Relationships of State Alcohol Policy Environments with Homicides and Suicides.

INTRODUCTION: Alcohol use is involved in a large proportion of homicides and suicides each year in the United States, but there is limited evidence on how policies targeting alcohol influence violence in the U.S. CONTEXT: Extant studies generally focus on individual policies in isolation of each other. This study examines of the effects of changes in states' alcohol policy restrictions on overall homicide and suicide rates and firearm-related homicide and suicide rates using a holistic measure of states' alcohol policy environments. METHODS: Using a composite measure of state-level alcohol policies (Alcohol Policy Scale) and data from the National Vital Statistics System from 2002 to 2018, this study applied a Bayesian time series model to estimate the effects of alcohol policy changes on overall and firearm-involved homicide and suicide rates. The analysis was performed in 2023 and 2024. RESULTS: A one standard deviation change in the Alcohol Policy Scale was associated with a 6 percent decline in homicide rates both overall (IRR=0.94; 95-percent credibility interval = [0.89, 1.00]) and for firearm homicides specifically (IRR=0.94, 95-percent CI=[0.88, 1.01]). There was no clear association of alcohol policy with suicides. The model predicts that a nationwide increase in alcohol restrictions equivalent to a shift from the 25th to 75th percentile of the scale's distribution would result in almost 1200 fewer homicides annually. CONCLUSIONS: Increases in the restrictiveness of state-level alcohol policies are associated with reductions in homicides. More restrictive alcohol policy environments may offer an opportunity to reduce homicides.

Issue alignment and partisanship in the American public: Revisiting the 'partisans without constraint' thesis.

Prior studies of American polarization suggest that the public gradually sorted themselves into partisan camps in the late 20th century while remaining largely non-ideological. Drawing on more recent data, we reassess these trends and discover a striking increase in the ideological organization of American public opinion in the beginning of the 21st century. Using a broad set of issues from the American National Election Studies, we identify rapid growth in the correlations between political attitudes from 2004 to 2016. This emergence of issue alignment is most pronounced within the economic and civil rights domains, challenging the notion that current "culture wars" are grounded in moral issues. While elite subpopulations show the greatest gains, we find that economic issues become more highly correlated across the electorate. We also find accelerated growth in the association between partisanship and issue attitudes during this period. These findings paint a new picture of the American electorate as not only highly partisan but increasingly ideological.

Decline in primary care providers' prescribing of Schedule II opioids following the implementation of federal and state guidelines.

OBJECTIVE: Prescription opioid misuse represents a social and economic dilemma in the United States. The authors evaluated primary care providers' (PCPs) prescribing of Schedule II opioids at our institution in Kentucky. DESIGN: Prospective evaluation of PCPs' prescribing practices over a 3-year period (October 1, 2014 to September 30, 2017) in an outpatient setting. METHODS: An analysis of Schedule II opioid prescribing following the implementation of federal and state guidelines and evidence-based standards. Special attention focused on Schedule II opioid prescriptions with a quantity > 90, Opana/Oxycontin, and morphine equivalent daily dosage. RESULTS: A statistically significant increase in the total number of PCPs and PCPs who prescribed Schedule II opioids was observed, while there was a concurrent significant decrease in the average number of Schedule II opioid pills prescribed per PCP, Schedule II opioid prescriptions per PCP, Schedule II opioid pills prescribed per patient by PCPs, Schedule II opioid prescriptions with a quantity > 90 per PCP, and Opana/Oxycontin prescriptions per PCP. A statistically significant decline in the average morphine equivalent daily dosage of Schedule II opioids per PCP was noted. CONCLUSIONS: This study reports the benefit of incorporating federal and state regulations and institutional evidence-based guidelines into primary care practice to decrease the number of Schedule II opioids prescribed. Further preventive measures include selecting alternative treatments to opioids and reducing the rates of opioid nonmedical use and overdose while maintaining access to prescription opioids when indicated.

Contributions of Kansas rangeland burning to ambient O3: Analysis of data from 2001 to 2016.

Prescribed range/pasture burning is a common practice in Kansas to enhance the nutritional value of native grasses and control invading weeds, trees, and brush. A major concern associated with the burning is the contribution of smoke to elevated ground level ambient ozone (O3). The objective of this study is to estimate contributions of Kansas rangeland burning to ambient O3 mixing ratios through regression analysis (1) between observed O3 data and available satellite burn activity data from 2001 to 2016; and (2) between observed O3 data and the smoke contributions to PM2.5 which were resolved from receptor modeling. Positive correlations were observed between ambient O3 levels and the acres burned each year estimated from satellite imagery. When burned acres in April were larger than or equal to 1.9 million, O3>70ppb occurred at least at one of the ten monitoring sites in Kansas. Statistical regression models of daily maximum 8-hour O3 mixing ratios were developed at each of the ten monitoring sites using meteorological predictors. The O3 model residuals that were not explained by the meteorological effect models were affected by PM2.5 contributors including sulfate/industrial sources and emissions that generated secondary organic particles, such as rangeland burning, which were derived from receptor modeling. The average O3 model residual on the high O3 days in April was 21±9ppb, which was likely associated with smoke emissions from burning. Research will continue to obtain daily satellite burn activity data and to correlate burn data with daily O3 data, so that modeling of O3 levels can be improved under influences of daily burn activities. Less frequency of high O3 days was observed in April since 2011, which may be partly due to implementation of the Flint Hills Smoke Management Plan which promoted better timing of burns.

