bluuebunny/crossref_metadata_2025 huggingface dataset:
Pulmonary capillary endothelial metabolic dysfunction: Severity in pulmonary arterial hypertension related to connective tissue disease versus idiopathic pulmonary arterial hypertension
Authors: Langleben David , Orfanos Stylianos E. , Giovinazzo Michele , Hirsch Andrew , Baron Murray , Senécal Jean‐Luc , Armaganidis Apostolos , Catravas John D.
Published: March 2008

Objective

Pulmonary endothelial dysfunction is intertwined with the development and progression of pulmonary arterial hypertension (PAH). Pulmonary endothelium is an active metabolic tissue in healthy human subjects. This study was undertaken to determine the effects of PAH on pulmonary endothelial angiotensin‐converting enzyme (ACE) activity and to identify differences between common PAH types, i.e., PAH related to connective tissue disease (PAH‐CTD) versus idiopathic PAH (IPAH).

Methods

Nineteen patients with PAH‐CTD, 25 patients with IPAH, and 23 control subjects were evaluated. The single‐pass transpulmonary percent metabolism (%M) and hydrolysis (both reflecting enzyme activity per capillary) of an ACE synthetic substrate were determined. In addition, the calculated functional capillary surface area (FCSA), normalized to body surface area (BSA), was determined.

Results

The %M values in patients with PAH‐CTD (mean ± SEM 53.6 ± 3.6%) were significantly reduced compared with those in control subjects (P < 0.01) and those in patients with IPAH (P < 0.03), but were similar between the IPAH and control groups (mean ± SEM 66.2 ± 3.6% and 74.7 ± 2.7%, respectively). Substrate hydrolysis was also significantly reduced in patients with PAH‐CTD. The FCSA/BSA was significantly reduced in patients with PAH‐CTD (mean ± SEM 1,068 ± 118 ml/minute/m2) and in patients with IPAH (1,443 ± 186 ml/minute/m2) compared with that in controls (2,948 ± 245 ml/minute/m2; P < 0.01 for both). At a given cardiac index, the FCSA/BSA tended to be lower in the PAH‐CTD group than in the IPAH group. Moreover, unlike in IPAH, a linear relationship between the FCSA/BSA and the diffusing capacity for carbon monoxide (DLCO) was observed in PAH‐CTD (r = 0.54, P < 0.03).

Conclusion

The metabolically functional pulmonary capillary bed appears to be reduced to an equal extent in PAH‐CTD and IPAH. However, %M and hydrolysis appear to be reduced in PAH‐CTD but not in IPAH, reflecting relatively diminished ACE activity on the pulmonary capillary endothelial cells of patients with PAH‐CTD, and showing that pulmonary endothelial metabolic function differs between PAH types. This study also provides the first functional evidence that a reduced DLCO value in patients with PAH‐CTD is related to the degree of FCSA loss.
T cell polarization identifies distinct clinical phenotypes in scleroderma lung disease
Authors: Boin Francesco , De Fanis Umberto , Bartlett Susan J. , Wigley Fredrick M. , Rosen Antony , Casolaro Vincenzo
Published: March 2008

Objective

Lung involvement is the leading cause of morbidity and mortality in systemic sclerosis (SSc; scleroderma), and interstitial lung disease (ILD) is the most common pulmonary manifestation. An abnormal profibrotic Th2/Tc2‐polarized T cell response is postulated to mediate tissue damage and fibrosis. The aim of this study was to investigate whether a polarized T cell phenotype in SSc is associated with lung disease or other clinical manifestations of SSc.

Methods

Circulating T cells were characterized by flow cytometry in 62 patients with SSc and 36 healthy control subjects, using antibodies against CD3, CD4, CD8, chemokine receptor CCR5 (Th1/Tc1‐specific), and prostaglandin D2 receptor CRTH2 (Th2/Tc2‐specific). The ratio between CCR5 and CRTH2 T cell frequencies was used to quantify type 1 (high‐ratio) or type 2 (low‐ratio) immune polarization.

Results

Patients with SSc exhibited lower CCR5/CRTH2 T cell ratios than those exhibited by control subjects (P < 0.0001), indicating a Th2/Tc2‐polarized phenotype. Markedly reduced CCR5/CRTH2 T cell ratios were observed in SSc patients with ILD compared with SSc patients without ILD (P < 0.0001), particularly in patients with active ILD (P < 0.0001) compared with those with stable lung function. Lower CCR5/CRTH2 ratios were strongly associated with a lower value for the percent predicted forced vital capacity (P < 0.0001). In patients with an estimated right ventricular systolic pressure >35 mm Hg, suggestive of pulmonary vascular disease, a lower value for the percent predicted diffusing capacity (DLCO) was associated with higher CCR5/CRTH2 T cell ratios (Th1/Tc1) (P = 0.009), while in those with right ventricular systolic pressure <35 mm Hg, a lower value for the percent predicted DLCO correlated with lower ratios (Th2/Tc2) (P < 0.0001), as observed for ILD.

Conclusion

T cell polarization in SSc is strongly associated with specific manifestations of lung disease. Measurement of T cell polarization may represent a valuable tool to monitor disease activity and predict clinical outcomes in SSc patients with lung disease.
Requirement of toll‐like receptor 7 for pristane‐induced production of autoantibodies and development of murine lupus nephritis
Authors: Savarese Emina , Steinberg Christian , Pawar Rahul D. , Reindl Wolfgang , Akira Shizuo , Anders Hans‐Joachim , Krug Anne
Published: March 2008

Objective

The detection of high titers of antibodies against small nuclear ribonucleoproteins (snRNP) is a diagnostic finding in patients in whom systemic lupus erythematosus (SLE) is suspected. Endogenous RNA molecules within snRNP trigger Toll‐like receptor 7 (TLR‐7) activation in B cells and dendritic cells, leading to anti‐snRNP antibody production, which is associated with the development of immune complex nephritis in SLE. The purpose of this study was to investigate the role of TLR‐7 in anti‐snRNP antibody production and renal disease in SLE induced by an exogenous factor in the absence of genetic predisposition, using the pristane‐induced murine lupus model.

