Human epidermal Langerhans cells (LCs) bind IgE via the high affinity receptor (Fc epsilon RI), a... more Human epidermal Langerhans cells (LCs) bind IgE via the high affinity receptor (Fc epsilon RI), and therefore are suspected to be involved in the genesis of atopic diseases. In this study, we report that surface expression of Fc epsilon RI is increased dramatically on LCs from patients with atopic dermatitis (AD) when compared with nonatopic individuals. Cross-linking of Fc epsilon RI on LCs from nonatopic individuals and patients with AD leads to a rapid tyrosine phosphorylation of several proteins, including p72, p77, and p95. However, upon receptor ligation, calcium mobilization is only detected in LCs freshly isolated from patients with AD (responder LCs), but not in those from normal skin of healthy individuals (nonresponder LCs). The beta-chain of Fc epsilon RI is not detected in normal LCs and only in a minority of LCs from atopic individuals, indicating that it is not related to the capacity of LCs to respond to Fc epsilon RI-mediated activation. In contrast, LCs from both nonatopic and atopic individuals internalize Fc epsilon RI by receptor-mediated endocytosis as a prerequisite for Ag focusing. Therefore, LCs from normal individuals and individuals with AD differ functionally by their Fc epsilon RI expression and by a distinct ability to respond to Fc epsilon RI-mediated activation.
Addition of 10 mg prednisone daily to a methotrexate-based tight control strategy does not lead t... more Addition of 10 mg prednisone daily to a methotrexate-based tight control strategy does not lead to bone loss in early rheumatoid arthritis (RA) patients receiving preventive treatment for osteoporosis. A small increase in lumbar bone mineral density (BMD) during the first year of treatment was recorded, regardless of use of glucocorticoids. Introduction This study aims to describe effects on BMD of treatment according to EULAR guidelines with a methotrexate-based tight control strategy including 10 mg prednisone daily versus the same strategy without prednisone in early RA patients who received preventive therapy for osteoporosis. Methods Early RA patients were included in the CAMERA-II trial: a randomized, placebo-controlled, double-blind 2-year trial, in which effects of addition of 10 mg prednisone daily to a methotrexate-based tight control strategy were studied. All patients received calcium, vitamin D and bisphosphonates. Disease activity was assessed every 4 weeks. Radiographs of hands and feet and dual-energy X-ray absorptiometry of lumbar spine and left hip were performed at baseline and after 1 and 2 years of treatment. Results BMD increased significantly over time in both treatment groups at the lumbar spine with a mean of 2.6 % during the first year (p<0.001), but not at the hip; at none of the time points did BMD differ significantly between the prednisone and placebo group. Higher age and lower weight at baseline and higher disease activity scores during the trial, but not glucocorticoid therapy, were associated with lower BMD at both the lumbar spine and the hip in mixed-model analyses. Conclusion Addition of 10 mg prednisone daily to a methotrexate-based tight control strategy does not lead to bone loss in early RA patients on bisphosphonates. A small increase in lumbar BMD during the first year of treatment was found, regardless of use of glucocorticoids.
Thirty crossbred sows and their pigs were evaluated through two parities to determine any reprodu... more Thirty crossbred sows and their pigs were evaluated through two parities to determine any reproductive or growth performance effects of an active dry yeast supplement added to corn-soybean meal diets. Sow reproductive performance from d 93 of gestation through d 21 of lactation and sow milk composition were evaluated. Pig growth performance was measured from birth to 28 d after weaning. Active dry yeast was added at 0, .1, or .2% of the sow gestation diet, 0, .15, or .3% of the sow lactation diet, 0, .2, or .4% of the pig prestarter diet, 1 wk before and 1 wk after weaning, and 0, .125, or .25% during the last 3 wk in the nursery. The yeast source consisted of a concentrate of live yeast cells of the Saccharomyces cerevisiae strain containing more than 15 × 109 live cells/g. Sow body weight at d 93 of gestation, at farrowing, and at d 21 of lactation did not differ ( P > .10) among treatment groups. Milk from sows fed active dry yeast contained higher amounts of total solids ( P ...
