Spatial transcriptomics reveals organized and distinct immune activation in cutaneous granulomatous disorders.

BACKGROUND: Noninfectious (inflammatory) cutaneous granulomatous disorders include cutaneous sarcoidosis (CS), granuloma annulare (GA), necrobiosis lipoidica (NL), and necrobiotic xanthogranuloma (NXG). These disorders share macrophage-predominant inflammation histologically, but the inflammatory architecture and the pattern of extracellular matrix alteration varies. The underlying molecular explanations for these differences remain unclear. OBJECTIVE: We sought to understand spatial gene expression characteristics in these disorders. METHODS: We performed spatial transcriptomics in cases of CS, GA, NL, and NXG to compare patterns of immune activation and other molecular features in a spatially resolved fashion. RESULTS: CS is characterized by a polarized, spatially organized type 1-predominant response with classical macrophage activation. GA is characterized by a mixed but spatially organized pattern of type 1 and type 2 polarization with both classical and alternative macrophage activation. NL showed concomitant activation of type 1, type 2, and type 3 immunity with a mixed pattern of macrophage activation. Activation of type 1 immunity was shared among, CS, GA, and NL and included upregulation of IL-32. NXG showed upregulation of CXCR4-CXCL12/14 chemokine signaling and exaggerated alternative macrophage polarization. Histologic alteration of extracellular matrix correlated with hypoxia and glycolysis programs and type 2 immune activation. CONCLUSIONS: Inflammatory cutaneous granulomatous disorders show distinct and spatially organized immune activation that correlate with hallmark histologic changes.

Heitt Mjölnir: a heated miniature triaxial apparatus for 4D synchrotron microtomography.

Third- and fourth-generation synchrotron light sources with high fluxes and beam energies enable the use of innovative X-ray translucent experimental apparatus. These experimental devices access geologically relevant conditions whilst enabling in situ characterization using the spatial and temporal resolutions accessible at imaging beamlines. Here, Heitt Mjölnir is introduced, a heated miniature triaxial rig based on the design of Mjölnir, but covering a wider temperature range and larger sample volume at similar pressure capacities. This device is designed to investigate coupled thermal, chemical, hydraulic and mechanical processes from grain to centimetre scales using cylindrical samples of 10 mm × 20 mm (diameter × length). Heitt Mjölnir can simultaneously reach confining (hydraulic) pressures of 30 MPa and 500 MPa of axial stress with independently controlled sample pore fluid pressure < 30 MPa. This internally heated apparatus operates to temperatures up to 573 K with a minimal vertical thermal gradient in the sample of <0.3 K mm-1. This new apparatus has been deployed in operando studies at the TOMCAT (Swiss Light Source), I12 JEEP (Diamond Light Source) and PSICHÉ (Synchrotron SOLEIL) beamlines for 4D X-ray microtomography with scan intervals of a few minutes. Heitt Mjölnir is portable and modular, allowing a wide range of 4D characterizations of low-grade metamorphism and deformational processes. It enables spatially and temporally resolved fluid-rock interaction studies at conditions of crustal reservoirs and is suitable for characterization of material properties in geothermal, carbonation or subsurface gas storage applications. Technical drawings and an operation guide are included in this publication.

Anisotropic diffusion creep in postperovskite provides a new model for deformation at the core-mantle boundary.

