Seafood consumption has been identified as one of the major contributors of per- and poly(fluoroalkyl) substances (PFASs) to the human diet. To assess dietary exposure, highly consumed seafood ...products in the United States were selected for analysis. The analytical method previously used for processed food was extended to include four additional long-chain perflurocarboxylic acids (PFCAs), which have been reported in seafood samples. This method was single-lab-validated, and method detection limits were reported at 345 ng kg–1 for perfluorobutanoic acid (PFBA) and 207 ng kg–1 for perfluoropentanoic acid (PFPeA) and below 100 ng kg–1 for the rest of the PFAS analytes. The 81 seafood samples (clams, crab, tuna, shrimp, tilapia, cod, salmon, pollock) were analyzed for 20 PFASs using the updated analytical method. Most of the seafood packaging was also analyzed by Fourier transform infrared-attenuated total reflectance (FTIR-ATR) to identify packaging potentially coated with PFASs. None of the packaging samples in this study were identified as having PFASs. A wide range of concentrations was observed among the seafood samples, ranging from below the method detection limit to the highest concentration of 23 μg kg–1 for the sum of PFASs in one of the canned clam samples. Such a wide range is consistent with those reported in previous studies. The highest concentrations were reported in clams and crabs, followed by cod, tuna, pollock, tilapia, salmon, and shrimp. Technical perfluorooctanoic acid (PFOA) dominated the profile of the clam samples, which has been consistently found in other clam samples, especially in Asia. Long-chain PFCAs, specifically perfluoroundecanoic (PFUdA) and perfluorododecanoic (PFDoA), were the most frequently detected analytes across all seafood samples. The trends observed are comparable with those in the literature where benthic organisms tend to have the highest PFAS concentrations, followed by lean fish, fatty fish, and aquaculture. The results from this study will be used to prioritize future studies and to inform steps to reduce consumer exposure to PFASs.
Abstract Purpose Standard of care (SOC) treatment for locally advanced cervical cancer includes pelvic external beam radiation (EBRT) with chemotherapy and interdigitated brachytherapy. We evaluated ...national utilization trends and factors associated with receiving SOC therapy. Materials and methods We utilized the National Cancer Database (NCDB) to identify women with locally advanced cervical cancer treated with definitive radiation or chemoradiation therapy and stratified these patients by treatment received. Results We identified 15,194 patients. Only 44.3% of patients received SOC treatment and this group had significantly improved OS. High volume centers, academic centers, comprehensive community cancer centers, private insurance, and higher income, were all associated with an increased likelihood of receiving SOC, whereas Black patients were less likely to receive SOC. We found 26.8% of patients received no radiation boost, 23.8% received an EBRT boost only, and 49.5% of patients received EBRT with brachytherapy. Although an EBRT boost was advantageous over no boost at all (HR 0.720, p < 0.001), OS was superior in patients who received brachytherapy (HR 0.554, p < 0.001). Patients were more likely to receive no radiotherapy boost if they had lower incomes, Medicaid, were treated at low volume centers, or were treated at non-comprehensive community cancer centers. Conclusions SOC for locally advanced cervical cancer offers superior outcomes, yet less than half of patients receive SOC and there are disparities in which patients receive SOC treatment. No additional treatment, including sophisticated EBRT techniques including IMRT or SBRT, can make up for the survival decrement from lack of brachytherapy as a component of definitive care.
Additional occurrence data are needed to better understand human exposure to per- and poly-fluoroalkyl substances (PFAS) from commercially available foods in the United States. The Food and Drug ...Administration’s (FDA) Total Diet Study (TDS) collects foods that are both nationally and regionally distributed. In 2018, 172 processed foods were collected from grocery stores around Lenexa, KS, as part of the TDS national collection. A previously developed method for the analysis of PFAS in foods as part of the TDS regional collection was modified and optimized for these samples. This method was single lab validated using 5 different matrices and method detection limits were calculated. During the analysis of these samples, challenges arose with method blanks and further investigation into statistical methods to distinguish between blank and sample concentrations were done. The confirmation of two short chain PFAS, perfluorobutanoic acid (PFBA) and perfluoropentanoic acid (PFPeA), was not possible using triple quadrupole mass spectrometry and a confirmation method was developed using high-resolution mass spectrometry. This technique was also used to investigate potential detections and interferents that fell within the retention time criteria for positive detections. In the national collection, positive detections of perfluorooctanesulfonic acid (PFOS) and perfluorononanoic acid (PFNA) were found in frozen fish sticks/patties, PFOS and perfluorodecanoic acid (PFDA) in canned tuna, and PFOS in protein powder. Concentrations were all below 150 ppt, and no other detects were confirmed above the method detection limits in any other foods.
