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Sarilumab for the treatment of ankylosing spondylitis: results of a Phase II, randomised, double-blind, placebo-controlled study (ALIGN)
OBJECTIVES: The ALIGN study (NCT01061723) evaluated the efficacy and safety of sarilumab, the first fully human monoclonal antibody against interleukin-6 receptor-alpha (IL-6Ralpha), in patients with ankylosing spondylitis (AS).
METHODS: Patients with active AS despite conventional treatment were randomised to placebo, or one of five subcutaneous dose regimens of sarilumab (100, 150 or 200 mg every other week, or 100 or 150 mg every week), for 12 weeks. The primary efficacy end point was the percentage of patients achieving the Axial SpondyloArthritis international Society (ASAS) 20 response criteria at week 12. Secondary endpoints included ASAS40 response, ASAS partial remission, AS Disease Activity Score, high-sensitivity C-reactive protein (hs-CRP) value, and safety.
RESULTS: Baseline demographic and disease characteristics of the 301 patients enrolled were similar across treatment groups. At week 12, there was no statistically significant difference in ASAS20 response rate between placebo (ASAS20 = 24.0%) and any sarilumab dose group. A significantly greater reduction in hs-CRP value was achieved with the higher sarilumab doses versus placebo. No other statistically significant differences were evident for secondary efficacy endpoints.The most common treatment-emergent adverse events reported for sarilumab included infections (non-serious), neutropenia, and increase in alanine aminotransferase. No cases of tuberculosis, opportunistic, or fungal infections, or bowel perforations were reported. Seven patients experienced a treatment-emergent serious adverse event (all in sarilumab treatment groups). No deaths occurred.
CONCLUSIONS: The ALIGN study shows that IL-6Ralpha blockade with sarilumab was not an effective treatment for AS. Sarilumab was generally well tolerated with a manageable safety profile.
Golimumab 3-year safety update: an analysis of pooled data from the long-term extensions of randomised, double-blind, placebo-controlled trials conducted in patients with rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis
OBJECTIVE: To assess pooled golimumab safety up to year 3 of rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) trials.
METHODS: Golimumab 50 and 100 mg, administered subcutaneously (SC) every 4 weeks (q4wk), were assessed in patients with active RA (methotrexate-naive, methotrexate-experienced and anti-TNF (tumour necrosis factor)-experienced), PsA or AS, despite conventional therapy. Placebo control continued up to week (wk) 24 (wk 52, methotrexate-naive), with early escape at wk 16 (wk 28, methotrexate-naive); subsequently, all patients received golimumab 50 or 100 mg q4wk. After the blinded controlled period, golimumab doses could be adjusted per investigator discretion. Pooled safety analyses reported herein include data from placebo-controlled and uncontrolled study periods up to wk 160. Determinations of incidences/100 patient-years (pt-yrs) for rare events also included RA patients from a phase IIb trial.
RESULTS: Across five phase III trials of SC golimumab, 639 patients received placebo and 2226 received golimumab 50 mg (n=1249) and/or 100 mg (n=1501) up to wk 160 (patients may be included in more than one group because non-responders were allowed early escape); 1179 patients were treated for > /=156 weeks. For placebo, golimumab 50 mg and golimumab 100 mg, respective adverse event incidences/100 pt-yrs (95% CIs) up to wk 160 were: 0.28 (0.01 to 1.56), 0.30 (0.12 to 0.62), 0.41 (0.23 to 0.69) for death; 5.31 (3.20 to 8.30), 3.03 (2.36 to 3.82), 5.09 (4.36 to 5.90) for serious infection; 0.00 (0.00 to 0.84), 0.17 (0.05 to 0.44), 0.35 (0.18 to 0.62) for tuberculosis; 0.00 (0.00 to 0.84), 0.13 (0.03 to 0.38), 0.24 (0.10 to 0.46) for opportunistic infection; 0.00 (0.00 to 0.84), 0.00 (0.00 to 0.13), 0.12 (0.03 to 0.30) for demyelination; and 0.00 (0.00 to 0.84), 0.04 (0.00 to 0.24), 0.18 (0.06 to 0.38) for lymphoma.
CONCLUSIONS: SC golimumab safety up to 3 years remained consistent with that of other TNF antagonists. Golimumab 100 mg showed numerically higher incidences of serious infections, demyelinating events and lymphoma than 50 mg; safety follow-up up to year 5 continues.
Nephrogenic systemic fibrosis is associated with hypophosphataemia: a case-control study
OBJECTIVE: Nephrogenic systemic fibrosis (NSF) is an iatrogenic fibrosing disorder that primarily affects individuals with chronic kidney disease (CKD) following exposure to gadolinium-based contrast agents (GBCAs). Derangements of calcium and phosphorus have been reported in patients with NSF. The aim of this study was to investigate potential factors in addition to GBCA exposure that may be involved in the pathogenesis of NSF. We hypothesized that patients with stage 5 CKD and NSF would manifest greater alterations in calcium, phosphorus and fibroblast growth factor 23 (FGF23) levels than those who do not have NSF.
METHODS: Levels of phosphorus, calcium, FGF23 and 25-hydroxy-vitamin D were measured in 10 patients with stage 5 CKD and biopsy-proven NSF and in 19 patients with stage 5 CKD without NSF. Statistical analyses were performed using Fisher's exact test for categorical variables and the Kruskal-Wallis test for continuous variables.
RESULTS: Patients with NSF had significantly lower phosphorus levels compared with controls (P = 0.01). There were no significant differences between NSF patients and controls in calcium, 25-hydroxy-vitamin D, intact parathyroid hormone or FGF23 levels.
CONCLUSION: Differences in phosphorus metabolism may exist between patients with stage 5 CKD and NSF compared with patients with stage 5 CKD without NSF. British Society for Rheumatology. All rights reserved.
Insights into the efficacy of golimumab plus methotrexate in patients with active rheumatoid arthritis who discontinued prior anti-tumour necrosis factor therapy: post-hoc analyses from the GO-AFTER study
OBJECTIVE: Evaluate golimumab in patients with active rheumatoid arthritis (RA) and previous tumour necrosis factor-alpha (TNF) inhibitor use.
METHODS: Patients (n=461) previously receiving > /=1 TNF inhibitor were randomised to subcutaneous injections of placebo, golimumab 50 mg or golimumab 100 mg q4 weeks. Primary endpoint ( > /=20% improvement in American College of Rheumatology (ACR20) criteria at week 14) findings have been reported for all patients in the trial. Reported herein are further assessments of efficacy/safety among patients receiving golimumab+methotrexate (MTX).
RESULTS: Among efficacy-evaluable patients who received MTX at baseline, more receiving golimumab+MTX (n=201) than placebo+MTX (n=103) achieved ACR20 (40.8% vs 14.6%), ACR50 (20.9% vs 3.9%), and ACR70 (11.4% vs 2.9%) responses at week 24. Among the 137 patients who had received only one prior TNF inhibitor (adalimumab, n=33; etanercept, n=47; and infliximab, n=57), week 24 ACR20 rates were 30.3%, 46.8% and 50.9%, respectively, and thus lowest among those who previously used adalimumab. ACR20 response rates were 44.5% (61/137), 36.2% (17/47) and 23.5% (4/17) among patients who had received one, two or three TNF inhibitors, respectively. Adverse event (AE) rates were comparable across type/number of prior anti-TNF agents, but appeared somewhat higher among patients who discontinued previous TNF inhibitor(s) due to intolerance (37/49, 75.5%) versus lack of efficacy (LOE, 113/191, 59.2%).
CONCLUSIONS: Patients with active RA previously treated with > /=1 TNF inhibitor had clinically relevant improvement with golimumab+MTX, which appeared somewhat enhanced among those who received only etanercept or infliximab as their prior TNF inhibitor. Golimumab+MTX safety appeared similar across patients, regardless of TNF inhibitor(s) previously used, with fewer AEs occurring among patients who discontinued prior therapy for LOE. already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Prevalence of comorbidities in rheumatoid arthritis and evaluation of their monitoring: results of an international, cross-sectional study (COMORA)
PATIENTS with rheumatoid arthritis (RA) are at increased risk of developing comorbid conditions.
OBJECTIVES: To evaluate the prevalence of comorbidities and compare their management in RA patients from different countries worldwide.
METHODS: STUDY DESIGN: international, cross-sectional.
PATIENTS: consecutive RA patients.
DATA COLLECTED: demographics, disease characteristics (activity, severity, treatment), comorbidities (cardiovascular, infections, cancer, gastrointestinal, pulmonary, osteoporosis and psychiatric disorders).
RESULTS: Of 4586 patients recruited in 17 participating countries, 3920 were analysed (age, 56+/-13 years; disease duration, 10+/-9 years (mean+/-SD); female gender, 82%; DAS28 (Disease Activity Score using 28 joints)-erythrocyte sedimentation rate, 3.7+/-1.6 (mean+/-SD); Health Assessment Questionnaire, 1.0+/-0.7 (mean+/-SD); past or current methotrexate use, 89%; past or current use of biological agents, 39%. The most frequently associated diseases (past or current) were: depression, 15%; asthma, 6.6%; cardiovascular events (myocardial infarction, stroke), 6%; solid malignancies (excluding basal cell carcinoma), 4.5%; chronic obstructive pulmonary disease, 3.5%. High intercountry variability was observed for both the prevalence of comorbidities and the proportion of subjects complying with recommendations for preventing and managing comorbidities. The systematic evaluation of comorbidities in this study detected abnormalities in vital signs, such as elevated blood pressure in 11.2%, and identified conditions that manifest as laboratory test abnormalities, such as hyperglycaemia in 3.3% and hyperlipidaemia in 8.3%.
CONCLUSIONS: Among RA patients, there is a high prevalence of comorbidities and their risk factors. In this multinational sample, variability among countries was wide, not only in prevalence but also in compliance with recommendations for preventing and managing these comorbidities. Systematic measurement of vital signs and laboratory testing detects otherwise unrecognised comorbid conditions.
The effect of golimumab on haemoglobin levels in patients with rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis
OBJECTIVE: To evaluate the effect of golimumab on haemoglobin levels in patients with RA, PsA or AS.
METHODS: Secondary analysis was performed on integrated data from five randomized controlled studies: three RA, one PsA and one AS (2303 patients total). Golimumab 50 or 100 mg was injected s.c. every 4 weeks with or without MTX. Control groups received placebo injections plus MTX or background therapy. Patients with haemoglobin levels below the age- and sex-specific normal ranges were considered to have anaemia. Ferritin levels were used to distinguish anaemia of mixed aetiology ( > /= 15 and < 60 ng/ml) and anaemia of inflammation ( > /= 60 ng/ml). Changes from baseline to weeks 14 and 24 in haemoglobin level were compared between treatment groups using an analysis of variance on the van der Waerden normal scores.
RESULTS: At baseline, 21% of RA patients, 9% of PsA patients and 15% of AS patients had anaemia. Of these, 24%, 57% and 25%, respectively, had anaemia of inflammation. The median increase from baseline to week 14 in the haemoglobin level of anaemic patients was 0.3 g/dl in the control group and 0.9 g/dl in the golimumab group (P < 0.001). Haemoglobin levels improved within the subgroups of patients with anaemia of mixed aetiology (control, 0.4 g/dl vs golimumab, 0.7 g/dl) (P = 0.305) and with anaemia of inflammation (0.2 vs 1.4 g/dl, respectively) (P < 0.001).
CONCLUSION: Compared with the control group, patients receiving golimumab treatment had significantly improved haemoglobin levels, particularly among patients with anaemia of inflammation.
Validation of a screening instrument for nephrogenic systemic fibrosis
OBJECTIVE: To develop and pilot test a screening tool to identify cases of nephrogenic systemic fibrosis (NSF) among patients exposed to gadolinium-containing contrast agents.
METHODS: Sixty English-speaking subjects were enrolled: 10 subjects diagnosed as having NSF, 10 subjects with other fibrosing skin diseases, 20 subjects with nonfibrosing skin diseases, and 20 subjects without a skin disease. Subjects answered a questionnaire with 8 closed-ended (yes/no) questions focusing on cutaneous and musculoskeletal manifestations of NSF. The subjects were evaluated by a dermatologist for the presence of clinical signs of NSF. We compared the number of affirmative responses in the NSF group to those in the other groups, and the optimal cutoff that would differentiate groups was calculated. Discrimination, positive and negative predictive values, and internal consistency were also assessed.
