Early Flare Research Articles

Shocks in nova outflows – I. Thermal emission

Growing evidence for shocks in nova outflows includes (1) multiple velocity components in the optical spectra; (2) hard X-ray emission starting weeks to months after the outburst; (3) an early radio flare on time-scales of months, in excess of that predicted from the freely expanding photoionized gas; and, perhaps most dramatically, (4) ∼ GeV gamma-ray emission. We present a one-dimensional model for the shock interaction between the fast nova outflow and a dense external shell (DES) and its associated thermal X-ray, optical, and radio emission. The lower velocity DES could represent an earlier stage of mass-loss from the white dwarf or ambient material not directly related to the thermonuclear runaway. The forward shock is radiative initially when the density of shocked gas is highest, at which times radio emission originates from the dense cooling layer immediately downstream of the shock. Our predicted radio light curve is characterized by sharper rises to maximum and later peak times at progressively lower frequencies, with a peak brightness temperature that is approximately independent of frequency. We apply our model to the recent gamma-ray producing classical nova V1324 Sco, obtaining an adequate fit to the early radio maximum assuming that the DES possesses a characteristic velocity ∼103 km s−1 and mass ∼ few 10−4 M⊙; the former is consistent with the velocities of narrow-line absorption systems observed previously in nova spectra, while the total ejecta mass of the DES and fast outflow is consistent with that inferred independently by modelling the late radio peak as uniformly expanding photoionized gas. Importantly, however, our thermal model can only explain the peak radio fluxes if line cooling of the post-shock gas at temperatures ∼106 K is suppressed below its collisional ionization equilibrium value for solar abundances due to photoionization; if this condition is not satisfied, this strongly suggests that the early radio peak is instead non-thermal (e.g. synchrotron) in origin. Rapid evolution of the early radio light curves requires the DES to possess a steep outer density profile, which may indicate that the onset of mass-loss from the white dwarf was rapid, providing indirect evidence that the DES was expelled as the result of the thermonuclear runaway event. Re-processed X-rays from the shock absorbed by the DES at early times are found to contribute significantly to the optical/UV emission.

X-ray afterglow of GRB 050712: multiple energy injections into the external shock

As indicated by observed X-ray flares, a great amount of energy can be intermittently released from the postburst central engine of gamma-ray bursts (GRBs). As a natural consequence, the GRB's external shock could be repeatedly energized. With such a multiple energy injection model, we explore the unique X-ray afterglow light curve of GRB 050712, which exhibits four shallow decay plateaus. Together with three early X-ray flares, the central engine of GRB 050712 is believed to have released energy at least seven times after the burst. Furthermore, we find that the energies released during the four plateaus are all on the same order of magnitude, but the luminosity significantly decreased with time. These results may provide some interesting implications for the GRB central engine.

CHARACTERISTICS OF THE PHOTOSPHERIC MAGNETIC FIELD ASSOCIATED WITH SOLAR FLARE INITIATION

The physical environment governing the solar flare initiation is not fully understood, although there are significant efforts to address the relationship between magnetic non-potential parameters and early flare signatures. In this study, we attempt to characterize the flare initiation based on the processed Helioseismic and Magnetic Imager vector magnetograms, Atmospheric Imaging Assembly 1600 A, and RHESSI hard X-ray observations. Three flare events, the M6.6 flare on 2011 February 13, the X2.2 flare on 2011 February 15, and the X2.1 flare on 2011 September 6, in two active regions AR 11158 and AR 11283 are investigated. We analyze the source field strength in the photosphere, which is defined as the magnitude of the observed magnetic field deviation from the potential field. It is found that one of the strong source field regions above the magnetic polarity inversion line well connects the initial bright kernels of two conjugate ribbons. The results imply that the distribution of the photospheric source field strength can be used to locate the initiation site of flaring loops regardless of the configuration of pre-flare magnetic fields or the evolution of active regions. Moreover, the field configuration in the strong source field regions tends to become more inclined after flares, which is consistent with the coronal implosion scenario. We also employ a fast method to derive the total current density from the photospheric vector magnetogram in the framework of force-free field. This method can provide fast estimation of photospheric current density within a reasonable accuracy without appealing for the more accurate calculation from a model extrapolation.

