Observations of Binary Stars with the Differential Speckle Survey Instrument. VII. Measures from 2010 September to 2012 February at the WIYN Telescope

We report on speckle observations of binary stars carried out at the WIYN Telescope over the period from September 2010 through February 2012, providing relative astrometry for 2521 observations of 883 objects, 856 of which are double stars and 27 of which are triples. The separations measured span a range of 0.01 to 1.75 arc seconds. Wavelengths of 562 nm, 692 nm, and 880 nm were used, and differential photometry at one or more of these wavelengths is presented in most cases. Sixty-six components were resolved for the first time. We also estimate detection limits at 0.2 and 1.0 arc seconds for high-quality observations in cases where no companion was seen, a total of 176 additional objects. Detection limits vary based on observing conditions and signal-to-noise ratio, but are approximately 4 magnitudes at 0.2 arc seconds and 6 magnitudes at 1.0 arc seconds on average. Analyzing the measurement precision of the data set, we find that the individual separations obtained have linear measurement uncertainties of approximately 2 mas, and photometry is uncertain to approximately 0.1 magnitudes in general. This work provides fundamental, well-calibrated data for future orbit and mass determinations, and we present three first orbits and total mass estimates of nearby K-dwarf systems as examples of this potential

Automated recognition of malignancy mentions in biomedical literature

BACKGROUND: The rapid proliferation of biomedical text makes it increasingly difficult for researchers to identify, synthesize, and utilize developed knowledge in their fields of interest. Automated information extraction procedures can assist in the acquisition and management of this knowledge. Previous efforts in biomedical text mining have focused primarily upon named entity recognition of well-defined molecular objects such as genes, but less work has been performed to identify disease-related objects and concepts. Furthermore, promise has been tempered by an inability to efficiently scale approaches in ways that minimize manual efforts and still perform with high accuracy. Here, we have applied a machine-learning approach previously successful for identifying molecular entities to a disease concept to determine if the underlying probabilistic model effectively generalizes to unrelated concepts with minimal manual intervention for model retraining. RESULTS: We developed a named entity recognizer (MTag), an entity tagger for recognizing clinical descriptions of malignancy presented in text. The application uses the machine-learning technique Conditional Random Fields with additional domain-specific features. MTag was tested with 1,010 training and 432 evaluation documents pertaining to cancer genomics. Overall, our experiments resulted in 0.85 precision, 0.83 recall, and 0.84 F-measure on the evaluation set. Compared with a baseline system using string matching of text with a neoplasm term list, MTag performed with a much higher recall rate (92.1% vs. 42.1% recall) and demonstrated the ability to learn new patterns. Application of MTag to all MEDLINE abstracts yielded the identification of 580,002 unique and 9,153,340 overall mentions of malignancy. Significantly, addition of an extensive lexicon of malignancy mentions as a feature set for extraction had minimal impact in performance. CONCLUSION: Together, these results suggest that the identification of disparate biomedical entity classes in free text may be achievable with high accuracy and only moderate additional effort for each new application domain

