Pencil-Beam Surveys for Faint Trans-Neptunian Objects

We have conducted pencil-beam searches for outer solar system objects to a limiting magnitude of R ~ 26. Five new trans-neptunian objects were detected in these searches. Our combined data set provides an estimate of ~90 trans-neptunian objects per square degree brighter than ~ 25.9. This estimate is a factor of 3 above the expected number of objects based on an extrapolation of previous surveys with brighter limits, and appears consistent with the hypothesis of a single power-law luminosity function for the entire trans-neptunian region. Maximum likelihood fits to all self-consistent published surveys with published efficiency functions predicts a cumulative sky density Sigma(<R) obeying log10(Sigma) = 0.76(R-23.4) objects per square degree brighter than a given magnitude R.Comment: Accepted by AJ, 18 pages, including 6 figure

Assessing structural damage progression in psoriatic arthritis and its role as an outcome in research.

Psoriatic arthritis (PsA) is an immune-mediated, clinically heterogeneous disease characterized by arthritis, enthesitis, dactylitis, spondylitis, and psoriasis of the skin and nails. Persistent articular inflammation in patients with PsA can lead to structural damage, which can result in reduced physical function and quality of life. Structural damage can occur rapidly, and irreversible joint damage may be observed if patients are not treated promptly and appropriately. Therefore, evaluating therapeutic agents for their ability to inhibit structural progression has become increasingly important, with radiographic progression becoming a key efficacy outcome in clinical trials in PsA. Here, we review how structural damage and progression are assessed in clinical trials and the use of radiographic progression as a study outcome. We also discuss possible limitations in the current assessment of radiographic progression as well as areas of research that may improve the assessment of structural damage in clinical trials of PsA

Prediction and benefits of minimal disease activity in patients with psoriatic arthritis and active skin disease in the ADEPT trial

Objectives: To determine the proportion of patients with psoriatic arthritis in the Adalimumab Effectiveness in Psoriatic Arthritis trial achieving minimal disease activity (MDA) and its individual components at 1 or more visits over 144 weeks, identify baseline predictors of MDA achievement, and evaluate the association of MDA status with independent quality of life (QoL)-related patient-reported outcomes (PROs). Methods: Univariate and multivariate analyses were used to identify the baseline characteristics that predicted achievement of MDA at individual time points (weeks 12 through 144) or sustained MDA (achievement of MDA at 2 consecutive time points 12 weeks apart). The association of independent QoL-related PROs with MDA achievement was evaluated at weeks 24 and 144. Results: In univariate analyses, higher baseline patient assessment of pain, tender joint count (TJC), enthesitis and Health Assessment Questionnaire-Disability Index (HAQ-DI) score were significantly associated with lower likelihood of achieving MDA at later time points. Multivariate analyses confirmed higher baseline HAQ-DI as a significant predictor for failure to achieve MDA at later time points. Achievement of sustained MDA was associated with lower baseline TJC and HAQ-DI score. Achievement of different MDA components appeared to be treatment dependent. MDA achievers had significantly better QoL-related PROs and greater improvements in PROs from baseline to week 24 compared with non-achievers. Conclusions: Higher HAQ-DI score was the most consistent baseline factor that decreased the likelihood of achieving MDA and sustained MDA at later time points. Achieving MDA was associated with better independent QoL-related PROs

Clinical efficacy, radiographic and safety findings through 2 years of golimumab treatment in patients with active psoriatic arthritis: results from a long-term extension of the randomised, placebo-controlled GO-REVEAL study