A44: High Levels of DEK Autoantibodies May Predict Early Flare Following Cessation of Anti‐TNF Therapy

Background/Purpose:The nuclear oncoprotein DEK is a biochemically distinct protein, modulating heterochromatin integrity, chemoattractant of neutrophils and T‐cells and vital for the formation of neutrophil extracellular traps (NETs). NETs are important for resolution of inflammation suggesting that DEK contributes to the development of autoimmune diseases. High levels of DEK autoantibodies have been found in several autoimmune diseases including juvenile idiopathic arthritis (JIA) but their role in disease pathogenesis is not clear. Since DEK and DEK autoantibodies can contribute to the development of immune complexes and NET formation we suggest that DEK antibody levels can predict flare with the discontinuation of anti‐TNF therapy.Methods:In16 pediatric rheumatology centers, sera samples were collected from 137 children with polyarticular JIA with clinically inactive disease (CID) on anti‐TNF therapy. The therapy was stopped and disease activity was monitored for at least 8 months or until disease flare. DEK antibody levels were measured in sera collected at time of enrollment and 6 months (when anti‐TNF therapy was stopped) by ELISA. DEK antibody levels relative to healthy controls were calculated by area under the curve (AUC), expressed as unit‐free ratios.Results:103 females and 34 males patients were enrolled. Mean age 11.3 years and disease duration 5.0 years. JIA included: 13% extended oligoarthritis, 74% polyarthritis rheumatoid factor (RF) negative and 12 % polyarthritis RF positive and 46% positive ANA. 77% were taking etanercept, 18% adalimumab, 5% infliximab and 40% methotrexate. 31 patients (23%) discontinued the study prior stopping the therapy for various reasons, including loss of CID. Of 106 subjects who stopped the therapy, 39 (37%) flared within 8 months (mean of 104.8 days). 67 subjects (63%) had no flares within 8 months after stopping the therapy. 71 out of 106 patients samples were analyzed thus far for DEK antibody levels. DEK antibody level ratios compared to healthy controls was −0.36 (some patients had lower antibody levels than did healthy controls) to 1.41, median ratio of 0.11 (Q1–Q3 of 0.09–0.24) and 0.13 (SD, 0.3). High levels of DEK antibodies, mean and SD of 0.209 ± 0.36 were detected in the 21 patients that flared within 8 months compared to lower levels of DEK antibodies (0.09 ± 0.27) in 50 patients with CID for at least 8 months (ANOVA P= 0.1832). Negative correlation was observed between the days to flare and DEK antibody levels (spearman rho = −0.31, P = 0.07), suggesting that when therapy stopped, patients with higher levels of DEK antibodies will flare sooner with estimated odds ratio of 3.3 (95% CI, 0.61, 18.0), suggesting that each unit increase in DEK antibodies is associated (P = 0.17) with more than a 2‐fold increased risk of flare within 8 months.Conclusion:In children with JIA extended oligoarthritis and polyarthritis on anti‐TNF therapy that maintain CID for at least 6 months while on therapy, high DEK antibody levels may be correlated with flare within the first 8 months after stopping the therapy. This study suggests that DEK antibody levels can predict the outcome of discontinuation of anti‐TNF therapy, although more patient samples need to be analyzed from this study and future studies.

A Study of Hepcidin and Monocyte Chemoattractant Protein‐1 in Egyptian Females With Systemic Lupus Erythematosus