The lowermost portion of Earth's mantle (D″) above the core-mantle boundary shows anomalous seismic features, such as strong seismic anisotropy, related to the properties of the main mineral MgSiO3 postperovskite. But, after over a decade of investigations, the seismic observations still cannot be explained simply by flow models which assume dislocation creep in postperovskite. We have investigated the chemical diffusivity of perovskite and postperovskite phases by experiment and ab initio simulation, and derive equations for the observed anisotropic diffusion creep. There is excellent agreement between experiments and simulations for both phases in all of the chemical systems studied. Single-crystal diffusivity in postperovskite displays at least 3 orders of magnitude of anisotropy by experiment and simulation (Da = 1,000 Db; Db ≈ Dc) in zinc fluoride, and an even more extreme anisotropy is predicted (Da = 10,000 Dc; Dc = 10,000 Db) in the natural MgSiO3 system. Anisotropic chemical diffusivity results in anisotropic diffusion creep, texture generation, and a strain-weakening rheology. The results for MgSiO3 postperovskite strongly imply that regions within the D″ region of Earth dominated by postperovskite will 1) be substantially weaker than regions dominated by perovskite and 2) develop a strain-induced crystallographic-preferred orientation with strain-weakening rheology. This leads to strain localization and the possibility to bring regions with significantly varying textures into close proximity by strain on narrow shear zones. Anisotropic diffusion creep therefore provides an attractive alternative explanation for the complexity in observed seismic anisotropy and the rapid lateral changes in seismic velocities in D″.

Glyphosate and Polyoxyethyleneamine Ingestion Leading to Renal, Hepatic, and Pulmonary Failure.

ABSTRACT: Glyphosate is an organophosphorus compound and the active ingredient in commonly used herbicides, whereas polyoxyethyleneamine (POEA) is a nonionic surfactant often coupled with glyphosate in these herbicides to increase their efficacy. Cases of glyphosate-POEA ingestion have shown a variety of outcomes, ranging from skin and mucosal surface irritation to death. Here, we report mortality after ingestion of at least 237 mL of an herbicide confirmed to contain both glyphosate and POEA. The decedent's electronic medical record indicates presentation to the emergency department shortly after ingestion and rapid decompensation, with death occurring on the fourth day of admission. The autopsy report showed extensive pulmonary edema and congestion with no alimentary tract abnormalities. Microscopically, airway inflammation, edema, and hemorrhage were shown as well as pericentral necrosis and macrovascular hepatic steatosis. This case is unusual for several reasons including the fatal outcome in a young 30-year-old patient, the large volume of the herbicide consumed, the associated large volume aspirated, and the lung pathology associated with exposure to glyphosate-POEA since inhalation, and in this case, aspiration is an uncommon route of glyphosate-POEA exposure. This report therefore offers rare respiratory tract pathological findings and the clinical course after aspiration of a large volume of glyphosate-POEA.

Integrating Stakeholder Mapping and Risk Scenarios to Improve Resilience of Cyber-Physical-Social Networks.

The future of energy mobility involves networks of users, operators, organizations, vehicles, charging stations, communications, materials, transportation corridors, points of service, and so on. The integration of smart grids with plug-in electric vehicle technologies has societal and commercial advantages that include improving grid stability, minimizing dependence on nonrenewable fuels, reducing vehicle emissions, and reducing the cost of electric vehicle ownership. However, ineffective or delayed participation of particular groups of stakeholders could disrupt industry plans and delay the desired outcomes. This article develops a framework to address enterprise resilience for two modes of disruptions-the first being the influence of scenarios on priorities and the second being the influence of multiple groups of stakeholders on priorities. The innovation of this study is to obtain the advantages of integrating two recent approaches: scenario-based preferences modeling and stakeholder mapping. Public agencies, grid operators, plug-in electric vehicle owners, and vehicle manufacturers are the four groups of stakeholders that are considered in this framework, along with the influence of four scenarios on priorities.

Synthesis of cis-[Cr(diimine)2(1-methylimidazole)2](3+) Complexes and an Investigation of Their Interaction with Mononucleotides and Polynucleotides.

A protocol is presented for the synthesis of chromium(III) complexes of the type cis-[Cr(diimine)2(1-methylimidazole)2](3+). These compounds exhibit large excited-state oxidizing powers and strong luminescence in solution. Emission is quenched by added guanine, yielding rate constants that track the driving force for guanine oxidation. The cis-[Cr(TMP)(DPPZ)(1-MeImid)2](3+) species binds strongly to duplex DNA with a preference for AT base sites in the minor groove and may serve as a precursor for photoactivated DNA covalent adduct formation.

Cost-effectiveness analysis of antiviral therapy in patients with advanced hepatitis B virus-related hepatocellular carcinoma treated with sorafenib.