HIV-1 Protease, Reverse Transcriptase, and Integrase Variation

ABSTRACT HIV-1 protease (PR), reverse transcriptase (RT), and integrase (IN) variability presents a challenge to laboratories performing genotypic resistance testing. This challenge will grow with increased sequencing of samples enriched for proviral DNA such as dried blood spots and increased use of next-generation sequencing (NGS) to detect low-abundance HIV-1 variants. We analyzed PR and RT sequences from >100,000 individuals and IN sequences from >10,000 individuals to characterize variation at each amino acid position, identify mutations indicating APOBEC-mediated G-to-A editing, and identify mutations resulting from selective drug pressure. Forty-seven percent of PR, 37% of RT, and 34% of IN positions had one or more amino acid variants with a prevalence of ≥1%. Seventy percent of PR, 60% of RT, and 60% of IN positions had one or more variants with a prevalence of ≥0.1%. Overall 201 PR, 636 RT, and 346 IN variants had a prevalence of ≥0.1%. The median intersubtype prevalence ratios were 2.9-, 2.1-, and 1.9-fold for these PR, RT, and IN variants, respectively. Only 5.0% of PR, 3.7% of RT, and 2.0% of IN variants had a median intersubtype prevalence ratio of ≥10-fold. Variants at lower prevalences were more likely to differ biochemically and to be part of an electrophoretic mixture compared to high-prevalence variants. There were 209 mutations indicative of APOBEC-mediated G-to-A editing and 326 mutations nonpolymorphic treatment selected. Identification of viruses with a high number of APOBEC-associated mutations will facilitate the quality control of dried blood spot sequencing. Identifying sequences with a high proportion of rare mutations will facilitate the quality control of NGS. IMPORTANCE Most antiretroviral drugs target three HIV-1 proteins: PR, RT, and IN. These proteins are highly variable: many different amino acids can be present at the same position in viruses from different individuals. Some of the amino acid variants cause drug resistance and occur mainly in individuals receiving antiretroviral drugs. Some variants result from a human cellular defense mechanism called APOBEC-mediated hypermutation. Many variants result from naturally occurring mutation. Some variants may represent technical artifacts. We studied PR and RT sequences from >100,000 individuals and IN sequences from >10,000 individuals to quantify variation at each amino acid position in these three HIV-1 proteins. We performed analyses to determine which amino acid variants resulted from antiretroviral drug selection pressure, APOBEC-mediated editing, and naturally occurring variation. Our results provide information essential to clinical, research, and public health laboratories performing genotypic resistance testing by sequencing HIV-1 PR, RT, and IN

Resistance Mutations to Zidovudine and Saquinavir in Patients Receiving Zidovudine plus Saquinavir or Zidovudine and Zalcitabine plus Saquinavir in AIDS Clinical Trials Group 229

The relationships among treatment regimens, plasma human immunodeficiency virus (HIV) RNA levels, and resistance mutations to saquinavir (codons 48 and 90) and zidovudine (codon 215) were examined in a cohort of 144 patients from the AIDS Clinical Trials Group 229 study. After 24-40 weeks of therapy, no patients who had received the two-drug combination (zidovudine plus saquinavir) had only codon 48 mutations, 45.8% had only codon 90 mutations, and 8.3% had both codon 48 and 90 mutations. Mutations developed by patients who had received the three-drug combination (zidovudine and zalcitabine plus saquinavir) were codon 48 alone in 1.4%, codon 90 alone in 33.3%, and both codons 48 and 90 in 4.2%. The difference between the groups showed a trend toward reduced mutations with three versus two drugs but did not reach significance (p = .11, two-sided χ2). Higher baseline HIV RNA levels correlated with the development of protease mutations. Mutations at codon 215 were present in 82% of all patients at baseline and in 87% after therap

An Automated Procedure to Identify Biomedical Articles that Contain Cancer-associated Gene Variants

The proliferation of biomedical literature makes it increasingly difficult for researchers to find and manage relevant information. However, identifying research articles containing mutation data, a requisite first step in integrating large and complex mutation data sets, is currently tedious, time-consuming and imprecise. More effective mechanisms for identifying articles containing mutation information would be beneficial both for the curation of mutation databases and for individual researchers. We developed an automated method that uses information extraction, classifier, and relevance ranking techniques to determine the likelihood of MEDLINE abstracts containing information regarding genomic variation data suitable for inclusion in mutation databases. We targeted the CDKN2A (p16) gene and the procedure for document identification currently used by CDKN2A Database curators as a measure of feasibility. A set of abstracts was manually identified from a MEDLINE search as potentially containing specific CDKN2A mutation events. A subset of these abstracts was used as a training set for a maximum entropy classifier to identify text features distinguishing relevant from not relevant abstracts. Each document was represented as a set of indicative word, word pair, and entity tagger-derived genomic variation features. When applied to a test set of 200 candidate abstracts, the classifier predicted 88 articles as being relevant; of these, 29 of 32 manuscripts in which manual curation found CDKN2A sequence variants were positively predicted. Thus, the set of potentially useful articles that a manual curator would have to review was reduced by 56%, maintaining 91% recall (sensitivity) and more than doubling precision (positive predictive value). Subsequent expansion of the training set to 494 articles yielded similar precision and recall rates, and comparison of the original and expanded trials demonstrated that the average precision improved with the larger data set. Our results show that automated systems can effectively identify article subsets relevant to a given task and may prove to be powerful tools for the broader research community. This procedure can be readily adapted to any or all genes, organisms, or sets of documents

Annual Feedback Is an Effective Tool for a Sustained Increase in Calcium Intake among Older Women

