Functional Imaging of the Outer Retinal Complex using High Fidelity Imaging Retinal Densitometry

We describe a new technique, high fidelity Imaging Retinal Densitometry (IRD), which probes the functional integrity of the outer retinal complex. We demonstrate the ability of the technique to map visual pigment optical density and synthesis rates in eyes with and without macular disease. A multispectral retinal imaging device obtained precise measurements of retinal reflectance over space and time. Data obtained from healthy controls and 5 patients with intermediate AMD, before and after photopigment bleaching, were used to quantify visual pigment metrics. Heat maps were plotted to summarise the topography of rod and cone pigment kinetics and descriptive statistics conducted to highlight differences between those with and without AMD. Rod and cone visual pigment synthesis rates in those with AMD (v = 0.043 SD 0.019 min-1 and v = 0.119 SD 0.046 min-1, respectively) were approximately half those observed in healthy controls (v = 0.079 SD 0.024 min-1 for rods and v = 0.206 SD 0.069 min-1 for cones). By mapping visual pigment kinetics across the central retina, high fidelity IRD provides a unique insight into outer retinal complex function. This new technique will improve the phenotypic characterisation, diagnosis and treatment monitoring of various ocular pathologies, including AMD

{HST Studies of the WLM Galaxy. II. The Star Formation History from Field Stars

HST F555W and F814W photometry of a portion of the WLM galaxy are presented. The distance modulus is determined via fitting of the entire color-magnitude diagram to be (m-M)_0 = 24.88 +/- 0.09, which is consistent with the RGB tip distance. The galaxy's measurable star formation history appears to have begun no more than 12 Gyr ago, with about half of WLM's total star formation (by mass) formed before 9 Gyr ago. The star formation rate gradually decreased, until a recent increase in activity starting between 1 and 2.5 Gyr ago. This is still continuing to the present time, and is concentrated in the bar of the galaxy, as shown by the difference in recent star formation rates in the three WF chips.Comment: 20 pages, 7 figures to be published in Ap

Turbulent superfluid profiles in a counterflow channel

We have developed a two-dimensional model of quantised vortices in helium II moving under the influence of applied normal fluid and superfluid in a counterflow channel. We predict superfluid and vortex-line density profiles which could be experimentally tested using recently developed visualization techniques.Comment: 3 double figures, 9 page

Diagnostic DNA Methylation Biomarkers for Renal Cell Carcinoma:A Systematic Review

CONTEXT: The 5-yr survival of early-stage renal cell carcinoma (RCC) is approximately 93%, but once metastasised, the 5-yr survival plummets to 12%, indicating that early RCC detection is crucial to improvement in survival. DNA methylation biomarkers have been suggested to be of potential diagnostic value; however, their current state of clinical translation is unclear and a comprehensive overview is lacking. OBJECTIVE: To systematically review and summarise all literature regarding diagnostic DNA methylation biomarkers for RCC. EVIDENCE ACQUISITION: We performed a systematic literature review of PubMed, EMBASE, Medline, and Google Scholar up to January 2019, according to the Preferred Reporting Items for Systematic Review and Meta-Analysis of Diagnostic Test Accuracy Studies (PRISMA-DTA) guidelines. Included studies were scored according to the Standards for Reporting of Diagnostic Accuracy Studies (STARD) criteria. Forest plots were generated to summarise diagnostic performance of all biomarkers. Level of evidence (LoE) and potential risk of bias were determined for all included studies. EVIDENCE SYNTHESIS: After selection, 19 articles reporting on 44 diagnostic DNA methylation biomarkers and 11 multimarker panels were included; however, only 15 biomarkers were independently validated. STARD scores varied from 4 to 13 out of 23 points, with a median of 10 points. Large variation in subgroups, methods, and primer locations was observed. None of the reported biomarkers exceeded LoE III, and the majority of studies reported inadequately. CONCLUSIONS: None of the reported biomarkers exceeded LoE III, indicating their limited clinical utility. Moreover, study reproducibility and further development of these RCC biomarkers are greatly hampered by inadequate reporting. PATIENT SUMMARY: In this report, we reviewed whether specific biomarkers could be used to diagnose the most common form of kidney cancer. We conclude that due to limited evidence and reporting inconsistencies, none of these biomarkers can be used in clinical practice, and further development towards clinical use is hindered

Flow Phase Diagram for the Helium Superfluids

The flow phase diagram for He II and $^3$He-B is established and discussed based on available experimental data and the theory of Volovik [JETP Letters {\bf{78}} (2003) 553]. The effective temperature - dependent but scale - independent Reynolds number $Re_{eff}=1/q=(1+\alpha')/\alpha$, where $\alpha$ and $\alpha'$ are the mutual friction parameters and the superfluid Reynolds number characterizing the circulation of the superfluid component in units of the circulation quantum are used as the dynamic parameters. In particular, the flow diagram allows identification of experimentally observed turbulent states I and II in counterflowing He II with the turbulent regimes suggested by Volovik.Comment: 2 figure

Instability of vortex array and transitions to turbulent states in rotating helium II

