What patients see online: assessing the online identities of Pennsylvania dermatologists

Introduction: Patients use the internet to search for health-related information. We sought to characterize the information that patients find when searching for dermatologists on Google. Methods: The Centers for Medicare and Medicaid Services (CMS) Physician Comparable Downloadable File was utilized to identify all Medicare-participating dermatologists practicing in Pennsylvania (PA). A custom Google-based search engine was used to search each dermatologist. Up to the top 10 results for each physician were then sorted into: (1) physician, hospital, or healthcare system, (2) third-party, (3) social media, (4) academic journal articles, or (5) other. Results: Within the CMS, 519 health care providers (53.9% male, 46.1% female) self-identified as dermatologists practicing in PA. At least one search result was obtained for each physician (4,963 total search results). About 30.6% (1,519) search results were hospital, health system, or physician-controlled websites, and 26.6% (1,318) were third-party websites (1,318; 26.6%). Social media websites accounted for 601 (12.1%) hits whereas peer-reviewed academic journal websites generated 135 (2.7%) results. One-way chi-square analysis showed domains were not randomly distributed across the five categories (P<0.0001). Conclusion: Dermatologists should be better aware of their digital presence and the strategies to better control their online identity

Polygenic adaptation of rosette growth in Arabidopsis thaliana

Altres ajuts: CERCA Programme/Generalitat de CatalunyaThe rate at which plants grow is a major functional trait in plant ecology. However, little is known about its evolution in natural populations. Here, we investigate evolutionary and environmental factors shaping variation in the growth rate of Arabidopsis thaliana. We used plant diameter as a proxy to monitor plant growth over time in environments that mimicked latitudinal differences in the intensity of natural light radiation, across a set of 278 genotypes sampled within four broad regions, including an outgroup set of genotypes from China. A field experiment conducted under natural conditions confirmed the ecological relevance of the observed variation. All genotypes markedly expanded their rosette diameter when the light supply was decreased, demonstrating that environmental plasticity is a predominant source of variation to adapt plant size to prevailing light conditions. Yet, we detected significant levels of genetic variation both in growth rate and growth plasticity. Genome-wide association studies revealed that only 2 single nucleotide polymorphisms associate with genetic variation for growth above Bonferroni confidence levels. However, marginally associated variants were significantly enriched among genes with an annotated role in growth and stress reactions. Polygenic scores computed from marginally associated variants confirmed the polygenic basis of growth variation. For both light regimes, phenotypic divergence between the most distantly related population (China) and the various regions in Europe is smaller than the variation observed within Europe, indicating that the evolution of growth rate is likely to be constrained by stabilizing selection. We observed that Spanish genotypes, however, reach a significantly larger size than Northern European genotypes. Tests of adaptive divergence and analysis of the individual burden of deleterious mutations reveal that adaptive processes have played a more important role in shaping regional differences in rosette growth than maladaptive evolution. The rate at which plants grow is a major functional trait in plant ecology. However, little is known about its genetic variation in natural populations. Here, we investigate genetic and environmental factors shaping variation in the growth rate of Arabidopsis thaliana and ask whether genetic variation in plant growth contributes to adaptation to local environmental conditions. We grew plants under two light regimes that mimic latitudinal differences in the intensity of natural light radiation, and measured plant diameter as it grew over time. When the light supply was decreased, plant diameter grew more slowly but reached a markedly larger final size, confirming that plants can adjust their growth to prevailing light conditions. Yet, we also detected significant levels of genetic variation both in growth rate and in how the growth dynamics is adjusted to the light conditions. We show that this variation is encoded by many loci of small effect that are hard to locate in the genome but overall significantly enriched among genes associated with growth and stress reactions. We further observe that Spanish genotypes tended to reach, on average, a significantly larger rosette size than Northern European genotypes. Tests of adaptive divergence indicate that these differences may reflect adaptation to local environmental conditions