This study evaluated the preparedness of Emergency Departments (EDs) in the greater Philadelphia ... more This study evaluated the preparedness of Emergency Departments (EDs) in the greater Philadelphia area to evaluate and treat victims of a terrorist biological or chemical agent release. All hospitals with EDs in the survey target area were included. A survey instrument consisting of 38 questions was mailed to the physician director of each ED. Fifty-four of 62 directors returned usable
Evidence-Based Complementary and Alternative Medicine, 2009
The purpose of this project was to conduct a systematic review to identify instruments designed t... more The purpose of this project was to conduct a systematic review to identify instruments designed to evaluate the quality of randomized controlled trials (RCTs) of natural health products (NHPs). Instruments were examined for inclusion of items assessing methods, identity and content of the NHP, generalizability of results and instructions for use. Online databases, websites, textbooks and reference lists were searched to identify instruments. Relevance assessment and data extraction of articles were completed by two investigators and disagreements were settled by the third investigator. Data were analyzed using descriptive statistics. Of the 4442 citations identified, 29 were potentially relevant with 16 meeting the criteria for inclusion. None of the instruments stated they were validated; content in the four areas of interest varied considerably. The most common items included randomization sequence generation (100%), blinding (100%), allocation concealment (75%) and participant fl...
Corporate reputation in Europe and North America is increasingly seen as a function of how firms ... more Corporate reputation in Europe and North America is increasingly seen as a function of how firms treat their stakeholders. In the United States, stakeholder theory has been touted as a paradigm of good management; yet despite enlightened stakeholder practice at home, US ...
Different single phase polycrystalline samples of high-T c superconducting compounds YBa2CU3OT_ x... more Different single phase polycrystalline samples of high-T c superconducting compounds YBa2CU3OT_ x have been prepared and characterized. They have been investigated by ac and dc susceptibility, resistivity and specific heat experiments to study the influence of the oxygen content. The y-value and the T-independent susceptibility are found to be not sensitive to the oxygen content.
Protein-protein interactions mediated by modular protein domains are critical for cell scaffoldin... more Protein-protein interactions mediated by modular protein domains are critical for cell scaffolding, differentiation, signaling, and ultimately, evolution. Given the vast number of ligands competing for binding to a limited number of domain families, it is often puzzling how specificity can be achieved. Selectivity may be modulated by intradomain allostery, whereby a remote residue is energetically connected to the functional binding site via side chain or backbone interactions. Whereas several energetic pathways, which could mediate intradomain allostery, have been predicted in modular protein domains, there is a paucity of experimental data to validate their existence and roles. Here, we have identified such functional energetic networks in one of the most common protein-protein interaction modules, the PDZ domain. We used double mutant cycles involving site-directed mutagenesis of both the PDZ domain and the peptide ligand, in conjunction with kinetics to capture the fine energetic details of the networks involved in peptide recognition. We performed the analysis on two homologous PDZ-ligand complexes and found that the energetically coupled residues differ for these two complexes. This result demonstrates that amino acid sequence rather than topology dictates the allosteric pathways. Furthermore, our data support a mechanism whereby the whole domain and not only the binding pocket is optimized for a specific ligand. Such cross-talk between binding sites and remote residues may be used to fine tune target selectivity.
The paper is concerned with regularization concepts for the inversion of diffusion processes. The... more The paper is concerned with regularization concepts for the inversion of diffusion processes. The application of the involved evolution operators is based on Dunford integral representations combined with the adaptive application of resolvents using recent wavelet methods. In particular, this allows us to develop and realize numerically, to our knowledge for the first time in this context, an SVD projection method which is compared to several versions of Tikhonov-type schemes. The theoretical findings are complemented by numerical tests shedding some light on the quantitative performance of the schemes.
