Prostate cancer treatment with Irreversible Electroporation (IRE): Safety, efficacy and clinical experience in 471 treatments.

BackgroundIrreversible Electroporation (IRE) is a novel image-guided tissue ablation technology that induces cell death via very short but strong pulsed electric fields. IRE has been shown to have preserving properties towards vessels and nerves and the extracellular matrix. This makes IRE an ideal candidate to treat prostate cancer (PCa) where other treatment modalities frequently unselectively destroy surrounding structures inducing severe side effects like incontinence or impotence. We report the retrospective assessment of 471 IRE treatments in 429 patients of all grades and stages of PCa with 6-year maximum follow-up time.Material and findingsThe patient cohort consisted of low (25), intermediate (88) and high-risk cancers (312). All had multi-parametric magnetic resonance imaging, and 199 men had additional 3D-mapping biopsy for diagnostic work-up prior to IRE. Patients were treated either focally (123), sub-whole-gland (154), whole-gland (134) or for recurrent disease (63) after previous radical prostatectomy, radiation therapy, etc. Adverse effects were mild (19.7%), moderate (3.7%) and severe (1.4%), never life-threatening. Urinary continence was preserved in all cases. IRE-induced erectile dysfunction persisted in 3% of the evaluated cases 12 months post treatment. Mean transient IIEF-5-Score reduction was 33% within 12-month post IRE follow-up and 15% after 12 months. Recurrences within the follow-up period occurred in 10% of the treated men, 23 in or adjacent to the treatment field and 18 outside the treatment field (residuals). Including residuals for worst case analysis, Kaplan Maier estimation on recurrence rate at 5 years resulted in 5.6% (CI95: 1.8-16.93) for Gleason 6, 14.6% (CI95: 8.8-23.7) for Gleason 7 and 39.5% (CI95: 23.5-61.4) for Gleason 8-10.ConclusionThe results indicate comparable efficacy of IRE to standard radical prostatectomy in terms of 5-year recurrence rates and better preservation of urogenital function, proving the safety and suitability of IRE for PCa treatment. The data also shows that IRE, besides focal therapy of early PCa, can also be used for whole-gland ablations, in patients with recurrent PCa, and as a problem-solver for local tumor control in T4-cancers not amenable to surgery and radiation therapy anymore

Cosmological Evolution of Supergiant Star-Forming Clouds

In an exploration of the birthplaces of globular clusters, we present a careful examination of the formation of self-gravitating gas clouds within assembling dark matter haloes in a hierarchical cosmological model. Our high-resolution smoothed particle hydrodynamical simulations are designed to determine whether or not hypothesized supergiant molecular clouds (SGMCs) form and, if they do, to determine their physical properties and mass spectra. It was suggested in earlier work that clouds with a median mass of several 10^8 M_sun are expected to assemble during the formation of a galaxy, and that globular clusters form within these SGMCs. Our simulations show that clouds with the predicted properties are indeed produced as smaller clouds collide and agglomerate within the merging dark matter haloes of our cosmological model. We find that the mass spectrum of these clouds obeys the same power-law form observed for globular clusters, molecular clouds, and their internal clumps in galaxies, and predicted for the supergiant clouds in which globular clusters may form. We follow the evolution and physical properties of gas clouds within small dark matter haloes up to z = 1, after which prolific star formation is expected to occur. Finally, we discuss how our results may lead to more physically motivated "rules" for star formation in cosmological simulations of galaxy formation.Comment: Accepted to The Astrophysical Journal; 17 pages, 8 figure

The Upper Asymptotic Giant Branch of the Elliptical Galaxy Maffei 1, and Comparisons with M32 and NGC 5128

Deep near-infrared images obtained with adaptive optics systems on the Gemini North and Canada-France-Hawaii telescopes are used to investigate the bright stellar content and central regions of the nearby elliptical galaxy Maffei 1. Stars evolving on the upper asymptotic giant branch (AGB) are resolved in a field 3 arcmin from the center of the galaxy. The locus of bright giants on the (K, H-K) color-magnitude diagram is consistent with a population of stars like those in Baade's Window reddened by E(H-K) = 0.28 +/- 0.05 mag. This corresponds to A_V = 4.5 +/- 0.8 mag, and is consistent with previous estimates of the line of sight extinction computed from the integrated properties of Maffei 1. The AGB-tip occurs at K = 20.0, which correponds to M_K = -8.7; hence, the AGB-tip brightness in Maffei 1 is comparable to that in M32, NGC 5128, and the bulges of M31 and the Milky-Way. The near-infrared luminosity functions (LFs) of bright AGB stars in Maffei 1, M32, and NGC 5128 are also in excellent agreement, both in terms of overall shape and the relative density of infrared-bright stars with respect to the fainter stars that dominate the light at visible and red wavelengths. It is concluded that the brightest AGB stars in Maffei 1, NGC 5128, M32, and the bulge of M31 trace an old, metal-rich population, rather than an intermediate age population. It is also demonstrated that Maffei 1 contains a distinct red nucleus, and this is likely the optical signature of low-level nuclear activity and/or a distinct central stellar population. Finally, there is an absence of globular clusters brighter than the peak of the globular cluster LF in the central 700 x 700 parsecs of Maffei 1.Comment: 22 pages of text and 9 postscript figures; to appear in the Astronomical Journa

