The use of admissions simulation to stabilize ancillary workloads

As part of the planning of a new hospital, an analysis was per formed to determine the number of procedures that would be performed in each of nineteen ancillary departments on a day of the week basis. Because the planned occupancy was not the maximum possible, attempts were made using simulation to smooth the daily ancillary loads by varying the admission day of elective, urgent inpatient and outpatient loads. The methodology, sample outputs, and main conclusions are presented.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/69095/2/10.1177_003754978404300203.pd

Optical Detection of Degraded Therapeutic Proteins

The quality of therapeutic proteins such as hormones, subunit and conjugate vaccines, and antibodies is critical to the safety and efficacy of modern medicine. Identifying malformed proteins at the point-of-care can prevent adverse immune reactions in patients; this is of special concern when there is an insecure supply chain resulting in the delivery of degraded, or even counterfeit, drug product. Identification of degraded protein, for example human growth hormone, is demonstrated by applying automated anomaly detection algorithms. Detection of the degraded protein differs from previous applications of machine-learning and classification to spectral analysis: only example spectra of genuine, high-quality drug products are used to construct the classifier. The algorithm is tested on Raman spectra acquired on protein dilutions typical of formulated drug product and at sample volumes of 25 μL, below the typical overfill (waste) volumes present in vials of injectable drug product. The algorithm is demonstrated to c orrectly classify anomalous recombinant human growth hormone (rhGH) with 92% sensitivity and 98% specificity even when the algorithm has only previously encountered high-quality drug product.United States. Defense Advanced Research Projects Agency (Contract N66001-13-C-4025

The properties of extragalactic radio sources selected at 20 GHz

We present some first results on the variability, polarization and general properties of radio sources selected in a blind survey at 20 GHz, the highest frequency at which a sensitive radio survey has been carried out over a large area of sky. Sources with flux densities above 100 mJy in the AT20G Pilot Survey at declination -60 to -70 were observed at up to three epochs during 2002-4, including near-simultaneous measurements at 5, 8 and 18 GHz in 2003. Of the 173 sources detected, 65% are candidate QSOs, BL Lac objects or blazars, 20% galaxies and 15% faint (b > 22 mag) optical objects or blank fields. On a 1-2 year timescale, the general level of variability at 20 GHz appears to be low. For the 108 sources with good-quality measurements in both 2003 and 2004, the median variability index at 20 GHz was 6.9% and only five sources varied by more than 30% in flux density. Most sources in our sample show low levels of linear polarization (typically 1-5%), with a median fractional polarization of 2.3% at 20 GHz. There is a trend for fainter sources to show higher fractional polarization. At least 40% of sources selected at 20GHz have strong spectral curvature over the frequency range 1-20 GHz. We use a radio `two-colour diagram' to characterize the radio spectra of our sample, and confirm that the radio-source population at 20 GHz (which is also the foreground point-source population for CMB anisotropy experiments like WMAP and Planck) cannot be reliably predicted by extrapolating the results of surveys at lower frequencies. As a result, direct selection at 20 GHz appears to be a more efficient way of identifying 90 GHz phase calibrators for ALMA than the currently-proposed technique of extrapolation from all-sky surveys at 1-5 GHz.Comment: 14-page paper plus 5-page data table. Replaced with published versio

An image-based search for pulsars among Fermi unassociated LAT sources

We describe an image-based method that uses two radio criteria, compactness, and spectral index, to identify promising pulsar candidates among Fermi Large Area Telescope (LAT) unassociated sources. These criteria are applied to those radio sources from the Giant Metrewave Radio Telescope all-sky survey at 150 MHz (TGSS ADR1) found within the error ellipses of unassociated sources from the 3FGL catalogue and a preliminary source list based on 7 yr of LAT data. After follow-up interferometric observations to identify extended or variable sources, a list of 16 compact, steep-spectrum candidates is generated. An ongoing search for pulsations in these candidates, in gamma rays and radio, has found 6 ms pulsars and one normal pulsar. A comparison of this method with existing selection criteria based on gamma-ray spectral and variability properties suggests that the pulsar discovery space using Fermi may be larger than previously thought. Radio imaging is a hitherto underutilized source selection method that can be used, as with other multiwavelength techniques, in the search for Fermi pulsars

Mutation-enrichment next-generation sequencing for quantitative detection of KRAS mutations in urine cell-free DNA from patients with advanced cancers

Purpose: Tumor-derived cell-free DNA (cfDNA) from urine of patients with cancer offers noninvasive biological material for detection of cancer-related molecular abnormalities such as mutations in Exon 2 of KRASExperimental Design: A quantitative, mutation-enrichment next-generation sequencing test for detecting KRASG12/G13 mutations in urine cfDNA was developed, and results were compared with clinical testing of archival tumor tissue and plasma cfDNA from patients with advanced cancer.Results: With 90 to 110 mL of urine, the KRASG12/G13 cfDNA test had an analytical sensitivity of 0.002% to 0.006% mutant copies in wild-type background. In 71 patients, the concordance between urine cfDNA and tumor was 73% (sensitivity, 63%; specificity, 96%) for all patients and 89% (sensitivity, 80%; specificity, 100%) for patients with urine samples of 90 to 110 mL. Patients had significantly fewer KRASG12/G13 copies in urine cfDNA during systemic therapy than at baseline or disease progression (P = 0.002). Compared with no changes or increases in urine cfDNA KRASG12/G13 copies during therapy, decreases in these measures were associated with longer median time to treatment failure (P = 0.03).Conclusions: A quantitative, mutation-enrichment next-generation sequencing test for detecting KRASG12/G13 mutations in urine cfDNA had good concordance with testing of archival tumor tissue. Changes in mutated urine cfDNA were associated with time to treatment failure

Zirconium complexes of bipyrrolidine derived salan ligands for the isoselective polymerisation of rac-lactide

We report a series of Zr(iv) 2,2′-bipyrrolidine–salan derived complexes and their exploitation for the ROP of rac-lactide to afford highly isotactically enriched PLA.</p

Structure of Metaphase Chromosomes: A Role for Effects of Macromolecular Crowding

In metaphase chromosomes, chromatin is compacted to a concentration of several hundred mg/ml by mechanisms which remain elusive. Effects mediated by the ionic environment are considered most frequently because mono- and di-valent cations cause polynucleosome chains to form compact ∼30-nm diameter fibres in vitro, but this conformation is not detected in chromosomes in situ. A further unconsidered factor is predicted to influence the compaction of chromosomes, namely the forces which arise from crowding by macromolecules in the surrounding cytoplasm whose measured concentration is 100–200 mg/ml. To mimic these conditions, chromosomes were released from mitotic CHO cells in solutions containing an inert volume-occupying macromolecule (8 kDa polyethylene glycol, 10.5 kDa dextran, or 70 kDa Ficoll) in 100 µM K-Hepes buffer, with contaminating cations at only low micromolar concentrations. Optical and electron microscopy showed that these chromosomes conserved their characteristic structure and compaction, and their volume varied inversely with the concentration of a crowding macromolecule. They showed a canonical nucleosomal structure and contained the characteristic proteins topoisomerase IIα and the condensin subunit SMC2. These observations, together with evidence that the cytoplasm is crowded in vivo, suggest that macromolecular crowding effects should be considered a significant and perhaps major factor in compacting chromosomes. This model may explain why ∼30-nm fibres characteristic of cation-mediated compaction are not seen in chromosomes in situ. Considering that crowding by cytoplasmic macromolecules maintains the compaction of bacterial chromosomes and has been proposed to form the liquid crystalline chromosomes of dinoflagellates, a crowded environment may be an essential characteristic of all genomes