation of CpxR-dependent regulation of PrtA expression. We found that in S. marcescen s, the CpxAR system is more active at 37°C than at 30°C. In good agreement with these results, in a cpxR mutant background, prtA is derepressed at 37°C, while overexpression of the NlpE lipoprotein, a well-known CpxAR-inducing condition, inhibits PrtA expression, suggesting that the levels of the activated form of CpxR are increased at 37°C over those at 30°C. In addition, we establish that PrtA is involved in the ability of S. marcescens to develop biofilm. In accordance, CpxR influences the biofilm phenotype only when bacteria are grown at 37°C. In sum, our findings shed light on regulatory mechanisms that fine-tune PrtA expression and reveal a novel role for PrtA in the lifestyle of S. marcescens IMPORTANCE We demonstrate that S. marcescens metalloprotease PrtA expression is transcriptionally thermoregulated. While strongly activated below 30°C, its expression is downregulated at 37°C. We found that in S. marcescens , the CpxAR signal transduction system, which responds to envelope stress and bacterial surface adhesion, is

The Secreted Protease PrtA Controls Cell Growth, Biofilm Formation and Pathogenicity in Xylella fastidiosa.

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Gouran, Hossein; Gillespie, Hyrum; Nascimento, Rafael; Chakraborty, Sandeep; Zaini, Paulo A; Jacobson, Aaron; Phinney, Brett S; Dolan, David; Durbin-Johnson, Blythe P; Antonova, Elena S; Lindow, Steven E; Mellema, Matthew S; Goulart, Luiz R; Dandekar, Abhaya M

2016-08-05

Pierce's disease (PD) is a deadly disease of grapevines caused by the Gram-negative bacterium Xylella fastidiosa. Though disease symptoms were formerly attributed to bacteria blocking the plant xylem, this hypothesis is at best overly simplistic. Recently, we used a proteomic approach to characterize the secretome of X. fastidiosa, both in vitro and in planta, and identified LesA as one of the pathogenicity factors of X. fastidiosa in grapevines that leads to leaf scorching and chlorosis. Herein, we characterize another such factor encoded by PD0956, designated as an antivirulence secreted protease "PrtA" that displays a central role in controlling in vitro cell proliferation, length, motility, biofilm formation, and in planta virulence. The mutant in X. fastidiosa exhibited reduced cell length, hypermotility (and subsequent lack of biofilm formation) and hypervirulence in grapevines. These findings are supported by transcriptomic and proteomic analyses with corresponding plant infection data. Of particular interest, is the hypervirulent response in grapevines observed when X. fastidiosa is disrupted for production of PrtA, and that PD-model tobacco plants transformed to express PrtA exhibited decreased symptoms after infection by X. fastidiosa.

Presence of fibronectin-binding protein gene prtF2 in invasive group A streptococci in tropical Australia is associated with increased internalisation efficiency.

Science.gov (United States)

Gorton, Davina; Norton, Robert; Layton, Ramon; Smith, Helen; Ketheesan, Natkunam

2005-03-01

The fibronectin-binding proteins (FnBPs) PrtF1 and PrtF2 are considered to be major group A streptococcal virulence factors, mediating adherence to and internalisation of host cells. The present study investigated an association between the presence of prtF1 and prtF2 genes and internalisation efficiency in group A streptococci (GAS) isolated from patients with invasive disease. Of the 80 isolates tested, 58 (73%) had prtF1 and 71 (89%) possessed prtF2. Three isolates (4%) had neither gene, seven (9%) had prtF1 only, 19 (24%) had prtF2 only and 51 isolates (64%) had both prtF1 and prtF2. prtF2-positive isolates internalised up to three times more efficiently than isolates that had prtF1 alone (Pinternalisation efficiency and presence of the prtF1 gene. Analysis of the fibronectin-binding repeat domain (FBRD) of prtF2 revealed that this gene can contain 2, 3, 4 or 5 repeat regions and that five repeat regions conferred very high internalisation efficiency in invasive GAS isolates.

Can palliative radiotherapy influence prostate-specific antigen response in patients with castrate-resistant prostate cancer treated with systemic therapy (chemotherapy or abiraterone)?—a report of three cases

International Nuclear Information System (INIS)

Hingorani, Mohan; Dixit, Sanjay; Pugazhenthi, Pattu; Hawkyard, Simon; Robertson, Andrew; Khafagy, Richard

2015-01-01

Palliative radiotherapy (pRT) is primarily employed for palliation of bone pain in patients with castrate-resistant prostate cancer (CRPC). However, evidence that pRT influences prostate-specific antigen response in patients with CRPC on systemic therapy is lacking. We describe three cases of CRPC progressing after treatment with docetaxel (n=2) and abiraterone (n=1), who responded unusually after pRT for bone pain with the development of a significant biochemical response and restoration of response to systemic therapy. The possibility of pRT influencing metastatic disease in CRPC has not been previously reported, and raises the possibility of radiation-induced modulation of anti-tumor immune response mechanisms that may play a role in the restoration of response to systemic treatment

Increasing Opportunities for Question-Asking in School-Aged Children with Autism Spectrum Disorder: Effectiveness of Staff Training in Pivotal Response Treatment.

Science.gov (United States)

Verschuur, Rianne; Huskens, Bibi; Verhoeven, Ludo; Didden, Robert

2017-02-01

Deficits in question-asking are common in children with autism spectrum disorder (ASD). Furthermore, their opportunities to self-initiate questions are often hindered by directive behavior of their conversation partners. This study assessed the effectiveness of staff training in pivotal response treatment (PRT) on staff member-created opportunities and self-initiated questions of school-aged children with ASD. Generalization and maintenance were also assessed. Participants were 14 staff members and children with ASD attending an inpatient treatment facility. Data showed that PRT resulted in significant increases in both staff member-created opportunities and child-initiated questions. Generalization to group situations and collateral changes in children's language, pragmatic, and adaptive skills, and maladaptive behaviors did not occur. Implications for clinical practice and directions for future research are discussed.

Phenotypic and Proteomic Analysis of the Aspergillus fumigatus ΔPrtT, ΔXprG and ΔXprG/ΔPrtT Protease-Deficient Mutants

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Einav Shemesh

2017-12-01

Full Text Available Aspergillus fumigatus is the most common mold species to cause disease in immunocompromised patients. Infection usually begins when its spores (conidia are inhaled into the airways, where they germinate, forming hyphae that penetrate and destroy the lungs and disseminate to other organs, leading to high mortality. The ability of hyphae to penetrate the pulmonary epithelium is a key step in the infectious process. A. fumigatus produces extracellular proteases that are thought to enhance penetration by degrading host structural barriers. This study explores the role of the A. fumigatus transcription factor XprG in controlling secreted proteolytic activity and fungal virulence. We deleted xprG, alone and in combination with prtT, a transcription factor previously shown to regulate extracellular proteolysis. xprG deletion resulted in abnormal conidiogenesis and formation of lighter colored, more fragile conidia and a moderate reduction in the ability of culture filtrates (CFs to degrade substrate proteins. Deletion of both xprG and prtT resulted in an additive reduction, generating a mutant strain producing CF with almost no ability to degrade substrate proteins. Detailed proteomic analysis identified numerous secreted proteases regulated by XprG and PrtT, alone and in combination. Interestingly, proteomics also identified reduced levels of secreted cell wall modifying enzymes (glucanases, chitinases and allergens following deletion of these genes, suggesting they target additional cellular processes. Surprisingly, despite the major alteration in the secretome of the xprG/prtT null mutant, including two to fivefold reductions in the level of 24 proteases, 18 glucanases, 6 chitinases, and 19 allergens, it retained wild-type virulence in murine systemic and pulmonary models of infection. This study highlights the extreme adaptability of A. fumigatus during infection based on extensive gene redundancy.

Increasing Opportunities for Question-Asking in School-Aged Children with Autism Spectrum Disorder: Effectiveness of Staff Training in Pivotal Response Treatment

Science.gov (United States)

Verschuur, Rianne; Huskens, Bibi; Verhoeven, Ludo; Didden, Robert

2017-01-01

Deficits in question-asking are common in children with autism spectrum disorder (ASD). Furthermore, their opportunities to self-initiate questions are often hindered by directive behavior of their conversation partners. This study assessed the effectiveness of staff training in pivotal response treatment (PRT) on staff member-created…

Research on strategy and optimization method of PRT empty vehicles resource allocation based on traffic demand forecast

Science.gov (United States)

Xiang, Yu; Tao, Cheng

2018-05-01

During the operation of the personal rapid transit system(PRT), the empty vehicle resources is distributed unevenly because of different passenger demand. In order to maintain the balance between supply and demand, and to meet the passenger needs of the ride, PRT empty vehicle resource allocation model is constructed based on the future demand forecasted by historical demand in this paper. The improved genetic algorithm is implied in distribution of the empty vehicle which can reduce the customers waiting time and improve the operation efficiency of the PRT system so that all passengers can take the PRT vehicles in the shortest time. The experimental result shows that the improved genetic algorithm can allocate the empty vehicle from the system level optimally, and realize the distribution of the empty vehicle resources reasonably in the system.

The S-layer Associated Serine Protease Homolog PrtX Impacts Cell Surface-Mediated Microbe-Host Interactions of Lactobacillus acidophilus NCFM

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Brant R. Johnson

2017-06-01

Full Text Available Health-promoting aspects attributed to probiotic microorganisms, including adhesion to intestinal epithelia and modulation of the host mucosal immune system, are mediated by proteins found on the bacterial cell surface. Notably, certain probiotic and commensal bacteria contain a surface (S- layer as the outermost stratum of the cell wall. S-layers are non-covalently bound semi-porous, crystalline arrays of self-assembling, proteinaceous subunits called S-layer proteins (SLPs. Recent evidence has shown that multiple proteins are non-covalently co-localized within the S-layer, designated S-layer associated proteins (SLAPs. In Lactobacillus acidophilus NCFM, SLP and SLAPs have been implicated in both mucosal immunomodulation and adhesion to the host intestinal epithelium. In this study, a S-layer associated serine protease homolog, PrtX (prtX, lba1578, was deleted from the chromosome of L. acidophilus NCFM. Compared to the parent strain, the PrtX-deficient strain (ΔprtX demonstrated increased autoaggregation, an altered cellular morphology, and pleiotropic increases in adhesion to mucin and fibronectin, in vitro. Furthermore, ΔprtX demonstrated increased in vitro immune stimulation of IL-6, IL-12, and IL-10 compared to wild-type, when exposed to mouse dendritic cells. Finally, in vivo colonization of germ-free mice with ΔprtX led to an increase in epithelial barrier integrity. The absence of PrtX within the exoproteome of a ΔprtX strain caused morphological changes, resulting in a pleiotropic increase of the organisms’ immunomodulatory properties and interactions with some intestinal epithelial cell components.

Mirasol PRT system inactivation efficacy evaluated in platelet concentrates by bacteria-contamination model

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Jocić Miodrag

2011-01-01

Full Text Available Background/Aim. Bacterial contamination of blood components, primarily platelet concentrates (PCs, has been identified as one of the most frequent infectious complications in transfusion practice. PC units have a high risk for bacterial growth/multiplication due to their storage at ambient temperature (20 ± 2°C. Consequences of blood contamination could be effectively prevented or reduced by pathogen inactivation systems. The aim of this study was to determine the Mirasol pathogen reduction technology (PRT system efficacy in PCs using an artificial bacteria-contamination model. Methods. According to the ABO blood groups, PC units (n = 216 were pooled into 54 pools (PC-Ps. PC-Ps were divided into three equal groups, with 18 units in each, designed for an artificial bacteria-contamination. Briefly, PC-Ps were contaminated by Staphylococcus epidermidis, Staphylococcus aureus or Escherichia coli in concentrations 102 to 107 colony forming units (CFU per unit. Afterward, PC-Ps were underwent to inactivation by Mirasol PRT system, using UV (l = 265-370 nm activated riboflavin (RB. All PC-Ps were assayed by BacT/Alert Microbial Detection System for CFU quantification before and after the Mirasol treatment. Samples from non-inactivated PC-P units were tested after preparation and immediately following bacterial contamination. Samples from Mirasol treated units were quantified for CFUs one hour, 3 days and 5 days after inactivation. Results. A complete inactivation of all bacteria species was obtained at CFU concentrations of 102 and 103 per PC-P unit through storage/ investigation period. The most effective inactivation (105 CFU per PC-P unit was obtained in Escherichia coli setting. Contrary, inactivation of all the three tested bacteria species was unworkable in concentrations of ≥ 106 CFU per PC-P unit. Conclusion. Efficient inactivation of investigated bacteria types with a significant CFU depletion in PC-P units was obtained - 3 Log for all

Survey for collagenase gene prtC in Porphyromonas gingivalis and Porphyromonas endodontalis isolated from endodontic infections.

Science.gov (United States)

Odell, L J; Baumgartner, J C; Xia, T; David, L L

1999-08-01

Collagenase is a potential virulence factor shown to be expressed by Porphyromonas gingivalis associated with periodontal disease. The purpose of this study was to use the polymerase chain reaction (PCR) to detect the presence of the collagenase gene (prtC) in 21 strains of Porphyromonas species isolated from endodontic infections. Type strains for P. gingivalis (ATCC 33277), P. endodontalis (ATCC 35406), Prevotella intermedia (ATCC 25611), and Prevotella nigrescens (ATCC 33563) were used as controls. When PCR primers specific for the 16S ribosomal RNA gene of P. gingivalis or P. endodontalis were used, 16 of the strains were identified as P. gingivalis, and five strains were identified as P. endodontalis. The presence of the prtC gene for collagenase was detected using PCR. Amplicons were analyzed by agarose gel electrophoresis, with an 815 bp amplicon representing the presence of the collagenase gene. Type strain ATCC 33277 and all 16 clinical isolates of P. gingivalis produced the collagenase gene amplicon. Neither type strain ATCC 35406 nor the five strains from clinical isolates of P. endodontalis produced the collagenase gene amplicon. These results indicate that P. gingivalis from endodontic infections possesses the prtC gene. P. endodontalis does not seem to exhibit prtC. The virulence of P. gingivalis may be related to its production of collagenase.

Simultaneous Presence of PrtH and PrtH2 Proteinases in Lactobacillus helveticus Strains Improves Breakdown of the Pure αs1-Casein▿ †

Science.gov (United States)

Sadat-Mekmene, L.; Jardin, J.; Corre, C.; Mollé, D.; Richoux, R.; Delage, M.-M.; Lortal, S.; Gagnaire, V.

2011-01-01

Lactobacillus helveticus can possess one or two cell envelope proteinases (CEPs), called PrtH2 and PrtH. The aim of this work was to explore the diversity of 15 strains of L. helveticus, isolated from various origins, in terms of their proteolytic activities and specificities on pure caseins or on milk casein micelles. CEP activity differed 14-fold when the strains were assayed on a synthetic substrate, but no significant differences were detected between strains possessing one or two CEPs. No correlation was observed between the proteolytic activities of the strains and their rates of acidification in milk. The kinetics of hydrolysis of purified αs1- and β-casein by L. helveticus whole cells was monitored using Tris-Tricine sodium dodecyl sulfate (SDS) electrophoresis, and for four strains, the peptides released were identified using mass spectrometry. While rapid hydrolysis of pure β-casein was observed for all strains, the hydrolysis kinetics of αs1-casein was the only criterion capable of distinguishing between the strains based on the number of CEPs. Fifty-four to 74 peptides were identified for each strain. When only PrtH2 was present, 22 to 30% of the peptides originated from αs1-casein. The percentage increased to 41 to 49% for strains in which both CEPs were expressed. The peptide size ranged from 6 to 33 amino acids, revealing a broad range of cleavage specificities, involving all classes of amino acids (Leu, Val, Ala, Ile, Glu, Gln, Lys, Arg, Met, and Pro). Regions resistant to proteolysis were identified in both caseins. When strains were grown in milk, a drastic reduction in the number of peptides was observed, reflecting changes in accessibility and/or peptide assimilation during growth. PMID:21037305

Interaction of the RNP1 motif in PRT1 with HCR1 promotes 40S binding of eukaryotic initiation factor 3 in yeast

DEFF Research Database (Denmark)

Nielsen, Klaus H; Valásek, Leos; Sykes, Caroah

2006-01-01

We found that mutating the RNP1 motif in the predicted RRM domain in yeast eukaryotic initiation factor 3 (eIF3) subunit b/PRT1 (prt1-rnp1) impairs its direct interactions in vitro with both eIF3a/TIF32 and eIF3j/HCR1. The rnp1 mutation in PRT1 confers temperature-sensitive translation initiation...

El PRT-La Verdad entre los trabajadores de la carne de Berisso: La agrupación El Activista de la Carne y la Lista Gris [1967-1972

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Christian Carlos Hernán Castillo

2011-10-01

Full Text Available This article is part of a research about the working class and students struggles and the strategies of the left parties in La Plata city and Gran La Plata between 1966 and 1973. This work is focused on the study of the political activity of the PRT-La Verdad during this period. At the beginning of 1968 the Partido Revolucionario de los Trabajadores -PRT split in two fractions. The fraction led by Nahuel Moreno -named PRT-La Verdad [PRT- The Truth]- was the largest of the two in La Plata y Gran La Plata. In this area the PRT had many members among the students and in the workers movement. This article studies the political activity of the PRT, and the PRT-LV after the split- in the Sindicato de Obreros y Empleados de la Industria de la Carne y Afines de Berisso [Meat Processing Plants Workers Union], between 1967 and 1972 at the Swift and Armour meat processing plants. During the period analyzed in the article, the members and supporters of the PRT-LV were organized in a rank and file union group named El Activista de la Carne - Lista Gris [The Activist-Gray List]. The sources of this research are the bulletins and leaflets edited by El Activista de la Carne. We also consulted the files of DIPBA as well as the bibliography on the subject

Technological and Genomic Analysis of Roles of the Cell-Envelope Protease PrtS in Yoghurt Starter Development

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Hui Tian

2018-04-01

Full Text Available The cell-envelope protease PrtS was proved to be efficient in optimal bacterial growth and fast acidification in pure culture, while its positive effect on the performance of mixed-cultures in milk fermentation was not defined. The aim was to analyze effects of the PrtS on the symbiosis between strains during yoghurt production and cold storage. Two Streptococcus thermophilus strains, KLDS3.1012 and KLDS SM, and two different proteolytic strains of Lactobacillus delbrueckii subsp. Bulgaricus, L7 and L12, were used. Technological properties (viability, acid production, and proteolysis were determined. Comparative genomics was used to analyze the proteolytic system (cell-envelope protease, transport system, intracellular peptidase of Streptococcus thermophilus strains. S. thermophilus KLDS SM possesses an intact gene encoding PrtS (A9497_00420, which was not found in the genome of S. thermophilus KLDS3.1012. This gene is the main difference in the proteolytic system between the two genomes. PrtS endowed KLDS SM high levels of viability during fermentation and cold storage. When combined with a weaker lactobacillus strain during fermentation, the acceleration of acid production of mixed-culture by KLDS SM would start at an earlier time. KLDS SM increased the post-acidification of yoghurts during cold storage, but the pH was steadily maintained during 14–28 days. Results suggest that strains of Streptococcus thermophilus with strong proteolytic ability could be used in a wide range of dairy production. The present study provided data for yoghurt starter development from the point of view of proteolysis.

Biofilm Formation on Stainless Steel by Streptococcus thermophilus UC8547 in Milk Environments Is Mediated by the Proteinase PrtS.

Science.gov (United States)

Bassi, D; Cappa, F; Gazzola, S; Orrù, L; Cocconcelli, P S

2017-04-15

In Streptococcus thermophilus , gene transfer events and loss of ancestral traits over the years contribute to its high level of adaptation to milk environments. Biofilm formation capacity, a phenotype that is lost in the majority of strains, plays a role in persistence in dairy environments, such as milk pasteurization and cheese manufacturing plants. To investigate this property, we have studied S. thermophilus UC8547, a fast-acidifying dairy starter culture selected for its high capacity to form biofilm on stainless steel under environmental conditions resembling the dairy environment. Using a dynamic flow cell apparatus, it was shown that S. thermophilus UC8547 biofilm formation on stainless steel depends on the presence of milk proteins. From this strain, which harbors the prtS gene for the cell wall protease and shows an aggregative phenotype, spontaneous mutants with impaired biofilm capacity can be isolated at high frequency. These mutants lack the PrtS expendable island, as confirmed by comparison of the genome sequence of UC8547Δ3 with that of the parent strain. The prtS island excision occurs between two 26-bp direct repeats located in the two copies of the IS Sth1 flanking this genomic island. The central role of PrtS was confirmed by analyzing the derivative strain UC8547Δ16, whose prtS gene was interrupted by an insertional mutation, thereby making it incapable of biofilm formation. PrtS, acting as a binding substance between the milk proteins adhered to stainless steel and S. thermophilus cell envelopes, mediates biofilm formation in dairy environments. This feature provides S. thermophilus with an ecological benefit for its survival and persistence in this environment. IMPORTANCE The increased persistence of S. thermophilus biofilm has consequences in the dairy environment: if, on the one hand, the release of this microorganism from biofilm can promote the fermentation of artisanal cheeses, under industrial conditions it may lead to undesirable

Proton radiation therapy (prt) for pediatric optic pathway gliomas: comparison with 3d planned conventional photons and a standard photon technique

International Nuclear Information System (INIS)

Fuss, Martin; Hug, Eugen B.; Schaefer, Rosemary A.; Nevinny-Stickel, Meinhard; Miller, Daniel W.; Slater, James M.; Slater, Jerry D.

1999-01-01

Purpose: Following adequate therapy, excellent long-term survival rates can be achieved for patients with optic pathway gliomas. Therefore, avoidance of treatment-related functional long-term sequelae is of utmost importance. Optimized sparing of normal tissue is of primary concern in the development of new treatment modalities. The present study compares proton radiation therapy (PRT) with a three-dimensional (3D)-planned multiport photon and a lateral beam photon technique for localized and extensive optic pathway tumors. Methods and Materials: Between February 1992 and November 1997, seven children with optic pathway gliomas underwent PRT. For this study, we computed proton, 3D photon, and lateral photon plans based on the same CT data sets, and using the same treatment planning software for all plans. Radiation exposure for normal tissue and discrete organs at risk was quantified based on dose-volume histograms. Results: Gross tumor volume (GTV) ranged from 3.9 cm 3 to 127.2 cm 3 . Conformity index (relation of encompassing isodose to GTV volume) was 2.3 for protons, 2.9 for 3D photons, and 7.3 for lateral photons. The relative increase of normal tissue (NT) encompassed at several isodose levels in relation to NT encompassed by the 95% proton isodose volume was computed. Relative NT volume of proton plan isodoses at the 95%, 90%, 80%, 50%, and 25% isodose level increased from 1 to 1.6, 2.8, 6.4, to a maximum of 13.3. Relative volumes for 3D photons were 1.6, 2.4, 3.8, 11.5, and 34.8. Lateral plan relative values were 6, 8.3, 11.5, 19.2, and 26.8. Analysis for small ( 3 ) and larger (> 80 cm 3 ) tumors showed that protons encompassed the smallest volumes of NT at all isodose levels. Comparable conformity and high-dose gradient were achieved for proton and 3D photon plans in small tumors. However, with increasing tumor volume and complexity, differences became larger. At the 50% isodose level, 3D photons were superior to lateral photons for small tumors; this

Interaction of hyperthermia and photoradiation therapy

International Nuclear Information System (INIS)

Waldow, S.M.; Dougherty, T.J.

1984-01-01

Local microwave hyperthermia (2450 MHz) was applied to auxillary implants of the SMT-F mammary carcinoma in mice in combination with photoradiation therapy (PRT) in an attempt to determine if the two modalities interact. When 40.5 0 C was applied for 30 min immediately prior to or immediately following PRT enhancement of tumor response over that of PRT alone was seen as judged by lack of tumor regrowth (35 days or longer after treatment). A temperature of 41.5 0 C applied for 30 min immediately following the 30-min PRT treatment produced a result slightly greater than that seen at 40.5 0 C. When a temperature of 44.5 0 C for 30 min was applied immediately following PRT, a substantial enhancement of tumor control at 35 days post-treatment was found. These results suggest that tumor response to PRT is enhanced by both a sublethal hyperthermic treatment (40.5 0 C, 41.5 0 C) and a moderately lethal heat treatment (44.5 0 C) given for a short duration, when applied immediately before or after photoradiation

ETR fuel element shipping container addendum to PR-T-79-011 (TR-466). Internal technical report

International Nuclear Information System (INIS)

Smith, M.C.

1979-01-01

In July, 1979, EG and G Idaho, Inc. was requested to evaluate the ETR Fuel Element Shipping Container for compliance with existing transport regulations, in order to ship GETR fuel elements from Vallecitos, California to the INEL. Technical report PR-T-79-011 (TR-466), ATR Fuel Element Shipping Container Safety Analysis, was used as a basis for this evaluation. The safety analysis contained in technical report PR-T-79-011 (TR-466) was performed utilizing the ATR, ETR, MTR, and SPERT shipping containers. The report determined the ETR Fuel Element Shipping Container does comply with the existing transport regulations for a Type A quantity, Fissile Class I shipping container. The ETR and GETR fuel elements are essentially identical in physical size, construction, and fissile material content, the analysis documented in this report has determined the shipment of GETR fuel elements in the ETR shipping container to be safe and pose no threat to the public health and safety

A comparison of efficacy of photoradiation therapy and other conventional treatment modalities on experimental MS-2 sarcoma

International Nuclear Information System (INIS)

Pazzoni, Gabriella; Savi, Giuseppina; Melloni, Elsa; Marchesini, Renato; Fava, Giannino; Locati, Lucia; Zunino, Franco

1984-01-01

The therapeutic efficacy of photoradiation therapy (PRT) following hematoporthyrin derivative (HpD) administration was compared in the experimental MS-2 tumour model to that of conventional treatment methods for local control of neoplastic diseases (i.e. surgery and radiotherapy). The therapeutic effects of PRT and surgical removal of primary tumour were comparable in these experiments. However, optimal effects were critically dependent on the stage of tumour development. In addition, the therapeutic advantage of PRT over radiotherapy suggests an interesting role of a new approach in tumours resistant to this conventional treatment. (author)

Characterization of an extensin-modifying metalloprotease: N-terminal processing and substrate cleavage pattern of Pectobacterium carotovorum Prt1

DEFF Research Database (Denmark)

Feng, Tao; Nyffenegger, Christian; Højrup, Peter

2014-01-01

Compared to other plant cell wall-degrading enzymes, proteases are less well understood. In this study, the extracellular metalloprotease Prt1 from Pectobacterium carotovorum (formerly Erwinia carotovora) was expressed in Escherichia coli and characterized with respect to N-terminal processing...

Proton Radiation Therapy for the Treatment of Retinoblastoma

Energy Technology Data Exchange (ETDEWEB)

Mouw, Kent W. [Harvard Radiation Oncology Program, Boston, Massachusetts (United States); Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Sethi, Roshan V.; Yeap, Beow Y.; MacDonald, Shannon M.; Chen, Yen-Lin E.; Tarbell, Nancy J.; Yock, Torunn I.; Munzenrider, John E.; Adams, Judith [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Grabowski, Eric [Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts (United States); Mukai, Shizuo [Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts (United States); Shih, Helen A., E-mail: hshih@partners.org [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

2014-11-15

Purpose: To investigate long-term disease and toxicity outcomes for pediatric retinoblastoma patients treated with proton radiation therapy (PRT). Methods and Materials: This is a retrospective analysis of 49 retinoblastoma patients (60 eyes) treated with PRT between 1986 and 2012. Results: The majority (84%) of patients had bilateral disease, and nearly half (45%) had received prior chemotherapy. At a median follow-up of 8 years (range, 1-24 years), no patients died of retinoblastoma or developed metastatic disease. The post-PRT enucleation rate was low (18%), especially in patients with early-stage disease (11% for patients with International Classification for Intraocular Retinoblastoma [ICIR] stage A-B disease vs 23% for patients with ICIR stage C-D disease). Post-PRT ophthalmologic follow-up was available for 61% of the preserved eyes (30 of 49): 14 of 30 eyes (47%) had 20/40 visual acuity or better, 7 of 30 (23%) had moderate visual acuity (20/40-20/600), and 9 of 30 (30%) had little or no useful vision (worse than 20/600). Twelve of 60 treated eyes (20%) experienced a post-PRT event requiring intervention, with cataracts the most common (4 eyes). No patients developed an in-field second malignancy. Conclusions: Long-term follow-up of retinoblastoma patients treated with PRT demonstrates that PRT can achieve high local control rates, even in advanced cases, and many patients retain useful vision in the treated eye. Treatment-related ocular side effects were uncommon, and no radiation-associated malignancies were observed.

What works for you? Using teacher feedback to inform adaptations of pivotal response training for classroom use.

Science.gov (United States)

Stahmer, Aubyn C; Suhrheinrich, Jessica; Reed, Sarah; Schreibman, Laura

2012-01-01

Several evidence-based practices (EBPs) have been identified as efficacious for the education of students with autism spectrum disorders (ASD). However, effectiveness research has rarely been conducted in schools and teachers express skepticism about the clinical utility of EBPs for the classroom. Innovative methods are needed to optimally adapt EBPs for community use. This study utilizes qualitative methods to identify perceived benefits and barriers of classroom implementation of a specific EBP for ASD, Pivotal Response Training (PRT). Teachers' perspectives on the components of PRT, use of PRT as a classroom intervention strategy, and barriers to the use of PRT were identified through guided discussion. Teachers found PRT valuable; however, they also found some components challenging. Specific teacher recommendations for adaptation and resource development are discussed. This process of obtaining qualitative feedback from frontline practitioners provides a generalizable model for researchers to collaborate with teachers to optimally promote EBPs for classroom use.

El PRT-La Verdad entre los trabajadores de la carne de Berisso: La agrupación El Activista de la Carne y la Lista Gris (1967-1972)

OpenAIRE

Castillo, Christian

2011-01-01

Este trabajo se enmarca dentro de un proyecto más general referido al estudio de los conflictos obreros y estudiantiles y las estrategias de la izquierda en La Plata y Gran La Plata entre 1966 y 1973 y, más en particular, del estudio de la actividad en la región durante ese período del PRT-La Verdad. De las dos fracciones en las que se escindió el Partido Revolucionario de los Trabajadores a comienzos de 1968, el sector encabezado por Nahuel Moreno ?que pasó a denominarse "PRT-La Verdad"- fue...

Replicative phenotyping adds value to genotypic resistance testing in heavily pre-treated HIV-infected individuals - the Swiss HIV Cohort Study

Directory of Open Access Journals (Sweden)

Martinetti Gladys

2011-01-01

Full Text Available Abstract Background Replicative phenotypic HIV resistance testing (rPRT uses recombinant infectious virus to measure viral replication in the presence of antiretroviral drugs. Due to its high sensitivity of detection of viral minorities and its dissecting power for complex viral resistance patterns and mixed virus populations rPRT might help to improve HIV resistance diagnostics, particularly for patients with multiple drug failures. The aim was to investigate whether the addition of rPRT to genotypic resistance testing (GRT compared to GRT alone is beneficial for obtaining a virological response in heavily pre-treated HIV-infected patients. Methods Patients with resistance tests between 2002 and 2006 were followed within the Swiss HIV Cohort Study (SHCS. We assessed patients' virological success after their antiretroviral therapy was switched following resistance testing. Multilevel logistic regression models with SHCS centre as a random effect were used to investigate the association between the type of resistance test and virological response (HIV-1 RNA Results Of 1158 individuals with resistance tests 221 with GRT+rPRT and 937 with GRT were eligible for analysis. Overall virological response rates were 85.1% for GRT+rPRT and 81.4% for GRT. In the subgroup of patients with >2 previous failures, the odds ratio (OR for virological response of GRT+rPRT compared to GRT was 1.45 (95% CI 1.00-2.09. Multivariate analyses indicate a significant improvement with GRT+rPRT compared to GRT alone (OR 1.68, 95% CI 1.31-2.15. Conclusions In heavily pre-treated patients rPRT-based resistance information adds benefit, contributing to a higher rate of treatment success.

The role of peer review in responsive decisions - a case study of clean-up and safe long-term management of historic waste at Port Hope and Clarington

International Nuclear Information System (INIS)

Hardy, D.

2006-01-01

'Full text:' The Municipalities of Port Hope and Clarington ('Municipalities') are committed to leading the clean- up and safe long-term management of historic low- level radioactive and hazardous wastes deposited in Port Granby (in the Municipality of Clarington) and several locations in the Municipality of Port Hope. They are supported by the Government of Canada through Atomic Energy of Canada Limited's (AECL) Low- Level Radioactive Waste Management Office (LLRWMO). The wastes are the result of radium and uranium processing in Port Hope by Eldorado since the 1930s. To establish the parameters of the clean- up, including the ability to veto the project, the local municipalities negotiated and signed a Legal Agreement with the Government of Canada in 2001. As a Responsible Authority, Natural Resources Canada has defined and approved the scope of the two projects. The LLRWMO is designated as the proponent. Accordingly, the LLRWMO is conducting the Environmental Assessment (EA) Studies and seeking approval of a preferred method of conducting the clean up for each municipality. The municipalities recognized that these large and complex environmental assessment studies would challenge the resources of citizens, municipal professional staff and politicians. Thus, the Legal Agreement specified that both municipalities would have funded staff to work together to coordinate and expedite the project. A Peer Review Team (PRT) would be retained by the municipalities and funded by the Government of Canada. The PRT is made up of experienced professionals led by Hardy Stevenson and Associates Limited in disciplines appropriate to the peer review tasks on hand. The PRT has brought a unique approach to the peer review. The PRT is headed by planners and social scientists trained to be sensitive to the 'people aspects' of the EA process as a major priority. They are supported by engineers and technical specialists. The team includes a physician with a family practice who is also an

Considering patient values and treatment preferences enhances patient involvement in rectal cancer treatment decision making.

Science.gov (United States)

Kunneman, Marleen; Marijnen, Corrie A M; Baas-Thijssen, Monique C M; van der Linden, Yvette M; Rozema, Tom; Muller, Karin; Geijsen, Elisabeth D; Stiggelbout, Anne M; Pieterse, Arwen H

2015-11-01

The shared decision making (SDM) model states that patients' values and preferences should be clarified to choose a strategy that best fits the patient. This study aimed to assess whether values and preferences of rectal cancer patients are voiced and considered in deciding about preoperative radiotherapy (PRT), and whether this makes patients feel more involved in treatment decision making. Pre-treatment consultations of radiation oncologists and patients eligible for PRT were audiotaped (N=90). Tapes were transcribed and coded to identify patients' values and treatment preferences. Patients filled in a post-consultation questionnaire on their perceived involvement in decision making (N=60). Patients' values were voiced for 62/611 of benefits/harms addressed (10%), in 38/90 consultations (42%; maximum 4 values per consultation), and most often related to major long-term treatment outcomes. Patients' treatment preferences were discussed in 20/90 consultations (22%). In 16/90 consultations (18%), the oncologists explicitly indicated to consider patients' values or preferences. Patients perceived a significantly more active role in decision making if their values or preferences had been voiced or considered. Patients' values and treatment preferences are voiced or considered in a minority of consultations. If they are, this increases patients' perceived involvement in the decision making process. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Photoradiation therapy of animal tumors and nasopharyngeal carcinoma

International Nuclear Information System (INIS)

Zhao, S.P.; Tao, Z.D.; Xiao, J.Y.; Peng, Y.Y.; Yang, Y.H.; Zeng, Q.S.; Liu, Z.W.

1990-01-01

Both animal tumors and human nasopharyngeal carcinoma were submitted to a photoradiation therapy (PRT) trial in order to determine the efficacy and side effects of PRT, as well as to elucidate its mechanism of cytotoxicity. In animal tumors, the inhibition rate was 70%, and of 20 patients, eight achieved complete remission, and ten, significant remission, with an overall response rate of 90%. The blood picture and the values of serum IgG, IgM, IgA, and C3 all remained stable post-PRT. Only three patients developed mild generalized skin photosensitive reactions, and these did not affect subsequent treatment. There was no immunosuppressive effect as evidenced by a tritium-labeled thymidine-incorporated lymphocytoblast transformation assay performed both before and after PRT. Ultrastructural studies at different time intervals after PRT highly suggested that the mitochondria and rough endoplasmic reticulum were among the first organelles to be damaged

Photobiology of porphyrins

International Nuclear Information System (INIS)

Gomer, C.J.

1984-01-01

Hematoporphyrin derivative (HpD) photoradiation therapy (PRT) continues to show promise as a modality for the treatment of certain solid tumors. However, there are still numerous photobiological parameters pertaining to HpD PRT which are not fully defined. This presentation describes preclinical studies performed to examine the efficacy of HpD PRT for the treatment of ocular tumors. In addition, results of photobiological experiments designed to define the action spectrum characteristics, light dose rate properties and mutagenic potential of HpD PRT are discussed. Preclinical studies have examined the pharmacology of HpD and the toxicology of HpD PRT in both normal and malignant structures in the eye of pigmented rabbits. Distribution of HpD was measured by an acid extraction procedure. Vascular structures of the eye such as the choroid, iris and the experimental tumor retained significant levels of HpD following I.V. administration. Non-vascular structures such as cornea and lens did not take up HpD. Toxicity studies demonstrated that HpD administration (1-10 mg/kg) followed 48 hr later with a transpupil irradiation of red light (630 nm, 40-90 J/cm/sup 2/) resulted in well defined areas of retinal damage within the treatment field. The lenses of 18 eyes have remained clear during a 24 month follow-up. Tumor response following HpD PRT is rapid and is characterized by massive vascular disruption and tumor tissue necrosis

El PRT-ERP y la lucha por la libertad de los presos políticos: 1971-1973

OpenAIRE

Eidelman, Ariel

2009-01-01

Este trabajo aborda la represión política de la militancia revolucionaria por parte del régimen militar y la problemática de los presos políticos en la etapa 1971-1973 en Argentina. Se realiza un análisis de las principales características de la legislación represiva. Centralmente refiere a las diferentes iniciativas desarrolladas por el PRT-ERP en relación con sus militantes presos y en particular a la constitución de una Comisión de familiares de presos políticos, estudiantiles y gremiales ...

Impact of Preoperative Radiotherapy on General and Disease-Specific Health Status of Rectal Cancer Survivors: A Population-Based Study

International Nuclear Information System (INIS)

Thong, Melissa S.Y.; Mols, Floortje; Lemmens, Valery E.P.P.; Rutten, Harm J.T.; Roukema, Jan A.; Martijn, Hendrik; Poll-Franse, Lonneke V. van de

2011-01-01

Purpose: To date, few studies have evaluated the impact of preoperative radiotherapy (pRT) on long-term health status of rectal cancer survivors. Using a population-based sample, we assessed the impact of pRT on general and disease-specific health status of rectal cancer survivors up to 10 years postdiagnosis. The health status of older (≥75 years old at diagnosis) pRT survivors was also compared with that of younger survivors. Methods and Materials: Survivors identified from the Eindhoven Cancer Registry treated with surgery only (SU) or with pRT between 1998 and 2007 were included. Survivors completed the Short Form-36 (SF-36) health survey questionnaire and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal 38 (EORTC QLQ-CR38) questionnaire. The SF-36 and EORTC QLQ-CR38 (sexuality subscale) scores of the survivors were compared to an age- and sex-matched Dutch normal population. Results: A total of 340 survivors (response, 85%; pRT survivors, 71%) were analyzed. Overall, survivors had similar general health status. Both short-term (<5 years) and long-term (≥5 years) pRT survivors had significantly poorer body image and more problems with gastrointestinal function, male sexual dysfunction, and defecation than SU survivors. Survivors had comparable general health status but greater sexual dysfunction than the normal population. Older pRT survivors had general and disease-specific health status comparable to that of younger pRT survivors. Conclusions: For better survivorship care, rectal cancer survivors could benefit from increased clinical and psychological focus on the possible long-term morbidity of treatment and its effects on health status.

Gamma knife surgery for pineal region tumors: an alternative strategy for negative pathology

Energy Technology Data Exchange (ETDEWEB)

Wang, Peng [Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu (China); Department of Neurosurgery, The Fifth People' s Hospital of Chengdu, Chengdu (China); Mao, Qing; Wang, Wei; Zhou, Liang-Xue; Liu, Yan-Hui, E-mail: liuyanhui9@gmail.com [Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu (China)

2014-03-01

Objective: pineal region tumors (PRTs) are uncommon, and treatments vary among neoplasm types. The authors report their experience with gamma knife surgery (GKS) as an initial treatment in a series of PRT patients with unclear pathological diagnoses. Method: seventeen PRT patients with negative pathology who underwent GKS were retrospectively studied. Nine patients had further whole-brain and spinal cord radiotherapy and chemotherapy 6-9 months after GKS. Results: Sixteen of 17 cases were followed up over a mean of 33.3 months. The total response rate was 75%, and the control rate was 81.3%. No obvious neurological deficits or complications were attributable to GKS. Conclusion: the findings indicate that GKS may be an alternative strategy in selected PRT patients who have negative pathological diagnoses, and that good outcomes and quality of life can be obtained with few complications. (author)

Speed of recovery from disorientation may predict the treatment outcome of electroconvulsive therapy (ECT) in elderly patients with major depression.

Science.gov (United States)

Magne Bjølseth, Tor; Engedal, Knut; Šaltytė Benth, Jūratė; Bergsholm, Per; Strømnes Dybedal, Gro; Lødøen Gaarden, Torfinn; Tanum, Lars

2016-01-15

No study has previously investigated whether the speed of recovery from disorientation in the post-ictal period may predict the short-term treatment outcome of electroconvulsive therapy (ECT). This longitudinal cohort study included 57 elderly patients with unipolar or bipolar major depression, aged 60-85 years, treated with formula-based ECT. Treatment outcome was assessed weekly during the ECT course using the 17-item Hamilton Rating Scale for Depression (HRSD17). The post-ictal reorientation time (PRT) was assessed at the first and third treatments. Longer PRTs at the first and third treatments predicted a more rapid decline and a lower end-point in continuous HRSD17 scores (p=0.002 and 0.019, respectively). None of the patients who recovered from disorientation in less than 5 min met the remission criterion, defined as an HRSD17 score of 7 or less. A greater increment in stimulus dosage from the first to the third ECT session rendered a smaller relative decline in PRT (p<0.001). The limited number of subjects may reduce the generalizability of the findings. The speed of recovery from disorientation at the first and third sessions seems to be a predictor of the treatment outcome of formula-based ECT, at least in elderly patients with major depression. It remains to be clarified how the PRT may be utilized to guide stimulus dosing. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Neurorehabilitation with versus without resistance training after botulinum toxin treatment in children with cerebral palsy

DEFF Research Database (Denmark)

Bandholm, Thomas Quaade; Jensen, Bente Rona; Nielsen, Lone M

2012-01-01

Objective: To compare the effects of physical rehabilitation with (PRT) and without (CON) progressive resistance training following treatment of spastic plantarflexors with botulinum toxin type A (BoNT) in children with cerebral palsy (CP). Methods: Fourteen children with CP performed supervised...

Controlled comparison of family cognitive behavioral therapy and psychoeducation/relaxation training for child obsessive-compulsive disorder.

Science.gov (United States)

Piacentini, John; Bergman, R Lindsey; Chang, Susanna; Langley, Audra; Peris, Tara; Wood, Jeffrey J; McCracken, James

2011-11-01

To examine the efficacy of exposure-based cognitive-behavioral therapy (CBT) plus a structured family intervention (FCBT) versus psychoeducation plus relaxation training (PRT) for reducing symptom severity, functional impairment, and family accommodation in youths with obsessive-compulsive disorder (OCD). A total of 71 youngsters 8 to 17 years of age (mean 12.2 years; range, 8-17 years, 37% male, 78% Caucasian) with primary OCD were randomized (70:30) to 12 sessions over 14 weeks of FCBT or PRT. Blind raters assessed outcomes with responders followed for 6 months to assess treatment durability. FCBT led to significantly higher response rates than PRT in ITT (57.1% vs 27.3%) and completer analyses (68.3% vs. 35.3%). Using HLM, FCBT was associated with significantly greater change in OCD severity and child-reported functional impairment than PRT and marginally greater change in parent-reported accommodation of symptoms. These findings were confirmed in some, but not all, secondary analyses. Clinical remission rates were 42.5% for FCBT versus 17.6% for PRT. Reduction in family accommodation temporally preceded improvement in OCD for both groups and child functional status for FCBT only. Treatment gains were maintained at 6 months. FCBT is effective for reducing OCD severity and impairment. Importantly, treatment also reduced parent-reported involvement in symptoms with reduced accommodation preceding reduced symptom severity and functional impairment. CLINICAL TRIALS REGISTRY INFORMATION: Behavior Therapy for Children and Adolescents with Obsessive-Compulsive Disorder (OCD); http://www.clinicaltrials.gov; NCT00000386. Copyright © 2011 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Analysis of patterns of palliative radiotherapy in north west India: A regional cancer center experience

Directory of Open Access Journals (Sweden)

Akhil Kapoor

2015-01-01

Full Text Available Background: Palliative radiotherapy (PRT is the eventual requirement in 30-50% of all cancer patients. PRT is primarily aimed to relieve pain and prevent/treat collapse or fracture in case of bone metastasis, to reduce edema in patients with cranial metastasis, and to control distressing symptoms of rapid primary growth. An audit of PRT planned in a busy cancer center can help in the characterization of the requirements of the patients and the formulation of institutional policies. Materials and Methods: In total, 516 patients who received PRT in our regional cancer center from January 2012 to December 2012 and whose complete records were available for analysis were selected for this retrospective study. Medical records and radiotherapy files were analyzed to obtain data such as sociodemographic parameters, prescription of PRT, and follow up. Descriptive statistics were evaluated in terms of frequencies and percentages to allow comparisons. Results: Of the 516 patients, 73% patients were male; the median age of the patients receiving PRT was 62 years (range 13-83 years. About 48% ( n = 248 patients received PRT at the primary site while rest (52% were given PRT at the metastatic site. The most common indication of PRT was pain (56.8% cases, followed by cytostatic PRT (19.8% and raised ICT (12.4%. The median dose prescribed was 30 Gy (range 8-36 Gy delivered in 1-12 fractions over the duration of 1-18 days. The overall response rate was about 43% at 2 weeks of completion of PRT; the median follow-up of the patients was 154 days (range 9-256 days. The long-term symptom relief at median follow up was 8%. Conclusions: Good clinical judgment and expertise is required in prescribing correct fractionation schedule to achieve effective symptom palliation with lowest possible cost and inconvenience to the patients and relatives. Hypofractionated radiotherapy is a feasible treatment option in patients with advanced incurable disease to achieve effective

Reward Learning, Neurocognition, Social Cognition, and Symptomatology in Psychosis.

Science.gov (United States)

Lewandowski, Kathryn E; Whitton, Alexis E; Pizzagalli, Diego A; Norris, Lesley A; Ongur, Dost; Hall, Mei-Hua

2016-01-01

Patients with psychosis spectrum disorders exhibit deficits in social and neurocognition, as well as hallmark abnormalities in motivation and reward processing. Aspects of reward processing may overlap behaviorally and neurobiologically with some elements of cognitive functioning, and abnormalities in these processes may share partially overlapping etiologies in patients. However, whether reward processing and cognition are associated across the psychoses and linked to state and trait clinical symptomatology is unclear. The present study examined associations between cognitive functioning, reward learning, and clinical symptomatology in a cross-diagnostic sample. Patients with schizophrenia (SZ; n = 37), bipolar I disorder with psychosis (BD; n = 42), and healthy controls (n = 29) were assessed for clinical symptoms (patients only), neurocognitive functioning using the MATRICS Battery (MCCB) and reward learning using the probabilistic reward task (PRT). Groups were compared on neurocognition and PRT response bias, and associations between PRT response bias and neurocognition or clinical symptoms were examined controlling for demographic variables and PRT task difficulty (discriminability). Patients with SZ performed worse than controls on most measures of neurocognition; patients with BD exhibited deficits in some domains between the level of patients with SZ and controls. The SZ - but not BD - group exhibited deficits in social cognition compared to controls. Patients and controls did not differ on PRT response bias, but did differ on PRT discriminability. Better response bias across the sample was associated with poorer social cognition, but not neurocognition; conversely, discriminability was associated with neurocognition but not social cognition. Symptoms of psychosis, particularly negative symptoms, were associated with poorer response bias across patient groups. Reward learning was associated with symptoms of psychosis - in particular negative

Pupillary Response and Phenotype in ASD: Latency to Constriction Discriminates ASD from Typically Developing Adolescents.

Science.gov (United States)

Lynch, Georgina T F; James, Stephen M; VanDam, Mark

2018-02-01

Brain imaging data describe differences in the ASD brain, including amygdala overgrowth, neural interconnectivity, and a three-phase model of neuroanatomical changes from early post-natal development through late adolescence. The pupil reflex test (PRT), a noninvasive measure of brain function, may help improve early diagnosis and elucidate underlying physiology in expression of ASD endophenotype. Commonly observed characteristics of ASD include normal visual acuity but difficulty with eye gaze and photosensitivity, suggesting deficient neuromodulation of cranial nerves. Aims of this study were to confirm sensitivity of the PRT for identifying adolescents with ASD, determine if a phenotype for a subtype of ASD marked by pupil response is present in adolescence, and determine whether differences could be observed on a neurologic exam testing cranial nerves II and III (CNII; CNIII). Using pupillometry, constriction latency was measured serving as a proxy for recording neuromodulation of cranial nerves underlying the pupillary reflex. The swinging flashlight method, used to perform the PRT for measuring constriction latency and return to baseline, discriminated ASD participants from typically developing adolescents on 72.2% of trials. Results further confirmed this measure's sensitivity within a subtype of ASD in later stages of development, serving as a correlate of neural activity within the locus-coeruleus norepinephrine (LC-NE) system. A brainstem model of atypical PRT in ASD is examined in relation to modulation of cranial nerves and atypical arousal levels subserving the atypical pupillary reflex. Autism Res 2018, 11: 364-375. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Milder forms of autism spectrum disorder (ASD) can be difficult to diagnose based on behavioral testing alone. This study used eye-tracking equipment and a hand-held penlight to measure the pupil reflex in adolescents with "high functioning" ASD and in adolescents

Cigarette craving is associated with blunted reward processing in nicotine-dependent smokers.

Science.gov (United States)

Peechatka, Alyssa L; Whitton, Alexis E; Farmer, Stacey L; Pizzagalli, Diego A; Janes, Amy C

2015-10-01

Dysfunctional reward processing leading to the undervaluation of non-drug rewards is hypothesized to play a crucial role in nicotine dependence. However, it is unclear if blunted reward responsivity and the desire to use nicotine are directly linked after a brief period of abstinence. Such an association would suggest that individuals with reduced reward responsivity may be at increased risk to experience nicotine craving. Reward function was evaluated with a probabilistic reward task (PRT), which measures reward responsivity to monetary incentives. To identify whether smoking status influenced reward function, PRT performance was compared between non-depressed, nicotine-dependent smokers and non-smokers. Within smokers, correlations were conducted to determine if blunted reward responsivity on the PRT was associated with increased nicotine craving. Time since last nicotine exposure was standardized to 4h for all smokers. Smokers and non-smokers did not differ in reward responsivity on the PRT. However, within smokers, a significant negative correlation was found between reward responsivity and intensity of nicotine craving. The current findings show that, among smokers, the intensity of nicotine craving is linked to lower sensitivity to non-drug rewards. This finding is in line with prior theories that suggest reward dysfunction in some clinical populations (e.g., depressive disorders, schizophrenia) may facilitate nicotine use. The current study expands on such theories by indicating that sub-clinical variations in reward function are related to motivation for nicotine use. Identifying smokers who show blunted sensitivity to non-drug rewards may help guide treatments aimed at mitigating the motivation to smoke. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Effects of Combining Medication and Pivotal Response Treatment on Aberrant Behavior in Children with Autism Spectrum Disorder

Directory of Open Access Journals (Sweden)

Mohammad Rezaei

2018-01-01

Full Text Available Abstract: The purpose of this study was to investigate the effects of combined risperidone (RIS and pivotal response treatment (PRT on children with autism spectrum disorder (ASD. A total of 34 children diagnosed with ASD according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V (mean age of 12.36 years were randomly assigned to either of two groups; the first group (n = 17 received combined PRT–RIS while the second group (n = 17 received RIS only. Behavioral problems were evaluated with the Aberrant Behavior Checklist (ABC, whereas global improvement (GI was measured with the Clinical Global Impressions (CGI. Assessment of ABC was performed before intervention, after intervention (12 weeks, and following 3 months of the intervention (follow-up. Total ABC scores were seen to decrease in both groups after 3 months, as compared with the scores prior to the interventions. Also, in both groups, mean scores of behavioral problems after the intervention were not significantly different from those prior to the intervention, in all subscales but the inappropriate speech (p < 0.001. However, both groups showed significant differences in mean scores of ABC subscales in both of the post-intervention evaluation stages. It was concluded that the combination of behavioral and drug interventions can further improve behavioral problems, ultimately improving patient’s communication and social skills.

In vitro blood compatibility of poly (hydroxybutyrate-co-hydroxyhexanoate) and the influence of surface modification by alkali treatment

International Nuclear Information System (INIS)

Shen Feng; Zhang Erlin; Wei Zunjie

2010-01-01

In vitro blood compatibility of poly (hydroxybutyrate-co-hydroxyhexanoate) (PHBHHx) was evaluated in comparison with poly (L-lactic acid) (PLLA) by a haemolysis assay, in vitro platelet adhesion test and coagulation measurements including plasma recalcification time (PRT), plasma prothrombin time (PT) and kinetic clotting time. The results showed that PHBHHx exhibited better blood compatibility than PLLA. Furthermore, PHBHHx film was modified by NaOH treatment to improve the surface hydrophilic property and the influence of the surface modification on the blood compatibility was investigated. Surface properties including hydrophilic property, surface appearance and functional groups were characterized by water contact angle measurement, scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). The results showed that the hydrophilic property of PHBHHx film was obviously improved by the NaOH treatment. It was also shown that the NaOH treatment could significantly enhance the blood compatibility of PHBHHx by prolonging PRT, PT, and kinetic clotting time and decreasing platelet activation. It is thought that the improvement in the hydrophilic property mainly contributes to the enhancement of blood compatibility.

The effect of trigger point management by positional release therapy on tension type headache.

Science.gov (United States)

Ghanbari, Ali; Rahimijaberi, Abbas; Mohamadi, Marzieh; Abbasi, Leila; Sarvestani, Fahimeh Kamali

2012-01-01

The aim of this study was to compare the effectiveness of trigger points' management by Positional Release Therapy (PRT) and routine medical therapy in treatment of Tension Type Headache. Tension Type Headache is the most frequent headache with the basis of myofascial and trigger point disorders. PRT is an indirect technique that treats trigger points. 30 Patients with active trigger points in cervical muscles entered to the study. They were randomly assigned to PRT or medical therapy group. Headache frequency, intensity and duration and tablet count were recorded by use of a daily headache diary. Sensitivity of trigger points was assessed by numeric pain intensity and by use of a digital force gauge (FG 5020). Both groups showed significant reduction in headache frequency and duration and tablet count after treatment phase. However, the reduction of study variables was persisted only in PRT group after follow up phase. There was no significant reduction in headache intensity, neither in PRT and nor in medication group. Sensitivity of trigger points was significantly reduced. In comparison of the two study groups, there was no significant difference in headache frequency, intensity, duration and tablet count (p> 0.05). Both procedures were equally effective according to the study. Thus, PRT can be a treatment choice for patients with T.T.H.

El PRT-ERP y la lucha por la libertad de los presos políticos, 1971-1973

Directory of Open Access Journals (Sweden)

Ariel Eidelman

2009-11-01

Full Text Available Este trabajo aborda la represión política de la militancia revolucionaria por parte del régimen militar y la problemática de los presos políticos en la etapa 1971-1973 en Argentina. Se realiza un análisis de las principales características de la legislación represiva. Centralmente refiere a las diferentes iniciativas desarrolladas por el PRT-ERP en relación con sus militantes presos y en particular a la constitución de una Comisión de familiares de presos políticos, estudiantiles y gremiales para la organización de la solidaridad y defensa de los mismos. Apuntamos a destacar la amplia actividad de defensa y solidaridad con los presos políticos desarrollada por un conjunto de organizaciones como un antecedente importante, pero no reconocido, para la constitución del movimiento de derechos humanos de la Argentina en 1975-1976

Pulsed Radiation Therapy With Concurrent Cisplatin Results in Superior Tumor Growth Delay in a Head and Neck Squamous Cell Carcinoma Murine Model

Energy Technology Data Exchange (ETDEWEB)

Meyer, Kurt; Krueger, Sarah A.; Kane, Jonathan L.; Wilson, Thomas G.; Hanna, Alaa; Dabjan, Mohamad; Hege, Katie M.; Wilson, George D.; Grills, Inga; Marples, Brian, E-mail: brian.marples@beaumont.edu

2016-09-01

Purpose: To assess the efficacy of 3-week schedules of low-dose pulsed radiation treatment (PRT) and standard radiation therapy (SRT), with concurrent cisplatin (CDDP) in a head and neck squamous cell carcinoma xenograft model. Methods and Materials: Subcutaneous UT-SCC-14 tumors were established in athymic NIH III HO female mice. A total of 30 Gy was administered as 2 Gy/d, 5 d/wk for 3 weeks, either by PRT (10 × 0.2 Gy/d, with a 3-minute break between each 0.2-Gy dose) or SRT (2 Gy/d, uninterrupted delivery) in combination with concurrent 2 mg/kg CDDP 3 times per week in the final 2 weeks of radiation therapy. Treatment-induced growth delays were defined from twice-weekly tumor volume measurements. Tumor hypoxia was assessed by {sup 18}F-fluoromisonidazole positron emission tomography imaging, and calculated maximum standardized uptake values compared with tumor histology. Tumor vessel density and hypoxia were measured by quantitative immunohistochemistry. Normal tissues effects were evaluated in gut and skin. Results: Untreated tumors grew to 1000 mm{sup 3} in 25.4 days (±1.2), compared with delays of 62.3 days (±3.5) for SRT + CDDP and 80.2 days (±5.0) for PRT + CDDP. Time to reach 2× pretreatment volume ranged from 8.2 days (±1.8) for untreated tumors to 67.1 days (±4.7) after PRT + CDDP. Significant differences in tumor growth delay were observed for SRT versus SRT + CDDP (P=.04), PRT versus PRT + CDDP (P=.035), and SRT + CDDP versus PRT + CDDP (P=.033), and for survival between PRT versus PRT + CDDP (P=.017) and SRT + CDDP versus PRT + CDDP (P=.008). Differences in tumor hypoxia were evident by {sup 18}F-fluoromisonidazole positron emission tomography imaging between SRT and PRT (P=.025), although not with concurrent CDDP. Tumor vessel density differed between SRT + CDDP and PRT + CDDP (P=.011). No differences in normal tissue parameters were seen. Conclusions: Concurrent CDDP was more effective in combination PRT than SRT at

Contribution of plasmid-encoded peptidase S8 (PrtP) to adhesion and transit in the gut of Lactococcus lactis IBB477 strain.

Science.gov (United States)

Radziwill-Bienkowska, Joanna Maria; Robert, Véronique; Drabot, Karolina; Chain, Florian; Cherbuy, Claire; Langella, Philippe; Thomas, Muriel; Bardowski, Jacek Karol; Mercier-Bonin, Muriel; Kowalczyk, Magdalena

2017-07-01

The ability of Lactococcus lactis to adhere to the intestinal mucosa can potentially prolong the contact with the host, and therefore favour its persistence in the gut. In the present study, the contribution of plasmid-encoded factors to the adhesive and transit properties of the L. lactis subsp. cremoris IBB477 strain was investigated. Plasmid-cured derivatives as well as deletion mutants were obtained and analysed. Adhesion tests were performed using non-coated polystyrene plates, plates coated with mucin or fibronectin and mucus-secreting HT29-MTX intestinal epithelial cells. The results indicate that two plasmids, pIBB477a and b, are involved in adhesion of the IBB477 strain. One of the genes localised on plasmid pIBB477b (AJ89_14230), which encodes cell wall-associated peptidase S8 (PrtP), mediates adhesion of the IBB477 strain to bare, mucin- and fibronectin-coated polystyrene, as well as to HT29-MTX cells. Interactions between bacteria and mucus secreted by HT29-MTX cells were further investigated by fluorescent staining and confocal microscopy. Confocal images showed that IBB477 forms dense clusters embedded in secreted mucus. Finally, the ability of IBB477 strain and its ΔprtP deletion mutant to colonise the gastrointestinal tract of conventional C57Bl/6 mice was determined. Both strains were present in the gut for up to 72 h. In summary, adhesion and persistence of IBB477 were analysed by in vitro and in vivo approaches, respectively. Our studies revealed that plasmidic genes encoding cell surface proteins are more involved in the adhesion of IBB477 strain than in the ability to confer a selective advantage in the gut.

Riboflavin and ultraviolet light for pathogen reduction of murine cytomegalovirus in blood products.

Science.gov (United States)

Keil, Shawn D; Saakadze, Natia; Bowen, Richard; Newman, James L; Karatela, Sulaiman; Gordy, Paul; Marschner, Susanne; Roback, John; Hillyer, Christopher D

2015-04-01

Two studies were performed to test the effectiveness of riboflavin and ultraviolet (UV) light treatment (Mirasol PRT, Terumo BCT) against murine cytomegalovirus (MCMV). The first study utilized immune-compromised mice to measure the reduction of cell-free MCMV. A second study used a murine model to evaluate the ability of Mirasol PRT to prevent transfusion-transmitted (TT)-MCMV infection. Human plasma was inoculated with MCMV and then treated with Mirasol PRT. The viral titer was measured using an infectious dose 50% assay in nude mice. Mice were euthanized on Day 10 posttransfusion, and their spleens were tested for the presence of MCMV DNA using polymerase chain reaction (PCR). Mirasol PRT was also evaluated to determine its effectiveness in preventing TT-MCMV in platelets (PLTs) stored in PLT additive solution. PLTs were inoculated with either cell-associated MCMV or cell-free MCMV and then treated with Mirasol PRT. Mice were transfused with treated or untreated product and were euthanized 14 days posttransfusion. Blood and spleens were assayed for MCMV DNA by real-time-PCR. Using nude mice to titer MCMV, a modest 2.1-log reduction was observed in plasma products after Mirasol PRT treatment. TT-MCMV was not observed in the mouse transfusion model when either cell-free or cell-associated MCMV was treated with Mirasol PRT; MCMV transmission was uniformly observed in mice transfused with untreated PLTs. These results suggest that using riboflavin and UV light treatment may be able to reduce the occurrence of transmission of human CMV from infectious PLTs and plasma units. © 2014 AABB.