BACKGROUND AND AIM: Antiviral therapy has been demonstrated to significantly improve the survival in patients with advanced hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). The aim of the study was to investigate the cost-effectiveness of antiviral therapy in patients with advanced HBV-related HCC treated with sorafenib. METHODS: To conduct the analysis, a Markov model comprising three health states (progression-free survival, progressive disease, and death) was created. The efficacy data were derived from medical records. Cost data were collected based on the Chinese national drug prices. Utility data came from the previously published studies. One-way sensitivity analyses as well as probabilistic sensitivity analyses were performed to explore model uncertainties. RESULTS: In the base-case analysis, addition of antiviral therapy to sorafenib generated an effectiveness of 0.68 quality-adjusted life years (QALYs) at a cost of $25 026.04, while sorafenib monotherapy gained an effectiveness of 0.42 QALYs at a cost of $20 249.64. The incremental cost-effectiveness ratio (ICER) was $18 370.77/QALY for antiviral therapy group versus non-antiviral therapy group. On the other hand, the ICER between the two groups in patients with high or low HBV-DNA load, with or without cirrhosis, normal or elevated alanine aminotransferase/aspartate aminotransferase were $16 613.97/QALY, $19 774.16/QALY, $14 587.66/QALY, $19 873.84/QALY, $17 947.07/QALY, and $18 785.58/QALY, respectively. CONCLUSIONS: Based on the cost-effectiveness threshold ($20 301.00/QALY in China), addition of antiviral therapy to sorafenib is considered to be a cost-effective option compared with sorafenib monotherapy in patients with advanced HBV-related HCC in China from the patient's perspective.

Ten-atom silver cluster signaling and tempering DNA hybridization.

Silver clusters with ∼10 atoms are molecules, and specific species develop within DNA strands. These molecular metals have sparsely organized electronic states with distinctive visible and near-infrared spectra that vary with cluster size, oxidation, and shape. These small molecules also act as DNA adducts and coordinate with their DNA hosts. We investigated these characteristics using a specific cluster-DNA conjugate with the goal of developing a sensitive and selective biosensor. The silver cluster has a single violet absorption band (λ(max) = 400 nm), and its single-stranded DNA host has two domains that stabilize this cluster and hybridize with target oligonucleotides. These target analytes transform the weakly emissive violet cluster to a new chromophore with blue-green absorption (λ(max) = 490 nm) and strong green emission (λ(max) = 550 nm). Our studies consider the synthesis, cluster size, and DNA structure of the precursor violet cluster-DNA complex. This species preferentially forms with relatively low amounts of Ag(+), high concentrations of the oxidizing agent O2, and DNA strands with ≳20 nucleotides. The resulting aqueous and gaseous forms of this chromophore have 10 silvers that coalesce into a single cluster. This molecule is not only a chromophore but also an adduct that coordinates multiple nucleobases. Large-scale DNA conformational changes are manifested in a 20% smaller hydrodynamic radius and disrupted nucleobase stacking. Multidentate coordination also stabilizes the single-stranded DNA and thereby inhibits hybridization with target complements. These observations suggest that the silver cluster-DNA conjugate acts like a molecular beacon but is distinguished because the cluster chromophore not only sensitively signals target analytes but also stringently discriminates against analogous competing analytes.

Blood transfusion practices in dialysis patients in a dynamic regulatory environment.