RESULTS: Subjects in the NSF group tended to provide more affirmative answers. Using a cutoff of >/=3 affirmative responses yields a sensitivity of 90% and a specificity of 70%, with an area under the curve of 0.85, indicating good discrimination. Sensitivity analysis using modified control group or weighted scores exhibited only slightly better discriminatory power. The positive predictive value of the questionnaire ranged from 0.3% to 39.7%, and its negative predictive values ranged from 97% to >99% with the different proposed prevalence estimates. The instrument had high internal consistency.
CONCLUSION: This pilot study demonstrates that this questionnaire has both high internal consistency and good discriminatory ability. Thus, it may be used to screen populations for NSF.
Systemic sclerosis without antinuclear antibodies or Raynaud's phenomenon: a multicentre study in the prospective EULAR Scleroderma Trials and Research (EUSTAR) database
OBJECTIVE: To assess patients with SSc who present without circulating ANAs or RP.
METHODS: Five thousand three hundred and ninety patients who fulfilled the ACR criteria for SSc and were enrolled in the EULAR Scleroderma Trials and Research (EUSTAR) database were screened for the absence of both RP and circulating ANA. To differentiate SSc from its mimics, additional information was gathered using a standardized questionnaire.
RESULTS: Five thousand three hundred and seventy-eight (99.8%) of the 5390 SSc patients in the EUSTAR database had either detectable ANA or a history of RP. Twelve (0.2%) patients lacked both circulating ANA and RP. Details of the medical history could be obtained for seven patients. Three cases were compatible with ANA-negative and RP-negative SSc and were not typical of any known SSc mimic. Four patients had a malignancy: two had breast cancer, one had multiple myeloma with possible scleromyxoedema and one had bladder carcinoma. There was no temporal relationship between the onset of skin fibrosis and that of the tumour. Although no patient with confirmed nephrogenic systemic fibrosis was identified among the cases of ANA-negative and RP-negative SSc, the presentation of one patient could be compatible with that of nephrogenic systemic fibrosis other than for the absence of chronic kidney disease or of known prior gadolinium exposure.
CONCLUSION: We have identified a very small subgroup of SSc patients who lack both circulating ANA and RP, none of whom fulfils the diagnostic criteria for any known SSc mimic. Prospective studies are needed to elucidate the clinical presentation, evolution and outcome of such patients.
Golimumab in patients with active rheumatoid arthritis who have previous experience with tumour necrosis factor inhibitors: results of a long-term extension of the randomised, double-blind, placebo-controlled GO-AFTER study through week 160
OBJECTIVE: The aim of this study was to assess long-term golimumab therapy in patients with rheumatoid arthritis (RA) who discontinued previous tumour necrosis factor alpha (TNFalpha) inhibitor(s) for any reason.
METHODS: Results through week 24 of this multicentre, randomised, double-blind, placebo-controlled study of active RA ( > /=4 tender, > /=4 swollen joints) were previously reported. Patients received placebo (Group 1), 50 mg golimumab (Group 2) or 100 mg golimumab (Group 3) subcutaneous injections every 4 weeks. Patients from Groups 1 and 2 with < 20% improvement in tender/swollen joints at week 16 early escaped to golimumab 50 mg and 100 mg, respectively. At week 24, Group 1 patients crossed over to golimumab 50 mg, Group 2 continued golimumab 50/100 mg per escape status and Group 3 maintained dosing. Data through week 160 are reported.
RESULTS: 459 of the 461 randomised patients were treated; 236/459 (51%) continued treatment through week 160. From week 24 to week 100, ACR20 ( > /=20% improvement in American College of Rheumatology criteria) response and > /=0.25 unit HAQ (Health Assessment Questionnaire) improvement were sustained in 70-73% and 75-81% of responding patients, respectively. Overall at week 160, 63%, 67% and 57% of patients achieved ACR20 response and 59%, 65% and 64% had HAQ improvement > /=0.25 unit in Groups 1, 2 and 3, respectively. Adjusted for follow-up duration, adverse event incidences (95% CI) per 100 patient-years among patients treated with golimumab 50 mg and 100 mg were 4.70 (2.63 to 7.75) and 8.07 (6.02 to 10.58) for serious infection, 0.95 (0.20 to 2.77) and 2.04 (1.09 to 3.49) for malignancy and 0.00 (0.00 to 0.94) and 0.62 (0.17 to 1.59) for death, respectively.
CONCLUSION: In patients with active RA who discontinued previous TNF-antagonist treatment, golimumab 50 and 100 mg injections every 4 weeks yielded sustained improvements in signs/symptoms and physical function in approximately 57-67% of patients who continued treatment. Golimumab safety was consistent with other anti-TNF agents, although definitive conclusions regarding long-term safety require further monitoring.
Nephrogenic systemic fibrosis: clinicopathological definition and workup recommendations
BACKGROUND: The condition that came to be known as nephrogenic systemic fibrosis (NSF) was first reported in 2000 and, in 2001, was termed "nephrogenic fibrosing dermopathy." Since then, NSF has been the subject of a wide-ranging multidisciplinary medical investigation that has proven an indisputable link to renal disease and a compelling association with the increasing use of gadolinium-containing magnetic resonance imaging contrast agents in the renally impaired.
OBJECTIVE: Although precise causation and risk factors continue to be elucidated, the need for reproducible prospective epidemiologic data demands clear and objective criteria for the diagnosis of NSF.
METHODS: Experts in NSF diagnosis used their experience and the resources of the Yale International NSF Registry to develop a clinicopathological diagnostic system for NSF.
RESULTS: A consensus scoring system incorporating a clinical and histopathological atlas was devised to guide and standardize the evaluation and diagnosis of NSF.
LIMITATIONS: There is no laboratory test that can be used as a gold standard to diagnose NSF. To overcome this, we relied on classic clinicopathological presentations, published sources, and consensus clinical expertise to ensure the integrity of the study population.
CONCLUSION: The clinicopathological definition of NSF provides guidance to physicians for the evaluation and diagnosis of NSF. Clinical, laboratory, and histopathological features comprise a schema that excludes conditions mimicking NSF while facilitating its reproducible and accurate diagnosis, even among physicians with little prior clinical experience with this entity. This definition can serve as a working diagnostic standard for future research and as the basis for adjudicating borderline cases. All rights reserved.
Quantitative assessment of dermal cellularity in nephrogenic systemic fibrosis: a diagnostic aid
BACKGROUND: Nephrogenic systemic fibrosis (NSF) affects patients with impaired renal function who have received gadolinium-containing contrast agents (GCCAs). Increased dermal cellularity is a key diagnostic feature of NSF, however, the histologic findings can be subtle.
OBJECTIVE: We sought to determine whether dermal cellularity in skin biopsy specimens from NSF cases: (1) differs significantly from that of controls; and (2) correlates with duration of the skin lesions, level of plasma creatinine, GCCA dose, or a combination of these.
METHODS: Seventeen NSF skin biopsy specimens and age-, sex-, and site-matched controls were retrieved from the dermatopathology files of the Massachusetts General Hospital in Boston. Dermal cellularity was manually quantified on hematoxylin-eosin-stained sections and patient medical records were reviewed for demographic and clinical data.
RESULTS: NSF cases showed a mean dermal cellularity of 70.8/high-power field (control mean: 14.4/high-power field, P < .001) and a cut-off range of 19 to 26/high-power field was established. No significant correlation was identified between dermal cellularity and demographic and clinical data.
LIMITATIONS: In this retrospective analysis, duration of skin lesion was defined as the interval from most recent prior GCCA study, rather than the actual clinical onset, to time of skin biopsy, and the cumulative GCCA dose may reflect a minimum if GCCA was received at an outside institution.
CONCLUSION: Enumeration of dermal cellularity on hematoxylin-eosin-stained sections can aid in the histologic diagnosis of NSF in the setting of chronic kidney disease and GCCA exposure and is independent of patient age, sex, plasma creatinine, time from last GCCA exposure, and GCCA dose. All rights reserved.
The 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for rheumatoid arthritis: Phase 2 methodological report
OBJECTIVE: The American College of Rheumatology and the European League Against Rheumatism have developed new classification criteria for rheumatoid arthritis (RA). The aim of Phase 2 of the development process was to achieve expert consensus on the clinical and laboratory variables that should contribute to the final criteria set.
METHODS: Twenty-four expert RA clinicians (12 from Europe and 12 from North America) participated in Phase 2. A consensus-based decision analysis approach was used to identify factors (and their relative weights) that influence the probability of "developing RA," complemented by data from the Phase 1 study. Patient case scenarios were used to identify and reach consensus on factors important in determining the probability of RA development. Decision analytic software was used to derive the relative weights for each of the factors and their categories, using choice-based conjoint analysis.
RESULTS: The expert panel agreed that the new classification criteria should be applied to individuals with undifferentiated inflammatory arthritis in whom at least 1 joint is deemed by an expert assessor to be swollen, indicating definite synovitis. In this clinical setting, they identified 4 additional criteria as being important: number of joints involved and site of involvement, serologic abnormality, acute-phase response, and duration of symptoms in the involved joints. These criteria were consistent with those identified in the Phase 1 data-driven approach.
CONCLUSION: The consensus-based, decision analysis approach used in Phase 2 complemented the Phase 1 efforts. The 4 criteria and their relative weights form the basis of the final criteria set.
The 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for rheumatoid arthritis: methodological report phase I
OBJECTIVE: To apply a data-driven approach to investigate, in patients newly presenting with undifferentiated inflammatory synovitis, key variables that discriminate the subset of patients at sufficiently high risk of persistent or erosive disease for the purpose of developing new criteria for rheumatoid arthritis (RA).
METHODS: In this first phase of the collaborative effort of the American College of Rheumatology and European League Against Rheumatism to develop new criteria for RA, a pooled analysis of early arthritis cohorts made available by the respective investigators is presented. All the variables associated with the gold standard of treatment with methotrexate during the first year after enrolment were first identified. Principal component analysis was then used to identify among the significant variables those sets that represent similar domains. In a final step, from each domain one representative variable was extracted, all of which were then tested for their independent effects in a multivariate regression model. From the OR in that final model, the relative weight of each variable was estimated.
RESULTS: The final domains and variables identified by this process (and their relative weights) were: swelling of a metacarpophalangeal joint (MCP; 1.5), swelling of a proximal interphalangeal joint (PIP; 1.5), swelling of the wrist (1.5), tenderness of the hand (ie, MCP, PIP or wrist (2)), acute phase reaction (ie, C reactive protein or erythrocyte sedimentation rate and weights for moderate or high elevations of either one (1 for moderate, 2 for high elevation)) and serological abnormalities (ie, rheumatoid factors or anti-citrullinated protein antibodies, again with separate weights for moderate or high elevations (2 and 4, respectively)).
CONCLUSION: The results of this first phase were subsequently used in the second phase of the project, which is reported in a separate methodological paper, and for derivation of the final set of criteria.
