High-resolution infrared spectroscopy in pursuit of C60 and other astrochemical targets

This work is primarily concerned with the development of a mid-infrared cavity ringdown spectrometer with the intent of observing rotationally-resolved vibrational spectra of C60 and other astronomically relevant molecules, including the polyoxymethylene 1,3,5-trioxane. C60 was first discovered during experiments intended to simulate the conditions found in carbon stars, and has since been observed via emission spectroscopy in several planetary nebulae as well as the inerstellar medium. Due to its low ionization potential, much of the C60 in interstellar space is expected to be ionized to C60+, which has long been suspected as one of the carriers of the diffuse interstellar bands; recent work supports this assignment, further increasing interest in the astrochemistry of C60. While these observations through emission spectroscopy have had a significant impact, emission spectroscopy is not an effective approach in cold regions of space with low ultraviolet flux - as such, obtaining a high-resolution absorption spectrum remains an important goal. This is an extension of previous development work and attempts to observe the spectrum of C60 - as the principle shortfall of those previous attempts was the the inability to vibrationally cool C60 produced via thermal vaporization, much of this following will focus on the development and validation of an alternative vaporization method involving the expansion of supercritical fluids containing the target molecules. This should allow vapor to be produced at much lower temperatures, allowing more C60 to reach the ground state in spite of inefficient supersonic cooling. The first generation source has been constructed and tested, with the results informing the design of a second-generation source that has been constructed and is currently being evaluated. In addition to the development of an improved source for cold C60, we have also implemented a new external-cavity quantum cascade laser as the light source in our instrument. This new laser has significantly improved spectral coverage when compared to the previous light source, in addition to considerably easier and more reliable frequency tuning. However, the addition of a vibration-sensitive grating as a wavelength selective element introduced an unacceptable jitter in the lasing frequency. To address this, we developed a novel laser locking system based on side-of-fringe locking to a solid germanium etalon; in order to maintain continuous wavelength tuning, the free spectral range of the etalon is tuned by stepping its angle with respect to the incident laser. This has allowed us to stabilize the laser to acceptable levels while maintaining the ability to tune its lasing frequency very precisely. Finally, we recorded, simulated, and assigned the rotationally-resolved absorption spectrum of the v16 vibrational band of 1,3,5-trioxane. In addition to the importance of trioxane to understanding formaldehyde chemistry in comets, trioxane was chosen as a means of testing the various improvements made to the spectrometer. The spectrum described in this work was obtained using the new external-cavity quantum cascade laser and locking system; efforts to evaluate the second-generation supercritical fluid expansion source will use trioxane spectroscopy to estimate the efficiency of rotational and vibrational cooling

Surveying Public Research 2 University Libraries’ Programs Supporting Digital Scholarship: A Report

Librarians at Ball State University designed and distributed a survey to libraries personnel at all public R2 research universities to assess the nature of university libraries’ engagement with digital scholarship, digital humanities, or digital research. Project researchers received 36 usable responses to the survey from individuals at 26 institutions, for an individual response rate of 12% and an institutional response rate of 35%. This report communicates core data and findings as a result of the survey project. Included is data regarding services and expertise offered by the libraries, the nature of libraries’ collaborations with researchers, technology infrastructure to support digital scholarship/digital research/digital humanities, and the nature of libraries’ participation in scholarship and public presentation regarding digital scholarship/digital research/digital humanities

Francisella tularensis Schu S4 lipopolysaccharide core sugar and o-antigen mutants are attenuated in a mouse model of tularemia

The virulence factors mediating Francisella pathogenesis are being investigated, with an emphasis on understanding how the organism evades innate immunity mechanisms. Francisella tularensis produces a lipopolysaccharide (LPS) that is essentially inert and a polysaccharide capsule that helps the organism to evade detection by components of innate immunity. Using an F. tularensis Schu S4 mutant library, we identified strains that are disrupted for capsule and O-antigen production. These serum-sensitive strains lack both capsule production and O-antigen laddering. Analysis of the predicted protein sequences for the disrupted genes (FTT1236 and FTT1238c) revealed similarity to those for waa (rfa) biosynthetic genes in other bacteria. Mass spectrometry further revealed that these proteins are involved in LPS core sugar biosynthesis and the ligation of O antigen to the LPS core sugars. The 50% lethal dose (LD(50)) values of these strains are increased 100- to 1,000-fold for mice. Histopathology revealed that the immune response to the F. tularensis mutant strains was significantly different from that observed with wild-type-infected mice. The lung tissue from mutant-infected mice had widespread necrotic debris, but the spleens lacked necrosis and displayed neutrophilia. In contrast, the lungs of wild-type-infected mice had nominal necrosis, but the spleens had widespread necrosis. These data indicate that murine death caused by wild-type strains occurs by a mechanism different from that by which the mutant strains kill mice. Mice immunized with these mutant strains displayed >10-fold protective effects against virulent type A F. tularensis challenge

A public health response to the methamphetamine epidemic: the implementation of contingency management to treat methamphetamine dependence