We aimed to optimize calcium intake among the 2,000+ older women taking part in the Vital D study. Calcium supplementation was not included in the study protocol. Our hypothesis was that annual feedback of calcium intake and informing women of strategies to improve calcium intake can lead to a sustained increase in the proportion of women who consume adequate levels of the mineral. Calcium intake was assessed on an annual basis using a validated short food frequency questionnaire (FFQ). Supplemental calcium intake was added to the dietary estimate. Participants and their nominated doctor were sent a letter that the participant’s estimated daily calcium intake was adequate or inadequate based on a cutoff threshold of 800 mg/day. General brief statements outlining the importance of an adequate calcium intake and bone health were included in all letters. At baseline, the median daily consumption of calcium was 980 mg/day and 67 percent of 1,951 participants had calcium intake of at least 800 mg per day. Of the 644 older women advised of an inadequate calcium intake at baseline (<800 mg/day), 386 (60%) had increased their intake by at least 100 mg/day when re-assessed twelve months later. This desirable change was sustained at 24 months after baseline with almost half of these women (303/644) consuming over 800 mg calcium per day. This study devised an efficient method to provide feedback on calcium intake to over 2,000 older women. The improvements were modest but significant and most apparent in those with a low intake at baseline. The decreased proportion of these women with an inadequate intake of calcium 12- and 24-months later, suggests this might be a practical, low cost strategy to maintain an adequate calcium intake among older women

The aesthetic items scale: A tool for the evaluation of aesthetic outcome after breast reconstruction

__Background:__ Valid tools to assess aesthetic outcomes after breast reconstructive surgery are scarce. Previously a professional aesthetic assessment scale was introduced, the Aesthetic Items Scale (AIS). We aim to determine if this method is a valid and reliable tool to assess aesthetic outcome after breast reconstructive surgery. __Methods:__ The study population was consenting women who underwent prophylactic mastectomy with subsequent implant-based breast reconstruction. The aesthetic outcome with regard to breast volume, shape, symmetry, scars, and nipple areola complex was rated on a 5-point scale using standardized photographs to give a summed total score. Photographs were evaluated by the patient, 5 plastic surgeons, and 3 mammography nurses. An overall rating of aesthetic outcome on a 1-10 scale was given separately. We determined the intraclass correlation coefficient and assessed interobserver agreement. To assess validity, we calculated the correlation between total score and overall rating of aesthetic outcome. __Results:__ Interobserver reliability was highest between plastic surgeons for the subitem and overall scores and ranged between 0.56 and 0.82. The summed score of the AIS correlates strongly with the overall rating in professionals but not in patients. __Conclusions:__ The AIS is a valid and reliable method for evaluating aesthetic outcome of breast reconstruction by plastic surgeons. The results indicate that patients judge aesthetic outcome differently, taking into account factors that are not represented in the AIS. Professionals can use this method to evaluate surgical results, but other measurements are needed to map satisfaction of the patient with her breasts

Observations with the Differential Speckle Survey Instrument. X. Preliminary Orbits of K Dwarf Binaries and Other Stars

This paper details speckle observations of binary stars taken at the Lowell Discovery Telescope, the WIYN Telescope, and the Gemini telescopes between 2016 January and 2019 September. The observations taken at Gemini and Lowell were done with the Differential Speckle Survey Instrument (DSSI), and those done at WIYN were taken with the successor instrument to DSSI at that site, the NN-EXPLORE Exoplanet Star and Speckle Imager (NESSI). In total, we present 378 observations of 178 systems and we show that the uncertainty in the measurement precision for the combined data set is ~2 mas in separation, ~1-2 degrees in position angle depending on the separation, and $\sim$0.1 magnitudes in magnitude difference. Together with data already in the literature, these new results permit 25 visual orbits and one spectroscopic-visual orbit to be calculated for the first time. In the case of the spectroscopic-visual analysis, which is done on the trinary star HD 173093, we calculate masses with precision of better than 1% for all three stars in that system. Twenty-one of the visual orbits calculated have a K dwarf as the primary star; we add these to the known orbits of K dwarf primary stars and discuss the basic orbital properties of these stars at this stage. Although incomplete, the data that exist so far indicate that binaries with K dwarf primaries tend not to have low-eccentricity orbits at separations of one to a few tens of AU, that is, on solar-system scales