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Per- and polyfluoroalkyl substances (PFAS) are a large group of anthropogenic chemicals that have been applied in a wide range of industrial, commercial, and domestic products since the 1950s. Because of their toxicity, persistence, and bioaccumulation potential, PFAS have become global environmental pollutants. Besides the environment, the food chain represents another source of exposure, and the risk to consumers related to the presence of PFAS in foods has recently become of increased interest. In this respect, whole milk, infant formula, and ingredients used in infant formula production represent important foodstuffs that require sensitive methods with reporting limits at low parts per billion levels or lower for multiple PFAS. This article summarizes optimization experiments and validation of a complete workflow, including sample preparation and a liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for determination of sixteen priority PFAS analytes listed by the U.S. Food and Drug Administration (FDA).

Per- and polyfluoroalkyl substances (PFAS) are a large group of anthropogenic chemicals that have been applied in a wide range of industrial, commercial, and domestic products since the 1950s. Because of their toxicity, persistence, and bioaccumulation potential, PFAS have become global environmental pollutants. Besides the environment, the food chain represents another source of exposure, and the risk to consumers related to the presence of PFAS in foods has recently become of increased interest. In this respect, whole milk, infant formula, and ingredients used in infant formula production represent important foodstuffs that require sensitive methods with reporting limits at low parts per billion levels or lower for multiple PFAS. This article summarizes optimization experiments and validation of a complete workflow, including sample preparation and a liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for determination of sixteen priority PFAS analytes listed by the U.S. Food and Drug Administration (FDA).

Tick-borne diseases (TBD), including spotted fever group rickettsiosis (SFGR), ehrlichiosis, and, increasingly, Lyme disease, represent a substantial public health concern throughout much of the southeastern United States. Yet, there is uncertainty about the epidemiology of these diseases because of pitfalls in existing diagnostic test methods.To examine patterns of diagnostic testing and incidence of TBD in a large, academic health care system.This cross-sectional study included diagnostic test results for TBD at UNC Health, a large academic health care system with inpatient and outpatient facilities, from January 1, 2017, to November 30, 2020. Participants included all individuals seeking routine care at UNC Health facilities who had testing for SFGR, ehrlichiosis, or Lyme disease performed during the study period.Rates of test positivity, testing completeness, and incidence of TBD.During the 4-year study period, 11 367 individuals (6633 [58.4%] female; 10 793 [95%] non-Hispanic individuals and 8850 [77.9%] White individuals; median [IQR] age, 53 [37-66] years) were tested for TBD. Among the 20 528 diagnostic tests performed, 47 laboratory-confirmed, incident cases of SFGR, 27 cases of ehrlichiosis, and 76 cases of Lyme were confirmed, representing incidence rates of 4.7%, 7.1%, and 0.7%, respectively. However, 3984 of SFGR tests (79.3%) and 3606 of Ehrlichia tests (74.3%) lacked a paired convalescent sample. Of 20 528 tests, there were 11 977 tests (58.3%) for Lyme disease from 10 208 individuals, 5448 tests (26.5%) for SFGR from 4520 individuals, and 3103 tests (15.1%) for ehrlichiosis from 2507 individuals. Most striking, testing for ehrlichiosis was performed in only 55% of patients in whom SFGR was ordered, suggesting that ehrlichiosis remains underrecognized. An estimated 187 incident cases of SFGR and 309 of ehrlichiosis were potentially unidentified because of incomplete testing.In this cross-sectional study, most of the patients suspected of having TBD did not have testing performed in accordance with established guidelines, which substantially limits understanding of TBD epidemiology. Furthermore, the data revealed a large discrepancy between the local burden of disease and the testing performed. These findings underscore the need to pursue more robust, active surveillance strategies to estimate the burden of TBD and distribution of causative pathogens.

