text:
Infliximab maintains a high degree of clinical response in patients with active psoriatic arthritis through 1 year of treatment: results from the IMPACT 2 trial
Extended report
A Kavanaugh1,
G G Krueger2,
A Beutler3,
C Guzzo3,
B Zhou3,
L T Dooley3,
P J Mease4,
D D Gladman5,
K de Vlam6,
P P Geusens7,
C Birbara8,
D G Halter9,
C Antoni10,
for the IMPACT 2 Study Group
1Center for Innovative Therapy, Division of Rheumatology, Allergy, and Immunology, University of California at San Diego, La Jolla, CA, USA
2University of Utah Health Sciences Center, Salt Lake City, UT, USA
3Centocor, Inc, Malvern, PA, USA
4Seattle Rheumatology Associates, Swedish Medical Center, Seattle, WA, USA
5University of Toronto, Toronto, ON, Canada
6University Hospital Leuven, Leuven, Belgium
7University Hasselt, Diepenbeek, Belgium, and University Hospital, Maastricht, The Netherlands
8University of Massachusetts School of Medicine, Worcester, MA, USA
9Houston Institute for Clinical Research, Houston, TX, USA
10Schering Plough Corp., Kenilworth, NJ, USA
Dr A Kavanaugh
Center for Innovative Therapy, Division of Rheumatology, Allergy and Immunology, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0943, USA; akavanaugh{at}ucsd.edu
Objective: To evaluate the efficacy and safety of infliximab through 1 year in patients with psoriatic arthritis (PsA) enrolled in the IMPACT 2 trial.
Methods: In this double blind, placebo controlled, phase III study, 200 patients with active PsA were randomised to receive infusions of infliximab 5 mg/kg or placebo at weeks 0, 2, 6, and every 8 weeks thereafter through 1 year. Patients with persistent disease activity could enter early escape at week 16, and all remaining placebo patients crossed over to infliximab at week 24. Patients randomised to infliximab who had no response or who lost response could escalate their dose to 10 mg/kg starting at week 38. Clinical efficacy was assessed based on the proportion of patients achieving ACR 20 and PASI 75 responses. Major clinical response (that is, maintenance of ACR 70 response for 24 continuous weeks) was assessed for the first time in PsA.
Results: Through 1 year of treatment, 58.9% and 61.4% of patients in the randomised infliximab and placebo/infliximab groups, respectively, achieved ACR 20; corresponding figures for PASI 75 were 50.0% and 60.3%. At week 54, major clinical response was achieved by 12.1% of patients in the infliximab group. The safety profile of infliximab through week 54 was consistent with that seen through week 24. Two malignancies occurred: basal cell skin cancer (placebo) and stage I Hodgkin's lymphoma (infliximab).
Conclusion: Infliximab maintains a high degree of clinical efficacy and continues to be well tolerated in patients with PsA through 1 year of treatment.
ACR, American College of Rheumatology
AE, adverse event
ALT, alanine aminotransferase
anti dsDNA, antibodies to double stranded DNA
AST, aspartate aminotransferase
ANAs, antinuclear antibodies
BSA, body surface area
HAQ, Health Assessment Questionnaire
MTX, methotrexate
NSAIDs, non-steroidal anti-inflammatory drugs
PASI, Psoriasis Area and Severity Index
PsA, psoriatic arthritis
PsARC, Psoriatic Arthritis Response Criteria
SAE, serious adverse effect
SF-36, Short Form-36
TNFα, tumour necrosis factor α
infliximab
tumour necrosis factor α
ACR 20
PASI 75
http://dx.doi.org/10.1136/ard.2006.058339
Psoriatic arthritis (PsA), an inflammatory arthropathy occurring in 6–39% of patients with psoriasis,1–3 can result in substantial morbidity,4,5 increased mortality,6,7 and impaired physical function and quality of life.8,9,10 The proinflammatory cytokine, tumour necrosis factor α (TNFα), has a key role in the pathogenesis of this disease,11–18 and the efficacy of biological agents that neutralise TNFα has been demonstrated in several studies of patients with PsA.19–24
IMPACT 2 was a 54 week, multicentre study of infliximab 5 mg/kg in patients with active PsA. The 1 year efficacy and safety findings from IMPACT 2 in this report expand the published clinical response data from the initial, 24 week, double blind, placebo controlled period.21 The study design allowed for evaluation of changes in skin and joint efficacy measures in patients initially randomised to placebo and then switched to infliximab relative to those receiving 1 year of infliximab treatment. This report evaluates the effect of concomitant methotrexate (MTX) use on the efficacy and safety profile in patients with PsA and, further, it assesses the effect of infliximab dose escalation from 5 to 10 mg/kg on arthritis and skin response. It also presents the effect of long term infliximab treatment on PsA-specific features of joint disease, such as dactylitis and enthesopathy, and on quality of life and physical function. The first report of major clinical response in PsA based on a definition used to evaluate patients with rheumatoid arthritis—that is, maintenance of the American College of Rheumatology (ACR) 70 response for at least 6 consecutive months—is generated.
Details of patient eligibility criteria for the IMPACT 2 study have been published previously.21 Briefly, 200 adult patients with active PsA were enrolled. Active disease was defined as five or more swollen joints and five or more tender joints and either C reactive protein levels of at least 15 mg/l or morning stiffness lasting 45 minutes or longer, or both. All patients had active psoriasis, with at least one plaque of 2 cm or greater in diameter. A negative rheumatoid factor result and an inadequate response to current or previous disease modifying antirheumatic drugs or non-steroidal anti-inflammatory drugs (NSAIDs) were also required. Concomitant MTX treatment (up to 25 mg/wk) was allowed but not mandatory.
The details of the study design have been reported previously.21 Patients in this phase III, multicentre, double blind, placebo controlled study were randomised (1:1) to infliximab 5 mg/kg (Remicade, Centocor, Inc, Malvern, PA, USA) or placebo as induction treatment at weeks 0, 2, and 6 followed by infusions at weeks 14 and 22 through week 24, at which time patients receiving placebo crossed over to active treatment; all patients received infliximab for the remainder of the 54 week study. Based on predefined criteria (that is, <10% improvement from baseline in both swollen and tender joint counts), placebo patients could enter early escape to infliximab at week 16. To maintain the blind, patients in the infliximab group meeting the same definition of lack of response also entered early escape by receiving additional placebo infusions but continued to receive infliximab on the original dosing schedule. Patients randomised to infliximab who had <20% improvement from baseline in the combined number of swollen and tender joints at week 38 could also escalate their dose from 5 to 10 mg/kg at weeks 38 and 46.
Study procedures and evaluations
Clinical efficacy was assessed by the ACR core set,25 the Psoriatic Arthritis Response Criteria (PsARC),26 and duration of morning stiffness. Major clinical response was defined as maintenance of ACR 70 response for a 24 week continuous period.27 The presence and severity of dactylitis (on a scale of 0–3) were assessed in the hands and feet, and the presence of active enthesopathy was evaluated in the feet.21 In patients with at least 3% body surface area (BSA) psoriasis at baseline, psoriasis activity was assessed using the Psoriasis Area and Severity Index (PASI).28 Regardless of baseline BSA, the target skin lesion was assessed for scaling, erythema, and plaque induration on a scale of 0 to 4. Functional status was evaluated using the Disability Index of the Health Assessment Questionnaire (HAQ)29; a decrease of at least 0.3 in HAQ was considered clinically significant.30 Health-related quality of life was evaluated using the Short Form-36 (SF-36).31
Safety evaluations
Adverse events (AEs) and routine haematology and chemistry variables were evaluated at every visit through week 54. Blood samples were drawn to determine the presence of antibodies to infliximab through week 66 (20 weeks after the last infusion) and antinuclear antibodies (ANAs; antibody titre of 1/160 or more was considered positive) through week 54. Samples positive for ANAs were tested for the presence of antibodies to double stranded DNA (anti-dsDNA).
A sample size of 200 patients was chosen to ensure an adequate safety evaluation. With 100 patients in each group, the study had at least 90% power to detect a significant treatment difference in the proportion of ACR 20 responders at week 24. At randomisation, patients were stratified by baseline MTX use and investigational site. The primary analysis was based on all randomised patients according to the treatment assigned. Patients with missing ACR data and those who entered early escape at week 16 were considered non-responders at week 24. For the PASI analyses at week 24, the last observation before week 16 was carried forward. Analyses at week 54 were based on the subset of patients who completed study evaluations and included patients with imputed data based on treatment failure rules. Treatments were considered to have failed if infusions were discontinued for lack of efficacy, if they lost response, if prohibited treatment was started or the concomitant dose of the drug was increased, or if patients underwent more than two surgical joint procedures for PsA. For these patients, the percentage change for ACR response was imputed to 0. Patients with missing data for other reasons were excluded. All efficacy analyses presented were prespecified, unless otherwise noted.
Data were summarised using descriptive summary statistics for continuous variables, and counts and percentages for discrete variables. The Cochran-Mantel-Haenszel χ2 test stratified by baseline MTX usage was used to analyse the co-primary end point of ACR 20 response at week 14 and other secondary end points with categorical data. A two sided F test using an analysis of variance method with baseline MTX usage as a factor on the van der Waerden normal scores was employed to analyse end points with continuous data.
Safety analyses were performed using data from patients who received at least one infusion of infliximab, regardless of treatment assignment. Safety data through week 54 are presented for the placebo group (that is, only data before the first dose of infliximab reported) and the combined infliximab group (that is, data for patients randomised to infliximab and data from week 16 onward for patients randomised to placebo who entered early escape at week 16, from week 24 onward for those who crossed over to infliximab at week 24, and from the first dose of infliximab onward for those who received a dose of infliximab in error).
Baseline characteristics and patient disposition
Figure 1 summarises patient disposition through week 54. With the exception of the distribution of men and women, demographics and baseline disease characteristics were similar between treatment groups (table 1).
Baseline characteristics of the patients
Patient disposition chart, including patients who entered early escape, escalated the infliximab dose, or discontinued the study or study agent. *Any patient in either treatment group with <10% improvement from baseline in both tender and swollen joints entered early escape to active treatment at week 16. †Includes 3 patients in the placebo group who received infliximab at week 0 in error. ‡All patients in the placebo group crossed over to active treatment at week 24. §Any patient in the infliximab group with <20% improvement from baseline in combined tender and swollen joints had their infliximab dose increased to 10 mg/kg at weeks 38 and 46.
Post hoc analyses suggested that the demographic characteristics of patients randomised to placebo who entered early escape at week 16 did not differ from those of patients who crossed over to infliximab at week 24 (data not shown). However, the demographics of the small number of infliximab randomised patients who required dose escalation from 5 to 10 mg/kg at week 38 were different from those in patients who did not increase their dose. Patients who escalated their infliximab dose were older (mean age 55.0 v 45.9 years) and higher proportions were taking MTX (66.7% v 44.1%) or NSAIDs (86.7% v 67.7%) or had arthritis affecting distal interphalangeal joints (46.7% v 23.5%).
As previously reported, patients receiving infliximab 5 mg/kg had significantly better outcomes than those receiving placebo for joint response (ACR criteria, enthesopathy, and dactylitis), skin response (PASI), physical function (HAQ), and quality of life (SF-36) at week 24 (table 2).21
Clinical responses at week 24 and week 54
Joint response
Through week 54, ACR 20, ACR 50, and ACR 70 responses were maintained with continued infliximab treatment in the randomised infliximab group and were substantial after crossover to infliximab in the placebo/infliximab group (table 2; fig 2). The ACR response at week 54 was consistent, regardless of baseline MTX use (for example, 56.8% of patients receiving infliximab plus MTX and 60.9% of patients receiving infliximab only achieved ACR 20 response). A major clinical response was achieved by 12.1% of patients in the infliximab group at week 54.
Joint response over time through week 54, as measured by various degrees of ACR response in patients treated with infliximab and/or placebo. Data are reported for 100 patients and 90 patients in the infliximab groups and 100 and 83 patients in the placebo groups at weeks 24 and 54, respectively. ACR = American College of Rheumatology.
By week 54, there was a marked decrease from baseline in the numbers of patients with active enthesopathy and with at least one dactylitis digit in both treatment groups (table 2). Other efficacy results, including the proportion of patients achieving PsARC, percentage improvement in individual ACR components, and duration of morning stiffness, confirmed the maintenance of efficacy of infliximab through week 54. Furthermore, by week 54, all efficacy measures improved in the placebo/infliximab group to an extent similar to that in the randomised infliximab group.
Skin response
Through week 54, the PASI 75 and PASI 90 responses seen at week 24 were generally maintained in the randomised infliximab group (table 2; fig 3). By week 54, similar proportions of patients achieved both PASI 75 and PASI 90 across treatment groups (table 2; fig 3). Compared with patients not receiving MTX at baseline, those receiving MTX in combination with infliximab had similar PASI 75 responses at week 54 (that is, 47.5% and 53.1%, respectively).
Skin response over time through week 54, as measured by various degrees of PASI response in patients treated with infliximab and/or placebo. Data are reported for 83 and 72 patients in the infliximab groups and 87 and 73 patients in the placebo groups at weeks 24 and 54, respectively. PASI = Psoriasis Area and Severity Index.
Effect of dose escalation
Among the 15 patients who were randomised to infliximab 5 mg/kg but whose dose was escalated to 10 mg/kg at week 38 (that is, by definition did not achieve an ACR 20 response), nine had previously achieved an ACR 20 response and six had not. Among these nine patients, five also achieved an ACR 20 response at week 54. None of the six patients who failed to respond through week 38 achieved an ACR 20 response after dose escalation to 10 mg/kg. Only 12 of 15 patients whose dose was escalated had baseline BSA of at least 3% and were included in the PASI analyses. Of these 12 patients, five achieved PASI 75 at week 38, and all five maintained PASI 75 response at week 54. Conversely, the seven patients who did not achieve PASI at week 38 were unable to achieve the response after dose escalation. Post hoc analyses showed that body mass index did not affect PASI response to dose escalation (data not shown).