Swallowing therapy and progressive resistance training in head and neck cancer patients undergoing radiotherapy treatment

DEFF Research Database (Denmark)

Hajdú, Sara F; Wessel, Irene; Johansen, Christoffer

2017-01-01

BACKGROUND: Head and neck cancer (HNC) patients are often challenged by treatment induced dysphagia and trismus. Traditionally, rehabilitation is initiated when loss of function has already occurred. There is increasing evidence that it is of benefit to patients to initiate an early rehabilitation...... process before and during treatment. HNC patients have a unique set of functional challenges such as pre- and post-treatment dysphagia, pain and weight loss. The aim of the trial is to investigate the effects of swallowing and mouth-opening exercises combined with progressive resistance training (PRT...

Effectiveness of a Novel Community-Based Early Intervention Model for Children with Autistic Spectrum Disorder

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Smith, Isabel M.; Koegel, Robert L.; Koegel, Lynn K.; Openden, Daniel A.; Fossum, Kristin L.; Bryson, Susan E.

2010-01-01

The Nova Scotia early intensive behavior intervention model--NS EIBI (Bryson et al., 2007) for children with autistic spectrum disorders was designed to be feasible and sustainable in community settings. It combines parent training and naturalistic one-to-one behavior intervention employing Pivotal Response Treatment--PRT (R. Koegel & Koegel,…

New experimental treatments of core social domain in Autism Spectrum Disorders

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Roberto eCanitano

2014-06-01

Full Text Available Current therapeutics in Autism Spectrum Disorders (ASD only treat the associated symptoms, without addressing core social dysfunctions. A paradigm shift in research of the pathogenesis of ASD, its synaptic abnormalities and altered signaling in multiple dynamic systems, have led to new experimental treatments for treating the core social abnormalities of ASD. NMDA antagonists, especially memantine, have been introduced in clinical trials addressing glutamatergic transmission in children and adolescents with ASD. GABAergic signaling has been targeted in trials using the GABAB receptor agonist arbaclofen for ASD patients with promising results. Oxytocin has been recognized as implicated in social development and affiliative behaviours. Preliminary findings from clinical trials using oxytocin in children with ASD show encouraging improvements in social cognition, but larger studies are needed. In two of the single gene disorders associated with ASD, Insulin Growth Factor (IGF-1 is a new treatment that has been tested in Rett Syndrome and Phelan-McDermid Syndrome (Chromosome 22 deletion syndrome. IGF-1 has been demonstrated to reverse the reduction in the number of excitatory synapses and the density of neurons that characterize these conditions in animal studies and it is being introduced as an experimental treatment..As a novel approach to verify treatment efficacy,neural processing modifications were recently evaluated by fMRI after a Pivotal Response Training (PRT intervention. Another study of neural changes in response to treatment examined variations in EEG signaling in patientsafter an Early Start Denver Model (ESDM intervention.

Solar Powered Remediation and pH Control

Science.gov (United States)

2017-04-13

zone. The PRT system was completely powered via an off-the-grid solar power system . The system consisted of four 85 watt photovoltaic solar panels...polarity of the proton reduction system can be periodically alternated (i.e., the anode becomes a cathode) to increase the size of the treatment area, to...PRT System The PRT system was completely powered via an off-the-grid solar power system . The system consisted of four 85 watt photovoltaic solar

Treatment non-response: Associations with smoking expectancies among treatment-seeking smokers.

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Garey, Lorra; Taha, Samar A; Kauffman, Brooke Y; Manning, Kara F; Neighbors, Clayton; Schmidt, Norman B; Zvolensky, Michael J

2017-10-01

Despite the high rate of smoking cessation treatment non-response, relatively little empirical work has examined predictors of treatment non-response. The present study sought to explore the effect of smoking outcome expectancies on treatment response in a sample of treatment-seeking adult daily smokers (N=182; 53.3% female; M age =40.67; SD=13.63). Results indicated that expectancies for smoking to reduce negative affect were related to an increased likelihood of treatment non-response (OR=0.73, CI: 0.54, 0.98). These findings remained significant after controlling for sex, presence of Axis I disorder, tobacco-related health problems, tobacco dependence, anxiety sensitivity, and condition assignment as well as other smoking expectancy dimensions. Post hoc analyses revealed that this relation was stronger for smokers in the integrated care condition vs. the standard care condition (Interaction: OR=1.69, CI: 1.05, 2.73). Additionally, expectancies for smoking to enhance positive affect and provide sensory satisfaction were associated with an increased likelihood of treatment response in the standard care condition. The current findings suggest expectancies that smoking will alleviate negative affect may be a risk factor of smoking cessation treatment non-response. Additionally, findings provide evidence that the relation between smoking expectancies and treatment non-response may differ by smoking cessation treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Treatment response in HCV related chronic hepatitis

International Nuclear Information System (INIS)

Hussain, A.B.; Hussain, T.; Hussain, S.; Masood, A.; Kazmi, Y.; Tariq, W.Z.; Karamat, K.A.

2004-01-01

Objective: To evaluate the virological response to treatment with interferon and ribavirin in-patients with hepatitis C related liver disease. Material and Methods: Two hundred seventy-nine patients were included in the study. These patients had taken interferon and ribavirin treatment for HCV related chronic hepatitis, and were referred to AFIP for HCV RNA testing by polymerase chain reaction (PCR) between January 2002 and September 2002. Out of 279 cases, 229 had taken the treatment for 06 or 12 months and were tested for end-of-treatment response (ETR). Fifty patients had completed there treatment regimens of 6 or 12 months treatment, at least 24 weeks before their PCR test and were having follow-up testing for sustained viral response (SVR). The sera of these patients were tested for HCV RNA by PCR, using a commercial kit of Amplicor (Roche) for qualitative detection of HCV RNA. Results: Out of 229 cases tested for end-of-treatment response, 198 (86.5%) had no detectable HCV RNA (responders) and 31 (13.50%) were PCR positive (non-responders). Thirty-eight out of 50 cases, tested for a sustained viral response, had a negative result for HCV PCR thus showing sustained response rate of 76%. Conclusion: The viral remission/response to interferon and ribavirin combination therapy in our patients was better than that quoted in other regions. (author)

N-terminomics reveals control of Arabidopsis seed storage proteins and proteases by the Arg/N-end rule pathway.

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Zhang, Hongtao; Gannon, Lucy; Hassall, Kirsty L; Deery, Michael J; Gibbs, Daniel J; Holdsworth, Michael J; van der Hoorn, Renier A L; Lilley, Kathryn S; Theodoulou, Frederica L

2018-05-01

The N-end rule pathway of targeted protein degradation is an important regulator of diverse processes in plants but detailed knowledge regarding its influence on the proteome is lacking. To investigate the impact of the Arg/N-end rule pathway on the proteome of etiolated seedlings, we used terminal amine isotopic labelling of substrates with tandem mass tags (TMT-TAILS) for relative quantification of N-terminal peptides in prt6, an Arabidopsis thaliana N-end rule mutant lacking the E3 ligase PROTEOLYSIS6 (PRT6). TMT-TAILS identified over 4000 unique N-terminal peptides representing c. 2000 protein groups. Forty-five protein groups exhibited significantly increased N-terminal peptide abundance in prt6 seedlings, including cruciferins, major seed storage proteins, which were regulated by Group VII Ethylene Response Factor (ERFVII) transcription factors, known substrates of PRT6. Mobilisation of endosperm α-cruciferin was delayed in prt6 seedlings. N-termini of several proteases were downregulated in prt6, including RD21A. RD21A transcript, protein and activity levels were downregulated in a largely ERFVII-dependent manner. By contrast, cathepsin B3 protein and activity were upregulated by ERFVIIs independent of transcript. We propose that the PRT6 branch of the pathway regulates protease activities in a complex manner and optimises storage reserve mobilisation in the transition from seed to seedling via control of ERFVII action. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

Exposure Plus Response-Prevention Treatment of Bulimia Nervosa.

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Leitenberg, Harold; And Others

1988-01-01

Evaluated exposure plus response-prevention treatment of bulimia nervosa among 47 women. Subjects were assigned to either exposure plus response-prevention in one setting, exposure plus response-prevention in multiple settings, cognitive-behavioral therapy, or waiting-list control conditions. Found three treatment groups improved significantly on…

Predicting Treatment Response for Oppositional Defiant and Conduct Disorder Using Pre-treatment Adrenal and Gonadal Hormones.

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Shenk, Chad E; Dorn, Lorah D; Kolko, David J; Susman, Elizabeth J; Noll, Jennie G; Bukstein, Oscar G

2012-12-01

Variations in adrenal and gonadal hormone profiles have been linked to increased rates of oppositional defiant disorder (ODD) and conduct disorder (CD). These relationships suggest that certain hormone profiles may be related to how well children respond to psychological treatments for ODD and CD. The current study assessed whether pre-treatment profiles of adrenal and gonadal hormones predicted response to psychological treatment of ODD and CD. One hundred five children, 6 - 11 years old, participating in a randomized, clinical trial provided samples for cortisol, testosterone, dehydroepiandrosterone, and androstenedione. Diagnostic interviews of ODD and CD were administered up to three years post-treatment to track treatment response. Group-based trajectory modeling identified two trajectories of treatment response: 1) a High-response trajectory where children demonstrated lower rates of an ODD or CD diagnosis throughout follow-up, and 2) a Low-response trajectory where children demonstrated higher rates of an ODD or CD diagnosis throughout follow-up. Hierarchical logistic regression predicting treatment response demonstrated that children with higher pre-treatment concentrations of testosterone were four times more likely to be in the Low-response trajectory. No other significant relationship existed between pre-treatment hormone profiles and treatment response. These results suggest that higher concentrations of testosterone are related to how well children diagnosed with ODD or CD respond to psychological treatment over the course of three years.

Predictors of response to neuroleptic treatment in schizophrenia.

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Stern, R G; Kahn, R S; Davidson, M

1993-06-01

Baseline symptom severity, early reduction in symptom severity, initial subjective response to neuroleptic treatment, the degree of brain atrophy, and early changes in pHVA levels appear to predict treatment outcome in schizophrenic patients. Computerized EEG results, neuropsychological and neurophysiologic tests, and baseline pHVA concentrations require further examination. Only a limited proportion of variance in treatment response, however, could be explained by either of the nine predictors alone or combined. Therefore, further research is necessary to discover yet unidentified determinants of treatment response. Future studies should test the validity and reliability of these five promising predictors in large groups of male and female patients, employ high standards for assessment reliability of clinical parameters, and use absolute rating scores on psychopathology as well as functional scales for the definition of good and poor treatment response. Furthermore, the statistical approach for data analysis should take in consideration the need for appropriate corrections when multiple correlations are performed and should test the extent to which these predictors are interdependent.

Publication bias in studies of an applied behavior-analytic intervention: an initial analysis.

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Sham, Elyssa; Smith, Tristram

2014-01-01

Publication bias arises when studies with favorable results are more likely to be reported than are studies with null findings. If this bias occurs in studies with single-subject experimental designs(SSEDs) on applied behavior-analytic (ABA) interventions, it could lead to exaggerated estimates of intervention effects. Therefore, we conducted an initial test of bias by comparing effect sizes, measured by percentage of nonoverlapping data (PND), in published SSED studies (n=21) and unpublished dissertations (n=10) on 1 well-established intervention for children with autism, pivotal response treatment (PRT). Although published and unpublished studies had similar methodologies, the mean PND in published studies was 22% higher than in unpublished studies, 95% confidence interval (4%, 38%). Even when unpublished studies are included, PRT appeared to be effective (PNDM=62%). Nevertheless, the disparity between published and unpublished studies suggests a need for further assessment of publication bias in the ABA literature.

Habituation of exploratory activity in aged rats: effects of pyritinol Habituação da atividade exploratória em ratos idosos: efeitos do piritinol

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Roberto DeLucia

2005-03-01

Full Text Available Acetylcholine (Ach is a neurotransmitter considered to play a critical role in processes underlying behavior, learning, and memory. Pyritinol (pyrithioxine, Encephabolâ, PRT is a nootropic drug that increases cholinergic transmission in the central nervous system. Behavioral habituation following multiple exposures to an open field is an experimental paradigm frequently used to assess the cognitive actions of drugs. In this paradigm the decrease of exploratory activity as a function of repeated exposure to the same environment is taken as an index memory. In the present study, effects PRT administrated to aged rats in powder form added to the diet (200 mg /kg / day, p.o., for 14 days were evaluated in the habituation to an open field. A total of 18 aged rats were randomly assigned to one of two groups control (vehicle-treated rats, n = 8 and experimental group (PRT-treated rats, n = 10 and were used in the following procedure. In the exploratory task, the post-training treatment with PRT significantly decreased the number of total area crossings and rears when compared to the control group, indicating habituation. PRT treatment enhanced retention in the total number of area crossings and rears when compared with control animals. Taken together, the data of present study suggest that muscarinic cholinergic systems could be involved in the effect of PRT in habituation of exploratory activity to an open field in aged rats.A acetilcolina é um neurotransmissor que desempenha considerável papel crítico nos processos subjacentes ao comportamento, aprendizagem e memória. Piritinol (piritioxina, Encefabolâ, PRT é um fármaco nootrópico que aumenta a transmissão colinérgica no sistema nervoso central. Habituação comportamental seguida de múltipla exposição no campo aberto é um paradigma experimental freqüentemente usado na avaliação das ações cognitivas de fármacos. Neste paradigma, a diminuição da atividade exploratória em fun

Excessive biologic response to IFNβ is associated with poor treatment response in patients with multiple sclerosis.

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Richard A Rudick

Full Text Available BACKGROUND: Interferon-beta (IFNβ is used to inhibit disease activity in multiple sclerosis (MS, but its mechanisms of action are incompletely understood, individual treatment response varies, and biological markers predicting response to treatment have yet to be identified. METHODS: The relationship between the molecular response to IFNβ and treatment response was determined in 85 patients using a longitudinal design in which treatment effect was categorized by brain magnetic resonance imaging as good (n = 70 or poor response (n = 15. Molecular response was quantified using a customized cDNA macroarray assay for 166 IFN-regulated genes (IRGs. RESULTS: The molecular response to IFNβ differed significantly between patients in the pattern and number of regulated genes. The molecular response was strikingly stable for individuals for as long as 24 months, however, suggesting an individual 'IFN response fingerprint'. Unexpectedly, patients with poor response showed an exaggerated molecular response. IRG induction ratios demonstrated an exaggerated molecular response at both the first and 6-month IFNβ injections. CONCLUSION: MS patients exhibit individually unique but temporally stable biological responses to IFNβ. Poor treatment response is not explained by the duration of biological effects or the specific genes induced. Rather, individuals with poor treatment response have a generally exaggerated biological response to type 1 IFN injections. We hypothesize that the molecular response to type I IFN identifies a pathogenetically distinct subset of MS patients whose disease is driven in part by innate immunity. The findings suggest a strategy for biologically based, rational use of IFNβ for individual MS patients.

A cost-effectiveness analysis of adjuvant therapies for resected adenocarcinoma of the rectum

International Nuclear Information System (INIS)

Lee, Jason H.

1997-01-01

PURPOSE: Several prospective randomized trials have shown a significant survival advantage with adjuvant chemotherapy and radiation therapy following surgical resection of adenocarcinoma of the rectum. Recent and ongoing trials are evaluating the role of modulated and/or protracted venous infusion [PVI] chemotherapy with pelvic irradiation [PRT]. The economic implications of additional therapies compared with their incremental benefits have not been rigorously analyzed. This study attempts to assess the incremental cost effectiveness of adjuvant therapy over surgery alone, and secondly, adjuvant therapy with PVI delivery systems versus rapid infusion. METHODS: A Markov model was constructed to describe the natural history of rectal carcinoma [stage B2, C] following surgical resection in a hypothetical cohort of 60 year old patients. This model was used to perform two sets of comparisons: [1] surgery alone versus adjuvant bolus fluorouracil [5-FU] with PRT, and [2] bolus 5-FU with PRT versus PVI 5-FU with PRT. Relapse rates and overall survival were derived from an early GITSG trial for the first comparison and from the NCCTG 86-47-51 trial for the second comparison. Medicare reimbursement rates and reports from health maintenance organizations were used to obtain net medical costs of adjuvant treatments, routine follow-up, advanced recurrent disease, and terminal illness as a result of rectal carcinoma. Total years of life and medical costs were projected over an 8-year time horizon for the first comparison [GITSG data] and over a 5-year time horizon for the second comparison [NCCTG data]. Monetary and nonmonetary benefits were discounted at 5% per year. Adjustments for quality of life, costs of adverse effects from treatment, and indirect costs of disease or treatment were not included in this current analysis. RESULTS: The main survival and economic outcomes for each treatment arm in the two comparisons are reported in the table below. For the first comparison

Prediction of treatment response to adalimumab

DEFF Research Database (Denmark)

Krintel, S B; Dehlendorff, C; Hetland, M L

2016-01-01

At least 30% of patients with rheumatoid arthritis (RA) do not respond to biologic agents, which emphasizes the need of predictive biomarkers. We aimed to identify microRNAs (miRNAs) predictive of response to adalimumab in 180 treatment-naïve RA patients enrolled in the OPtimized treatment algori...... of low expression of miR-22 and high expression of miR-886.3p was associated with EULAR good response. Future studies to assess the utility of these miRNAs as predictive biomarkers are needed.The Pharmacogenomics Journal advance online publication, 5 May 2015; doi:10.1038/tpj.2015.30....

Hepatitis B viral factors and treatment responses in chronic hepatitis B

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Chih-Lin Lin

2013-06-01

Full Text Available Baseline and on-treatment hepatitis B viral factors are reported to affect treatment responses. A lower baseline hepatitis B virus (HBV DNA level is a strong predictor of the response to antiviral therapy. HBV genotype A/B patients have better responses to interferon-based therapy than those with genotypes C/D. Regarding the association of HBV mutants with responses to antiviral therapy, current evidence is limited. On-treatment viral suppression is the most important predictor of response to nucleoside analogs. On-treatment hepatitis B surface antigen decline is significantly associated with response to pegylated interferon. In the future, individualized therapy should be based on treatment efficacy, adverse effects, baseline and on-treatment predictors of antiviral therapy.

A randomized trial comparison of the effects of verbal and pictorial naturalistic communication strategies on spoken language for young children with autism.

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Schreibman, Laura; Stahmer, Aubyn C

2014-05-01

Presently there is no consensus on the specific behavioral treatment of choice for targeting language in young nonverbal children with autism. This randomized clinical trial compared the effectiveness of a verbally-based intervention, Pivotal Response Training (PRT) to a pictorially-based behavioral intervention, the Picture Exchange Communication System (PECS) on the acquisition of spoken language by young (2-4 years), nonverbal or minimally verbal (≤9 words) children with autism. Thirty-nine children were randomly assigned to either the PRT or PECS condition. Participants received on average 247 h of intervention across 23 weeks. Dependent measures included overall communication, expressive vocabulary, pictorial communication and parent satisfaction. Children in both intervention groups demonstrated increases in spoken language skills, with no significant difference between the two conditions. Seventy-eight percent of all children exited the program with more than 10 functional words. Parents were very satisfied with both programs but indicated PECS was more difficult to implement.

Mechanisms Underlying the Antidepressant Response and Treatment Resistance

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Marjorie Rose Levinstein

2014-06-01

Full Text Available Depression is a complex and heterogeneous disorder affecting millions of Americans. There are several different medications and other treatments that are available and effective for many patients with depression. However, a substantial percentage of patients fail to achieve remission with these currently available interventions, and relapse rates are high. Therefore, it is necessary to determine both the mechanisms underlying the antidepressant response and the differences between responders and non-responders to treatment. Delineation of these mechanisms largely relies on experiments that utilize animal models. Therefore, this review provides an overview of the various mouse models that are currently used to assess the antidepressant response, such as chronic mild stress, social defeat, and chronic corticosterone. We discuss how these mouse models can be used to advance our understanding of the differences between responders and non-responders to antidepressant treatment. We also provide an overview of experimental treatment modalities that are used for treatment-resistant depression, such as deep brain stimulation and ketamine administration. We will then review the various genetic polymorphisms and transgenic mice that display resistance to antidepressant treatment. Finally, we synthesize the published data to describe a potential neural circuit underlying the antidepressant response and treatment resistance.

Pattern of palliative care, pain management and referral trends in patients receiving radiotherapy at a tertiary cancer center

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Kuldeep Sharma

2009-01-01

Full Text Available Background: Pain is a common primary symptom of advanced cancer and metastatic disease, occurring in 50-75% of all patients. Although palliative care and pain management are essential components in oncology practice, studies show that these areas are often inadequately addressed. Materials and Methods: We randomly selected 152 patients receiving palliative radiotherapy (PRT from October 2006 to August 2008, excluding metastatic bone lesions. Patients′ records were studied retrospectively. Results: A median follow-up of 21 weeks was available for 119 males and 33 females with a median age of 55 years. Maximum (60% patients were of head and neck cancers followed by esophagus (14%, lung (10% and others. Dysphagia, growth/ulcer and pain were the chief indications for PRT. Pain was present in 93 (61% cases out of which, 56 (60% were referred to pain clinic. All except one consulted pain clinic with a median pain score of 8 (0-10 point scale. Fifty-three of these 56 patients (96% received opioid-based treatment with adequate pain relief in 33% cases and loss of follow-up in 40% cases. Only five (3% cases were referred to a hospice. Twenty-two (14% cases were considered for radical treatment following excellent response to PRT. Conclusion: In this selective sample, the standard of analgesic treatment was found to be satisfactory. However, there is a lot of scope for improvement regarding referral to pain clinic and later to the hospice. Patients′ follow-up needs to be improved along with future studies evaluating those patients who were considered for further RT till radical dose. Programs to change the patients′ attitude towards palliative care, physicians′ (residents′ training to improve communication skills, and institutional policies may be promising strategies.

Pathogen inactivation efficacy of Mirasol PRT System and Intercept Blood System for non-leucoreduced platelet-rich plasma-derived platelets suspended in plasma.

Science.gov (United States)

Kwon, S Y; Kim, I S; Bae, J E; Kang, J W; Cho, Y J; Cho, N S; Lee, S W

2014-10-01

This study was conducted to evaluate the efficacy of pathogen inactivation (PI) in non-leucoreduced platelet-rich plasma-derived platelets suspended in plasma using the Mirasol PRT System and the Intercept Blood System. Platelets were pooled using the Acrodose PL system and separated into two aliquots for Mirasol and Intercept treatment. Four replicates of each viral strain were used for the evaluation. For bacteria, both low-titre (45-152 CFU/unit) inoculation and high-titre (7·34-10·18 log CFU/unit) inoculation with two replicates for each bacterial strain were used. Platelets with non-detectable bacterial growth and platelets inoculated with a low titre were stored for 5 days, and culture was performed with the BacT/ALERT system. The inactivation efficacy expressed as log reduction for Mirasol and Intercept systems for viruses was as follows: human immunodeficiency virus 1, ≥4·19 vs. ≥4·23; bovine viral diarrhoea virus, 1·83 vs. ≥6·03; pseudorabies virus, 2·73 vs. ≥5·20; hepatitis A virus, 0·62 vs. 0·76; and porcine parvovirus, 0·28 vs. 0·38. The inactivation efficacy for bacteria was as follows: Escherichia coli, 5·45 vs. ≥9·22; Staphylococcus aureus, 4·26 vs. ≥10·11; and Bacillus subtilis, 5·09 vs. ≥7·74. Postinactivation bacterial growth in platelets inoculated with a low titre of S. aureus or B. subtilis was detected only with Mirasol. Pathogen inactivation efficacy of Intercept for enveloped viruses was found to be satisfactory. Mirasol showed satisfactory inactivation efficacy for HIV-1 only. The two selected non-enveloped viruses were not inactivated by both systems. Inactivation efficacy of Intercept was more robust for all bacteria tested at high or low titres. © 2014 International Society of Blood Transfusion.

Ovarian steroid hormones modulate the expression of progesterone receptors and histone acetylation patterns in uterine leiomyoma cells.

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Sant'Anna, Gabriela Dos Santos; Brum, Ilma Simoni; Branchini, Gisele; Pizzolato, Lolita Schneider; Capp, Edison; Corleta, Helena von Eye

2017-08-01

Uterine leiomyomas are the most common benign smooth muscle cell tumors in women. Estrogen (E2), progesterone (P4) and environmental factors play important roles in the development of these tumors. New treatments, such as mifepristone, have been proposed. We evaluated the gene expression of total (PRT) and B (PRB) progesterone receptors, and the histone acetyltransferase (HAT) and deacetylase (HDAC) activity after treatment with E2, P4 and mifepristone (RU486) in primary cell cultures from uterine leiomyoma and normal myometrium. Compared to myometrium, uterine leiomyoma cells showed an increase in PRT mRNA expression when treated with E2, and increase in PRB mRNA expression when treated with E2 and P4. Treatment with mifepristone had no significant impact on mRNA expression in these cells. The HDAC activity was higher in uterine leiomyoma compared to myometrial cells after treatment with E2 and E2 + P4 + mifepristone. HAT activity was barely detectable. Our results suggest that ovarian steroid hormones modulate PR, and mifepristone was unable to decrease PRT and PRB mRNA. The higher activity of HDAC leiomyoma cells could be involved in transcriptional repression of genes implicated in normal myometrium cell function, contributing to the maintenance and growth of uterine leiomyoma.

Patterns of Response After Preoperative Treatment in Gastric Cancer

International Nuclear Information System (INIS)

Diaz-Gonzalez, Juan A.; Rodriguez, Javier; Hernandez-Lizoain, Jose L.; Ciervide, Raquel; Gaztanaga, Miren; San Miguel, Inigo; Arbea, Leire; Aristu, J. Javier; Chopitea, Ana; Martinez-Regueira, Fernando; Valenti, Victor; Garcia-Foncillas, Jesus; Martinez-Monge, Rafael; Sola, Jesus J.

2011-01-01

Purpose: To analyze the rate of pathologic response in patients with locally advanced gastric cancer treated with preoperative chemotherapy with and without chemoradiation at our institution. Methods and Materials: From 2000 to 2007 patients were retrospectively identified who received preoperative treatment for gastric cancer (cT3-4/ N+) with induction chemotherapy (Ch) or with Ch followed by concurrent chemoradiotherapy (45 Gy in 5 weeks) (ChRT). Surgery was planned 4-6 weeks after the completion of neoadjuvant treatment. Pathologic assessment was used to investigate the patterns of pathologic response after neoadjuvant treatment. Results: Sixty-one patients were analyzed. Of 61 patients, 58 (95%) underwent surgery. The R0 resection rate was 87%. Pathologic complete response was achieved in 12% of the patients. A major pathologic response (<10% of residual tumor) was observed in 53% of patients, and T downstaging was observed in 75%. Median follow-up was 38.7 months. Median disease-free survival (DFS) was 36.5 months. The only patient-, tumor-, and treatment-related factor associated with pathologic response was the use of preoperative ChRT. Patients achieving major pathologic response had a 3-year actuarial DFS rate of 63%. Conclusions: The patterns of pathologic response after preoperative ChRT suggest encouraging intervals of DFS. Such a strategy may be of interest to be explored in gastric cancer.

HPA axis response to psychological stress and treatment retention in residential substance abuse treatment: a prospective study.

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Daughters, Stacey B; Richards, Jessica M; Gorka, Stephanie M; Sinha, Rajita

2009-12-01

Substance abuse treatment programs are often characterized by high rates of premature treatment dropout, which increases the likelihood of relapse to drug use. Negative reinforcement models of addiction emphasize an individual's inability to tolerate stress as a key factor for understanding poor substance use treatment outcomes, and evidence indicates that dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis contributes to an individual's inability to respond adaptively to stress. The aim of the current study was to examine whether HPA axis response to stress is predictive of treatment retention among a sample of drug users in residential substance abuse treatment. Prospective study assessing treatment retention among 102 individuals enrolled in residential substance abuse treatment. Participants completed two computerized stress tasks, and HPA axis response to stress was measured via salivary cortisol at five time points from baseline (pre-stress) to 30 min post-stress exposure. The main outcome measures were treatment dropout (categorical) and total number of days in treatment (continuous). A significantly higher salivary cortisol response to stress was observed in treatment dropouts compared to treatment completers. Further, Cox proportional hazards survival analyses indicated that a higher peak cortisol response to stress was associated with a shorter number of days to treatment dropout. Results indicate that a higher salivary cortisol level in response to stress is associated with an inability to remain in substance abuse treatment. These findings are the first to document a biological marker of stress as a predictor of substance abuse treatment dropout, and support the development and implementation of treatments targeting this vulnerability.

Estimating the Need for Palliative Radiation Therapy: A Benchmarking Approach

Energy Technology Data Exchange (ETDEWEB)

Mackillop, William J., E-mail: william.mackillop@krcc.on.ca [Cancer Care and Epidemiology, Queen' s Cancer Research Institute, Queen' s University, Kingston, Ontario (Canada); Department of Public Health Sciences, Queen' s University, Kingston, Ontario (Canada); Department of Oncology, Queen' s University, Kingston, Ontario (Canada); Kong, Weidong [Cancer Care and Epidemiology, Queen' s Cancer Research Institute, Queen' s University, Kingston, Ontario (Canada)

2016-01-01

Purpose: Palliative radiation therapy (PRT) benefits many patients with incurable cancer, but the overall need for PRT is unknown. Our primary objective was to estimate the appropriate rate of use of PRT in Ontario. Methods and Materials: The Ontario Cancer Registry identified patients who died of cancer in Ontario between 2006 and 2010. Comprehensive RT records were linked to the registry. Multivariate analysis identified social and health system-related factors affecting the use of PRT, enabling us to define a benchmark population of patients with unimpeded access to PRT. The proportion of cases treated at any time (PRT{sub lifetime}), the proportion of cases treated in the last 2 years of life (PRT{sub 2y}), and number of courses of PRT per thousand cancer deaths were measured in the benchmark population. These benchmarks were standardized to the characteristics of the overall population, and province-wide PRT rates were then compared to benchmarks. Results: Cases diagnosed at hospitals with no RT on-site and residents of poorer communities and those who lived farther from an RT center, were significantly less likely than others to receive PRT. However, availability of RT at the diagnosing hospital was the dominant factor. Neither socioeconomic status nor distance from home to nearest RT center had a significant effect on the use of PRT in patients diagnosed at a hospital with RT facilities. The benchmark population therefore consisted of patients diagnosed at a hospital with RT facilities. The standardized benchmark for PRT{sub lifetime} was 33.9%, and the corresponding province-wide rate was 28.5%. The standardized benchmark for PRT{sub 2y} was 32.4%, and the corresponding province-wide rate was 27.0%. The standardized benchmark for the number of courses of PRT per thousand cancer deaths was 652, and the corresponding province-wide rate was 542. Conclusions: Approximately one-third of patients who die of cancer in Ontario need PRT, but many of them are never

Support to X-33/Resusable Launch Vehicle Technology Program

Science.gov (United States)

2000-01-01

The X-33 Guidance, Navigation, and Control (GN&C) Peer Review Team (PRT) was formed to assess the integrated X-33 vehicle GN&C system in order to identify any areas of disproportionate risk for initial flight. The eventual scope of the PRT assessment encompasses the GN&C algorithms, software, avionics, control effectors, applicable models, and testing. The initial (phase 1) focus of the PRT was on the GN&C algorithms and the Flight Control Actuation Subsystem (FCAS). The PRT held meetings during its phase 1 assessment at X-33 assembly facilities in Palmdale, California on May 17-18, 2000 and at Honeywell facilities in Tempe, Arizona on June 7, 2000. The purpose of these meetings was for the PRT members to get background briefings on the X-33 vehicle and for the PRT team to be briefed on the design basis and current status of the X-33 GN&C algorithms as well as the FCAS. The following material is covered in this PRT phase 1 final report. Some significant GN&C-related accomplishments by the X-33 development team are noted. Some topics are identified that were found during phase 1 to require fuller consideration when the PRT reconvenes in the future. Some new recommendations by the PRT to the X-33 program will likely result from a thorough assessment of these subjects. An initial list of recommendations from the PRT to the X-33 program is provided. These recommendations stem from topics that received adequate review by the PRT in phase 1. Significant technical observations by the PRT members as a result of the phase 1 meetings are detailed. (These are covered in an appendix.) There were many X-33 development team members who contributed to the technical information used by the PRT during the phase 1 assessment, who supported presentations to the PRT, and who helped to address the many questions posed by the PRT members at and after the phase 1 meetings. In all instances the interaction between the PRT and the X-33 development team members was cordial and very

The Impact of Early Substance Use Disorder Treatment Response on Treatment Outcomes Among Pregnant Women With Primary Opioid Use.

Science.gov (United States)

Tuten, Michelle; Fitzsimons, Heather; Hochheimer, Martin; Jones, Hendree E; Chisolm, Margaret S

2018-03-13

This study examined the impact of early patient response on treatment utilization and substance use among pregnant participants enrolled in substance use disorder (SUD) treatment. Treatment responders (TRs) and treatment nonresponders (TNRs) were compared on pretreatment and treatment measures. Regression models predicted treatment utilization and substance use. TR participants attended more treatment and had lower rates of substance use relative to TNR participants. Regression models for treatment utilization and substance use were significant. Maternal estimated gestational age (EGA) and baseline cocaine use were negatively associated with treatment attendance. Medication-assisted treatment, early treatment response, and baseline SUD treatment were positively associated with treatment attendance. Maternal EGA was negatively associated with counseling attendance; early treatment response was positively associated with counseling attendance. Predictors of any substance use at 1 month were maternal education, EGA, early treatment nonresponse, and baseline cocaine use. The single predictor of any substance use at 2 months was early treatment nonresponse. Predictors of opioid use at 1 month were maternal education, EGA, early treatment nonresponse, and baseline SUD treatment. Predictors of opioid use at 2 months were early treatment nonresponse, and baseline cocaine and marijuana use. Predictors of cocaine use at 1 month were early treatment nonresponse, baseline cocaine use, and baseline SUD treatment. Predictors of cocaine use at 2 months were early treatment nonresponse and baseline cocaine use. Early treatment response predicts more favorable maternal treatment utilization and substance use outcomes. Treatment providers should implement interventions to maximize patient early response to treatment.

Acute Effects of Plyometric and Resistance Training on Running Economy in Trained Runners.

Science.gov (United States)

Marcello, Richard T; Greer, Beau K; Greer, Anna E

2017-09-01

Marcello, RT, Greer, BK, and Greer, AE. Acute effects of plyometric and resistance training on running economy in trained runners. J Strength Cond Res 31(9): 2432-2437, 2017-Results regarding the acute effects of plyometrics and resistance training (PRT) on running economy (RE) are conflicting. Eight male collegiate distance runners (21 ± 1 years, 62.5 ± 7.8 ml·kg·min V[Combining Dot Above]O2 peak) completed V[Combining Dot Above]O2 peak and 1 repetition maximum (1RM) testing. Seven days later, subjects completed a 12 minutes RE test at 60 and 80% V[Combining Dot Above]O2 peak, followed by a PRT protocol or a rested condition of equal duration (CON). The PRT protocol consisted of 3 sets of 5 repetitions at 85% 1RM for barbell squats, Romanian deadlifts, and barbell lunges; the same volume was used for resisted lateral lunges, box jumps, and depth jumps. Subjects completed another RE test immediately after the treatments and 24 hours later. Subjects followed an identical protocol 6 days later with condition assignment reversed. Running economy was determined by both relative V[Combining Dot Above]O2 (ml·kg·min) and energy expenditure (EE) (kcal·min). There was a significant (p ≤ 0.05) between-trial increase in V[Combining Dot Above]O2 (37.1 ± 4.2 ml·kg·min PRT vs. 35.5 ± 3.9 ml·kg·min CON) and EE (11.4 ± 1.3 kcal·min PRT vs. 11.0 ± 1.4 kcal·min CON) immediately after PRT at 60% V[Combining Dot Above]O2 peak, but no significant changes were observed at 80% V[Combining Dot Above]O2 peak. Respiratory exchange ratio was significantly (p ≤ 0.05) reduced 24 hours after PRT (0.93 ± 0.0) as compared to the CON trial (0.96 ± 0.0) at 80% V[Combining Dot Above]O2 peak. Results indicate that high-intensity PRT may acutely impair RE in aerobically trained individuals at a moderate running intensity, but that the attenuation lasts less than 24 hours in duration.

Antisocial Traits as Modifiers of Treatment Response in Borderline Inpatients

OpenAIRE

CLARKIN, JOHN F.; HULL, JAMES; YEOMANS, FRANK; KAKUMA, TATSUYUKI; CANTOR, JENNIFER

1994-01-01

The relationship of antisocial traits to treatment response in 35 female inpatients with borderline personality disorder was studied. Antisocial traits were measured with the Personality Assessment Inventory. Treatment response was measured by weekly ratings on the Symptom Checklist-90—Revised over 25 weeks of hospitalization. Treatment course was found to be significantly associated with the level of antisocial behavior reported at admission.

Preference for Blocking or Response Redirection during Stereotypy Treatment

Science.gov (United States)

Giles, Aimee F.; St. Peter, Claire C.; Pence, Sacha T.; Gibson, Alexandra B.

2012-01-01

Response redirection and response blocking reduce stereotypy maintained by automatic reinforcement. The current study evaluated the effects of redirection and response blocking on the stereotypic responding of three elementary-age children diagnosed with autism. During the treatment evaluation, redirection and response blocking were evaluated…

Imaging tools to measure treatment response in gout.

Science.gov (United States)

Dalbeth, Nicola; Doyle, Anthony J

2018-01-01

Imaging tests are in clinical use for diagnosis, assessment of disease severity and as a marker of treatment response in people with gout. Various imaging tests have differing properties for assessing the three key disease domains in gout: urate deposition (including tophus burden), joint inflammation and structural joint damage. Dual-energy CT allows measurement of urate deposition and bone damage, and ultrasonography allows assessment of all three domains. Scoring systems have been described that allow radiological quantification of disease severity and these scoring systems may play a role in assessing the response to treatment in gout. This article reviews the properties of imaging tests, describes the available scoring systems for quantification of disease severity and discusses the challenges and controversies regarding the use of imaging tools to measure treatment response in gout. © The Author 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Prognostic value of neoadjuvant treatment response in locally advanced rectal cancer.

Science.gov (United States)

Sada, Yvonne H; Tran Cao, Hop S; Chang, George J; Artinyan, Avo; Musher, Benjamin L; Smaglo, Brandon G; Massarweh, Nader N

2018-06-01

For locally advanced rectal cancer, response to neoadjuvant radiation has been associated with improved outcomes but has not been well characterized in general practice. The goals of this study were to describe disease response rates after neoadjuvant treatment and to evaluate the association between disease response and survival. Retrospective cohort study of patients aged 18-80 y with clinical stage II and III rectal adenocarcinoma in the National Cancer Database (2006-2012). All patients underwent radical resection after neoadjuvant treatment. Treatment responses were defined as follows: no tumor response; intermediate-T and/or N downstaging with residual disease; and complete-ypT0N0. Multivariable, multinomial regression was used to evaluate the association between neoadjuvant radiation use and disease response. Multivariable Cox regression was used to evaluate the association between disease response and overall risk of death. Among 12,024 patients, 12% had a complete and 30% an intermediate response. Neoadjuvant chemotherapy alone was less likely to achieve an intermediate (relative risk ratio: 0.70 [0.56-0.88]) or a complete response (relative risk ratio: 0.59 [0.41-0.84]) relative to neoadjuvant radiation. Tumor response was associated with improved 5-y overall survival (complete = 90.2%, intermediate = 82.0%, no response = 70.5%; log-rank, P < 0.001). Complete and intermediate pathologic responses were associated with decreases in risk of death (hazard ratio: 0.40 [0.34-0.48] and 0.63 [0.57-0.69], respectively) compared to no response. Primary tumor and nodal response were independently associated with decreased risk of death. Neoadjuvant radiation is associated with treatment response, and pathologic response is associated with improved survival. Pathologic response may be an early benchmark for the oncologic effectiveness of neoadjuvant treatment. Published by Elsevier Inc.

Motivation for change as a predictor of treatment response for dysthymia.

Science.gov (United States)

Frías Ibáñez, Álvaro; González Vallespí, Laura; Palma Sevillano, Carol; Farriols Hernando, Núria

2016-05-01

Dysthymia constitutes a chronic, mild affective disorder characterized by heterogeneous treatment effects. Several predictors of clinical response and attendance have been postulated, although research on the role of the psychological variables involved in this mental disorder is still scarce. Fifty-four adult patients, who met criteria for dysthymia completed an ongoing naturalistic treatment based on the brief interpersonal psychotherapy (IPT-B), which was delivered bimonthly over 16 months. As potential predictor variables, the therapeutic alliance, coping strategies, perceived self-efficacy, and motivation for change were measured at baseline. Outcome variables were response to treatment (Clinical Global Impression and Beck’s Depression Inventory) and treatment attendance. Stepwise multiple linear regression analyses revealed that higher motivation for change predicted better response to treatment. Moreover, higher motivation for change also predicted treatment attendance. Therapeutic alliance was not a predictor variable of neither clinical response nor treatment attendance. These preliminary findings support the adjunctive use of motivational interviewing (MI) techniques in the treatment of dysthymia. Further research with larger sample size and follow-up assessment is warranted.

Predicting post-traumatic stress disorder treatment response in refugees: Multilevel analysis.

Science.gov (United States)

Haagen, Joris F G; Ter Heide, F Jackie June; Mooren, Trudy M; Knipscheer, Jeroen W; Kleber, Rolf J

2017-03-01

Given the recent peak in refugee numbers and refugees' high odds of developing post-traumatic stress disorder (PTSD), finding ways to alleviate PTSD in refugees is of vital importance. However, there are major differences in PTSD treatment response between refugees, the determinants of which are largely unknown. This study aimed at improving PTSD treatment for adult refugees by identifying PTSD treatment response predictors. A prospective longitudinal multilevel modelling design was used to predict PTSD severity scores over time. We analysed data from a randomized controlled trial with pre-, post-, and follow-up measurements of the safety and efficacy of eye movement desensitization and reprocessing and stabilization in asylum seekers and refugees suffering from PTSD. Lack of refugee status, comorbid depression, demographic, trauma-related and treatment-related variables were analysed as potential predictors of PTSD treatment outcome. Treatment outcome data from 72 participants were used. The presence (B = 6.5, p = .03) and severity (B = 6.3, p disorder predicted poor treatment response and explained 39% of the variance between individuals. Refugee patients who suffer from PTSD and severe comorbid depression benefit less from treatment aimed at alleviating PTSD. Results highlight the need for treatment adaptations for PTSD and comorbid severe depression in traumatized refugees, including testing whether initial targeting of severe depressive symptoms increases PTSD treatment effectiveness. There are differences in post-traumatic stress disorder (PTSD) treatment response between traumatized refugees. Comorbid depressive disorder and depression severity predict poor PTSD response. Refugees with PTSD and severe depression may not benefit from PTSD treatment. Targeting comorbid severe depression before PTSD treatment is warranted. This study did not correct for multiple hypothesis testing. Comorbid depression may differentially impact alternative PTSD treatments

Daily Spiritual Experiences and Adolescent Treatment Response.

Science.gov (United States)

Lee, Matthew T; Veta, Paige S; Johnson, Byron R; Pagano, Maria E

2014-04-01

The purpose of this study is to explore changes in belief orientation during treatment and the impact of increased daily spiritual experiences (DSE) on adolescent treatment response. One-hundred ninety-five adolescents court-referred to a 2-month residential treatment program were assessed at intake and discharge. Forty percent of youth who entered treatment as agnostic or atheist identified themselves as spiritual or religious at discharge. Increased DSE was associated with greater likelihood of abstinence, increased prosocial behaviors, and reduced narcissistic behaviors. Results indicate a shift in DSE that improves youth self-care and care for others that may inform intervention approaches for adolescents with addiction.

Daily Spiritual Experiences and Adolescent Treatment Response

Science.gov (United States)

LEE, MATTHEW T.; VETA, PAIGE S.; JOHNSON, BYRON R.; PAGANO, MARIA E.

2014-01-01

The purpose of this study is to explore changes in belief orientation during treatment and the impact of increased daily spiritual experiences (DSE) on adolescent treatment response. One-hundred ninety-five adolescents court-referred to a 2-month residential treatment program were assessed at intake and discharge. Forty percent of youth who entered treatment as agnostic or atheist identified themselves as spiritual or religious at discharge. Increased DSE was associated with greater likelihood of abstinence, increased prosocial behaviors, and reduced narcissistic behaviors. Results indicate a shift in DSE that improves youth self-care and care for others that may inform intervention approaches for adolescents with addiction. PMID:25525291

Opportunities for Automated Demand Response in California Wastewater Treatment Facilities

Energy Technology Data Exchange (ETDEWEB)

Aghajanzadeh, Arian [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Wray, Craig [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); McKane, Aimee [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

2015-08-30

Previous research over a period of six years has identified wastewater treatment facilities as good candidates for demand response (DR), automated demand response (Auto-­DR), and Energy Efficiency (EE) measures. This report summarizes that work, including the characteristics of wastewater treatment facilities, the nature of the wastewater stream, energy used and demand, as well as details of the wastewater treatment process. It also discusses control systems and automated demand response opportunities. Furthermore, this report summarizes the DR potential of three wastewater treatment facilities. In particular, Lawrence Berkeley National Laboratory (LBNL) has collected data at these facilities from control systems, submetered process equipment, utility electricity demand records, and governmental weather stations. The collected data were then used to generate a summary of wastewater power demand, factors affecting that demand, and demand response capabilities. These case studies show that facilities that have implemented energy efficiency measures and that have centralized control systems are well suited to shed or shift electrical loads in response to financial incentives, utility bill savings, and/or opportunities to enhance reliability of service. In summary, municipal wastewater treatment energy demand in California is large, and energy-­intensive equipment offers significant potential for automated demand response. In particular, large load reductions were achieved by targeting effluent pumps and centrifuges. One of the limiting factors to implementing demand response is the reaction of effluent turbidity to reduced aeration at an earlier stage of the process. Another limiting factor is that cogeneration capabilities of municipal facilities, including existing power purchase agreements and utility receptiveness to purchasing electricity from cogeneration facilities, limit a facility’s potential to participate in other DR activities.

Rapid response in psychological treatments for binge eating disorder.

Science.gov (United States)

Hilbert, Anja; Hildebrandt, Thomas; Agras, W Stewart; Wilfley, Denise E; Wilson, G Terence

2015-06-01

Analysis of short- and long-term effects of rapid response across 3 different treatments for binge eating disorder (BED). In a randomized clinical study comparing interpersonal psychotherapy (IPT), cognitive-behavioral therapy guided self-help (CBTgsh), and behavioral weight loss (BWL) treatment in 205 adults meeting Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; APA, 1994) criteria for BED, the predictive value of rapid response, defined as ≥70% reduction in binge eating by Week 4, was determined for remission from binge eating and global eating disorder psychopathology at posttreatment, 6-, 12-, 18-, and 24-month follow-ups. Rapid responders in CBTgsh, but not in IPT or BWL, showed significantly greater rates of remission from binge eating than nonrapid responders, which was sustained over the long term. Rapid and nonrapid responders in IPT and rapid responders in CBTgsh showed a greater remission from binge eating than nonrapid responders in CBTgsh and BWL. Rapid responders in CBTgsh showed greater remission from binge eating than rapid responders in BWL. Although rapid responders in all treatments had lower global eating disorder psychopathology than nonrapid responders in the short term, rapid responders in CBTgsh and IPT were more improved than those in BWL and nonrapid responders in each treatment. Rapid responders in BWL did not differ from nonrapid responders in CBTgsh and IPT. Rapid response is a treatment-specific positive prognostic indicator of sustained remission from binge eating in CBTgsh. Regarding an evidence-based, stepped-care model, IPT, equally efficacious for rapid and nonrapid responders, could be investigated as a second-line treatment in case of nonrapid response to first-line CBTgsh. (c) 2015 APA, all rights reserved).

Rapid Response in Psychological Treatments for Binge-Eating Disorder

Science.gov (United States)

Hilbert, Anja; Hildebrandt, Thomas; Agras, W. Stewart; Wilfley, Denise E.; Wilson, G. Terence

2015-01-01

Objective Analysis of short- and long-term effects of rapid response across three different treatments for binge-eating disorder (BED). Method In a randomized clinical study comparing interpersonal psychotherapy (IPT), cognitive-behavioral guided self-help (CBTgsh), and behavioral weight loss (BWL) treatment in 205 adults meeting DSM-IV criteria for BED, the predictive value of rapid response, defined as ≥ 70% reduction in binge-eating by week four, was determined for remission from binge-eating and global eating disorder psychopathology at posttreatment, 6-, 12-, 18-, and 24-month follow-up. Results Rapid responders in CBTgsh, but not in IPT or BWL, showed significantly greater rates of remission from binge-eating than non-rapid responders, which was sustained over the long term. Rapid and non-rapid responders in IPT and rapid responders in CBTgsh showed a greater remission from binge-eating than non-rapid responders in CBTgsh and BWL. Rapid responders in CBTgsh showed greater remission from binge-eating than rapid responders in BWL. Although rapid responders in all treatments had lower global eating disorder psychopathology than non-rapid responders in the short term, rapid responders in CBTgsh and IPT were more improved than those in BWL and non-rapid responders in each treatment. Rapid responders in BWL did not differ from non-rapid responders in CBTgsh and IPT. Conclusions Rapid response is a treatment-specific positive prognostic indicator of sustained remission from binge-eating in CBTgsh. Regarding an evidence-based stepped care model, IPT, equally efficacious for rapid and non-rapid responders, could be investigated as a second-line treatment in case of non-rapid response to first-line CBTgsh. PMID:25867446

Implementing peer review of teaching: a guide for dental educators.

Science.gov (United States)

Cunningham, I M; Johnson, I; Lynch, C D

2017-04-07

Peer review of teaching (PRT) is well established and valued within higher education. Increasingly, dental educators involved in undergraduate or postgraduate teaching are required to undertake PRT as part of their teaching development. Despite this, there is a paucity of literature relating to PRT within dental education, and none that considers the implementation of PRT within large dental teaching establishments. This article describes in detail a staged process for the planning and implementation of PRT within a UK dental school. It uses relevant educational literature to supplement the authors' experiences and recommendations. By highlighting aspects of the process which are key to successful implementation, it is a useful guide for all dental educator teams who wish to successfully introduce, restructure or refresh a PRT scheme.

MicroRNAs as putative mediators of treatment response in prostate cancer.

LENUS (Irish Health Repository)

O'Kelly, Fardod

2012-05-22

MicroRNAs (miRNAs) are an abundant class of noncoding RNAs that function to regulate post-transcriptional gene expression, predominantly by translational repression. In addition to their role in prostate cancer initiation and progression, recent evidence suggests that miRNAs might also participate in treatment response across a range of therapies including radiation treatment, chemotherapy and androgen suppression. The mechanism of this regulation is thought to be multifactorial and is currently poorly understood. To date, only a small number of studies have examined the functional role of miRNAs in response to prostate cancer treatment. Elucidating the role of miRNAs in treatment response following radiotherapy, chemotherapy and androgen suppression will provide new avenues of investigation for the development of novel therapies for the treatment of prostate cancer.

Improving Treatment Response for Paediatric Anxiety Disorders: An Information-Processing Perspective.

Science.gov (United States)

Ege, Sarah; Reinholdt-Dunne, Marie Louise

2016-12-01

Cognitive behavioural therapy (CBT) is considered the treatment of choice for paediatric anxiety disorders, yet there remains substantial room for improvement in treatment outcomes. This paper examines whether theory and research into the role of information-processing in the underlying psychopathology of paediatric anxiety disorders indicate possibilities for improving treatment response. Using a critical review of recent theoretical, empirical and academic literature, the paper examines the role of information-processing biases in paediatric anxiety disorders, the extent to which CBT targets information-processing biases, and possibilities for improving treatment response. The literature reviewed indicates a role for attentional and interpretational biases in anxious psychopathology. While there is theoretical grounding and limited empirical evidence to indicate that CBT ameliorates interpretational biases, evidence regarding the effects of CBT on attentional biases is mixed. Novel treatment methods including attention bias modification training, attention feedback awareness and control training, and mindfulness-based therapy may hold potential in targeting attentional biases, and thereby in improving treatment response. The integration of novel interventions into an existing evidence-based protocol is a complex issue and faces important challenges with regard to determining the optimal treatment package. Novel interventions targeting information-processing biases may hold potential in improving response to CBT for paediatric anxiety disorders. Many important questions remain to be answered.

The Prognostic Value of Hemoglobin Concentration in Postoperative Radiotherapy of 835 Patients With Laryngeal Cancer

International Nuclear Information System (INIS)

Rutkowski, Tomasz; Suwinski, Rafal; Idasiak, Adam

2007-01-01

Purpose: To investigate the prognostic value of hemoglobin (Hb) concentration in patients with laryngeal cancer treated with postoperative radiotherapy (pRT). Methods and Materials: The records of 835 patients who underwent pRT between 1980 and 2003 were reviewed. Most patients (526 of 835 patients; 63%) were in advanced clinical stages (T3-T4) and 371 of 835 patients (44%) were node positive. Total laryngectomy had been performed in 676 of 835 patients (81%). Median Hb concentration before (Hb0) and after pRT (Hb1) was the same (13.3 g/dl). However, individual differences between Hb1 and Hb0 (dHb) varied within a broad range (-8.8; 5.0 g/dl). Univariate and multivariate analyses were performed to identify variables significantly associated with locoregional control (LRC), metastases-free survival, and overall survival. Results: Patients with dHb greater than 0 had significantly improved 5-year LRC compared with those with dHb of 0 or less (80% vs. 72%, p = 0.01). Conversely, when categorized, neither Hb0 nor Hb1 had a significant influence on LRC. In multivariate analysis, dHb remained a prognostic factor for LRC (p = 0.01) among the other variables, which included overall radiation treatment time and nodal status. None of the Hb-related variables significantly influenced metastases-free or overall survival. Conclusion: Individual change in Hb concentration during the course of pRT (dHb) rather than Hb level before or after pRT appeared as an independent prognostic factor for LRC in this set of patients

Psychobiologic correlates of treatment response in schizophrenia.

Science.gov (United States)

Lieberman, J A; Alvir, J M; Koreen, A; Geisler, S; Chakos, M; Sheitman, B; Woerner, M

1996-03-01

In studies conducted on largely treatment naive patients in their first episode of psychosis, we have found that treatment outcome is quite good and that most patients recover or at least achieve a substantial degree of symptom remission. However, over the course of their illness and in the context of subsequent psychotic episodes, they may experience some decrease in their treatment response from illness progression. In addition, the heterogeneity of treatment outcome is associated with specific clinical (gender, primary negative symptoms of the deficit state, duration of psychosis) and biological variables (pHVA, ventricular volume). It is unclear whether these variables represent aspects of discrete subtypes of schizophrenia or dimensional measures of pathology within the broad context of a unitary disease entity.

Dosimetric Study of Pelvic Proton Radiotherapy for High-Risk Prostate Cancer

International Nuclear Information System (INIS)

Chera, Bhishamjit S.; Vargas, Carlos; Morris, Christopher G.; Louis, Debbie; Flampouri, Stella; Yeung, Daniel; Duvvuri, Srividya; Li Zuofeng; Mendenhall, Nancy Price

2009-01-01

Purpose: To compare dose distributions in targeted tissues (prostate, seminal vesicles, pelvic regional nodes) and nontargeted tissues in the pelvis with intensity-modulated radiotherapy (IMRT) and forward-planned, double-scattered, three-dimensional proton radiotherapy (3D-PRT). Methods and Materials: IMRT, IMRT followed by a prostate 3D-PRT boost (IMRT/3D-PRT), and 3D-PRT plans were created for 5 high-risk prostate cancer patients (n = 15 plans). A 78-CGE/Gy dose was prescribed to the prostate and proximal seminal vesicles and a 46-CGE/Gy was prescribed to the pelvic nodes. Various dosimetric endpoints were compared. Results: Target coverage of the prostate and nodal planning target volumes was adequate for all three plans. Compared with the IMRT and IMRT/3D-PRT plans, the 3D-PRT plans reduced the mean dose to the rectum, rectal wall, bladder, bladder wall, small bowel, and pelvis. The relative benefit of 3D-PRT (vs IMRT) at reducing the rectum and rectal wall V5-V40 was 53% to 71% (p < 0.05). For the bladder and bladder wall, the relative benefit for V5 to V40 CGE/Gy was 40% to 63% (p < 0.05). The relative benefit for reducing the volume of small bowel irradiated from 5 to 30 CGE/Gy in the 3D-PRT ranged from 62% to 69% (p < 0.05). Use of 3D-PRT did not produce the typical low-dose 'bath' of radiation to the pelvis seen with IMRT. Femoral head doses were higher for the 3D-PRT. Conclusions: Use of 3D-PRT significantly reduced the dose to normal tissues in the pelvis while maintaining adequate target coverage compared with IMRT or IMRT/3D-PRT. When treating the prostate, seminal vesicles, and pelvic lymph nodes in prostate cancer, proton therapy may improve the therapeutic ratio beyond what is possible with IMRT.

Tooth for a tooth: Tissue engineering made easy at dental chairside

Directory of Open Access Journals (Sweden)

Vandana Kharidhi Laxman

2017-01-01

Full Text Available Background: Stem cells are unspecialized, multipotent cells which can differentiate into different cell types. The human periodontal ligament encloses subpopulation of Periodontal Ligament Stem Cells (PDLSCs which are able to regenerate the periodontium by differentiating into various cells of PDL. Literature have shown the promising results of periodontal regeneration by exvivo cultured transplantation of PDLSCs into the osseous defects. Methods: Based on current literature on use of ex vivo culture and associated problems, a novel technique is being presented , Stem cell application in periodontal regeneration (SAI-PRT which uses autologous PDLSCs along with its niche adhering to extracted tooth root for direct application using gelatin sponge as scaffold in regeneration of intrabony periodontal defect bypassing ex-vivo culture. Results: The cases initiated under SAI-PRT protocol, and have shown excellent clinical and radiographic improvement in intrabony defect using direct transplant of autologous PDLSCs . Conclusions: SAI-PRT can be used for the treatment of periodontal osseous defects at chair side.

FDG-PET/CT response evaluation during EGFR-TKI treatment in patients with NSCLC

Institute of Scientific and Technical Information of China (English)

Matthijs; H; van; Gool; Tjeerd; S; Aukema; Koen; J; Hartemink; Renato; A; Valdés; Olmos; Houke; M; Klomp; Harm; van; Tinteren

2014-01-01

Over recent years,[18F]-fluorodeoxyglucose positron emission tomography acquired together with low dose computed tomography(FDG-PET/CT)has proven its role as a staging modality in patients with non-small cell lung cancer(NSCLC).The purpose of this review was to present the evidence to use FDG-PET/CT for response evaluation in patients with NSCLC,treated with epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitors(TKI).All published articles from 1November 2003 to 1 November 2013 reporting on 18FFDG-PET response evaluation during EGFR-TKI treatment in patients with NSCLC were collected.In total 7studies,including data of 210 patients were eligible for analyses.Our report shows that FDG-PET/CT responseduring EGFR-TKI therapy has potential in targeted treatment for NSCLC.FDG-PET/CT response is associated with clinical and radiologic response and with survival.Furthermore FDG-PET/CT response monitoring can be performed as early as 1-2 wk after initiation of EGFR-TKI treatment.Patients with substantial decrease of metabolic activity during EGFR-TKI treatment will probably benefit from continued treatment.If metabolic response does not occur within the first weeks of EGFR-TKI treatment,patients may be spared(further)unnecessary toxicity of ineffective treatment.Refining FDG-PET response criteria may help the clinician to decide on continuation or discontinuation of targeted treatment.

Patient Characteristics Associated with HCV Treatment Adherence, Treatment Completion, and Sustained Virologic Response in HIV Coinfected Patients

Directory of Open Access Journals (Sweden)

Glenn Wagner

2011-01-01

Full Text Available Background. Hepatitis C (HCV treatment efficacy among HIV patients is limited by poor treatment adherence and tolerance, but few studies have examined the psychosocial determinants of treatment adherence and outcomes. Methods. Chart abstracted and survey data were collected on 72 HIV patients who had received pegylated interferon and ribavirin to assess correlates of treatment adherence, completion, and sustained virologic response (SVR. Results. Nearly half (46% the sample had active psychiatric problems and 13% had illicit drug use at treatment onset; 28% reported <100% treatment adherence, 38% did not complete treatment (mostly due to virologic nonresponse, and intent to treat SVR rate was 49%. Having a psychiatric diagnosis was associated with nonadherence, while better HCV adherence was associated with both treatment completion and SVR. Conclusions. Good mental health may be an indicator of HCV treatment adherence readiness, which is in turn associated with treatment completion and response, but further research is needed with new HCV treatments emerging.

Subjective response as a consideration in the pharmacogenetics of alcoholism treatment.

Science.gov (United States)

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.

Maternal care and paternal protection influence response to psychotherapy treatment for adult depression.

Science.gov (United States)

Johnstone, Jeanette M; Carter, Janet D; Luty, Suzanne E; Mulder, Roger T; Frampton, Christopher M; Joyce, Peter R

2013-07-01

Adverse childhood experiences of neglect, overprotection and abuse, well-recognized risk factors for the development of adult psychopathology, were examined as predictors of response to psychotherapy treatment for adults with depression. Outpatients in a randomized clinical trial of interpersonal psychotherapy (IPT) or cognitive-behavioral therapy (CBT) completed the parental bonding instrument (PBI) at baseline to establish levels of care and protection. Childhood abuse was asked about using clinical interviews. The PBI variables were examined in tertiles while the abuse variables were categorized as "none," "some," and "severe." Associations between these childhood adversities and treatment response were examined in those who completed the trial. Of 177 outpatients with depression who were randomized, 159 completed an adequate trial of therapy. Within these 159 patients, 57% were categorized as responders to treatment. The mean percentage improvement on the MADRS was 57.7% (±31.4). Across both treatments, patients reporting intermediate levels of maternal care had the best response to treatment. Also across both treatments, the interaction effects of maternal care and paternal protection by treatment were statistically significant. Examining the two therapies independently, maternal care and paternal protection were associated with a differential response to IPT but not CBT. Reports of abuse, whether physical, emotional or sexual, did not impact treatment response. This study examined patients who completed treatment, which may have attenuated the findings. Two categories of childhood adversity were measured although a range of other adverse childhood experiences exist. The results were from exploratory analyses and require replication. Maternal care, demonstrating a robust main effect across treatments, appears to be the childhood variable most strongly associated with response to psychotherapy in this sample. In addition, maternal care and paternal protection

Anthranilate phosphoribosyltransferase: Binding determinants for 5'-phospho-alpha-d-ribosyl-1'-pyrophosphate (PRPP) and the implications for inhibitor design.