Metallicity and Alpha-Element Abundance Measurement in Red Giant Stars from Medium Resolution Spectra

We present a technique that applies spectral synthesis to medium resolution spectroscopy (MRS, R ~ 6000) in the red (6300 A < lambda < 9100 A) to measure [Fe/H] and [alpha/Fe] of individual red giant stars over a wide metallicity range. We apply our technique to 264 red giant stars in seven Galactic globular clusters and demonstrate that it reproduces the metallicities and alpha enhancements derived from high resolution spectroscopy (HRS). The MRS technique excludes the three Ca II triplet lines and instead relies on a plethora of weaker lines. Unlike empirical metallicity estimators, such as the equivalent width of the Ca II triplet, the synthetic method presented here is applicable over an arbitrarily wide metallicity range and is independent of assumptions about the alpha enhancement. Estimates of cluster mean [Fe/H] from different HRS studies show typical scatter of ~0.1 dex but can be larger than 0.2 dex for metal-rich clusters. The scatter in HRS abundance estimates among individual stars in a given cluster is also comparable to 0.1 dex. By comparison, the scatter among MRS [Fe/H] estimates of individual stars in a given cluster is ~0.1 dex for most clusters but 0.17 dex for the most metal-rich cluster, M71 ( = -0.8). A star-by-star comparison of HRS vs. MRS [alpha/Fe] estimates indicates that the precision in [alpha/Fe]_MRS is 0.05 dex. The errors in [Fe/H]_MRS and [alpha/Fe]_MRS increase beyond 0.25 dex only below signal-to-noise ratios of 20 A^(-1), which is typical for existing MRS of the red giant stars in Leo I, one of the most distant Milky Way satellites (250 kpc).Comment: 16 pages, 17 figures, 7 tables, accepted for publication in Ap

Population sequencing data reveal a compendium of mutational processes in human germline

Mechanistic processes underlying human germline mutations remain largely unknown.Variation in mutation rate and spectra along the genome is informative about the biological mechanisms. We statistically decompose this variation into separate processes using a blind source separation technique. The analysis of a large-scale whole genome sequencing dataset (TOPMed) reveals nine processes that explain the variation in mutation properties between loci. Seven of these processes lend themselves to a biological interpretation. One process is driven by bulky DNA lesions that resolve asymmetrically with respect to transcription and replication. Two processes independently track direction of replication fork and replication timing. We identify a mutagenic effect of active demethylation primarily acting in regulatory regions. We also demonstrate that a recently discovered mutagenic process specific to oocytes can be localized solely from population sequencing data. This process is spread across all chromosomes and is highly asymmetric with respect to the direction of transcription, suggesting a major role of DNA damage

Linking dwarf galaxies to halo building blocks with the most metal-poor star in Sculptor

Current cosmological models indicate that the Milky Way's stellar halo was assembled from many smaller systems. Based on the apparent absence of the most metal-poor stars in present-day dwarf galaxies, recent studies claimed that the true Galactic building blocks must have been vastly different from the surviving dwarfs. The discovery of an extremely iron-poor star (S1020549) in the Sculptor dwarf galaxy based on a medium-resolution spectrum cast some doubt on this conclusion. However, verification of the iron-deficiency and measurements of additional elements, such as the alpha-element Mg, are mandatory for demonstrating that the same type of stars produced the metals found in dwarf galaxies and the Galactic halo. Only then can dwarf galaxy stars be conclusively linked to early stellar halo assembly. Here we report high-resolution spectroscopic abundances for 11 elements in S1020549, confirming the iron abundance of less than 1/4000th that of the Sun, and showing that the overall abundance pattern mirrors that seen in low-metallicity halo stars, including the alpha-elements. Such chemical similarity indicates that the systems destroyed to form the halo billions of years ago were not fundamentally different from the progenitors of present-day dwarfs, and suggests that the early chemical enrichment of all galaxies may be nearly identical.Comment: 16 pages, including 2 figures. Accepted for publication in Nature. It is embargoed for discussion in the press until formal publication in Natur