Physical function and quality of life
By week 54, the percentage improvement in HAQ was markedly better than at baseline in both treatment groups (table 2). At week 54, 58.9% in the randomised infliximab group and 53.0% in the placebo/infliximab group had achieved a clinically significant change (⩾0.3 units decrease) in HAQ. Through week 54, the mean improvement in SF-36 achieved at week 24 was maintained in the randomised infliximab group and was similar between treatment groups for both the Physical Component Summary score and the Mental Component Summary score (table 2).
The safety profile of infliximab through week 54 was consistent with that observed through week 24. About 85% of patients experienced an AE in the combined infliximab group at week 54 and 67% at week 24. The incidence of AEs in the combined infliximab group was generally similar between patients receiving MTX (87.5%) and those not receiving MTX (82.5%) at baseline. Twenty two patients (11.5%) in the combined infliximab group experienced a serious adverse event (SAE) through week 54; one patient whose dose was escalated experienced worsening of pre-existing carotid arterial stenosis that required surgery about 4 months after the last infusion.
Sixteen patients (8.4%) in the combined infliximab group had infusions stopped owing to an AE; seven of these patients had raised liver function tests. Two patients in the placebo group (cellulitis, bronchitis) and three in the infliximab group (infectious hepatitis, cellulitis, and pneumonia) experienced serious infections. Two patients had malignancies: one placebo patient had basal cell carcinoma and one infliximab patient, who had been treated with MTX and alefacept before the study, had stage I Hodgkin's lymphoma. No reports of tuberculosis or opportunistic infection, autoimmune disorders, central demyelinating events, or congestive heart failure were received.
Infusion reactions were reported with 2.1% of infusions in the combined infliximab group and 1.6% of infusions in patients receiving placebo only. In the combined infliximab group, the infusion reaction rate was lower in patients receiving MTX at baseline (0.9% v 3.2% without MTX). Most infusion reactions were mild to moderate, and none were considered serious. No anaphylactic reactions or delayed hypersensitivity reactions occurred.
Of the 15 patients in whom the dose of infliximab was escalated to 10 mg/kg, four (27%) experienced at least one SAE from baseline through week 54. These SAEs included arthralgia, bone fracture, extracardiac aneurysm, abdominal hernia, and carotid arterial stenosis, the last of which was the only SAE that occurred after dose escalation. Twelve of these 15 patients experienced an AE of infection from baseline through week 54, although none were considered SAEs, and only three patients had an infection (including one case of pneumonia) after dose escalation. Through week 54, one patient receiving an escalated dose experienced an infusion reaction and another had a markedly abnormal alanine aminotransferase (ALT) level. One patient discontinued infliximab after dose escalation at week 38 owing to hives, which had also been experienced during previous treatment with the 5 mg/kg dose.
As reported previously, markedly abnormal ALT and aspartate aminotransferase (AST) values (that is, predefined as >150 IU/l and ⩾100% increase from baseline for ALT and AST) occurred in five patients in the infliximab group through week 24.21 Through week 54, markedly abnormal ALT and AST values were reported in 8/191 (4.2%) and 4/191 (2.1%) patients, respectively, in the combined infliximab group. These rises occurred in the same patients in whom increases were reported at week 24 and in three additional patients; they resolved in all but one patient who was lost to follow-up. Of the 191 patients in the combined infliximab group, ALT and AST values increased from normal at baseline to high (that is, any value above normal) through week 54 in 81 patients (42.4%) and 51 patients (26.7%), respectively. Slightly more infliximab treated patients not receiving MTX had an ALT value that rose from normal to high compared with those receiving MTX (46.6% v 39.5%); similar findings were observed for AST (31.1% v 21.6%). Post hoc analyses showed that slightly more male patients had levels changing from normal to high, especially for ALT values (data not shown). Other baseline factors, including body mass index, prior drug treatment for PsA or psoriasis, and drugs for pain, did not affect the proportion of patients with a shift in ALT/AST values from normal to high (data not shown). No cases of liver failure or clinically significant liver dysfunction occurred through week 54.
Through week 66, 15.4% of patients in the combined infliximab group were positive for antibodies to infliximab; most had low antibody titres. As only five patients had a titre above 1/80, the correlation between antibody status and patient outcome could not be evaluated. While only 3.6% of patients receiving MTX at baseline were positive for antibodies to infliximab, 26.1% of those not receiving MTX at baseline tested positive. Among the 14 patients receiving an escalated dose with available samples, 2 (14.3%) were positive for antibodies. Through week 66, 41.3% of the patients in the combined infliximab group were newly positive for ANA, and 8.6% were newly positive for anti-dsDNA antibodies; however, no patient developed drug-induced lupus. No patients in the placebo-only group were newly positive for anti-dsDNA antibodies. In the combined infliximab group, the median percentage ACR improvement at week 54 for patients who were positive for antibodies to infliximab (21.7%) was lower than that for the antibody negative patients (33.3%) and for the patients whose test results were inconclusive (44.8%). Among antibody positive patients, an approximately 3.5-fold increase in the incidence of mild to moderate infusion reactions occurred compared with antibody negative subjects; however, no severe or serious infusion reactions or possible delayed-type hypersensitivity or possible anaphylactic reactions were experienced by antibody positive patients.
Several studies have demonstrated the safety and efficacy of anti-TNFα agents in the treatment of PsA.19–24 This report demonstrates improvement in the signs and symptoms of arthritis and associated psoriasis, quality of life, and physical function in patients with PsA through 1 year of infliximab treatment, thereby broadening the knowledge of the benefits and risks of long term infliximab treatment, both with and without MTX. One year of treatment with infliximab resulted in a high degree of sustained ACR and PASI response, regardless of concomitant MTX use, in addition to continued benefit with regard to dactylitis and enthesopathy.
Although it was our intention to evaluate infliximab dose escalation in this study, only 15 patients met the predefined criteria for escalation. This suggests that 5 mg/kg is the appropriate dose for most patients. Interestingly, in the subgroup requiring dose escalation, patients who had not achieved ACR 20 before dose escalation were unable to achieve this response despite doubling the dose of infliximab from 5 to 10 mg/kg. In contrast, patients who demonstrated ACR 20 improvement at some point before dose escalation were able to regain ACR 20 responses by doubling the dose. Dose escalation did not appear to improve PASI responses; however, the protocol requirement for increasing the dose was not contingent upon PASI response. The fact that the percentage of antibody positive patients was similar between patients receiving an escalated dose (14.3%) and the combined infliximab group (15.4%) suggests that a positive antibody to infliximab status was not necessarily a factor leading to dose escalation. However, the small number of patients whose dose was increased from 5 to 10 mg/kg precludes the drawing of definitive inferences about the efficacy and safety of higher doses in patients with PsA.
Attainment of "major clinical response" (that is, ACR 70 improvement for 24 consecutive weeks) was also evaluated. Designed originally to measure response in patients with rheumatoid arthritis, major clinical response is evaluated here for the first time in a group of patients with PsA. Although this definition confirms a high degree of sustained improvement in arthritis, it does not make provisions for improvement in the dermatological component of the disease. Further research is needed to better identify a definition that is specific for major response in both skin and joint components of PsA and to evaluate the effect of infliximab on major clinical response over time.
Skin response, as measured by PASI, was impressive for both patients treated with infliximab from baseline and those who crossed over to active treatment at week 16 or week 24. At week 54, more than half of all patients achieved a PASI 75 response and 42% achieved a PASI 90 response, which is consistent with a clear or almost clear status. Although patients were not randomised to receive MTX, randomisation was stratified by baseline MTX use, and it is especially notable that skin response did not appear to be affected by concomitant MTX use. These results are particularly relevant because, as a dermatological manifestation, psoriasis is a critical factor in decreased quality of life and physical function in patients with PsA.8,9,10 Accordingly, notable improvement was seen with infliximab in the physical and mental aspects of quality of life as well as the ability to function in daily life, indicating that the substantial effects observed at 6 months21 continued through 1 year.
Infliximab was generally well tolerated over the 1 year treatment period. The incidence of predefined markedly abnormal transaminase levels, which were higher in the infliximab group than in the placebo group at week 24, did not increase disproportionately with an additional 30 weeks of treatment. Methotrexate use at baseline appeared to result in fewer patients with increases in transaminase levels compared with patients not using MTX. However, the effect of MTX on transaminase levels must be interpreted with caution, as patients receiving MTX before enrolment were required to have tolerated MTX for at least 3 months without significant toxicity, suggesting that these patients may have been less prone to abnormal liver enzymes than the other patients. No cases of opportunistic infections, congestive heart failure, demyelination, or liver failure were reported. One patient treated with infliximab, who had received MTX and alefacept before study entry, was diagnosed with stage I Hodgkin's lymphoma; one placebo patient developed basal skin carcinoma. Fewer infusion reactions occurred among patients receiving MTX at baseline than among those not receiving MTX. However, most infusion reactions were mild to moderate, and no patients developed a serious infusion reaction or anaphylaxis. Similarly, at the end of the study, the proportion of patients positive for antibodies to infliximab was lower among patients receiving MTX at baseline than among those not receiving MTX; however, ACR and PASI responses were consistent irrespective of MTX use.
Through 1 year of infliximab treatment, a high degree of clinical response, as measured by both ACR and PASI responses, was sustained, with corresponding improvements in physical function and quality of life, as measured by the HAQ and SF-36. Infliximab was generally well tolerated. These results indicate that the positive benefit/risk ratio of infliximab seen at 6 months remains favourable after 1 year of treatment in patients with PsA.
We acknowledge the IMPACT 2 investigators:
Dr C Birbara, Worcester, Massachusetts; Dr EP Boling, Upland, California; Dr C Codding, Oklahoma City, Oklahoma; Dr JJ Fiechtner, Lansing, Michigan; Dr RM Fleischmann, Dallas, Texas; Dr SI Goodman, Delray Beach, Florida; Dr AB Gottlieb, New Brunswick, New Jersey; Dr DG Halter, Houston, Texas; Dr JL Harshbarger, Wilmington, North Carolina; Dr K Hobbs, Denver, Colorado; Dr A Kavanaugh, La Jolla, California; Dr SM Lourie, Greenbelt, Maryland; Dr P Mease, Seattle, Washington; Dr A Menter, Dallas, Texas; Dr DM Pariser, Norfolk, Virginia; Dr WJ Shergy, Huntsville, Alabama; Dr EL Siegel, Wheaton, Maryland; Dr DJ Wallace, Los Angeles, California; Dr ME Wenger, Lancaster, Pennsylvania.
Dr R Bissonnette, Montreal, Quebec; Dr J Carter Thorne, New Market, Ontario; Dr DD Gladman, Toronto, Ontario; Dr W Gulliver, St John's, New Foundland; Dr E Keystone, Toronto, Ontario; Dr K Papp, Waterloo, Ontario; Dr Y Poulin, Quebec, Quebec; Dr L Rosoph, North Bay, Ontario.
Dr C Antoni, Erlangen; Dr G R Burmester, Berlin; Dr C Fiehn, Heidelberg; Dr J Sieper, Berlin; Dr J Wollenhaupt, Hamburg.
Dr P Geusens, Diepenbeek; Dr R Westhovens, Leuven.
Dr P Emery, Leeds; Dr B Kirkham, London.
We acknowledge C Arnold of Centocor, Inc for her editorial assistance and writing support in the preparation of this manuscript.
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Fredriksson T, Pettersson U. Severe psoriasis: oral therapy with a new retinoid. Dermatologica1978;157:238–44.
Fries JF, Spitz PW, Young DY. The dimensions of health outcomes: the health assessment questionnaire, disability and pain scales. J Rheumatol1982;9:789–93.
Mease PJ, Ganguly R, Wanke L, Yu E, Singh A. How much improvement in functional status is considered important by patients with active psoriatic arthritis: applying the outcome measures in rheumatoid arthritis clinical trials (OMERACT) group guidelines [abstract] Ann Rheum Dis2004;63 (suppl I) :391.
Ware JE, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). Conceptual framework and item selection. Med Care1992;30:473–83.
Published Online First 17 November 2006
Funding: The IMPACT 2 study was sponsored by Centocor, Inc in Malvern, Pennsylvania, and Schering-Plough Corp in Kenilworth, New Jersey.
Competing interests: A Kavanaugh and DG Halter have received funds for research from Centocor, Inc and its competitors. GG Krueger and C Birbara have received speaking and consulting fees from Centocor, Inc and its competitors. PJ Mease has received research grants and consulting and speaking fees from Centocor, Inc and its competitors. DD Gladman has received consulting fees and research support from Centocor, Inc and Schering Canada. K de Vlam has received consulting fees and reimbursement for attending symposia from Schering-Plough Corp PP Geusens has no competing interests to declare. C Antoni, who was affiliated with the Friedrich Alexander University of Erlangen-Nurnberg, Erlangen, Germany, at the time the study was conducted, is now a full time employee of Schering-Plough Corp, Kenilworth, New Jersey; he has received reimbursement for symposia and funds for research, consulting, speaking, and organising education from Centocor, Inc and its competitors. A Beutler, C Guzzo, B Zhou, and LT Dooley are employees of, and hold stock in, Centocor, Inc, Malvern, Pennsylvania, USA.
Copyright 2007 by Annals of the Rheumatic Diseases