Science.gov (United States)

Evans, Genevieve L; Furkert, Daniel P; Abermil, Nacim; Kundu, Preeti; de Lange, Katrina M; Parker, Emily J; Brimble, Margaret A; Baker, Edward N; Lott, J Shaun

2018-02-01

Phosphoribosyltransferases (PRTs) bind 5'-phospho-α-d-ribosyl-1'-pyrophosphate (PRPP) and transfer its phosphoribosyl group (PRib) to specific nucleophiles. Anthranilate PRT (AnPRT) is a promiscuous PRT that can phosphoribosylate both anthranilate and alternative substrates, and is the only example of a type III PRT. Comparison of the PRPP binding mode in type I, II and III PRTs indicates that AnPRT does not bind PRPP, or nearby metals, in the same conformation as other PRTs. A structure with a stereoisomer of PRPP bound to AnPRT from Mycobacterium tuberculosis (Mtb) suggests a catalytic or post-catalytic state that links PRib movement to metal movement. Crystal structures of Mtb-AnPRT in complex with PRPP and with varying occupancies of the two metal binding sites, complemented by activity assay data, indicate that this type III PRT binds a single metal-coordinated species of PRPP, while an adjacent second metal site can be occupied due to a separate binding event. A series of compounds were synthesized that included a phosphonate group to probe PRPP binding site. Compounds containing a "bianthranilate"-like moiety are inhibitors with IC 50 values of 10-60μM, and K i values of 1.3-15μM. Structures of Mtb-AnPRT in complex with these compounds indicate that their phosphonate moieties are unable to mimic the binding modes of the PRib or pyrophosphate moieties of PRPP. The AnPRT structures presented herein indicated that PRPP binds a surface cleft and becomes enclosed due to re-positioning of two mobile loops. Copyright © 2017 Elsevier B.V. All rights reserved.

Progressive resistance training rebuilds lean body mass in head and neck cancer patients after radiotherapy – Results from the randomized DAHANCA 25B trial

International Nuclear Information System (INIS)

Lønbro, Simon; Dalgas, Ulrik; Primdahl, Hanne; Johansen, Jørgen; Nielsen, Jakob Lindberg; Aagaard, Per; Hermann, Anne Pernille; Overgaard, Jens; Overgaard, Kristian

2013-01-01

Purpose: The critical weight loss observed in head and neck squamous cell carcinoma (HNSCC) patients following radiotherapy is mainly due to loss of lean body mass. This is associated with decreases in muscle strength, functional performance and Quality of Life (QoL). The present study investigated the effect of progressive resistance training (PRT) on lean body mass, muscle strength and functional performance in HNSCC patients following radiotherapy. Patients and methods: Following radiotherapy HNSCC patients were randomized into two groups: Early Exercise (EE, n = 20) initiated 12 weeks of PRT followed by 12 weeks of self-chosen physical activity. Delayed Exercise (DE, n = 21) initiated 12 weeks of self-chosen physical activity followed by 12 weeks of PRT. Lean body mass, muscle strength, functional performance and QoL were evaluated at baseline and after week 12 and 24. Results: In the first 12 weeks lean body mass increased by 4.3% in EE after PRT and in the last 12 weeks by 4.2% in DE after PRT. These increases were significantly larger than the changes after self-chosen physical activity (p ⩽ 0.005). Regardless of PRT start-up time, the odds ratio of increasing lean body mass by more than 4% after PRT was 6.26 (p < 0.05). PRT significantly increased muscle strength, whereas functional performance increased significantly more than after self-chosen physical activity only after delayed onset of PRT. Overall QoL improved significantly more in EE than DE from baseline to week 12. Conclusion: PRT effectively increased lean body mass and muscle strength in HNSCC patients following radiotherapy, irrespectively of early or delayed start-up

Low-Dose Involved-Field Radiation in the Treatment of Non-Hodgkin Lymphoma: Predictors of Response and Treatment Failure

Energy Technology Data Exchange (ETDEWEB)

Russo, Andrea L., E-mail: alrusso@partners.org [Harvard Radiation Oncology Program, Boston, Massachusetts (United States); Chen, Yu-Hui [Biostatistics Core, Dana Farber Cancer Institute, Boston, Massachusetts (United States); Martin, Neil E.; Vinjamoori, Anant; Luthy, Sarah K. [Department of Radiation Oncology, Brigham and Women' s Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Freedman, Arnold [Department of Hematologic Oncology, Brigham and Women' s Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Michaelson, Evan M.; Silver, Barbara; Mauch, Peter M.; Ng, Andrea K. [Department of Radiation Oncology, Brigham and Women' s Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts (United States)

2013-05-01

Purpose: To investigate clinical and pathologic factors significant in predicting local response and time to further treatment after low-dose involved-field radiation therapy (LD-IFRT) for non-Hodgkin lymphoma (NHL). Methods and Materials: Records of NHL patients treated at a single institution between April 2004 and September 2011 were retrospectively reviewed. Low-dose involved-field radiation therapy was given as 4 Gy in 2 fractions over 2 consecutive days. Treatment response and disease control were determined by radiographic studies and/or physical examination. A generalized estimating equation model was used to assess the effect of tumor and patient characteristics on disease response. A Cox proportional hazards regression model was used to assess time to further treatment. Results: We treated a total of 187 sites in 127 patients with LD-IFRT. Histologies included 66% follicular, 9% chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma, 10% marginal zone, 6% mantle cell lymphoma (MCL), and 8% other. Median follow-up time was 23.4 months (range, 0.03-92.2 months). The complete response, partial response, and overall response rates were 57%, 25%, and 82%, respectively. A CLL histology was associated with a lower response rate (odds ratio 0.2, 95% confidence interval 0.1-0.5, P=.02). Tumor size, site, age at diagnosis, and prior systemic therapy were not associated with response. The median time to first recurrence was 13.6 months. Those with CLL and age ≤50 years at diagnosis had a shorter time to further treatment for local failures (hazard ratio [HR] 3.63, P=.01 and HR 5.50, P=.02, respectively). Those with CLL and MCL had a shorter time to further treatment for distant failures (HR 11.1 and 16.3, respectively, P<.0001). Conclusions: High local response rates were achieved with LD-IFRT across most histologies. Chronic lymphocytic leukemia and MCL histologies and age ≤50 years at diagnosis had a shorter time to further treatment after LD-IFRT.

Sequence analysis of PROTEOLYSIS 6 from Solanum lycopersicum

Science.gov (United States)

Roslan, Nur Farhana; Chew, Bee Lyn; Goh, Hoe-Han; Isa, Nurulhikma Md

2018-04-01

The N-end rule pathway is a protein degradation pathway that relates the protein half-life with the identity of its N-terminal residues. A destabilizing N-terminal residues is created by enzymatic reaction or chemical modifications. This destabilized substrate will be recognized by PROTEOLYSIS 6 (PRT6) protein, which encodes an E3 ligase enzyme and resulted in substrate degradation by proteasome. PRT6 has been studied in Arabidopsis thaliana and barley but not yet been studied in fleshy fruit plants. Hence, this study was carried out in tomato that is known as the model for fleshy fruit plants. BLASTX analysis identified that Solyc09g010830 which encodes for a PRT6 gene in tomato based on its sequence similarity with PRT6 in A. thaliana. In silico gene expression analysis shows that PRT6 gene was highly expressed in tomato fruits breaker +5. Co-expression analysis shows that PRT6 may not only involved in abiotic stresses but also in biotic stresses. The objective is to analyze the sequence and characterize PRT6 gene in tomato.

Exercise in myasthenia gravis: A feasibility study of aerobic and resistance training.

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Rahbek, Martin Amadeus; Mikkelsen, Erik Elgaard; Overgaard, Kristian; Vinge, Lotte; Andersen, Henning; Dalgas, Ulrik

2017-10-01

It has not been established whether progressive resistance training (PRT) and aerobic training (AT) are feasible and efficient in myasthenia gravis (MG). Fifteen subjects with generalized MG (Myasthenia Gravis Foundation of America (MGFA) clinical classification II-IV) were randomly assigned to 20 training sessions during 8 weeks of either PRT or AT. Feasibility was evaluated based on adherence, drop-out rate, adverse events, and Quantitative Myasthenia Gravis (QMG) score. Twelve subjects (MGFA II, n = 11; MGFA III, n=1) completed the intervention with a mean adherence of 95 % ± 8. One dropout (PRT) could potentially be related to PRT. Both groups reported adverse events, including bulbar symptoms (n = 2) and increased fatigue (n = 3), but no change in QMG score was observed in either group. The PRT group showed increases in maximal strength and functional capacity. Eight weeks of moderate to high intensity AT and PRT were feasible for most patients with mild MG. Maximal strength and functional capacity increased in the PRT group. Muscle Nerve 56: 700-709, 2017. © 2017 Wiley Periodicals, Inc.

Metabolomics biomarkers to predict acamprosate treatment response in alcohol-dependent subjects.

Science.gov (United States)

Hinton, David J; Vázquez, Marely Santiago; Geske, Jennifer R; Hitschfeld, Mario J; Ho, Ada M C; Karpyak, Victor M; Biernacka, Joanna M; Choi, Doo-Sup

2017-05-31

Precision medicine for alcohol use disorder (AUD) allows optimal treatment of the right patient with the right drug at the right time. Here, we generated multivariable models incorporating clinical information and serum metabolite levels to predict acamprosate treatment response. The sample of 120 patients was randomly split into a training set (n = 80) and test set (n = 40) five independent times. Treatment response was defined as complete abstinence (no alcohol consumption during 3 months of acamprosate treatment) while nonresponse was defined as any alcohol consumption during this period. In each of the five training sets, we built a predictive model using a least absolute shrinkage and section operator (LASSO) penalized selection method and then evaluated the predictive performance of each model in the corresponding test set. The models predicted acamprosate treatment response with a mean sensitivity and specificity in the test sets of 0.83 and 0.31, respectively, suggesting our model performed well at predicting responders, but not non-responders (i.e. many non-responders were predicted to respond). Studies with larger sample sizes and additional biomarkers will expand the clinical utility of predictive algorithms for pharmaceutical response in AUD.

Effect of oral levamisole treatment of cockerels on their responses to ...

African Journals Online (AJOL)

This study was conducted to evaluate the effect of oral levamisole treatment of cockerels on their responses to experimental intraocular infection with velogenic Newcastle disease virus (NDV) and to assess whether the treatment would affect the course of the disease process by altering the immune response. There were 3 ...

Feasibility and efficacy of progressive resistance training and dietary supplements in radiotherapy treated head and neck cancer patients - the DAHANCA 25A study

DEFF Research Database (Denmark)

Lønbro, Simon; Dalgas, Ulrik; Primdahl, Hanne

2013-01-01

weeks of PRT ± protein and creatine supplementation among HNSCC patients. Secondly, to investigate group changes over time and group differences regarding lean body mass (LBM), muscle strength and functional performance following PRT ± dietary supplementation. Material and methods. Thirty patients were...... supplementation. Before the pre-trial and pre- and post-PRT evaluation of LBM, maximal isometric and isokinetic muscle strength and functional performance were performed. Results. Seventy percent of the patients completed the intervention and the PRT adherence rate was 97%. No significant group differences were...... found in any endpoints. From pre- to post-PRT, LBM increased significantly in the PROCR group by 2.6 ± 2.2 kg (p

Socio-demographic correlates of treatment response among ...

African Journals Online (AJOL)

Mark S. Ezeme, Richard Uwakwe, Appolos C. Ndukuba, Monday N. Igwe, Paul C. Odinka, Kennedy Amadi, Nichodemus O. Obayi ... Conclusion: Knowledge about these variables in relation to treatment response would improve mental health services as regards articulation of prognosis and psycho education. Keywords: ...

Yield Responses of Black Spruce to Forest Vegetation Management Treatments: Initial Responses and Rotational Projections

Directory of Open Access Journals (Sweden)

Peter F. Newton

2012-01-01

Full Text Available The objectives of this study were to (1 quantitatively summarize the early yield responses of black spruce (Picea mariana (Mill. B.S.P. to forest vegetation management (FVM treatments through a meta-analytical review of the scientific literature, and (2 given (1, estimate the rotational consequences of these responses through model simulation. Based on a fixed-effects meta-analytic approach using 44 treated-control yield pairs derived from 12 experiments situated throughout the Great Lakes—St. Lawrence and Canadian Boreal Forest Regions, the resultant mean effect size (response ratio and associated 95% confidence interval for basal diameter, total height, stem volume, and survival responses, were respectively: 54.7% (95% confidence limits (lower/upper: 34.8/77.6, 27.3% (15.7/40.0, 198.7% (70.3/423.5, and 2.9% (−5.5/11.8. The results also indicated that early and repeated treatments will yield the largest gains in terms of mean tree size and survival. Rotational simulations indicated that FVM treatments resulted in gains in stand-level operability (e.g., reductions of 9 and 5 yr for plantations established on poor-medium and good-excellent site qualities, resp.. The challenge of maintaining coniferous forest cover on recently disturbed sites, attaining statutory-defined free-to-grow status, and ensuring long-term productivity, suggest that FVM will continue to be an essential silvicultural treatment option when managing black spruce plantations.

Effect of praziquantel treatment during pregnancy on cytokine responses to schistosome antigens

DEFF Research Database (Denmark)

Tweyongyere, Robert; Mawa, Patrice A.; Ngom-Wegi, Sophy

2008-01-01

. Cytokine responses to S. mansoni worm and egg antigens were measured in whole blood culture before and 6 weeks after each treatment. RESULTS: Schistosome-specific cytokine responses were suppressed during pregnancy. Praziquantel treatment during pregnancy caused significant boosts in interferon-gamma (IFN......Praziquantel treatment of schistosomiasis boosts antischistosome responses, with type 2 helper T cell bias that may contribute to immunologically mediated killing and to protection against reinfection. Praziquantel treatment during pregnancy was recommended in 2002, but the immunological effects...... of the treatment had not been investigated. METHODS: A cohort of 387 Schistosoma mansoni-infected women were recruited from a larger trial of deworming during pregnancy. Women were randomized to receive either praziquantel or placebo during pregnancy. Six weeks after delivery, all women received praziquantel...

Towards personalized therapy for multiple sclerosis: prediction of individual treatment response.

Science.gov (United States)

Kalincik, Tomas; Manouchehrinia, Ali; Sobisek, Lukas; Jokubaitis, Vilija; Spelman, Tim; Horakova, Dana; Havrdova, Eva; Trojano, Maria; Izquierdo, Guillermo; Lugaresi, Alessandra; Girard, Marc; Prat, Alexandre; Duquette, Pierre; Grammond, Pierre; Sola, Patrizia; Hupperts, Raymond; Grand'Maison, Francois; Pucci, Eugenio; Boz, Cavit; Alroughani, Raed; Van Pesch, Vincent; Lechner-Scott, Jeannette; Terzi, Murat; Bergamaschi, Roberto; Iuliano, Gerardo; Granella, Franco; Spitaleri, Daniele; Shaygannejad, Vahid; Oreja-Guevara, Celia; Slee, Mark; Ampapa, Radek; Verheul, Freek; McCombe, Pamela; Olascoaga, Javier; Amato, Maria Pia; Vucic, Steve; Hodgkinson, Suzanne; Ramo-Tello, Cristina; Flechter, Shlomo; Cristiano, Edgardo; Rozsa, Csilla; Moore, Fraser; Luis Sanchez-Menoyo, Jose; Laura Saladino, Maria; Barnett, Michael; Hillert, Jan; Butzkueven, Helmut

2017-09-01

Timely initiation of effective therapy is crucial for preventing disability in multiple sclerosis; however, treatment response varies greatly among patients. Comprehensive predictive models of individual treatment response are lacking. Our aims were: (i) to develop predictive algorithms for individual treatment response using demographic, clinical and paraclinical predictors in patients with multiple sclerosis; and (ii) to evaluate accuracy, and internal and external validity of these algorithms. This study evaluated 27 demographic, clinical and paraclinical predictors of individual response to seven disease-modifying therapies in MSBase, a large global cohort study. Treatment response was analysed separately for disability progression, disability regression, relapse frequency, conversion to secondary progressive disease, change in the cumulative disease burden, and the probability of treatment discontinuation. Multivariable survival and generalized linear models were used, together with the principal component analysis to reduce model dimensionality and prevent overparameterization. Accuracy of the individual prediction was tested and its internal validity was evaluated in a separate, non-overlapping cohort. External validity was evaluated in a geographically distinct cohort, the Swedish Multiple Sclerosis Registry. In the training cohort (n = 8513), the most prominent modifiers of treatment response comprised age, disease duration, disease course, previous relapse activity, disability, predominant relapse phenotype and previous therapy. Importantly, the magnitude and direction of the associations varied among therapies and disease outcomes. Higher probability of disability progression during treatment with injectable therapies was predominantly associated with a greater disability at treatment start and the previous therapy. For fingolimod, natalizumab or mitoxantrone, it was mainly associated with lower pretreatment relapse activity. The probability of

The limits of parental responsibility regarding medical treatment decisions.

Science.gov (United States)

Woolley, Sarah L

2011-11-01

Parental responsibility (PR) was a concept introduced by the Children Act (CA) 1989 which aimed to replace the outdated notion of parental rights and duties which regarded children as parental possessions. Section 3(1) CA 1989 defines PR as 'all the rights, duties, powers, responsibilities and authority which by law a parent of a child has in relation to the child'. In exercising PR, individuals may make medical treatment decisions on children's behalf. Medical decision-making is one area of law where both children and the state can intercede and limit parental decision-making. Competent children can consent to treatment and the state can interfere if parental decisions are not seemingly in the child's 'best interests'. This article examines the concept, and limitations, of PR in relation to medical treatment decision-making.

Reirradiation on recurrent cervical cancer case: Treatment response and side effects

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Siregar, M. F.; Supriana, N.; Nuranna, L.; Prihartono, J.

2017-08-01

Management of recurrent cervical cancer by reirradiation after radiation treatment remains controversial. In Indonesia, there is currently no data about reirradiation tumor response and side effects. This study aims to assess the tumor response to and side effects of reirradiation, the effect of time interval between first radiation treatment and cancer recurrence on the tumor response and side effects, and the effect of tumor size on tumor response. A cohort retrospective study with no comparison was done with the Radiotherapy Department at Cipto Mangunkusumo General Hospital, Jakarta. Participants were recurrent cervical cancer patients undergoing reirradiation. Data was collected from patients’ medical records and follow-up phone calls. Twenty-two patients participated in this study. Nine patients (40.9%) had complete responses, 10 patients (45.5%) had partial responses, 1 patient (4.5%) had a stable response, and 2 patients (9.1%) had tumor progressions. In general, 15 patients (68.2%) had no to light side effects (grade 0-2 RTOG) and 7 patients (31.8%) had severe side effects (grade 3-4 RTOG). Four patients (18.1%) had severe gastrointestinal acute side effects, 6 patients (27.3%) had severe gastrointestinal late side effects, 2 patients (9.1%) had severe urogenital side effects, and there were no patients had severe urogenital late side effects. There was no significant difference in tumor response between patients with time interval between first radiation treatment and recurrence of 4 cm. Reirradiation can be considered as a modality in recurrent cervical cancer management since good tumor response was achieved and the majority of patients had no to light side effects (grade 0-2 RTOG). This study found no correlation between tumor response, side effects, and time gap between first radiation treatment and recurrence of 4 cm.

Further evaluation in field tests of the activity of three anthelmintics (fenbendazole, oxibendazole, and pyrantel pamoate) against the ascarid Parascaris equorum in horse foals on eight farms in Central Kentucky (2009-2010).

Science.gov (United States)

Lyons, Eugene T; Tolliver, Sharon C; Kuzmina, Tetiana A; Collins, Sandra S

2011-10-01

The activity of three anthelmintics (fenbendazole-FBZ; oxibendazole-OBZ; and pyrantel pamoate-PRT) was ascertained against the ascarid Parascaris equorum in horse foals on eight farms in Central Kentucky (2009-2010) in field tests. A total of 316 foals were treated, and 168 (53.2%) were passing ascarid eggs on the day of treatment. Evaluation of drug efficacy was determined qualitatively by comparing the number of foals passing ascarid eggs in their feces before and after treatment. The main purpose was to obtain data on current activity of these compounds against ascarids. Additionally, the objective was to compare these findings with those from earlier data on the efficacy of these three compounds on nematodes in foals in this geographical area. Efficacies (average) for the foals ranged for FBZ (10 mg/kg) from 50% to 100% (80%), for OBZ (10 mg/kg) from 75% to 100% (97%), and for PRT at 1× (6.6 mg base/kg) from 0% to 71% (2%) and at 2× (13.2 mg base/kg) 0% to 0% (0%). Although the efficacy varied among the drugs, combined data for all farms indicated a significant reduction of ascarid infections for FBZ (p < 0.0001) and OBZ (p < 0.0001) but not for PRT (p = 0.0953).

Projected Second Tumor Risk and Dose to Neurocognitive Structures After Proton Versus Photon Radiotherapy for Benign Meningioma

Energy Technology Data Exchange (ETDEWEB)

Arvold, Nils D. [Harvard Radiation Oncology Program, Harvard Medical School, Boston, MA (United States); Niemierko, Andrzej; Broussard, George P.; Adams, Judith; Fullerton, Barbara; Loeffler, Jay S. [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Shih, Helen A., E-mail: hshih@partners.org [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States)

2012-07-15

Purpose: To calculated projected second tumor rates and dose to organs at risk (OAR) in patients with benign intracranial meningioma (BM), according to dosimetric comparisons between proton radiotherapy (PRT) and photon radiotherapy (XRT) treatment plans. Methods and Materials: Ten patients with BM treated at Massachusetts General Hospital during 2006-2010 with PRT were replanned with XRT (intensity-modulated or three-dimensional conformal radiotherapy), optimizing dose to the tumor while sparing OAR. Total dose was 54 Gy in 1.8 Gy per fraction for all plans. We calculated equivalent uniform doses, normal tissue complication probabilities, and whole brain-based estimates of excess risk of radiation-associated intracranial second tumors. Results: Excess risk of second tumors was significantly lower among PRT compared with XRT plans (1.3 vs. 2.8 per 10,000 patients per year, p < 0.002). Mean equivalent uniform doses were lower among PRT plans for the whole brain (19.0 vs. 22.8 Gy, p < 0.0001), brainstem (23.8 vs. 35.2 Gy, p = 0.004), hippocampi (left, 13.5 vs. 25.6 Gy, p < 0.0001; right, 7.6 vs. 21.8 Gy, p = 0.001), temporal lobes (left, 25.8 vs. 34.6 Gy, p = 0.007; right, 25.8 vs. 32.9 Gy, p = 0.008), pituitary gland (29.2 vs. 37.0 Gy, p = 0.047), optic nerves (left, 28.5 vs. 33.8 Gy, p = 0.04; right, 25.1 vs. 31.1 Gy, p = 0.07), and cochleas (left, 12.2 vs. 15.8 Gy, p = 0.39; right,1.5 vs. 8.8 Gy, p = 0.01). Mean normal tissue complication probability was <1% for all structures and not significantly different between PRT and XRT plans. Conclusions: Compared with XRT, PRT for BM decreases the risk of RT-associated second tumors by half and delivers significantly lower doses to neurocognitive and critical structures of vision and hearing.

Projected Second Tumor Risk and Dose to Neurocognitive Structures After Proton Versus Photon Radiotherapy for Benign Meningioma

International Nuclear Information System (INIS)

Arvold, Nils D.; Niemierko, Andrzej; Broussard, George P.; Adams, Judith; Fullerton, Barbara; Loeffler, Jay S.; Shih, Helen A.

2012-01-01

Purpose: To calculated projected second tumor rates and dose to organs at risk (OAR) in patients with benign intracranial meningioma (BM), according to dosimetric comparisons between proton radiotherapy (PRT) and photon radiotherapy (XRT) treatment plans. Methods and Materials: Ten patients with BM treated at Massachusetts General Hospital during 2006–2010 with PRT were replanned with XRT (intensity-modulated or three-dimensional conformal radiotherapy), optimizing dose to the tumor while sparing OAR. Total dose was 54 Gy in 1.8 Gy per fraction for all plans. We calculated equivalent uniform doses, normal tissue complication probabilities, and whole brain–based estimates of excess risk of radiation-associated intracranial second tumors. Results: Excess risk of second tumors was significantly lower among PRT compared with XRT plans (1.3 vs. 2.8 per 10,000 patients per year, p < 0.002). Mean equivalent uniform doses were lower among PRT plans for the whole brain (19.0 vs. 22.8 Gy, p < 0.0001), brainstem (23.8 vs. 35.2 Gy, p = 0.004), hippocampi (left, 13.5 vs. 25.6 Gy, p < 0.0001; right, 7.6 vs. 21.8 Gy, p = 0.001), temporal lobes (left, 25.8 vs. 34.6 Gy, p = 0.007; right, 25.8 vs. 32.9 Gy, p = 0.008), pituitary gland (29.2 vs. 37.0 Gy, p = 0.047), optic nerves (left, 28.5 vs. 33.8 Gy, p = 0.04; right, 25.1 vs. 31.1 Gy, p = 0.07), and cochleas (left, 12.2 vs. 15.8 Gy, p = 0.39; right,1.5 vs. 8.8 Gy, p = 0.01). Mean normal tissue complication probability was <1% for all structures and not significantly different between PRT and XRT plans. Conclusions: Compared with XRT, PRT for BM decreases the risk of RT-associated second tumors by half and delivers significantly lower doses to neurocognitive and critical structures of vision and hearing.

RAMAN SPECTROSCOPIC STUDY ON PREDICTION OF TREATMENT RESPONSE IN CERVICAL CANCERS

Directory of Open Access Journals (Sweden)

S. RUBINA

2013-04-01

Full Text Available Concurrent chemoradiotherapy (CCRT is the choice of treatment for locally advanced cervical cancers; however, tumors exhibit diverse response to treatment. Early prediction of tumor response leads to individualizing treatment regimen. Response evaluation criteria in solid tumors (RECIST, the current modality of tumor response assessment, is often subjective and carried out at the first visit after treatment, which is about four months. Hence, there is a need for better predictive tool for radioresponse. Optical spectroscopic techniques, sensitive to molecular alteration, are being pursued as potential diagnostic tools. Present pilot study aims to explore the fiber-optic-based Raman spectroscopy approach in prediction of tumor response to CCRT, before taking up extensive in vivo studies. Ex vivo Raman spectra were acquired from biopsies collected from 11 normal (148 spectra, 16 tumor (201 spectra and 13 complete response (151 CR spectra, one partial response (8 PR spectra and one nonresponder (8 NR spectra subjects. Data was analyzed using principal component linear discriminant analysis (PC-LDA followed by leave-one-out cross-validation (LOO-CV. Findings suggest that normal tissues can be efficiently classified from both pre- and post-treated tumor biopsies, while there is an overlap between pre- and post-CCRT tumor tissues. Spectra of CR, PR and NR tissues were subjected to principal component analysis (PCA and a tendency of classification was observed, corroborating previous studies. Thus, this study further supports the feasibility of Raman spectroscopy in prediction of tumor radioresponse and prospective noninvasive in vivo applications.

Hyperthyroid dementia: clinicoradiological findings and response to treatment.

Science.gov (United States)

Fukui, T; Hasegawa, Y; Takenaka, H

2001-02-15

Dementia associated with hyperthyroidism is less well documented than is hypothyroid dementia. Therapeutic response of hyperthyroid dementia and associated cerebral circulatory and/or metabolic abnormalities has not been elucidated. We described a patient with hyperthyroid dementia and clinicoradiological response to treatment. Single photon emission computed tomographic (SPECT) study was repeated and analyzed semiquantitatively. A 67-year-old man experienced progressive impairments of attention, memory, constructive skills and behavior as well as hand tremor and weight loss of two-year duration. Laboratory findings were compatible with Graves' disease. The initial SPECT showed diffuse tracer uptake defect with an accentuation in the bilateral temporoparietal regions. Clinical and SPECT findings both suggested concurrent "possible" Alzheimer's disease. However, initial treatment with a beta-blocker improved behavior and attention-related cognitive functions as well as tracer uptake in the frontal lobes. Subsequent treatment with additional methimazole then improved memory and constructive abilities when a euthyroid state was established. Uptake defect in the temporoparietal regions also responded gradually to the medication. We suggest that the present patient represent hyperthyroid dementia, which responds favorably to treatment with regard to clinical symptoms and SPECT findings. We also suggest that thyroid function be measured in patients with "possible" Alzheimer's disease because treatable hyperthyroid dementia may not be identified.

Hepatitis C Prevalence and Responses to Pegylated Interferon + Ribavirin Treatment Among Prisoners

Directory of Open Access Journals (Sweden)

Hasan Selçuk ÖZGER

2017-12-01

Full Text Available Objective: The aim of our study was to identify the hepatitis C prevalence in prisoners and to share experiences of pegylated interferon (peg-IFN + ribavirin (RBV treatment. Materials and Methods: The study was conducted by assessing the records of prisoners between January 2014 and 2016, retrospectively. Patients in whom planned treatments were applied in a given time were determined and, virologic responses at the end of treatment and 6 months after treatment were evaluated. Chi-square test was used and a p value of less than 0.05 was considered statistically significant. Results: Among prisoners, the anti-hepatitis C virus (HCV positivity rate was 7.82% and HCV-RNA positivity rate was 5.72%. The most common genotype was genotype 3a (66 of 99 patients. End-of-treatment and 6th month sustained virologic response rates were 84.6% and 80.5%, respectively. In genotype 3a group, end-of-treatment and 6th month sustained virologic response rates were found to be higher than other genotypes but not statistically significant. Conclusion: In our study, which assessed prisoners, the rate of HCV positivity was higher than hepatitis C in the general population in Turkey. In accordance with the literature, genotype 3 was the most common genotype among prisoners. Sustained virologic response rates obtained with peg-IFN+RBV treatment suggested that peg-IFN treatment should be used with current treatment combinations in prisoners infected with HCV genotype 3.

Consumer factors predicting level of treatment response to illness management and recovery.

Science.gov (United States)

White, Dominique A; McGuire, Alan B; Luther, Lauren; Anderson, Adrienne I; Phalen, Peter; McGrew, John H

2017-12-01

This study aims to identify consumer-level predictors of level of treatment response to illness management and recovery (IMR) to target the appropriate consumers and aid psychiatric rehabilitation settings in developing intervention adaptations. Secondary analyses from a multisite study of IMR were conducted. Self-report data from consumer participants of the parent study (n = 236) were analyzed for the current study. Consumers completed prepost surveys assessing illness management, coping, goal-related hope, social support, medication adherence, and working alliance. Correlations and multiple regression analyses were run to identify self-report variables that predicted level of treatment response to IMR. Analyses revealed that goal-related hope significantly predicted level of improved illness self-management, F(1, 164) = 10.93, p consumer-level predictors of level of treatment response have not been explored for IMR. Although 2 significant predictors were identified, study findings suggest more work is needed. Future research is needed to identify additional consumer-level factors predictive of IMR treatment response in order to identify who would benefit most from this treatment program. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression.

Science.gov (United States)

Roseman, Leor; Demetriou, Lysia; Wall, Matthew B; Nutt, David J; Carhart-Harris, Robin L

2017-12-27

Recent evidence indicates that psilocybin with psychological support may be effective for treating depression. Some studies have found that patients with depression show heightened amygdala responses to fearful faces and there is reliable evidence that treatment with SSRIs attenuates amygdala responses (Ma, 2015). We hypothesised that amygdala responses to emotional faces would be altered post-treatment with psilocybin. In this open-label study, 20 individuals diagnosed with moderate to severe, treatment-resistant depression, underwent two separate dosing sessions with psilocybin. Psychological support was provided before, during and after these sessions and 19 completed fMRI scans one week prior to the first session and one day after the second and last. Neutral, fearful and happy faces were presented in the scanner and analyses focused on the amygdala. Group results revealed rapid and enduring improvements in depressive symptoms post psilocybin. Increased responses to fearful and happy faces were observed in the right amygdala post-treatment, and right amygdala increases to fearful versus neutral faces were predictive of clinical improvements at 1-week. Psilocybin with psychological support was associated with increased amygdala responses to emotional stimuli, an opposite effect to previous findings with SSRIs. This suggests fundamental differences in these treatments' therapeutic actions, with SSRIs mitigating negative emotions and psilocybin allowing patients to confront and work through them. Based on the present results, we propose that psilocybin with psychological support is a treatment approach that potentially revives emotional responsiveness in depression, enabling patients to reconnect with their emotions. ISRCTN, number ISRCTN14426797. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Amotivation in schizophrenia: integrated assessment with behavioral, clinical, and imaging measures.

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Wolf, Daniel H; Satterthwaite, Theodore D; Kantrowitz, Jacob J; Katchmar, Natalie; Vandekar, Lillie; Elliott, Mark A; Ruparel, Kosha

2014-11-01

Motivational deficits play a central role in disability caused by schizophrenia and constitute a major unmet therapeutic need. Negative symptoms have previously been linked to hypofunction in ventral striatum (VS), a core component of brain motivation circuitry. However, it remains unclear to what extent this relationship holds for specific negative symptoms such as amotivation, and this question has not been addressed with integrated behavioral, clinical, and imaging measures. Here, 41 individuals with schizophrenia and 37 controls performed a brief, computerized progressive ratio task (PRT) that quantifies effort exerted in pursuit of monetary reward. Clinical amotivation was assessed using the recently validated Clinical Assessment Interview for Negative Symptoms (CAINS). VS function was probed during functional magnetic resonance imaging using a monetary guessing paradigm. We found that individuals with schizophrenia had diminished motivation as measured by the PRT, which significantly and selectively related to clinical amotivation as measured by the CAINS. Critically, lower PRT motivation in schizophrenia was also dimensionally related to VS hypofunction. Our results demonstrate robust dimensional associations between behavioral amotivation, clinical amotivation, and VS hypofunction in schizophrenia. Integrating behavioral measures such as the PRT will facilitate translational efforts to identify biomarkers of amotivation and to assess response to novel therapeutic interventions. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Hormonal receptors and response to treatment of breast cancer

International Nuclear Information System (INIS)

Loven, D.; Rakowsky, E.; Stein, J.A.

1981-01-01

Response to several types of endocrine therapy or chemotherapy was evaluated in 60 patients with breast cancer. Estrogen and progesterone receptors were determined by radioimmunoassay. Response to endocrine therapy was significantly higher (P<0.01) among estrogen receptor (ER)-positive cases than among ER-negative cases. The response to chemotherapy did not differ significantly between the two groups. The results of this small series support the conclusion that determination of ER is valuable in planning endocrine treatment of the breast cancer patient, whereas response to chemotherapy does not correlate with ER levels. (author)

Integrating Civilian Agencies in Stability Operations

Science.gov (United States)

2009-01-01

maternal health and nutrition, HIV/AIDS, infectious disease, population, family planning and related reproductive health, and health systems. GH is also... authoritative definition of the PRT goal. Several sources, including the PRT Charter,7 the ISAF PRT Handbook,8 and statements 6 Perito, 2005, p. 11

Allogeneic Hematopoietic Stem Cell Transplantation in patients with Acute Myeloid Leukemia : a personalized approach : Allogene hematopoïetische stamcel transplantatie voor patiënten met acute myeloïde leukemie : een gepersonaliseerde benadering

NARCIS (Netherlands)

J. Versluis (Jurjen)

2017-01-01

textabstractThe majority of patients with newly diagnosed acute myeloid leukemia (AML) obtain complete hematological remission (CR) after induction chemotherapy, but the incidence of relapse is considerable despite chemotherapeutic consolidation therapy. Currently, post-remission treatment (PRT) for

Osteopontin splice variants are differential predictors of breast cancer treatment responses.

Science.gov (United States)

Zduniak, Krzysztof; Agrawal, Anil; Agrawal, Siddarth; Hossain, Md Monir; Ziolkowski, Piotr; Weber, Georg F

2016-07-11

Osteopontin is a marker for breast cancer progression, which in previous studies has also been associated with resistance to certain anti-cancer therapies. It is not known which splice variants may mediate treatment resistance. Here we analyze the association of osteopontin variant expression before treatment, differentiated according to immunohistochemistry with antibodies to exon 4 and to the osteopontin-c splice junction respectively, with the ensuing therapy responses in 119 Polish breast cancer patients who presented between 1995 and 2008. We found from Cox hazard models, logrank test and Wilcoxon test that osteopontin exon 4 was associated with a favorable response to tamoxifen, but a poor response to chemotherapy with CMF (cyclophosphamide, methotrexate, fluorouracil). Osteopontin-c is prognostic, but falls short of being a significant predictor for sensitivity to treatment. The addition of osteopontin splice variant immunohistochemistry to standard pathology work-ups has the potential to aid decision making in breast cancer treatment.

Osteopontin splice variants are differential predictors of breast cancer treatment responses

International Nuclear Information System (INIS)

Zduniak, Krzysztof; Agrawal, Anil; Agrawal, Siddarth; Hossain, Md Monir; Ziolkowski, Piotr; Weber, Georg F.

2016-01-01

Osteopontin is a marker for breast cancer progression, which in previous studies has also been associated with resistance to certain anti-cancer therapies. It is not known which splice variants may mediate treatment resistance. Here we analyze the association of osteopontin variant expression before treatment, differentiated according to immunohistochemistry with antibodies to exon 4 and to the osteopontin-c splice junction respectively, with the ensuing therapy responses in 119 Polish breast cancer patients who presented between 1995 and 2008. We found from Cox hazard models, logrank test and Wilcoxon test that osteopontin exon 4 was associated with a favorable response to tamoxifen, but a poor response to chemotherapy with CMF (cyclophosphamide, methotrexate, fluorouracil). Osteopontin-c is prognostic, but falls short of being a significant predictor for sensitivity to treatment. The addition of osteopontin splice variant immunohistochemistry to standard pathology work-ups has the potential to aid decision making in breast cancer treatment

77 FR 298 - Endangered Species Receipt of Applications for Permit

Science.gov (United States)

2012-01-04

... fruit bat (Pteropus rodricensis) Applicant: Disney's Animal Kingdom, Lake Buena Vista, FL; PRT-812907... applicant over a 5-year period. Applicant: Feld Entertainment Inc., Vienna, VA; PRT-702230 The applicant... Anderson, Hastings, NE; PRT-59366A The applicant requests a permit to import a sport-hunted trophy of one...

Covalent Modification of Human Serum Albumin by the Natural Sesquiterpene Lactone Parthenolide

Directory of Open Access Journals (Sweden)

Michael Plöger

2015-04-01

Full Text Available The reactivity of parthenolide (PRT, a natural sesquiterpene lactone from Tanacetum parthenium (Asteraceae, with human serum albumin (HSA was studied by UHPLC/+ESI-QqTOF MS analysis after tryptic digestion of albumin samples after incubation with this compound. It was found that the single free cysteine residue, C34, of HSA (0.6 mM reacted readily with PRT when incubated at approximately 13-fold excess of PRT (8 mM. Time-course studies with PRT and its 11β,13-dihydro derivative at equimolar ratios of the reactants revealed that PRT under the chosen conditions reacts preferably with C34 and does so exclusively via its α-methylene-γ-lactone moiety, while the epoxide structure is not involved in the reaction.

Basal blood DHEA-S/cortisol levels predicts EMDR treatment response in adolescents with PTSD.

Science.gov (United States)

Usta, Mirac Baris; Gumus, Yusuf Yasin; Say, Gokce Nur; Bozkurt, Abdullah; Şahin, Berkan; Karabekiroğlu, Koray

2018-04-01

In literature, recent evidence has shown that the hypothalamic-pituitary-adrenal (HPA) axis can be dysregulated in patients with post-traumatic stress disorder (PTSD) and HPA axis hormones may predict the psychotherapy treatment response in patients with PTSD. In this study, it was aimed to investigate changing cortisol and DHEA-S levels post-eye movement desensitization and reprocessing (EMDR) therapy and the relationship between treatment response and basal cortisol, and DHEA-S levels before treatment. The study group comprised 40 adolescents (age, 12-18 years) with PTSD. The PTSD symptoms were assessed using the Child Depression Inventory (CDI) and Child Post-traumatic Stress Reaction Index (CPSRI) and the blood cortisol and DHEA-S were measured with the chemiluminescence method before and after treatment. A maximum of six sessions of EMDR therapy were conducted by an EMDR level-1 trained child psychiatry resident. Treatment response was measured by the pre- to post-treatment decrease in self-reported and clinical PTSD severity. Pre- and post-treatment DHEA-S and cortisol levels did not show any statistically significant difference. Pre-treatment CDI scores were negatively correlated with pre-treatment DHEA-S levels (r: -0.39). ROC analysis demonstrated that the DHEA-S/cortisol ratio predicts treatment response at a medium level (AUC: 0.703, p: .030, sensitivity: 0.65, specificity: 0.86). The results of this study suggested that the DHEA-S/cortisol ratio may predict treatment response in adolescents with PTSD receiving EMDR therapy. The biochemical parameter of HPA-axis activity appears to be an important predictor of positive clinical response in adolescent PTSD patients, and could be used in clinical practice to predict PTSD treatment in the future.

The evolution of the female sexual response concept: Treatment implications

Directory of Open Access Journals (Sweden)

Damjanović Aleksandar

2013-01-01

Full Text Available Sexual dysfunctions have been the most prevalent group of sexual disorders and include a large number of populations of both sexes. The research of sexual behavior and treatment of women with sexual distress arises many questions related to differences in sexual response of men and women. The conceptualization of this response in modern sexology has changed over time. The objective of our paper was to present the changes and evolution of the female’s sexual response concept in a summarized and integrated way, to analyze the expanded and revised definitions of the female sexual response as well as implications and recommendations of new approaches to diagnostics and treatment according to the established changes. The lack of adequate empirical basis of the female sexual response model is a critical question in the literature dealing with this issue. Some articles report that linear models demonstrate more correctly and precisely the sexual response of women with normal sexual functions in relation to women with sexual dysfunction. Modification of this model later resulted in a circular model which more adequately presented the sexual response of women with sexual function disorder than of women with normal sexual function. The nonlinear model of female sexual response constructed by Basson incorporates the value of emotional intimacy, sexual stimulus and satisfaction with the relationship. Female functioning is significantly affected by multiple psychosocial factors such as satisfaction with the relationship, self-image, earlier negative sexual experience, etc. Newly revised, expanded definitions of female sexual dysfunction try to contribute to new knowledge about a highly contextual nature of woman’s sexuality so as to enhance clinical treatment of dysfunctions. The definitions emphasize the evaluation of the context of women’s problematic sexual experiences.

Response-guided telaprevir combination treatment for hepatitis C virus infection

NARCIS (Netherlands)

Sherman, Kenneth E.; Flamm, Steven L.; Afdhal, Nezam H.; Nelson, David R.; Sulkowski, Mark S.; Everson, Gregory T.; Fried, Michael W.; Adler, Michael; Reesink, Hendrik W.; Martin, Marie; Sankoh, Abdul J.; Adda, Nathalie; Kauffman, Robert S.; George, Shelley; Wright, Christopher I.; Poordad, Fred; Adler, M.; Delwaide, Jean; Horsmans, Y.; van Vlierberghe, H.; Richter, C.; Afdhal, N.; Araya, V.; Arora, S.; Balart, L.; Bennett, M.; Berk, B.; Bernstein, D.; Bloomer, J.; Brown, R.; Bzowej, N.; Chasen, R.; Cochran, J.; Crippin, J.; Davis, G.; Davis, M.; Dejesus, E.; Di Bisceglie, A.; Dieterich, D.; Esposito, S.; Everson, G.; Flamm, S. L.; Franco, J.; Freilich, B.; Fried, M. W.; Ghalib, R.; Godofsky, E.; Gordon, S.; Howell, C.; Hutson, W.

2011-01-01

Patients with chronic infection with hepatitis C virus (HCV) genotype 1 often need 48 weeks of peginterferon-ribavirin treatment for a sustained virologic response. We designed a noninferiority trial (noninferiority margin, -10.5%) to compare rates of sustained virologic response among patients

Tension - Type - Headache treated by Positional Release Therapy: a case report.

Science.gov (United States)

Mohamadi, Marzieh; Ghanbari, Ali; Rahimi Jaberi, Abbas

2012-10-01

Tension Type Headache (T.T.H) is the most prevalent headache. Myofascial abnormalities & trigger points are important in this type of headache which can be managed by Positional Release Therapy (PRT). This is a report of a 47 years old female patient with Tension Type Headache treated by Positional Release Therapy for her trigger points. She had a constant dull headache, which continued all the day for 9 months. A physiotherapist evaluated the patient and found active trigger points in her cervical muscles. Then, she received Positional Release Therapy for her trigger points. After 3 treatment sessions, the patient's headache stopped completely. During the 8 months following the treatment she was without pain, and did not use any medication. Positional Release Therapy was effective in treating Tension Type Headache. This suggests that PRT could be an alternative treatment to medication in patients with T.T.H if the effectiveness of that can be confirmed by further studies. Copyright © 2012 Elsevier Ltd. All rights reserved.

Gallium 67 imaging in monitoring lymphoma response to treatment

International Nuclear Information System (INIS)

Israel, O.; Front, D.; Lam, M.; Ben-Haim, S.; Kleinhaus, U.; Ben-Shachar, M.; Robinson, E.; Kolodny, G.M.

1988-01-01

The value of gallium 67 (Ga) imaging in monitoring lymphoma response to treatment was assessed in 25 patients with Ga-avid tumors and compared to body computed tomography (CT), chest radiographs, and palpation of tumor infiltrated peripheral lymph nodes. Ga imaging was negative in 95% (20/21) of the patients who were clinically considered to be in remission and in whom treatment was stopped. The disease did not recur during a follow-up of 12 to 26 months in 15 patients. Six patients developed recurrence of the disease 3 to 12 months after treatment was stopped. In all six patients Ga imaging became positive again at the time of the appearance of active disease. In the group of patients in remission, CT was negative in 57% (11/19), chest x-rays in 55% (6/11) and peripheral lymph nodes were palpated in none of the patients (13/13). In four patients that did not achieve remission after treatment, Ga scans were positive. Ga imaging appears useful in monitoring lymphoma response to treatment. This is probably because Ga imaging monitors tumor cell viability, whereas body CT and chest radiographs show the tumor mass, which may consist of fibrotic or necrotic tissue

Space Transportation Technology Workshop: Propulsion Research and Technology

Science.gov (United States)

2000-01-01

This viewgraph presentation gives an overview of the Space Transportation Technology Workshop topics, including Propulsion Research and Technology (PR&T) project level organization, FY 2001 - 2006 project roadmap, points of contact, foundation technologies, auxiliary propulsion technology, PR&T Low Cost Turbo Rocket, and PR&T advanced reusable technologies RBCC test bed.

Pre-treatment amygdala volume predicts electroconvulsive therapy response

NARCIS (Netherlands)

ten Doesschate, Freek; van Eijndhoven, Philip; Tendolkar, Indira; van Wingen, Guido A.; van Waarde, Jeroen A.

2014-01-01

Electroconvulsive therapy (ECT) is an effective treatment for patients with severe depression. Knowledge on factors predicting therapeutic response may help to identify patients who will benefit most from the intervention. Based on the neuroplasticity hypothesis, volumes of the amygdala and

PET/CT in staging and treatment response evaluation in lymphomas

International Nuclear Information System (INIS)

Bochev, P.

2015-01-01

Full text:The introduction of positron emission tomography (PET) and especially PET/CT with FDG in 2001 resulted in new concepts of overall management of patients with lymphoma and changed significantly the staging process and treatment response assessment. The considerable amount of literature and clinical trial data allowed leading cancer organizations like NCCN to incorporate in their current guidelines FDG-PET as a sole imaging modality in the management of Hodgkin‘s lymphoma, and an essential one in the management of FDG avid non-Hodgkin lymphoma (where indications vary based on particular histology). Main indications of FDG PET/CT in lymphoma are initial staging, restaging upon completion of therapy (EOT PET) and treatment response assessment. While staging with FDG and EOT PET restaging alone or combined with CECT have a straight-forward advantage over CT in evaluating small and borderline sized lymph nodes, bone marrow involvement and residual masses, treatment response assessment is rather challenging. By now and after long term trial evaluations, the response assessment is based on a visual assessment five point scale – Deauvillae criteria for response evaluation in HD and combined lugano criteria for NHL. The scale defines PET negative and PET positive cases as a presentation of responders versus non-responders which directly affects management. Although ESMO restricts the use of FDG-PET response evaluation in clinical trials only, NCCN go further, and bases its treatment recommendations on FDG-PET (Interim PET). Nowadays PET/CT is extensively used also in radiotherapy planning, which, in lymphoma patients include initial staging scans on a flat table, in order to assure similar position of future involved sites RT. Despite the extensive use of FDG with the above mentioned indications, neither evidence based guidelines, nor routine clinical practice could recommend follow up of lymphoma patients with FDG-PET. An exception could be made for ositive or

Body mass index and response to a multidisciplinary treatment of fibromyalgia.

Science.gov (United States)

Castel, Antoni; Castro, Sonia; Fontova, Ramon; Poveda, Maria José; Cascón-Pereira, Rosalia; Montull, Salvador; Padrol, Anna; Qanneta, Rami; Rull, Maria

2015-02-01

The purpose of this study is to determine whether there are some differences in the treatment responses to a multidisciplinary fibromyalgia (FM) treatment related with the baseline body mass index (BMI) of the participants. Inclusion criteria consisted of female sex, a diagnosis of FM (American College of Rheumatology criteria), age between 18 and 60 years, and between 3 and 8 years of schooling. Baseline BMI was determined, and patients were randomly assigned to one of the two treatment conditions: conventional pharmacologic treatment or multidisciplinary treatment. Outcome measures were pain intensity, functionality, catastrophizing, psychological distress, health-related quality of life, and sleep disturbances. One hundred thirty patients participated in the study. No statistical significant differences regarding pre-treatment outcomes were found among the different BMI subgroups, and between the two experimental conditions for each BMI category. General linear model analysis showed a significant interaction group treatment × time in pain intensity (p treatment × time. There are not differences among normal weight, overweight and obese patients with FM regarding their response to a multidisciplinary treatment programme for FM which combines pharmacological treatment, education, physical therapy and cognitive behavioural therapy.

Hemostatic function of buffy coat platelets in additive solution treated with pathogen reduction technology

DEFF Research Database (Denmark)

Ostrowski, Sisse R; Bochsen, Louise; Windeløv, Nis Agerlin

2011-01-01

BACKGROUND: Pathogen reduction technologies (PRTs) may influence the hemostatic potential of stored platelet (PLT) concentrates. To investigate this, buffy coat PLTs (BCPs) stored in PLT additive solution (SSP+) with or without Mirasol PRT treatment (CaridianBCT Biotechnologies) were compared...

Uveitis profile and treatment response in Iranian patients with sarcoidosis.

Science.gov (United States)

Mahmoudzadeh, Pouya; Tousi, Adib; Ramezani, Alireza; Soheilian, Roham; Soheilian, Masoud

2015-06-01

The aim of the study was to assess the clinical features and treatment responses in Iranian patients with sarcoid uveitis. A retrospective review of patients diagnosed with sarcoid uveitis from 1996 to 2010 was performed in a referral clinic in Tehran, Iran. Demographic and clinical features of patients, treatment modalities and therapeutic responses, and outcomes were recorded. Sixty-six eyes from 36 patients were studied. Twenty cases had biopsy-proven sarcoidosis. Mean duration of follow-up was 44.7 ± 45 months (range 3-175). Thirty-six eyes (54.5 %) had intermediate uveitis, 25 (37.9 %) panuveitis, and 5 (7.6 %) anterior uveitis. Twenty patients (55.5 %) responded to both systemic and/or topical corticosteroids, and 16 (44.4 %) required immunomodulatory drugs for control of uveitis. All of the patients finally responded to treatment in the form of inflammation reduction and/or vision improvement. The average time interval before initial clinical response following treatment was 3.2 ± 3 months (range 1-72). This study disclosed a higher predominance of females and intermediate form of uveitis in Iranian patients with sarcoid uveitis. Use of immunomodulatory drugs combined with corticosteroids resulted in good visual outcome and control of uveitis with a possible fewer corticosteroid side effects.

Bladder cancer treatment response assessment with radiomic, clinical, and radiologist semantic features

Science.gov (United States)

Gordon, Marshall N.; Cha, Kenny H.; Hadjiiski, Lubomir M.; Chan, Heang-Ping; Cohan, Richard H.; Caoili, Elaine M.; Paramagul, Chintana; Alva, Ajjai; Weizer, Alon Z.

2018-02-01

We are developing a decision support system for assisting clinicians in assessment of response to neoadjuvant chemotherapy for bladder cancer. Accurate treatment response assessment is crucial for identifying responders and improving quality of life for non-responders. An objective machine learning decision support system may help reduce variability and inaccuracy in treatment response assessment. We developed a predictive model to assess the likelihood that a patient will respond based on image and clinical features. With IRB approval, we retrospectively collected a data set of pre- and post- treatment CT scans along with clinical information from surgical pathology from 98 patients. A linear discriminant analysis (LDA) classifier was used to predict the likelihood that a patient would respond to treatment based on radiomic features extracted from CT urography (CTU), a radiologist's semantic feature, and a clinical feature extracted from surgical and pathology reports. The classification accuracy was evaluated using the area under the ROC curve (AUC) with a leave-one-case-out cross validation. The classification accuracy was compared for the systems based on radiomic features, clinical feature, and radiologist's semantic feature. For the system based on only radiomic features the AUC was 0.75. With the addition of clinical information from examination under anesthesia (EUA) the AUC was improved to 0.78. Our study demonstrated the potential of designing a decision support system to assist in treatment response assessment. The combination of clinical features, radiologist semantic features and CTU radiomic features improved the performance of the classifier and the accuracy of treatment response assessment.

Molecular characterization of a subtilase from the vascular wilt fungus Fusarium oxysporum.

Science.gov (United States)

Di Pietro, A; Huertas-González, M D; Gutierrez-Corona, J F; Martínez-Cadena, G; Méglecz, E; Roncero, M I

2001-05-01

The gene prt1 was isolated from the tomato vascular wilt fungus Fusarium oxysporum f. sp. lycopersici, whose predicted amino acid sequence shows significant homology with subtilisin-like fungal proteinases. Prt1 is a single-copy gene, and its structure is highly conserved among different formae speciales of F. oxysporum. Prt1 is expressed constitutively at low levels during growth on different carbon and nitrogen sources and strongly induced in medium containing collagen and glucose. As shown by reverse transcription-polymerase chain reaction and fluorescence microscopy of F. oxysporum strains carrying a prt1-promoter-green fluorescent protein fusion, prt1 is expressed at low levels during the entire cycle of infection on tomato plants. F. oxysporum strains transformed with an expression vector containing the prt1 coding region fused to the inducible endopolygalacturonase pg1 gene promoter and grown under promoter-inducing conditions secreted high levels of extracellular subtilase activity that resolved into a single peak of pI 4.0 upon isoelectric focusing. The active fraction produced two clearing bands of 29 and 32 kDa in sodium dodecyl sulfate gels containing gelatin. Targeted inactivation of prt1 in F. oxysporum f. sp. lycopersici had no detectable effect on mycelial growth, sporulation, and pathogenicity on tomato plants.

Managing inadequate responses to frontline treatment of chronic myeloid leukemia: a case-based review.

Science.gov (United States)

Bixby, Dale L

2013-05-01

The tyrosine kinase inhibitors (TKIs) imatinib, nilotinib, and dasatinib are the standard of care for treating patients with newly diagnosed chronic-phase chronic myeloid leukemia (CML). Compared with interferon-based treatment, the previous standard of care, imatinib is associated with significantly higher cytogenetic response rates and prolonged overall survival. Nilotinib and dasatinib, both newer and more potent TKIs, significantly improve cytogenetic and molecular response rates compared with imatinib. Despite significant advances in CML treatment enabled by the TKIs, a fraction of patients who receive frontline treatment with a TKI demonstrate inadequate response. The reasons for this vary, but in many cases, inadequate response can be attributed to non-adherence to the treatment regimen, intolerance to the drug, intrinsic or acquired resistance to the drug, or a combination of reasons. More often than not, strategies to improve response necessitate a change in treatment plan, either a dose adjustment or a switch to an alternate drug, particularly in the case of drug intolerance or drug resistance. Improved physician-patient communication and patient education are effective strategies to address issues relating to adherence and intolerance. Because inadequate response to TKI treatment correlates with poor long-term outcomes, it is imperative that patients who experience intolerance or who fail to achieve appropriate responses are carefully evaluated so that appropriate treatment modifications can be made to maximize the likelihood of positive long-term outcome. Copyright © 2012. Published by Elsevier Ltd.

Pharmacogenetics of clozapine treatment response and side-effects in schizophrenia: an update.

Science.gov (United States)

Sriretnakumar, Venuja; Huang, Eric; Müller, Daniel J

2015-01-01

Clozapine (CLZ) is the most effective treatment for treatment-resistant schizophrenia (SCZ) patients, with potential added benefits of reduction in suicide risk and aggression. However, CLZ is also mainly underused due to its high risk for the potentially lethal side-effect of agranulocytosis as well as weight gain and related metabolic dysregulation. Pharmacogenetics promises to enable the prediction of patient treatment response and risk of adverse effects based on patients' genetics, paving the way toward individualized treatment. This article reviews pharmacogenetics studies of CLZ response and side-effects with a focus on articles from January 2012 to February 2015, as an update to the previous reviews. Pharmacokinetic genes explored primarily include CYP1A2, while pharmacodynamic genes consisted of traditional pharmacogenetic targets such as brain-derived neurotrophic factor as well novel mitochondrial genes, NDUFS-1 and translocator protein. Pharmacogenetics is a promising avenue for individualized medication of CLZ in SCZ, with several consistently replicated gene variants predicting CLZ response and side-effects. However, a large proportion of studies have yielded mixed results. Large-scale Genome-wide association studies (e.g., CRESTAR) and targeted gene studies with standardized designs (response measurements, treatment durations, plasma level monitoring) are required for further progress toward clinical translation. Additionally, in order to improve study quality, we recommend accounting for important confounders, including polypharmacy, baseline measurements, treatment duration, gender, and age at onset.

Time to Response to Citalopram Treatment for Agitation in Alzheimer Disease.

Science.gov (United States)

Weintraub, Daniel; Drye, Lea T; Porsteinsson, Anton P; Rosenberg, Paul B; Pollock, Bruce G; Devanand, Devangere P; Frangakis, Constantine; Ismail, Zahinoor; Marano, Christopher; Meinert, Curtis L; Mintzer, Jacobo E; Munro, Cynthia A; Pelton, Gregory; Rabins, Peter V; Schneider, Lon S; Shade, David M; Yesavage, Jerome; Lyketsos, Constantine G

2015-11-01

Agitation is a common and significant problem in Alzheimer disease (AD). In the recent Citalopram for Agitation in Alzheimer's Disease (CitAD) study, citalopram was efficacious for the treatment of AD agitation. Here we examined the time course and predictors of response to treatment. Response in CitAD was defined as a modified Alzheimer Disease Cooperative Study Clinical Global Impression of Change (CGIC) score of 1 or 2 or a Neurobehavioral Rating Scale agitation subscale (NBRS-A) score reduction ≥ 50% from baseline. "Stable early response" was defined as meeting the aforementioned criteria at both weeks 3 and 9, "late response" was response at week 9 but not at week 3, and "unstable response" was response at week 3 but not at week 9. In the primary analyses, citalopram was superior to placebo on both the CGIC and the NBRS-A response measures. Little between-group differences were found in response rates in the first 3 weeks of the study (21% versus 19% on the CGIC). Citalopram patients were more likely than placebo patients to be a late responder (18% versus 8% on CGIC, Fisher's exact p = 0.09; 31% versus 15% on NBRS-A, Fisher's exact p = 0.02). Approximately half of citalopram responders (45%-56%) at end of study achieved response later in the study compared with 30%-44% of placebo responders. Treatment with citalopram for agitation in AD needs to be at least 9 weeks in duration to allow sufficient time for full response. Study duration is an important factor to consider in the design of clinical trials for agitation in AD. Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

THE INFLUENCE OF BALL VELOCITY AND COURT ILLUMINATION ON REACTION TIME FOR TENNIS VOLLEY

Directory of Open Access Journals (Sweden)

Jui-hung Tu

2010-03-01

Full Text Available The he purpose of this study is to examine the effects of ball velocity, court illumination, and volley type on the reaction time (RT of a tennis athlete for a volley stroke. Eights cases with two different ball velocities (high and low, two volley types (forehand and backhand and two court illumination levels (dark and bright were studied. The 30 participating subjects consisted of 18 male and 12 female college tennis athletes (age: 24 ± 3.2 yr, with a United States Tennis Association (USTA ranking above 2.5. In order to ensure the validity of real-world correlations, the experiments were designed to simulate real competition situations. Reaction times were measured for volley strokes in response to different approaching ball velocities (high: 25.05 ± 0.37 m/s and low: 17.56 ± 0.92 m·s-1 for several volley types (forehand and backhand and court illumination levels (55649 ± 4292 lux and 363.24 ± 6.53 lux on the court. During the tests, the signals from an electromyogram sensor and a 3-axis accelerometer (± 50 g were recorded using an NI DAQ card (NI PXI-6251 and then analyzed to determine reaction time (RT, premotor reaction time (PRT, and motor reaction time (MRT through the LabVIEW system. Subsequent 3-way ANOVA analysis indicated no RT, PRT, or MRT interaction between ball velocity, volley type and illumination. The ball velocity and illumination parameters did affect RT and PRT values significantly with p < 0.05, no significant variation in MRT was observed across any implemented experimental conditions. All experimental results indicate that ball velocity and illumination levels strongly affect the value of PRT, but have no significant effect on the value of MRT, the changes in RT were dominated by PRT

Race, Genetic Ancestry and Response to Antidepressant Treatment for Major Depression

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Murphy, Eleanor; Hou, Liping; Maher, Brion S; Woldehawariat, Girma; Kassem, Layla; Akula, Nirmala; Laje, Gonzalo; McMahon, Francis J

2013-01-01

The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study revealed poorer antidepressant treatment response among black compared with white participants. This racial disparity persisted even after socioeconomic and baseline clinical factors were taken into account. Some studies have suggested genetic contributions to this disparity, but none have attempted to disentangle race and genetic ancestry. Here we used genome-wide single-nucleotide polymorphism (SNP) data to examine independent contributions of race and genetic ancestry to citalopram response. Secondary data analyses included 1877 STAR*D participants who completed an average of 10 weeks of citalopram treatment and provided DNA samples. Participants reported their race as White (n=1464), black (n=299) or other/mixed (n=114). Genetic ancestry was estimated by multidimensional scaling (MDS) analyses of about 500 000 SNPs. Ancestry proportions were estimated by STRUCTURE. Structural equation modeling was used to examine the direct and indirect effects of observed and latent predictors of response, defined as change in the Quick Inventory of Depressive Symptomatology (QIDS) score from baseline to exit. Socioeconomic and baseline clinical factors, race, and anxiety significantly predicted response, as previously reported. However, direct effects of race disappeared in all models that included genetic ancestry. Genetic African ancestry predicted lower treatment response in all models. Although socioeconomic and baseline clinical factors drive racial differences in antidepressant response, genetic ancestry, rather than self-reported race, explains a significant fraction of the residual differences. Larger samples would be needed to identify the specific genetic mechanisms that may be involved, but these findings underscore the importance of including more African-American patients in drug trials. PMID:23827886

[Mantle cell lymphoma, response to treatment and prognosis in 45 patients].