2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative
OBJECTIVE: The 1987 American College of Rheumatology (ACR; formerly, the American Rheumatism Association) classification criteria for rheumatoid arthritis (RA) have been criticized for their lack of sensitivity in early disease. This work was undertaken to develop new classification criteria for RA.
METHODS: A joint working group from the ACR and the European League Against Rheumatism developed, in 3 phases, a new approach to classifying RA. The work focused on identifying, among patients newly presenting with undifferentiated inflammatory synovitis, factors that best discriminated between those who were and those who were not at high risk for persistent and/or erosive disease--this being the appropriate current paradigm underlying the disease construct "rheumatoid arthritis."
RESULTS: In the new criteria set, classification as "definite RA" is based on the confirmed presence of synovitis in at least 1 joint, absence of an alternative diagnosis that better explains the synovitis, and achievement of a total score of 6 or greater (of a possible 10) from the individual scores in 4 domains: number and site of involved joints (score range 0-5), serologic abnormality (score range 0-3), elevated acute-phase response (score range 0-1), and symptom duration (2 levels; range 0-1).
CONCLUSION: This new classification system redefines the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease, rather than defining the disease by its late-stage features. This will refocus attention on the important need for earlier diagnosis and institution of effective disease-suppressing therapy to prevent or minimize the occurrence of the undesirable sequelae that currently comprise the paradigm underlying the disease construct "rheumatoid arthritis."
Nephrogenic systemic fibrosis: a pathologic study of autopsy cases
CONTEXT: Nephrogenic systemic fibrosis (NSF) is a rare but serious disorder initially described as a purely dermatologic process. Isolated autopsy reports have described multiorgan involvement by this disease.
OBJECTIVE: To further illustrate the varied and systemic involvement of NSF by describing the autopsy experience at the Massachusetts General Hospital.
DESIGN: We describe the findings in a series of 4 autopsy cases of patients diagnosed with NSF. This report describes the history of renal dysfunction, exposure to gadolinium-containing contrast agents, specific laboratory parameters, and the extent of systemic involvement identified by postmortem examination.
RESULTS: Causes of death included systemic thromboembolic disease (n = 3) and pneumonia (n = 1). Laboratory parameters and type, dose, or timing of gadolinium-containing contrast-agent exposure did not correlate with clinical findings and outcomes. All patients demonstrated cutaneous manifestations of the disease and nephrocalcinosis, with some exhibiting calcification and fibrosis of the dura, thyroid, and heart including the cardiac conduction system, on postmortem examination. Soft tissue calcification was associated with concurrent hyperparathyroidism or high serum parathyroid hormone levels.
CONCLUSIONS: Thromboembolic disease can be a significant clinical complication of NSF. Patients with NSF may also develop characteristic histologic features of fibrosis and calcification in multiple organs, with significant morbidity and mortality. This autopsy series highlights the variability of systemic manifestations of NSF.
Retrospective assessment of prevalence of nephrogenic systemic fibrosis (NSF) after implementation of a new guideline for the use of gadobenate dimeglumine as a sole contrast agent for magnetic resonance examination in renally impaired patients
From May 2007 to January 2008, patients with Stage 3-5 chronic kidney disease (CKD) undergoing gadobenate dimeglumine (GBD)-enhanced magnetic resonance (MR) examinations were included in the retrospective investigation. The electronic medical records were reviewed to assess the prevalence of nephrogenic systemic fibrosis (NSF) in renally impaired patients underwent GBD-enhanced MR examinations. In all, 250 patients (98 men, mean age 72.6 years) were included: 97% of the patients had Stage 3 CKD (estimated GFR 30-59 mL/min/1.73 m(2)); 37% had been exclusively exposed to GBD. The remaining were exposed to GBD and other gadolinium-based contrast agents (GBCAs). The mean dose of GBD was 22 mL (standard deviation [SD], 11.2). Including exposure to other GBCAs, the mean cumulative dose of gadolinium was 61 mL (SD, 62.3). A total of 206 patients (82%) had skin examinations following the last GBD administration (mean duration, 108 days). No evidence of suspected or diagnosed NSF was found. In conclusion, on the basis of a retrospective chart review there was no skin evidence of NSF in predominantly Stage 3 CKD patients who were exposed to GBD at an average follow-up of 108 days, either solely or in combination with other GBCAs. J. Magn. Reson. Imaging 2009;30:1335-1340. (c) 2009 Wiley-Liss, Inc.
Nephrogenic systemic fibrosis after gadopentetate dimeglumine exposure: case series of 36 patients
PURPOSE: To retrospectively assess the association between gadopentetate dimeglumine exposure at magnetic resonance imaging and the development of nephrogenic systemic fibrosis (NSF).
MATERIALS AND METHODS: This HIPAA-compliant study had institutional review board approval. Informed consent was waived. A search of medical and pathologic records was performed to identify patients with NSF that was diagnosed between January 1998 and December 2007. Patients with known exposure to gadolinium-based contrast agents other than gadopentetate dimeglumine were excluded. Medical records were then reviewed for gadopentetate dimeglumine exposure, renal status, concomitant diseases, timing of NSF symptom onset, date of NSF diagnosis, and clinical outcome. Skin gadolinium deposition was assessed for those patients with adequate available tissue. Spearman rank correlations were estimated to assess the relationship between the dose of gadopentetate dimeglumine and the time to onset of NSF.
RESULTS: Thirty-six patients (mean age, 62.6 years; range, 30-83 years) had been exposed to gadopentetate dimeglumine prior to NSF onset. All had stage 5 chronic kidney disease and all but one were undergoing dialysis at the time of exposure. NSF developed within 3 months after the last gadopentetate dimeglumine exposure (range, 1-59 months) in 21 (66%) of 32 patients. The patients had been exposed to median cumulative gadopentetate dimeglumine volumes of 35, 40, 85, and 117.5 mL over the 3, 12, and 24 months and up to 11 years preceding the onset of NSF, respectively. Patients who received higher cumulative and total gadopentetate dimeglumine doses had a higher risk of developing NSF than did those who received lower doses (odds ratio = 1.2). Twenty (56%) of 36 patients died, with a median interval of 18 months between NSF symptom onset and death.
CONCLUSION: NSF develops in patients with renal impairment after exposure to gadopentetate dimeglumine in a dose- and time-dependent manner.
SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.2531082160/-/DC1.
E-selectin, interleukin 18, serum amyloid a, and matrix metalloproteinase 9 are associated with clinical response to golimumab plus methotrexate in patients with active rheumatoid arthritis despite methotrexate therapy
OBJECTIVE: To assess the effect of golimumab (human monoclonal antibody to tumor necrosis factor-alpha) plus methotrexate (MTX) on selected inflammatory biomarkers, and to determine if these effects predict clinical response in rheumatoid arthritis (RA).
METHODS: Sera from adults with active RA despite MTX therapy, who received subcutaneous injections of placebo + MTX (MTX alone, n = 34) or golimumab 50 or 100 mg every 2 or 4 weeks + MTX (n = 137), were analyzed for levels of C-reactive protein (CRP), serum amyloid A (SAA), interleukin 18 (IL-18), E-selectin, matrix metalloproteinase 9 (MMP-9), and tissue inhibitor of matrix metalloproteinase 1 (TIMP-1).
RESULTS: Golimumab + MTX treatment significantly decreased serum CRP, SAA, IL-18, E-selectin, TIMP-1, and MMP-9 levels (median percent changes of -4.1% to -74.3% across treatment groups) versus MTX alone (-5.8% to 9.7%) when first measured at Week 4; decreases were sustained through Week 16. Larger magnitudes of decrease in all biomarkers were observed for clinical responders versus nonresponders. For golimumab + MTX, regression analyses including all biomarkers and select clinical measures showed that reductions in levels of several markers (SAA, E-selectin, MMP-9) as early as Week 4 correlated significantly with improvement in swollen joint count (SJC) at Week 16, as did reductions in E-selectin with improvement in tender joint count at Week 16. After accounting for the biomarkers, however, treatment group was no longer significant for SJC.
CONCLUSION: Significant decreases in several inflammatory biomarkers were associated with golimumab + MTX therapy. Decreases in serum levels of SAA, E-selectin, and MMP-9 at Week 4 may be useful in predicting clinical response at Week 16.
Physician ability to assess rheumatoid arthritis disease activity using an electronic medical record-based disease activity calculator
OBJECTIVE: To assess physicians' concordance with Disease Activity Score in 28 joints (DAS28) categories calculated by an electronic medical record (EMR)-embedded disease activity calculator, as well as attitudes toward this application.
METHODS: Fifteen rheumatologists used the EMR-embedded disease activity calculator to predict a rheumatoid arthritis (RA) DAS28 disease activity category at the time of each clinical encounter.
RESULTS: Physician-predicted DAS28 disease activity categories ranged from high ( > 5.1, 15% of cohort, 66 of 429 patient visits) to moderate ( > 3.2-5.1, 21% of cohort, 90 of 429 patient visits) to low (2.6-3.2, 29% of cohort, 123 of 429 patient visits) to remission ( < 2.6, 35% of cohort, 150 of 429 patient visits). Overall concordance between calculated DAS28 results and physician-predicted RA disease activity was 64%. Using either the physician-predicted or the calculated DAS28 category as the gold standard, accuracy was greatest for patients in remission (75% and 88% accuracy, respectively) and those with high disease activity (68% and 79% accuracy, respectively), and less for patients with moderate (48% and 62% accuracy, respectively) or low disease activity (62% and 31% accuracy, respectively).
CONCLUSION: Accurate physician prediction of DAS28 remission and high disease activity categories, even without immediate availability of the erythrocyte sedimentation rate or the C-reactive protein level at the time of the visit, may be used to guide quantitatively driven outpatient RA management.
A rheumatology-specific informatics-based application with a disease activity calculator
OBJECTIVE: To design a rheumatology-specific tool with a disease activity calculator integrated into the electronic medical records (EMRs) at our institution and assess physicians' attitudes toward the use of this tool.
METHODS: The Rheumatology OnCall (ROC) application culls rheumatology-pertinent data from our institution's laboratory, microbiology, pathology, radiology, and pharmacy information systems. Attending rheumatologists and rheumatology fellows accessed the ROC and disease activity calculator during outpatient visits at the time of the clinical encounter.
RESULTS: During the 12-week study period, 15 physicians used the ROC application and the disease activity calculator during 474 and 429 outpatient clinic visits, respectively. In weekly survey responses, physicians reported that use of the ROC interface improved patient care in 140 (78%) of 179 visits, and that the Disease Activity Score in 28 joints (DAS28) results at the time of the visit would not have changed patient management in 157 (88%) of these, although seeing a trend in DAS28 was useful in 149 (96%) of 156 visits. At the study's conclusion, most physicians reported that the ROC application was useful (11 of 12 physicians) and that seeing a trend in DAS28 improved daily patient care (12 of 13 physicians).
CONCLUSION: The ROC application is useful in daily rheumatologic care, and the disease activity calculator facilitates management of patients with rheumatoid arthritis. However, widespread acceptance and use of such tools depend upon the general acceptance of and access to EMRs in the clinical setting. The utility of the disease activity calculator may be limited by the lack of available acute-phase reactant results at the time of the clinical encounter.


