Analysis of intermittency in submillimeter radio and hard x-ray data during the impulsive phase of a solar flare

We present an analysis of intermittent processes occurring during the impulsive phase of the flare SOL2012-03-13, using hard X-rays and submillimeter radio data. Intermittency is a key characteristic in turbulent plasmas and has so far only been analyzed for hard X-ray data. Since in a typical flare the same accelerated electron population is believed to produce both hard X-rays and gyrosynchrotron radiation, we compare the two time profiles by searching for intermittency signatures. For this, we define a cross-wavelet power spectrum, which is used to obtain the local intermittency measure, or LIMLIM. When greater than three, the square LIMLIM coefficients indicate a local intermittent process. The LIM2LIM2 coefficient distribution in time and scale helps to identify avalanche or cascade energy release processes. We find two different and well-separated intermittent behaviors in the submillimeter data: for scales greater than 20 s, a broad distribution during the rising and maximum phases of the emission seems to favor a cascade process; for scales below 1 s, short pulses centered on the peak time are representative of avalanches. When applying the same analysis to hard X-rays, we find that only the scales above 10 s produce a distribution related to a cascade energy fragmentation. Our results suggest that different acceleration mechanisms are responsible for tens of keV and MeV energy ranges of electrons

Macrophage migration inhibitory factor downregulation: a novel mechanism of resistance to anti-angiogenic therapy.

Anti-angiogenic therapies for cancer such as VEGF neutralizing antibody bevacizumab have limited durability. While mechanisms of resistance remain undefined, it is likely that acquired resistance to anti-angiogenic therapy will involve alterations of the tumor microenvironment. We confirmed increased tumor-associated macrophages in bevacizumab-resistant glioblastoma patient specimens and two novel glioblastoma xenograft models of bevacizumab resistance. Microarray analysis suggested downregulated macrophage migration inhibitory factor (MIF) to be the most pertinent mediator of increased macrophages. Bevacizumab-resistant patient glioblastomas and both novel xenograft models of resistance had less MIF than bevacizumab-naive tumors, and harbored more M2/protumoral macrophages that specifically localized to the tumor edge. Xenografts expressing MIF-shRNA grew more rapidly with greater angiogenesis and had macrophages localizing to the tumor edge which were more prevalent and proliferative, and displayed M2 polarization, whereas bevacizumab-resistant xenografts transduced to upregulate MIF exhibited the opposite changes. Bone marrow-derived macrophage were polarized to an M2 phenotype in the presence of condition-media derived from bevacizumab-resistant xenograft-derived cells, while recombinant MIF drove M1 polarization. Media from macrophages exposed to bevacizumab-resistant tumor cell conditioned media increased glioma cell proliferation compared with media from macrophages exposed to bevacizumab-responsive tumor cell media, suggesting that macrophage polarization in bevacizumab-resistant xenografts is the source of their aggressive biology and results from a secreted factor. Two mechanisms of bevacizumab-induced MIF reduction were identified: (1) bevacizumab bound MIF and blocked MIF-induced M1 polarization of macrophages; and (2) VEGF increased glioma MIF production in a VEGFR2-dependent manner, suggesting that bevacizumab-induced VEGF depletion would downregulate MIF. Site-directed biopsies revealed enriched MIF and VEGF at the enhancing edge in bevacizumab-naive patients. This MIF enrichment was lost in bevacizumab-resistant glioblastomas, driving a tumor edge M1-to-M2 transition. Thus, bevacizumab resistance is driven by reduced MIF at the tumor edge causing proliferative expansion of M2 macrophages, which in turn promotes tumor growth

Use of archival versus newly collected tumor samples for assessing PD-L1 expression and overall survival : an updated analysis of KEYNOTE-010 trial