Methods

Serum autoantibodies, IgG isotypes, and cytokine levels in pristane‐treated wild‐type and TLR‐7–deficient mice were analyzed by enzyme‐linked immunosorbent assay. Histopathologic changes in mouse kidneys were determined by light immunofluorescence microscopy. Cell subsets in splenocytes and peritoneal lavage cells from the mice were examined by flow cytometry.

Results

We found that anti‐snRNP antibody production induced by pristane treatment was entirely dependent on the expression of TLR‐7, whereas anti–double‐stranded DNA antibody production was not affected by a lack of TLR‐7. Impaired anti‐snRNP antibody production in TLR‐7–deficient mice was paralleled by lower levels of glomerular IgG and complement deposits, as well as less severe glomerulonephritis.

Conclusion

TLR‐7 is specifically required for the production of RNA‐reactive autoantibodies and the development of glomerulonephritis in pristane‐induced murine lupus, a model of environmentally triggered SLE in the absence of genetic susceptibility to autoimmunity. Specific interference with TLR‐7 activation by endogenous TLR‐7 ligands may therefore be a promising novel strategy for the treatment of SLE.
Impact of ankylosing spondylitis on work and family life: Comparisons with the US population
Authors: Ward Michael M. , Reveille John D. , Learch Thomas J. , Davis John C. , Weisman Michael H.
Published: March 2008

Objective

To examine the impact of ankylosing spondylitis (AS) on work disability, nonparticipation in the labor force, marriage, divorce, and childbearing.

Methods

In this cross‐sectional survey, we asked AS patients (n = 591, 72.8% men, mean age 48.9 years) from the Los Angeles, Houston, San Francisco, and Washington, DC metropolitan areas about work and family life. The proportion of patients who were work disabled, did not participate in the labor force, had never been married, were divorced, or had a biological child were compared with the proportions expected for each outcome based on data from population surveys.

Results

Patients with AS were more likely to be work disabled (13.3% versus 5.7%; P < 0.0001) and somewhat more likely to not participate in the labor force compared with the proportion expected (25.1% versus 21.8%; P = 0.07). These associations were stronger among patients age ≥45 years and those with AS for ≥20 years. AS patients were more likely than expected to have never been married (22.8% versus 15.4%; P < 0.0001) or to be divorced (13.2% versus 10.0%; P = 0.02). Women with AS were less likely than expected to have had children (54.7% versus 64.9%; P = 0.02), but the proportion of men with AS who had children was not different from that of the general population.

Conclusion

Patients with AS in this study were more likely to have never been married, more likely to be divorced, and more than twice as likely to be work disabled than members of the general population. Women with AS were also less likely to have had children than women in the general population.
Prevalence and clinical correlates of symptoms of depression in patients with systemic sclerosis
Authors: Thombs Brett D. , Hudson Marie , Taillefer Suzanne S. , Baron Murray ,   Canadian Scleroderma Research Group
Published: March 2008

Objective

To assess the prevalence and predictors of symptoms of depression in a large sample of patients with systemic sclerosis (SSc).

Methods

We conducted a cross‐sectional, multicenter study of 376 patients with SSc from the Canadian Scleroderma Research Group Registry. Patients were assessed with the Center for Epidemiologic Studies Depression Scale (CES‐D) and through extensive clinical histories and medical examinations. Hierarchical multiple linear regression was used to assess the relationship of sociodemographic and clinical variables with symptoms of depression.

Results

The percentages of patients who scored ≥16 and ≥23 on the CES‐D were 35.1% and 18.1%, respectively. Patients with less education; patients who were not married; patients with higher physician‐rated overall disease severity; and patients with more tender joints, more gastrointestinal symptoms, and more difficulty breathing had significantly higher total CES‐D scores. As a group, specific symptom indicators (tender joints, gastrointestinal symptoms, breathing) predicted the most incremental variance in depressive symptoms (ΔR2 = 14.2%, P < 0.001) despite being added to the model after demographic, socioeconomic, and global disease duration/severity indicators.

Conclusion

High levels of depressive symptoms are common in patients with SSc and are related to overall SSc disease severity, as well as specific medical symptoms. Screening for depression among patients with SSc is recommended, although more research is needed to determine the best method for doing this. Successfully treating dyspnea, gastrointestinal symptoms, and joint pain may improve mood, although this has not yet been demonstrated.
Evaluation of the patient acceptable symptom state as an outcome measure in patients with ankylosing spondylitis: Data from a randomized controlled trial
Authors: Dougados Maxime , Luo Michelle P. , Maksymowych Walter P. , Chmiel Joseph J. , Chen Naijun , Wong Robert L. , Davis John C. , Heijde DÉsirÉe van der ,   ATLAS STUDY GROUP
Published: March 2008

Objective

To evaluate the feasibility/acceptability, reliability, external validity, and discriminant capacity of the Patient Acceptable Symptom State (PASS) concept in patients with active ankylosing spondylitis (AS).

Methods

PASS was assessed by asking patients to respond yes or no to a single question: “Considering all the different ways your disease is affecting you, if you would stay in this state for the next months, do you consider that your current state is satisfactory?” during the 24‐week, randomized (2:1 ratio), double‐blind, placebo‐controlled portion of an adalimumab study of 315 patients.