Accounting for variability when resurrecting dormant propagules substantiates their use in eco-evolutionary studies

There has been a steady rise in the use of dormant propagules to study biotic responses to environmental change over time. This is particularly important for organisms that strongly mediate ecosystem processes, as changes in their traits over time can provide a unique snapshot into the structure and function of ecosystems from decades to millennia in the past. Understanding sources of bias and variation is a challenge in the field of resurrection ecology, including those that arise because often-used measurements like seed germination success are imperfect indicators of propagule viability. Using a Bayesian statistical framework, we evaluated sources of variability and tested for zero-inflation and overdispersion in data from 13 germination trials of soil-stored seeds of Schoenoplectus americanus, an ecosystem engineer in coastal salt marshes in the Chesapeake Bay. We hypothesized that these two model structures align with an ecological understanding of dormancy and revival: zero-inflation could arise due to failed germinations resulting from inviability or failed attempts to break dormancy, and overdispersion could arise by failing to measure important seed traits. A model that accounted for overdispersion, but not zero-inflation, was the best fit to our data. Tetrazolium viability tests corroborated this result: most seeds that failed to germinate did so because they were inviable, not because experimental methods failed to break their dormancy. Seed viability declined exponentially with seed age and was mediated by seed provenance and experimental conditions. Our results provide a framework for accounting for and explaining variability when estimating propagule viability from soil-stored natural archives which is a key aspect of using dormant propagules in eco-evolutionary studies

The SPLASH Survey: A Spectroscopic Portrait of Andromeda's Giant Southern Stream

The giant southern stream (GSS) is the most prominent tidal debris feature in M31's stellar halo. The GSS is composed of a relatively metal-rich, high surface-brightness "core" and a lower metallicity, lower surface brightness "envelope." We present Keck/DEIMOS spectroscopy of red giant stars in six fields in the vicinity of M31's GSS and one field on Stream C, an arc-like feature on M31's SE minor axis at R=60 kpc. Several GSS-related findings and measurements are presented here. We present the innermost kinematical detection of the GSS core to date (R=17 kpc). This field also contains the continuation of a second kinematically cold component originally seen in a GSS core field at R=21 kpc. The velocity gradients of the GSS and the second component in the combined data set are parallel over a radial range of 7 kpc, suggesting a possible bifurcation in the line-of-sight velocities of GSS stars. We also present the first kinematical detection of substructure in the GSS envelope. Using kinematically identified samples, we show that the envelope debris has a ~0.7 dex lower mean photometric metallicity and possibly higher intrinsic velocity dispersion than the GSS core. The GSS is also identified in the field of the M31 dSph satellite And I; the GSS in this field has a metallicity distribution identical to that of the GSS core. We confirm the presence of two kinematically cold components in Stream C, and measure intrinsic velocity dispersions of ~10 and ~4 km/s. This compilation of the kinematical (mean velocity, intrinsic velocity dispersion) and chemical properties of stars in the GSS core and envelope, coupled with published surface brightness measurements and wide-area star-count maps, will improve constraints on the orbit and internal structure of the dwarf satellite progenitor.Comment: Accepted for publication in Ap

Multi-Element Abundance Measurements from Medium-Resolution Spectra. II. Catalog of Stars in Milky Way Dwarf Satellite Galaxies