Effluent discharges at Rodbourne sewage treatment works (STWs) were assessed using chemical and i... more Effluent discharges at Rodbourne sewage treatment works (STWs) were assessed using chemical and in vitro biological analysis as well as modelling predictions. Results showed that Rodbourne STW discharged less estrone (E1) than expected, but similar 17beta-estradiol (E2) and 17alpha-ethinyl estradiol (EE2) to those predicted by a widely cited effluent prediction model. The Exposure Analysis Modelling System (EXAMS) model was set up using measured effluent concentrations as its starting point to predict estrogen concentrations along a 10 km length of the receiving water of the River Ray. The model adequately simulated estrogen concentrations along the river when compared to July 2007 measured data. The model predicted combined estrogen equivalents in reasonable agreement with estrogenicity as measured by passive sampler (POCIS) extracts using the yeast estrogen screen. Using gauged mean flow values for 2007 the model indicated that the most important determinand for estrogen exposure in the Ray was not season, but proximity to the Rodbourne effluent. Thus, fish in the first 3 km downstream of Rodbourne were typically exposed to two or even three times more estrogens than those living 7-10 km further downstream. The modelling indicated that, assuming the effluent estrogen concentrations measured in February 2008 were typical, throughout the year the whole length of the Ray downstream of Rodbourne would be estrogenic, i.e. exceeding the 1 ng/L E2 equivalent threshold for endocrine disruption.
Background With Canadians increasing their use of the Internet to find health-related information... more Background With Canadians increasing their use of the Internet to find health-related information, especially regarding natural health products (NHPs), there is a need for high-quality, evidence-based information on Web sites to aid consumers in making informed decisions regarding the appropriate and safe use of NHPs. Objective To determine the quality of Web sites that target consumers and advocate the use of NHPs in the management of osteoporosis in postmenopausal women. Methods Web sites were identified via the Google search engine using the key words “natural treatment osteoporosis.” The first pages of the first 91 Web sites identified were assessed for relevance based on the following criteria: (1) written in English, (2) contained consumer information, and (3) claimed a benefit of a single NHP in the management of osteoporosis. This task was completed by 2 investigators; differences were resolved by consensus after discussion with the third investigator. Quality of relevant si...
Human epidermal Langerhans cells (LCs) bind IgE via the high affinity receptor (Fc epsilon RI), a... more Human epidermal Langerhans cells (LCs) bind IgE via the high affinity receptor (Fc epsilon RI), and therefore are suspected to be involved in the genesis of atopic diseases. In this study, we report that surface expression of Fc epsilon RI is increased dramatically on LCs from patients with atopic dermatitis (AD) when compared with nonatopic individuals. Cross-linking of Fc epsilon RI on LCs from nonatopic individuals and patients with AD leads to a rapid tyrosine phosphorylation of several proteins, including p72, p77, and p95. However, upon receptor ligation, calcium mobilization is only detected in LCs freshly isolated from patients with AD (responder LCs), but not in those from normal skin of healthy individuals (nonresponder LCs). The beta-chain of Fc epsilon RI is not detected in normal LCs and only in a minority of LCs from atopic individuals, indicating that it is not related to the capacity of LCs to respond to Fc epsilon RI-mediated activation. In contrast, LCs from both nonatopic and atopic individuals internalize Fc epsilon RI by receptor-mediated endocytosis as a prerequisite for Ag focusing. Therefore, LCs from normal individuals and individuals with AD differ functionally by their Fc epsilon RI expression and by a distinct ability to respond to Fc epsilon RI-mediated activation.
