How to Extract the Geometry and Topology from Very Large 3D Segmentations

Segmentation is often an essential intermediate step in image analysis. A volume segmentation characterizes the underlying volume image in terms of geometric information--segments, faces between segments, curves in which several faces meet--as well as a topology on these objects. Existing algorithms encode this information in designated data structures, but require that these data structures fit entirely in Random Access Memory (RAM). Today, 3D images with several billion voxels are acquired, e.g. in structural neurobiology. Since these large volumes can no longer be processed with existing methods, we present a new algorithm which performs geometry and topology extraction with a runtime linear in the number of voxels and log-linear in the number of faces and curves. The parallelizable algorithm proceeds in a block-wise fashion and constructs a consistent representation of the entire volume image on the hard drive, making the structure of very large volume segmentations accessible to image analysis. The parallelized C++ source code, free command line tools and MATLAB mex files are avilable from http://hci.iwr.uni-heidelberg.de/software.phpComment: C++ source code, free command line tools and MATLAB mex files are avilable from http://hci.iwr.uni-heidelberg.de/software.ph

Runtime-Flexible Multi-dimensional Arrays and Views for C++98 and C++0x

Multi-dimensional arrays are among the most fundamental and most useful data structures of all. In C++, excellent template libraries exist for arrays whose dimension is fixed at runtime. Arrays whose dimension can change at runtime have been implemented in C. However, a generic object-oriented C++ implementation of runtime-flexible arrays has so far been missing. In this article, we discuss our new implementation called Marray, a package of class templates that fills this gap. Marray is based on views as an underlying concept. This concept brings some of the flexibility known from script languages such as R and MATLAB to C++. Marray is free both for commercial and non-commercial use and is publicly available from www.andres.sc/marrayComment: Free source code availabl

The Lazy Flipper: MAP Inference in Higher-Order Graphical Models by Depth-limited Exhaustive Search

This article presents a new search algorithm for the NP-hard problem of optimizing functions of binary variables that decompose according to a graphical model. It can be applied to models of any order and structure. The main novelty is a technique to constrain the search space based on the topology of the model. When pursued to the full search depth, the algorithm is guaranteed to converge to a global optimum, passing through a series of monotonously improving local optima that are guaranteed to be optimal within a given and increasing Hamming distance. For a search depth of 1, it specializes to Iterated Conditional Modes. Between these extremes, a useful tradeoff between approximation quality and runtime is established. Experiments on models derived from both illustrative and real problems show that approximations found with limited search depth match or improve those obtained by state-of-the-art methods based on message passing and linear programming.Comment: C++ Source Code available from http://hci.iwr.uni-heidelberg.de/software.ph

Four-dimensional ultrafast electron microscopy of phase transitions

Reported here is direct imaging (and diffraction) by using 4D ultrafast electron microscopy (UEM) with combined spatial and temporal resolutions. In the first phase of UEM, it was possible to obtain snapshot images by using timed, single-electron packets; each packet is free of space–charge effects. Here, we demonstrate the ability to obtain sequences of snapshots ("movies") with atomic-scale spatial resolution and ultrashort temporal resolution. Specifically, it is shown that ultrafast metal–insulator phase transitions can be studied with these achieved spatial and temporal resolutions. The diffraction (atomic scale) and images (nanometer scale) we obtained manifest the structural phase transition with its characteristic hysteresis, and the time scale involved (100 fs) is now studied by directly monitoring coordinates of the atoms themselves

Increased systemic inflammation is associated with cardiac and vascular dysfunction over the first 12 weeks of antiretroviral therapy among undernourished, HIV-infected adults in Southern Africa.