BACKGROUND: In 2011, Medicare implemented a prospective payment system (PPS) covering an expanded bundle of services that excluded blood transfusions. This led to concern about inappropriate substitution of transfusions for other anemia management methods. STUDY DESIGN: Medicare claims were used to calculate transfusion rates among dialysis patients pre- and post-PPS. Linear probability regressions adjusted transfusion trends for patient characteristics. SETTING & PARTICIPANTS: Dialysis patients for whom Medicare was the primary payer between 2008 and 2012. PREDICTOR: Pre-PPS (2008-2010) versus post-PPS (2011-2012). OUTCOMES & MEASUREMENTS: Monthly and annual probability of receiving one or more blood transfusions. RESULTS: Monthly rates of one or more transfusions varied from 3.8%-4.8% and tended to be lowest in 2010. Annual rates of transfusion events per patient were -10% higher in relative terms post-PPS, but the absolute magnitude of the increase was modest (-0.05 events/patient). A larger proportion received 4 or more transfusions (3.3% in 2011 and 2012 vs 2.7%-2.8% in prior years). Controlling for patient characteristics, the monthly probability of receiving a transfusion was significantly higher post-PPS (ß = 0.0034; P < 0.001), representing an -7% relative increase. Transfusions were more likely for females and patients with more comorbid conditions and less likely for blacks both pre- and post-PPS. LIMITATIONS: Possible underidentification of transfusions in the Medicare claims, particularly in the inpatient setting. Also, we do not observe which patients might be appropriate candidates for kidney transplantation. CONCLUSIONS: Transfusion rates increased post-PPS, but these increases were modest in both absolute and relative terms. The largest increase occurred for patients already receiving several transfusions. Although these findings may reduce concerns regarding the impact of Medicare's PPS on inappropriate transfusions that impair access to kidney transplantation or stress blood bank resources, transfusions should continue to be monitored.

Patient perceptions of asthma-related financial burden: public vs. private health insurance in the United States.

BACKGROUND: Given the complexity of the health insurance market in the United States and the confusion that often stems from these complexities, patient perception about the value of health insurance in managing chronic disease is important to understand. OBJECTIVE: To examine differences between public and private health insurance in perceptions of financial burden with managing asthma, outcomes, and factors that explain these perceptions. METHODS: Secondary analysis was performed using baseline data from a randomized clinical trial that were collected through telephone interviews with 219 African American women seeking services for asthma and reporting perceptions of financial burden with asthma management. Path analysis with multigroup models and multiple variable regression analyses were used to examine associations. RESULTS: For public (P < .001) and private (P < .01) coverage, being married and more educated were indirectly associated with greater perceptions of financial burden through different explanatory pathways. When adjusted for multiple morbidities, asthma control, income, and out-of-pocket expenses, those with private insurance used fewer inpatient (P < .05) and emergency department (P < .001) services compared with those with public insurance. When also adjusted for health insurance, greater financial burden was associated with more urgent office visits (P < .001) and lower quality of life (P < .001). CONCLUSION: African American women who perceive asthma as a financial burden regardless of health insurance report more urgent health care visits and lower quality of life. Burden may be present despite having and being able to generate economic resources and health insurance. Further policy efforts are indicated and special attention should focus on type of coverage.

Weighted Burgers Vector analysis of orientation fields from high-angular resolution electron backscatter diffraction.

The Weighted Burgers Vector (WBV) method can extract information about dislocation types and densities present in distorted crystalline materials from electron backscatter diffraction (EBSD) maps, using no assumptions about which slip systems might be present. Furthermore, high-angular resolution EBSD (HR-EBSD) uses a cross-correlation procedure to increase the angular precision of EBSD measurements by an order of magnitude compared to conventional EBSD. However, the WBV technique has not previously been applied to HR-EBSD data and therefore it remains unclear as to which low-angle substructures can be reliably characterised by WBV analysis of conventional EBSD data and which require additional HR-EBSD processing. To establish some practical examples that can be used to guide future data-acquisition strategies, we compare the output of the WBV method when applied to conventional EBSD data and HR-EBSD data collected from the most common minerals in Earth's lower crust (plagioclase feldspar) and upper mantle (olivine). The results demonstrate that HR-EBSD and WBV processing are complementary techniques. The increase in angular precision achieved with HR-EBSD processing allows low-angle (on the order of 0.1°) structures, which are obscured by noise in conventional EBSD data, to be analyzed quantitatively using the WBV method. Combining the WBV and HR-EBSD methods increases the precision of calculated WBV directions, which is essential when using information about active slip systems to infer likely deformation mechanisms from naturally deformed microstructures. This increase in precision is particularly important for low-symmetry crystals, such as plagioclase, that have a wide range of available slip systems that vary in relative activity with changing pressure, temperature and differential stress. Because WBV directions are calculated using no assumptions about which slip systems may be present, combining this technique with HR-EBSD to refine the precision of lattice orientation gradients is ideal for investigating complex natural materials with unknown deformation histories.