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Adolescent and Young Adult Medicine
Contact Adolescent and Young Adult Medicine
- Children's Health℠ Specialty Center Dallas Campus 214-456-9099
Be happy. Be Healthy. We're here to help.
Our Adolescent and Young Adult program provides comprehensive patient care that considers the physical, emotional, social, economic and spiritual needs for male and female patient's ages 11 to 21 years of age.
Contact Us
Please contact the clinic if you would like more information about our clinic, appointment information, prescription refills or have questions about your medications.
Please leave a message when calling this number. All voicemails are forwarded to a confidential line and will receive a call back from our nursing or scheduling staff. Please be sure to provide the patient's name, the patient's date of birth, and the reason for the call.
Board Certified
All of the physicians who practice at Children's Health are board certified by either the American Board of Pediatrics or the American Board of Obstetrics. As the main pediatric teaching hospital for UT Southwestern Medical Center, your child's physicians are all on the faculty at the Center.
Magnet Hospital
Children's has also been designated as a Magnet Hospital by the American Nurses Credentialing Center. Being a Magnet Hospital puts us in the top 7% of the world's hospitals and is a reflection of the excellence of our nursing staff.
What We Treat
The physicians who practice at Children's Health work with patients and their families on a wide variety of needs. Procedures performed or problems diagnosed and treated:
- Sports participation physicals (with PCP permission)
- Pre-college physicals and immunizations (with PCP permission)
- Education and prevention of substance abuse
- Nutrition and weight management plans
- Evaluation and treatment of mood disorders or mental health issues associated with chronic illness
- Laboratory testing and radiologic tests
- Contraceptive and reproductive counseling
- Sexually transmitted disease treatment and prevention
- Acne management and wart removal (with PCP referral)
Why Children's Health℠
For more than a century, Children's Medical Center Dallas has been at the forefront of making life better for children. Today it is the seventh largest pediatric hospital in the country, and is consistently ranked among the nation's best by U.S. News & World Report.
A 490-bed full-service hospital, offering tertiary and quaternary expertise in more than 50 pediatric specialties and the highest level
of trauma care in North Texas as a Level I Trauma Center.