Results

PASS reliability was high (κ = 0.86) in patients with stable disease. Significantly more patients who answered yes to PASS than patients who answered no to PASS were responders based on the ASsessment in Ankylosing Spondylitis (ASAS) International Working Group criteria for 20% improvement (75% who answered yes versus 29% who answered no), the ASAS criteria for 40% improvement (61% versus 16%), the ASAS partial remission criteria (37% versus 3%), and ≥50% improvement on the Bath Ankylosing Spondylitis Disease Activity Index (65% versus 19%; P < 0.001 for all comparisons), demonstrating external validity of the PASS concept. More adalimumab‐treated than placebo‐treated patients achieved PASS at week 12 (42.3% versus 22.4%; P < 0.001), and more adalimumab‐treated than placebo‐treated patients achieved sustained PASS through week 20 (34.6% versus 12.3%; P < 0.001), indicating excellent discriminant capacity.

Conclusion

PASS is a feasible, acceptable, reliable, and valid assessment of satisfactory health state in patients with AS.
Validity, reproducibility, and responsiveness of a twelve‐joint simplified power doppler ultrasonographic assessment of joint inflammation in rheumatoid arthritis
Authors: Naredo Esperanza , Rodríguez Manuel , Campos Cristina , Rodríguez‐heredia José Manuel , Medina Julio A. , Giner Emilio , Martínez Olga , Toyos Francisco Javier , Ruíz Teresa , Ros Inmaculada , Pujol Manuel , Miquel Xavier , García Luz , Aznar Juan José , Chamizo Eugenio , Páez Manuel , Morales Pilar , Rueda Amalia , Tuneu Roser , Corominas Hector , de Agustín Juan José , Moragues Carmen , Mínguez Dolores , Willisch Alfredo , González‐cruz Isabel , Aragón Angel , Iglesias Gerardo , Armas Carlos , Pablo valdazo Juan , Vargas Carmen , Calvo‐alén Jaime , Juan‐mas Antonio , Salvador Georgina , Puigdollers Angels , Galíndez Eva , Garrido Noemi , Salaberri José , Raya Enrique , Salles Meritxell , Díaz César , Cuadra José luis , Garrido Jesús ,   Ultrasound group of the spanish society of rheumatology
Published: March 2008

Objective

To investigate the validity, reproducibility, and responsiveness of a simplified power Doppler ultrasound (PDUS) assessment of joint inflammation compared with a comprehensive 44‐joint PDUS assessment in patients with rheumatoid arthritis (RA) who started therapy with a biologic agent.

Methods

A total of 160 patients with active RA who started a biologic agent were prospectively recruited in 18 Spanish centers. The patients underwent clinical and laboratory assessment and blinded PDUS examination at baseline and 6 months. A PDUS examination of 128 synovial sites in 44 joints was performed. US synovitis and PD signal were semiquantitatively graded from 1 to 3 in all synovial sites. US count and index for synovitis and PD signal were obtained. PDUS intraobserver and interobserver reliability were evaluated. A process of data reduction based on the frequency of involvement of synovial sites by both synovitis and PD signal was conducted. Construct and discriminant validity of a simplified PDUS assessment was investigated.

Results

A PDUS simplified assessment including 24 synovial sites from 12 joints detected 100% of patients with synovitis and 91% of patients with PD signal. There was a highly significant correlation between the 44‐joint count and index for synovitis and PD signal and the 12‐joint count and index for synovitis and PD signal at baseline and 6 months (r = 0.84–0.90, P < 0.0005). The smallest detectable difference was lower than the mean change in simplified PDUS variables.

Conclusion

A 12‐joint PDUS assessment of RA joint inflammation may be a valid, feasible method for multicenter monitoring of therapeutic response to biologic agents.
Determinants of the use of wrist working splints in rheumatoid arthritis
Authors: Veehof Martine M. , Taal Erik , Willems Marjanne J. , van de Laar Mart A. F. J.
Published: March 2008

Objective

To gain insight into the determinants of the use of wrist working splints among patients with rheumatoid arthritis (RA).

Methods

A qualitative descriptive study was performed among 18 patients with RA who recently received a fabric wrist working splint because of pain due to arthritis of the wrist. Patients were interviewed at home using semistructured in‐depth interviews. Interviews were audiotaped and transcribed verbatim and analyzed using the framework approach.

Results

The majority of patients indicated that their splint use was dependent on the seriousness of the symptoms (pain, swelling, or tingling feelings) they perceived. Important reasons to wear the splint were reduction of symptoms, wrist support, and immobilization of the wrist. Important reasons to stop wearing the splint were reduced functional abilities using the splint and the performance of dirty or wet activities.

Conclusion

The reasons for patients to wear and not wear wrist working splints are related to intentional decisions of the patients, which are primarily based on perceived benefits and barriers of splint wearing. The results of this study have been used to develop educational and behavioral strategies to increase adherence to wearing wrist working splints.
Long‐term followup of temporomandibular joint involvement in juvenile idiopathic arthritis
Authors: Twilt Marinka , Schulten Alcuin J. M. , Verschure Femke , Wisse Lauke , Prahl‐Andersen Birte , van Suijlekom‐Smit Lisette W. A.
Published: March 2008

Objective

Temporomandibular joint (TMJ) involvement is a frequent feature in cross‐sectional prevalence studies among patients with juvenile idiopathic arthritis (JIA). In this followup study, patients were reviewed after 5 years to study the course of TMJ involvement in relation to disease characteristics.

Methods

Children with JIA from a previous study on TMJ involvement were included. A rheumatologic evaluation including the 6 parameters of the JIA core set and an orthodontic evaluation including an orthopantomogram (OPT) were performed. OPTs were scored according to Rohlin's grading system (grades 0–5).

