Optimal precision and accuracy in 4Pi-STORM using dynamic spline PSF models

Coherent fluorescence imaging with two objective lenses (4Pi detection) enables single-molecule localization microscopy with sub-10 nm spatial resolution in three dimensions. Despite its outstanding sensitivity, wider application of this technique has been hindered by complex instrumentation and the challenging nature of the data analysis. Here we report the development of a 4Pi-STORM microscope, which obtains optimal resolution and accuracy by modeling the 4Pi point spread function (PSF) dynamically while also using a simpler optical design. Dynamic spline PSF models incorporate fluctuations in the modulation phase of the experimentally determined PSF, capturing the temporal evolution of the optical system. Our method reaches the theoretical limits for precision and minimizes phase-wrapping artifacts by making full use of the information content of the data. 4Pi-STORM achieves a near-isotropic three-dimensional localization precision of 2–3 nm, and we demonstrate its capa-bilities by investigating protein and nucleic acid organization in primary neurons and mammalian mitochondria

British Lung Foundation/United Kingdom primary immunodeficiency network consensus statement on the definition, diagnosis, and management of granulomatous-lymphocytic interstitial lung disease in common variable immunodeficiency disorders

A proportion of people living with common variable immunodeficiency disorders develop granulomatous-lymphocytic interstitial lung disease (GLILD). We aimed to develop a consensus statement on the definition, diagnosis, and management of GLILD. All UK specialist centers were contacted and relevant physicians were invited to take part in a 3-round online Delphi process. Responses were graded as Strongly Agree, Tend to Agree, Neither Agree nor Disagree, Tend to Disagree, and Strongly Disagree, scored +1, +0.5, 0, −0.5, and −1, respectively. Agreement was defined as greater than or equal to 80% consensus. Scores are reported as mean ± SD. There was 100% agreement (score, 0.92 ± 0.19) for the following definition: “GLILD is a distinct clinico-radio-pathological ILD occurring in patients with [common variable immunodeficiency disorders], associated with a lymphocytic infiltrate and/or granuloma in the lung, and in whom other conditions have been considered and where possible excluded.” There was consensus that the workup of suspected GLILD requires chest computed tomography (CT) (0.98 ± 0.01), lung function tests (eg, gas transfer, 0.94 ± 0.17), bronchoscopy to exclude infection (0.63 ± 0.50), and lung biopsy (0.58 ± 0.40). There was no consensus on whether expectant management following optimization of immunoglobulin therapy was acceptable: 67% agreed, 25% disagreed, score 0.38 ± 0.59; 90% agreed that when treatment was required, first-line treatment should be with corticosteroids alone (score, 0.55 ± 0.51)

Direct Imaging of a Cold Jovian Exoplanet in Orbit around the Sun-like Star GJ 504

Several exoplanets have recently been imaged at wide separations of >10 AU from their parent stars. These span a limited range of ages (<50 Myr) and atmospheric properties, with temperatures of 800--1800 K and very red colors (J - H > 0.5 mag), implying thick cloud covers. Furthermore, substantial model uncertainties exist at these young ages due to the unknown initial conditions at formation, which can lead to an order of magnitude of uncertainty in the modeled planet mass. Here, we report the direct imaging discovery of a Jovian exoplanet around the Sun-like star GJ 504, detected as part of the SEEDS survey. The system is older than all other known directly-imaged planets; as a result, its estimated mass remains in the planetary regime independent of uncertainties related to choices of initial conditions in the exoplanet modeling. Using the most common exoplanet cooling model, and given the system age of 160 [+350, -60] Myr, GJ 504 b has an estimated mass of 4 [+4.5, -1.0] Jupiter masses, among the lowest of directly imaged planets. Its projected separation of 43.5 AU exceeds the typical outer boundary of ~30 AU predicted for the core accretion mechanism. GJ 504 b is also significantly cooler (510 [+30, -20] K) and has a bluer color (J-H = -0.23 mag) than previously imaged exoplanets, suggesting a largely cloud-free atmosphere accessible to spectroscopic characterization. Thus, it has the potential of providing novel insights into the origins of giant planets, as well as their atmospheric properties.Comment: 20 pages, 12 figures, Accepted for publication in ApJ. Minor updates from the version

Fast fluorescence microscopy for imaging the dynamics of embryonic development

Live imaging has gained a pivotal role in developmental biology since it increasingly allows real-time observation of cell behavior in intact organisms. Microscopes that can capture the dynamics of ever-faster biological events, fluorescent markers optimal for in vivo imaging, and, finally, adapted reconstruction and analysis programs to complete data flow all contribute to this success. Focusing on temporal resolution, we discuss how fast imaging can be achieved with minimal prejudice to spatial resolution, photon count, or to reliably and automatically analyze images. In particular, we show how integrated approaches to imaging that combine bright fluorescent probes, fast microscopes, and custom post-processing techniques can address the kinetics of biological systems at multiple scales. Finally, we discuss remaining challenges and opportunities for further advances in this field