Science.gov (United States)

Sorigue, Marc; Sancho, Juan-Manuel; García, Olga; Vila, Jordi; Moreno, Miriam; Ribera, Josep-Maria

2016-07-01

Mantle cell lymphoma (MCL) is a rare lymphoproliferative disorder, with frequent relapses and a poor prognosis. This study analyzes response to treatment and prognosis in a series of MCL patients. Retrospective study of MCL patients diagnosed in a single institution between 1996 and 2013. The cohort was divided according to the treatment received. Forty-five patients were included (32 male) with a median age of 66 years old. Twenty-one received intensive chemotherapy or chemoimmunotherapy (based on high-dose cytarabine), 13 semi-intensive (without high-dose cytarabine), 8 not intensive and 3 did not require treatment. Overall response rate was 85% in the intensive and 77% in the semi-intensive treatment groups. In multivariate analysis, intensive treatment was correlated with a longer progression-free survival (hazard ratio 9.8 [95% CI 2.7-35.5], P=.001) and overall survival (4.5 [1.2-17.8], P=.03). In this retrospective series of MCL patients, intensive treatment was correlated with better outcomes than the other treatment modalities. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Mycobacteria-specific cytokine responses as correlates of treatment response in active and latent tuberculosis.

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Clifford, Vanessa; Tebruegge, Marc; Zufferey, Christel; Germano, Susie; Forbes, Ben; Cosentino, Lucy; McBryde, Emma; Eisen, Damon; Robins-Browne, Roy; Street, Alan; Denholm, Justin; Curtis, Nigel

2017-08-01

A biomarker indicating successful tuberculosis (TB) therapy would assist in determining appropriate length of treatment. This study aimed to determine changes in mycobacteria-specific antigen-induced cytokine biomarkers in patients receiving therapy for latent or active TB, to identify biomarkers potentially correlating with treatment success. A total of 33 adults with active TB and 36 with latent TB were followed longitudinally over therapy. Whole blood stimulation assays using mycobacteria-specific antigens (CFP-10, ESAT-6, PPD) were done on samples obtained at 0, 1, 3, 6 and 9 months. Cytokine responses (IFN-γ, IL-1ra, IL-2, IL-10, IL-13, IP-10, MIP-1β, and TNF-α) in supernatants were measured by Luminex xMAP immunoassay. In active TB cases, median IL-1ra (with CFP-10 and with PPD stimulation), IP-10 (CFP-10, ESAT-6), MIP-1β (ESAT-6, PPD), and TNF-α (ESAT-6) responses declined significantly over the course of therapy. In latent TB cases, median IL-1ra (CFP-10, ESAT-6, PPD), IL-2 (CFP-10, ESAT-6), and IP-10 (CFP-10, ESAT-6) responses declined significantly. Mycobacteria-specific cytokine responses change significantly over the course of therapy, and their kinetics in active TB differ from those observed in latent TB. In particular, mycobacteria-specific IL-1ra responses are potential correlates of successful therapy in both active and latent TB. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Study of Variable Turbulent Prandtl Number Model for Heat Transfer to Supercritical Fluids in Vertical Tubes

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Tian, Ran; Dai, Xiaoye; Wang, Dabiao; Shi, Lin

2018-06-01

In order to improve the prediction performance of the numerical simulations for heat transfer of supercritical pressure fluids, a variable turbulent Prandtl number (Prt) model for vertical upward flow at supercritical pressures was developed in this study. The effects of Prt on the numerical simulation were analyzed, especially for the heat transfer deterioration conditions. Based on the analyses, the turbulent Prandtl number was modeled as a function of the turbulent viscosity ratio and molecular Prandtl number. The model was evaluated using experimental heat transfer data of CO2, water and Freon. The wall temperatures, including the heat transfer deterioration cases, were more accurately predicted by this model than by traditional numerical calculations with a constant Prt. By analyzing the predicted results with and without the variable Prt model, it was found that the predicted velocity distribution and turbulent mixing characteristics with the variable Prt model are quite different from that predicted by a constant Prt. When heat transfer deterioration occurs, the radial velocity profile deviates from the log-law profile and the restrained turbulent mixing then leads to the deteriorated heat transfer.

Placebo-like response in absence of treatment in children with Autism.

Science.gov (United States)

Jones, Rebecca M; Carberry, Caroline; Hamo, Amarelle; Lord, Catherine

2017-09-01

Caregiver report is the most common measure of change in pediatric psychiatry. Yet, placebo response rates pose significant challenges to reliably detect a treatment response. The present study simulated an eight-week clinical trial protocol for Autism Spectrum Disorder (ASD) for the purpose of testing the feasibility and validity of several outcome measures. Twenty caregivers answered questions about their child's behavior on their smartphone each week and completed a battery of paper questionnaires during weeks one and eight. No treatment was administered. Caregivers reported a significant decrease in problem behaviors on the Aberrant Behavior Checklist (ABC) (29% decrease) and general ASD behaviors on the Social Responsiveness Scale (SRS) (7% decrease). There was also a trend of behavior improvement from smartphone questions but no significant changes in clinical ratings of core diagnostic features of ASD. Participation in a comprehensive protocol in the absence of a particular treatment significantly influenced how caregivers perceived the severity of their children's problem behaviors. These placebo-like effects represent substantial challenges for randomized controlled trials (RCTs) that use treatment as usual and have implications for future behavioral and pharmacological treatment trial designs. Autism Res 2017, 10: 1567-1572. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

Is patient responsibility for managing musculoskeletal disorders related to self-reported better outcome of physiotherapy treatment?

Science.gov (United States)

Larsson, Maria E H; Kreuter, Margareta; Nordholm, Lena

2010-07-01

Musculoskeletal disorders are prevalent and a major burden on individuals and society. Information on relationships of patient involvement and responsibility to outcome is limited. This study aimed to explore relationships between self-reported outcome of physiotherapy treatment and attitudes toward responsibility for musculoskeletal disorders. A cross-sectional postal survey design was used. Patients (n=615) from an outpatient physiotherapy clinic, who had finished their physiotherapy treatment within the last 6 months were sent a questionnaire that included the Attitudes regarding Responsibility for Musculoskeletal disorders instrument (ARM), self-reported outcome of treatment and sociodemographic data. A total of 279 (45%) completed forms were returned. Multiple logistic regression analysis was used. The patients' scores on the four dimensions of ARM ("responsibility self active," "responsibility out of my hands," "responsibility employer," and "responsibility medical professionals"), controlled for age, sex, education, and physical activity as well as for number of treatments, main treatment, and physiotherapist, were associated with the patients' self-reported treatment outcome. Patients who attributed responsibility more to themselves were more likely (OR 2.37 and over) to report considerable improvement as the outcome of physiotherapy treatment. Because this study was conducted at only one physiotherapy outpatient clinic and had a cross-sectional design, the results should be replicated in other settings. Because patients' attitudes regarding responsibility for musculoskeletal disorders can possibly affect the outcome of physiotherapy treatment, it might be useful to decide whether to systematically try to influence the person's attitude toward responsibility for the management of the disorder or to match treatment to attitude.

Early Cognitive Outcomes Following Proton Radiation in Pediatric Patients With Brain and Central Nervous System Tumors

International Nuclear Information System (INIS)

Pulsifer, Margaret B.; Sethi, Roshan V.; Kuhlthau, Karen A.; MacDonald, Shannon M.; Tarbell, Nancy J.; Yock, Torunn I.

2015-01-01

Purpose: To report, from a longitudinal study, cognitive outcome in pediatric patients treated with proton radiation therapy (PRT) for central nervous system (CNS) tumors. Methods and Materials: Sixty patients receiving PRT for medulloblastoma (38.3%), gliomas (18.3%), craniopharyngioma (15.0%), ependymoma (11.7%), and other CNS tumors (16.7%) were administered age-appropriate measures of cognitive abilities at or near PRT initiation (baseline) and afterward (follow-up). Patients were aged ≥6 years at baseline to ensure consistency in neurocognitive measures. Results: Mean age was 12.3 years at baseline; mean follow-up interval was 2.5 years. Treatment included prior surgical resection (76.7%) and chemotherapy (61.7%). Proton radiation therapy included craniospinal irradiation (46.7%) and partial brain radiation (53.3%). At baseline, mean Wechsler Full Scale IQ was 104.6; means of all 4 Index scores were also in the average range. At follow-up, no significant change was observed in mean Wechsler Full Scale IQ, Verbal Comprehension, Perceptual Reasoning/Organization, or Working Memory. However, Processing Speed scores declined significantly (mean 5.2 points), with a significantly greater decline for subjects aged <12 years at baseline and those with the highest baseline scores. Cognitive outcome was not significantly related to gender, extent of radiation, radiation dose, tumor location, histology, socioeconomic status, chemotherapy, or history of surgical resection. Conclusions: Early cognitive outcomes after PRT for pediatric CNS tumors are encouraging, compared with published outcomes from photon radiation therapy

Early Cognitive Outcomes Following Proton Radiation in Pediatric Patients With Brain and Central Nervous System Tumors

Energy Technology Data Exchange (ETDEWEB)

Pulsifer, Margaret B., E-mail: mpulsifer@mgh.harvard.edu [Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts (United States); Sethi, Roshan V. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Kuhlthau, Karen A. [Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts (United States); MacDonald, Shannon M.; Tarbell, Nancy J.; Yock, Torunn I. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

2015-10-01

Purpose: To report, from a longitudinal study, cognitive outcome in pediatric patients treated with proton radiation therapy (PRT) for central nervous system (CNS) tumors. Methods and Materials: Sixty patients receiving PRT for medulloblastoma (38.3%), gliomas (18.3%), craniopharyngioma (15.0%), ependymoma (11.7%), and other CNS tumors (16.7%) were administered age-appropriate measures of cognitive abilities at or near PRT initiation (baseline) and afterward (follow-up). Patients were aged ≥6 years at baseline to ensure consistency in neurocognitive measures. Results: Mean age was 12.3 years at baseline; mean follow-up interval was 2.5 years. Treatment included prior surgical resection (76.7%) and chemotherapy (61.7%). Proton radiation therapy included craniospinal irradiation (46.7%) and partial brain radiation (53.3%). At baseline, mean Wechsler Full Scale IQ was 104.6; means of all 4 Index scores were also in the average range. At follow-up, no significant change was observed in mean Wechsler Full Scale IQ, Verbal Comprehension, Perceptual Reasoning/Organization, or Working Memory. However, Processing Speed scores declined significantly (mean 5.2 points), with a significantly greater decline for subjects aged <12 years at baseline and those with the highest baseline scores. Cognitive outcome was not significantly related to gender, extent of radiation, radiation dose, tumor location, histology, socioeconomic status, chemotherapy, or history of surgical resection. Conclusions: Early cognitive outcomes after PRT for pediatric CNS tumors are encouraging, compared with published outcomes from photon radiation therapy.

Radiological evaluation of response to treatment: Application to metastatic renal cancers receiving anti-angiogenic treatment

International Nuclear Information System (INIS)

Ammari, S.; Hernigou, A.; Grataloup, C.; Thiam, R.; Cuenod, C.A.; Siauve, N.; Fournier, L.S.; Oudard, S.; Medioni, J.

2014-01-01

Targeted therapies have considerably improved the prognosis of patients with metastatic renal cancer (mRCC) but there are no reliable response assessment criteria reflecting the clinical benefits, because there is no regression in size, or it is delayed. Such criteria would help early identification of non-responders, who would then benefit from a change of treatment, and would avoid their being subjected to unnecessary side effects related to the treatment. We will review the imaging techniques currently available for evaluating tumour response in mRCC patients, including the response evaluation criteria in solid tumours (RECIST), the Choi criteria, the modified Choi criteria, and the CT size and attenuation criteria (SACT). We will also discuss functional imaging techniques, which are based on the physiological characteristics of the tumours, such as perfusion CT, magnetic resonance imaging or ultrasound (DCE-CT, DCE-MRI, DCE-US), diffusion MRI, BOLD MRI and new positron emission tomography (PET) tracers. It is not possible at present to propose a unanimously acknowledged criterion for evaluating tumour response to targeted therapy. However, there is a real need for this according to oncologists and the pharmaceutical industry, and radiologists need to be involved in reflecting on the subject. (authors)

Response of Human Prostate Cancer Cells to Mitoxantrone Treatment in Simulated Microgravity Environment

Science.gov (United States)

Zhang, Ye; Wu, Honglu

2012-07-01

RESPONSE OF HUMAN PROSTATE CANCER CELLS TO MITOXANTRONE TREATMENT IN SIMULATED MICROGRAVITY ENVIRONMENT Ye Zhang1,2, Christopher Edwards3, and Honglu Wu1 1 NASA-Johnson Space Center, Houston, TX 2 Wyle Integrated Science and Engineering Group, Houston, TX 3 Oregon State University, Corvallis, OR This study explores the changes in growth of human prostate cancer cells (LNCaP) and their response to the treatment of an antineoplastic agent, mitoxantrone, under the simulated microgravity condition. In comparison to static 1g, microgravity and simulated microgravity have been shown to alter global gene expression patterns and protein levels in various cultured cell models or animals. However, very little is known about the effect of altered gravity on the responses of cells to the treatment of drugs, especially chemotherapy drugs. To test the hypothesis that zero gravity would result in altered regulations of cells in response to antineoplastic agents, we cultured LNCaP cells in either a High Aspect Ratio Vessel (HARV) bioreactor at the rotating condition to model microgravity in space or in the static condition as control, and treated the cells with mitoxantrone. Cell growth, as well as expressions of oxidative stress related genes, were analyzed after the drug treatment. Compared to static 1g controls, the cells cultured in the simulated microgravity environment did not present significant differences in cell viability, growth rate, or cell cycle distribution. However, after mitoxantrone treatment, a significant proportion of bioreactor cultured cells became apoptotic or was arrested in G2. Several oxidative stress related genes also showed a higher expression level post mitoxantrone treatment. Our results indicate that simulated microgravity may alter the response of LNCaP cells to mitoxantrone treatment. Understanding the mechanisms by which cells respond to drugs differently in an altered gravity environment will be useful for the improvement of cancer treatment on

Predictors of response to combined wake and light therapy in treatment-resistant inpatients with depression

DEFF Research Database (Denmark)

Kragh, Mette; Roj Larsen, Erik; Martiny, Klaus

2018-01-01

There is growing evidence for combined chronotherapeutic interventions as adjunctive treatments for major depression. However, as the treatments can be demanding, we need to identify predictors of response. This study aimed to describe predictors of response, remission and deterioration in the sh......There is growing evidence for combined chronotherapeutic interventions as adjunctive treatments for major depression. However, as the treatments can be demanding, we need to identify predictors of response. This study aimed to describe predictors of response, remission and deterioration...... in the short-term phase, as well as predictors of long-term response. The predictors investigated were gender, type of depression, severity of depression, treatment resistance, quetiapine use, general self-efficacy, educational level and positive diurnal variation. Follow-up data from 27 inpatients...... with moderate-to-severe depression participating in a chronotherapeutic intervention were analysed. As a supplement to standard treatment, they completed 3 wake therapy sessions in the first week, 30 min daily light treatment and sleep-time stabilisation in the entire 9-week study period. Patients had...

Treatment dose-response in amblyopia therapy: the Monitored Occlusion Treatment of Amblyopia Study (MOTAS).

Science.gov (United States)

Stewart, Catherine E; Moseley, Merrick J; Stephens, David A; Fielder, Alistair R

2004-09-01

Amblyopia is the commonest visual disorder of childhood. Yet the contributions of the two principal treatments (spectacle wear and occlusion) to outcome are unknown. This study was undertaken to investigate the dose-response relationship of amblyopia therapy. The study comprised three distinct phases: baseline, in which repeat measures of visual function were undertaken to confirm the initial visual deficit; refractive adaptation: an 18-week period of spectacle wear with six weekly measurements of logarithm of the minimum angle of resolution (logMAR) visual acuity; occlusion: in which participants were prescribed 6 hours of "patching" per day. In the latter phase, occlusion was objectively monitored and logMAR visual acuity recorded at 2-week intervals until any observed gains had ceased. Data were obtained from 94 participants (mean age, 5.1 +/- 1.4 years) with amblyopia associated with strabismus (n = 34), anisometropia (n = 23), and both anisometropia and strabismus (n = 37). Eighty-six underwent refractive adaptation. Average concordance with patching was 48%. The relationship between logMAR visual acuity gain and total occlusion dose was monotonic and linear. Increasing dose rate beyond 2 h/d hastened the response but did not improve outcome. More than 80% of the improvement during occlusion occurred within 6 weeks. Treatment outcome was significantly better for children younger than 4 years (n = 17) than in those older than 6 years (n = 24; P = 0.0014). Continuous objective monitoring of the amount of patching therapy received has provided insight into the dose-response relationship of occlusion therapy for amblyopia. Patching is most effective within the first few weeks of treatment, even for those in receipt of a relatively small dose. Further studies are needed to elucidate the neural basis for the dose-response functions. Copyright Association for Research in Vision and Ophthalmology

Predictors of response in the treatment of moderate depression

Directory of Open Access Journals (Sweden)

Andre G. Bastos

Full Text Available Objective: To identify neurocognitive and sociodemographic variables that could be associated with clinical response to three modalities of treatment for depression, as well as variables that predicted superior response to one treatment over the others. Method: The present study derives from a research project in which depressed patients (n=272 received one of three treatments – long-term psychodynamic psychotherapy (n=90, fluoxetine therapy (n=91, or a combination thereof (n=91 – over a 24-month period. Results: Sociodemographic variables were not found to be predictive. Six predictive neurocognitive variables were identified: three prognostic variables related to working memory and abstract reasoning; one prescriptive variable related to working memory; and two variables found to be moderators. Conclusions: The results of this study indicate subgroups of patients who might benefit from specific therapeutic strategies and subgroups that seem to respond well to long-term psychodynamic psychotherapy and combined therapy. The moderators found suggest that abstract reasoning and processing speed may influence the magnitude and/or direction of clinical improvement.

Executive functioning complaints and escitalopram treatment response in late-life depression.

Science.gov (United States)

Manning, Kevin J; Alexopoulos, George S; Banerjee, Samprit; Morimoto, Sarah Shizuko; Seirup, Joanna K; Klimstra, Sibel A; Yuen, Genevieve; Kanellopoulos, Theodora; Gunning-Dixon, Faith

2015-05-01

Executive dysfunction may play a key role in the pathophysiology of late-life depression. Executive dysfunction can be assessed with cognitive tests and subjective report of difficulties with executive skills. The present study investigated the association between subjective report of executive functioning complaints and time to escitalopram treatment response in older adults with major depressive disorder (MDD). 100 older adults with MDD (58 with executive functioning complaints and 42 without executive functioning complaints) completed a 12-week trial of escitalopram. Treatment response over 12 weeks, as measured by repeated Hamilton Depression Rating Scale scores, was compared for adults with and without executive complaints using mixed-effects modeling. Mixed effects analysis revealed a significant group × time interaction, F(1, 523.34) = 6.00, p = 0.01. Depressed older adults who reported executive functioning complaints at baseline demonstrated a slower response to escitalopram treatment than those without executive functioning complaints. Self-report of executive functioning difficulties may be a useful prognostic indicator for subsequent speed of response to antidepressant medication. Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

[Exposure to addictogenic substances, conditioned response and treatment of the exposure with response prevention].

Science.gov (United States)

Khazaal, Y; Frésard, E; Zullino, D

2007-01-01

Exposure to drugs or related cues is associated with psycho-physiological reactivity. These responses are conditioned during periods of active consumption. Exposure with response prevention (EPR) is a treatment established for anxiety disorder and aims to reduce anxiety by an extinction of previously conditioned responses. The conditioning recognized in additive processes has led to research into EPR's therapeutic potential for treating addiction. This paper is a review of the main studies on reactivity to cues, and EPR, particularly with respect to addiction to alcohol, opiates, cocaine and tobacco. This review is based on information from the Medline database, dealing with cue reactivity, attentional bias during exposure to cues and exposure treatment for addiction in general and, in particular, for each of the aforementioned substances. Exposure to drug-related cues is clearly associated with psycho-physiological reactivity and with attentional bias. Those phenomena are associated with craving and more difficulty in maintaining abstinence. The subject's attention is thus held by a large number of drug-related environmental stimuli. These observations are linked with conditioning phenomena and suggest the possibility of treatment by EPR conditioning extinction procedures. EPR has been most widely studied for abuse and alcohol addiction. Case reports give favourable outcomes. Results from controlled studies are less clear. Studies on patients addicted to cocaine or heroine are still limited and not conclusive. Different controlled studies on EPR for nicotine addiction have not produced conclusions in favour of this treatment. Generally, the EPR procedures used vary among studies. Studies focussing particularly on the evolution of physiological responses in a laboratory setting after EPR have demonstrated reduced autonomic nervous system activity. These results do not consistently lead to a reduction in consumption behaviour and in craving when the patient is in

Treatment Response in CP/ADHD Children with Callous/Unemotional Traits

Science.gov (United States)

Haas, Sarah M.; Waschbusch, Daniel A.; Pelham, William E.; King, Sara; Andrade, Brendan F.; Carrey, Normand J.

2011-01-01

The current study examines the role of callous/unemotional (CU) traits in response to treatment among children with conduct problems (CP) and attention-deficit/hyperactivity disorder (ADHD). Fifty-four children with CP/ADHD and 16 controls (age = 9.48, SD = 1.58) took part in a summer treatment and research program. Simple correlations showed that…

Non-proinflammatory and responsive nanoplatforms for targeted treatment of atherosclerosis.

Science.gov (United States)

Dou, Yin; Chen, Yue; Zhang, Xiangjun; Xu, Xiaoqiu; Chen, Yidan; Guo, Jiawei; Zhang, Dinglin; Wang, Ruibing; Li, Xiaohui; Zhang, Jianxiang

2017-10-01

Atherosclerosis is the leading cause of many fatal cardiovascular and cerebrovascular diseases. Whereas nanomedicines are promising for targeted therapy of atherosclerosis, great challenges remain in development of effective, safe, and translational nanotherapies for its treatment. Herein we hypothesize that non-proinflammatory nanomaterials sensitive to low pH or high reactive oxygen species (ROS) may serve as effective platforms for triggerable delivery of anti-atherosclerotic therapeutics in cellular and tissue microenvironments of inflammation. To demonstrate this hypothesis, an acid-labile material of acetalated β-cyclodextrin (β-CD) (Ac-bCD) and a ROS-sensitive β-CD material (Ox-bCD) were separately synthesized by chemical modification of β-CD, which were formed into responsive nanoparticles (NPs). Ac-bCD NP was rapidly hydrolyzed in mildly acidic buffers, while hydrolysis of Ox-bCD NP was selectively accelerated by H 2 O 2 . Using an anti-atherosclerotic drug rapamycin (RAP), we found stimuli-responsive release of therapeutic molecules from Ac-bCD and Ox-bCD nanotherapies. Compared with non-responsive poly(lactide-co-glycolide) (PLGA)-based NP, Ac-bCD and Ox-bCD NPs showed negligible inflammatory responses in vitro and in vivo. By endocytosis in cells and intracellularly releasing cargo molecules in macrophages, responsive nanotherapies effectively inhibited macrophage proliferation and suppressed foam cell formation. After intraperitoneal (i.p.) delivery in apolipoprotein E-deficient (ApoE -/- ) mice, fluorescence imaging showed accumulation of NPs in atherosclerotic plaques. Flow cytometry analysis indicated that the lymphatic translocation mediated by neutrophils and monocytes/macrophages may contribute to atherosclerosis targeting of i.p. administered NPs, in addition to targeting via the leaky blood vessels. Correspondingly, i.p. treatment with different nanotherapies afforded desirable efficacies. Particularly, both pH and ROS-responsive

Prepotent response inhibition predicts treatment outcome in attention deficit/hyperactivity disorder

NARCIS (Netherlands)

van der Oord, S.; Geurts, H.M.; Prins, P.J.M.; Emmelkamp, P.M.G.; Oosterlaan, J.

2012-01-01

Objective: Inhibition deficits, including deficits in prepotent response inhibition and interference control, are core deficits in ADHD. The predictive value of prepotent response inhibition and interference control was assessed for outcome in a 10-week treatment trial with methylphenidate. Methods:

Implicit Learning Abilities Predict Treatment Response in Autism Spectrum Disorders

Science.gov (United States)

2015-09-01

early behavioral interventions are the most effective treatment for Autism Spectrum Disorder (ASD), but almost half of the children do not make...behavioral intervention . 2. KEYWORDS Autism Spectrum Disorder , implicit learning, associative learning, individual differences, functional Magnetic...2 AWARD NUMBER: W81XWH-14-1-0261 TITLE: Implicit Learning Abilities Predict Treatment Response in Autism Spectrum Disorders PRINCIPAL

Time to response to citalopram treatment for agitation in Alzheimer's disease

Science.gov (United States)

Weintraub, Daniel; Drye, Lea T.; Porsteinsson, Anton P.; Rosenberg, Paul B.; Pollock, Bruce G.; Devanand, D.P.; Frangakis, Constantine; Ismail, Zahinoor; Marano, Christopher; Meinert, Curtis L.; Mintzer, Jacobo E.; Munro, Cynthia A.; Pelton, Gregory; Rabins, Peter V.; Schneider, Lon S.; Shade, David M.; Yesavage, Jerome; Lyketsos, Constantine G.

2015-01-01

Background Agitation is a common and significant problem in Alzheimer’s disease (AD). In the recent Citalopram for Agitation in Alzheimer’s Disease (CitAD) study, citalopram was efficacious for the treatment of AD agitation. Here we examined the time course and predictors of response to treatment. Methods Response in CitAD was defined as a modified Alzheimer Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC) score of 1 or 2, or a Neurobehavioral Rating Scale agitation subscale (NBRS-A) score reduction ≥50% from baseline. “Stable early response” was defined as meeting the aforementioned criteria at both weeks 3 and 9, “late response” was response at week 9 but not at week 3, and “unstable response” was response at week 3 but not at week 9. Results In the primary analyses, citalopram was superior to placebo on both the CGIC and the NBRS-A response measures. There were little between-group differences in response rates in the first three weeks of the study (21% vs 19% on the CGIC). Citalopram patients were more likely than placebo patients to be a late responder (18% vs. 8% on CGIC, Fisher’s exact p=0.09; 31% vs. 15% on NBRS-A, Fisher’s exact p=0.02). Approximately half (45–56%) of citalopram responders at end-of-study achieved response later in the study, compared with 30–44% of placebo responders. Discussion Treatment with citalopram for agitation in AD needs to be at least nine weeks in duration to allow sufficient time for full response, and study duration is an important factor to consider in the design of clinical trials for agitation in Alzheimer’s disease. PMID:26238225

The feasibility of progressive resistance training in women with polycystic ovary syndrome: a pilot randomized controlled trial.

Science.gov (United States)

Vizza, Lisa; Smith, Caroline A; Swaraj, Soji; Agho, Kingsley; Cheema, Birinder S

2016-01-01

To evaluate the feasibility of executing a randomized controlled trial of progressive resistance training (PRT) in women with polycystic ovary syndrome (PCOS). Women with PCOS were randomized to an experimental (PRT) group or a no-exercise (usual care) control group. The PRT group was prescribed two supervised and two unsupervised (home-based) training sessions per week for 12 weeks. Feasibility outcomes included recruitment and attrition, adherence, adverse events, and completion of assessments. Secondary outcomes, collected pre and post intervention, included a range of pertinent physiological, functional and psychological measures. Fifteen participants were randomised into the PRT group (n = 8) or control group (n = 7); five women (n = 2 in PRT group and n = 3 in control group) withdrew from the study. The most successful recruitment sources were Facebook (40 %) and online advertisement (27 %), while least successful methods were referrals by clinicians, colleagues and flyers. In the PRT group, attendance to supervised sessions was higher (95 %; standard deviation ±6 %) compared to unsupervised sessions (51 %; standard deviation ±28 %). No adverse events were attributed to PRT. Change in menstrual cycle status was not significantly different between groups over time (p = 0.503). However, the PRT group significantly increased body weight (p = 0.01), BMI (p = 0.04), lean mass (p = 0.01), fat-free mass (p = 0.005) and lower body strength (p = 0.03), while reducing waist circumference (p = 0.03) and HbA1c (p = 0.033) versus the control group. The PRT group also significantly improved across several domains of disease-specific and general health-related quality of life, depression, anxiety and exercise self-efficacy. A randomized controlled trial of PRT in PCOS would be feasible, and this mode of exercise may elicit a therapeutic effect on clinically important outcomes in this cohort. The success of a large

Synovial Tissue Response to Treatment with TNF Blockers in Peripheral Spondyloarthritis

NARCIS (Netherlands)

Paramarta, Jacqueline E.; Baeten, Dominique; de Rycke, Leen

2011-01-01

This review describes the synovial response to treatment in peripheral spondyloarthritis (SpA). A series of recent studies demonstrates that the synovial histopathology is largely homogenous between different SpA subtypes and can be strongly modulated by effective treatment such as tumor necrosis

Loss of response to melatonin treatment is associated with slow melatonin metabolism

NARCIS (Netherlands)

Braam, W.J.; Geijlswijk, I.M. van; Keijzer, H.; Smits, M.G.; Didden, H.C.M.; Curfs, L.M.G.

2010-01-01

Background In some of our patients with intellectual disability (ID) and sleep problems, the initial good response to melatonin disappeared within a few weeks after starting treatment, while the good response returned only after considerable dose reduction. The cause for this loss of response to

Pre-treatment cortisol awakening response predicts symptom reduction in posttraumatic stress disorder after treatment

NARCIS (Netherlands)

Rapcencu, A.E.; Gorter, R.; Kennis, Mitzy; van Rooij, S.J.H.; Geuze, E.

2017-01-01

Dysfunction of the HPA-axis has frequently been found in the aftermath of trauma exposure with or without PTSD. Decreasing HPA-axis reactivity to different stress cues has been reported during PTSD treatment. The cortisol awakening response (CARi) is a well-validated, standardized measure of

Pre-treatment cortisol awakening response predicts symptom reduction in posttraumatic stress disorder after treatment

NARCIS (Netherlands)

Rapcencu, A E; Gorter, R; Kennis, M; van Rooij, S J H; Geuze, E

Dysfunction of the HPA-axis has frequently been found in the aftermath of trauma exposure with or without PTSD. Decreasing HPA-axis reactivity to different stress cues has been reported during PTSD treatment. The cortisol awakening response (CARi) is a well-validated, standardized measure of

Three-dimensional volumetric assessment of response to treatment

International Nuclear Information System (INIS)

Willett, C.G.; Stracher, M.A.; Linggood, R.M.; Leong, J.C.; Skates, S.J.; Miketic, L.M.; Kushner, D.C.; Jacobson, J.O.

1988-01-01

From 1981 to 1986, 12 patients with Stage I and II diffuse large cell lymphoma of the mediastinum were treated with 4 or more cycles of multiagent chemotherapy and for nine patients this was followed by mediastinal irradiation. The response to treatment was assessed by three-dimensional volumetric analysis utilizing thoracic CT scans. The initial mean tumor volume of the five patients relapsing was 540 ml in contrast to an initial mean tumor volume of 360 ml for the seven patients remaining in remission. Of the eight patients in whom mediastinal lymphoma volumes could be assessed 1-2 months after chemotherapy prior to mediastinal irradiation, the three patients who have relapsed had volumes of 292, 92 and 50 ml (mean volume 145 ml) in contrast to five patients who have remained in remission with residual volume abnormalities of 4-87 ml (mean volume 32 ml). Four patients in prolonged remission with CT scans taken one year after treatment have been noted to have mediastinal tumor volumes of 0-28 ml with a mean value of 10 ml. This volumetric technique to assess the extent of mediastinal large cell lymphoma from thoracic CT scans appears to be a useful method to quantitate the amount of disease at presentation as well as objectively monitor response to treatment. 13 refs.; 2 figs.; 1 table

Interpersonal impacts mediate the association between personality and treatment response in major depression.

Science.gov (United States)

Dermody, Sarah S; Quilty, Lena C; Bagby, R Michael

2016-07-01

Personality, as characterized by the Five-Factor Model, predicts response to psychotherapy for depression. To explain how personality impacts treatment response, the present study investigated patient and therapist interpersonal processes in treatment sessions as an explanatory pathway. A clinical trial was conducted in which 103 outpatients (mean age: 41.17 years, 65% female) with primary major depressive disorder completed 16-20 weeks of cognitive-behavioral or interpersonal therapy. Before treatment, patients completed the Revised NEO Personality Inventory to assess personality domains (neuroticism, extraversion, openness-to-experience, agreeableness, and conscientiousness). After 3 and 13 weeks, patient interpersonal behavior was rated by the therapist and vice versa to determine levels of patient and therapist communal and agentic behaviors. Depression levels were measured before and after treatment. Structural equation modeling supported that patients' interpersonal behavior during therapy mediated the associations between pretreatment personality and depression treatment outcome. Specifically, extraversion, conscientiousness, and neuroticism (inverse) predicted higher levels of patient communion throughout treatment, which was in turn associated with improved treatment outcomes. Furthermore, patient agreeableness was inversely associated with agency throughout treatment, which was linked to poorer treatment response. Therapist interpersonal behavior was not a significant mediator. Results suggest that patient interpersonal behavior during treatment may be one way that patient personality impacts clinical outcomes in depression. Results underscore the clinical utility of Five-Factor Model domains in treatment process and outcome. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Regulation of Cancer Cell Responsiveness to Ionizing Radiation Treatment by Cyclic AMP Response Element Binding Nuclear Transcription Factor

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Francesca D’Auria

2017-05-01

Full Text Available Cyclic AMP response element binding (CREB protein is a member of the CREB/activating transcription factor (ATF family of transcription factors that play an important role in the cell response to different environmental stimuli leading to proliferation, differentiation, apoptosis, and survival. A number of studies highlight the involvement of CREB in the resistance to ionizing radiation (IR therapy, demonstrating a relationship between IR-induced CREB family members’ activation and cell survival. Consistent with these observations, we have recently demonstrated that CREB and ATF-1 are expressed in leukemia cell lines and that low-dose radiation treatment can trigger CREB activation, leading to survival of erythro-leukemia cells (K562. On the other hand, a number of evidences highlight a proapoptotic role of CREB following IR treatment of cancer cells. Since the development of multiple mechanisms of resistance is one key problem of most malignancies, including those of hematological origin, it is highly desirable to identify biological markers of responsiveness/unresponsiveness useful to follow-up the individual response and to adjust anticancer treatments. Taking into account all these considerations, this mini-review will be focused on the involvement of CREB/ATF family members in response to IR therapy, to deepen our knowledge of this topic, and to pave the way to translation into a therapeutic context.

Novel enzymatic assay predicts minoxidil response in the treatment of androgenetic alopecia.

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Goren, Andy; Castano, Juan Antonio; McCoy, John; Bermudez, Fernando; Lotti, Torello

2014-01-01

Topical minoxidil is the most common drug used for the treatment of androgenetic alopecia (AGA) in men and women. Although topical minoxidil exhibits a good safety profile, the efficacy in the overall population remains relatively low at 30-40%. To observe significant improvement in hair growth, minoxidil is typically used daily for a period of at least 3-4 months. Due to the significant time commitment and low response rate, a biomarker for predicting patient response prior to therapy would be advantageous. Minoxidil is converted in the scalp to its active form, minoxidil sulfate, by the sulfotransferase enzyme SULT1A1. We hypothesized that SULT1A1 enzyme activity in the hair follicle correlates with minoxidil response for the treatment of AGA. Our preliminary retrospective study of a SULT1A1 activity assay demonstrates 95% sensitivity and 73% specificity in predicting minoxidil treatment response for AGA. A larger prospective study is now under way to further validate this novel assay. © 2013 Wiley Periodicals, Inc.

A comprehensive proteomics study on platelet concentrates: Platelet proteome, storage time and Mirasol pathogen reduction technology.

Science.gov (United States)

Salunkhe, Vishal; De Cuyper, Iris M; Papadopoulos, Petros; van der Meer, Pieter F; Daal, Brunette B; Villa-Fajardo, María; de Korte, Dirk; van den Berg, Timo K; Gutiérrez, Laura

2018-03-19

Platelet concentrates (PCs) represent a blood transfusion product with a major concern for safety as their storage temperature (20-24°C) allows bacterial growth, and their maximum storage time period (less than a week) precludes complete microbiological testing. Pathogen inactivation technologies (PITs) provide an additional layer of safety to the blood transfusion products from known and unknown pathogens such as bacteria, viruses, and parasites. In this context, PITs, such as Mirasol Pathogen Reduction Technology (PRT), have been developed and are implemented in many countries. However, several studies have shown in vitro that Mirasol PRT induces a certain level of platelet shape change, hyperactivation, basal degranulation, and increased oxidative damage during storage. It has been suggested that Mirasol PRT might accelerate what has been described as the platelet storage lesion (PSL), but supportive molecular signatures have not been obtained. We aimed at dissecting the influence of both variables, that is, Mirasol PRT and storage time, at the proteome level. We present comprehensive proteomics data analysis of Control PCs and PCs treated with Mirasol PRT at storage days 1, 2, 6, and 8. Our workflow was set to perform proteomics analysis using a gel-free and label-free quantification (LFQ) approach. Semi-quantification was based on LFQ signal intensities of identified proteins using MaxQuant/Perseus software platform. Data are available via ProteomeXchange with identifier PXD008119. We identified marginal differences between Mirasol PRT and Control PCs during storage. However, those significant changes at the proteome level were specifically related to the functional aspects previously described to affect platelets upon Mirasol PRT. In addition, the effect of Mirasol PRT on the platelet proteome appeared not to be exclusively due to an accelerated or enhanced PSL. In summary, semi-quantitative proteomics allows to discern between proteome changes due to

Large granular lymphocyte leukemia: natural history and response to treatment.

LENUS (Irish Health Repository)

Fortune, Anne F

2012-02-01

Large granular lymphocyte leukemia (T-LGL) is an indolent T lymphoproliferative disorder that was difficult to diagnose with certainty until clonality testing of the T cell receptor gene became routinely available. We studied the natural history and response to treatment in 25 consecutive patients with T-LGL diagnosed between 2004 and 2008 in which the diagnosis was confirmed by molecular analysis, to define an effective treatment algorithm. The median age at diagnosis was 61 years (range 27-78), with a male to female ratio of 1:1.8 and presenting features of fatigue (n = 13), recurrent infections (n = 9), and\\/or abnormal blood counts (n = 5). Thirteen patients with symptomatic disease were treated as follows: pentostatin (nine patients), cyclosporine (six patients), methotrexate (three patients), and alemtuzumab in two patients in whom pentostatin was ineffective. Pentostatin was the single most effective therapy, with a response rate of 75% and minimal toxicity. The overall survival (OS) and progression-free survival (PFS) 37 months from diagnosis were 80% and 52%, respectively. Treatment of T-LGL should be reserved for patients with symptomatic disease, but in this series, pentostatin treatment was less toxic and more effective than cyclosporine or methotrexate.

How Do Psychiatrists Apply the Minimum Clinically Important Difference to Assess Patient Responses to Treatment?

Directory of Open Access Journals (Sweden)

Alan J. McMichael BSc

2016-11-01

Full Text Available Symptom report scales are used in clinical practice to monitor patient outcomes. Using them permits the definition of a minimum clinically important difference (MCID beyond which a patient may be judged as having responded to treatment. Despite recommendations that clinicians routinely use MCIDs in clinical practice, statisticians disagree about how MCIDs should be used to evaluate individual patient outcomes and responses to treatment. To address this issue, we asked how clinicians actually use MCIDs to evaluate patient outcomes in response to treatment. Sixty-eight psychiatrists made judgments about whether hypothetical patients had responded to treatment based on their pre- and posttreatment change scores on the widely used Positive and Negative Syndrome Scale. Psychiatrists were provided with the scale’s MCID on which to base their judgments. Our secondary objective was to assess whether knowledge of the patient’s genotype influenced psychiatrists’ responder judgments. Thus, psychiatrists were also informed of whether patients possessed a genotype indicating hyperresponsiveness to treatment. While many psychiatrists appropriately used the MCID, others accepted a far lower posttreatment change as indicative of a response to treatment. When psychiatrists accepted a lower posttreatment change than the MCID, they were less confident in such judgments compared to when a patient’s posttreatment change exceeded the scale’s MCID. Psychiatrists were also less likely to identify patients as responders to treatment if they possessed a hyperresponsiveness genotype. Clinicians should recognize that when judging patient responses to treatment, they often tolerate lower response thresholds than warranted. At least some conflate their judgments with information, such as the patient’s genotype, that is irrelevant to a post hoc response-to-treatment assessment. Consequently, clinicians may be at risk of persisting with treatments that have failed

[Occlusion treatment for amblyopia. Age dependence and dose-response relationship].

Science.gov (United States)

Fronius, M

2016-04-01

Based on clinical experience and studies on animal models the age of 6-7 years was regarded as the limit for treatment of amblyopia, although functional improvement was also occasionally reported in older patients. New technical developments as well as insights from clinical studies and the neurosciences have attracted considerable attention to this topic. Various aspects of the age dependence of amblyopia treatment are discussed in this article, e. g. prescription, electronic monitoring of occlusion dosage, calculation of indicators for age-dependent plasticity of the visual system, and novel, alternative treatment approaches. Besides a discussion of the recent literature, results of studies by our "Child Vision Research Unit" in Frankfurt are presented: results of a questionnaire about prescription habits concerning age limits of patching, electronic recording of occlusion in patients beyond the conventional treatment age, calculation of dose-response function and efficiency of patching and their age dependence. The results of the questionnaire illustrate the uncertainty about age limits of prescription with significant deviations from the guideline of the German Ophthalmological Society (DOG). Electronic recording of occlusion allowed the quantification of declining dose-response function and treatment efficiency between 5 and 16 years of age. Reports about successful treatment with conventional and novel methods in adults are at variance with the notion of a rigid adult visual system lacking plasticity. Electronic recording of patching allowed new insights into the age-dependent susceptibility of the visual system and contributes to a more evidence-based treatment of amblyopia. Alternative approaches for adults challenge established notions about age limits of amblyopia therapy. Further studies comparing different treatment options are urgently needed.

Neurofilament light antibodies in serum reflect response to natalizumab treatment in multiple sclerosis.

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Amor, Sandra; van der Star, Baukje J; Bosca, Isabel; Raffel, Joel; Gnanapavan, Sharmilee; Watchorn, Jonathan; Kuhle, Jens; Giovannoni, Gavin; Baker, David; Malaspina, Andrea; Puentes, Fabiola

2014-09-01

Increased levels of antibodies to neurofilament light protein (NF-L) in biological fluids have been found to reflect neuroinflammatory responses and neurodegeneration in multiple sclerosis (MS). To evaluate whether levels of serum antibodies against NF-L correlate with clinical variants and treatment response in MS. The autoantibody reactivity to NF-L protein was tested in serum samples from patients with relapsing-remitting MS (RRMS) (n=22) and secondary progressive MS (SPMS) (n=26). Two other cohorts of RRMS patients under treatment with natalizumab were analysed cross-sectionally (n=16) and longitudinally (n=24). The follow-up samples were taken at 6, 12, 18 and 24 months after treatment, and the NF-L antibody levels were compared against baseline levels. NF-L antibodies were higher in MS clinical groups than healthy controls and in RRMS compared to SPMS patients (ptreatment compared with baseline measurements (p=0.001). Drug efficacy in MS treatment indicates the potential use of monitoring the content of antibodies against the NF-L chain as a predictive biomarker of treatment response in MS. © The Author(s) 2014.

CT-guided periradicular therapy in cervical and lumbar radicular syndromes

International Nuclear Information System (INIS)

Nian Dingfang; Zhou Jun; Li Wenhua; Cao Qingxuan; Xia Baosu; Apitzsch, D.E.

2007-01-01

Objective: To evaluate the effectiveness of CT-guided periradicular therapy (PRT) in cervical and lumber radicular syndromes. Methods: Seventy two cases of cervical and lumbar radicular syndromes were treated by CT-guided PRT. During PRT, 10-20 mg of Triamhexal and 3-4 ml of Carbostesin 0.25%(Bupivacainhydrochlorid) were injected into the space around the corresponding spinal root, once a week, all together six times as a course. Results: Four hundreds and forty six PRT procedures were carried out in 72 patients having a successful puncture and a satisfying spread of Triamhexal and Carbostesin around the spinal nerve root space for every time. After 6 to 24 months follow up, 62 patients showed a significant pain reduction or complete disappearance. Moderate improvement was not noted in 6 and no improvement in 4. The effective rate was 94.4% without any correlative complication. Conclusions: CT-guided PRT is an effective, easy and safe procedure to treat patients with refractory cervical or lumbar radicular pain syndromes. (authors)

Hubble Space Telescope EVA Power Ratchet Tool redesign

Science.gov (United States)

Richards, Paul W.; Park, Chan; Brown, Lee

The Power Ratchet Tool (PRT) is a self contained, power-driven, 3/8 inch drive ratchet wrench which will be used by astronauts during Extravehicular Activities (EVA). This battery-powered tool is controlled by a dedicated electonic controller. The PRT was flown during the Hubble Space Telescope (HST) Deployment Mission STS-31 to deploy the solar arrays if the automatic mechanisms failed. The PRT is currently intended for use during the first HST Servicing Mission STS-61 as a general purpose power tool. The PRT consists of three major components; the wrench, the controller, and the battery module. Fourteen discrete combinations of torque, turns, and speed may be programmed into the controller before the EVA. The crewmember selects the desired parameter profile by a switch mounted on the controller. The tool may also be used in the manual mode as a non-powered ratchet wrench. The power is provided by a silver-zinc battery module, which fits into the controller and is replaceable during an EVA. The original PRT did not meet the design specification of torque output and hours of operation. To increase efficiency and reliability the PRT underwent a redesign effort. The majority of this effort focused on the wrench. The original PRT drive train consisted of a low torque, high speed brushless DC motor, a face gear set, and a planocentric gear assembly. The total gear reduction was 300:1. The new PRT wrench consists of a low speed, high torque brushless DC motor, two planetary gear sets and a bevel gear set. The total gear reduction is now 75:1. A spline clutch has also been added to disengage the drive train in the manual mode. The design changes to the controller will consist of only those modifications necessary to accomodate the redesigned wrench.

Frontal lobe functioning during a simple response conflict task in first-episode psychosis and its relationship to treatment response.

Science.gov (United States)

Shafritz, Keith M; Ikuta, Toshikazu; Greene, Allison; Robinson, Delbert G; Gallego, Juan; Lencz, Todd; DeRosse, Pamela; Kingsley, Peter B; Szeszko, Philip R

2018-05-09

Prior functional magnetic resonance imaging (fMRI) studies have investigated the neural mechanisms underlying cognitive control in patients with psychosis with findings of both hypo- and hyperfrontality. One factor that may contribute to inconsistent findings is the use of complex and polyfactorial tasks to investigate frontal lobe functioning. In the current study we employed a simple response conflict task during fMRI to examine differences in brain activation between patients experiencing their first-episode of psychosis (n = 33) and age- and sex-matched healthy volunteers (n = 33). We further investigated whether baseline brain activation among patients predicted changes in symptom severity and treatment response following 12 weeks of controlled antipsychotic treatment. During the task subjects were instructed to press a response button on the same side or opposite side of a circle that appeared on either side of a central fixation point. Imaging data revealed that for the contrast of opposite-side vs. same-side, patients showed significantly greater activation compared with healthy volunteers in the anterior cingulate cortex and intraparietal sulcus. Among patients, greater baseline anterior cingulate cortex, temporal-parietal junction, and superior temporal cortex activation predicted greater symptom reduction and therapeutic response following treatment. All findings remained significant after covarying for task performance. Intact performance on this relatively parsimonious task was associated with frontal hyperactivity suggesting the need for patients to utilize greater neural resources to achieve task performance comparable to healthy individuals. Moreover, frontal hyperactivity observed using a simple fMRI task may provide a biomarker for predicting treatment response in first-episode psychosis.

Atomoxetine pharmacogenetics: associations with pharmacokinetics, treatment response and tolerability.

Science.gov (United States)

Brown, Jacob T; Bishop, Jeffrey R

2015-01-01

Atomoxetine is indicated for the treatment of attention deficit hyperactivity disorder and is predominantly metabolized by the CYP2D6 enzyme. Differences in pharmacokinetic parameters as well as clinical treatment outcomes across CYP2D6 genotype groups have resulted in dosing recommendations within the product label, but clinical studies supporting the use of genotype guided dosing are currently lacking. Furthermore, pharmacokinetic and clinical studies have primarily focused on extensive as compared with poor metabolizers, with little information known about other metabolizer categories as well as genes involved in the pharmacodynamics of atomoxetine. This review describes the pharmacogenetic associations with atomoxetine pharmacokinetics, treatment response and tolerability with considerations for the clinical utility of this information.

Loss of Response to Melatonin Treatment Is Associated with Slow Melatonin Metabolism

Science.gov (United States)

Braam, W.; van Geijlswijk, I.; Keijzer, Henry; Smits, Marcel G.; Didden, Robert; Curfs, Leopold M. G.

2010-01-01

Background: In some of our patients with intellectual disability (ID) and sleep problems, the initial good response to melatonin disappeared within a few weeks after starting treatment, while the good response returned only after considerable dose reduction. The cause for this loss of response to melatonin is yet unknown. We hypothesise that this…

Accuracy and differential bias in copy number measurement of CCL3L1 in association studies with three auto-immune disorders.

Science.gov (United States)

Carpenter, Danielle; Walker, Susan; Prescott, Natalie; Schalkwijk, Joost; Armour, John Al

2011-08-18

Copy number variation (CNV) contributes to the variation observed between individuals and can influence human disease progression, but the accurate measurement of individual copy numbers is technically challenging. In the work presented here we describe a modification to a previously described paralogue ratio test (PRT) method for genotyping the CCL3L1/CCL4L1 copy variable region, which we use to ascertain CCL3L1/CCL4L1 copy number in 1581 European samples. As the products of CCL3L1 and CCL4L1 potentially play a role in autoimmunity we performed case control association studies with Crohn's disease, rheumatoid arthritis and psoriasis clinical cohorts. We evaluate the PRT methodology used, paying particular attention to accuracy and precision, and highlight the problems of differential bias in copy number measurements. Our PRT methods for measuring copy number were of sufficient precision to detect very slight but systematic differential bias between results from case and control DNA samples in one study. We find no evidence for an association between CCL3L1 copy number and Crohn's disease, rheumatoid arthritis or psoriasis. Differential bias of this small magnitude, but applied systematically across large numbers of samples, would create a serious risk of false positive associations in copy number, if measured using methods of lower precision, or methods relying on single uncorroborated measurements. In this study the small differential bias detected by PRT in one sample set was resolved by a simple pre-treatment by restriction enzyme digestion.

Accuracy and differential bias in copy number measurement of CCL3L1 in association studies with three auto-immune disorders

Directory of Open Access Journals (Sweden)

Carpenter Danielle

2011-08-01

Full Text Available Abstract Background Copy number variation (CNV contributes to the variation observed between individuals and can influence human disease progression, but the accurate measurement of individual copy numbers is technically challenging. In the work presented here we describe a modification to a previously described paralogue ratio test (PRT method for genotyping the CCL3L1/CCL4L1 copy variable region, which we use to ascertain CCL3L1/CCL4L1 copy number in 1581 European samples. As the products of CCL3L1 and CCL4L1 potentially play a role in autoimmunity we performed case control association studies with Crohn's disease, rheumatoid arthritis and psoriasis clinical cohorts. Results We evaluate the PRT methodology used, paying particular attention to accuracy and precision, and highlight the problems of differential bias in copy number measurements. Our PRT methods for measuring copy number were of sufficient precision to detect very slight but systematic differential bias between results from case and control DNA samples in one study. We find no evidence for an association between CCL3L1 copy number and Crohn's disease, rheumatoid arthritis or psoriasis. Conclusions Differential bias of this small magnitude, but applied systematically across large numbers of samples, would create a serious risk of false positive associations in copy number, if measured using methods of lower precision, or methods relying on single uncorroborated measurements. In this study the small differential bias detected by PRT in one sample set was resolved by a simple pre-treatment by restriction enzyme digestion.

Stream periphyton responses to mesocosm treatments of ...

Science.gov (United States)

A stream mesocosm experiment was designed to compare biotic responses among streams exposed to an equal excess specific conductivity target of 850 µS/cm relative to a control that was set for 200 µS/cm and three treatments comprised of different major ion contents. Each treatment and the control was replicated 4 times at the mesocosm scale (16 mesocosms total). The treatments were based on dosing the background mesocosm water, a continuous flow-through mixture of natural river water and reverse osmosis treated water, with stock salt solutions prepared from 1) a mixture of sodium chloride and calcium chloride (Na/Cl chloride), 2) sodium bicarbonate, and 3) magnesium sulfate. The realized average specific conductance over the first 28d of continuous dosing was 827, 829, and 847 µS/cm, for the chloride, bicarbonate, and sulfate based treatments, respectively, and did not differ significantly. The controls averaged 183 µS/cm. Here we focus on comparing stream periphyton communities across treatments based on measurements obtained from a Pulse-Amplitude Modulated (PAM) fluorometer. The fluorometer is used in situ and with built in algorithms distributes the total aerial algal biomass (µg/cm2) of the periphyton among cyanobacteria, diatoms, and green algae. A measurement is recorded in a matter of seconds and, therefore, many different locations can be measured with in each mesocosm at a high return frequency. Eight locations within each of the 1 m2 (0.3 m W x 3

Ghrelin Serum Concentrations Are Associated with Treatment Response During Lithium Augmentation of Antidepressants.

Science.gov (United States)

Ricken, Roland; Bopp, Sandra; Schlattmann, Peter; Himmerich, Hubertus; Bschor, Tom; Richter, Christoph; Elstner, Samuel; Stamm, Thomas J; Schulz-Ratei, Brigitte; Lingesleben, Alexandra; Reischies, Friedel M; Sterzer, Philipp; Borgwardt, Stefan; Bauer, Michael; Heinz, Andreas; Hellweg, Rainer; Lang, Undine E; Adli, Mazda

2017-09-01

Lithium augmentation of antidepressants is an effective strategy in treatment-resistant depression. The proteohormone ghrelin is thought to be involved in the pathophysiology of depression. The purpose of this study was to investigate the association of treatment response with the course of ghrelin levels during lithium augmentation. Ghrelin serum concentrations and severity of depression were measured in 85 acute depressive patients before and after 4 weeks of lithium augmentation. In a linear mixed model analysis, we found a significant effect of response*time interaction (F1.81=9.48; P=.0028): under treatment, ghrelin levels increased in nonresponders and slightly decreased in responders to lithium augmentation. The covariate female gender had a significant positive effect (F1.83=4.69; P=.033), whereas time, response, appetite, and body mass index (kg/m2) did not show any significant effect on ghrelin levels (P>.05). This is the first study showing that the course of ghrelin levels separates responders and nonresponders to lithium augmentation. Present results support the hypothesis that ghrelin serum concentrations might be involved in response to pharmacological treatment of depression. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Prediction of treatment response and metastatic disease in soft tissue sarcoma

Science.gov (United States)

Farhidzadeh, Hamidreza; Zhou, Mu; Goldgof, Dmitry B.; Hall, Lawrence O.; Raghavan, Meera.; Gatenby, Robert A.

2014-03-01

Soft tissue sarcomas (STS) are a heterogenous group of malignant tumors comprised of more than 50 histologic subtypes. Based on spatial variations of the tumor, predictions of the development of necrosis in response to therapy as well as eventual progression to metastatic disease are made. Optimization of treatment, as well as management of therapy-related side effects, may be improved using progression information earlier in the course of therapy. Multimodality pre- and post-gadolinium enhanced magnetic resonance images (MRI) were taken before and after treatment for 30 patients. Regional variations in the tumor bed were measured quantitatively. The voxel values from the tumor region were used as features and a fuzzy clustering algorithm was used to segment the tumor into three spatial regions. The regions were given labels of high, intermediate and low based on the average signal intensity of pixels from the post-contrast T1 modality. These spatially distinct regions were viewed as essential meta-features to predict the response of the tumor to therapy based on necrosis (dead tissue in tumor bed) and metastatic disease (spread of tumor to sites other than primary). The best feature was the difference in the number of pixels in the highest intensity regions of tumors before and after treatment. This enabled prediction of patients with metastatic disease and lack of positive treatment response (i.e. less necrosis). The best accuracy, 73.33%, was achieved by a Support Vector Machine in a leave-one-out cross validation on 30 cases predicting necrosis treatment and metastasis.

Whole blood pathogen reduction technology and blood safety in sub-Saharan Africa: A systematic review with regional discussion.

Science.gov (United States)

Nkohkwo, Asa'ah; Agbor, Gabriel; Asongalem, Emmanuel; Tagny, Claude; Asonganyi, Tazoacha

2016-01-01

Despite vast improvements in transfusion services in sub-Saharan Africa over the last decade, there remain serious concerns on the safety and adequacy of the blood supply across the region. This review paper ascertains the role of pathogen reduction technology (PRT) in improving blood safety and supply adequacy in the region. The state of blood safety in sub-Saharan Africa was reviewed. Meetings, seminars and correspondence were undertaken with key clinicians, scientists and professional bodies in the region, including the World Health Organization's Regional Office for Africa, to examine the suitability of PRT for improving the safety of whole blood transfusion, a prevalent transfusion format in the region. Existing literature suggests that combining PRT with current blood safety measures (such as serology) would improve the safety and adequacy of the blood supply for transfusions in sub-Saharan Africa. This was echoed by the findings of the stakeholder meetings. Following a detailed appraisal of two leading PRT systems, the Mirasol ® PRT System and the Cerus S-303 System, we suggest that companies conduct comprehensive toxicological evaluation of the agents used for PRT and publish this in the scientific literature. We also recommend that the safety and efficacy of these technologies should be established in a randomised clinical trial conducted in sub-Saharan Africa.

Poor Response to Periodontal Treatment May Predict Future Cardiovascular Disease.

Science.gov (United States)

Holmlund, A; Lampa, E; Lind, L

2017-07-01

Periodontal disease has been associated with cardiovascular disease (CVD), but whether the response to the treatment of periodontal disease affects this association has not been investigated in any large prospective study. Periodontal data obtained at baseline and 1 y after treatment were available in 5,297 individuals with remaining teeth who were treated at a specialized clinic for periodontal disease. Poor response to treatment was defined as having >10% sites with probing pocket depth >4 mm deep and bleeding on probing at ≥20% of the sites 1 y after active treatment. Fatal/nonfatal incidence rate of CVD (composite end point of myocardial infarction, stroke, and heart failure) was obtained from the Swedish cause-of-death and hospital discharge registers. Poisson regression analysis was performed to analyze future risk of CVD. During a median follow-up of 16.8 y (89,719 person-years at risk), those individuals who did not respond well to treatment (13.8% of the sample) had an increased incidence of CVD ( n = 870) when compared with responders (23.6 vs. 15.3%, P 4 mm, and number of teeth, the incidence rate ratio for CVD among poor responders was 1.28 (95% CI, 1.07 to 1.53; P = 0.007) as opposed to good responders. The incidence rate ratio among poor responders increased to 1.39 (95% CI, 1.13 to 1.73; P = 0.002) for those with the most remaining teeth. Individuals who did not respond well to periodontal treatment had an increased risk for future CVD, indicating that successful periodontal treatment might influence progression of subclinical CVD.

The effects of genetic polymorphism on treatment response of recombinant human growth hormone.

Science.gov (United States)

Chen, Shi; You, Hanxiao; Pan, Hui; Zhu, Huijuan; Yang, Hongbo; Gong, Fengying; Wang, Linjie; Jiang, Yu; Yan, Chengsheng

2017-12-06

Recombinant human growth hormone (rhGH) has been widely used in clinical treatment of growth hormone deficiency (GHD) or non GHD since 1985 and technology have achieved a great development in different long-acting formulations. Although the mathematical models for predicting the growth hormone response could help clinicians get to an individual personalized growth dose, many patients just can't reach the target height and the growth hormone responses differed.Genetic polymorphisms may play a role in the varies of individual responses in this treatment process.This article gives an overview of the genetic polymorphisms research of growth hormone in recent years, in order to give some potential suggestion and guide for the dose titration during treatment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Improved growth response to GH treatment in irradiated children

International Nuclear Information System (INIS)

Lannering, B.; Albertsson-Wikland, K.

1989-01-01

The growth response to two years of GH treatment was studied in fifteen children after radiotherapy for a cranial tumour. The growth response was compared to that of short children (-2 SD) and that of children with idiopathic growth hormone deficiency (GHD) of similar ages. All children were treated with hGH 0.1 IU/kg/day s.c.; which is a higher dose and frequency than previously reported for irradiated children. On this protocol the growth rate increased 5.0 +- 0.5 cm/y (mean +- SEM) the first year and 3.8 +- 0.7 cm/y the second year compared to the growth rate the year before GH-treatment. Although the net gain in growth was higher than previously reported, the first year growth response was significantly reduced (p less than 0.05) compared to that of GHD-children (7.6 +- 0.5 cm/y) but exceeded (p less than 0.05) that of short children (3.4 +- 0.3 cm/y). The median spontaneous 24 h-GH secretion was 209 mU/l in the short children, 52 mU/l in the irradiated children and 16 mU/l in the idiopathic GHD children. Thus the growth increment varied inversely to the spontaneous GH secretion observed in the three groups

Treatment of patients with multiple myeloma over 65 yr: more tolerability or better response?

Science.gov (United States)

Tarkun, Pinar; Atalay, Figen; Atesoglu, Elif Birtas; Mehtap, Ozgur; Simsek, Melih; Terzi, Esra; Geduk, Ayfer; Balli, Fatih; Batman, Adnan; Baydemir, Canan; Hacihanefioglu, Abdullah

2015-05-01

Two-thirds of newly diagnosed patients with multiple myeloma (MM) are over 65 yr and/or physically unfit. Such patients are not eligible for high-dose chemotherapy or stem cell transplantation. The treatment aims in these patients should be to prolong survival by obtaining the best possible response, while maintaining good tolerability. The aim of our study was to evaluate the response to treatment and treatment-related toxicities in patients treated with conventional and novel protocols. The records of 138 elderly (≥65 yr) patients with MM were retrospectively evaluated. The median overall survival(OS) of the patients was 46 months. The median progression-free survival (PFS) was 18 months. The OS and PFS of the patients treated with the conventional protocols did not differ significantly from those treated with the novel protocols. The statistical analysis of the quality of the response to the treatment with the conventional and novel therapies showed that complete remission (CR), combined with a very good partial response (VGPR), was significantly higher in the latter. However, the toxicities were higher in the novel treatment group. The novel drug protocols significantly increased the quality of the responses of elderly patients with MM to therapy, but they did not increase the patients' tolerability. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Evaluation of treatment response in depression studies using a Bayesian parametric cure rate model.