Lupus nephritis is one of the most serious manifestations of systemic lupus erythematosus (SLE). Novel biomarkers are necessary to enhance the diagnostic accuracy, prognostic stratification, monitoring of treatment response, and detection of early renal flares. Our study was conducted on 90 participants. They were divided into three groups, group I (controls) encompassed 30 ages and sex-matched healthy personnel. Group II included 30 non-nephritic SLE patients and finally group III included 30 SLE nephritic patients. Urinary monocyte chemoattractant protein-1 (UMCP-1) and hepcidin were evaluated by ELISA technique, compared and correlated in different groups, with each other and with other routine variables and with renal biopsy done to study group (III). Both UMCP-1 and hepcidin in group III showed significant increase compared to other two groups (controls and group II) (468 ± 128, 111 ± 12, 252 ± 56 pg/ml, respectively, for UMCP-1 and 40 ± 12, 11 ± 2, 20 ± 5 ng/ml, respectively, for hepcidin, P < 0.01). Also both UMCP-1 and hepcidin in group III showed significant increase in diffuse proliferative subgroup compared to focal proliferative and mesangioproliferative subgroups (580 ± 43, 502 ± 46, and 352.6 ± 100 pg/ml, respectively, for UMCP-1 and 47.8 ± 9.5, 41.4 ± 6, and 32.9 ± 10.8 ng/ml, respectively, for urinary hepcidin, P < 0.05). UMCP-1 and hepcidin could be associated with the susceptibility of lupus nephritis.

Treatment of Gout—A new Approach

Since a long time back allopurinol has been constantly use to subsidize uric acid level in blood by competitive and suicidal inhibition of xanthine oxidase. Barring a few side few tolerable effects there was never felt any emergency for invention of an alternative. But a dire research was going on to bring into light an alternative which is better than allopurinol in some aspects. Now a non-purine xanthine oxidase Febuxostat is a new non-purine xanthine oxidase inhibitor that is more potent than allopurinol 300 mg daily. Febuxostat was more effective than allopurinol in the subset with impaired renal function. Long-term extension studies at different levels confirmed the efficacy and tolerability of Febuxostat. In patients who achieved the Serum uric acid level of 6 mg/dl (360 μmol/l), the incidence of gout flares fell steadily and tophi resolved in many patients. The incidence of adverse events such as dizziness, diarrhoea, headache and nausea with Febuxostat was similar to allopurinol. The incidence of cardiovascular side-effects was numerically higher with Febuxostat than with allopurinol, but this was not statistically significant. Co-administration of Febuxostat with AZA or 6mercaptopurine is not recommended. Prophylaxis (colchicines and/or NSAIDs) against acute attacks should be used for at least the first 6 months, since early mobilization flares were observed in the clinical trials. In conclusion, Febuxostat is more effective than allopurinol 300 mg daily in reducing uric acid level 6 mg/dl (360 μmol/l), the target recommended long term option for treatment of gout.

PReS13-SPK-1030: Juvenile dermatomyositis

Juvenile Dermatomyositis (JDM) is a systemic, inflammatory, idiopathic disease, mainly affecting the skin and the muscles, starting before the age of 16 with an incidence around one case per million children. Some patients display typical features of JDM without skin involvement or even without muscle involvement, however both tissues are affected over time in most cases. Diagnosis criteria have been established by Bohan and Peter 35 years ago, based on the presence of typical skin rash and proximal muscle involvement. Other conditions have to be rulled out before making a diagnosis of JDM, such us other connective tissue diseases, polymyositis, infectious/post-infectious myositis, genetic diseases, metabolic or drug-induced myopathies. Unlike adult-onset dermatomyositis, JDM is exceptionnaly associated with a malignant disease. JDM may also affect several organs including the lungs and the digestive tract. In a subset of patients, glucose intolerance, lipodystrophia and/or calcinosis develop. Delay in treatment initiation or inadequate treatment may favour diffuse, debilitating calcinosis. JDM patients have to be referred to reference pediatric centers with a multidisciplinary team to properly assess disease activity, disease-related damage (including low bone density in most cases) and define the best treatment. Long-lasting corticosteroid therapy remains the gold standard, together with physiotherapy. Physiotherapists often play an important rule not only through their participation to patients care but also by assessing disease activity at each stage, using several tools including CMAS and MMT assessment of muscle strength. Other tools have been developed to assess extra-muscular disease and disease-related damage. Patients quality of life also needs to be properly assessed. Several collaborative efforts have been conducted to improve the way we assess patients health and response to treatment. Most patient respond to treatment, relapses are frequent but a complete disease remission is achieved in most cases before adulthood, with or without sequellae. Ongoing clinical trials are assessing the effect of several immunosuppressive and immunomodulatory drugs; preliminary results from a PRINTO international trial suggest that both methotrexate and cyclosporine may help controlling the disease, reducing the rate of early flares and may hence have a corticosteroid-sparing effect. On the short term, methotrexate seems better tolerated. Some preliminary data suggest that other drugs may also be of interest.