Optimizing microsurgical skills with EEG neurofeedback

Background By enabling individuals to self-regulate their brainwave activity in the field of optimal performance in healthy individuals, neurofeedback has been found to improve cognitive and artistic performance. Here we assessed whether two distinct EEG neurofeedback protocols could develop surgical skill, given the important role this skill plays in medicine. Results National Health Service trainee ophthalmic microsurgeons (N = 20) were randomly assigned to either Sensory Motor Rhythm-Theta (SMR) or Alpha-Theta (AT) groups, a randomized subset of which were also part of a wait-list 'no-treatment' control group (N = 8). Neurofeedback groups received eight 30-minute sessions of EEG training. Pre-post assessment included a skills lab surgical procedure with timed measures and expert ratings from video-recordings by consultant surgeons, together with state/trait anxiety self-reports. SMR training demonstrated advantages absent in the control group, with improvements in surgical skill according to 1) the expert ratings: overall technique (d = 0.6, p < 0.03) and suture task (d = 0.9, p < 0.02) (judges' intraclass correlation coefficient = 0.85); and 2) with overall time on task (d = 0.5, p = 0.02), while everyday anxiety (trait) decreased (d = 0.5, p < 0.02). Importantly the decrease in surgical task time was strongly associated with SMR EEG training changes (p < 0.01), especially with continued reduction of theta (4–7 Hz) power. AT training produced marginal improvements in technique and overall performance time, which were accompanied by a standard error indicative of large individual differences. Notwithstanding, successful within session elevation of the theta-alpha ratio correlated positively with improvements in overall technique (r = 0.64, p = 0.047). Conclusion SMR-Theta neurofeedback training provided significant improvement in surgical technique whilst considerably reducing time on task by 26%. There was also evidence that AT training marginally reduced total surgery time, despite suboptimal training efficacies. Overall, the data set provides encouraging evidence of optimised learning of a complex medical specialty via neurofeedback training

Characterization of the gaseous companion {\kappa} Andromedae b: New Keck and LBTI high-contrast observations

We previously reported the direct detection of a low mass companion at a projected separation of 55+-2 AU around the B9 type star {\kappa} Andromedae. The properties of the system (mass ratio, separation) make it a benchmark for the understanding of the formation and evolution of gas giant planets and brown dwarfs on wide-orbits. We present new angular differential imaging (ADI) images of the Kappa Andromedae system at 2.146 (Ks), 3.776 (L'), 4.052 (NB 4.05) and 4.78 {\mu}m (M') obtained with Keck/NIRC2 and LBTI/LMIRCam, as well as more accurate near-infrared photometry of the star with the MIMIR instrument. We derive a more accurate J = 15.86 +- 0.21, H = 14.95 +- 0.13, Ks = 14.32 +- 0.09 mag for {\kappa} And b. We redetect the companion in all our high contrast observations. We confirm previous contrasts obtained at Ks and L' band. We derive NB 4.05 = 13.0 +- 0.2 and M' = 13.3 +- 0.3 mag and estimate Log10(L/Lsun) = -3.76 +- 0.06. We build the 1-5 microns spectral energy distribution of the companion and compare it to seven PHOENIX-based atmospheric models in order to derive Teff = 1900+100-200 K. Models do not set constrains on the surface gravity. ``Hot-start" evolutionary models predict masses of 14+25-2 MJup based on the luminosity and temperature estimates, and considering a conservative age range for the system (30+120-10 Myr). ``warm-start" evolutionary tracks constrain the mass to M >= 11 MJup. Therefore, the mass of {\kappa} Andromedae b mostly falls in the brown-dwarf regime, due to remaining uncertainties in age and mass-luminosity models. According to the formation models, disk instability in a primordial disk could account for the position and a wide range of plausible masses of {\kappa} And b.Comment: 20 pages, 16 figures, accepted for publication in Astronomy and Astrophysics on August 6, 201

New Techniques for High-Contrast Imaging with ADI: the ACORNS-ADI SEEDS Data Reduction Pipeline

We describe Algorithms for Calibration, Optimized Registration, and Nulling the Star in Angular Differential Imaging (ACORNS-ADI), a new, parallelized software package to reduce high-contrast imaging data, and its application to data from the SEEDS survey. We implement several new algorithms, including a method to register saturated images, a trimmed mean for combining an image sequence that reduces noise by up to ~20%, and a robust and computationally fast method to compute the sensitivity of a high-contrast observation everywhere on the field-of-view without introducing artificial sources. We also include a description of image processing steps to remove electronic artifacts specific to Hawaii2-RG detectors like the one used for SEEDS, and a detailed analysis of the Locally Optimized Combination of Images (LOCI) algorithm commonly used to reduce high-contrast imaging data. ACORNS-ADI is written in python. It is efficient and open-source, and includes several optional features which may improve performance on data from other instruments. ACORNS-ADI requires minimal modification to reduce data from instruments other than HiCIAO. It is freely available for download at www.github.com/t-brandt/acorns-adi under a BSD license.Comment: 15 pages, 9 figures, accepted to ApJ. Replaced with accepted version; mostly minor changes. Software update

Subaru Imaging of Asymmetric Features in a Transitional Disk in Upper Scorpius

We report high-resolution (0.07 arcsec) near-infrared polarized intensity images of the circumstellar disk around the star 2MASS J16042165-2130284 obtained with HiCIAO mounted on the Subaru 8.2 m telescope. We present our $H$-band data, which clearly exhibits a resolved, face-on disk with a large inner hole for the first time at infrared wavelengths. We detect the centrosymmetric polarization pattern in the circumstellar material as has been observed in other disks. Elliptical fitting gives the semimajor axis, semiminor axis, and position angle (P.A.) of the disk as 63 AU, 62 AU, and -14 $^{\circ}$, respectively. The disk is asymmetric, with one dip located at P.A.s of $\sim85^{\circ}$. Our observed disk size agrees well with a previous study of dust and CO emission at submillimeter wavelength with Submillimeter Array. Hence, the near-infrared light is interpreted as scattered light reflected from the inner edge of the disk. Our observations also detect an elongated arc (50 AU) extending over the disk inner hole. It emanates at the inner edge of the western side of the disk, extending inward first, then curving to the northeast. We discuss the possibility that the inner hole, the dip, and the arc that we have observed may be related to the existence of unseen bodies within the disk.Comment: 21 pages, 3 figures, published 2012 November 7 by ApJL, typo correcte