Graphical abstract
•Most observed compounds were shared between samples but varied in abundance.•The molecular variability was greater between brands/oat type than date of purchase.•Differential analysis successfully ...highlighted spiked compounds in food samples.•> 50% of features were reduced from a variety of oat products using in-house databases.•A combination of approaches was beneficial for samples with multiple ingredients.
While analytical methods targeting specific compounds are critical for food safety, analytes excluded from the targeted list will not be identified. Non-targeted analyses (NTA) using LC/HR-MS complement these approaches by producing information-rich data sets where molecular formula can be generated for each detected compound; however, data mining can be labor intensive. Thus, we examined different NTA approaches to reduce the number of compounds needing further investigation, without relying on a suspect list or MS/MS database, both in single ingredient foods (i.e., oats) and more complex, oat-containing samples. We investigated inherent sample variability and utilized this information to build in-house databases for removing food compounds from sample data. While food databases were useful for data reduction, differential analysis was the most promising approach for single ingredient foods because it substantially reduced the number of features while retaining spiked QC compounds; however, a combination of approaches was necessary with greater sample complexity.
Nontargeted (NTA) and suspect screening analyses (SSA) aim to detect and identify unknown compounds of interest from a given sample. The complexity and diversity of NTA and SSA methodologies ...necessitate the use of a comprehensive quality control standard mixture to determine if methods are fit for purpose, but to our knowledge, such a standard has not been developed that can be used by multiple disciplines, nor is one readily available. This work describes the development and analysis of a proposed nontargeted standard/quality control mixture for NTA and SSA applications using liquid chromatography/electrospray ionization-high resolution-mass spectrometry. Considerations in its development included achieving diversity of compounds with respect to elemental composition, molecular weight, retention time, and ionization in positive and/or negative ion modes, which resulted in the inclusion of 89 compounds. The utility of the standard mixture was applied on our own NTA and SSA workflows where sample preparation efficiency and potential sources of error due to instrumental and data processing methods were evaluated. Some areas in need of improvement were identified, such as hydrophilic compound detection and molecular formula generation for compounds containing fluorine. However, our overall methodology was found to be fit for purpose and we were able to establish thresholds to increase reliability and throughput of reported results.
The development of breast-conserving treatment for early-stage breast cancer is one of the most important success stories in radiation oncology in the latter half of the twentieth century. Lumpectomy ...followed by radiotherapy provides an appealing alternative to mastectomy for many women. In recent years, there has been a shift in clinical investigational focus toward refinements in the methods of delivering adjuvant radiotherapy that provide shorter, more convenient schedules of external-beam radiotherapy and interstitial treatment. Expedited courses of whole-breast treatment have been demonstrated to be equivalent to traditional lengthier courses in terms of tumor control and cosmetic outcome and to provide an opportunity for cost efficiencies.
The development and expansion of analytical methods for per- and polyfluoroalkyl substances (PFAS) in food are essential for the continued monitoring of the United States (US) food supply and ...assessments of dietary exposure. In March 2022, the European Union Reference Laboratory for Halogenated Persistent Organic Pollutants in Feed and Food (EURL POPs) released a guidance document covering priority PFAS of interest, including analytical method parameters and limits of quantification (LOQs). As a result, the Food and Drug Administration (FDA) began method extension work to incorporate ten new additional analytes to method C-010.02 including long-chain perfluorosulfonic acids, fluorotelomer sulfonates, and perfluorooctane sulfonamide. Four long-chain carboxylic acids were also validated across all foods, which were previously added to C-010.02 but only validated in seafood. In December 2022, the European Union published Commission Regulation 2022/2388, establishing maximum levels for perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS) in certain foodstuffs, primarily fish, molluscs, crustaceans, and eggs. As a result, the FDA method was evaluated for performance in reaching LOQs defined in Commission Regulation (EU) 2022/1431. The FDA method was found to be able to reach all required LOQs for analytes in matrices with established maximum levels. Currently, method detection limits (MDLs), which are used by the FDA as the lower limit for reporting PFAS in surveillance samples, were in the same range as defined indicative levels. With further method modifications, required LOQs could be met in fruits, vegetables, and milk. Reaching the lower targeted LOQs for these food matrices will require moving the method to an instrument that can provide increased signal:noise gains at the lower limits of quantification.