FRI0355 Treatment and outcome of ANCA-associated vasculitis in children: A pilot study

BackgroundChildhood ANCA vasculitides are rare, yet organ- or even life-threatening systemic vasculitides. Children most frequently present with rapidly evolving, severe disease such as pulmonary-renal syndrome. In 2009, evidence-based EULAR treatment...

Early response assessment and bone flare phenomenon on 18F-fluorocholine positron emission tomography/computed tomography (FCH-PET/CT) in patients (pts) with metastatic castration-resistant prostate cancer (CRPC) treated with abiraterone acetate.

134 Background: In this prospective study, in patients with CRPC previously treated with docetaxel, we evaluated prostate specific antigen (PSA) and FCH-PET/CT for early response assessment to abiraterone acetate, and assessed frequency of early FCH-PET/CT discordant with PSA and clinical response. Methods: Twenty nine metastatic CRPC pts progressing after docetaxel chemotherapy received abiraterone acetate 1,000 mg daily with prednisone 5 mg twice daily in continuous 28-day cycles. Patients were evaluated monthly for serological PSA response and safety. FCH-PET/CT was repeated after 4-6 weeks and a CT scan was done after 3 months of abiraterone acetate. FCH-PET/CT bone flare was defined as the combination, after 3 months of therapy, of an interpreting radiologist’s report indicating progressive disease (PD) in context of a ≥50% decline in PSA, no PD at 3-month CT scan, with FCH-PET/CT improvement or stability 2-3 months later. Results: Three of 29 patients treated with abiraterone acetate did not perform the follow-up FCH-PET/CT due to rapidly PD with a decline in performance status. Of the remaining 26 patients, 4 are still undergoing early response evaluation. Twenty two pts, median age was 71 yrs (range, 57-86 yrs) were evaluable for this analysis. A ≥50% PSA decline was observed in 15/22 (68%) evaluable pts. Undetectable PSA levels (≤0.1 ng/mL) occurred in one case. Early FCH PET/CT response assessment was as follows: complete response (n=2, 9%), partial response (n=7, 32%), stable disease (n=3, 14%), PD (n=10, 45%), but in 4 of 10 pts with PD a bone flare phenomenon on FCH PET/CT was observed. PSA decline ≥50% and FCH PET/CT response correlated in 19 of 22 pts (86%). Conclusions: Discordant findings between serologic PSA response and increases in early FCH-PET/CT bone lesion intensity are reported here for the first time in CRPC. Further investigation is needed to clarify the confounding effect of FCH-PET/CT bone flare on patient management and interpretation of results.

Working length changes in curved canals after coronal flaring by using rotary files and hand file: An in vitro study

Aim:This in vitro investigation examined the effect of early coronal flaring (CF) and late CF on the working length (WL) in curved root canals.Background:The objective of this study was to determine if canal length is altered as a result of CF in curved canals of molar roots.Study Design:The conditions compared were combinations of (a) stainless steel hand files using Gates Glidden (G. G.) drills (SS) versus nickel-titanium rotary files (Ni-Ti); and (b) early CF (flaring completed before WL determination) versus late CF (flaring completed after WL determination). Selected were 90 canals of extracted maxillary or mandibular first molars (mesial root of mandibular molars and the mesiobuccal root of the maxillary molars) from three groups. CF was accomplished for the SS group using G. G. drills and for the Ni-Ti group using rotary ProTaper and Hero Shaper files. WL was determined by a digital vernier caliper before CF, immediately after CF, and again after canal preparation.Statistical Analysis:A repeated measures analysis of variance (ANOVA) test and a Tukey's multiple prosthoc test were used for this study.Results:Results indicated that WL decreased for all canals as a result of canal preparation. The mean decrease in WL was significantly greater for the SS group (−0.77 ± 0.42 mm) than for the Ni-Ti groups (−0.33 mm ± 0.44). Less change in WL occurred in all groups when initial WL was determined after CF.Conclusion:WL in curved canals consistently decreases during the course of instrumentation. Clinician should keep this in mind for better treatment outcome.

