The interface between perfluorosulfonic acid polymer electrolytes and Pt nanoparticles in a model hydrogen fuel-cell catalyst layer was analyzed using high-resolution scanning transmission X-ray ...microscopy. After electrochemical cycling, thin films of damaged ionomer, enriched in CC bonds, are observed near the Pt surface. This local degradation of the Pt–ionomer interface triggered by electrochemical oxidation contrasts with that from peroxide radical exposure. Peroxide damage is catalyzed by Pt and leads instead to thin films containing carboxylic acids. Direct mapping of the degradation at these nanoscale interfaces inside hydrogen fuel-cell catalyst layers exposes a previously unknown electrochemical reactivity of perfluorinated ionomers.
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IJS, KILJ, NUK, PNG, UL, UM
A disodium phosphonooxymethyl prodrug of the antitumor agent triptolide was prepared from the natural product in three steps (39% yield) and displayed excellent aqueous solubility at pH 7.4 (61 ...mg/mL) compared to the natural product (17 μg/mL). The estimated shelf life (t 90) for hydrolysis of the prodrug at 4 °C and pH 7.4 was found to be two years. In a mouse model of human colon adenocarcinoma (HT-29), the prodrug administered intraperitoneally was effective in reducing or eliminating xenograft tumors at dose levels as low as 0.3 mg/kg when given daily and at 0.9 mg/kg when given less frequently. When given via intraperitoneal and oral routes at daily doses of 0.6 and 0.9 mg/kg, the prodrug was also effective and well tolerated in a mouse model of human ovarian cancer (A2780).
X‐ray absorption is a sensitive and versatile tool for chemical speciation. However, when high doses are used, the absorbed energy can change the composition, amount and structure of the native ...material, thereby changing the aspects of the absorption process on which speciation is based. How can one calculate the dose when X‐ray irradiation affects the chemistry and changes the amount of the material? This paper presents an assumption‐free approach which can retrieve from the experimental data all dose‐sensitive parameters – absorption coefficients, composition (elemental molecular units), material densities – which can then be used to calculate accurate doses as a function of irradiation. This approach is illustrated using X‐ray damage to a solid film of a perfluorosulfonic acid fluoropolymer in a scanning transmission soft X‐ray microscope. This new approach is compared against existing dose models which calculate the dose by making simplifying assumptions regarding the material quantity, density and chemistry. While the detailed measurements used in this approach go beyond typical methods to experimental analytical X‐ray absorption, they provide a more accurate quantitation of radiation dose, and help to understand mechanisms of radiation damage.
A general method for calculating the dose absorbed in X‐ray irradiation of a material when the irradiation changes the physical properties of the material is presented. The method considers cases where X‐ray irradiation alters the chemical structure, the amount of material in the irradiated area, the linear absorption coefficient and the density of the material.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Bioelectrical impedance analysis (BIA) is an easy-to-use, non-invasive and reproducible technique to evaluate changes in body composition and nutritional status. Phase angle, determined by BIA, has ...been found to be a prognostic indicator in several chronic conditions, such as HIV, liver cirrhosis, chronic obstructive pulmonary disease and lung cancer, and in patients undergoing dialysis. The present study investigated the prognostic role of phase angle in advanced pancreatic cancer. We evaluated a case series of fifty-eight stage IV pancreatic cancer patients treated at Cancer Treatment Centers of America® at Midwestern Regional Medical Center (Zion, IL, USA) between January 2000 and July 2003. BIA was conducted on all patients using a bioelectrical impedance analyser that operated at 50kHz. The phase angle was calculated as capacitance (Xc)/resistance (R) and expressed in degrees. The Kaplan–Meier method was used to calculate survival. Cox proportional hazard models were constructed to evaluate the prognostic effect of phase angle independent of other clinical and nutritional variables. The correlations between phase angle and traditional nutritional measures were evaluated using Pearson and Spearman coefficients. Patients with phase angle <5·0° had a median survival time of 6·3 (95% CI 3·5, 9·2) months (n 29), while those with phase angle >5·0° had a median survival time of 10·2 (95% CI 9·6, 10·8) months (n 29); this difference was statistically significant (P=0·02). The present study demonstrates that phase angle is a strong prognostic indicator in advanced pancreatic cancer. Similar studies in other cancer settings with larger sample sizes are needed to further validate the prognostic significance of the phase angle.