ImportanceTick-borne diseases (TBD) including Spotted Fever Group Rickettsiosis (SFGR), ehrlichiosis, and increasingly Lyme disease represent a substantial public health concern throughout much of the Southeastern United States. Yet, there is uncertainty about the epidemiology of these diseases due to pitfalls in existing diagnostic test methodologies.ObjectiveTo examine patterns of diagnostic testing and incidence of TBD in a large, academic healthcare system.DesignCross-sectional study of diagnostic test results from UNC Health for the period January 1st, 2017 to November 30th, 2020.SettingLarge, academic healthcare system in central North Carolina including inpatient and outpatient facilities.ParticipantsAll Individuals seeking routine care at UNC Health facilities who had testing for SFGR, ehrlichiosis or Lyme disease performed during the study periodMeasurementsRates of test positivity, testing completeness, and incidence of TBDResultsAmong the 20,528 diagnostic tests performed, we identified 47 laboratory-confirmed, incident cases of SFGR, 27 of ehrlichiosis, and 76 of Lyme, representing incidence rates of 4.7%, 7.1%, and 0.7% respectively. However, 79.3% of SFGR tests and 74.3% Ehrlichia tests lacked a paired convalescent sample. The total number of tests for Lyme disease was more than SFGR and ehrlichiosis combined, despite the relatively low incidence of disease in region. Most striking, testing for ehrlichiosis was performed in only half of patients in whom SFGR was ordered, suggesting that this disease remains underrecognized. Overall, we estimate that there were 187 incident cases of SFGR and 309 of ehrlichiosis that were not identified due to incomplete testing; a number that would drastically increase – and in the case of ehrlichiosis, nearly double – the total number of cases reported.Conclusions and RelevanceA majority of patients suspected of having TBD did not have testing performed in accordance with established guidelines, substantially limiting our understanding of TBD epidemiology. Furthermore, there appears to be a large discrepancy between the local burden of disease and the testing that is performed. These findings underscore the need to pursue more robust, active surveillance strategies to estimate the burden of TBDs and distribution of causative pathogens.

The objective of this disease state clinical review is to provide clinicians with a summary of the nonsurgical, minimally invasive approaches to managing thyroid nodules/malignancy, including their indications, efficacy, side effects, and outcomes.A literature search was conducted using PubMed and appropriate key words. Relevant publications on minimally invasive thyroid techniques were used to create this clinical review.Minimally invasive thyroid techniques are effective and safe when performed by experienced centers. To date, percutaneous ethanol injection therapy is recommended for recurrent benign thyroid cysts. Both ultrasound-guided laser and radiofrequency ablation can be safely used for symptomatic solid nodules, both toxic and nontoxic. Microwave ablation and high-intensity focused ultrasound are newer approaches that need further clinical evaluation. Despite limited data, encouraging results suggest that minimally invasive techniques can also be used in small-size primary and locally recurrent thyroid cancer.Surgery and radioiodine treatment remain the conventional and established treatments for nodular goiters. However, the new image-guided minimally invasive approaches appear safe and effective alternatives when used appropriately and by trained professionals to treat symptomatic or enlarging thyroid masses.

Single-event characterization of a Xilinx 16nm UltraScale+ Virtex high bandwidth memory (HBM)-enabled FPGA was performed using both the 64 MeV proton beam at Crocker Nuclear Laboratory and the neutron beam at LANSCE. Both single-event upset (SEU) and single-event functional interrupt (SEFI) analysis were performed on HBM stacks, fabric interface and HBM interface.

This paper examines the single-event upset response of a customer memory interface design on the Xilinx 20nm XCKU040 Field Programmable Gate Array (FPGA) irradiated with 64MeV proton source. Results for single-event upsets on configuration RAM (CRAM) cells are provided. The difference between architectural vulnerability factor (AVF) and design vulnerability factor (DVF) of the customer memory interface design is also discussed in this work.