Factors Predicting Disease Flare in Inactive Ulcerative Colitis

Ulcerative Colitis (UC) tends toward a chronic relapsing pattern in most patients. Predicting severity of disease course in Ulcerative Colitis is important to achieve optimal relapse prevention, limit hospitalizations, and prevent surgery. The aim of the current study was to examine which factors might be associated with a disease relapse in a high risk group of patients with inactive UC. 49 patients with inactive UC were recruited into the study. UC subjects had a documented moderate to severe flare in the last 6 months (Mayo Score >6), but were inactive at the time of enrollment (Mayo Score <2). All subjects were on a stable course of medications (5ASA, immunomodulators, biologics, and off prednisone) for at least 3 months before enrollment. All subjects underwent a gastroenterologist visit with a clinical assessment, blood draw, stool collection, an unprepped flexible sigmoidoscopy with biopsies at the time of enrollment. In addition all subjects completed a series of validated psychosocial questionnaires including: IBD Quality of Life Questionnaire (IBDQ), Perceived Health Competence Scale (PHCS), Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI), Perceived Stress Questionnaire (PSQ), and Mindful Attention Awareness Scale (MAAS). Patients were then followed up in the study at 8 weeks, 6 months, and 12 months with all the same measures at enrollment. If patients developed symptoms of a flare during the trial they were seen by the study gastroenterologist. Of the subjects that flared, those that flared in the first 90 days were defined as “early flare.” The remainder of patients who flared were then defined as “late flare.” Baseline factors were then examined to determine which were associated with a disease flare. Statistical calculations were performed by Cox proportional model analysis. Over the course of the 12 month study 28/49 subjects had a disease relapse (57%). 11 patients had an early flare, and 17 had a late flare. In our study baseline factors that were associated with an early flare included elevated IL-6, Mayo Score, and lack of normal vascularity or mild granularity on first endoscopy (P < 0.05). Baseline factors not significantly associated with an early disease flare included pathology, cytokines (TNF, IL-8, and IL-10), stool calprotectin, urinary cortisol, validated psychological questionnaires, or quality of life. Patients with UC are at significant risk of disease relapse. Factors such as a mild increase in clinical disease activity (Mayo Score 1 or 2), elevated IL-6, or loss of normal vascular pattern or mild granularity on endoscopy were associated with a relapse of disease. Findings on pathology, stool calprotectin, and symptoms of stress, depression, or decreased quality of life were not able to accurately predict a disease flare. Further studies are needed to confirm these findings, but adding IL-6, a noninvasive marker of disease activity, or noting subtle changes in endoscopic findings may be important in clinical decision making to limit disease relapse.

THERMAL TO NONTHERMAL ENERGY PARTITION AT THE EARLY RISE PHASE OF SOLAR FLARES

In some flares the thermal component appears much earlier than the nonthermal component in X-ray range. Using sensitive microwave observations we revisit this finding made by Battaglia et al. (2009) based on RHESSI data analysis. We have found that nonthermal microwave emission produced by accelerated electrons with energy of at least several hundred keV, appears as early as the thermal soft X-ray emission indicative that the electron acceleration takes place at the very early flare phase. The non-detection of the hard X-rays at that early stage of the flares is, thus, an artifact of a limited RHESSI sensitivity. In all considered events, the microwave emission intensity increases at the early flare phase. We found that either thermal or nonthermal gyrosynchrotron emission can dominate the low-frequency part of the microwave spectrum below the spectral peak occurring at 3-10 GHz. In contrast, the high-frequency optically thin part of the spectrum is always formed by the nonthermal, accelerated electron component, whose power-law energy spectrum can extend up to a few MeV at this early flare stage. This means that even though the total number of accelerated electrons is small at this stage, their nonthermal spectrum is fully developed. This implies that an acceleration process of available seed particles is fully operational. While, creation of this seed population (the process commonly called `injection' of the particles from the thermal pool into acceleration) has a rather low efficiency at this stage, although, the plasma heating efficiency is high. This imbalance between the heating and acceleration (in favor of the heating) is difficult to reconcile within most of available flare energization models. Being reminiscent of the tradeoff between the Joule heating and runaway electron acceleration, it puts additional constraints on the electron injection into the acceleration process.