In the grand life scheme of individual wants and desires there is one goal that's universal: to be, as the classic song says, Forever Young. No one, not even the kids who have 'old souls' want to look like wrinkled up old crones with a barely functioning body and one foot firmly in the grave.
Luckily there's a booming anti-ageing beauty industry with everything from face cream to fillers to anti-ageing hair care available to keep our visage smooth and our hair free of tell tale greys. But what if all that good work is being undone by what we're putting into our bodies? What if we're eating our way towards early entry into crone town?
Nutritionist Fiona Tuck, author of The Forensic Nutritionist, says there are certain foods that do accelerate ageing and we should avoid them if we want to keep the fountain of youth flowing. On a positive note, Fiona also says there are anti-ageing foods which slow that age train right down.
Sugar robs the body of nutrients, particularly magnesium and is inflammatory in the body. Inflammation accelerates the ageing process. It also accelerates the formation of advanced glycation end products (AGE) in the body, which may lead to premature ageing.
Deep fried foods increase production of free radicals potentially damaging cells in the body. Frying oil at high temperatures can cause the oil to lose its nutrients and at worse create inflammatory toxic compounds.
Barbecued foods that are browned, roasted or chargrilled can create toxic compounds called acrylamides. The darker, crispier the food the more acrylamides it contains. Acrylamides have been linked to being carcinogenic in lab rats leading to concerns about the potential carcinogenic properties of eating browned or grilled foods for humans.
Processed food tends to be high in salt, sugar and artificial additives and low in nutritional value.
Alcohol is high in sugar and can rob the body of nutrients such as magnesium and the B vitamins. The B vitamins are particularly important for energy production and cognitive health.
Are there any foods that are anti-ageing?
Yes, salmon and oily fish have anti-inflammatory omega 3 essential fatty acids, which helps to reduce inflammation in the body and strengthens cell integrity.
From the fruit family, blueberries and blackberries are rich in antioxidants protecting the cells from damage and premature ageing. Grapeseed extract and grapes are high in antioxidants. The more antioxidants we eat the more our cells are protected from oxidative stress, a cause of premature ageing.
And in terms of nuts and veg, walnuts are high in fibre, omega 3, omega 6, magnesium and vitamin B6 which helps with healthy cells, hormones and mood. Carrots are full of fibre and rich in antioxidants protecting cells from damage. Eating carrots regularly may also protect the skin from oxidative stress and premature ageing plus carrots are wonderful for keeping the immune system strong and healthy.