Objectives: To assess long-term golimumab efficacy/safety in patients with active psoriatic arthritis (PsA).&lt;p&gt;&lt;/p&gt; Methods Adult PsA patients (&#8805;3 swollen, &#8805;3 tender joints, active psoriasis) were randomly assigned to subcutaneous injections of placebo, golimumab 50 mg or 100 mg every 4 weeks (q4wks) through week 20. All patients received golimumab 50 or 100 mg beginning week 24. Findings through 2 years are reported. Efficacy evaluations included &#8805;20% improvement in American College of Rheumatology (ACR20) response, good/moderate response in Disease Activity Scores incorporating 28 joints and C-reactive protein (DAS28-CRP), &#8805;75% improvement in Psoriasis Area and Severity Index (PASI75) and changes in PsA-modified Sharp/van der Heijde scores (SHS).&lt;p&gt;&lt;/p&gt; Results: Golimumab treatment through 2 years was effective in maintaining clinical response (response rates: ACR20 63%–70%, DAS28-CRP 77%–86%, PASI75 56%–72%) and inhibiting radiographic progression (mean change in PsA-modified SHS in golimumab-treated patients: −0.36), with no clear difference between doses. No new safety signals were identified through 2 years. With the study's tuberculosis screening and prophylactic measures, no patient developed active tuberculosis through 2 years.&lt;p&gt;&lt;/p&gt; Conclusions: Golimumab 50 and 100 mg for up to 2 years yielded sustained clinical and radiographic efficacy when administered to patients with active PsA. Increasing the golimumab dose from 50 to 100 mg q4wks added limited benefit. Golimumab safety through up to 2 years was consistent with other antitumour necrosis factor α agents used to treat PsA. Treatment of patients with latent tuberculosis identified at baseline appeared to be effective in inhibiting the development of active tuberculosis.&lt;p&gt;&lt;/p&gt

Efficacy and Safety of Abatacept, a T-cell Modulator, in a Randomised, Double-blind, Placebo-controlled, Phase III Study in Psoriatic Arthritis

OBJECTIVES: To assess the efficacy and safety of abatacept, a selective T-cell costimulation modulator, in a phase III study in psoriatic arthritis (PsA). METHODS: This study randomised patients (1:1) with active PsA (~60% with prior exposure to a tumour necrosis factor inhibitor) to blinded weekly subcutaneous abatacept 125 mg (n=213) or placebo (n=211) for 24 weeks, followed by open-label subcutaneous abatacept. Patients without \u3e/=20% improvement in joint counts at week 16 were switched to open-label abatacept. The primary end point was the proportion of patients with \u3e/=20% improvement in the American College of Rheumatology (ACR20) criteria at week 24. RESULTS: Abatacept significantly increased ACR20 response versus placebo at week 24 (39.4% vs 22.3%; p/=0.35) at week 24, this was not statistically significant (31.0% vs 23.7%; p=0.097). The benefits of abatacept were seen in ACR20 responses regardless of tumour necrosis factor inhibitor exposure and in other musculoskeletal manifestations, but significance could not be attributed due to ranking below Health Assessment Questionnaire-Disability Index response in hierarchical testing. However, the benefit on psoriasis lesions was modest. Efficacy was maintained or improved up to week 52. Abatacept was well tolerated with no new safety signals. CONCLUSIONS: Abatacept treatment of PsA in this phase III study achieved its primary end point, ACR20 response, showed beneficial trends overall in musculoskeletal manifestations and was well tolerated. There was only a modest impact on psoriasis lesions. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number, NCT01860976 (funded by Bristol-Myers Squibb)

Importance of cumulative exposure to elevated cholesterol and blood pressure in development of atherosclerotic coronary artery disease in systemic lupus erythematosus: a prospective proof-of-concept cohort study

INTRODUCTION: Previous studies have shown that traditional risk factors such as hypercholesterolemia and hypertension account for only a small proportion of the dramatically increased risk of atherosclerotic coronary artery disease (CAD) in systemic lupus erythematosus (SLE). However, in these studies, exposure to risk factors was measured only at baseline. In this study, our objective was to compare measures of cumulative exposure with remote and recent values for each of total cholesterol (TC), systolic (SBP), and diastolic (DBP) blood pressure in terms of ability to quantify risk of atherosclerotic CAD in patients with SLE. METHODS: Patients in the Toronto lupus cohort had TC and BP measured at each clinic visit and were followed up prospectively for the occurrence of CAD. For each patient, arithmetic mean, time-adjusted mean (AM) and area-under-the-curve (AUC) were calculated for serial TC, SBP, and DBP measurements. Proportional hazards regression models were used to compare these summary measures with recent and first-available ("remote") measurements in terms of ability to quantify risk of CAD events, defined as myocardial infarction, angina, or sudden cardiac death. RESULTS: The 991 patients had a mean ± SD of 19 ± 19 TC measurements per patient. Over a follow-up of 6.7 ± 6.4 years, 86 CAD events occurred; although remote TC was not significantly predictive of CAD, mean and AM TC were more strongly predictive (hazard ratio (HR) 2.07; P = 0.003) than recent TC (HR 1.86, P = 0.001). AUC TC was not predictive of CAD. A similar pattern was seen for DBP and SBP. Older age, male sex, higher baseline and recent disease activity score, and corticosteroid use also increased CAD risk, whereas antimalarials were protective. CONCLUSIONS: In contrast to the population-based Framingham model, first-available TC and BP are not predictive of CAD among patients with SLE, in whom measures reflecting cumulative exposure over time are better able to quantify CAD risk. This is an important consideration in future studies of dynamic risk factors for CAD in a chronic relapsing-remitting disease such as SLE. Our findings also underpin the importance of adequate control of SLE disease activity while minimizing corticosteroid use, and highlight the cardioprotective effect of antimalarials