MCP-1 in urine as biomarker of disease activity in Systemic Lupus Erythematosus

Conventional clinical parameters are not sensitive or specific enough for detecting ongoing disease activity in the Systemic Lupus Erythematosus (SLE). Measurement of cytokines in urine is an encouraging approach to detection of early flares in this disease. Here we have profiled 27 different cytokines, chemokines and celular growth factors in the urine of 48 patients previously diagnosed of SLE as potential biomarkers of disease activity. Correlation analysis with Bonferroni correction showed that MCP-1 was the only immune mediator which levels in urine correlated directly with the SLE Disease Activity Index 2000 (SLEDAI-2K) score (correlation coefficient, p): MCP-1 (0.45,0.003). MCP-1 correlated inversely with levels of C3 complement protein in serum (−0.50,0.001). MCP-1 showed significant higher levels in patients with severe disease activity in comparison with those exhibiting mild activity. Levels of this chemokine were also higher in patients with severe disease activity in comparison with patients with inactive disease and healthy controls. Areas under receiver operating characteristic curves (AUROC) for detection of severe disease (SLEDAI⩾8) was as follows for MCP-1: [AUROC, (IC95%), p]: [0.81 (0.65–0.96) 0.003]. In addition, MCP-1 showed a good result in the AUROC analysis for detecting renal involvement [0.70 (0.52–0.87) 0.050]. When correlation analysis were repeated excluding those patients with active renal disease (n=14), levels of MCP-1 in urine kept on showing a significant positive association with SLEDAI-2K score. In conclusion, multiplex-based cytokine profiling in urine demonstrated the superiority of MCP-1 over a wide range of cytokines as biomarker of disease activity in SLE.

Clinical remission in juvenile idiopathic arthritis after termination of etanercept

Biologicals are very effective for inhibiting disease progression in active juvenile idiopathic arthritis (JIA). To date, there have been no recommendations on how and when to stop therapy with TNF inhibitors. Our objective was to analyze characteristics and the disease course of JIA patients who discontinued etanercept due to achievement of inactive disease. Data of 39 patients with JIA from two clinical pediatric rheumatology centers in Bydgoszcz and Lublin (Poland) were analyzed retrospectively. All patients discontinued etanercept due to a remission on treatment. Etanercept was started after a mean 33.7 ± 36 (range 3–137) months of disease. The mean duration of therapy with etanercept was 34.7 ± 16.7 (range 6–72) months, with a mean duration of remission on medication 21.3 ± 9.6 (range 4–42) months before withdrawal of etanercept. The mean duration of remission after etanercept discontinuation was 14.2 ± 12.1 (range of 1–60) months. Only 12/39 (30.8 %) patients did not develop a disease exacerbation until the end of the study. Early flares, that is less than 6 months after termination of etanercept, were observed in 15/39 (38.5 %) patients. Twelve (30.8 %) patients restarted etanercept after exacerbation—all patients responded satisfactorily. Our data show that etanercept discontinuation in a substantial proportion of JIA patients results in early disease exacerbation. In many cases, reintroduction of etanercept is needed. Patients, in whom etanercept was restarted, responded satisfactorily.

Ultrasound-detected synovial abnormalities are frequent in clinically inactive juvenile idiopathic arthritis, but do not predict a flare of synovitis

ObjectivesTo investigate whether children with juvenile idiopathic arthritis (JIA) in clinical remission have subclinical synovial disease on ultrasound, and whether ultrasound abnormalities predict an early flare of synovitis.MethodsThirty-nine consecutive children...