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ILO's International Labour Conference has opened its doors
By Franz Christian Ebert on 6 June 2009
From 3 June to 19 June, the International Labour Organisation (ILO) hosts this year's International Labour Conference (ILC). The ILC, also referred to as the "international parliament of labour" is the main legislative body of the ILO which has the competence to adopt Conventions and Recommendations on international labour standards. The ILC can also adopt Declarations on social and economic issues, the last ones being the Declaration on Fundamental Principles and Rights at Work of 1998 and the Declaration on Social Justice for a Fair Globalisation of 2008. The ILC also deals with the supervision of the ILO's labour standards, and adopts the ILO's biennial budget and work programme.
In addition, the ILC is a forum for discussions of global social and labour issues. Unsurprisingly, this year the main focus lies on the social implications of the economic crisis. Issues to be addressed include the question how the looming jobs crisis can be tackled and how a social dimension can be included in economic and financial rescue packages. In this respect, the Director General has proposed a "Global Works Pact", a set of social and economic policy tools in order to mitigate the social effects of the crisis at the international and national level (see here fore more information).
The ILC will also discuss how the crisis affects the implementation of international labour standards, in particular basic rights such as abolition of forced and child labour, non-discrimination at work and freedom of association and collective bargaining.
Furthermore, the ILC will address the adoption of a new labour standard on HIV/AIDS and the world of work. This instrument will set out obligations and rights of workers and employers relating to the prevention and the handling of this disease, taking particular account of gender- and migrant-related problems that arise in this regard (for further information see here).
The results of the ILC will be published in a final document at the end of the conference.
Published in Human Rights, International and National Law, Public International Law and United Nations (UN)
Franz Christian Ebert
More posts from Franz Christian Ebert
blogartik 8 June 2009
many workers who suffer life

