Multiband variability studies and novel broadband SED modeling of Mrk 501 in 2009

Aims. We present an extensive study of the BL Lac object Mrk 501 based on a data set collected during the multi-instrument campaign spanning from 2009 March 15 to 2009 August 1, which includes, among other instruments, MAGIC, VERITAS, Whipple 10 m, and Fermi-LAT to cover the gamma-ray range from 0.1 GeV to 20 TeV; RXTE and Swift to cover wavelengths from UV to hard X-rays; and GASP-WEBT, which provides coverage of radio and optical wavelengths. Optical polarization measurements were provided for a fraction of the campaign by the Steward and St. Petersburg observatories. We evaluate the variability of the source and interband correlations, the gamma-ray flaring activity occurring in May 2009, and interpret the results within two synchrotron self-Compton (SSC) scenarios.Methods. The multiband variability observed during the full campaign is addressed in terms of the fractional variability, and the possible correlations are studied by calculating the discrete correlation function for each pair of energy bands where the significance was evaluated with dedicated Monte Carlo simulations. The space of SSC model parameters is probed following a dedicated grid-scan strategy, allowing for a wide range of models to be tested and offering a study of the degeneracy of model-to-data agreement in the individual model parameters, hence providing a less biased interpretation than the "single-curve SSC model adjustment" typically reported in the literature.Results. We find an increase in the fractional variability with energy, while no significant interband correlations of flux changes are found on the basis of the acquired data set. The SSC model grid-scan shows that the flaring activity around May 22 cannot be modeled adequately with a one-zone SSC scenario (using an electron energy distribution with two breaks), while it can be suitably described within a two (independent) zone SSC scenario. Here, one zone is responsible for the quiescent emission from the averaged 4.5-month observing period, while the other one, which is spatially separated from the first, dominates the flaring emission occurring at X-rays and very-high-energy (> 100 GeV, VHE) gamma-rays. The flaring activity from May 1, which coincides with a rotation of the electric vector polarization angle (EVPA), cannot be satisfactorily reproduced by either a one-zone or a two-independent-zone SSC model, yet this is partially affected by the lack of strictly simultaneous observations and the presence of large flux changes on sub-hour timescales (detected at VHE gamma rays).Conclusions. The higher variability in the VHE emission and lack of correlation with the X-ray emission indicate that, at least during the 4.5-month observing campaign in 2009, the highest energy (and most variable) electrons that are responsible for the VHE gamma rays do not make a dominant contribution to the similar to 1 keV emission. Alternatively, there could be a very variable component contributing to the VHE gamma-ray emission in addition to that coming from the SSC scenario. The studies with our dedicated SSC grid-scan show that there is some degeneracy in both the one-zone and the two-zone SSC scenarios probed, with several combinations of model parameters yielding a similar model-to-data agreement, and some parameters better constrained than others. The observed gamma-ray flaring activity, with the EVPA rotation coincident with the first gamma-ray flare, resembles those reported previously for low frequency peaked blazars, hence suggesting that there are many similarities in the flaring mechanisms of blazars with different jet properties

Intermittent androgen deprivation therapy (IADT) for patients with non-metastatic prostate cancer: A retrospective review

