• Title/Summary/Keyword: Low response

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Factors associated with effectiveness of and rash occurrence by Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in patients with non-small cell lung cancer (비소세포폐암 환자에 있어서 Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors의 약효 및 rash 발생과 관련한 인자에 대한 연구)

  • Bae, Na-Rae;Choi, Hye-Jin;Lee, Byung-Koo;Gwak, Hye-Sun
    • Korean Journal of Clinical Pharmacy
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    • v.18 no.2
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    • pp.75-83
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    • 2008
  • Purpose: Currently lung cancer ranks second in cancer for incidence rate and is a disease that ranks first for a death rate by cancerous growth because it is already advanced at the time of diagnosis. The purpose of this paper was to analyze the factors that affect the effectiveness of and rash occurrence by Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI) in patients with non-small cell lung cancer. Methods: A retrospective chart review of 100 patients, who took EGFR TKI (erlotinib, gefitinib) among patients who were diagnosed with non-small cell lung cancer in a Hospital in Korea between May 2005 and February 2008, was conducted. The drug effectiveness was evaluated by Response Evaluation Criteria In Solid Tumor. Results: EGFR mutation was the only factor associated with drug response (complete response and partial response). When stable disease was added to drug response as the evaluation parameter, ECOG and rash as well as EGFR mutation were found to be important factors. Survival, however, was not affected by EGFR mutation. The factors influenced on survival were older age (${\geq}65$), low ECOG ($1{\sim}2$), adenocarcinoma and rash. In the case of rash, group with EGFR mutation or low ECOG showed significantly higher chance of occurrence. There was no significant difference in rash occurrence between gefitinib and erlotinib groups. Conclusions: Based on the results, EGFR mutation positive and low ECOG ($1{\sim}2$) were significantly important factors for both effectiveness of EGFR TKI and rash occurrence. Also, rash itself was found to be an independently significant factor for the disease control and survival. Therefore, while administering EGFR TKI, patients who have the factors associated with rash occurrence should be closely monitored for effective and safe drug therapy.

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Wind induced internal pressure overshoot in buildings with opening

  • Guha, T.K.;Sharma, R.N.;Richards, P.J.
    • Wind and Structures
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    • v.16 no.1
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    • pp.1-23
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    • 2013
  • The wind-induced transient response of internal pressure following the creation of a sudden dominant opening during the occurrence of high external pressure, in low-rise residential and industrial buildings was numerically investigated. The values of the ill-defined parameters namely the flow contraction coefficient, loss coefficient and the effective slug length were calibrated by matching the analytical response with the computational fluid dynamics predictions. The effect of a sudden i.e., "instantaneously created" windward opening in the Texas Technical University (TTU) test building envelope was studied for two different envelope flexibility-leakage combinations namely: (1) a quasi-statically flexible and non-porous envelope and (2) a quasi-statically flexible and porous envelope. The responses forced by creating the openings at different time leads/lags with respect to the occurrence of the peak external pressure showed that for cases where the openings are created in close temporal proximity to the peak pressure, the transient overshoot values of internal pressure could be higher than the peak values of internal pressure in the pre-sequent or subsequent resonant response. In addition, the influence of time taken for opening creation on the level of overshoot was also investigated for the TTU building for the two different envelope characteristics. Non-dimensional overshoot factors are presented for a variety of cavity volume-opening area combinations for (1) buildings with rigid/quasi-statically flexible non-porous envelope, and (2) buildings with rigid/quasi-statically flexible and porous envelope (representing most low rise residential and industrial buildings). While the factors appear slightly on the high side due to conservative assumptions made in the analysis, a careful consideration regarding the implication of the timing and magnitude of such overshoots during strong gusts, in relation to the steady state internal pressure response in cyclonic regions, is warranted.