Science.gov (United States)

Santen, Gijs; Danhof, Meindert; Della Pasqua, Oscar

2008-10-01

Efficacy trials with antidepressant drugs often fail to show significant treatment effect even though efficacious treatments are investigated. This failure can, amongst other factors, be attributed to the lack of sensitivity of the statistical method as well as of the endpoints to pharmacological activity. For regulatory purposes the most widely used efficacy endpoint is still the mean change in HAM-D score at the end of the study, despite evidence from literature showing that the HAM-D scale might not be a sensitive tool to assess drug effect and that changes from baseline at the end of treatment may not reflect the extent of response. In the current study, we evaluate the prospect of applying a Bayesian parametric cure rate model (CRM) to analyse antidepressant effect in efficacy trials with paroxetine. The model is based on a survival approach, which allows for a fraction of surviving patients indefinitely after completion of treatment. Data was extracted from GlaxoSmithKline's clinical databases. Response was defined as a 50% change from baseline HAM-D at any assessment time after start of therapy. Survival times were described by a log-normal distribution and drug effect was parameterised as a covariate on the fraction of non-responders. The model was able to fit the data from different studies accurately and results show that response to treatment does not lag for two weeks, as is mythically believed. In conclusion, we demonstrate how parameterisation of a survival model can be used to characterise treatment response in depression trials. The method contrasts with the long-established snapshot on changes from baseline, as it incorporates the time course of response throughout treatment.

Interferon-gamma response to the treatment of active pulmonary and extra-pulmonary tuberculosis.

Science.gov (United States)

Liang, L; Shi, R; Liu, X; Yuan, X; Zheng, S; Zhang, G; Wang, W; Wang, J; England, K; Via, L E; Cai, Y; Goldfeder, L C; Dodd, L E; Barry, C E; Chen, R Y

2017-10-01

Interferon-gamma (IFN-γ) release assays (IGRAs) are used to diagnose tuberculosis (TB) but not to measure treatment response. To measure IFN-γ response to active anti-tuberculosis treatment. Patients from the Henan Provincial Chest Hospital, Henan, China, with TB symptoms and/or signs were enrolled into this prospective, observational cohort study and followed for 6 months of treatment, with blood and sputum samples collected at 0, 2, 4, 6, 8, 16 and 24 weeks. The QuantiFERON® TB-Gold assay was run on collected blood samples. Participants received a follow-up telephone call at 24 months to determine relapse status. Of the 152 TB patients enrolled, 135 were eligible for this analysis: 118 pulmonary (PTB) and 17 extra-pulmonary TB (EPTB) patients. IFN-γ levels declined significantly over time among all patients (P = 0.002), with this decline driven by PTB patients (P = 0.001), largely during the initial 8 weeks of treatment (P = 0.019). IFN-γ levels did not change among EPTB patients over time or against baseline culture or drug resistance status. After 6 months of effective anti-tuberculosis treatment, IFN-γ levels decreased significantly in PTB patients, largely over the initial 8 weeks of treatment. IFN-γ concentrations may offer some value for monitoring anti-tuberculosis treatment response among PTB patients.

Hepatitis C treatment response kinetics and impact of baseline predictors

DEFF Research Database (Denmark)

Lindh, M; Arnholm, B; Eilard, A

2011-01-01

Summary. The optimal duration of treatment for hepatitis C virus (HCV) infections is highly variable but critical for achieving cure (sustained virological response, SVR). We prospectively investigated the impact of age, fibrosis, baseline viraemia and genotype on the early viral kinetics...... above 400 000 IU/mL were strongly associated with slower second phase declines of HCV RNA. Genotype 2/3 infections responded more rapidly than genotype 1, reaching week 4 negativity (RVR) in 59%vs 22%. We conclude that baseline response predictors such as age, fibrosis and viral load were well reflected...... by the early viral kinetics as assessed by repeated HCV RNA quantifications. The kinetic patterns and the high relapse rate in genotype 2/3 patients without RVR suggest that this group might benefit from treatment durations longer than 24 weeks....

United States Army physical readiness training: rationale and evaluation of the physical training doctrine.

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Knapik, Joseph J; Rieger, William; Palkoska, Frank; Van Camp, Steven; Darakjy, Salima

2009-07-01

This paper reviews the rationale and evaluations of Physical Readiness Training (PRT), the new U.S. Army physical training doctrine designed to improve soldiers' physical capability for military operations. The purposes of PRT are to improve physical fitness, prevent injuries, progressively train soldiers, and develop soldiers' self-confidence and discipline. The PRT follows the principles of progressive overload, regularity, specificity, precision, variety, and balance. Specificity was achieved by examining the standard list of military (warrior) tasks and determining 1) the physical requirements, 2) the fitness components involved, and 3) the training activities that most likely could improve the military tasks. Injury-prevention features include reduced running mileage, exercise variety (cross-training), and gradual, progressive training. In 3 military field studies, the overall adjusted risk of injury was 1.5-1.8 times higher in groups of soldiers performing traditional military physical training programs when compared with groups using a PRT program. Scores on the Army Physical Fitness Test were similar or higher in groups using PRT programs. In an 8-week laboratory study comparing PRT with a weightlifting/running program, both programs resulted in major improvements in militarily relevant tasks (e.g., 3.2-km walk/run with 32-kg load, 400-m run with 18-kg load, 5- to 30-second rushes to and from prone position, 80-kg casualty drag, obstacle course). When compared with traditional military physical training programs, PRT consistently resulted in fewer injuries and in equal or greater improvements in fitness and military task performance.

Substance abuse treatment response in a Latino sample: the influence of family conflict.

Science.gov (United States)

Fish, Jessica N; Maier, Candice A; Priest, Jacob B

2015-02-01

Latino Americans report underutilization of treatment and poor treatment response for substance use and abuse compared to other racial/ethnic groups; thus, it is important to assess factors that contribute to these disparities. The current study objective was to assess the influence of family conflict on substance abuse treatment response in a sample of Latino Americans using two different yet complementary analyses. First, ordinary least squares regression was used to assess the association between overall family conflict and pre- and post-treatment substance use. Second, repeated measures latent class analysis was used to identify groups based on family member conflict and timing of conflict during treatment. Findings indicated that family conflict contributed unique variance to concurrent substance use; however pre-treatment family conflict was not related to post-treatment outcomes. Results also identified three distinct family conflict groups: no/low conflict, pre-treatment conflict, and post-treatment conflict who differed in pre- and post-treatment substance use. Post hoc investigation revealed that those who experienced pre-treatment conflict but low post-treatment conflict showed the greatest decrease in substance use. Findings highlight the importance of considering family conflict during all stages of treatment for Latino American substance users. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of Irradiation on Tumor Microenvironment and Bone Marrow Cell Migration in a Preclinical Tumor Model

Energy Technology Data Exchange (ETDEWEB)

Kane, Jonathan L. [Department of Biological Sciences, Oakland University, Rochester, Michigan (United States); Department of Radiation Oncology, William Beaumont Health System, Royal Oak, Michigan (United States); Krueger, Sarah A.; Hanna, Alaa [Department of Radiation Oncology, William Beaumont Health System, Royal Oak, Michigan (United States); Raffel, Thomas R. [Department of Biological Sciences, Oakland University, Rochester, Michigan (United States); Wilson, George D. [Department of Radiation Oncology, William Beaumont Health System, Royal Oak, Michigan (United States); Madlambayan, Gerard J. [Department of Biological Sciences, Oakland University, Rochester, Michigan (United States); Marples, Brian, E-mail: Brian.Marples@beaumont.edu [Department of Radiation Oncology, William Beaumont Health System, Royal Oak, Michigan (United States)

2016-09-01

Purpose: To characterize the tumor microenvironment after standard radiation therapy (SRT) and pulsed radiation therapy (PRT) in Lewis lung carcinoma (LLC) allografts. Methods and Materials: Subcutaneous LLC tumors were established in C57BL/6 mice. Standard RT or PRT was given at 2 Gy/d for a total dose of 20 Gy using a 5 days on, 2 days off schedule to mimic clinical delivery. Radiation-induced tumor microenvironment changes were examined after treatment using flow cytometry and antibody-specific histopathology. Normal tissue effects were measured using noninvasive {sup 18}F-fluorodeoxyglucose positron emission tomography/computed tomography after naïve animals were given whole-lung irradiation to 40 Gy in 4 weeks using the same 2-Gy/d regimens. Results: Over the 2 weeks of therapy, PRT was more effective than SRT at reducing tumor growth rate (0.31 ± 0.02 mm{sup 3}/d and 0.55 ± 0.04 mm{sup 3}/d, respectively; P<.007). Histopathology showed a significant comparative reduction in the levels of Ki-67 (14.5% ± 3%), hypoxia (10% ± 3.5%), vascular endothelial growth factor (2.3% ± 1%), and stromal-derived factor-1α (2.5% ± 1.4%), as well as a concomitant decrease in CD45{sup +} bone marrow–derived cell (BMDC) migration (7.8% ± 2.2%) after PRT. The addition of AMD3100 also decreased CD45{sup +} BMDC migration in treated tumors (0.6% ± 0.1%). Higher vessel density was observed in treated tumors. No differences were observed in normal lung tissue after PRT or SRT. Conclusions: Pulsed RT–treated tumors exhibited slower growth and reduced hypoxia. Pulsed RT eliminated initiation of supportive mechanisms utilized by tumors in low oxygen microenvironments, including angiogenesis and recruitment of BMDCs.

WE-D-BRE-03: Late Toxicity Following Photon Or Proton Radiotherapy in Patients with Brain Tumors

Energy Technology Data Exchange (ETDEWEB)

Munbodh, R; Ding, X; Yin, L; Anamalayil, S; Dorsey, J; Lustig, R; Alonso-Basanta, M [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA (United States)

2014-06-15

Purpose: To identify indicators of Late Grade 3 (LG3) toxicity, late vision and hearing changes in patients treated for primary brain tumors with photon (XRT) or proton radiotherapy (PRT). Methods: We retrospectively reviewed 102 patients who received brain XRT or PRT to doses of 54 or 59.6 Gy in daily fractions of 1.8–2 Gy. Of the 80 patients (34 XRT, 39 PRT and 7 both modalities) reviewed for indicators of LG3 toxicity, 25 developed LG3 toxicity 90 to 500 days after radiotherapy completion. 55 patients had less than LG3 toxicity > 500 days after treatment. In that time, late vision and hearing changes were seen in 44 of 75 and 25 of 78 patients, respectively. The correlation between late toxicity and prescription dose, planning target volume (PTV) size, and doses to the brainstem, brain, optic chiasm, optic nerves, eyes and cochlea was evaluated. A two-tailed Fisher's exact test and Wilcoxon rank sum test were used for the statistical analysis for XRT, PRT and all patients combined. Results: Exceeding the 54 Gy-5% dose-volume brainstem constraint, but not the optic structure constraints, was significantly correlated (p < 0.05) with late vision changes in all three groups. Exceeding maximum and mean cochlear doses of 45 and 30 Gy, respectively, was a significant indicator of hearing changes (p < 0.05) in PRT patients and all patients combined. In a sub-group of 52 patients in whom the brain was contoured, the absolute brain volume receiving ≤ 50 Gy and > 60 Gy was significantly larger in patients with LG3 toxicity for all patients combined (p < 0.05). Prescription dose, brainstem dose and PTV volume were not correlated to LG3 toxicity. Conclusion: Our results indicate the importance of minimizing the brain volume irradiated, and brainstem and cochlea doses to reduce the risk of late toxicities following brain radiotherapy.

Overall response rates to radiation therapy for patients with painful uncomplicated bone metastases undergoing initial treatment and retreatment

International Nuclear Information System (INIS)

Bedard, Gillian; Hoskin, Peter; Chow, Edward

2014-01-01

Introduction: Radiation therapy has been shown to successfully palliate bone metastases. A number of systematic reviews and large clinical trials have reported response rates for initial treatment and retreatment. Objective: To determine overall response rates of patients with painful uncomplicated bone metastases undergoing initial treatment and retreatment. Methods: Intent-to-treat and evaluable patient statistics from a systematic review of palliative radiotherapy trials for initial treatment of bone metastases and a randomized clinical trial of retreatment were pooled and analyzed to determine the overall response rates for patients receiving initial treatment and retreatment. Results: In the intent-to-treat calculation, 71–73% of patients had an overall response to radiation treatment and in the evaluable patient population; 85–87% of patients did so. Response rates varied slightly whether patients underwent single or multiple fractions in initial treatment or retreatment. Conclusions: Single and multiple fraction radiation treatment yielded very similar overall response rates. Patients treated with a single fraction for both initial and repeat radiation experience almost identical overall response to those patients treated with multiple fraction treatment. It is therefore recommended that patients with uncomplicated painful bone metastases be treated with a single 8 Gy fraction of radiation at both the initial treatment and retreatment

Effects of a chronic stress treatment on vaccinal response in lambs.

Science.gov (United States)

Destrez, A; Boissy, A; Guilloteau, L; Andanson, S; Souriau, A; Laroucau, K; Chaillou, E; Deiss, V

2017-05-01

Farming systems can expose animals to chronic mild stress which is known to induce negative affective state. Affective state in animals, as in humans, can be assessed through behavioral cues. This study aimed to describe the effect of a chronic mild stress, known to induce a negative affective state, on sheep health through their response to vaccination. The study used 15 lambs subjected to a model of chronic mild stress for 15 weeks and 15 lambs reared under conventional farming as a control group. After 7 weeks of stressful treatment, the lambs were individually exposed to a judgment bias test to assess a putative stress-induced 'pessimism.' After 15 weeks of stressful treatment, antibody immune response was measured after an injection of a live vaccine challenge (Chlamydia abortus attenuated vaccine strain 1B). Stressed lambs displayed a pessimistic-like perception in the judgment bias test, revealing a negative affective state. Stressed and control animals showed different immunological reactions to vaccine challenge: stressed sheep had lower hemoglobin concentrations and higher platelet, granulocyte and acute-phase protein concentrations. Antibody response induced by the vaccine strain was not different between stressed and control sheep. Our results suggest that negative affective state induced by chronic stress treatment may induce a stronger inflammatory response to vaccine challenge in sheep. Improvement of animal health may be achieved through consideration of stressors that may affect the emotional and immunological state of sheep.

Selective albumin-binding surfaces modified with a thrombin-inhibiting peptide.

Science.gov (United States)

Freitas, Sidónio C; Maia, Sílvia; Figueiredo, Ana C; Gomes, Paula; Pereira, Pedro J B; Barbosa, Mário A; Martins, M Cristina L

2014-03-01

Blood-contacting medical devices have been associated with severe clinical complications, such as thrombus formation, triggered by the activation of the coagulation cascade due to the adsorption of certain plasma proteins on the surface of biomaterials. Hence, the coating of such surfaces with antithrombotic agents has been used to increase biomaterial haemocompatibility. Biomaterial-induced clotting may also be decreased by albumin adsorption from blood plasma in a selective and reversible way, since this protein is not involved in the coagulation cascade. In this context, this paper reports that the immobilization of the thrombin inhibitor D-Phe-Pro-D-Arg-D-Thr-CONH2 (fPrt) onto nanostructured surfaces induces selective and reversible adsorption of albumin, delaying the clotting time when compared to peptide-free surfaces. fPrt, synthesized with two glycine residues attached to the N-terminus (GGfPrt), was covalently immobilized onto self-assembled monolayers (SAMs) having different ratios of carboxylate-hexa(ethylene glycol)- and tri(ethylene glycol)-terminated thiols (EG6-COOH/EG3) that were specifically designed to control GGfPrt orientation, exposure and density at the molecular level. In solution, GGfPrt was able to inactivate the enzymatic activity of thrombin and to delay plasma clotting time in a concentration-dependent way. After surface immobilization, and independently of its concentration, GGfPrt lost its selectivity to thrombin and its capacity to inhibit thrombin enzymatic activity against the chromogenic substrate n-p-tosyl-Gly-Pro-Arg-p-nitroanilide. Nevertheless, surfaces with low concentrations of GGfPrt could delay the capacity of adsorbed thrombin to cleave fibrinogen. In contrast, GGfPrt immobilized in high concentrations was found to induce the procoagulant activity of the adsorbed thrombin. However, all surfaces containing GGfPrt have a plasma clotting time similar to the negative control (empty polystyrene wells), showing resistance to

Enteric microbiome metabolites correlate with response to simvastatin treatment.

Directory of Open Access Journals (Sweden)

Rima Kaddurah-Daouk

Full Text Available Although statins are widely prescribed medications, there remains considerable variability in therapeutic response. Genetics can explain only part of this variability. Metabolomics is a global biochemical approach that provides powerful tools for mapping pathways implicated in disease and in response to treatment. Metabolomics captures net interactions between genome, microbiome and the environment. In this study, we used a targeted GC-MS metabolomics platform to measure a panel of metabolites within cholesterol synthesis, dietary sterol absorption, and bile acid formation to determine metabolite signatures that may predict variation in statin LDL-C lowering efficacy. Measurements were performed in two subsets of the total study population in the Cholesterol and Pharmacogenetics (CAP study: Full Range of Response (FR, and Good and Poor Responders (GPR were 100 individuals randomly selected from across the entire range of LDL-C responses in CAP. GPR were 48 individuals, 24 each from the top and bottom 10% of the LDL-C response distribution matched for body mass index, race, and gender. We identified three secondary, bacterial-derived bile acids that contribute to predicting the magnitude of statin-induced LDL-C lowering in good responders. Bile acids and statins share transporters in the liver and intestine; we observed that increased plasma concentration of simvastatin positively correlates with higher levels of several secondary bile acids. Genetic analysis of these subjects identified associations between levels of seven bile acids and a single nucleotide polymorphism (SNP, rs4149056, in the gene encoding the organic anion transporter SLCO1B1. These findings, along with recently published results that the gut microbiome plays an important role in cardiovascular disease, indicate that interactions between genome, gut microbiome and environmental influences should be considered in the study and management of cardiovascular disease. Metabolic

Dosimetric Comparison of Three-Dimensional Conformal Proton Radiotherapy, Intensity-Modulated Proton Therapy, and Intensity-Modulated Radiotherapy for Treatment of Pediatric Craniopharyngiomas

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Boehling, Nicholas S. [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Grosshans, David R., E-mail: dgrossha@mdanderson.org [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Bluett, Jaques B. [Department of Radiation Physics, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Palmer, Matthew T. [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Song, Xiaofei; Amos, Richard A.; Sahoo, Narayan [Department of Radiation Physics, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Meyer, Jeffrey J.; Mahajan, Anita; Woo, Shiao Y. [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States)

2012-02-01

Purpose: Cranial irradiation in pediatric patients is associated with serious long-term adverse effects. We sought to determine whether both three-dimensional conformal proton radiotherapy (3D-PRT) and intensity-modulated proton therapy (IMPT) compared with intensity-modulated radiotherapy (IMRT) decrease integral dose to brain areas known to harbor neuronal stem cells, major blood vessels, and other normal brain structures for pediatric patients with craniopharyngiomas. Methods and Materials: IMRT, forward planned, passive scattering proton, and IMPT plans were generated and optimized for 10 pediatric patients. The dose was 50.4 Gy (or cobalt Gy equivalent) delivered in 28 fractions with the requirement for planning target volume (PTV) coverage of 95% or better. Integral dose data were calculated from differential dose-volume histograms. Results: The PTV target coverage was adequate for all modalities. IMRT and IMPT yielded the most conformal plans in comparison to 3D-PRT. Compared with IMRT, 3D-PRT and IMPT plans had a relative reduction of integral dose to the hippocampus (3D-PRT, 20.4; IMPT, 51.3%{sup Asterisk-Operator }), dentate gyrus (27.3, 75.0%{sup Asterisk-Operator }), and subventricular zone (4.5, 57.8%{sup Asterisk-Operator }). Vascular organs at risk also had reduced integral dose with the use of proton therapy (anterior cerebral arteries, 33.3{sup Asterisk-Operator }, 100.0%{sup Asterisk-Operator }; middle cerebral arteries, 25.9%{sup Asterisk-Operator }, 100%{sup Asterisk-Operator }; anterior communicating arteries, 30.8{sup Asterisk-Operator }, 41.7%{sup Asterisk-Operator }; and carotid arteries, 51.5{sup Asterisk-Operator }, 77.6{sup Asterisk-Operator }). Relative reduction of integral dose to the infratentorial brain (190.7{sup Asterisk-Operator }, 109.7%{sup Asterisk-Operator }), supratentorial brain without PTV (9.6, 26.8%{sup Asterisk-Operator }), brainstem (45.6, 22.4%{sup Asterisk-Operator }), and whole brain without PTV (19.4{sup Asterisk

Use of cerebral CT as prognosticator of treatment response of brain metastases

International Nuclear Information System (INIS)

Asbell, S.O.; Hitchon, H.D.; Sklaroff, D.M.

1986-01-01

The authors analyzed data on 43 patients at the Albert Einstein Medical Center in Philadelphia who participated in RTOG phase III protocol 79-16 (evaluation of misonidazole combined with varying dose schedules of radiation therapy in the treatment of brain metastases). Karnofsky status and brain CT findings were correlated as prognosticators of response to radiation therapy. CT was performed at specific intervals before treatment and at 6 and 12 weeks after completion of therapy. Based on CT appearance, the maximum response to radiation therapy occurred 1.5 months after the initiation of treatment. Average survival, defined from the first day of treatment, was 5.9 months. Patients with total resolution on CT at 6 weeks had an average survival of 9.5 months, while those who showed improvement only on 6-week CT scans had an average survival of 7.2 months, and those who showed no change had an average survival of 5.2 months. Patients whose Karnofsky score improved with radiation therapy or remained the same had an average survival of 8.5 months; those whose score decreased had an average survival of 5.8 months. CT is a valuable indicator of response to radiation therapy, and CT findings closely correlate with the Karnofsky score

RESPONSE OF TOMATO PLANTS EXPOSED TO TREATMENT WITH NANOPARTICLES

Directory of Open Access Journals (Sweden)

Tommaso Giordani

2012-07-01

Full Text Available In this work the response of Tomato plants cv. Micro-Tom to nanoparticles (NPs treatment was investigated. Tomato seedlings were grown in hydroponic condition and NPs treatments were carried out by adding Fe3O4 or TiO2 NPs to nutrient solution. At the end of treatments, NPs root uptake and tissue deposition were investigated using Environmental Scanning Electron Microscope, equipped with energy dispersive spectroscopy for chemical identification. At morphological level, one week after the beginning of NP treatment, seedlings grown with high concentration of TiO2 NPs showed an abnormal proliferation of root hairs, as compared to the control seedlings and to the seedlings exposed to Fe3O4 NPs, Shoot morphology did not differ in tomato seedlings grown under different conditions and no symptoms of toxicity were observed in NP-treated plants. In order to analyse genetic effects of NPs treatments, RNA transcription was studied in roots of NP-exposed and control plants by Illumina RNA sequencing, evidencing the induction of transposable elements.

Highly polygenic architecture of antidepressant treatment response: Comparative analysis of SSRI and NRI treatment in an animal model of depression.

Science.gov (United States)

Malki, Karim; Tosto, Maria Grazia; Mouriño-Talín, Héctor; Rodríguez-Lorenzo, Sabela; Pain, Oliver; Jumhaboy, Irfan; Liu, Tina; Parpas, Panos; Newman, Stuart; Malykh, Artem; Carboni, Lucia; Uher, Rudolf; McGuffin, Peter; Schalkwyk, Leonard C; Bryson, Kevin; Herbster, Mark

2017-04-01

Response to antidepressant (AD) treatment may be a more polygenic trait than previously hypothesized, with many genetic variants interacting in yet unclear ways. In this study we used methods that can automatically learn to detect patterns of statistical regularity from a sparsely distributed signal across hippocampal transcriptome measurements in a large-scale animal pharmacogenomic study to uncover genomic variations associated with AD. The study used four inbred mouse strains of both sexes, two drug treatments, and a control group (escitalopram, nortriptyline, and saline). Multi-class and binary classification using Machine Learning (ML) and regularization algorithms using iterative and univariate feature selection methods, including InfoGain, mRMR, ANOVA, and Chi Square, were used to uncover genomic markers associated with AD response. Relevant genes were selected based on Jaccard distance and carried forward for gene-network analysis. Linear association methods uncovered only one gene associated with drug treatment response. The implementation of ML algorithms, together with feature reduction methods, revealed a set of 204 genes associated with SSRI and 241 genes associated with NRI response. Although only 10% of genes overlapped across the two drugs, network analysis shows that both drugs modulated the CREB pathway, through different molecular mechanisms. Through careful implementation and optimisations, the algorithms detected a weak signal used to predict whether an animal was treated with nortriptyline (77%) or escitalopram (67%) on an independent testing set. The results from this study indicate that the molecular signature of AD treatment may include a much broader range of genomic markers than previously hypothesized, suggesting that response to medication may be as complex as the pathology. The search for biomarkers of antidepressant treatment response could therefore consider a higher number of genetic markers and their interactions. Through

Effects of diabetes mellitus on the clinical presentation and treatment response in tuberculosis.

Science.gov (United States)

Leung, Chi C; Yew, Wing W; Mok, Thomas Y W; Lau, Kam S; Wong, Chi F; Chau, Chi H; Chan, Chi K; Chang, Kwok C; Tam, Greta; Tam, Cheuk M

2017-08-01

With the colliding global epidemics of diabetes mellitus (DM) and tuberculosis (TB), we studied the effects of DM on the presentation of TB and its response to treatment. Consecutive TB patients from 2006 to 2010 in a territory-wide treatment programme offering 9-month extended treatment for TB patients with DM were examined and followed up prospectively to assess their treatment response. Successful treatment completers were tracked through the TB registry and death registry for relapse, death or till 31 December 2014, whichever was the earliest. DM was independently associated with more chest symptoms (adjusted OR (AOR): 1.13) and systemic symptoms (AOR: 1.30) but less with other site-specific symptoms (AOR: 0.58) at TB presentation. There was more frequent pulmonary involvement (AOR: 1.69), with more extensive lung lesion (AOR: 1.25), lung cavity (AOR: 2.00) and positive sputum smear (AOR: 1.83) and culture (AOR: 1.38), but no difference in the proportion of retreatment cases or isoniazid and/or rifampicin resistance. After treatment initiation, there was higher overall incidence (AOR: 1.38) of adverse effects (mainly gastrointestinal symptoms, renal impairment and peripheral neuropathy but less fever and skin hypersensitivity reactions), more smear non-conversion (AOR: 1.59) and culture non-conversion (AOR: 1.40) at 2 months, and lower combined cure/treatment completion rate at 12 months (AOR: 0.79), but no difference in the relapse rate after having successfully completed treatment. DM adversely affected the clinical presentation and treatment response of TB, but there was no difference in the drug resistance and relapse rates. © 2017 Asian Pacific Society of Respirology.

Systematic review genetic biomarkers associated with anti-TNF treatment response in inflammatory bowel diseases

DEFF Research Database (Denmark)

Sørensen, Signe Bek; Nielsen, J V; Bo Bojesen, Anders

2016-01-01

BACKGROUND: Personalised medicine, including biomarkers for treatment selection, may provide new algorithms for more effective treatment of patients. Genetic variation may impact drug response and genetic markers could help selecting the best treatment strategy for the individual patient. AIM......2430561) [OR = 1.66 (1.05-2.63)], IL6 (rs10499563) [OR = 1.65 (1.04-2.63)] and IL1B (rs4848306) [OR = 1.88 (1.05-3.35)] were significantly associated with response among IBD patients using clinical response criteria. A positive predictive value of 0.96 was achieved by combining five genetic markers...... in an explorative analysis. CONCLUSIONS: There are no genetic markers currently available which are adequately predictive of anti-TNF response for use in the clinic. Genetic markers bear the advantage that they do not change over time. Therefore, hypothesis-free approaches, testing a large number of polymorphisms...

Clinical manifestations and treatment response of steroid in pediatric Hashimoto encephalopathy.

Science.gov (United States)

Yu, Hee Joon; Lee, Jeehun; Seo, Dae Won; Lee, Munhyang

2014-07-01

Hashimoto encephalopathy is a steroid-responsive encephalopathy associated with elevated titers of antithyroid antibodies. Clinical symptoms are characterized by behavioral and cognitive changes, speech disturbance, seizures, myoclonus, psychosis, hallucination, involuntary movements, cerebellar signs, and coma. The standard treatment is the use of corticosteroids along with the treatment of any concurrent dysthyroidism. Other options are immunoglobulins and plasmapheresis. We described symptoms and outcomes on 3 teenage girls with Hashimoto encephalopathy. Presenting symptoms were seizure or altered mental status. One patient took levothyroxine due to hypothyroidism before presentation of Hashimoto encephalopathy. After confirmation of elevated antithyroid antibodies, all patients were treated with steroids. One patient needed plasmapheresis because of the lack of response to steroids and immunoglobulins. Hashimoto encephalopathy should be considered in any patient presenting with acute or subacute unexplained encephalopathy and seizures. Even though the use of steroids is the first line of treatment, plasmapheresis can rescue steroid-resistant patients. © The Author(s) 2013.

Response to Various Treatments in the Patients With Chronic Hepatitis B; A Cross-Sectional Study

Directory of Open Access Journals (Sweden)

Mamani

2014-04-01

Full Text Available Background Hepatitis B is one of the most common chronic viral infections worldwide, especially in developing countries. The insufficient treatment of the disease increases the risk of cirrhosis and hepatocellular carcinoma, which impose heavy costs to the patient and the society. Different studies evaluated several protocols for the treatment of the disease. Objectives The aim of this study was to evaluate the response rate of the different treatments in patients with chronic hepatitis B (CHB. Patients and Methods In a cross-sectional study, 89 patients with CHB who were referred to Infectious Diseases Clinics during 2004 to 2009 were studied. Serological and biochemical outcomes to the different treatments were evaluated. The data were analyzed by SPSS 16. Results CHB was more frequent in men (74.2% than women (25.8%. The mean age of the patients was 36 ± 1.36 years. Fifty-three patients (59.6% had active CHB while 36 (40.4% were asymptomatic carriers. Serologic and biochemical responses to the treatment were 50% and 69.44%, respectively. However, 50% of the patients with positive HBeAg showed serologic response to the treatment, 37.5% showed HBeAb as well as reduced amounts of HBeAg, and 12.5% just showed reduced amounts of HBeAg. Patients treated by lamivudine showed the highest serologic response rate (75%. Conclusions Serologic and biochemical response to the different treatments in the patients were better than other similar studies. Besides, it is recommended to begin antiviral therapy against CHB infection with lamivudine alone as a first-line therapy.

Characterization of the mature cell surface proteinase of Lactobacillus delbrueckii subsp. lactis CRL 581.

Science.gov (United States)

Villegas, Josefina M; Brown, Lucía; Savoy de Giori, Graciela; Hebert, Elvira M

2015-05-01

The cell envelope-associated proteinase (CEP) of Lactobacillus delbrueckii subsp. lactis CRL 581 (PrtL) has an essential role in bacterial growth, contributes to the flavor and texture development of fermented products, and can release bioactive health-beneficial peptides during milk fermentation. The genome of L. delbrueckii subsp. lactis CRL 581 possesses only one gene that encodes PrtL, which consists of 1924 amino acids and is a multidomain protein anchored to the cell via its W domain. PrtL was extracted from the cell under high ionic strength conditions using NaCl, suggesting an electrostatic interaction between the proteinase and the cell envelope. The released PrtL was purified and biochemically characterized; its activity was maximal at temperatures between 37 and 40 °C and at pH between 7 and 8. Under optimal conditions, PrtL exhibited higher affinity for succinyl-alanyl-alanyl-prolyl-phenylalanine-p-nitroanilide than for succinyl-alanyl-glutamyl-prolyl-phenylalanine-p-nitroanilide, while methoxy-succinyl-arginyl-prolyl-tyrosyl-p-nitroanilide was not degraded. A similar α- and β-casein degradation pattern was observed with the purified and the cell envelope-bound proteinase. Finally, on the basis of its specificity towards caseins and the unique combination of amino acids at residues thought to be involved in substrate specificity, PrtL can be classified as a representative of a new group of CEP.

Response of Human Prostate Cancer Cells to Mitoxantrone Treatment in Simulated Microgravity Environment

Science.gov (United States)

Zhang, Ye; Edwards, Christopher; Wu, Honglu

2011-01-01

This study explores the changes in growth of human prostate cancer cells (LNCaP) and their response to the treatment of antineoplastic agent, mitoxantrone, under the simulated microgravity condition. In comparison to static 1g, microgravity and simulated microgravity have been shown to alter global gene expression patterns and protein levels in various cultured cell models or animals. However, very little is known about the effect of altered gravity on the responses of cells to drugs, especially chemotherapy drugs. To test the hypothesis that zero gravity would result in altered regulation of cells in response to antineoplastic agents, we cultured LNCaP cells for 96 hr either in a High Aspect Ratio Vessel (HARV) bioreactor at the rotating condition to model microgravity in space or in the static condition as a control. 24 hr after the culture started, mitoxantrone was introduced to the cells at a final concentration of 1 M. The mitoxantrone treatment lasted 72 hr and then the cells were collected for various measurements. Compared to static 1g controls, the cells cultured in the simulated microgravity environment did not show significant differences in cell viability, growth rate, or cell cycle distribution. However, in response to mitoxantrone (1uM), a significant proportion of bioreactor cultured cells (30%) was arrested at G2 phase and a significant number of these cells were apoptotic in comparison to their static controls. The expressions of 84 oxidative stress related genes were analyzed using Qiagen PCR array to identify the possible mechanism underlying the altered responses of bioreactor culture cells to mitoxantrone. Nine out of 84 genes showed higher expression at four hour post mitoxantrone treatment in cells cultured at rotating condition compared to those at static. Taken together, the results reported here indicate that simulated microgravity may alter the responses of LNCaP cells to mitoxantrone treatment. The alteration of oxidative stress pathways

Reevaluating response and failure of medical treatment of endometriosis: a systematic review.

Science.gov (United States)

Becker, Christian M; Gattrell, William T; Gude, Kerstin; Singh, Sukhbir S

2017-07-01

To assess patient response rates to medical therapies used to treat endometriosis-associated pain. A systematic review with the use of Medline and Embase. Not applicable. Women receiving medical therapy to treat endometriosis. None. The proportions of patients who: experienced no reduction in endometriosis-associated pain symptoms; had pain symptoms remaining at the end of the treatment period; had pain recurrence after treatment cessation; experienced an increase or no change in disease score during the study; were satisfied with treatment; and discontinued therapy owing to adverse events or lack of efficacy. The change in pain symptom severity experienced during and after treatment, as measured on the visual analog scale, was also assessed. In total, 58 articles describing 125 treatment arms met the inclusion criteria. Data for the response of endometriosis-associated pain symptoms to treatment were presented in only 29 articles. The median proportions of women with no reduction in pain were 11%-19%; at the end of treatment, 5%-59% had pain remaining; and after follow-up, 17%-34% had experienced recurrence of pain symptoms after treatment cessation. After median study durations of 2-24 months, the median discontinuation rates due to adverse events or lack of efficacy were 5%-16%. Few studies of medical therapies for endometriosis report outcomes that are relevant to patients, and many women gain only limited or intermittent benefit from treatment. Copyright © 2017. Published by Elsevier Inc.

Resistance Exercise Impacts Lean Muscle Mass in Women with Polycystic Ovary Syndrome.

Science.gov (United States)

Kogure, Gislaine Satyko; Miranda-Furtado, Cristiana Libardi; Silva, Rafael Costa; Melo, Anderson Sanches; Ferriani, Rui Alberto; De Sá, Marcos Felipe Silva; Dos Reis, Rosana Maria

2016-04-01

This study investigated the effects of progressive resistance training (PRT) on lean muscle mass (LMM) in women with or without polycystic ovary syndrome (PCOS) and its effects on metabolic factors and concentrations of related steroid hormones. This was a nonrandomized, therapeutic, open, single-arm study. All in all, 45 sedentary women with PCOS and 52 without (non-PCOS), 18-37 yr of age, with body mass indexes (BMI) of 18-39.9 kg·m(-2) of all races and social status, performed PRT three times a week for 4 months. Before and after PRT, the concentrations of hormones and metabolic factors and waist circumference were measured. LMM and total body fat percentage were determined using dual-energy x-ray absorptiometry. Clinical characteristics, LMM, and fasting glucose were adjusted for confounding covariables and compared using general linear mixed models. Each patient's menstrual history was taken before study enrollment and after PRT. PRT resulted in reduced plasma testosterone and fasting glucose levels. After PRT, the androstenedione concentration increased and the sex hormone-binding globulin concentration decreased in women with PCOS. The waist circumference was reduced (P lean mass (LM)/height2, increased in women with PCOS (P = 0.04). Women with PCOS showed increased muscle mass indexes of appendicular LM/height2 (P = 0.03) and LM/height2 (P women with PCOS (P = 0.01) at the baseline and after PRT. To our knowledge, this is the first report to show that resistance exercise alone can improve hyperandrogenism, reproductive function, and body composition by decreasing visceral fat and increasing LMM, but it has no metabolic impact on women with PCOS.

A Population-based Study of the Fractionation of Palliative Radiotherapy for Bone Metastasis in Ontario

International Nuclear Information System (INIS)

Kong, Weidong; Zhang-Salomons, Jina; Hanna, Timothy P.; Mackillop, William J.

2007-01-01

Purpose: To describe the use of palliative radiotherapy (PRT) for bone metastases in Ontario between 1984 and 2001 and identify factors associated with the choice of fractionation. Methods and Materials: Electronic RT records from the nine provincial RT centers in Ontario were linked to the Ontario Cancer Registry to identify all courses of PRT for bone metastases. Results: Between 1984 and 2001, 44,884 patients received 74,432 courses of PRT for bone metastases in Ontario. The mean number of courses per patient was 1.7, and 65% of patients received only a single course of PRT for bone metastasis. The mean number of fractions per course was 3.9. The proportion of patients treated with a single fraction increased from 27.2% in 1984-1986 to 40.3% in 1987-1992 and decreased thereafter. Single fractions were used more frequently in patients with a shorter life expectancy, in older patients, and in patients who lived further from an RT center. Single fractions were used more frequently when the prevailing waiting time for RT was longer. There were wide variations in the use of single fractions among the different RT centers (intercenter range, 11.8-62.3%). Intercenter variations persisted throughout the study period and were not explained by differences in case mix. Conclusions: Despite increasing evidence of the effectiveness of single-fraction PRT for bone metastases, most patients continued to receive fractionated PRT throughout the two decades of this study. Single fractions were used more frequently when waiting times were longer. There was persistent, unexplained variation in the fractionation of PRT among different centers

Deep-Sea Trench Microbiology Down to 10.9 Kilometers Below the Surface

Science.gov (United States)

Bartlett, D. H.

2012-12-01

Deep-sea trenches, extending to more than 10.9 km below the sea surface, are among the most remote and infrequently sampled habitats. As a result a global perspective of microbial diversity and adaptation is lacking in these extreme settings. I will present the results of studies of deep-sea trench microbes collected in the Puerto Rico Trench (PRT), Tonga Trench, New Britain Trench and Mariana Trench. The samples collected include sediment, seawater and animals in baited traps. The analyses to be described include microbial community activity and viability measurements as a function of hydrostatic pressure, microbial culturing at high pressure under various physiological conditions, phylogenetics and metagenome and single-cell genome characterizations. Most of the results to date stem from samples recovered from the PRT. The deep-sea PRT Trench microbes have more in common at the species level with other deep-sea microbial communities previously characterized in the Pacific Ocean and the Mediterranean Sea than with the microbial populations above them in shallow waters. They also harbor larger genomes with more genes assigned to signal transduction, transcription, replication, recombination and repair and inorganic ion transport. The overrepresented transporters in the PRT metagenome include di- and tri-carboxylate transporters that correspond to the prevailing catabolic processes such as butanoate, glyoxylate and dicarboxylate metabolism. A surprisingly high abundance of sulfatases for the degradation of sulfated polysaccharides were also present in the PRT. But, perhaps the most dramatic adaptational feature of the PRT microbes is heavy metal resistance, as reflected in the high numbers of metal efflux systems present. Single-cell genomics approaches have proven particularly useful for placing PRT metagenomic data into context.

Qualifications of Bonding Process of Temperature Sensors to Deep-Space Missions

Science.gov (United States)

Ramesham, Rajeshuni; Kitiyakara, Amarit; Redick, Richard W., III; Sunada, Eric T.

2011-01-01

A process has been examined for bonding a platinum resistance thermometer (PRT) onto potential aerospace materials such as flat aluminum surfaces and a flexible copper tube to simulate coaxial cables for flight applications. Primarily, PRTs were inserted into a silver-plated copper braid to avoid stresses on the sensor while the sensor was attached with the braid to the base material for long-duration, deep-space missions. A1-1145/graphite composite (planar substrate) and copper tube have been used in this study to assess the reliability of PRT bonding materials. A flexible copper tube was chosen to simulate the coaxial cable to attach PRTs. The substrate materials were cleaned with acetone wipes to remove oils and contaminants. Later, the surface was also cleaned with ethyl alcohol and was air-dried. The materials were gently abraded and then were cleaned again the same way as previously mentioned. Initially, shielded (silver plated copper braid) PRT (type X) test articles were fabricated and cleaned. The base antenna material was pretreated and shielded, and CV-2566 NuSil silicone was used to attach the shielded PRT to the base material. The test articles were cured at room temperature and humidity for seven days. The resistance of the PRTs was continuously monitored during the thermal cycling, and the test articles were inspected prior to, at various intermediate steps during, and at the end of the thermal cycling as well. All of the PRTs survived three times the expected mission life for the JUNO project. No adhesion problems were observed in the PRT sensor area, or under the shielded PRT. Furthermore, the PRT resistance accurately tracked the thermal cycling of the chamber.

Can resistance training impact MRI outcomes in relapsing-remitting multiple sclerosis?

DEFF Research Database (Denmark)

Kjølhede, Tue; Siemonsen, Susanne; Wenzel, Damian

2017-01-01

BACKGROUND: Multiple sclerosis (MS) is characterised by accelerated brain atrophy, which relates to disease progression. Previous research shows that progressive resistance training (PRT) can counteract brain atrophy in other populations. OBJECTIVE: To evaluate the effects of PRT by magnetic...... lifestyle followed by PRT). Assessments included disability measures and MRI (lesion load, global brain volume, percentage brain volume change (PBVC) and cortical thickness). RESULTS: While the MS Functional Composite score improved, Expanded Disability Status Scale, lesion load and global brain volumes did...

77 FR 30547 - Endangered Species; Receipt of Applications for Permit

Science.gov (United States)

2012-05-23

.... Applicant: James Bruner, Comfort, TX; PRT-72932A The applicant requests a captive-bred wildlife registration... conducted by the applicant over a 5-year period. Applicant: James Bruner, Comfort, TX; PRT-72933A The...

Incidence of CNS Injury for a Cohort of 111 Patients Treated With Proton Therapy for Medulloblastoma: LET and RBE Associations for Areas of Injury

Energy Technology Data Exchange (ETDEWEB)

Giantsoudi, Drosoula; Sethi, Roshan V. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Yeap, Beow Y. [Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts (United States); Eaton, Bree R. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Ebb, David H. [Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts (United States); Caruso, Paul A.; Rapalino, Otto [Department of Radiology (O.R.) at the Massachusetts General Hospital, Boston, Massachusetts (United States); Chen, Yen-Lin E.; Adams, Judith A.; Yock, Torunn I.; Tarbell, Nancy J.; Paganetti, Harald [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); MacDonald, Shannon M., E-mail: smacdonald@mgh.harvard.edu [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

2016-05-01

Background: Central nervous system (CNS) injury is a rare complication of radiation therapy for pediatric brain tumors, but its incidence with proton radiation therapy (PRT) is less well defined. Increased linear energy transfer (LET) and relative biological effectiveness (RBE) at the distal end of proton beams may influence this risk. We report the incidence of CNS injury in medulloblastoma patients treated with PRT and investigate correlations with LET and RBE values. Methods and Materials: We reviewed 111 consecutive patients treated with PRT for medulloblastoma between 2002 and 2011 and selected patients with clinical symptoms of CNS injury. Magnetic resonance imaging (MRI) findings for all patients were contoured on original planning scans (treatment change areas [TCA]). Dose and LET distributions were calculated for the treated plans using Monte Carlo system. RBE values were estimated based on LET-based published models. Results: At a median follow-up of 4.2 years, the 5-year cumulative incidence of CNS injury was 3.6% for any grade and 2.7% for grade 3+. Three of 4 symptomatic patients were treated with a whole posterior fossa boost. Eight of 10 defined TCAs had higher LET values than the target but statistically nonsignificant differences in RBE values (P=.12). Conclusions: Central nervous system and brainstem injury incidence for PRT in this series is similar to that reported for photon radiation therapy. The risk of CNS injury was higher for whole posterior fossa boost than for involved field. Although no clear correlation with RBE values was found, numbers were small and additional investigation is warranted to better determine the relationship between injury and LET.

Incidence of CNS Injury for a Cohort of 111 Patients Treated With Proton Therapy for Medulloblastoma: LET and RBE Associations for Areas of Injury

International Nuclear Information System (INIS)

Giantsoudi, Drosoula; Sethi, Roshan V.; Yeap, Beow Y.; Eaton, Bree R.; Ebb, David H.; Caruso, Paul A.; Rapalino, Otto; Chen, Yen-Lin E.; Adams, Judith A.; Yock, Torunn I.; Tarbell, Nancy J.; Paganetti, Harald; MacDonald, Shannon M.

2016-01-01

Background: Central nervous system (CNS) injury is a rare complication of radiation therapy for pediatric brain tumors, but its incidence with proton radiation therapy (PRT) is less well defined. Increased linear energy transfer (LET) and relative biological effectiveness (RBE) at the distal end of proton beams may influence this risk. We report the incidence of CNS injury in medulloblastoma patients treated with PRT and investigate correlations with LET and RBE values. Methods and Materials: We reviewed 111 consecutive patients treated with PRT for medulloblastoma between 2002 and 2011 and selected patients with clinical symptoms of CNS injury. Magnetic resonance imaging (MRI) findings for all patients were contoured on original planning scans (treatment change areas [TCA]). Dose and LET distributions were calculated for the treated plans using Monte Carlo system. RBE values were estimated based on LET-based published models. Results: At a median follow-up of 4.2 years, the 5-year cumulative incidence of CNS injury was 3.6% for any grade and 2.7% for grade 3+. Three of 4 symptomatic patients were treated with a whole posterior fossa boost. Eight of 10 defined TCAs had higher LET values than the target but statistically nonsignificant differences in RBE values (P=.12). Conclusions: Central nervous system and brainstem injury incidence for PRT in this series is similar to that reported for photon radiation therapy. The risk of CNS injury was higher for whole posterior fossa boost than for involved field. Although no clear correlation with RBE values was found, numbers were small and additional investigation is warranted to better determine the relationship between injury and LET.

Incidence of CNS Injury for a Cohort of 111 Patients Treated With Proton Therapy for Medulloblastoma: LET and RBE Associations for Areas of Injury.

Science.gov (United States)

Giantsoudi, Drosoula; Sethi, Roshan V; Yeap, Beow Y; Eaton, Bree R; Ebb, David H; Caruso, Paul A; Rapalino, Otto; Chen, Yen-Lin E; Adams, Judith A; Yock, Torunn I; Tarbell, Nancy J; Paganetti, Harald; MacDonald, Shannon M

2016-05-01

Central nervous system (CNS) injury is a rare complication of radiation therapy for pediatric brain tumors, but its incidence with proton radiation therapy (PRT) is less well defined. Increased linear energy transfer (LET) and relative biological effectiveness (RBE) at the distal end of proton beams may influence this risk. We report the incidence of CNS injury in medulloblastoma patients treated with PRT and investigate correlations with LET and RBE values. We reviewed 111 consecutive patients treated with PRT for medulloblastoma between 2002 and 2011 and selected patients with clinical symptoms of CNS injury. Magnetic resonance imaging (MRI) findings for all patients were contoured on original planning scans (treatment change areas [TCA]). Dose and LET distributions were calculated for the treated plans using Monte Carlo system. RBE values were estimated based on LET-based published models. At a median follow-up of 4.2 years, the 5-year cumulative incidence of CNS injury was 3.6% for any grade and 2.7% for grade 3+. Three of 4 symptomatic patients were treated with a whole posterior fossa boost. Eight of 10 defined TCAs had higher LET values than the target but statistically nonsignificant differences in RBE values (P=.12). Central nervous system and brainstem injury incidence for PRT in this series is similar to that reported for photon radiation therapy. The risk of CNS injury was higher for whole posterior fossa boost than for involved field. Although no clear correlation with RBE values was found, numbers were small and additional investigation is warranted to better determine the relationship between injury and LET. Published by Elsevier Inc.

The Responsiveness of Patients' Quality of Life to Dental Caries Treatment-A Prospective Study.

Science.gov (United States)

Yeh, Ding-Yu; Kuo, Hsiao-Ching; Yang, Yi-Hsin; Ho, Pei-Shan

2016-01-01

The objective of this study was to determine the responsiveness of oral health-related quality of life (OHRQoL) (oral health impact profile [OHIP] and oral impact on daily performance [OIDP]) and health-related quality of life (HRQoL) (World Health Organization quality of life scale, brief [WHOQOL-BREF]) in dental caries restoration treatment. The study also aimed to assess the influence of treatment on the responsiveness of patients' quality of life (QoL). A total of 126 patients (aged 16-40 years) received dental caries restoration treatment with a 2-week follow-up and pre- and posttreatment interviews by questionnaire. Patients were assessed for their perceptions of OHRQoL and HRQoL by using the OHIP, OIDP, and WHOQOL-BREF measures. The responsiveness of all outcome measurements was assessed by effect size (ES). Stepwise multiple regression analysis was used to examine the association with the responsiveness of all outcome measurements. Significant differences were found between OIDP (ES = 0.39), OHIP (ES = 0.54), and WHOQOL-BREF (ES = 0.13) with regard to pretreatment and posttreatment (p-values: caries status at baseline were significantly associated with responsiveness by all measurements. This study suggests that dental caries treatment moderately improves OHRQoL, but is less related to HRQoL. Furthermore, the number of dental caries and restoration are important factors affecting the improvement of patients' perceived OHRQoL.

CADrx for GBM Brain Tumors: Predicting Treatment Response from Changes in Diffusion-Weighted MRI

Directory of Open Access Journals (Sweden)

Matthew S. Brown

2009-11-01

Full Text Available The goal of this study was to develop a computer-aided therapeutic response (CADrx system for early prediction of drug treatment response for glioblastoma multiforme (GBM brain tumors with diffusion weighted (DW MR images. In conventional Macdonald assessment, tumor response is assessed nine weeks or more post-treatment. However, we will investigate the ability of DW-MRI to assess response earlier, at five weeks post treatment. The apparent diffusion coefficient (ADC map, calculated from DW images, has been shown to reveal changes in the tumor’s microenvironment preceding morphologic tumor changes. ADC values in treated brain tumors could theoretically both increase due to the cell kill (and thus reduced cell density and decrease due to inhibition of edema. In this study, we investigated the effectiveness of features that quantify changes from pre- and post-treatment tumor ADC histograms to detect treatment response. There are three parts to this study: first, tumor regions were segmented on T1w contrast enhanced images by Otsu’s thresholding method, and mapped from T1w images onto ADC images by a 3D region of interest (ROI mapping tool using DICOM header information; second, ADC histograms of the tumor region were extracted from both pre- and five weeks post-treatment scans, and fitted by a two-component Gaussian mixture model (GMM. The GMM features as well as standard histogram-based features were extracted. Finally, supervised machine learning techniques were applied for classification of responders or non-responders. The approach was evaluated with a dataset of 85 patients with GBM under chemotherapy, in which 39 responded and 46 did not, based on tumor volume reduction. We compared adaBoost, random forest and support vector machine classification algorithms, using ten-fold cross validation, resulting in the best accuracy of 69.41% and the corresponding area under the curve (Az of 0.70.

Stochastic responses of tumor–immune system with periodic treatment

International Nuclear Information System (INIS)

Li Dong-Xi; Li Ying

2017-01-01

We investigate the stochastic responses of a tumor–immune system competition model with environmental noise and periodic treatment. Firstly, a mathematical model describing the interaction between tumor cells and immune system under external fluctuations and periodic treatment is established based on the stochastic differential equation. Then, sufficient conditions for extinction and persistence of the tumor cells are derived by constructing Lyapunov functions and Ito’s formula. Finally, numerical simulations are introduced to illustrate and verify the results. The results of this work provide the theoretical basis for designing more effective and precise therapeutic strategies to eliminate cancer cells, especially for combining the immunotherapy and the traditional tools. (paper)

Implication of ultrasound bladder parameters on treatment response in patients with benign prostatic hyperplasia under medical management

Directory of Open Access Journals (Sweden)

Rajeev Thekumpadam Puthenveetil

2015-10-01

Conclusion: Ultrasound bladder parameters are useful tools for measuring the treatment response in BPH patients. Our study shows that RI and DWT significantly correlate with the treatment response in BPH patients. More importantly, pretreatment values of increased IPP and PUA determines the non-improvement of symptoms in BPH patients. Our study suggests the importance of transabdominal ultrasonography (KUB–P with Doppler for evaluating treatment responses to medical management.

A Randomized Clinical Trial Comparison between Pivotal Response Treatment (PRT) and Structured Applied Behavior Analysis (ABA) Intervention for Children with Autism

Science.gov (United States)

Mohammadzaheri, Fereshteh; Koegel, Lynn Kern; Rezaee, Mohammad; Rafiee, Seyed Majid

2014-01-01

Accumulating studies are documenting specific motivational variables that, when combined into a naturalistic teaching paradigm, can positively influence the effectiveness of interventions for children with autism spectrum disorder (ASD). The purpose of this study was to compare two applied behavior analysis (ABA) intervention procedures, a…

The effects of chronic resveratrol treatment on vascular responsiveness of streptozotocin-induced diabetic rats.

Science.gov (United States)

Silan, Coskun

2008-05-01

Deficiency in the vasorelaxant capacity is a result of an oxidative stress in diabetic animals and seems to be an etiological factor of vascular complications of diabetes. The present study was designed to examine whether resveratrol (RSV), a polyphenolic compound which is naturally present in grape and red wine, has a protective effect on diabetic aorta. Resveratrol (5 mg/kg/d, i.p.) was administered for 42 d to streptozotocin (STZ) (60 mg/kg) induced diabetic rats. Loss of weight, hyperglycemia, and elevated levels of plasma malondialdehyde (MDA) were observed in diabetic rats. Resveratrol treatment was significantly effective for these metabolic and biochemical abnormalities. The contractile responses of the aorta were recorded. Compared with control subjects, the aorta showed significantly enhanced contractile responses to noradrenaline (NA), but not to potassium chloride (KCl), in diabetic rats. Treatment of diabetic rats with resveratrol significantly reversed the increases in responsiveness and sensitivity of aorta to noradrenaline. In diabetic aorta, the relaxation response to acetylcholine (Ach) was found to be significantly decreased compared with control subjects, and resveratrol treatment reversed this; no such change was observed in the relaxation response to sodium nitroprusside (SNP). These results indicated that resveratrol significantly improved not only glucose metabolism and oxidative injury but also impaired vascular responses in streptozotocin induced diabetic rats.

Osteopontin splice variants are differential predictors of breast cancer treatment responses

OpenAIRE

Zduniak, Krzysztof; Agrawal, Anil; Agrawal, Siddarth; Hossain, Md Monir; Ziolkowski, Piotr; Weber, Georg F.

2016-01-01

Background Osteopontin is a marker for breast cancer progression, which in previous studies has also been associated with resistance to certain anti-cancer therapies. It is not known which splice variants may mediate treatment resistance. Methods Here we analyze the association of osteopontin variant expression before treatment, differentiated according to immunohistochemistry with antibodies to exon 4 and to the osteopontin-c splice junction respectively, with the ensuing therapy responses i...

Physical Readiness Training: A Meta-Analysis

National Research Council Canada - National Science Library

Vickers, Jr, Ross R

2007-01-01

.... This meta-analysis of available PRT studies (k = 3) indicated that (a) Fitness gains in the PRT program were equal to the gains in traditional fitness programs, and (b) the injury rate (i.e., hazard ratio...

Diffusion-weighted magnetic resonance imaging: biomarker for treatment response in oncology

Directory of Open Access Journals (Sweden)

Maria Luiza Testa

2013-06-01

Full Text Available The authors report a case where a quantitative assessment of the apparent diffusion coefficient (ADC of liver metastasis in a patient undergoing chemotherapy has shown to be an effective early marker for predicting therapeutic response, anticipating changes in tumor size. A lesion with lower initial ADC value and early increase in such value in the course of the treatment tends to present a better therapeutic response.

Adolescents with Internet Gaming Disorder (IGD): profiles and treatment response.

Science.gov (United States)

Martín-Fernández, María; Matalí, Josep Lluís; García-Sánchez, Sara; Pardo, Marta; Lleras, María; Castellano-Tejedor, Carmina

2016-10-07

Demand for treatment for problems related to the use of video games have increased significantly in adolescents. Most cases have a comorbid mental disorder that jeopardises both pathologies. The aim of this study is to describe profiles of adolescents with Internet Gaming Disorder (IGD) according to comorbidity and analyze treatment response at 3 and 6 months. A sample of 86 patients which consulted in the Addictive Behavior Unit of a hospital was assessed with diagnostic criteria for IGD, the interview K-SADS-PL for mental disorders and the Clinical Global Impression (CGI) to treatment progress. Of the initial sample, 68,6% (n = 59) met diagnostic criteria for IGD. Of these, the 45,76% matched an internalizing profile, presenting comorbidity with Mood Disorders (44,4%), Anxiety Disorders (44,4%) and Personality Disorders (11,1%). The externalizing profile would comprise 52,54% of the sample presenting Disruptive Behavior Disorder (48,4%=, ADHD (29%) and Disruptive Behavior Disorders not otherwise specified (22,6%). Unlike externalizing, the internalizing patients had a family history of psychiatric problems (63%), difficulties in social relationships (77,8%) and seemed to use video games preferably to escape discomfort (66,7%). After 3 months the externalizing profile showed improvements. Comorbid disorders allow the discrimination of two IGD profiles in adolescents and these could influence treatment response. Therefore, it is important to assess comorbidities to design a more accurate intervention focused on the specificities of each profile.

UNDERSTANDING THE NEUROINFLAMMATORY RESPONSE FOLLOWING CONCUSSION TO DEVELOP TREATMENT STRATEGIES

Directory of Open Access Journals (Sweden)

Zachary Robert Patterson

2012-12-01

Full Text Available Mild traumatic brain injuries (mTBI have been associated with long-term cognitive deficits relating to trauma-induced neurodegeneration. These long-term deficits include impaired memory and attention, changes in executive function, emotional instability and sensorimotor deficits. Furthermore, individuals with concussions show a high co-morbidity with a host of psychiatric illnesses (e.g. depression, anxiety, addiction and dementia. The neurological damage seen in mTBI patients is the result of the direct impact and mechanical injury, followed by a delayed neuroimmune response that can last hours, days and even months after the injury. As part of the neuroimmune response, a cascade of pro- and anti-inflammatory cytokines are released and can be detected at the site of injury as well as subcortical, and often contralateral, regions. It has been suggested that the delayed neuroinflammatory response to concussions is more damaging then the initial impact itself. However, evidence exists for favourable consequences of cytokine production following traumatic brain injuries as well. In some cases, treatments that reduce the inflammatory response will also hinder the brain's intrinsic repair mechanisms. At present, there is no evidence-based pharmacological treatment for concussions in humans. The ability to treat concussions with drug therapy requires an in-depth understanding of the pathophysiological and neuroinflammatory changes that accompany concussive injuries. The use of neurotrophic factors (e.g. nerve growth factor and anti-inflammatory agents as an adjunct for the management of post-concussion symptomology will be explored in this review.

Neurobehavioral response to increased treatment dosage in chronic, severe aphasia

Directory of Open Access Journals (Sweden)

Jennifer L Mozeiko

2014-04-01

•\tIncreased activation in S2’s bilateral inferior frontal gyrus following the second treatment session indicates that a second Treatment Period can influence continued neuroplastic change in severe, chronic aphasia. •\tS1 appears to show the most activation following Treatment Period I. It is possible that his greater lesion volume or site did not allow for benefit from a second dose to the same degree as S2. •\tActivation changes (or lack thereof in both cases corresponded with performance on the naming task in the scanner, reflecting the effect of treatment. •\tFor S2, neuroimaging supported the behavioral results which favor a second dose of ILAT. For S1, behavioral results, particularly in his consistent increases on the BNT, are not supported by either the behavioral results in the scanner or the BOLD response.

Intensity-modulated proton therapy, volumetric-modulated arc therapy, and 3D conformal radiotherapy in anaplastic astrocytoma and glioblastoma. A dosimetric comparison

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Adeberg, S.; Debus, J. [Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg (Germany); Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg (Germany); University Hospital Heidelberg, Department of Radiation Oncology, Heidelberg (Germany); German Cancer Research Center (DKFZ), Clinical Cooperation Unit Radiation Oncology, Heidelberg (Germany); Harrabi, S.B.; Bougatf, N.; Rieber, J.; Koerber, S.A.; Herfarth, K.; Rieken, S. [Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg (Germany); Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg (Germany); University Hospital Heidelberg, Department of Radiation Oncology, Heidelberg (Germany); Bernhardt, D.; Syed, M.; Sprave, T.; Mohr, A. [Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg (Germany); University Hospital Heidelberg, Department of Radiation Oncology, Heidelberg (Germany); Abdollahi, A. [University Hospital Heidelberg, Department of Radiation Oncology, Heidelberg (Germany); Haberer, T. [Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg (Germany); Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg (Germany); Combs, S.E. [Technische Universitaet Muenchen, Department of Radiation Oncology, Muenchen (Germany); Helmholtz Zentrum Muenchen, Institut fuer Innovative Radiotherapie (iRT), Department of Radiation Sciences (DRS), Neuherberg (Germany)

2016-11-15

The prognosis for high-grade glioma (HGG) patients is poor; thus, treatment-related side effects need to be minimized to conserve quality of life and functionality. Advanced techniques such as proton radiation therapy (PRT) and volumetric-modulated arc therapy (VMAT) may potentially further reduce the frequency and severity of radiogenic impairment. We retrospectively assessed 12 HGG patients who had undergone postoperative intensity-modulated proton therapy (IMPT). VMAT and 3D conformal radiotherapy (3D-CRT) plans were generated and optimized for comparison after contouring crucial neuronal structures important for neurogenesis and neurocognitive function. Integral dose (ID), homogeneity index (HI), and inhomogeneity coefficient (IC) were calculated from dose statistics. Toxicity data were evaluated. Target volume coverage was comparable for all three modalities. Compared to 3D-CRT and VMAT, PRT showed statistically significant reductions (p < 0.05) in mean dose to whole brain (-20.2 %, -22.7 %); supratentorial (-14.2 %, -20,8 %) and infratentorial (-91.0 %, -77.0 %) regions; brainstem (-67.6 %, -28.1 %); pituitary gland (-52.9 %, -52.5 %); contralateral hippocampus (-98.9 %, -98.7 %); and contralateral subventricular zone (-62.7 %, -66.7 %, respectively). Fatigue (91.7 %), radiation dermatitis (75.0 %), focal alopecia (100.0 %), nausea (41.7 %), cephalgia (58.3 %), and transient cerebral edema (16.7 %) were the most common acute toxicities. Essential dose reduction while maintaining equal target volume coverage was observed using PRT, particularly in contralaterally located critical neuronal structures, areas of neurogenesis, and structures of neurocognitive functions. These findings were supported by preliminary clinical results confirming the safety and feasibility of PRT in HGG. (orig.) [German] Die Prognose bei ''High-grade''-Gliomen (HGG) ist infaust. Gerade bei diesen Patienten sollten therapieassoziierte Nebenwirkungen minimiert werden

Personality, Stressful Life Events, and Treatment Response in Major Depression

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Bulmash, Eric; Harkness, Kate L.; Stewart, Jeremy G.; Bagby, R. Michael

2009-01-01

The current study examined whether the personality traits of self-criticism or dependency moderated the effect of stressful life events on treatment response. Depressed outpatients (N = 113) were randomized to 16 weeks of cognitive-behavioral therapy, interpersonal psychotherapy, or antidepressant medication (ADM). Stressful life events were…

Predicting Response of ADHD Symptoms to Methylphenidate Treatment Based on Comorbid Anxiety

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Blouin, Brittany; Maddeaux, Cindy; Stanley Firestone, Jill; van Stralen, Judy

2010-01-01

Objective: In this small pilot study, the association of comorbid anxiety with the treatment of ADHD is studied. Methods: Eighteen volunteers from a pediatric clinic are tested for ADHD and anxiety and assessed for behavioral and cognitive ADHD symptomology. Response to methylphenidate as treatment for ADHD symptoms is measured 2 to 3 weeks, and…

Impact of response shift on the assessment of treatment effects using the Oral Health Impact Profile.