Results

The overall prevalence of patients with condylar alterations decreased from 49% to 40%. Improvement of the alterations was seen in 69% of the initially affected condyles, and consequently improvement was seen in 83% of the initially affected patients. Normalization of the alterations was seen in 67% of the improved condyles, and consequently in 44% of the patients. This proves that the condyle has a regenerative capacity. Improvement was related to low disease activity and a less extensive therapeutic regimen.

Conclusion

In patients with JIA, condylar alterations can improve and even regenerate. Condylar improvement is associated with a low disease activity.
Fitness, fatigue, disease activity, and quality of life in pediatric lupus
Authors: Houghton Kristin M. , Tucker Lori B. , Potts James E. , Mckenzie Donald C.
Published: March 2008

Objective

To measure aerobic fitness (maximum oxygen consumption [VO2peak]), fatigue, quality of life (QOL), and disease activity in young persons with systemic lupus erythematosus (SLE), and to determine an equation for predicting VO2peak from the distance walked in 6 minutes (6MW).

Methods

Fifteen young patients ages 12–19 years with SLE participated. VO2 was measured by a graded treadmill exercise test. Submaximal exercise intensity was determined from the ventilatory anaerobic threshold. Submaximal aerobic capacity was measured using the 6MW. Patient questionnaires included measures of fatigue, QOL, and physical activity. Physician questionnaires included the Systemic Lupus Erythematosus Disease Activity Index and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index.

Results

Compared with age‐matched norms, our patients had moderate impairment in aerobic fitness, with a mean ± SD VO2peak of 31.1 ± 7.9 ml/minute/kg and a mean 6MW distance Z score of −2.4 ± 2.3. The regression equation to predict VO2peak (ml/minute/kg) from 6MW was as follows: 57.1 + [0.038 × distance (meters)] + (−0.35 × maximal heart rate) (R = 0.67, P = 0.027). Ten subjects (67%) reported significant fatigue. There was no significant correlation of fatigue with fitness measures. Neither fatigue nor fitness was significantly correlated with disease activity, disease damage, or QOL measures.

Conclusion

Young SLE patients have lower aerobic fitness than reference norms. The 6MW may be used as a marker of fitness, but it is preferable to determine VO2 with a graded exercise test. Fatigue is a significant symptom in young SLE patients. The application of fatigue measures in young persons is exploratory. The relationship between fatigue and aerobic fitness is not clear.
Contemporary prevalence and incidence of work disability associated with rheumatoid arthritis in the US
Authors: Allaire Saralynn , Wolfe Frederick , Niu Jingbo , Lavalley Michael P.
Published: March 2008

Objective

To provide a contemporary estimate of the prevalence and incidence of rheumatoid arthritis (RA) work disability and examine its permanence over time.

Methods

Data were collected semiannually from 5,384 subjects with rheumatologist‐diagnosed RA. We examined prevalence in subgroups formed by ∼5‐year disease duration intervals using data from subjects age ≤64 years who were employed at disease onset. Annual incidence was examined longitudinally among subjects who supplied data in 2003, 2004, or 2005, were employed at disease onset and in a year's first survey, and were age ≤63 years. For work disability permanence we used longitudinal data from all subjects who became work disabled and observed whether they later returned to work.

Results

Mean age of subjects was 52 years, 82% were female, 63% had more than a high school education, mean disease duration was 14 years, and mean Health Assessment Questionnaire score was 1.0. The prevalence of any premature work cessation was 23% in subjects with 1–3 years duration, 35% in those with 10 years, and 51% in those with ≥25 years RA duration. Arthritis‐attributed work cessation was 14%, 29%, and 42%, respectively. Annual incidence of any premature work cessation was ∼10% and arthritis‐attributed work cessation incidence was ∼6%. Thirty‐nine percent of subjects who stopped working later returned to work.

Conclusion

Work disability prevalence in this sample was high (35% within 10 years disease duration), but may represent a decline from the 50% prevalence reported in 1987. Annual incidence of work disability was higher than prior studies, but the return to work rate was also higher.
Two aspects of the clinical and humanistic burden of systemic lupus erythematosus: Mortality risk and quality of life early in the course of disease
Authors: Campbell Robert , Cooper Glinda S. , Gilkeson Gary S.
Published: March 2008

Objective

To evaluate mortality risk and predictors among recently diagnosed systemic lupus erythematosus (SLE) patients.

Methods

The vital status of 265 SLE patients and 355 controls enrolled in the Carolina Lupus Study (median time since diagnosis 13 months) was determined ∼5 years after enrollment. We also assessed the utility of an 8‐item quality of life instrument, derived from the standard 36‐item Medical Outcomes Study Short Form 36, as an additional measure of disease impact.

Results

Five years after diagnosis, 9.7% of patients compared with 0.3% of controls had died (P < 0.0001). Increased mortality risk was seen among older patients (adjusted hazard ratio [HR] 1.03, 95% confidence interval [95% CI] 1.01–1.06 per 1‐year increment in age) and among men, African Americans, patients with lupus nephritis, and patients with anti–double‐stranded DNA antibodies (adjusted HR ∼2.0 for each of these factors). In addition, patients who did not provide a blood sample at study enrollment experienced increased mortality risk (age‐, sex‐, and race‐adjusted HR 3.7, 95% CI 1.5–9.1). Similar results were seen in analyses limited to time from study enrollment. Physical component scores of the quality of life measure were 7.7 points lower (P < 0.0001) and mental component scores were 1.8 points lower (P = 0.07) in patients compared with controls.