subset: commoncrawl


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Home →
→ Activities Tips
| Activities Tips
Pastimes and More A national franchise of toy and hobby stores, HobbyTown USA, recently opened a new location in Nanuet with a lineup of items from remote control cars to model planes, trains, helicopters, boats, and rockets. They also carry paints and tools to create your own. With slot cars, board and card games, plush and baby toys, action figures, dolls, arts and crafts, a large selection of educational items, puzzles, and science kits, HobbyTown USA caters to casual fans and serious hobbyists alike. HobbyTown USA also hosts national model contests, special events, themed birthday parties, and gaming nights every Saturday. HobbyTown USA, 418-A Nanuet Mall South, Nanuet. 845-623-3261 or www.hobbytown.com.More Martial Arts Triumph Tae Kwon Do, a martial arts school in Pearl River, has opened its newest location in Norwood, NJ. Triumph Tae Kwon Do is owned and operated by Master Oh, who is educated in child psychology and has more than 15 years of teaching experience. With a full range of martial arts programs for ages 2 and older, students learn self-discipline and self-defense while developing balance, coordination, concentration, and strength and improving their social skills, confidence, and self-esteem. Toddlers learn skills that prepare them for school, while older children learn martial arts techniques. Teens learn respect for themselves and others as they discover how to relieve stress in a positive and supportive surrounding. Adult classes are also offered and the Family Training program helps parents and children realize the benefits of greater health, fitness, and self defense while bonding as a family. Triumph Tae Kwon Do is offering a free, two-week trial offer that will be honored at either location. Students can meet Master Oh and attend up to four classes without any commitment. Triumph Tae Kwon Do, 474 Livingston Street - Unit 103, Norwood, NJ; 201-768-2471. Also at 54 N. Middletown Road, Pearl River; 845-732-0292.
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Fairfield County, CT
Nutritionist Robin Werner shares nutrition guidelines for young athletes and active children, as well as ideas for healthy snacks for athletic children and how to teach your child to make healthy food choices.
Bike riding is a great warm-weather activity, and wearing a helmet is the most important part of bike safety. Sandhya Katz Katz, M.D., an emergency medicine physician at Nyack Hospital, shares tips to pick a properly fitting bike helmet.
Copyright 2015 | All Rights Reserved | Davler Media


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Linear Encoder
POSITAL-FRABA Offers Sensor Buyers - A Million Possibilities
POSITAL-FRABA has committed to provide buyers of position and motion sensors with an unparalleled range of choices in terms of device options and performance characteristics. "Our objective is to provide machine builders, system integrators and OEMs with exactly the right devices for their projects," explains Christian Fell, head of POSITAL-FRABA's North American operations.
MicroE Systems releases the new Optical Positioning Sensor Series
MicroE Systems has recently released it's the new Optical Positioning Sensor (OPS™) Series, which delivers high performance and advanced positioning system features. The OPS™ sensor is equipped with MicroE's patented optical design and features built-in interpolation and AGC ensuring optimal performance and reliability.
Compact, Precision Ball-Screw Stage with Linear Encoder
A compact, high-performance linear positioning stage, Aerotech's MPS75SLE features exceptionally smooth travel combined with outstanding accuracy, repeatability and positioning resolution capability to 25 nm. Ideal applications include optics positioning, z-axis positioning of sensors in surface metrology, and in general purpose high-precision alignment.
Fiber Optic Junction Boxes protect Optical Links in Harsh Environments
MR398-JB series Fiber Optic Junction Boxes are designed to join two fiber optic cables and environmentally protect the connection. The product provides system designers with a turnkey solution for installing optical interconnect "hard points" as part of a complete the cabling solution for the Micronor MR320/MR330 series fiber optic rotary and linear encoder systems.
LINARIX linear sensors selected for Rockwell Automation's Encompass™ program
POSITAL-FRABA's LINARIX linear position sensors have been added to the list of products referenced by the Rockwell Automation PartnerNetwork™. Through Encompass™ Product Partners, customers can quickly locate complementary products that best solve any application challenges. These products are critical components of connectivity solutions that extend and enhance Rockwell Automation installations.
ST46-EZA® Linear Encoders set-up without oscilloscope
The new ST46-EZA® Series linear encoders from Mitutoyo America Corporation offer advanced features that make them an ideal choice for linear motion systems.
Durable Linear Position Encoder with Analog Output
Compact Housing
Lika Electronic adds the SMEx Series of Linear Encoders to its family of Position Sensors
Adding to its growing family of reliable, durable position sensors, Lika Electronic introduces a new line of linear encoders. The SMEx series linear encoders provide rapid, accurate and repeatable position feedback with a small and strong design.
BEI Releases Second Edition of Industrial Encoders for Dummies
Goleta, CA - Select and install encoders correctly for trouble-free performance with BEI Sensors' newly updated Industrial Encoder for Dummies 2nd Edition. This edition features new sections including in-depth explanations of resolution vs. accuracy, natural binary vs. gray code, and how to choose an encoder for your specific needs. Additionally this 44 page book will help you recognize which encoder features really matter, discover the lingo of encoders and understand potential electrical and environmental problems so you can avoid common pitfalls.
Linear Encoder - Boost Productivity with High-Speed BEI Linear Encoders
The rugged LN linear encoder provides fast, accurate and repeatable position feedback for a wide range of motion control applications. The LN, an inductive linear encoder, is not subject to the speed limits imposed on its optical counterparts. The encoder's sealed read head completely surrounds the scale, eliminating the risk of the critical gap between sensor and scale varying with speed. With onboard digital signal processing (DSP) capability, the LN boasts traverse times of up to 20 meters per second.&nb


