Safety and Efficacy of Vocacapsaicin for Management of Postsurgical Pain: A Randomized Clinical Trial.

BACKGROUND: Nonopioid management of postsurgical pain remains a major unmet need. Few studies have evaluated TRPV1 agonists for analgesia after surgery. We studied intraoperative vocacapsaicin, a novel prodrug of the TRPV1 agonist capsaicin, in a validated model of postsurgical pain. METHODS: This was a triple-blinded, randomized, placebo-controlled, dose-ranging trial in patients undergoing bunionectomy. We randomized patients 1:1:1:1 to surgical site administration of 14 mL of placebo or one of three vocacapsaicin concentrations: 0.30, 0.15, or 0.05 mg/mL. The prespecified primary endpoint was the area-under-the-curve of the Numerical Rating Scale (NRS) pain score at rest through 96 hours for the 0.3 mg/mL group. Prespecified ordered, secondary endpoints for the 0.3 mg/mL group included percent of patients who did not require opioids from 0-96 hours, total opioid consumption through 96 hours, and the area-under-the-curve of the NRS pain score for the first week. RESULTS: We randomized 147 patients. During the first 96 hours, vocacapsaicin 0.30 mg/mL reduced pain at rest by 33% vs. placebo (primary endpoint, 95% CI [10%, 52%], effect size (Cohen's D) = 0.61, p = 0.005). Twenty-six percent of patients receiving vocacapsaicin 0.30 mg/mL did not require postoperative opioids for analgesia (p=0.025) vs. 5% of patients receiving placebo. Vocacapsaicin 0.30 mg/mL reduced opioid consumption over the first 96 hours by 50% vs. placebo (95% CI [26%, 67%], effect size = 0.76, p = 0.002). Vocacapsaicin 0.30 mg/mL reduced pain over the first week by 37% vs. placebo (95% CI [12%, 57%], effect size = 0.62, p = 0.004). Treatment effect persisted for at least 2 weeks. All study endpoints showed an administered concentration vs. response relationship. Vocacapsaicin was well-tolerated with no differences between groups in any safety parameter. CONCLUSIONS: A single, local administration of vocacapsaicin during surgery reduced pain and opioid consumption for at least 96 hours after surgery compared to control. TRIAL REGISTRATION: ClinicalTrials.gov NCT03599089.

Barriers to liver transplant referral in safety net settings: A national provider survey.

BACKGROUND AND AIMS: Safety net systems care for patients with a high burden of liver disease, yet experience many barriers to liver transplant (LT) referral. This study aimed to assess safety net providers' perspectives on barriers to LT referrals in the United States (US). METHODS: We conducted a nationwide anonymous online survey of self-identified safety net gastroenterologists and hepatologists from March through November 2022. This 27-item survey was disseminated via e-mail, society platforms, and social media. Survey sections included practice characteristics, transplant referral practices, perceived multilevel barriers to referral, potential solutions, and respondent characteristics. RESULTS: 50 complete surveys were included in analysis. 60.0% of respondents self-identified as White, 54.0% male. 90.0% practiced in an urban setting, 82.0% in tertiary medical centers, and 16.0% in community settings with all four US regions represented. Perceived patient-level barriers ranked as most significant, followed by practice-level, then provider-level barriers. Patient-level barriers such as lack of insurance (72.0%), finances (66.0%), social support (66.0%), and stable housing/transportation (64.0%) were ranked as significant barriers to referral, while medical mistrust and lack of interest were not. Limited access to financial services (36.0%) and addiction/mental health resources (34.0%) were considered important practice-level barriers. Few reported existing access to patient navigators (12.0%), and patient navigation was ranked as most likely to improve referral practices, followed by an expedited/expanded pathway for insurance coverage for LT. CONCLUSION: In this national survey, safety net providers reported highest barriers to LT referral at the patient- and practice-level. These data can inform development of multilevel interventions in safety net settings to enhance equity in LT access for vulnerable patients.

Strengthening COVID-19 vaccine confidence & demand during the US COVID-19 emergency response.