The initial impact of Medicare's new prospective payment system for kidney dialysis.

BACKGROUND: Medicare implemented a new prospective payment system (PPS) on January 1, 2011. This PPS covers an expanded bundle of services, including services previously paid on a fee-for-service basis. The objectives of the new PPS include more efficient decisions about treatment service combinations and modality choice. METHODS: Primary data for this study are Medicare claims files for all dialysis patients for whom Medicare is the primary payer. We compare use of key injectable medications under the bundled PPS to use when those drugs were separately billable and examine variability across providers. We also compare each patient's dialysis modality before and after the PPS. RESULTS: Use of relatively expensive drugs, including erythropoiesis-stimulating agents, declined substantially after institution of the new PPS, whereas use of iron products, often therapeutic substitutes for erythropoiesis-stimulating agents, increased. Less expensive vitamin D products were substituted for more expensive types. Drug spending overall decreased by ∼$25 per session, or about 5 times the mandated reduction in the base payment rate of ∼$5. Use of peritoneal dialysis increased in 2011 after being nearly flat in the years prior to the PPS, with the increase concentrated in patients in their first or second year of dialysis. Home hemodialysis continued to increase as a percentage of total dialysis services, but at a rate similar to the pre-PPS trend. CONCLUSION: The expanded bundle dialysis PPS provided incentives for the use of lower cost therapies. These incentives seem to have motivated dialysis providers to move toward lower cost methods of care in both their use of drugs and choice of modalities.

Selection and maturation of antibodies by phage display through fusion to pIX.

Antibody discovery and optimization by M13 phage display have evolved significantly over the past twenty years. Multiple methods of antibody display and selection have been developed - direct display on pIII or indirect display through a Cysteine disulfide linkage or a coiled-coil adapter protein. Here we describe display of Fab libraries on the smaller pIX protein at the opposite end of the virion and its application to discovery of novel antibodies from naive libraries. Antibody selection based on pIX-mediated display produces results comparable to other in vitro methods and uses an efficient direct infection of antigen-bound phages, eliminating any chemical dissociation step(s). Additionally, some evidence suggests that pIX-mediated display can be more efficient than pIII-mediated display in affinity selections. Functional assessment of phage-derived antibodies can be hindered by insufficient affinities or lack of epitopic diversity. Here we describe an approach to managing primary hits from our Fab phage libraries into epitope bins and subsequent high-throughput maturation of clones to isolate epitope- and sequence-diverse panels of high affinity binders. Use of the Octet biosensor was done to examine Fab binding in a facile label-free method and determine epitope competition groups. A receptor extracellular domain and chemokine were subjected to this method of binning and affinity maturation. Parental clones demonstrated improvement in affinity from 1-100nM to 10-500pM.

Distinct in vivo requirements for establishment versus maintenance of transcriptional repression.

Low-level ectopic expression of the Runt transcription factor blocks activation of the Drosophila melanogaster segmentation gene engrailed (en) in odd-numbered parasegments and is associated with a lethal phenotype. Here we show, by using a genetic screen for maternal factors that contribute in a dose-dependent fashion to Runt-mediated repression, that there are two distinct steps in the repression of en by Runt. The initial establishment of repression is sensitive to the dosage of the zinc-finger transcription factor Tramtrack. By contrast, the co-repressor proteins Groucho and dCtBP, and the histone deacetylase Rpd3, do not affect establishment but instead maintain repression after the blastoderm stage. The distinction between establishment and maintenance is confirmed by experiments with Runt derivatives that are impaired specifically for either co-repressor interaction or DNA binding. Other transcription factors can also establish repression in Rpd3-deficient embryos, which indicates that the distinction between establishment and maintenance may be a general feature of eukaryotic transcriptional repression.