redpajama_set_name: RedPajamaCommonCrawl


Costs for the Champagne producer are made up of many elements, some of which have a greater or lesser impact on the profit-and-loss account of their business depending on the individual circumstances of the firm. These might include: the cost of capital; harvested yields (differentiating between permitted and reserve stock – so-called blocage); how they use the pressings (some Champagne houses use only the cuvée – the first pressing); stock turnover that impacts cash flow: stock holding has in fact increased almost every year with levels at an all-time high in 2009, estimated by the CIVC to be around 1,344m bottles (almost five years worth of stock) and which might incur further finance charges apart from storage implications; the ageing of wines, particularly any vintage Champagne; retail prices that can be charged given prevailing economic conditions; and last but not least the price of the grapes charged by the growers – a significant cost to the large maison. Indeed, grape prices peaked in 2008 – see Table E. If 1.2kg is required to make one 75cl bottle of Champagne then this is the factor which needs to be applied to the grapes price/kg, but these are only averages across the appellation. In some areas the prices will be considerably higher. Thus, the average cost of grapes to make one bottle of Champagne in 2008 could be estimated at €6.48 per bottle, a significant component in the cost of any bottle.


• 175g soft St Maures goats cheese, broken into small pieces.
1. Warm the milk in a sauté pan, add the goats cheese and let it melt gently to form a thick sauce. Grind in black pepper to taste.
2. Bring large pot of salted water to the boil. Cook gnocchi and stir until they rise to the surface, then lift out with a slotted spoon and place into sauce.
3. Sprinkle in the chopped chives and toss the gnocchi around carefully, just to coat them in sauce.
4. Add the parmesan and a little of the cooking water if you think the sauce is a little thick. Sprinkle with batons of chive and serve immediately.


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Is Bench Press Enough for Chest?
How Much Variance Does It Take to Build Your Chest?
The question of whether or not bench press is enough for chest development has plagued lifters for generations. While I'd like to give a simple, definitive answer on the matter, the best I can honestly do is say "maybe?"
Fact is, there's no magic combination of workouts that's going to give you the "missing piece" and unlock unlimited growth potential. That's because your chest isn't growing because you're benching, it's growing because you're putting load on the muscle.
So instead of asking if standard, flat bench press is enough for chest, let's ask it a different way. Does Bench Press put enough load on your pectorals to get them to grow?
Bench press typically has a more intense load than accessory chest exercises.
What's Your Focus? Strength or Size?
The real question is not simply if the movement itself is enough, but rather if the pecs are getting in enough stimulus to promote muscle growth. To answer that, we'll drill down into the two main factors that determine stimulus: Intensity and Volume. How do these influence the way you build muscle?
We touched on intensity and volume in our last post about Floor Press vs Bench Press. Check it out.
In its simplest form, intensity refers to the amount of weight used. And you can't talk about intensity without talking about the two main types of muscle fibers.
Like every other muscle in your body, pectoralis major consists of Type I and Type II muscle fibers. For building your chest, we're mostly concerned with your Type II's.
While Type I (endurance fibers) are excellent at making strength gains, they don't really yield much of a difference in size. That's where Type II fibers come in. Whereas Type I fibers get stronger in response to stress, Type II fibers get larger.
If all you care about is a bigger chest (not necessarily a stronger one), you're focusing on recruiting your Type II fibers.
The thing is, your Type II fibers only come into play when your Type I fibers can't handle the load by themselves. That's why the rep range for hypertrophy is typically between 8 and 12. You need to subject the muscle to enough volume to exhaust the Type I fibers and force your Type II fibers to join the game.
In this category, the barbell bench press excels as it generally allows a lifter to use significantly more weight than any other free weight chest exercise. This is not without its caveats however, as where the load is carried during the bench press can vary greatly from lifter to lifter.
For some, the leg drive generates a ton of force development. Others rely more on their triceps or front delts. All of these factors will take away from the recruitment of the pecs. They're all elements of proper form, too, so trying to eliminate one won't do you any favors.
This should not be seen as a reason not to bench, but rather a reason to include more chest-specific exercises in addition to the barbell bench press.
Volume simply refers to the amount of work done by a muscle group. Some calculate this as total poundage (sets x reps x pounds) while others simply calculate this as the total amount of reps performed.
But volume takes other factors into consideration too. For example, Range of Motion (ROM) and time under tension (TUT) are both big factors in determining volume.
This relates to the bench press in that lifters with a bigger arch have a smaller ROM, and thus less TUT. This lesser volume provides less stimulus for chest growth. This can be accounted for however by performing more sets and/or reps.
First thing we need to know, though, is how much you're benching! Without knowing the volume of bench press in your program, we just can't say for sure. If you're performing an incredibly high number of really difficult sets, it's hard to say you need more intensity and volume.
Dumbbell Bench is a popular accessory that mimics the flat bench movement with less intensity, even at higher weights.
However, the heavy loads associated with the bench press likely make it difficult to recover from these incredible volumes. Therefore instead of taking a yes or no approach, I suggest asking "what is optimal for chest growth?"
Don't get me wrong, the answer to this question depends extremely on your specific body, recoverability, and experience as a lifter. Still, it always comes back to the same balancing act every strength program has to achieve: balancing MRV (maximal recoverable volume) and MEV (minimum effective volume).
If you're doing too many sets of bench, you're going to exceed your MRV more quickly than you would with more accessories added in. The heavy loads from Bench Press induce more fatigue at a faster rate than less intense accessories like chest press or dumbbell flyes.
Combining bench press with other assistance exercises still allows you to push the pecs past their MEV without going beyond the MRV. The result is better chest development and proper recovery. Common upper body accessories include:
Incline Bench Press (for more emphasis on upper pecs)
Dumbbell Bench Press
The inclusion of assistance exercises will also allow for lifters lacking chest development to isolate the chest by itself, instead of letting the triceps or shoulders take over. So while yes, bench press can be made to be "enough" for chest development, bench press alone is likely far from optimal.
Still have questions? Let us know!
It's one thing to read it; it's another to do it. And when you're training without a coach, you need to make sure you know what you're doing. That's why we're happy to answer anyone's training questions, no membership required.
Simply send us a DM on Instagram, or click here to email us.
Alex Gaynor
Ask Questions. Get Updates. Connect with Fellow Athletes.
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The goals that you should be looking for that will lead to the right Warm-Up routine for YOU.
Hatfield Squat Technique, Uses, and Benefits
By allowing you to use a ton of weight in a new and unconventional way, the Hatfield squat has its benefits. But is it right for you?
Is a Parallel Squat ALWAYS the Best Squat?
Are you in that 1% of people who have a good reason to not squat to depth? Probably not. Read more to find out!
The Benefits of Deficit Deadlifts
Deficit deadlifts can help address weakness in the small range of motion at the bottom portion of a deadlift. Keep reading to learn more!
How to Find the Perfect Bench Rack Height
Finding the right rack height is essential to proper joint stacking on bench for powerlifters. So what's the perfect height?
Accessory Review: Lat Pulldowns
The lat pulldown is an absolute staple back accessory, and for good reason. Let's take a close look lat pulldowns and what makes them work.
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Sky_dancer said:At the moment is The Punisher. Major crush on anti heroes!
Damn it! I forgot about him, one of favorite, too.
First film I can remember is Lion King..
Who is the greatest actor / actress of all time in your opinion?
Anybody have any original questions?
What is one thing that truly keeps you up at night?
If you knew exactly when you were going to die, would you live out your remaining time, any differently than you do now?
When was the last time you were truly afraid?
Miss_Sub said:Earth. She's my Goddess.
Before me and my ex knew her 5 year old daughter is Bi-Polar. My step daughter was acting kind of like she was spirit possessed.
Could You pick up and pack and leave in a moment of temporary insanity to another land and start all over?


