A Pilot Study of the Performance Characteristics of the D-dimer in Presumed Sepsis

Objectives: To determine if a sensitive D-dimer assay can exclude progression to organ dysfunction, death, and intensive care unit (ICU) admission in patients presenting to the emergency department (ED) with suspected infection, and if increasing levels of D-dimer are predictive of those end points.Methods: The study took place at two academic EDs, both located in tertiary care hospitals. This was a prospective convenience sample of adult patients presenting with an infective process and at least two of four criteria for the Systemic Inflammatory Response Syndrome. We measured D-dimer levels in the participants and abstracted their records for the end points. Sensitivity and specificity were calculated and receiver operating characteristic analysis was performed to determine if a higher cutoff would have a greater specificity for our end points.Results: We enrolled 134 patients. Twelve were excluded from analysis (10 for lack of a D-dimer, one for recent surgery, and one for complete loss to follow up). Using the cutoff of 0.4 established by our laboratories as positive, the D-dimer had a sensitivity of 94% (CI95; 76-99) for organ dysfunction in the ED, 93% (72-99) for organ dysfunction at 48 hours, 93% (81-98) for ICU admission, and 100% (63-100) for 30-day mortality. However, at this cutoff, specificity was not statistically significant. Significantly raising the cutoff for a positive resulted in a decrease in sensitivity but improved specificity.Conclusion: This study was limited by its nonconsecutive patient recruitment and sample size. A normal D-dimer may exclude progression to organ dysfunction, ICU admission, and death and, at higher cutoff levels, could help risk stratify patients presenting to the ED with signs of sepsis.[West J Emerg Med. 2010;11(2):173-179.

The Sextet Arcs: a Strongly Lensed Lyman Break Galaxy in the ACS Spectroscopic Galaxy Survey towards Abell 1689

We present results of the HST Advanced Camera for Surveys spectroscopic ground-based redshift survey in the field of A1689. We measure 98 redshifts, increasing the number of spectroscopically confirmed objects by sixfold. We present two spectra from this catalog of the Sextet Arcs, images which arise from a strongly-lensed Lyman Break Galaxy (LBG) at a redshift of z=3.038. Gravitational lensing by the cluster magnifies its flux by a factor of ~16 and produces six separate images with a total r-band magnitude of r_625=21.7. The two spectra, each of which represents emission from different regions of the LBG, show H I and interstellar metal absorption lines at the systemic redshift. Significant variations are seen in Ly-alpha profile across a single galaxy, ranging from strong absorption to a combination of emission plus absorption. A spectrum of a third image close to the brightest arc shows Ly-alpha emission at the same redshift as the LBG, arising from either another spatially distinct region of the galaxy, or from a companion galaxy close to the LBG. Taken as a group, the Ly-alpha equivalent width in these three spectra decreases with increasing equivalent width of the strongest interstellar absorption lines. We discuss how these variations can be used to understand the physical conditions in the LBG. Intrinsically, this LBG is faint, ~0.1L*, and forming stars at a modest rate, ~4 solar masses per year. We also detect absorption line systems toward the Sextet Arcs at z=2.873 and z=2.534. The latter system is seen across two of our spectra.Comment: Accepted for publication in Ap

Distinct ECM mechanosensing pathways regulate microtubule dynamics to control endothelial cell branching morphogenesis

The compliance and dimensionality of the ECM regulate distinct changes in microtubule growth speed and growth persistence

The genetic architecture of DNA replication timing in human pluripotent stem cells.

DNA replication follows a strict spatiotemporal program that intersects with chromatin structure but has a poorly understood genetic basis. To systematically identify genetic regulators of replication timing, we exploited inter-individual variation in human pluripotent stem cells from 349 individuals. We show that the human genome's replication program is broadly encoded in DNA and identify 1,617 cis-acting replication timing quantitative trait loci (rtQTLs) - sequence determinants of replication initiation. rtQTLs function individually, or in combinations of proximal and distal regulators, and are enriched at sites of histone H3 trimethylation of lysines 4, 9, and 36 together with histone hyperacetylation. H3 trimethylation marks are individually repressive yet synergistically associate with early replication. We identify pluripotency-related transcription factors and boundary elements as positive and negative regulators of replication timing, respectively. Taken together, human replication timing is controlled by a multi-layered mechanism with dozens of effectors working combinatorially and following principles analogous to transcription regulation

Hubble Space Telescope WFC3 Early Release Science: Emission-Line Galaxies from Infrared Grism Observations