A single-laboratory validation study of a method for screening and identification of phosphodiesterase type 5 (PDE5) inhibitors in dietary ingredients and supplements is described. PDE5 inhibitors were extracted from the samples using a 50:50 (v/v) mixture of acetonitrile and water and centrifuged. Supernatant was diluted, filtered, and analyzed by LC–high-resolution MS. Data were collected in MS acquisition mode that combined full-scan MS experiment with all-ion fragmentation and data-dependent MS/MS product from the ion scan experiment. This approach enabled collection of MS and tandem MS (MS/MS) data for both targeted and nontargeted PDE5 inhibitors in a single chromatographic run. Software-facilitated identification of targeted analytes was performed based on the retention time, accurate mass, and isotopic pattern of pseudomolecular ions, and accurate masses of fragment ions using an in-house compound database. Detection and identification of other PDE5 inhibitors and novel analogs were performed by retrospective evaluation of MS and MS/MS experimental data. The method validation results obtained for evaluated matrixes fulfilled the probability of identification requirements and probability of detection requirements (for the pooled data) set at 90% (95% confidence interval) in the respective AOAC Standard Method Performance Requirements for identification and screening methods for PDE5 inhibitors. Limited data demonstrating the quantification capability of the method were also generated. Mean recovery and repeatability obtained for the evaluated PDE5 inhibitors were in the range 69–90% and 0.4–1.8%, respectively.

In this study, sponsored by PepsiCo Inc., a method was validated for measurement of 11 pesticide residues in soft drinks and sports drinks. The pesticide residues determined in this validation were alachlor, atrazine, butachlor, isoproturon, malaoxon, monocrotophos, paraoxon-methyl, phorate, phorate sulfone, phorate sulfoxide, and 2,4-dichlorophenoxyacetic acid (2,4-D) when spiked at 0.100 g/L (1.00 g/L for phorate). Samples were filtered (if particulate matter was present), degassed (if carbonated), and analyzed using liquid chromatography with tandem mass spectrometry. Quantitation was performed with matrix-matched external standard calibration solutions. The standard curve range for this assay was 0.0750 to 10.0 g/L. The calibration curves for all agricultural residues had coefficient of determination (r2) values greater than or equal to 0.9900 with the exception of 2 values that were 0.9285 and 0.8514. Fortification spikes at 0.100 g/L (1.00 g/L for phorate) over the course of 2 days (n = 8 each day) for 3 matrixes (7UP, Gatorade, and Diet Pepsi) yielded average percent recoveries (and percent relative standard deviations) as follows (n = 48): 94.4 (15.2) for alachlor, 98.2 (13.5) for atrazine, 83.1 (41.6) for butachlor, 89.6 (24.5) for isoproturon, 87.9 (24.4) for malaoxon, 96.1 (9.26) for monocrotophos, 101 (25.7) for paraoxon-methyl, 86.6 (20.4) for phorate, 101 (16.5) for phorate sulfone, 93.6 (25.5) for phorate sulfoxide, and 98.2 (6.02) for 2,4-D.

In conjunction with an AOAC Task Group on dietary supplements, a liquid chromatography/tandem mass spectrometry (LC–MS/MS) method was validated for measurement of 6 major alkaloids in raw ephedra sinica herb, ephedra extracts, ephedra tablets, complex dietary supplements containing ephedra, and a high-protein drink mix containing ephedra. The amount of ephedrine-type alkaloids present was determined by LC with mass selective detection. Six replicates of each matrix were analyzed on 3 separate occasions. The presence of 6 ephedrine-type alkaloids was detected at a level >0.5 μg/g based on a 0.5 g sample. The standard curve range for this assay is from 0.02 to 1.0 μg/mL. Appropriate dilutions covered a wide range of specific alkaloid concentrations. The calibration curves for all 6 analytes had correlation coefficients >0.995.

Summary We propose the expected integrated mean-squared error (EIMSE) experimental design criterion and show how we used it to design experiments to meet the needs of researchers in die casting engineering. This criterion expresses in a direct way the researchers’ goal to minimize the expected meta-model prediction errors, taking into account the effects of both random experimental errors and errors deriving from our uncertainty about the true model form. Because we needed to make assumptions about the prior distribution of model coefficients to estimate the EIMSE, we performed a sensitivity analysis to verify that the relative prediction performance of the design generated was largely insensitive to our assumptions. Also, we discuss briefly the general advantages of EIMSE optimal designs, including lower expected bias errors compared with popular response surface designs and substantially lower variance errors than certain Box–Draper all-bias designs.

