The Radio Synchrotron Background: Conference Summary and Report

We summarize the radio synchrotron background workshop that took place 2017 July 19–21 at the University of Richmond. This first scientific meeting dedicated to the topic was convened because current measurements of the diffuse radio monopole reveal a surface brightness that is several times higher than can be straightforwardly explained by known Galactic and extragalactic sources and processes, rendering it by far the least well understood photon background at present. It was the conclusion of a majority of the participants that the radio monopole level is at or near that reported by the ARCADE 2 experiment and inferred from several absolutely calibrated zero-level lower frequency radio measurements, and unanimously agreed that the production of this level of surface brightness, if confirmed, represents a major outstanding question in astrophysics. The workshop reached a consensus on the next priorities for investigations of the radio synchrotron background

Designing an automated clinical decision support system to match clinical practice guidelines for opioid therapy for chronic pain

Abstract Background Opioid prescribing for chronic pain is common and controversial, but recommended clinical practices are followed inconsistently in many clinical settings. Strategies for increasing adherence to clinical practice guideline recommendations are needed to increase effectiveness and reduce negative consequences of opioid prescribing in chronic pain patients. Methods Here we describe the process and outcomes of a project to operationalize the 2003 VA/DOD Clinical Practice Guideline for Opioid Therapy for Chronic Non-Cancer Pain into a computerized decision support system (DSS) to encourage good opioid prescribing practices during primary care visits. We based the DSS on the existing ATHENA-DSS. We used an iterative process of design, testing, and revision of the DSS by a diverse team including guideline authors, medical informatics experts, clinical content experts, and end-users to convert the written clinical practice guideline into a computable algorithm to generate patient-specific recommendations for care based upon existing information in the electronic medical record (EMR), and a set of clinical tools. Results The iterative revision process identified numerous and varied problems with the initially designed system despite diverse expert participation in the design process. The process of operationalizing the guideline identified areas in which the guideline was vague, left decisions to clinical judgment, or required clarification of detail to insure safe clinical implementation. The revisions led to workable solutions to problems, defined the limits of the DSS and its utility in clinical practice, improved integration into clinical workflow, and improved the clarity and accuracy of system recommendations and tools. Conclusions Use of this iterative process led to development of a multifunctional DSS that met the approval of the clinical practice guideline authors, content experts, and clinicians involved in testing. The process and experiences described provide a model for development of other DSSs that translate written guidelines into actionable, real-time clinical recommendations.http://deepblue.lib.umich.edu/bitstream/2027.42/78267/1/1748-5908-5-26.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/2/1748-5908-5-26.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/3/1748-5908-5-26-S3.TIFFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/4/1748-5908-5-26-S2.TIFFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/5/1748-5908-5-26-S1.TIFFPeer Reviewe

A Blue Spectral Shift of the Hemoglobin Soret Band Correlates with the Age (Time Since Deposition) of Dried Bloodstains

The ability to determine the time since deposition of a bloodstain found at a crime scene could prove invaluable to law enforcement investigators, defining the time frame in which the individual depositing the evidence was present. Although various methods of accomplishing this have been proposed, none has gained widespread use due to poor time resolution and weak age correlation. We have developed a method for the estimation of the time since deposition (TSD) of dried bloodstains using UV-VIS spectrophotometric analysis of hemoglobin (Hb) that is based upon its characteristic oxidation chemistry. A detailed study of the Hb Soret band (λmax = 412 nm) in aged bloodstains revealed a blue shift (shift to shorter wavelength) as the age of the stain increases. The extent of this shift permits, for the first time, a distinction to be made between bloodstains that were deposited minutes, hours, days and weeks prior to recovery and analysis. The extent of the blue shift was found to be a function of ambient relative humidity and temperature. The method is extremely sensitive, requiring as little as a 1 µl dried bloodstain for analysis. We demonstrate that it might be possible to perform TSD measurements at the crime scene using a portable low-sample-volume spectrophotometer

Changes in Dry State Hemoglobin over Time Do Not Increase the Potential for Oxidative DNA Damage in Dried Blood