We present grism spectra of emission-line galaxies (ELGs) from 0.6-1.6 microns from the Wide Field Camera 3 on the Hubble Space Telescope. These new infrared grism data augment previous optical Advanced Camera for Surveys G800L 0.6-0.95 micron grism data in GOODS-South from the PEARS program, extending the wavelength covereage well past the G800L red cutoff. The ERS grism field was observed at a depth of 2 orbits per grism, yielding spectra of hundreds of faint objects, a subset of which are presented here. ELGs are studied via the Ha, [OIII], and [OII] emission lines detected in the redshift ranges 0.2<z<1.4, 1.2<z<2.2 and 2.0<z<3.3 respectively in the G102 (0.8-1.1 microns; R~210) and G141 (1.1-1.6 microns; R~130) grisms. The higher spectral resolution afforded by the WFC3 grisms also reveals emission lines not detectable with the G800L grism (e.g., [SII] and [SIII] lines). From these relatively shallow observations, line luminosities, star-formation rates, and grism spectroscopic redshifts are determined for a total of 48 ELGs to m(AB)~25 mag. Seventeen GOODS-South galaxies that previously only had photometric redshifts now have new grism-spectroscopic redshifts, in some cases with large corrections to the photometric redshifts (Delta(z)~0.3-0.5). Additionally, one galaxy had no previously-measured redshift but now has a secure grism-spectroscopic redshift, for a total of 18 new GOODS-South spectroscopic redshifts. The faintest source in our sample has a magnitude m(AB)=26.9 mag. The ERS grism data also reflect the expected trend of lower specific star formation rates for the highest mass galaxies in the sample as a function of redshift, consistent with downsizing and discovered previously from large surveys. These results demonstrate the remarkable efficiency and capability of the WFC3 NIR grisms for measuring galaxy properties to faint magnitudes and redshifts to z>2.Comment: Accepted for publication in AJ. Updated to include referee comments. Updated sample using improved reduction contains 23 new galaxies (Table 1; Figures 2 & 3

The Neutral Hydrogen Properties of Galaxies in Gas-rich Groups

We present an analysis of the integrated neutral hydrogen (Hi) properties for 27 galaxies within nine low mass, gas-rich, late-type dominated groups which we denote \Choirs". We find that majority of the central Choir galaxies have average Hi content: they have a normal gas-mass fraction with respect to isolated galaxies of the same stellar mass. In contrast, we find more satellite galaxies with a lower gas-mass fraction than isolated galaxies of the same stellar mass. A likely reason for the lower gas content in these galaxies is tidal stripping. Both the specific star formation rate and the star formation efficiency of the central group galaxies are similar to galaxies in isolation. The Choir satellite galaxies have similar specific star formation rate as galaxies in isolation, therefore satellites that exhibit a higher star formation efficiency simply owe it to their lower gas-mass fractions. We find that the most Hi massive galaxies have the largest Hi discs and fall neatly onto the Hi size-mass relation, while outliers are galaxies that are experiencing interactions. We find that high specific angular momentum could be a reason for galaxies to retain the large fraction of Hi gas in their discs. This shows that for the Choir groups with no evidence of interactions, as well as those with traces of minor mergers, the internal galaxy properties dominate over the effects of residing in a group. The probed galaxy properties strengthen evidence that the Choir groups represent the early stages of group assembly

Directed evolution of a magnetic resonance imaging contrast agent for noninvasive imaging of dopamine

The development of molecular probes that allow in vivo imaging of neural signaling processes with high temporal and spatial resolution remains challenging. Here we applied directed evolution techniques to create magnetic resonance imaging (MRI) contrast agents sensitive to the neurotransmitter dopamine. The sensors were derived from the heme domain of the bacterial cytochrome P450-BM3 (BM3h). Ligand binding to a site near BM3h's paramagnetic heme iron led to a drop in MRI signal enhancement and a shift in optical absorbance. Using an absorbance-based screen, we evolved the specificity of BM3h away from its natural ligand and toward dopamine, producing sensors with dissociation constants for dopamine of 3.3–8.9 μM. These molecules were used to image depolarization-triggered neurotransmitter release from PC12 cells and in the brains of live animals. Our results demonstrate the feasibility of molecular-level functional MRI using neural activity–dependent sensors, and our protein engineering approach can be generalized to create probes for other targets.Charles A. Dana Foundation. Brain and Immuno-ImagingRaymond and Beverley Sackler FoundationNational Institutes of Health (U.S.) (grant R01-DA28299)National Institutes of Health (U.S.) (grant DP2-OD2441)National Institutes of Health (U.S.) (grant R01-GM068664)Jacobs Institute for Molecular Engineering for Medicine. Jacobs Institute for Molecular Engineering for MedicineNational Institutes of Health (U.S.) (grant R01-DE013023