This paper describes a new gas turbine research facility that was designed and is currently being constructed with a number of unique features that allow experiments which aim at developing and improving sealing and cooling technologies at a reasonable cost. Experiments will include engine-representative rotating turbine hardware in a continuous, steady-state, high-pressure flow environment. The facility includes a 1.5 stage turbine that will simulate the aerodynamic flow and thermal field interactions in the engine between the hot mainstream gas path and the secondary air flows at relevant corrected operating conditions and scaling parameters. Testing in the new facility is planned to begin in 2014 and will take place in two phases. The first phase is focused on understanding the behavior of inner-stage gap flow leakages in the presence of the main gas path and the rotating blade platform. The second phase is focused on developing and testing novel cooling methods for turbine airfoils, platforms, and disks, ultimately leading to an integrated approach for more effective use of the secondary cooling flow. The uniqueness of this facility includes a continuous duration facility with engine-relevant rotational and axial Reynolds and Mach numbers at the blade inlet.

There is a paucity of data concerning the correlation of complement component 4d (C4d) staining in liver allografts and antibody-mediated rejection. Data about the location and character of C4d deposits in native and allograft liver tissues are inconsistent. We performed C4d immunofluorescence (IF) on 141 fresh-frozen liver allograft biopsy samples and native livers, documented the pattern of C4d IF staining, and correlated the findings with the presence of donor-specific alloantibodies (DSAs). A linear/granular sinusoidal pattern of C4d IF was noted in 18 of 28 biopsy samples obtained after transplantation from patients with positive crossmatch and detectable donor-specific alloantibody (pos-XM/DSA) findings. None of the 59 tested biopsy samples from patients with negative crossmatch and detectable donor-specific alloantibody (neg-XM/DSA) findings were C4d-positive (P0.001). No significant association was found between pos-XM/DSA and C4d IF staining in other nonsinusoidal liver compartments. To compare the results of sinusoidal C4d staining with IF and 2 immunohistochemistry (IHC) techniques, C4d IHC was performed on 19 liver allograft biopsy samples in which a sinusoidal pattern of C4d IF had been noted. Sinusoidal C4d IHC findings were negative for 17 of the 19 biopsy samples; 2 showed weak and focal staining, and both patients had pos-XM/DSA findings. Portal vein endothelium staining was present in only 1 IF-stained biopsy sample (pos-XM/DSA) but in 11 IHC-stained biopsy samples (2 of the 11 samples had neg-XM/DSA findings). We conclude that sinusoidal C4d deposits detected by IF in frozen tissue samples from liver allograft recipients correlate with the presence of DSAs and an antibody-mediated alloresponse. These observations are similar to findings reported for other solid organ transplants and can provide relevant information for patient management. Further validation of IHC techniques for C4d detection in liver allograft tissue is required.

By forcing the CVD-W reactor in extreme starvation conditions it is possible to obtain low (tensile or compressive) stress tungsten film even at wafer temperatures as low as 400 o C. By combining different steps it is possible to come to a deposition process which can be used for all (interconnect, contact fill, and via fill) application needs in ULSI metallization systems. Using a sample population in which the stress varies more than one order of magnitude, the origin of the stress in the tungsten film is studied further using a substrate bending method for macrostress determination and x-ray techniques for microstress determination and grain size. Microstress in the grains can be higher than the corresponding macrostress of the film

The importance of antibody-mediated rejection (AMR) in ABO-compatible liver transplantation is controversial. Here we report a prospective series of liver recipients with a preoperative positive crossmatch. To establish the diagnosis of AMR in liver recipients, the criteria described for kidney allografts were adopted. In approximately 10% of 197 liver transplants, we observed a positive T and B cell flow crossmatch before transplantation. Fifteen of 19 patients converted to negative crossmatches early after transplantation and displayed normal liver function while they were on routine immunosuppression. Four patients maintained positive crossmatches. Three of the 4 met the criteria for AMR and showed evidence of graft dysfunction, the presence of donor-specific antibodies (DSAs), morphological tissue destruction with positive C4d linear staining on the graft sinusoidal endothelium, and improved function with attempts to eliminate DSAs. A persistently positive crossmatch after liver transplantation may lead to early, severe AMR and liver failure. C4d staining in the liver sinusoidal endothelium should alert one to the possibility of AMR. In our experience, patients with a positive crossmatch should have it repeated at 2 weeks and, if it is positive, again at 3 to 5 weeks. Recipients with an unknown preoperative crossmatch who develop early cholestasis of unclear etiology should be crossmatched or tested for the presence of DSAs to evaluate for AMR.