In October 2020, the CDC's Vaccinate with Confidence strategy specific to COVID-19 vaccines rollout was published. Adapted from an existing vaccine confidence framework for childhood immunization, the Vaccinate with Confidence strategy for COVID-19 aimed to improve vaccine confidence, demand, and uptake of COVID-19 vaccines in the US. The objectives for COVID-19 were to 1. build trust, 2. empower healthcare personnel, and 3. engage communities and individuals. This strategy was implemented through a dedicated unit, the Vaccine Confidence and Demand (VCD) team, which collected behavioral insights; developed and disseminated toolkits and best practices in collaboration with partners; and collaborated with health departments and community-based organizations to engage communities and individuals in behavioral interventions to strengthen vaccine demand and increase COVID-19 vaccine uptake. The VCD team collected and used social and behavioral data through establishing the Insights Unit, implementing rapid community assessments, and conducting national surveys. To strengthen capacity at state and local levels, the VCD utilized "Bootcamps," a rapid training of trainers on vaccine confidence and demand, "Confidence Consults", where local leaders could request tailored advice to address local vaccine confidence challenges from subject matter experts, and utilized surge staffing to embed "Vaccine Demand Strategists" in state and local public health agencies. In addition, collaborations with Prevention Research Centers, the Institute of Museum and Library Services, and the American Psychological Association furthered work in behavioral science, community engagement, and health equity. The VCD team operationalized CDC's COVID-19 Vaccine with Confidence strategy through behavioral insights, capacity building opportunities, and collaborations to improve COVID-19 vaccine confidence, demand, and uptake in the US. The inclusion of applied behavioral science approaches were a critical component of the COVID-19 vaccination program and provides lessons learned for how behavioral science can be integrated in future emergency responses.

Oncologic Safety of Close Margins in Patients With Low- to Intermediate-Grade Major Salivary Gland Carcinoma.

Importance: Postoperative radiation therapy for close surgical margins in low- to intermediate-grade salivary carcinomas lacks multi-institutional supportive evidence. Objective: To evaluate the oncologic outcomes for low- and intermediate-grade salivary carcinomas with close and positive margins. Design, Setting, and Participants: The American Head and Neck Society Salivary Gland Section conducted a retrospective cohort study from 2010 to 2019 at 41 centers. Margins were classified as R0 (negative), R1 (microscopically positive), or R2 (macroscopically positive). R0 margins were subclassified into clear (>1 mm) or close (≤1 mm). Data analysis was performed from June to October 2023. Main Outcomes and Measures: Main outcomes were risk factors for local recurrence. Results: A total of 865 patients (median [IQR] age at surgery, 56 [43-66] years; 553 female individuals [64%] and 312 male individuals [36%]) were included. Of these, 801 (93%) had parotid carcinoma and 64 (7%) had submandibular gland carcinoma, and 748 (86%) had low-grade tumors and 117 (14%) had intermediate-grade tumors, with the following surgical margins: R0 in 673 (78%), R1 in 168 (19%), and R2 in 24 (3%). Close margins were found in 395 of 499 patients with R0 margins (79%), for whom margin distances were measured. A total of 305 patients (35%) underwent postoperative radiation therapy. Of all 865 patients, 35 (4%) had local recurrence with a median (IQR) follow-up of 35.3 (13.9-59.1) months. In patients with close margins as the sole risk factor for recurrence, the local recurrence rates were similar between those who underwent postoperative radiation therapy (0 of 46) or observation (4 of 165 [2%]). Patients with clear margins (n = 104) had no recurrences. The local recurrence rate in patients with R1 or R2 margins was better in those irradiated (2 of 128 [2%]) compared to observed (13 of 64 [20%]) (hazard ratio [HR], 0.05; 95% CI, 0.01-0.24). Multivariable analysis for local recurrence found the following independent factors: age at diagnosis (HR for a 10-year increase in age, 1.33; 95% CI, 1.06-1.67), R1 vs R0 (HR, 5.21; 95% CI, 2.58-10.54), lymphovascular invasion (HR, 4.47; 95% CI, 1.43-13.99), and postoperative radiation therapy (HR, 0.10; 95% CI, 0.04-0.29). The 3-year local recurrence-free survivals for the study population were 96% vs 97% in the close margin group. Conclusions and Relevance: In this cohort study of patients with low- and intermediate-grade major salivary gland carcinoma, postoperative radiation therapy for positive margins was associated with decreased risk of local recurrence. In isolation from other risk factors for local recurrence, select patients with close surgical margins (≤1 mm) may safely be considered for observation.

