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An oral dose of the organophosphate insecticide methamidophos was administered to six volunteers at the acceptable daily intake (ADI, 0.004 mg/kg). Urine was collected from the volunteers at timed intervals for 24 h post-exposure. Methamidophos itself was quantified in urine using liquid/liquid extraction and LC–MS-MS analysis (detection limit 7 nmol/L/1 μg/L). Methamidophos exhibited a rapid elimination half-life of 1.1 h, (range 0.4–1.5 h). Mean metabolite levels found in 24 h total urine collections (normalised for a 70 kg volunteer) were 9.2 nmol/L (range 1.0–19.1). One volunteer was anomalous; excluding this result the range was 6.7–19.1 nmol/L, with a mean of 10.9 nmol/L. Individual urine samples collected during the first 24 h ranged from below the detection limit (ND) to 237 nmol/L. The mean dose recovery excreted as methamidophos in urine was 1.1% (range 0.04–1.71%). Three environmental studies have been reported in the literature with levels ranging from ND to 66 nmol/L. The number of positive results in all three studies was low (<1.5% of total samples analyzed). When compared with our results (ND – 237 nmol/L), the studies suggest general population exposures are within the ADI. However, the very short half-life makes determining intermittent environmental exposures difficult. [ABSTRACT FROM AUTHOR]

In order to study the potential swelling behavior of the ODS ferritic alloy MA957 at very high dpa levels, specimens were prepared from pressurized tubes that were unirradiated archives of tubes previously irradiated in FFTF to doses as high as 110 dpa. These unirradiated specimens were irradiated with 1.8 MeV Cr+ ions to doses ranging from 100 to 500 dpa and examined by transmission electron microscopy. No co-injection of helium or hydrogen was employed. It was shown that compared to several tempered ferritic/martensitic steels irradiated in the same facility, these tubes were rather resistant to void swelling, reaching a maximum value of only 4.5% at 500 dpa and 450 °C. In this fine-grained material, the distribution of swelling was strongly influenced by the presence of void denuded zones along the grain boundaries. [ABSTRACT FROM AUTHOR]

This article describes the derivation of system transfer functions, the analysis of this using Mathematica software, and the construction of Matlab/Simulink system models. Matlab/Simulink system models developed then needed to use a negative-acceleration feedback term, in order to produce a good stabilisation performance. Negative-acceleration minor feedback loops have been used for many years, in rate and position control systems, to modify system responses. However, there is some doubt that this method of modifying system responses had been adequately analysed. [ABSTRACT FROM AUTHOR]

Background: The safety, reactogenicity, immunogenicity, and efficacy of the mRNA-1273 coronavirus disease 2019 (Covid-19) vaccine in young children are unknown.Methods: Part 1 of this ongoing phase 2-3 trial was open label for dose selection; part 2 was an observer-blinded, placebo-controlled evaluation of the selected dose. In part 2, we randomly assigned young children (6 months to 5 years of age) in a 3:1 ratio to receive two 25-μg injections of mRNA-1273 or placebo, administered 28 days apart. The primary objectives were to evaluate the safety and reactogenicity of the vaccine and to determine whether the immune response in these children was noninferior to that in young adults (18 to 25 years of age) in a related phase 3 trial. Secondary objectives were to determine the incidences of Covid-19 and severe acute respiratory syndrome coronavirus 2 infection after administration of mRNA-1273 or placebo.Results: On the basis of safety and immunogenicity results in part 1 of the trial, the 25-μg dose was evaluated in part 2. In part 2, 3040 children 2 to 5 years of age and 1762 children 6 to 23 months of age were randomly assigned to receive two 25-μg injections of mRNA-1273; 1008 children 2 to 5 years of age and 593 children 6 to 23 months of age were randomly assigned to receive placebo. The median duration of follow-up after the second injection was 71 days in the 2-to-5-year-old cohort and 68 days in the 6-to-23-month-old cohort. Adverse events were mainly low-grade and transient, and no new safety concerns were identified. At day 57, neutralizing antibody geometric mean concentrations were 1410 (95% confidence interval [CI], 1272 to 1563) among 2-to-5-year-olds and 1781 (95% CI, 1616 to 1962) among 6-to-23-month-olds, as compared with 1391 (95% CI, 1263 to 1531) among young adults, who had received 100-μg injections of mRNA-1273, findings that met the noninferiority criteria for immune responses for both age cohorts. The estimated vaccine efficacy against Covid-19 was 36.8% (95% CI, 12.5 to 54.0) among 2-to-5-year-olds and 50.6% (95% CI, 21.4 to 68.6) among 6-to-23-month-olds, at a time when B.1.1.529 (omicron) was the predominant circulating variant.Conclusions: Two 25-μg doses of the mRNA-1273 vaccine were found to be safe in children 6 months to 5 years of age and elicited immune responses that were noninferior to those in young adults. (Funded by the Biomedical Advanced Research and Development Authority and National Institute of Allergy and Infectious Diseases; KidCOVE ClinicalTrials.gov number, NCT04796896.). [ABSTRACT FROM AUTHOR]