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Reissmann, Daniel R; Remmler, Antje; John, Mike T; Schierz, Oliver; Hirsch, Christian

2012-12-01

The assessment of changes in oral health-related quality of life (OHRQoL) is challenging because individuals' concepts and internal standards of OHRQoL may change over time. The aim of this study was to detect response shifts in OHRQoL assessments made using the Oral Health Impact Profile (OHIP). Oral health-related quality of life was assessed in a consecutive sample of 126 patients seeking prosthodontic care. Patients were asked to rate their OHRQoL before treatment started and 1 month after treatment was finished, using the German 49-item version of the OHIP. When rating their OHRQoL after treatment, patients were also asked to rate their pre-treatment OHRQoL without having access to their baseline data. The response shift was calculated as the difference in OHIP summary scores between the initial assessment and the retrospective baseline assessment. The OHIP mean scores decreased from 31.8 at the initial baseline assessment to 24.4 after treatment. The retrospective baseline assessment resulted in an OHIP mean score of 38.1, corresponding to a response shift of 6.3 OHIP points. The effect size (Cohen's d = 0.21) of the response shift was considered small. The response shift phenomenon and its magnitude have important implications for dental practice, where patients and dentists often assess perceived treatment effects retrospectively. © 2012 Eur J Oral Sci.

Verbal memory functioning moderates psychotherapy treatment response for PTSD-Related nightmares.

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Scott, J Cobb; Harb, Gerlinde; Brownlow, Janeese A; Greene, Jennifer; Gur, Ruben C; Ross, Richard J

2017-04-01

Posttraumatic stress disorder (PTSD) is associated with cognitive deficits in attention, executive control, and memory, although few studies have investigated the relevance of cognitive difficulties for treatment outcomes. We examined whether cognitive functioning and history of traumatic brain injury (TBI) were associated with response to cognitive-behavioral therapy (CBT) for PTSD-related sleep problems. In a randomized controlled trial of Imagery Rehearsal (IR) added to components of CBT for Insomnia (IR + cCBT-I) compared to cCBT-I alone for PTSD-related recurrent nightmares, 94 U.S. veterans completed a battery of cognitive tests. TBI was assessed via structured clinical interview. Mixed-effects models examined main effects of cognitive functioning and interactions with time on primary sleep and nightmare outcomes. Significant verbal immediate memory by time interactions were found for nightmare distress, nightmare frequency, and sleep quality, even after controlling for overall cognitive performance and depression. TBI exhibited main effects on outcomes but no interactions with time. Findings indicated that individuals with lower verbal memory performance were less likely to respond to treatment across two sleep interventions. Veterans with TBI displayed greater symptoms but no altered trajectories of treatment response. Together with prior literature, findings suggest that verbal memory functioning may be important to consider in PTSD treatment implementation. Published by Elsevier Ltd.

The FasX Small Regulatory RNA Negatively Regulates the Expression of Two Fibronectin-Binding Proteins in Group A Streptococcus.

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Danger, Jessica L; Makthal, Nishanth; Kumaraswami, Muthiah; Sumby, Paul

2015-12-01

The group A Streptococcus (GAS; Streptococcus pyogenes) causes more than 700 million human infections each year. The success of this pathogen can be traced in part to the extensive arsenal of virulence factors that are available for expression in temporally and spatially specific manners. To modify the expression of these virulence factors, GAS use both protein- and RNA-based regulators, with the best-characterized RNA-based regulator being the small regulatory RNA (sRNA) FasX. FasX is a 205-nucleotide sRNA that contributes to GAS virulence by enhancing the expression of the thrombolytic secreted virulence factor streptokinase and by repressing the expression of the collagen-binding cell surface pili. Here, we have expanded the FasX regulon, showing that this sRNA also negatively regulates the expression of the adhesion- and internalization-promoting, fibronectin-binding proteins PrtF1 and PrtF2. FasX posttranscriptionally regulates the expression of PrtF1/2 through a mechanism that involves base pairing to the prtF1 and prtF2 mRNAs within their 5' untranslated regions, overlapping the mRNA ribosome-binding sites. Thus, duplex formation between FasX and the prtF1 and prtF2 mRNAs blocks ribosome access, leading to an inhibition of mRNA translation. Given that FasX positively regulates the expression of the spreading factor streptokinase and negatively regulates the expression of the collagen-binding pili and of the fibronectin-binding PrtF1/2, our data are consistent with FasX functioning as a molecular switch that governs the transition of GAS between the colonization and dissemination stages of infection. More than half a million deaths each year are a consequence of infections caused by GAS. Insights into how this pathogen regulates the production of proteins during infection may facilitate the development of novel therapeutic or preventative regimens aimed at inhibiting this activity. Here, we have expanded insight into the regulatory activity of the GAS small

Concurrent transcranial direct current stimulation and progressive resistance training in Parkinson's disease: study protocol for a randomised controlled trial.

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Hendy, Ashlee M; Tillman, Alex; Rantalainen, Timo; Muthalib, Makii; Johnson, Liam; Kidgell, Dawson J; Wundersitz, Daniel; Enticott, Peter G; Teo, Wei-Peng

2016-07-19

Parkinson's disease (PD) results from a loss of dopamine in the brain, leading to movement dysfunctions such as bradykinesia, postural instability, resting tremor and muscle rigidity. Furthermore, dopamine deficiency in PD has been shown to result in maladaptive plasticity of the primary motor cortex (M1). Progressive resistance training (PRT) is a popular intervention in PD that improves muscular strength and results in clinically significant improvements on the Unified Parkinson's Disease Rating Scale (UPDRS). In separate studies, the application of anodal transcranial direct current stimulation (a-tDCS) to the M1 has been shown to improve motor function in PD; however, the combined use of tDCS and PRT has not been investigated. We propose a 6-week, double-blind randomised controlled trial combining M1 tDCS and PRT of the lower body in participants (n = 42) with moderate PD (Hoehn and Yahr scale score 2-4). Supervised lower body PRT combined with functional balance tasks will be performed three times per week with concurrent a-tDCS delivered at 2 mA for 20 minutes (a-tDCS group) or with sham tDCS (sham group). Control participants will receive standard care (control group). Outcome measures will include functional strength, gait speed and variability, balance, neurophysiological function at rest and during movement execution, and the UPDRS motor subscale, measured at baseline, 3 weeks (during), 6 weeks (post), and 9 weeks (retention). Ethical approval has been granted by the Deakin University Human Research Ethics Committee (project number 2015-014), and the trial has been registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615001241527). This will be the first randomised controlled trial to combine PRT and a-tDCS targeting balance and gait in people with PD. The study will elucidate the functional, clinical and neurophysiological outcomes of combined PRT and a-tDCS. It is hypothesised that combined PRT and a-tDCS will significantly

Favorable Responsiveness of the Hand10 Questionnaire to Assess Treatment Outcomes for Lateral Epicondylitis.

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Nishizuka, Takanobu; Iwatsuki, Katsuyuki; Kurimoto, Shigeru; Yamamoto, Michiro; Onishi, Tetsuro; Hirata, Hitoshi

2018-06-01

The aim of our study was to compare the responsiveness of the Hand10 questionnaire and the Pain visual analogue scale (VAS) for the assessment of lateral epicondylitis. The standardized response mean and effect size were used as indicators of responsiveness, measured at baseline and after 6 months of treatment. Among the 54 patients enrolled, 28 were treated using a forearm band, compress and stretching, with the other 26 patients treated using compress and stretching. The standardized response mean and the effect size were 1.18 and 1.38, respectively, of the Hand10 and 1.39 and 1.75, respectively, for the Pain VAS. The responsiveness of both tests was considered to be large, based on Cohen's classification of effect size, supporting the use of the Hand10 questionnaire to assess treatment outcomes for lateral epicondylitis.

Comparison of the heat treatment response of wrought and SSM-HPDC alloy 6082

CSIR Research Space (South Africa)

Möller, H

2011-06-01

Full Text Available The natural and artificial aging responses of wrought and SSM-HPDC alloy 6082 are compared. It is shown that the heat treatment response of this Al-Mg-Si alloy is not influenced by differences in microstructures produced by different processing...

Osteoarthritis of the thumb carpometacarpal joint: Correlation of ultrasound appearances to disability and treatment response

International Nuclear Information System (INIS)

Mallinson, P.I.; Tun, J.K.; Farnell, R.D.; Campbell, D.A.; Robinson, P.

2013-01-01

Aim: To evaluate grading of thumb carpometacarpal joint (CMCJ) osteoarthritis (OA) using ultrasound, correlating findings with disability and treatment response. Materials and methods: Patients with symptomatic thumb OA attending for ultrasound-guided CMCJ steroid injection and a group of asymptomatic controls were recruited prospectively. Thumb CMCJ ultrasound was graded (osteophytes, joint-space narrowing, capsule size, and measured capsule size), and a Disabilities of the Arm Shoulder and Hand (DASH) questionnaire was completed for each patient. Symptomatic patients then underwent injection with DASH repeated 6 weeks post-treatment. Ultrasound features were correlated with the initial DASH disability score and response as defined by change in DASH 6 weeks after treatment. Results: Thirty-one patients with symptomatic OA and 37 asymptomatic controls were recruited. With the exception of osteophytes (p = 0.017), no statistically significant correlation was demonstrated between severity of ultrasound features and patient disability. However, all features demonstrated statistically significant higher grades in the symptomatic group compared to controls. Ultrasound grading did not have statistical correlation with treatment response. Conclusion: No correlation was found between the majority of ultrasound features and the clinical severity of OA or likely response to treatment. However, these features are significantly more common in the symptomatic population

Moving toward Personalized Medicine in the Methadone Maintenance Treatment Program: A Pilot Study on the Evaluation of Treatment Responses in Taiwan

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Hsin-Ya Lee

2013-01-01

Full Text Available This pilot study simultaneously evaluated the effects of various factors, including genetic variations of CYP2B6, CYP2C19, and ABCB1, demographic characteristics, disease states, methadone-drug interactions (MDIs, and poly-substance use, on the treatment responses among non-HIV patients in the methadone maintenance treatment program (MMTP in Taiwan. A total of 178 patients were recruited from two major hospitals that provided MMTP services in southern Taiwan, and information regarding concomitant medications and diseases was acquired from the National Health Insurance (NHI program. The results demonstrated that the methadone maintenance dose, CYP2B6 785G allele, and ABCB1 2677T allele have positive effects on the methadone plasma concentration. In contrast, patients with HCV coinfection, alcohol problems, and psychiatric diseases may have a negative response to treatment. Thus, a comprehensive evaluation of treatment responses in the MMTP should include not only genetic polymorphisms in methadone metabolism and transporter proteins, but also concomitant diseases, MDIs, and poly-substance use. The results also suggest that personalized medicine may be indispensable for a better outcome of the MMTP.

Laser light and magnetic field stimulation effect on biochemical, enzymes activities and chlorophyll contents in soybean seeds and seedlings during early growth stages.

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Asghar, Tehseen; Jamil, Yasir; Iqbal, Munawar; Zia-Ul-Haq; Abbas, Mazhar

2016-12-01

Laser and magnetic field bio-stimulation attracted the keen interest of scientific community in view of their potential to enhance seed germination, seedling growth, physiological, biochemical and yield attributes of plants, cereal crops and vegetables. Present study was conducted to appraise the laser and magnetic field pre-sowing seed treatment effects on soybean sugar, protein, nitrogen, hydrogen peroxide (H 2 O 2 ) ascorbic acid (AsA), proline, phenolic and malondialdehyde (MDA) along with chlorophyll contents (Chl "a" "b" and total chlorophyll contents). Specific activities of enzymes such as protease (PRT), amylase (AMY), catalyst (CAT), superoxide dismutase (SOD) and peroxides (POD) were also assayed. The specific activity of enzymes (during germination and early growth), biochemical and chlorophyll contents were enhanced significantly under the effect of both laser and magnetic pre-sowing treatments. Magnetic field treatment effect was slightly higher than laser treatment except PRT, AMY and ascorbic acid contents. However, both treatments (laser and magnetic field) effects were significantly higher versus control (un-treated seeds). Results revealed that laser and magnetic field pre-sowing seed treatments have potential to enhance soybean biological moieties, chlorophyll contents and metabolically important enzymes (degrade stored food and scavenge reactive oxygen species). Future study should be focused on growth characteristics at later stages and yield attributes. Copyright © 2016 Elsevier B.V. All rights reserved.

Plasma homovanillic acid levels in first-episode schizophrenia. Psychopathology and treatment response.

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Koreen, A R; Lieberman, J; Alvir, J; Mayerhoff, D; Loebel, A; Chakos, M; Amin, F; Cooper, T

1994-02-01

To examine plasma homovanillic acid (pHVA) levels in first-episode schizophrenia, to compare pHVA levels in patients and controls, and to assess the association of pHVA levels with psychopathology and treatment response. Forty-one patients entered the study, and pHVA levels were measured at baseline and on a weekly basis for up to 6 weeks of open standardized neuroleptic treatment. Psychopathology was evaluated with the Schedule for Affective Disorders and Schizophrenia, the Scale for Assessment of Negative Symptoms, and the Clinical Global Impressions scale. Ten healthy controls were used for comparison of baseline pHVA levels. No differences were observed between patients and controls. Baseline pHVA level was not associated with psychopathology but was associated with time to reach remission. Baseline pHVA levels and week-1 pHVA levels were higher in responders than nonresponders. Regardless of responsiveness, female participants had higher pHVA levels than male participants throughout the study. The pattern of pHVA levels with treatment was similar in all patients with a short-term rise initially and then a decrease toward baseline values. These findings suggest that pHVA levels have prognostic significance for response and time to reach remission. Qualitative and quantitative differences between first-episode patients' pHVA levels and studies using a long-term, neuroleptic-exposed population suggest that changes occur with neuroleptic treatment or the progression of the illness.

Favorable Growth Hormone Treatment Response in a Young Boy with Achondroplasia.

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Krstevska-Konstantinova, Marina; Stamatova, Ana; Gucev, Zoran

2016-04-01

Achondroplasia is a skeletal dysplasia, the most common cause of rhizomelic dwarfism. This is a ten year old boy who was first diagnosed prenatally. He had a mutation c1138G>A in the gene FGFR3 in a heterozygotic constellation. His IGF1 and IGFBP3 levels were normal. Two stimulation tests for growth hormone were performed with values within the reference range. His psychomotor development was adequate for his age except for speech difficulty. He started with recombinant hGH (r-hGH) at the age of 3.4 years in a dose of 0.06 mg/kg. His mean Height SDS (HtSDS) was -2.2. The growth increased to 10 cm/year in the first year of therapy (HtSDS -1.1). It decreased during the second year to 4 cm (HtSDS -1.7) and again increased during the third year to 8 cm/year (HtSDS-1.3). In the next years the growth was constant (6.5, 2.3, 3.5 cm / year). He is still growing in the 3(rd) percentile of the growth curve (HtSDS - 1.2) under GH treatment. The body disproportion remained the same. The growth response on GH treatment was satisfactory in the first 4 years of treatment, and the boy still continued to grow. The young age at the start of treatment was also of importance. Our other patients with achondroplasia who started treatment older had a poor response to growth hormone.

Lactocepin secreted by Lactobacillus exerts anti-inflammatory effects by selectively degrading proinflammatory chemokines.

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von Schillde, Marie-Anne; Hörmannsperger, Gabriele; Weiher, Monika; Alpert, Carl-Alfred; Hahne, Hannes; Bäuerl, Christine; van Huynegem, Karolien; Steidler, Lothar; Hrncir, Tomas; Pérez-Martínez, Gaspar; Kuster, Bernhard; Haller, Dirk

2012-04-19

The intestinal microbiota has been linked to inflammatory bowel diseases (IBD), and oral treatment with specific bacteria can ameliorate IBD. One bacterial mixture, VSL#3, containing Lactobacillus, Bifidobacterium, and Streptococcus, was clinically shown to reduce inflammation in IBD patients and normalize intestinal levels of IP-10, a lymphocyte-recruiting chemokine, in a murine colitis model. We identified Lactobacillus paracasei prtP-encoded lactocepin as a protease that selectively degrades secreted, cell-associated, and tissue-distributed IP-10, resulting in significantly reduced lymphocyte recruitment after intraperitoneal injection in an ileitis model. A human Lactobacillus casei isolate was also found to encode lactocepin and degrade IP-10. L. casei feeding studies in a murine colitis model (T cell transferred Rag2(-/-) mice) revealed that a prtP-disruption mutant was significantly less potent in reducing IP-10 levels, T cell infiltration and inflammation in cecal tissue compared to the isogenic wild-type strain. Thus, lactocepin-based therapies may be effective treatments for chemokine-mediated diseases like IBD. Copyright © 2012 Elsevier Inc. All rights reserved.

Intravoxel incoherent motion (IVIM histogram biomarkers for prediction of neoadjuvant treatment response in breast cancer patients

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Gene Y. Cho

Full Text Available Objective: To examine the prognostic capabilities of intravoxel incoherent motion (IVIM metrics and their ability to predict response to neoadjuvant treatment (NAT. Additionally, to observe changes in IVIM metrics between pre- and post-treatment MRI. Methods: This IRB-approved, HIPAA-compliant retrospective study observed 31 breast cancer patients (32 lesions. Patients underwent standard bilateral breast MRI along with diffusion-weighted imaging before and after NAT. Six patients underwent an additional IVIM-MRI scan 12–14 weeks after initial scan and 2 cycles of treatment. In addition to apparent diffusion coefficients (ADC from monoexponential decay, IVIM mean values (tissue diffusivity Dt, perfusion fraction fp, and pseudodiffusivity Dp and histogram metrics were derived using a biexponential model. An additional filter identified voxels of highly vascular tumor tissue (VTT, excluding necrotic or normal tissue. Clinical data include histology of biopsy and clinical response to treatment through RECIST assessment. Comparisons of treatment response were made using Wilcoxon rank-sum tests. Results: Average, kurtosis, and skewness of pseudodiffusion Dp significantly differentiated RECIST responders from nonresponders. ADC and Dt values generally increased (∼70% and VTT% values generally decreased (∼20% post-treatment. Conclusion: Dp metrics showed prognostic capabilities; slow and heterogeneous pseudodiffusion offer poor prognosis. Baseline ADC/Dt parameters were not significant predictors of response. This work suggests that IVIM mean values and heterogeneity metrics may have prognostic value in the setting of breast cancer NAT. Keywords: Breast cancer, Diffusion weighted MRI, Intravoxel incoherent motion, Neoadjuvant treatment, Response evaluation criteria in solid tumors

Positron emission tomography/computed tomography and biomarkers for early treatment response evaluation in metastatic colon cancer

DEFF Research Database (Denmark)

Engelmann, Bodil E.; Loft, Annika; Kjær, Andreas

2014-01-01

BACKGROUND: Treatment options for metastatic colon cancer (mCC) are widening. We prospectively evaluated serial 2-deoxy-2-[18F]fluoro-d-glucose positron-emission tomography/computed tomography (PET/CT) and measurements of tissue inhibitor of metalloproteinases-1 (TIMP-1), carcinoembryonic antigen...... evaluated by PET/CT before treatment, after one and four treatment series. Morphological and metabolic response was independently assessed according to Response Evaluation Criteria in Solid Tumors and European Organization for Research and Treatment of Cancer PET criteria. Plasma TIMP-1, plasma u...

Comparison of quantitative methods on FDG PET/CT for treatment response evaluation of metastatic colorectal cancer

Energy Technology Data Exchange (ETDEWEB)

Bang, Ji In; Paeng, Jin Chul; Park, So Hyun [Dept. of Nuclear Medicine, Seoul National University Hospital, Seoul (Korea, Republic of); and others

2017-06-15

FDG PET is effective in treatment response evaluation of cancer. However, there is no standard method for quantitative evaluation of FDG PET, particularly regarding cytostatic drugs. We compared various FDG PET quantitative methods in terms of response determination. A total of 39 refractory metastatic colorectal cancer patients who received a multikinase inhibitor treatment were included. Baseline and posttreatment FDG PET/CT scans were performed before and two cycles after treatment. Standardized uptake value (SUV) and total lesion glycolysis (TLG) values using various margin thresholds (30–70 % of maximum SUV with increment 10 %, twice mean SUV of blood pool, SUV 3.0, and SUV 4.0) were measured, with measurement target of the hottest lesion or a maximum of five hottest lesions. Treatment response by the PERCIST criteria was also determined. Predictive values of the PET indexes were evaluated in terms of the treatment response determined by the RECIST 1.1 criteria. The agreement rate was 38 % between response determined by the PERCIST and the RECIST criteria (κ = 0.381). When patients were classified into disease control group (PR, SD) and non-control group (PD) by the RECIST criteria, percent changes of TLG with various margin thresholds (particularly, 30–50 % of maximum SUV) exhibited significant differences between the two groups, and high diagnostic power for the response by the RECIST criteria. TLG-based criteria, which used a margin threshold of 50 % of maximum SUV, exhibited a high agreement with the RECIST criteria compared with the PERCIST criteria (κ = 0.606). In metastatic colorectal cancer, FDG PET/CT could be effective for treatment response evaluation by using TLG measured by margin thresholds of 30–50 % of maximum SUV. Further studies are warranted regarding the optimal cutoff values for this method.

Concordance between patient and clinician assessment of dry eye severity and treatment response in Taiwan.

Science.gov (United States)

Yeh, Po-Ting; Chien, Hsu-Chih; Ng, Kwong; Tseng, Sung-Huei; Chen, Wei-Li; Hou, Yu-Chih; Wang, I-Jong; Chu, Hsiao-Sung; Kao Yang, Yea-Huei; Hu, Fung-Rong

2015-05-01

Accurate diagnosis and early recognition of dry eye symptoms are important in the management of dry eye disease (DED). This study aimed to evaluate concordance between patient and clinician assessment of DED severity and treatment response. This cross-sectional study was conducted in 2 ophthalmology clinics in Taiwan. Clinicians assessed severity based on the Dry Eye Workshop severity grading (levels 1-4; where 4 = most severe), whereas patients completed the Ocular Surface Disease Index questionnaire. To evaluate the treatment response, patients completed the Subject Global Assessment scale, and clinicians independently assessed patients using the Clinical Global Impression scale. A total of 466 patients were included. Clinicians graded 88.3% of patients as level 1/2, 9.0% as level 3, and 2.7% as level 4 Dry Eye Workshop severity, whereas 44.9% of patients reported normal/mild symptoms, 17.1% with moderate severity, and 38.0% with severe DED. Patients were primarily treated with artificial tears. The clinician assessed 10.3% of patients as unchanged on disease severity after treatment and 88.0% as improved, whereas 49.2% of patients reported dry eye symptoms being almost the same after treatment and 34.6% reported improved symptoms. There was low agreement between clinician and patient assessments in terms of disease severity (rho = 0.17, P treatment response (rho = 0.22, P treatment response between patient and clinician assessment. Clinicians may underestimate DED severity and persistence of dry eye symptoms after treatment with artificial tears.Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01942226.

Clinical characteristics and treatment response to SSRI in a female pedophile.

Science.gov (United States)

Chow, Eva W C; Choy, Alberto L

2002-04-01

Although much investigation has been done with male sex offenders, there have been few studies on female sex offenders. Female sex offenders have been reported as having a high incidence of psychiatric disorders, but female paraphilics were rarely described. The literature on the treatment of female sex offenders is also limited and treatment with a selective serotonin reuptake inhibitor (SSRI) has not been reported. This paper presents the case of a woman with DSM-IV pedophilia. Her clinical characteristics, her offense history, and her positive response to treatment with sertraline (a SSRI) are described. This case adds to the limited literature on female pedophiles and suggests that SSRIs may be an effective treatment for paraphilic disorders in female sex offenders.

Analysis of image heterogeneity using 2D Minkowski functionals detects tumor responses to treatment.

Science.gov (United States)

Larkin, Timothy J; Canuto, Holly C; Kettunen, Mikko I; Booth, Thomas C; Hu, De-En; Krishnan, Anant S; Bohndiek, Sarah E; Neves, André A; McLachlan, Charles; Hobson, Michael P; Brindle, Kevin M

2014-01-01

The acquisition of ever increasing volumes of high resolution magnetic resonance imaging (MRI) data has created an urgent need to develop automated and objective image analysis algorithms that can assist in determining tumor margins, diagnosing tumor stage, and detecting treatment response. We have shown previously that Minkowski functionals, which are precise morphological and structural descriptors of image heterogeneity, can be used to enhance the detection, in T1 -weighted images, of a targeted Gd(3+) -chelate-based contrast agent for detecting tumor cell death. We have used Minkowski functionals here to characterize heterogeneity in T2 -weighted images acquired before and after drug treatment, and obtained without contrast agent administration. We show that Minkowski functionals can be used to characterize the changes in image heterogeneity that accompany treatment of tumors with a vascular disrupting agent, combretastatin A4-phosphate, and with a cytotoxic drug, etoposide. Parameterizing changes in the heterogeneity of T2 -weighted images can be used to detect early responses of tumors to drug treatment, even when there is no change in tumor size. The approach provides a quantitative and therefore objective assessment of treatment response that could be used with other types of MR image and also with other imaging modalities. Copyright © 2013 Wiley Periodicals, Inc.

IgG Responses to Tissue-Associated Antigens as Biomarkers of Immunological Treatment Efficacy

Directory of Open Access Journals (Sweden)

Heath A. Smith

2011-01-01

Full Text Available We previously demonstrated that IgG responses to a panel of 126 prostate tissue-associated antigens are common in patients with prostate cancer. In the current report we questioned whether changes in IgG responses to this panel might be used as a measure of immune response, and potentially antigen spread, following prostate cancer-directed immune-active therapies. Sera were obtained from prostate cancer patients prior to and three months following treatment with androgen deprivation therapy (=34, a poxviral vaccine (=31, and a DNA vaccine (=21. Changes in IgG responses to individual antigens were identified by phage immunoblot. Patterns of IgG recognition following three months of treatment were evaluated using a machine-learned Bayesian Belief Network (ML-BBN. We found that different antigens were recognized following androgen deprivation compared with vaccine therapies. While the number of clinical responders was low in the vaccine-treated populations, we demonstrate that ML-BBN can be used to develop potentially predictive models.

CSF inflammatory biomarkers responsive to treatment in progressive multiple sclerosis capture residual inflammation associated with axonal damage.

Science.gov (United States)

Romme Christensen, Jeppe; Komori, Mika; von Essen, Marina Rode; Ratzer, Rikke; Börnsen, Lars; Bielekova, Bibi; Sellebjerg, Finn

2018-05-01

Development of treatments for progressive multiple sclerosis (MS) is challenged by the lack of sensitive and treatment-responsive biomarkers of intrathecal inflammation. To validate the responsiveness of cerebrospinal fluid (CSF) inflammatory biomarkers to treatment with natalizumab and methylprednisolone in progressive MS and to examine the relationship between CSF inflammatory and tissue damage biomarkers. CSF samples from two open-label phase II trials of natalizumab and methylprednisolone in primary and secondary progressive MS. CSF concentrations of 20 inflammatory biomarkers and CSF biomarkers of axonal damage (neurofilament light chain (NFL)) and demyelination were analysed using electrochemiluminescent assay and enzyme-linked immunosorbent assay (ELISA). In all, 17 natalizumab- and 23 methylprednisolone-treated patients had paired CSF samples. CSF sCD27 displayed superior standardised response means and highly significant decreases during both natalizumab and methylprednisolone treatment; however, post-treatment levels remained above healthy donor reference levels. Correlation analyses of CSF inflammatory biomarkers and NFL before, during and after treatment demonstrated that CSF sCD27 consistently correlates with NFL. These findings validate CSF sCD27 as a responsive and sensitive biomarker of intrathecal inflammation in progressive MS, capturing residual inflammation after treatment. Importantly, CSF sCD27 correlates with NFL, consistent with residual inflammation after anti-inflammatory treatment being associated with axonal damage.

Global DNA methylation is altered by neoadjuvant chemoradiotherapy in rectal cancer and may predict response to treatment - A pilot study.

LENUS (Irish Health Repository)

Tsang, J S

2014-07-28

In rectal cancer, not all tumours display a response to neoadjuvant treatment. An accurate predictor of response does not exist to guide patient-specific treatment. DNA methylation is a distinctive molecular pathway in colorectal carcinogenesis. Whether DNA methylation is altered by neoadjuvant treatment and a potential response predictor is unknown. We aimed to determine whether DNA methylation is altered by neoadjuvant chemoradiotherapy (CRT) and to determine its role in predicting response to treatment.

Immunological correlates of treatment and response in stage IV malignant melanoma patients treated with Ipilimumab

DEFF Research Database (Denmark)

Bjoern, Jon; Juul Nitschke, Nikolaj; Zeeberg Iversen, Trine

2016-01-01

Introduction: Ipilimumab is effective in the treatment of metastatic malignant melanoma, but few biomarkers reliably predict treatment response. Methods: Patients were treated with Ipilimumab for metastatic malignant melanoma. Blood and serum samples were collected before and during treatment. Mo...

Rapid response predicts 12-month post-treatment outcomes in binge-eating disorder: theoretical and clinical implications

Science.gov (United States)

Grilo, C. M.; White, M. A.; Wilson, G. T.; Gueorguieva, R.; Masheb, R. M.

2011-01-01

Background We examined rapid response in obese patients with binge-eating disorder (BED) in a clinical trial testing cognitive behavioral therapy (CBT) and behavioral weight loss (BWL). Method Altogether, 90 participants were randomly assigned to CBT or BWL. Assessments were performed at baseline, throughout and post-treatment and at 6- and 12-month follow-ups. Rapid response, defined as ≥70% reduction in binge eating by week four, was determined by receiver operating characteristic curves and used to predict outcomes. Results Rapid response characterized 57% of participants (67% of CBT, 47% of BWL) and was unrelated to most baseline variables. Rapid response predicted greater improvements across outcomes but had different prognostic significance and distinct time courses for CBT versus BWL. Patients receiving CBT did comparably well regardless of rapid response in terms of reduced binge eating and eating disorder psychopathology but did not achieve weight loss. Among patients receiving BWL, those without rapid response failed to improve further. However, those with rapid response were significantly more likely to achieve binge-eating remission (62% v. 13%) and greater reductions in binge-eating frequency, eating disorder psychopathology and weight loss. Conclusions Rapid response to treatment in BED has prognostic significance through 12-month follow-up, provides evidence for treatment specificity and has clinical implications for stepped-care treatment models for BED. Rapid responders who receive BWL benefit in terms of both binge eating and short-term weight loss. Collectively, these findings suggest that BWL might be a candidate for initial intervention in stepped-care models with an evaluation of progress after 1 month to identify non-rapid responders who could be advised to consider a switch to a specialized treatment. PMID:21923964

MRI predictors of treatment response for perianal fistulizing Crohn disease in children and young adults

Energy Technology Data Exchange (ETDEWEB)

Shenoy-Bhangle, Anuradha; Nimkin, Katherine; Gee, Michael S. [Massachusetts General Hospital for Children, Harvard Medical School, Department of Radiology, Boston, MA (United States); Goldner, Dana; Israel, Esther J. [Massachusetts General Hospital for Children, Harvard Medical School, Department of Pediatrics, Boston, MA (United States); Bradley, William F. [Analog Devices, Lyric Labs, Cambridge, MA (United States)

2014-01-15

Magnetic resonance imaging (MRI) is considered the imaging standard for diagnosis and characterization of perianal complications associated with Crohn disease in children and adults. To define MRI criteria that could act as potential predictors of treatment response in fistulizing Crohn disease in children, in order to guide more informed study interpretation. We performed a retrospective database query to identify all children and young adults with Crohn disease who underwent serial MRI studies for assessment of perianal symptoms between 2003 and 2010. We examined imaging features of perianal disease including fistula number, type and length, presence and size of associated abscess, and disease response/progression on follow-up MRI. We reviewed imaging studies and electronic medical records. Statistical analysis, including logistic regression, was performed to associate MR imaging features with treatment response and disease progression. We included 36 patients (22 male, 14 female; age range 8-21 years). Of these, 32 had a second MRI exam and 4 had clinical evidence of complete response, obviating the need for repeat imaging. Of the parameters analyzed, presence of abscess, type of fistula according to the Parks classification, and multiplicity were not predictors of treatment outcome. Maximum length of the dominant fistula and aggregate fistula length in the case of multiple fistulae were the best predictors of treatment outcome. Maximum fistula length <2.5 cm was a predictor of treatment response, while aggregate fistula length ≥2.5 cm was a predictor of disease progression. Perianal fistula length is an important imaging feature to assess on MRI of fistulizing Crohn disease. (orig.)

MRI predictors of treatment response for perianal fistulizing Crohn disease in children and young adults

International Nuclear Information System (INIS)

Shenoy-Bhangle, Anuradha; Nimkin, Katherine; Gee, Michael S.; Goldner, Dana; Israel, Esther J.; Bradley, William F.

2014-01-01

Magnetic resonance imaging (MRI) is considered the imaging standard for diagnosis and characterization of perianal complications associated with Crohn disease in children and adults. To define MRI criteria that could act as potential predictors of treatment response in fistulizing Crohn disease in children, in order to guide more informed study interpretation. We performed a retrospective database query to identify all children and young adults with Crohn disease who underwent serial MRI studies for assessment of perianal symptoms between 2003 and 2010. We examined imaging features of perianal disease including fistula number, type and length, presence and size of associated abscess, and disease response/progression on follow-up MRI. We reviewed imaging studies and electronic medical records. Statistical analysis, including logistic regression, was performed to associate MR imaging features with treatment response and disease progression. We included 36 patients (22 male, 14 female; age range 8-21 years). Of these, 32 had a second MRI exam and 4 had clinical evidence of complete response, obviating the need for repeat imaging. Of the parameters analyzed, presence of abscess, type of fistula according to the Parks classification, and multiplicity were not predictors of treatment outcome. Maximum length of the dominant fistula and aggregate fistula length in the case of multiple fistulae were the best predictors of treatment outcome. Maximum fistula length <2.5 cm was a predictor of treatment response, while aggregate fistula length ≥2.5 cm was a predictor of disease progression. Perianal fistula length is an important imaging feature to assess on MRI of fistulizing Crohn disease. (orig.)

The impact of transient combination antiretroviral treatment in early HIV infection on viral suppression and immunologic response in later treatment.

Science.gov (United States)

Pantazis, Nikos; Touloumi, Giota; Meyer, Laurence; Olson, Ashley; Costagliola, Dominique; Kelleher, Anthony D; Lutsar, Irja; Chaix, Marie-Laure; Fisher, Martin; Moreno, Santiago; Porter, Kholoud

2016-03-27

Effects of transient combination antiretroviral treatment (cART) initiated during early HIV infection (EHI) remain unclear. We investigate whether this intervention affects viral suppression and CD4 cell count increase following its reinitiation in chronic infection (CHI). Longitudinal observational study. We identified adult patients from Concerted Action of Seroconversion to AIDS and Death in Europe who seroconverted after 1/1/2000, had a 12 months or less HIV test interval and initiated cART from naive. We classified individuals as 'pretreated in EHI' if treated within 6 months of seroconversion, interrupted for at least 12 weeks, and reinitiated during CHI. Statistical analysis was performed using survival analysis methods and mixed models. Pretreated and initiated in CHI groups comprised 202 and 4263 individuals, with median follow-up after CHI treatment 4.5 and 3 years, respectively. Both groups had similar virologic response and relapse rates (P = 0.585 and P = 0.206) but pretreated individuals restarted treatment with higher baseline CD4 cell count (∼80 cells/μl; P treatment (re)initiation. Assuming common baseline CD4 cell count, differences in CD4 cell count slopes were nonsignificant. Immunovirologic response to CHI treatment was not associated with timing or duration of the transient treatment. Although treatment interruptions are not recommended, stopping cART initiated in EHI does not seem to reduce the chance of a successful outcome of treatment in CHI.

Anti-angiogenic treatment (Bevacizumab) improves the responsiveness of photodynamic therapy in colorectal cancer.

Science.gov (United States)

Peng, Cheng-Liang; Lin, Hua-Ching; Chiang, Wei-Lun; Shih, Ying-Hsia; Chiang, Ping-Fang; Luo, Tsai-Yueh; Cheng, Chun-Chia; Shieh, Ming-Jium

2018-06-09

Photodynamic therapy (PDT) is a new treatment utilizing the combined action of photosensitizers and light for the treatment of various cancers. The mechanisms for tumor destruction after PDT include direct tumor cell kill by singlet oxygen species (OS), indirect cell kill via vascular damage, and an elicited immune response. However, it has been reported that many cellular activators, including vascular endothelial growth factor (VEGF), are produced by tumor cells after PDT. In this study, we demonstrate that meta-tetra(hydroxyphenyl) chlorin (mTHPC)-based photodynamic therapy combined with bevacizumab (Avastin™), an anti-VEGF neutralizing monoclonal antibody that blocks the binding of VEGF to its receptor, can enhance the effectiveness of each treatment modality. We evaluated the efficacy of bevacizumab-based anti-angiogenesis in combination with PDT as well as the resulting VEGF levels in a mouse model of human colon cancer. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) were performed to assess VEGF concentrations in the various treatment groups, and confocal imaging and high performance liquid chromatography (HPLC) analyses were used to measure the distribution and concentration of mTHPC in tumors. Our results demonstrate that combination of PDT followed by bevacizumab significantly elicits a greater tumor response whereas bevacizumab treatment prior to PDT led to a reduced tumor response. Immunostaining and ELISA analyses revealed a lower expression of VEGF in tumors treated with combination therapy of PDT followed by bevacizumab. However, bevacizumab treatment decreased the accumulation of mTHPC in tumors 24 h after administration, which complemented the results of decreased anti-tumor efficacy of bevacizumab followed by PDT. Copyright © 2018. Published by Elsevier B.V.

The utility of PET/CT in staging and assessment of treatment response of naso pharyngeal cancer

International Nuclear Information System (INIS)

Law, Alastair; Peters, L.J.; Dutu, Gaelle; Rischin, Danny; Lau, Eddie; Drummond, Elizabeth; Corry, June

2011-01-01

Full text: The aim of this study was to evaluate the impact of positron emission tomography/computerised tomography (PET/CT) as an adjunct to conventional imaging (CI) in the management of nasopharyngeal cancer (NPC) both for initial staging and assessment of post-treatment response. Methods: All NPC cases referred to the Peter MacCallum Centre for Metabolic Imaging between January 2002 and December 2007 were identified, In patients undergoing initial staging, any differences between the pre PET/CT management plan based on CI and that following performance of the PET/CT scan were noted. Clinical impact was scored using the Centre's published criteria: 'high' if PET /CT changed the primary treatment modality or intent, 'medium' if treatment modality was unchanged but the radiotherapy technique or dose was altered, and 'low' if there was no change in treatment modality or intent. Patients undergoing PET/CT following definitive treatment were scored according to whether or not they achieved a complete metabolic response. Results: Forty-eight patients underwent a staging PET/CT. The clinical impact was high in 8%, medium in 25% and low in 66% of patients. Twenty-one patients were scanned for post-treatment response. PET/CT was less frequently equivocal than MRI (3 vs 8/21). A complete metabolic response on PET /CT was associated with a 93% negative predictive value for subsequent recurrence. Conclusion: PET /CT is a valuable staging tool for the detection of occult metastatic disease and defining the extent of neck nodal disease, Pos treatment, a complete metabolic response on PET /CT has a very high negative predictive value with fewer equivocal results than MRI.

Tissue As A Medium For Laser Light Transport-Implications For Photoradiation Therapy

Science.gov (United States)

Preuss, L. E.; Bolin, F. P.; Cain, B. W.

1982-12-01

An important medical laser application is in the emerging field of photoradiation therapy (PRT). PRT is the process in which malignant tissue is destroyed by administration of light to a specific photosensitized site. Filtered arcs, incandescents and dye lasers have been used as sources of activating light. We have carried out light experiments in tissue to study such PRT light distributions. The results of this research have shown that a number of important optical phenomena occurring within illuminated tissue must be accounted for in order to make good predictions of tumor light dosage. Among these are; tissue type, interface effects and anomalies due to composition. These effects substantially influence light levels in PRT and, thus, the therapeutic effect. The uniqueness of tissue as a medium for light transport presents special problems for optics research and instrumentation. Successful solutions necessarily will involve collaboration between the life sciences and optic specialists. Attempts at treatment of human disease using non-ionizing radiation have a history archaeologically traceable to archaic societies (in which the sun's photons were used and often worshipped).1 Western medicine in the past, has used visible light beneficially, albeit empirically, on a few ailments. However, in this century, a significant development in the understanding and in the therapeutic use of this electromagnetic radiation in the UV, visible and IR has occurred, based on scientific study. This utilization of radiation in the visible and ultraviolet can be by two distinct processes. One is through the direct action of the photons which serve as the sole treatment agent. In this case the photon interacts with the cell, or its components, in a single step, to produce a desired effect. An example is the successful use of blue light for treatment of bilirubinemia in newborns. The second process is a biological effect produced through the combination of electromagnetic radiation

Radiotherapy does not cause increase psychological fatigue in prostate cancer patients: a prospective study

International Nuclear Information System (INIS)

Monga, Uma; Kerrigan, Anthony J.; Monga, Trilok N.

1997-01-01

Objectives: The origin of fatigue, a common symptom in cancer patients undergoing radiotherapy(RT), remains unresolved. The objectives of this study were to evaluate subjective fatigue in patients with localized prostate cancer utilizing validated instruments and to examine the relationship of fatigue with radiotherapy. Methods: Instruments used included: Piper Fatigue Scale (PFS), Beck Depression Inventory (BDI), Epworth Sleepiness Scale (ESS) and Functional Assessment of Cancer Therapy - Prostate (FACT-P). Patients are evaluated before radiation therapy (PRT), at 4 weeks' (RT4), at completion of RT (7-8 weeks, RTC) of radiotherapy, and at 4 weeks follow-up (RTF). Seventeen prostate cancer subjects with a mean age of 64.6 years (range 55-73) were assessed. Results: PRT median scores on BDI, PFS, ESS, FACT(G), and FACT (P) were 4.00, 2.41, 6.0, 94, and 130 respectively. No significant changes in these scores were noted at RT4, RTC and RTF. Significant negative relationship was noted between PFS and physical well being sub-scale of FACT (G) at PRT(r=-0.76), RTC(r=-0.58), and RTF(r=-0.86). On BDI, four subjects reported depressive symptoms PRT. Two of these four subjects also scored higher on PFS. However, no significant changes were noted on their BDI and PFS scores during the study. No other patients reported depressive symptoms during treatment. Conclusions: These findings indicate: (1) No significant change in the baseline scores of fatigue and psychological measures during radiotherapy. (2) Self reported fatigue is not common in our patient population. (3) A significant relationship exists between scores on PFS and Physical well being sub-scale of FACT (G). Relationship between PFS, FACT-P and psychological functioning, severity of disease and PSA levels will also be presented

Palliative Radiotherapy in the Presence of Well-Controlled Metastatic Disease after Initial Chemotherapy May Prolong Survival in Patients with Metastatic Esophageal and Gastric Cancer.

Science.gov (United States)

Hingorani, Mohan; Dixit, Sanjay; Johnson, Miriam; Plested, Victoria; Alty, Kevin; Colley, Peter; Beavis, Andrew W; Roy, Rajarshi; Maraveyas, Anthony

2015-10-01

We report the outcomes of patients treated with palliative radiotherapy (pRT) to the primary tumour in the context of well-controlled metastatic disease after initial chemotherapy. Clinical records of 132 patients with metastatic esophago-gastric (OG) cancer treated with palliative chemotherapy (pCT) between January 2009 and June 2013 were reviewed. Ninetyseven patients had responding or stable disease after 3 months of chemotherapy, of whom 53 patients received pRT to the primary tumour after initial chemotherapy in the presence of well-controlled metastatic disease (group A, pCT-RT). The remaining 44 patients were treated with pCT alone (group B, pCT). Treatment-related outcomes were assessed in above groups including time to local progression (TTLP), progression-free and overall survival. The median overall survival for patients treated with pRT after initial chemotherapy (group A) was 23.3 months (95% confidence interval [CI], 17.70 to 28.89 months) and significantly higher than the 14 months (95% CI, 10.91 to 17.08 months) in patients treated with pCT alone (group B) (p < 0.001). The use of pCT-RT was an independent predictor of OS in multivariate analysis. Local recurrence was observed in 12/53 of patients (23%) in group A compared to 16/44 (36%) in group B. The median TTLP was significantly higher in patients after pCT-RT at 17.3 months (5.23 months to 44.50 months) compared to 8.3 months (range, 4.10 to 25.23 months) in patients treated with pCT alone (p=0.006). The possibility of pRT influencing systemic disease in advanced OG cancer has not been reported, and results from the present study present strong arguments for investigation of this therapeutic strategy in a randomized trial.

Treatment response in psychotic patients classified according to social and clinical needs, drug side effects, and previous treatment; a method to identify functional remission.

Science.gov (United States)

Alenius, Malin; Hammarlund-Udenaes, Margareta; Hartvig, Per; Sundquist, Staffan; Lindström, Leif

2009-01-01

Various approaches have been made over the years to classify psychotic patients according to inadequate treatment response, using terms such as treatment resistant or treatment refractory. Existing classifications have been criticized for overestimating positive symptoms; underestimating residual symptoms, negative symptoms, and side effects; or being to open for individual interpretation. The aim of this study was to present and evaluate a new method of classification according to treatment response and, thus, to identify patients in functional remission. A naturalistic, cross-sectional study was performed using patient interviews and information from patient files. The new classification method CANSEPT, which combines the Camberwell Assessment of Need rating scale, the Udvalg for Kliniske Undersøgelser side effect rating scale (SE), and the patient's previous treatment history (PT), was used to group the patients according to treatment response. CANSEPT was evaluated by comparison of expected and observed results. In the patient population (n = 123), the patients in functional remission, as defined by CANSEPT, had higher quality of life, fewer hospitalizations, fewer psychotic symptoms, and higher rate of workers than those with the worst treatment outcome. In the evaluation, CANSEPT showed validity in discriminating the patients of interest and was well tolerated by the patients. CANSEPT could secure inclusion of correct patients in the clinic or in research.

Analysis of Transcriptional Responses of the Inflorescence Meristems in Jatropha curcas Following Gibberellin Treatment

Directory of Open Access Journals (Sweden)

Wen-Kai Hui

2018-02-01

Full Text Available Jatropha curcas L. seeds an oilseed plant with great potential for biodiesel production. However, low seed yield, which was limited by its lower female flowers, was a major drawback for its utilization. Our previous study found that the flower number and female-to-male ratio were increased by gibberellin treatment. Here, we compared the transcriptomic profiles of inflorescence meristem at different time points after gibberellic acid A3 (GA3 treatment. The present study showed that 951 differentially expressed genes were obtained in response to gibberellin treatment, compared with control samples. The 6-h time point was an important phase in the response to exogenous gibberellin. Furthermore, the plant endogenous gibberellin, auxin, ethylene, abscisic acid, and brassinolide-signaling transduction pathways were repressed, whereas the genes associated with cytokinin and jasmonic acid signaling were upregulated for 24-h time point following GA3 treatment. In addition, the floral meristem determinacy genes (JcLFY, JcSOC1 and floral organ identity genes (JcAP3, JcPI, JcSEP1-3 were significantly upregulated, but their negative regulator (JcSVP was downregulated after GA3 treatment. Moreover, the effects of phytohormone, which was induced by exogenous plant growth regulator, mainly acted on the female floral differentiation process. To the best of our knowledge, this data is the first comprehensive analysis of the underlying transcriptional response mechanism of floral differentiation following GA3 treatment in J. curcas, which helps in engineering high-yielding varieties of Jatropha.

White matter integrity as a predictor of response to treatment in first episode psychosis.

Science.gov (United States)

Reis Marques, Tiago; Taylor, Heather; Chaddock, Chris; Dell'acqua, Flavio; Handley, Rowena; Reinders, A A T Simone; Mondelli, Valeria; Bonaccorso, Stefania; Diforti, Marta; Simmons, Andrew; David, Anthony S; Murray, Robin M; Pariante, Carmine M; Kapur, Shitij; Dazzan, Paola

2014-01-01

The integrity of brain white matter connections is central to a patient's ability to respond to pharmacological interventions. This study tested this hypothesis using a specific measure of white matter integrity, and examining its relationship to treatment response using a prospective design in patients within their first episode of psychosis. Diffusion tensor imaging data were acquired in 63 patients with first episode psychosis and 52 healthy control subjects (baseline). Response was assessed after 12 weeks and patients were classified as responders or non-responders according to treatment outcome. At this second time-point, they also underwent a second diffusion tensor imaging scan. Tract-based spatial statistics were used to assess fractional anisotropy as a marker of white matter integrity. At baseline, non-responders showed lower fractional anisotropy than both responders and healthy control subjects (P psychosis. These data, together with earlier findings on cortical grey matter, suggest that grey and white matter integrity at the start of treatment is an important moderator of response to antipsychotics. These findings can inform patient stratification to anticipate care needs, and raise the possibility that antipsychotics may restore white matter integrity as part of the therapeutic response.

Identification of Predictive Response Markers and Novel Treatment Targets for Gliomas

NARCIS (Netherlands)

L. Erdem-Eraslan (Lale)

2016-01-01

markdownabstractGliomas are the most frequent primary brain tumors in adults. Despite multimodality treatment strategies, the survival of patients with a diffuse glioma remains poor. There has been an increasing use of molecular markers to assist diagnosis and predict prognosis and response to

Early change in coping strategies in responsive treatments for borderline personality disorder: A mediation analysis.

Science.gov (United States)

Kramer, Ueli; Keller, Sabine; Caspar, Franz; de Roten, Yves; Despland, Jean-Nicolas; Kolly, Stéphane

2017-05-01

Difficulty in emotion regulation is a hallmark feature of patients with borderline personality disorder (BPD). Therefore, change in the frequency of certain patients' coping strategies-aiming at emotion regulation-are among the most promising mechanisms of change in treatments for BPD. In parallel, it was highlighted that therapist responsiveness significantly contributed to outcome across treatment approaches (Stiles, 2009). Based on a randomized controlled trial (Kramer et al., 2014), the present process-outcome mediation analysis aims at examining the patient's early change in frequency of coping strategies-in particular the decrease in behavioral forms of coping-as potential mechanism of change in responsive treatments for BPD. A total of 57 patients with BPD were included in the present analysis, out of whom 27 were randomly assigned to a 10-session psychiatric treatment and 30 to a 10-session psychiatric treatment augmented with the responsive intervention of the motive-oriented therapeutic relationship (Caspar, 2007). The 1st, 5th, and 9th session of each therapy were transcribed and analyzed using the Coping Action Pattern Rating Scale (Perry et al., 2005; 171 sessions analyzed in total), a validated observer-rated method for assessing coping strategies in the therapy process. Psychological distress was assessed using the OQ-45 at intake, after Session 5, and after Session 10. The results confirmed a responsiveness effect associated with the motive-oriented therapeutic relationship and showed a significant decrease in frequency of behavioral forms of coping, F(1, 54) = 3.09, p = .05, d = .56, which was not different between the 2 conditions. In addition, we demonstrated that the early decrease in behavioral forms of coping between Sessions 1 and 5 partially mediated the link between the group assignment and the change in psychological distress between Sessions 5 and 10. These results shed light on the centrality of therapist responsiveness in treatments for

Monitoring Cancer Response to Treatment with Hyperpolarized ¹³C MRS

DEFF Research Database (Denmark)

Eldirdiri, Abubakr

, and the patient is exposed to ionizing radiation. The introduction of hyperpolarized 13C MRS has opened completely new possibilities to study the biochemical changes in disease processes. Numerous 13C-labeled compounds were proposed to interrogate various aspects of cancer cell metabolism. The aim of this study......Monitoring the cancer response to treatment, non-invasively, by medical imaging is a key element in the management of cancer. For patients undergoing treatment, it is crucial to determine responders from non-responders in order to guide treatment decisions. Currently, PET is the most widely used...

Treatment response in psychotic patients classified according to social and clinical needs, drug side effects, and previous treatment; a method to identify functional remission

DEFF Research Database (Denmark)

Alenius, Malin; Hammarlund-Udenaes, Margareta; Honoré, Per Gustaf Hartvig

2009-01-01

, fewer psychotic symptoms, and higher rate of workers than those with the worst treatment outcome. CONCLUSION: In the evaluation, CANSEPT showed validity in discriminating the patients of interest and was well tolerated by the patients. CANSEPT could secure inclusion of correct patients in the clinic......BACKGROUND: Various approaches have been made over the years to classify psychotic patients according to inadequate treatment response, using terms such as treatment resistant or treatment refractory. Existing classifications have been criticized for overestimating positive symptoms......; underestimating residual symptoms, negative symptoms, and side effects; or being to open for individual interpretation. The aim of this study was to present and evaluate a new method of classification according to treatment response and, thus, to identify patients in functional remission. METHOD: A naturalistic...

Time to treatment as an important factor for the response to methotrexate in juvenile idiopathic arthritis.

Science.gov (United States)

Albers, H M; Wessels, J A M; van der Straaten, R J H M; Brinkman, D M C; Suijlekom-Smit, L W A; Kamphuis, S S M; Girschick, H J; Wouters, C; Schilham, M W; le Cessie, S; Huizinga, T W J; Ten Cate, R; Guchelaar, H J

2009-01-15

Methotrexate (MTX) is the most commonly used disease-modifying antirheumatic drug in juvenile idiopathic arthritis (JIA). Currently, individual response to MTX cannot be reliably predicted. Identification of clinical and genetic factors that influence the response to MTX could be helpful in realizing the optimal treatment for individual patients. A cohort of 128 JIA patients treated with MTX were studied retrospectively. Eleven clinical parameters and genotypes of 6 single nucleotide polymorphisms in 5 genes related to the mechanism of action of MTX were compared between MTX responders and nonresponders using a multivariate regression analysis. The time from diagnosis to start of MTX treatment, physician's global assessment at baseline, and the starting dose were significantly associated with the response to MTX at 6 months after initiation. Patients with a shorter time from diagnosis to start of MTX and a higher disease activity according to the physician but with a lower MTX dose showed an increased response. The effect of the starting dose on MTX response seemed to be mainly due to the influence of the systemic JIA subtype. The time from diagnosis to start of MTX treatment and physician's global assessment at baseline were highly correlated. Therefore, the precise effect size of each independent variable could not be determined. In children with JIA, the time from diagnosis to start of MTX appears to be an important factor for MTX response. Our results suggest that an earlier start of MTX treatment will lead to an increased response.

Opportunities for Energy Efficiency and Open Automated Demand Response in Wastewater Treatment Facilities in California -- Phase I Report

Energy Technology Data Exchange (ETDEWEB)

Lekov, Alex; Thompson, Lisa; McKane, Aimee; Song, Katherine; Piette, Mary Ann

2009-04-01

This report summarizes the Lawrence Berkeley National Laboratory?s research to date in characterizing energy efficiency and automated demand response opportunities for wastewater treatment facilities in California. The report describes the characteristics of wastewater treatment facilities, the nature of the wastewater stream, energy use and demand, as well as details of the wastewater treatment process. It also discusses control systems and energy efficiency and automated demand response opportunities. In addition, several energy efficiency and load management case studies are provided for wastewater treatment facilities.This study shows that wastewater treatment facilities can be excellent candidates for open automated demand response and that facilities which have implemented energy efficiency measures and have centralized control systems are well-suited to shift or shed electrical loads in response to financial incentives, utility bill savings, and/or opportunities to enhance reliability of service. Control technologies installed for energy efficiency and load management purposes can often be adapted for automated demand response at little additional cost. These improved controls may prepare facilities to be more receptive to open automated demand response due to both increased confidence in the opportunities for controlling energy cost/use and access to the real-time data.

Bryoid layer response to soil disturbance by fuel reduction treatments in a dry conifer forest

Science.gov (United States)

Amanda Hardman; Bruce McCune

2010-01-01

We investigated the response of the bryoid layer, bryophyte and lichen communities on the soil surface three years after fuel reduction treatment (logging and burning) in the central Blue Mountains of eastern Oregon. Both treatment and control areas had been decimated by spruce budworm and drought before the fuel reduction treatments. Treatments reduced overstory and...

Eosinophilic Esophagitis: Clinical Features, Endoscopic Findings and Response to Treatment

Directory of Open Access Journals (Sweden)

Robert Enns

2010-01-01

Full Text Available Eosinophilic esophagitis (EE is a motility disorder of the esophagus that typically presents with dysphagia. The objective of the present study was to explore patient characteristics, clinical and endoscopic features, and response to treatment of patients with EE. Patients were selected retrospectively based on a review of biopsy results from previous endoscopies performed between 2004 and 2008. A total of 54 patients (41 men and 13 women with biopsy-proven EE were included in the study. Further information regarding the patients’ clinical and endoscopic features, and response to treatment were obtained through chart reviews and patient telephone interviews. The mean age of the patients at symptom onset was 30 years. All patients complained of dysphagia, 81% had a history of bolus obstruction, 43% had a history of asthma and 70% had a history of environmental allergies. Thirty-three per cent had a family history of asthma, while 52% had a family history of food or seasonal allergies. The most common endoscopic findings were rings and/or corrugations, which were found in 63% of patients. Swallowed fluticasone therapy resulted in symptom resolution in 74% of patients; however, 79% of these patients relapsed after discontinuing fluticasone therapy and required repeat treatments. Esophageal dilation was complication free and resulted in improvement in 80% of patients. However, 83% of those reporting improvement relapsed within one year. The clinical and endoscopic findings were similar to those found in the literature, with most patients requiring ongoing, repeated therapies. Further studies are needed to assess the safety and efficacy of treatment modalities ideally suited to patients with EE.

Catatonia: Etiopathological diagnoses and treatment response in a tertiary care setting: A clinical study

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Santosh Ramdurg

2013-01-01

Full Text Available Aim: Catatonia is caused by a variety of psychiatric and organic conditions. The onset, clinical profile, and response to treatment may vary depending on the underlying cause. The study is an attempt to explore clinical profile, possible etiological correlates with neurotic/psychotic spectrum illnesses, and response to treatment and outcome in patients of catatonia. Materials and Methods: Retrospective chart analysis by using semistructured data sheet for the analysis of sociodemographic data, clinical profile, precipitating event, and response to treatment in patients with catatonic symptoms admitted to IHBAS (Institute of Human Behaviour and Allied Sciences, New Delhi, India from January 2009 to December 2010 was undertaken. Results: Catatonia was commonly observed in patients with the following profile - late twenties, female, Hindu religion, urban background, and housewives. Psychotic spectrum disorder (57%, N=35 was the most commonly entertained diagnosis and affective disorder (18%, N=11 being the second common. Thirty four percent of the subjects responded to lorazepam treatment and rest required modified electroconvulsive therapy (MECT. Conclusion: Catatonia is more likely to be associated with Schizophrenia and Other Psychotic Disorders in Indian settings. Majority of patients responded to therapy either by lorazepam alone or to its augmentation with modified ECT. The study being a retrospective one, the sample being representative of the treatment seeking group only, and unavailability of the follow up data were the limitations of the study

Predicting post-traumatic stress disorder treatment response in refugees : Multilevel analysis

NARCIS (Netherlands)

Haagen, Joris F G; Ter Heide, F Jackie June; Mooren, Trudy M; Knipscheer, Jeroen W; Kleber, Rolf J

2017-01-01

OBJECTIVES: Given the recent peak in refugee numbers and refugees' high odds of developing post-traumatic stress disorder (PTSD), finding ways to alleviate PTSD in refugees is of vital importance. However, there are major differences in PTSD treatment response between refugees, the determinants of

Risk factors and treatment responses in patients with vitiligo in Japan—A retrospective large-scale study

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Ryoko Ohguchi

2015-05-01

Full Text Available Vitiligo is a refractory skin disease. To investigate the risk factors and treatment responses of patients with vitiligo in Japan, we recorded and analyzed the details of 713 vitiligo patients (comorbidity, treatment responses, family history, age, and sex who visited the dermatology clinic of the Nagoya City University Hospital, Nagoya, Japan between January 2004 and August 2010 (mean age, 35.2 years; 302 men, 411 women using logistic regression analysis. The results are expressed as odds ratios (OR with 95% confidence interval (CI. Patients were diagnosed with vitiligo [n = 644; 338 generalized type (47.4%, 170 segmental type (23.8%, and 136 localized type (19.1%], nevus depigmentosus (n = 53, 7.4%, halo nevus (n = 14, 2.0%, and hypomelanosis of Ito (n = 2, 0.3%. For generalized and localized types, none of the analyzed factors were statistically significant. For the segmental type, antinuclear antibody (OR = 1.005; 95% CI, 1.00–1.01; p 55 years (OR = 0.0171; 95% CI, 0.00333–0.0879; p < 0.001. The treatment response rates for narrow-band UV-B, topical vitamin D3, and punch graft (1 mm minigraft were, respectively, as follows: (1 generalized type: 46.3%, 21.1%, and 38.9%; (2 segmental type: 20.3%, 29.0%, and 77.3%; and (3 localized type: 29.2%, 54.8%, and 73.3%. We report the comorbidities and efficacy rates of these treatments. The response data for these treatments, in particular, would be of assistance to the previous explanations, because there were only a few reports on the response data for these treatments. The appropriate treatment should be selected depending on the type of vitiligo.

Tacrolimus drug level and response to treatment in idiopathic childhood steroid resistant nephrotic syndrome

International Nuclear Information System (INIS)

Shah, S.S.; Hafeez, F.; Akhtar, N.