Artificial intelligence and classic methods to segment and characterize spherical objects in micrographs of industrial emulsions.

The stability of emulsions is a critical concern across multiple industries, including food products, agricultural formulations, petroleum, and pharmaceuticals. Achieving prolonged emulsion stability is challenging and depends on various factors, with particular emphasis on droplet size, shape, and spatial distribution. Addressing this issue necessitates an effective investigation of these parameters and finding solutions to enhance emulsion stability. Image analysis offers a powerful tool for researchers to explore these characteristics and advance our understanding of emulsion instability in different industries. In this review, we highlight the potential of state-of-the-art deep learning-based approaches in computer vision and image analysis to extract relevant features from emulsion micrographs. A comprehensive summary of classic and cutting-edge techniques employed for characterizing spherical objects, including droplets and bubbles observed in micrographs of industrial emulsions, has been provided. This review reveals significant deficiencies in the existing literature regarding the investigation of highly concentrated emulsions. Despite the practical importance of these systems, limited research has been conducted to understand their unique characteristics and stability challenges. It has also been identified that there is a scarcity of publications in multimodal analysis and a lack of a complete automated in-line emulsion characterization system. This review critically evaluates the existing challenges and presents prospective directions for future advancements in the field, aiming to address the current gaps and contribute to the scientific progression in this area.

A New Method for Dead Time Calibration and a New Expression for Correction of WDS Intensities for Microanalysis.

Observed photon count rates must be corrected for detector dead time effects for accurate quantification, especially at high count rates. We present the "constant k-ratio" method, a new approach for calibrating dead time for wavelength dispersive spectrometers by measuring k-ratios as a function of beam current. The method is based on the observation that for a given emission line at a specific take-off angle and electron beam energy, the intensity ratio from two materials containing the element should remain constant as a function of beam current, if the dead time calibration is accurate. The method has the advantage that it does not rely on the linearity of the beam current picoammeter, yet also allows the analyst to evaluate the picoammeter linearity, another critical parameter in EPMA calibration. By simultaneously comparing k-ratios for all spectrometers, one can also ascertain k-ratio consensus, essential for inter-laboratory comparisons. We also introduce improved dead time expressions and provide best practices on how to perform these instrument calibrations using this new "constant k-ratio" method. These improvements enable quantitative analysis of major and minor elements with high accuracy at high beam currents, simultaneously with trace elements with high sensitivity, for point analyses and X-ray mapping.

Operationalizing the Centers for Disease Control and Prevention's Vaccinate With Confidence Framework During the COVID-19 Emergency Response in the United States.

In December 2020, 11 months after identifying the first laboratory-confirmed case of COVID-19 in the United States, the U.S. Food and Drug Administration authorized emergency use of two COVID-19 vaccines. To prepare the public for a large-scale vaccination campaign and build confidence in COVID-19 vaccines, the U.S. Centers for Disease Control and Prevention (CDC) funded more than 200 partners and developed a national Vaccinate with Confidence (VwC) COVID-19 framework to support Americans in their decision to get vaccinated. The evolving nature of the pandemic and highly variable confidence in vaccines across populations has resulted in many unique complexities and challenges to reaching universally high vaccination coverage. Here, we describe how 23 professional health associations and national partner organizations, focused solely on building vaccine confidence, operationalized CDC's VwC COVID-19 framework from February 2021 to March 2022. Capturing how partners deployed and adapted their activities to meet a shifting pandemic landscape, which began with high demand for vaccines that waned over time, is an important first step to understanding how this new strategy was utilized and could be implemented for future surges in COVID-19 cases and other routine immunization efforts. Going forward, evaluation of partner activities should be prioritized to capture learnings and assess VwC program effectiveness.

An Improved Average Atomic Number Calculation for Estimating Backscatter and Continuum Production in Compounds.