15635 Background: IADT is a therapeutic option frequently utilized in men with progressive non-castrate prostate cancer (PCa) which, compared to continuous ADT, may result in an improvement in quality of life while potentially prolonging time to androgen independence (AI). Methods: The records of 43 consecutive men with non-metastatic progressive non-castrate PCa treated with IADT were analyzed. 21 men had received no prior primary treatment (tx), and 22 had developed recurrent disease after previous local therapy. Therapy for this cohort of patients (pts) consisted of combined androgen blockade for 32 pts and a leutenizing hormone-releasing hormone agonist alone for 11. Pts were allowed to come off androgen deprivation (AD) when (a) PSA became undetectable, (b) after 9 to 12 months (mos) of receiving AD, (c) or per patient request. AD was re-initiated when (a) serum PSA reached 50% or greater of the pre-tx level, (b) at physician discretion, or (c) at patient's request. A tx cycle was defined as the number of months on tx plus the number of months off tx until the reinstitution of AD. Progressive disease and AI were defined by consensus criteria (climbing PSA despite AD). Results: Follow up ranged from 18 to 153 mos (median 68.2 mos) from the start of tx. Pts received from 1 to 10 cycles (median 4), with a median cycle length of 19 mos. The median pre-tx PSA value was 8.9, and the median nadir serum PSA level with ADT was 0.09 and was reached within an average of 6.4 mos (range 2–25) after beginning tx. Pts spent an average of 50.7% of time on hormones and 49.3% off hormones. Eleven pts developed AI progressive disease, with a median time to progression of 47 mos. When examining for potential characteristics that contributed to AI, such as duration of ADT, PSA at start of therapy, nadir PSA, stage, or Gleason score, no consistent patterns of failure emerged. Conclusions: IADT appears to be a viable tx option for men with non-metastatic progressive non-castrate PCa, resulting in prolonged duration of response. However, with a median follow up of nearly 6 years, AI still develops in over a quarter of pts, at a median of 47 months from starting ADT. No significant financial relationships to disclose. </jats:p

Time-dependent prognostic value of bispectral index and suppression ratio during targeted temperature management: an early triage tool for treatment escalation plans

Abstract Funding Acknowledgements Type of funding sources: None. Background Post-cardiac arrest myocardial dysfunction contributes to morbidity in survivors of cardiac arrest (CA) and, in case of refractory shock, some patients will benefit from aggressive mechanical support. In this scenario, a non-invasive, reliable and real-time estimation of potential neurological recovery is required to establish personalized treatment escalation plans. Methods We prospectively collected data of bispectral index (BIS) and suppression ratio (SR) monitoring of adult comatose survivors of CA consecutively admitted to an acute cardiac care unit and managed with targeted temperature management (TTM). Neurological status was assessed according to the Cerebral Performance Category (CPC) scale. Results We included 340 patients, 72.1% had an initial shockable rhythm, 72 (21.2%) were females and their mean age was 61.7 ± 14.3 years. Throughout 3-month follow-up, 210 patients (61.8%) achieved a CPC of 1-2 and 130 (38.2%) a CPC of 3-5. Mean BIS values were significantly higher and median SR lower in patients with CPC 1-2 (Figure 1). An average BIS value &amp;gt;26 during first 12 hours of TTM predicted good outcome with 89.3% sensitivity and 75.2% specificity (AUC of 0.86), while average SR values &amp;gt;24 during first 12 hours of TTM predicted poor outcome (CPC 3-5) with 83.6% of sensitivity and 91.8% of specificity (AUC of 0.92). Hourly BIS and SR values exhibited a good predictive performance (AUC &amp;gt; 0.85), starting as soon as hour 2 for SR and 4 for BIS. Conclusions BIS and SR real-time monitoring correlates with patient´s potential of neurological recovery after CA. This finding could help establish personalized treatment escalation plans that reduce consequences of inappropriate interventions, economic costs and uncertainty burden of the patient´s family. </jats:sec

Therapeutic Cancer Vaccines

Therapeutic cancer vaccines represent an emerging therapeutic modality that may play a more prominent role in cancer treatment in the future. Therapeutic cancer vaccines are designed to generate a targeted, immune-mediated antitumor response. There are two main types of therapeutic vaccines: patient-specific (generated either from a patient's own cells or tumor) and patient-nonspecific, where a peptide- or vector-based vaccine induces an immune response in vivo against specific tumor-associated antigens. Studies are currently underway to investigate methods to enhance vaccine strategies, including combinations with standard anticancer therapies or immune-modulating agents. Cancer vaccines are usually well tolerated, with minimal toxicity compared to chemotherapy. This review summarizes selected therapeutic cancer vaccines in late clinical development