Moderate alcohol consumption is associated with a decreased risk of coronary artery disease. The mechanism of the putative protective effect of alcohol intake, however, remains elusive. Recent studies suggest that a ratio of apolipoprotein A-I/apolipoprotein B and Lp(a) are better indicators of the risk of atherosclerosis than total cholesterol and high density lipoprotein cholesterol. To assess the effect of alcohol on these analytes, we determined the concentration of Lp(a), apolipoprotein A-I, apolipoprotein B, total cholesterol, and high-density lipoprotein cholesterol, and calculated low-density lipoprotein cholesterol in serum of 12 patients meeting DSM-III-R criteria for alcohol dependence at the time of admission for treatment of alcohol withdrawal (before). The analyses were repeated after 4 weeks of supervised abstinence on a locked research unit (after). With abstinence, there was a significant increase in the concentration of Lp(a), the atherogenic index and the ratio of low-density to high-density lipoprotein cholesterol but a significant decrease in total cholesterol, high-density lipoprotein cholesterol, apolipoprotein A-I, and the apolipoprotein A-I/B ratio. Apolipoprotein B and low-density lipoprotein cholesterol showed no significant changes before and after alcohol abstinence. Thus, decreased Lp(a) and increased high-density lipoprotein cholesterol and apolipoprotein A-I may be factors mediating the putative protective effect of alcohol in coronary artery disease.

A national trade model of the fresh onion (Allium cepa L.) market is used to identify the capability of Texas to compete with other production areas in dry onion sales throughout the United States. The analysis shows Texas and western U.S. producers to be major competitors in the spring and summer seasons. While Texas producers' proximity to major eastern markets yields a cost advantage, their market share is vulnerable to cost reductions by western U.S. shippers. Thus, both cost-reducing innovations (production) and quality improvements are important in maintaining the competitiveness of Texas producers.

Cells interact with specific molecular components of the extracellular matrix via cell surface receptors [1]. The principal cell surface receptors that mediate cell-extracellular matrix interactions are termed integrins [2, 3]. Integrins are transmembrane receptors that interact with several intracellular proteins, including elements of the cytoskeleton by cytoplasmic domains. Therefore, integrins serve as a molecular linkage between the extracellular matrix and the cytoskeleton. Some investigators have suggested that many of these vital cellular activities are regulated, at least in part, by intercellular and intracellular forces that are generated by a continuous molecular connection that includes components of the extracellular matrix, integrins, and cytoskeletal elements (i.e., f-actin, microtubules). It is believed that individual cells “sense” and generate forces transmitted through the extracellular environment by these intricate linkages [4]. Furthermore, this linkage, referred to as the “extended cytoskeleton,” could provide a mechanical signaling mechanism that may underlie many vital cellular activities, including gene expression. It is apparent that the physical properties of a cell may also be affected by this mechanism. Thus, cells grown on different extracellular matrix substrates should be expected to vary their cytoskeletal architecture and have concomitant changes in their biomechanical properties. The objectives of this study were 1) to obtain the intrinsic material properties of the individual cell as a function of the type of substrate matrix and therefore, 2) to investigate fundamental aspects of the response mechanism of individual cells to alterations in their biophysical environment.

Three hundred and eight subjects were screened over the phone for admission to an inpatient alcohol treatment research unit. Using a structured interview, the prospective patients were asked questions regarding demographics, drinking history, previous treatments, physical health, family history, and a detailed history of past and present substance use. Drug use was studied as regular use versus no use or brief experimental use of five drug categories: cannabinoids, stimulants, sedatives, opiates, and hallucinogens. Fifty-one percent of the men and 48% of the women reported regular use of one or more of the drugs in addition to alcohol. For women, the amount of alcohol intake was positively correlated with use of stimulants (r = .32, p = .001), cannabinoids (r = .24, p = .019), sedatives (r = .30, p = .003), and hallucinogens (r = .30, p = .003). For men, correlations between the amount of alcohol intake and drug use were weaker but significant for stimulants (r = .21, p = .002), opiates (r = .15, p = .028), and hallucinogens (r = .15, p = .029). Women with alcoholic mothers displayed higher alcohol intake than women with nonalcoholic mothers (p = .02) and also showed more frequent use of most drugs. Although men with alcoholic fathers also showed greater alcohol intake compared to men with nonalcoholic fathers, the two groups did not differ in drug use. Younger subjects of both sexes were more likely to use cannabinoids, stimulants, opiates, and hallucinogens. Alcohol and sedative use was relatively constant across all age groups.