Improving sensitivity and linear dynamic range of intact protein analysis using a robust and easy to use microfluidic device.

We demonstrate an integrated microfluidic LC device coupled to a QTOF capable of improving sensitivity and linearity for intact protein analysis while also tuning the charge state distributions (CSD) of whole antibodies. The mechanism for sensitivity improvement using microflow ESI is demonstrated by shifting of the CSD to higher charge state, and narrowing of the overall CSD. Both of these aspects serve to improve ion current of the most abundant charge state of antibodies and lead to improvement in sensitivity over high flow ESI by a factor of 15×. Current limits of detection are 0.1 ng (on-column) (n = 100, %RSD = 17.5) using IgG glycosylated antibody, as compared to 5 ng (on-column) (n = 10, %RSD = 15) for high flow LC-ESI-MS. In addition to improvements in sensitivity we also observe improvements in linear dynamic range for microflow ESI that results from a combination of lower limits of detection and narrower CSD. An improvement of linear dynamic range of 1.5 orders of magnitude was observed over conventional high flow LC-MS. In cases where the complexity of the antibody limited both sensitivity and spectral charge state resolution, we employed supercharging and decharging mechanisms to further improve sensitivity and charge state spacing resolution. We demonstrate an 89% increase in sensitivity using glycerol that was added post column, with retention of the glycoform resolution. Since large proteins reside in a relatively low noise region of the mass spectra it is possible to realize effects of supercharging for intact proteins, specifically antibodies of 150 kDa, that are less pronounced for peptide supercharging. We also demonstrate a 51% increase in charge state resolution as imidazole was used to generate lower charge states for high-mass ions. The increase in charge state resolution enables more complex antibodies, or antibody mixtures that coelute in the LC, to be deconvoluted more efficiently. In summary, we demonstrate an analytical technique that yields improved sensitivity and quantitative linear dynamic range for intact protein analysis over conventional LC-MS, and yields ease of use for more complex experimentation such as supercharging and decharging experiments.

An integrated ceramic, micro-fluidic device for the LC/MS/MS analysis of pharmaceuticals in plasma.

An integrated capillary scale (300 µm id) ceramic microfluidic LC system combined with MS/MS has been successfully employed for the quantitative analysis of pharmaceutical compounds in human plasma. The capillary ceramic microfluidic LC/MS/MS system showed an approximate 20-fold (range 11-38-fold) increase in sensitivity compared with a standard 2.1 mm scale UPLC/MS/MS system for a broad range of analytes. The loading capacity of the devices capillary separations channel allowed injection of 2 µL of an aqueous solution, and up to 1.2 µL of a typical protein-precipitated plasma sample, onto the reversed-phase chromatography system. The system also showed excellent chromatographic performance and robustness, with no deleterious effects on the chromatography observed over the course of 1000 injections of protein-precipitated plasma. The ability of the ceramic microfluidic LC/MS/MS system to deliver this level of sensitivity and performance enables the routine quantification of pharmaceutical compounds from small format samples, such as those obtained by dried blood spot or other blood microsampling approaches, to be performed.

Wide injection zone compression in gradient reversed-phase liquid chromatography.

Chromatographic zone broadening is a common issue in microfluidic chromatography, where the sample volume introduced on column often exceeds the column void volume. To better understand the propagation of wide chromatographic zones on a separation device, a series of MS Excel spreadsheets were developed to simulate the process. To computationally simplify these simulations, we investigated the effects of injection related zone broadening and its gradient related zone compression by tracking only the movements of zone boundaries on column. The effects of sample volume, sample solvent, gradient slope, and column length on zone broadening were evaluated and compared to experiments performed on 0.32mm I.D. microfluidic columns. The repetitive injection method (RIM) was implemented to generate experimental chromatograms where large sample volume scenarios can be emulated by injecting two discrete small injection plugs spaced in time. A good match between predicted and experimental RIM chromatograms was observed. We discuss the performance of selected retention models on the accuracy of predictions and use the developed spreadsheets for illustration of gradient zone focusing for both small molecules and peptides.