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campbx-java
===========

CampBX Java API Bindings

redpajama_set_name: RedPajamaGithub


Outdoor daybed swing plans – There's nothing more relaxing than going home and resting in your bed. Now you can create an even more conducive environment for nerve soothing with an oscillating sofa bed. All you need is a couple of hours, a little wood and some basic knowledge. Buy or use a double size mattress. A standard twin is usually 39 inches by 75 inches, but the size may vary depending on the manufacturer.
Outdoor daybed swing plans, choose a high quality wood. Look for pieces that are straight have no knots or other defects visible and that are not deformed. Cut four 2×4 legs, making them every 26 inches long. Next, cut four 2×6 boards, each 31 inches long, which will be used as the horizontal beams on the sides.
Outdoor daybed swing plans, prepare to attach two of the legs to two of the aprons. The upper skirt attached two inches below the top of the legs, the skirt less than two inches above the bottom of the legs. Drill the wood where you want the screws (to keep the wood from splitting). Place the legs with wood screws and delay glue, then use a carpenter's square to check all angles. Screw the screws and plug. Make sure the second end matches the first and let the glue dry.


Mark Wadsworth: Boo hoo, frankly.
... The scheme, which was entirely legal, allowed AML contractors to become staff and were paid via its base on the Isle of Man.
They appear to have been paid a low salary with the rest of the cash paid as a loan with zero or little interest from its 'employee benefit trust' on the Crown dependency. Staff would then pay as little as three per cent income tax.
One client John Dickinson was paid a £11,826 salary in 2009/10 with £85,718 in the form of interest-free loans, according to the Mirror. At the time he paid just under £9,000 in income tax - but HMRC has now asked for almost £27,000.
Clearly, it is morally and economically wrong for employment income to be taxed at the highest rates of all forms of income, but HMRC has spent the last decade cracking down on 'workers' (i.e. employees) being paid in the form of soft/non-repayable loans, whether directly from their actual employer, or via an 'Employment Benefit Trust', an umbrella company or some even more bizarre offshore trust/company arrangement.
A couple of years ago HMRC made it quite clear that all outstanding loans would simply be treated as employment income, earned and taxable on a certain cut-off date.
The sensible thing to have done is to take money out of an umbrella company as dividends, that gives you slightly lower rate than taking it out subject to PAYE. You can always argue that in reality you were self-employed rather than employed, so you might have got away with it. Pretending that you were receiving a loan and paying next to no tax was taking the piss and was bound to blow up in people's faces later on.
As to "entirely legal", of course it is perfectly legal for an employer to lend an employee money, but there is also tax law that says how the loan will be taxed. And the law is the law, whether unfair or not, and there is no point whining now IMHO.
It was a very good scheme for those who have left the country - good luck to HMRC in chasing them. Had a few ex-pats who recommended it to me but I'm in the UK for the long term.
Good point about employment income being the most heavily taxed. But of course the homeownerist/landownerist dream is not having to bother with doing anything for a living.
"But of course the homeownerist/landownerist dream is not having to bother with doing anything for a living."
A quick glance at history shows that this has been the aspiration of the British for centuries, even before employment was taxed at all. Those who got rich by working bought land so that their heirs could live off the rents and join the landed gentry. It is a natural human desire to live without needing to work, but with the British, it's social.
Never tell an accountant that - he will not be sympathetic.
M, good point about bunking off. My non-res clients ask me how HMRC will enforce X Y or Z against them when they are abroad again, and I tell them I don't know, and they probably can't, but that's no excuse to break the law while you are here.
L, agreed that stupid tax rules = gaming = opportunities for pin striped ponces to hawk their schemes, another reason why flattening tax rates is a good thing. But actually, HMRC doesn't have that many staff. As much as people may hate them, they are quite efficient and are only obeying orders.
B, agreed, we are all lazy, that's fine, but let's not make a virtue out of it.
JH, it was crooked accountants persuading people to sign up to this crap.
L, twice as many people work in DWP and dishing out welfare as work for HMRC. If you want immediate cost savings, simplifying welfare is the easy target.
MW. Indeed. But we are on taxes. That's Monday morning's work. DWP is Monday afternoon's job.


I have already posted several articles about mobile application for learning sanskrit. Some times, some people might feel uncomfortable with mobile because of screen size or any other reason. I have found several wonderful videos in youtube and the author of those mobile apps is same for these youtube videos.
Find several series of classes to learn sanskrit through youtube videos. The author has done wonderful job, they are teaching sanskrit basics with series of classes on Vibhakti and most importantly they are teaching sanskrit through Yoga and Tinantaprakriya . These videos helps you to learn sanskrit from home.
After investigating a lot finally I figured out one of the best mobile app for learning sanskrit. I have my own analysis for saying this as Best Mobile app, let me explain about it, Vyoma Linguistic Labs has released series of mobile applications and each mobile application has a rich content, innovative techniques of learning sanskrit, most importantly the content is framed keeping value based education in mind. The sanskrit learning apps helps you to learn sanskrit at home.
In this modern age certainly we have forgotten all good sayings, proverbs and subhashitaas. Well learning such good sayings in sanskrit, subhashitaas in sanskrit is really great.


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Asia Pacific Network Information Centre (APNIC)
What Does Asia Pacific Network Information Centre (APNIC) Mean?
Techopedia Explains Asia Pacific Network Information Centre (APNIC)
The Asia Pacific Network Information Centre (APNIC) is an organization that manages the assignment of Internet number recourses within the Asian continent.
APNIC sets the rules, regulations and standards that all designated organizations must abide by and implement. End-user organizations and Internet service providers take direction from Regional Internet Registries (RIRs) like APNIC to provide Internet resources within certain regions. The Internet number resources include antonymous system numbers as well as IP addresses that assist in clearly defined routing policies and numbers corresponding with individual computers or other devices.
One of the purposes of APNIC is to provide standards-based inter-networking methods for the Internet such as IPv4 and IPv6 across networks such as Ethernet. This uses a best-efforts delivery model for private networks or multicast addresses by using a 32-bit integer.
APNIC serves a multitude of organizations who use autonomous system numbers (private) that all connect to the Internet. APNIC also serves as the Whois database within the Asian continent, storing regional domain names and IP addresses and accepting queries.
APNIC provides a reverse pointer record, or reverse domain name service lookup, which associates an IP address with its domain name.
There are four other RIRs in the world that function similarly to APNIC:
The African Network Information Center (AfriNIC)
The American Registry for Internet Numbers (ARIN) (includes Canada and parts of the Caribbean)
Latin America and Caribbean Network Information Centre (LACNIC)
The Réseaux IP Européens Network Coordination Centre (RIPE NCC) (serving Europe and the Middle East, along with parts of Central Asia)
Internet Service Provider
Autonomous System
Internet Protocol Version 4
Multicast Address
The Laws of Computing
NetworkingInternet