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.INTRODUCTION: Persistent systemic inflammation is associated with mortality among undernourished, HIV-infected adults starting antiretroviral therapy (ART) in sub-Saharan Africa, but the etiology of these deaths is not well understood. We hypothesized that greater systemic inflammation is accompanied by cardiovascular dysfunction over the first 12 weeks of ART. METHODS: In a prospective cohort of 33 undernourished (body mass index <18.5 kg/m2) Zambian adults starting ART, we measured C-reactive protein (CRP), tumor necrosis factor-α receptor 1 (TNF-α R1), and soluble CD163 and CD14 at baseline and 12 weeks. An EndoPAT device measured the reactive hyperemia index (LnRHI; a measure of endothelial responsiveness), peripheral augmentation index (AI; a measure of arterial stiffness), and heart rate variability (HRV; a general marker of autonomic tone and cardiovascular health) at the same time points. We assessed paired changes in inflammation and cardiovascular parameters, and relationships independent of time point (adjusted for age, sex, and CD4+ T-cell count) using linear mixed models. RESULTS: Serum CRP decreased (median change -3.5 mg/l, p=0.02), as did TNF-α R1 (-0.31 ng/ml, p<0.01), over the first 12 weeks of ART. A reduction in TNF-α R1 over 12 weeks was associated with an increase in LnRHI (p=0.03), and a similar inverse relationship was observed for CRP and LnRHI (p=0.07). AI increased in the cohort as a whole over 12 weeks, and a reduction in sCD163 was associated with a rise in the AI score (p=0.04). In the pooled analysis of baseline and 12 week data, high CRP was associated with lower HRV parameters (RMSSD, p=0.01; triangular index, p<0.01), and higher TNF- α R1 accompanied lower HRV (RMSSD, p=0.07; triangular index, p=0.06). CONCLUSIONS: Persistent inflammation was associated with impaired cardiovascular health over the first 12 weeks of HIV treatment among undernourished adults in Africa, suggesting cardiac events may contribute to high mortality in this population.This work was supported by the Vanderbilt Meharry Center for AIDS Research (NIH grant number P30 AI54999); the NIH Fogarty International Center, Office of the Director, National Institutes of Health, National Heart, Blood, and Lung Institute, and National Institute of Mental Health, through the Vanderbilt-Emory-Cornell-Duke Consortium for Global Health Fellows (grant number R25 TW009337); the National Center for Advancing Translational Sciences (CTSA award number UL1TR000445) and the European and Developing Countries Clinical Trials Partnership (grant IP.2009.33011.004)

Effects on mortality of a nutritional intervention for malnourished HIV-infected adults referred for antiretroviral therapy: a randomised controlled trial.

Malnourished HIV-infected African adults are at high risk of early mortality after starting antiretroviral therapy (ART). We hypothesized that short-course, high-dose vitamin and mineral supplementation in lipid nutritional supplements would decrease mortality

Electronic structure of REREAuMg and REREAgMg (RERE = Eu, Gd, Yb)

We have investigated the electronic structure of the equiatomic EuAuMg, GdAuMg, YbAuMg and GdAgMg intermetallics using x-ray photoelectron spectroscopy. The spectra revealed that the Yb and Eu are divalent while the Gd is trivalent. The spectral weight in the vicinity of the Fermi level is dominated by the mix of Mg $s$, Au/Ag $sp$ and $RE$ $spd$ bands, and not by the $RE$ $4f$. We also found that the Au and Ag $d$ bands are extraordinarily narrow, as if the noble metal atoms were impurities submerged in a low density $sp$ metal host. The experimental results were compared with band structure calculations, and we found good agreement provided that the spin-orbit interaction in the Au an Ag $d$ bands is included and correlation effects in an open $4f$ shell are accounted for using the local density approximation + Hubbard $U$ scheme. Nevertheless, limitations of such a mean-field scheme to explain excitation spectra are also evident.Comment: 4 pages, 3 figures, Brief Repor

Time Resolved Stroboscopic Neutron Scattering of Vortex Lattice Dynamics in Superconducting Niobium

Superconducting vortex lattices, glasses and liquids attract great interest as model systems of crystallization and as a source of microscopic information of the nature of superconductivity. We report for the first time direct microscopic measurements of the vortex lattice tilt modulus c44 in ultra-pure niobium using time-resolved small angle neutron scattering. Besides a general trend to faster vortex lattice dynamics for increasing temperatures we observe a dramatic changeover of the relaxation process associated with the non-trivial vortex lattice morphology in the intermediate mixed state. This changeover is attributed to a Landau-branching of the Shubnikov domains at the surface of the sample. Our study represents a showcase for how to access directly vortex lattice melting and the formation of vortex matter states for other systems.Comment: 14 pages, 14 figure

Weight gain among treatment-naïve persons with HIV starting integrase inhibitors compared to non-nucleoside reverse transcriptase inhibitors or protease inhibitors in a large observational cohort in the United States and Canada.