It is often assumed that electron backscatter and continuum (bremsstrahlung) productions emitted from electron-solid interactions during X-ray microanalysis in compounds can be extrapolated from pure element observations by means of the assumption of average atomic number, or Z-bar (Z¯). For pure elements the average Z is equal to the atomic number, but this direct approach fails for compounds. The use of simple atomic fractions yields completely spurious results, and while the commonly used mass fraction Z averaging produces fairly reasonable results, we know from physical considerations that the mass of the neutron plays only a negligible role in such interactions below ∼1 MeV. Therefore, including the mass or atomic weight in such calculations can only introduce further errors in these models. We present an expression utilizing atomic fractions of the atomic numbers of the elements in the compound (Z fraction), with an exponent to account for the variation in nuclear screening as a function of the element Z value.

A Pilot Study of a Palliative Care Service Embedded in a Hepatology Clinic at a Large Public Hospital.

Background: End-stage liver disease (ESLD) patients carry heavy symptom burdens and risk receiving aggressive and sometimes unwanted care at end of life. Palliative care (PC), which aims to alleviate symptoms and facilitate goal-concordant care in serious illness, may offer substantial benefits for ESLD patients but is not widely provided. Objectives: To assess the impact of PC integrated within hepatology (PCIH) services on health care utilization, advance care planning (ACP), and hospice enrollment. Design: We compared patients who received PCIH (n = 55) to a retrospective cohort (n = 57) receiving usual care in an outpatient hepatology clinic. Setting/Subjects: From June 2016 to November 2017, we enrolled patients receiving care in a U.S. public hospital clinic who met the following inclusion criteria: (1) ESLD with a Model for End-Stage Liver Disease score ≥20, (2) hepatology approval for PC referral, and (3) at least one advanced complication of ESLD. Measurements: We assessed patient demographics, clinical information, health care insurance status, health care utilization, completion of psychosocial assessments, and ACP using two-sided Fisher's exact test and Mann-Whitney U tests. Results: Patients receiving PCIH more frequently had goals of care discussions (87.3% vs. 21.2% p ≤ 0.01), completed ACP documentation (56.4% vs. 7.0%, p ≤ 0.01), psychosocial assessments (98.2% vs. 35.1%, p ≤ 0.01), and hospice enrollment (25.5% vs. 7.0%, p = 0.01). Patients receiving PCIH who were hospitalized also had fewer mean hospitalization days (13 vs. 19.7 days, p ≤ 0.01). Conclusions: Embedding PC services in a hepatology clinic is a promising strategy to improve care for ESLD patients in public hospitals.

A phase II, multicenter, open-label, randomized trial of pegfilgrastim for patients with alcohol-associated hepatitis.

Background: In trials conducted in India, recombinant granulocyte colony stimulating factor (GCSF) improved survival in alcohol-associated hepatitis (AH). The aim of this trial was to determine the safety and efficacy of pegfilgrastim, a long-acting recombinant GCSF, in patients with AH in the United States. Methods: This prospective, randomized, open label trial conducted between March 2017 and March 2020 randomized patients with a clinical diagnosis of AH and a Maddrey discriminant function score ≥32 to standard of care (SOC) or SOC+pegfilgrastim (0.6 mg subcutaneously) on Day 1 and Day 8 (clinicaltrials.gov NCT02776059). SOC was 28 days of either pentoxifylline or prednisolone, as determined by the patient's primary physician. The second injection of pegfilgrastim was not administered if the white blood cell count exceeded 30,000/mm3 on Day 8. Primary outcome was survival at Day 90. Secondary outcomes included the incidence of acute kidney injury (AKI), hepatorenal syndrome (HRS), hepatic encephalopathy, or infections. Findings: The study was terminated early due to COVID19 pandemic. Eighteen patients were randomized to SOC and 16 to SOC+pegfilgrastim. All patients received prednisolone as SOC. Nine patients failed to receive a second dose of pegfilgrastin due to WBC > 30,000/mm3 on Day 8. Survival at 90 days was similar in both groups (SOC: 0.83 [95% confidence interval [CI]: 0.57-0.94] vs. pegfilgrastim: 0.73 [95% CI: 0.44-0.89]; p > 0.05; CI for difference: -0.18-0.38). The incidences of AKI, HRS, hepatic encephalopathy, and infections were similar in both treatment arms and there were no serious adverse events attributed to pegfilgrastim. Interpretation: This phase II trial found no survival benefit at 90 days among subjects with AH who received pegfilgrastim+prednisolone compared with subjects receiving prednisolone alone. Funding: was provided by the United States National Institutes of Health and National Institute on Alcohol Abuse and Alcoholism U01-AA021886 and U01-AA021884.