Ternary austenitic model alloys were modified with 0.25?wt.% titanium and irradiated in the Fast Flux Test Reactor (FFTF) at dose rates ranging over more than two orders in magnitude. While lowering of the dose rate strongly increases swelling by shortening the incubation dose, the steady-state swelling rate is not affected by dose rate. Although titanium addition strongly alters the void microstructure, swelling at about 420°C does not change with titanium additions, but the sensitivity to dose rate is preserved. [ABSTRACT FROM AUTHOR]

The changes due to pulsed plasma flow irradiation on the near-surface microstructure and mechanical properties of the high-chromium, ferritic–martensitic steel EK-181 (Fe16Cr12W2VTaB) have been quantified. Irradiation of EK-181 in this manner produces a microstructural gradient near the material surface, with a two dimensional nanostructured cellular surface. The microstructure and mechanical properties of the modified layer are independent of the initial microstructure and phase composition, and are strongly defined solely by parameters of the plasma flow. High thermal stability of the pulsed plasma-modified layer was explicitly demonstrated. [ABSTRACT FROM AUTHOR]

Ion irradiation has been widely used to simulate neutron-induced radiation damage. There are a number of features of ion-induced damage that differ from neutron-induced damage, however, and these differences require investigation before ion data can be confidently used to predict behavior arising from neutron bombardment. In this study 3.5 MeV self-ion irradiation of pure iron was used to study the influence on void swelling of the depth-dependent defect imbalance between vacancies and interstitials that arises from various surface effects, forward scattering of displaced atoms, and especially the injected interstitial effect. It was observed that the depth dependence of void swelling does not follow the behavior anticipated from the depth dependence of the damage rate. Void nucleation and growth develop first in the lower-dose, near-surface region, and then moves to progressively deeper and higher-damage depths during continued irradiation. This indicates a strong initial suppression of void nucleation in the peak damage region that is eventually overcome with continued irradiation. Using the Boltzmann transport equation method, this phenomenon is shown to be due to depth-dependent defect imbalances created under ion irradiation. These findings demonstrate that void swelling does not depend solely on the local dose level and that this sensitivity of swelling to depth must be considered in extraction and interpretation of ion-induced swelling data. [ABSTRACT FROM AUTHOR]

Objective The objective of this study was to develop metrics to assess opioid prescribing behavior as part of the evaluation of the Extended- Release/ Long- Acting ( ER/ LA) Opioid Analgesic Risk Evaluation and Mitigation Strategies ( REMS). Design Candidate metrics were selected using published guidelines, examined using sensitivity analyses, and applied to cross-sectional rolling cohorts of Medicare patients prescribed with extended-release oxycodone ( ERO) between July 2, 2006 and July 1, 2011. Potential metrics included prescribing opioid-tolerant-only ER/LA opioid analgesics to non-opioid-tolerant patients, prescribing early fills to patients, and ordering drug screens. Results Proposed definitions for opioid tolerance were seven continuous days of opioid usage of at least 30 mg oxycodone equivalents, within the 7 days (primary) or 30 days (secondary) prior to first opioid-tolerant-only ERO prescription. Forty-four percent of opioid-tolerant-only ERO episodes met the primary opioid tolerance definition; 56% met the secondary definition. Fills were deemed 'early' if a prescription was filled before 70% (primary) or 50% (secondary) of the prior prescription's days' supply was to be consumed. Five percent (primary) and 2% (secondary) of episodes had more than or equal to two early fills during treatment. At least one drug screen was billed in 14% of episodes. Stratified analyses indicated that older patients were less likely to be opioid tolerant at the time of the first opioid-tolerant-only ERO prescription. Conclusions Investigators propose three metrics to monitor changes in prescribing behaviors for opioid analgesics that might be used to evaluate the ER/ LA Opioid Analgesics REMS. Low frequencies of patients, particularly those >85 years, were likely to be opioid tolerant prior to receiving prescriptions for opioid-tolerant-only ERO. [ABSTRACT FROM AUTHOR]