IntroductionWeight gain following antiretroviral therapy (ART) initiation is common, potentially predisposing some persons with HIV (PWH) to cardio-metabolic disease. We assessed relationships between ART drug class and weight change among treatment-naïve PWH initiating ART in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD).MethodsAdult, treatment-naïve PWH in NA-ACCORD initiating integrase strand transfer inhibitor (INSTI), protease inhibitor (PI) or non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based ART on/after 1 January 2007 were followed through 31 December 2016. Multivariate linear mixed effects models estimated weight up to five years after ART initiation, adjusting for age, sex, race, cohort site, HIV acquisition mode, treatment year, and baseline weight, plasma HIV-1 RNA level and CD4+ cell count. Due to shorter follow-up for PWH receiving newer INSTI drugs, weights for specific INSTIs were estimated at two years. Secondary analyses using logistic regression and all covariates from primary analyses assessed factors associated with &gt;10% weight gain at two and five years.ResultsAmong 22,972 participants, 87% were male, and 41% were white. 49% started NNRTI-, 31% started PI- and 20% started INSTI-based regimens (1624 raltegravir (RAL), 2085 elvitegravir (EVG) and 929 dolutegravir (DTG)). PWH starting INSTI-based regimens had mean estimated five-year weight change of +5.9kg, compared to +3.7kg for NNRTI and +5.5kg for PI. Among PWH starting INSTI drugs, mean estimated two-year weight change was +7.2kg for DTG, +5.8kg for RAL and +4.1kg for EVG. Women, persons with lower baseline CD4+ cell counts, and those initiating INSTI-based regimens had higher odds of &gt;10% body weight increase at two years (adjusted odds ratio&nbsp;=&nbsp;1.37, 95% confidence interval: 1.20 to 1.56 vs. NNRTI).ConclusionsPWH initiating INSTI-based regimens gained, on average, more weight compared to NNRTI-based regimens. This phenomenon may reflect heterogeneous effects of ART agents on body weight regulation that require further exploration

A Cluster Randomized Trial of Routine HIV-1 Viral Load Monitoring in Zambia: Study Design, Implementation, and Baseline Cohort Characteristics

The benefit of routine HIV-1 viral load (VL) monitoring of patients on antiretroviral therapy (ART) in resource-constrained settings is uncertain because of the high costs associated with the test and the limited treatment options. We designed a cluster randomized controlled trial to compare the use of routine VL testing at ART-initiation and at 3, 6, 12, and 18 months, versus our local standard of care (which uses immunological and clinical criteria to diagnose treatment failure, with discretionary VL testing when the two do not agree).Dedicated study personnel were integrated into public-sector ART clinics. We collected participant information in a dedicated research database. Twelve ART clinics in Lusaka, Zambia constituted the units of randomization. Study clinics were stratified into pairs according to matching criteria (historical mortality rate, size, and duration of operation) to limit the effect of clustering, and independently randomized to the intervention and control arms. The study was powered to detect a 36% reduction in mortality at 18 months.From December 2006 to May 2008, we completed enrollment of 1973 participants. Measured baseline characteristics did not differ significantly between the study arms. Enrollment was staggered by clinic pair and truncated at two matched sites.A large clinical trial of routing VL monitoring was successfully implemented in a dynamic and rapidly growing national ART program. Close collaboration with local health authorities and adequate reserve staff were critical to success. Randomized controlled trials such as this will likely prove valuable in determining long-term outcomes in resource-constrained settings.Clinicaltrials.gov NCT00929604