Cytomegalovirus reactivation (CMV-R) is an important cause of morbidity and mortality in immunocompromised patients. CMV-R has been recognized in critically ill patients. Severe burn injury leads to early and prolonged immune and adaptive immune dysfunction. We hypothesized that CMV-R would occur in burn patients correlating with specific changes in T cell phenotype. We prospectively evaluated incidence of CMV-R longitudinally among patients with >10% total body surface area (TBSA) injury using serum PCR. We determined changes in CMV specific CD8+ T cells by utilizing CMV-specific MHC Class I tetramers, functional responsiveness to CMV peptide and the generation of Tregs using qPCR for FoxP3. 24 burn patients enrolled, with CMV-R occurring in 36.8% of patients. We detected no difference in frequency of CMV-reactive CD8+ T cells nor in vitro anti-CMV CD8+ T cell response by IFN-γ staining between R and non-R patients. CMV-R patients had a significantly decreased proportion of CMV-specific CD8+ T cells that were central-memory (CD45RO+CD62L+CD28+) and increased effector-memory phenotype (CD28-) during the first week following injury. Elevated FoxP3 expression in the 10 days prior to R correlated with R in 4/6 patients tested. CMV-R occurred following burn injury and may be related to remodeling of the CD8+ T cell population after burn. Increased T cell regulatory activity after burn may also predict for CMV-R in a subset of patients.

To the Editor.— Consumption of alcoholic beverages increased throughout the 50s, 60s, and 70s but since 1981, an apparent downward trend has occurred. 1 During this same time, substance use patterns have changed considerably. 2,3 New, more potent, and dangerous drugs such as "crack" cocaine, "ecstasy," and "ice" have become available and use of multiple substances may have become more common, particularly among young subjects. To explore the incidence and clinical characteristics of coaddictions to alcohol and other drugs in a population seeking inpatient treatment for alcoholism, we analyzed telephone interview data from 308 subjects who were being considered for admission to the National Institute on Alcohol Abuse and Alcoholism (NIAAA) (Bethesda, Md) Laboratory of Clinical Studies at the National Institutes of Health (Bethesda) Clinical Center. Patients and Methods.— We included data from 308 individuals who were interviewed by telephone following inquiry about admittance to the NIAAA clinical research

The growth, structure, and thermal stability of ultra-thin metal films (Rh on Ag(100); Au on Pd(110) and Pt on Pd(110)) is investigated using surface sensitive techniques. The three systems studied present a variety of differing characteristics which can contribute to the growth mode, two-dimensional structure, and thermal stability of the films. The main factors contributing to the differing properties of the three systems presented here are: (1) the different substrate morphologies; (2) the differences in surface free energies between the overlayer and the substrate; (3) the degree of lattice mismatch for a particular system; and (4) the extent of miscibility of the two metals. 200 refs., 38 figs.

SummaryThe limited evidence in this paper supports the claim that hemorrhagic shock profoundly alters the morphology of the motor end plates and finally produces loss of structural innervation of many muscle fibers in a single voluntary muscle. This histologic change is highly irregular in the different muscles of the rat, therefore large numbers of specimens from different muscles were teased. Gold staining masses of axonic materials drain out into and between the muscle fibers coincident in time with the loss of motor innervation due to the increased permeability of the end plates. The epilemmal axons, exhausted of their substances, are in many places likewise denuded of their hypolemmal end plates. There is therefore a real anatomic breakdown of many motor end plates and histologic alteration of certain skeletal muscles in hemorrhagic shock.