Conclusion

The mortality risk among SLE patients is significant, particularly among African Americans, even early in the disease process and even with currently available treatments. Differences between cases and controls in health‐related quality of life using the Short Form 8 also demonstrate the multidimensional burden of SLE.
A pilot study of subclinical coronary atherosclerosis in systemic sclerosis: Coronary artery calcification in cases and controls
Authors: Khurma Vandana , Meyer Cris , Park Grace S. , McMahon Maureen , Lin Jan , Singh Ram Raj , Khanna Dinesh
Published: March 2008

Objective

Systemic sclerosis (SSc) is associated with vasculopathy and endothelial cell injury, which could potentially increase the risk of coronary atherosclerosis. Multidetector computed tomography, a noninvasive procedure, generates a coronary calcium score (CCS) as a marker for coronary atherosclerosis. Serum proinflammatory high‐density lipoprotein (piHDL) is a potential novel marker of atherosclerotic risk. The objective of the pilot study was to determine 1) the prevalence of subclinical coronary atherosclerosis in SSc and 2) serum piHDL levels as a potential novel marker of atherosclerotic risk in SSc.

Methods

A cross‐sectional study of 17 patients with SSc and 17 age‐, sex‐, and race‐matched healthy controls in Cincinnati, Ohio, was conducted. Measurements included CCS; body mass index; lipid profile; and serum levels of high‐sensitivity C‐reactive protein, homocysteine, and piHDL.

Results

Patients with SSc were slightly older (mean 52.8 years) than control subjects (mean 50.6 years; P = 0.01). Coronary calcium was found in 12 participants (9 with SSc, 3 controls; P = 0.03). The mean ± SD CCS in patients with SSc was significantly greater than the controls (126.6 ± 251.0 versus 14.7 ± 52.2; P = 0.003). Five patients with SSc (29%), but no controls, had detectable levels of piHDL (P = 0.06).

Conclusion

Prevalence of subclinical coronary atherosclerosis is greater in patients with SSc compared with healthy controls. These findings should be confirmed in a larger study.
Comparison of employability outcomes among patients with early or long‐standing rheumatoid arthritis
Authors: Han Chenglong , Smolen Josef , Kavanaugh Arthur , St.clair E. William , Baker Daniel , Bala Mohan
Published: March 2008

Objective

To compare employability between patients with early and long‐standing rheumatoid arthritis (RA) and examine the relationships between improvement in employability and disease stage after adjustment for demographic characteristics, disease activity, physical functioning, and response to therapy.

Methods

We evaluated the employability data from 2 double‐blind, randomized, placebo‐controlled studies of infliximab plus methotrexate (MTX) in patients with RA. Patients were incomplete responders to MTX in 1 study and had never taken MTX in the other study. Patients age <65 years were categorized as having early RA (≤3 years disease duration) or long‐standing RA (>3 years disease duration). Physical functioning was assessed using the Health Assessment Questionnaire (HAQ) and clinical response was determined based on the American College of Rheumatology 20% improvement criteria (ACR20).

Results

Patients with early RA were more likely to be employable at baseline than those with long‐standing RA, even after adjusting for baseline HAQ scores. Among patients who were not employable at baseline but achieved an ACR20 response after 1 year of treatment, after adjusting for baseline HAQ score, the patients with early RA who had never taken MTX were 3 times more likely to become employable compared with those with long‐standing RA who had an incomplete response to MTX at baseline.

Conclusion

In 2 clinical trials, patients with early RA were more likely to show improved employment outcomes after treatment than those with long‐standing RA, suggesting intervention as early as possible in the disease course maximizes an individual patient's employment potential.
Fabrication of Selenium/Carbon Core–Shell Submicrowires and Carbon Submicrotubes by a Facile Solution Process
Authors: Wang Weizhi , Qiu Sheng , Xi Baojuan , Chen Liyong , Xiong Shenglin , Zhang Zude
Published: March 2008

We show a facile one‐step surfactant‐assisted solution process to fabricate selenium/carbon (Se/C) coaxial core–shell submicrowires and their transformation into carbon submicrotubes by dissolution of the Se cores at ambient temperature. The formation process of the Se/C core–shell submicrowires was investigated. The results of the investigation and further experiments confirm that the thickness of the carbon shell could be tailored by controlling the experimental conditions. The as‐synthesized Se/C core–shell submicrowires and the carbon submicrotubes are potentially useful in applications such as in nanodevices or biomedicine.
A General Approach for Sample Size and Power Calculations Based on the Haseman–Elston Method
Authors: Hädicke Oliver , Pahlke Friedrich , Ziegler Andreas
Published: March 2008

Risch and Zhang (1995; Science 268: 1584‐9) reported a simple sample size and power calculation approach for the Haseman–Elston method and based their computations on the null hypothesis of no genetic effect. We argue that the more reasonable null hypothesis is that of no recombination. For this null hypothesis, we provide a general approach for sample size and power calculations within the Haseman–Elston framework. We demonstrate the validity of our approach in a Monte‐Carlo simulation study and illustrate the differences using data from published segregation analyses on body weight and heritability estimates on carotid artery artherosclerotic lesions. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
A Simple Numerical Approach Towards Improving the Two One‐Sided Test for Average Bioequivalence
Authors: Cao Li , Mathew Thomas
Published: March 2008

For testing average bioequivalence, a simple test that improves upon the two‐one sided test (TOST) is derived. The new test uses a critical value that is a non‐increasing continuous function of the sample standard deviation, and the function is numerically obtained. Simulation results show that the resulting test performs well in terms of type I error probability; in particular, the test avoids the conservatism of the TOST. Consequently, the test provides better power compared to the TOST, especially when the variance becomes large. Numerical results also show that our test results in power that is very similar to the other improved tests available in the literature. An advantage of our improved test is that it is just as easy to carry out as the TOST. An example is used to illustrate the new test. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Inferences About the Between‐Study Variance in Meta‐Analysis with Normally Distributed Outcomes
Authors: Tian Lili
Published: March 2008