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Vintage Motorcycles
Motorcycles have figured prominently in just about every aspect of 20th-century life. Classic and vintage motorcycles have become highly collectible, especially among baby boomers.
The first motorcycles were produced in the late 19th century, on both sides of the Atlantic. Some of the earliest efforts were simply small motors attached to a bicycle. In the 20th century, hundreds of makers produced motorcycles of all varieties, including Indian, Harley-Davidson, Ducati, Crocker, BMW, Triumph, Honda and more.
Two American companies, Indian and Harley-Davidson, dominated the market in the U.S. until the waves of British and Japanese imports in the 1950s and 1960s respectively. While Indian ultimately failed, Harley-Davidson made a comeback in the 1980s, and its vintage 'hogs' are now a favorite of riders and collectors.
Best of the Web ("Hall of Fame")
Classic Motorcycle Archive
This simple website contains photos and descriptions of over a thousand classic antique motorcycles and motorized b… [read review or visit site]
Clubs & Associations
Other Great Reference Sites
Most watched eBay auctions
Recent News: Motorcycles
Source: Google News
AMA Vintage Motorcycle Days seminar program to cover riding, racing ...North Denver News, June 30th
Attendees at AMA Vintage Motorcycle Days, July 10-12, at Mid-Ohio Sports Car Course in Lexington, Ohio, will have numerous opportunities to hear from motorcycling experts, including AMA Motorcycle Hall of Famers, as part of the event's seminar program...Read more
AMA Vintage Motorcycle Days Swap Meet - Heaven for ManyUltimateMotorcycling.com, June 26th
AMA Vintage Motorcycle Days Swap Meet - Heaven for Many Vintage motorcycle racers, collectors, restorers, enthusiasts and dreamers will be in motorcycling swap-meet heaven this July 10-12 during AMA Vintage Motorcycle Days at Mid-Ohio Sports Car ...Read more
Aldana to serve as grand marshal of AMA Vintage Motorcycle DaysMorrow County Sentinel, June 25th
"Those same people are now coming out to events like AMA Vintage Motorcycle Days to re-live and re-experience those memories. They are dedicated enthusiasts and die-hard motorcyclists, and I love to spend time with them and connect over motorcycles."...Read more
India's Vintage Motorcycle Royal Enfield Is On Full ThrottleForbes, June 24th
Two years ago, when Hrishikesh Kathe, 29, a Mumbai perfume distributor, decided to buy what he calls his "dream bike," he had to wait up to ten months for his first ride, as the motorcycle he wanted wasn't available off the shelf. Kathe's dream machine...Read more
BMW Demo Rides at AMA Vintage Motorcycle DaysUltimateMotorcycling.com, June 19th
"We recently launched five new models and are proud to offer them and many more for attendees of AMA Vintage Motorcycle Days to demo," said Sarah Schilke, BMW Motorrad national marketing manager. "BMW has a huge line-up this year and this event ...Read more
American Motorcyclist Association Ramps up Vintage Motocross Program at ...Off-Road.com (blog), June 16th
AMA-logo-230 PICKERINGTON, Ohio — The American Motorcyclist Association's national championship vintage motocross program during AMA Vintage Motorcycle Days, July 10-12 at Mid-Ohio Sports Car Course in Lexington, Ohio, will include more ...Read more
AHRMA Vintage Motorcycle Festival Happening July 10-12 At New Jersey ...RoadracingWorld.com, June 15th
MILLVILLE, N.J. The American Historic Motorcycle Racing Association returns to NJMP July 10-12 for the 3rd Annual AHRMA Vintage Motorcycle Festival presented by Flying Fish Brewing Company featuring The South Jersey Wine Festival presented by the ...Read more
Appeal for help with vintage motorcycle draws immediate responseIsle of Man Today, June 9th
Mr East explained: 'They didn't make many of them, although it was very well engineered and very advanced for what it was. There are very few of them about. 'This particular model belonged to Fred Wyeth, of Laxey, a member of the Vintage Motorcycle Club...Read more


text:
\dah-MEER mar-KO-tah\
Damir Markota
(born Damir Omerhodzic)
Position: Power Forward ▪ Shoots: Right
Height: 6-10 ▪ Weight: 225 lbs.
Born: December 26, 1985 in Sarajevo, Bosnia and Herzegovina
Draft: San Antonio Spurs, 2nd round (29th pick, 59th overall), 2006 NBA Draft
NBA Debut: November 3, 2006
D-League: 10 G, 10.4 PPG, 4.8 RPG, 1.8 APG (Full Record)
Other Pages: Europe Stats
Sponsor this page for $5 and help Basketball-Reference.com provide this service. Your message will replace this ad.


text:
Stock Vector Illustration:
red style electrical symbol with AC outlet and plug
- Image ID: 123901285
- Copyright: kelttt
High quality images curated from over 150 countries.
Over 50 million photos, vectors, illustrations, and more.
Simple and flat pricing by image or by month.
Over 230,000 images downloaded every day.


text:
Marc Jacobs shares the latest image along with a sentimental message to the supermodel.
Style A to Zee: True Jeanius
Laura Freedman, Jewelry Designer and Curator
Digital Inspiration:
The Coveteur captures the personal wardrobe and homes of today's top tastemakers.
Heavy Metal
"These are some sexy shoes. I wear them with jeans and a T-shirt. Kelly, who works with me, designed these bracelets—her line is called Situ, after her grandma. They come in rose, yellow, and white gold and look great with all your other accessories."
It's All About: Island Life


text:
VIDEO: New Trailer for James Franco's CHILD OF GOD
|Related Links
|James Franco Receives Venice Film Festival's 2014 Glory to the Filmmaker Award
August 08, 2014
|VIDEO: James Franco Talks New Film 'Child of God' on COLBERT
July 31, 2014
|Related: CHILD OF GOD, James Franco, Cormac McCarthy
James Franco's adaptation of Cormac McCarthy's CHILD OF GOD, set to hit the big screen on August 1, just unveiled a new, and chilling, trailer. Check it out below!
Scott Haze, Tim Blake Nelson, and Franco star in the film, which follows a violent social outcast in the 1960s who descends into madness, becoming a serial killer in Tennessee.
About Author
- Mark Wahlberg Partners With Indian Motorcycle on Limited Edition Apparel Line
- VIDEO: Oscar Winner Eddie Redmayne Joins All-Star Cast in New SAG Foundation PSA
- VIDEO: Joan Rivers Snubbed? Watch OSCARS' In Memoriam Tribute
- Kirk Cameron, Kelsey Grammer, ANNIE and More Top 2015 RAZZIE AWARDS; Full List!
- LA Kings & San Jose Sharks Face-Off in First Outdoor NHL Game, Live in Theaters Today
- VIDEO: New Trailer for HBO Scientology Doc 'GOING CLEAR'
- Actor Joe Mantegna Becomes Saint Pio Foundation Goodwill Ambassador
- VIDEO: Behind the Scenes - Neil Patrick Harris Shares His OSCARS Creative Process!
- Rebecca Wang Supports 68th BAFTA Film Awards Ceremony
- Gay Men's Health Crisis to Honor THE NORMAL HEART's Larry Kramer with Lifetime Achievement Award


text:
Nokia may have a big booth at CTIA, but so far the company's news has been light. Besides the E71x for AT&T, Nokia's only other new cell phone in Las Vegas is the 1661 for T-Mobile's prepaid service. The low-end handset sports a simple candy bar design with basic features. The handset is dual-band (GSM 850/1900), which means it will only work in North America.
Inside you'll find an FM radio, messaging, a 250-contact phone book, a speakerphone, a calendar, and an alarm clock. Yet, there is one unique touch. On the 1661's top end is a large and bright flashlight. The 1661 will be available later in April. We don't know pricing yet, but we're sure it will be cheap.


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Jun 6
Cosplay scene: Two Princess Leias
I did some serious nerding out in today's Pioneer Press.
I wrote a feature story about Twin Cities cosplayers, a business story about professional cosplay-costume makers, and a third story about girl geeks (including Minneapolis Mayor Betsy Hodges).
Here's some more cosplay coolness for you. I met two cosplayers with two very different variations on the "Star Wars" character Princess Leia. Read More
May 20
US Internet proposes a TV service
The Twin Cities, or at least Minneapolis, could have a third cable-television provider before long.
US Internet, the Minnetonka-based provider of wireless and fiber-optic broadband service in Minneapolis, is lobbying to deploy a paid-television service in that city. Read More
May 15
Andy the cord-cutting councilman
CenturyLink celebrated today when the city of Minneapolis gave it the all-clear to deploy its Prism TV service as a direct competitor to longtime cable monopolist Comcast.
That momentous occasion, for many, was the highlight of today's Minneapolis city-council meeting.
For me, though, the most memorable moment came towards the end of pre-vote chatter about CenturyLink when council member Andrew Johnson revealed that he is … a cord cutter. Read More
May 14
A lukewarm Postmates experience
Postmates, the new-to-the-Twin-Cities service that fetches you food and retail goods on demand, has a free-pizza promotion via Punch Pizza today and tomorrow.
This was a great way to test the service, so I ordered up a Margherita pizza (you can opt for a Napoli, instead, as part of this deal) via my iPhone this afternoon.
I got my pizza in due course, but this experience wasn't entirely positive. Read More
May 14
Comcast X1 voice remote is neat-o
I'm a cord cutter at heart if not in practice — my household's Comcast cable-television setup isn't going anywhere because my wife likes it too much, and she's the boss.
I grudgingly agree that Comcast's Xfinity-branded X1 cable-TV equipment is neat-o. Read More
May 14
More about cord-cutting consultant
I wrote a story this week about Cable Alternatives.
The Fridley-based consumer consultancy helps wannabe cord cutters go through the sometimes-complicated steps of ditching expensive cable TV or satellite TV, and setting up lower-cost alternatives.
To learn more about Cable Alternatives, watch a nifty KARE report about the company. Read More


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iHerb Customer Reviews
Items 31-34 of 34 total
« Previous | 3 4 5 6 7 | Next »
a good basic moisturizer
Posted by Reviewer3275280 on Aug 02, 2012
very light, easily absorbed into the skin. not really useful for me, i need an SPF for the day, and something a little more concentrated at night. still use once in awhile around the house during the day, however. great company/products.
Too thick
Posted by Reviewer3036917 on Mar 12, 2010
This moisturizeer really clogged my pores. I tried to barely pat some on my dry patches, but still upset my skin.
Not sold on it!
Posted by Reviewer1333756 on May 12, 2009
I purchased this due to good reviews and decent ingredients. It's a decent basic moisturizer, but didn't impress me. I actually caused breakouts, but I do have sensitive skin.
not great for combination skin
Posted by 5326898299720780389 on Sep 02, 2014
I have combination skin prone to breakouts and this isn't the best. It's not scented, which is good for my sensitive skin but it has not been effective at providing moisture for my face. However it is good for the body
Items 31-34 of 34 total
« Previous | 3 4 5 6 7 | Next »