Objective. To evaluate the relationship between self-reported satisfaction with service quality and overall survival in non-small cell lung cancer (NSCLC). Design. A prospective cohort study. ...Setting. Cancer Treatment Centers of America® from July 2007 and December 2010. Participants. Nine hundred and eighty-six returning NSCLC patients. Intervention. Overall patient experience 'considering everything, how satisfied are you with your overall experience' was measured on a 7-point Likert scale ranging from 'completely dissatisfied' to 'completely satisfied.'. Main Outcome Measure. Patient survival was the primary end point. Results. The response rate for this study was 69%. Six hundred patients were newly diagnosed, while 386 were previously treated. Four hundred sixty-nine were males, while 517 were females. 101, 59, 288 and 538 patients had stage I, II, III and IV disease, respectively. Mean age was 58.9 years. Six hundred and thirty (63.9%) patients had expired at the time of this analysis. Seven hundred and sixty-two (77.3%) patients were 'completely satisfied'. Median overall survival was 12.1 months (95% confidence interval (CI): 10.9-13.2 months). On univariate analysis, 'completely satisfied' patients had a significantly lower risk of mortality compared with those not 'completely satisfied' hazard ratio (HR) = 0.70; 95% CI: 0.59-0.84; P < 0.001. On multivariate analysis controlling for stage at diagnosis, prior treatment history, age and gender, 'completely satisfied' patients demonstrated significantly lower mortality (HR = 0.71; 95% CI: 0.60-0.85; P < 0.001) compared with those not 'completely satisfied'. Conclusions. Self-reported experience with service quality was an independent predictor of survival in NSCLC patients undergoing oncologic treatment, a novel finding in the literature. Based on these provocative findings, further exploration of this relationship is warranted in well-designed prospective studies.
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BFBNIB, NMLJ, NUK, PNG, UL, UM, UPUK
Matrix metalloproteinases (MMPs) regulated by their tissue inhibitors (TIMPs) play a significant role in the pathogenesis of multiple sclerosis (MS) and its mouse model, experimental autoimmune ...encephalomyelitis (EAE), as they degrade extracellular matrix including vascular basal laminae and by damaging blood-brain barrier (BBB) facilitate transmigration of immune cells into the central nervous system. MMPs are also involved in destruction of myelin sheaths, leading to axonal and neuronal loss. The aim of the present study was to assess whether natalizumab, a transmigration-inhibiting monoclonal antibody against α4β1 integrin, influences expression of MMPs and TIMPs in the central nervous system of mice with EAE. MMP-2 and MMP-9, their respective inhibitors TIMP-2 and TIMP-1 and laminin were assessed by quantitative immunohistochemistry in the spinal cord cryosections of C57BL/6 mice with EAE in the successive phases of the disease (onset, peak and chronic). The percentage of immunopositive areas were calculated in sections encompassing the whole spinal cord cross-sectional area occupied by the gray and white matter. Results obtained in animals administered with 5 mg/kg natalizumab were compared with those collected from control mice receiving 5 mg/kg IgG. Both studied MMPs and both TIMPs were upregulated in control EAE mice. Natalizumab treatment significantly reduced expression of MMPs and increased expression of TIMPs in the peak and chronic phases of the disease. This effect was accompanied by inhibition of laminin degradation in the vascular basal laminae and reduction of inflammatory infiltration. Results of this study demonstrate that in addition to its well known anti-integrin activity counteracting transmigration of immune cells into the central nervous system, natalizumab strengthens this effect by its probably indirect influence on MMPs and TIMPs leading to protection of blood-brain barrier integrity.
Bioelectrical Impedance (BIA) derived phase angle is increasingly being used as an objective indicator of nutritional status in advanced cancer. Subjective Global Assessment (SGA) is a subjective ...method of nutritional status. The objective of this study was to investigate the association between BIA derived phase angle and SGA in advanced colorectal cancer.
We evaluated a case series of 73 stages III and IV colorectal cancer patients. Patients were classified as either well-nourished or malnourished using the SGA. BIA was conducted on all patients and phase angle was calculated. The correlation between phase angle and SGA was studied using Spearman correlation coefficient. Receiver Operating Characteristic curves were estimated using the non-parametric method to determine the optimal cut-off levels of phase angle.