This paper presents a new approach for confidence interval estimation of the between‐study variance in meta‐analysis with normally distributed responses based on the concepts of generalized variables. Simulation study shows that the coverage probabilities of the proposed confidence intervals are generally satisfactory. Moreover, the proposed approach can easily provide P ‐values for hypothesis testing. For meta‐analysis of controlled clinical trials or epidemiological studies, within which the responses are normally distributed, the proposed approach is an ideal candidate for making inference about the between‐study variance. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Nearest Neighbour Adjustment and Linear Variance Models in Plant Breeding Trials
Authors: Piepho Hans‐Peter , Richter Christel , Williams Emlyn
Published: March 2008

This paper reviews methods for nearest neighbour analysis that adjust for local trend in one dimension. Such methods are commonly used in plant breeding and variety testing. The focus is on simple differencing methods, including first differences and the Papadakis method. We discuss mixed model representations of these methods on the scale of the observed data. Modelling observed data has a number of practical advantages compared to differencing, for example the facility to conveniently compute adjusted cultivar means. Most models considered involve a linear variance‐covariance structure and can be represented as state‐space models. The reviewed methods and models are exemplified using three datasets. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
The Inner‐Shell Film: An Immediate Structure Participating in Pearl Oyster Shell Formation
Authors: Yan Zhenguang , Ma Zhuojun , Zheng Guilan , Feng Qiaoli , Wang Hongzhong , Xie Liping , Zhang Rongqing
Published: March 2008

In mollusks, the inner shell film is located in the shell‐mantle zone and it is important in shell formation. In this study, we found that the film was composed of two individual films under certain states and some columnar structures were observed between the two individual films. The inner shell film was separated with the process of ethylenediaminetetraacetic acid (EDTA) treatment and the film proteins were extracted. Amino acid analysis showed that the film proteins may consist of shell framework proteins. The calcite crystallization experiment showed that the film proteins could inhibit the growth of calcite, while the CaCO3precipitation experiment showed that the film proteins could accelerate the rate of CaCO3precipitation. All these results suggested that the film plays an important role in shell formation. It may facilitate the aragonite formation by inhibiting the growth of calcite and accelerate the shell growth by promoting the precipitation of CaCO3crystals.
Control of Porosity Geometry in Amino Acid Derived Nanoporous Materials
Authors: Perez Barrio Jorge , Rebilly Jean‐Noël , Carter Benjamin , Bradshaw Darren , Bacsa John , Ganin Alexey Y. , Park Hyunsoo , Trewin Abbie , Vaidhyanathan Ramanathan , Cooper Andrew I. , Warren John E. , Rosseinsky Matthew J.
Published: March 2008

Substitution of the pillaring ligand in the homochiral open‐framework [Ni2(L‐asp)2(bipy)] by extended bipy‐type ligands leads to a family of layer‐structured, homochiral metal‐organic frameworks. The 1D channel topology can be modified by the nature of the organic linker, with shape, cross‐section and the chemical functionality tuneable. In addition, the volume of these channels can be increased by up to 36 % compared to the parent [Ni2(L‐asp)2(bipy)]. The linker 1,4‐dipyridylbenzene (3rbp) gives access to a new layered homochiral framework [Ni2(L‐asp)2(3rbp)] with channels of a different shape. In specific cases, non‐porous analogues with the linker also present as a guest can be activated to give porous materials after sublimation. Their CO2 uptake shows an increase of up to 30 % with respect to the parent [Ni2(L‐asp)2(bipy)] framework.
Copper(II) Coordination Chemistry of Westiellamide and Its Imidazole, Oxazole, and Thiazole Analogues
Authors: Comba Peter , Gahan Lawrence R. , Haberhauer Gebhard , Hanson Graeme R. , Noble Christopher J. , Seibold Björn , van den Brenk Anna L.
Published: March 2008

The copper(II) coordination chemistry of westiellamide (H3Lwa), as well as of three synthetic analogues with an [18]azacrown‐6 macrocyclic structure but with three imidazole (H3L1), oxazole (H3L2), and thiazole (H3L3) rings instead of oxazoline, is reported. As in the larger patellamide rings, the Nheterocycle‐Npeptide‐Nheterocycle binding site is highly preorganized for copper(II) coordination. In contrast to earlier reports, the macrocyclic peptides have been found to form stable mono‐ and dinuclear copper(II) complexes. The coordination of copper(II) has been monitored by high‐resolution electrospray mass spectrometry (ESI‐MS), spectrophotometric and polarimetric titrations, and EPR and IR spectroscopies, and the structural assignments have been supported by time‐dependent studies (UV/Vis/NIR, ESI‐MS, and EPR) of the complexation reaction of copper(II) with H3L1. Density functional theory (DFT) calculations have been used to model the structures of the copper(II) complexes on the basis of their spectroscopic data. The copper(II) ion has a distorted square‐pyramidal geometry with one or two coordinated solvent molecules (CH3OH) in the mononuclear copper(II) cyclic peptide complexes, but the coordination sphere in [Cu(H2Lwa)(OHCH3)]+ differs from those in the synthetic analogues, [Cu(H2L)(OHCH3)2]+ (L=L1, L2, L3). Dinuclear copper(II) complexes ([CuII2(HL)(μ‐X)]+; X=OCH3, OH; L=L1, L2, L3, Lwa) are observed in the mass spectra. While a dipole–dipole coupled EPR spectrum is observed for the dinuclear copper(II) complex of H3L3, the corresponding complexes with H3L (L=L1, L2, Lwa) are EPR‐silent. This may be explained in terms of strong antiferromagnetic coupling (H3L1) and/or a low concentration of the dicopper(II) complexes (H3Lwa, H3L2), in agreement with the mass spectrometric observations.
Nucleophilic Additions to Alkylidene Bis(sulfoxides)—Stereoelectronic Effects in Vinyl Sulfoxides
Authors: Wedel Tobias , Gehring Timo , Podlech Joachim , Kordel Elena , Bihlmeier Angela , Klopper Wim
Published: March 2008