Addition of 10 mg prednisone daily to a methotrexate-based tight control strategy does not lead t... more Addition of 10 mg prednisone daily to a methotrexate-based tight control strategy does not lead to bone loss in early rheumatoid arthritis (RA) patients receiving preventive treatment for osteoporosis. A small increase in lumbar bone mineral density (BMD) during the first year of treatment was recorded, regardless of use of glucocorticoids. Introduction This study aims to describe effects on BMD of treatment according to EULAR guidelines with a methotrexate-based tight control strategy including 10 mg prednisone daily versus the same strategy without prednisone in early RA patients who received preventive therapy for osteoporosis. Methods Early RA patients were included in the CAMERA-II trial: a randomized, placebo-controlled, double-blind 2-year trial, in which effects of addition of 10 mg prednisone daily to a methotrexate-based tight control strategy were studied. All patients received calcium, vitamin D and bisphosphonates. Disease activity was assessed every 4 weeks. Radiographs of hands and feet and dual-energy X-ray absorptiometry of lumbar spine and left hip were performed at baseline and after 1 and 2 years of treatment. Results BMD increased significantly over time in both treatment groups at the lumbar spine with a mean of 2.6 % during the first year (p<0.001), but not at the hip; at none of the time points did BMD differ significantly between the prednisone and placebo group. Higher age and lower weight at baseline and higher disease activity scores during the trial, but not glucocorticoid therapy, were associated with lower BMD at both the lumbar spine and the hip in mixed-model analyses. Conclusion Addition of 10 mg prednisone daily to a methotrexate-based tight control strategy does not lead to bone loss in early RA patients on bisphosphonates. A small increase in lumbar BMD during the first year of treatment was found, regardless of use of glucocorticoids.
Thirty crossbred sows and their pigs were evaluated through two parities to determine any reprodu... more Thirty crossbred sows and their pigs were evaluated through two parities to determine any reproductive or growth performance effects of an active dry yeast supplement added to corn-soybean meal diets. Sow reproductive performance from d 93 of gestation through d 21 of lactation and sow milk composition were evaluated. Pig growth performance was measured from birth to 28 d after weaning. Active dry yeast was added at 0, .1, or .2% of the sow gestation diet, 0, .15, or .3% of the sow lactation diet, 0, .2, or .4% of the pig prestarter diet, 1 wk before and 1 wk after weaning, and 0, .125, or .25% during the last 3 wk in the nursery. The yeast source consisted of a concentrate of live yeast cells of the Saccharomyces cerevisiae strain containing more than 15 × 109 live cells/g. Sow body weight at d 93 of gestation, at farrowing, and at d 21 of lactation did not differ ( P > .10) among treatment groups. Milk from sows fed active dry yeast contained higher amounts of total solids ( P ...
This study evaluated the preparedness of Emergency Departments (EDs) in the greater Philadelphia ... more This study evaluated the preparedness of Emergency Departments (EDs) in the greater Philadelphia area to evaluate and treat victims of a terrorist biological or chemical agent release. All hospitals with EDs in the survey target area were included. A survey instrument consisting of 38 questions was mailed to the physician director of each ED. Fifty-four of 62 directors returned usable
Evidence-Based Complementary and Alternative Medicine, 2009
The purpose of this project was to conduct a systematic review to identify instruments designed t... more The purpose of this project was to conduct a systematic review to identify instruments designed to evaluate the quality of randomized controlled trials (RCTs) of natural health products (NHPs). Instruments were examined for inclusion of items assessing methods, identity and content of the NHP, generalizability of results and instructions for use. Online databases, websites, textbooks and reference lists were searched to identify instruments. Relevance assessment and data extraction of articles were completed by two investigators and disagreements were settled by the third investigator. Data were analyzed using descriptive statistics. Of the 4442 citations identified, 29 were potentially relevant with 16 meeting the criteria for inclusion. None of the instruments stated they were validated; content in the four areas of interest varied considerably. The most common items included randomization sequence generation (100%), blinding (100%), allocation concealment (75%) and participant fl...
Corporate reputation in Europe and North America is increasingly seen as a function of how firms ... more Corporate reputation in Europe and North America is increasingly seen as a function of how firms treat their stakeholders. In the United States, stakeholder theory has been touted as a paradigm of good management; yet despite enlightened stakeholder practice at home, US ...
Different single phase polycrystalline samples of high-T c superconducting compounds YBa2CU3OT_ x... more Different single phase polycrystalline samples of high-T c superconducting compounds YBa2CU3OT_ x have been prepared and characterized. They have been investigated by ac and dc susceptibility, resistivity and specific heat experiments to study the influence of the oxygen content. The y-value and the T-independent susceptibility are found to be not sensitive to the oxygen content.
