Improving healthcare supply chains and decision making in the management of pharmaceuticals

The rising cost of quality healthcare is becoming an increasing concern. A significant part of healthcare cost is the pharmaceutical supply component. Improving healthcare supply chains is critical not only because of the financial magnitude but also because it impacts so many people. Efforts such as this project are essential in understanding the current operations of healthcare pharmacy systems and in offering decision support tools to managers struggling to make the best use of organizational resources. The purpose of this study is to address the objectives of a local hospital that exhibits typical problems in pharmacy supply chain management. We analyze the pharmacy supply network structure and the different, often conflicting goals in the decisions of the various stakeholders. We develop quantitative models useful in optimizing supply chain management and inventory management practices. We provide decision support tools that improve operational, tactical, and strategic decision making in the pharmacy supply chain and inventory management of pharmaceuticals. On one hand, advanced computerized technology that manages pharmaceutical dispensation and automates the ordering process offers considerable progress to support pharmacy product distribution. On the other hand, the available information is not utilized to help the managers in making the appropriate decisions and control the supply chain management. Quantitative methods are presented that provide simplified, practical solutions to pharmacy objectives and serve as decision support tools. For operational inventory decisions we provide the min and max par levels (reorder point and order up to level) that control the automated ordering system for pharmaceuticals. These parameters are based on two near-optimal allocation policies of cycle stock and safety stock under storage space constraint. For the tactical decision we demonstrate the influence of varying inventory holding cost rates on setting the optimal reorder point and order quantity for items. We present a strategic decision support tool to analyze the tradeoffs among the refill workload, the emergency workload, and the variety of drugs offered. We reveal the relationship of these tradeoffs to the three key performance indicators at a local care unit: the expected number of daily refills, the service level, and the storage space utilization

The Birth of a Galaxy. II. The Role of Radiation Pressure

Massive stars provide feedback that shapes the interstellar medium of galaxies at all redshifts and their resulting stellar populations. Here we present three adaptive mesh refinement radiation hydrodynamics simulations that illustrate the impact of momentum transfer from ionising radiation to the absorbing gas on star formation in high-redshift dwarf galaxies. Momentum transfer is calculated by solving the radiative transfer equation with a ray tracing algorithm that is adaptive in spatial and angular coordinates. We find that momentum input partially affects star formation by increasing the turbulent support to a three-dimensional rms velocity equal to the circular velocity of early haloes. Compared to a calculation that neglects radiation pressure, the star formation rate is decreased by a factor of five to 1.8 x 10^{-2} Msun/yr in a dwarf galaxy with a dark matter and stellar mass of 2.0 x 10^8 and 4.5 x 10^5 solar masses, respectively, when radiation pressure is included. Its mean metallicity of 10^{-2.1} Z_sun is consistent with the observed dwarf galaxy luminosity-metallicity relation. However, what one may naively expect from the calculation without radiation pressure, the central region of the galaxy overcools and produces a compact, metal-rich stellar population with an average metallicity of 0.3 Z_sun, indicative of an incorrect physical recipe. In addition to photo-heating in HII regions, radiation pressure further drives dense gas from star forming regions, so supernovae feedback occurs in a warmer and more diffuse medium, launching metal-rich outflows. Capturing this aspect and a temporal separation between the start of radiative and supernova feedback are numerically important in the modeling of galaxies to avoid the "overcooling problem". We estimate that dust in early low-mass galaxies is unlikely to aid in momentum transfer from radiation to the gas.Comment: 18 pages, 11 figures, replaced with accepted version, MNRAS. Minor changes with the conclusions unaffecte

Catching Element Formation In The Act

Gamma-ray astronomy explores the most energetic photons in nature to address some of the most pressing puzzles in contemporary astrophysics. It encompasses a wide range of objects and phenomena: stars, supernovae, novae, neutron stars, stellar-mass black holes, nucleosynthesis, the interstellar medium, cosmic rays and relativistic-particle acceleration, and the evolution of galaxies. MeV gamma-rays provide a unique probe of nuclear processes in astronomy, directly measuring radioactive decay, nuclear de-excitation, and positron annihilation. The substantial information carried by gamma-ray photons allows us to see deeper into these objects, the bulk of the power is often emitted at gamma-ray energies, and radioactivity provides a natural physical clock that adds unique information. New science will be driven by time-domain population studies at gamma-ray energies. This science is enabled by next-generation gamma-ray instruments with one to two orders of magnitude better sensitivity, larger sky coverage, and faster cadence than all previous gamma-ray instruments. This transformative capability permits: (a) the accurate identification of the gamma-ray emitting objects and correlations with observations taken at other wavelengths and with other messengers; (b) construction of new gamma-ray maps of the Milky Way and other nearby galaxies where extended regions are distinguished from point sources; and (c) considerable serendipitous science of scarce events -- nearby neutron star mergers, for example. Advances in technology push the performance of new gamma-ray instruments to address a wide set of astrophysical questions.Comment: 14 pages including 3 figure