Conjugate additions of nucleophiles (e.g. enolates, amines and malonate anions) to bis(p‐tolylsulfinyl)alkenes, alkylidene‐1,3‐dithiane‐1,3‐dioxides and alkylidene‐1,3‐dithiolane‐1,3‐dioxides have recently been published. Reasons for different selectivities and reaction rates will be discussed by consideration of steric and electronic effects. The preferred mode of attack can be explained by stereoelectronic effects (hyperconjugation) in the primarily carbanion, which is stabilized by n→S‐O‐σ* interaction with an antiperiplanar SO group. Calculation of the transition states [BP86/aug‐TZVP] for the addition of acetone enolate to the dithiane‐derived alkylidene bis(sulfoxide) revealed that 6.6–7.3 kJ mol−1 more energy is needed for an attack leading to a less‐stabilized carbanion. Two axial SO groups in dithiolane‐derived alkylidene bis(sulfoxides) lead to a higher reactivity towards nucleophiles.
Exploring Helical Folding of Oligoureas During Chain Elongation by High‐Resolution Magic‐Angle‐Spinning (HRMAS) NMR Spectroscopy
Authors: Violette Aude , Lancelot Nathalie , Poschalko Alexander , Piotto Martial , Briand Jean‐Paul , Raya Jesus , Elbayed Karim , Bianco Alberto , Guichard Gilles
Published: March 2008

The development of novel folding oligomers (foldamers) for biological and biomedical applications requires both precise structural information and appropriate methods to detect folding propensity. However, the synthesis and the systematic conformational investigation of large arrays of oligomers to determine the influence of factors, such as chain length, side chains, and surrounding environment, on secondary structure can be quite tedious. Herein, we show for 2.5‐helical N,N′‐linked oligoureas (γ‐peptide lineage) that the whole process of foldamer characterization can be accelerated by using high‐resolution magic‐angle‐spinning (HRMAS) NMR spectroscopy. This was achieved by monitoring a simple descriptor of conformational homogeneity (e.g., chemical shift difference between diastereotopic main chain CH2 protons) at different stages of oligourea chain growth on a solid support. HRMAS NMR experiments were conducted on two sets of oligoureas, ranging from dimer to hexamer, immobilized on DEUSS, a perdeuterated poly(oxyethylene)‐based solid support swollen in solvents of low to high polarity. One evident advantage of the method is that only minute amount of material is required. In addition, the resonance of the deuterated resin is almost negligeable. On‐bead NOESY spectra of high quality and with resolution comparable to that of liquid samples were obtained for longer oligomers, thus allowing detailed structural characterization.
Coordination Chemistry of the cyclo‐(P5tBu4)− Ion: Monomeric and Oligomeric Copper(I), Silver(I) and Gold(I) Complexes
Authors: Gómez‐Ruiz Santiago , Wolf Robert , Bauer Sebastian , Bittig Henry , Schisler Andrea , Lönnecke Peter , Hey‐Hawkins Evamarie
Published: March 2008

[Na{cyclo‐(P5tBu4)}] (1) reacts with [CuCl(PCyp3)2] (Cyp=cyclo‐C5H9) and [CuCl(PPh3)3] (1:1) to give the corresponding copper(I) complexes with a tetra‐tert‐butylcyclopentaphosphanide ligand, [Cu{cyclo‐ (P5tBu4)}(PCyp3)2] (2) and [Cu{cyclo‐(P5tBu4)}(PPh3)2] (3). The CuCl adduct of 2, [Cu2(μ‐Cl){cyclo‐(P5tBu4)}(PCyp3)2] (4), was obtained from the reaction of 1 with [CuCl(PCyp3)2] (1:2). Compounds 2 and 3 rearrange, even at −27 °C, to give [Cu4{cyclo‐ (P4tBu3)PtBu}4] (5), in which ring contraction of the [cyclo‐(P5tBu4)]− anion has occurred. The reaction of 1 with [AgCl(PCyp3)]4 or [AgCl(PPh3)2] (1:1) leads to the formation of [Ag4{cyclo‐(P4tBu3)PtBu}4] (6). Intermediates, which are most probably mononuclear, “[Ag{cyclo‐(P5tBu4)}(PR3)2]” (R=Cyp, Ph) could be detected in the reaction mixtures, but not isolated. Finally, the reaction of 1 with [AuCl(PCyp3)] (1:1) yielded [Au{cyclo‐(P5tBu4)}(PCyp3)] (7), whereas an inseparable mixture of [Au3{cyclo‐(P5tBu4)}3] (8) and [Au4{cyclo‐(P4tBu3)PtBu}4] (9) was obtained from the analogous reaction with [AuCl(PPh3)]. Complexes 3–7 were characterised by 31P NMR spectroscopy, and X‐ray crystal structures were determined for 3–9.
Ring‐Closing Metathesis: Novel Routes to Aromatic Heterocycles
Authors: Donohoe Timothy J. , Fishlock Lisa P. , Procopiou Panayiotis A.
Published: March 2008

Olefin metathesis has been established as an important and general reaction in synthetic organic chemistry. Recently, it has attracted interest as a powerful tool for the construction of aromatic heterocycles. The importance of heteroaromatic motifs in medicinal chemistry and biology, as well as the efficiency and wealth of metathesis transformations, have resulted in significant success in this rapidly developing area.
Studies on para‐selectivity and yield enhancement in zeolite catalyzed toluene nitration
Authors: Sreedhar I. , Reddy K. Suresh Kumar , Ramakrishna M. , Kulkarni S. J. , Raghavan K.V.
Published: March 2008