Protein-protein interactions mediated by modular protein domains are critical for cell scaffoldin... more Protein-protein interactions mediated by modular protein domains are critical for cell scaffolding, differentiation, signaling, and ultimately, evolution. Given the vast number of ligands competing for binding to a limited number of domain families, it is often puzzling how specificity can be achieved. Selectivity may be modulated by intradomain allostery, whereby a remote residue is energetically connected to the functional binding site via side chain or backbone interactions. Whereas several energetic pathways, which could mediate intradomain allostery, have been predicted in modular protein domains, there is a paucity of experimental data to validate their existence and roles. Here, we have identified such functional energetic networks in one of the most common protein-protein interaction modules, the PDZ domain. We used double mutant cycles involving site-directed mutagenesis of both the PDZ domain and the peptide ligand, in conjunction with kinetics to capture the fine energetic details of the networks involved in peptide recognition. We performed the analysis on two homologous PDZ-ligand complexes and found that the energetically coupled residues differ for these two complexes. This result demonstrates that amino acid sequence rather than topology dictates the allosteric pathways. Furthermore, our data support a mechanism whereby the whole domain and not only the binding pocket is optimized for a specific ligand. Such cross-talk between binding sites and remote residues may be used to fine tune target selectivity.
The paper is concerned with regularization concepts for the inversion of diffusion processes. The... more The paper is concerned with regularization concepts for the inversion of diffusion processes. The application of the involved evolution operators is based on Dunford integral representations combined with the adaptive application of resolvents using recent wavelet methods. In particular, this allows us to develop and realize numerically, to our knowledge for the first time in this context, an SVD projection method which is compared to several versions of Tikhonov-type schemes. The theoretical findings are complemented by numerical tests shedding some light on the quantitative performance of the schemes.
Effluent discharges at Rodbourne sewage treatment works (STWs) were assessed using chemical and i... more Effluent discharges at Rodbourne sewage treatment works (STWs) were assessed using chemical and in vitro biological analysis as well as modelling predictions. Results showed that Rodbourne STW discharged less estrone (E1) than expected, but similar 17beta-estradiol (E2) and 17alpha-ethinyl estradiol (EE2) to those predicted by a widely cited effluent prediction model. The Exposure Analysis Modelling System (EXAMS) model was set up using measured effluent concentrations as its starting point to predict estrogen concentrations along a 10 km length of the receiving water of the River Ray. The model adequately simulated estrogen concentrations along the river when compared to July 2007 measured data. The model predicted combined estrogen equivalents in reasonable agreement with estrogenicity as measured by passive sampler (POCIS) extracts using the yeast estrogen screen. Using gauged mean flow values for 2007 the model indicated that the most important determinand for estrogen exposure in the Ray was not season, but proximity to the Rodbourne effluent. Thus, fish in the first 3 km downstream of Rodbourne were typically exposed to two or even three times more estrogens than those living 7-10 km further downstream. The modelling indicated that, assuming the effluent estrogen concentrations measured in February 2008 were typical, throughout the year the whole length of the Ray downstream of Rodbourne would be estrogenic, i.e. exceeding the 1 ng/L E2 equivalent threshold for endocrine disruption.
Background With Canadians increasing their use of the Internet to find health-related information... more Background With Canadians increasing their use of the Internet to find health-related information, especially regarding natural health products (NHPs), there is a need for high-quality, evidence-based information on Web sites to aid consumers in making informed decisions regarding the appropriate and safe use of NHPs. Objective To determine the quality of Web sites that target consumers and advocate the use of NHPs in the management of osteoporosis in postmenopausal women. Methods Web sites were identified via the Google search engine using the key words “natural treatment osteoporosis.” The first pages of the first 91 Web sites identified were assessed for relevance based on the following criteria: (1) written in English, (2) contained consumer information, and (3) claimed a benefit of a single NHP in the management of osteoporosis. This task was completed by 2 investigators; differences were resolved by consensus after discussion with the third investigator. Quality of relevant si...
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Papers by Matika Jurgens