Diversity of multiwavelength emission bumps in the GRB 100219A afterglow

Context. Multi-wavelength observations of gamma-ray burst (GRB) afterglows provide important information about the activity of their central engines and their environments. In particular, the short timescale variability, such as bumps and/or rebrightening features visible in the multi-wavelength light curves, is still poorly understood. Aims. We analyze the multi-wavelength observations of the GRB100219A afterglow at redshift 4.7. In particular, we attempt to identify the physical origin of the late achromatic flares/bumps detected in the X-ray and optical bands. Methods. We present ground-based optical photometric data and Swift X-ray observations on GRB100219A. We analyzed the temporal behavior of the X-ray and optical light curves, as well as the X-ray spectra. Results. The early flares in the X-ray and optical light curves peak simultaneously at about 1000 s after the burst trigger, while late achromatic bumps in the X-ray and optical bands appear at about 20000 s after the burst trigger. These are uncommon features in the afterglow phenomenology. Considering the temporal and spectral properties, we argue that both optical and X-ray emissions come from the same mechanism. The late flares/bumps may be produced by late internal shocks from long-lasting activity of the central engine. An off-axis origin for a structured jet model is also discussed to interpret the bump shapes. The early optical bump can be interpreted as the afterglow onset, while the early X-ray flare could be caused by the internal activity. GRB 100219A exploded in a dense environment as revealed by the strong attenuation of X-ray emission and the optical-to-X-ray spectral energy distribution.

The Prostate Cancer Clinical Trials Consortium (PCCTC) bone scan data capture tool for clinical trials using Prostate Cancer Working Group 2 (PCWG2) criteria: Effect on data accuracy and workload.

121 Background: PCWG2 Concensus Criteria proposed time-to-event endpoints in early phase clinical trials. Chief among these was time to radiographic progression for bone scintigraphy (BS), based on a standardized definition with additional rulesets to account for early flare. The PCCTC created a tool to operationalize these definitions in clinical trials. We tested the impact of the tool on clinical trial workload and data adequacy. Methods: The BS capture tool was vetted and amended through nine versions by a multidisciplinary group from PCCTC participating institutions. Accruals at Memorial Sloan-Kettering Cancer Center on two phase III trials using the same drug, contracting research organization (CRO), and electronic data capture system were analyzed. The first trial did not use the PCCTC tool. The second incorporated the tool in its data collection plan and case report form. Workload and data capture adequacy for each trial were determine by examining the total number of imaging queries from the database query reports obtained from the CRO as a function of the total number of scans and patients. Results: Data from this analysis are found in the table . The relative number of queries per scan was reduced by 85.33% by use of the tool. The queries:scan ratios were 0.82 versus 0.12 before and after the use of the tool respectively; likewise, the ratios of queries: patient were 2.81 vs. 0.44. Conclusions: Using the PCCTC BS tool to standardize data capture and operationalize PCWG2 radiographic progression criteria, imaging data are more completely reported and workload for study research staff decreased. The reproducibility and feasibility of the BS tool is further being tested in two ongoing phase III studies in which PCWG2 criteria are being clinically qualified. These efforts to quantitate, standardize, and qualify imaging data advance the goal of developing an imaging biomarker in metastatic prostate cancer. [Table: see text] No significant financial relationships to disclose.

Markers of childhood lupus nephritis indicating disease activity

Current treatment regimens for childhood lupus nephritis (LN) are associated with significant side-effects and toxicity in vulnerable phases of growth and development. The paucity of biomarkers particularly in childhood impedes the appropriate clinical management and the development of new therapeutics. We analyzed markers of immune system (BAFF, RANTES), complement (Bb, C1q, C3d-CIC, C5a) and endothelial cell activation (sVCAM-1) in children with LN (n=22, mean age 14.8±4.7 years), nephrotic syndrome (n=13) and age-matched healthy controls (n=20) to define parameters that correlate with LN activity. Complement fragments of the alternative (Bb, p=0.0004) classical (C3d-CIC, p<0.0001) and common pathway (C5a, p<0.0001) and the levels of BAFF (p<0.0001), RANTES (p=0.0002) and sVCAM-1 (p=0.0004) were significantly higher in active compared to inactive LN. Activation of complement was associated with the occurrence of anti-C1q antibodies and reduced complement C1q. Complement-activation fragments highly correlated with the markers for immune system and endothelial cell activation. The ensemble of these parameters may be of great value in identifying early flares or remissions of childhood LN, and moreover may prove useful in the assessment of new treatments and in determining the optimization of their use.