Examining financial performance indicators for acute care hospitals.

Measuring financial performance in acute care hospitals is a challenge for those who work daily with financial information. Because of the many ways to measure financial performance, financial managers and researchers must decide which measures are most appropriate. The difficulty is compounded for the non-finance person. The purpose of this article is to clarify key financial concepts and describe the most common measures of financial performance so that researchers and managers alike may understand what is being measured by various financial ratios.

The identification of synthetic cannabinoids in English prisons.

Synthetic cannabinoids (SC) are extremely prevalent within the prison system and cause problems for prisoners, law enforcement and health services. SC are often soaked into paper then posted into prisons therefore one of the aims of this research is to collaborate with Rapiscan Systems Ltd. and local prisons in England to measure the effectiveness of trace detection methods for the indication of SC in prison post using the Itemiser 3E®. To ensure compounds did not go undetected, samples with Ion Trap Mobility Spectrometry™ peaks indicative of synthetic cannabinoids on the Itemiser 3E® were analysed using Gas Chromatography-Mass Spectrometry, Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry and Nuclear Magnetic Resonance Spectroscopy to identify chemical characteristics which allowed comparison to reference spectra. Sample data spanning three years from one prison's Itemiser 3E® were collated to identify trends in drug prevalence and the influence of library updates. To date, the method has identified four compounds: 5F-MDMB-PICA, MMB-4en-PICA, 4F-MDMB-BUTINACA and MDMB-4en-PINACA on prison post which were not already included on, or needed confirmatory analysis to update, the Itemiser 3E® library. As a result, the libraries on prison Itemiser 3E®s have been updated to ensure future detection of such compounds. Trends and influences from the processed Itemiser 3E® data were also reported back to the West Midlands Prison Group. This research directly benefitted both the West Midlands Prison Group and Rapiscan Systems Ltd. and it is anticipated that the continuation of this research could be expanded to a national scale.

The relationship between time spent communicating and communication outcomes on a hospital medicine service.

BACKGROUND: Quality care depends on effective communication between caregivers, but it is unknown whether time spent communicating is associated with communication outcomes. OBJECTIVE: To assess the association between time spent communicating, agreement on plan of care, and patient satisfaction. DESIGN: Time-motion study with cross-sectional survey. SETTING: Academic medical center. PARTICIPANTS: Physicians, patients, and nurses on a hospital medicine service. MEASUREMENTS: Hospitalists' forms of communication were timed with a stopwatch. Physician-nurse agreement on the plan of care and patient satisfaction with physician communication were assessed via survey. RESULTS: Eighteen hospitalists were observed caring for 379 patients. On average, physicians spent more time per patient on written than verbal communication (median: 9.2 min. vs. 6.3 min, p<0.001). Verbal communication was greatest with patients (mean time 5.3 min, range 0-37 min), then other physicians (1.4 min), families (1.1 min), nurses (1.1 min), and case managers (0.4 min). There was no verbal communication with nurses in 30% of cases. Nurses and physicians agreed most about planned procedures (87%), principal diagnosis (74%), tests ordered (73%), anticipated discharge date (69%) and least regarding medication changes (59%). There was no association between time spent communicating and agreement on plan of care. Among 123 patients who completed surveys (response rate 32%), time physicians spent talking to patients was not correlated with patients' satisfaction with physician communication (Pearson correlation coefficient = 0.09, p=0.30). CONCLUSIONS: Hospitalists vary in the amount of time they spend communicating, but we found no association between time spent and either patient satisfaction or nurse-physician agreement on plan of care.

Hospital financial management: what is the link between revenue cycle management, profitability, and not-for-profit hospitals' ability to grow equity?