A central limit theorem for the zeroes of the zeta function

On the assumption of the Riemann hypothesis, we generalize a central limit theorem of Fujii regarding the number of zeroes of Riemann's zeta function that lie in a mesoscopic interval. The result mirrors results of Soshnikov and others in random matrix theory. In an appendix we put forward some general theorems regarding our knowledge of the zeta zeroes in the mesoscopic regime.Comment: 22 pages. Incorporates referees suggestions. Contains minor corrections to published versio

Star Formation and Feedback in Dwarf Galaxies

We examine the star formation history and stellar feedback effects of dwarf galaxies under the influence of extragalactic ultraviolet radiation. We consider the dynamical evolution of gas in dwarf galaxies using a one-dimensional, spherically symmetric, Lagrangian numerical scheme to compute the effects of radiative transfer and photoionization. We include a physically-motivated star formation recipe and consider the effects of feedback. Our results indicate that star formation in the severe environment of dwarf galaxies is a difficult and inefficient process. For intermediate mass systems, such as the dSphs around the Galaxy, star formation can proceed with in early cosmic epochs despite the intense background UV flux. Triggering processes such as merger events, collisions, and tidal disturbance can lead to density enhancements, reducing the recombination timescale, allowing gas to cool and star formation to proceed. However, the star formation and gas retention efficiency may vary widely in galaxies with similar dark matter potentials, because they depend on many factors, such as the baryonic fraction, external perturbation, IMF, and background UV intensity. We suggest that the presence of very old stars in these dwarf galaxies indicates that their initial baryonic to dark matter content was comparable to the cosmic value. This constraint suggests that the initial density fluctuation of baryonic matter may be correlated with that of the dark matter. For the more massive dwarf elliptical galaxies, the star formation efficiency and gas retention rate is much higher. Their mass to light ratio is regulated by star formation feedback, and is expected to be nearly independent of their absolute luminosity. The results of our theoretical models reproduce the observed $M/L-M_v$ correlation.Comment: 35 pages, 13 figure

Magnetic properties of the low-dimensional spin-1/2 magnet \alpha-Cu_2As_2O_7

In this work we study the interplay between the crystal structure and magnetism of the pyroarsenate \alpha-Cu_2As_2O_7 by means of magnetization, heat capacity, electron spin resonance and nuclear magnetic resonance measurements as well as density functional theory (DFT) calculations and quantum Monte Carlo (QMC) simulations. The data reveal that the magnetic Cu-O chains in the crystal structure represent a realization of a quasi-one dimensional (1D) coupled alternating spin-1/2 Heisenberg chain model with relevant pathways through non-magnetic AsO_4 tetrahedra. Owing to residual 3D interactions antiferromagnetic long range ordering at T_N\simeq10K takes place. Application of external magnetic field B along the magnetically easy axis induces the transition to a spin-flop phase at B_{SF}~1.7T (2K). The experimental data suggest that substantial quantum spin fluctuations take place at low magnetic fields in the ordered state. DFT calculations confirm the quasi-one-dimensional nature of the spin lattice, with the leading coupling J_1 within the structural dimers. QMC fits to the magnetic susceptibility evaluate J_1=164K, the weaker intrachain coupling J'_1/J_1 = 0.55, and the effective interchain coupling J_{ic1}/J_1 = 0.20.Comment: Accepted for publication in Physical Review

Lymphatic Filariasis Control in Tanzania: Effect of Six Rounds of Mass Drug Administration with Ivermectin and Albendazole on Infection and Transmission.

Control of lymphatic filariasis (LF) in most countries of sub-Saharan Africa is based on annual mass drug administration (MDA) with a combination of ivermectin and albendazole, in order to interrupt transmission. We present findings from a detailed study on the effect of six rounds of MDA with this drug combination as implemented by the National Lymphatic Filariasis Elimination Programme (NLFEP) in a highly endemic rural area of north-eastern Tanzania.\ud The effect of treatment on transmission and human infection was monitored in a community- and a school-based study during an 8-year period (one pre-intervention and 7 post-intervention years) from 2003 to 2011. Before intervention, 24.5% of the community population had microfilariae (mf) in the blood, 53.3% had circulating filarial antigens (CFA) and 78.9% had specific antibodies to the recombinant filarial antigen Bm14. One year after the sixth MDA, these values had decreased considerably to 2.7%, 19.6% and 27.5%, respectively. During the same period, the CFA prevalence among new intakes of Standard 1 pupils in 10 primary schools decreased from 25.2% to 5.6%. In line with this, transmission by the three vectors (Anopheles gambiae, An. funestus and Culex quinquefasciatus) as determined by dissection declined sharply (overall vector infectivity rate by 99.3% and mean monthly transmission potential by 99.2% between pre-intervention and fifth post-intervention period). A major shift in vector species composition, from predominantly anopheline to almost exclusively culicine was observed over the years. This may be largely unrelated to the MDAs but may have important implications for the epidemiology of LF in the area. Six MDAs caused considerable decrease in all the measured indices for transmission and human infection. In spite of this, indices were still relatively high in the late period of the study, and it may take a long time to reach the recommended cut-off levels for interruption of transmission unless extra efforts are made. These should include increased engagement of the target population in the control activities, to ensure higher treatment coverage. It is expected that the recent initiative to distribute insecticide impregnated bed nets to every household in the area will also contribute towards reaching the goal of successful LF elimination