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The Giant Beastcast: Episode 06
Become Premium to Watch
Her Story is a bold and largely successful experiment in interactive crime fiction.
Rocksteady's gorgeous-looking third Arkham game refines its open-world format a bit and lets you drive a whole hell of a lot of Batmobile.
It's squid kids and ink blasting abound in Nintendo's exceptionally fun new online shooter.
Game »
consists of 3 releases.
Released Dec 14, 2000
An action RPG for PS2 set in the Summon Night universe.
White Knight Chronicles is a mixture of traditional fantasy JRPG and good old fashioned mecha. The story features Leonard, a protagonist who can transform into the White Knight with the use of an ancient technology. The game also allows players to join forces over the internal multiplayer mode, Geonet.
My Life As a Darklord is a tower defense game set in the Crystal Chronicles continuity of the Final Fantasy universe.
Manage your town and send adventurers out on quests in this Final Fantasy-based strategy game. "It's good to be the king"
Atelier Iris 3: Grand Phantasm is a console role-playing game developed by GUST for the PlayStation 2. It is the third and final game in the Atelier Iris saga.
Phantasy Star Universe tells the story of a Guardian named Ethan Waber who is on a mission to save his sister and stop a mysterious life form known as the SEED.
Atelier Iris 2: Tha Azoth of Destiny is a console role-playing game developed by GUST for the Playstation 2. It was released in North America by NIS America and in Europe by KOEI. The game is a prequel to Atelier Iris: Eternal Mana.
The eighth main entry in the Dragon Quest franchise. It was the first game in the series to utilize a full 3D environment and featured a cel-shaded graphics style which would become standard for all future games in the franchise.
Atelier Iris: Eternal Mana is a console role-playing game developed by GUST for the PlayStation 2. It was published in North America by NIS America and in Europe by KOEI. It is the first game in the Atelier series to get a release outside of Japan.
A unique mix of Disney and Square Enix characters join spiky-haired hero Sora on his epic journey to save multiple worlds from the evil of the Heartless and find his lost friends Riku and Kairi.
Metal Dungeon is an RPG dungeon crawler featuring randomized maps.
Unlock sidequests and save the world in Square's follow up to Secret of Mana.
Soul Blazer is an action-RPG published by Enix for the SNES
ActRaiser is a hybrid of two genres: city-building and action platformer. The player takes control of the powerful entity known as the Master in his quest to rebuild civilization.
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text:
YIELD: Makes about 2 cups
In a baking pan roast the onions in the middle of a preheated 475°F. oven for 2 hours. While the onions are roasting, in a small saucepan melt the butter over low heat, whisk in the flour, and cook the roux, whisking, for 3 minutes. Add the cream and the wine in a stream, whisking, bring the mixture to a boil, whisking, and simmer it whisking, for 5 minutes. Remove the saucepan from the heat and stir in the capers, the vinegar, the tarragon, the parsley, and the chives.
Let the onions cool until they can be handled, discard the tough outer layers, the stems, the root ends, and the juices in the baking pan, and in a food processor purée the onions until they are smooth. Transfer the purée to a small saucepan, bring it to a boil, and boil it, stirring, until it is thickened and the excess liquid is evaporated. Stir in the purée into the cream sauce and stir in salt and pepper to taste. The sauce may be made 1 day in advance and kept covered and chilled. Serve the sauce warm or at room temperature.


text:
FIFA has accepted a court decision to release a document naming officials who took millions in kickbacks from World Cup broadcast deals.
Lionel Messi scored twice as Barcelona topped Brazil's Santos 4-0 to win its second Club World Cup in three years.
Defending champion Barcelona got the luck of the draw on Friday and will play Bayer Leverkusen in the last 16 of the Champions League.
Didier Drogba scored two goals and set up another to power Chelsea to a 3-0 victory over Valencia, advancing them to the second round.
Standings, scores and matchup information for soccer leagues around the world.
Five Mexican players who tested positive for clenbuterol won't face sanctions after FIFA determined the tests were due to contaminated meat.
Brazil striker Neymar has dismissed reports that he's reached a transfer deal, saying he will stay put at least until next year's Olympics.
South American powerhouses Brazil and Argentina drew 0-0 on Tuesday in a friendly featuring only locally-based players.
The English and Scottish Football Associations called on FIFA to postpone Wednesday's presidential election in the wake of the bribery scandal that led to Sepp Blatter's only challenger withdrawing.
As Chelsea's season unravels, its early supremacy becomes a distant memory and the Champions League offers under-pressure manager Carlo Ancelotti the last realistic chance of redemption.
Arsenal was brought down to earth by third-tier London rival Leyton Orient on Sunday, drawing 1-1 in the FA Cup fifth round after beating Barcelona in midweek.
England's World Cup bid team predicts a $240 million profit will be made if it stages the event in 2018.
Aston Villa defender Eric Lichaj and Schalke midfielder Jermaine Jones were selected Thursday for the 20-man roster for the United States' exhibitions against Poland and Colombia next month and could make their national team debuts.
France's highest scorer, Thierry Henry, will never consider playing for the team again even if new coach and former teammate Laurent Blanc asked him to.
Substitute Mohamed Gedo scored in the 85th minute Sunday to help Egypt beat Ghana 1-0 and secure its third straight title at the African Cup of Nations.
FIFA has banned Diego Maradona from all soccer activities for two months for the Argentina's coach expletive-filled rants after his team qualified for the World Cup.


text:
The Distance between Keshod to Ahmedabad is 356Kms by road. A total of 6 operators provide bus service from Keshod to Ahmedabad, connecting two important cities of India and a total of 12. Major operators who operate buses from Keshod to Ahmedabad are Patel Tours & Travels, Mahasagar Travels, Shri Hari Travels having the maximum number of services. Keshod to Ahmedabad bus timings vary with different operator and bus type, the journey takes 4hrs 18min to 21hrs 15min to complete this journey depending on the operator, type of bus and traffic conditions. The first bus takes off around 09:30 PM and last bus at 11:30 PM. The lowest Keshod to Ahmedabad bus fare being Rs.280 and the highest being Rs.650 depending on the type of bus.
Travelling from Keshod to Ahmedabad can be comfortable and easy as there are many types of buses available for travellers. Different type of buses are available in this route like Non A/C Seater & Sleeper, A/C Sleeper, Isuzu A/C Sleeper (2+1), Non A/C Sleeper (2+1). Now that redbus has tied up with many operators, booking tickets from Keshod to Ahmedabad has become very easy.
Ahmedabad is one of the largest and fastest growing cities of India. Located along the banks of river Sabarmati, Ahmedabad is fondly called Amdavad by the locals. It is one of the cities of India with historic imporatnce as well, because of its close association with Mahatma Gandhi, the father of the nation. The Sabarmati Ashram here is one of the most visited places of the city.Ahmedabad is also known as the "Manchester of the East" as it is renowned for its textile mills.An ancient city called Karnavati, Ahmedabad was renamed thus after being defeated by Sultan Ahmed Shah. The major attractions here include the Bhadra Fort, the tombs of Ahmed Shah and his queens, Ahmed Shah's Mosque, Jama Masjid, Mosque of Sidi Sayid, Teen Darwaza or Triple Gateway, to list a few.Ahmedabad can be easily reached by road and rail. Several buses connect the city to other important cities and towns nearby.
it is satisfactory
newly build Coach. space between 2 raws are not enough for seating section.
Journey is d good but as you provided pick up point office in keshod is closed at that day of journey they creat problem for me....but after all finally i got the bus...