Effective revenue cycle management--from appointment scheduling and patient registration at the front end of the revenue cycle to billing and cash collections at the back end--plays a crucial role in hospitals' efforts to improve their financial performance. Using data for 1,397 bond-issuing, not-for-profit US hospitals for 2000 to 2007, this study analyzed the relationship between hospitals' performance at managing the revenue cycle and their profitability and ability to build equity capital. Hospital-level fixed effects regression analysis was used to model four different measures of profitability and equity capital as functions of two key financial indicators of revenue cycle management--amount of patient revenue and speed of revenue collection. The results indicated that higher amounts of patient revenue in relation to a hospital's assets were associated with statistically significant increases in operating and total profit margins, free cash flow, and equity capital (p < 0.01 for all four models); that is, hospitals that generated more patient revenue per dollar of assets invested reported improved financial performance. Likewise, a statistically significant link existed between lower revenue collection periods and all four indicators of hospital financial performance (p < 0.01 for three models; p < 0.05 for one model). Hospitals that collected faster on their patient revenue reported higher profit margins and larger equity values. For revenue cycle managers, these findings represent good news: Streamlining a hospital's management of the patient revenue cycle can advance the organization's financial viability by improving profitability and enabling equity growth.

Prediction of acute mammalian toxicity using QSAR methods: a case study of sulfur mustard and its breakdown products.

Predicting toxicity quantitatively, using Quantitative Structure Activity Relationships (QSAR), has matured over recent years to the point that the predictions can be used to help identify missing comparison values in a substance's database. In this manuscript we investigate using the lethal dose that kills fifty percent of a test population (LD50) for determining relative toxicity of a number of substances. In general, the smaller the LD50 value, the more toxic the chemical, and the larger the LD50 value, the lower the toxicity. When systemic toxicity and other specific toxicity data are unavailable for the chemical(s) of interest, during emergency responses, LD50 values may be employed to determine the relative toxicity of a series of chemicals. In the present study, a group of chemical warfare agents and their breakdown products have been evaluated using four available rat oral QSAR LD50 models. The QSAR analysis shows that the breakdown products of Sulfur Mustard (HD) are predicted to be less toxic than the parent compound as well as other known breakdown products that have known toxicities. The QSAR estimated break down products LD50 values ranged from 299 mg/kg to 5,764 mg/kg. This evaluation allows for the ranking and toxicity estimation of compounds for which little toxicity information existed; thus leading to better risk decision making in the field.

The importance of working capital management for hospital profitability: evidence from bond-issuing, not-for-profit U.S. hospitals.

BACKGROUND: Increased financial pressures on hospitals have elevated the importance of working capital management, that is, the management of current assets and current liabilities, for hospitals' profitability. Efficient working capital management allows hospitals to reduce their holdings of current assets, such as inventory and accounts receivable, which earn no interest income and require financing with short-term debt. The resulting cash inflows can be reinvested in interest-bearing financial instruments or used to reduce short-term borrowing, thus improving the profitability of the organization. PURPOSE: This study examines the relationship between hospitals' profitability and their performance at managing two components of working capital: accounts receivable, measured in terms of hospitals' average collection periods, and accounts payable, measured in terms of hospitals' average payment periods. METHODOLOGY/APPROACH: Panel data derived from audited financial statements for 1,397 bond-issuing, not-for-profit U.S. hospitals for 2000-2007 were analyzed using hospital-level fixed-effects regression analysis. FINDINGS: The results show a negative relationship between hospitals' average collection period and profitability. That is, hospitals that collected on their patient revenue faster reported higher profit margins than did hospitals that have larger balances of accounts receivable outstanding. We also found a negative relationship between hospitals' average payment period and their profitability. Hospital managers did not appear to delay paying their vendors. Rather, the findings indicated that more profitable hospitals paid their suppliers faster, possibly to avoid high effective interest rates on outstanding accounts payable, whereas less profitable hospitals waited longer to pay their bills. PRACTICE IMPLICATIONS: The findings of this study suggest that working capital management indeed matters for hospitals' profitability. Efforts aimed at reducing large balances in both accounts receivable and accounts payable may frequently be worthwhile investments that have the potential to reduce the costs associated with working capital management and thus improve the profitability of an organization.