NIR-Based Intelligent Sensing of Product Yield Stress for High-Value Bioresorbable Polymer Processing.

PLA (polylactide) is a bioresorbable polymer used in implantable medical and drug delivery devices. Like other bioresorbable polymers, PLA needs to be processed carefully to avoid degradation. In this work we combine in-process temperature, pressure, and NIR spectroscopy measurements with multivariate regression methods for prediction of the mechanical strength of an extruded PLA product. The potential to use such a method as an intelligent sensor for real-time quality analysis is evaluated based on regulatory guidelines for the medical device industry. It is shown that for the predictions to be robust to processing at different times and to slight changes in the processing conditions, the fusion of both NIR and conventional process sensor data is required. Partial least squares (PLS), which is the established 'soft sensing' method in the industry, performs the best of the linear methods but demonstrates poor reliability over the full range of processing conditions. Conversely, both random forest (RF) and support vector regression (SVR) show excellent performance for all criteria when used with a prior principal component (PC) dimension reduction step. While linear methods currently dominate for soft sensing of mixture concentrations in highly conservative, regulated industries such as the medical device industry, this work indicates that nonlinear methods may outperform them in the prediction of mechanical properties from complex physicochemical sensor data. The nonlinear methods show the potential to meet industrial standards for robustness, despite the relatively small amount of training data typically available in high-value material processing.

Pharmacokinetics and local tissue response to local instillation of vocacapsaicin, a novel capsaicin prodrug, in rat and rabbit osteotomy models.

Vocacapsaicin is a novel prodrug of trans-capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) being developed as a nonopioid, long-lasting, site-specific treatment for postsurgical pain management. The objective of these studies was to examine the safety and tolerability of vocacapsaicin in an osteotomy model in two animal species and to evaluate bone healing parameters. Rats undergoing unilateral femoral osteotomy received a single perioperative administration (by instillation) of vocacapsaicin (vehicle, 0.15, 0.3, and 0.6 mg/kg). Rabbits undergoing unilateral ulnar osteotomy received a single perioperative administration (by infiltration and instillation) of vocacapsaicin (vehicle, 0.256 and 0.52 mg) alone or in combination with 0.5% ropivacaine. Clinical signs, body weights, food consumption, radiography, histopathologic examinations, ex vivo bone mineral density measurements (rats only), and biomechanical testing were evaluated at 4 and 8 weeks in rats and at 2 and 10 weeks in rabbits. Plasma samples were also collected in rabbits. There were no vocacapsaicin-related effects on mortality, clinical observations, body weight, or food consumption in either species. Systemic exposure to vocacapsaicin and its metabolites, including capsaicin, was transient. In rats, vocacapsaicin was devoid of deleterious effects on bone healing parameters, and there was a trend for enhanced bone healing in rats treated with the mid-dose. In rabbits, vocacapsaicin administered alone or in combination with ropivacaine did not adversely affect bone healing parameters. In conclusion, a single perioperative administration of vocacapsaicin in unilateral osteotomy models was well tolerated, locally and systemically, supporting its continued development as a novel, nonopioid treatment for postsurgical pain management.

Disseminated Mycobacterium bovis infection after deceased donor liver transplantation: A case report.

This case demonstrates the significance, and ongoing relevance of mycobacterial infections, especially in patients who have recently been started on immunosuppression.

An Objective Pain Score for Chronic Pain Clinic Patients.