The Swift Ultra-Violet/Optical Telescope

The UV/Optical Telescope (UVOT) is one of three instruments flying aboard the Swift Gamma-ray Observatory. It is designed to capture the early (approximately 1 minute) UV and optical photons from the afterglow of gamma-ray bursts in the 170-600 nm band as well as long term observations of these afterglows. This is accomplished through the use of UV and optical broadband filters and grisms. The UVOT has a modified Ritchey-Chretien design with micro-channel plate intensified charged-coupled device detectors that record the arrival time of individual photons and provide sub-arcsecond positioning of sources. We discuss some of the science to be pursued by the UVOT and the overall design of the instrument.Comment: 55 Pages, 28 Figures, To be published in Space Science Review

Evidence for Type Ia Supernova Diversity from Ultraviolet Observations with the Hubble Space Telescope

We present ultraviolet (UV) spectroscopy and photometry of four Type Ia supernovae (SNe 2004dt, 2004ef, 2005M, and 2005cf) obtained with the UV prism of the Advanced Camera for Surveys on the Hubble Space Telescope. This dataset provides unique spectral time series down to 2000 Angstrom. Significant diversity is seen in the near maximum-light spectra (~ 2000--3500 Angstrom) for this small sample. The corresponding photometric data, together with archival data from Swift Ultraviolet/Optical Telescope observations, provide further evidence of increased dispersion in the UV emission with respect to the optical. The peak luminosities measured in uvw1/F250W are found to correlate with the B-band light-curve shape parameter dm15(B), but with much larger scatter relative to the correlation in the broad-band B band (e.g., ~0.4 mag versus ~0.2 mag for those with 0.8 < dm15 < 1.7 mag). SN 2004dt is found as an outlier of this correlation (at > 3 sigma), being brighter than normal SNe Ia such as SN 2005cf by ~0.9 mag and ~2.0 mag in the uvw1/F250W and uvm2/F220W filters, respectively. We show that different progenitor metallicity or line-expansion velocities alone cannot explain such a large discrepancy. Viewing-angle effects, such as due to an asymmetric explosion, may have a significant influence on the flux emitted in the UV region. Detailed modeling is needed to disentangle and quantify the above effects.Comment: 17 pages, 13 figures, accepted by Ap

Development and Validation of a Symptom-Based Activity Index for Adults With Eosinophilic Esophagitis

Standardized instruments are needed to assess the activity of eosinophilic esophagitis (EoE), to provide endpoints for clinical trials and observational studies. We aimed to develop and validate a patient-reported outcome (PRO) instrument and score, based on items that could account for variations in patients’ assessments of disease severity. We also evaluated relationships between patients’ assessment of disease severity and EoE-associated endoscopic, histologic, and laboratory findings

The agora high-resolution galaxy simulations comparison project

We introduce the Assembling Galaxies Of Resolved Anatomy (AGORA) project, a comprehensive numerical study of well-resolved galaxies within the ΛCDM cosmology. Cosmological hydrodynamic simulations with force resolutions of ~100 proper pc or better will be run with a variety of code platforms to follow the hierarchical growth, star formation history, morphological transformation, and the cycle of baryons in and out of eight galaxies with halo masses Mvir 1010, 1011, 1012, and 1013 M☉ at z = 0 and two different ("violent" and "quiescent") assembly histories. The numerical techniques and implementations used in this project include the smoothed particle hydrodynamics codes GADGET and GASOLINE, and the adaptive mesh refinement codes ART, ENZO, and RAMSES. The codes share common initial conditions and common astrophysics packages including UV background, metal-dependent radiative cooling, metal and energy yields of supernovae, and stellar initial mass function. These are described in detail in the present paper. Subgrid star formation and feedback prescriptions will be tuned to provide a realistic interstellar and circumgalactic medium using a non-cosmological disk galaxy simulation. Cosmological runs will be systematically compared with each other using a common analysis toolkit and validated against observations to verify that the solutions are robust—i.e., that the astrophysical assumptions are responsible for any success, rather than artifacts of particular implementations. The goals of the AGORA project are, broadly speaking, to raise the realism and predictive power of galaxy simulations and the understanding of the feedback processes that regulate galaxy "metabolism." The initial conditions for the AGORA galaxies as well as simulation outputs at various epochs will be made publicly available to the community. The proof-of-concept dark-matter-only test of the formation of a galactic halo with a z = 0 mass of Mvir 1.7 × 1011 M☉ by nine different versions of the participating codes is also presented to validate the infrastructure of the project