Well-nourished patients had a statistically significantly higher (p = 0.005) median phase angle score (6.12) as compared to those who were malnourished (5.18). The Spearman rank correlation coefficient between phase angle and SGA was found to be 0.33 (p = 0.004), suggesting better nutritional status with higher phase angle scores. A phase angle cut-off of 5.2 was 51.7% sensitive and 79.5% specific whereas a cut-off of 6.0 was 82.8% sensitive and 54.5% specific in detecting malnutrition. Interestingly, a phase angle cut-off of 5.9 demonstrated high diagnostic accuracy in males who had failed primary treatment for advanced colorectal cancer.
Our study suggests that bioimpedance phase angle is a potential nutritional indicator in advanced colorectal cancer. Further research is needed to elucidate the optimal cut-off levels of phase angle that can be incorporated into the oncology clinic for better nutritional evaluation and management.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
A dose integral of time‐dependent X‐ray absorption under conditions of variable photon energy and changing sample mass is derived from first principles starting with the Beer–Lambert (BL) absorption ...model. For a given photon energy the BL dose integral D(e, t) reduces to the product of an effective time integral T(t) and a dose rate R(e). Two approximations of the time‐dependent optical density, i.e. exponential A(t) = c + aexp(−bt) for first‐order kinetics and hyperbolic A(t) = c + a/(b + t) for second‐order kinetics, were considered for BL dose evaluation. For both models three methods of evaluating the effective time integral are considered: analytical integration, approximation by a function, and calculation of the asymptotic behaviour at large times. Data for poly(methyl methacrylate) and perfluorosulfonic acid polymers measured by scanning transmission soft X‐ray microscopy were used to test the BL dose calculation. It was found that a previous method to calculate time‐dependent dose underestimates the dose in mass loss situations, depending on the applied exposure time. All these methods here show that the BL dose is proportional to the exposure time D(e, t) ≃ K(e)t.
Calculation of the X‐ray irradiation dose is developed from first principles. For absorption dependent on photon energy and time, and sample mass dependent on time, the dose integral is formulated. Exact, approximate and asymptotic expressions are evaluated and applied to scanning transmission soft X‐ray microscopy radiation damage experiments.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract Fatigue affects a majority of patients undergoing cancer-related therapies. We conducted a study of 954 adult cancer patients presenting for treatment at our hospital between April 2001 and ...November 2004 to quantify the relationship between fatigue and patient satisfaction with quality of life (QoL). Fatigue was measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire fatigue subscale. Patient satisfaction with QoL was measured using the Ferrans and Powers Quality of Life Index (QLI). The relationship between fatigue and QLI was evaluated using univariate and multivariate linear regression after controlling for the effects of clinical and demographic factors. Of the 954 patients, 579 were females and 375 males, with a median age at presentation of 56 years (range 20–90 years). Sixty-six percent had failed prior treatment. The most common cancers were breast (26%), colorectal (19%), and lung (16%) cancers. After controlling for the effects of age and prior treatment history, every 10-unit increase in fatigue was statistically significantly associated with 1.5-, 0.22-, 0.77-, 0.27-, and 0.85-unit declines in QLI health and physical, social and economic, psychological and spiritual, family, and global function scores, respectively. Consequently, a 30-point increase in fatigue score correlates with a 4.5-point decline in QLI health functioning—a clinically significant decline. In our study, we found that fatigue is strongly associated with patient satisfaction with QoL independent of the effects of age and prior treatment history.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Gunshot residues (GSR) from a total of nine different caliber ammunitions produced in Brazil were analyzed and characterized by transmission (TEM) and scanning electron microscopy (SEM). GSR ...particles are composed of spherical particles of several micrometers of diameter containing distinct amounts of lead, barium and antimony, along with other organic and inorganic elements arising from the primer, gunpowder, the gun and the bullet itself. This study was carried out to obtain additional information on the properties of GSR nanoparticles originated from different types of regular ammunition produced in Brazil by CBC. Besides the SEM, we have used a TEM, exploring its high magnification capability and ability to explore internal structure and chemical composition of submicron particles. We observed that CBC ammunition generated smaller particles than usually reported for other ammunitions and that the three component particles are not a majority. TEM analysis revealed that GSR are partially composed of sub-micron particles as well. The electron diffraction pattern from these particles confirmed them to be mainly composed of lead oxides crystalline nanoparticles that may be agglomerated into larger particles. Energy dispersive X-ray spectroscopy revealed that most of them were composed of two elements, especially PbSb. Ba was not a common element found in the nanoparticles.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, VSZLJ