Objectives: Although numerous studies have looked at the numeric rating scale (NRS) in chronic pain patients and several studies have evaluated objective pain scales, no known studies have assessed an objective pain scale for use in the evaluation of adult chronic pain patients in the outpatient setting. Subjective scales require patients to convert a subjective feeling into a quantitative number. Meanwhile, objective pain scales utilize, for the most part, the patient's behavioral component as observed by the provider in addition to the patient's subjective perception of pain. This study aims to examine the reliability and validity of an objective Chronic Pain Behavioral Pain Scale for Adults (CBPS) as compared to the traditional NRS. Methods: In this cross-sectional study, patients were assessed before and after an interventional pain procedure by a researcher and a nurse using the CBPS and the NRS. Interrater reliability, concurrent validity, and construct validity were analyzed. Results: Interrater reliability revealed a fair-good agreement between the nurse's and researcher's CBPS scores, weighted kappa values of 0.59 and 0.65, preprocedure and postprocedure, respectively. Concurrent validity showed low positive correlation for the preprocedure measurements, 0.34 (95% CI 0.16-0.50) and 0.47 (95% CI 0.31-0.61), and moderate positive correlation for the postprocedure measurements, 0.68 (95% CI 0.56-0.77) and 0.67 (95% CI 0.55-0.77), for the nurses and researchers, respectively. Construct validity demonstrated an equally average significant reduction in pain from preprocedure to postprocedure, CBPS and NRS median (IQR) scores preprocedure (4 (2-6) and 6 (4-8)) and postprocedure (1 (0-2) and 3 (0-5)), p < 0.001. Discussion. The CBPS has been shown to have interrater reliability, concurrent validity, and construct validity. However, further testing is needed to show its potential benefits over other pain scales and its effectiveness in treating patients with chronic pain over a long-term. This study was registered with ClinicalTrial.gov with National Clinical Trial Number NCT02882971.

IgG:IgM Ratios of Liver Plasma Cells Reveal Similar Phenotypes of Primary Biliary Cholangitis With and Without Features of Autoimmune Hepatitis.

Within the spectrum of autoimmune liver diseases, there are patients who manifest features of more than one disease, which was previously identified as having overlap syndrome1,2 and is now referred to as variant syndromes. The most common variant syndrome is between primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH). Typically, AIH presents with elevated serum immunoglobulin (Ig) G, whereas PBC is associated with elevated serum IgM.3,4 Previous studies have suggested that plasma cells in liver biopsies of AIH patients are predominantly IgG+, whereas in PBC, there is an abundance of IgM+ cells.5,6 We wanted to determine the immunostaining pattern for IgG and IgM of liver plasma cells among Hispanic patients in Los Angeles with features of both PBC-AIH compared with those with PBC or AIH alone.

Effects of plant growth regulator application on the malting quality of barley.

BACKGROUND: Lodging can negatively affect yield and quality of barley grain. Synthetic plant growth regulators (PGRs) reduce lodging by producing shorter, thicker, and stronger stems. However, the impact of applying PGRs on malting performance of barley is not known. The objective of this work was to assess the effect of application of three PGRs (ethephon, chlormequat chloride, and trinexapac-ethyl) in combination with different seeding rates on the malting quality of barley grown in several locations and years in western Canada. RESULTS: The kernel weight in PGR-treated barley was reduced by 1.7% to 6.5% compared with the nontreated grain. Application of PGRs had no effect on the concentration of proteins and germination energy. Seeding rates significantly affected kernel weight, protein content, and germination index (GI), but no interactions between PGRs and seeding rates were observed. The smaller kernels of ethephon- and trinexapac-treated barley showed good hydration and grain modification during malting, as indicated by high levels of starch-converting enzymes, high Kolbach indices, and low levels of wort ß-glucans. Overall, the fine extract of malt from PGR-treated barley was slightly lower than that of the control malt; however, the extract reduction was statistically significant only for chlormequat- and trinexapac-treated barley. CONCLUSIONS: The application of PGRs had significant effects on kernel plumpness and kernel weight, but the effects of PGR application on the malting quality were generally small and insignificant. The decision of PGRs application on malting barley needs to be considered in combination with potential benefits of PGRs in mitigating lodging and their effects on the agronomic performance of barley. © Her Majesty the Queen in Right of Canada 2019.

High Speed Matrix Corrections for Quantitative X-ray Microanalysis Based on Monte Carlo Simulated K-Ratio Intensities.