Cytokines Expression and Nitric Oxide Production under Induced Infection to Salmonella Typhimurium in Chicken Lines Divergently Selected for Cutaneous Hypersensitivity

  • Singh, Rani;Jain, Preeti;Pandey, N.K.;Saxena, V.K.;Saxena, M.;Singh, K.B.;Ahmed, K.A.;Singh, R.P.
    • Asian-Australasian Journal of Animal Sciences
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    • v.25 no.7
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    • pp.1038-1044
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    • 2012
  • In the present study, the impact of Salmonella Typhimurium on cell-mediated immunity (CMI) was investigated in 5 week-old immuno divergent broiler lines selected for the high and low response to phytohemagglutinin-P. The immune response was assessed in peripheral-blood mononuclear cells (PBMCs) induced with Salmonella Typhimurium at different time intervals (0 h, 0.5 h, 2 h, 4 h, 6 h, 12 h and 24 h). The differential mRNA expression patterns of IFN-${\gamma}$, IL-2 and iNOS were evaluated by quantitative real time PCR. In-vitro production of nitric oxide (NO) was also estimated in the culture supernatant and correlated with iNOS mRNA expression. Present study showed higher production of NO in the high cell-mediated line (HCMI) as compared to the low cell-mediated line (LCMI) upon stimulation with Salmonella Typhimurium. Correspondingly, higher mRNA expression of iNOS and IFN-${\gamma}$ were observed in high response birds (HCMI); but IL-2 was down regulated in this line compared to the low response birds (LCMI). Significantly (p<0.05) higher expression of iNOS, IFN-${\gamma}$ and higher production of NO in high line indicated that the selection for PHA-P response might be employed for increasing the immune competence against Salmonella Typhimurium in chicken flocks.

Differential Inhibitory Action of Taurine between Electrically Evoked Response and Low $Mg^{++}-Induced$ Spontaneous Activity in the CA1 Area of the Rat Hippocampal Slices

  • Baek, Soo-Youn;Yang, Sung-Gu;Lee, Chang-Joong
    • The Korean Journal of Physiology and Pharmacology
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    • v.1 no.5
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    • pp.467-475
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    • 1997
  • Although one of the major physiological functions of taurine(2-aminoethanesulfonic acid) is the inhibitory action on the central nervous system(CNS), the mechanism of taurine in controlling the neuronal excitation in the CNS has been in controversy. Electrically evoked pEPSP and spontaneous activity induced by the perfusion of low $Mg^{++}-ACSF$ were recorded in the CA1 pyramidal cell layer of the hippocampal slice. To test the inhibitory effect of taurine on spontaneous responses, taurine was treated for 2 min at various concentrations(1 mM-10 mM). Taurine reduced the spontaneous activity by 22.2% at 1 mM, and 100% at 2 mM in low $Mg^{++}-ACSF$. Evoked response was induced by electrical stimulation of Schaffer collateral-commissural fibers. Taurine reduced the evoked response by 11.68% at 3 mM, and 24.25% at 5 mM. Even 20 mM of taurine reduced the evoked response only by 24 % after 5 min treatment. That is, the inhibitory efficacy was much higher in spontaneous activity than in evoked response. The $GABA_A$ receptor antagonist, 100 uM bicuculline, blocked the inhibitory action of taurine, while $GABA_B$ receptor antagonist, 700 uM phaclofen, did not. Taurine blocked the spontaneous activity in the presence of CNQX, and did not block the electrically evoked responce in the presence of APV. The results suggest that taurine causes hyperpolarization in the cell by binding to $GABA_A$ receptor and preferentially attenuates NMDA receptor-mediated hyperexcitation, leaving synaptic transmission unmodified.

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High and Low Dose Folinic Acid, 5-Fluorouracil Bolus and Continuous Infusion for Poor-Prognosis Patients with Advanced Colorectal Carcinoma

  • Bano, Nusrat;Najam, Rahila;Mateen, Ahmed;Qazi, Faaiza
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.8
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    • pp.3589-3593
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    • 2012
  • Objective: Evaluation and assessment of response rate, duration and toxicity in patients subjected to 5-FU based chemotherapy. Background: The therapeutic ratio shifts with different 5FU/LV regimens and none yet serve as the internationally accepted Gold Standard. A bimonthly regimen of high dose leucovorin is reported to be less toxic and more effective than monthly low dose regimens. We here compare therapeutic responses and survival benefit of the two regimens in poor prognosis patients with advanced colorectal carcinoma. Patients and Methods: A total of 35 patients with histologically confirmed colorectal carcinoma were subjected to de Gramont and Mayo Clinic regimen. Nineteen patients were treated with high dose folinic acid ($200mg/m^2$), glucose 5%, 5-FU ($400mg/m^2$) and 22 hr. CIV ($600mg/m^2$) for two consecutive days every two weeks. These patients had failed responses to previous chemotherapy and were above sixty years of age with poor general status. Sixteen patients (six below 60 years) with progressive disease were subjected to low dose folinic acid ($20mg/m^2$)for five days, 5FU($425mg/m^2$) injection bolus for 5 days, every five weeks. An initial evaluation was made in sixty days and responders were reevaluated at sixty days interval or earlier in case of clinical impairment. Based on positive prognosis, the therapy was continued. Evaluation of treatment response was made on the basis of WHO criteria. Results: The response rate was 44% in thirty four evaluable patients, with 4 complete responses (11.8%) and 11 (32.4%) partial responses. The two schedules were well tolerated, whereas, mild toxicity without WHO Grade ${\geq}2$ events was assessed. The response duration was extended (12 months) in a few patients with age above sixty years treated by high dose bimonthly regimen of 5FU/LV. Conclusion: The regimens are safe and effective in advanced colorectal carcinoma patients with poor general status.