2015-01-01

The management of Steroid Resistant Nephrotic Syndrome (SRNS) is an uphill task for paediatric nephrologists as immunosuppressive agents are the mainstay of treatment in these patients. Tacrolimus is used along with steroids. This study is conducted to see the relationship between the tacrolimus dose, drug level and response in the management of SRNS. Methods: This quasi experimental study was conducted at The Childrens Hospital Lahore over a period of one year. Patients with SRNS of either sex and 1-10 years of age were included and those with secondary nephrotic syndrome were excluded. Tacrolimus was given at a dose of 0.05-0.1 mg/kg/day in 2 divided doses along with steroids. The follow-up was done for six months with proteinuria monitoring and tacrolimus drug levels done two weeks after initiation of treatment. Results: Out of 42 patients, 27 (64.3%) were males and 15 (35.7%) were females. The most common histological diagnosis observed was mesangio-proliferative glomerulonephritis in 30 (71.4%) patients. The tacrolimus trough level range was 0.5-15.20 ng/ml with a mean value of 4.68 ng/ml±2.85. Forty-one (97.6%) children showed complete response to treatment while one patient showed partial response. Conclusion: This study suggests that tacrolimus is an effective drug for treatment of SRNS in paediatric patients and there is no linear relationship between the drug dose, response and drug level. (author)

Agouron and immune response to commercialize remune immune-based treatment.

Science.gov (United States)

James, J S

1998-06-19

Agouron Pharmaceuticals agreed in June to collaborate with The Immune Response Corporation on the final development and marketing of an immune-based treatment for HIV. Remune, the vaccine developed by Dr. Jonas Salk, is currently in Phase III randomized trials with 2,500 patients, and the trials are expected to be completed in April 1999. Immune-based treatments have been difficult to test, as there is no surrogate marker, like viral load, to determine if the drug is working. Agouron agreed to participate in the joint venture after reviewing encouraging results from preliminary trials in which remune was taken in combination with highly active antiretroviral drugs.

Evaluation of an adjustable epidemiologic information system.

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Jiunn-Shyan Julian Wu

Full Text Available BACKGROUND: In order to facilitate public health response and to achieve early control of infectious disease epidemics, an adjustable epidemiologic information system (AEIS was established in the Taiwan public health network in February 2006. METHODOLOGY/PRINCIPAL FINDINGS: The performance of AEIS for the period 2006 through 2008 was evaluated based on a number of response times (RT and the public health impact. After implementation of the system, the apparent overall shortened RT was mainly due to the shortening of personnel response time (PRT and the time needed to draft a new questionnaire that incurred as personnel-system interface (PSI; PRT dropped from a fluctuating range of 9.8 ∼28.8 days in the first four months to <10 days in the following months and remained low till 2008 (0.88±1.52 days. The PSIs for newly emerged infectious diseases were 2.6 and 3.4 person-hours for H5N1 in 2007 and chikungunya in 2008, respectively, a much improvement from 1142.5 person-hours for SARS in 2003. The duration of each rubella epidemic cluster was evaluated as public health impact and showed a shortening trend (p = 0.019 that concurred with the shortening of PRT from 64.8±47.3 to 25.2±38.2 hours per cluster (p<0.0001. CONCLUSIONS/SIGNIFICANCE: The first evaluation of the novel instrument AEIS that had been used to assist Taiwan's multi-level government for infectious diseases control demonstrated that it was well integrated into the existing public health infrastructure. It provided flexible tools and computer algorithms with friendly interface for timely data collection, integration, and analysis; as a result, it shortened RTs, filled in gaps of personnel lacking sufficient experiences, created a more efficient flow of response, and identified asymptomatic/mild cases early to minimize further spreading. With further development, AEIS is anticipated to be useful in the application of other acute public health events needing immediate

Progress in the understanding and utilization of biologic response modifiers in the treatment of uveitis.

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Maleki, Arash; Meese, Halea; Sahawneh, Haitham; Foster, C Stephen

2016-07-01

Uveitis is the third most common cause of blindness in developed countries. Considering the systemic and local complications of long-term corticosteroid therapy and the intolerance due to side effects and ineffectiveness of conventional chemotherapy, use of biologic response modifiers is a reasonable alternative in the treatment of non-infectious uveitis and persistent uveitic macular edema. The majority of the evidence presented here comes from open uncontrolled analyses. Based on these studies, tumor necrosis factor alpha inhibitors, especially infliximab and adalimumab, have been shown to be effective in the treatment of non-infectious uveitis in numerous studies. More research is necessary, particularly multi-center randomized clinical trials, to address the choice of biologic response modifier agent and the length of treatment as we employ biologic response modifiers in different types of uveitis and persistent uveitic macular edema.

Measuring treatment response in psychotic depression

DEFF Research Database (Denmark)

Østergaard, Søren D; Meyers, Barnett S; Flint, Alastair J

2014-01-01

). The response to the two regimens was compared using both a mixed effects model and effect size statistics on the total scores of three rating scales: the 17-item Hamilton Depression Rating Scale (HAM-D17), its 6-item melancholia subscale (HAM-D6), and the 11-item PDAS consisting of the HAM-D6 plus five items......BACKGROUND: There is no established psychometric instrument dedicated to the measurement of severity in psychotic depression (PD). The aim of this study was to investigate whether a new composite rating scale, the Psychotic Depression Assessment Scale (PDAS), covering both the psychotic...... and the depressive domains of PD, could detect differences in effect between two psychopharmacological treatment regimens. METHODS: We reanalyzed the data from the Study of Pharmacotherapy of Psychotic Depression (STOP-PD), which compared the effect of Olanzapine+Sertraline (n=129) versus Olanzapine+Placebo (n=130...

Preparing patients with cancer who work and treatment responsiveness.

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Kamau, Caroline

2017-03-01

Many patients with life-limiting illnesses continue to work because of financial reasons and because work provides good psychosocial support. A lack of appropriate advice/support through patient education could, however, make having a job detrimental to well-being (eg, symptom worsening). This study investigated the frequency with which patients received information that empowers their understanding of their condition, treatment, side effects of treatment and the likely impact on occupational functioning. A cross-sectional study. An analysis of survey data from 3457 patients with cancer in employment. Logistic regression showed that patients who received information about the impact of cancer on work life or education are 1.72 times more likely to have a positive treatment outcome. Patients who receive written information about the type of cancer are 1.99 times more likely to have a positive treatment outcome. Also, patients who receive written information before a cancer-related operation are 1.90 times more likely to have a positive treatment outcome. Information about the side effects of cancer treatment produces worse odds of a positive treatment outcome (0.65-1). A stepwise logistic regression analysing the effects irrespective of current employment status in 6710 patients showed that preparing them produces nearly twice better odds of cancer treatment responsiveness. Palliative care teams should consider ways of actively advising patients who work. Whereas the results showed evidence of good practice in cancer care, there is a need to ensure that all working patients with potentially life-limiting illnesses receive similar support. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Use of PET to monitor the response of lung cancer to radiation treatment

International Nuclear Information System (INIS)

Erdi, Y.E.; Humm, J.L.; Erdi, A.K.; Yorke, E.D.; Macapinlac, H.; Larson, S.M.; Rosenzweig, K.E.

2000-01-01

Approximately 170,000 people are diagnosed with lung cancer in the United States each year. Many of these patients receive external beam radiation for treatment. Fluorine-18 2-fluoro-2-deoxy-d-glucose positron emission tomography (FDG PET) is increasingly being used in evaluating non-small cell lung cancer and may be of clinical utility in assessing response to treatment. In this report, we present FDG PET images and data from two patients who were followed with a total of eight and seven serial FDG PET scans, respectively, through the entire course of their radiation therapy. Changes in several potential response parameters are shown versus time, including lesion volume (V FDG ) by PET, SUV av , SUV max , and total lesion glycolysis (TLG) during the course of radiotherapy. The response parameters for patient 1 demonstrated a progressive decrease; however, the response parameters for patient 2 showed an initial decrease followed by an increase. The data presented here may suggest that the outcome of radiation therapy can be predicted by PET imaging, but this observation requires a study of additional patients. (orig.)

Early positron emission tomography response-adapted treatment in stage I and II hodgkin lymphoma

DEFF Research Database (Denmark)

André, Marc P.E.; Girinsky, Théodore; Federico, Massimo

2017-01-01

Purpose Patients who receive combined modality treatment for stage I and II Hodgkin lymphoma (HL) have an excellent outcome. Early response evaluation with positron emission tomography (PET) scan may improve selection of patients who need reduced or more intensive treatments. Methods We performed...

Epilepsy with myoclonic absences - favourable response to add-on rufinamide treatment in 3 cases

DEFF Research Database (Denmark)

Häusler, M; Kluger, G; Nikanorova, M

2011-01-01

Epilepsy with myoclonic absences (EMA) is a rare epileptic syndrome with frequently poor response to antiepileptic treatment. Rufinamide (RUF) is a relatively new EMEA- and FDA-approved anticonvulsant licensed as an orphan drug for the adjunctive treatment of patients with Lennox-Gastaut syndrome....

Early treatment with tolvaptan improves diuretic response in acute heart failure with renal dysfunction

NARCIS (Netherlands)

Matsue, Yuya; ter Maaten, Jozine M.; Suzuki, Makoto; Torii, Sho; Yamaguchi, Satoshi; Fukamizu, Seiji; Ono, Yuichi; Fujii, Hiroyuki; Kitai, Takeshi; Nishioka, Toshihiko; Sugi, Kaoru; Onishi, Yuko; Noda, Makoto; Kagiyama, Nobuyuki; Satoh, Yasuhiro; Yoshida, Kazuki; van der Meer, Peter; Damman, Kevin; Voors, Adriaan A.; Goldsmith, Steven R.

2017-01-01

Background: Poor response to diuretics is associated with worse prognosis in patients with acute heart failure (AHF). We hypothesized that treatment with tolvaptan improves diuretic response in patients with AHF. Methods: We performed a secondary analysis of the AQUAMARINE open-label randomized

A novel approach to assess the treatment response using Gaussian random field in PET

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Wang, Mengdie [Department of Biomedical Engineering, Tsinghua University, Beijing 100084, China and Center for Advanced Medical Imaging Science, Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, Boston, Massachusetts 02114 (United States); Guo, Ning [Center for Advanced Medical Imaging Science, Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, Boston, Massachusetts 02114 (United States); Hu, Guangshu; Zhang, Hui, E-mail: hzhang@mail.tsinghua.edu.cn, E-mail: li.quanzheng@mgh.harvard.edu [Department of Biomedical Engineering, Tsinghua University, Beijing 100084 (China); El Fakhri, Georges; Li, Quanzheng, E-mail: hzhang@mail.tsinghua.edu.cn, E-mail: li.quanzheng@mgh.harvard.edu [Center for Advanced Medical Imaging Science, Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, Boston, Massachusetts 02114 and Department of Radiology, Harvard Medical School, Boston, Massachusetts 02115 (United States)

2016-02-15

Purpose: The assessment of early therapeutic response to anticancer therapy is vital for treatment planning and patient management in clinic. With the development of personal treatment plan, the early treatment response, especially before any anatomically apparent changes after treatment, becomes urgent need in clinic. Positron emission tomography (PET) imaging serves an important role in clinical oncology for tumor detection, staging, and therapy response assessment. Many studies on therapy response involve interpretation of differences between two PET images, usually in terms of standardized uptake values (SUVs). However, the quantitative accuracy of this measurement is limited. This work proposes a statistically robust approach for therapy response assessment based on Gaussian random field (GRF) to provide a statistically more meaningful scale to evaluate therapy effects. Methods: The authors propose a new criterion for therapeutic assessment by incorporating image noise into traditional SUV method. An analytical method based on the approximate expressions of the Fisher information matrix was applied to model the variance of individual pixels in reconstructed images. A zero mean unit variance GRF under the null hypothesis (no response to therapy) was obtained by normalizing each pixel of the post-therapy image with the mean and standard deviation of the pretherapy image. The performance of the proposed method was evaluated by Monte Carlo simulation, where XCAT phantoms (128{sup 2} pixels) with lesions of various diameters (2–6 mm), multiple tumor-to-background contrasts (3–10), and different changes in intensity (6.25%–30%) were used. The receiver operating characteristic curves and the corresponding areas under the curve were computed for both the proposed method and the traditional methods whose figure of merit is the percentage change of SUVs. The formula for the false positive rate (FPR) estimation was developed for the proposed therapy response

Qualitative assessment of awake nasopharyngoscopy for prediction of oral appliance treatment response in obstructive sleep apnoea.

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Sutherland, Kate; Chan, Andrew S L; Ngiam, Joachim; Darendeliler, M Ali; Cistulli, Peter A

2018-01-23

Clinical methods to identify responders to oral appliance (OA) therapy for obstructive sleep apnoea (OSA) are needed. Awake nasopharyngoscopy during mandibular advancement, with image capture and subsequent processing and analysis, may predict treatment response. A qualitative assessment of awake nasopharyngoscopy would be simpler for clinical practice. We aimed to determine if a qualitative classification system of nasopharyngoscopic observations reflects treatment response. OSA patients were recruited for treatment with a customised two-piece OA. A custom scoring sheet was used to record observations of the pharyngeal airway (velopharynx, oropharynx, hypopharynx) during supine nasopharyngoscopy in response to mandibular advancement and performance of the Müller manoeuvre. Qualitative scores for degree ( 75%), collapse pattern (concentric, anteroposterior, lateral) and diameter change (uniform, anteroposterior, lateral) were recorded. Treatment outcome was confirmed by polysomnography after a titration period of 14.6 ± 9.8 weeks. Treatment response was defined as (1) Treatment AHI  50% AHI reduction and (3) > 50% AHI reduction. Eighty OSA patients (53.8% male) underwent nasopharyngoscopy. The most common naspharyngoscopic observation with mandibular advancement was a small ( 75% velopharyngeal collapse on performance of the Müller manoeuvre. Mandibular advancement reduced the observed level of pharyngeal collapse at all three pharyngeal regions (p < 0.001). None of the nasopharyngoscopic qualitative scores differed between responder and non-responder groups. Qualitative assessment of awake nasopharyngoscopy appears useful for assessing the effect of mandibular advancement on upper airway collapsibility. However, it is not sensitive enough to predict oral appliance treatment outcome.

Bladder cancer treatment response assessment using deep learning in CT with transfer learning

Science.gov (United States)

Cha, Kenny H.; Hadjiiski, Lubomir M.; Chan, Heang-Ping; Samala, Ravi K.; Cohan, Richard H.; Caoili, Elaine M.; Paramagul, Chintana; Alva, Ajjai; Weizer, Alon Z.

2017-03-01

We are developing a CAD system for bladder cancer treatment response assessment in CT. We compared the performance of the deep-learning convolution neural network (DL-CNN) using different network sizes, and with and without transfer learning using natural scene images or regions of interest (ROIs) inside and outside the bladder. The DL-CNN was trained to identify responders (T0 disease) and non-responders to chemotherapy. ROIs were extracted from segmented lesions in pre- and post-treatment scans of a patient and paired to generate hybrid pre-post-treatment paired ROIs. The 87 lesions from 82 patients generated 104 temporal lesion pairs and 6,700 pre-post-treatment paired ROIs. Two-fold cross-validation and receiver operating characteristic analysis were performed and the area under the curve (AUC) was calculated for the DL-CNN estimates. The AUCs for prediction of T0 disease after treatment were 0.77+/-0.08 and 0.75+/-0.08, respectively, for the two partitions using DL-CNN without transfer learning and a small network, and were 0.74+/-0.07 and 0.74+/-0.08 with a large network. The AUCs were 0.73+/-0.08 and 0.62+/-0.08 with transfer learning using a small network pre-trained with bladder ROIs. The AUC values were 0.77+/-0.08 and 0.73+/-0.07 using the large network pre-trained with the same bladder ROIs. With transfer learning using the large network pretrained with the Canadian Institute for Advanced Research (CIFAR-10) data set, the AUCs were 0.72+/-0.06 and 0.64+/-0.09, respectively, for the two partitions. None of the differences in the methods reached statistical significance. Our study demonstrated the feasibility of using DL-CNN for the estimation of treatment response in CT. Transfer learning did not improve the treatment response estimation. The DL-CNN performed better when transfer learning with bladder images was used instead of natural scene images.

Post-treatment vascular leakage and inflammatory responses around brain cysts in porcine neurocysticercosis.

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Siddhartha Mahanty

2015-03-01

Full Text Available Cysticidal treatment of neurocysticercosis, an infection of humans and pig brains with Taenia solium, results in an early inflammatory response directed to cysts causing seizures and focal neurological manifestations. Treatment-induced pericystic inflammation and its association with blood brain barrier (BBB dysfunction, as determined by Evans blue (EB extravasation, was studied in infected untreated and anthelmintic-treated pigs. We compared the magnitude and extent of the pericystic inflammation, presence of EB-stained capsules, the level of damage to the parasite, expression of genes for proinflammatory and regulatory cytokines, chemokines, and tissue remodeling by quantitative PCR assays between treated and untreated infected pigs and between EB-stained (blue and non stained (clear cysts. Inflammatory scores were higher in pericystic tissues from EB-stained cysts compared to clear cysts from untreated pigs and also from anthelmintic-treated pigs 48 hr and 120 hr after treatment. The degree of inflammation correlated with the severity of cyst wall damage and both increased significantly at 120 hours. Expression levels of the proinflammatory genes for IL-6, IFN-γ, TNF-α were higher in EB-stained cysts compared to clear cysts and unaffected brain tissues, and were generally highest at 120 hr. Additionally, expression of some markers of immunoregulatory activity (IL-10, IL-2Rα were decreased in EB-stained capsules. An increase in other markers for regulatory T cells (CTLA4, FoxP3 was found, as well as significant increases in expression of two metalloproteases, MMP1 and MMP2 at 48 hr and 120 hr post-treatment. We conclude that the increase in severity of the inflammation caused by treatment is accompanied by both a proinflammatory and a complex regulatory response, largely limited to pericystic tissues with compromised vascular integrity. Because treatment induced inflammation occurs in porcine NCC similar to that in human cases, this model

Anti-TNF treatment response in rheumatoid arthritis patients is associated with genetic variation in the NLRP3-inflammasome

DEFF Research Database (Denmark)

Sode, Jacob; Vogel, Ulla; Bank, Steffen

2014-01-01

OBJECTIVE: Many patients with rheumatoid arthritis (RA) benefit from tumor necrosis factor-α blocking treatment (anti-TNF), but about one third do not respond. The objective of this study was to replicate and extend previously found associations between anti-TNF treatment response and genetic...... logistic regression analyses were performed to test associations between genotypes and treatment response at 3-6 months using the European League Against Rheumatism (EULAR) response criterion. American College of Rheumatology treatment response (ACR50) and relative change in 28-joint disease activity score.......36-0.98), p = 0.040, q = 0.76). Current smokers who carried the NLRP3(rs4612666) variant allele were less likely to benefit from anti-TNF treatment (OR = 0.24 (0.10-0.56), p = 0.001, q = 0.04). CONCLUSIONS: In a population of Danish RA patients, we confirm the NLRP3 gene as associated with EULAR anti...

Clinical course and treatment response in patients with thyroid hot nodule

International Nuclear Information System (INIS)

Fard Esfahani, A; Aghayousefi, H.R.; Eftekhari, M.; Fallahi, B.; Saghari, M.

2002-01-01

This is a retrospective study on clinical course and treatment response of patients with thyroid hot nodule, referred to nuclear medicine department of shariaty hospital from 1360 to 1377. From the total 58 patients with average age of 43 year and incidence peak of 40 year, 81 % were female and 19 % were male. 64 % of the patients were thyrotoxic and 36 % were euthyroid at presentation. Thyrotoxic symptoms and signs increased with age (p= 0.04). 57% of patients received I-131 therapy without premedication. 7% received antithyroid drugs first and then underwent iodine therapy. From 36% of the patients who were euthyroid at presentation, 15.5 % became thyrotoxic on follow up studies and received I-131 therapy, but 20.7 % remained euthyroid without receiving andy therapy. The average of first and cumulative radioiodine doses were 16.9 mci and 21.8 mci, respectively. Treatment response during 6 and 12 month follow up were 80 % and 86.7 %, respectively. The more administered the first dose, the better was the response (p= 0.03). Men appeared to need more I-131 dosage and times of therapy as compared to women. Post radioiodine hypothyroidism incidence was 7.5 % during one year follow up. No meaningful relation was found between times of radioiodine therapy and thyroid or nodule size

Strontium-89 in palliative treatment of widespread painful bone metastases: Response rate and duration

International Nuclear Information System (INIS)

Haddad, Peiman; Ghadiri, Farhad

2005-01-01

Full text: Intravenous injection of Strontium-89 (Sr-89) is an accepted palliative treatment for bone metastases. We evaluated the pain relief achieved with this radiopharmaceutical in patients with widespread painful bone metastases from prostate and breast cancers. Pain intensity on a 9-grade scale and use of narcotics was recorded before and after Sr-89 injection, and the ensuing palliative effect was divided into complete, partial and no response. The duration of response was also recorded. Thirty-five patients with widespread painful bone metastases were treated with Sr-89, of whom 22 had prostate and 13 breast cancers. Mean follow-up was 227 days, during which death was recorded for 32 patients. Fourteen patients (40%) had a complete response, 9 (26%) partial and 12 (34%) no response. In the 23 responding patients, mean duration of response was 6 months. In 17 patients the response was present until death. There was no significant relationship between pain response and patients' age or type of primary cancer. No side effects were recorded other than mild and temporary drop in white blood cell and platelet counts. Three patients with a complete response had a second injection of Sr-89 after progression of pain. One of these patients had a second partial response; the other 2 did not show a response to the second injection. The use of Sr-89 for treatment of widespread painful bone metastases from prostate and breast cancers in our department showed a 66% rate of response and a mean response duration of 6 months, with no significant side effects. (author)

Effect of nabumetone treatment on vascular responses of the thoracic aorta in rat experimental arthritis.

Science.gov (United States)

Ulker, S; Onal, A; Hatip, F B; Sürücü, A; Alkanat, M; Koşay, S; Evinç, A

2000-04-01

Nabumetone is a nonsteroidal anti-inflammatory (NSAI) drug which is known to cause less gastrointestinal damage than other NSAI drugs. This study was performed to evaluate whether nabumetone treatment might alter the vascular aberrations related to inflammation in a rat model of adjuvant-induced arthritis. Nabumetone treatment (120 or 240 mg x kg(-1) x day(-1), orally) was initiated on the 15th day of adjuvant inoculation and continued for 14 days. Arthritic lesions, vascular contractile and relaxant responses and gastroduodenal histopathological preparations were evaluated 29 days after adjuvant inoculation. The contractile responses of aortic rings to phenylephrine and KCl were increased in grade 2 arthritic rats. In grade 3 arthritis only the phenylephrine contractility was decreased. The relaxant responses to acetylcholine and sodium nitroprusside were decreased in grades 2 and 3. In healthy rats, nabumetone did not change the vascular responses. After treatment of arthritic rats with nabumetone, both the contractile and relaxant response of the aortic rings returned to normal, and arthritic score and paw swelling were reduced. Gastroduodenal histopathology did not show erosions or ulcers in any of the groups. In conclusion, nabumetone improved the systemic signs and vascular alterations in experimental arthritis without showing any gastrointestinal side effects. Copyright 2000 S. Karger AG, Basel.

Treatment of chronic myeloid leukemia: assessing risk, monitoring response, and optimizing outcome.

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Shanmuganathan, Naranie; Hiwase, Devendra Keshaorao; Ross, David Morrall

2017-12-01

Over the past two decades, tyrosine kinase inhibitors have become the foundation of chronic myeloid leukemia (CML) treatment. The choice between imatinib and newer tyrosine kinase inhibitors (TKIs) needs to be balanced against the known toxicity and efficacy data for each drug, the therapeutic goal being to maximize molecular response assessed by BCR-ABL RQ-PCR assay. There is accumulating evidence that the early achievement of molecular targets is a strong predictor of superior long-term outcomes. Early response assessment provides the opportunity to intervene early with the aim of ensuring an optimal response. Failure to achieve milestones or loss of response can have diverse causes. We describe how clinical and laboratory monitoring can be used to ensure that each patient is achieving an optimal response and, in patients who do not reach optimal response milestones, how the monitoring results can be used to detect resistance and understand its origins.

Posterior urethral injuries associated with pelvic injuries in young adults: computerized finite element model creation and application to improve knowledge and prevention of these lesions.

Science.gov (United States)

Bréaud, J; Baqué, P; Loeffler, J; Colomb, F; Brunet, C; Thollon, L

2012-05-01

Young adult males involved in motorcycle accidents are particularly at risk for posterior urethral injury whenever pelvic injury occurs. Posterior urethral injuries remain problematic because their diagnosis may be missed, and during the initial treatment response the urethral injury can be aggravated by urethral catheterization. Few anatomical and clinical tools exist that establish a correlation between injuries and fractures of the pelvic ring and the risk of posterior urethral injury. Based on experience with traffic accident modeling, a computerized finite element model was conceived integrating the specific anatomic structures concerned. This model was extrapolated from a CAT scan of a young adult. The anatomic structures concerned in urethral and pelvic ring trauma (PRT) were isolated, placed in 3D and given biomechanical properties. The model was verified according to available experiments on PRT. To apply the model, we recreated a lateral impact mechanism on the pelvic ring. Stretching between the prostatic and membranous portions of the urethra (before and after visualization of a pelvic fracture) as well as timing of injury was studied. The model's application permitted us to analyze precisely the link between lateral impact trauma of the pelvic ring and lesions of the posterior urethra and to identify an urethra stretching prior to visualization of a pelvic fracture. Utilization of the model with other mechanisms of injury should allow for better comprehension of this associated trauma, improved prevention, iatrogenic aggravation of, and care for, these serious injuries. © Springer-Verlag 2011

Identifying a predictive model for response to atypical antipsychotic monotherapy treatment in south Indian schizophrenia patients.

Science.gov (United States)

Gupta, Meenal; Moily, Nagaraj S; Kaur, Harpreet; Jajodia, Ajay; Jain, Sanjeev; Kukreti, Ritushree

2013-08-01

Atypical antipsychotic (AAP) drugs are the preferred choice of treatment for schizophrenia patients. Patients who do not show favorable response to AAP monotherapy are subjected to random prolonged therapeutic treatment with AAP multitherapy, typical antipsychotics or a combination of both. Therefore, prior identification of patients' response to drugs can be an important step in providing efficacious and safe therapeutic treatment. We thus attempted to elucidate a genetic signature which could predict patients' response to AAP monotherapy. Our logistic regression analyses indicated the probability that 76% patients carrying combination of four SNPs will not show favorable response to AAP therapy. The robustness of this prediction model was assessed using repeated 10-fold cross validation method, and the results across n-fold cross-validations (mean accuracy=71.91%; 95%CI=71.47-72.35) suggest high accuracy and reliability of the prediction model. Further validations of these results in large sample sets are likely to establish their clinical applicability. Copyright © 2013 Elsevier Inc. All rights reserved.

Anxiety, stress, depression, and patients' responses to periodontal treatment: periodontists' knowledge and professional behavior.

Science.gov (United States)

Kloostra, Paul W; Eber, Robert M; Inglehart, Marita Rohr

2007-01-01

Anxiety, stress, and depression affect the use of health care services, treatment decision-making, and responses to periodontal treatment. This study explored periodontists' confidence in detecting patient anxiety, stress, or depression, as well as their knowledge concerning the relationships between these factors and patients' pain, use of pain medication, and wound healing after periodontal treatment. In addition, this research surveyed if (and which) special accommodations were offered when treating patients with high levels of anxiety, stress, or depression. Data were collected from 171 members of the American Academy of Periodontology (response rate = 34.41%). Most respondents were male (82.2%), white (88.2%), and practiced in solo practices (60.9%). The respondents were more knowledgeable about the effects of anxiety and stress on pain, the use of pain medication, and wound healing than about the impact of depression on these outcomes. They agreed more strongly with statements that they were more confident in their ability to perceive when patients were anxious and stressed than when they were depressed. They also offered more special accommodations for patients with anxiety and stress than for patients with depression. The respondents were significantly less knowledgeable about the impact of depression on patients' responses to periodontal treatment than about the effect of anxiety and stress. Given the evidence concerning the relationships among depression, pain, pain medication use, and wound healing, it is important to educate periodontists about the role of anxiety and stress and the significance of depression on their patients' responses to periodontal therapy.

Impact of the Definition of Peak Standardized Uptake Value on Quantification of Treatment Response

Science.gov (United States)

Vanderhoek, Matt; Perlman, Scott B.; Jeraj, Robert

2012-01-01

PET-based treatment response assessment typically measures the change in maximum standardized uptake value (SUVmax), which is adversely affected by noise. Peak SUV (SUVpeak) has been recommended as a more robust alternative, but its associated region of interest (ROIpeak) is not uniquely defined. We investigated the impact of different ROIpeak definitions on quantification of SUVpeak and tumor response. Methods Seventeen patients with solid malignancies were treated with a multitargeted receptor tyrosine kinase inhibitor resulting in a variety of responses. Using the cellular proliferation marker 3′-deoxy-3′-18F-fluorothymidine (18F-FLT), whole-body PET/CT scans were acquired at baseline and during treatment. 18F-FLT–avid lesions (~2/patient) were segmented on PET images, and tumor response was assessed via the relative change in SUVpeak. For each tumor, 24 different SUVpeaks were determined by changing ROIpeak shape (circles vs. spheres), size (7.5–20 mm), and location (centered on SUVmax vs. placed in highest-uptake region), encompassing different definitions from the literature. Within each tumor, variations in the 24 SUVpeaks and tumor responses were measured using coefficient of variation (CV), standardized deviation (SD), and range. For each ROIpeak definition, a population average SUVpeak and tumor response were determined over all tumors. Results A substantial variation in both SUVpeak and tumor response resulted from changing the ROIpeak definition. The variable ROIpeak definition led to an intratumor SUVpeak variation ranging from 49% above to 46% below the mean (CV, 17%) and an intratumor SUVpeak response variation ranging from 49% above to 35% below the mean (SD, 9%). The variable ROIpeak definition led to a population average SUVpeak variation ranging from 24% above to 28% below the mean (CV, 14%) and a population average SUVpeak response variation ranging from only 3% above to 3% below the mean (SD, 2%). The size of ROIpeak caused more

Targeted Proteomics to Assess the Response to Anti-Angiogenic Treatment in Human Glioblastoma (GBM).

Science.gov (United States)

Demeure, Kevin; Fack, Fred; Duriez, Elodie; Tiemann, Katja; Bernard, Amandine; Golebiewska, Anna; Bougnaud, Sébastien; Bjerkvig, Rolf; Domon, Bruno; Niclou, Simone P

2016-02-01

Glioblastoma (GBM) is a highly aggressive primary brain tumor with dismal outcome for affected patients. Because of the significant neo-angiogenesis exhibited by GBMs, anti-angiogenic therapies have been intensively evaluated during the past years. Recent clinical studies were however disappointing, although a subpopulation of patients may benefit from such treatment. We have previously shown that anti-angiogenic targeting in GBM increases hypoxia and leads to a metabolic adaptation toward glycolysis, suggesting that combination treatments also targeting the glycolytic phenotype may be effective in GBM patients. The aim of this study was to identify marker proteins that are altered by treatment and may serve as a short term readout of anti-angiogenic therapy. Ultimately such proteins could be tested as markers of efficacy able to identify patient subpopulations responsive to the treatment. We applied a proteomics approach based on selected reaction monitoring (SRM) to precisely quantify targeted protein candidates, selected from pathways related to metabolism, apoptosis and angiogenesis. The workflow was developed in the context of patient-derived intracranial GBM xenografts developed in rodents and ensured the specific identification of human tumor versus rodent stroma-derived proteins. Quality control experiments were applied to assess sample heterogeneity and reproducibility of SRM assays at different levels. The data demonstrate that tumor specific proteins can be precisely quantified within complex biological samples, reliably identifying small concentration differences induced by the treatment. In line with previous work, we identified decreased levels of TCA cycle enzymes, including isocitrate dehydrogenase, whereas malectin, calnexin, and lactate dehydrogenase A were augmented after treatment. We propose the most responsive proteins of our subset as potential novel biomarkers to assess treatment response after anti-angiogenic therapy that warrant future

Effect of previous exposure to hbv on liver histology and treatment response in chc patients

International Nuclear Information System (INIS)

Khan, H.A.

2015-01-01

Objective: To analyze the influence of previous exposure to HBV on liver histology and treatment outcomes in chronic hepatitis C (CHC) patients. Study Design: Case control study. Place and Duration of Study: Rawalian Liver Clinic, Department of Medicine, Holy Family Hospital, Rawalpindi, from January 2011 to December 2012. Methodology: Medical records of CHC patients attending the Rawalian Liver Clinic were retrospectively analyzed. Virological and treatment responses along with histological changes were compared between cases (anti-HBc positive) and controls (anti-HBc negative). Significance was determined through chi-square test at p < 0.05. Results: Among the 592 CHC patients, 254 (42.9%) had serological evidence of a positive anti-HBc (cases) and 338 (57.1%), patients had negative anti-HBc (controls). No significant difference was found between ETR, SVR and treatment responses (n=220) between the two groups. Out of 65 patients whose liver biopsy data was available, cases were more likely to respond in the absence of fibrosis (63.2%, (n=24) vs. 36.8%, (n=14), p=0.001). The controls responded more in the presence of fibrosis (100% (n=9) vs. 0, p=0.001). There was no significant effect of anti-HBc positivity on grades of inflammation and consequent treatment response (p=0.14). Conclusion: There are a significant number of CHC patients with markers of previous HBV infection in Pakistani population. Previous HBV (anti-HBc positive) does not seem to have an adverse effect on liver histology and treatment responses in HBV infection. (author)

Gender effects on treatment response to interferon-beta in multiple sclerosis

DEFF Research Database (Denmark)

Magyari, M; Koch-Henriksen, N; Laursen, B

2014-01-01

BACKGROUND: Gender appears to play a role in incidence and disease course of multiple sclerosis (MS). OBJECTIVE: The objective was to determine whether male and female patients with MS respond differently to interferon-beta treatment in terms of reduction in relapse rates. METHODS: We included all....... Patients served as their own controls, and relapse rates were compared between NAb-negative and NAb-positive periods. RESULTS: NAbs significantly abrogated the interferon-beta treatment efficacy in both genders. The all-over women:men relapse rate ratio irrespective of NAb status was 1.47 (95%CI; 1.......28-1.68). In a generalized linear Poisson models analysis with relapse counts as response variable, the main effects NAbs, sex, age at treatment start and number of relapses in 2 years before treatment start were strongly significant, but the effect of NAbs on relapse rates did not differ significantly between men and women...

Response to standard interferon A2b and ribavirin combination therapy in chronic hepatitis C treatment naive patients

International Nuclear Information System (INIS)

Jadoon, S.M.K.; Muhammad, I.

2010-01-01

Background: Treatment of Chronic Hepatitis C is now well established with conventional interferon or pegylated interferon in combination with ribavirin. Peginterferon Alfa and Ribavirin for 6 to 12 months is currently approved initial therapy, which is expensive. Response of our patients to standard Interferon-alpha-2b and ribavirin for 24 weeks have been studied. The objective of this study was to asses Sustained Viral Response (SVR) with standard Interferon A2b and Ribavirin combination treatment in chronic Hepatitis C patients. Methods: This quasi-experimental study was conducted at Combined Military Hospital, Quetta from Jan 2006 to Jun 2007. One hundred and three patients, with 20-60 years of age suffering from chronic Hepatitis C were selected on the basis of raised ALT, positive anti-HCV antibodies, evidence of viraemia by quantitative PCR for HCV RNA and liver biopsy. All patients were started on same brand of Interferon alpha-2b, 3 MIU subcutaneously, thrice weekly and oral Ribavirin (1,000-1,200 mg/day) for 24 weeks. End treatment response (ETR) after completion of treatment and SVR six months after ETR were recorded. Results: The 103 patients, 85 males and 18 females with mean age of 21-48 years completed the treatment for 24 weeks. Mean ALT was 96.17 (SD +- 49.98). End treatment response (ETR) was 89.3% (p=0.032). Sustained Viral Response after 6 months of treatment was 86.4% (p=0.034). Conclusion: Standard Interferon and Ribavirin had excellent SVR. It is effective as well as economical treatment in Chronic Hepatitis C patients. (author)

Addressing the risk of bacterial contamination in platelets: a hospital economic perspective.

Science.gov (United States)

Li, Justin W; Brecher, Mark E; Jacobson, Jessica L; Harm, Sarah K; Chen, Dorothy; El-Gamil, Audrey; Dobson, Al; Mintz, Paul D

2017-10-01

Bacterially contaminated platelets (PLTs) remain a serious risk. The Food and Drug Administration has issued draft guidance recommending hospitals implement secondary testing or transfuse PLTs that have been treated with pathogen reduction technology (PRT). The cost implications of these approaches are not well understood. We modeled incurred costs when hospitals acquire, process, and transfuse PLTs that are PRT treated with INTERCEPT (Cerus Corp.) or secondary tested with the PLT PGD Test (Verax Biomedical). Hospitals will spend $221.27 (30.0%) more per PRT-treated apheresis PLT unit administered compared to a Zika-tested apheresis PLT unit that is irradiated and PGD tested in hospital. This difference is reflected in PRT PLT units having: 1) a higher hospital purchase price ($100.00 additional charge compared to an untreated PLT); 2) lower therapeutic effectiveness than untreated PLTs among hematologic-oncologic patients, which contributes to additional transfusions ($96.05); or 3) fewer PLT storage days, which contributes to higher outdating cost from expired PLTs ($67.87). Only a small portion of the incremental costs for PRT-treated PLTs are offset by costs that may be avoided, including primary bacterial culture, secondary bacterial testing ($26.65), hospital irradiation ($8.50), Zika testing ($4.47), and other costs ($3.03). The significantly higher cost of PRT-treated PLTs over PGD-tested PLTs should interest stakeholders. For hospitals that outdate PLTs, savings associated with expiration extension to 7 days by adding PGD testing will likely be substantially greater than the cost of implementing PGD-testing. Our findings might usefully inform a hospital's decision to select a particular blood safety approach. © 2017 The Authors Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.

Lower limb progressive resistance training improves leg strength but not gait speed or balance in Parkinson's disease: a systematic review and meta-analysis.

Science.gov (United States)

Tillman, Alex; Muthalib, Makii; Hendy, Ashlee M; Johnson, Liam G; Rantalainen, Timo; Kidgell, Dawson J; Enticott, Peter G; Teo, Wei-Peng

2015-01-01

The use of progressive resistance training (PRT) to improve gait and balance in people with Parkinson's disease (PD) is an emerging area of interest. However, the main effects of PRT on lower limb functions such as gait, balance, and leg strength in people with PD remain unclear. Therefore, the aim of the meta-analysis is to evaluate the evidence surrounding the use of PRT to improve gait and balance in people with PD. Five electronic databases, from inception to December 2014, were searched to identify the relevant studies. Data extraction was performed by two independent reviewers and methodological quality was assessed using the PEDro scale. Standardized mean differences (SMD) and 95% confidence intervals (CIs) of fixed and random effects models were used to calculate the effect sizes between experimental and control groups and I (2) statistics were used to determine levels of heterogeneity. In total, seven studies were identified consisting of 172 participants (experimental n = 84; control n = 88). The pooled results showed a moderate but significant effect of PRT on leg strength (SMD 1.42, 95% CI 0.464-2.376); however, no significant effects were observed for gait speed (SMD 0.418, 95% CI -0.219 to 1.055). No significant effects were observed for balance measures included in this review. In conclusion, our results showed no discernable effect of PRT on gait and balance measures, although this is likely due to the lack of studies available. It may be suggested that PRT be performed in conjunction with balance or task-specific functional training to elicit greater lower limb functional benefits in people with PD.

Lower Limb Progressive Resistance Training Improves Leg Strength but Not Gait Speed or Balance in Parkinson’s Disease: A Systematic Review and Meta-Analysis

Science.gov (United States)

Tillman, Alex; Muthalib, Makii; Hendy, Ashlee M.; Johnson, Liam G.; Rantalainen, Timo; Kidgell, Dawson J.; Enticott, Peter G.; Teo, Wei-Peng

2015-01-01

The use of progressive resistance training (PRT) to improve gait and balance in people with Parkinson’s disease (PD) is an emerging area of interest. However, the main effects of PRT on lower limb functions such as gait, balance, and leg strength in people with PD remain unclear. Therefore, the aim of the meta-analysis is to evaluate the evidence surrounding the use of PRT to improve gait and balance in people with PD. Five electronic databases, from inception to December 2014, were searched to identify the relevant studies. Data extraction was performed by two independent reviewers and methodological quality was assessed using the PEDro scale. Standardized mean differences (SMD) and 95% confidence intervals (CIs) of fixed and random effects models were used to calculate the effect sizes between experimental and control groups and I2 statistics were used to determine levels of heterogeneity. In total, seven studies were identified consisting of 172 participants (experimental n = 84; control n = 88). The pooled results showed a moderate but significant effect of PRT on leg strength (SMD 1.42, 95% CI 0.464–2.376); however, no significant effects were observed for gait speed (SMD 0.418, 95% CI −0.219 to 1.055). No significant effects were observed for balance measures included in this review. In conclusion, our results showed no discernable effect of PRT on gait and balance measures, although this is likely due to the lack of studies available. It may be suggested that PRT be performed in conjunction with balance or task-specific functional training to elicit greater lower limb functional benefits in people with PD. PMID:25852550

[Intramuscular depot steroids : Possible treatment of postsurgical cystoid macula edema with steroid response?

Science.gov (United States)

Seuthe, A-M; Szurman, P; Boden, K T

2017-11-01

We report on a patient with postsurgical cystoid macular edema (CME) after phacoemulsification and multifocal intraocular lens (MIOL) implantation. At first, there was a very good reaction to intravitreal triamcinolone, inducing complete regression of the edema without increasing intraocular pressure (IOP). One year later the patient suffered from retinal detachment and was treated with vitrectomy, laser, and gas tamponade. Afterward, he developed macular pucker with edema. After surgical treatment with pucker peeling and intravitreal triamcinolone, the patient showed a steroid response and an increase IOP. Postoperatively, there was a recurrence of CME. A coincidental administration of a steroid injection intramuscularly by the general practitioner achieved a prompt reduction of the CME without increasing IOP. This case shows that an initially good reaction to triamcinolone without increasing IOP does not rule out a future steroid response, and that a potential treatment option for CME in patients with a known steroid response could consist of intramuscularly injected steroids.

Omitting cytogenetic assessment from routine treatment response monitoring in chronic myeloid leukemia is safe.

Science.gov (United States)

Geelen, Inge G P; Thielen, Noortje; Janssen, Jeroen J W M; Hoogendoorn, Mels; Roosma, Tanja J A; Valk, Peter J M; Visser, Otto; Cornelissen, Jan J; Westerweel, Peter E

2018-04-01

The monitoring of response in chronic myeloid leukemia (CML) is of great importance to identify patients failing their treatment in order to adjust TKI choice and thereby prevent progression to advanced stage disease. Cytogenetic monitoring has a lower sensitivity, is expensive, and requires invasive bone marrow sampling. Nevertheless, chronic myeloid leukemia guidelines continue to recommend performing routine cytogenetic response assessments, even when adequate molecular diagnostics are available. In a population-based registry of newly diagnosed CML patients in the Netherlands, all simultaneous cytogenetic and molecular assessments performed at 3, 6, and 12 months were identified and response of these matched assessments was classified according to European Leukemia Net (ELN) recommendations. The impact of discrepant cytogenetic and molecular response classifications and course of patients with additional chromosomal abnormalities were evaluated. The overall agreement of 200 matched assessments was 78%. In case of discordant responses, response at 24 months was consistently better predicted by the molecular outcome. Cytogenetic response assessments provided relevant additional clinical information only in some cases of molecular "warning." The development of additional cytogenetic abnormalities was always accompanied with molecular failure. We conclude that it is safe to omit routine cytogenetics for response assessment during treatment and to only use molecular monitoring, in order to prevent ambiguous classifications, reduce costs, and reduce the need for invasive bone marrow sampling. Cytogenetic re-assessment should still be performed when molecular response is suboptimal. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A Model for Spheroid versus Monolayer Response of SK-N-SH Neuroblastoma Cells to Treatment with 15-Deoxy-PGJ2

Directory of Open Access Journals (Sweden)

Dorothy I. Wallace

2016-01-01

Full Text Available Researchers have observed that response of tumor cells to treatment varies depending on whether the cells are grown in monolayer, as in vitro spheroids or in vivo. This study uses data from the literature on monolayer treatment of SK-N-SH neuroblastoma cells with 15-deoxy-PGJ2 and couples it with data on growth rates for untreated SK-N-SH neuroblastoma cells grown as multicellular spheroids. A linear model is constructed for untreated and treated monolayer data sets, which is tuned to growth, death, and cell cycle data for the monolayer case for both control and treatment with 15-deoxy-PGJ2. The monolayer model is extended to a five-dimensional nonlinear model of in vitro tumor spheroid growth and treatment that includes compartments of the cell cycle (G1,S,G2/M as well as quiescent (Q and necrotic (N cells. Monolayer treatment data for 15-deoxy-PGJ2 is used to derive a prediction of spheroid response under similar treatments. For short periods of treatment, spheroid response is less pronounced than monolayer response. The simulations suggest that the difference in response to treatment of monolayer versus spheroid cultures observed in laboratory studies is a natural consequence of tumor spheroid physiology rather than any special resistance to treatment.

Predictors of response to radio-embolization (TheraSphere®) treatment of neuroendocrine liver metastasis.

Science.gov (United States)

Shaheen, Mohammed; Hassanain, Mazen; Aljiffry, Murad; Cabrera, Tatiana; Chaudhury, Prosanto; Simoneau, Eve; Kongkaewpaisarn, Nuttawut; Salman, Ayat; Rivera, Juan; Jamal, Mohammad; Lisbona, Robert; Khankan, Azzam; Valenti, David; Metrakos, Peter

2012-01-01

Neuroendocrine tumours (NET) frequently metastasize to the liver. NET liver metastasis has been shown to respond to Yttrium-90 microspheres therapy. The aims of the present study were to define factors that predict the response to radio-embolization in patients with NET liver metastases. From January 2006 until March 2009, all patients with NET liver metastasis that received radio-embolization using TheraSphere® (glass microspheres) were reviewed. The response was determined by a change in the percentage of necrosis (ΔN%) after the first radio-embolization based on the modified RECIST criteria (mRECIST) criteria. The following confounding variables were measured: age, gender, size of the lesions, liver involvement, World Health Organization (WHO) classification, the presence of extra-hepatic metastasis, octereotide treatment and previous operative [surgery and (RFA)] and non-operative treatments (chemo-embolization and bland-embolization). In all, 25 patients were identified, with a median follow-up of 21.7 months. The median age was 64.6 years, 28% had extra-hepatic metastasis and 56% were WHO stage 2. Post-treatment, the mean ΔN% was 48.4%. Previous surgical therapy was a significant predictor of the response with a response rate of 66.7 ΔN% vs. 31.5 ΔN% (P= 0.02). Bilateral liver disease, a high percentage of liver involvement and large metastatic lesions were inversely related to the degree of tumour response although did not reach statistical significance. Radio-embolization increased the necrosis of NET liver metastasis mainly in patients with less bulky disease. This may imply that surgical therapy before radio-embolization would increase the response rates. © 2011 International Hepato-Pancreato-Biliary Association.

Clinical and clinicopathologic response of canine bone tumor patients to treatment with samarium-153-EDTMP

International Nuclear Information System (INIS)

Lattimer, J.C.; Corwin, L.A. Jr.; Stapleton, J.; Volkert, W.A.; Ehrhardt, G.J.; Ketring, A.R.; Anderson, S.K.; Simon, J.; Goeckeler, W.F.

1990-01-01

Forty dogs with spontaneous skeletal neoplasia were treated with 153Sm-EDTMP (ethylenediaminetetramethylene phosphonic acid). Both primary and metastatic lesions were treated. Two treatment regimes, a single (37 MBq (1.0 mCi)/kg dose or two 37 MBq (1.0 mCi)/kg doses separated by 1 wk) were tested. Response to treatment was varied. Large lesions with minimal tumor bone formation responded poorly, while primary lesions with substantial ossification usually exhibited a transient response. Small lesions with minimal lysis, metastatic lesions, and axial skeleton lesions generally responded well. The major adverse side effects of treatment were platelet and white blood cell count depression below baseline values for up to 4 wk (p less than 0.05). Minor depression of packed cell volume and transient elevation of serum alkaline phosphatase were also noted (p less than 0.05). No significant differences (p greater than 0.05) between the two treatment groups, either in treatment effect or undesirable side effects, were detected

Paradoxical response during antituberculous treatment for abdominal tuberculosis

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Kim, Ji Young; Kwon, Jung Hyeok; Kim, Mi Jeong; Chang, Hyuk Won; Hwang, Jae Seok; Cho, Kwang Bum; Park, Kyung Sik; Jang, Byoung Kuk; Chung, Woo Jin [Dongsan Medical Center, Keimyung University School of Medicine, Daegu (Korea, Republic of)

2006-12-15

The purpose of our study was to evaluate clinical and CT findings of paradoxical response during treatment for abdominal tuberculosis. Authors reviewed the patient records of 138 patients with abdominal tuberculosis during a recent 6-year period and we selected 11 patients with a paradoxical response. The CT findings and pathologic findings of the initial lesions and new lesions were reviewed. The intervals between initiation of therapy and the detection of new lesions, improvement of new lesion and the final follow-up were evaluated. At the initial presentation, we identified tuberculous peritonitis in 8 patients, tuberculous lymphadenitis in 3 patients and ileocolic tuberculosis in two patients. New lesions were identified at 2-10 months (mean: 3.8 months) after the initiation of therapy and following improvement of the initial lesions. The new lesions were perihepatic caseous abscess (n=4), hepatic tuberculoma (n=3), hepatic caseous abscess (n=1), tuberculous lymphadenitis (n=3), ileocolic tuberculosis (n=3), and splenic tuberculoma (n=1). Improvement of new lesions was noted at 4-14 months (mean: 7.6 months). At the final follow-up of seven patients, the new lesions disappeared and four patients still had small residual lesions. New lesions that develop in a patient with initial improvement should be considered a paradoxical response that will ultimately improve with continuation of the original medication.

Paradoxical response during antituberculous treatment for abdominal tuberculosis

International Nuclear Information System (INIS)

Kim, Ji Young; Kwon, Jung Hyeok; Kim, Mi Jeong; Chang, Hyuk Won; Hwang, Jae Seok; Cho, Kwang Bum; Park, Kyung Sik; Jang, Byoung Kuk; Chung, Woo Jin

2006-01-01

The purpose of our study was to evaluate clinical and CT findings of paradoxical response during treatment for abdominal tuberculosis. Authors reviewed the patient records of 138 patients with abdominal tuberculosis during a recent 6-year period and we selected 11 patients with a paradoxical response. The CT findings and pathologic findings of the initial lesions and new lesions were reviewed. The intervals between initiation of therapy and the detection of new lesions, improvement of new lesion and the final follow-up were evaluated. At the initial presentation, we identified tuberculous peritonitis in 8 patients, tuberculous lymphadenitis in 3 patients and ileocolic tuberculosis in two patients. New lesions were identified at 2-10 months (mean: 3.8 months) after the initiation of therapy and following improvement of the initial lesions. The new lesions were perihepatic caseous abscess (n=4), hepatic tuberculoma (n=3), hepatic caseous abscess (n=1), tuberculous lymphadenitis (n=3), ileocolic tuberculosis (n=3), and splenic tuberculoma (n=1). Improvement of new lesions was noted at 4-14 months (mean: 7.6 months). At the final follow-up of seven patients, the new lesions disappeared and four patients still had small residual lesions. New lesions that develop in a patient with initial improvement should be considered a paradoxical response that will ultimately improve with continuation of the original medication

Genotype distribution and treatment response among incarcerated drug-dependent patients with chronic hepatitis C infection.

Directory of Open Access Journals (Sweden)

Chun-Han Cheng

Full Text Available The prevalence of hepatitis C virus (HCV infection is disproportionately high among prisoners, especially among those who are drug-dependent. However, current screening and treatment recommendations are inconsistent for this population, and appropriate care is not reliably provided. To address these problems, the present study aimed to identify unique characteristics and clinical manifestations of incarcerated patients with HCV infection. We included incarcerated patients who received treatment with pegylated-interferon combined with ribavirin at Mackay Memorial Hospital in Taitung and were serving sentences at either the Taiyuan Skill Training Institute or the Yanwan Training Institute. HCV genotypes 1 (41.4%, 3 (25.9%, and 6 (24.1% were the most prevalent in the incarcerated patients. During the study period, we analyzed treatment response among 58 incarcerated patients and compared obtained results with treatment response among 52 patients who were living in the community. Higher sustained virological response rate was observed among patients with incarceration and HCV genotype other than 1. The odds ratios (corresponding 95% confidence intervals for incarceration and genotype 1 were 2.75 (1.06-7.11 and 0.37 (0.14-0.99, respectively. Better treatment compliance among incarcerated patients might partially explain these results. The results of this study suggest that treatment of prisoners with HCV infection is feasible and effective. More appropriate and timely methods are needed to prevent HCV transmission among injection drug users inside prisons.

Ship motion effects in CTD-data from weakly stratified waters of the Puerto Rico trench

NARCIS (Netherlands)

van Haren, H.

2015-01-01

Shipborne SBE 911plus Conductivity Temperature Depth (CTD)-casts have been made to maximum 7220 m in the Puerto Rico Trench (PRT). In PRT-waters from 5500 m and deeper and specifically below the 6500 m transition to the hadal-zone, the vertical density stratification is found very weak, with

Antecedents and Consequences of Parental Rights Termination for Abused and Neglected Children.

Science.gov (United States)

Borgman, Robert

1981-01-01

This study of 29 adopted children examines the consequences of parental rights termination (PRT) for neglected or abused children in relation to antecedent characteristics of children, parents, and circumstances in the foster care process. Suggests alternative plans for children whose PRT has not been followed by permanent adoptive placement.…

Dexamethasone-suppressed cortisol awakening response predicts treatment outcome in posttraumatic stress disorder

NARCIS (Netherlands)

Nijdam, M. J.; van Amsterdam, J. G. C.; Gersons, B. P. R.; Olff, M.

2015-01-01

Posttraumatic stress disorder (PTSD) has been associated with several alterations in the neuroendocrine system, including enhanced cortisol suppression in response to the dexamethasone suppression test. The aim of this study was to examine whether specific biomarkers of PTSD predict treatment

Chronic nailbiting: a controlled comparison of competing response and mild aversion treatments.

Science.gov (United States)

Allen, K W

1996-03-01

Recent studies have suggested that competing response, an abridged version of Azrin and Nunn's (1973) habit reversal method (Behaviour Research and Therapy, 11, 619-628), is a key component in the treatment of chronic nailbiting (Horne & Wilkinson, 1980, Behaviour Research and Therapy, 18, 287-291; Silber & Haynes, 1992, Behaviour Research and Therapy, 30, 15-22). This study replicated and extended the latter by adding an 8 week follow-up period and by using a non-student sample. Forty-five chronic nailbiter Ss were divided into three experimental groups. One method involved the use of mild aversion in which Ss painted a bitter substance on their nails. A second method required the subject to perform a competing response whenever they had the urge to nailbite or found themselves biting their nails. Both methods included self-monitoring of the behaviour and a third group of Ss performed self-monitoring alone as a control condition. The study lasted 12 weeks. Mild aversion resulted in significant improvements in nail length, with the competing response method just failing to show significance in this regard. There was no significant improvement for the control group. The implications for further study and the benefits of competing response in the light of these findings are discussed in terms of treatment success and use of therapist time.

Clinical and histological responses of congenital melanocytic nevi after single treatment with Q-switched lasers

NARCIS (Netherlands)

Grevelink, JM; vanLeeuwen, RL; Anderson, RR; Byers, HR

Background: Laser irradiation of congenital melanocytic nevi is a controversial treatment. Recurrence of lesions after laser treatment appears to be the rule, and the effects of laser irradiation on cellular biological behavior and the possible mutagenic responses of nevomelanocytes that have

Discriminate the response of Acute Myeloid Leukemia patients to treatment by using proteomics data and Answer Set Programming.

Science.gov (United States)

Chebouba, Lokmane; Miannay, Bertrand; Boughaci, Dalila; Guziolowski, Carito

2018-03-08

During the last years, several approaches were applied on biomedical data to detect disease specific proteins and genes in order to better target drugs. It was shown that statistical and machine learning based methods use mainly clinical data and improve later their results by adding omics data. This work proposes a new method to discriminate the response of Acute Myeloid Leukemia (AML) patients to treatment. The proposed approach uses proteomics data and prior regulatory knowledge in the form of networks to predict cancer treatment outcomes by finding out the different Boolean networks specific to each type of response to drugs. To show its effectiveness we evaluate our method on a dataset from the DREAM 9 challenge. The results are encouraging and demonstrate the benefit of our approach to distinguish patient groups with different response to treatment. In particular each treatment response group is characterized by a predictive model in the form of a signaling Boolean network. This model describes regulatory mechanisms which are specific to each response group. The proteins in this model were selected from the complete dataset by imposing optimization constraints that maximize the difference in the logical response of the Boolean network associated to each group of patients given the omic dataset. This mechanistic and predictive model also allow us to classify new patients data into the two different patient response groups. We propose a new method to detect the most relevant proteins for understanding different patient responses upon treatments in order to better target drugs using a Prior Knowledge Network and proteomics data. The results are interesting and show the effectiveness of our method.

Globally Efficient Brain Organization and Treatment Response in Psychosis: A Connectomic Study of Gyrification.

Science.gov (United States)

Palaniyappan, Lena; Marques, Tiago Reis; Taylor, Heather; Mondelli, Valeria; Reinders, A A T Simone; Bonaccorso, Stefania; Giordano, Annalisa; DiForti, Marta; Simmons, Andrew; David, Anthony S; Pariante, Carmine M; Murray, Robin M; Dazzan, Paola

2016-11-01

Converging evidence suggests that patients with first-episode psychosis who show a poor treatment response may have a higher degree of neurodevelopmental abnormalities than good Responders. Characterizing the disturbances in the relationship among brain regions (covariance) can provide more information on neurodevelopmental integrity than searching for localized changes in the brain. Graph-based connectomic approach can measure structural covariance thus providing information on the maturational processes. We quantified the structural covariance of cortical folding using graph theory in first-episode psychosis, to investigate if this systems-level approach would improve our understanding of the biological determinants of outcome in psychosis. Magnetic Resonance Imaging data were acquired in 80 first-episode psychosis patients and 46 healthy controls. Response to treatment was assessed after 12 weeks of naturalistic follow-up. Gyrification-based connectomes were constructed to study the maturational organization of cortical folding. Nonresponders showed a reduction in the distributed relationship among brain regions (high segregation, poor integration) when compared to Responders and controls, indicating a higher burden of aberrant neurodevelopment. They also showed reduced centrality of key regions (left insula and anterior cingulate cortex) indicating a marked reconfiguration of gyrification. Nonresponders showed a vulnerable pattern of covariance that disintegrated when simulated lesions removed high-degree hubs, indicating an abnormal dependence on highly central hub regions in Nonresponders. These findings suggest that a perturbed maturational relationship among brain regions underlies poor treatment response in first-episode psychosis. The information obtained from gyrification-based connectomes can be harnessed for prospectively predicting treatment response and prognosis in psychosis. © The Author 2016. Published by Oxford University Press on behalf of the

The effect of three-monthly albendazole treatment on Th2 responses: Differential effects on IgE and IL-5.

Science.gov (United States)

de Ruiter, K; Tahapary, D L; Wammes, L J; Wiria, A E; Hamid, F; van Lieshout, L; Smit, J W A; Houwing-Duistermaat, J J; Sartono, E; Supali, T; Yazdanbakhsh, M

2017-06-01

Helminth parasites induce a strong Th2 response, characterized by high levels of IgE and elevated signature cytokines such as IL-5. As many global deworming programmes are underway, there is concern that this might lead to emergence of Th1-mediated pathologies when the counterbalancing helminth-induced Th2 response is absent. Therefore, we assessed the effect of deworming on Th2-mediated responses in a household-clustered randomized controlled trial in Indonesia. Total plasma IgE and whole-blood IL-5 responses to mitogen phytohaemagglutinin (PHA) were measured in 1494 and 682 subjects, respectively, at baseline, 9 and 21 months after three-monthly single-dose treatment with albendazole or placebo. Anthelmintic treatment did not result in complete removal of helminth infections in the community. However, treatment significantly decreased IgE levels in albendazole- compared to placebo-treated subjects. IL-5 responses to PHA were not significantly affected by anthelmintic treatment and tended to increase in albendazole-treated subjects, indicating that intensive treatment of helminth parasites has different outcomes on B-cell (IgE levels) and T-cell (IL-5) responses. The data shows that 2 years of deworming can have differential effects on responses typified as Th2-mediated, which needs to be taken into account when examining the impact of helminths on noncommunicable diseases. © 2017 John Wiley & Sons Ltd.

Shrub resprouting response after fuel reduction treatments: comparison of prescribed burning, clearing and mastication.

Science.gov (United States)

Fernández, Cristina; Vega, José A; Fonturbel, Teresa

2013-03-15

Fuel reduction treatments are commonly used to reduce the risk of severe wildfire. However, more information about the effects on plant resprouting is needed to help land managers select the most appropriate treatment. To address this question, we evaluated the resprouting ability of five shrub species after the application of different types of fuel reduction methods (prescribed burning, clearing and mastication) in two contrasting shrubland areas in northern Spain. The shrub species were Erica australis, Pterospartum tridentatum and Halimium lasianthum spp. alyssoides, Ulex gallii and Erica cinerea. For most of the species under study (E. australis, P. tridentatum, H. lasianthum spp. alyssoides and U. gallii), neither plant mortality nor the number nor length of sprouted shoots per plant differed between treatments, although in E. cinerea the number of shoots was more negatively affected by prescribed burning than by clearing or mastication. The pre-treatment plant size did not affect plant mortality or plant resprouting response, suggesting that this parameter alone is not a good indicator of plant resprouting after fuel reduction treatments. Stem minimum diameter after treatments, a proxy of treatment severity, was not related to plant mortality, number or length of resprouted shoots. The duration of temperatures higher than 300 °C during burning in plant crown had a negative effect on the length of resprouted shoots, only in E. cinerea. The results show that fuel reduction treatments did not prevent shrub response in any case. Some reflections on the applicability of treatments are discussed. Copyright © 2013 Elsevier Ltd. All rights reserved.

Personality and Differential Treatment Response in Major Depression: A Randomized Controlled Trial Comparing Cognitive-Behavioural Therapy and Pharmacotherapy

Science.gov (United States)

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

Treatment response in child anxiety is differentially related to the form of maternal anxiety disorder

OpenAIRE

Cooper, P. J.; Gallop, C.; Willetts, L.; Creswell, C.