Development of a Core Outcome Set for Therapeutic Studies in Eosinophilic Esophagitis (COREOS).

BACKGROUND Endpoints used to determine treatment efficacy in eosinophilic esophagitis (EoE) have evolved over time. With multiple novel therapies in development for EoE, harmonization of outcomes measures will facilitate evidence synthesis and appraisal when comparing different treatments. OBJECTIVE To develop a core outcome set (COS) for controlled and observational studies of pharmacologic and diet interventions in adult and pediatric patients with EoE. METHODS Candidate outcomes were generated from systematic literature reviews and patient engagement interviews and surveys. Consensus was established using an iterative Delphi process, with items voted on using a 9-point Likert scale and with feedback from other participants to allow score refinement. Consensus meetings were held to ratify the outcome domains of importance and the core outcome measures. Stakeholders were recruited internationally and included adult and pediatric gastroenterologists, allergists, dieticians, pathologists, psychologists, researchers, and methodologists. RESULTS The COS consists of four outcome domains for controlled and observational studies: histopathology, endoscopy, patient-reported symptoms, and EoE-specific quality of life (QoL). A total of 69 stakeholders (response rate 95.8%) prioritized 42 outcomes in a two-round Delphi process and the final ratification meeting generated consensus on 33 outcome measures. These included measurement of the peak eosinophil count, EoE Histology Scoring System, EoE Endoscopic Reference Score, and patient-reported measures of dysphagia and QoL. CONCLUSIONS This interdisciplinary collaboration involving global stakeholders has produced a COS that can be applied to adult and pediatric studies of pharmacologic and diet therapies for EoE, which will facilitate meaningful treatment comparisons and improve the quality of data synthesis

Symptoms Have Modest Accuracy in Detecting Endoscopic and Histologic Remission in Adults With Eosinophilic Esophagitis.

Background &amp; aimsIt is not clear whether symptoms alone can be used to estimate the biologic activity of eosinophilic esophagitis (EoE). We aimed to evaluate whether symptoms can be used to identify patients with endoscopic and histologic features of remission.MethodsBetween April 2011 and June 2014, we performed a prospective, observational study and recruited 269 consecutive adults with EoE (67% male; median age, 39 years old) in Switzerland and the United States. Patients first completed the validated symptom-based EoE activity index patient-reported outcome instrument and then underwent esophagogastroduodenoscopy with esophageal biopsy collection. Endoscopic and histologic findings were evaluated with a validated grading system and standardized instrument, respectively. Clinical remission was defined as symptom score &lt;20 (range, 0-100); histologic remission was defined as a peak count of &lt;20 eosinophils/mm(2) in a high-power field (corresponds to approximately &lt;5 eosinophils/median high-power field); and endoscopic remission as absence of white exudates, moderate or severe rings, strictures, or combination of furrows and edema. We used receiver operating characteristic analysis to determine the best symptom score cutoff values for detection of remission.ResultsOf the study subjects, 111 were in clinical remission (41.3%), 79 were in endoscopic remission (29.7%), and 75 were in histologic remission (27.9%). When the symptom score was used as a continuous variable, patients in endoscopic, histologic, and combined (endoscopic and histologic remission) remission were detected with area under the curve values of 0.67, 0.60, and 0.67, respectively. A symptom score of 20 identified patients in endoscopic remission with 65.1% accuracy and histologic remission with 62.1% accuracy; a symptom score of 15 identified patients with both types of remission with 67.7% accuracy.ConclusionsIn patients with EoE, endoscopic or histologic remission can be identified with only modest accuracy based on symptoms alone. At any given time, physicians cannot rely on lack of symptoms to make assumptions about lack of biologic disease activity in adults with EoE. ClinicalTrials.gov, Number: NCT00939263