We consider superfluid helium inside a container which rotates at constant angular velocity and investigate numerically the stability of the array of quantized vortices in the presence of an imposed axial counterflow. This problem was studied experimentally by Swanson {\it et al.}, who reported evidence of instabilities at increasing axial flow but were not able to explain their nature. We find that Kelvin waves on individual vortices become unstable and grow in amplitude, until the amplitude of the waves becomes large enough that vortex reconnections take place and the vortex array is destabilized. The eventual nonlinear saturation of the instability consists of a turbulent tangle of quantized vortices which is strongly polarized. The computed results compare well with the experiments. Finally we suggest a theoretical explanation for the second instability which was observed at higher values of the axial flow

What next for preimplantation genetic screening? High mitotic chromosome instability rate provides the biological basis for the low success rate

Preimplantation genetic screening is being scrutinized, as recent randomized clinical trials failed to observe the expected significant increase in live birth rates following fluorescence in situ hybridization (FISH)-based screening. Although these randomized clinical trials are criticized on their design, skills or premature stop, it is generally believed that well-designed and well-executed randomized clinical trials would resolve the debate about the potential benefit of preimplantation genetic screening. Since FISH can analyze only a limited number of chromosomal loci, some of the embryos transferred might be diagnosed as ‘normal’ but in fact be aneuploid for one or more chromosomes not tested. Hence, genome-wide array comparative genome hybridization screening enabling aneuploidy detection of all chromosomes was thought to be a first step toward a better design. We recently showed array screening indeed enables accurate determination of the copy number state of all chromosomes in a single cell. Surprisingly, however, this genome-wide array screening revealed a much higher frequency and complexity of chromosomal aberrations in early embryos than anticipated, with imbalances in a staggering 90% of all embryos. The mitotic error rate in cleavage stage embryos was proven to be higher than the meiotic aneuploidy rate and as a consequence, the genome of a single blastomere is not representative for the genome of the other cells of the embryo. Hence, potentially viable embryos will be discarded upon screening a single blastomere. This observation provides a biological basis for the failure of the randomized clinical trials to increase baby-take-home rates using FISH on cleavage stage embroys

Investigating The Possible Anomaly Between Nebular and Stellar Oxygen Abundances in the Dwarf Irregular Galaxy WLM

We obtained new optical spectra of 13 H II regions in WLM with EFOSC2; oxygen abundances are derived for nine H II regions. The temperature-sensitive [O III] 4363 emission line was measured in two bright H II regions HM7 and HM9. The direct oxygen abundances for HM7 and HM9 are 12+log(O/H) = 7.72 +/- 0.04 and 7.91 +/- 0.04, respectively. We adopt a mean oxygen abundance of 12+log(O/H) = 7.83 +/- 0.06. This corresponds to [O/H] = -0.83 dex, or 15% of the solar value. In H II regions where [O III] 4363 was not measured, oxygen abundances derived with bright-line methods are in general agreement with direct values of the oxygen abundance to an accuracy of about 0.2 dex. In general, the present measurements show that the H II region oxygen abundances agree with previous values in the literature. The nebular oxygen abundances are marginally consistent with the mean stellar magnesium abundance ([Mg/H] = -0.62). However, there is still a 0.62 dex discrepancy in oxygen abundance between the nebular result and the A-type supergiant star WLM15 ([O/H] = -0.21). Non-zero reddening values derived from Balmer line ratios were found in H II regions near a second H I peak. There may be a connection between the location of the second H I peak, regions of higher extinction, and the position of WLM15 on the eastern side of the galaxy.Comment: Accepted, Ap.J.; 19 pages (AASTeX 5.2) with 6 figures. Full paper with color figures at http://www.astro.umn.edu/~hlee

The Resolved Structure and Dynamics of an Isolated Dwarf Galaxy: A VLT and Keck Spectroscopic Survey of WLM

We present spectroscopic data for 180 red giant branch stars in the isolated dwarf irregular galaxy WLM. Observations of the Calcium II triplet lines in spectra of RGB stars covering the entire galaxy were obtained with FORS2 at the VLT and DEIMOS on Keck II allowing us to derive velocities, metallicities, and ages for the stars. With accompanying photometric and radio data we have measured the structural parameters of the stellar and gaseous populations over the full galaxy. The stellar populations show an intrinsically thick configuration with $0.39 \leq q_{0} \leq 0.57$. The stellar rotation in WLM is measured to be $17 \pm 1$ km s$^{-1}$, however the ratio of rotation to pressure support for the stars is $V/\sigma \sim 1$, in contrast to the gas whose ratio is seven times larger. This, along with the structural data and alignment of the kinematic and photometric axes, suggests we are viewing WLM as a highly inclined oblate spheroid. Stellar rotation curves, corrected for asymmetric drift, are used to compute a dynamical mass of $4.3\pm 0.3\times10^{8}$M$_{\odot}$ at the half light radius ($r_{h} = 1656 \pm 49$ pc). The stellar velocity dispersion increases with stellar age in a manner consistent with giant molecular cloud and substructure interactions producing the heating in WLM. Coupled with WLM's isolation, this suggests that the extended vertical structure of its stellar and gaseous components and increase in stellar velocity dispersion with age are due to internal feedback, rather than tidally driven evolution. These represent some of the first observational results from an isolated Local Group dwarf galaxy which can offer important constraints on how strongly internal feedback and secular processes modulate SF and dynamical evolution in low mass isolated objects.Comment: 14 Pages, 17 figures, 3 tables. Accepted for publication in Ap