MedZIM: Mediation analysis for Zero-Inflated Mediators with applications to microbiome data

The human microbiome can contribute to the pathogenesis of many complex diseases such as cancer and Alzheimer's disease by mediating disease-leading causal pathways. However, standard mediation analysis is not adequate in the context of microbiome data due to the excessive number of zero values in the data. Zero-valued sequencing reads, commonly observed in microbiome studies, arise for technical and/or biological reasons. Mediation analysis approaches for analyzing zero-inflated mediators are still lacking largely because of challenges raised by the zero-inflated data structure: (a) disentangling the mediation effect induced by the point mass at zero; and (b) identifying the observed zero-valued data points that are actually not zero (i.e., false zeros). We develop a novel mediation analysis method under the potential-outcomes framework to fill this gap. We show that the mediation effect of the microbiome can be decomposed into two components that are inherent to the two-part nature of zero-inflated distributions. The first component corresponds to the mediation effect attributable to a unit-change over the positive relative abundance and the second component corresponds to the mediation effect attributable to discrete binary change of the mediator from zero to a non-zero state. With probabilistic models to account for observing zeros, we also address the challenge with false zeros. A comprehensive simulation study and the applications in two real microbiome studies demonstrate that our approach outperforms existing mediation analysis approaches.Comment: Corresponding: Zhigang L

K-shell photoionization of ground-state Li-like boron ions [B2+^{2+}]: Experiment and Theory

Absolute cross sections for the K-shell photoionization of ground-state Li-like boron [B$^{2+}$(1s$^2$2s $^2$S)] ions were measured by employing the ion-photon merged-beams technique at the Advanced Light Source synchrotron radiation facility. The energy ranges 197.5--200.5 eV, 201.9--202.1 eV of the [1s(2s\,2p)$^3$P]$^2$P${\rm ^o}$ and [1s(2s\,2p)$^1$P] $^2$P${\rm ^o}$ resonances, respectively, were investigated using resolving powers of up to 17\,600. The energy range of the experiments was extended to about 238.2 eV yielding energies of the most prominent [1s(2$\ell$\,n$\ell^{\prime}$)]$^2$P$^o$ resonances with an absolute accuracy of the order of 130 ppm. The natural linewidths of the [1s(2s\,2p)$^3$P] $^2$P${\rm ^o}$ and [1s(2s\,2p)$^1$P] $^2$P${\rm ^o}$ resonances were measured to be $4.8 \pm 0.6$ meV and $29.7 \pm 2.5$ meV, respectively, which compare favourably with theoretical results of 4.40 meV and 30.53 meV determined using an intermediate coupling R-matrix method.Comment: 6 figures and 2 table

Photoionization of Metastable O^+ Ions: Experiment and Theory

Relevant data is available at: http://www.astronomy.ohio-state.edu/~nahar/nahar_radiativeatomicdata/index.htmlHigh-resolution absolute experimental measurements and two independent theoretical calculations were performed for photoionization of O^+ ions from the ^2 P° and ^2 D° metastable levels and from the ^4 S° ground state in the photon energy range 30–35.5 eV. This is believed to be the first comparison of experiment and theory to be reported for photoionization from metastable states of ions. While there is correspondence between the predicted and measured positions and relative strengths of the resonances, the cross-section magnitudes and fine structure are sensitive to the choice of basis states.The experimental work was supported in part by the DOE Divisions of Chemical Sciences, Geosciences and Biosciences, and Materials Sciences, by the DOE Facilities Initiative, by Nevada DOE/EPSCoR, by CONACyT and DGAPA (Mexico), and by CNPq (Brazil). The theoretical work was supported in part by NSF, by the Ohio Supercomputer Center, by ITAMP/Harvard-Smithsonian, and by EPSRC (UK)

Photoionization of the fullerene ion C60+

Photoionization cross section of the fullerene ion C60+ has been calculated within a single-electron approximation and also by using a consistent many-body theory accounting for many-electron correlations.Comment: 8 pages, 3 figure

In Vivo assessment of a tissue-engineered vascular graft combining a biodegradable elastomeric scaffold and muscle-derived stem cells in a rat model

Limited autologous vascular graft availability and poor patency rates of synthetic grafts for bypass or replacement of small-diameter arteries remain a concern in the surgical community. These limitations could potentially be improved by a tissue engineering approach. We report here our progress in the development and in vivo testing of a stem-cell-based tissue-engineered vascular graft for arterial applications. Poly(ester urethane)urea scaffolds (length=10mm; inner diameter=1.2mm) were created by thermally induced phase separation (TIPS). Compound scaffolds were generated by reinforcing TIPS scaffolds with an outer electrospun layer of the same biomaterial (ES-TIPS). Both TIPS and ES-TIPS scaffolds were bulk-seeded with 10×106 allogeneic, LacZ-transfected, muscle-derived stem cells (MDSCs), and then placed in spinner flask culture for 48h. Constructs were implanted as interposition grafts in the abdominal aorta of rats for 8 weeks. Angiograms and histological assessment were performed at the time of explant. Cell-seeded constructs showed a higher patency rate than the unseeded controls: 65% (ES-TIPS) and 53% (TIPS) versus 10% (acellular TIPS). TIPS scaffolds had a 50% mechanical failure rate with aneurysmal formation, whereas no dilation was observed in the hybrid scaffolds. A smooth-muscle-like layer of cells was observed near the luminal surface of the constructs that stained positive for smooth muscle α-actin and calponin. LacZ+ cells were shown to be engrafted in the remodeled construct. A confluent layer of von Willebrand Factor-positive cells was observed in the lumen of MDSC-seeded constructs, whereas acellular controls showed platelet and fibrin deposition. This is the first evidence that MDSCs improve patency and contribute to the remodeling of a tissue-engineered vascular graft for arterial applications. © 2010 Mary Ann Liebert, Inc