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Knotty And Nice
Location Details: Pigeon Forge / Twin Moutain
Bedrooms: 1 Bathrooms: 2.5 Sleeps: 4
Knotty and Nice is a lovely three story, Appalachian style log cabin located on a paved road just 6/10 of a mile off of Wears Valley road in Pigeon Forge. The cabin is secluded with a nice mountain view from the wrap around porch.
The main level features rustic reclaimed yellow pine flooring, expansive cathedral ceilings, a stone gas fireplace, a 47" TV, VCR/DVD with HBO and Showtime. The charming fully equipped kitchen offers upscale appliances and a convenient breakfast bar. Take in the mountain view from the dining table, or play a game of pool overlooking the small spring fed pond just outside the bay windows. The covered porch has a round six person hot tub, rocking chairs, a porch swing, and a rustic table for six. The loft bedroom has a cathedral ceiling, elegant king bed with a carved mountain scene headboard, and a TV with DVD/VCR. The master bath has an over sized whirlpool tub for two and a separate shower.
The lower level features a TV Room with comfy furnishings including a sleeper sofa and a 43" high definition flat screen TV with surround sound, along with DVD/VCR, cable with premium channels HBO and Showtime for your viewing pleasure. A game room with a air hockey table, Foosball table, a 27" TV a full bath and a washer/dryer for your convenience.
Knotty and Nice will provide you with everything you are looking for! Seclusion, serenity, scenery and a convenient location close to the Great Smoky Mountain National Park, exciting attractions and dining.
While staying at Knotty and Nice there is access to the use of a pool pass to the outdoor pool area only at the Pigeon Forge Community Center.
All cabin stays are provided a free starter pack of coffee, paper towels, toilet tissue, hand soap, dish washer and dish washing detergent for your immediate use.
To ensure your cabin is ready, Please call our office for same day booking!
- Secluded
- Home Theater
- Pets Allowed
- Air Hockey
- Wi-Fi
- Pool Table
- Laundry
- Internet
What people are saying about this property
Loved the cabin. Although the pull out bed needs repair. Bad spring i think. The kids slept on it folded up.
From the reservation to arrival, everyone answered all questions completely. The cabin was beautiful, very relaxing weekend.
Very professional in every way. Your representatives were always very polite and eager to help, from the beginning with making our reservation to the departing phone call. My family and I thoroughly enjoyed our stay. Thank you.
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UPDATE: Ex Missouri Governor Wilson Gets Probation
Roger Wilson pleaded guilty in April to one count of misdemeanor campaign finance fraud.
Ex Missouri Sheriff Could Get 10 Years for Stolen Firearms
Tommy Adams also faces state drug charges.
Mo. Minister Gets 4 Years In Prison For Child Porn
A southwest Missouri minister who told federal investigators he was addicted to pornography has been sentenced for nearly four years in federal prison.
Alyssa Bustamante Sentenced To Life With Possibility Of Parole
18-year-old faces possible life prison term in 9-year-old neighbor's murder.
Appeal is Blagojevich's Last Hope to Cut Sentence
Blagojevich's lawyers must convince a higher court that trial Judge James Zagel made serious errors at trial and in calculating a sentence.
Blagojevich Sentencing Could Take 2 Days
Blagojevich faces between 15 and 20 years in prison.
Government: Blagojevich Should Get 15 to 20 Years
His sentencing hearing will be Dec. 6 and 7 before a federal judge.
Man To Be Sentenced For Killing 4-Year-Old
Beat child because he interrupted him playing a video game
Blagojevich Sentencing Set for December 6
Earlier this year a jury found the 54-year-old impeached governor guilty on 17 of 20 corruption charges.
Blago Uses Facebook To Ask Supports To Write Judge
Blagojevich's sentencing date has not been set.


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Leon Black 's Apollo Global Management LLC agreed to buy CKX Inc. , owner of the "American Idol" television show, for about $509 million in cash.
CKX Inc., the owner of "American Idol," said Robert F.X. Sillerman resigned as chairman and chief executive officer to pursue a possible acquisition of the company.
Robert F.X. Sillerman , the former chief executive officer of CKX Inc. , said he is preparing a cash offer of $5.50 to $5.75 a share for a controlling stake in the owner of the "American Idol" television show.
CKX Inc. , the owner of "American Idol," adopted a shareholder rights plans that may prevent company founder Robert F.X. Sillerman and another potential investor from acquiring a majority stake.
CKX Inc. , the owner of "American Idol," said there may soon be discussions about founder Robert F.X. Sillerman's possible plan to take the entertainment company private.
The trial of Jerome Kerviel, beginning more than two years after Societe Generale SA accused him of losing 4.9 billion euros ($5.8 billion) on unauthorized market bets, may turn on whether the trader can show the bank knew what he was doing.
CKX Inc. , owner of the "American Idol" television show, said it ended discussions to sell the company or a controlling stake, seven months after the talks were first acknowledged.
Simon Fuller , the founder of 19 Entertainment and creator of the "Idol" TV series, is planning a $600 million bid for CKX Inc. , according to a person with knowledge of the situation. CKX jumped the most in three years.


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Original recipe yields 8 servings
Amount per serving ({{servings}} total)
Based on a 2,000 calorie diet
Fairly easy to make, unique pie but wonderful flavor & rave reviews from everyone. Hint: dont let the pie cool too much before you flip it as becomes impossible to remove from the pan. If this h...
I tried this recipe because we were tired of plain old apple pie. It is so good. This has become a family tradition for the holidays! I don't know who came up with this recipe, but THANK YOU!
top (or bottom), the flipped side, didn't cook for me. Just a doughy mess. Not too flavorful.


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Location was great! Very close to Legoland and restaurants.
They are remodeling the hotel. They are not only remodeling it during the day. They are working with drills and workers who enjoy loud music while they work at 2am!!! The sound came right through the vents. Seriously?!
I liked the value of the pricing and it was near Lakeland during Sun and Fun which drives hotel rates up. Linen was clean and the bed comfortable but dated.
The hotel was old and looked as it was being renovated slowly. Attention to detail was lacking; the property can be old and well maintained, this was not dirty thresholds, elevator, balcony all could use a good cleaning. The dated room furniture was dirty and stained some broken lamp fixtures. Breakfast area looked dirty and uninviting we did not use. Pool area was dirty so we did not swim. Overall the facility was worn; however, that is what the low rate provided. Skip breakfast and put money into cleaning the facility.
table lamps were not working.
Facilities were subpar. It is a very old hotel and it shows. The staff while outwardly friendly did not seem to very well trained. The bar staff was friendly but the selection made it seem more like a cash bar at a cheap wedding than a quality full service bar. The breakfast is not a breakfast. It is coffee and a snack as you decide where you are actually going to go to eat breakfast.
I liked that they let us into breakfast early
The girl who checked us in wAsnt friendly
Ran towards this hotel after a disastrous experience with a "local" hotel closer to the Legoland site. This hotel in contrast was clean, with good accommodations, and great staff.
First of all its attached to a strip club which would be nice to know....also shady people in parking lot while going into room. Then sheets and pillowcase had stains on them AND 3 cockroaches belly up still alive in the bathroom... It was HORRIBLE was there 10 minutes and could not stay!
We liked that the location was close to the wedding venue. We were grateful for the recliner in our room... The nighttime crying was soothed much easier with it!
The surrounding area is not the safest. But for the money they did a swell job. It was difficult staying with an 8mo old the light shined through the curtains so it wasn't "night time" for him.
Clean, friendly staff, good breakfast, close parking, close to lego land
The location was great if you are going to LEGOLAND. Also the restaurants were within walking distance.
The breakfast was ok but nothing like other Hampton breakfasts. The yogurt had mold in it and when I notified the attendant she thanked me and continued to clean. Also the shower curtain needed to be replaced as well as the ironing board and iron.
I have food sensitivities and often bring my own food. So I was very pleasantly surprised to see that I had a refrigerator to keep my food (I was not aware of this), but I knew there was a microwave. The room was cozy, comfortable, and private.
Cleaner than most. Excellent hot breakfast. Nice kitchenette. Free wifi. Restaurants within a short walking distance.
I found the bed to be too firm and uncomfortable. Mobile phone service was impossible in the room and generally spotty in the building.
Rooms very clean and fresh
Not very much. Lame breakfast. Carpet in my room was dirty (my white socks turned brown on the bottoms just from walking around in the room).
Location with close proximity to LEGOLAND.
Breakfast was only fair, but for the price acceptable.
Close to Legoland. Clean and comfortable. Friendly staff.
Landscaping needs a clean up. Not a big deal though.
Very friendly and helpful staff. Loved every aspect of this hotel. Continental breakfast excellant. Would definitely stay here again.
Loud music from local bar on Friday a little annoying. Exhaust fan in bathroom broken. Very slow elevators. All things that were manageable.
Close to shopping, restaurants and the Lakeland Center.
I have no complaints.
Rooms were comfortable and clean. Staff is super friendly and accommodating. On top of that the breakfast spread is delicious!
Staff was nice !!
The room was musky smell and the rugs had nasty stains all over. its located in a really dark and Not to Safe feeling at Night to walk !
Staff was friendly, rooms were clean!
Breakfast was very limited!
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2004 GMC Envoy Q&A
2004 GMC Envoy Question: melting headlight plug
the plug on my low beam headlight keeps melting on one side and I don't know why. I've put 2 new ones on with new bulbs and it keeps melting - coles3941
2 Answers
Answer 2
I've got a GMC Envoy and have the same problem except it is on both sides and has happened multiple times. I've burned the bulbs and connectors several times. They usually only last for a couple of months. I was just informed that NHTSA RECALL BULLETIN ref # 070E014000 addresses this issues and recommends replacing the bulb and connector with OEM parts only and that will solve the problem. Basically, buy your parts from the dealership and you'll be fine. - Visitor
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Low beam headlight plugs keep melting. I replaced them with aftermarket parts and those melted.
In the last 2 months 4 headlight plugs have burned/melted out,two on each side. The headlight itself is alright and not burned out. Seemsto be common problem with GM. Any ideas on how to stop this....
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