Serviceability Limit State and Response Modification Factors (기능수행수준과 응답수정계수)

  • Kook, Seung-Kyu
    • Journal of the Computational Structural Engineering Institute of Korea
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    • v.25 no.2
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    • pp.149-154
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    • 2012
  • While the Earthquake Resistant Design Part of Korean Roadway Bridge Design Code provides design procedures for the No Collapse Requirement, requirements for the Serviceability Limit State are not clearly provided. The basic design method to meet the No Collapse Requirement is the spectrum analysis method using response modification factors and the Serviceability Limit State is determined by both the importance factor and the response modification factor applied in the design procedure. The importance factor can be simply applied according to the bridge importance category, however, in moderate/low seismic regions the application of the response modification factor may bring different result according to design conditions. In this study, for a typical bridge in the moderate/low seismic regions, determination procedures for the Serviceability Limit State are reviewed by carrying out earthquake resistant design and supplementary provisions for the Earthquake Resistant Design Part are identified based on the study results.

CaPUB1, a Hot Pepper U-box E3 Ubiquitin Ligase, Confers Enhanced Cold Stress Tolerance and Decreased Drought Stress Tolerance in Transgenic Rice (Oryza sativa L.)

  • Min, Hye Jo;Jung, Ye Jin;Kang, Bin Goo;Kim, Woo Taek
    • Molecules and Cells
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    • v.39 no.3
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    • pp.250-257
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    • 2016
  • Abiotic stresses such as drought and low temperature critically restrict plant growth, reproduction, and productivity. Higher plants have developed various defense strategies against these unfavorable conditions. CaPUB1 (Capsicum annuum Putative U-box protein 1) is a hot pepper U-box E3 Ub ligase. Transgenic Arabidopsis plants that constitutively expressed CaPUB1 exhibited drought-sensitive phenotypes, suggesting that it functions as a negative regulator of the drought stress response. In this study, CaPUB1 was over-expressed in rice (Oryza sativa L.), and the phenotypic properties of transgenic rice plants were examined in terms of their drought and cold stress tolerance. Ubi:CaPUB1 T3 transgenic rice plants displayed phenotypes hypersensitive to dehydration, suggesting that its role in the negative regulation of drought stress response is conserved in dicot Arabidopsis and monocot rice plants. In contrast, Ubi:CaPUB1 progeny exhibited phenotypes markedly tolerant to prolonged low temperature ($4^{\circ}C$) treatment, compared to those of wild-type plants, as determined by survival rates, electrolyte leakage, and total chlorophyll content. Cold stress-induced marker genes, including DREB1A, DREB1B, DREB1C, and Cytochrome P450, were more up-regulated by cold treatment in Ubi:CaPUB1 plants than in wild-type plants. These results suggest that CaPUB1 serves as both a negative regulator of the drought stress response and a positive regulator of the cold stress response in transgenic rice plants. This raises the possibility that CaPUB1 participates in the cross-talk between drought and low-temperature signaling pathways.