Repetitive injection method: a tool for investigation of injection zone formation and its compression in microfluidic liquid chromatography.

Sample introduction in microfluidic liquid chromatography often generates wide zones rather than peaks, especially when a large sample volume (relative to column volume) is injected. Formation of wide injection zones can be further amplified when the sample is dissolved in a strong eluent. In some cases sample breakthrough may occur, especially when the injection is performed into short trapping columns. To investigate the band formation and subsequent zone focusing under gradient elution in situations such as these, we developed the Repetitive Injection Method (RIM), based on the temporally resolved introduction of two discrete peaks to a column, mimicking both the leading and trailing edges of a larger, singly injected sample zone. Using titanium microfluidic 0.32 mm I.D. columns, the results of RIM experiments were practically identical to injection of a correspondingly larger single zone volume. It was also experimentally shown that zone width (spacing between two injected peaks) decreases during gradient elution. We utilized RIM experiments to investigate wide sample zones created by strong sample solvent, and subsequent gradient zone focusing for a series of compounds. This experimental work was compared with computationally simulated chromatograms. The success of sample focusing during injection and gradient elution depends not only on an analyte's absolute retention, but also on how rapidly the analyte's retention changes during the mobile phase gradient.

A case of small-bowel obstruction secondary to inadvertent ingestion of impression material.

BACKGROUND: Small-bowel obstruction (SBO) is responsible for approximately 12 to 16 percent of surgical hospital admissions and more than 300,000 operations annually in the United States. This has resulted in more than $2.3 billion in health care delivery per year. SBO is a serious complication, carrying a 10 percent risk of mortality. CASE DESCRIPTION: The authors report a case of SBO resulting from inadvertent ingestion of polysulfide impression material. A 74-year-old man visited the emergency department with diffuse, nonradiating, colicky periumbilical pain. The patient was admitted to the general surgery service of the hospital, and after four days of supportive therapy without evidence of progression of the foreign body, he underwent an exploratory laparotomy. The authors later identified the foreign body as polysulfide impression material. PRACTICAL IMPLICATIONS: SBO is a rare but significant complication that can result from a procedure that clinicians perform on a routine basis. Dentists should consider this complication whenever they are concerned that a high-risk patient may have ingested dental materials.

Multiplexed analysis of steroid hormones in human serum using novel microflow tile technology and LC-MS/MS.

A novel microfluidic chromatography device coupled with tandem mass spectrometry (LC-MS/MS) was utilized for the multiplex analysis of 5 steroids (testosterone, dihydrotestosterone, progesterone, cortisol, cortisone) in human serum. The use of microfluidics allowed for reduction of the chromatographic flow rate to 3µl/min with overall method run times comparable to standard flow LC-MS/MS methods reported in the literature, corresponding to a 150 fold decrease in solvent consumption. Furthermore, a simple sample preparation protocol was employed requiring injection of only 0.5µl of sample, corresponding to a 100-400 fold increase in on-column sensitivity as compared to published standard flow assays. The measured LOQ for both testosterone and progesterone was 0.4ng/mL, representing an improvement over reported literature values obtained by standard flow methods employing comparable sample preparation and large injection volumes. The LOQs for cortisol (1.9ng/mL), cortisone (0.3ng/mL), and dihydrotestosterone (1.4ng/mL) were all within a biologically relevant range. A comparison of clinical serum samples was performed for the analysis of testosterone using this microfluidic LC-MS/MS assay and the Beckman Access II automated antibody-based measurement system. The immunoassay results were systematically higher due to matrix interference which was easily resolved with the increased chromatographic resolution obtained in the microflow LC-MS/MS assay.

Particulate matter emission rates from beef cattle feedlots in Kansas-reverse dispersion modeling.

Open beef cattle feedlots emit various air pollutants, including particulate matter (PM) with equivalent aerodynamic diameter of 10 microm or less (PM10); however limited research has quantified PM10 emission rates from feedlots. This research was conducted to determine emission rates of PM10 from large cattle feedlots in Kansas. Concentrations of PM10 at the downwind and upwind edges of two large cattle feedlots (KS1 and KS2) in Kansas were measured with tapered element oscillating microbalance (TEOM) PM10 monitors from January 2007 to December 2008. Weather conditions at the feedlots were also monitored. From measured PM10 concentrations and weather conditions, PM10 emission rates were determined using reverse modeling with the American Meteorological Society/U.S. Environmental Protection Agency Regulatory Model (AERMOD). The two feedlots differed significantly in median PM10 emission flux (1.60 g/m2-day for KS1 vs. 1.10 g/m2-day for KS2) but not in PM10 emission factor (27 kg/1000 head-day for KS1 and 30 kg/1000 head-day KS2). These emission factors were smaller than published U.S. Environmental Protection Agency (EPA) emission factor for cattle feedlots.