Background: In KEYNOTE-010, pembrolizumab versus docetaxel improved overall survival (OS) in patients with programmed death-1 protein (PD)-L1-positive advanced non-small-cell lung cancer (NSCLC). A prespecified exploratory analysis compared outcomes in patients based on PD-L1 expression in archival versus newly collected tumor samples using recently updated survival data. Patients and methods: PD-L1 was assessed centrally by immunohistochemistry (22C3 antibody) in archival or newly collected tumor samples. Patients received pembrolizumab 2 or 10 mg/kg Q3W or docetaxel 75 mg/m2 Q3W for 24 months or until progression/intolerable toxicity/other reason. Response was assessed by RECIST v1.1 every 9 weeks, survival every 2 months. Primary end points were OS and progression-free survival (PFS) in tumor proportion score (TPS) 50% and 1%; pembrolizumab doses were pooled in this analysis. Results: At date cut-off of 24 March 2017, median follow-up was 31 months (range 23-41) representing 18 additional months of follow-up from the primary analysis. Pembrolizumab versus docetaxel continued to improve OS in patients with previously treated, PD-L1-expressing advanced NSCLC; hazard ratio (HR) was 0.66 [95% confidence interval (CI): 0.57, 0.77]. Of 1033 patients analyzed, 455(44%) were enrolled based on archival samples and 578 (56%) on newly collected tumor samples. Approximately 40% of archival samples and 45% of newly collected tumor samples were PD-L1 TPS 50%. For TPS 50%, the OS HRs were 0.64 (95% CI: 0.45, 0.91) and 0.40 (95% CI: 0.28, 0.56) for archival and newly collected samples, respectively. In patients with TPS 1%, OS HRs were 0.74 (95% CI: 0.59, 0.93) and 0.59 (95% CI: 0.48, 0.73) for archival and newly collected samples, respectively. In TPS 50%, PFS HRs were similar across archival [0.63 (95% CI: 0.45, 0.89)] and newly collected samples [0.53 (95% CI: 0.38, 0.72)]. In patients with TPS 1%, PFS HRs were similar across archival [0.82 (95% CI: 0.66, 1.02)] and newly collected samples [0.83 (95% CI: 0.68, 1.02)]. Conclusion: Pembrolizumab continued to improve OS over docetaxel in intention to treat population and in subsets of patients with newly collected and archival samples

No entropy enigmas for N=4 dyons

We explain why multi-centered black hole configurations where at least one of the centers is a large black hole do not contribute to the indexed degeneracies in theories with N=4 supersymmetry. This is a consequence of the fact that such configurations, although supersymmetric, belong to long supermultiplets. As a result, there is no entropy enigma in N=4 theories, unlike in N=2 theories.Comment: 14 page

Pathway to an excitonic coherence

This paper discusses the combined effects of optical excitation power, interface roughness, lattice temperature, and applied magnetic fields on the spin-coherence of excitonic states in GaAs/AlGaAs multiple quantum wells. For low optical powers, at lattice temperatures between 4 K and 50 K, the scattering with acoustic phonons and short-range interactions appear as the main decoherence mechanisms. Statistical fluctuations of the band-gap however become also relevant in this regime and we were able to deconvolute them from the decoherence contributions. The circularly polarized magneto-photoluminescence unveils a non-monotonic tuning of the coherence for one of the spin components at low magnetic fields. This effect has been ascribed to the competition between short-range interactions and spin-flip scattering, modulated by the momentum relaxation time

Evaluation of bone texture imaging parameters on panoramic radiographs of patients with Sheehan’s syndrome: a STROBE-compliant case-control study

