Mitochondrial cristae revealed with focused light.

Because of the diffraction resolution barrier, optical microscopes have so far failed in visualizing the mitochondrial cristae, that is, the folds of the inner membrane of this 200 to 400 nm diameter sized tubular organelle. Realizing a ∼30 nm isotropic subdiffraction resolution in isoSTED fluorescence nanoscopy, we have visualized these essential structures in the mitochondria of intact cells. We find a pronounced heterogeneity in the cristae arrangements even within individual mitochondrial tubules

Theoretical Limits on Errors and Acquisition Rates in Localizing Switchable Fluorophores

A variety of recent imaging techniques are able to beat the diffraction limit in fluorescence microcopy by activating and localizing subsets of the fluorescent molecules in the specimen, and repeating this process until all of the molecules have been imaged. In these techniques there is a tradeoff between speed (activating more molecules per imaging cycle) and error rates (activating more molecules risks producing overlapping images that hide information on molecular positions), and so intelligent image-processing approaches are needed to identify and reject overlapping images. We introduce here a formalism for defining error rates, derive a general relationship between error rates, image acquisition rates, and the performance characteristics of the image processing algorithms, and show that there is a minimum acquisition time irrespective of algorithm performance. We also consider algorithms that can infer molecular positions from images of overlapping blurs, and derive the dependence of the minimimum acquisition time on algorithm performance.Comment: 3 pages, 2 figures, 1 table Updated to show published version with minor revision

Children’s particulate matter exposure characterization as part of the new hampshire birth cohort study

As part of the New Hampshire Birth Cohort Study, children 3 to 5 years of age participated in a personal PM2.5 exposure study. This paper characterizes the personal PM2.5 exposure and protocol compliance measured with a wearable sensor. The MicroPEM™ collected personal continuous and integrated measures of PM2.5 exposure and compliance data on 272 children. PM2.5, black carbon (BC), and brown carbon tobacco smoke (BrC-ETS) exposure was measured from the filters. We per-formed a multivariate analysis of woodstove presence and other factors that influenced PM2.5, BC, and BrC exposures. We collected valid exposure data from 258 of the 272 participants (95%). Children wore the MicroPEM for an average of 46% of the 72-h period, and over 80% for a 2-day, 1-night period (with sleep hours counted as non-compliance for this study). Elevated PM2.5 exposures oc-curred in the morning, evening, and overnight. Median PM2.5, BC, and BrC-ETS concentrations were 8.1 μg/m3, 3.6 μg/m3, and 2.4 μg/m3. The combined BC and BrC-ETS mass comprised 72% of the PM2.5. Woodstove presence, hours used per day, and the primary heating source were associated with the children’s PM2.5 exposure and air filters were associated with reduced PM2.5 concentrations. Our findings suggest that woodstove smoke contributed significantly to this cohort’s PM2.5 expo-sure. The high sample validity and compliance rate demonstrated that the MicroPEM can be worn by young children in epidemiologic studies to measure their PM2.5 exposure, inform interventions to reduce the exposures, and improve children’s health

Discovery of the Coldest Imaged Companion of a Sun-Like Star

We present the discovery of a brown dwarf or possible planet at a projected separation of 1.9" = 29 AU around the star GJ 758, placing it between the separations at which substellar companions are expected to form by core accretion (~5 AU) or direct gravitational collapse (typically >100 AU). The object was detected by direct imaging of its thermal glow with Subaru/HiCIAO. At 10-40 times the mass of Jupiter and a temperature of 550-640 K, GJ 758 B constitutes one of the few known T-type companions, and the coldest ever to be imaged in thermal light around a Sun-like star. Its orbit is likely eccentric and of a size comparable to Pluto's orbit, possibly as a result of gravitational scattering or outward migration. A candidate second companion is detected at 1.2" at one epoch.Comment: 5 pages, 3 figures, 2 tables. Accepted for publication in ApJ Letter

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)

Human noise blindness drives suboptimal cognitive inference

Humans typically make near-optimal sensorimotor judgements but show systematic biases when making more cognitive judgements. Here we test the hypothesis that, while humans are sensitive to the noise present during early sensory encoding, the “optimality gap” arises because they are blind to noise introduced by later cognitive integration of variable or discordant pieces of information. In six psychophysical experiments, human observers judged the average orientation of an array of contrast gratings. We varied the stimulus contrast (encoding noise) and orientation variability (integration noise) of the array. Participants adapted near-optimally to changes in encoding noise, but, under increased integration noise, displayed a range of suboptimal behaviours: they ignored stimulus base rates, reported excessive confidence in their choices, and refrained from opting out of objectively difficult trials. These overconfident behaviours were captured by a Bayesian model blind to integration noise. Our study provides a computationally grounded explanation of human suboptimal cognitive inference