We present a catalog of Fe, Mg, Si, Ca, and Ti abundances for 2961 red giant stars that are likely members of eight dwarf satellite galaxies of the Milky Way (MW): Sculptor, Fornax, Leo I, Sextans, Leo II, Canes Venatici I, Ursa Minor, and Draco. For the purposes of validating our measurements, we also observed 445 red giants in MW globular clusters and 21 field red giants in the MW halo. The measurements are based on Keck/DEIMOS medium-resolution spectroscopy combined with spectral synthesis. We estimate uncertainties in [Fe/H] by quantifying the dispersion of [Fe/H] measurements in a sample of stars in monometallic globular clusters. We estimate uncertainties in Mg, Si, Ca, and Ti abundances by comparing our medium-resolution spectroscopic measurements to high-resolution spectroscopic abundances of the same stars. For this purpose, our DEIMOS sample included 132 red giants with published high-resolution spectroscopy in globular clusters, the MW halo field, and dwarf galaxies. The standard deviations of the differences in [Fe/H] and [alpha/Fe] (the average of [Mg/Fe], [Si/Fe], [Ca/Fe], and [Ti/Fe]) between the two samples is 0.15 and 0.16, respectively. This catalog represents the largest sample of multi-element abundances in dwarf galaxies to date. The next papers in this series draw conclusions on the chemical evolution, gas dynamics, and star formation histories from the catalog presented here. The wide range of dwarf galaxy luminosity reveals the dependence of dwarf galaxy chemical evolution on galaxy stellar mass.Comment: 26 pages, 22 figures, 4 machine-readable tables (available in the source file; click "Other formats"); accepted for publication in ApJ Supplements; updated acknowledgments in v

In silico design and biological evaluation of a dual specificity kinase inhibitor targeting cell cycle progression and angiogenesis

Methodology: We have utilized a rational in silico-based approach to demonstrate the design and study of a novel compound that acts as a dual inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2) and cyclin-dependent kinase 1 (CDK1). This compound acts by simultaneously inhibiting pro-Angiogenic signal transduction and cell cycle progression in primary endothelial cells. JK-31 displays potent in vitro activity against recombinant VEGFR2 and CDK1/cyclin B proteins comparable to previously characterized inhibitors. Dual inhibition of the vascular endothelial growth factor A (VEGF-A)-mediated signaling response and CDK1-mediated mitotic entry elicits anti-Angiogenic activity both in an endothelial-fibroblast co-culture model and a murine ex vivo model of angiogenesis

Where do stars explode in the ISM? -- The distribution of dense gas around massive stars and supernova remnants in M33

Star formation in galaxies is regulated by turbulence, outflows, gas heating and cloud dispersal -- processes which depend sensitively on the properties of the interstellar medium (ISM) into which supernovae (SNe) explode. Unfortunately, direct measurements of ISM environments around SNe remain scarce, as SNe are rare and often distant. Here we demonstrate a new approach: mapping the ISM around the massive stars that are soon to explode. This provides a much larger census of explosion sites than possible with only SNe, and allows comparison with sensitive, high-resolution maps of the atomic and molecular gas from the Jansky VLA and ALMA. In the well-resolved Local Group spiral M33, we specifically observe the environments of red supergiants (RSGs, progenitors of Type II SNe), Wolf-Rayet stars (WRs, tracing stars $>$30 M$_{\odot}$, and possibly future stripped-envelope SNe), and supernova remnants (SNRs, locations where SNe have exploded). We find that massive stars evolve not only in dense, molecular-dominated gas (with younger stars in denser gas), but also a substantial fraction ($\sim$45\% of WRs; higher for RSGs) evolve in lower-density, atomic-gas-dominated, inter-cloud media. We show that these measurements are consistent with expectations from different stellar-age tracer maps, and can be useful for validating SN feedback models in numerical simulations of galaxies. Along with the discovery of a 20-pc diameter molecular gas cavity around a WR, these findings re-emphasize the importance of pre-SN/correlated-SN feedback evacuating the dense gas around massive stars before explosion, and the need for high-resolution (down to pc-scale) surveys of the multi-phase ISM in nearby galaxies.Comment: 34 pages, 14 figures. Submitted to ApJ. Comments welcome! The density distributions will be made publicly available after journal acceptance of manuscript. Please feel free to contact us in the meantime if you would like to use the