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David Ledden Debunks British Press Claims of Pro-War Backlash
March 7, 2003 Author: gabriel Category: Free News Experiment
"BACKLASH!" declared the London's Daily Mail after a new poll revealed that 75% of Britons now support a war on Iraq. But while the right-wing media trumpets this purported turnaround in public sentiment, it fails to accurately qualify the truth behind the figures. Crucially, support for war is still closely tied with both a UN mandate for war, and UN arms inspections. The figures actually show that 70% of British people oppose military action against Iraq without the backing of the United Nations, and 67% of those polled oppose war if the UN inspectors currently in Iraq turn up empty-handed.
"BACKLASH!" declared the Daily Mail, one of London's right-wing papers, this morning after a new Mori poll* revealed that 75% of Britons now support a war on Iraq. But a closer examination of the survey shows that little has changed in the public mood.
While the right-wing media trumpets this sudden turnaround in public sentiment it fails to accurately qualify the truth behind the figures.
The survey does show that of 985 people surveyed 75% support war, but "this support is conditional both on UN inspectors finding proof that Iraq is trying to hide weapons of mass destruction, and on the UN Security Council voting in favour of military action."
Mori analysis goes even further: "In the absence of these two conditions, only a quarter (24%) would support British involvement, and opposition rises from 18% to 67%." *
Crucially, support for war is still closely tied with both a UN mandate for war, and UN arms inspections.
The new figures show that 70% of British people oppose military action against Iraq without the backing of the United Nations, and 67% of those polled oppose war if the UN inspectors currently in Iraq turn up empty-handed.
The Prime Minister still rates poorly over his handling of the crisis.
When asked by Mori: Do you approve or disapprove of the way the Prime Minister, Tony Blair, is handling the current situation with Iraq? 53% of those polled disapproved of his actions.
But Blair can take heart that his rating is still above that of President Bush who received a 65% disapproval rating of his handling of the current crisis in Iraq.
*Mood Shifts On War With Iraq, http://www.mori.com/polls/2003/iraq2.shtml
Author: David Ledden
News Service: TheExperiment
URL: http://www.theexperiment.org/articles.php?news_id=1910


If you've always thought that the Civic needed more power and a bigger wing, then Honda has read your mind for 2018 with the all-new Type-R. It also happens to be one of the best hot hatches in America, but can it beat the Golf R or Focus RS? That depends on how much you value all-wheel-drive, which Honda deliberately skipped for the Type-R in order to save weight, improve handling and deliver shockingly good fuel economy for a performance car. Until we can get our hands on one for a full week, enjoy our first stab at the 306 horsepower Honda.


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China�s Overcapacity: A Waste But Not a Mortal Danger
At the start of the decade, perhaps only one family in three in Oufang village was growing citrus trees. They earned a good living until five years ago nearly all their neighbors piled in and started planting.
The result has been predictable.
�There are too many oranges here. Nobody wants them and we can�t sell them,� said one of the growers, Peng Xiaomin.
Peng, 27, who has posted an advertisement on a fruit website to try to sell his oranges, said the villagers were now just scraping by.
�The farmers have planted too many citrus trees,� he said. �Development has just been too fast.�
Oufang, in southern Jiangxi province, is a microcosm of China�s economy: overcapacity blights an array of sectors, notably in heavy industries that are dominated by state-owned enterprises.
By diverting capital from areas in dire need like health and education, unproductive investment is a drag on Chinese living standards. If manufacturers dump their excess production abroad, trade strains flare up.
But is the problem serious enough to warrant all the government hand-wringing lately?
Yolanda Fernandez-Lommen, an economist with the Asian Development Bank in Beijing, said excess capacity represents an opportunity cost for China, which could put the resources to better use in, say, the stunted services sector.
�Overcapacity is a reminder that the economy is now mature enough for China to start looking into new sources of growth,� she said. �But when I think of the risks facing the economy, overcapacity is not high on the list.�
For a start, the problem is not new.
Excess capacity is almost hard-wired into China�s economic model of industrialization based on high levels of public investment. With a host of factors suppressing spending, surplus savings are channeled to state-owned firms that gorge on cheap capital and subsidized inputs.
For their part, private entrepreneurs have a gold-rush mentality, plunging headlong into the hot sectors of the day. Solar panels and electric bikes come to mind. Grabbing market share by swamping the competition, not by building brands, is the usual approach. Excess capacity is the usual outcome.
�We need to know that overcapacity is a necessary evil of market competition. Socialist central planning economies were marked with shortages, while capitalist economies are frequently haunted by overcapacities,� Ting Lu, an economist with Bank of America Merrill Lynch, said in a recent note.
At the macro level, profitability, sales growth and returns on investment do not suggest a serious overcapacity problem, according to some economists.
The six sectors targeted in the latest government drive to curb blind expansion � steel, cement, flat glass, chemically processed coal, polysilicon and wind turbines � account for just five percent of total fixed asset investment, Lu noted.
Doomsayers warn that it is only a matter of time before excess capacity leads to a wave of bankruptcies and sour loans.
But Mingchun Sun, Nomura�s chief China economist, sees things differently. Projects in the pipeline from the government�s 4 trillion yuan ($585 billion) fiscal stimulus as well as a revival of private capital spending could propel growth in fixed asset investment, now running at 33.4 percent, to 38 percent or higher in the first half of 2010.
�By then, investment demand for capital goods, raw materials and energy could be so strong that even upstream sectors with overcapacity now may experience very high capacity utilisation, or even shortages,� he said.
Optimists also cite the composition of the pump-priming package as evidence that Beijing is at last getting serious about tackling structural defects in the economy � including the innate tendency to create too much capacity.
The lion�s share of the stimulus has gone to areas where it is needed. In the first three quarters, investment in infrastructure rose by 52.6 percent from a year earlier; in railways, by 87.5 percent; in health, social security and social welfare, by 72.9 percent, according to government figures.
True, parallel programs of incentives and tax breaks have boosted sales of cars and household appliances, but economists say little of the stimulus money has gone into manufacturing.
�There was concern when the fiscal stimulus was launched that a lot would go into sectors with overcapacity and that we�d get oversupply and deflation. But it hasn�t,� said Fernandez-Lommen at the ADB.
This is not to say that all is for the best in the best of all possible worlds. Chinese manufacturing is crying out for consolidation � not for the 26.9 percent expansion in capacity recorded in the first three quarters.
China, for example, makes as much steel as the next eight producers combined. The runaway rate of expansion looks like an accident waiting to happen.
�International experience tells us that it is very important to avoid exporting overcapacity � steel, shipbuilding, chemicals, etc � to prevent trade frictions that harm the political atmosphere and interrupt supply chains,� said Joerg Wuttke, president of the European Union Chamber of Commerce in China.
A root cause of the problem is that local governments forced to attract tax-generating investment, even if there is surplus capacity nationwide, because they are starved of revenue from other sources. Unlike the United States and most of Europe, for example, China does not levy local property taxes.
So getting local party chiefs to toe the line on overcapacity will be a tall order for the central government, which has struggled down the ages to impose its will on distant provinces.
�Implementation depends on local authorities, and it will not be easy,� said Ken Peng, Citigroup�s economist in Beijing.
Source: Alan Wheatley / Reuters
Experts: Meteorite Crater Was Hoax
A Molecule of Motivation, Dopamine Excels at Its Task


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» Fluphenazine Hydrochloride Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of fluphenazine hydrochloride (C22H26F3N3OS·2HCl).
Identification— Transfer a portion of finely powdered Tablets, equivalent to about 10 mg of fluphenazine hydrochloride, to a separator, and to a second separator transfer 10 mg of USP Fluphenazine Hydrochloride RS. Add 5 mL of water and 20 mL of dilute hydrochloric acid (1 in 120) to each separator, shake for 10 minutes, and to each mixture add 20 mL of chloroform-saturated sodium carbonate solution (1 in 10). Extract each mixture with five 20-mL portions of chloroform, shaking gently to avoid emulsion formation, and pass the extracts through separate chloroform-washed cotton filters into separate 150-mL beakers. Evaporate the extracts on a steam bath to dryness, and dissolve the residues in 0.5-mL portions of a mixture of 4 volumes of methanol and 1 volume of water. Apply 10 µL of each solution to a suitable thin-layer chromatographic plate (see Chromatography 621 ) coated with a 0.25-mm layer of chromatographic silica gel mixture. Allow the spots to dry, and develop the chromatogram in a solvent system consisting of a mixture of acetone, cyclohexane, and diethylamine (40:15:1) until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the developing chamber, mark the solvent front, and allow the solvent to evaporate. Locate the spots on the plate by lightly spraying with a solution of sulfuric acid in methanol (2 in 5): the RF value and color of the principal spot obtained from the test solution correspond to those obtained from the Standard solution.
Procedure— Determine the amount of C22H26F3N3OS·2HCl dissolved by employing the procedure set forth in the Assay, with the following differences: in the Mobile phase, use 0.3% triethylamine; in the Assay preparation, dilute the amount of sample to be withdrawn with an equal volume of Mobile phase; in the Standard preparation, use a concentration and composition similar to that of the Assay preparation; in the Chromatographic system, use a flow rate of about 2.0 mL per minute; in the Procedure, inject a volume of about 100 µL.
Tolerances— Not less than 75% (Q) of the labeled amount of C22H26F3N3OS·2HCl is dissolved in 45 minutes.
Diluent solution , Mobile phase, Standard preparation, and Chromatographic system—Proceed as directed in the Assay under Fluphenazine Hydrochloride.
Assay preparation— Transfer 6 Tablets to a suitable volumetric flask, add Diluent solution, shake for 1 hour, and sonicate for 10 minutes or until a fine suspension is obtained. Dilute quantitatively, and stepwise if necessary, with Diluent solution to obtain a final concentration of 0.06 mg of fluphenazine hydrochloride per mL. Filter, discarding the first 5 mL of the filtrate.
in which C is the concentration, in mg per mL, of USP Fluphenazine Hydrochloride RS in the Standard preparation;T is the labeled quantity, in mg, of fluphenazine hydrochloride in the Tablet; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.