Due to recent advances in modeling the production of characteristic X-rays, Monte Carlo simulation of electron-solid interactions can provide improved quantitative estimates of X-ray intensities for both homogeneous and heterogeneous interaction volumes. In the case of homogeneous materials, these modeled X-ray intensities can predict with excellent accuracy, matrix corrections for arbitrary compositions, arbitrary emission lines, and electron energies. By pre-calculating these Monte Carlo X-ray intensities for pure element standards and a range of compositions of binary systems, we can derive matrix corrections for complex compositions in real-time by parameterizing these k-ratios as the so-called alpha factors. This method allows one to perform Monte Carlo-based bulk matrix corrections in seconds for arbitrary and complex compositions (with two or more elements), by combining these binary alpha factors using the so-called beta expression. We are systematically calculating X-ray intensities for 11 compositions from 1 to 99 wt% for binary pairs of all emitters and absorbers in the periodic table, for the main emission lines (Kα, Kß, Lα, Lß, Mα, and Mß) at beam energies from 5 to 50 keV, using Monte Carlo calculations based on a modified PENELOPE electron-photon transport code, although any other Monte Carlo software could also be utilized. Comparison of k-ratios calculated with the proposed method and experimental k-ratios from the Pouchou and Pichoir database suggest improvements over typical φ(ρz) methods. Additional comparisons with k-ratio measurements from more complex compositions would be ideal, but our testing of the additivity of the beta equation suggests that arbitrary compositions can be handled as well, except in cases of extreme fluorescence or absorption.

Multipoint Background Analysis: Gaining Precision and Accuracy in Microprobe Trace Element Analysis.

Electron microprobe trace element analysis is a significant challenge. Due to the low net intensity of peak measurements, the accuracy and precision of such analyses relies critically on background measurements, and on the accuracy of any pertinent peak interference corrections. A linear regression between two points selected at appropriate background positions is a classical approach for electron probe microanalysis (EPMA). However, this approach neglects the accurate assessment of background curvature (exponential or polynomial), and the presence of background interferences, a hole in the background, or an absorption edge can dramatically affect the results if underestimated or ignored. The acquisition of a quantitative wavelength-dispersive spectrometry (WDS) scan over the spectral region of interest remains a reasonable option to determine the background intensity and curvature from a fitted regression of background portions of the scan, but this technique can be time consuming and retains an element of subjectivity, as the analyst has to select areas in the scan which appear to represent background. This paper presents a new multi-point background (MPB) method whereby the background intensity is determined from up to 24 background measurements from wavelength positions on either side of analytical lines. This method improves the accuracy and precision of trace element analysis in a complex matrix through careful regression of the background shape, and can be used to characterize the background over a large spectral region covering several elements to be analyzed. The overall efficiency improves as systematic WDS scanning is not required to assess background interferences. The method is less subjective compared to methods that rely on WDS scanning, including selection of two interpolation points based on WDS scans, because "true" backgrounds are selected through an exclusion method of possible erroneous backgrounds. The first validation of the MPB method involves blank testing to ensure the method can accurately measure the absence of an element. The second validation involves the analysis of U-Th-Pb in several monazite reference materials of known isotopic age. The impetus for the MPB method came from efforts to refine EPMA monazite U-Th-Pb dating, where it was recognized that background errors resulting from interference or strong background curvature could result in errors of several tens of millions of years on the calculated date. Results obtained on monazite reference materials using two different microprobes, a Cameca SX-100 Ultrachron and a JEOL JXA-8230, yield excellent agreement with ages obtained by isotopic methods (Thermal Ionization Mass Spectrometry [TIMS], Sensitive High-Resolution Ion MicroProbe [SHRIMP], or Secondary Ion Mass Spectrometry [SIMS]). Finally, the MPB method can be used to model the background over a large spectrometer range to improve the accuracy of background measurement of minor and trace elements acquired on a same spectrometer, a method called the shared background measurement. This latter significantly improves the accuracy of minor and trace element analysis in complex matrices, as demonstrated by the analysis of Rare Earth Elements (REE) in REE-silicates and phosphates and of trace elements in scheelite.