BACKGROUND: Hemoglobin (Hb) is the iron-containing oxygen transport protein present in the red blood cells of vertebrates. Ancient DNA and forensic scientists are particularly interested in Hb reactions in the dry state because both regularly encounter aged, dried bloodstains. The DNA in such stains may be oxidatively damaged and, in theory, may be deteriorated by the presence of Hb. To understand the nature of the oxidative systems potentially available to degrade DNA in the presence of dried Hb, we need to determine what molecular species Hb forms over time. These species will determine what type of iron (i.e. Fe(2+)/Fe(3+)/Fe(4+)) is available to participate in further chemical reactions. The availability of "free" iron will affect the ability of the system to undergo Fenton-type reactions which generate the highly reactive hydroxyl radical (OH*). The OH* can directly damage DNA. METHODOLOGY/PRINCIPAL FINDINGS: Oxygenated Hb (oxyHb) converts over time to oxidized Hb (metHb), but this happens more quickly in the dry state than in the hydrated state, as shown by monitoring stabilized oxyHb. In addition, dry state oxyHb converts into at least one other unknown species other than metHb. Although "free" iron was detectable as both Fe(2+) and Fe(3+) in dry and hydrated oxyHb and metHb, the amount of ions detected did not increase over time. There was no evidence that Hb becomes more prone to generating OH* as it ages in either the hydrated or dry states. CONCLUSIONS: The Hb molecule in the dried state undergoes oxidative changes and releases reactive Fe(II) cations. These changes, however, do not appear to increase the ability of Hb to act as a more aggressive Fenton reagent over time. Nevertheless, the presence of Hb in the vicinity of DNA in dried bloodstains creates the opportunity for OH*-induced oxidative damage to the deoxyribose sugar and the DNA nucleobases

The Case for Probe-class NASA Astrophysics Missions

Astrophysics spans an enormous range of questions on scales from individual planets to the entire cosmos. To address the richness of 21st century astrophysics requires a corresponding richness of telescopes spanning all bands and all messengers. Much scientific benefit comes from having the multi-wavelength capability available at the same time. Most of these bands,or measurement sensitivities, require space-based missions. Historically, NASA has addressed this need for breadth with a small number of flagship-class missions and a larger number of Explorer missions. While the Explorer program continues to flourish, there is a large gap between Explorers and strategic missions. A fortunate combination of new astrophysics technologies with new, high capacity, low dollar-per-kg to orbit launchers, and new satellite buses allow for cheaper missions with capabilities approaching strategic mission levels. NASA has recognized these developments by calling for Probe-class mission ideas for mission studies, spanning most of the electromagnetic spectrum from GeV gamma-rays to the far infrared, and the new messengers of neutrinos and ultra-high energy cosmic rays. The key insight from the Probes exercise is that order-of-magnitude advances in science performance metrics are possible across the board for initial total cost estimates in the range 500M-1B dollars

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Pleiotropy among common genetic loci identified for cardiometabolic disorders and C-reactive protein.

Pleiotropic genetic variants have independent effects on different phenotypes. C-reactive protein (CRP) is associated with several cardiometabolic phenotypes. Shared genetic backgrounds may partially underlie these associations. We conducted a genome-wide analysis to identify the shared genetic background of inflammation and cardiometabolic phenotypes using published genome-wide association studies (GWAS). We also evaluated whether the pleiotropic effects of such loci were biological or mediated in nature. First, we examined whether 283 common variants identified for 10 cardiometabolic phenotypes in GWAS are associated with CRP level. Second, we tested whether 18 variants identified for serum CRP are associated with 10 cardiometabolic phenotypes. We used a Bonferroni corrected p-value of 1.1×10-04 (0.05/463) as a threshold of significance. We evaluated the independent pleiotropic effect on both phenotypes using individual level data from the Women Genome Health Study. Evaluating the genetic overlap between inflammation and cardiometabolic phenotypes, we found 13 pleiotropic regions. Additional analyses showed that 6 regions (APOC1, HNF1A, IL6R, PPP1R3B, HNF4A and IL1F10) appeared to have a pleiotropic effect on CRP independent of the effects on the cardiometabolic phenotypes. These included loci where individuals carrying the risk allele for CRP encounter higher lipid levels and risk of type 2 diabetes. In addition, 5 regions (GCKR, PABPC4, BCL7B, FTO and TMEM18) had an effect on CRP largely mediated through the cardiometabolic phenotypes. In conclusion, our results show genetic pleiotropy among inflammation and cardiometabolic phenotypes. In addition to reverse causation, our data suggests that pleiotropic genetic variants partially underlie the association between CRP and cardiometabolic phenotypes