Gamma-ray burst long lasting X-ray flaring activity

In this paper we shed light on late time (i.e. with peak time t_{pk} \gtrsim 1000 s) flaring activity. We address the morphology and energetic of flares in the window \sim 10^3-10^6 s to put constraints on the temporal evolution of the flare properties and to identify possible differences in the mechanism producing the early and late time flaring emission, if any. This requires the complete understanding of the observational biases affecting the detection of X-ray flares superimposed on a fading continuum at t > 1000 s. We consider all the Swift GRBs that exhibit late time flares. Our sample consists of 36 flares, 14 with redshift measurements. We inherit the strategy of data analysis from Chincarini et al. (2010) in order to make a direct comparison with the early time flare properties. The morphology of the flare light curve is the same for both early time and late time flares, while they differ energetically. The width of late time flares increases with time similarly to the early time flares. Simulations confirmed that the increase of the width with time is not due to the decaying statistics, at least up to 10^4 s. The energy output of late time flares is one order of magnitude lower than the early time flare one, being \sim 1% E_{prompt}. The evolution of the peak luminosity as well as the distribution of the peak flux-to-continuum ratio for late time flares indicate that the flaring emission is decoupled from the underlying continuum, differently from early time flares/steep decay. A sizable fraction of late time flares are compatible with afterglow variability. The internal shock origin seems the most promising explanation for flares. However, some differences that emerge between late and early time flares suggest that there could be no unique explanation about the nature of late time flares.

An Animal Model for Assessing Cardiovascular Cell Therapy with Human Bone Marrow Stem Cells

AbstractAbstract 4693 Introduction:Ischemic cardiovascular diseases are still the leading cause of morbidity and mortality in the western world. Incomplete surgical myocardial revascularization is a determining factor for early flare of subsequent angina which results in lower patient survival. Cell-based cardiac therapy in the treatment of ischemic heart disease is a new concept that has been studied using numerous cell types, delivery systems, and strategies. Bone-marrow derived stem/progenitor cells (BMDC) have been used in a number of different studies in both animal and human models. Adult BMDC is composed of a multitud of cell types: hematopoietic, mesenchimal, stromal stem cells and other cell types yet to be characterized. More studies are needed to address the timing, relative concentrations, source and route of delivery of each cellular populations in animals models of myocardial ischemia. In vivo studies are clear prerequisites for clinical translation and appropriate animal models are needed. Objective:The aim of this study was to produce a xenogenic large animal model of myocardical infartation and investigate whether this model allows evaluation of angiogenic cell therapy with human BMDC. Methods:The proposed strategy was to develop myocardial ischemia in a human cell graft tolerant sheep model. Chimeric tolerant sheeps were created by human BMDC transplant into early gestational sheep fetuses during the “preimmune” stage. Human CD34+ cells (x = 315×103) were implanted in 45+3 days sheep fetuses (n = 10) by echocardiographic-guided injection (modified Zanjani model).Myocardial infarction (MI) was produced by a combined technique of surgical ligature of the first marginal of the circumflex artery and cryoablation with liquid nitrogen achieving an infarction area with total fibrotic replacement (n=8). MI was created in 1 year chimeric sheep and infarcted areas were treated with saline (control group, n=3) or 260×103 human CD34+cells (treated group, n=7). Animals were euthanazied 1 month after MI and the heart were excised for pathology study. The infarct region was divided for study into three areas respect to the center of the infarct. Blood vessels were identified by BS-1 lectin-histochemistry and capillary density determined. Results:Our results showed no differences in capillary density in the three areas studied but a slightly increase in arteriolar component in the treated group compared with the control group (not significant). Neither significant differences were observed when comparing epicardial, medium and endocardial areas. No immune rejection or graft vs. host disease were observed in all treated animals. Conclusion:This study shows that this model is a useful tool for preclinic in vivo evaluation of human cell therapy strategies in ischemic cardiovascular disease. Using human CD34+ cells at doses mentioned above our results did not showed significantly more angiogenesis and arteriogenesis than in the control group. To improve this model, further studies are needed to fully charaterize the role of dose, cell type and time for the angiogenic effect of cell-based therapies. Understanding the potentential of defined lineages of stem cells or undifferentiated progenitors, will lead to better and more focussed clinical trial designs using each cell type indenpendently or in combination, depending on which particular clinical indication is being targeted. Disclosures:No relevant conflicts of interest to declare.