Graphical abstract
Borosilicate theta glass capillaries pulled to serve as nanoelectrospray ionization emitters are used for short time-scale mixing of protein and acid solutions during the electrospray process to ...alter protein charge state distributions (CSDs) without modifying the sample solution. The extent of protein CSD shifting/denaturing can be tailored by acid identity and concentration. The observed CSD(s) are protein dependent, and the short mixing time-scale enables the study of short-lived unfolding intermediates and higher charge states of noncovalent protein complexes, including those of holomyoglobin. Additionally, the theta tips provide a simple and inexpensive method for mixing nonvolatile reagents such as supercharging agents, which cannot be used with previously developed vapor leak-in techniques, with protein solutions during the electrospray process.
Patients with human EGFR2-positive (HER2
) breast cancer have a high incidence of brain metastases, and trastuzumab emtansine (T-DM1) is often employed. Stereotactic radiosurgery (SRS) is frequently ...utilized, and case series report increased toxicity with combination SRS and T-DM1. We provide an update of our experience of T-DM1 and SRS evaluating risk of clinically significant radionecrosis (CSRN) and propose a mechanism for this toxicity.
Patients with breast cancer who were ≤45 years regardless of HER2 status or had HER2
disease regardless of age and underwent SRS for brain metastases were included. Rates of CSRN, SRS data, and details of T-DM1 administration were recorded. Proliferation and astrocytic swelling studies were performed to elucidate mechanisms of toxicity.
A total of 45 patients were identified; 66.7% were HER2
, and 60.0% were ≤ 45 years old. Of the entire cohort, 10 patients (22.2%) developed CSRN, 9 of whom received T-DM1. CSRN was observed in 39.1% of patients who received T-DM1 versus 4.5% of patients who did not. Receipt of T-DM1 was associated with a 13.5-fold (
= 0.02) increase in CSRN. Mechanistically, T-DM1 targeted reactive astrocytes and increased radiation-induced cytotoxicity and astrocytic swelling via upregulation of Aquaporin-4 (Aqp4).
The strong correlation between development of CSRN after SRS and T-DM1 warrants prospective studies controlling for variations in timing of T-DM1 and radiation dosing to further stratify risk of CSRN and mitigate toxicity. Until such studies are completed, we advise caution in the combination of SRS and T-DM1.
The 2017–2027 National Academies' Decadal Survey, Thriving on Our Changing Planet, recommended Surface Biology and Geology (SBG) as a “Designated Targeted Observable” (DO). The SBG DO is based on the ...need for capabilities to acquire global, high spatial resolution, visible to shortwave infrared (VSWIR; 380–2500 nm; ~30 m pixel resolution) hyperspectral (imaging spectroscopy) and multispectral midwave and thermal infrared (MWIR: 3–5 μm; TIR: 8–12 μm; ~60 m pixel resolution) measurements with sub-monthly temporal revisits over terrestrial, freshwater, and coastal marine habitats. To address the various mission design needs, an SBG Algorithms Working Group of multidisciplinary researchers has been formed to review and evaluate the algorithms applicable to the SBG DO across a wide range of Earth science disciplines, including terrestrial and aquatic ecology, atmospheric science, geology, and hydrology. Here, we summarize current state-of-the-practice VSWIR and TIR algorithms that use airborne or orbital spectral imaging observations to address the SBG DO priorities identified by the Decadal Survey: (i) terrestrial vegetation physiology, functional traits, and health; (ii) inland and coastal aquatic ecosystems physiology, functional traits, and health; (iii) snow and ice accumulation, melting, and albedo; (iv) active surface composition (eruptions, landslides, evolving landscapes, hazard risks); (v) effects of changing land use on surface energy, water, momentum, and carbon fluxes; and (vi) managing agriculture, natural habitats, water use/quality, and urban development. We review existing algorithms in the following categories: snow/ice, aquatic environments, geology, and terrestrial vegetation, and summarize the community-state-of-practice in each category. This effort synthesizes the findings of more than 130 scientists.
•The 2017 Decadal Survey recommended Surface Biology and Geology mission•Visible to shortwave infrared hyperspectral and multi-band thermal data•Global high resolution measurements at sub-monthly temporal resolution•Applications in snow/ice, aquatic environment, geology, and terrestrial vegetation•We review existing relevant algorithms and community-state-of-practice
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