K-shell photoionization of ground-state Li-like carbon ions [C3+^{3+}]: experiment, theory and comparison with time-reversed photorecombination

Absolute cross sections for the K-shell photoionization of ground-state Li-like carbon [C$^{3+}$(1s$^2$2s $^2$S)] ions were measured by employing the ion-photon merged-beams technique at the Advanced Light Source. The energy ranges 299.8--300.15 eV, 303.29--303.58 eV and 335.61--337.57 eV of the [1s(2s2p)$^3$P]$^2$P, [1s(2s2p)$^1$P]$^2$P and [(1s2s)$^3$S 3p]$^2$P resonances, respectively, were investigated using resolving powers of up to 6000. The autoionization linewidth of the [1s(2s2p)$^1$P]$^2$P resonance was measured to be $27 \pm 5$ meV and compares favourably with a theoretical result of 26 meV obtained from the intermediate coupling R-Matrix method. The present photoionization cross section results are compared with the outcome from photorecombination measurements by employing the principle of detailed balance.Comment: 3 figures and 2 table

Predictors of vitamin D status and its association with parathyroid hormone in young New Zealand children.

BACKGROUND: Despite increased awareness of the adverse health effects of low vitamin D status, few studies have evaluated 25-hydroxyvitamin D [25(OH)D] status in young children. OBJECTIVES: We aimed to assess vitamin D status on the basis of 25(OH)D and its relation with parathyroid hormone (PTH) and to identify possible predictors of 25(OH)D status in young children living in a country with minimal vitamin D fortification. DESIGN: Serum 25(OH)D and PTH concentrations were measured in a cross-sectional sample of children aged 12-22 mo [n = 193 for 25(OH)D, n = 144 for PTH] living in Dunedin, New Zealand (latitude: 45 degrees S). Anthropometric, dietary, and sociodemographic data were collected. RESULTS: The majority of children sampled in the summer (94%; 47 of 50) had 25(OH)D >50 nmol/L; however, nearly 80% of children sampled in the winter (43 of 55) had serum concentrations 60-65 nmol/L, a plateau in PTH was evident. CONCLUSIONS: Seasonal variation in 25(OH)D concentration implies that postsummer vitamin D stores were insufficient to maintain status >50 nmol/L year-round. Examination of the predictors of 25(OH)D in our model shows few modifiable risk factors, and thus effective dietary strategies may be required if future research determines that children with 25(OH)D concentrations <50 nmol/L are at significant health risk. This trial was registered at www.actr.org.au as ACTRN12605000487617

Landmarking the brain for geometric morphometric analysis: An error study

Neuroanatomic phenotypes are often assessed using volumetric analysis. Although powerful and versatile, this approach is limited in that it is unable to quantify changes in shape, to describe how regions are interrelated, or to determine whether changes in size are global or local. Statistical shape analysis using coordinate data from biologically relevant landmarks is the preferred method for testing these aspects of phenotype. To date, approximately fifty landmarks have been used to study brain shape. Of the studies that have used landmark-based statistical shape analysis of the brain, most have not published protocols for landmark identification or the results of reliability studies on these landmarks. The primary aims of this study were two-fold: (1) to collaboratively develop detailed data collection protocols for a set of brain landmarks, and (2) to complete an intra- and inter-observer validation study of the set of landmarks. Detailed protocols were developed for 29 cortical and subcortical landmarks using a sample of 10 boys aged 12 years old. Average intra-observer error for the final set of landmarks was 1.9 mm with a range of 0.72 mm-5.6 mm. Average inter-observer error was 1.1 mm with a range of 0.40 mm-3.4 mm. This study successfully establishes landmark protocols with a minimal level of error that can be used by other researchers in the assessment of neuroanatomic phenotypes. © 2014 Chollet et al

Ultrasound Biomicroscopy Measurements of the Normal Thickness for the Ciliary Body and the Iris in a Middle East Population

Purpose: Ciliary body (CB) and iris thicknesses may change with certain eye diseases as well as between different populations. Here, we report Ultrasound Biomicroscopy Measurements (UBM) of the normal thickness for the CB and the iris from a homogenous population in the Middle East. Patients and Methods: Sonomed 35-MHz (SONOMED, INC. New York, USA) images were obtained at 4 radial meridians, and the thickness was measured at 3 locations along the radial length of the iris and at the thickest part of the CB. Parameters included mean thickness, median thickness, range, and standard deviation. Results: Of 46 adult patients, 83 normal eyes were included in this analysis. The overall mean, median iris thicknesses at the iris root, midway along the radial length of the iris, and at the juxtapupillary margin in mm were 0.42, 0.41 ± 0.08, 0.52, 0.51± 0.08, and 0.72, 0.71± 0.1, respectively. The overall mean, median thicknesses of the CB and CB + ciliary processes in mm were 0.72, 0.71 ± 0.1, and 1.42, 1.37 ± 0.2 respectively. Gender, age, side, and height had no impact on iris and/or CB thickness (p&gt;0.05). However, the iris thickness was significantly thicker in the superior quadrant than inferiorly, and in the nasal quadrant than the temporal quadrant (p=0.04), and the CB thickness and the CB + ciliary processes thickness were significantly thicker in the superior quadrant than inferiorly (P = 0.04 and 0.02 consecutively). Conclusion: We measured in this study the normal thickness of the CB and the iris in normal eyes from homogenous population in the Middle East using ultrasound biomicroscopy. Our findings are essential for the ophthalmic community worldwide and in the Middle East region and can be used as a normative thickness data for the iris and CB in healthy eyes