Summary Sheehan’s syndrome (SHS) is a rare condition related to the risk of osteoporosis and evaluation of bone texture imaging features on panoramic radiographs would be suitable for this condition, which was the aim of the present study. Fractal dimension, lacunarity, and trabecular morphologic aspects were significantly altered in these patients. Introduction SHS is an important public health problem particularly in developing countries. It is characterized as postpartum hypopituitarism secondary to obstetric complications-related ischemic pituitary necrosis that shows significant systemic metabolic repercussions. Thus, this study aimed to evaluate bone texture parameters in digital panoramic radiographs of patients with SHS. Methods A case-control study was conducted with 30 SHS patients from an Endocrinology and Diabetology Service of reference in Brazil, and 30 age- and sex-matched healthy controls. A custom computer program measured fractal dimension, lacunarity, and some morphologic features in the following mandibular regions of interest (50 × 50 pixels): below the mental foramen (F1), between the first and second molars (M1), and at the center of the mandibular ramus (R1). Results The fractal analysis showed a statistically significant difference between the studied groups in all regions of interest. The fractal dimension in F1 (p = 0.016), M1 (p = 0.043), and R1 (p = 0.028) was significantly lower in SHS group, as well as lacunarity in R1 (p = 0.008). Additionally, several morphologic features were statistically significant in the SHS group (p < 0.05). Conclusion Therefore, individuals with SHS showed altered imaging texture parameters on panoramic radiographs, which reflect a smaller spatial organization of the bone trabeculae and, possibly, a state of reduced mineral bone density

Hybrid Equation/Agent-Based Model of Ischemia-Induced Hyperemia and Pressure Ulcer Formation Predicts Greater Propensity to Ulcerate in Subjects with Spinal Cord Injury

Pressure ulcers are costly and life-threatening complications for people with spinal cord injury (SCI). People with SCI also exhibit differential blood flow properties in non-ulcerated skin. We hypothesized that a computer simulation of the pressure ulcer formation process, informed by data regarding skin blood flow and reactive hyperemia in response to pressure, could provide insights into the pathogenesis and effective treatment of post-SCI pressure ulcers. Agent-Based Models (ABM) are useful in settings such as pressure ulcers, in which spatial realism is important. Ordinary Differential Equation-based (ODE) models are useful when modeling physiological phenomena such as reactive hyperemia. Accordingly, we constructed a hybrid model that combines ODEs related to blood flow along with an ABM of skin injury, inflammation, and ulcer formation. The relationship between pressure and the course of ulcer formation, as well as several other important characteristic patterns of pressure ulcer formation, was demonstrated in this model. The ODE portion of this model was calibrated to data related to blood flow following experimental pressure responses in non-injured human subjects or to data from people with SCI. This model predicted a higher propensity to form ulcers in response to pressure in people with SCI vs. non-injured control subjects, and thus may serve as novel diagnostic platform for post-SCI ulcer formation. © 2013 Solovyev et al

Assessment of potential cardiotoxic side effects of mitoxantrone in patients with multiple sclerosis

Previous studies showed that mitoxantrone can reduce disability progression in patients with multiple sclerosis (MS). There is, however, concern that it may cause irreversible cardiomyopathy with reduced left ventricular (LV) ejection fraction (EF) and congestive heart failure. The aim of this prospective study was to investigate cardiac side effects of mitoxantrone by repetitive cardiac monitoring in MS patients. The treatment protocol called for ten courses of a combined mitoxantrone (10 mg/m(2) body surface) and methylprednisolone therapy. Before each course, a transthoracic echocardiogram was performed to determine the LV end-diastolic diameter, the end-systolic diameter and the fractional shortening; the LV-EF was calculated. Seventy-three patients participated (32 males; age 48 +/- 12 years, range 20-75 years; 25 with primary progressive, 47 with secondary progressive and 1 with relapsing-remitting MS) who received at least four courses of mitoxantrone. Three of the 73 patients were excluded during the study (2 patients discontinued therapy; 1 patient with a previous history of ischemic heart disease developed atrial fibrillation after the second course of mitoxantrone). The mean cumulative dose of mitoxantrone was 114.0 +/- 33.8 mg. The mean follow-up time was 23.4 months (range 10-57 months). So far, there has been no significant change in any of the determined parameters (end-diastolic diameter, end-systolic diameter, fractional shortening, EF) over time during all follow-up investigations. Mitoxantrone did not cause signs of congestive heart failure in any of the patients. Further cardiac monitoring is, however, needed to determine the safety of mitoxantrone after longer follow-up times and at higher cumulative doses. Copyright (C) 2005 S. Karger AG, Basel