Madison Capital Funding closed a $35,000,000 senior debt facility to finance the Leveraged Buyout of Oil Changer, Inc. by Trivest Partners. Madison Capital Funding served as the Sole Lead Arranger and Administrative Agent. Further terms were not disclosed.
Oil Changer, Inc. is a chain of thirty-four quick lube locations in California.


Many brands are trying to lure you with the promise of quick result skincare products. And it can seem very tempting as seeing instant results and a quick cure could be the answer to all your skin concerns! Especially if have oily skin or suffer from skin conditions such as acne, for example. But ultimately, those quick result skincare products can do more harm than good. They won't lead to long-lasting results and can even make your skin worse. So I sat down with the amazing Yelena Serebryakova, the co-founder of Lena Wild to discuss this further.
Nobody understands this topic better than Yelena. As someone who always had really good skin, she then developed severe adult acne in her 20's.
Quick result skincare products will only ever treat the symptoms!
Yelena realised that by only treating the symptoms, her acne was always going to come back.
Because the moment you stop using your quick result skincare products, the problem you had in the first place will reoccur. And sometimes even worse than before!
She knew then that the only way to truly treat, and cure, her adult acne was to dig a lot deeper. She discovered that she needed to stop thinking of her skin as a separate organ. But rather to look at her entire body and how every organ has a huge impact on the other.
Out of something so painful came something so great!
As not only did this lead to her overcoming her acne and skin issues.
It also led her on such an amazing path in her life. She actually used her skin condition and this tough time in her life that affected her self-confidence so much, to her advantage to make a dream come true and create something truly wonderful in her life. And in the world!
And has so much great advice and knowledge to share about how to have a happier and healthier relationship with your skin. And with yourself in general.
Regardless of whether you suffer from acne or not, I highly recommend you have a watch or listen to this interview with her.
You'll not only pick up some amazing tips that you can implement in your own life and beauty routine right away.
You'll also feel so uplifted after listening to her. Yelena's beautiful smile and her warm, friendly personality are so infectious. And bound to make you feel great too as she's an absolute joy to be around.
Yelena has so kindly offered us an exclusive 15% discount off her amazing natural and organic beauty products.
To avail of this discount, head to the Lena Wild website and enter the code NOLEENSLINEY at the checkout. It's valid until 31st March 2019.
I highly recommend you do avail of this really generous discount and give the products a try for yourself. Because they're simply amazing! And it's why I included them in my Glamorous Zero Waste Beauty Gifts guide.
Yelena, along with her husband Dany, is the co-founder of Lena Wild. She's an organic skincare formulator who believes in the superpowers of plants.
Advocating for a holistic approach to beauty, she trusts in nature's ability to provide everything that our skin needs. She's also a very passionate organic and sustainable lifestyle advocate.
You can also find her with the handle @wearewildbeautyon on Instagram, Facebook and Twitter.


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Column: Brad Keselowski Hoping To Add Another NASCAR Cup Series Win In Vegas
March 2, 2019 raceproweekly Syndicated Columnist: Holly Cain
Column By: HOLLY CAIN / NASCAR – LAS VEGAS, NV – For more reasons than you think, Brad Keselowski seems especially satisfied to have won early in the 2019 season. His victory last week in the second race of the schedule – at Atlanta – all but insures a place in the Monster Energy NASCAR Cup Series Playoffs this Fall.
The win also takes a little stress off his Team Penske organization as it – along with the rest of the field – figures out a new technical package for this season's Cup cars. In Sunday's Pennzoil 400 (3:30 p.m. ET, FOX, PRN, SiriusXM NASCAR Radio) at Las Vegas Motor Speedway the cars will not only run a reduced horsepower package, but will have special aero ducts installed in the front of the car – both creating competitive challenges for drivers and teams.
The idea is to create closer racing similar to the package used in last year's All-Star Race on the 1.5-mile Charlotte Motor Speedway – an event that created record lead changes and earned rave reviews.
Most of the drivers conceded during Friday practice sessions that there were no sure-bets in Vegas this weekend. It's a learning process and with a victory already in Keselowski's pocket, it will be easier to gamble.
"When you have a car that's locked in, you can kinda throw some bones at them,'' Keselowski explained of the victory-luxury. "If it works? Good. If it doesn't? Ehhhh.,'' he said smiling. "Then it seems like it kinda flips right before the playoffs start."
One thing Keselowski concedes he'd like his No. 2 Team Penske Ford crew to focus more on is qualifying. This week it could play an especially important role in collecting early race stage points – something he didn't do last week despite his victory. He started 19th at Atlanta and 35th in the season-opening Daytona 500.
"By not qualifying well last week, probably cost our team a lot of stage points,'' Keselowski said. "We won the race and only scored the fifth or sixth most points because of that.
"If we had scored some stage points, we'd be leading the points right now. That stinks. I want to qualify well and get some stage points and that really starts with Friday."
He added, that he was hopeful that being a part of the offseason test session at Vegas would be helpful to that end.
"Based off the test if you're really fast in qualifying you'll be really fast here leading in the race but if you lose track position you'll never get it back.
"I really have no idea what to expect in qualifying. Part of me thinks the 3 (Austin Dillon) and 8 car (Daniel Hemric) will pull away and sit on the pole. Part of me thinks we'll see a 10-car drafting pack and part of me things we'll see cars sit on pit road until time expires. I really don't know what to expect, if I'm being honest."
And, he noted, "The stages for this kind of rule settings have a bigger effect than before because the strategy will be even more mixed, it'll be hard to keep track position so you'll do things to win the stage that might bury you for the next stage. … it will be interesting to see how it all plays out."
It has certainly played out well historically-speaking for Keselowski at Las Vegas. His three wins here are second only to Jimmie Johnson's four victories among active drivers. Keselowski has won three times in the last six races at the 1.5-mile track, an unmatched mark of late. His worst finish in the last seven Vegas races is seventh – in 2015. He's either won the pole position or won the race in five of the last seven races
And with a playoff berth all but assured already, only two races into the season, Keselowski is feeling ready to gamble. He certainly has had the field covered at Las Vegas and says he really feels like the season settles in after the series returns from the western swing of Vegas, Phoenix (next week) and then Auto Club Speedway in California in two weeks.
"I put Kansas as a big marker,'' Keselowski said of judging championship progress. "We're out here on the West Coast and the teams don't really get a good chance to innovate on the cars and kind of re-do them. But by the time we get through Texas (March 31) and get to Kansas (May 3), generally we see the field kind of settle in to where it's going to be and I'd expect that to be the case with the way the schedule plays out this year.
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