Item Analysis using Classical Test Theory and Item Response Theory, Validity and Reliability of the Korean version of a Pressure Ulcer Prevention Knowledge (한국어판 욕창예방지식도구의 고전검사이론과 문항반응이론을 적용한 문항분석, 타당도와 신뢰도)

  • Kang, Myung Ja;Kim, Myoung Soo
    • Journal of Korean Biological Nursing Science
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    • v.20 no.1
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    • pp.11-19
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    • 2018
  • Purpose: The purposes of this study were to perform items analysis using the classical test theory (CTT) and the item response theory (IRT), and to establish the validity and reliability of the Korean version of pressure ulcer prevention knowledge. Methods: The 26-item pressure ulcer prevention knowledge instrument was translated into Korean, and the item analysis of the 22 items having an adequate content validity index (CVI), was conducted. A total of 240 registered nurses in 2 university hospitals completed the questionnaire. Each item was analyzed applying CTT and IRT according to 2-parameter logistic model. Response alternatives quality, item difficulty and item discrimination were evaluated. For testing validity and reliability, Pearson correlation coefficient and Kuder Richardson-20 (KR-20) were used. Results: Scale CVI was .90 (Item-CVI range= .75-1.00). The total correct answer rate for this study population was relatively low as 52.5%. The quality of response alternatives was found to be relatively good (range= .02-.83). The item difficulty of the questions ranged form .10 to .86 according to CTT and -12.19 to 29.92 according to the IRT. This instrument had 12-low, 2-medium and 8-high item difficulty applying IRT. The values for the item discrimination ranged .04-.57 applying CTT and .00-1.47 applying IRT. And overall internal consistency (KR-20) was .62 and stability (test-retest) was .82. Conclusion: The instrument had relatively weak construct validity, item discrimination according to the IRT. Therefore, the cautious usage of a Korean version of this instrument would be recommended for discrimination because there are so many attractive response alternatives and low internal consistency.

Structural impact response characteristics of an explosion-resistant profiled blast walls in arctic conditions

  • Sohn, Jung Min;Kim, Sang Jin;Seong, Dong Jin;Kim, Bong Ju;Ha, Yeon Chul;Seo, Jung Kwan;Paik, Jeom Kee
    • Structural Engineering and Mechanics
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    • v.51 no.5
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    • pp.755-771
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    • 2014
  • Environmental changes, especially global climate change, are creating new challenges to the development of the Arctic regions, which have substantial energy resources. And attention to offshore structures has increased with oil and gas development. The structural impact response of an explosion-resistant profiled blast walls normally changes when it operates in low temperatures. The main objectives of this study are to investigate the structural response of blast walls in low temperature and suggest useful guidelines for understanding the characteristics of the structural impact response of blast walls subjected to hydrocarbon explosions in Arctic conditions. The target temperatures were based on the average summer temperature ($-20^{\circ}C$), the average winter temperature ($-40^{\circ}C$) and the coldest temperature recorded (approximately $-68^{\circ}C$) in the Arctic. The nonlinear finite element analysis was performed to design an explosion-resistant profiled blast wall for use in Arctic conditions based on the behaviour of material properties at low temperatures established by performing a tensile test. The conclusions and implications of the findings are discussed.

Aerodynamic behaviour of double hinged articulated loading platforms

  • Zaheer, Mohd Moonis;Hasan, Syed Danish;Islam, Nazrul;Aslam, Moazzam
    • Ocean Systems Engineering
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    • v.11 no.1
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    • pp.17-42
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    • 2021
  • Articulated loading platforms (ALPs) belongs to a class of offshore structures known as compliant. ALP motions have time periods falling in the wind excitation frequency range due to their compliant behaviour. This paper deals with the dynamic behavior of a double hinged ALP subjected to low-frequency wind forces with random waves. Nonlinear effects due to variable submergence, fluctuating buoyancy, variable added mass, and hydrodynamic forces are considered in the analysis. The random sea state is characterized by the Pierson-Moskowitz (P-M) spectrum. The wave forces on the submerged elements of the platform's shaft are calculated using Morison's Equation with Airy's linear wave theory ignoring diffraction effects. The fluctuating wind load has been estimated using Ochi and Shin wind velocity spectrum for offshore structures. The nonlinear dynamic equation of motion is solved in the time domain by the Wilson-θ method. The wind-structure interactions, along with the effect of various other parameters on the platform response, are investigated. The effect of offset of aerodynamic center (A.C.) with the center of gravity (C.G.) of platform superstructure has also been investigated. The outcome of the analyses indicates that low-frequency wind forces affect the response of ALP to a large extent, which otherwise is not enhanced in the presence of only waves. The mean wind modifies the mean position of the platform surge response to the positive side, causing an offset. Various power spectral densities (PSDs) under high and moderate sea states show that apart from the significant peak occurring at the two natural frequencies, other prominent peaks also appear at very low frequencies showing the influence of wind on the response.