Formation of Kuiper-belt binaries through multiple chaotic scattering encounters with low-mass intruders

The discovery that many trans-neptunian objects exist in pairs, or binaries, is proving invaluable for shedding light on the formation, evolution and structure of the outer Solar system. Based on recent systematic searches it has been estimated that up to 10% of Kuiper-belt objects might be binaries. However, all examples discovered to-date are unusual, as compared to near-Earth and main-belt asteroid binaries, for their mass ratios of order unity and their large, eccentric orbits. In this article we propose a common dynamical origin for these compositional and orbital properties based on four-body simulations in the Hill approximation. Our calculations suggest that binaries are produced through the following chain of events: initially, long-lived quasi-bound binaries form by two bodies getting entangled in thin layers of dynamical chaos produced by solar tides within the Hill sphere. Next, energy transfer through gravitational scattering with a low-mass intruder nudges the binary into a nearby non-chaotic, stable zone of phase space. Finally, the binary hardens (loses energy) through a series of relatively gentle gravitational scattering encounters with further intruders. This produces binary orbits that are well fitted by Kepler ellipses. Dynamically, the overall process is strongly favored if the original quasi-bound binary contains comparable masses. We propose a simplified model of chaotic scattering to explain these results. Our findings suggest that the observed preference for roughly equal mass ratio binaries is probably a real effect; that is, it is not primarily due to an observational bias for widely separated, comparably bright objects. Nevertheless, we predict that a sizeable population of very unequal mass Kuiper-belt binaries is likely awaiting discovery.Comment: This is a preprint of an Article accepted for publication in Monthly Notices of the Royal Astronomical Society, (C) 2005 The Royal Astronomical Societ

Markers of inflammation and bone remodelling associated with improvement in clinical response measures in psoriatic arthritis patients treated with golimumab

&lt;p&gt;Objective To determine serum biomarker associations with clinical response to golimumab treatment in patients with psoriatic arthritis (PsA).&lt;/p&gt; &lt;p&gt;Methods GO–REVEAL was a randomised, placebo-controlled study of golimumab in patients with active PsA. Samples were collected from 100 patients at baseline, week 4 and week 14, and analysed for serum-based biomarkers and protein profiling (total 92 markers); data were correlated with clinical measures at week 14.&lt;/p&gt; &lt;p&gt;Results Serum levels of a subset of proteins (apolipoprotein C III, ENRAGE, IL-16, myeloperoxidase, vascular endothelial growth factor, pyridinoline, matrix metalloproteinase 3, C-reactive protein (CRP), carcinoembryonic antigen, intercellular adhesion molecule 1 and macrophage inflammatory protein 1α) at baseline or week 4 were strongly associated with American College of Rheumatology 20% improvement (ACR20) response and/or disease activity score in 28 joints (DAS28) at week 14. A smaller subset of proteins was significantly associated with a 75% improvement in the psoriasis area and severity index score (PASI75) at week 14, (adiponectin, apolipoprotein CIII, serum glutamic oxaloacetic transaminase, and tumour necrosis factor α). Subsets of proteins were identified as potentially predictive of clinical response for each of the clinical measures, and the power of these biomarker panels to predict clinical response to golimumab treatment was stronger than for CRP alone.&lt;/p&gt; &lt;p&gt;Conclusions This analysis provides insight into several panels of markers that may have utility in identifying PsA patients likely to have ACR20, DAS28, or PASI75 responses following golimumab treatment.&lt;/p&gt

A prospective evaluation of the feasibility of using enrolled nursing auxiliaries to triage patients in the emergency unit of an urban public hospital in South Africa

Includes bibliographical references (leaves 73-80)