Given the increased risk of Guillain-Barré Syndrome (GBS) found with the 1976 swine influenza vaccine, both active surveillance and end-of-season analyses on chart-confirmed cases were performed across multiple US vaccine safety monitoring systems, including the Medicare system, to evaluate the association of GBS after 2009 monovalent H1N1 influenza vaccination. Medically reviewed cases consisted of H1N1-vaccinated Medicare beneficiaries who were hospitalized for GBS. These cases were then classified by using Brighton Collaboration diagnostic criteria. Thirty-one persons had Brighton level 1, 2, or 3 GBS or Fisher Syndrome, with symptom onset 1-119 days after vaccination. Self-controlled risk interval analyses estimated GBS risk within the 6-week period immediately following H1N1 vaccination compared with a later control period, with additional adjustment for seasonality. Our results showed an elevated risk of GBS with 2009 monovalent H1N1 vaccination (incidence rate ratio = 2.41, 95% confidence interval: 1.14,5.11; attributable risk = 2.84 per million doses administered, 95% confidence interval: 0.21, 5.48). This observed risk was slightly higher than that seen with previous seasonal influenza vaccines; however, additional results that used a stricter case definition (Brighton level 1 or 2) were not statistically significant, and our ability to account for preceding respiratory/gastrointestinal illness was limited. Furthermore, the observed risk was substantially lower than that seen with the 1976 swine influenza vaccine. [ABSTRACT FROM AUTHOR]

Abstract: Depending on reactor design and component location, austenitic stainless steels may experience significantly different irradiation dose rates in the same reactor. Understanding the effect of dose rate on radiation performance is important to predicting component lifetime. This study examined the effect of dose rate on swelling, grain boundary segregation, and tensile properties in austenitic stainless steels through the examination of components retrieved from the Experimental Breeder Reactor-II (EBR-II) following its shutdown. Annealed 304 stainless steel, stress-relieved 304 stainless steel, 12% cold-worked 316 stainless steel, and 20% cold-worked 316 stainless steel were irradiated over a dose range of 1–56dpa at temperatures from 371 to 440°C and dose rates from 0.5 to 5.8×10−7 dpa/s. Density and tensile properties were measured for 304 and 316 stainless steel. Changes in grain boundary composition were examined for 304 stainless steel. Swelling appears to increase at lower dose rates in both 304 and 316 stainless steel, although the effect was not always statistically significant. Grain boundary segregation also appears to increase at lower dose rate in 304 stainless steel. For the range of dose rates examined, no measurable dose rate effect on tensile properties was noted for any of the steels. [Copyright &y& Elsevier]

A 59-year-old man with a 4-year history of light chain myeloma relapsing after two preceding autografts and salvage therapy with thalidomide underwent a peripheral blood stem cell (PBSC) transplant from his HLA-identical sister after conditioning with 100 mg/m2melphalan. Graft-versus-host disease (GVHD) prophylaxis comprised cyclosporine. Despite pulmonary infiltrates and sinusitis at the time of the allograft, it was decided to proceed with the transplant because the myeloma was refractory and rapidly progressive. Sputum cultures obtained 2 days before the allograft grew Aspergillus fumigatus 2 days post transplant. A fumigatus grew repeatedly on specimens obtained post transplant. Prompt hematologic recovery was seen with full donor-type chimerism. The fungal infection subsided gradually on a combination of amphotericin B lipid complex and itraconazole. A second aliquot of donor PBSC was infused electively on day +42 to induce graft-versus-myeloma. Complete remission of the myeloma was achieved by 75 days post transplant. No acute GVHD was seen. No chronic GVHD was seen at 16 weeks when he received the third PBSC infusion. He is currently alive and well in remission 9 months post transplant. This case demonstrates the safety and potential usefulness of allogeneic PBSC transplantation with reduced-intensity conditioning in patients with markedly compromised performance status. Bone Marrow Transplantation (2000) 26, 1231–1233. [ABSTRACT FROM AUTHOR]