The nitration of toluene using solid acid catalyst is carried out in batch and semi‐batch reactors with or without continuous water withdrawal. The effect of process parameters viz., nature of catalyst, agitation speed, nitric acid‐toluene dispersion morphology, catalyst to toluene ratio, temperature, nitric acid dosing and boil‐up rates (BRs) on overall conversions, and para‐selectivity is investigated. The micro‐reaction environment around the catalyst particle and its influence on lattice aluminum transformation to achieve improved para‐selectivity has received special attention. These studies have established the importance of dispersion morphology of reactants and microenvironment around catalyst particles for achieving preferred conversion and para‐selectivity in toluene nitration.
Hydrosulphide oxidation pathways in oxic alkaline media containing iron/cerium oxide‐hydroxide
Authors: Petre Catalin F. , Larachi Faïçal
Published: March 2008

The oxidation kinetics of hydrosulphide by iron/cerium oxide‐hydroxide (FeCeOx) and dissolved oxygen (DO2) was studied at 0.1 MPa and 298 K in a batch slurry reactor. The oxidation of hydrosulphide by the FeCeOx/DO2 system proceeded via a combined heterogeneous–homogeneous pathway to yield zerovalent sulphur and thiosulphate. The role of dissolved oxygen was twofold: (i) it reoxidized the iron from Fe(II) to active Fe(III), (ii) it prompted the homogeneous oxidation of hydrosulphide to polysulphides and of polysulphides to thiosulphate. The Fe(III) in situ regeneration by DO2 showed that FeCeOx holds promise for a redox scrubbing process targeting the elimination of H2S from the Kraft mill effluents.
Modelling and process development for gaseous separation with silicone‐coated polymeric membranes
Authors: Jiang Xin , Kumar Ashwani
Published: March 2008

This paper proposes a permeance equation for vapour–permanent gas mixtures in a silicone‐coated polymeric membrane. The equation was derived from the Arrhenius relationship by combining an apparent activation energy and interaction parameter. Accurate values of transmembrane flux were obtained by incorporating this proposed equation, which was dependent on temperature and feed composition. The equation parameters were correlated with the experimental data of eight mixtures consisting of hydrocarbons such as ethylene, ethane, propylene and propane with nitrogen covering a broad range of temperature and concentration. A numerical integration scheme was used for developing a crossflow model utilizing the above equation, which allowed the estimation of product properties including the membrane plasticization cases. The study also reports examples of implementation of this approach in potential industrial applications for the recovery of ethylene and propylene from nitrogen.
Adsorption of mercaptan from model gasoline on 13X loaded with Zn2+
Authors: Yongping Zeng , Shengui Ju , Weihong Xing , Changlin Chen
Published: March 2008

Adsorption of mercaptan on 13X loaded with Zn2+ from model gasoline was studied at different concentration and temperatures. The results indicate that high temperature and low concentration favour the removal of mercaptan from the model gasoline. The adsorptive amount of the untreated adsorbents loaded with Zn2+ is less than the treated with heat obviously, but the adsorbed amount is not enhanced distinctly by the way of increasing the treating temperature. A pseudo‐first‐order mechanism has been proposed to describe the adsorption in the model gasoline system. The desulphurizing capability increases due to the Zn2+ impregnated. With the concentration of Zn2+ higher, the adsorptive amount for ethanethiol increases. Adsorption mechanism shows that it is a chemical adsorption. Two different methods of regeneration were investigated.
Heterogeneous kinetics of oxidation of alcohols: PTC techniques
Authors: Sankarshana T. , Rao M. Bhagvanth
Published: March 2008

2‐ethyl‐1‐hexanol, n‐heptanol, and n‐hexanol oxidation by potassium permanganate was carried out in a baffled stirred reactor under heterogeneous conditions using phase transfer techniques. Tricaprylylmethylammonium chloride (Aliquat 336) was employed as the phase transfer catalyst. Kinetics of the oxidation was investigated. The rate constants were determined by varying the concentration of the catalyst, the concentration of alcohols and temperature. The rate constants agree well with those obtained under homogeneous conditions for all the three alcohols. The variation in the values under heterogeneous conditions were found to be less than 6 %.
Energy‐efficient complex distillation sequences: Control properties
Authors: Robles‐Zapiain Salvador , Segovia‐Hernández Juan Gabriel , Bonilla‐Petriciolet Adrián , Maya‐Yescas Rafael
Published: March 2008

Four thermally coupled distillation systems were designed for the separation of five‐component mixtures (the light‐ends separation section of a crude distillation plant); their steady‐state design was obtained by starting from a conventional distillation sequence and then optimizing for minimum energy consumption. The thermally coupled distillation systems were compared to sequence based on conventional columns design. Comparison was based on controllability properties under open and closed loop operation, following the dynamic behaviour after common industrial operating disturbances. Simulation results were analyzed by the singular value decomposition technique and with the performance examination of elimination of feed disturbances using PI controllers. It was found that thermally coupled distillation systems are controllable and, sometimes, they exhibit dynamic responses that are easier to manage than in the case of conventional distillation sequences; this result is innovative in the study of this kind of systems.
Alkylation of benzene with isopropanol over SAPO‐5: A kinetic study
Authors: Upadhyayula S.
Published: March 2008

The kinetics of benzene alkylation with isopropanol has been studied in vapour phase over SAPO‐5 catalyst. On the basis of the product distribution pattern obtained over this large pore molecular sieve, a reaction mechanism has been proposed. Based on this reaction network, suitable phenomenological models have been derived and fitted to the kinetic data. A Langmuir‐Hinshelwood model with surface reaction involving single site mechanism fitted the data better than the other models. The deactivation kinetics has also been investigated in the low temperature chosen. The activation energy for the deactivation reaction in this range is found to be lower than that for the main reaction.