Gas-phase hydrogen/deuterium exchange in a traveling wave ion guide for the examination of protein conformations.

Accumulating evidence suggests that solution-phase conformations of small globular proteins and large molecular protein assemblies can be preserved for milliseconds after electrospray ionization. Thus, the study of proteins in the gas phase on this time scale is highly desirable. Here we demonstrate that a traveling wave ion guide (TWIG) of a Synapt mass spectrometer offers a highly suitable environment for rapid and efficient gas-phase hydrogen/deuterium exchange (HDX). Gaseous ND(3) was introduced into either the source TWIG or the TWIG located just after the ion mobility cell, such that ions underwent HDX as they passed through the ND(3) on the way to the time-of-flight analyzer. The extent of deuterium labeling could be controlled by varying the quantity of ND(3) or the speed of the traveling wave. The gas-phase HDX of model peptides corresponded to labeling of primarily fast exchanging sites due to the short labeling times (ranging from 0.1 to 10 ms). In addition to peptides, gas-phase HDX of ubiquitin, cytochrome c, lysozyme, and apomyoglobin were examined. We conclude that HDX of protein ions in a TWIG is highly sensitive to protein conformation, enables the detection of conformers present on submilliseconds time scales, and can readily be combined with ion mobility spectrometry.

Ion mobility adds an additional dimension to mass spectrometric analysis of solution-phase hydrogen/deuterium exchange.

The goal of this study was to determine the utility of adding ion mobility spectrometry to studies probing the solution-phase hydrogen/deuterium exchange (HX) of proteins. The HX profile of the Hck SH3 domain was measured at both the intact protein and the peptic peptide levels in the Waters Synapt HDMS system which uses a traveling wave to accomplish ion mobility separation prior to time-of-flight (Tof) m/z analysis. The results indicated a similar loss of deuterium with or without use of mobility in the Synapt and a level of deuterium loss comparable with a non-mobility Q-Tof instrument. The drift time of this small protein and its peptic peptides did not noticeably change due to solution-based deuterium incorporation. Importantly, ion mobility separations provided an orthogonal dimension of separation in addition to the reversed-phase high-performance liquid chromatography (RP-HPLC). The additional dimension of separation allowed for the deconvolution of overlapping isotopic patterns for co-eluting peptides and extraction of valuable deuterium incorporation data for those peptides. Taken together, these results indicate that including ion mobility separation in HX MS analyses further improves the mass spectrometry portion of such experiments.

Automated orthogonal control system for electrospray ionization.

Low-flow electrospray ionization is typically a purely electrostatic method, used without supporting sheath-gas nebulization. Complex spray morphology results from a large number of possible spray emission modes. Spray morphology may assume the optimal Taylor cone-jet spray mode under equilibrium conditions. When coupling to nanobore gradient elution chromatography, however, stability of the Taylor cone-jet spray mode is compromised by the gradient of mobile phase physiochemical properties. The common spray modes for aqueous/organic mobile phases were characterized using orthogonal (strobed illumination) transmitted light and (continuous illumination) scattered light imaging. Correlation of image sets from these complementary illumination methods provides the basis for spray mode identification using qualitative and quantitative image analysis. An automated feedback-controlled electrospray source was developed on a computer capable of controlling electrospray potential using an image-processing based algorithm for spray mode identification. The implementation of the feedback loop results in a system that is both self-starting and self-tuning for a specific spray mode or modes. Thus, changes in mobile phase composition and/or flow rate are compensated in real-time and the source is maintained in the cone-jet or pulsed cone-jet spray modes.

Effects of fragile ions on mass resolution and on isolation for tandem mass spectrometry in the quadrupole ion trap mass spectrometer.

In the quadrupole ion trap, it has been noted that factors other than an ion's mass and charge may affect its measured m/z, resulting in compound-dependent, or "chemical", mass shifts. We propose that ions can exhibit a chemical mass shift because they are "fragile" and may fragment during the application of resonance ejection during mass analysis; these effects were studied using ions that include protonated, deprotonated, and adduct ions of explosives, acylcarnitines, and macrolide antibiotics. Fragile ions affect mass resolution by causing broader peaks than nonfragile ions, especially at slower scan speeds, as the result of the application of resonance ejection. Fragile ions may also be fragmented by the application of the isolation waveform during selection of the parent ion for tandem mass spectrometry experiments, making it impossible to achieve unit isolation of a fragile ion. To obtain adequate isolation intensity, the isolation waveform notch width must be increased and the time period of isolation must be decreased. Fragile ions also require lower optimum collision energy to achieve efficient collision-induced dissociation. We have developed criteria for the determination of the degree of ion fragility based upon experimental results.