2008-01-01

An examination was made of the extent to which maternal anxiety predicted response to treatment of children presenting with an anxiety disorder. In a sample of 55 children referred to a local NHS CAMH service for treatment of an anxiety disorder, systematic mental state interview assessment was made of both mothers and children, and both completed self-report questionnaires to assess aspects of anxiety, both immediately before the children received treatment and following treatment. Children ...

Site-Specific Seismic Site Response Model for the Waste Treatment Plant, Hanford, Washington

Energy Technology Data Exchange (ETDEWEB)

Rohay, Alan C.; Reidel, Steve P.

2005-02-24

This interim report documents the collection of site-specific geologic and geophysical data characterizing the Waste Treatment Plant site and the modeling of the site-specific structure response to earthquake ground motions.

Epidemiological and Clinical Baseline Characteristics as Predictive Biomarkers of Response to Anti-VEGF Treatment in Patients with Neovascular AMD

Directory of Open Access Journals (Sweden)

Miltiadis K. Tsilimbaris

2016-01-01

Full Text Available Purpose. To review the current literature investigating patient response to antivascular endothelial growth factor-A (VEGF therapy in the treatment of neovascular age-related macular degeneration (nAMD and to identify baseline characteristics that might predict response. Method. A literature search of the PubMed database was performed, using the keywords: AMD, anti-VEGF, biomarker, optical coherence tomography, treatment outcome, and predictor. The search was limited to articles published from 2006 to date. Exclusion criteria included phase 1 trials, case reports, studies focusing on indications other than nAMD, and oncology. Results. A total of 1467 articles were identified, of which 845 were excluded. Of the 622 remaining references, 47 met all the search criteria and were included in this review. Conclusion. Several baseline characteristics correlated with anti-VEGF treatment response, including best-corrected visual acuity, age, lesion size, and retinal thickness. The majority of factors were associated with disease duration, suggesting that longer disease duration before treatment results in worse treatment outcomes. This highlights the need for early treatment for patients with nAMD to gain optimal treatment outcomes. Many of the identified baseline characteristics are interconnected and cannot be evaluated in isolation; therefore multivariate analyses will be required to determine any specific relationship with treatment response.

Comparison of symptom severity and treatment response in patients with incontinent and continent overactive bladder

NARCIS (Netherlands)

Michel, Martin C.; de La Rosette, Jean J. M. C. H.; Piro, Maria; Schneider, Tim

2005-01-01

Purpose: Two thirds of patients with overactive bladder (OAB) are continent, but our knowledge on the treatment of the syndrome is largely based on studies with incontinent patients. Therefore, we have explored baseline symptoms and treatment responses to tolterodine in continent relative to

Does a family history of RA influence the clinical presentation and treatment response in RA?

Science.gov (United States)

Frisell, Thomas; Saevarsdottir, Saedis; Askling, Johan

2016-06-01

To assess whether family history of rheumatoid arthritis (RA), among the strongest risk factors for developing RA, also carries information on the clinical presentation and treatment response. The prospective Swedish Rheumatology register was linked to family history of RA, defined as diagnosed RA in any first-degree relative, ascertained through the Swedish Multi-Generation and Patient registers. Clinical presentation was examined among patients with early RA 2000-2011 (symptom onset clinical characteristics, drug survival, European League Against Rheumatism (EULAR) response and change in disease activity at 3 and 6 months was estimated using linear and generalised logistic regression models. Correlation in relatives' response measures was also assessed. Patients with early RA with family history of RA were more often rheumatoid factor positive, but with no other clinically meaningful differences in their clinical presentation. Family history of RA did not predict response to MTX or TNFi, with the possible exception of no versus good EULAR response to TNFi at 6 months (OR=1.4, 95% CI 1.1 to 1.7). Having a relative who discontinued TNFi within a year increased the odds of doing the same (OR=3.7, 95% CI 1.8 to 7.5), although we found no significant familial correlations in change in disease activity measures. Family history of RA did not modify the clinical presentation of RA or predict response to standard treatment with MTX or TNFi. Treatment response, particularly drug survival, may itself be familial. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Topology Optimization for Minimizing the Resonant Response of Plates with Constrained Layer Damping Treatment

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Zhanpeng Fang

2015-01-01

Full Text Available A topology optimization method is proposed to minimize the resonant response of plates with constrained layer damping (CLD treatment under specified broadband harmonic excitations. The topology optimization problem is formulated and the square of displacement resonant response in frequency domain at the specified point is considered as the objective function. Two sensitivity analysis methods are investigated and discussed. The derivative of modal damp ratio is not considered in the conventional sensitivity analysis method. An improved sensitivity analysis method considering the derivative of modal damp ratio is developed to improve the computational accuracy of the sensitivity. The evolutionary structural optimization (ESO method is used to search the optimal layout of CLD material on plates. Numerical examples and experimental results show that the optimal layout of CLD treatment on the plate from the proposed topology optimization using the conventional sensitivity analysis or the improved sensitivity analysis can reduce the displacement resonant response. However, the optimization method using the improved sensitivity analysis can produce a higher modal damping ratio than that using the conventional sensitivity analysis and develop a smaller displacement resonant response.

Cognitive-behavioral therapy as continuation treatment to sustain response after electroconvulsive therapy in depression: a randomized controlled trial.

Science.gov (United States)

Brakemeier, Eva-Lotta; Merkl, Angela; Wilbertz, Gregor; Quante, Arnim; Regen, Francesca; Bührsch, Nicole; van Hall, Franziska; Kischkel, Eva; Danker-Hopfe, Heidi; Anghelescu, Ion; Heuser, Isabella; Kathmann, Norbert; Bajbouj, Malek

2014-08-01

Although electroconvulsive therapy (ECT) is the most effective acute antidepressant intervention, sustained response rates are low. It has never been systematically assessed whether psychotherapy, continuation ECT, or antidepressant medication is the most efficacious intervention to maintain initial treatment response. In a prospective, randomized clinical trial, 90 inpatients with major depressive disorder (MDD) were treated with right unilateral ultra-brief acute ECT. Electroconvulsive therapy responders received 6 months guideline-based antidepressant medication (MED) and were randomly assigned to add-on therapy with cognitive-behavioral group therapy (CBT-arm), add-on therapy with ultra-brief pulse continuation electroconvulsive therapy (ECT-arm), or no add-on therapy (MED-arm). After the 6 months of continuation treatment, patients were followed-up for another 6 months. The primary outcome parameter was the proportion of patients who remained well after 12 months. Of 90 MDD patients starting the acute phase, 70% responded and 47% remitted to acute ECT. After 6 months of continuation treatment, significant differences were observed in the three treatment arms with sustained response rates of 77% in the CBT-arm, 40% in the ECT-arm, and 44% in the MED-arm. After 12 months, these differences remained stable with sustained response rates of 65% in the CBT-arm, 28% in the ECT-arm, and 33% in the MED-arm. These results suggest that ultra-brief pulse ECT as a continuation treatment correlates with low sustained response rates. However, the main finding implicates cognitive-behavioral group therapy in combination with antidepressants might be an effective continuation treatment to sustain response after successful ECT in MDD patients. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Rectal bleeding after conformal 3D treatment of prostate cancer: time to occurrence, response to treatment and duration of morbidity

International Nuclear Information System (INIS)

Teshina, Teruki; Hanks, Gerald E.; Peters, Ruth S.; Hanlon, Alexandra L.; Schultheiss, Timothy E.

1996-01-01

Purpose: Late rectal bleeding is the most common sequelae of high dose 3D conformal treatment (3DCRT) for prostate cancer and limits attempts to improve local control by dose escalation. The clinical course of this complication is reported including time to onset, response to treatment, duration of morbidity and risk factor analysis by multivariate analysis. Materials and Methods: From March, 1989 to June 1996, 670 patients with prostate cancer were treated with 3DCRT. Eighty-nine patients developed grade 2 or 3 complications due to rectal bleeding and are analyzed (Grade 2 LENT scale, Grade 3 Fox Chase modification of LENT including >2 coagulations as Grade 3). They are compared to 581 patients without Grade 2,3 morbidity in multivariate analysis. Time to development, response to initial and retreatment and duration of morbidity are tabulated. Results: The median time to occurrence is not significantly different (p=.09) for Grade 2 (13 mo. range 4-41 mo.) compared to Grade 3 (18 mo. range 4-40 mo.). The corresponding median duration of symptoms >Grade 1 were significantly different (p=.0001) being 1 month (range 1-<12) versus 10 months (1-34) respectively. The response to treatment and retreatment is shown in Table 1. For Grade 2 complications medication or coagulation was highly effective as initial or retreatment resolving 66 of 73 patients. For Grade 3 a few responded to only transfusion and with multiple coagulations and medication (12(16)) patients improved to ≤ Grade 1. Multivariate analysis demonstrates that dose is the only significant factor associated with Grade 2 (LENT) (p=.01) or Grade 3 (FC-LENT) (p=.01) complication. Lack of response to treatment was associated with hypertension on univariate analysis only. Of 7 non-responders to treatment of Grade 2 bleeding, 3 have died of intercurrent disease at 10, 19 and 26 months while 4 are alive with continuing Grade 2 bleeding at 26, 34, 41 and 45 months after onset. Of 4 non-responders to treatment of

Rectal bleeding after conformal 3D treatment of prostate cancer: Time to occurrence, response to treatment and duration of morbidity

International Nuclear Information System (INIS)

Teshima, Teruki; Hanks, Gerald E.; Hanlon, Alexandra L.; Peter, Ruth S.; Schultheiss, Timothy E.

1997-01-01

Purpose: Rectal bleeding is the most common late sequelae of high-dose 3D conformal treatment (3DCRT) for prostate cancer and may limit attempts to improve local control by dose escalation. The clinical course of this complication is reported including time to onset, response to treatment, duration of morbidity, and multivariate analysis for predictors. Methods and Materials: From March 1989 to June 1995, 670 patients with prostate cancer were treated with 3DCRT at Fox Chase Cancer Center. Eighty-nine patients developed Grade 2 or Grade 3 complications due to rectal bleeding and are analyzed. Multivariate analysis results for predictors of Grade 2 and 3 rectal bleeding are reported as well as time to development, response to initial and retreatment, and duration of morbidity. Results: The median time to occurrence is not significantly different (p = 0.09) for Grade 2 (13 months, range 4-41 months) compared to Grade 3 rectal bleeding (18 months, range 4-40 months), while the corresponding median duration of symptoms was significantly different (p < 0.0001) being 1 month (range 1-12) vs. 10 months (1-34) for Grade 2 and Grade 3 bleeding, respectively. For Grade 2 bleeding, medication or coagulation was highly effective as initial or retreatment resolving 66 of 73 patients. For Grade 3 bleeding, three patients responded without medication following blood transfusion only, while with multiple coagulations and medication 12 of 16 patients improved to ≤ Grade 1. Multivariate analysis demonstrates that dose is the only significant factor associated with Grade 2 (p = 0.01) or Grade 3 (p = 0.01) rectal bleeding. Of seven nonresponders to treatment for Grade 2 bleeding, three have died of intercurrent disease at 10, 19, and 26 months, while four are alive with continuing Grade 2 bleeding at 12, 14, 15, and 30 months after onset. The four nonresponders to treatment for Grade 3 bleeding continue to bleed 1, 9, 32, and 35 months after the third coagulation despite continuing

Subcutaneous fluid collection: An imaging marker for treatment response of infectious thoracolumbar spondylodiscitis

International Nuclear Information System (INIS)

Kakigi, Takahide; Okada, Tomohisa; Sakai, Osamu; Iwamoto, Yoshitaka; Kubo, Soichi; Yamamoto, Akira; Togashi, Kaori

2015-01-01

Highlights: • No imaging marker for treatment response of spondylodiscitis (SD) has been proposed. • Volume changes of subcutaneous fluid collection (SFC) had significant correlation with changes of C-reactive protein (CRP). • SFC can be used as an imaging marker for treatment response of SD on magnetic resonance imaging (MRI). - Abstract: Purpose: To evaluate prevalence of subcutaneous fluid collection (SFC) in infectious thoracolumbar spondylodiscitis (SD) compared with control patients and to investigate correlation between volume changes of SFC and treatment response of SD. Materials and methods: This retrospective study was approved by our institutional review board. From April 2011 to March 2012, 49 patients (24 SD and 25 non-SD patients) were enrolled. Prevalence of SFC was evaluated respectively for SD and non-SD patients using magnetic resonance imaging (MRI) on the sagittal short tau inversion recovery (STIR) imaging or fat-saturated T2-weighted imaging (T2WI), and compared. In SD patients with SFC, correlation was investigated between SFC volume on the 1st MRI and initial clinical status. The same analysis was conducted also for SFC volume changes from the 1st to 2nd or last MRI. Results: SFC was found in 20 patients with SD (83.3%) and 3 non-SD patients (12%) with significant difference (p < .001). In 20 SD patients with SFC, 17 patients had follow-up MRI. For the 1st MRI, no significant correlation was found between volume of SFC and initial status of patients, including body weight, body mass index (BMI), white blood cell (WBC), and erythrocyte sedimentation rate (ESR). However, significant positive correlations were found between changes of C-reactive protein (CRP) and SFC volume from the 1st to 2nd as well as from the 1st to the last MRI (each p < .05). Conclusion: SD patients had significantly higher prevalence of SFC than non-SD patients. Volume changes of SFC had significant correlation with changes of CRP, which can be used as an imaging

Subcutaneous fluid collection: An imaging marker for treatment response of infectious thoracolumbar spondylodiscitis

Energy Technology Data Exchange (ETDEWEB)

Kakigi, Takahide, E-mail: tkakigi@kuhp.kyoto-u.ac.jp [Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507 (Japan); Okada, Tomohisa, E-mail: tomokada@kuhp.kyoto-u.ac.jp [Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507 (Japan); Sakai, Osamu, E-mail: osamu.sakai@bmc.org [Department of Radiology, Boston Medical Center, Boston University School of Medicine, FGH Building, 3rd Floor, 820 Harrison Avenue, Boston, MA 02118 (United States); Iwamoto, Yoshitaka, E-mail: iwacame@hotmail.co.jp [Department of General Internal Medicine, Rakuwakai Otowa Hospital, 2 Otowachoinji-cho, Yamashina-ku, Kyoto 607-8062 (Japan); Kubo, Soichi, E-mail: kubo-s@mbox.kyoto-inet.or.jp [Department of Radiology, Rakuwakai Otowa Hospital, 2 Otowachoinji-cho, Yamashina-ku, Kyoto 607-8062 (Japan); Yamamoto, Akira, E-mail: yakira@kuhp.kyoto-u.ac.jp [Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507 (Japan); Togashi, Kaori, E-mail: nmdioffice@kuhp.kyoto-ac.jp [Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507 (Japan)

2015-07-15

Highlights: • No imaging marker for treatment response of spondylodiscitis (SD) has been proposed. • Volume changes of subcutaneous fluid collection (SFC) had significant correlation with changes of C-reactive protein (CRP). • SFC can be used as an imaging marker for treatment response of SD on magnetic resonance imaging (MRI). - Abstract: Purpose: To evaluate prevalence of subcutaneous fluid collection (SFC) in infectious thoracolumbar spondylodiscitis (SD) compared with control patients and to investigate correlation between volume changes of SFC and treatment response of SD. Materials and methods: This retrospective study was approved by our institutional review board. From April 2011 to March 2012, 49 patients (24 SD and 25 non-SD patients) were enrolled. Prevalence of SFC was evaluated respectively for SD and non-SD patients using magnetic resonance imaging (MRI) on the sagittal short tau inversion recovery (STIR) imaging or fat-saturated T2-weighted imaging (T2WI), and compared. In SD patients with SFC, correlation was investigated between SFC volume on the 1st MRI and initial clinical status. The same analysis was conducted also for SFC volume changes from the 1st to 2nd or last MRI. Results: SFC was found in 20 patients with SD (83.3%) and 3 non-SD patients (12%) with significant difference (p < .001). In 20 SD patients with SFC, 17 patients had follow-up MRI. For the 1st MRI, no significant correlation was found between volume of SFC and initial status of patients, including body weight, body mass index (BMI), white blood cell (WBC), and erythrocyte sedimentation rate (ESR). However, significant positive correlations were found between changes of C-reactive protein (CRP) and SFC volume from the 1st to 2nd as well as from the 1st to the last MRI (each p < .05). Conclusion: SD patients had significantly higher prevalence of SFC than non-SD patients. Volume changes of SFC had significant correlation with changes of CRP, which can be used as an imaging

Conformal treatment of prostate cancer with improved targeting: superior prostate-specific antigen response compared to standard treatment

Energy Technology Data Exchange (ETDEWEB)

Corn, Benjamin W; Hanks, Gerald E; Schultheiss, Timothy E; Hunt, Margie A; Lee, W Robert; Coia, Lawrence R

1995-05-15

Purpose: Conformal radiation therapy (CRT) decreases the morbidity of prostate cancer treatment, but no published data attest to the improved ability of CRT to control disease. Therefore, we compared Prostate-Specific Antigen (PSA) response at 1 year among similarly staged patients treated by conformal techniques to those treated with conventional approaches, looking for an early indicator of tumor response. Method and Materials: Patients with locally advanced disease were treated by pelvic fields followed by prostate field conedowns; those with early stage/low grade disease received only prostate field irradiation. Between October, 1987 and November, 1991, conventional treatments used rectangular beams with or without corner blocks. Neither urethrography nor immobilization casts were used for conventionally treated patients. Between April, 1989 and December, 1992, conformal treatments have used rigid immobilization and Computed Tomography-based, beams-eye-view field design. As such, our conformal approach allowed improved targeting. Median prescribed doses (minimal doses to the Planning Target Volume) were 70 Gy (66-73 Gy) and 70.2 Gy (64.8-75 Gy) for conventionally and conformally treated patients, respectively. Median daily fraction size was 1.8 Gy for conventional treatment and 2.0 Gy for conformal therapy. Baseline PSA data were available on 170 consecutive patients treated conformally and 90 consecutive patients treated conventionally. Results: Among those receiving only prostatic field irradiation, 12-month PSA values returned to normal in 96% and 85% of conformally and conventionally treated patients, respectively, when normalization was defined as {<=} 4 ng/ml (p < 0.03) and in 76% vs. 55% of patients when PSA normalization was defined as {<=} 1.5 ng/ml (p < 0.02). Among those receiving pelvic irradiation prior to prostatic conedown, PSA normalization ({<=} 4 ng/ml) occurred in 82% and 61% (p < 0.01) of conformally and conventionally treated patients

Identification of SlpB, a Cytotoxic Protease from Serratia marcescens.

Science.gov (United States)

Shanks, Robert M Q; Stella, Nicholas A; Hunt, Kristin M; Brothers, Kimberly M; Zhang, Liang; Thibodeau, Patrick H

2015-07-01

The Gram-negative bacterium and opportunistic pathogen Serratia marcescens causes ocular infections in healthy individuals. Secreted protease activity was characterized from 44 ocular clinical isolates, and a higher frequency of protease-positive strains was observed among keratitis isolates than among conjunctivitis isolates. A positive correlation between protease activity and cytotoxicity to human corneal epithelial cells in vitro was determined. Deletion of prtS in clinical keratitis isolate K904 reduced, but did not eliminate, cytotoxicity and secreted protease production. This indicated that PrtS is necessary for full cytotoxicity to ocular cells and implied the existence of another secreted protease(s) and cytotoxic factors. Bioinformatic analysis of the S. marcescens Db11 genome revealed three additional open reading frames predicted to code for serralysin-like proteases noted here as slpB, slpC, and slpD. Induced expression of prtS and slpB, but not slpC and slpD, in strain PIC3611 rendered the strain cytotoxic to a lung carcinoma cell line; however, only prtS induction was sufficient for cytotoxicity to a corneal cell line. Strain K904 with deletion of both prtS and slpB genes was defective in secreted protease activity and cytotoxicity to human cell lines. PAGE analysis suggests that SlpB is produced at lower levels than PrtS. Purified SlpB demonstrated calcium-dependent and AprI-inhibited protease activity and cytotoxicity to airway and ocular cell lines in vitro. Lastly, genetic analysis indicated that the type I secretion system gene, lipD, is required for SlpB secretion. These genetic data introduce SlpB as a new cytotoxic protease from S. marcescens. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

MR Imaging in Monitoring and Predicting Treatment Response in Multiple Sclerosis.

Science.gov (United States)

Río, Jordi; Auger, Cristina; Rovira, Àlex

2017-05-01

MR imaging is the most sensitive tool for identifying lesions in patients with multiple sclerosis (MS). MR imaging has also acquired an essential role in the detection of complications arising from these treatments and in the assessment and prediction of efficacy. In the future, other radiological measures that have shown prognostic value may be incorporated within the models for predicting treatment response. This article examines the role of MR imaging as a prognostic tool in patients with MS and the recommendations that have been proposed in recent years to monitor patients who are treated with disease-modifying drugs. Copyright © 2017 Elsevier Inc. All rights reserved.

Peer Collaboration: Improving Teaching through Comprehensive Peer Review

Science.gov (United States)

Smith, Shelley L.

2014-01-01

This article includes a brief rationale and review of the literature on peer review of teaching (PRT). Based on that literature review, it offers a proposal for an optimal formative review process that results in a teaching portfolio that would reflect a faculty member's efforts and successes in a critically reflective PRT process, and contributes…

The Effectiveness of Peer Review of Teaching When Performed between Early-Career Academics

Science.gov (United States)

Woodman, Richard J.; Parappilly, Maria B.

2015-01-01

The success of peer review of teaching (PRT) in shaping teaching practice during an academic's formative years may depend on the peers' teaching experience and the frequency of evaluation. Two Australian early-career University lecturers with no previous experience of peer review performed a single PRT on one another following a one week academic…

Optimization of Electrochemical Treatment Process Conditions for Distillery Effluent Using Response Surface Methodology

Directory of Open Access Journals (Sweden)

P. Arulmathi

2015-01-01

Full Text Available Distillery industry is recognized as one of the most polluting industries in India with a large amount of annual effluent production. In this present study, the optimization of electrochemical treatment process variables was reported to treat the color and COD of distillery spent wash using Ti/Pt as an anode in a batch mode. Process variables such as pH, current density, electrolysis time, and electrolyte dose were selected as operation variables and chemical oxygen demand (COD and color removal efficiency were considered as response variable for optimization using response surface methodology. Indirect electrochemical-oxidation process variables were optimized using Box-Behnken response surface design (BBD. The results showed that electrochemical treatment process effectively removed the COD (89.5% and color (95.1% of the distillery industry spent wash under the optimum conditions: pH of 4.12, current density of 25.02 mA/cm2, electrolysis time of 103.27 min, and electrolyte (NaCl concentration of 1.67 g/L, respectively.

Hypophosphatemic osteomalacia induced by tenofovir in HIV-infected patients.

Science.gov (United States)

Mateo, Lourdes; Holgado, Susana; Mariñoso, Maria Luisa; Pérez-Andrés, Ricard; Bonjoch, Anna; Romeu, Joan; Olivé, Alejandro

2016-05-01

Tenofovir disoproxil fumarate (TDF) is an adenine analogue reverse transcription inhibitor widely used in first-line treatment of human immunodeficiency virus (HIV) infection and also in hepatitis B virus infection. Its use has been linked to sporadic Fanconi syndrome, renal failure and bone disease. We present the clinical characteristics of tenofovir-induced osteomalacia, discuss bone biopsy findings, describe predisposing factors and compare our results with other reported cases. We describe five cases of hypophosphatemic osteomalacia induced by TDF and recorded at the rheumatology service of a university hospital between 2010 and 2014. We also report the characteristics of bone biopsies of this pathology, which have not been previously described. We include a review of published cases of proximal renal tubulopathy (PRT) and osteomalacia induced by TDF (PubMed 1995-2014; keywords: osteomalacia, tenofovir, Fanconi syndrome, hypophosphatemic osteomalacia, proximal renal tubulopathy, bone biopsy). Five HIV patients who developed hypophosphatemic osteomalacia under TDF treatment (>5 years) presented increasing bone pain and a progressive inability to walk without assistance as a result of multiple insufficiency fractures. Bone biopsy performed in three patients after tetracycline labelling showed increased osteoid thickness, confirming osteomalacia. A literature review retrieved 17 publications on this condition, including 53 cases: 26 patients developed isolated PRT, 25 presented PRT and with multiple insufficiency fractures and two presented isolated bone disease, including osteomalacia and osteoporosis. Rheumatologists should be alert to this complication in patients receiving tenofovir. The main complaint reported by these patients is diffuse pain, predominantly in the lower limbs, indicating multiple stress fractures. Serum phosphate and appropriate screening for abnormal proximal tubule function should be monitored. Bone scintigraphy should be carried out in

Serum Adiponectin, Vitamin D, and Alpha-Fetoprotein in Children with Chronic Hepatitis C: Can They Predict Treatment Response?

Science.gov (United States)

Khedr, Mohamed Ahmed; Sira, Ahmad Mohamed; Saber, Magdy Anwar; Raia, Gamal Yousef

2015-01-01

Background & Aims. The currently available treatment for chronic hepatitis C (CHC) in children is costly and with much toxicity. So, predicting the likelihood of response before starting therapy is important. Methods. Serum adiponectin, vitamin D, and alpha-fetoprotein (AFP) were measured before starting pegylated-interferon/ribavirin therapy for 50 children with CHC. Another 21 healthy children were recruited as controls. Results. Serum adiponectin, vitamin D, and AFP were higher in the CHC group than healthy controls (p < 0.0001, p = 0.071, and p = 0.87, resp.). In univariate analysis, serum adiponectin was significantly higher in responders than nonresponders (p < 0.0001) and at a cutoff value ≥8.04 ng/mL it can predict treatment response by 77.8% sensitivity and 92.9% specificity, while both AFP and viremia were significantly lower in responders than nonresponders, p < 0.0001 and p = 0.0003, respectively, and at cutoff values ≤3.265 ng/mL and ≤235,384 IU/mL, respectively, they can predict treatment response with a sensitivity of 83.3% for both and specificity of 85.7% and 78.6%, respectively. In multivariate analysis, adiponectin was found to be the only independent predictor of treatment response (p = 0.044). Conclusions. The pretreatment serum level of adiponectin can predict the likelihood of treatment response, thus avoiding toxicities for those unlikely to respond to therapy.

Interferon-γ gene polymorphisms at +874T/A loci associated with response to treatment with hepatitis C virus

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Hosein Norozian

2016-02-01

Full Text Available Background: Hepatitis C virus (HCV is a worldwide health problem, which associated with cirrhosis and hepatocellular carcinoma. Interferon-α and Ribavirin are only acceptable treatment regimen for these patients. These regimen are effective only on 50% of the patients. The aim of this study was to evaluate the response to treatment with interferon gamma gene polymorphism in patients with hepatitis C. Materials and Methods: In this study, a cross - sectional study, response or lack of response to treatment in 78 patients treated with interferon gamma gene polymorphism were studied at Shiraz Namazi Hospital from 2011-2012 . DNA samples extract by salt (salting out and interferon gamma gene polymorphism (+874T/A IFN–gamma was evaluate with ARMS-PCR technique. Data were analyzed using EPI Info2000 and SPSS 16 software (chi-square test. Results: Results showed that 39 patients (50% out of 78 studied patients had TT alleles, 11 patients (1.14% had AA alleles and 28 patients (9.39% had TA alleles. 49 patients (62.82% responded to treatment. TT genotype and allele frequencies between the studied groups showed significant differencey (P=0.002. Conclusion: Interferon gamma is a key cytokine in the immune response against hepatitis C. Polymorphism in the interferon-gamma gene is (+874T/AIFN–gamma One of the most important factors interferes with treatment response in hepatitis C patients.

Treatment Recommendation Actions, Contingencies, and Responses: An Introduction.

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Stivers, Tanya; Barnes, Rebecca K

2017-08-21

In the era of patient participation in health care decision making, we know surprisingly little about the ways in which treatment recommendations are made, the contexts that shape their formulation, and the consequences of these formulations. In this article, we introduce a systematic collective investigation of how recommendations for medications are responded to and made in primary versus secondary care, in the US versus the UK, and in contexts where the medication was over the counter versus by prescription. This article provides an overview of the coding system that was used in this project including describing what constitutes a recommendation, the primary action types clinicians use for recommendations, and the types of responses provided by patients to recommendations.

Utilizing temporal variations in chemotherapeutic response to improve breast cancer treatment efficacy

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Daniel J. McGrail

2015-09-01

Full Text Available Though survival rates for women with stage I breast cancer have radically improved, treatment options remain poor for the 40% of women diagnosed with later-stage disease. For these patients, improved chemotherapeutic treatment strategies are critical to eradicate any disseminated tumor cells. Despite many promising new drugs in vitro, most ultimately fail in the clinic. One aspect often lost during testing is in vivo circulation half-lives rarely exceed 24 hours, whereas in vitro studies involve drug exposure for 2-3 days. Here, we show how mimicking these exposure times alters efficacy. Next, using this model we show how drug response is highly time-dependent by extending analysis of cell viability out to two weeks. Variations in response both with feeding and time were dependent on drug mechanism of action. Finally, we show that by implementing this temporal knowledge of drug effects to optimize scheduling of drug administration we are able to regain chemosensitivity in a Carboplatin-resistant cell line.

Enhancement of gas sensor response of nanocrystalline zinc oxide for ammonia by plasma treatment

International Nuclear Information System (INIS)

Hou, Yue; Jayatissa, Ahalapitiya H.

2014-01-01

The effect of oxygen plasma treatment on nanocrystalline ZnO thin film based gas sensor was investigated. ZnO thin films were synthesized on alkali-free glass substrates by a sol–gel process. ZnO thin films were treated with oxygen plasma to change the number of vacancies/defects in ZnO. The effect of oxygen plasma on the structural, electrical, optical and gas sensing properties was investigated as a function of plasma treatment time. The results suggest that the microstructure and the surface morphology can be tuned by oxygen plasma treatment. The optical transmission in the visible range varies after the oxygen plasma treatment. Moreover, it is found that the oxygen plasma has significant impact on the electrical properties of ZnO thin films indicating a variation of resistivity. The oxygen plasma treated ZnO thin film exhibits an enhanced sensing response towards NH 3 in comparison with that of the as-deposited ZnO sensor. When compared with the as-deposited ZnO film, the sensing response was improved by 50% for the optimum oxygen plasma treatment time of 8 min. The selectivity of 8 min plasma treated ZnO sensor was also examined for an important industrial gas mixture of H 2 , CH 4 and NH 3 .

Selection of response criteria for clinical trials of sarcoma treatment.

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Schuetze, Scott M; Baker, Laurence H; Benjamin, Robert S; Canetta, Renzo

2008-01-01

Soft tissue sarcomas are a heterogeneous group of malignancies arising from mesenchymal tissues. A large number of new therapies are being evaluated in patients with sarcomas, and consensus criteria defining treatment responses are essential for comparison of results from studies completed by different research groups. The 1979 World Health Organization (WHO) handbook set forth operationally defined criteria for response evaluation in solid tumors that were updated in 2000 with the publication of the Response Evaluation Criteria in Solid Tumors (RECIST). There have been significant advances in tumor imaging, however, that are not reflected in the RECIST. For example, computed tomography (CT) slice thickness has been reduced from 10 mm to < or =2.5 mm, allowing for more reproducible and accurate measurement of smaller lesions. Combination of imaging techniques, such as positron emission tomography with fluorine-18-fluorodeoxyglucose (18FDG-PET) and CT can provide investigators and clinicians with both anatomical and functional information regarding tumors, and there is now a large body of evidence demonstrating the effectiveness of PET/CT and other newer imaging methods for the detection and staging of tumors as well as early determination of responses to therapy. The application of newer imaging methods has the potential to decrease both the sample sizes required for, and duration of, clinical trials by providing an early indication of therapeutic response that is well correlated with clinical outcomes, such as time to tumor progression or overall survival. The results summarized in this review support the conclusion that the RECIST and the WHO criteria for evaluation of response in solid tumors need to be modernized. In addition, there is a current need for prospective trials to compare new response criteria with established endpoints and to validate imaging-based response rates as surrogate endpoints for clinical trials of new agents for sarcoma and other solid

Stathmin protein level, a potential predictive marker for taxane treatment response in endometrial cancer.

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Henrica M J Werner

Full Text Available Stathmin is a prognostic marker in many cancers, including endometrial cancer. Preclinical studies, predominantly in breast cancer, have suggested that stathmin may additionally be a predictive marker for response to paclitaxel. We first evaluated the response to paclitaxel in endometrial cancer cell lines before and after stathmin knock-down. Subsequently we investigated the clinical response to paclitaxel containing chemotherapy in metastatic endometrial cancer in relation to stathmin protein level in tumors. Stathmin level was also determined in metastatic lesions, analyzing changes in biomarker status on disease progression. Knock-down of stathmin improved sensitivity to paclitaxel in endometrial carcinoma cell lines with both naturally higher and lower sensitivity to paclitaxel. In clinical samples, high stathmin level was demonstrated to be associated with poor response to paclitaxel containing chemotherapy and to reduced disease specific survival only in patients treated with such combination. Stathmin level increased significantly from primary to metastatic lesions. This study suggests, supported by both preclinical and clinical data, that stathmin could be a predictive biomarker for response to paclitaxel treatment in endometrial cancer. Re-assessment of stathmin level in metastatic lesions prior to treatment start may be relevant. Also, validation in a randomized clinical trial will be important.

Spasmodic dysphonia: onset, course, socioemotional effects, and treatment response.

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Tanner, Kristine; Roy, Nelson; Merrill, Ray M; Sauder, Cara; Houtz, Daniel R; Smith, Marshall E

2011-07-01

This investigation explored the onset, progression, socioemotional effects, and treatment outcomes of spasmodic dysphonia (SD). A cross-sectional epidemiological approach was used to examine questionnaire responses from 150 individuals with SD. Symptoms of SD (mean age at onset, 46 years) began gradually in 76% of cases and were progressive (ie, failed to plateau) in 34% of cases. Botulinum toxin A (Botox) helped to attenuate voice symptoms in 91% of cases; however, the scores on the Voice-Related Quality of Life questionnaire (V-RQOL) were not associated with this effect. The V-RQOL scores improved with time since symptom onset, independent of age and treatment. The patients with only SD experienced onset, course, and progression of symptoms similar to those of the patients with SD and coexisting vocal tremor. The symptoms of SD begin gradually and worsen over time. New evidence indicates that SD symptoms may continue to progress without plateau in at least a subset of patients. Individuals with SD and coexisting vocal tremor experience symptom trajectories similar to those of patients with SD only. Although Botox may attenuate voice symptoms, these effects do not appear to be strongly related to the V-RQOL scores. These results provide new and valuable insights regarding the onset, course, progression, and treatment of SD.

Survey and online discussion groups to develop a patient-rated outcome measure on acceptability of treatment response in vitiligo

Science.gov (United States)

2014-01-01

Background Vitiligo is a chronic depigmenting skin disorder which affects around 0.5-1% of the world’s population. The outcome measures used most commonly in trials to judge treatment success focus on repigmentation. Patient-reported outcome measures of treatment success are rarely used, although recommendations have been made for their inclusion in vitiligo trials. This study aimed to evaluate the face validity of a new patient-reported outcome measure of treatment response, for use in future trials and clinical practice. Method An online survey to gather initial views on what constitutes treatment success for people with vitiligo or their parents/carers, followed by online discussion groups with patients to reach consensus on what constitutes treatment success for individuals with vitiligo, and how this can be assessed in the context of trials. Participants were recruited from an existing database of vitiligo patients and through posts on the social network sites Facebook and Twitter. Results A total of 202 survey responses were received, of which 37 were excluded and 165 analysed. Three main themes emerged as important in assessing treatment response: a) the match between vitiligo and normal skin (how well it blends in); b) how noticeable the vitiligo is and c) a reduction in the size of the white patches. The majority of respondents said they would consider 80% or more repigmentation to be a worthwhile treatment response after 9 months of treatment. Three online discussion groups involving 12 participants led to consensus that treatment success is best measured by asking patients how noticeable their vitiligo is after treatment. This was judged to be best answered using a 5-point Likert scale, on which a score of 4 or 5 represents treatment success. Conclusions This study represents the first step in developing a patient reported measure of treatment success in vitiligo trials. Further work is now needed to assess its construct validity and responsiveness to

RADIOIODINE TREATMENT OF GRAVES’ DISEASE – DOSE/RESPONSE ANALYSIS

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Jitka Čepková

2014-01-01

Full Text Available The clinical outcome of 153 Graves’ disease patients treated with a wide dose range of radioactive iodine-131 (RAI was analyzed retrospectively. Six to nine months after the first dose of RAI 60 patients (39% were hypothyroid (or rather thyroxine-substituted and 26 (17% were euthyroid, while 67 patients (44% did not respond properly: in 32 (21% their antithyroid drug (ATD dose could be reduced but not withdrawn (partial response and 35 (23% remained hyperthyroid or the same dose of ATD was necessary (no response. The outcome did not correspond significantly to the administered activity of RAI (medians 259, 259, 222, and 259 MBq for hypothyroid, euthyroid, partial, and no response subgroups, respectively, or the activity retained in the gland at 24 h (medians 127, 105, 143, and 152 MBq. The effect was, however, clearly, and in a stepwise pattern, dependent on initial thyroid volume (17, 26, 33 and 35 ml, P  6 MBq/g, cure rate 80% and lower (≤ 6 MBq/g, cure rate 46% doses gave highly significant difference (P < 0.001. With our dosing range we found a dose-dependent clinical outcome that suggests an optimum delivered dose near 6.5 MBq/g, resulting in successful treatment of ca 80% patients.

Mediation and Moderation of Psychological Pain Treatments: Response Expectancies and Hypnotic Suggestibility

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Milling, Leonard S.; Reardon, John M.; Carosella, Gina M.

2006-01-01

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,…

78 FR 50083 - Endangered Species; Marine Mammals; Receipt of Applications for Permit

Science.gov (United States)

2013-08-16

... a 5-year period. Applicant: Zoological Society of San Diego, San Diego, CA; PRT-08827B The applicant requests a permit to re-import a live female African elephant (Loxodonta africana) born in the wild for the... conducted by the applicant over a 5-year period. Applicant: Pinto Ranch, Hunt, TX; PRT-13263B The applicant...

Letter-By-Letter Reading: Natural Recovery and Response to Treatment

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Pélagie M. Beeson

2005-01-01

Full Text Available The present investigation provides a longitudinal study of an individual (RB with acquired alexia following left posterior cerebral artery stroke. At initial testing, RB exhibited acquired alexia characterized by letter-by-letter (LBL reading, mild anomic aphasia, and acquired agraphia. Repeated measures of reading accuracy and rate were collected for single words and text over the course of one year, along with probes of naming and spelling abilities. Improvements associated with natural recovery (i.e., without treatment were documented up to the fourth month post onset, when text reading appeared to be relatively stable. Multiple oral reading (MOR treatment was initiated at 22 weeks post-stroke, and additional improvements in reading rate and accuracy for text were documented that were greater than those expected on the basis of spontaneous recovery alone. Over the course of one year, reading reaction times for single words improved, and the word-length effect that is the hallmark of LBL reading diminished. RB's response to treatment supports the therapeutic value of MOR treatment to in LBL readers. His residual impairment of reading and spelling one-year post stroke raised the question as to whether further progress was impeded by degraded orthographic knowledge.

Treatment of landfill leachate by irrigation of willow coppice - Plant response and treatment efficiency

International Nuclear Information System (INIS)

Aronsson, Paer; Dahlin, Torleif; Dimitriou, Ioannis

2010-01-01

Landfill leachates usually need to be treated before discharged, and using soil-plant systems for this has gained substantial interest in Sweden and in the UK. A three-year field study was conducted in central Sweden to quantify plant response, treatment efficiency and impact on groundwater quality of landfill leachate irrigation of short-rotation willow coppice (Salix). Two willow varieties were tested and four irrigation regimes in sixteen 400-m 2 plots. The willow plants did not react negatively, despite very high annual loads of nitrogen (≤2160 kg N/ha), chloride (≤8600 kg Cl/ha) and other elements. Mean annual growth was 1.5, 9.8 and 12.6 tonnes DM/ha during years 1-3. For one of two willow varieties tested, relative leaf length accurately predicted growth rate. Irrigation resulted in elevated groundwater concentrations of all elements applied. Treatment efficiency varied considerably for different elements, but was adequate when moderate loads were applied. - Short-rotation willow coppice was successfully used for treating a strong landfill leachate in central Sweden over three years.

Withholding and withdrawing life-sustaining treatment: criminal responsibility for established medical practice?

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White, Ben; Willmott, Lindy; Allen, John

2010-05-01

The law recognises the right of a competent adult to refuse medical treatment even if this will lead to death. Guardianship and other legislation also facilitates the making of decisions to withhold or withdraw life-sustaining treatment in certain circumstances. Despite this apparent endorsement that such decisions can be lawful, doubts have been raised in Queensland about whether decisions to withhold or withdraw life-sustaining treatment would contravene the criminal law, and particularly the duty imposed by the Criminal Code (Qld) to provide the "necessaries of life". This article considers this tension in the law and examines various arguments that might allow for such decisions to be made lawfully. It ultimately concludes, however, that criminal responsibility may still arise and so reform is needed.

Guided parent-delivered cognitive behavioral therapy for childhood anxiety: Predictors of treatment response

OpenAIRE

Thirlwall, Kerstin; Cooper, Peter; Creswell, Cathy

2017-01-01

Background: Guided Parent-delivered Cognitive Behaviour Therapy (GPD-CBT) is a brief, effective treatment for childhood anxiety disorders, however not all children respond favourably. \\ud Aims: To examine predictors of response to GPD-CBT.\\ud Methods: Parents of 125 children (7 – 12 years) with an anxiety disorder received GPD-CBT over 2.6 or 5.3 hours). Recovery was measured post treatment and six months later. \\ud Results: Younger children and those with primary Generalised Anxiety Disorder...

Behavioural treatment of tics: habit reversal and exposure with response prevention.

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van de Griendt, J M T M; Verdellen, C W J; van Dijk, M K; Verbraak, M J P M

2013-07-01

Behaviour therapy has been shown to be an effective strategy in treating tics; both habit reversal (HR) and exposure and response prevention (ER) are recommended as first-line interventions. This review provides an overview of the history, theoretical concepts and evidence at present for HR and ER. In addition, treatment manuals for HR and ER are described. Despite the evidence and availability of treatment manuals, many patients do not receive a first-line psychological intervention for tics. Barriers to the acceptance and dissemination of behaviour therapy are discussed as are ways to overcome these barriers, such as the use of E-health and E-learning. Copyright © 2012 Elsevier Ltd. All rights reserved.

Response expectancies, treatment credibility, and hypnotic suggestibility: mediator and moderator effects in hypnotic and cognitive-behavioral pain interventions.

Science.gov (United States)

Milling, Leonard S; Shores, Jessica S; Coursen, Elizabeth L; Menario, Deanna J; Farris, Catherine D

2007-04-01

Several studies have shown that response expectancies are an important mechanism of popular psychological interventions for pain. However, there has been no research on whether response expectancies and treatment credibility independently mediate hypnotic and cognitive-behavioral pain interventions and whether the pattern of mediation is affected by experience with the interventions. Also, past research has indicated that hypnotic pain interventions may be moderated by hypnotic suggestibility. However, these studies have typically failed to measure the full range of suggestibility and have assessed pain reduction and suggestibility in the same experimental context, possibly inflating the association between these variables. To clarify the mediator role of response expectancies and treatment credibility, and the moderator role of hypnotic suggestibility in the hypnotic and cognitive-behavioral reduction of pain. Approximately 300 participants were assessed for suggestibility. Then, as part of an apparently unrelated experiment, 124 of these individuals received analogue cognitive-behavioral, hypnotic, or placebo control pain interventions. Response expectancies and credibility independently mediated treatment. The extent of mediation increased as participants gained more experience with the interventions. Suggestibility moderated treatment and was associated with relief only from the hypnotic intervention. Response expectancies and treatment credibility are unique mechanisms of hypnotic and cognitive-behavioral pain interventions. Hypnotic suggestibility predicts relief from hypnotic pain interventions and this association is not simply an artifact of measuring suggestibility and pain reduction in the same experimental context. The relationship between suggestibility and hypnotic pain reduction appears to be linear in nature.

Serum Adiponectin, Vitamin D, and Alpha-Fetoprotein in Children with Chronic Hepatitis C: Can They Predict Treatment Response?

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Mohamed Ahmed Khedr

2015-01-01

Full Text Available Background & Aims. The currently available treatment for chronic hepatitis C (CHC in children is costly and with much toxicity. So, predicting the likelihood of response before starting therapy is important. Methods. Serum adiponectin, vitamin D, and alpha-fetoprotein (AFP were measured before starting pegylated-interferon/ribavirin therapy for 50 children with CHC. Another 21 healthy children were recruited as controls. Results. Serum adiponectin, vitamin D, and AFP were higher in the CHC group than healthy controls (p<0.0001, p=0.071, and p=0.87, resp.. In univariate analysis, serum adiponectin was significantly higher in responders than nonresponders (p<0.0001 and at a cutoff value ≥8.04 ng/mL it can predict treatment response by 77.8% sensitivity and 92.9% specificity, while both AFP and viremia were significantly lower in responders than nonresponders, p<0.0001 and p=0.0003, respectively, and at cutoff values ≤3.265 ng/mL and ≤235,384 IU/mL, respectively, they can predict treatment response with a sensitivity of 83.3% for both and specificity of 85.7% and 78.6%, respectively. In multivariate analysis, adiponectin was found to be the only independent predictor of treatment response (p=0.044. Conclusions. The pretreatment serum level of adiponectin can predict the likelihood of treatment response, thus avoiding toxicities for those unlikely to respond to therapy.

Creatine fails to augment the benefits from resistance training in patients with HIV infection: a randomized, double-blind, placebo-controlled study.

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Giorgos K Sakkas

Full Text Available Progressive resistance exercise training (PRT improves physical functioning in patients with HIV infection. Creatine supplementation can augment the benefits derived from training in athletes and improve muscle function in patients with muscle wasting. The objective of this study was to determine whether creatine supplementation augments the effects of PRT on muscle strength, energetics, and body composition in HIV-infected patients.This is a randomized, double blind, placebo-controlled, clinical research center-based, outpatient study in San Francisco. 40 HIV-positive men (20 creatine, 20 placebo enrolled in a 14-week study. Subjects were randomly assigned to receive creatine monohydrate or placebo for 14 weeks. Treatment began with a loading dose of 20 g/day or an equivalent number of placebo capsules for 5 days, followed by maintenance dosing of 4.8 g/day or placebo. Beginning at week 2 and continuing to week 14, all subjects underwent thrice-weekly supervised resistance exercise while continuing on the assigned study medication (with repeated 6-week cycles of loading and maintenance. The main outcome measurements included muscle strength (one repetition maximum, energetics ((31P magnetic resonance spectroscopy, composition and size (magnetic resonance imaging, as well as total body composition (dual-energy X-ray absorptiometry. Thirty-three subjects completed the study (17 creatine, 16 placebo. Strength increased in all 8 muscle groups studied following PRT, but this increase was not augmented by creatine supplementation (average increase 44 vs. 42%, difference 2%, 95% CI -9.5% to 13.9% in creatine and placebo, respectively. There were no differences between groups in changes in muscle energetics. Thigh muscle cross-sectional area increased following resistance exercise, with no additive effect of creatine. Lean body mass (LBM increased to a significantly greater extent with creatine. CONCLUSIONS / SIGNIFICANCE: Resistance exercise improved

Effect of abacavir on sustained virologic response to HCV treatment in HIV/HCV co-infected patients, Cohere in Eurocoord

DEFF Research Database (Denmark)

Smit, Colette; Arends, Joop; Peters, Lars

2015-01-01

BACKGROUND: Contradicting results on the effect of abacavir (ABC) on hepatitis C virus (HCV) treatment responses in HIV/HCV co-infected patients have been reported. We evaluated the influence of ABC on the response to pegylated interferon (pegIFN) and ribavirin (RBV)-containing HCV treatment in H...

Guided parent-delivered cognitive behavioral therapy for childhood anxiety: Predictors of treatment response.

Science.gov (United States)

Thirlwall, Kerstin; Cooper, Peter; Creswell, Cathy

2017-01-01

Guided Parent-delivered Cognitive Behaviour Therapy (GPD-CBT) is a brief, effective treatment for childhood anxiety disorders, however not all children respond favourably. To examine predictors of response to GPD-CBT. Parents of 125 children (7-12 years) with an anxiety disorder received GPD-CBT over 2.6 or 5.3h. Recovery was measured post treatment and six months later. Younger children and those with primary Generalised Anxiety Disorder (GAD) improved more post treatment, but older children and those without primary GAD had better outcomes at six month follow up. Fewer children allocated to 2.6h had recovered post treatment compared to those allocated to the 5.2h intervention, but did not differ significantly six months later. The identification of predictors of short and longer-term treatment outcomes can guide treatment decisions following this low-intensity approach. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Clinical profile of congenital adrenal hyperplasia and short-term response to treatment

International Nuclear Information System (INIS)

Lal, S.; Lal, S.; Jamro, B.U.; Jamro, S.

2015-01-01

To determine the clinical presentation of congenital adrenal hyperplasia and short- term response to treatment. Background: Congenital adrenal hyperplasia (CAH) is a genetic disorder which usually presents with life threatening emergencies. Awareness of physicians regarding these presentations is an essential for early diagnosis and lifesaving treatment. In view of the prevalence of the condition as reported from tertiary care centers within the country and other parts of the globe, we had carried out a study in the paediatric department of Shaheed Mohtrama Benazir Bhutto Medical University Larkana. Material and Methods: The study was conducted over a period of one year from July 2012 to June 2013. All infants presenting with vomiting, dehydration, shock, failure to thrive and ambiguous genitalia were examined and investigated thoroughly. The diagnosis was based upon a raised level of serum 17 OHP in a child with suggestive clinical features. Results: A total of 40 children were diagnosed to have CAH during the study period. The major presenting features were vomiting in 13 (32.5%), ambiguous genitalia 17 (42.5%), vomiting and ambiguous genitalia 10 (25%), shock 5(12.5%) and failure to thrive in 13 (32.5%) of cases. All the patients were followed up after initiation of treatment and good response was observed to short-term treatment. Conclusion: This study highlights the importance of common clinical features like vomiting, unreasonable dehydration, shock and ambiguous genitalia being the presenting features of CAH and the effectiveness of replacement therapy in amending life threatening emergencies due to this condition. (author)

Assessing Tumor Response to Treatment in Patients with Lung Cancer Using Dynamic Contrast-Enhanced CT

DEFF Research Database (Denmark)

Strauch, Louise S; Eriksen, Rie Ø; Sandgaard, Michael

2016-01-01

Reviews and Meta-Analyses (PRISMA) guidelines. Only original research articles concerning treatment response in patients with lung cancer assessed with DCE-CT were included. To assess the validity of each study we implemented Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). The initial search......The aim of this study was to provide an overview of the literature available on dynamic contrast-enhanced computed tomography (DCE-CT) as a tool to evaluate treatment response in patients with lung cancer. This systematic review was compiled according to Preferred Reporting Items for Systematic...... yielded 651 publications, and 16 articles were included in this study. The articles were divided into groups of treatment. In studies where patients were treated with systemic chemotherapy with or without anti-angiogenic drugs, four out of the seven studies found a significant decrease in permeability...

The thyroid-related quality of life measure ThyPRO has good responsiveness and ability to detect relevant treatment effects

DEFF Research Database (Denmark)

Watt, Torquil; Cramon, Per; Hegedüs, Laszlo

2014-01-01

responsiveness of the thyroid-related quality of life (QoL) instrument ThyPRO in patients undergoing relevant clinical treatments for benign thyroid diseases and to compare it with responsiveness of the generic SF-36 Health Survey. METHODS: A sample of 435 patients undergoing treatment completed the ThyPRO...... nontoxic goiter treated with surgery or radioactive iodine and remaining euthyroid (n = 62). Changes in QoL were evaluated in terms of effect size and compared to the changes predicted by clinical experts. The responsiveness of equivalent scales from ThyPRO and SF-36 Health Survey were compared...... with the relative validity index. RESULTS: The ThyPRO demonstrated good responsiveness across the whole range of QoL aspects in patients with hyper- and hypothyroidism. Responsiveness to treatment of nontoxic goiter was also demonstrated for physical and mental symptoms and overall QoL, but not for impact on social...

Pathological gambling and age: differences in personality, psychopathology, and response to treatment variables.

Science.gov (United States)

González-Ibáñez, A; Mora, M; Gutiérrez-Maldonado, J; Ariza, A; Lourido-Ferreira, M R

2005-02-01

The aim of this study was to ascertain the possible differences in personality, psychopathology, and response to treatment in pathological gambling according to age. The sample, comprising 67 participants, was divided into three groups: 32.6% with ages ranging between 17 and 26 years, 31.3% between 27 and 43 years, and 35.8% over 44 years of age. The participants were administered the following tests, Minnesota Multiphasic Personality Inventory [MMPI; Hathaway, S.R. & McKinley, J.C. (1943, 1961). Cuestionario de personalidad MMPI. Madrid Seccion de Estudios de TEA ed. 1970, 1975], sensation-seeking questionnaire [SSS; Zuckerman, M. (1979). Sensation seeking; beyond the optimal level of arousal. Hillsdale, NJ: Lawrence Erlbaum Associates], and the Symptom Check List Revised [SCL-90-R; Derogatis, L.R. (1977). Symptom check list-90 revised. Administration scoring and procedures manual. Baltimore]. All underwent a group treatment programme that was carried out in the Pathological Gambling Unit at Ciutat Sanitaria i Universitaria de Bellvitge (CSUB), Teaching hospital, Barcelona, Spain. The findings show differences depending on age in the participants' personality and in psychopathology and in their response to treatment.

Response of peripheral blood to 131I treatment in Swiss albino mice

International Nuclear Information System (INIS)

Jagetia, G.C.; Gupta, S.M.; Kumar, S.; Devi, P.U.

1982-01-01

Adult Swiss albino mice were treated with 333 kBq/g body weight (approximately 10.22 Gy/day) intraperitoneally and sacrificed at different post-treatment intervals. It was observed that erythrocyte counts, hemoglobin and hematocrit values decreased gradually, while the depletion in leukocyte count was abrupt at early intervals after treatment. The early decline in the leukocytes followed by more gradual may be due to the direct cell killing by the isotope. The indirect effect on the hematopoietic tissues may be responsible for the continued low levels of the different blood constituents during the later intervals. (author)

Monitoring treatment response and metastatic relapse in advanced bladder cancer by liquid biopsy analysis

DEFF Research Database (Denmark)

Birkenkamp-Demtröder, Karin; Christensen, Emil; Nordentoft, Iver Kristiansen

2017-01-01

of circulating tumour DNA (ctDNA) in plasma and urine to detect metastatic relapse after cystectomy and measure treatment efficacy. We exome sequenced tumour and germline DNA from patients with muscle-invasive bladder cancer and monitored ctDNA in 370 liquid biopsies throughout the disease courses by 84......DNA detection in plasma and diagnosis of relapse was 101 d after cystectomy (range 0-932 d). Early detection of metastatic relapse and treatment response using liquid biopsies represents a novel, highly sensitive tool for monitoring patients, supporting clinicians, and guiding treatment decisions. PATIENT...

Global gene expression analysis of early response to chemotherapy treatment in ovarian cancer spheroids

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Tetu Bernard

2008-02-01

Full Text Available Abstract Background Chemotherapy (CT resistance in ovarian cancer (OC is broad and encompasses diverse unrelated drugs, suggesting more than one mechanism of resistance. To better understand the molecular mechanisms controlling the immediate response of OC cells to CT exposure, we have performed gene expression profiling in spheroid cultures derived from six OC cell lines (OVCAR3, SKOV3, TOV-112, TOV-21, OV-90 and TOV-155, following treatment with 10,0 μM cisplatin, 2,5 μM paclitaxel or 5,0 μM topotecan for 72 hours. Results Exposure of OC spheroids to these CT drugs resulted in differential expression of genes associated with cell growth and proliferation, cellular assembly and organization, cell death, cell cycle control and cell signaling. Genes, functionally involved in DNA repair, DNA replication and cell cycle arrest were mostly overexpressed, while genes implicated in metabolism (especially lipid metabolism, signal transduction, immune and inflammatory response, transport, transcription regulation and protein biosynthesis, were commonly suppressed following all treatments. Cisplatin and topotecan treatments triggered similar alterations in gene and pathway expression patterns, while paclitaxel action was mainly associated with induction of genes and pathways linked to cellular assembly and organization (including numerous tubulin genes, cell death and protein synthesis. The microarray data were further confirmed by pathway and network analyses. Conclusion Most alterations in gene expression were directly related to mechanisms of the cytotoxics actions in OC spheroids. However, the induction of genes linked to mechanisms of DNA replication and repair in cisplatin- and topotecan-treated OC spheroids could be associated with immediate adaptive response to treatment. Similarly, overexpression of different tubulin genes upon exposure to paclitaxel could represent an early compensatory effect to this drug action. Finally, multicellular

Carbon dioxide test as an additional clinical measure of treatment response in panic disorder

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Valença Alexandre M.

2002-01-01

Full Text Available OBJECTIVE: We aim to determine if a treatment with a dose of clonazepam - 2 mg/day, for 6 weeks, blocks spontaneous panic attacks and the ones induced by the inhalation of 35% carbon dioxide (CO2 in panic disorder (PD patients. The CO2 challenge-test may be a useful addition tool for measuring the pharmacological response during the initial phase (6 weeks in the treatment of PD. METHOD: Eighteen PD patients drug free for a week participated in a carbon dioxide challenge test. Fourteen had a panic attack and were openly treated for a 6-week period with clonazepam. At the end of the 6-week period they were submitted again to the CO2 challenge test. RESULTS: After 6 weeks of treatment with clonazepam, 12 of 14 PD patients (85.7% did not have a panic attack after the CO2 challenge test. Just 2 of 14 patients (14.3% had a panic attack after the CO2 challenge test. Ten of 14 (71.4% PD patients had panic free status after clonazepam treatment. The 2 patients who had a panic attack in the sixth week, after the CO2 test, did not have panic free status after the treatment with clonazepam. CONCLUSION: The CO2-test may be a valid tool for testing and predicting the drug response.

A responsive evaluation of mental health treatment in Cambodia: Intentionally addressing poverty to increase cultural responsiveness in therapy.

Science.gov (United States)

Seponski, Desiree M; Lewis, Denise C; Megginson, Maegan C

2014-01-01

Mental health issues are significant contributors to the global burden of disease with the highest incidence in resource poor countries; 90% of those in need of mental health treatment reside in low resource countries but receive only 10% of the world's resources. Cambodia, the eighth least developed country in the world, serves as one example of the need to address mental health concerns in low-income, resource poor countries. The current study utilises responsive evaluation methodology to explore how poverty-stricken Cambodian clients, therapists and supervisors experience Western models of therapy as culturally responsive to their unique needs. Quantitative and qualitative data were triangulated across multiple stakeholders using numerous methods including a focus group, interviews, surveys, case illustrations and live supervision observation and analysed using constant comparative analysis. Emerging findings suggest that poverty, material needs, therapy location and financial situations greatly impact the daily lives and mental health conditions of Cambodians and hinder clients' therapeutic progress. The local community needs and context of poverty greatly hinder clients' therapeutic progress in therapy treatment and when therapy does not directly address the culture of poverty, clients did not experience therapy as valuable despite some temporary decreases in mental health symptoms.

Penile growth in response to hormone treatment in children with micropenis

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Rajendra B Nerli

2013-01-01

Full Text Available Introduction: Micropenis is defined as a stretched penile length 2.5 standard deviations less than the mean for age without the presence of any other penile anomalies, such as hypospadias. The term refers to a specific disorder that has a known set of causative factors and defined treatment modalities. The purpose of this study was to determine the effect of hormonal therapy on the gonadal response and penile growth in children who presented with micropenis. Materials and Methods: Children (<18 years who met the criteria for micropenis were included in this study. Children more than 11 years old were treated using a standard protocol of 1,500 to 2,000 IU human chorionic gonadotrophin administrated intramuscularly, once per week, for 6 weeks. Children less than 11 years old were treated with parenteral testosterone enanthate 25 mg once a month for 3 months. Response was evaluated in terms of change in testosterone levels and size of penis. Results: Serum testosterone levels at baseline and after 8 weeks of hormonal treatment were <20 and 449.4 ng/mL, respectively (P < 0.0001 in all children more than 11 years old. Stretched penile length after hormonal treatment increased from 15.54 to 37.18 mm in children less than 11 years old and from 26.42 to 64.28 mm in children more than 11 years old (P < 0.001. Conclusions: Management of isolated micropenis revolves around testosterone (direct administration or encouraging the patient′s body to make its own, and results with respect to increase in penile length are promising.

Response after Infection-Associated Rise in Clozapine Levels in Treatment-Resistant Schizoaffective Disorder

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Nina H. Grootendorst-van Mil

2018-01-01

Full Text Available The clinical management of patients with treatment-resistant psychotic disorders is still challenging despite years of extensive research. If first-line antipsychotic treatment proves ineffective, clozapine is considered golden standard. Herein, we report on a patient with schizoaffective disorder that initially showed no response to treatment with clozapine and ECT and therefore reached a therapeutic dead end. After an unintentional exposure to supratherapeutic clozapine levels, related to a pneumonia, a significant and persistent reduction of psychotic symptoms occurred. The report suggests a careful reevaluation of the clozapine dose in cases of treatment-resistant psychotic disorders with failed trials of clozapine. Further increase of dose may prove efficacious, although side effects should be closely monitored. Research to determine the upper threshold of clozapine for antipsychotic efficacy is warranted.

Dynamic contrast-enhanced CT in advanced lung cancer after chemotherapy with/within radiation therapy: Can it predict treatment responsiveness of the tumor?

Energy Technology Data Exchange (ETDEWEB)

Yoo, Mi Ri; Whang, Sung Ho; Park, Chul Hwan; Kim, Sang Jin; Kim, Tae Hoon [Dept. of Radiology and Research Institute of Radiological Science, Yonsei University Health System, Seoul (Korea, Republic of)

2013-08-15

To evaluate the contrast enhancement patterns of lung cancer after chemotherapy using a dynamic contrast-enhanced (DCE) CT and to determine whether the enhancement patterns of tumors at early stages of treatment can predict treatment responses. Forty-two patients with advanced lung cancers underwent DCE-CT and follow-up CT after chemotherapy. We evaluated peak and net enhancement (PE and NE, respectively) and time-density curves (TDCs) (type A, B, C, and D) on DCE-CT images. Treatment responses were evaluated using revised Response Evaluation Criteria in Solid Tumor criteria. NE and PE values were significantly higher in the progressive disease (PD) groups than in the stable disease (SD) or partial response (PR) groups (p < 0.05). Types B, C, and D on TDCs were observed mostly in the PR and SD groups (96.0%), whereas type A was most frequent in the SD and PD groups (97.2%), which were significantly different in terms of PE and NE. Contrast enhancement pattern regarding the response of treatment on DCE-CT images could be helpful in predicting treatment response of advanced lung cancer after treatment.