BACKGROUND: In response to increases in methamphatemine-associated sexually transmitted diseases, the San Francisco Department of Public Health implemented a contingency management (CM) field program called the Positive Reinforcement Opportunity Project (PROP). METHODS: Methamphetamine-using men who have sex with men (MSM) in San Francisco qualified for PROP following expressed interest in the program, provision of an observed urine sample that tested positive for methamphetamine metabolites and self-report of recent methamphetamine use. For 12 weeks, PROP participants provided observed urine samples on Mondays, Wednesdays and Fridays and received vouchers of increasing value for each consecutive sample that tested negative to metabolites of methamphetamine. Vouchers were exchanged for goods and services that promoted a healthy lifestyle. No cash was provided. Primary outcomes included acceptability (number of enrollments/time), impact (clinical response to treatment and cost-effectiveness as cost per patient treated). RESULTS: Enrollment in PROP was brisk indicating its acceptability. During the first 10 months of operation, 143 men sought treatment and of these 77.6% were HIV-infected. Of those screened, 111 began CM treatment and averaged 15 (42%) methamphetamine-free urine samples out of a possible 36 samples during the 12-week treatment period; 60% completed 4 weeks of treatment; 48% 8 weeks and 30% 12 weeks. Across all participants, an average of $159 (SD =$165) in vouchers or 35.1% of the maximum possible ($453) was provided for these participants. The average cost per participant of the 143 treated was$800. CONCLUSION: Clinical responses to CM in PROP were similar to CM delivered in drug treatment programs, supporting the adaptability and effectiveness of CM to non-traditional drug treatment settings. Costs were reasonable and less than or comparable to other methamphetamine outpatient treatment programs. Further expansion of programs like PROP could address the increasing need for acceptable, feasible and cost-effective methamphetamine treatment in this group with exceptionally high rates of HIV-infection

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 PI3-kinase delta inhibitor idelalisib (GS-1101) targets integrin-mediated adhesion of chronic lymphocytic leukemia (CLL) cell to endothelial and marrow stromal cells

CLL cell trafficking between blood and tissue compartments is an integral part of the disease process. Idelalisib, a phosphoinositide 3-kinase delta (PI3K\u3b4) inhibitor causes rapid lymph node shrinkage, along with an increase in lymphocytosis, prior to inducing objective responses in CLL patients. This characteristic activity presumably is due to CLL cell redistribution from tissues into the blood, but the underlying mechanisms are not fully understood. We therefore analyzed idelalisib effects on CLL cell adhesion to endothelial and bone marrow stromal cells (EC, BMSC). We found that idelalisib inhibited CLL cell adhesion to EC and BMSC under static and shear flow conditions. TNF\u3b1-induced VCAM-1 (CD106) expression in supporting layers increased CLL cell adhesion and accentuated the inhibitory effect of idelalisib. Co-culture with EC and BMSC also protected CLL from undergoing apoptosis, and this EC- and BMSC-mediated protection was antagonized by idelalisib. Furthermore, we demonstrate that CLL cell adhesion to EC and VLA-4 (CD49d) resulted in the phosphorylation of Akt, which was sensitive to inhibition by idelalisib. These findings demonstrate that idelalisib interferes with integrin-mediated CLL cell adhesion to EC and BMSC, providing a novel mechanism to explain idelalisib-induced redistribution of CLL cells from tissues into the blood

Australia\u27s health 2000 : the seventh biennial report of the Australian Institute of Health and Welfare

Australia\u27s Health 2000 is the seventh biennial health report of the Australian Institute of Health and Welfare. It is the nation\u27s authoritative source of information on patterns of health and illness, determinants of health, the supply and use of health services, and health services costs and performance.This 2000 edition serves as a summary of Australia\u27s health record at the end of the twentieth century. In addition, a special chapter is presented on changes in Australia\u27s disease profile over the last 100 years.Australia\u27s Health 2000 is an essential reference and information source for all Australians with an interest in health

Evaluation of individual and ensemble probabilistic forecasts of COVID-19 mortality in the United States

Short-term probabilistic forecasts of the trajectory of the COVID-19 pandemic in the United States have served as a visible and important communication channel between the scientific modeling community and both the general public and decision-makers. Forecasting models provide specific, quantitative, and evaluable predictions that inform short-term decisions such as healthcare staffing needs, school closures, and allocation of medical supplies. Starting in April 2020, the US COVID-19 Forecast Hub (https://covid19forecasthub.org/) collected, disseminated, and synthesized tens of millions of specific predictions from more than 90 different academic, industry, and independent research groups. A multimodel ensemble forecast that combined predictions from dozens of groups every week provided the most consistently accurate probabilistic forecasts of incident deaths due to COVID-19 at the state and national level from April 2020 through October 2021. The performance of 27 individual models that submitted complete forecasts of COVID-19 deaths consistently throughout this year showed high variability in forecast skill across time, geospatial units, and forecast horizons. Two-thirds of the models evaluated showed better accuracy than a naïve baseline model. Forecast accuracy degraded as models made predictions further into the future, with probabilistic error at a 20-wk horizon three to five times larger than when predicting at a 1-wk horizon. This project underscores the role that collaboration and active coordination between governmental public-health agencies, academic modeling teams, and industry partners can play in developing modern modeling capabilities to support local, state, and federal response to outbreaks

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care